key: cord- -t cnjwpd authors: sung, ming-hua; lin, chao-nan; chiou, ming-tang; cheng, i-ju; thanh, quang-hien; chao, day-yu; lan, yu-ching title: phylogeographic investigation of porcine epidemic diarrhea virus (pedv) transmission in taiwan date: - - journal: plos one doi: . /journal.pone. sha: doc_id: cord_uid: t cnjwpd the porcine epidemic diarrhea virus (pedv) that emerged and spread throughout taiwan in triggered significant concern in the country’s swine industry. acknowledging the absence of a thorough investigation at the geographic level, we used outbreak sequence information from the taiwan government’s open access databases plus genbank records to analyze pedv dissemination among taiwanese pig farms. genetic sequences, locations, and dates of identified pedv-positive cases were used to assess spatial, temporal, clustering, gis, and phylogeographic factors affecting pedv dissemination. our conclusion is that s gene sequences from pedv-positive clinical samples collected in taiwan were part of the same genogroup identified in the us in . according to phylogenetic and phylogeographic data, viral strains collected in different areas were generally independent of each other, with certain clusters identified across different communities. data from gis and multiple potential infection factors were used to pinpoint cluster dissemination in areas with large numbers of swine farms in southern taiwan. the data indicate that the taiwan pedv epidemic resulted from the spread of multiple strains, with strong correlations identified with pig farm numbers and sizes (measured as animal concentrations), feed mill numbers, and the number of slaughterhouses in a specifically defined geographic area. porcine epidemic diarrhea virus (pedv) causes acute diarrhea, vomiting, and dehydration, resulting in high mortality rates for suckling piglets [ ] . since , a new pedv variant belonging to genogroup has spread throughout the united states and across multiple asian countries, including china and taiwan [ , ] . an initial identification in the us was made in april of [ ] . a . % premises-level incidence of pedv caused the deaths of more than a a a a a million newborn piglets in a single year-an event that significantly affected the american swine industry [ ] [ ] [ ] [ ] [ ] . subsequent genogroup epidemics have been reported in major swineproducing countries such as canada, mexico, taiwan, korea and japan [ , [ ] [ ] [ ] [ ] . one of the most notable pedv outbreaks occurred in south korea in late [ ] , more than a half million pigs died from pedv infections in japan between and [ ] , and a significant increase in pedv outbreaks occurred in taiwan around the same time [ ] . pedv is now considered the world's most catastrophic swine disease, with major financial impacts noted throughout the global pork industry. the pedv genome is comprised of at least seven open reading frames (orf a, orf b and orf - ) encoding four structural (s), envelope (e), membrane (m), and nucleocapsid (n) proteins [ ] . a high degree of genetic diversity has been observed in the s glycoprotein gene [ ] [ ] [ ] . partial spike (s) polyprotein genes located in the virus envelope are central to pedv biological properties such as interactions with cellular receptors during virus entry, the neutralizing of antibody induction in natural hosts, growth adaptation in vitro, and virulence attenuation in vivo [ ] . the pedv spike (s) protein is a type transmembrane envelope glycoprotein with a , nucleotide sequence divided into s and s domains. the s region (aa - ) is responsible for viral binding, while the s domain (aa - ) serves as an anchor for viral membrane and fusion activity [ , ] . thus, the s glycoprotein is considered a primary target for pedv vaccine development. as the major envelope glycoprotein found in virion, s serves as an important viral component for studying genetic relationships among pedv isolates, and for determining pedv epidemiological status [ , ] . pedv is believed to infect pigs by both direct and indirect fecal-oral routes. due to the scales and complexities of modern swine production systems, pedv is likely transmitted between farms via diarrheic feces or vomitus; contaminated environmental sources involving clinically or sub-clinically infected pigs; trailers used to transport livestock, manure, or food sources; farmers or visitors wearing contaminated clothes; or wild animals and birds [ , ] . other potential sources include contaminated fomites (e.g., raw food, feed, sow milk), food ingredients or additives, and environmental features such as wind direction, farm altitude, terrain slope, and tree coverage [ ] . after an initial outbreak, pedv may spread at an increasingly rapid rate due to inadequate farm hygiene management procedures such as improper disinfection and poor biosecurity. the virus can remain dormant in weaning pigs or growth finishing units, eventually triggering mild symptoms and resulting in low mortality rates [ ] . although researchers believe that pedv infections primarily result via fecal-oral routes, the rapid regional spread of the disease raises the possibility of airborne transmission [ ] . support for this hypothesis includes an identified correlation between disease-spread direction and prevailing wind direction [ ] , with environmental features such as land coverage, altitude, and slope possibly influencing airborne disease dissemination [ ] . to determine specific temporal and geographic relationships associated with pedv strain transmission, we used phylogenetic, phylodynamic and phylogeographic methods to systematically evaluate potential temporal and spatial transmission routes among taiwanese swine farms during the outbreak. epidemiological and geographic data were collected from animal lab reports of pedv viral infections involving , pig farms, pig feed mills, slaughterhouses, and , , animals. these reports are available from an open database maintained by the taiwan government. additional epidemiological and genetic information was gathered for purposes of determining details of the disease spread. a total of global pedv whole genome sequences (s table) and taiwan partial s gene sequences ( nucleotide of pedv s gene position - ) (s table) were downloaded from genbank, and information for the tw whole genome sequence was collected from a previous study [ ] . information datasets focused on pig feeding and disease were collected from the taiwan open data website (http:// data.gov.tw/), the animal health research institute of the taiwan executive yuan's agricultural council (http://eng.nvri.gov.tw/fmodule/default.aspx), and genbank (https://www.ncbi. nlm.nih.gov/genbank/). in the first stage of this study, pedv phylogenetic and phylogeographic data analyses were performed for purposes of organizing viral transmission evidence and tracking possible transmission routes. in the second, data for variables of interest associated with the pig feed industry were collected and combined with geographic information system (gis) data for investigation using open source quantum gis (qgis v . . ) software [ ] . an sas mixed procedure was used to create linear regression models, with livestock breeding variables employed to predict pedv infections. gene sequences for the global pedv whole genomes and taiwan pedv partial s gene sequences were downloaded from genbank and aligned with a single taiwan pedv complete genome from a previous study [ ] using the clustalw multiple alignment feature in bioedit [ ] . the best-fit model, as determined using jmodeltest . . [ ] , had a gamma distribution (gtr+g+i). to ensure topological consistency, phylogenetic trees were constructed using maximum likelihood (ml) and bayesian methods (mega version . and beast v . . , respectively). branch support was evaluated using bootstrap analyses based on , ml tree replications. bootstrap values > % were considered as belonging to the same monophyletic group. to identify the specific locations of migration events, we grouped the pedv isolates into different counties and used various pedv viral strains as references. spatial location reconstruction and viral migration activity were estimated using discrete coalescent tree and bayesian phylogeographic methods. bayesian markov chain monte carlo (mcmc) sampling using beast v . . [ ] was employed to infer the time-scaled phylogenies of partial pedv s genes. hky+g and relaxed clock exponential models were used prior to setting coalescent population constants in the mcmc simulations. estimated convergence and effective sampling sizes were visually assessed using tracer v . . multiple chains were combined based on a % burnin using the version of logcombiner (v . . ) included in the beast package. maximum clade credibility trees with temporal and spatial annotations were summarized with the % burn-in removed using treeannotator (v . . , also in the beast package). figtree (v . . ) was used to generate presentation figures. bayes factor (bf) tests were conducted to build statistical support for transmission routes among geographic locations using spread (v . . ; bf cutoff = ) [ ] . bf values were used to indicate differences between posterior and prior probabilities so that rates between any two locations were non-zero. routes with high bf values were considered as having greater potential for viral strain migration. to create animations of viral dispersion over time, annotated mcc trees were converted into a keyhole markup language (kml) file using spread (v . . ). the kml file can be visualized with an open-access earth map downloaded from natural earth (http://www. naturalearthdata.com) as a qgis software base layer. the maximum-likelihood phylogenetic tree (fig ) was constructed from global pedv whole genome sequences. sequences found in taiwan clustered with % bootstraps containing viruses from other asian countries and the us between and . a correlation was determined between this cluster and the genogroup originally identified in the us. among the taiwan sequences, some of the viruses collected and identified in were strongly correlated with one another (bootstrap values > %), while others were mixed with viral strains collected in other countries at different times, suggesting multiple transmission events (fig & table ). to further evaluate transmission periods and to verify viral strain origins, all partial s gene sequences determined from the taiwan pedv samples were used for phylodynamic data analyses (fig ) . four clusters (a, b, c and d) exhibited statistically significant posterior probabilities (> . ), including viral strains on monophyletic branches. the most recent common ancestor (mrca) for the viral strains was traced to july . all other coalescent tree sequences were determined as independent. viral branches had mrcas in or the spring of , with none identified as statistically significant. thus, the phylodynamic coalescent tree established for this study indicates the involvement of multiple virus strains in the pedv outbreak. results from our phylogeographic analysis were matched to a map of the country to specify the geographic boundaries of the taiwan outbreak (fig ) . next, molecular sequence data were combined with isolation time data and geographic coordinates to determine the spatiotemporal distribution of taiwan pedv strains. lineages were identified in several agricultural communities in the far south, with additional virus strains found in central taiwan at approximately the same time. the southern infections were spatially closer to each other. the data indicate an absence of natural and artificial barriers restricting the spread of the virus. the pig feed industry risk map shown was created to assist in the identification of significant risk factors associated with infections ( fig ) . results from our gis system analysis of positive cases indicate correlations between pedv infection transmission and both pig farm size (number of pigs, not physical size) ( . , % ci [ . , . ]) and slaughterhouse distribution ( . , % ci [ . , . ]) ( table ). our data also indicate higher infection rates in counties with fewer pig feed mills (- . , % ci [- . , - . ]). phylogeographic inferences are a potential tool for identifying the transmission and dissemination routes of pedv and other potentially much deadlier infectious diseases. however, to date very few research efforts in asia have utilized full genome sequencing for determining geographic structures due to the high costs and enormous amounts of computational time phylogeographic investigation of porcine epidemic diarrhea virus transmission in taiwan required for analyses [ , ] . several researchers have suggested using partial s genes for phylogenetic tree construction and for phylodynamic analyses specifically aimed at studying the genetic relatedness of pedv strains [ , , ] . in this study, we investigated temporal and geographic relationships among pedv strains identified as having been transmitted among farms in taiwan in , using partial sequences from s genes extracted from porcine fetus samples and genbank sequences as reference panels. according to the phylogenetic tree we constructed based on these partial s gene sequences, the primary pedv strain in taiwan is related to the genogroup strain identified in samples collected in the us in [ ] . as previously suggested, the most recently identified taiwan pedv strains have greater similarity with us strains than with chinese or earlier taiwanese strains [ , ] . transmission may have occurred as early as december [ ] , but the crossborder route to taiwan remains unknown. results from our phylogenetic analysis of pedv viruses associated with the taiwan outbreak confirm independence in multiple counties. although these viruses share a common ancestry with the us genogroup pedv, our coalescent tree data indicate that only of the taiwanese viruses were significantly clustered (fig ) . further, no recombination involving taiwanese strains was observed in the present study. five independent pedv strains were identified in taiwan on or before september , in wanda (km and km ) and jhutian (km , km and km ) townships. these are considered starting points for pedv complex dissemination throughout sections of taiwan up to may , . according to a mix of phylogenetic and coalescent data ( table ) , clustering was limited to counties in southern taiwan (wanluan, jiouru and daliao) (fig ) , with most of the identified viruses existing independently. combined, data for pedv divergence during the taiwan outbreak suggest a common ancestry shared by multiple virus lineages. since that time period, no evidence has been found indicating outbreaks involving multiple virus strains in taiwan. according to our phylogenetic analysis, most of the identified pedv strains from the outbreak were independent, despite sharing a common ancestor. multiple pedv invasions from abroad were also identified in japan during the outbreak [ , ] . the widespread dissemination that followed presumably resulted from the movement of pigs, agricultural vehicles, farmers, farm visitors, commercial feed products, and other materials [ , ] . reproducing novel approaches used in the molecular and spatial surveillance of the porcine reproductive and respiratory syndrome virus (prrsv) in the us and in pedv studies in japan [ , ] , we utilized a combination of phylogeographic and gis approaches in our effort to profile the taiwan pedv outbreak. gis has been used to investigate correlations between diseases and factors that include pig farm size, number of feed mills, and number of pig slaughterhouses in a specified geographic zone (fig ) . we used a mixed linear regression to identify factors associated with the number of pedv cases in taiwan. results indicate positive correlations between the number of cases and both slaughterhouse number and pig farm size, and a negative correlation with number of feed mills ( table ). the highest concentration of pedv cases was identified in a multi-county section of southern taiwan characterized by a large number of pig farms with high animal densities. our results are in agreement with findings from previous studies suggesting that excessive farm capacity (measured as the total number of pigs on a farm) is a risk factor for the spread of pedv [ ] . further, aerosol transmission is considered a viable dissemination route in environments marked by high pig densities and close animal proximities [ ] . regarding the negative correlation between pedv cases and number of feed mills, our data indicate that pig farms at the end of feed routes likely have higher probabilities of infections. some reports suggest that vehicles used for the dual purposes of transporting swine to slaughterhouses and delivering feed to farms may increase the potential for pedv due to feedbag contamination [ , , , ] . our finding of a high correlation between the number of pedv cases and the number of pig slaughterhouses suggests that transport trucks may have been a factor in the taiwan outbreak. other risk factors requiring further research include spray-dried porcine plasma (sdpp, an important blood-based component of nursery pig diets) and improper disposal procedures when pig corpses are collected and sent to rendering plants. there is a clear need to collect more data on feed truck routes, sdpp supplement distribution, rendering plant procedures (especially delivery), and slaughterhouse processes when trying to identify the sources of various strains in taiwan. due to the potential for significant financial losses, there is a strong need to act on these and other possible factors before detailed studies can be designed, funded, and completed. farms, slaughterhouses, and feed suppliers in counties with high pig densities need to immediately enhance their biosecurity measures to prevent future pedv outbreaks, and greater effort is required to monitor potential transmission routes. table. https://doi.org/ . /journal.pone. .g supporting information s conceptualization: yu-ching lan. porcine epidemic diarrhea, diagnosis, and elimination introduction of pedv outbreak and prevention method evolutionary characterization of the emerging porcine epidemic diarrhea virus worldwide and epidemic in taiwan. infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases evidence of infectivity of airborne porcine epidemic diarrhea virus and detection of airborne viral rna at long distances from infected herds epidemiological factors associated to spread of porcine epidemic diarrhea in japan. preventive veterinary medicine porcine epidemic diarrhea virus: an emerging and re-emerging epizootic swine virus a porcine epidemic diarrhea virus outbreak in one geographic region of the united states: descriptive epidemiology and investigation of the possibility of airborne virus spread deadly pig virus slips through us borders risk factors for porcine reproductive and respiratory syndrome virus infection and resulting challenges for effective disease surveillance isolation and characterization of porcine epidemic diarrhea viruses associated with the disease outbreak among swine in the united states fighting a deadly pig disease. industry, veterinarians trying to contain ped virus, new to the us comparison of porcine epidemic diarrhea viruses from germany and the united states novel porcine epidemic diarrhea virus variant with large genomic deletion, south korea. emerging infectious diseases isolation of porcine epidemic diarrhea virus during outbreaks in south korea phylogeographic investigation of porcine epidemic diarrhea virus transmission in taiwan plos one isolation and molecular characterization of porcine epidemic diarrhea viruses collected in japan in us-like strain of porcine epidemic diarrhea virus outbreaks in taiwan porcine epidemic diarrhoea virus: a comprehensive review of molecular epidemiology, diagnosis, and vaccines novel porcine epidemic diarrhea virus (pedv) variants with large deletions in the spike (s) gene coexist with pedv strains possessing an intact s gene in domestic pigs in japan: a new disease situation. plos one heterogeneity in spike protein genes of porcine epidemic diarrhea viruses isolated in korea detection and molecular diversity of spike gene of porcine epidemic diarrhea virus in china the s glycoprotein subunit of porcine epidemic diarrhea virus contains immunodominant neutralizing epitopes cellular entry of the porcine epidemic diarrhea virus sequence analysis of the partial spike glycoprotein gene of porcine epidemic diarrhea viruses isolated in korea coronaviruses: structure and genome expression role of transportation in spread of porcine epidemic diarrhea virus infection, united states. emerging infectious diseases land altitude, slope, and coverage as risk factors for porcine reproductive and respiratory syndrome (prrs) outbreaks in the united states molecular characterization of the porcine epidemic diarrhea virus tw / in taiwan. austin virology and retro virology qgis geographic information system. open source geospatial foundation bioedit: a user-friendly biological sequence alignment editor and analysis program for windows / /nt jmodeltest : more models, new heuristics and parallel computing bayesian phylogeography finds its roots spread: spatial phylogenetic reconstruction of evolutionary dynamics origin, evolution, and genotyping of emergent porcine epidemic diarrhea virus strains in the united states porcine epidemic diarrhea virus infection: etiology, epidemiology, pathogenesis and immunoprophylaxis distinct characteristics and complex evolution of pedv strains us-like strain of porcine epidemic diarrhea virus outbreaks in taiwan molecular characterization of pig epidemic diarrhoea viruses isolated in japan from to . infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases spatial dynamics of porcine epidemic diarrhea (ped) spread in the southern kyushu, japan. preventive veterinary medicine an evaluation of contaminated complete feed as a vehicle for porcine epidemic diarrhea virus infection of naive pigs following consumption via natural feeding behavior: proof of concept an evaluation of a liquid antimicrobial (sal curb(r)) for reducing the risk of porcine epidemic diarrhea virus infection of naive pigs during consumption of contaminated feed key: cord- -mh pslnv authors: breda, zélia; costa, carlos title: safety and security issues affecting inbound tourism in the people's republic of china date: - - journal: tourism, security and safety doi: . /b - - - - . - sha: doc_id: cord_uid: mh pslnv nan over the past few years, the tourism industry has been seriously undermined by the growing lack of safety and security. this factor has been identified as one of the five forces causing changes in the tourism sector in the new millennium. crime, terrorism, food safety, health issues, and natural disasters are the main areas of concern. however, these issues only started to gain more visibility after the september events. terrorist attacks have also been experienced in other parts of the world and they are pushing the travel industry to deal with a major travel paradigm shift, which is based on the fact that tourism security is now a key concern for travelers. it is now widely accepted by the international community that the success of the tourist industry in a particular country or region is directly linked to its ability to offer tourists a safe and pleasant visit. governments, travel agents, and news media periodically issue warnings about the risks associated with international tourism. tourists are urged to buy guidebooks and obtain vaccinations as precautions against such risks. for quite a long time the influence of safety and security for tourism had been ignored in the literature, particularly the issue of safety in the destination country as a determinant of tourism demand. tourism literature is now turning its attention to matters of safety and security, which were classified among the ten most important world tourism issues for . previous research has pointed out four major risk factors: crime (de albuquerque and mcelroy, ; alleyne and boxill, ; barker, page, and meyer, ; barker, page, and meyer, ; brunt, mawby, and hambly, ; dimanche and lepetic, ; george, ; lepp and gibson, ; levantis and gani, ; lindqvist and björk, ; mawby, ; roehl and fesenmaker, ) ; health-related risks (cartwright, ; maclaurin, ; maclaurin, maclaurin, and loi, ) ; terrorism (coshall, ; kuto and groves, ; leslie, ; pizam and fleischer, ; pizam and smith, ; sönmez, ; sönmez, apostolopoulos, and tarlow, ; sönmez and graefe, ; tarlow, ) ; and war and political instability (ioannides and apostolopoulos, ; neumayer, ; richter, ; weaver, ) . concern for crime and safety, whether real or perceived, has been clearly identified as adversely affecting tourism behavior, influencing destination choice and experience satisfaction. political instability and war can increase the perception of risk at a destination. similarly, terrorism can cause a profound impact on destination image. health hazards are also regarded as potential issues that can undermine tourism development. all disasters can divert tourism flows away from affected destinations, but war, terrorism, or political instability have a much greater negative psychological effect on potential tourists when planning their vacations (cavlek, ) . this applies not only to the time of crisis, but also to the period following it. although there is no evidence of a threat from global terrorism in the people's republic of china (prc) and the country's image is seen as generally safe, there are some issues related to political instability, health, safety and security concerns that have caused disruptions in growth rates. since safety and security directly influence decisions in international travel, this chapter researches the consequences of relevant events that have caused major disturbances in inbound tourism in the prc, namely the tiananmen square incident and the outbreak of severe acute respiratory syndrome (sars). in addition to these two main issues, which until now were the only ones capable of deterring china's booming domestic and international tourism industry, other important issues will be discussed. other epidemic diseases (such as hiv/aids, avian influenza, and mosquito-borne diseases); crime directed at foreigners in major cities and tourist areas; road and air safety; natural disasters (earthquakes, flooding, and typhoons); crossstrait relations; and restrictions on public demonstrations, political, and religious activities constitute important considerations that will be also addressed throughout the chapter. tourism security and safety: from theory to practice a useful way to study the evolution of the traveler safety situation in china is through guidebooks. although these do not constitute scholarly works, they convey the impressions of professional travel observers and are widely disseminated among prospective travelers, playing a large part in the creation of a destination image. although nowadays there is no lack of travel guides, the present work has focused on lonely planet because it is one of the best-selling english-language guidebooks, and it was the first to be published on china (the next guide to be published on china-the rough guide-wasn't published until years later). lonely planet's first edition was issued in october , six years after the country's opening up to international tourism, targeting primarily budget and independent english-speaking travelers, particularly young people. the comparison between lonely planet's first edition (hereafter referred to interchangeably as the first edition or the edition) and the latest edition (the th, published in august ) is very useful to identify the consumer image of china's safety and security evolution over the past years. the edition's section on health sounded a bit alarming, starting with the notification that cholera and yellow fever vaccinations were required for travelers going to certain areas. malaria and hepatitis were identified as serious infectious diseases in china. tetanus, diarrhea, and drinking water problems also received special attention. the th edition expanded on the health risks section, but was more reassuring. it noted that although china had particular health hazards and that some problems can be encountered in isolated areas, it is a healthier place to travel to compared to other parts of the world. sexually transmitted diseases, with special attention given to hiv/aids, were pointed out as something that foreigners should be cautious about, due to the fact that they are becoming more widespread in china. regarding physical safety, the first edition presented china as not exactly a crime-free country, but not especially dangerous. however, the authors devoted several paragraphs to the unsettling nature of the chinese justice. the edition of identified economic crimes as the most common offenses committed against international travelers. foreigners were pointed out as natural targets for pickpockets and thieves, with certain cities, like guangzhou, guiyang, and xi'an, as the most notorious examples of this type of crime. high-risk places were mainly train and bus stations. nevertheless, some more violent crimes, with foreigners being attacked or even killed for their valuables, were reported in more rural locations, thereby stressing that individual traveling to those areas should be regarded as at high risk. terrorism activities were also reported, although it was highlighted that foreign travelers were not specific targets. racism in china is not a real problem. its existence is not recognized by the chinese people; however, racial (ethnic) purity is still the desired norm. the isolationist position imposed by the communist leaders over more than three decades, coupled with a millenary self-centered vision of the world, did really have a lasting effect on chinese people (huyton and ingold, ) . although it is unusual to encounter direct racism in the form of insults or to be refused services in china, tourism safety and security in the prc especially directed at white people coming from prosperous nations, africans or people of african ancestry and travelers from other asian nations can face discrimination. the old dual-pricing system for foreigners was identified in the edition as fundamentally racist. this discriminatory pricing was exemplified in the edition, referring several times to the higher costs charged to foreigners. the cost of hotel rooms depends on what you are. if you have a white face and a big nose then you pay the most. the chinese also attempt to plug you into the most expensive of the tourist hotels, and to give you the most expensive rooms. they do this for two reasons; they want the money, but also they think you're spectacularly wealthy, and that you'll want to do things in spectacular style . . . they're not trying to rip you off, they're just trying to please you. (samalgaski and buckley, , p. ) prices and services showed racial disparities, regardless of the person's willingness to pay. overseas chinese (holders of a chinese passport who reside outside china in countries or regions other than taiwan, macao, and hong kong) or compatriots (visitors from taiwan, macao, and hong kong) were frequently refused service, or given poor service (anyway the quality was generally low, as employees had very little knowledge of international standards), just because they paid less than foreign visitors. foreign visitors, on the other hand, often felt embarrassed and annoyed by their preferential treatment (zhang, ) . this special treatment took place not long after the end of the cultural revolution. the hard-line communist leaders' way of thinking that characterized the cultural revolution period had fostered anti-foreign sentiments, resulting in foreigners in china being insulted and badly treated. under the new government's kowtowing policy foreigners received special treatment, while the government relegated its citizens to an inferior condition (richter, ) . the campaign against "spiritual pollution" from the west was launched in china in the mid- s, but it did not affect tourism, as the attack on spiritual pollution was deliberately kept as a low key internal affair, and most tourists were quite unaware of it (lynn, ) . nonetheless, the ambivalent chinese attitude toward foreigners has naturally affected how they handle tourists. as a s writer once said, "throughout the ages, chinese have had only two ways of looking at foreigners, up to them as superior beings or down on them as wild animals. they have never been able to treat them as friends, to consider them as people like themselves" (quoted in richter, , p. ). travel warnings and advice issued by governments of the main outbound tourist markets to china were analyzed in an attempt to verify major concerns regarding the safety and security of their citizens while traveling in china. with the aim of acquiring a broad picture of the nature of those concerns, research was conducted in order to identify what type of information had been released to travelers to china in each world region. government organizations, as well as some international agencies, were the main source of information regarding potential disruptions to tourism in china. although nine countries were firstly considered as significant to analyze (japan, usa, uk, canada, malaysia, korea, germany, russia, and australia), it was soon realized that only english-speaking countries, with the exception of japan, had such information available to their citizens on the tourism security and safety: from theory to practice internet, which is a useful and rapid way to disseminate information. as tourists tend to be better informed about destinations prior to their trip, travel advisories issued by competent entities are of crucial significance. the facts presented below are thus based on the information collected from travel advisories issued by governmental agencies (the content of those warnings was found to be very similar), thus permitting the construction of an image of china's safety and security situation, and how it is regarded by its main tourist-generating markets. (see table .) because of the economic damage that can be inflicted on a country's tourism industry, its visibility, and the leverage it may have on governments, some terrorist and organized crime groups have targeted tourism directly. the fact that in the september terrorist attacks, passenger airplanes, which are a key part of the tourism system, were used as weapons, has had a damaging psychological effect. these attacks strikingly impacted the tourism sector worldwide, being more dramatic than any other crisis in recent years (wto, ) . in asia, the situation has deteriorated as a result of regional terrorism, especially the october bali bombings, which exacerbated people's reactions regarding asia as a tourist destination. there is no evidence of global terrorism in china, although a small number of bomb-related actions and incidents of unrest do occur. over the past years there has been an increase in bombing events throughout the country. however, this does not constitute a serious threat to tourists, since foreigners are not specific targets. nonetheless, there is always the risk of indiscriminate attacks against civilian targets in public places, including tourist sites. these bombings are often the result of commercial disputes among chinese. it is true that terrorist attacks are also common, many of which have been linked to the eastern turkistan islamic movement (etim), also known as the xinjiang-uyghur separatist movement. etim was designated a terrorist organization by the united nations in and is currently active in the xinjiang autonomous region. xinjiang is largely constituted by muslim turkic-speaking minorities (uygurs, kazakhas, kirghizs, and uzbeks) and there has been ethnic tension between these four groups and the han people for quite a long time. these conflicts have promoted the upsurge of a movement calling for the turkic-speaking people to unite and form an east turkistan state tourism safety and security in the prc under islam. since the s, various factions of the etim have engaged in a series of violent incidents (supported and funded by al qaeda), both inside and outside china, which were responsible for a total of deaths and more than injuries, and for a serious negative impact on social stability in china and in neighboring countries (wang, ) . crimes against tourists result in bad publicity for destinations and create a negative image in the minds of prospective visitors. tour operators tend to avoid destinations that have the reputation for crimes against tourists (goeldner and ritchie, ) . they also play a very important role in creating the image of a destination and can significantly influence international tourism flow toward a country hit by safety and security risks (cavlek, ) . overall, china is a safe country, with a low but increasing crime rate. serious crimes against foreigners are rare. nevertheless, crime does occur both in chinese cities and in the countryside. crime directed at foreigners is becoming more frequent in major cities and at tourist sites, which attract thieves and pickpockets. robberies and attacks on foreigners in popular expatriate bar and nightclub areas in beijing and shanghai, and in the shopping district of shenzhen, are common. minor thefts and sexual harassment on overnight trains and buses tend also to occur. the most remote areas of china are poorly policed and there is the risk of attack from armed bandits. in yunnan, drug smuggling and related crimes are increasing. money exchange on the black market at better rates is frequent in china. foreigners tempted to exchange money this way, besides breaking the law and possibly having to incur charges, face the risk of shortchanging, rip-offs, and receiving counterfeit currency, which is a problem in china. since china started its economic reforms, social institutions (which molded thought and behavior, rewarded compliance, and punished deviance) have been seriously weakened. the loosening of formal and informal controls as a result of the changes in social structure that have accompanied economic reform, alongside the unequal distribution of wealth, has led to a significant increase in crime (deng and cordilia, ; xiang, ) . one of the most notable trends is the dramatic rise in serious economic crimes; it seems that getting rich is becoming an obsession. indeed, since the official slogan proclaimed that "to get rich is glorious," materialism became the dominant ethos of the reform era. juvenile delinquency has also drastically increased, becoming more serious and violent in nature; the criminal motivation is mainly money (xiang, ) . some of the responses adopted by the chinese government aiming to maintain social order and to reduce crime consist of intensification of programs of legal education that teach people about the law and its requirements. the revival of traditional confucian values to increase people's awareness of the appropriate balance between individualism and collective responsibilities, and the revitalization of informal social controls programs, can also be felt (deng and cordilia, ; xiang, ) . indeed, social control has always been successfully attained through informal organizations and indigenous institutions, which regulate much of social life. the empowerment of the masses to take control of their community's welfare (mass-policing) is one of the best ways to engage people in fighting crime. tourism security and safety: from theory to practice people are normally more susceptible to health hazards while traveling. these can range from minor upsets to infections caused by serious diseases. the world health organization (who) reported that the following diseases can occur in china: cholera, hepatitis a, malaria, tuberculosis, and typhoid fever. mosquitoborne diseases, such as dengue fever and encephalitis b (endemic in rural areas of southern china from june to august) can also be encountered, although they do not pose a serious risk to travelers. rabies infection is also frequent; china has , human rabies cases every year. travelers planning to visit regions where these diseases are common are advised to take medication against them. the use of mosquito repellent is also recommended. western-style medical facilities with international staff are available in large cities in china. however, in rural areas, medical personnel are often poorly trained and have little medical equipment or availability of medications. air pollution is also a problem throughout china; seasonal smog and heavy particulate pollution are an issue for travelers, especially for those with respiratory problems. avian influenza epidemics of avian influenza (bird flu) were reported in the beginning of in parts of asia and human cases were confirmed in vietnam and thailand, with a total of deaths. although an outbreak of bird flu was confirmed in china, no human cases were reported, but even if travelers were unlikely to be affected, they were warned to avoid bird markets, farms, and places where they might come in contact with live poultry. a second wave of avian influenza infection was reported in late june , when new fatal cases among poultry were communicated to the who, and subsequently there were more fatal human cases in vietnam and thailand. in july , china was affected by this new outbreak, and one month later it was discovered that pigs had been infected with the strain of avian influenza. although findings on the possible spread of the infection among pigs (and its transmission to people) are still preliminary, human infection with avian influenza viruses still remains a public health hazard. travel precautions are being issued in order to provide information to travelers, but no recommendation to avoid the affected areas has been made. although two thirds of the world's population infected with hiv is located in sub-saharan africa, the preponderance of new infections is likely to shift to asia in the coming decades (burgess, watkins, and williams, ) , being already well established in the region. recent social and economic changes in china greatly increased the potential for a substantial hiv/aids epidemic, which is already causing great concern, given the growth rates observed in the past decade. ignorance about the disease, poor sterilization practices, and unsafe blood transfusions contribute to hiv/aids transmission, as well as transmission of hepatitis. china is one of the world's great reservoirs of hepatitis b infection. in , china ranked thirteenth in the world, with , people infected with hiv/aids; the number of deaths reached , . it presented an adult prevalence rate (estimated number of adults living with hiv/aids) of . %. hiv is currently concentrated in the southwestern province of yunnan, near the golden triangle. the increasing use of drugs, the rapid expansion of open commercial sex activity tourism safety and security in the prc (prostitution has become a massive industry in china over the past decade, most noticeable in zhuhai, shenzhen, and macao), and a more liberal sexual climate (the emergence of the homosexual "underground") may support an expanding epidemic throughout the country. some experts speculate that china will have million cases of hiv by (harper et al., ) . in august , china revised its law on the prevention of infectious diseases to include the first reference in the legal code to aids, which reflects a shift in the government's aids policy. the new law, which contains specific clauses on blood donation, stipulates that governments of various levels should strengthen prevention and control of aids and take measures to prevent the spread of the disease. it also specifies punishments for anyone concealing the spread of a disease, clearly showing a reaction to failed attempts to cover up the extent of the sars problem. severe acute respiratory syndrome (sars) sars was first recognized as a new disease in asia in mid-february . however, it had already started to spread to other parts of the country and to the world since the first case was reported in november in guangdong province. according to the who, between november and july , more than , cases were reported, causing deaths, from countries and regions on the five continents. the most affected country by this new epidemic was china, with more than % of the cases. in face of this unknown disease, and as a measure of precaution, the who decided to issue travel advisories to areas that reported the most sars cases. travel advisories are intended to limit further international spread of sars by restricting and reducing travel to high-risk areas. it was the first time in more than a decade that the who had advised travelers to avoid a particular area. figure shows a chronology of travel recommendations to china issued by the who. in april , the chinese ministry of health reported a total of nine new cases of sars (including one death) in china. these were the first cases of severe illness and secondary spread of sars after the outbreak. however, no further cases in china or anywhere else in the world have been reported since april , . on may , the who reported that the outbreak in china appeared to have been contained with relatively limited secondary transmission. nonetheless, within a relatively short period of time the sars epidemic had already caused major damage to china's economy, particularly affecting its tourism industry. the impact of the sars outbreak on tourism will be expanded upon in the next section. while in china, foreigners may encounter substantial differences in traveling conditions compared to those in their home countries. in general, many accidents occur, some of them serious, resulting from the poor quality of roads, the often chaotic traffic, and the generally low driving standards (although driving etiquette in china is progressing). safety standards in public transportation differ from those in the west as well; child safety seats and seat belts are not widely available. pedestrians and cyclists, if not cautious, are also at risk while near traffic. they are frequently involved in collisions or encounter unexpected road hazards. in fact, it is not unusual to see a pedestrian or a cyclist on a sidewalk being hit by a car or bus driving in the wrong lane. air accidents have been reported on internal flights, mainly in routes to the north and east of beijing. nonetheless, the us federal aviation administration (faa) has assessed the chinese civil aviation authority as category , which means that it complies with international aviation safety standards for overseeing china's air carrier operations. similarly, there have been several incidents of overcrowded ferries sinking, resulting in the loss of lives. attacks of piracy in the south china sea should also be regarded as a threat to yachting safety. china has been greatly affected by natural disasters. the country is located in an active seismic zone and is subject to earthquakes, notably in inner mongolia, yunnan, and xinjiang. the most recent earthquakes occurred in october in gansu province, measuring . and . on the richter scale. typhoons can occur along the southern and eastern coasts, affecting hainan, guangdong, fujian, and zhejiang provinces during the summer rainy season. travelers are advised that prior to departing to affected areas they should monitor weather reports. from april to october there are also many severe rainstorms that can cause flooding and landslides. in , floods along the yangtze river devastated parts of central china, killing more than , people, destroying . million houses, and swamping million acres of land (lang, ) . this situation is not new, and is part of the list of environmental problems that china is facing as a consequence of its rapid economic growth. loss of forest cover as a result of massive tree clear-cutting over the years (especially during the great leap forward, when huge areas were logged to provide fuel for backyard furnaces in a disastrous campaign to make steel) led to an increasing severity in the flooding. reforestation and a ban on logging china's natural forests in the upper reaches of the yellow and yangtze rivers, along with the completion of the three gorges dam project, are some of the measures of the chinese government to help control flooding. a study using the data envelopment analysis (dea)-based model for the analysis of vulnerability to natural disasters in china from to (wei, fan, lu, tourism safety and security in the prc and tsai, ) concluded that, in general, the western region was affected more severely. some provinces in central china were also badly affected, with hunan, guizhou, and jianxi provinces being the worst-hit areas. there are restrictions on undertaking certain religious activities, including preaching and distributing religious materials. foreigners are also under strictly enforced regulations against any public demonstrations that do not have prior approval from the authorities. travelers from australia have been specifically advised to avoid large public gatherings or demonstrations, particularly of a political nature. the most well-known case of severe measures taken by the chinese authorities upon religious activities is the ban of the falungong movement and the imprisonment of some of its followers. nonetheless, it was not the falungong movement, but the spread of a christian-inspired group called the "shouters" that initiated the "fight for investigation and the banning of heretical teachings campaign, launched by the chinese leadership" (kupfer, ) . the elimination of groups that are perceived as a potential danger to underpinning political unrest, posing an ideological and organizational threat to the chinese state, is still the guiding principle of the communist regime. tiananmen square incident the june , , incident in tiananmen square showed that the way in which china approaches and solves its domestic economic and political problems will no doubt be reflected in the extent to which foreign tourism is encouraged or constrained. the government's declaration of martial law and the subsequent crackdown on the student democracy movement by the people's liberation army (pla) led to the death of hundreds of protesters. the reaction of the international community to those events and how this new political environment in china has affected tourism will be further developed later in this chapter. since the military confrontations, political relations between taiwan and the mainland did not begin to improve until the s. after almost years of strict restrictions on travel between the two divided states, the ban on travel via a third country was finally lifted in , allowing taiwan residents to enter mainland china for the purpose of visiting families. leisure and recreational travel was, however, still prohibited. notwithstanding the change in policy, many obstacles still remain in the development of tourism and travel between taiwan and the mainland, being highly dependent on the political relations between the two governments. nevertheless, as a result of the policy change, the flow of taiwan visitors to china increased rapidly. yet, the increased travel activities did suffer a severe setback in , as a result of the global economic recession in the first half of the year. the china airlines plane crash at nagoya airport in central japan, which resulted in the deaths of taiwanese passengers; and the qiandao lake incident, where taiwanese visitors were murdered while on a sightseeing tour on a boat on qiandao lake in zhejiang province, were also instrumental in exacerbating this setback (huang, yung, and huang, ) . the chinese authorities' initial dismissal of the lake tragedy, and its attempt to cover up the case, renewed the political tension tourism security and safety: from theory to practice between the two governments. it also led a large number of people in taiwan to reassess their position and shift in favor of taiwanese independence. following the incident, the taiwanese government temporarily halted group travel to china, as well as other types of cultural exchanges and business activities with the mainland. as a result, tourist arrivals from taiwan decreased by % in . however, this political tension did not last long, and travel activities were soon reinstated, restoring the normal development of tourist arrivals from taiwan. in , taiwan tourists accounted for . % of the country's total arrivals and contributed % of china's total tourist receipts. taiwan tourism has since then become a major component of china's tourism industry. despite this rapid recovery, the qiandao lake tragedy might have caused a long-term impact, similar to the one tiananmen square massacre had on the people of hong kong, which deeply affected the perception of mainland china, thus strengthening general feelings for independence. the independence of taiwan is still in debate. however, it is something that mainland china will never accept, thus posing the question as to whether a clash between the two states will be unavoidable. according to sheng ( ) a war across the taiwan strait is neither inevitable nor imminent, and is less likely in the future since china is rather confident in the face of taiwan's current political and economic deterioration. this situation gives beijing the opportunity to exploit, weaken, and paralyze any demand of independence. the pla has boosted its military pressure over taiwan by modernizing its warfare capacity. by doing so, china also intends to deter us intervention in the taiwan strait, placing emphasis on its strike capability, rather than on its power-projection capability (sheng, ) . however, china's claim of sovereignty over taiwan and its threat to attack the island if it formally declares independence have led security analysts to see the taiwan strait as the most dangerous flashpoint in asia. tensions between china and taiwan have been escalating since the march reelection of president chen shuibian, who is a keen independence supporter. the strain was aggravated by the recent announcement of taiwan's intention to buy weapons in order to help to maintain a balance of power with china, thus permitting it to make a counterstrike to hit shanghai (china's financial center) if the pla attacks taipei. international tourism in china started to develop after as a result of the "opendoor" policy. since the chinese government's decision to open the country to the outside world and to promote tourism as a vital economic force to earn foreign exchange earnings to help finance its modernization program, there has been a dramatic increase in tourist arrivals. tourist arrivals rose from . million in up to . million in , representing a -fold increase, with an average annual growth rate of %. although the growth trend of china's international tourism industry has been quite consistent over the last decade (excluding the year ), growth rates were not stable during the initial development period, with fluctuations occurring, and even experiencing a major decline in (the students' demonstration in tiananmen square was the cause of a decline of . %). figure shows the annual percentage variation of international tourist arrivals in china for the period - . over the period as a whole, the average annual growth rate of tourist arrivals showed a downward trend. problems with accommodation, service, and transport are indicated as possible reasons for this slowdown in the growth of arrivals of overseas visitors. however, richter ( ) contends that deng xiaoping's theories about china's socialist economy might have been considered too controversial, or may have been only temporary policies designed to get deng xiaoping into power, and were not necessarily created to be an ongoing program. the worldwide recession of the early s apparently had an impact on china's tourism industry, as tour cancellations increased from % in previous years to % in (lew, ) . overseas visitor arrivals grew only by %. to offset the slowdown in tourism, china instituted a number of new policies. foreign tour operators were allowed to open offices in china, and the "open city" program was introduced, giving more freedom of movement to foreign travelers. this program achieved great popularity, and the number of cities and regions opened to tourists has grown ever since. the incident in tiananmen square resulted in a severe decline in arrivals from all market segments, with the exception of taiwanese. however, even before the events of , there was a slowdown of the growth rate in international visitor numbers. declining interest in china as a destination, as a consequence of overseas perception of poor management, service problems, and congested transport infrastructure, could also have contributed to the low growth rates (choy, dong, and wen, ) . the figures of total annual visitor arrivals indicate that tourism in china began to pick up shortly after . in the mid- s, china again experienced sluggish growth rates, motivated by a slowdown in the overseas chinese and the compatriots' segments, partly due to the incident in zhejiang province. again in the s, china's tourism withstood severe tests-the impact of the asian financial crisis in (which was felt mainly in the overseas chinese market segment) and the devastating floods occurring in the tourist season along the yangtze river. in may , demonstrations mostly aimed at the united states were held in the major chinese cities, due to the north atlantic treaty organization's bombing of the chinese embassy in belgrade. as the demonstrations turned violent, the governments of the united states and the united kingdom issued travel advisories, causing thousands of cancellations from potential visitors (breda, ) . but the explosion of annual growth rate (%) figure annual percentage variation of international tourist arrivals in china, xenophobia that hit china during this period had a limited impact on tourism. after a sharp drop in bookings, airlines and hotels reported a return to normality. the lifting of travel advisories from foreign governments also helped the industry bounce back. however, these events did not have a long-lasting negative impact in the chinese tourism industry; to prove it, in that year, china ranked fifth in the world. the september terrorist attacks had a severe impact on long-haul tourism, leading to a shift towards intraregional travel, partly compensating the loss of american and european inbound traffic. intraregional travel is the major kind of travel in the east asia and the pacific region, accounting for nearly % of total arrivals, and was a major factor in offsetting the impact felt in the travel and tourism industry. china was the best performing destination within this region (with a more than % increase compared to the year ), partly because of the close proximity to its main generating markets. for example, the japanese outbound market, one of the world leaders in the field, replaced destinations in america by china, thailand, and australia (wto, ) . despite the fact that china showed a robust increase in tourist arrivals over those in , these events contributed to slow down china's growth rates. in , china again faced a severe test. until the sars epidemic became public, china was one of the few countries that did not experience a decline in tourism, even during the recent war in iraq. despite the good results in the beginning of the year, figures had been significantly impacted as a result of the who's travel advisory for sars affected areas in china (ap, ) , resulting in a . decline in total arrivals over . this was the most damaging event for the chinese tourism industry since the tiananmen square incident in . since the traveler must physically be in the destination country to consume the tourist product that it has to offer, any event that persuades the potential traveler to either stay at home or travel elsewhere directly impacts that destination's exports earnings (roehl, ) . there is no doubt the tiananmen square conflict severely damaged the international tourism industry of the prc, at least in the short term, mostly because of the economic sanctions imposed by the world community. "tour cancellations and a drop in foreign business activity sent hotel occupancy rates in the prc to the lowest point since the country opened its doors to tourists in " (gartner and shen, , p. ) . political events of this nature clearly influence tourist demand. the low occupancy rates reflected many hotels' reliance on business travelers. business visits were affected by both perceptions of stability, which influenced business confidence, and also by the formal and informal sanctions that were imposed on corporations conducting business in china (hall, ) . the political unrest of has led to considerable difficulties for planning and investing within the chinese tourism industry and posed substantial problems for improving the image of china as a tourist destination. "the conflict in tiananmen square was carried out by major news networks throughout the world and, owing to the nature of the conflict, did not portray the prc in a light favorable to improve its tourist image" (gartner and shen, , p. ) . "many people in western nations demonstrated moral sup-port for the democracy-loving chinese students by not traveling to china" (yu, , p. ) . in a study targeting the mature travel market in the united states, before and after the conflict (gartner and shen, ) , the extent of the damage to china's tourism image was analyzed. it was concluded that its overall image was still favorable and positive. the hospitality component appeared to be directly affected by the conflict, much more than the image of the attractions of its tourist sites. "safety and security, pleasant attitudes of service personnel, receptiveness of local people to tourists, and cleanliness of environment were all down significantly, indicating that respondents felt the prc was less likely, after tiananmen square, to provide the hospitality needed for an enjoyable visit" (gartner and shen, , p. ) . not all countries of origin responded to the tiananmen square incident in the same way. while almost all tourist-generating markets for china registered recessions in , taiwan and the soviet union became the top generating markets for china's international tourism industry, at the time when tourists from western democratic countries declined. the decline of tourists from the western democratic countries immediately after the tiananmen incident is logical and understandable. the perception of china as an international destination held both by the tourists and the travel industry in the west was dramatically altered by the anti-democratic actions of the chinese government in . as moral support for the democratic demonstrators in china, tourists cancelled their already scheduled trips or put off their travel plans to a later date. (yu, , p. ) the drastic decline in the number of tourists was evident at beijing's joint-venture hotels, where all hotels reduced both their chinese and expatriate staffs, and most remaining employees were working at some % of their normal wage package (breda, ) . it was also estimated that , tourism workers underwent compulsory political indoctrination aiming "to cleanse their socialist minds, deepen their love of the communist party, and, alarmingly, to cultivate their suspicions of foreigners" (hall, , p. ) . the crackdown on the students' demonstration in beijing definitely created a new environment for chinese tourism, which affected both the chinese and global travel industries. there was an immediate drop in the number of incoming visitors, a total decrease of %, and a % decrease in terms of international tourism receipts. visitation from japan and the united states, china's two largest markets and sources of high-expenditure visitors, showed even larger declines. roehl ( ) estimated that the impact of the tiananmen square incident on arrivals was greater than previously estimated. overall, his study suggests that the impact of the events led to a decrease of million compatriot arrivals than might otherwise have occurred. likewise, foreign visitors registered more than , fewer arrivals. the incident also affected foreign investment in china, particularly in the hotel industry, which had serious consequences for both investors and lending institutions. a breakdown of the quarter-by-quarter tourist arrivals in is shown in figure . although political events greatly affect the tourism industry, it seemed that the situation in china in only had a short-term impact. the crisis was between the government and its internal critics; there was no violence directed towards international visitors. china's tourism industry responded to this event rather well as it only experienced a % decline in receipts in and was fully recovered years tourism security and safety: from theory to practice later. this quick recovery can be attributed especially to the "continued government's commitment to reform and open-door policies; the rapid growth of the chinese economy; and the industry's successful responding strategies in terms of product development, market positioning, and overseas promotion" (jenkins and liu, , p. ) . after the tiananmen incident, the government attempted to rebuild its international tourism industry by improving the country's tourist image. a press release from the cnta in june stated: the cnta solemnly proclaims that the safety of overseas tourists who come to china has never been affected and can be guaranteed. tourists may carry on their visits and tours as planned. they are welcome to visit china and do not need to change their scheduled travel plans. (quoted in wei, crompton, and reid, , p. ) china's booming domestic and international tourism industry has recently suffered losses in tourism and related service industries as a result of the sars epidemic. in light of the events concerning the disease, the who advised international travelers to avoid visiting some areas in china that had the most sars cases. china was the worst affected country. the outbreak of sars in china led to a sharp decline in inbound and domestic travel, with social and economic impact, but also had a disproportionately large psychological influence on the public, considering the relatively low morbidity and mortality of the disease. the pronounced psychological impact of sars can be attributed to a combination of two aspects regarding information about the illness percentage variation in china's arrivals, by quarter, from its major inbound tourist markets in . source: china national bureau of statistics. (breda, ) . first, there was a rapid transmission of information about the number of people infected by sars, as a result of modern media and highly developed networks of communication. second, there was insufficient medical information on sars and great uncertainty over the nature of the disease. the lack of accurate, timely, and transparent provision of information on the nature and extent of sars increased the public's fears, caused second-guessing, and naturally led to an exaggerated perception about the danger of the disease. concealing health information from tourists, as well as not taking adequate measures to prevent the outbreak of communicable diseases, can be almost as lethal for tourism as the disease itself. tourism was thus especially affected by the sars-induced panic (mckercher and chon, ) . even some destinations that had not recorded any cases of infection suffered almost as much as the areas actually affected. the rapid and wide geographical spread of the disease by travelers, cases of transmission during hotel stays, in restaurants, places of entertainment, or even during airplane trips, made sars a phenomenon that was perceived to be linked with tourism itself. the intraregional tourism market is an important source of visitors to china. as the sars epidemic started to spread into other countries within the asia-pacific region, china suffered a major decline in tourist arrivals. some airlines that offer service to china cancelled regularly scheduled flights due to insufficient bookings. governments from some foreign countries advised their citizens not to visit china, thus causing the cancellation of a significant number of package tours (chien and law, ; overby, rayburn, hammond, and wyld, ) . china's inbound travel suffered seriously, but had a somewhat lower accumulated loss of . % in the first two quarters of the year, due to the positive results in the first months of . the worst period recorded was during the months of april and may, both for foreign and compatriot arrivals, registering decreases of . and . , respectively. with the sars outbreak over in june, decrease rates started to become less and less accentuated, showing that recovery was under way. foreign arrivals suffered greater losses and took a little longer to recover. at the beginning of , arrivals from both markets already showed positive growth rates. figure according to the international labour organization (ilo), countries or areas directly affected by sars were estimated to lose more than % of their travel and tourism employment. the world travel and tourism council (wttc) estimated that china was expected to lose more than . million jobs. however, if also taking into consideration the indirect impact of sars, its real impact would be even greater. china was expected to suffer, directly and indirectly, a sars related loss of . million jobs and . billion us$ worth of gdp (wttc, ) . although the sars outbreak significantly slowed the development of chinese tourism, it also facilitated the reorganization of chinese tourist agencies. many hotels, restaurants, and other attractions remained closed while the public continued to avoid such frequented locations; however they seized the opportunity to undertake renovation projects and to introduce unprecedented hygiene measures, in an attempt to build consumer confidence (breda, ) . this slow growth period was thus used to perform renovations and employee training, representing a means of improving china's service industry. during the post-sars period, the tourist industry of various parts of china, driven by new changes and new market demands, has been absorbing new ideas and approaches to future strategies. these positive developments and improved public health measures have added weight to arguments that sars, although serious, contributed to the improvement of sanitary conditions and caused only a temporary shock to economic growth. the industry players designed aggressive revitalization campaigns in an attempt to accelerate recovery; and a series of high-profile special events have been organized, beginning with the asean tourism ministers meeting in august , the wto general assembly in october, and the travel fair in kunming in november, all part of the "seeing is believing" campaign (wto, ) . the women's world cup in , combined with the olympics in beijing in and the international world's fair and exposition to be held in shanghai in , which is considered the world's third largest event after the olympics and the world cup, will contribute to boosting the image of the country. there was hardly any international tourism in china before the chinese government's decision to open the country to the outside world, and to promote tourism as a vital economic force to earn foreign exchange to help finance its modernization program. with the introduction of reform and the open-door policy since , china entered the international tourist market. in recent decades, tourism has been a boom industry in china, and has come to play an extremely significant role in economic and regional development, as well as in international relations. it has become one of the most important tourist destinations in the world. in , it ranked fifth in the world, showing a substantial increase over the total international tourist arrivals achieved during the initial stage of tourism development. the spectacular boom experienced during this period was partly due to the fact that initial policies affecting tourism were directed toward maximizing growth rates of visitor arrivals, especially foreign travelers. however, unlike the domestic and compatriot tourism industry, which is conditioned largely by location and access, the foreign tourism market is competitive and risky; it is highly dependent upon fashion trends and political, economic, and social stability. experience and tourism security and safety: from theory to practice studies have shown that the special character of the tourism industry makes it more liable to independent events than other sectors. it is vulnerable to variations in politics and economics, as well as any major change in policy or ideology, and these changes can significantly modify its development process. however, until now there is no evidence that china might want to change its reform and open-door policy; on the contrary, major policies within the tourism sector show a greater openness to the outside world. the increased dependence on tourism as a source of economic growth also shows that it would be extremely difficult for china to halt tourism development. the wto estimates that china will receive million foreign tourists by , making china the world's number one tourist destination. terrorism use of premeditated violence (or threat of violence) by organized groups, against civilians or unarmed military personnel, in order to attain political, religious, or ideological goals. crime any act punishable by law, motivated by economic, political, racial, or religious reasons. it can range from petty offenses to violent crimes. health hazard any source of danger that can be harmful to people's physical condition, ranging from minor upsets to infections caused by serious diseases. natural disaster a phenomenon not caused by humans, involving the structure or composition of the earth, ranging from eruptions, avalanches, or earthquakes to landslides, floods, hurricanes, or typhoons. political instability disturbances motivated by political, racial, ethnic, or religious conflicts, which can lead to social disorder and instability. . what are the main factors regarding safety and security affecting the tourism industry? what might be the implications of those issues for destinations? . how do the main tourist markets see the safety and security situation in china, and how do they perceive it as a tourist destination? . the growth trend of china's international tourism industry has not been consistent over the years. what factors have caused disruptions in tourism growth? . explain the major implications of the tiananmen square incident to china's tourism industry. . why did the sars outbreak have such a repercussion on china's tourism sector? the impact of crime on tourist arrivals in jamaica encountering sars: a perspective from an infected area. e-review of tourism research (ertr visitor safety in urban tourism environments: the case of auckland modeling tourism crime: the urban visitor perceptions of safety during a special event tourism in the people's republic of china: policies and economic development the impact of severe acute respiratory syndrome (sars) on china's tourism sector tourist victimisation and the fear of crime on holiday hiv in china reducing the health risks associated with travel tour operators and destination safety the impact of the severe acute respiratory syndrome on hotels: a case study of hong kong tourism in pr china: market trends and changing policies the threat of terrorism as an intervention on international travel flows tourism and crime in the caribbean to get rich is glorious: rising expectations, declining control, and escalating crime in contemporary china new orleans tourism and crime: a case study the impact of tiananmen square on china's tourism image tourist's perceptions of safety and security while visiting cape town tourism: principles, practices, philosophies tourism in the pacific rim: development, impacts and markets lonely planet: china trends in outbound tourism from taiwan some considerations of impacts of attitude to foreigners by hotel workers in the people's republic of china on hospitality service political instability, war, and tourism in cyprus: effects, management, and prospects for recovery economic liberalization and tourism development: the case of the people's republic of china christian-inspired groups in the people's republic of china after : reaction of state and party authorities the effect of terrorism: evaluating kenya's tourism crisis. e-review of tourism research (ertr forests, floods and the environmental state in china tourist roles, perceived risk and international tourism terrorism and tourism: the northern ireland situation-a look behind the veil of certainty tourism demand and the nuisance of crime the history, policies and social impact of international tourism in the people's republic of china perceived safety as an important quality dimension among senior tourists the development and impact of foreign tourism in china and thailand food safety in travel and tourism impact of food-borne illness on food safety concerns of international air travelers tourists' perception of security: the risk-fear paradox the over-reaction to sars and the collapse of asian tourism the impact of political violence on tourism: dynamic crossnational estimation the china syndrome: the impact of the sars epidemic in southeast asia severity versus frequency of acts of terrorism: which has a larger impact on tourism demand tourism and terrorism: a quantitative analysis of major terrorist acts and their impact on tourism destinations the political implications of chinese tourism policy the politics of tourism in asia after political turmoil: the lessons of rebuilding tourism in three asian countries travel agent attitudes toward china after tiananmen square tiananmen square incident and chinese tourism risk perceptions and pleasure travel: an explanatory analysis lonely planet: china peace over the taiwan strait? security dialogue tourism, terrorism and political instability tourism in crisis: managing the effects of terrorism influence of terrorism risk on foreign tourism decisions ideas on how tourism can confront the terrorism menace. e-review of tourism research (ertr eastern turkistan islamic movement: a case study of a new terrorist organization in china the exploratory war-distorted destination life cycle cultural conflicts: experiences of us visitors to china the assessment of vulnerability to natural disasters in china by using the dea method special report number -tourism after special report number -fifth meeting of the tourism recovery committee. madrid: wto world travel and tourism council (wttc) delinquency and its prevention in china emerging markets for china's tourism industry china's tourism development since : policies, experiences and lessons learned key: cord- -v d c authors: yen, wei‐ting title: taiwan’s covid‐ management: developmental state, digital governance, and state‐society synergy date: - - journal: nan doi: . /aspp. sha: doc_id: cord_uid: v d c this article examines the reasons behind taiwan’s effective covid‐ response. while some have argued that taiwan’s success with covid‐ is based on its experience with sars, i argue that we should not attribute taiwan’s effective response solely to its sars experience. the country’s success mainly lies in three factors: ( ) reliance on the mask policy as the main disease prevention measure and the ability to quickly expand mask production capacity; ( ) use of big data and technology to enhance effective implementation of disease prevention and detection measures; and ( ) strong state‐society relations favoring transparency, communication, and collaboration. the first two factors can trace their roots to the country’s developmental state model. democracy provides the institutional underpinning for a vibrant civil society and the synergy between state and civil society, strengthening taiwan’s crisis governance legitimacy and increasing citizens’ voluntary compliance. d ue to its geographical proximity to china and the intensive flow of people from/to china, taiwan was believed to be at the highest risk for importation of covid- when news of the virus first broke in january (gardner, ) . yet, at the time of writing (june, ), taiwan only has covd- cases and seven deaths in total. what explains taiwan's success? what are the lessons policymakers can learn from taiwan's experience? the author appreciates li-ying liu, chia-chien chang, and tsung-hsin lee's feedback on the earlier version of this paper. building upon the crisis management framework, i argue that there are three major elements in taiwan's successful response. first, the government relies heavily on the face mask policy for disease prevention. the government ramped up the production capacity quickly by solving the coordination problem that could have emerged from the production process. second, the government fully leverages the digital governance infrastructure and big data for effective implementation of measures related to disease prevention and detection, albeit that intrusive tracking and tracing raise privacy concerns (ngerng, ) . these first two elements demonstrate how taiwan manages to overcome the coordination and surge capacity challenges, two key obstacles to effective crisis response (ansell, boin, & keller, ) . the developmental state model paved the foundation for these two elements. third, there is a strong two-way communication channel between the government and taiwan's vibrant civil society. the strong state-society relation also facilitates more synergy in fighting covid- . in some cases, the civil society took the lead in initiating solutions which the government then adopted. because the ongoing crisis is characterized by immense levels of uncertainty, transparency and communication are crucial for defining and making sense of the crisis for the society. the state-society collaboration also facilitates revision and refinement of crisis response. it increases citizens' voluntary compliance, which in turn helps enhance the overall effectiveness of taiwan's crisis management. a lively democratic regime provides the political underpinning for the demand and supply of transparency, communication, and collaboration between state and society. i organize the rest of the article in the following way. i first address sars's legacy in taiwan. taiwan's successful covid- response is widely attributed to its past sars experiences, but i contend that even though the sars experience has certainly had an impact, it cannot fully account for taiwan's remarkable achievements in . i then turn to the crisis management framework, discussing how the developmental state foundations and the democratic regime lead to taiwan's success on mask policy, digital governance, and strong state-society collaboration and communication. i end by providing some concrete policy suggestions for policymakers. there is a strong perception that taiwan's effective covid- response is mostly the result of its sars experience (e.g., graham-harrison, ) . it is worthwhile to address the extent to which sars affects taiwan's covid- response first before we move on to other factors. i contend that taiwan's covid- response benefits from sars's legacy mainly in two aspects: ( ) the creation of legal and institutional foundations for the future epidemic outbreak; and ( ) a cohort of experienced technocrats whose knowledge becomes valuable in the covid- fight. yet, besides sars, taiwan also possesses other unique factors that would prompt the country to take a more cautious and "self-help" approach to public health crises too, making it hard to tease out the causal effect of sars. sars left a painful mark on taiwan. like covid- , sars was a fatal respiratory disease caused by a coronavirus and was first discovered in southern china in . taiwan's handling of sars was initially viewed as a success as there were only sporadic cases in the first month. nevertheless, following the world health organization's (who) praise on taiwan's response, clusters started to appear and spread in hospitals, causing an immediate lockdown of a major hospital in taipei. within the next month, clusters were identified in another five hospitals (centers for disease control and prevention, ) . the sudden spike and ongoing local clusters sent society into outright panic. multiple nurses and doctors died of sars because of inadequate protection gears and unknowing exposure to the virus. taiwan's people criticized the government's sudden lockdown and the ill-prepared detecting and reporting mechanism. the who offered limited help too at the time because taiwan was not a who member (lin, wu, & wu, ) . in the end, taiwan became one of the most severely affected countries by sars. there were cases, of which % were associated with hospital clusters, and deaths (taiwan, ) . sars's direct legacy in taiwan was the creation of the national health command center (nhcc) and the overhaul of the communicable disease control act (cdc act). the new organization and the amended law are the central pillar in taiwan's covid- institutional design. responding to sars's regulatory failure, the nhcc became the centralized command point for any type of public health emergency moving forward, including epidemic outbreaks and bioterrorism. the central epidemic command center (cecc) is one of its subunits composed of experts from all fields, which became essential for taiwan's covid- fight. (taiwan cdc, ) . the streamlined response system helped shorten the government's reaction time, effectively mobilized and allocated resources, and facilitated communication with the public. during the covid- crisis, the cecc was quickly activated on january th, one day before the first case was detected in taiwan, and coordination was set at the ministerial level to maximize cecc's authority. the cdc act provides the legal framework for government actions, including how the central and local governments should coordinate with each other, procedures for resource mobilization, and compulsory measures on social behaviors. the law also grants the cecc the authority to penalize lawbreakers. even though there was criticism of granting the cecc too much authority, the post-sars institutional design authorizes the cecc with great power and discretion during public health emergencies (huang, ; lin et al., ) . another legacy of sars was that many government officials and experts in the covid- fight had direct experiences of sars. such experience created a cohort of technocrats who are more agile and cautious about any possible "second sars" in taiwan. from very early on in the covid- crisis, government officials constantly and repeatedly mentioned sars in media interviews. this consensus directed the administration to take a more preemptive approach toward covid- . for example, out of precaution, taiwan immediately sent doctors to wuhan china on january th to gather more information once experts suspected a new epidemic. there is also a strong consensus within the government that taiwan cannot and should not repeat the mistakes made during sars. the technocrats' sars experience leads to their emphasis on face mask policy. during the sars epidemic, panic buying of face masks became a major issue. as a result, the government foresaw that mask hoarding would occur again during this crisis. the government swiftly imposed export bans on n and surgical masks on january , one day after china decided to lockdown wuhan. to combat panic buying, the government also took over the private sector mask distribution lines and launched a mask rationing system. sars's panic buying was partially the consequence of inadequate face mask supply at the time. during covid- , to secure sufficient supplies of masks, the government leveraged its close public-private sector partnership to ramp up the mask production, a point i will elaborate more in the next section. even though sars certainly contributed to taiwan's quick reaction to covid- , there are other concurrent factors that contributed to taiwan's quick reaction. the first was taiwan's exclusion from the who. research shows that countries excluded from international organizations would make more cautious and responsible policies (lipscy & lee, ) . deprived of the who's support, taiwan must resort to the "self-help" approach, nudging the administration to be more prudent (chang, a) . another factor is china's growing hostile relations with taiwan. taiwan's trust toward china has come to a new low. two weeks before the wuhan lockdown, taiwan held its presidential election, during which president tsai ing-wen of the democratic progressive party, the party more antagonistic to china, won her second term with a landslide victory. voters endorse her firm stance against china. taiwan's distrust of china can also lead to a quicker response. observationally, it is hard to tease out the effect of sars, and it is likely that there are multi-factors leading to taiwan's quick reaction. as such, we should not exaggerate sars's legacy on the country's covid- response. taiwan is not unique in its quick response to the new coronavirus outbreak either. almost all china's neighboring countries (except for japan) activated their response system to a greater or lesser extent in early january after china notified the who about the potential coronavirus disease. some of these countries do not have painful sars memories. south korea is considered very successful in its comprehensive testing capacity; vietnam, as a country that directly borders china but with only less than cases in june , is also another remarkable example. neither of them suffered sars. moreover, not all sars veteran countries orchestrate successful crisis responses this time. judging from the number of covid- cases, past sars experiences do not fully shield singapore and canada, two sars veteran countries, from this crisis. even though a coronavirus is the cause of both epidemics, covid- and sars are still different. unlike sars, the defining features of covid- include longer incubation periods, higher transmission rates, more virus mutations, but lower death rates. patients can be asymptomatic when spreading the virus. relying solely on sars's experience would not be adequate for containing the crisis. in addition, covid- is a prolonged and ongoing crisis. orchestrating a successful multi-agency response requires complex and different policy tools at different stages. an early reaction itself would not be sufficient. therefore, while sars's legacy is important and the sars experience can be informative for the current crisis, we should not exaggerate sars's impacts on taiwan's success, or on any country's success. an effective covid- response still hinges on a country's governance structure, capacity, and legitimacy. covid- is a transboundary epidemic crisis. facing an epidemic, all governments must compose a response strategy combining disease prevention, detection, and treatment. disease prevention includes measures such as border control, regulations on mask wearing and social distancing, etc.; disease detection includes measures such as screening incoming travelers, contact tracing, quarantine policy, and testing policy, etc.; disease treatment measures focus on healthcare facility surge capacity and vaccine research and development. as a transboundary and unprecedented crisis, covid- also confronts all governments with a common governance challenge (ansell et al., ) . that is, how to cope with the uncertainty brought by or embedded in this crisis? how do the public perceive the risks? amid high uncertainty, how to make collective sense of this crisis as a society? the four tasks are part of the public health crisis management framework, as illustrated in figure . the framework suggests that there is no one-size-fits-all strategy, and there are multiple routes to effective crisis management. no matter what the strategies are, an effective response would balance resources between disease detection, treatment, and prevention, while minimizing the uncertainty and panic the public may feel. for an effective response, it is of vital importance that a government can mobilize resources to provide surge capacity and to coordinate a coherent response (ansell et al., ) . moreover, the capacity of a government to define and communicate the uncertainty the crisis brings is also an essential element in an effective response because collective sense-making can help increase citizens' voluntary compliance. of the three epidemic tasks, taiwan relies heavily on disease prevention and detection in their covid- response. relatively, the country spends fewer resources on disease treatment, such as increasing health care beds or investment in vaccine development. moreover, the synergy and transparent communication between the government and civil society strengthen governance legitimacy and citizens' cooperation. in this section, i will show that taiwan's developmental state lineage benefits the country through resource mobilization and inter-and intra-agency coordination for their disease prevention and treatment measures. its democratic regime and robust civil society also conducive to more • the screening of incoming travelers; quarantine policy; testing policy; contact tracing, etc. • healthcare facility surge capacity; vaccine research and development, etc. • disease sense making (how serious is the disease); uncertainty on origin, transmission, and disease features, etc. transparency and open communication with the society, which in turn enhances the country's governance legitimacy and cooperative compliance. taiwan adopts a border control and strict quarantine policy to block the outside-in transmission route for disease prevention. domestically, taiwan relies heavily on the mask policy to prevent the disease from spreading. as mentioned above, the government quickly imposed export bans on masks and introduced a rationing system after the cecc was activated, but a crucial piece to a successful mask policy is ensuring sufficient mask supplies. in normal times, taiwan imports facemasks from china. therefore, at the beginning of the crisis, domestic production was only . million masks per day, far short of the quantity needed. yet taiwan managed to ramp up its mask production eightfold in months to million per day (yen, ) . under the real-name rationing system, people can receive two masks per week in early february; by mid-april, the quantity was increased to nine masks per days. taiwan was even able to start "mask diplomacy" to supply masks to other countries (horton, li, & cheng, ) . facemask production is not a skill-intensive industry. nevertheless, one of the most baffling issues during covid- is the mask shortage around the globe. taiwan's ability to produce sufficient mask, in contrast, stands out. why can't other countries mass-produce facemasks like taiwan does? according to economics , if there is demand, there is supply. there is obviously huge demand for facemasks during this crisis, but why isn't there corresponding supply? the reasons why it is hard to rely on the market to sort out the demand and supply issue are that, first, developing a production line poses high transaction costs. even though facemasks are not a skill-intensive product, challenges still exist in sourcing raw materials, especially the melt-blown fabric for filtration, and re-tooling machines for rapid production. it would require a substantial amount of effort and time to coordinate and assemble a production line if the task was left to the private sector. second, from the private sector's perspective, it is not clear if investment in facemask machinery now can be profitable in the post-covid- world. china has been the major facemask supplier for the world because facemask is an industry of slim profit margins where other countries no longer have a comparative advantage. therefore, for private sector companies, investment without guaranteed returns or high yield would hamper their interest in massive investment in the first place. taiwan's mask policy success lies exactly in the government intervention in lowering transaction cost and enlarging future profitability for the private sector. the developmental state model, which governed taiwan's industrial policy from the post-war era, provided the foundations for resolving these issues. briefly speaking, a developmental state is characterized by the government's active role in the economic growth process. under this model, the government maintains a very close relationship with the private sector but keeps its autonomy in making policy (evans, ) . with the goal of rapid economic growth, the government would nudge specific industries by proactively solving growth-induced coordination problems, which, under a more market-oriented economy, are usually solved by the market's invisible hand. in general, there are three types of coordination the government helps overcome. first, the government coordinates the supply chain, linking upstream to downstream companies in an industry. second, the government would also coordinate between the financial sector and industry by channeling the capital needed to grow the targeted industries. last, to facilitate industrial upgrading, the government would support r&d and coordinate knowledge transfer between public research institutes and industries (haggard, ) . the developmental state logic is applied extensively behind the massive increase in mask production. first, to lower the transaction and coordination costs between different companies in the industry, the government directly intervened to coordinate the production line. the industrial development bureau of the ministry of economic affairs (moe) and the taiwan textile research institute, a government-funded agency supporting r&d for the textile industry, were both involved in the effort. in early february, the moe directly gathered all facemask-industry related manufacturers, including machine tool companies (for producing face mask machines), raw material providers, and the downstream facemask manufacturers. by the end of the lengthy meeting, an ambitious facemask production plan was drafted and agreed upon by all companies. the government coordinated all the machine tool companies to produce more facemask machines, matched raw materials suppliers with downstream facemask manufacturers, assigned quotas to every company, and set the purchasing price structure. it was not coincidental that taiwan successfully assembled and coordinated among relevant companies for mask production within such a short time. the long public-private partnership tradition made such a task possible. though the government played a big role in the process, it is still different from a planned economy in the sense that, in a developmental state, the government does not directly force the private sector to reach certain production capacities. instead, the government incentivizes or nudges (i.e., tax incentives, knowledge transfer, capital investment, etc.) industries to enhance voluntary compliance. in the covid- fight, the government incentivized the companies to participate in the government's plan through several measures that can guarantee and increase companies' future profitability. on the one hand, the government directly supported the infrastructure needed for rapid mask production, which essentially lowered the private sector's machinery costs. the government intervened with a us$ . million subsidy and built new mask production lines. when it realized that the production capacity still fell short of expectations, a second tranche of us$ million dollars was released to add another production lines. in total, taiwan's government added new production lines in months. in the traditional developmental state, the government would channel the capital the industry needs through financial institutions. in this crisis, direct government interventions solved both the capital and the basic infrastructure issues (yen, ) . on the other hand, the government relied on price setting and guaranteed demand to further guarantee companies' profitability in working with the government. at the onset, a big concern for the manufacturers is how to tackle the potential oversupply issue when the crisis demand wanes. amid the pandemic, the demand can easily be bigger than the supply, but in a post-covid world, that demand might disappear. oversupply could also create an undesirable price war situation between mask suppliers. to tame the concern and to incentivize production increase, taiwan's government set the purchasing price structure and guaranteed that face masks will become a national security necessity. the government will continue purchasing a fixed number of masks to ensure the demand stream (yen, ) . moreover, with the government-supplied facemask machines, the government promised that once the export bans are lifted, companies can re-start facemask export for more profit. the facemask export ban in taiwan was lifted in june, and the facemask companies are now realizing a substantial facemask profit margin given that the pandemic is still severe around the globe. the second element to taiwan's successful covid- response lies in its full utilization of digital governance. digital tools are not the main infrastructure to fight coronavirus, but when combined with other policy tools, digital governance reinforces the effectiveness of disease prevention and detection measures, such as gps tracking, which greatly expands the government's governance capacity. specifically, during covid- , digital governance helped improve disease detection through integrated databases of people's health records and travel history, through more accurate contact tracing, and through active surveillance tracking for people under quarantine. on disease prevention, the mask rationing system also benefited from the digitized mask distribution platform. the most important e-governance step the government took early on was to link individual international travel history to the national health insurance system on january th. the database integration relies on the inter-agency collaboration between the national health administration and customs. with the data integration, all healthcare facilities can have access to patients' immediate travel history (first limited to days and then extended to days) when seeing the patient. such measures enhance local health facilities' real-time classifying and monitoring capacity. meanwhile, taiwan asked incoming travelers to submit a mandatory health declaration form before entering the border. such information would be further integrated into the database. travelers could then be classified into different risk levels based on their flight origin and health symptoms, allowing proactive monitoring and testing. digital tools are also used for active surveillance of quarantined people. due to taiwan's geographical advantage as an island, the coronavirus risks come mostly from imported cases. therefore, taiwan imposed a strict quarantine policy with a high monetary penalty (compared to other asian countries) (duchâtel, godement, & zhu, ) . effective enforcement of the quarantine policy was further enhanced through active surveillance. taiwan's government works with telecom companies to track quarantined people's whereabouts through their phones' gps data. to ensure accurate implementation, the standard operating procedure is as follows: the cdc first compiles the quarantine list, which is then reviewed by local health facilities and local civil departments (i.e., village chiefs) to check the accuracy of the quarantine people's phones and addresses. the local authorities then call the individuals twice a day to check on their physical and mental wellbeing. the quarantined individuals can also self-report their health conditions to the centralized tracking system through the mobile chat app (e.g., line). meanwhile, local authorities send these numbers to the telecom companies who can start tracking the quarantined people's movement. if the individual could not be reached or if the phone location changed based on triangulating the base station data, an alarm would be triggered. the quarantined person and local authorities (i.e., village chiefs, police, etc.) would all receive a text message. local authorities would also pay an in-person visit to verify the individual's whereabouts (ngerng, ) . despite its effectiveness, active digital surveillance tools raised substantial concerns about individual privacy. the cecc claims such invasive monitoring is authorized by the cdc act and the special act on covid- prevention, relief, and restoration. based on the acts, the cecc can take any measures that deem necessary for disease prevention. however, this did not ease the public's concern. the government promised that all the data collected during the pandemic or for the quarantine purpose will be deleted after covid- . yet, the issue of how to strike a balance between individual privacy and public interest remains an issue all societies must confront in the digital governance era. to summarize, it is obvious that digital governance itself is not adequate for successful disease detection and prevention. the state is already capable of penetrating society and collecting people's information. for example, the prerequisite for database integration was the existence of such health data in the cloud space, which taiwan's national health insurance had already completed when it digitalized individual health records in recent years (ngerng, ) . another example is that the central government was capable of working with local authorities to check the quarantined. the function of digital governance infrastructure is to help facilitate and further enhance the effectiveness of government regulations. thanks to the digital governance infrastructure, taiwan achieved the intended policy goals more effectively. to some extent, taiwan's comprehensive digital infrastructure has its roots in the developmental state as well. under the government's intentional planning in the s, taiwan upgraded its economic engines to semiconductor and technology-related industries, leveling up the basic digital infrastructure in taiwan. the industrial transformation not only created the infrastructure hardware but also a population with high levels of digital literacy. the tech-savvy civil society also played a big role in the covid- fight. despite its impact on the world, we still know relatively little about covid- . for months, the world was learning whether and how the virus is transmitted from human to human and the complete range of symptoms. six months after the outbreak, it is still not entirely clear how contagious asymptomatic cases can be (yan, ) . the who also changed its policy from discouraging masks on healthy individuals to encouraging wide-spread mask use in june . still, it is unclear when or if a vaccine will become available. simply put, covid- is an epidemiological crisis with high levels of ongoing uncertainty. amid the immense level of uncertainty, governments around the world are confronted with two tasks. first, as the crisis and the inherent uncertainty are evolving, it is almost impossible for a government to identify best practices. governments are likely to make mistakes. the task at hand is to continue calibrating the national response after considering the structural and moving factors. second, since there are many unknowns, government responses are of vital importance. with an uncertain crisis, the public depends on the government to help define the nature of the crisis. this "meaning making" step is essential for how the public perceive the risk. different perceptions can result in different health-related behaviors and compliance levels (kushner gadarian, goodman, & pepinsky, ). taiwan's government dealt with such uncertainty through continuing and transparent communication with the country's vibrant civil society. active communication helped the government define the crisis as dangerous at an early stage. the cecc used the analogy of "war time mobilization" to warn the seriousness of covid- . it helped the society's collective sense-making of the virus. the major communication channel between the government and people during covid- has been a daily press conference. starting on january th, taiwan's cdc hosted a daily press briefing, during which the cecc provides the most recent update on covid- and responds to questions. moreover, the daily conference is used as an educational platform to address false information, social stigmas, and bias. for example, one case of covid was an illegal migrant caregiver, which triggered panic and demands for crackdowns on illegal migrant workers. the cecc used the conference platform to educate the public that every migrant worker, legal or illegal, should be included and treated the same during the coronavirus fight. the cecc stated that illegal foreign workers should not be excluded from the healthcare system, explaining that a crackdown would only result in a bigger loophole in the fight against covid . in another example, a schoolboy was bullied because he wore a pink mask; the cecc team all appeared wearing pink masks at the next press briefing, fighting gender stereotypes (chang, b) . these daily conferences are informative, educational, and morale boosting. it is not an exaggeration to say that the daily press briefing anchored and calmed taiwanese society. people listened to and followed the instructions provided in those daily briefings. communications are not only top-down but bottom-up, and a robust civil society is essential for the bottom-up effort. taiwan has developed a vibrant civil society since democratization in the late s. after the sunflower movement in , civil society networks have grown even stronger and can easily be mobilized. a democratic political structure is the institutional foundation that makes a strong civil society possible. not all democracies breed strong civil societies, but strong civil societies only exist in democratic settings. during the covid- fight, civil society sometimes challenges the government, sometimes collaborates with the government, and sometimes even pioneers and leads the government. instead of imposing rules and regulations on society, the government must persuade the society of the necessity of those regulations. the government has also benefited from the wisdom of the crowd as it sought to refine regulations. two-way communications between the government and societal actors have been a hallmark of the taiwanese response, rather than strictly topdown communications. during the covid- fight, there have been several collaborative efforts between digital civil society and the government. one example is fighting misinformation. of the active civil society, a civic-tech community, pioneered by the g v("gov-zero") movement, has grown rapidly. these "civic hackers" advocate for open government, transparency, and citizens' agenda-setting power (tang, ) . during the crisis, they worked with the government to quickly correct misinformation about covid- on the internet (quito, ) . such synergy was possible partially due to audrey tang, taiwan's current digital minister. tang was once a civic hacker and was one of the g v's core members. her long-term advocacy for big data and open government facilitated active collaboration between the government and the digital civil society. another example of civil society's energy is the "taiwan can help" campaign. during covid- , taiwan and the who had several disputes over taiwan's exclusion from the who. while taiwan's effective crisis response has gained attention, it remains isolated from the global health governance body. the dispute, at some point, developed into a heated fight over racist slurs. taiwan's civil society was furious about the response of who's director-general. in response, the civil society initiated the "taiwan can help" crowdfunded campaign. the goal was to place a full-page advertisement in the new york times to promote taiwan's effective crisis response and to increase cooperation with the international community despite being excluded from the who. the campaign received more than enough money within a few days. with the #taiwancanhelp hashtag on twitter, the campaign began a wave of activism works. later, when the government launched its mask diplomacy, the same hashtag #taiwancanhelp was used to promote its ability to contribute to the international community. in some cases, the tech-savvy community even pioneered better solutions that were later adopted by the government. one example is the optimization of mask distribution. as mentioned above, taiwan launched a mask rationing system. administration of the real-name rationing system was initially difficult, requiring long lines at pharmacies. civic hackers voluntarily created mask apps combining the stock at local pharmacies and google maps to show mask stocks in different locations to help shorten the waiting queues during the early stages of distribution. the government adopted the idea and later developed an online mask purchasing platform. people can now pre-order masks online either through the government website, the national health insurance app, or through the wide-spread convenience stores on the island. the state-society synergy indirectly contributed to e-governance expansion too. in the online purchasing platform example, to accommodate the surplus traffic, the national health insurance administration set up extra servers to expand the cloud capacity (duchâtel et al., ) . one myth about taiwan's success is that confucianism plays a role. some have argued that the successful asian experiences can be attributed to asian values, which emphasize social order and hierarchy. asian people do not question the government as often and are more submissive to strict government regulation. however, taiwan's experience suggests otherwise. in taiwan, governments are subject to frequent criticism. even when the government's measures are necessary, it does not mean that society accepts those decisions submissively. society questions the government, forcing the government to be transparent and be responsive. the positive consequence is that when the regulatory measures are perceived as necessary and approved by the civil society, it increases citizens' cooperation and compliance. governance legitimacy is reinforced through this interaction. in this article, i laid out some of the factors behind taiwan's success in fighting covid- . the legacy of the developmental state helped taiwan create the "mask economy" within a short period of time as well as contributing to the digital governance infrastructure. transparent communication helped define the nature of covid- early on in taiwan, decreasing public panic and increasing public trust in the government and citizens' compliance level. the tech-savvy civil society also collaborated with the government in refining crisis measures. the successful crisis management strategy has also had international repercussions, enhancing taiwan's standing on the international stage. the information presented above suggests a few policy lessons. first, while taiwan has relied on the face mask policies, there are multiple routes to a successful covid policy. central to success is governance capacity, given a society's social, cultural, and economic factors. a centralized command center benefits inter-and intra-agency coordination to produce more coherent response strategies and to mobilize and allocate resources more efficiently. second, for best crisis management outcomes, government legitimacy matters too. people must perceive regulatory measures as necessary to generate high cooperative behaviors. therefore, the way a government defines the crisis is of utmost importance. transparency and communication can also help generate higher cooperation and compliance. additional benefit transparency and communication bring to the table is to allow experts to debate and calibrate a more refined strategy moving forward. third, the wisdom of the crowd can be useful in the covid- fight. when possible, citizens' active engagement can be helpful for the government. through repeated interactions with the society, the government can also refine its crisis to manage strategies to better align the intended policy goals and people's behaviors. notes nhcc includes the central epidemic command center (cecc), the biological pathogen disaster command center, the counter-bioterrorism command center and the central medical emergency operations center ("nhcc" n.d.). originally, the chief commander was the director-general of taiwan's cdc, but soon after china locked down wuhan on january rd, the minister of ministry of health and welfare (mohw), the superior unit of taiwan cdc, became the new chief commander of cecc. leveling up the command center to the ministerial level helps ease inter-ministry cooperation. china also shortened its reaction time compared to the country's reaction time to sars. the first sars case in china appeared on november th, , but china only reported the outbreak to the who in february when there were already cases and deaths in china. during this crisis, the first reported official case appeared on december th , and china reported the outbreak to the who on december st when there were only reported cases (wu & mcgoogan, ) . countries that were affected the most by sars include china, hong kong, taiwan, singapore, and canada. the rationale behind the government's active role is to address the latecomer issue that many asian countries, taiwan included, had after world war ii. however, at the beginning, the pricing mechanism was set in a way that only a few manufacturers met their quota in the first week of production. after reviewing the gaps within the production line, the government identified ways to increase capacity and revise its purchasing and bonus structure to encourage suppliers to produce at maximum capacity. using the integrated database, the government was able to proactively re-test cases that were tested negative for influenza for covid- . out of the cases was covid- positive (jason wang, ng, & brook, ) . when permitted, the health authorities can also trace the infected or high-risk individuals' contact history to prevent any possible virus spread. in one navy ship cluster infection case, the government sent out , text messages to people who may have close contact with the infected individuals based on location information from mobile phones. with taiwan's national health insurance program, every legal resident living in taiwan for more than months (citizens or not) can have access to health resources. the illegal migrant workers are the only group with no access to health resources. to further fix the hole, from april through june , taiwan ran the second amnesty program for illegal migrant workers to encourage them to come forward (wei, ) . the website of the campaign. retrieved from https://taiwa ncanh elp.us/ retrieved from https://mask.pdis.nat.gov.tw/ retrieved from https://www.nhi.gov.tw/conte nt_list.aspx?n= f d f b c managing transboundary crises: identifying the building blocks of an effective response system severe acute respiratory syndrome -taiwan, (morbidity and mortality weekly report a discussion on imf's governance bias and global financial crisis: lessons for who and the covid- pandemic crisis [從imf與金融危機談國際組織、偏 差治理、與全球危機:兼論對who處理武漢肺炎危機 (covid- )的問題]. who governs taiwan pink (mask) is the new black: fighting gender stereotypes. taipei times fighting covid- : east-asian responses to the pandemic embedded autonomy: states and industrial transformation partisanship, health behavior, and policy attitudes in the early stages of the covid- pandemic update january : modeling the spreading risk of -ncov. the center for systems science and engineering (csse) at jhu experience of sars a key factor in countries' response to coronavirus. the guardian developmental states taiwan counters china's isolation campaign with mask diplomacy. nikkei asian review soft regulation and hard compliance in taiwan|the regulatory review. the regulatory review (blog) response to covid- in taiwan: big data analytics, new technology, and proactive testing reimagining the administrative state in times of global health crisis: an anatomy of taiwan's regulatory actions in response to the covid- pandemic the imf as a biased global insurance mechanism: asymmetrical moral hazard, reserve accumulation, and financial crises taiwan's digital response to covid- : impressive, but is privacy respected? the news lens international edition nhcc taiwan is using humor to quash coronavirus fake news taiwan cdc announces activation of central epidemic command center (cecc) for severe special infectious pneumonia to comprehensively prevent novel coronavirus pneumonia outbreak in china and ensure health of taiwanese public. taiwan cdc inside taiwan's new digital democracy coronavirus: taiwan making progress in getting illegal migrant workers to come forward. the straits times characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china fauci says the who's comment on asymptomatic spread is wrong. here's the difference between asymptomatic and pre-symptomatic spread the secrete behind . times of mask production in months: how did taiwan do it? room for industrial upgrade? key: cord- - sfkhg authors: sun, hsin-yun; wang, jann-yuan; chen, yee-chun; hsueh, po-ren; chen, yi-hsuan; chuang, yu-chung; fang, chi-tai; chang, shan-chwen; wang, jung-der title: impact of introducing fluorescent microscopy on hospital tuberculosis control: a before-after study at a high caseload medical center in taiwan date: - - journal: plos one doi: . /journal.pone. sha: doc_id: cord_uid: sfkhg background: undiagnosed tuberculosis (tb) patients hospitalized because of comorbidities constitute a challenge to tb control in hospitals. we aimed to assess the impact of introducing highly sensitive fluorescent microscopy for examining sputum smear to replace conventional microscopy under a high tb risk setting. methods: we measured the impact of switch to fluorescent microscopy on the smear detection rate of culture-confirmed pulmonary tb, timing of respiratory isolation, and total non-isolated infectious person-days in hospital at a high-caseload medical center (approximately tb cases annually) in taipei. multivariable cox regression was applied to adjust for effects of covariates. the effect attributable to the improved smear detection rate was determined using causal mediation analysis. results: after switch to fluorescence microscopy, median non-isolated infectious duration decreased from . days to days (p< . ). compared with conventional microscopy, fluorescence microscopy increased sputum smear detection rate by two-fold (for all patients: from . % to . %, p< . ; for patients with cavitary lung lesion: from % to %, p = . ) and was associated with a -fold higher likelihood of prompt respiratory isolation (odds ratio mediated by the increase in sputum smear detection rate: . , % ci . – . ). total non-isolated infectious patient-days in hospital decreased by % (from , patient-days per year to , patient-days per year). conclusions: in a high tb caseload setting, highly sensitive rapid diagnostic tools could substantially improve timing of respiratory isolation and reduce the risk of nosocomial tb transmission. a a a a a pulmonary tuberculosis (tb) is an airborne disease [ ] . unless promptly isolated, hospitalized patients with active pulmonary tb can transmit to both healthcare workers (hcws) and other patients [ ] . hcws could have an incidence rate of active tb -to -fold higher than that in general population [ ] . the discovery of hospital-acquired extensively drug-resistant tb, with an extremely high mortality among hiv-positive patients, further highlights this deadly hazard [ , ] . rapid isolation of hospitalized patients with pulmonary tb is the pivotal step to prevent nosocomial transmission [ ] . however, undiagnosed tb patients hospitalized for treatment of comorbidities constitute a challenge to tb control within hospitals. clinical predictive rules had been proposed to guide the decision to implement respiratory isolation [ ] . an expanded isolation policy which pre-emptively isolated all patients with possibility of tb achieved immediate isolation of > % of patients with tb in low tb risk settings [ ] . nevertheless, the same policy would be impractical in a high tb risk setting because there would be too many patients to be pre-emptively isolated [ , ] . for a laboratory diagnosisbased respiratory isolation policy, an important barrier is the limited sensitivity of conventional sputum smear [ , ] . compared with conventional microscopy, fluorescence microscopy has a superior sensitivity for detecting tb bacilli [ ] . in , world health organization (who) recommends switching conventional to fluorescence microscopy [ ] , under the condition that the switch should be carefully planned at country level with training, quality assurance, and monitoring on tb detection rate [ ] . who also endorsed highly sensitive tb nucleic acid amplification test (tb-pcr) such as xpert mtb/rif (cepheid, sunnyvale, ca) [ ] . point-of-care xpert mtb/rif reduces all-cause -month mortality in patients positive for tb symptoms at the time of hiv diagnosis [ ] . nevertheless, to our knowledge, the effect of introducing these more sensitive diagnostic tools on reducing risk of nosocomial tb transmission has not been documented. taiwan is a developed country with an incidence of tb at the range of approximately per , general population in [ ] . in , severe acute respiratory syndrome (sars)related chest radiograph screenings led to the discovery of a large nosocomial tb outbreak at a rehabilitation facility in taipei, involving cases of active tb in hcws [ ] . the index case of this outbreak was an elderly patient hospitalized for stroke rehabilitation without suspicion of tb [ ] . subsequent investigations found that the problem of delayed isolation of undiagnosed tb patients also existed in other hospitals [ , ] . in response, taiwan centers for disease control (cdc) issued guidance on nosocomial tb control [ ] . to facilitate laboratory diagnosis-based isolation, medical center a started to roll out auramine-rhodamine staining with fluorescence microscopy since and completed the switch by early s. we aimed to assess whether switching from conventional microscopy to a more sensitive rapid diagnostic tool improves early detection and prompt isolation of hospitalized patients with undiagnosed tb. medical center a, a leading university-affiliated general hospital having the second-highest tb caseload (approximately cases annually) in taiwan, was chosen for this study. the center in taipei had a , -bed capacity and provided both primary and tertiary referral care reimbursed by national health insurance (nhi). the service amount steadily increased from to . there were , , outpatient visits and , admissions in , nearly -fold than that in . medical center a followed the guidance on hospital respiratory isolation policies issued by taiwan cdc [ ] . contact investigation had been expanded to all hcws who were exposed to tb patients since . sputum smear auramine-rhodamine staining with fluorescent microscopy started in . the national laboratory personnel training programs for quality assurance of acid-fast staining [ ] , mandated by taiwan cdc, helped to ensure the technical proficiency and performance quality of fluorescence microscopy (see details in s table) [ ] . this before-after retrospective cohort study included all hospitalized patients with cultureconfirmed pulmonary tb in wards/units in and those in . we compared the duration from admission/arrival to respiratory isolation in (conventional microscopy with ziehl-neelsen staining, represented the baseline situation before sars outbreak) with that in (after full switching to fluorescent microscopy with auramine-rhodamine staining and the quality assurance program). cox regression was used to adjust for effects of covariates. the effect mediated by improved smear detection rate was precisely identity using causal mediation analysis. the study procedure and exemption of informed consent were reviewed and approved by research ethics committee of national taiwan university hospital (taipei, taiwan). for each included tb case, medical and administrative records were reviewed to determine the infectious duration. a computerized data collection form was used to systematically collect the following information from the medical records: demographic data, sputum smear and culture results, presentations, comorbidities, reasons of hospitalization, and other relevant data, with pre-defined criteria. hospitalized patients had typical presentations of pulmonary tb if they had: (a) a prolonged cough for > weeks; (b) clinical suspicion of pulmonary tb based on chest radiography, such as cavitary pulmonary lesions, upper lobe diseases, or miliary lesions; or (c) already received a confirmed diagnosis of pulmonary tb by a positive sputum culture of mycobacterium tuberculosis, positive acid-fast stain (afs), or positive tb pcr, before the hospitalization. the hospitalization was considered as tb-related if the chief complaint suggested an infectious etiology or the admission was for inpatient tb treatment. the hospitalization was considered comorbidities-related when the patients was admitted for management of acute complications of non-infectious diseases, such as myocardial infarction, pulmonary edema, malignancy, or acute exacerbation of chronic lung diseases. we retrospectively identified all cases of culture-confirmed pulmonary tb patients in (january to december , ) and in (january to december , ), using a computerized registry of mycobacteriology laboratory. the diagnosis was verified in each case with review of medical records. for each included infectious tb case, the zero time was the date of admission to the hospital or the date of arrival to emergency department (er). the end of follow-up was the date when the patients was sent to a respiratory isolation room (event), the date of discharge (from hospital or er) before respiratory isolation can be implemented (censored), the date of completion -day anti-tb treatment (censored), or the date of mortality due to any cause (censored). for patients who had multiple admissions or multiple positive sputum cultures, only the admission with or following the first positive sputum culture (the index culture) was used to calculate the kaplan-meier estimates for time to respiratory isolation. to estimate the total non-isolated infectious patient-days in hospital, each tb case/patient was considered infectious from months prior to the first positive sputum culture unless being put in a respiratory isolation room or had already received a -day course of at least two in vitro active anti-tuberculous agents after the last positive sputum culture. for those who had multiple hospitalization or had ever been transferred between wards/units before being diagnosed with pulmonary tb or adequately treated, all hospitalizations or stay in each ward/unit were counted in the calculation of total infectious patient-days. statistical analyses were performed using spss . (ibm, armonk, new york, usa). cox regression, with backward selection, was used to adjust for covariates. causal mediation analyses were performed using proc causalmed (based on logistic regression for isolation status on day ) in sas . (sas institute, cary, north carolina, usa). all analyses were two-sided. p values less than . was considered statistically significant. in and , of ( %) and of ( %) patients with culture-confirmed pulmonary tb were hospitalized, respectively ( table ). the median non-isolated infectious duration decreased from . in to days in (p< . ) ( table ) . improvement occurred over all subgroups of patients (s table) . fig shows kaplan-meier estimates for time to respiratory isolation (discharge of undiagnosed tb is counted as censored rather than as the end of infectiousness) in versus that in (median: vs. days, p = . , logrank test). patients with cavitary lung lesions were more quickly isolated, while lack of typical clinical presentation and hospitalized due to comorbidities were associated with delayed respiratory isolation ( switching to auramine-rhodamine staining with fluorescent microscopy doubled the overall positive sputum smear rate from . % ( ) to . % ( ) (p< . ), particularly in patients with non-cavitary lung lesions ( . % to . %, p< . ) ( table ). cox regression analyses shows that a positive sputum smear was associated with an earlier respiratory isolation (ahr . , % ci . - . , p< . ) ( table : model ). causal mediation analyses show that the two-fold higher sputum smear detection rate of fluorescence microscopy doubled the (fig ) . in patients with positive sputum smear, the use of tb-pcr grew from . % ( ) alertness of physicians, measured by duration from patient arrival to physician's ordering of smear or culture, also improved from to (median: vs. days, p< . ) (s table) . cox regression analysis shows that physician alertness was also associated with earlier respiratory isolation (ahr . for each additional day before physician ordering tb smear/culture, % ci . - . , p = . ) ( in , there were a total of , infectious patient-days in hospital ( from smear-positive patients, , from smear-negative patients). in , the total non-isolated infectious patient-days in hospital decreased by %, to , infectious patient-days ( from smearpositive patients and , from smear-negative patients). improvement occurred over all types of wards/units, including er, internal medicine wards, surgical wards, and intensive care units (fig , s and s figs) . our study showed that introducing highly sensitive rapid diagnostic tools decreases the risk of nosocomial tb transmission from hospitalized patients with undiagnosed tb in a high tb risk setting. switching from conventional to fluorescence microscopy doubles the sputum smear detection rate and was associated with a two-fold increase in likelihood of prompt respiratory isolation. a genuine improvement in time-to-respiratory-isolation of hospitalized tb patients should reduce nosocomial tb transmission, especially to hwcs. this is precisely what we observed in medical center a. our previous survey on age/sex-standardised tb incidence ratio of hcws (using general population as reference)---the excess tb risk that are attributable to nosocomial tb transmission---in medical center a showed a drop of this risk, from . in to . in [ ] , and the decrease in time-to-isolation and total non-isolated infectious patient-days was in parallel in the present study. traditional ziehl-neelsen staining and conventional light microscopy have unsatisfactory sensitivity in detecting acid-fast bacilli [ ] . a systematic review showed that, compared with conventional method, fluorescence microscopy has higher sensitivity and similar specificity [ ] . this present study found that, after switch to fluorescent microscopy, the overall sputum smear detection rate doubled ( % vs. %, p< . ), particularly in patients with non-cavitary lung lesions ( . % to . %, p< . ) but also in patients with cavitary lesion ( % to %, p = . ). furthermore, the superior detection rate of fluorescence microscopy translated to a more timely respiratory isolation. the %- % difference in sensitivity between fluorescence and conventional microscopy from our real life data is much larger than the % (on-average) reported in previous studies that compared the diagnostic performance of fluorescent versus conventional microscopy under the optimal conditions [ ] . this highlights an often overlooked problem of traditional ziehl-neelsen staining, i.e. the majority of clinical laboratories just did not have the manpower to adequately check high-power fields [ ] (which takes around minutes) per sample that are required for conventional microscopy [ ] , particularly in a busy, high clinical caseload settings. in contrast, it takes only - seconds per sample for an adequate check with fluorescent microscopy [ ] which would have a decisive advantage in the real world implementation. although tb-pcr has been considered an important rapid diagnostic tool, this study did not show a significant role of tb-pcr in the reduction in time-to-respiratory isolation from to . there were several probable reasons. first, the low adoption rate (due to cost issues) may not be enough to make an impact on shortening the overall infectious duration. second, because of the lower sensitivity of tb-pcr in smear-negative respiratory specimens, tb-pcr was performed predominantly in specimens with positive afs to distinguish m. tuberculosis from non-tuberculous mycobacteria. the negative result does not exclude the possibility that universal use of automatic tb-pcr, such as xpert mtb/rif, may further shorten the time to respiratory isolation. in keeping with previous observations (s table) , the absence of cough and other typical symptoms is a barrier to prompt respiratory isolation of tb patients (s table) . another cause of delay is hospitalization due to comorbidities, a problem that was previously neglected or confused with the lack of typical clinical presentations. to distinguish these two different situations, we defined hospitalization due to comorbidities as the reason of admission being for the management of acute complications from non-infectious diseases, while lack of typical presentation was defined as the absence of prolonged cough for more than weeks, clinical suspicion of pulmonary tb based on chest radiography, or already having a confirmed diagnosis. multivariable regression established that hospitalization due to comorbidities was a risk factor independent from lack of typical presentations ( table ) . the diverse distribution of hospitalized infectious tb patients across medical/surgical sub-specialities wards/units (s and s figs) further supports that hospitalization of patients with undiagnosed tb for treatment of comorbidities is an unrecognized but important issue requiring to be addressed. the hcws in specialties units often concentrate on the management of acute complications of non-infectious chronic diseases and are not trained or prepared for diagnosing concomitant tb in their patients. the large nosocomial tb outbreak in taipei [ ] involving more than hcws, occurred exactly under such scenario -an elderly patient with acute stroke was hospitalized to a rehabilitation unit, without being suspected to also have active tb. the harm is two-way. first, the patients are at increased risk for morbidities and mortality from delayed diagnosis and treatment of tb. second, the hcws are at increased risk of nosocomial tb outbreak, which could be fatal if the strain is multidrugresistant or extensively drug-resistant [ ] . the interplay between tb and chronic diseases further complicates the clinical scenarios. chronic non-communicable diseases increase the risk of tb-the associations have been well established for diabetes mellitus [ ] and rheumatoid arthritis treated with anti-tumour necrosis factor (tnf) agents [ ] . on the other hand, tb may increases the risk of complications from chronic diseases, e.g. hyperglycaemia in diabetes mellitus and ischemic stroke in people with atherosclerosis [ ] . moreover, certain risk factor, such as smoking, increases the risk of both tb and chronic diseases [ ] . therefore, hospitalization of undiagnosed tb patients for treatment of comorbidities is more than just a coincidence by chance. in low hiv prevalence countries, tb is a disease of elderly [ ] . with population aging, concurrence of tb and comorbidities could be an increasing challenge to clinicians. currently, most hospitals in taiwan still used traditional ziehl-neelsen staining (or kinyoun staining, a similar method) and conventional light microscopy in laboratory diagnosis of tb. an analysis of - taiwan national health insurance database revealed that frequent exposure to hospital environment is a risk factor for contracting tb in taiwan (adjusted odds ratio: . , for those with � outpatient care visit annually) [ ] . our findings on the impact of switching to auramine-rhodamine staining with fluorescence microscopy suggest that a nationwide adoption and roll-out might cut the risk of nosocomial tb transmission to both patients and healthcare workers. to address the remaining barriers to respiratory isolation of hospitalized tb patients, "fast (find cases actively by cough surveillance and rapid molecular sputum testing, separate safely, and treat effectively based on rapid drug susceptibility test)" is an option to decrease the time to respiratory isolation [ , ] although the substantial cost of rapid molecular testing could be a barrier to nhi reimbursement. alternatively, environmental controlsthe second level in the hierarchy of tb control-with adequate ventilation (> - air changes per hour) or upper room ultraviolet germicidal irradiation (to disinfect the air) can be applied to reduce the concentration of infectious droplet nuclei in hospital indoor air, and decrease risk of nosocomial transmission [ , ] . the present study has several important limitations. first, it was not a randomized controlled trial (which cannot be performed in the context, due to ethical reasons). physician education and expansion of respiratory isolation facilities were simultaneously implemented along with the switching to fluorescence microscopy during the same intervention period. nevertheless, we applied multivariable regression and causal mediation analyses to estimate the effect attributable to switching to fluorescence microscopy. second, the study hospital closely followed the national guidance on nosocomial tb control policies issued by taiwan cdc. therefore, our findings might not be generalizable to hospitals with less proficiency. third, the study hospital is a medical center, and therefore might not represent situations in smaller hospitals. nevertheless, under nhi in taiwan, people can and did directly seek health care in medical centers, without the need of referral from general practitioners. the million annual outpatient visits and more than thousand hospitalizations per year in the study hospital were predominantly from primary care services, rather than tertiary referral care. finally, since taiwan has a low hiv prevalence [ ] , only two of tb patients had hiv coinfection in our study. thus, our conclusions might not be generalized to countries with a high hiv prevalence. in conclusion, highly sensitive rapid diagnostic tools could substantially improve timing of respiratory isolation and reduce risk of nosocomial tuberculosis transmission in high tb risk settings. lack of typical presentations and hospitalization due to comorbidities continued to be main reasons of delayed isolation. studies will be required to assess whether routine sputum smear or tb-pcr of all hospitalized patients with cough or abnormal chest radiograph is effective in overcoming these remaining barriers. supporting information s table. tuberculosis aerial dissemination of pulmonary tuberculosis. a two-year study of contagion in a tuberculosis ward world health organization. guidelines for prevention of tuberculosis in healthcare facilities in resourcelimited settings. geneva: world health organization risk of tuberculosis infection and disease associated with work in health care settings extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and hiv in a rural area of south africa nosocomial transmission of extensively drug-resistant tuberculosis in a rural hospital in south africa guidelines for preventing the transmission of mycobacterium tuberculosis in health-care settings systematic review with meta-analyses and critical appraisal of clinical prediction rules for pulmonary tuberculosis in hospitals preventing the nosocomial transmission of tuberculosis clinical predictors of tuberculosis as a guide for a respiratory isolation policy evaluation of clinical prediction rules for respiratory isolation of inpatients with suspected pulmonary tuberculosis delays in suspicion and isolation among hospitalized persons with pulmonary tuberculosis at public and private us hospitals during to delay in diagnosis among hospitalized patients with active tuberculosis-predictors and outcomes fluorescence versus conventional sputum smear microscopy for tuberculosis: a systematic review fluorescent light-emitting diode (led) microscopy for diagnosis of tuberculosis screening for tuberculosis with xpert mtb/rif assay versus fluorescent microscopy among adults newly diagnosed with human immunodeficiency virus in rural malawi: a cluster randomized trial (chepetsa) trends in tuberculosis in taiwan nosocomial transmission of mycobacterium tuberculosis found through screening for severe acute respiratory syndrome-taipei delayed suspicion, treatment and isolation of tuberculosis patients in pulmonology/infectious diseases and non-pulmonology/infectious diseases wards why is in-hospital diagnosis of pulmonary tuberculosis delayed in southern taiwan? guidance on prevention and control of nosocomial tuberculosis transmisison sputum smear microscopy: evaluation of impact of training, microscope distribution, and use of external quality assessment guidelines for resource-poor settings tuberculosis in healthcare workers: a matched cohort study in taiwan fluorescence microscopy for tuberculosis diagnosis extensively drugresistant tuberculosis (xdr-tb) among health care workers in south africa diabetes mellitus increases the risk of active tuberculosis: a systematic review of observational studies safety and effectiveness of tocilizumab in treating patients with rheumatoid arthritis-a three-year study in taiwan tuberculosis and the risk of ischemic stroke: a -year follow-up study effects of smoking and solid-fuel use on copd, lung cancer, and tuberculosis in china: a time-based, multiple risk factor, modelling study treatment delay and fatal outcomes of pulmonary tuberculosis in advanced age: a retrospective nationwide cohort study health care visits as a risk factor for tuberculosis in taiwan: a population-based case-control study a refocused, intensified, administrative tuberculosis transmission control strategy fast implementation in bangladesh: high frequency of unsuspected tuberculosis justifies challenges of scale-up guidelines for preventing the transmission of mycobacterium tuberculosis in health-care facilities we thank all staff in the hospital for their commitment to improving patient safety and reducing healthcare-associated infection.supervision: yee-chun chen, chi-tai fang, shan-chwen chang. hsin-yun sun, jann-yuan wang, yee-chun chen, po-ren hsueh, yi-hsuan chen, yu-chung chuang, chi-tai fang, shan-chwen chang, jung-der wang. key: cord- - abp oom authors: lan, yu-ching; liu, hsin-fu; shih, yi-ping; yang, jyh-yuan; chen, hour-young; chen, yi-ming arthur title: phylogenetic analysis and sequence comparisons of structural and non-structural sars coronavirus proteins in taiwan date: - - journal: infect genet evol doi: . /j.meegid. . . sha: doc_id: cord_uid: abp oom taiwan experienced a large number of severe acute respiratory syndrome (sars) viral infections between march and july ; by september of that year, sars cases were confirmed by rt-pcr or serological tests. in order to better understand evolutionary relationships among sars coronaviruses (scovs) from different international regions, we performed phylogenetic comparisons of full-length genomic and protein sequences from human scovs (including from taiwan) and two civet scovs. all the taiwanese sars-cov strains which associated with nosocomial infection formed a monophyletic clade within the late phase of the sars epidemic. this taiwanese clade could be further divided into two epidemic waves. taiwan scovs in the first wave clustered with three isolates from the amoy gardens housing complex in hong kong indicating their possible origin. of the human scovs, one isolate from guangdong province, china, exhibited an extra -nucleotide fragment between orf and orf —similar to the civet scov genome. nucleotide and protein sequence comparisons suggested that all scovs of late epidemic came from human-to-human transmission, while certain scovs of early epidemic might have originated in animals. on august , the world health organization (who, ) reported that the sars pandemic infection had spread to more than countries, affecting people and killing . later that year a novel coronavirus (sars-cov) was isolated from sars patients ksiazek et al., ; peiris et al., b; poutanen et al., ) ; an animal inoculation experiment identified a causal relationship between sars and sars-cov infection . zhong et al. ( ) identified the geographic origin of the epidemic as guangdong province, china, and the originating month as november . the first sars case in taiwan was diagnosed on march . its history was traced to a trip by the index case to guangdong in mid-february, when the sars epidemic in that province reached its peak (cdc, ; roc cdc, ) . the index case transmitted the virus to his wife and son; the first sars coronavirus in taiwan-scov tw -was isolated from the son (hsueh et al., ) . on march a male resident of the amoy gardens housing complex in hong kong (hereafter referred to as mr. x) flew to taiwan. on march he took a train from taipei to taichung city to visit his younger brother. that night he experienced a high fever; most likely he also read a local news report of a major sars outbreak in amoy gardens that same day (peiris et al., a) . he returned to hong kong on march. after he was admitted to a hospital, mr. www.elsevier.com/locate/meegid infection, genetics and evolution ( ) - x made a phone call to warn his younger brother, but it was too late. the younger brother who developed symptoms on march became the first sars-related fatality (tc ) in taiwan. a second index case (scov-twc) was isolated from this patient (the younger brother) by the roc cdc . the third index case was ms. a, a female adult who traveled on the same taiwanese train as mr. x on march. two days later she visited a hospital in taipei complaining of general fatigue. in addition to the local hospital, she visited two private clinics before being referred to taipei municipal hoping hospital on april. she spent less than h in that hospital's emergency room, but she probably transmitted the virus to two patients, an assistant nurse who escorted her to the x-ray room, and a laundry worker who handled her isolation gown. these individuals transmitted the sars virus to other medical personnel and patients, resulting in the entire hospital being shut down for more than months starting on april. according to the roc cdc, the hoping hospital nosocomial infection resulted in probable and suspected sars cases (wu et al., ) . even though the taiwanese government imposed a quarantine on april on all air travelers arriving from china, hong kong, singapore, macau, or toronto, the virus still spread to different parts of the main island of taiwan and the adjacent penghu islands. by september, sars cases in taiwan had been confirmed by rt-pcr or serological tests (who, ) . the size of the scov genome is approximately . kb (marra et al., ; rota et al., ) . the portion of the genome ( kb, about two-thirds) contains the code for the replicase gene, including two large open reading frames (orfs), referred to as orfs a and b. the other onethird of the genome contains orfs for four structural proteins (spike [s], envelope [e], membrane [m], and nucleocapsid [n] ) and nine putative non-structural proteins (orfs , , , , , , , and ) . recently, guan et al. ( ) isolated scov-like viruses from himalayan palm civets and raccoon dogs in southern china. according to a comparative analysis of human and animal scov genomes, the three animal scovs (sz , sz and sz ) all retain a -nucleotide sequence inserted between orfs and . for this study, we used phylogenetic analysis to investigate relationship among taiwanese sars-covs and between those scovs from other countries. one specific goal was to determine whether the sars-cov isolate from mr. x's younger brother (twc) clustered with the isolate from ms. a (twc ), and whether either one of those isolates clustered with isolates from other amoy gardens residents (chim et al., ) . we also compared the amino acid sequences of the s, e, m, and n structural proteins and three of the nine putative non-structural proteins (orfs , , and ) for sars-covs including taiwanese strains. twelve taiwanese scov strains were included in this study: tw (hsueh et al., ) , twc, twc , twc , twh, tc , tc , tc , twj, twk, tws and twy. tw was isolated from a patient whose father spent time in guangdong province in mid-february . twc was isolated from taiwan's first sars-related fatality. twc and twc were isolated from taipei municipal hoping hospital patients, and twc was from ms. a, the third index case. an additional full-length genomic sequences from human scov strains were selected from the genbank: nine from beijing (bj , bj , bj , bj , pumc , pumc , pumc , sino - and sino - ), six from hong kong (cuhk-w , cuhk-ag , cuhk-ag , cuhk-ag , cuhk-su and hku- ), five from singapore (sin , sin , sin , sin and sin ), two from guangzhou (gd and gz ), two from frankfurt (frankfurt and fra), two from milan (as and hsr ), two from guangdong province (zmy and gd ), and one each from wuhan (whu), zhejiang province (zj ), moscow (sod), toronto (tor ), and hanoi (urbani). a blast search was performed to locate sars cov sequences in the genbank database. a total of full-length nucleotide sequences from sars cov isolates (including two civet isolates) were aligned and edited using the bioedit program (hall, ) . phylogenetic analyses were conducted with the phylip . b (felsenstein, ) and mega programs (kumar et al., ) using the neighbor-joining (nj) and fitch and wagner parsimony (pars) methods. evolutionary distances were estimated with the kimura twoparameter model (kimura, ) . nj and pars tree robustness were statistically evaluated by bootstrap analysis ( samples). scov nucleotide sequence variation was analyzed with the simplot program (johns hopkins university, baltimore, md). the scovs used for this task were the urbani, cuhk-w , tor , hku- , bj , bj , bj , bj , gd , tw , twc, sin , sin , sin , sin , sin , hsr , cuhk-su , frankfurt , and gz . two civet scovs (sz and sz ) were used as references for comparison. sequence variation distance plots were generated with bp windows, bp steps, and a jukes-cantor correction. nucleotide sequences for the four structural genes, orf , and orf were edited and translated into amino acid sequences using the bioedit program prior to alignment for comparisons. the accession numbers for the scovs used in this study are urbani: to better understand evolutionary relationships between scovs isolated in taiwan and those isolated in other parts of the world, we constructed phylogenetic trees with two different methods using full-length genomic sequences from human ( taiwanese) and two civet scovs. tree topologies were consistent for the nj (fig. a) and pars (fig. b) methods. two human scov epidemics were identified. the late epidemic scovs formed a well-supported monophyletic clade with bootstrap values of and for the nj and pars trees, respectively. the early epidemic sequences did not cluster into a monophyletic clade, even though they did clearly differed from those of late epidemic. fig. . human and civet scov phylogenetic trees, produced with the neighbor-joining (nj) method using full-length ( . kb) sequences. branch bootstrap values from reps: (a) using the sz civet scov as a root; (b) a tree produced using the parsimony (pars) method. all early epidemic scovs had chinese origins: beijing (bj , bj , bj and bj ), guangzhou (gd and gz ), and hong kong (cuhk-w ). all the taiwanese scovs sequences which associated with nosocomial infection clustered into a monophyletic clade (bootstrap values and for nj and pars trees, respectively) within the late epidemic and could be further classified into two epidemic waves. second wave was a monophyletic clade supported by bootstrap values of and for nj and pars tree, respectively, while first wave was not a fully resolved cluster. twc (from mr. x's younger brother) did not cluster with three isolates from amoy gardens (cuhk-ag , cuhk-ag , cuhk-ag ), but did cluster with an isolate (whu) from wuhan, china (bootstrap value for nj tree) (fig. a) . pairwise comparison methods were used to analyze nucleotide sequence variation within the full-length genomes of human scovs ( from early epidemic and from late epidemic) (fig. ) . two civet scov sequences (sz and sz ) were used as references for comparison. our results revealed that the highest variation rate was in the one-third of the viral genome, especially the nucleotide sequences near the junction between the replicase b and spike genes; orf also had a relatively high sequence variation rate. amino acid sequences for the s, m, e, and n structural proteins of human scovs were compared with those of the sz- civet scov (fig. ) . the s protein was divided into s and s domains according to the molecular model proposed by spiga et al. ( ) . the s domain (n-terminal - amino acid residues, responsible for receptorbinding) had ( . %) amino acid differences; the s domain ( - amino acid residues) had ( . %)-a total of ( . %) differences in the s proteins of scovs. the s genes of whu and zmy contained several nucleotide insertions that interrupted the open reading frames. the amino acid distances of s proteins were . % ( . / ) for early epidemic scovs and . % ( . / ) for late epidemic scovs in comparison with civet scovs. intra-group sequence variation for early epidemic was . % (n = ) and for late epidemic . % (n = ) ( table ). the numbers of amino acid differences were for the e protein ( . %), for m ( . %), for n ( . %), and for orf ( . %) (fig. ) . amino acid distances among the human scovs were . % ( . / ) for the e protein, . % ( . / ) for m, . % ( . / ) for n, and . % ( . / ) for orf (table and fig. ) . among the human scovs that we analyzed, an isolate (gd ) from guangdong province china, contained an extra -nucleotide fragment. both whu and twc had dinucleotide deletions at the th and st nucleotides of orf , resulting in a frame shift and premature stop of the putative protein (fig. ). in addition, we observed a nucleotide deletion at the nd nucleotide of orf in sin ; this also resulted in a frame shift and premature translation stop. both the nj and pars trees separated the human scovs into two epidemics, even though early epidemic scovs failed to cluster into a well-supported monophyletic clade ( fig. a and b) . the early epidemic sequences were more closely related than the late epidemic sequences to civet scovs; all seven early epidemic scovs were from either fig. . plot analyses were used to compare diversity distributions among genes from human scovs. the average genetic distance from the reference genome of civet scovs of human scovs are plotted over the entire genome of scov. genomic sequences from the sz and sz civet scovs were used as references. the x-axis is the nucleotide location of the sars-cov genome. the y-axis is the rate of nucleotide differences between human scovs and civet scovs. sequence variation distance plots were generated with a bp window, bp steps by simplot program. guangdong province or beijing. among all the analyzed human scovs, gd was the only one having an extra nucleotide fragment which was also found in the civet scovs . furthermore, the average intragroup amino acid distance for the s gene in early epidemic was higher than for late epidemic (table ) . we also identified a signature amino acid sequence pattern (amino acid residues and ; fig. ) shared by early epidemic isolates and civet scovs. these evidences suggested that late epidemic scovs were transmitted from human-tohuman, while certain early epidemic scovs (e.g., gd ) might have been transmitted from animals to humans before spreading among various human populations. among the taiwanese scovs, our phylogenetic analysis does not support the hypothesis of an epidemiological link between the first and third index cases (mr. x and ms. a). according to our nj tree, twc (a scov isolate from mr. x's younger brother) clustered with the whu scov from wuhan, china (bootstrap = ), while twc- (ms. a's isolate) clustered with cuhk-ag and cuhk-ag , both of which originated in hong kong's amoy gardens housing complex. a sequence analysis demonstrated that twc and whu had di-nucleotide deletions in orf , resulting in a shift in the open reading frame (fig. ) . therefore, even though mr. x and ms. a took the same train from taipei to taichung, the evidence indicates that mr. x was not the source of ms. a's infection; that source has yet to be identified. as shown in the diversity plot, the s gene and orf at the junction between the replicase b and s genes had a higher number of sequence variations compared to other genomic regions (fig. ) . this influenced our decision to perform additional sequence comparisons of the s, e, m and n structural genes and orfs and . the s proteins of coronaviruses have been described as large, type i membrane glycoproteins that are responsible for both the binding of receptors to host cells and membrane fusion xiao et al., ) . the type i glycoproteins of coronaviruses, whose trimers resemble typical viral spikes, is transformed into virions through noncovalent interactions with m proteins. coronavirus s proteins contain two domains (or two subunits, depending on whether or not s is cleaved) (spiga et al., ) . the s domain contains virus-neutralizing epitopes and the receptor-binding domain (leparc-goffart et al., ; sanchez et al., ) . xiao et al. ( ) recently localized the scov receptor-binding domain (rbd) to amino acid residues - of the s protein. as shown in fig. , we observed seven amino acid differences in the rbd of the s protein, including amino acid residues , , , , , and . if we assume that the rbd is (a) conserved among different scovs, including civet scovs (bonavia et al., ) , and (b) more than - amino acids in length (lasky et al., ) , then it is possible that the rbd can be mapped onto amino acid residues - . identification of a receptor-binding domain of the spike glycoprotein of human coronavirus hcov- e memoir of severe acute respiratory syndrome control in taiwan severe acute respiratory syndrome analysis of the whole-length sequences of ten strains of sars coronavirus in taiwan and its epidemiological implications amino acid comparisons of s proteins from human and civet scovs. the urbani scov was used as a reference. a period (.) indicates concurrence with the top reference sequence (urbani) in the alignment genomic characterisation of the severe acute respiratory syndrome coronavirus of amoy gardens outbreak in hong kong identification of a novel coronavirus in patients with severe acute respiratory syndrome phylip -phylogeny inference package, version . aetiology: koch's postulates fulfilled for sars virus isolation and characterization of viruses related to the sars coronavirus from animals in southern china bioedit: a user-friendly biological sequence alignment editor and analysis program for windows / /nt microbiologic characteristics, serologic responses, and clinical manifestations in severe acute respiratory syndrome a simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences a novel coronavirus associated with severe acute respiratory syndrome mega : molecular evolutionary genetics analysis software delineation of region of the human immunodeficiency virus type gp glycoprotein critical for interaction with the cd receptor targeted recombination within the spike gene of murine coronavirus mouse hepatitis virus-a : q is a determinant of hepatotropism angiotensin-converting enzyme is a functional receptor for the sars coronavirus clinical progression and viral load in a community outbreak of coronavirusassociated sars pneumonia: a prospective study coronavirus as a possible cause of severe acute respiratory syndrome identification of severe acute respiratory syndrome in canada targeted recombination demonstrates that the spike gene of transmissible gastroenteritis coronavirus is a determinant of its enteric tropism and virulence molecular modelling of s and s subunits of sars coronavirus spike glycoprotein summary table of sars cases by country epidemiological investigation of the sars outbreak in the taipei municipal hoping hospital. memoir of severe acute respiratory syndrome control in taiwan the sars-covs glycoprotein: expression and functional characterization epidemiology and cause of severe acute respiratory syndrome (sars) in guangdong, people's republic of china we thank mr. jon lindemann for editing our manuscript. this work was supported in part by a grant from the national sars research program of the republic of china national science council (grant no. svir ). key: cord- -cy j wq authors: koh, wee ming; bogich, tiffany; siegel, karen; jin, jing; chong, elizabeth y.; tan, chong yew; chen, mark ic; horby, peter; cook, alex r. title: the epidemiology of hand, foot and mouth disease in asia: a systematic review and analysis date: - - journal: pediatr infect dis j doi: . /inf. sha: doc_id: cord_uid: cy j wq context: hand, foot and mouth disease (hfmd) is a widespread pediatric disease caused primarily by human enterovirus (ev-a ) and coxsackievirus a (cv-a ). objective: this study reports a systematic review of the epidemiology of hfmd in asia. data sources: pubmed, web of science and google scholar were searched up to december . study selection: two reviewers independently assessed studies for epidemiologic and serologic information about prevalence and incidence of hfmd against predetermined inclusion/exclusion criteria. data extraction: two reviewers extracted answers for specific research questions on hfmd epidemiology. the results are checked by others. results: hfmd is found to be seasonal in temperate asia with a summer peak and in subtropical asia with spring and fall peaks, but not in tropical asia; evidence of a climatic role was identified for temperate japan. risk factors for hfmd include hygiene, age, gender and social contacts, but most studies were underpowered to adjust rigorously for confounding variables. both community-level and school-level transmission have been implicated, but their relative importance for hfmd is inconclusive. epidemiologic indices are poorly understood: no supporting quantitative evidence was found for the incubation period of ev-a ; the symptomatic rate of ev-a /coxsackievirus a infection was from % to % in studies; while the basic reproduction number was between . and . in studies. the uncertainty in these estimates inhibits their use for further analysis. limitations: diversity of study designs complicates attempts to identify features of hfmd epidemiology. conclusions: knowledge on hfmd remains insufficient to guide interventions such as the incorporation of an ev-a vaccine in pediatric vaccination schedules. research is urgently needed to fill these gaps. underground and aggregated at a weekly scale. incidence data from tokyo, hong kong, taiwan and singapore were extracted from routine surveillance data published by government agencies (the national institute of infectious diseases, japan ; the department of health, hong kong ; the taiwan national infectious disease statistics system and the ministry of health, singapore). nontabular data were extracted from figures using plot digitizer. data on weather and incidence were analyzed using a time series model. symptomatic proportions were pooled by aggregating denominators and numerators. other analyses used standard statistical methods and were conducted using r. outbreaks of hfmd do not occur uniformly throughout the year across asia. in fukuoka, japan, for example, weekly numbers of hfmd cases have been found to increase with average temperature and humidity, especially among younger children. by digitizing the incidence data from publications on japan , - and north china [ ] [ ] [ ] [ ] [ ] [ ] (fig. ) , we observe that may through july are the months with highest incidence in temperate regions of asia. however, this relationship is less clear for tropical and subtropical asia. the extracted data on southwest china, , south china, , , , hong kong , and taiwan [ ] [ ] [ ] show that outbreaks typically happen in late spring and fall. no distinct pattern is obvious for tropical regions as seen from data in thailand, [ ] [ ] [ ] vietnam, , malaysia and singapore, [ ] [ ] [ ] [ ] where outbreaks occur sporadically throughout the year, although models have been developed for singapore (≈ ° north) that show a positive statistical relationship between maximum daily temperature above °c with hfmd incidence in the subsequent - weeks. to assess how general the relationship between climate and transmissibility of hfmd was, we took incidence data from tokyo, hong kong, taiwan and singapore (fig. , appendix ) , that is, spanning temperate, subtropical and tropical latitudes, and fitted time series models to them. after controlling for contagion via autoregression terms, the effect of meteorologic factors was weak: a small positive increase in transmissibility with rising absolute humidity/temperature during the current week in tokyo and singapore. there was no evidence for temperature and humidity in having the same effect in hong kong or taiwan, although rising relative humidity seems to decrease transmissibility in singapore. the earliest recorded cases of hfmd in asia are from japan ( ), singapore ( ) , taiwan ( ) and shanghai, china ( ) . since then, outbreaks have been reported in many parts of asia, including mainland china, [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] korea, [ ] [ ] [ ] japan, [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] taiwan, , , [ ] [ ] [ ] [ ] hong kong, , , india, [ ] [ ] [ ] [ ] [ ] [ ] thailand, , , vietnam, malaysia, , , [ ] [ ] [ ] [ ] [ ] singapore , and brunei, as summarized in figure . these reported outbreaks are unlikely to reflect the true first outbreaks of hfmd, as serologic studies provide evidence that by the time surveillance systems were established, ev-a and cv-a were already endemic in many of these countries. early serologic tests conducted in japan in show evidence of ev-a and cv-a circulation. serum taken in the late s in singapore, before the start of surveillance in , shows that around % children and % cord blood, indicating maternal infection, had already seroconverted to ev-a . blood samples from taiwan ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) show %- % ev-a incidence per year, and up to % of children had serologic evidence of ev-a infection before the large hfmd outbreak of . similarly, although china has reported millions of hfmd cases since the beginning of the hfmd surveillance program in , evidence from anhui shows high seroprevalence of up to . % in older children before the outbreaks. retrospective seroepidemiologic tests from blood serum collected in also show that china had positive rates of . % to ev-a and . % to cv-a , indicating that outbreaks happened earlier but were simply not reported in the literature. risk factors for infection are depicted in figure (appendix ) and summarized below. evidence from qiaosi, china, indicates the importance of hygiene for protection against hfmd infection. children who always wash their hands before meals are about times less likely to contract hfmd, while those whose caregivers wash their hands before feeding are about times less likely. additional protective habits include washing of hands after play, washing of hands more than times per day, using soap, and not sucking fingers. a study in korea showed that sunshine could be protective against hfmd. this is agreed by a matched case-control study of preschoolers in beijing, which showed that uv radiation in classrooms is associated with lower hfmd attack rate (p value of . ), and recommended installing uv lamps to sterilize unoccupied classrooms. these findings are, however, inconsistent with the seasonal nature of hfmd, where outbreaks in temperate countries tend to occur in summer, when sunlight and uv exposure are strongest. the age distribution of hfmd cases in asia, compiled from a variety of sources including surveillance and cohort data, is summarized in figure . data from china [ ] [ ] [ ] , [ ] [ ] [ ] [ ] , [ ] [ ] [ ] [ ] [ ] [ ] [ ] and taiwan , , , - are particularly abundant. other sources include hong kong, , india, , japan, , korea, , malaysia, , singapore, , , thailand , and vietnam. the symptomatic hfmd incidence rate varies widely even within the narrow -to the literature is ambiguous about the importance of locations for transmission. four studies showed that contact with a case, particularly a household member, is as or more significant a risk factor than preschool attendance. , , , an early study in singapore observed families with secondary cases and found . middle and bottom panels show mean daily temperature, absolute and relative humidity at tokyo narita, hong kong international, taipei taoyuan international and singapore changi airports, downloaded from the weather underground. bottom: coefficients of meteorological variables at - week time lags in autoregressive models of z-scored hfmd case counts to facilitate comparison between locations. each city is analyzed separately using a model in which hfmd incidence in week t is (auto)regressed on incidence in weeks t- up to t- (using the akaike information criterion to select the order of the autoregression component) and, independently, on each meteorological variable. weather parameters are not regressed together in a single model because of collinearity. the effect of weather on hfmd incidence can be seen by coefficient mean (points) and % confidence intervals (lines), colored red if statistically significant at the % level. the secondary attack rate amongst children below years old to be %. similarly, in a large seroepidemiologic study of ev-a in taiwanese children, multivariate analysis showed attendance at a preschool imparted a similar magnitude of risk as contact with a case [adjusted ors: . ( . - . ) and . ( . - . ), respectively], as well as a strong concordance ( %) between seropositivity in younger and older siblings. also, a number of studies showed that a higher percentage of diagnoses occurred among children who did not attend a nursery or preschool. , liu et al note that about half of symptomatic cases in nanchang, china, are among children under years, the age at which preschooling starts in china. conversely, some studies suggest that preschool attendance is a key risk factor. , for example, a seroepidemiologic study in to in singapore showed that seropositivity to ev-a increases rapidly from age to , when attendance at childcare or preschool is the norm. also, a case-control study in japan showed that preschool attendance was associated with increased risk of severe disease. other studies suggest that both locations are important. in shanghai, china, there was a marked shift from to in the proportion of cases among children in preschools (from % to %) with a concurrent shift from local to migrant children, suggesting that the importance of routes of transmission can vary over time within the same locale. a case-control study from zhejiang showed that although attending preschool is a risk factor (or: . ), other factors such as contact with neighbors (or: ), going to hospital (or: ) and going to parties (or: ) impart greater risk. yet, a korean case-control study found no significant relationship between infection and school attendance or household size. overall, the evidence points to both home and school environments contributing to transmission, but the relative importance of these venues remains murky. several papers describe the incubation period (fig. , appendix ) though it is striking that the majority do not provide a source to justify the claimed period. these unsupported claims vary substantially from paper to paper, from the incubation period "is" - days or - days, "is usually - days, but can be ... days or more," or "is usually - days (range, - days)," is "typically" - days or - days, ranges from to days , or to days and the "usual period" is - days "with longest period of days." only a few provide evidence to justify the claim: one reports that the incubation period is usually - days, citing a us centers for disease control and prevention (cdc) factsheet on aseptic meningitis. another cites an early study from singapore, which presented the median and range for the serial interval ( days [ ] [ ] [ ] [ ] [ ] [ ] [ ] ), not the incubation period. another early study states that the incubation period is "said to be" - days, but notes that this is inconsistent with the serial interval observed in the study. it appears that there is no empirical support whatsoever for any distribution of incubation periods. although several studies report that the asymptomatic rate of ev-a infection is high, few studies report data (table ) . two studies, from taiwan and shanghai, tested sera for evidence of ev-a infection and asked patients or their families to recall past hfmd infection, deriving estimates of % and % of symptomatic infection, respectively. some hfmd cases may have been caused by other enteroviruses, biasing these estimates upwards, while some may have been diagnosed as another viral illness or forgotten, biasing them downwards. two additional studies in taiwan found much higher symptomatic infection rates. the first study recruited symptomatic cases suspected of having ev-a infection, and took throat and rectal swabs or stool samples, of cases and their household members. signs and symptoms of the entire household were monitored with follow-up telephone interviews. excluding the symptomatic index cases, % of confirmed infections in the household were symptomatic ( % of infected children and % of infected adults). a second study prospectively followed a cohort of neonates over years, taking repeat sera, requesting that parents report suspected hfmd and giving reminders during hfmd epidemics. this study found that % of serologically confirmed infections were symptomatic, though the sample size is only . the discrepancy between these pairs of papers is substantial, undoubtedly because of differences in methodology. an overall estimate, combining the studies, is % ( %- %), but given the large discrepancy between studies, this estimate does not appear reliable. the latter pair of studies is prospective, thereby circumventing recall bias, and thus appear to provide a more accurate description of the epidemiology of enterovirus infection. only papers have sought to estimate the reproduction number for hfmd or the viruses that cause it. one paper estimates what they call the "local effective reproduction number" in chinameaning using the average number of secondary cases from a randomly selected index to estimate the cases that would be caused in a fully susceptible population (note, this is substantially different from the effective reproduction number in a partially susceptible population)-using a sophisticated poisson regression model that incorporated infection from the environment, the prefecture and neighboring prefectures. this model did not, however, account for the accumulation of herd immunity and required arbitrary assignment of the infectious period, so the estimated local effective reproduction number of . - . during peak periods may be biased. a second paper used a method from choi and pak to estimate the basic reproduction number to be . (interquartile range, . - . ) for ev-a and . (interquartile range, . - . ) for cv-a . these estimates are likely inaccurate because the method assumes (i) a known generation time distribution, labeled incubation period in the paper; (ii) a completely immunonaïve population, though applied to groups of individuals for whom past exposure was highly plausible and (iii) an early exponential growth period, despite being applied to complete outbreak data. the third paper attempted to estimate the reproduction number using a seiqrs (susceptible, exposed, infectious, quarantined, recovered) simulation model and obtained an estimate of . for the years to in china. however, the model used % of china population as the initial susceptible population, but did not conduct a sensitivity analysis on this vital parameter. despite the substantial number of papers on hfmd, this systematic review shows that many fundamental questions about ev-a and cv-a persist. both viruses occur year round in tropical asia, but are epidemic in the summer in northeast asia. a role for temperature or humidity therefore seems distributions within age ranges were assumed to be constant. the black dots are average proportion for that age (with % ci). right: reported incubation periods for hfmd, by year of publication and provision of evidence to support claimed period. lines indicate that the incubation period "is x days." gray bars indicate that the incubation period is "usually" or "typically" x days. gray bars with lines shows an extended interval "can be up to x days." the point indicates a median. notes: ( ) provides information within the paper, which is inconsistent in this estimate; ( ) uses generation interval distribution as a proxy for incubation period; ( ) cites a us cdc factsheet on aseptic meningitis, which in turn provides no supporting evidence and ( ) cites goh et al. ci indicates confidence interval. plausible, , - although given the relative lack of seasonality in equatorial asia, it is not clear whether prediction of outbreaks is possible there. in japan, summer temperatures peak after hfmd incidence does, suggesting correlation but not temporality, and that it may not be possible to provide early warning of impending epidemics. this also differs from other human enteric viruses including poliovirus (also an enterovirus), hepatitis a and adenovirus that have been shown to survive longer on colder surfaces. urashima et al claimed that enteroviruses experience a more rapid virus decline during dry seasons than during wet seasons, which could explain the seasonality. this result is supported by wang et al, where they showed that precipitation patterns has the most similar structure as hfmd incidence, more so than other meteorologic variables, albeit with only months of data. while any causal relationship between climate and hfmd is unknown, speculations include a lower hfmd incidence because of decreased social contact during temperate zones' winter. , in contrast, increased social contacts during winter have been speculated to facilitate spread of other droplet-borne diseases, such as influenza, which are epidemic in winter. given the unknowns surrounding this issue, further research is clearly required to ascertain whether meteorologic factors or seasonal social contact patterns is an adequate explanation for the seasonality of hfmd. the next step to analyzing the dynamics of hfmd seasonality is likely to involve social and environmental factors, another under-researched area for this pediatric disease. for instance, the literature is unclear on the relative importance of school versus community transmission, with evidence to support both, yet knowledge of where hfmd most often is transmitted is important as school closure policies are employed to control outbreaks in some countries. further, the environment of schools in asia may vary widely, and attributes such as hygiene practices should be characterized and quantified to allow more definitive results and conclusions in future studies. even without being able to determine the relative importance of school versus community transmission, the effectiveness of school closure to prevent large-scale hfmd outbreaks is questionable, as the interruption to social networks cannot be enforced while children are out of school. additionally, although we know little about the infectiousness of asymptomatic cases of hfmd, the proportion of infections that are asymptomatic is substantial, and so even quite modest school closure attack rate thresholds, such as singapore's %, corresponds to a possible majority of students being infected before the trigger for closure being met. further, ev-a can be found in fecal samples for up to days after infection, and thus continue to be shed after a school is closed, disinfected and reopened. studies on risk factors were rare, and we identified only papers that describe risk factors for hygiene and contact patterns, making a meta-analysis of risk factors unfeasible. these typically were only powered to provide unadjusted effect sizes, and so provide evidence of correlation, not causation. one interesting finding was the apparent protective effect of a caregiver "always washing" their hands. this suggests that adult to child transmission might be important, even if adults are mostly asymptomatic with ev-a and cv-a , but may reflect confounding with general hygiene. future work may elicit hygiene factors at the preschool level and relate these to attack rates. a recently developed ev-a vaccine has undergone phase trials in china. [ ] [ ] [ ] to determine the cost-effectiveness of incorporating the vaccine in pediatric vaccination schedules, or of other interventions such as school closure or isolation, would require epidemiologic models that account for the protective effects of herd immunity. however, this review indicates that vital parameters for such models remain unknown. the asymptomatic rate and relative infectiousness of asymptomatic cases are both poorly known, while estimates of the incubation period, although commonly cited as - days, appear to be based solely on expert opinion. most importantly, estimates of the basic reproduction number range widely from . to . . this uncertainty prohibits utilitarian estimation of the necessary vaccine coverage to prevent epidemics of ev-a . to reconcile the differences between the disparate estimates, the age distributions of the samples need to be considered. as shown in this review, symptomatic hfmd incidence rate differ greatly even between ages and , and thus, studies conducted predominantly on preschoolers may derive higher estimates of r compared with studies in older children. accordingly, future studies on hfmd should use narrower age bands and also state the distribution clearly to allow adjustments or standardization. two final omissions from the literature are quantitative estimates of the impact of infection on complications, child and caregiver absenteeism and costings of complications, and qualitative evidence on the impact of infection and enforced isolation on families and schools. given the promising direct effects of the ev-a vaccine and the huge public health impacts of hfmd in east and southeast asia, research is urgently needed to fill these gaps. the research questions in this systematic review were generally answered only by a limited number of papers, with substantial differences in their study design, and thus, most data were not synthesized through meta-analysis. more research to assess risk factors and measure key epidemiologic parameters is needed. we were also unable to trace the earliest cases of hfmd in asia as our scope only covers published material on outbreaks, which leads us back to in japan. finally, we limited the scope of this study to exclude virologic characteristics or molecular epidemiology, which have been well reviewed elsewhere, , [ ] [ ] [ ] [ ] and clinical manifestations of ev-a and cv-a . , , , , a recent review of the case-fatality rate has recently been published, as has a review of the epidemiology in taiwan. an autoregressive (ar) model was used to investigate the effect of meteorological variables after correcting for contagion via autoregression. a lag model can be specified as follows: the a coefficients are the coefficients for the ar terms, while the b coefficients represent how a change in weather is correlated with changes in hfmd incidence. the number of lag terms is determined by the akaike information criterion values of the regression models. this same model was used for countries-japan (lag ), hong kong (lag ), taiwan (lag ) and singapore (lag )-and for meteorological parameters-temperature, absolute humidity and relative humidity. as this model carries autocorrelated terms, we used generalized least squares for model fitting. coefficients from the fitted models are presented in tables a -a . the outcome variable is the number of reported hfmd cases per sentinel per week (japan), the number of reported hfmd cases per general practitioner per week (hong kong), the number of reported severe enterovirus cases per week (taiwan) and the number of reported hfmd cases per week (singapore). to facilitate comparability, the incidence measures were standardized to have mean and variance . ci indicates confidence interval. the outcome variable is the same as the temperature model. coefficients for autoregressive model using temperature as predictor. the ar coefficients are generally statistically significant across models. significant ar terms indicate that incidence is highly autocorrelated, which is expected as the contagious nature of hfmd is the primary driver of temporal patterns of incidence. the primary parameters of interest are the coefficients of the meteorological variables, which represent how much temperature/humidity affects the z-score of incidence, after controlling for contagion. the results are tabulated in tables a -a , summarized in figure and the paper itself. incidence data are obtained from various sources, summarized in table a . for japan and hong kong, "cases per sentinel" and "cases per consultation" are used instead of the actual number of notified cases because these data are from voluntary sentinel reporting. thus, actual notified cases will increase with an increase of gp sentinel participation rate. ci indicates confidence interval. attached as supporting document eligibility criteria specify study characteristics (e.g., picos, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale. information sources describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched. search present full electronic search strategy for at least one database, including any limits used, such that it could be repeated. study selection state the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis). page and page (table ) data collection process describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators. data items list and define all variables for which data were sought (e.g., picos, funding sources) and any assumptions and simplifications made. data sought answers questions stated in page (table ) risk of bias in individual studies describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis. most studies are not synthesized due to small sample size. potential biases are discussed throughout the paper. summary measures state the principal summary measures (e.g., risk ratio, difference in means). risk factors: or, page - synthesis of results describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., i ) for each meta-analysis. epidemic patterns: page climate patterns: page section/topic # checklist item reported on page # specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies). cumulative evidence that might be biased were not synthesized. additional analyses describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified. study selection give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram. study characteristics for each study, present characteristics for which data were extracted (e.g., study size, picos, follow-up period) and provide the citations. present data on risk of bias of each study and, if available, any outcome level assessment (see item ) . studies that might be biased are identified throughout the review. results of individual studies for all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot. synthesis of results was avoided when i) data is too sparse; or ii) studies are too different. for these studies, we have summarized the key results into figures for comparison. synthesis of results present results of each meta-analysis done, including confidence intervals and measures of consistency. attached as supporting document. (gender and age data synthesis) risk of bias across studies present results of any assessment of risk of bias across studies (see item ) . cumulative evidence that might be biased were not synthesized. additional analysis give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see item ] ). summary of evidence summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers). long-term cognitive and motor deficits after enterovirus brainstem encephalitis in children neurodevelopment and cognition in children after enterovirus infection world health organization western pacific region. hand, foot, and mouth disease situation update epidemiology and control of hand, foot and mouth disease in singapore comparison of clinical features between coxsackievirus a and enterovirus during the enterovirus outbreak in taiwan, : a children's hospital experience clinical and epidemiologic features of coxsackievirus a infection in children in northern taiwan between idwr surveillance data table, sentinel-reporting diseases. available at updated situation of hand, foot and mouth disease (hfmd) and enterovirus infection taiwan national infectious disease statistics system plot digitizer (version . . ) r: a language and environment for statistical computing detecting spatial-temporal clusters of hfmd from spatial-temporal clusters and risk factors of hand, foot, and mouth disease at the district level in guangdong province circulation of coxsackievirus a in hand-footmouth disease in guangzhou epidemiology and clinical characteristics of hand foot, and mouth disease in a shenzhen sentinel hospital from the enterovirus epidemic in -public health implications for hong kong changing epidemiology of hand, foot, and mouth disease in hong kong diseases caused by enterovirus infection clinical features and factors of unfavorable outcomes for non-polio enterovirus infection of the central nervous system in northern taiwan clinical and molecular characterization of hand-foot-and-mouth disease in thailand epidemiology and seroepidemiology of human enterovirus among thai populations spatio-temporal distribution and hotspots of hand, foot and mouth disease (hfmd) in northern thailand epidemiologic and virologic investigation of hand, foot, and mouth disease, southern vietnam epidemiological and clinical characteristics of children who died from hand, foot and mouth disease in vietnam sentinel surveillance for human enterovirus in sarawak, malaysia: lessons from the first years epidemic hand, foot and mouth disease caused by human enterovirus short term effects of weather on hand, foot and mouth disease the largest outbreak of hand, foot and mouth disease in singapore in : the role of enterovirus and coxsackievirus a strains on the hand, foot and mouth disease prevailed in ohmiya city in summer hand-foot and mouth disease enterovirus in taiwan the prevalence of hand, foot and mouth disease an enterovirus epidemic in guangdong province of china, : epidemiological, clinical, and virogenic manifestations an outbreak of hand, foot, and mouth disease associated with subgenotype c of human enterovirus in shandong appearance of mosaic enterovirus in the outbreak of china epidemiological analysis, detection, and comparison of space-time patterns of beijing hand-foot-mouth disease estimating the number of hand, foot and mouth disease amongst children aged under-five in beijing during , based on a telephone survey of healthcare seeking behavior prevalence of multiple enteroviruses associated with hand, foot, and mouth disease in shijiazhuang city an epidemiological analysis of the beijing hand-foot-mouth epidemic a case-control study to identify environmental risk factors for hand, foot, and mouth disease outbreaks in beijing a large outbreak of hand, foot, and mouth disease caused by ev and cav in guangdong, china seroprevalence of human enterovirus and coxsackievirus a in guangdong, china, in pre-and post- hfmd epidemic period distribution of enteroviruses in hospitalized children with hand, foot and mouth disease and relationship between pathogens and nervous system complications an emerging recombinant human enterovirus responsible for the outbreak of hand foot and mouth disease in fuyang city of china molecular typing and epidemiology of non-polio enteroviruses isolated from yunnan province, the people's republic of china prevalence of antibodies against enterovirus in children from lu'an city in central china molecular epidemiology of human enterovirus strains and recent outbreaks in the asia-pacific region: comparative analysis of the vp and vp genes characterization of an outbreak of hand, foot, and mouth disease in nanchang, china in surveillance of hand, foot, and mouth disease in mainland china epidemiology of hand, foot, and mouth disease and genotype characterization of enterovirus in jiangsu characterization of enterovirus and coxsackievirus a isolated in hand, foot, and mouth disease patients in guangdong genetic analysis of the vp region of human enterovirus strains isolated in korea during epidemics of enterovirus infection in chungnam korea risk factors for neurologic complications of hand, foot and mouth disease in the republic of korea epidemic of hand, foot and mouth disease in gifu prefecture in properties of virus isolated from an epidemic of hand-foot-and-mouth disease in in the city of matsue. comparison with coxsackievirus group a type prototype epidemic of hand, foot and mouth disease associated with enterovirus infection epidemic of hand, foot and mouth disease in japan serologic relationship of coxsackie a- viruses from the epidemic of hand-foot-and mouth disease in japan, , to the prototype strain a survey on enterovirus infections in matsue city, shimane prefecture in the period from may epidemic of hand, foot and mouth disease in japan, - : difference in epidemiologic and virologic features from the previous one a survey on enterovirus infection in matsue city, shimane prefecture in the period from outbreaks of hand, foot, and mouth disease by enterovirus . high incidence of complication disorders of central nervous system a large-scale epidemic of hand, foot and mouth disease associated with enterovirus infection in japan in genetic diversity of coxsackievirus a associated with hand, foot, and mouth disease epidemics in japan from to frequent importation of enterovirus from surrounding countries into the local community of yamagata outbreak of severe neurologic involvement associated with enterovirus infection genetic evolution of enterovirus : epidemiological and pathological implications outbreak of central nervous system disease associated with hand, foot, and mouth disease in japan during the summer of : detection and molecular epidemiology of enterovirus an epidemic of enterovirus infection in taiwan. taiwan enterovirus epidemic working group change of major genotype of enterovirus in outbreaks of hand-foot-and-mouth disease in taiwan between an outbreak of enterovirus infection in taiwan, : epidemiologic and clinical manifestations an outbreak of enterovirus infection in taiwan, . ii. laboratory diagnosis and genetic analysis monoplegia caused by enterovirus : an outbreak in hong kong hand-foot-and-mouth disease in calicut etiology and clinico-epidemiological profile of acute viral encephalitis in children of western uttar pradesh, india foot and mouth disease in nagpur epidemic of hand, foot and mouth disease in west bengal an outbreak of hand, foot and mouth disease in bhubaneswar hand-foot-mouth disease: outbreak in shimla prevalence and characterization of enterovirus infections among pediatric patients with hand foot mouth disease, herpangina and influenza like illness in thailand isolation of subgenus b adenovirus during a fatal outbreak of enterovirus -associated hand, foot, and mouth disease in foot and mouth disease: university malaya medical centre experience fatal enterovirus encephalomyelitis deaths in children during an outbreak of hand, foot and mouth disease in peninsular malaysia-clinical and pathological characteristics identification and validation of clinical predictors for the risk of neurological involvement in children with hand, foot, and mouth disease in sarawak an outbreak of hand, foot, and mouth disease in singapore enterovirus outbreak seroepidemiology of human enterovirus incidence and case-fatality rates resulting from the enterovirus outbreak in taiwan retrospective seroepidemiology indicated that human enterovirus and coxsackievirus a circulated wildly in central and southern china before large-scale outbreaks from risk factors for hand, foot, and mouth disease and herpangina and the preventive effect of hand-washing transmission of seasonal outbreak of childhood enteroviral aseptic meningitis and hand-foot-mouth disease risk factors of enterovirus infection and associated hand, foot, and mouth disease/herpangina in children during an epidemic in taiwan breastfeeding, previous epstein-barr virus infection, enterovirus infection, and rural residence are associated with the severity of hand, foot, and mouth disease epidemiology and etiological characteristics of hand, foot and mouth disease in huizhou city between distribution and risk factors of hand, foot, and mouth disease in changchun, northeastern china a spatial-temporal arma model of the incidence of hand, foot, and mouth disease in wenzhou hand, foot, and mouth disease in china: patterns of spread and transmissibility a new factor influencing pathogen detection by molecular assay in children with both mild and severe hand, foot, and mouth disease epidemiology of hand, foot, and mouth disease in children in shanghai the changing seroepidemiology of enterovirus infection among children and adolescents in singapore epidemic characteristics of hand, foot, and mouth disease in shanghai from to : enterovirus subgenotype c as the primary causative agent and a high incidence of mixed infections with coxsackievirus a seroepidemiology of enterovirus infection prior to the season in children in shanghai characterization of hand, foot, and mouth disease in china between transmission and clinical features of enterovirus infections in household contacts in taiwan epidemiologic features of handfoot-mouth disease and herpangina caused by enterovirus in taiwan an eight-year study of epidemiologic features of enterovirus infection in taiwan coxsackieviruses infection in northern taiwan-epidemiology and clinical characteristics surveillance of enterovirus infections in yokohama city from enterovirus in malaysia: a decade later risk factors for severe hand foot and mouth disease human enterovirus and hand, foot and mouth disease estimation of the basic reproduction number of enterovirus and coxsackievirus a in hand, foot, and mouth disease outbreaks the influence of temperature and humidity on the incidence of hand, foot, and mouth disease in japan foot and mouth disease- clinical features and risk factors of pulmonary oedema after enterovirus- -related hand, foot, and mouth disease incidence rates of enterovirus infections in young children during a nationwide epidemic in taiwan different epidemic curves for severe acute respiratory syndrome reveal similar impacts of control measures a simple approximate mathematical model to predict the number of severe acute respiratory syndrome cases and deaths modeling and preventive measures of hand, foot and mouth disease (hfmd) in china seasonal models of herpangina and hand-foot-mouth disease to simulate annual fluctuations in urban warming in tokyo the association between enterovirus infections and meteorological parameters in taiwan is hand, foot and mouth disease associated with meteorological parameters? effect of meteorological variables on the incidence of hand, foot, and mouth disease in children: a time-series analysis in guangzhou, china survival of enteric viruses on environmental fomites foot and mouth disease: spatiotemporal transmission and climate influence of weather conditions and season on physical activity in adolescents influenza seasonality: underlying causes and modeling theories singapore ministry of health. hand, foot & mouth disease: updates excretion of enterovirus in persons infected with hand, foot and mouth disease efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus vaccine in children in china: a multicentre, randomised, double-blind, placebo-controlled, phase trial an inactivated enterovirus vaccine in healthy children efficacy, safety, and immunogenicity of an enterovirus vaccine in china virology, epidemiology, pathogenesis, and control of enterovirus global epidemiology of enterovirus human enterovirus epidemics: what's next? clinical features, diagnosis, and management of enterovirus risk factors of severe hand, foot and mouth disease: a meta-analysis case-fatality of hand, foot and mouth disease associated with ev : a systematic review and meta-analysis epidemiology of enterovirus infections in taiwan key: cord- -ztc holk authors: hsieh, ying-hen; cheng, kuang-fu; wu, trong-neng; li, tsai-chung; chen, chiu-ying; chen, jin-hua; lin, mei-hui title: transmissibility and temporal changes of ph n pandemic during summer and fall/winter waves date: - - journal: bmc infect dis doi: . / - - - sha: doc_id: cord_uid: ztc holk background: in order to compare the transmissibility of the ph n pandemic during successive waves of infections in summer and fall/winter in the northern hemisphere, and to assess the temporal changes during the course of the outbreak in relation to the intervention measures implemented, we analyze the epidemiological patterns of the epidemic in taiwan during july -march . methods: we utilize the multi-phase richards model to fit the weekly cumulative ph n epidemiological data (numbers of confirmed cases and hospitalizations) as well as the daily number of classes suspended under a unique " " partial school closing policy in taiwan, in order to pinpoint the turning points of the summer and fall/winter waves, and to estimate the reproduction numbers r for each wave. results: our analysis indicates that the summer wave had slowed down by early september when schools reopened for fall. however, a second fall/winter wave began in late september, approximately weeks after the school reopened, peaking at about - weeks after the start of the mass immunization campaign in november. r is estimated to be in the range of . - . for the first wave, and between . - . for the second wave. conclusions: transmissibility of the summer wave in taiwan during july-early september, as measured by r, was lower than that of the earlier spring outbreak in north america and europe, as well as that of the winter outbreak in southern hemisphere. furthermore, transmissibility during fall/winter in taiwan was noticeably lower than that of the summer, which is attributable to population-level immunity acquired from the earlier summer wave and also to the intervention measures that were implemented prior to and during the fall/winter wave. although the first known imported case of pandemic influenza (ph n ) arrived in taiwan on may from the u.s. via hong kong, serological evidence has indicated that the ph n virus had spread to central taiwan by april-june [ ] . local infections and laboratory-confirmed ph n cases in taiwan started to mount in significant numbers in july-august when the schools were in summer recess. by the time the schools reopened in september, multiple intervention measures had been implemented by the government, which include strict border temperature screening starting in may, a " " class suspension policy [ , ] implemented in september, and later a mass immunization program [ ] [ ] [ ] starting in november. the number of cases began to decline by the end of the year, and continued to do so into early next year, until the government announced on february the end of the fall/winter outbreak [ ] with over laboratory-confirmed cases reported, hospitalizations, and deaths [ ] . although school closing was a widely used method of intervention around the world during the ph n outbreak (see, e.g., [ ] [ ] [ ] [ ] [ ] [ ] ), its suitability, timing, and the manner of implementation remains controversial. when k- schools (kindergarten through high schools) reopened on august in taiwan, the government implemented a unique partial school closing policy called the " " class suspension policy aimed toward kindergarten through secondary schools (k- ), cram schools, and after-school institutions. under this policy, if within any three ( ) consecutive school days, two ( ) or more students in the same class are diagnosed with influenza, then that class will be suspended for the next five ( ) days including weekends and holidays [ , ] . the policy was designed to minimize the potential social impact of full-scale school closings in the event of a major influenza outbreak in the community; to detect cluster infections in school settings early and swiftly; and to contain the infections locally without disruption for the other students in the school. at the height of the class suspensions in late november, more than classes with more than , students from almost schools in taiwan were suspended on a single school day (figure ), yet without any visible disruption in the normal functioning of the society. moreover, starting november , a mass immunization program was initiated in taiwan sequentially, according to a priority list of target groups [ ] , with healthcare and public health personnel having the highest priority [ ] . subsequently, preschool children were immunized starting on november ; and followed by pregnant women, k- schoolchildren, and people with major illness/injury being vaccinated starting on november ; - year-olds on november ; and the general population on december . by march , a total of . million doses of adimflu-s (unadjuvanted h n v from adimmune) or focetria ® (mf ® adjuvanted h n v from novartis) were administered, and more than million of the million taiwanese had been immunized [ ] . children and under were advised to receive two doses of vaccine, although many of them eventually received only one dose due to various reasons. a simple mathematical model, the richards model, is utilized to fit publicly accessible cumulative epidemic data in order to obtain estimates for the turning points (the peaks and volleys of the incidence curve) and the reproduction number r of a particular wave of infections. examples of applications of the richards model to infectious diseases include those of sars [ , ] , dengue [ , ] , and the ph n epidemic [ , ] . in this study, we will make use of the richards model to pinpoint the turning points of each wave of the epidemic, in order to ascertain the temporal changes of the epidemic in taiwan in the summer months and during the fall and winter days. the transmissibility of the ph n virus during the outbreak is determined through its reproduction number. the data was accessed from the central epidemic command center website of the taiwan centers for disease control (tcdc). samples were collected from hospitals and clinics participating in the taiwan influenza surveillance system under the taiwan national influenza center (taiwan nic), which was established in to integrate all existing efforts of influenza surveillance and notification with laboratory analysis systems throughout taiwan in order to enhance the epidemic data collection capacity in taiwan [ ] . the weekly laboratory confirmed ph n case data (by the week when the samples were collected and sent to the tcdc-contracted laboratories) and the weekly hospitalization data (by the week the lab-confirmed cases were hospitalized) from june , (epidemiological week or e-week of ) to march , (e-week of ) was accessed from the weekly influenza express made publicly available on the internet by the tcdc [ ] during the epidemic. the surveillance protocols in taiwan remained essentially the same throughout the data period since, by the time the data were collected, clinical characteristics of the ph n infection had already been well understood from the spring outbreaks around the world. we also accessed the daily record of numbers of classes suspended and number of schools with at least one class suspended during the fall school semester (september , to january , ) from the tcdc daily ph n updates [ ] during the epidemic. the time series of class suspension data is given in figure . since this data is for school days only, the days are specified in the horizontal axis of figure in weekly increments of school days, except for weeks with less than school days at the beginning and the end of the school semester as well as the week containing the new year holiday (january ). the richards model [ ] is of the form: where the prime symbol "'" denotes the rate of change over time which is in eweeks. c(t) is the cumulative number of cases at time t (in weeks), k is the cumulative case number over a single wave or phase of outbreak, r is the per capita growth rate of the infected population, and a is the exponent of deviation. the explicit solution of the equation is here the parameter t m is related to the turning point t i of a wave (or the inflection point of the cumulative case curve) by the simple formula t m = t i + lna/(ra), where ln denotes the natural logarithm function. moreover, r = exp(rt) where t is the generation interval of the disease, or the average time interval from the onset of one infected person to the time when the onset of his or her contacts occurs. it has been shown mathematically [ ] that, given the growth rate r, the expression r = exp(rt) provides an upper bound of the basic reproduction number regardless of the distribution of the generation interval that is being used. in this work, we will use the term effective reproduction number r instead, due to the community-level immunity likely achieved by july and the interventions implemented during the two waves. the richards model is a phenomenological model which can be used to describe the phenomenon of a biological growth (of cumulative number in this case) without requiring detailed information on the actual process of disease transmission. the basic premise of the richards model is that the incidence curve of a single wave of infections contains a single peak of high incidence, resulting in an s-shaped cumulative epidemic curve and a single turning point (or peak incidence) of the outbreak. the turning point, defined as the point in time at which the rate of accumulation changes from increasing to decreasing, or vice versa in the event of a multi-wave outbreak, can be easily pinpointed by locating the inflection point of the cumulative case curve, i. e., the moment at which the trajectory begins to decline, as demonstrated in previous applications (see, e.g., [ ] [ ] [ ] [ ] [ ] [ ] . this quantity has important epidemiologic implications, indicating either the valley (i.e., moment of acceleration after deceleration) or peak (i.e., moment of deceleration after acceleration) of a disease incidence curve. multi-wave outbreaks also can be modeled by using the multi-phase richards model [ , ] . simultaneous estimates of the model parameters r, a, t i , and k, based on fitting the explicit solution of the richards model for c(t) to the epidemic data used in the study, can be obtained easily and efficiently using any standard software with a nonlinear least-squares approximation tool, such as sas or matlab. the procedure for locating multiple turning points for multi-wave outbreak, which required the use of the multistage richards model, is detailed in [ ] and hence is omitted here. we first fit the weekly laboratory confirmed ph n case data by sample receiving week in taiwan table with the model fit shown in figure . the turning points for the two waves are estimated at . weeks after e-week and . weeks e-week , respectively. subsequently, the weeks in which the turning points for temporal changes in the weekly confirmed ph n case number took place on e-week ( / - / ) for the first wave with a % ci range of ( . , . ), and on e-week ( / - / ) with a % ci range of ( . , . ) for the second wave. we note that the above results were obtained by rounding off the estimates to the next largest integer, e.g., e-week + . = . and hence e-week is the week during which the turning point for the first wave occurred, and similarly for the second wave. to compute the effective reproduction number r, we use the generation time t = . days ( % ci: . - . ) for the ph n in mexico estimated by fraser et al. [ ] . we note that the given ci's for r reflect the uncertainty in the generation time t as well as in the uncertainty in the least-squared estimates for r, and does not reflect the error due to the model itself, which is always difficult to measure. we also fit the weekly confirmed ph n hospitalization data by hospitalization week in taiwan from eweek ( / - / ) of to e-week ( / - / ) of to the richards model. the results are given in table . the data also fit a two-phase richards model with the first wave spanning e-weeks - ( / / - / / ) of and the second wave from e-week ( / - / ) of to e-week- ( / / - / / ) of ( figure ) . the turning points for the weekly confirmed ph n hospitalizations occurred on e-week ( / - / ) for the first wave with a % ci range of ( . , . ) and on e-week ( / - / ) with a % ci range of ( . , . ) for the second wave, which were the same weeks as the case number data turning points. the estimate for r using an estimated generation time t for ph n in mexico [ ] is again provided. to further analyze and compare our previous results, we also make use of the daily class suspension data in taiwan from september , to january , , which allows us to ascertain the temporal changes in this intervention measure during the time period. since this dataset started near the end of the first wave, according to our previous results, only one wave was modeled via the richards model. the estimation results for model fit using the daily class suspension number data as well as the daily number of schools with at least one class suspended are given in table the actual confirmed case number (approximated by k in our model) is during the first wave and for the two waves. point. a graphical illustration of the temporal timelines of the epidemic, as illustrated by the three model fits, is given in figure . moreover, an illustrative comparison of the estimates for r as obtained by the model fits is also provided in figure . in both figures and , the results from fitting the number of schools with class suspended are omitted for brevity, since they are similar to that of the fitting with class suspension data. figure model fit for the -wave richards model using weekly confirmed ph n case data by sample receiving week in taiwan. the dots are the real cumulative data, the blue curve denotes the first wave, and the red curve denotes the second wave. the arrows indicate the weeks in which turning points had occurred. the actual number of confirmed hospitalizations is for the first wave and for the two waves. the estimates for effective reproduction number r obtained from the confirmed case and hospitalization data are in good agreement, with r in the range of . - . for the first summer wave during july-september, and . - . for the second wave in fall/winter, using the generation time estimated by [ ] for the spring outbreak in mexico. serological evidence has indicated that approximately one in every ten persons was infected with the ph n virus in central taiwan by april- june [ , ] ; hence the estimates using data after july does not yield, and can reasonably be expected to be lower than, the more commonly known basic reproduction number r . a recent modeling study [ ] of the ph n epidemic by geographic region in mexico reveals a threewave pandemic, with an initial wave in april-may (mexico city area), a second wave in june-july (southeastern states), and a geographically widespread third wave in august-december. the estimates for the regional reproduction numbers r were . - . , . - . , and . - . for the spring, summer, and fall waves, respectively. the second and third waves in mexico occurred, respectively, one month earlier than the summer (july-early september) and fall/winter (late september-march ) waves in taiwan under study here and exhibit similar decreasing trend, although with higher r. transmissibility of the fist ph n wave in taiwan during the summer in july-september, as measured by r, was lower than that of the earlier spring outbreak in north america [ , , , ] and europe [ ] , most likely, at least in part, due to decreased social contacts among the population triggered by public awareness of the earlier, well-publicized outbreaks in mexico and north america as well as the subsequent preemptive government campaign to reduce transmissions. it was also lower than that of the winter outbreak in the southern hemisphere around the same time [ , , ] , perhaps attributable to the fact that it was the winter influenza season in the southern hemisphere. moreover, it is lower than the final size estimate of r ( . ; % ci: . - . ) obtained from serological study of a cohort household population in central taiwan during the same period of time [ ] . however, we note that this disparity is reasonable since the serologic data used for this estimate accounts for the asymptomatic cases among the cohort group. the decreased transmissibility (smaller r) during fall/winter can be reasonably attributed to increased community-wide immunity from the first wave, and perhaps to the class suspension policy initiated in early september before the start of the fall/winter wave. significantly higher estimate of r (focused on schoolchildren) in the range of . - . was found for the initial pandemic wave in japan [ ] . using updated epidemic data and an age-structured model, the same authors also estimated r for the subsequent community-wide wave in japan in early summer to be much lower ( . - . ) [ ] , although different population and modeling methodology also may have played a role in the decrease in r in subsequent waves. similar decreases in estimates of reproduction number of h n when more than one pandemic wave had occurred have been reported in many countries, including mexico [ ] , argentina and brazil [ ] , canada [ ] , and japan [ , ] . furthermore, these studies show that it is not uncommon for multiwave outbreaks to be more transmissible in a first wave but less widespread with a smaller number of infections (or perhaps limited to a small subpopulation as was in the case of ph n in japan), when compared to subsequent waves. moreover, the second wave in taiwan started shortly after the school opened in september, when additional infections occurring in school settings (as demonstrated by substantial number of class suspensions) contributed to a large number of cases, but perhaps with relatively less per contact transmissibility when compared to household contacts, as it has been reported that sitting next to a case or being the playmate of a case did not significantly increase the risk of h n infection [ ] . the estimates for r using laboratory-confirmed case data by sample receiving weeks are slightly lower than those obtained by using confirmed hospitalization data. although both the confirmed case and hospitalization datasets identify week as the cutoff week for the two waves, the estimates of turning points for each wave differ by about one week when using the two datasets. since only the more severe confirmed cases were hospitalized, the individuals in the resulting hospitalization time series is a selected subset of those in the confirmed case time series. subsequently, the temporal trends of the two time series might not be closely comparable. however, the cumulative curves in figures , , , indicate some similarity in the temporal trends of the cumulative data, mainly in the form of the turning points. the reproduction numbers of the two datasets, on the other hand, are indeed comparable since they mostly are generated from the initial growth rates and hence less affected by any selection bias. the confirmed case data is generated by sampling week, which could be different from the week of symptom onset and hence pose a potential source of some bias in data. however, samples were typically taken when the physicians diagnosed and reported h n cases. we refer to sars outbreak in taiwan, when it was estimated that the onset-to-diagnosis interval is . days for previously quarantined persons and . days for non-quarantined persons [ ] . given the similarity in symptoms of sars and influenza as well as the heightened public awareness due to the world-wide alarm over the seriousness of the ph n pandemic by september, it is more than likely that the time delay from symptom onset to diagnosis (and sample collection) of ph n cases in taiwan would be no more, if not less, than that of sars. moreover, one would expect that the lesson of sars and the subsequent efforts by the government to educate has taught the general public in taiwan to avoid delays in seeking medical care. subsequently, this delay of one or two days in the weekly data can be expected to be most likely not significant. the use of hospitalization data is mainly for the purpose of estimation of reproduction number and comparison with the resulting estimates using the confirmed case data, which is not affected by this delay that might be present in both data. estimates of r obtained by using other (larger) estimated generation time in literature result in larger values for r, but generally are well within the ranges of the other studies (see, e.g., [ , , , [ ] [ ] [ ] [ ] and table [ ]) and hence is omitted for brevity. note also that the formula for r used here yields an upper bound over all possible distributions for t given the growth rate r, and hence might result in an overestimate of its true value. in taiwan, the fall session for kindergarten to high school started on august , while the universities started the fall semester two weeks later, around mid-september. our analysis using the weekly confirmed case and confirmed hospitalization data shows that the initial summer wave of ph n epidemic in taiwan had peaked by e-week - ( / - / ), around the time schools from kindergarten to grade reopened on august . however, a second fall/winter wave of cases started to emerge near the end of september around eweek ( / - / ), approximately weeks after the schools reopened, which did not reach its peak until mid-november (e-week - or / - / ) and lasted until the turn of the year. it is interesting to note that the state-specific fall pandemic waves in mexico began - weeks after school reopened [ ] , which is consistent with our results on the start of the fall wave in taiwan. note that both turning points of the two waves in taiwan fell on neighboring week using either the lab-confirmed case or hospitalization data. this is reasonable since the hospitalization of confirmed cases and the time that the samples were received by laboratories are closely related, although not necessarily in any particular order. the class suspension data started on september near the end of the first wave when the earliest class suspension occurred, according to our -wave fitting in tables and , hence only one wave was modeled via the richards model (table ) . moreover, november ( % ci: november - ) was determined to be the turning point for the daily class suspension data, while november ( % ci: november - ) is the turning point for the daily number of schools with class suspended. both days fall on e-week , which coincides with the week where the turning point had occurred as pinpointed by using the confirmed case data and one week after the turning point obtained by using the hospitalization data. it is reasonable to expect the class suspension to take place following the occurrence of case reporting and hospitalization. moreover, the use of daily data allows a more precise estimation of the turning point. also of interest is the possible impact of major intervention measures implemented by the taiwan government during this time period, which including the aforementioned " class suspension" policy and the mass immunization program. the daily number of class suspensions started to increase in early september and continued until late november after the implementation of mass immunization campaign (figure ). in particular, the policy, which was designed to minimize the potential social impact of full-scale school closings in the event of a major influenza outbreak in the community; deserve special attention to ascertain its actual effectiveness. in fact, the lower estimates of r for the second wave and for the school closings data might indeed be attributable to the possible effects of school closings after september. however, more detailed class suspension data as well as age-specific epidemic data is needed to further quantify the actual impact or effectiveness of this very unique approach of partial school closure and localized class suspensions on the infections in the school and in the community in a qualitative modeling analysis (see, e.g., [ , , ] ). using routine influenza surveillance data, we modeled the temporal changes of the two waves of ph n epidemic in taiwan in summer and in fall/winter. the mass h n vaccination program was first initiated sequentially on november , where a typical delay of at least two weeks from immunization is needed for protection from the vaccine to take effect in human bodies. our results suggest that the turning point for the second wave of infections in the fall had occurred around mid-november (e-week - or / - / ). moreover, the class suspension data indicate that the number of class suspensions had peaked by november , less than three weeks after the start of mass immunization and most likely before the impact of mass immunizations started to become significant. however, the mass immunization, and perhaps the voluntarily decreased social contacts by the general public in response to the well-publicized mass immunization campaign by the government, could have contributed to the overall mitigation of the disease in the community, as indicated by the early saturation of the winter epidemic by early february. however, this cannot be modeled without detailed vaccination data. the richards model considers only the cumulative infected population size with saturation in growth as the outbreak progresses, which can be caused by other factors such as implementation of control measures. although data by reporting date is often and typically scrambled by artificial factors such as health system alertness, public response, and government responsiveness, the richards model is able to capture the turning points of outbreaks because they are often results of these artificial factors. we note, however, that the skewness in an epidemic curve, as quantified by the exponent of deviation "a" in the richards model which describes the curvature of a given cumulative case data, also could conceivably arise from various other intrinsic factors such as spatial heterogeneity and individual heterogeneity in contact (see [ ] , pp. for example) which is not captured by this simple model. this type of modeling, although somewhat simplistic and subsequently limited in its quantification of complex factors, nevertheless enables us to ascertain the impact of these artificial factors through the temporal changes of an outbreak, especially in the events when detailed epidemic data describing disease transmissions and other relevant data (such as that of intervention measures in this case) are not readily available for the construction of a complete disease transmission model and the reliable estimation of model parameters, as in this study moreover, the use of cumulative numbers could often, or at least partially, smooth out stochastic variations that typically occur in epidemic data, and hence the richards model could be a valuable tool in providing clues to the challenging task of public health policy evaluation and planning. serological evidence of hsieh et al. bmc infectious diseases subclinical transmission of the pandemic h n influenza virus outside of mexico taiwan centers for disease control: national standards for implementing school closure passed at twenty-first meeting held by the central epidemic command center central epidemic command center novel influenza a/h n pandemic (h n ) vaccination and class suspensions after outbreaks monitoring the safety of pandemic h n vaccine taiwan centers for disease control: central epidemic command center announces influenza a (h n ) vaccine priority list, press release date taiwan centers for disease control: second wave of h n virus activity in taiwan comes to an end, press release date central epidemic command center novel influenza a/h n infection and death from influenza a h n virus in mexico: a retrospective analysis pandemic (h n ) virus outbreak in a school in london evidenced-based tool for triggering school closures during influenza outbreaks effects of school closures school closure and mitigation of pandemic (h n ) , hong kong closure of schools during an influenza pandemic. the lancet infectious diseases summary of monovalent h n vaccine safety surveillance (data through am march central epidemic command center novel influenza a/h n sars epidemiology modeling. emerg infect dis real-time forecast of multi-wave epidemic outbreaks intervention measures, turning point, and reproduction number for dengue turning points, reproduction number, and impact of climatological events on multi-wave dengue outbreaks pandemic influenza a (h n ) during winter influenza season in the southern hemisphere. influenza and other respiratory viruses epidemic modeling in real time: novel a (h n ) influenza outbreak in canada novel influenza a/h n school closing updates a flexible growth function for empirical use how generation intervals shape the relationship between growth rates and reproductive numbers pandemic potential of a strain of influenza a (h n ): early findings serological response and persistence in schoolchildren with high baseline seropositive rate after receiving pandemic influenza a(h n ) vaccine. vaccine characterizing the epidemiology of the influenza a/h n pandemic in mexico estimation of the reproductive number and the serial interval in early phase of the influenza a/h n pandemic in the usa the transmissibility and control of pandemic influenza a (h n ) virus dutch new influenza a (h n )v investigation team: epidemiology and control of influenza a (h n )v in the netherlands: the first cases estimating the reproduction number of the novel influenza a virus (h n ) in a southern hemisphere setting: preliminary estimate in new zealand world health organization: transmission dynamics and impact of pandemic influenza a (h n ) virus transmission potential of the new influenza a(h n ) virus and its age-specificity in japan pros and cons of estimating the reproduction number from early epidemic growth rate of influenza a (h n ) . theoretical biology and medical modelling role of social networks in shaping disease transmission during a community outbreak of h n pandemic influenza quarantine for sars, taiwan. emerg infect dis modelling mitigation strategies for pandemic (h n ) modeling infectious diseases in humans and animals authors' contributions yhh conceived and organized the study, carried out the analysis, and wrote the first draft. yhh, kfc, tcl, tnw, cyc, and jwc participated in the study and the interpretation of study findings. kfc participated in the writing of the manuscript. mhl participated in the data collection and analysis. all authors have read and approved the final manuscript. the authors declare that they have no competing interests. key: cord- - f m kfc authors: che huei, lin; ya-wen, lin; chiu ming, yang; li chen, hung; jong yi, wang; ming hung, lin title: occupational health and safety hazards faced by healthcare professionals in taiwan: a systematic review of risk factors and control strategies date: - - journal: sage open med doi: . / sha: doc_id: cord_uid: f m kfc background: healthcare professionals in taiwan are exposed to a myriad of occupational health and safety hazards, including physical, biological, chemical, ergonomic, and psychosocial hazards. healthcare professionals working in hospitals and healthcare facilities are more likely to be subjected to these hazards than their counterparts working in other areas. objectives: this review aims to assess current research literature regarding this situation with a view to informing policy makers and practitioners about the risks of exposure and offer evidence-based recommendations on how to eliminate or reduce such risks. methods: using the preferred reporting items for systematic reviews and meta-analyses review strategy, we conducted a systematic review of studies related to occupational health and safety conducted between january and january using medline (ovid), pubmed, pmc, toxline, cinahl, plos one, and access pharmacy databases. results: the review detected studies addressing the issue of occupational health and safety hazards; of these, articles were included in this systematic review. these articles reported a variety of exposures faced by healthcare professionals. this review also revealed a number of strategies that can be adopted to control, eliminate, or reduce hazards to healthcare professionals in taiwan. conclusion: hospitals and healthcare facilities have many unique occupational health and safety hazards that can potentially affect the health and performance of healthcare professionals. the impact of such hazards on healthcare professionals poses a serious public health issue in taiwan; therefore, controlling, eliminating, or reducing exposure can contribute to a stronger healthcare workforce with great potential to improve patient care and the healthcare system in taiwan. eliminating or reducing hazards can best be achieved through engineering measures, administrative policy, and the use of personal protective equipment. implications: this review has research, policy, and practice implications and provides future students and researchers with information on systematic review methodologies based on the preferred reporting items for systematic reviews and meta-analyses strategy. it also identifies occupational health and safety risks and provides insights and strategies to address them. according to the world health organization (who), an estimated million people work in healthcare facilities globally, accounting for roughly % of the working population. the who also reports that all healthcare workers, including healthcare professionals, are exposed to occupational hazards. the international labour organization (ilo) reported that millions of healthcare workers suffer from work-related diseases and accidents, and many succumb to occupational hazards. scholars and practitioners in the field of healthcare and occupational health and safety (ohs) are striving to raise awareness of the risk factors and importance of workplace health and safety among this population. , , schulte et al. defined an occupational hazard as the shortterm and long-term dangers or risks associated with unhealthy workplace environments. tullar et al. and joseph and joseph stated that the healthcare workers at greatest risk are doctors, healthcare professionals, nurses, laboratory technicians, and medical waste handlers. occupational hazards pose health and safety risks and have negative impact on the economy, which accounts for roughly a % loss in global annual gross domestic product (i.e. $ . trillion annually). the who, ilo, and nelson et al. noted a lack of universally applicable data on the impact of occupational hazards. ohs hazards, and their negative impacts on health and well-being among healthcare professionals, is an issue of growing concern in the asia and pacific region, particularly in taiwan; however, research in this area has been somewhat limited. according to the taiwanese ministry of health and welfare (mohw) in taiwan, , health and medical personnel are working at health care organizations in taiwan, including , healthcare professionals and , pharmacist assistants. the healthcare professionals serve a taiwanese population of , , in , medical care institutions ( hospitals and , clinics). of the hospitals, are public and are privately owned; of the , clinics, are public and , are privately owned. taiwanese healthcare professionals face a variety of ohs hazards, which increase the incidences of work-related disease, the country's burden of disease, the total number of accidents, the incidences of job-related health problems, and the number of cases involving incapacitation or disablement. this study reviewed previous works on ohs hazards, as well as their risk factors and control strategies, with a focus on healthcare professionals in taiwan. cochrane identified eight steps of a systematic review, which are adopted in this study. this study employed the preferred reporting items for systematic reviews and meta-analyses (prisma) protocol to organize the flow of information through the various steps of the review. we used the following key words in our literature search: occupational health and safety, risk factors, healthcare professionals, control strategies, and taiwan to ensure specificity and exclude irrelevant studies, we employed boolean logic (and, or, not) in combining terms as search strings. the operator and was used to reduce the search yield for two key terms (e.g. "healthcare professionals (p) and occupational health and safety"). the operator or was used to increase the search yield (e.g. "healthcare professionals and occupational health and safety or risk factors"). note that in this example, the two search terms are synonyms. the operator "not" was used to exclude specific terms or term combinations. this research obtained a large number of initial articles (n initial = ); however, the application of inclusion and exclusion criteria considerably reduced the number of articles for inclusion in the review (n = articles). the articles focused on ohs, occupational hazards, and healthcare professionals in taiwan. figure presents a flow diagram depicting the application of eligibility criteria, the process of identification and screening, and the reasons for inclusion and exclusion. in documenting and assessing individual publications, we collected key information from the relevant studies to populate an evidence table (see appendix c) and conducted a critical appraisal of the included studies. the study population included adult pharmacy workers (male and female). data were extracted only from studies that included samples that were deemed significant given the justification of the authors of the studies. a critical appraisal of all studies was performed to assess their quality in terms of validity and reliability, as based on performance bias, information bias, selection bias, and detection bias. cochrane and khan et al. reported that biases tend to exaggerate or underestimate the "true" outcome of exposure to an occupational hazard. our ultimate objective was to compare (without any form of bias) groups that were exposed to occupational hazards and those that were not exposed in terms of risk factors and outcomes. for the sake of validity and reliability, all of the studies selected for inclusion were prospective in nature and included data pertaining to exposure and outcomes, while controlling confounding factors. we also looked for studies with high internal reliability (consistency across items within a test) and high external reliability (consistency in agreeability between uses/rates). in our final analysis, we considered whether the research had been conducted in an appropriate manner (internal validity). we also considered the generalizability of the results, that is, whether the results were pertinent to other situations (external validity). data synthesis. the final step involved the synthesis of evidence from the included studies; that is, organized into homogeneous categories, under which the results were to be summarized. the evidence was also graded (i.e. assessed in terms of quality) and integrated (i.e. weighted across categories to address the multidisciplinary nature of ohs research). in this review, the synthesis, grading, integration, interpretation, and summary of the evidence were presented in narrative form, due to difficulties in textual and statistical pooling. after completing our systematic review, we employed the prisma reporting scheme, which is endorsed for ohs studies by hempel et al. briefly, the prisma structure is laid out in the following format: topic, summary/abstract, introduction, methods, results, conclusion, and recommendations. a meta-analysis was not conducted. the ilo categorizes ohs hazards that affect healthcare professionals as biological, chemical, physical, ergonomics, and psychosocial. from the studies in this review, this study identified the ohs hazards, injuries, and diseases affecting healthcare professionals working in hospitals and healthcare facilities. this section provides the biological hazards, as identified in the review, as the most commonly encountered in hospitals and healthcare facilities in taiwan. according to who, the managers and administrators of hospital and healthcare facilities, in our case those in taiwan, should carefully assess the potential for exposure to biohazards and put effective biohazard control plans in place. the following chart provides a summary of the identified biological hazards, their risk factors, and control strategies (table ) . the review established some of the most commonly faced chemical hazards present in hospitals and healthcare immunization and vaccines; and biological safety cabinets, needleless systems or safety-engineered needles, suitable ventilation, and an appropriate medical waste management system. administrative controls: written and documented infection control plans; decontamination procedures; enforcement of these systems; and the training of hospital staff in the implementation of occupational health and safety measures. immunization programs; detection and followup of infections; periodic screening; codes of practice; and staff orientation. designing all work systems with the aim of minimizing the risk of exposure. personal protective equipment (ppe): includes devices for the protection of the eyes (e.g. face shields, goggles), respiratory system (e.g. surgical masks), and skin (e.g. latex gloves, protective aprons, gown. based on risk assessments and careful training. [ ] [ ] [ ] infection from human immunodeficiency virus (hiv), hepatitis b virus (hbv), and hepatitis c virus (hcv) needle-stick injuries (nsi) and accidents with other sharp objects: occupational exposure resulting in hiv, hbv surface antigen-positive, or hcv transmission is largely due to inoculation of pathogens into cutaneous abrasions, lesions, scratches, or burns, as well as mucocutaneous exposure involving inoculation or accidental splashes onto non-intact mucosal surfaces of the nose, mucous membranes, mouth, or eyes. facilities, as well as the documented control strategies, which are summarized in table . physical hazards, which are defined as environmental risk factors that can harm the body without contact, were found to account for a substantial proportion of risks among healthcare professionals in taiwan. , [ ] [ ] [ ] the physical hazards, risk factors, and control strategies are summarized in table . the review established that healthcare professionals are exposed to musculoskeletal disorders and injuries, such as low back pain due to the nature of their work, such as lifting patients. table summarizes the risk factors and control strategies for this hazard. psychosocial hazards have attracted considerable attention in the research community, as well as among policy makers and practitioners in healthcare. [ ] [ ] [ ] this study found that in taiwan, psychosocial hazards have prompted a larger number of studies combining physical, chemical, and biological hazards. the who reported that psychosocial hazards are closely linked to work-related stress, workplace violence (e.g. violent patients), and other workplace stressors. table provides a summary of the risk factors and control strategies of psychosocial hazards. this review provides detailed information regarding the ohs hazards that affect healthcare professionals working in hospitals and healthcare facilities in taiwan. the review summarizes the risk factors for hazards, as well as the control strategies to control, eliminate, or reduce them. from the reviewed studies, it was clear that ohs hazards can potentially result in a number of injuries, sickness, and harm. a wide range of ohs hazards were identified, including biological hazards chemical hazards, ergonomic hazards, psychosocial hazards, and physical hazards. , the review has shown that healthcare professionals are at a significantly high risk of occupational related hazards. injuries and sickness prevent healthcare workers from discharging their duties effectively, which can have negative impact on the overall healthcare system in taiwan. physical hazards, such as falls, noise, and mechanical hazards, could have long-term physiological effects, such as hearing impairments; therefore, there is need to introduce various control strategies, such as engineering noise control measures. there should be the provision of good ppe for healthcare professionals to protect themselves from physical harms in the workplace. according to our findings, it is evident that healthcare professionals are exposed to chemical hazards, some of which can be carcinogenic. there is also the risk of exposure to occupational dermatitis. it is therefore important that healthcare professionals are screened for cancer on a regular basis. the workers can also be trained about skin care and be provided with safety equipment and other useful interventions, such as sunscreen cream. such efforts can help in early detection, prevention, and intervention. as part of their routine occupation, biological hazards can affect healthcare professionals due to contact with patients and visitors. the review of healthcare professionals on duty demonstrates how important it is to manage blood borne and airborne biological pathogens in the healthcare workforce. there should be administrative guidance and training on how healthcare professionals can deal with biological hazards, and these professionals should be encouraged to report work-related incidents as soon as they occur or are suspected to have occurred to aid early intervention. ergonomic hazards in healthcare professionals tend to arise from lifting patients and hospital equipment. this requires careful prevention, assessment, and intervention, as the impact of ergonomic hazards on the musculoskeletal system of the affected healthcare professionals cannot be ignored. hospital administrators need to alleviate frequent job pressures by providing the necessary safe and ergonomic equipment, and hiring an adequate number of personnel. the professionals can work in properly planned shifts and teams to reduce fatigue, they should be trained in the correct techniques for lifting patients and equipment, and policies should be enforced to ensure compliance. the findings on psychosocial hazards show that healthcare professionals can be affected by mental and psychological hazards, such as stress, as it is evident that healthcare professionals who suffer from stress are likely to suffer from fatigue and exhaustion. healthcare professionals are trained to show less emotion, and thus, find it difficult to seek medical intervention. there is need for counseling and stress management for healthcare professionals, and the workers should be trained to manage stress. the workplace should be designed in such a manner as to prevent invasion, harassment, and violence against healthcare professionals. overall, hospital administrations and healthcare professionals should focus on evidence-based strategies (engineering, administrative, and ppe) to manage ohs hazards. the increasing prevalence of occupational hazards and work-related diseases among healthcare professionals in taiwan is a concern. risk factors include exposure to hazards and a failure to follow hierarchical control strategies. health care workers and administrators must work together to eliminate or minimize these hazards through the introduction of and strict adherence to engineering, administrative, and personal protective equipment (ppe) controls. the the main routes of exposure to chemical hazards include ingestion, injection, skin contact or absorption, and inhalation. , contamination and exposure are both affected by the duration and frequency of exposure, the quantity of drugs undergoing preparation, and the use of ppe. the adverse health effects can be attributed to compounds deemed carcinogenic (cancer causing), mutagenic (promoting mutations), teratogenic (causing birth defects), or toxic to various organs. alcohol hand sanitizers commonly used by healthcare professionals are flammable and harmful to the skin. there have also been reports on the dangers of detergents used to clean surfaces, which can lead to irritation and promote allergies of the skin, eyes, and respiratory tract. , there is also evidence that some detergents can react with other products commonly stocked in healthcare facilities to produce toxic vapors. , , it has been found that low concentration disinfectants, such as quaternary ammonium salts, alcohols, hydrogen peroxide, iodophors, and phenolic and chlorine compounds, can have toxic effects and irritate the skin, eyes, and respiratory system. the inhalation of powdered medications and vapors exposes healthcare professionals to the risk of poisoning and allergic reactions. , engineering control strategies: isolating and segregating hospital or healthcare facility areas and equipment; providing exhaust hoods to provide local ventilation when compounding and mixing drugs; providing biological safety cabinets to safeguard chemicals; and providing containers to prevent needle stick injuries. flammable chemicals should be stored away from sources of ignition and dangerous chemicals substituted with less harmful ones. cuts, burns, hearing loss, motion sickness, and muscle cramps. engineering controls: minimize the use of sharp tools, use machine guarding, use quality sockets, and close water faucets when not in use. administrative controls: promote and practice safe work procedures, such as when using electrical equipment (e.g. cords). educating workers about the cleaning equipment and cleaning up broken glass is also recommended. ppe: use of appropriate footwear, gloves, eye and nose protection, and protective clothing . tripping, slipping, cuts, and falling poor housekeeping, poor layout, and slippery tiled floors. open power cables, live wires, broken glassware, lancets, knives, scissors, and scalpels. bruised skin, cuts, broken bones, and muscular injuries. engineering control: proper lighting, the construction of safe stairwells, and regular building maintenance (e.g. floors and workspaces). ppe: use of appropriate footwear, gloves, eye and nose protection, and protective clothing . exposure to microwave radiation, and ionizing and non-ionizing radiation. risks imposed by radiation from x-ray machines and other diagnostic imaging systems, and the radionuclides used in nuclear medicine and radiation therapy. workers face risks from nonionizing radiation, lasers, ultraviolet rays, and magnetic resonance imaging. the risk increases when using heat sealers and poorly maintained or insulated radio-diagnostic equipment. tissue damage, risk of cancer, and abnormal cell mutation (e.g. abnormal leukocytes). , engineering control: reducing the time of exposure, increasing the distance to x-ray machines, and increasing the amount of shielding. ppe: use of appropriate footwear, gloves, eye and nose protection, and protective clothing perceptions of workers can greatly affect their implementation of risk-mitigation strategies. selection bias is a concern here, despite the fact that we selected published and peer-reviewed articles, as well as unpublished but authoritative gray articles; the fact is that other unverifiable but potentially valuable reports were no doubt excluded. our reliance on observational studies (to the exclusion of intervention studies) and the heterogeneity of the included articles (in terms of methodology) posed a risk of bias and limited standardization. this study discovered relatively little research focusing on hospital workers in taiwan, and thus, further empirical studies focusing on this group of healthcare givers are required and recommended. researchers should focus on the health status, work performance, and workplace retention of healthcare professionals, including the prevalence of morbidity and mortality. the insights in this review provide a valuable reference for policy makers in establishing goals to deal with workplace hazards. hazard control strategies must be based on objective assessments of existing risks and the most appropriate measures to deal with them. this systematic review confirmed a positive correlation between ohs hazards (biological, physical, chemical, and psychosocial), and work-related injuries, occupational health problems, and work-related diseases. the burden of disease and attributable fraction of work-related diseases and occupational injuries has been shown to cause considerable social and economic losses for employees, families, companies, countries, and societies at large. generally, the burden of disease is assessed using disease/disability adjusted life years. the burden of disease is measured as the impact of morbidity and premature mortality within a given area. , scholars and professionals agree that reducing, substituting, or eliminating ohs hazards in healthcare facilities is important for healthcare workers, helps to ensure patient safety, and enhances the overall quality of healthcare. many researchers have used the "hierarchy of controls," which is based on the assumption that interventions are most effective when implemented at the source and least effective when applied at the worker level. gorman et al. listed control interventions from most to least effective as follows: elimination, substitution, engineering, administrative, and ppe. researchers have also emphasized the importance of eliminating hazards or substituting hazardous materials with less hazardous materials. , taimela et al. argued that administrative controls, such as training and ensuring adequate staffing, are crucial to eliminating or minimizing occupational hazards. engineering controls, such as redesigning work spaces, ensuring adequate ventilation, and introducing automated systems for repetitive tasks, were emphasized by liberati et al. ppe, such as the use of gloves, clothing, and eye wear, are considered the least effective and have the most profound consequences in the event of failure by exposing the individual directly to the hazard. nonetheless, many researchers and professionals agree that all such controls should be applied collectively, in order to minimize the effects of hazards. , - musculoskeletal disorders (msds) due to repetitive actions, less than optimal computer equipment, and a poorly engineered workspace in which healthcare professionals are forced to overreach and/or sit while maintaining an awkward posture. healthcare professionals are tasked with lifting and transferring equipment, tools, and instruments. one's physical fitness level and demographic background were shown to affect the risk of developing msds. workplace and job-related demands, poor administrative and team support, and a negative attitude toward job tasks were all strongly correlated with msds. ergonomic hazards can lead to chronic pain in the arms, back, or neck. frequently, they lead to msds, such as carpel tunnel syndrome, which tends to reduce work performance and productivity and can have a serious detrimental effect on one's health-related quality of life. strained movement due to localized pain, stiffness, sleep disturbances, twitching muscles, burning sensations, and feelings of overworked muscles. engineering control strategies: redesign workstations with appropriate chairs and computer equipment. workstations should be configurable to a wide range of medical personnel with different body shapes and sizes. it is also recommended that lifting and handling equipment, such as trolleys, be installed in areas requiring heavy lifting. automation should be adopted when resources and practicability allow. healthcare professionals also face violence during robberies and the theft of addictive prescription pain killers, such as oxycontin and vicodin. we also identified organizational culture and structure, interpersonal relationships at work, job content and satisfaction, homework balance, and the changing nature of work as important psychosocial hazard risk factors among healthcare professionals. , , work-related stressors have a detrimental impact on worker's health and safety, in terms of mental, musculoskeletal, chronic degenerative disorders, metabolic syndrome diabetes, and cardiovascular diseases. psychological hazards at work were associated with heart disease, depression, physical health problems, and psychological strain. low back pain was the most common work-related ailment among healthcare workers in taiwan. employees who experience job insecurity and/or workplace injustice were more likely to suffer from burnout. job demands and the level of control experienced by the worker were significantly associated with fatigue; exposure to workplace violence affects psychological stress, sleep quality, and subjective health status among healthcare professionals. engineering control strategies: creation of isolation areas for agitated patients and designing an office layout that prevents the healthcare professionals from coming into direct contact with customers/patients or being trapped. spaces should be well lit and separated to ensure that client-care provider contact is controlled and access is allowed only when absolutely necessary. proper working communication devices and video surveillance, as well as panic buttons and alarm systems. administrative control: management policies make unequivocal declarations of non-violence/anti-abuse. management can encourage workers to participate in the design of forwardrotating (day-evening-night) shifts and work schedules that impose gradual shift changes and ease the adaptation to nonregular work shifts to ensure that all concerned get adequate sleep. educate healthcare professionals about the risks associated with shift work. well-trained security personnel should be hired to deal with unruly customers. training in conflict management and problem-solving could also help workers to prevent or de-escalate violence. , nametags should be used by employees, and reporting and response procedures should be enhanced. the manuscript has not previously been published and is not under consideration by another journal. the author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. the ethical approval was not sought for this study because this is a systematic review and all the literature has been published. the author(s) received no financial support for the research, authorship, and/or publication of this article. lin ming hung https://orcid.org/ - - - x supplemental material for this article is available online. occupational health: health workers occupational health: data and statistics international labour standards on occupational safety and health workplace safety and health: healthcare workers interaction of occupational and personal risk factors in workforce health and safety occupational safety and health interventions to reduce musculoskeletal symptoms in the health care sector the health of the healthcare workers the global burden of selected occupational diseases and injury risks: methodology and summary national development council (ndc) what is a systematic review systematic reviews for occupational safety and health questions: resources for evidence synthesis a search strategy for occupational health intervention studies risk and management of blood-borne infections in health care workers the occupational safety of health professionals working at community and family health centers five steps to conducting a systematic review sleep disorder in taiwanese nurses: a random sample survey safety culture in a pharmacy setting using a pharmacy survey on patient safety culture: a cross-sectional study in china science of safety topic coverage in experiential education in us and taiwan colleges and schools of pharmacy controlling health hazards to hospital workers perception and prevalence of work-related health hazards among health care workers in public health facilities in southern india the prevalence of occupational health-related problems in dentistry: a review of the literature workplace safety and health improvements through a labor/management training and collaboration tuberculosis in healthcare workers: a matched cohort study in taiwan health care visits as a risk factor for tuberculosis in taiwan: a population-based casecontrol study estimation of the risk of bloodborne pathogens to health care workers after a needlestick injury in taiwan epidemiological profile of tuberculosis cases reported among health care workers at the university hospital in vitoria, brazil risk of tuberculosis among healthcare workers in an intermediate-burden country: a nationwide population study risk of tuberculosis infection and disease associated with work in health care settings sars in healthcare facilities reproductive health risks associated with occupational exposures to antineoplastic drugs in health care settings: a review of the evidence overview of emerging contaminants and associated human health effects guidelines for safe handling of hazardous drugs: a systematic review critical care medicine in taiwan from to under national health insurance niosh health and safety practices survey of healthcare workers: training and awareness of employer safety procedures potential risks of pharmacy compounding development of taiwan's strategies for regulating nanotechnology-based pharmaceuticals harmonized with international considerations an overview of the healthcare system in taiwan chemical and biological work-related risks across occupations in europe: a review n-hexane intoxication in a chinese medicine pharmaceutical plant: a case report occupational neurotoxic diseases in taiwan the impact of physical and ergonomic hazards on poultry abattoir processing workers: a review musculoskeletal disorders and ergonomic hazards among iranian physicians occupational safety and related impacts on health and the environment prevalence of workplace violent episodes experienced by nurses in acute psychiatric settings occupational hazards in the thai healthcare sector prevalence of work related musculoskeletal disorders (wmsds) and ergonomic risk assessment among readymade garment workers of bangladesh: a cross sectional study the study of the effects of ionizing and non-ionizing radiations on birth weight of newborns to exposed mothers healthcare worker safety: a vital component of surgical capacity development in low-resource settings comparisons of musculoskeletal disorders among ten different medical professions in taiwan: a nationwide, population-based study occupational exposure to ionizing and non-ionizing radiation and risk of glioma effect of systematic ergonomic hazard identification and control implementation on musculoskeletal disorder and injury risk the impact of occupational psychological hazards and metabolic syndrome on the -year risk of cardiovascular diseases-a longitudinal study employment insecurity, workplace justice and employees' burnout in taiwanese employees: a validation study risks of treated anxiety, depression, and insomnia among nurses: a nationwide longitudinal cohort study occupational health: occupational and work-related diseases tackling psychosocial hazards at work violence against health workers in family medicine centers impact of workplace violence and compassionate behaviour in hospitals on stress, sleep quality and subjective health status among chinese nurses: a cross-sectional survey the association between jobrelated psychosocial factors and prolonged fatigue among industrial employees in taiwan psychosocial factors and workers' health and safety psychosocial hazard analysis in a heterogeneous workforce: determinants of work stress in blue-and white-collar workers of the european steel industry an evaluation of the policy context on psychosocial risks and mental health in the workplace in the european union: achievements, challenges, and the future a national study on nurses' exposure to occupational violence in lebanon: prevalence, consequences and associated factors review of the literature on determinants of chemical hazard information recall among workers and consumers prevalence and determinants of workplace violence of health care workers in a psychiatric hospital in taiwan a brief overview of systematic reviews and meta-analyses maximizing the impact of systematic reviews in health care decision making: a systematic scoping review of knowledge-translation resources the global burden of occupational disease hazard identification, risk assessment, and control measures as an effective tool of occupational health assessment of hazardous process in an iron ore pelletizing industry an occupational health intervention programme for workers at high risk for sickness absence. cost effectiveness analysis based on a randomised controlled trial learning from high risk industries may not be straightforward: a qualitative study of the hierarchy of risk controls approach in healthcare key: cord- -h eqnzn authors: kao, hui-yun; ko, hai-yun; guo, peng; chen, chang-hsun; chou, su-mei title: taiwan's experience in hospital preparedness and response for emerging infectious diseases date: - - journal: health secur doi: . /hs. . sha: doc_id: cord_uid: h eqnzn the communicable disease control medical network (cdcmn), established in after the sars outbreak in taiwan, has undergone several phases of modification in structure and activation. the main organizing principles of the cdcmn are centralized isolation of patients with severe highly infectious diseases and centralization of medical resources, as well as a network of designated regional hospitals like those in other countries. the cdcmn is made up of a command system, responding hospitals, and supporting hospitals. it was tested and activated in response to the h n influenza pandemic in - and the ebola outbreak in west africa in - , and it demonstrated high-level functioning and robust capacity. in this article, the history, structure, and operation of the cdcmn is introduced globally for the first time, and the advantages and challenges of this system are discussed. the taiwanese experience shows an example of a collaboration between the public health system and the medical system that may help other public health authorities plan management and hospital preparedness for highly infectious diseases. u nder the global health security agenda, hospital preparedness for highly infectious diseases is regarded as a critical strategy for disease control and prevention. hospital preparedness is particularly important to protect healthcare workers and reduce transmission of diseases within hospitals. following the anthrax attacks in the united states in , the sars outbreak in , and decades of medical system reforms, a number of countries have adopted an approach that designates specific responding hospitals at the national, regional, and/or local levels to centralize resources, build capacity, and train special medical staff. in japan, patients diagnosed with category i communicable diseases are referred to designated infection hospitals. , in singapore, its largest hospital, tan tock seng hospital, was appointed as the screening and treatment center for sars and other emerging infectious diseases. , the hong kong health authority established hospital clusters for resource sharing and a continuum of quality care. the european commission founded the european network of infectious diseases (enid), including setting up high-level isolation units (hlius). the us government made a new tiered hospital program in response to a domestic ebola outbreak, designating regional treatment centers and state treatment centers for the management of patients with ebola and other emerging infectious diseases. [ ] [ ] [ ] after the sars outbreak in in taiwan, where a series of nosocomial outbreaks resulted in the collapse of hospital operations, a new medical network for highly infectious diseases, named the communicable diseases control medical network (cdcmn), was established. it was funded through government mid-and long-term plans and had been modified in terms of the command system, how it is activated, and responding hospital criteria. in , additional changes were made to enhance response effectiveness and coordination with regional and local medical facilities. this article describes the establishment and history of the cdcmn, the framework of the medical network, responses to the h n pandemic and ebola in west africa, identification of its strengths and challenges, and how the system changed over time. an overview of taiwan's hospital preparedness efforts is provided to help public health authorities in countries with similar programs or plans to improve hospital preparedness for highly infectious diseases. during the sars outbreak in taiwan, several hospitals were forced to close because of nosocomial clusters of infections. some hospitals started to refuse to take in patients with similar and suspected syndromes. meanwhile, the public lost confidence in the medical system, and many people avoided seeking medical attention despite developing symptoms. it is estimated that outpatient visits were reduced by % in total and by % in public hospitals, indicating that public hospitals bore the brunt of this loss of trust. furthermore, because of patient referral procedures at that time, the referral system was disorganized, which may have expanded possible transmission to other hospitals, making the situation even worse. the department of health (now the ministry of health and welfare) established a sars coordination center to integrate resources and coordinate the academic, medical, and private sectors to combat sars. under the command structure, an infection prevention network was organized, comprised of designated sars treatment hospitals located in northern, central, southern, and eastern regions. a funded infection prevention network with regions (taipei, north, central, south, kao-ping, and east) was approved and incorporated into the plans for post-sars reconstruction and the - biological defense against emerging infections, establishing a permanent strategy of graded medical treatment. in each region, a commander and a deputy commander were selected to oversee the coordination and operation of responding hospitals (at the time they were called infectious disease hospitals), and a consulting committee composed of epidemiologists, lab researchers, medical workers, hospital managers, and jurists was set up to advise on policy formulation. a command center would be activated depending on the epidemic emergency and would be staffed by the local health bureaus, medical centers, and other coordinating organizations. from to , the number of responding hospitals varied from to in regions, with another supporting hospitals serving as backup for medical resources and manpower. nearly negative pressure isolation wards and nearly isolation wards were ready for patients with emerging infectious diseases. in terms of the activation mechanism, reforms were implemented in phases (table ). in phase ( july -march ), responding hospitals-initially based on the designated sars treatment hospitals and other public health hospitals affiliated with the department of health-were divided into categories based on disease and hospital capacity, and they were responsible for patient management of specific communicable diseases. in addition, based on different scenarios of outbreak scale and disease type, some of the hospitals could be activated for additional diseases. during phases and , the selection of the responding hospital candidates was handed over to local health authorities, who took into consideration factors such as local geography and traffic when designating responding hospitals. in phase (april -december ), the categorization framework was modified to a tiered approach of responding hospitals, including national treatment hospitals, regional hospitals, and local hospitals. in phase , starting in and continuing through the present, the tiered approach was adjusted to incorporate cross-regional cooperation. in accordance with cross-regional activation, during an epidemic regions in the network are activated depending on the outbreak location, and then they coordinate with and support one another with medical resource allocation since the completion of phase , taiwan has continued to adjust the number and composition of its responding hospitals. in , the responding hospitals were no longer categorized as national, regional, and local, because in the event of cross-regional activation it is more efficient and flexible to launch a responding hospital where an epidemic occurs, as shown by the h n influenza pandemic. in addition, considering the continuously improving healthcare system in taiwan, all the responding hospitals were able to take in patients with highly infectious diseases and rapidly activate the emergency response plan, regardless of the category level. the tiered system of responding hospitals was determined to be impractical and was abandoned. soon after a system review in , an expert consultation meeting held by taiwan cdc decided to gradually adjust the operation and the reimbursement scheme of cdcmn. in , the number of responding hospitals decreased to based on improved hospital capacity and readiness for highly infectious diseases and national-level budget constraints. in , the number of regional responding hospitals was further decreased to ( per region); however, taiwan's hospital preparedness and response hospitals that were no longer regional responding hospitals could be designated as local responding hospitals and funded by the local public health bureaus. in , the infection prevention network was formalized and renamed the communicable disease control medical network. this ensured that the activation of a command center, the assignment of a commander and a deputy commander, the selection process of responding hospitals (renamed from infectious disease hospitals), the allocation of resources and staffing, and the hospital response and preparedness work are regulated to effectively act to ensure disease control and patient treatment. the current elements of cdcmn are described below. since , the cdcmn has gradually adjusted the number of responding hospitals. in addition, the operation and reimbursement scheme was decided by a comprehensive review and discussion meeting that included attendees from local health bureaus, commanders and deputy commanders in each region, and policy officers from taiwan cdc in . now core elements comprise the medical network: ( ) a command system, ( ) responding hospitals, and ( ) supporting hospitals ( figure ). the network is divided into regions, and responding hospital and supporting hospital are designated in each region. one commander and deputy commander are assigned by the ministry of health and welfare in each network region. they review relevant plans of communicable disease control, and they supervise and provide consultation to local health bureaus. during an outbreak, the command center leads case investigation; infection control and patient transport in medical facilities; coordination; expropriation; requisition; and allocation of hospitals, hospital beds, and manpower. at the local level, public health bureaus may designate isolation hospitals based on the specific condition, distribution of medical care facilities, and hospital capacities. from these, local responding hospital is designated for specific disease control needs. currently there are isolation hospitals, including local responding hospitals. at the national level, taiwan cdc designates regional responding hospitals in regions based on the isolation hospital list and a swot (strengths, weaknesses, opportunities, and threats) analysis of candidates. in addition, other local responding hospitals in off-island areas receive funds from the taiwan cdc to tackle health discrepancies in demographic distribution and insufficient medical resources. table shows general groups of the regional responding hospitals, supporting hospitals, and the number of local responding hospitals in each region. the central and local responding hospitals may receive subsidies from the taiwan cdc and public health bureaus, respectively, on personnel training and drills and procurement and maintenance costs for facilities and equipment of isolation wards. the regional and local hospitals are responsible for taking in patients with category i and v communicable diseases (eg, smallpox, plague, rabies, novel influenza, mers, a in phases and , the total numbers of responding hospitals are and separately in administrative districts, with treatment center designated as both national and regional responding hospital. among administrative districts, districts in phase and district in phase did not have responding hospitals and instead coordinated with neighboring responding hospitals for geographic and traffic factors. ebola, and other hemorrhagic fevers). each regional responding hospital has qualified negative pressure isolation wards, with to beds per million population and beds in off-island areas. this is standard practice in line with japan, singapore, and hong kong. facilities and negative pressure equipment in regional responding hospitals are inspected and validated annually. every responding hospital is required to formulate an emergency response plan for emerging infectious diseases. plans should include the structure of the command and response task force, reporting procedures and information management, patient transport and care, medical personnel safety measures, environment maintenance, infection control, and risk assessment. drills and training courses are held to strengthen knowledge and clinical skills of healthcare workers and disease control personnel. in each region, supporting hospital is designated from regional medical centers. supporting hospitals are responsible for offering medical consultations to support the responding hospitals and serve as a back-up for manpower and medical resources during the period of outbreak. healthcare workers in supporting hospitals offer profes-sional consultations during ordinary times, while during an outbreak they are dispatched by the regional commander for medical care assistance. depending on the scale of the outbreak, a tiered activation process of a regional responding hospital is further defined as the initial launch of isolation wards (including negative pressure wards), the floor evacuation, the building evacuation, and the whole hospital evacuation (figure ). once the evacuation is activated, patients without the outbreak disease will be evacuated and transferred to other hospitals to allow the responding hospital to take in patients with category i and v communicable diseases. if the outbreak expands further, the commander may appoint isolation hospitals or requisition medical facilities at various levels to take in priority patients with emergency or outbreak diseases. the regional commander may request cross-regional assistance as well. upon the order of the regional commander, medical facilities transfer infected patients to the regional responding hospital or other appointed isolation hospitals. for off-island areas, patient transport is divided into options to be decided by the commander, based on the evaluation of the case status, the outbreak situation, hospital capacity, risk of transport, and other administrative factors. one option is to dispatch the support workforce to the local responding hospital in off-island areas where a patient could be treated directly. the other option is to transfer the patient by airplane to a regional responding hospital. however, the former option would be costly for the transport of the support team, and the latter option could increase the risk of transmission en route. therefore, the patient's status and the need for the patient's advanced medical care are major factors that the commander evaluates and decides for best patient care. in addition to healthcare workers in responding and supporting hospitals, a list of support healthcare workers, including physicians, nurses, respiratory therapists, radiographers, psychiatrists, medical technologists, and pharmacists, is made and updated regularly by local health bureaus. the support workforce in each region should be equivalent to % of the healthcare staffing in responding hospitals. this ensures that in the event of an outbreak, surge capacity is available. furthermore, frontline healthcare workers from local health centers or clinics may be requisitioned to expand workforce capacity. all healthcare workers on the support list are required to participate in training courses, personal protective equipment (ppe) donning and doffing exercises, and annual simulation drills held by responding and supporting hospitals to ensure safety and enhance willingness to serve. as h n influenza emerged in mexico and the united states in late april and the who announced a phase global influenza pandemic, the central epidemic command center (cecc) for h n influenza was established at the level of executive yuan. , h n novel influenza was listed as a category i notifiable disease, which meant that all patients under investigation for h n were prioritized to be treated in responding hospitals. , in the early phase, responding hospitals were notified to be ''ready for response.'' these hospitals were required to figure . activation procedure of a regional responding hospital taiwan's hospital preparedness and response report back to the cecc on the results of inspections of negative pressure isolation wards, manpower mobilization, training and drill plans, ppe stockpile status, and transport procedures. as the epidemic developed, the regional commanders were authorized to coordinate and organize isolation hospitals and negative pressure isolation wards in regulating regions. in late may , soon after several domestic cases were reported, the cecc commander decided to launch responding hospitals (at the activation level of building evacuation) to admit and treat patients confirmed with h n influenza. , as the who announced that the pandemic was of moderate severity, and the major strategy changed from containment to mitigation, the cecc decided to remove h n novel influenza from the notifiable disease list, and patients were no longer placed under compulsory isolation. they could also seek medical attention at clinics or emergency departments and directly receive treatment. in july , the cecc integrated the emergency medical services, the cdcmn, and medical institutions contracted with national health insurance. the regional commanders of cdcmn were further authorized to mobilize medical resources in the integrated system and to provide complicated cases with adequate treatment. [ ] [ ] [ ] during the h n pandemic, the average utilization rate of negative pressure isolation beds was around . %. the mortality of h n influenza in taiwan was . per million. this was the third lowest mortality rate compared to other organization for economic co-operation and development (oecd) members ( figure ) and onefifth of that in the united states, , indicating the epidemic was well controlled and the medical network operated robustly. in the early phase of the ebola outbreak in west africa, regional responding hospitals were instructed to be aware of patients who had a travel history to ebola-affected countries and to enhance infection prevention and control measures. as soon as the who declared the ebola outbreak a public health emergency of international concern (pheic) on august , , the taiwan cdc consulted with regional commanders and deputy commanders to establish an emergency response task force and strengthen areas: health education, quarantine control, hospital preparedness, and international cooperation. , in light of reported ebola cases among healthcare workers in spain and the united states, all regional-level hospitals, medical centers, and responding hospitals in the cdcmn were requested to hold training and drills on proper donning and doffing of ppe. furthermore, a series of conference calls were held by the taiwan cdc, covering ( ) the emergency response plan for managing a patient with ebola and other response efforts with medical directors in regional responding hospitals; ( ) public health measures with local health bureaus; and ( ) issues of healthcare personnel safety with relevant medical associations. meanwhile regional and off-island responding hospitals were prioritized to receive specific types of ppe procured by the taiwan cdc, in accordance with the who and the us cdc's guidance. no-notice inspections were also performed in regional hospitals and medical centers to understand current infection control measures and collection of travel kao et al history, occupation, contact history, and cluster information in emergency departments. the inspection showed rapid patient management and transfer flow; good infection control, with physicians and other medical staff dressed in full ppe; and timely reporting to local health authorities. other areas, such as the waiting time to access isolation wards, and collection of travel history, occupation, contact history, and cluster information in emergency departments, needed improvement. in total, suspected cases (none confirmed) were reported in taiwan before the who announced the ebola outbreak over. after american nurses contracted ebola from an imported case in a hospital in texas, the us cdc and the secretary for preparedness and response (aspr) of the department of health and human services (hhs) recognized that not all hospitals have the same capacity to manage ebola patients. a -year -tiered hospital program for ebola and other highly infectious diseases was announced in december . , in addition, the national ebola training and education center (netec) was established in , which recruits professionals with ebola experience to develop training courses and assess the preparedness of designated hospitals. , this new system shares many elements with the cdcmn in taiwan. for instance, both use a centralized patient isolation approach and designate hospitals with stronger capacity, personnel training, and adequate facility and resources. in addition, the center for infectious disease control and prevention in taiwan was established in as an avenue for training and drills in public health, medicine, disease control, and anti-bioterrorism, which is similar to the netec. the communicable disease control medical network has been tested and demonstrated to be flexible and have robust capacity in responding to epidemics over the past several years. the structure and activation mechanism has evolved over time. in , a comprehensive review of the operation of the cdcmn was conducted. this system has several strengths, which should be maintained. the command system as well as the responding and supporting hospitals, are empowered legally to effectively activate and coordinate isolation wards, medical resources, and manpower as needed during the early phase of an outbreak. in addition, the command structure connects public health authorities and the medical system to integrate medical resources and share information with coordinating partners. after the sars outbreak, awareness of healthcare workers' safety was raised. currently, most healthcare workers exercise good infection preven-tion and control practices. furthermore, emergency response plans in responding hospitals are in place, and the inspection of negative pressure isolation wards is conducted annually. in terms of the enhancement of healthcare workers' knowledge and clinical skills, systematic health personnel training and drills have been regularly performed in responding hospitals. there are other areas of challenges where improvement is needed. first, the role of the local public health authorities in the cdcmn is ambiguous in the command system, and their responsibilities should be further clarified. second, the government funds for cdcmn have been reduced, even though facilities and equipment need to be renewed and replaced after years of operation. also, since there are only a few confirmed cases with highly infectious disease treated in negative pressure isolation wards, the wards have rarely been used. however, maintenance of the negative pressure isolation wards is costly. as a result, economic factors may have reduced responding hospitals' willingness to be in the network. in a post-ebola time, training programs of comprehensive core clinical and infection control skills, such as hands-on practices while wearing ppe and mental health and behavior changes, should be further developed with reference to the who and other countries' guidance in response to future emerging disease epidemics. in addition, strategies are needed to incentivize participation of frontline medical workers to ensure a robust response team. further, fair risk compensation payments for caring for highly infectious diseases by healthcare workers is still a topic of debate despite existing regulations governing the operation procedures and compensation for requisitioned health personnel. however, these have not been reviewed since the sars outbreak. as discussed previously, the number of responding hospitals evolved over time. the challenges of identifying a role for local public health bureaus in the cdcmn, using negative pressure isolation wards during nonemergency operations, and operating within a decreasing cdcmn budget resulted in a change in the number of regional responding hospitals, from hospitals in to hospitals in to hospitals in . this alteration enhanced the local public health bureaus' role in the hospital preparedness efforts by allowing them to identify and coordinate local responding hospitals and enabled local hospitals to use negative pressure isolation rooms during daily operations, which better justified the investment required to maintain them. in addition, the regional responding hospitals received more cdcmn resources (previously diverted to hospitals) to maximize the effectiveness. the changes create a more cost-effective network that still maintains flexibility taiwan's hospital preparedness and response and surge capacity during an epidemic. although changes from to date showed improvement in the operation and budget allocation, current challenges, such as the cost for renewal and replacement of the medical equipment in responding hospitals, the development of integrated and comprehensive training courses of core skills for healthcare workers, and risk compensation payments, need the taiwanese government's ongoing commitment and collaboration with medical partners to continue efforts in enhancing a more solid and effective system. this is the first time that the taiwan cdc has shared its experience in constructing and operating the communicable disease control medical network. the framework has been further empowered since its legislation in , with an overarching structure divided into a command system, responding hospitals, and supporting hospitals. over the past years, the control strategies of the cdcmn have been tested during the h n influenza pandemic, the h n epidemic, ebola in west africa, and other outbreaks, demonstrating a high level of functioning and robust capacity. the command system also bridges the public health and medical systems to improve allocation of manpower and resources at the national and local levels. the taiwan cdc will continue to maintain the key elements of the cdcmn and resolve challenges through continued work with hospitals, local health bureaus, medical associations, and other cooperating partners, in order to protect people from emerging infectious disease threats. as national and global progress is made toward building a safe and secure network to respond to infectious diseases, hospital preparedness work highlights the critical functions needed to identify, isolate, and respond rapidly and coordinate smoothly. at the international level, countries could help each other to strengthen and build a more resilient healthcare system. it would be of great value for the cdcmn partner in global alliance to develop a strong international partnership with other similar designated hospital frameworks in japan, europe, and the united states. in this way, information exchange, health and safety issues of medical workers, technical and clinical skills, the response team framework, response workforce and logistics, and other key topics can be discussed and reviewed by experienced professionals across the world. this could help hospital preparedness networks to become more efficient while maintaining core capacities in preparing for the next emerging health threat. designated medical institutions for specific infectious disease public health challenges and legacies of japan's response to the ebola virus disease outbreak in west africa sars transmission and hospital containment public health measures implemented during the sars outbreak in singapore clusters, hospitals & institutions framework for the design and operation of high-level isolation units: consensus of the european network of infectious diseases us department of human health and services. hhs selects nine regional ebola and other special pathogen treatment centers us department of human health and services. hhs selects regional ebola treatment center for southwestern us interim guidance for u.s. hospital preparedness for patients under investigation (puis) or with confirmed ebola virus disease (evd): a framework for a tiered approach post-sars reconstruction plan: research project of social and economic impacts in the sars outbreak. the evaluation of activation mechanisms of different medical systems in responding to the sars crisis prevention and control of sars in taiwan infection disease prevention network (idpn) a decade after sars-lessons learned and preparedness. taipei: center for disease control, ministry of health and welfare, r.o.c. (taiwan) promotion plan of strategy adjustment on responding hospitals of communicable disease control medical network principal of the activation of responding hospitals and operation of support workforce in communicable disease control medical network taiwan's response to the h n influenza pandemic. taipei: center for disease control, department of health, r.o.c. (taiwan) response measures of the communicable disease control medical network to h n novel influenza focus h n pandemic preparedness and response statement on the st meeting of the ihr emergency committee on the ebola outbreak in west africa the current ebola outbreak in west africa and the response measures in taiwan emerging infectious diseases (eid) response a no-notice drill of hospital preparedness in responding to ebola virus disease in taiwan early identification and prevention of the spread of ebola-united states addressing infection prevention and control in the first u.s. community hospital to care for patients with ebola virus disease: context for national recommendations and future strategies key: cord- -odbaubqm authors: kuo, fang‐li; yang, pei‐hsuan; hsu, hsin‐tien; su, che‐yu; chen, chun‐hsien; yeh, i‐jeng; wu, yen‐hung; chen, li‐chin title: survey on perceived work stress and its influencing factors among hospital staff during the covid‐ pandemic in taiwan date: - - journal: kaohsiung j med sci doi: . /kjm . sha: doc_id: cord_uid: odbaubqm this study aimed to investigate the perceived work stress and its influencing factors among hospital staff during the novel coronavirus (covid‐ ) pandemic in taiwan. a web‐based survey was conducted at one medical center and two regional hospitals in southern taiwan, targeting physicians, nurses, medical examiners, and administrators. the questionnaire included items on the demographic characteristics of hospital staff and a scale to assess stress among healthcare workers caring for patients with a highly infectious disease. a total of valid questionnaires were collected. the hospital staff reported a moderate level of stress and nurses had a highest level of stress compared to staff in the other three occupational categories. the five highest stress scores were observed for the items “rough and cracked hands due to frequent hand washing and disinfectant use,” “inconvenience in using the toilet at work,” “restrictions on eating and drinking at work,” “fear of transmitting the disease to relatives and friends,” and “fear of being infected with covid‐ .” discomfort caused by protective equipment was the major stressor for the participants, followed by burden of caring for patients. among participants who experienced severe stress (n = ), work stress was higher among those with rather than without minor children. the present findings may serve as a reference for future monitoring of hospital staff's workload, and may aid the provision of support and interventions. the novel coronavirus pneumonia taiwan, to prevent disease spread, the government ordered the closure of a hospital due to severe cross infection. healthcare workers rushed out of the blockade line due to insufficient protective equipment and fear of the disease, which resulted in fear of the pandemic among medical staff and the public. as the covid- pandemic continues to grow, the collective memory of sars has been revived, and people have vowed not to repeat the same mistake. as a result, hospitals in taiwan have quickly implemented a containment campaign in response to the currently emerging pandemic by developing emergency response measures. staffs are required to wear protective equipment, screen patients and visitors entering and leaving the hospital, and set up an outdoor fever screening area in the emergency clinic. additionally, a scheduling roster has been set up, and all hospital staffs are deployed to fight against the pandemic by providing comprehensive care for patients in negative stress isolation wards or general inpatient wards, and by participating in rotational shifts to implement the quarantine measures at the hospital gate. the pandemic has disrupted the original schedule of hospital staff and has caused changes in their work or lives, resulting in substantial physical and mental stress. stress refers to individuals' reactions to different situations. it includes changes in their physiology or psychology in the face of events in the external environment that are evaluated as more than they can bear, such that they affect their physical and mental wellbeing. stress at work is regarded as the process of interaction between the individual and the work environment, which represents an accumulation of negative emotions generated by the work. , these negative reactions lead to the experience of high stress for a long period, which in turn affects physical and mental health. specifically, it causes multiple adverse symptoms, such as insomnia, headache, fatigue, anxiety, gastrointestinal discomfort, and immunity decline, as well as increased family conflicts, decreased work quality, interpersonal relationship disorders, and other negative effects. [ ] [ ] [ ] [ ] hospital staffs are under high stress during the care process. they have to tackle the effects of misunderstanding by the general public, face worries from family members, experience fear of the unknown disease and of becoming a transmitter of the disease, and experience challenges related to their professional skills of personal infection control. these were major stressors for healthcare workers during sars, and as such, several of them experienced fear, exhaustion, and stress. extensive research has been conducted to examine the correlation between personal demographics and work stress. studies have found that marital status, workplace, and educational level have significant effects on work stress. , for example, wang explored the relationship between work stress and social support among nurses, and found that the older they were and the higher years of work experience they had, the higher was their work stress. this finding suggests that, with the increase of age and accumulation of work experience, nurses are likely to have better attitudes toward and abilities to respond to problems, and accordingly, they would be more likely to be assigned the responsibility to handle unexpected situations at work. , , unmarried, female, younger medical staff were found to be more prone to high work stress, but work stress was also observed to decrease with the increase in age, years of work experience, and number of children. another study found that healthcare workers are busy at work, and work stress could result from the conflict of clinical work with family or personal affairs. however, mcgrath et al found that marital status, work experience, but educational level had no significant impacts on work stress. the contagion path of covid- is still unknown. therefore, since the outbreak of the pandemic, the taiwanese government has formulated an emergency response plan, and hospitals have adopted several preventive measures. moreover, hospital staffs have experienced the global impact of this highly communicable disease, whose sudden onset has caused a stress impact that is similar to that of sars. this leads to the question, "are hospital staff suffering from the same magnitude of stress as before?" accordingly, the objectives of the present study were a cross-sectional survey was conducted from the end of march to the beginning of april , at the peak of the covid- pandemic in taiwan. participants were selected from a -bed medical center and two -bed regional hospitals in southern taiwan. the survey was conducted using a web-based questionnaire and excluded new recruits, outsourced workers, research assistants, and other non-regular hospital employees. details of the survey website were provided to the survey participants through the mailboxes of the three hospitals, and the researchers compiled the responses from each hospital for analysis. this study recruited participants from the four main categories of hospital staff, namely physicians, nurses, medical technicians, and administrators. the questionnaire contained the following two sections for sars. the scale comprises subscales, namely, "worry and social isolation" with items, "discomfort caused by protective equipment" with items, "difficulties and anxieties related to infection control" with items, and "burden of caring for patients" with items, totaling items. each item is rated on a -point likert scale ( : not at all, : about the same as usual, : slightly more severe than usual, : more severe than usual) to assess the degree of stress caused by various stressors. the total score ranges from to , with a higher total score indicating a greater degree of stress. a total score of to indicates "severe stress," that from to indicates "moderate stress," that from to indicates "low stress," and indicates "no stress." the content validity index of the scale was . in the original study by chuang and lou ( ) , who tested it on healthcare workers (n = ) from medical centers in taiwan. the cronbach's α values for the four subscales were . to . in the original study. in the present study, the cronbach's α value of the complete scale was . , and that for the four subscales was . to . . data were analyzed using jmp . statistical package. regarding descriptive statistics, continuous variables related to demographic characteristics and perceived work stress were presented as mean ± sd; categorical variables were presented as counts and percentages. for inferential statistics, the pearson product moment correlation test was used to analyze the correlations between the study variables. since severe stress has a significant impact on the physical and mental health of employees and willingness to care for patients. with a projected power of %, an alpha of . , and an effect size of . one-way analysis of variance (anova) to identify if stress levels differed based on demographic characteristics, followed by a post hoc tukey-kramer comparison to identify groups with significant differences. this study was reviewed and approved by the institutional review the sample comprised hospital staff from one medical center and two regional hospitals in southern taiwan. as shown in table note: a score of indicates "not at all," "about the same as usual," "slightly more severe than usual," and "more severe than usual." note: rating scales: -point likert scale ( : not at all, : about the same as usual, : slightly more severe than usual, : more severe than usual). note: a score of indicates "not at all," "about the same as usual," "slightly more severe than usual," and "more severe than usual. stress could be attributed more to their fear of social isolation, discomfort due to protective equipment, and burden of patient care. in contrast, medical technicians had a higher degree of stress related to difficulties and anxieties related to infection control. the mean score for each of the items on work stress was . ± . (table ) , representing mild to moderate stress. the mean scores of each dimension and each item, and score rankings are presented in table . on items, more than % of the participants experienced moderate to severe work stress (with mean scores of over points). the five highest stress scores were observed for the items "rough and cracked hands due to frequent hand washing and disinfectant use," "inconvenience in using the toilet at work," "restrictions on eating and drinking at work," "fear of transmitting the disease to relatives and friends," and "fear of being infected with covid- ". "hospital staff experienced discomfort caused by the use of protective equipment" and "the burden of caring patients" reported higher scores than other two dimensions of the scale. further, for hospital staff with severe stress (n = ), we performed a t test or one-way anova to explore whether their stress levels differed based on their demographic characteristics of gender, marital status, years of work experience, educational level, staff type, and experience with caring for patients with sars. as shown in table this study was the first one conducted in taiwan to investigate the perceived stress of hospital staff and to identify relevant influencing factors during the covid- pandemic, using a web-based structured questionnaire. the results showed that the total stress was moderate and discomfort caused by protective equipment emerged as the major stressor. nurses generally perceived higher stress as compared to the other types of hospital staff. difficulties and anxieties related to infection control were major stressors for medical technicians, while administrators were the least stressed among all types of staff. further, those with minor children experienced a higher degree of work stress. this study found that discomfort caused by protective equipment was the major stressor for the participants, followed by burden of caring for patients. the overall stress was slight to moderate. this result was consistent with the findings of yu et al, but it was different from other similar studies conducted during the sars pandemic. specifically, those studies found that the main stressor among hospital staff was difficulties and anxieties related to infection control. , , participants in the present study were more stressed by the discomfort caused by wearing protective equipment for a long period, probably because, to effectively prevent the source of infection from entering the hospital and causing cross infection, the hospital staff were required to wear masks throughout their stay in the hospital. additionally, they had to set up simple triage stations at the emergency and outpatient departments' entrances, while different types of staff took turns to participate in monitoring individuals entering the hospital. the staff on duty was required to wear basic protective gear, including goggles, protective clothing, surgical masks or n masks, and gloves, which made it inconvenient for them to eat and drink at work, as well as to use the toilet. they were required to wash their hands and use disinfectants frequently, and the fear that hands would become rough and cracked made them stressed. the covid- pandemic has changed the work style and environment of the healthcare system, leading to physical and mental imbalance, and thereby, an increased level of stress among hospital staff. when the sars pandemic hit taiwan stressful events or stressors in the workplace can cause stress reactions, and an employee's personal characteristics and behaviors interact with the practice environment. strong physical and mental demands lead to an increase in stress levels of hospital staff, which may in turn influence patient care. a survey of regional hospital staff examined the correlation between perceived overwork and musculoskeletal symptoms. findings revealed that nurses ranked the highest among hospital staff in terms of overwork, followed by administrative staff, medical technicians, and physicians, in order of decreasing overwork. by nature, nursing is a highly stressful occupation. nurses reported highest stress level in this study. this could be attributed to physical discomfort caused by protective equipment, also, nurses often previous studies have shown that work stress is related to one's demographic characteristics, , and that child care at home is a common problem for hospital staff, , which is an important factor leading to work-family conflicts. the present results showed that hospital staff with minor children was more stressed, confirming the viewpoint presented in prior research. however, these findings were different from those reported by wang et al and lambert et al, who found that employees with children were less stressed than those without. perhaps this is due to the parenting style difference between the east and the west world. in the face of the covid- pandemic, since the end of january , hospitals started hospital-wide staff mobilization to contain the pandemic, such as setting up triage stations at the entrances and exits, and medical tents and special wards at the emergency department. these measures changed the existing work pattern of staff and caused unprecedented stress on all types of healthcare workers. as the temperature rises in southern taiwan, wearing of protective equipment for prolonged periods causes discomfort in staff. such discomfort can be alleviated by shortening shift durations and installing more mobile air conditioners in emergency and outpatient departments. since healthcare workers are in a high-stress occupation, it is recommended that they should be assessed and monitored regularly, and appropriate interventions need to be implemented. it is necessary to provide psychological counselling and stress relief measures for this population. during the pandemic containment, some staff was concerned that they could be carries of the infection after caring for patients with covid- , and that they would bring the source of infection home to their family and relatives. this led to higher work stress on hospital staff with minor children. to cope with this situation, it is recommended to assess the needs of hospital staff with minor children and provide appropriate arrangements for the transportation of employees' children to and from school or offer after-school programs. this would reduce the burden on frontline healthcare staff who are responsible for pandemic containment. in addition, hospitals may consider recruiting medical technicians as members in the emerging infectious diseases response drills in future, as this would familiarize them with various disposal processes. this would enable hospitals to commission these staff, as soon as necessary, for pandemic containment. such measures would in turn promote the response ability of medical technicians and reduce their stressors. due to workforce, financial, and time limitations, this study collected data only from one medical center and two regional hospitals in together, such findings could be used to provide appropriate support and response measures for hospital staff during a pandemic. the authors gratefully acknowledge the supports from kaohsiung medical university hospital, taiwan, grant number kmuh-c . taiwan centers for disease control: coronavirus disease (covid- ) world health organization. global alert and response (gar): novel coronavirus infection in the united kingdom stress, appraisal, and coping test of the reliability and validity of nurse stress checklist the copenhagen burnout inventory: a new tool for the assessment of burnout prevalence of burnout in paramedics: a systematic review of prevalence studies nurses' satisfaction with their work environment and the outcomes of clinical nursing supervision on nurses' experiences of well-being-a norwegian study ethical decision making in nurses. relationships among moral reasoning, coping style, and ethics stress stresses and adjustment behaviors of surgical nurses caring for sans patients courage and commitment: working the front during the first wave of the sars outbreak, nurses from toronto share their stories health care workers' stress and willingness to care for patients with severe acute respiratory syndrome stress level of nurses of caring patients with concealed infectious disease a study of the work stress and intention to quit related to nurses' turnover in a medical center a study of the social support and job stress among nursing staff. vgh nursing the influence of nurses' working motivation and job satisfaction on intention to quit: an empirical investigation in taiwan workplace stressors, ways of coping and demographic characteristics as predictors of physical and mental health of japanese hospital nurses prevalence and factors associated with burnout among healthcare professionals in india: a systematic review and meta-analysis occupational stress in nursing psychometric evaluation of the stress scale of caring for highly infectious disease patients among health care workersbased on sars the sage handbook of health psychology job stress and coping in emergency room nurses confronting severe acute respiratory syndrome crisis work-related stress and coping behaviors during sars outbreak period among emergency nurses in taiwan the immediate psychological and occupational impact of the sars outbreak in a teaching hospital understanding and addressing sources of anxiety among health care professionals during the covid- pandemic facing sars: psychological impacts on sars team nurses and psychiatric services in a taiwan general hospital occupational stress: toward a more integrated framework exploring the burden of emergency care: predictors of stress-health outcomes in emergency nurses analyses of burnout and musculoskeletal symptoms questionnaires and their relationships among employees in a regional hospital work-family conflict and job performance in nurses: the moderating effects of social support correlations of the "work-family conflict" with occupational stress-a cross-sectional study among university employees battle hymn of the tiger mom when middle-aged parents meet adolescent children: parent-child relationship patterns and parent's midlife perceptions survey on perceived work stress and its influencing factors among hospital staff during the covid- pandemic in taiwan the authors declare no potential conflict of interest. https://orcid.org/ - - - hsin-tien hsu https://orcid.org/ - - - che-yu su https://orcid.org/ - - - key: cord- - sfleb b authors: chan, ta-chien; hwang, jing-shiang; chen, rung-hung; king, chwan-chuen; chiang, po-huang title: spatio-temporal analysis on enterovirus cases through integrated surveillance in taiwan date: - - journal: bmc public health doi: . / - - - sha: doc_id: cord_uid: sfleb b background: severe epidemics of enterovirus have occurred frequently in malaysia, singapore, taiwan, cambodia, and china, involving cases of pulmonary edema, hemorrhage and encephalitis, and an effective vaccine has not been available. the specific aim of this study was to understand the epidemiological characteristics of mild and severe enterovirus cases through integrated surveillance data. methods: all enterovirus cases in taiwan over almost ten years from three main databases, including national notifiable diseases surveillance, sentinel physician surveillance and laboratory surveillance programs from july , to december , were analyzed. the pearson’s correlation coefficient was applied for measuring the consistency of the trends in the cases between different surveillance systems. cross correlation analysis in a time series model was applied for examining the capability to predict severe enterovirus infections. poisson temporal, spatial and space-time scan statistics were used for identifying the most likely clusters of severe enterovirus outbreaks. the directional distribution method with two standard deviations of ellipse was applied to measure the size and the movement of the epidemic. results: the secular trend showed that the number of severe ev cases peaked in , and the number of mild ev cases was significantly correlated with that of severe ones occurring in the same week [r = . , p < . ]. these severe ev cases showed significantly higher association with the weekly positive isolation rates of ev- than the mild cases [severe: . , p < . vs. mild: . , p < . ]. in a time series model, the increase of mild ev cases was the significant predictor for the occurrence of severe ev cases. the directional distribution showed that both the mild and severe ev cases spread extensively during the peak. before the detected spatio-temporal clusters in june , the mild cases had begun to rise since may , and the outbreak spread from south to north. conclusions: local public health professionals can monitor the temporal and spatial trends plus spatio-temporal clusters and isolation rate of ev- in mild and severe ev cases in a community when virus transmission is high, to provide early warning signals and to prevent subsequent severe epidemics. in july , children died of infections with enterovirus- (ev- ) in cambodia [ ] . before the laboratory results came back, the media called it a mystery disease, which made numerous asian parents worried. in fact, severe epidemics of enterovirus have occurred frequently in asia, including malaysia [ ] , singapore [ ] , taiwan [ , ] and china [ ] . the clinical severity varied from asymptomatic to mild symptoms [hand-foot-mouth disease (hfmd) and herpangina], severe pulmonary edema, hemorrhage and encephalitis [ ] . the ev- infections involved - % asymptomatic infection, - % non-specific viral syndrome, and %- % hfmd/ herpangina symptoms [ ] . among the non-polio enterovirus serotypes, ev- , which has caused severe clinical illness and many fatal cases [ ] , and particularly a high risk of poor prognosis for children under one year of age [ ] , has become one of the most important public health concerns since the world health organization (who) launched the "global polio eradication initiative" program in [ ] . however, children with an asymptomatic and mild infection of ev- still can carry the virus to transmit to others [ ] . during ~ , . % ( / , ) of severe ev cases in taiwan had only encephalitis complications, and . % ( / , ) had encephalitis with pulmonary edema or hemorrhage [ ] . in other words, whether increasing numbers of mild ev cases would provide a possible sentinel signal of the early stage of an epidemic is worth investigating, particularly as a vaccine and more effective drugs for ev- have not been available [ , ] . therefore, using an integrated surveillance system to monitor the enterovirus activity and fully understanding the difference in epidemiological characteristics between mild and severe enterovirus cases will be the most important prevention and control measures in public health. after the first nationwide epidemic of ev- occurred in taiwan in , there were another three cross-county figure geographical distribution in the cumulative incidence of pediatric severe ev cases (aged - ) in taiwan from july to december . epidemics in - , - , - [ ] . the question is, what are the important epidemiological characteristics that will be helpful in surveillance of ev- to minimize the severity of future epidemics? the specific aims of this study were: ( ) to elucidate the spatio-temporal correlations between the mild and severe enterovirus cases through integrating the data of the three enterovirusrelated surveillance systems, including the sentinel physician, national notifiable diseases and laboratory surveillance systems in taiwan, ( ) to find out the feasibility of establishing an early warning signal using the increasing numbers of mild ev- cases and their lag time periods to appearance of severe ev- cases, and ( ) to evaluate the trends of severe ev- cases over a . -year period for providing better recommendations on public health efforts in the future. with full understanding of the epidemiological characteristics, hopefully we can develop better measures and indicators from mild cases to provide early warning signals and thus minimizing subsequent numbers of severe cases. the temporal trend between severe ev cases and average mild ev cases per doctor. the x axis is the time in digits; the first four digits are the year, and the last digits are the week number. [ ] . for the sentinel-physician surveillance system, involving voluntary-based sentinel physicians in taiwan, there were around sentinel physicians from clinics and hospitals [ ] . the cases with hfmd or herpangina reported through this system were compiled on a weekly basis. for virological surveillance data, all those specimens that were collected by sentinel physicians for highly suspected ev cases and sent to the regional contracted laboratories of the tw-cdc were used to examine the viral types, including ev- , coxasackievirus groups a/b, echovirus, and other enterovirus [ ] . in this study, the temporal unit was the week, and the spatial unit was the city or county. to compare the trends between the mild and severe ev cases and between the isolation rates of different serotypes of ev and the number of severe ev cases, pearson's correlation coefficients were applied for measuring the consistency of the weekly data with the statistical software, spss (version . , spss science, the temporal trend between ev- isolation rate and severe ev cases. chicago, il). because the data of sentinel physicians were collected on a weekly basis, the counts of the severe ev cases and virological results were also aggregated into a weekly basis for better comparison. weekly numbers of severe cases and ev-positive isolation rates were used to compare their temporal trends, whereas the weekly incidence rates of severe ev-cases were employed to describe spatial distributions over time. a lag effect between mild and severe ev cases was taken into account to find out whether mild ev cases occurred earlier or later than severe ev cases, in order to determine whether mild cases might serve as early warning signals for severe cases. in addition, we applied cross-correlation analysis in a time series model to see whether there was any conditional correlation among the severe and mild ev cases and four types of ev isolation. an arma model (autoregressive moving average model) was fit using the sas release . software (cary, nc). the selection of the autoregressive (ar) and moving average (ma) was based on the minimum information criterion (minic) method [ ] . because the mild and severe ev cases were from different surveillance systems, the age definition of the ev cases we used was different. the mild ev cases were from sentinel surveillance, which had aggregated reported cases without age information. thus, the age definition of mild ev was all ages. the severe ev cases were from the notifiable infectious disease system, which had complete age information. because most of the high risk population of severe ev cases was children during the study period, we selected the cases aged equal or less than years ( . %, , / , , median age = . months) for further cluster analysis. the cumulative incidence of the pediatric severe ev cases was calculated with the corresponding mid-year population from july to . most likely clusters with high incidence of severe ev cases were detected retrospectively using spatial statistic, temporal statistic, and space-time scan statistic implemented in satscan v. . . . [ ] . the population data throughout the study period in each city or county were collected from taiwan's national statistics website (http://ebas .ebas.gov.tw/pxweb/dialog/statfile .asp). all the . years cases' data were used, with a maximum cluster population size of % to minimize false clusters, and a maximum temporal window of one month to examine the temporal-cluster using the software of satscan. the analyses of data with case counts were carried out using the poisson probability model (for a few pediatric ev cases among the child population) with monte carlo replications to test for the presence of statistically significant spatial clusters [ ] , and choosing the parameter for no geographic overlapping clusters to avoid repeated counting. after identifying the space-time clusters of the severe ev cases, the corresponding data of the mild ev cases from sentinel physician surveillance were further analyzed for consistent temporally increasing trends or even earlier increasing trends. space-time permutation was applied for detecting the mild ev clusters due to the lack information of the population at risk [ ] . the directional distribution method was employed, with two standard deviations of the ellipse size weighted by either the mild ev cases per doctor or the number of severe ev cases [ ] . then, we applied gis software (arcmap, version . ; esri inc.,redlands, ca, usa) for visualization of all detected statistically significant clusters. among the , severe ev cases notified to the taiwan-cdc during the study period, the mean age was months [mean ± standard deviation (s.d.) = ± . ], . % were male, % were hospitalizations or referrals, and % were fatal. in the virological surveillance database, the mean age of ev- cases was . months (s.d. = . months, n = , ) and that of non-ev- cases was . months (s.d. = . months, n = , ). most of the severe ev cases were aged less than years, [ . % ( , / , )] which was the group used for cluster analysis. the distribution of incidence of severe ev aged - during the study period was high in central and southern taiwan and surrounding islands including penghu county and kinmen county (figure ). temporal analysis in figure found that the mild ev cases and all the severe ev cases occurring in the same week were significantly correlated (pearson's correlation coefficient = . , p < . ). severe ev cases had two peaks starting from , but the second peak was less pronounced beginning in . after considering the lag effect, the correlation between mild ev cases and weeks ahead and the later severe ev cases was . (p < . ) and . (p < . ), respectively. on the other hand, the correlation between severe cases which were or weeks earlier and the subsequent mild ev cases was . (p < . ) and . (p < . ) in table , respectively. the highest correlation coefficients shifted from the mild ev cases earlier to severe ev cases earlier since - . in table , the correlation among mild and severe ev cases and the isolation rates of the major four types of nonpolio enterovirus are shown. the isolation rates of ev- were highly correlated with the occurrence of severe ev cases (r = . , p < . ). their temporal pattern is shown in figure . such weekly correlation coefficients were much lower for other types of ev [ . (p < . ) for coxsackie a virus, . (p < . ) for coxsackie b virus and . (p < . ) for echo virus]. in table , the dependent variable was the severe ev cases each week. the explanatory variables were the mild ev cases, the isolation rates of ev- , coxsackievirus a virus, coxsackievirus b virus, and echovirus in each week. in the first model, without considering the arma effect, only mild ev cases (coefficient = . , p < . ) and the ev- isolation rate (coefficient = . , p < . ) were significant predictors. in the second model, considering arma ( , ) which was selected by minic function in sas, only the ar effects and mild ev (coefficient = . , p < . ) were significant predictors. on the other hand, we also switched mild ev cases as the dependent variable and severe ev cases as an explanatory variable. after considering the ar effect, severe ev cases could not be significant predictors for mild ev cases (p = . , data are not shown). to fully understand the temporal, spatial and tempo-spatial distributions of ev cases, we then monitored the trends in ev cases using these three methods separately. with the temporal scan method alone, the temporal cluster was only detected in june , which had the highest number of monthly severe ev cases (n = ) during the study period. in the further analysis, the number of the severe ev cases from april to june was , which was also the highest value for any three-month period during the study period. with the spatial scan method alone, there were two years without statistical significant spatial clusters (i.e. , and ), while the other seven years had statistical significant spatial clusters: july july - july , july , july , july , july , july and . throughout the study period (figure ) , penghu county in july - , and had the highest local spatial risk ( . and . , p < . ). with the integrated space-time scan method, the five cities or counties which had the highest number ( ) of severe cases throughout the study period and the highest number ( ) of fatal cases in were identified ( figure a ). three space-time mild ev clusters were detected in ( figure b ). in tainan city, consistent mild and severe ev clusters were both detected in june . another two mild ev clusters in were found earlier, in april and may. penghu county also had the highest local tempo-spatial risk among these ( . , p < . ). then, we analyzed the temporal trend in mild ev cases per doctor in . in figure , the period of june , which is marked as the gray dashed square, was also the peak of the mild ev cases. however, the increasing trend of severe ev cases surged starting in week , , (april , and mild ev cases also surged in the following week (april , ). in figure (table ). epidemics of enterovirus have continued playing a major public health threat in the asia-pacific region [ ] . during the past decade, epidemics have also occurred in european countries, including denmark [ ] , the united kingdom [ ] , hungary [ ] , france [ ] and the netherlands [ ] . the integrated information from different enterovirus surveillance systems (rather than from a single source) plus spatio-temporal analyses of epidemiological data in taiwan might provide valuable experience for other countries. enhanced surveillance and non-pharmaceutical public health policy such as school closure have been the major strategies implemented for preventing enterovirus epidemics, because effective vaccines and antiviral drugs have not been available. in this study, we have shown that integrated surveillance, including sentinel physicianbased clinical surveillance, virological surveillance, and notifiable infectious disease surveillance, reflected not only the whole spectrum of ev cases from mild to severe but also the types of virus activity at the community level. with the spatial scan and spatio-temporal scan statistics, we found that central taiwan and penghu county, which is an island located km offshore, were the locations of major clusters of severe ev cases. in the temporal pattern, the severe ev cases occurred either one week earlier than the mild ev cases or surged simultaneously, during the same week. however, taking the autoregressive effects and ev isolation rates together, severe ev cases could not significantly explain the temporal trend of mild ev cases. in contrast, mild ev cases might have better prediction capability even after controlling for the ar effects. in this study, the peak of the mild and the severe ev cases occurred almost the same week. in the years of and , the increases of the mild ev cases occurred one to two weeks earlier than the increases of the severe ev cases. after , the pattern changed to consistently high in the same week, or severe cases rising even much earlier. several possible reasons might explain this phenomenon. first, the outbreak of sars in made physicians in taiwan more aware of unusual increases in case numbers of infectious diseases. once severe ev cases were reported and announced through mass media, even at the early stage, it might have alerted the physicians to pay attention to additional suspected ev cases. second, ev- was highly correlated with severe ev cases. this is consistent with the facts, that ev- was known to have high virulence, and pathogenicity in the central nervous system by inflammatory cytokines/chemokines [ , ] , severe pulmonary edema and heart failure [ ] . the early information on the positive isolation rate of ev- also can be helpful to predict the more likely occurrence of severe ev cases in the following one to two weeks. with the space-time scan method, we found temporal clusters in june , and spatial clusters in five cities and counties. one nearby island, penghu, where the seashore is a famous summer tourist destination, had the highest local risk in and . the possible reasons for this phenomenon might have been the smaller number of children amongst the population, lack of medical resources, and close transportation to another epidemic center, china. the data in this study have three major limitations. because of the de-identification between different released databases, direct linkage between the severe ev cases and the results of ev isolation was not feasible. hence, it was hard to elucidate the correlation between local epidemics and the specific types of enterovirus circulated. age-related data for mild ev incidence were not available in the sentinel surveillance database. therefore, it was hard to differentiate among incidence in preschool children or school-aged children. integration among different surveillance systems would be beneficial for disease surveillance. public health surveillance and clinical surveillance could help detect aberrations at the early stage. laboratory surveillance could help determine the severity of epidemics. in the future, utilizing community surveillance, hospitalbased syndromic surveillance and national health insurance data, which cover % of the population in taiwan, for monitoring age-specific enterovirus cases will offer the best chance to detect enterovirus activity with better sensitivity and timeliness at the local community level. local public health professionals can monitor the temporal and spatial trends plus spatio-temporal clusters and isolation rate of ev- in mild and severe ev cases in the community when virus transmission is high to provide early warning signals and to prevent subsequent severe epidemics. the increase of mild ev cases might be a possible predictor for the occurrence of severe ev cases with a time series model. in addition, comprehensive surveillance of school children might detect earlier signals and allow social distance intervention to minimize the size of spatial clustering. severe complications of hand, foot and mouth disease (hfmd) caused by ev- in cambodia -conclusion of the joint investigation hand foot and mouth disease due to enterovirus in malaysia the changing seroepidemiology of enterovirus infection among children and adolescents in singapore incidence rates of enterovirus infections in young children during a nationwide epidemic in taiwan enterovirus in taiwan epidemiology of hand, foot, and mouth disease and genotype characterization of enterovirus in jiangsu an eight-year study of epidemiologic features of enterovirus infection in taiwan challenges to licensure of enterovirus vaccines an epidemic of enterovirus infection in taiwan. taiwan enterovirus epidemic working group non-polio enteroviruses in acute flaccid paralysis children of india: vital assessment before polio eradication transmission and clinical features of enterovirus infections in household contacts in taiwan enterovirus vaccine: when will it be available? antiviral effect of geraniin on human enterovirus in vitro and in vivo guidelines for communicable disease surveillence. taipei, taiwan: taiwan cdc epidemiology and surveillance system of human influenza viruses circulating viruses associated with severe complicated enterovirus infection in taiwan: a multi-year analysis time series analysis: forecasting and control evaluating cluster alarms: a space-time scan statistic and brain cancer in a spatial scan statistic a space-time permutation scan statistic for disease outbreak detection novel measurement of spreading pattern of influenza epidemic by using weighted standard distance method: retrospective spatial statistical study of influenza virology, epidemiology, pathogenesis, and control of enterovirus clinical and virological features of enterovirus infections in denmark molecular epidemiology of human enterovirus in the united kingdom from to human enterovirus (ev ) in acute paediatric respiratory disease in hungary screening and detection of human enterovirus infection by a real-time rt-pcr assay detection of recombination breakpoints in the genomes of human enterovirus strains isolated in the netherlands in epidemic and non-epidemic years enterovirus infection with central nervous system involvement cytokine immunopathogenesis of enterovirus brain stem encephalitis cardiopulmonary manifestations of fulminant enterovirus infection submit your next manuscript to biomed central and take full advantage of: • convenient online submission • thorough peer review • no space constraints or color figure charges • immediate publication on acceptance • inclusion in pubmed, cas, scopus and google scholar • research which is freely available for redistribution the authors would like to express our sincere gratitude to public health professionals at local departments of health and central public health officials at the centers for diseases control in taiwan (taiwan-cdc) for their effort in surveillance of enterovirus-related diseases. this study was supported by grants from the center for disease control taiwan the authors declare that we do not have any competing interests related to this study.authors' contributions tcc did all spatio-temporal data analysis and writing for the whole manuscript. jsh participated in spatio-temporal statistics. rhc did most data analyses from surveillance by types of enteroviruses. cck guided epidemiological study between mild and severe enterovirus cases and also the revision of this manuscript. phc participated in gis analysis and the revision of this manuscript. all authors read and approved the final manuscript. key: cord- - ldtrjf authors: chuang, pei-hung; chuang, jen-hsiang; lin, i-feng title: a dynamic estimation of the daily cumulative cases during infectious disease surveillance: application to dengue fever date: - - journal: bmc infect dis doi: . / - - - sha: doc_id: cord_uid: ldtrjf background: in infectious disease surveillance, when the laboratory confirmation of the cases is time-consuming, there is often a time lag between the number of suspect cases and the number of confirmed cases. this study proposes a dynamic statistical model to estimate the daily number of new cases and the daily cumulative number of infected cases, which was then applied to historic dengue fever data. methods: the duration between the date of disease onset and date of laboratory confirmation was assumed to follow a gamma distribution or a nonparametric distribution. a conditional probability of a case being a real case among the unconfirmed cases on a given date was then calculated. this probability along with the observed confirmed cases was integrated to estimate the daily number of new cases and the cumulative number of infected cases. results: the distribution of the onset-to-confirmation time for the positive cases was different from that of the negative cases. the daily new cases and cumulative epidemic curves estimated by the proposed method have a lower absolute relative bias than the values estimated solely based on the available daily-confirmed cases. conclusion: the proposed method provides a more accurate real-time estimation of the daily new cases and daily cumulative number of infected cases. the model makes use of the most recent "moving window" of information relative to suspect cases and dynamically updates the parameters. the proposed method will be useful for the real-time evaluation of a disease outbreak when case classification requires a time-consuming laboratory process to identify a confirmed case. timeliness and accuracy of case reporting are two of the most important performance measures when evaluating an infectious disease surveillance system [ ] [ ] [ ] [ ] [ ] . laboratory confirmation is usually needed for case diagnosis in many infectious diseases. when laboratory confirmation of the diagnosis is time-consuming, however, there is often a time-lag between the onset date of symptoms and the diagnosis date [ ] . for example, the median time for confirmation of the meningococcal disease is about days based on the national notifiable diseases surveillance system (nndss) dataset for the united states from to [ ] . time from disease onset to diagnosis has been also reported to account for most of the delay in case reporting in korea [ ] . correct estimation of daily cases or daily-cumulative infected cases helps the implement of immediate disease control and allows prevention activities for infectious diseases to be instituted [ ] . using a disease surveillance system, one is able to apply statistical methods, such as cumulative sum (cusum) [ , ] or autoregressive integrated moving average (arima) [ ] [ ] [ ] [ ] [ ] , in order to forecast an epidemic curve or to detect aberrations in disease spread. these estimations are based on having a correct daily number of cases or a daily-cumulative number of cases. an epidemic of dengue fever occurs every year in southern taiwan. in the year in particular, there was a large-scale epidemic with , confirmed cases out of totally , suspect cases [ ] . this epidemic continued until march . surveillance and the control of dengue fever have become one of the most important routine areas of work at the taiwan centers for disease control (taiwan cdc) in recent years. by , taiwan cdc had defined a confirmed case of dengue fever as an acute febrile illness together with one of the following criteria: ( ) isolation of dengue virus; ( ) demonstration of positive results by real-time reverse transcription--polymerase chain reaction (real-time rt-pcr); ( ) demonstration of positive seroconversion or a fourfold increase in dengue-specific igm or igg antibody titers in paired serum samples; or ( ) demonstration of high-titer dengue-specific igm and igg antibodies in a single serum specimen [ ] [ ] [ ] . when the dengue fever case classification only included confirmed cases by this protocol, the time needed for isolating the agent or measuring the titers for the acute-and convalescent-phase serum specimens was significant. the result was that there was a gap between the available daily cases or the daily-cumulative cases for given a day and the actual final confirmed cases for the same day given that all diagnosis had been completed on that given day. assuming that a time cost for laboratory confirmation of diagnosis is sometimes inevitable, daily numbers of infected cases and daily-cumulative number of infected cases may be underestimated during an epidemic. the objective of this study was to develop a new method to estimate the number of daily cumulative cases and that this method will be applied to dengue fever in taiwan, as an example. since there are almost no dengue fever cases occurred during the winter in taiwan, we chose may as the beginning of the dengue epidemic season when estimating the cumulative epidemic curve. the data come from the dengue notification dataset containing suspect cases in taiwan whose date of onset was from may , to april , . all serum samples from suspect cases were sent to the two reference laboratories at the taiwan cdc in order to further identify if they were positive (dengue fever infected) or negative cases. the reason we retrieved data based on the date of onset rather than the report date was to avoid the influence of lag reporting on the course of the disease. all imported cases of the disease were removed. the variables we used were the date of onset, the date of laboratory confirmation (diagnosis date), and the final confirmed status of each suspect case (a binary variable that is either positive or negative). in this article, we use confirmed dengue cases and positive cases interchangeably. no personal identification information was contained in the dataset. our proposed method estimates the real-time daily new number of cases and the daily cumulative number of dengue cases; specifically, these numbers of dengue cases are updated daily. let c be the "current" date when the number of dengue cases is to be estimated. in this study, the date c runs from may , to april , . for the i th reported suspect case counting from the st day of the epidemic season, that is may in this study, we define the suspect case's onset date as o i and the laboratory confirmation date as d i if d i >c on date c, the case i does not have a confirmation result as of date c; on the other hand, if d i ≤ c, this case i is either confirmed to be a positive dengue case or has a negative result as of date c. let the final confirmation status for the i th suspect case be, where as a positive dengue case, and as a negative case. in the situation where there are unconfirmed suspect cases as of date c, we assigned a probability of being a dengue case, p(i), to those unconfirmed cases (d ≤ c). then for each suspect case i, the expected final confirmation status on date c, e i (c), can be written as the values of p i (c), and e i (c)are updated for each case i every day. without applying the proposed method, one would be only able to observe the case status from the upper part of e i (c)in equation ( ) . after e i (c)is calculated for each suspect case, daily new cases are easily estimated by summing the e i (c)over all new suspect cases on date c, and cumulative cases can be obtained by summing e i (c)over all cases from i = to the newest suspect cases on date c. is estimated for unconfirmed cases using information from the confirmed cases before date c within one year. let t i be the onset-to-confirmation time (oc-time), the time interval between the onset date and the lab-confirmation date. the oc-time for the i th suspect case as of date c, t i (c), is calculated as follows, the t i (c) is the oc-time for confirmed cases and the censored oc-time for unconfirmed cases on date c. by applying several steps of bayes' rules, the probability p i (c) is given by: to estimate p i (c) using the information as of date c, we applied the following steps. we first estimated p(y i = ) by calculating the proportion of confirmed positive dengue cases out of the suspect cases using the data with onset date within year before the date c. based on a parametric approach, we assumed the oc-time for a given case status, p(t|y i ), follow a gamma distribution. gamma distributions are frequently used to fit time-delay distributions or time event distributions when carrying out disease surveillance analysis [ , ] . the probability density function of the gamma distribution is , where . the gamma distribution is denoted by with two parameters, the shape parameter α and the scale parameter β, and the mean and variance are αβ and αβ , respectively. the values of α and β were estimated and solved by setting up the sample mean and the sample variance of the oc-time equal to αβ and αβ , respectively. as mentioned in the previous section, the mean and standard deviation of the oc-time were different between positive and negative cases, we estimated different sets of α and β for the positive dengue cases (y = ) and negative cases (y = ) separately. a nonparametric approach was also performed in which the probability p(t >t i (c)|y i ) was simply replaced with the cumulative proportion of confirmed data given their final status. both the parametric and nonparametric models were based on the data within a -year "moving window" before date c. the p i (c) and e i (c) were also updated everyday. to evaluate the performance of the proposed method, we estimated the daily new cases and daily cumulative cases for each calendar date c from may , to april , . four epidemic curves are presented. there are: ( ) the final status curve, which is the number of dengue cases based on their final confirmation status ("real data", "gold standard"). ( ) the daily confirmed curve, which is the number of dengue cases based on the confirmed cases as of date c. ( ) the gamma-model curve, which is the number of dengue cases, estimated using the gamma distribution. ( ) the nonparametric-model curve, which is the number of dengue cases, estimated using the nonparametric distribution. to summarize the magnitude of the bias, we defined the absolute relative bias (arb) at date c as: where are the cumulative cases estimated by the proposed methods or by the confirmed cases observed on date c without using the proposed methods, n c and are the cumulative confirmed cases based on the final status ("real data", "gold standard"). an arb closer to zero is a more accurate estimate. all analyses were performed using sas . . software (sas institute, inc., cary, nc). special sas macros for estimating the cumulative cases and daily new cases, based on our proposed model, were developed. figure compares the daily new cases estimated by the proposed models, the confirmed curve (confirmed new cases observed on date c without using the proposed models), and the final status curve (confirmed new cases based on final status; the "gold standard"). since the daily new cases estimated by the proposed methods or the daily new cases observed on date c were different when viewed on different dates, arbitrary view dates of august , (beginning of the epidemic), september , (rising stage, before the peak), october , (rising stage, before but closer the peak) and november , (around the peak), december , (downward stage, after the peak), and january , (end of the epidemic) were chosen to illustrate the results of the estimated daily new cases. each graph in figure shows the epidemic curves three weeks before the view dates. when viewed on august , most of suspect cases had been lab-confirmed before july thus all four curves were close to each others before that date. from july to august , the estimated curves by the proposed methods (red dashed lines with triangle symbols by gamma distribution and blue dashed lines with cross symbols by the nonparametric method) were much closer to the final status curve (shaded area) than that by simply observing the dailyconfirmed new cases (purple dashed line). similar patterns were observed when the results are viewed on september , october , november , and december . the observed daily-confirmed cases usually underestimated the true daily new cases as would be expected, especially within the two weeks before the view date. the curves estimated by gamma distribution or the nonparametric approach were quite similar. however, the daily new cases, as estimated by the proposed method, did not give an accurate estimate towards the end stage of the epidemic, namely when viewed on january , . the epidemic curves in terms of daily cumulative cases are shown on figure . in this figure, the cumulative number of positive cases was updated every day. the two estimated daily-cumulative curves by the proposed methods are quite similar to the final status curve before january but again the proposed method does not work well during the end stage of the epidemic. table compares the arb of the daily cumulative number of positive cases between the different methods. after the first confirmed positive case appeared on july , , the estimates based on the gamma model results in an estimate closer to the real data than the other methods. for other two curves, the nonparametric method performs worst at the end of the epidemic after january and there was about cases higher than the final status curve. the daily confirmed curve was about cases lower than the final status curve during the peak of epidemic. figure showed the daily parameter estimates, α and β, of the gamma distributions used to dynamically calculate the daily number of positive cases. the parameter estimates varied from day to day and thus the probability of being a positive case changes. for the negative cases, the parameters had a jump during late september. as noted previously, timeliness and accuracy are the two of most important characteristics when we evaluate an infectious disease surveillance system. our results show that when an infectious disease required a time-consuming process for diagnosis, such as the dengue fever using the previously mentioned protocol, the actual daily number of infected cases and cumulative positive cases are potentially underestimated. the proposed method dynamically updates the parameters daily by making use of the most recently available information on suspect cases, and then performed estimates with a lower absolute relative bias than when using observed daily lab-confirmed cases only. as shown in table , the proposed method performed a lower median absolute relative bias (abs range . % ~ . %) than those solely based on daily confirmed cases (abs range . % ~ . %) between july and december . these dates covered the rising stage and around the peak stage which were of public health interest. the proposed method provides a more accurate estimate of the epidemic curves when applied to the dengue fever dataset for taiwan during the - season. based on these results, this approach can be used for the real-time evaluation of the severity of a disease outbreak when case classification requires that a confirmed case involves a time-consuming process. in this study, we first established the different distributions for the onset-to-confirmation time of the positive cases and negative cases. next, either a gamma distribution was assumed in order to estimate the probability of being a confirmed case given cases status in equation ( ), or, alternatively, a nonparametric approach was used. we actually experimented with several types of distribution. the estimates using a log-normal distribution were numerically very similar to the results for the gamma distribution. the estimates using a weibull distribution did not perform as well as the gamma distribution applied in our dengue fever data. from figure , we learn that the shape parameter α changed from . to and therefore an exponential distribution may not be appropriate. for simplification, we have chosen to present only the results from the gamma distribution as one example of a parametric approach and compare this with a nonparametric approach. as shown in figure for daily new cases, the differences in the estimates based on parametric approach with gamma distribution and those with nonparametric approaches were minor. the figure and table for cumulative cases showed that a gamma distribution is a more appropriate assumption for the onset-todiagnosis time when estimating the probability of being a positive case using the dengue fever example; nonetheless, the difference between the gamma and the nonparametric method is again only slight except towards the end stage of the epidemic after january . the reason that the nonparametric method did not work well after january is because p(y i = ), p(y i = ), and p(t|y i ) had not changed substantially, resulting in a near constant estimate of the daily positive cases. in practice, any form of the probability of being a positive case can be assumed. it is also not restricted to certain distributions when the models are adapted to different types of infectious disease. when applying this approach to other diseases, researchers should investigate several distributions according to the shape of their data and choose an appropriate one based on some appropriate measures, for instance, those shown in table . our method estimated the probability of being a positive case based on the data within a -year "moving window" before date c and updated p i (c) and e i (c) everyday. the epidemic profiles of dengue fever are different from one year to another in taiwan. choosing the data from most recent one year was done in order to insure that there was enough information to cover a whole epidemic season. the study shows that before the first positive case appeared on july , the proposed method did not work well and are not that useful (table ). our method worked well after the first positive case appeared during the - season. indeed, it needed only four days to be able to consistently estimate the final status curve. in the - season, taiwan cdc activated a central command center for intensively dengue epidemic control on october . the task of this command center included expanded blood sample collection and it is likely that this resulted in more suspect cases for laboratory confirmation, which might have led to a lower proportion of positive cases. this would influence the estimation of probability of being a positive case over the following few days. as we can see on figure , it also influenced the estimation of the parameters for negative cases. while our manuscript was being prepared, the taiwan cdc changed their laboratory protocol for dengue fever to one that requires only a single laboratory test for dengue surveillance and control. the result is a substantial reduction in the waiting time for laboratory confirmation. however, confirmation time can never be completely avoided with dengue fever. a situation where a large number of serum specimens are sent for diagnosis at the same time will result in overloading at the laboratory, which might increase the confirmation waiting time. as described previously, the estimation used information based on a "moving window" time period before the estimated date and the parameters of the model are updated everyday. since the observed confirmed cases counts on date c are always underestimated as long as there is a time lag, our method potentially can be applied while waiting for further investigation of the status of cases. there are some limitations to our method. firstly, the approach needs sufficient historical data to be available in order estimate the parameters of the model; therefore our model cannot be applied effectively to an emerging disease, such as sars or avian flu. secondly, we used confirmed cases, the dates of onset of which were within year before the date estimated and if a case needs more than -year for diagnosis such a case might never provide any information to the parameter estimation; in such a circumstance a different "moving window" needs to be chosen. thirdly, when missing diagnosis dates exist, the estimated curve using the nonparametric method cannot converge with the final status curve. there were and cases missing confirmation results for the - season and the - season, respectively, at the time that the manuscript was prepared. the nonparametric method estimates by plugging in the cumulative proportion of confirmed data given the final status. as we mention before, at the end stage of epidemic, the probabilities in equation ( ) almost remained unchanged. in this study, we could only assume that the proportion of positive cases out of all suspect cases among the missing observations were similar to those having results, which basically assumes that the missing data were missing at random thus ignorable. when diagnosis of infectious diseases required laboratory confirmation, the time lag between onset and confirmation of a positive cases often exists and case counts are usually underestimated. this study has proposed a statistical method that more accurately estimates the real-time daily new cases and daily cumulative number of infected cases using a dengue fever epidemic as an example. the model makes use of the most recent "moving window" of information on suspect cases and dynamically updated the parameters of the assumed probability distributions. different parametric or nonparametric distributions of the onset-to-confirmation times can be specified for different infectious diseases. the results show that, after the first confirmed case occurred, the estimated daily new cases or the cumulative case count fit the real data well compared to the daily counts based only on the available confirmed cases; this was done by assuming a gamma distribution for the onset to confirmation times and involved the use of a dynamic one-year "moving window" of suspected cases when applied to dengue fever outbreaks in taiwan. this method can be used for the realtime evaluation of a disease outbreak when case diagnosis requires time-consuming laboratory process. how complete and accurate is meningococcal disease notification? public health surveillance of aids and hiv infections updated guidelines for evaluating public health surveillance systems: recommendations from the guidelines working group cdc's national violent death reporting system: background and methodology an outbreak of leptospirosis, thailand--the importance of the laboratory evaluation of reporting timeliness of public health surveillance systems for infectious diseases syndromic surveillance systems: public health and biodefense timeliness of national notifiable diseases surveillance system in korea: a crosssectional study methods for monitoring influenza surveillance data the relative efficiency of the sets and the cusum techniques in monitoring the occurrence of a rare event time series analysis forecasting and control on the application of integer-valued time series models for the analysis of disease incidence use of time-series analysis in infectious disease surveillance dynamic linear model and sarima: a comparison of their forecasting performance in epidemiology a monitoring system for detecting aberrations in public health surveillance reports number of reported and confirmed cases -by month world health organization: dengue haemorrhagic fever: diagnosis, treatment and control laboratory-based dengue surveillance in taiwan, : a molecular epidemiologic study current status of dengue diagnosis at the center for disease control epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in hong kong sars incubation and quarantine times: when is an exposed individual known to be disease free? this study was supported in part by the centers for disease control, department of health, taiwan, republic of china (doh -dc- and doh -dc- ) and was also supported by the aim for the top university plan of national yang-ming university. the authors would like to thank the reviewers' excellent comments for improving this manuscript. the authors declare that they have no competing interests. authors' contributions ifl designed and conducted the study, and finalized the manuscript. phc participated in the design of the study, performed the statistical analyses, and drafted the manuscript. jhc helped conceive the study, participated in the data collection, gave input to the manuscript, and provided medical advice from the public health perspective. all authors have read and approved the final manuscript. key: cord- -hxvadp authors: liu, jui-yao; chen, tzeng-ji; hwang, shinn-jang title: analysis of imported cases of covid- in taiwan: a nationwide study date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: hxvadp in the early stages of the novel coronavirus disease (covid- ) pandemic, containment of disease importation from epidemic areas was essential for outbreak control. this study is based on publicly accessible data on confirmed covid- cases in taiwan extracted from the taiwan centers for disease control website. we analysed the characteristics, infection source, symptom presentation, and route of identification of the imported cases that were identified from january to april . they were mostly returned taiwanese citizens who had travelled to one or more of countries for tourism, business, work, or study. half of these cases developed symptoms before arrival, most of the remainder developed symptoms – days (mean . days) after arrival, and . % never developed symptoms. three-quarters of the cases had respiratory symptoms, . % had fever, . % lost smell or taste, and . % had diarrhoea. body temperature and symptom screening at airports identified . % of the cases. of the remainder, . % were identified during home quarantining, . % were identified via contact tracing, and . % were reported by hospitals. under the strict enforcement of these measures, the incidence of locally acquired covid- cases in taiwan remains sporadic. in conclusion, proactive border control measures are effective for preventing community transmission of this disease. the novel coronavirus disease (covid- ) caused by severe acute respiratory syndrome (sars) coronavirus (sars-cov- ) that emerged in wuhan, china in december was declared a global pandemic on march by the world health organization [ ] . as of april , the disease has spread to countries, with , , confirmed cases and , deaths [ ] . the case fatality rate is about . % globally, but mortality in elderly patients with comorbidities is higher [ ] [ ] [ ] . under the current circumstances, in which there is no vaccine available for prevention and no effective antiviral drug for treatment, almost all people in the world are susceptible to this novel person-to-person transmitted disease [ ] . the complexity and high volume of international air travel has allowed the disease to spread rapidly [ ] [ ] [ ] . in the early stages of this pandemic, containment of disease importation from epidemic areas was essential for preventing indigenous outbreaks [ ] . without adequate control measures, persistent and imperceptible virus importation via air travellers may cause large-scale community transmission. this could lead to an outbreak that may exceed the capacity of the healthcare system with disastrous results [ ] . the taiwanese authorities have made efforts to contain the importation of the disease by issuing travel advisories and implementing flight bans, entry restrictions, airport screening, home quarantining of travellers from high-risk areas, isolation of confirmed cases, and thorough contact tracing [ ] [ ] [ ] . the taiwan centers for disease control (cdc) established fever screening sites with infrared thermal imaging cameras in international airports in following the sars outbreak of that year. during the covid- outbreak, they have been performing airport screening at these fever screening sites. travellers entering taiwan with fever or respiratory symptoms must have oropharyngeal specimens collected for covid- testing and are subject to home quarantining for days, as are travellers from areas where the disease is epidemic. people in home quarantine must stay at home (or at another designated location) and not go out, and they must maintain a distance of at least one metre from their family, record body temperature and health status every day, and cooperate with tracking measures implemented by their local borough chief. individuals who develop symptoms such as fever, coughing, or runny nose while in home quarantine are sent to designated medical facilities for covid- testing. when covid- cases are confirmed, they are immediately hospitalized in negative pressure isolation rooms, and taiwan cdc personnel conduct investigations within h to identify their contacts. any contacts who have covid- -related symptoms are hospitalized for testing. contacts who do not show symptoms or who test negative for covid- are placed in home isolation for days for further follow-up and testing. people in home isolation must stay at home (or other designated location) and not go out, similarly to those in home quarantines. the local health authority checks their health status twice daily, and symptomatic individuals are sent to hospital for medical attention and covid- testing. the approach of the taiwanese authorities appears to have been successful in the outbreak control, it is nevertheless important to understand the characteristics of the imported cases of the disease to know how it works. the aim of this study is to analyse the imported cases of covid- in taiwan to assess their basic demographic characteristics, disease source, symptom presentation, and routes of identification. open-access data and press releases concerning covid- in taiwan that were available on the website of the taiwan cdc were collected [ ] . the press releases, which included attached files, provided detailed information about the confirmed covid- cases in taiwan, including their category (imported or locally acquired), citizenship, sex, age group, travel history, date of arrival, reason for travel, date of disease onset, date of specimen collection for covid- testing, date of disease confirmation, and route of identification. the taiwan cdc listed covid- as a notifiable disease on january . this meant that hospitals and clinics had to notify the health authorities if patients were diagnosed with covid- and provide their travel details, contact histories and clinical presentation, as well as send specimens (throat swab and sputum) to the taiwan cdc for confirmation via reverse transcription polymerase chain reaction (rt-pcr). the date of disease onset was defined as the date of symptom onset. the countries or areas the imported cases had visited within days prior to disease onset were defined as the source of their infection. all imported covid- cases confirmed in taiwan from january to april were included in this study. descriptive statistics and plots of age group, sex, infection source, days from arrival to symptom onset, days from arrival to disease confirmation, and routes of identification were performed using pasw statistics (spss, chicago, il, usa). one-way analysis of variance (anova) was used to compare effective reproduction number (r) and mean number of days from arrival to disease confirmation between routes of identification, using bonferroni post hoc tests and % confidence intervals (ci). the case fatality rate of the imported cases was compared with that of the locally acquired cases using a chi-squared test. a two-tailed p-value of < . was considered statistically significant. there was a cumulative total of confirmed cases of covid- in taiwan from january to april , ( . %) of which were imported. of the imported cases, . % were taiwanese and . % were female. their age range was - years; young people occupied a large proportion. of them, . % were in age group of - years, . % were in age group of - years ( figure acquired cases using a chi-squared test. a two-tailed p-value of < . was considered statisticall significant. there was a cumulative total of confirmed cases of covid- in taiwan from january t april , ( . %) of which were imported. of the imported cases, . % were taiwanese an . % were female. their age range was - years; young people occupied a large proportion. o them, . % were in age group of - years, . % were in age group of - years ( figure ). th main reasons for travel were tourism ( , . %), business or work ( , . %), study ( , . % family visit ( , . %), or residency ( , . %) ( table ). the first confirmed imported cases were all from wuhan, china. the other imported cases were from east and south asia ( . %), the middle east and africa ( . %), europe ( . %), north america ( . %), south america ( . %), and oceania ( . %) ( figure ). of the cases aged - and - years, . % and . %, respectively, were studying abroad. they returned home because their educational institutions were closed in response to the outbreak. there were some instances of several cases who were studying at the same college in the united kingdom or spain, where clusters of infections occurred on campus. there were also several clusters of cases from tour groups that were travelling in egypt, turkey, or europe. an aeroplane that flew from new york to taipei on march carried passengers who were subsequently confirmed to be infected with covid- . only . % of the cases had fever. a large majority ( %) of the cases had respiratory symptoms, comprising cough ( . %), sore throat ( . %), rhinorrhoea or nasal stuffiness ( . %), chest tightness or pain ( . %), and dyspnea ( . %). some cases had flu-like symptoms, such as malaise ( . %), myalgia or arthralgia ( . %), or headache ( . %). a proportion of the cases ( %) had the neurological symptoms of loss of smell or taste. few of the cases ( %) had gastrointestinal symptoms, specifically diarrhoea ( . %), nausea or vomiting ( . %), and abdominal pain ( . %), and even fewer ( %) had ophthalmic symptoms such as itching, congestion, or pain in the eyes. eleven cases ( . %) did not have any symptoms (table ) . about half ( . %) of the imported cases had developed symptoms before arrival (mean . days, range - days before arrival) ( figure ). of the cases who did not display symptoms on arrival, most ( . %) developed symptoms - days after arrival (mean . days, median three days) ( figure ). eleven of the imported cases did not develop any symptoms; these were identified via contact testing. only . % of the cases had fever. a large majority ( %) of the cases had respiratory symptoms, comprising cough ( . %), sore throat ( . %), rhinorrhoea or nasal stuffiness ( . %), chest tightness or pain ( . %), and dyspnea ( . %). some cases had flu-like symptoms, such as malaise ( . %), myalgia or arthralgia ( . %), or headache ( . %). a proportion of the cases ( %) had the neurological symptoms of loss of smell or taste. few of the cases ( %) had gastrointestinal symptoms, specifically diarrhoea ( . %), nausea or vomiting ( . %), and abdominal pain ( . %), and even fewer ( %) had ophthalmic symptoms such as itching, congestion, or pain in the eyes. eleven cases ( . %) did not have any symptoms (table ) . about half ( . %) of the imported cases had developed symptoms before arrival (mean . days, range - days before arrival) (figure ). of the cases who did not display symptoms on arrival, most ( . %) developed symptoms - days after arrival (mean . days, median three days) ( figure ) . eleven of the imported cases did not develop any symptoms; these were identified via contact testing. of the imported cases, . % were identified in airport screening, . % during home quarantine, . % through contact tracing, and . % sought medical attention themselves and were reported by the hospitals (table ) . almost two-thirds ( . %) of the cases who had developed symptoms before arrival were identified in airport screening. of the cases who were asymptomatic on arrival, . % were identified during home quarantine, . % were identified through contact tracing, and . % were reported by hospitals (figure ) . table . reproduction number (r) and time from arrival to disease confirmation of the imported covid- cases in taiwan from january to april , stratified by route of identification. of the imported cases, . % were identified in airport screening, . % during home quarantine, . % through contact tracing, and . % sought medical attention themselves and were reported by the hospitals (table ). almost two-thirds ( . %) of the cases who had developed symptoms before arrival were identified in airport screening. of the cases who were asymptomatic on arrival, . % were identified during home quarantine, . % were identified through contact tracing, and . % were reported by hospitals (figure ). the number of imported cases increased dramatically after march , when covid- was declared a global pandemic ( figure ). the mandatory -day home quarantine was extended to all travellers from all countries on march . this measure kept all travellers from high-risk areas confined to their homes under close monitoring, and prevented them from moving around in their communities. after implementation of this measure, most of the imported cases were contained in the number of imported cases increased dramatically after march , when covid- was declared a global pandemic ( figure ). the mandatory -day home quarantine was extended to all travellers from all countries on march . this measure kept all travellers from high-risk areas confined to their homes under close monitoring, and prevented them from moving around in their communities. after implementation of this measure, most of the imported cases were contained in home quarantine or home isolation before they were identified ( figure ). the time from arrival to disease confirmation of the imported cases was - days (mean . days) ( figure ). few of the cases identified during home quarantining had longer than days of time from arrival to disease confirmation because they delayed reporting their symptoms or had borderline covid- test results, which necessitated repeat sampling and testing for confirmation. the cases identified through airport screening had the shortest time from arrival to disease confirmation (mean . days, % ci: . - . days, p < . ) as compared to cases identified via the other routes (table ). the time from symptom onset to disease confirmation was - days (mean . days). the time from arrival to disease confirmation of the imported cases was - days (mean . days) ( figure ). few of the cases identified during home quarantining had longer than days of time from arrival to disease confirmation because they delayed reporting their symptoms or had borderline covid- test results, which necessitated repeat sampling and testing for confirmation. the cases identified through airport screening had the shortest time from arrival to disease confirmation (mean . days, % ci: . - . days, p < . ) as compared to cases identified via the other routes ( table ) . the time from symptom onset to disease confirmation was - days (mean . days). the time from arrival to disease confirmation of the imported cases was - days (mean . days) ( figure ). few of the cases identified during home quarantining had longer than days of time from arrival to disease confirmation because they delayed reporting their symptoms or had borderline covid- test results, which necessitated repeat sampling and testing for confirmation. the cases identified through airport screening had the shortest time from arrival to disease confirmation (mean . days, % ci: . - . days, p < . ) as compared to cases identified via the other routes (table ). the time from symptom onset to disease confirmation was - days (mean . days). figure . time from arrival to disease confirmation for imported covid- cases in taiwan from january to april . the incidence of locally acquired covid- cases remains sporadic although there are hundreds of imported covid- cases in taiwan (figure ) . nineteen of the ( . %) locally acquired cases were infected by of the imported cases, yielding an r of . for all imported cases and . for the imported cases. these were family, friends, colleagues, and classmates of the imported cases. no locally acquired cases were infected by the cases who were identified via airport screening. the r was significantly related to the route of identification (p < . ; table ). that of the cases identified via contact tracing was significantly higher than that of the cases identified through airport screening ( . versus , p < . ; table ). three of the imported cases and three of the locally acquired cases had died. the case fatality rate of the imported cases was significantly lower than that of the locally acquired cases ( . % versus . %, p = . ). the incidence of locally acquired covid- cases remains sporadic although there are hundreds of imported covid- cases in taiwan (figure ) . nineteen of the ( . %) locally acquired cases were infected by of the imported cases, yielding an r of . for all imported cases and . for the imported cases. these were family, friends, colleagues, and classmates of the imported cases. no locally acquired cases were infected by the cases who were identified via airport screening. the r was significantly related to the route of identification (p < . ; table ). that of the cases identified via contact tracing was significantly higher than that of the cases identified through airport screening ( . versus , p < . ; table ). three of the imported cases and three of the locally acquired cases had died. the case fatality rate of the imported cases was significantly lower than that of the locally acquired cases ( . % versus . %, p = . ). there were two waves of covid- importation in taiwan. the first wave was from china, and was well contained by early preventive measures. the taiwan cdc performed onboard inspection for all direct flights arriving from wuhan since december . over the next few weeks, they gradually expanded the range of restrictions on travel to china and implemented the -day home quarantine for travellers from china after wuhan went into lockdown. the second wave of covid- importation came from other countries around the world, mainly the united states, the united kingdom, and several other european countries. inspection of the arrival dates of the second wave of imported cases reveals that these arrivals in taiwan were ahead of the timing of covid- outbreak in the other countries. the first cases imported from italy arrived on february, when there were only two confirmed cases in italy [ ]. these were four members of a taiwanese family that travelled to italy, with a transfer at the airport in hong kong, from january to february. three of the family members developed symptoms of cough or fever during the journey. there may have been many as-yet undiscovered cases of covid- in italy at that time. the mandatory -day home quarantine was extended to travellers from italy on february, from other european countries on march, from the middle east and africa on march, from east and south asia on march, and finally to travellers from all countries on march. the imported cases identified in home quarantine seemed to have a lower r than those identified via hospital notification or contact tracing (table ) . however, some individuals in home quarantine did not adhere to the instructions to stay at home, which would have exposed otherwise-unaffected people to the risk of infection [ , ] . there were two waves of covid- importation in taiwan. the first wave was from china, and was well contained by early preventive measures. the taiwan cdc performed onboard inspection for all direct flights arriving from wuhan since december . over the next few weeks, they gradually expanded the range of restrictions on travel to china and implemented the -day home quarantine for travellers from china after wuhan went into lockdown. the second wave of covid- importation came from other countries around the world, mainly the united states, the united kingdom, and several other european countries. inspection of the arrival dates of the second wave of imported cases reveals that these arrivals in taiwan were ahead of the timing of covid- outbreak in the other countries. the first cases imported from italy arrived on february, when there were only two confirmed cases in italy [ ]. these were four members of a taiwanese family that travelled to italy, with a transfer at the airport in hong kong, from january to february. three of the family members developed symptoms of cough or fever during the journey. there may have been many as-yet undiscovered cases of covid- in italy at that time. the mandatory -day home quarantine was extended to travellers from italy on february, from other european countries on march, from the middle east and africa on march, from east and south asia on march, and finally to travellers from all countries on march. the imported cases identified in home quarantine seemed to have a lower r than those identified via hospital notification or contact tracing (table ) . however, some individuals in home quarantine did not adhere to the instructions to stay at home, which would have exposed otherwise-unaffected people to the risk of infection [ , ] . airport screening of body temperature and respiratory symptoms was able to detect . % of the imported covid- cases and . % of those who had developed symptoms before arrival. the remaining cases who had developed symptoms before arrival evaded detection because they had taken antipyretic drugs, did not honestly declare their symptoms, or their symptoms were mild or not involving the respiratory tract. in fact, travellers with any suspicious symptoms are able to notify the airport health-screening personnel and be tested for covid- . nevertheless, airport screening is an effective measure to identify symptomatic imported cases soon after their arrival. there was clustering of the imported covid- cases among household members, members of the same tour group, passengers on the same aeroplane, and even students from the same overseas campus. the cases identified via contact tracing had a higher r and a longer interval between arrival and disease confirmation than those identified via other routes ( table ). the cases who never developed symptoms were difficult to identify without testing the contacts of confirmed cases. thus, thorough contact tracing and testing is important for interrupting all possible transmission chains [ ] . taiwan has several advantages in terms of outbreak control. first, more than . % of the population is enrolled in the national health insurance (nhi) program. individuals with a history of travel and suspicious symptoms have therefore been willing to seek medical attention because the costs of covid- testing and treatment are covered by the government. second, the nhi smart card stores information of border entry and exit records and the home quarantine or isolation status of the insured individual, which alerts medical personnel to high-risk patients. third, nhi claim data can provide a list of symptomatic patients who sought medical attention after returning from high-risk countries, which can be used to implement quarantine measures and retrospective contact tracing. most of the covid- cases who have moderate to severe disease present with fever [ ] , but half of our imported covid- cases did not have a fever. body temperature screening at the airport did not detect all cases, and in particular missed those without obvious symptoms. most of our imported cases had mild disease and would have been difficult to identify if their travel and contact history had not been available [ ] . in addition to respiratory symptoms, some cases had neurological symptoms, such as loss of smell or taste [ ] , or gastrointestinal symptoms like diarrhoea. the clinical presentations of covid- involve multi-organ systems not limited to the respiratory tract. some imported cases had long duration of symptoms display before arrival, the longest in this study was days, and still could be tested positive for sars-cov- nucleic acid by rt-pcr. prolonged viral shedding [ ] , a long transmissibility period, and the fact that asymptomatic or paucisymptomatic patients can transmit this disease make the disease control challenging [ ] [ ] [ ] . proactive border control measures to contain the importation of covid- via airport screening, quarantining of travellers from epidemic areas, and thorough contact tracing are effective for preventing community transmission of this disease. under the strict enforcement of these measures, the incidence of locally acquired covid- cases in taiwan remains sporadic. world health organization. coronavirus disease (covid- ) pandemic global cases clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention report of the who-china joint mission on coronavirus disease (covid- ) pandemic. available online potential for global spread of a novel coronavirus from travellers give wings to novel coronavirus ( -ncov) impact of international travel and border control measures on the global spread of the novel coronavirus outbreak the effect of travel restrictions on the spread of the novel coronavirus (covid- ) outbreak wuhan novel coronavirus (covid- ): why global control is challenging? public health initial rapid and proactive response for the covid- outbreak-taiwan's experience response to covid- in taiwan: big data analytics, new technology, and proactive testing isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus ( -ncov) outbreak cecc urges people subject to home quarantine/isolation to follow related regulations to protect everyone's health covid- -the law and limits of quarantine covid- epidemic in switzerland: on the importance of testing, contact tracing and isolation epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study coronavirus disease (covid- ) in a paucisymptomatic patient: epidemiological and clinical challenge in settings with limited community transmission a new symptom of covid- : loss of taste and smell. obes. (silver spring) clinical characteristics of asymptomatic infections with covid- screened among close contacts in nanjing transmission of -ncov infection from an asymptomatic contact in germany a novel coronavirus emerging in china-key questions for impact assessment we would like to thank the taiwan centers for disease control for providing open-access data pertaining to the confirmed covid- cases on website. we thank anthony abram for editing and proofreading this manuscript. the authors declare no conflicts of interest. int. j. environ. res. public health , , key: cord- -mtfqaepe authors: kuo, jia-hong; tseng, hui-hsin; rao, p. srinivasa; wey, ming-yen title: the prospect and development of incinerators for municipal solid waste treatment and characteristics of their pollutants in taiwan date: - - journal: appl therm eng doi: . /j.applthermaleng. . . sha: doc_id: cord_uid: mtfqaepe taiwan is a small, densely populated island with unique experiences in the construction and operation of incinerators. in such a small area, taiwan has built incinerators over a short span of time, combusting large amount of municipal solid waste as much as , tons per day. this study focuses on the history of construction and development of incinerators in taiwan as well as the characteristics of pollutants, such as heavy metals (pb, cd, and hg), acid gases (no(x), so(x), co, and hcl), and dioxins emitted from the incinerators. furthermore, the study also covers the generation and composition of municipal solid waste (msw), and the production of energy in taiwan. according to taiwan’s data on pollutant emissions, the emission level of pollutants is under control and meets the stringent regulations of taiwan environmental protection administration (tepa). researches have shown that using air pollution control devices (apcds) in the operation of incinerators provides effective measures for air pollutant control in taiwan. the main advantage of using incinerators is the generation of electricity (waste-to-energy) during the incineration of municipal solid waste, producing energy that can be consumed by the general public and the industry. taiwan’s extensive experience in incinerator construction and operation may serve as an example for developing countries in devising waste treatment technology, energy recovery, and the control of contagious viral diseases. waste management practices differ between developed and developing nations, urban and rural areas, residential and industrial areas. there are many methods for waste management, such as landfill [ ] , aerobic and anaerobic digestion [ ] , mechanical and biological treatments [ ] , pyrolysis [ ] , gasification [ ] and incineration [ ] . in densely populated areas like taiwan, finding space for additional landfills is becoming difficult. beginning in the s, however, alternative waste treatment technologies have become widely available. for instance, incineration functions as an alternative to landfill and biological treatment methods such as composting process and anaerobic digestion. by definition, incineration is the combustion of waste materials at a high temperature environment [ ] . in addition to volume reduction, incineration at high temperatures also destroys many of the toxins and pathogens in medical waste and other hazardous wastes. the most important functions of the incinerator are sanitary municipal solid waste (msw) treatment, volume reduction, and energy recovery [ ] . a waste-to-energy plant [ ] is a modern term for an incinerator that combusts wastes to produce electricity, which is deemed more publicly acceptable than the traditional incinerator. taiwan is a small and densely populated island located in the eastern part of asia with a total population of more than millions and a total area of , km [ , ] . over the decades, the economic improvement has led to the increasing amount of msw, causing serious environmental harms such as air quality deterioration and river water pollution. in order to speed up nation's msw treatment and resources recycling, the taiwan government has formulated policies concerning the reduction of waste volume in recent years. in correspondence, since the tepa has devised the construction of a number of msw incinerators to solve the msw problem. by , taiwan has msw incineration refuse plants in operation. the volume of msw materials and the treatment rate by incineration in are , , tons and . %, respectively, [ ] . however, incineration processes could generate many kinds of pollutants including heavy metals, acid gases, particulates and organic compounds. for instance, during the incineration process, most of the heavy metals react with oxygen and chlorine to form metallic compounds which have low boiling point. the cooling process then leads to the condensation of high volatility metallic vapors through both homogeneous nucleation and heterogeneous condensation on the surface of fly ash, therefore discharging toxic metals from msw incinerator [ , ] . nonetheless, pollutants produced by incinerators can be reduced by using air pollution control devices (apcds). in taiwan, scrubber and particulate removing devices are commonly used for toxic metal control in incineration. most incinerators use cyclone equipped with semi-dry (sd) and bag house (bg), while one uses electrostatistic precipitator (esp) and wet scrubber in series ( table ). the main function of these toxic metal emission control devices is to either remove particulates by filtration or to supply large amount of surface area with adsorbent to capture heavy metal contaminants. many reports are presented on the topic of capturing heavy metal contaminants through the injection of sorbents or additives into the apcds system [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . according to these studies, solid sorbents are used to capture heavy metals through two mechanisms: chemical adsorption and physical deposition during incineration processes. on the other hand, fluidized bed adsorber also provides good performance for heavy metals control [ , ] . furthermore, incinerators may also emit acid gas such as no x , so x , co, hcl and hf to the atmosphere during the incineration process and cause environmental damage. for instance, so x and no x react with other substances in the air to form acids, and precipitate in the forms of rain, fog, snow, or dry particles. the incinerator generates no x in two ways: ( ) n and o in air will react during the high temperature incineration process, producing no x (called as thermal no x ); ( ) nitrogen compounds found in either fuel or msw are oxidized to form no x (also called as fuel no x ) [ ] . so x are generated during the combustion of sulfur or materials containing sulfur [ ] . generally, co is generated by the incomplete combustion of any fuel containing carbon compounds. it can easily react with the hemoglobin in blood and prevent oxygen transfer; people who expose to high concentration of co may have health risk [ ] . according to the statistical data from tepa, the composition of msw in taiwan was including moisture, plastic, kitchen garbage, paper, metal and so on [ ] (see table ). most chlorine presents in the plastic and kitchen waste will be released in incineration process and react with hydrogen to form hcl. hcl and some organic compounds are the precursors of dioxins in msw incinerators [ , ] . fluorine that presents in the msw may also react with hydrogen to form hf. however, according to previous study [ ] , the concentration of hf emitted from msw incinerator is . mg/m . the concentration of hf emitted is too low compared with hcl ($ mg/m ). control of acid gaseous emissions depends on the chemical and physical characteristics of acid gases and the types of control devices. scrubbing technology, such as wet scrubbing, semi-dry scrubbing and dry scrubbing, is used to reduce acid gases in incineration systems [ ] . previous studies have demonstrated the effective control of acid gases like so and hcl by using fluidized bed adsorber, spray dryer and fabric filter in series [ , , , , ] . applying catalyst to oxidize or reduce the acid gases is in practice due to its high removal efficiency (above %) [ , [ ] [ ] [ ] [ ] [ ] . several researchers have indicated that the fundamental pathways of polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (pcdd/pcdfs) formation in incineration process, can be distinguished as the following: ( ) formation via precursor compounds; ( ) formation via the degradation of carbon species in the presence of a chlorine source (de novo synthesis) at low temperature ( - °c, especially in °c); and ( ) pyrosynthesis at high temperature, i.e. burners [ , ] . wang et al. [ ] illustrated the way of reducing pcdd/ pcdfs emissions in incineration system through: ( ) the addition of inhibitors (sulfur dioxide, ammonia, dimethylamine and methyl mercaptan), ( ) the decomposition at high temperature (secondary combustion), ( ) activated carbon injection to adsorb the pcdd/pcdfs, and ( ) the decomposition of dioxins using catalysts. the advantages of using catalyst in incineration are: it is easy to operate, requires no secondary treatment, and takes less space than traditional apcds [ ] . for catalyst oxidation, studies reported that fe o /tio , pt/al o , and v o /tio are generally used as catalyst for the dioxins oxidation [ , ] . v o -wo /tio -based catalysts are highly effective, reducing no x and decomposing dioxins at low temperatures ( °c) by % and %, respectively. this study emphasizes the history and development of incinerators in taiwan. taiwan is unique in the construction and development of incinerators in comparison with other countries, since taiwan has built more number of incinerators in a small area over a short period of time and has extensive experience in the operation of incinerations. in addition, this study also discusses the characteristics, emission, and control of the pollutants in incinerators. the main purpose of this paper is to offer taiwan's experiences in building and operating incinerators for developing countries facing problems in msw treatment. taiwan's industrialization and population growth in recent years may have affected nation's consumption habits and thus led to the increase of msw generation. (as shown in tables and ). according to table , over the past years, the population in taiwan has increased from , , to , , people, while the gross domestic product (gdp) per capita increased from usd$ to usd$ , [ ] . with the increases in population and economic activity, the amount of msw generation also increases continuously until year . however, the trend reverses as the amount of msw generated decreases between the years and . since year , the amount of msw generated per capita per day had less than kg due to the policy of resource recycling. ''the policy of resource recycling" means people should separate the useful resources, such as paper, metal, plastic, and kitchen garbage, from msw before incineration in taiwan since . according to table , the rate of resource recycling increased from . % to . % during the years - (january-october). moreover, as shown in table , the amount of msw generated was decreased from , , tons to , , tons. the results indicate that the policy of resource recycling resulted in the reducing of the amount of msw, which comparing with those of the past years. analysis of msw composition is complicated due to the mixture of various waste materials. therefore, controlling the compositions of msw is important for incinerator operation. basically, the composition of msw can be divided into two parts; one is combustible waste, including paper, fiber, rubber, kitchen waste, and plastic; and the other is noncombustible waste like metal, glass and moisture. table describes the breakdown of the msw composition in taiwan and the basic chemical analysis of waste in table the operation profiles of the incinerators in taiwan table . according to data on the chemical analysis of msw between the period of and , table shows a decreasing trend in the proportion of ash and organic chlorine, and an increasing percentage of sulfur in msw composition. in the meantime, other composition items presented in table indicate a stable trend. the trends show that people in taiwan have become more concerned with the clearance of msw and placed more importance on resource recycling. for instance, while the percentage of the combustible waste increased annually, the percentage of noncombustible waste became less owing to the separate collection of particular categories of waste from msw over the years. the statistical data presented in table suggest the success of taiwan's policies in promoting resource recycling. after the construction of the first incinerator in , incineration began to be a trend in the treatment of msw in taiwan gradually. as shown in table , until october , approximately . % of msw was treated by incineration, while resource recycling and landfill accounted for . % and . %, respectively. the rate of incineration and resource recycling in msw treatment increased significantly from to . contrary, the rate of landfill decreased significantly and now only accounts for a small fraction of msw treatment in taiwan. this phenomenon indicates that incineration had been considered as the main treatment method for msw in taiwan at the present. the data depicted in table describes the rate of garbage disposal, which increased from . % to . % in the period of to october . as we can see, the rate of landfill from to (including both general landfill and sanitary landfill) decreased significantly due to the construction and operation of incinerators. compared with landfill, incineration takes less space, provides faster treatment of msw, materials, and is more efficient than landfill. therefore, incineration can be considered as the best alternative to landfill for a densely populated country like taiwan. however, in addition to waste treatment techniques, factors like government policies, public's level of environmental awareness, and resource recycling (including resource recycling, waste bulk recycling, and wastes food recycling) will also play an important role in the future treatment of msw. taiwan had been an agricultural society for a long time, and during this period garbage was usually composted or burned outdoors. with the population increasing and the economy rising, the amount of garbage also increased, especially in big cities like taipei [ ] . garbage placed outdoors generates waste water, foul smell and disease germs. as a result, the phenomenon may make people feel uncomfortable and expose them to the risk of infection and disease [ ] . due to land scarcity and high density of population, it was imperative for taiwan to develop an efficient treatment for the large amount of wastes generated everyday. since it was difficult for taiwan to find space for additional landfill sites, the tepa decided to look for an alternative in waste treatment in order to meet the urgent need of taiwan. as a result, the tepa decided in to adopt incineration as the primary method for waste treatment and landfill as secondary. consequently, in , the tepa proposed a plan called ''construction project for msw resource recovery plants [ ] " for msw treatment. the tepa first planned to construct large scales msw incinerators, and incinerators had been constructed as a result. in the second during the past five years, the msw incinerators produced , , - , , kwh of electricity in taiwan [ ] . during incineration, the heat energy can be transferred by the steam through the turbine in order to generate power. the power sold rate increases from . % to . % during the period of - , with the highest power sold rate of . % in (fig. ) . the average power sold rate in the past five years is about . %. although incinerators were constructed for the purpose msw treatment, residual products such as ashes, waste water and other pollutants may become new problems to the environment. without good design and operation for the apcds, it may be difficult for incineration processes to meet the environmental protection standards and therefore incinerators may emit hazardous compounds during the processes [ , , , ] . the statistics presented in table gives the trend of pollutant emission, and the operating condition of each incinerator along with msw regulations and emission standards. consequently, this study discusses statistics about pollutants like acid gases, heavy metals, and organics captured by the apcds in incineration system during the past five years. based on the statistics of the emission of pollutants from all incinerators in taiwan, pb, cd and hg constitute most of the heavy metals detected due to their high quantities and relatively low boiling point. according to the emission regulations of incinerators in taiwan [ ] , the environmental protection standards of these three heavy metals (pb, cd and hg) were found to be . , . and . mg/nm , respectively. fig. shows the trend of heavy metals emitted from each incinerator in taiwan during - . due to the improvement of flue gas treatment instrument/technique and the policy of resource recovery, all incinerators met the regulations of tepa in heavy metal emission. many studies have indicated that conventional air pollution control devices such as bag house, wet, semi-dry, and dry scrubber also can effective in collecting metallic particulates. as the improvement of instruments, the emission of heavy metals should be reduced gradually by year. further, metallic materials such as waste metal containers, and waste dry cell batteries commonly exist in msw. before incineration, separating these metallic materials from msw can reduce the concentration of metals in flue gas. therefore, this led the emission of heavy metals decreased. the average concentration of heavy metals decreased from to . it demonstrates that the control of heavy metals emitted from incinerators in taiwan improved every year. fig. compares the emission concentration among three metals with the new environmental protection standards along with previous one. comparing both regulations, new environmental protection standards were much stricter than the previous one (table ) . with more stringent regulations, people in taiwan became more concerned about the pollutants, and this inevitably led to the improvement of incinerator operation and preservation techniques. concentration of no x in some incinerators was decreased. the average concentration range of no x emission was found to be - ppm. the emission standards of toxicity equivalent (teq) were used to measure dioxins and other compounds. fig. indicates that all incinerators in taiwan meet the emission standards of toxicity equivalent ( . ng-teq/ nm ) for dioxins. from the figure, the highest concentration of dioxins was observed in , with a record of . ng-teq/nm . the average value of dioxins emission in the past five years was found to be . ng-teq/nm , performed a steady trend. therefore, incinerators in taiwan performed well in the control of dioxins. in taiwan, incinerators applied activated carbon to adsorb the pcdd/pcdfs, except in mucha district where selective catalyst reduction (scr) system was used as a new technology for reducing dioxins emissions [ ] . in the past, the scr technology was used for deno x system, a thermal treatment which usually operates under °c (dioxins generated easily in this temperature). however, some researchers reported that scr can also be used for a dedioxins system [ , ] . chang, et al. [ ] [ ] [ ] compared the dioxin control of two incinerators in taiwan in which one used activated carbon injection (aci) while table comparisons of the previous/presently regulations of emission limit of heavy metals from large scale incinerators in taiwan incineration is projected to become popular in the coming years due to waste treatment, energy recovery and the reduction of viruses from contagious diseases. previously the purpose of incineration was primarily waste treatment followed by energy recovery; however, the order of preferences for the functions of incinerators has now changed to energy recovery, waste treatment, and the elimination of viruses. the preferences may change again years from now to the order of preferences like the elimination of viruses and bacteria, energy recovery, and waste treatment. msw, medical waste, and poultry farm waste may produce different bacteria and viruses. these viruses may lead to the generation of different contagious diseases like severe acute respiratory syndrome (sars), a rare contagious disease like bird flu. incineration treatment of msw and medical waste can avoid these infectious viruses and generation of energy for public and industrial utilization. the authors are optimistic that taiwan will play an important role in the development of incinerators and incineration tech- nology for both underdeveloped and developing countries in the future due to its vast experience in construction and operation of incinerators. since taiwan has paid great attention to msw incineration, and this has led to the rapid development in incineration technology. taiwan built incinerators in less than two decades, all running successfully in the treatment of msw and the production of energy. from the historical information and data presented here, most of taiwan's msw is treated by incineration. emission characteristics of incineration in taiwan showed that heavy metals, acid gases and dioxins are the major pollutants, and shed light on how these pollutants can be controlled by maintaining stable conditions. the amount of pollutants emitted during the past few years follows a decreasing trend, and the level of all emitted pollutants meet the environmental regulations of taiwan. in the future, there is a possibility that developing countries may adopt incineration technology for the treatment of msw and generation of renewable energy. moreover, because incineration of medical waste generates sterile and non-hazardous end products, switching from landfills to incineration may also minimize the risk of contamination and infection in developing countries. concetration (ppm) bioenergy from landfill gas (lfg) in taiwan comparison of selected aerobic and anaerobic procedures for msw treatment investigations on mechanical biological treatment of waste in south america: towards more sustainable msw management strategies chemical and mineralogical evaluation of slag products derived from the pyrolysis/melting treatment of msw analysis of using gasification and incineration for thermal processing of wastes pollutants in incineration flue gas combustion and incineration processes: applications in environmental engineering waste to energy in the field of thermal processing of waste taiwan land survey bureau, ministry of the interior (tlsb) taiwan area, roc municipal solid waste -incineration, air pollution control and ash management, resources, conservation and recycling the effect of operating conditions on the capture of metals with limestone during incineration metal capture during fluidized bed incineration of solid waste metal capture during fluidized bed incineration of wastes contaminated with lead chloride metal volatilization and separation during incineration behaviour, capture and inertization of some trace elements during combustion of refuse-derived char from municipal solid waste the adsorption characteristics of heavy metals by various particle sizes of mswi bottom ash the simulation of condensation removal of a heavy metal from exhaust gases onto sorbent particles screening of sorbents and capture of lead and cadmium compounds during sewage sludge combustion the major species of heavy metal aerosol resulted from water cooling system and spray dryer system size distribution of heavy metal aerosols in cooling and spray dryer system the utilization of catalystsorbent in scrubbing acid gases from incineration flue gas effects of different additives on the performance of semi-dryer during incineration process experimental testing of spray dryer for control of incineration emissions the adsorption of pahs and heavy metals on modified calcium hydroxides in a dry desulfurization process the capture of heavy metal from incineration using the spray dryer integrated with the fabric filter with different additives simultaneous control of heavy metals and organics using a fluidized bed adsorber control of acid gases using a fluidized bed adsorber characteristics of continuous analyzers for nitrous oxide in flue gas from municipal incinerators hazardous waste management problem: the case for incineration formations and controls of hcl and pahs by different additives during waste incineration influences of chlorine content on emission of hcl and organic compounds in waste incineration using fluidized beds emissions from a controlled fire in municipal solid waste bales reaction characteristic of ca(oh) . hcl and so at low temperature in a spray dryer integrated with a fabric filter simultaneous control of acid gases and pahs using a spray dryer integrated with a fabric filter using different additives catalytic treating of so , no, hcl from incineration flue gas over activated carbon supported metal oxides study of so adsorption and thermal regeneration over a spent activated carbon-supported copper oxide catalyst carbon material as catalyst supports for so oxidation: catalytic activity of cuo/ac catalytic oxidization of so from incineration flue gas over bimetallic cu-ce catalysts simultaneous treatment of organic compounds, co and no x in the incineration flue gas by three-way catalysts desorption behaviour of polychlorinated dibenzo-p-dioxins/dibenzofurans on a packed fly ash bed comparative evaluation of techniques for controlling the formation and emission of chlorinated dioxins/furans in municipal waste incineration formation and removal of pcdd/fs in a municipal waste incinerator during different operating periods chemical inhibition of pcdd/f formation in incineration processes low temperature decomposition of pcb by tio -based v o /wo catalyst: evaluation of the relevance of pcdf formation and insights into the first step of oxidative destruction of chlorinated aromatics low temperature decomposition of pcdd/pcdf, chlorobenzenes and pahs by tio -based v o -wo catalysts environmental protection statistics monthly taiwan directorate-general of budget, according and statistics (tdgbas) human exposure to heavy metals in the vicinity of portuguese solid waste incinerators -part : biomonitoring of pb, cd and hg in blood of the general population tepa, construction project for msw resource recovery plants monitoring internal exposure to metals and organic substances in workers at a hazardous waste incinerator after years of operation waste incinerator air pollutant emissions standards characterization of dioxin emissions from two municipal solid waste incinerators in taiwan reducing pcdd/f formation by adding sulfur as inhibitor in waste incineration processes destruction of pcdd/fs by scr from flue gases of municipal waste incinerator and metal smelting plant key: cord- -xcrshplk authors: yang, nan-ping; lee, yi-hui; lin, ching-heng; chung, yuan-chang; chen, wen-jone; chou, pesus title: utilization of and direct expenditure for emergency medical care in taiwan: a population-based descriptive study date: - - journal: j epidemiol doi: . /jea.je sha: doc_id: cord_uid: xcrshplk background: we surveyed the emergency medical system (ems) in taiwan to provide information to policymakers responsible for decisions regarding the redistribution of national medical resources. methods: a systematic sampling method was used to randomly sample a representative database from the national health insurance (nhi) database in taiwan, during the period from to . results: we identified , , , , , , , , and , emergency room visits in , , , , and , respectively. there were more males than females, and the majority of adults were younger than years. diagnose of injury/poisoning was the most frequently noted diagnostic category in emergency departments (eds) in taiwan. there were , ( . %) and , ( . %) patients with and concomitant diagnoses, respectively. there was a significant association between advanced age and the existence of multiple diagnoses (p < . ). with the exception of the ill-defined symptoms/signs/conditions, the two most frequent diagnoses were diseases of the circulatory system and diseases of the respiratory system in patients aged years or older. on average, treatment-associated expenditure and drug-associated expenditure in taiwan eds averaged nt$ , ($ . ) and nt$ ($ . ), respectively, which was equal to . % and . % of the total ed-associated cost. general ed medical expenditure increased with patient age; the increased cost ratio due to age was estimated at % per year (p < . ). conclusions: the frequency of major health problems diagnosed at ed visits varied by age: more complicated complaints and multiple diagnoses were more frequent in older patients. in taiwan, the ed system remains overloaded, possibly because of the low cost of an ed visit. the emergency department (ed) is a vital component of the health care "safety net". it is important for a developing country to establish a comprehensive emergency medical system; however, ed overcrowding and ambulance diversion have become increasingly significant national problems over the last decade. a recent survey revealed that % to % of hospital ed directors report that overcrowding is a problem; , it is a problem not limited to large urban centers, or academic and teaching hospitals. overcrowding in ed treatment areas threatens public health by compromising patient safety and jeopardizing the reliability of the entire emergency care system. one report noted that the problem of overcrowding was due to inappropriate use of emergency services by those without urgent conditions, that it is probably cyclical, and that it requires no specific policy response. in addition, the aging of the population has contributed to the increased number of visits, because older patients have higher visit rates. as compared with younger persons, older adults use emergency services at a higher rate, their visits are more urgent, and their stays in the emergency department are longer. as the elderly population grows, the emergency medical system (ems) must prepare for an increase in the number of older adults seeking treatment. in the united states, the average rate of ems utilization by the elderly (persons aged ≥ years) was more than times that of younger patients. despite these problems in the ems, the effort to improve the effectiveness of the ems is justified because emergency medicine offers many tools for improving public health. in , the average number of daily ed visits nationwide in taiwan was , . this increased to , in , , in , , in , , in , and , in . however, the numbers of accredited hospitals in taiwan decreased from , to , , , , and , respectively, in the same years. ed overcrowding has been a continuing problem in taiwan, as has the uneven distribution of ed visits. in , for example, there were tertiary medical centers in taiwan, and the average number of ed visits at these centers was . cases per day- . times higher than the national average. it is clear, therefore, that a nationwide descriptive study of ems utilization is needed in taiwan. we conducted an epidemiologic survey of ems in taiwan in order to provide sufficient information for policymakers to make decisions regarding the redistribution of national medical resources. taiwan launched a single-payer national health insurance (nhi) program on march , . as of , . million of taiwan's . million-person population were enrolled in this program. foreigners in taiwan are also eligible to enroll this program. therefore, taiwan's nhi plan has accumulated data on . million people and their claims, the largest set of such data in the world. in order to respond to current and emerging health issues rapidly and effectively, the national health research institute (nhri), in cooperation with the national health insurance bureau (nhib), has established an nhi research database. the nhri safeguards the privacy and confidentiality of subjects and routinely transfers health insurance data from the nhib to health researchers for analysis, with the aim of improving the health of taiwan's citizens. we used a systematic sampling method to randomly sample a representative database from the entire nhi research database. the size of the subset for each month was determined by the ratio of the amount of the data for that month to that for the entire year. then, systematic sampling was performed for each month, and a representative subset was randomly chosen. this sampling database was constructed by combining the subsets of the months. the sampling database for "ambulatory care expenditures by visits" was constructed first, and then analysis of the related observations for "details of ambulatory orders" was performed. the sampling database for "ambulatory care expenditures by visits" was . % of the size of the entire database. quality control of medical services and coding in taiwan's nhi system the nhib has established a uniform system to control the quality of medical services and codes. under the rules of this system, if medical services provided to beneficiaries by the contracted medical care institutions are judged by the professional peer review committee to be incompatible with the provisions of the nhi act, such expenses must be borne by the contracted medical care institutions. in cases where drugs, laboratory tests, or diagnostic examinations are provided by third-party medical care institutions in accordance with the physician's instructions, and the insurer-after conducting an examination according to established rulesdecides not to pay the benefits because the physician's instructions were improper, the expenses incurred must be borne by the medical institution where the physician practices. when disputes arise, there is a disputes settlement board, established under the national health insurance act, which settles disputes arising from cases approved by the insurer and raised by the insured, group insurance applicants, or the contracted medical care institutions. emergency cases served by the nhi systems were recorded within the database of "ambulatory care expenditures by visits," and were classified into case types. one case type concerned with emergency medical services and another concerned with "emergency dentist visits" do not concern the present research. cases during the period of to that were classified as a "medical emergency" were included in the analysis. descriptive statistics are presented as numbers of cases, percentages, and means with standard deviation (sd). pearson's chi-square (χ ) test, analysis of variances (anova), and post-hoc anova (scheffé test) were used to evaluate the significance of differences; the mantel-haenszel (m-h) χ test was used to examine trends. all statistical calculations were performed using the statistical package for social sciences for windows (spss for windows . ). based on the above inclusion criteria, there were , , , , , , , , and , cases identified in , , , , and , respectively. as calculated from the annual ed visits, the sampling rates were . %, . %, . %, . %, and . % respectively. table shows the detailed sex and age distributions of the , randomly sampled subjects who visited the ed during - in taiwan. there were more males than females, and the majority of adults were younger than years. the distribution of final principal diagnoses at all visits was determined by using the international classification of diseases, ninth revision, clinical modification (icd- -cm), as shown in table . diagnoses of injury or poisoning; ill-defined symptoms, signs, or conditions; and diseases of the respiratory system were the most common diagnostic categories in emergency units in taiwan. there were , ( . %) and ( . %) cases noted with and concomitant categorical diagnoses, respectively. these emergency visitors with multiple diagnoses were analyzed and the results are shown in figure a and b. the proportion of patients with multiple diagnoses significantly increased with age (p < . , by the m-h χ test), and subjects aged years or older had the highest percentage of multiple diagnoses ( %; figure a ). the most common diagnostic category among this subgroup was that of ill-defined symptoms, signs, or conditions, which was noted in . % of cases with multiple diagnoses. among these cases, the other diagnoses were calculated and ranked ( figure b ). the most common second diagnosis was diseases of the digestive system (diagnosis category x), followed by diseases of the respiratory system (diagnosis category ix). the rank of diseases of the circulatory system (diagnosis category viii) markedly increased with age, and was the most common second diagnosis of patients aged years or older, along with a diagnosis of ill-defined symptoms, signs, or conditions. in the present study, there were , , , , , , and , cases in the age strata of under , - , - , and years or older, respectively. the most common disease categories among these different age groups were calculated and are shown in table . in cases under years of age the greatest number of visits was due to diseases of the respiratory system, followed by injury/poisoning. with the exception of the diagnostic category of ill-defined symptoms, signs, or conditions, the most common disorders were injury/ poisoning and diseases of the digestive system in those aged - years and - years, and diseases of the circulatory patients ( . %) received multiple diagnoses from the disease categories. there was a significant difference between the youngest and oldest strata in the proportion of patients with multiple diagnoses. (b) among these patients with multiple diagnoses, the most common diagnosis was ill-defined symptoms, signs, or conditions, which was coded in . % of cases. for those in this subgroup, the ranks of the other diagnosis categories are shown by patient age system and diseases of the respiratory system in those aged or older. the distributions of the most common diagnostic categories among the age strata were significantly different (p < . , pearson's χ test). in particular, we noted a significant increase with age in diagnostic categories: endocrine/ immune associated disorders; diseases of the circulatory system; diseases of the genitourinary system; and ill-defined symptoms, signs, or conditions (p < . , m-h χ test). the direct medical expenditure (ie, cost) on emergency medicine provision in taiwan was also investigated (table ) . on average, a visit to a taiwan ed cost nt$ (us$ . ) for insurers. the total cost increased significantly from to ; the annual rate of increase was estimated at . % (p < . , examined by simple linear regression). diagnosisassociated expenditure is managed by the taiwan government. in addition, the average treatment-associated expenditure and drug-associated expenditure in taiwan eds were nt$ , ($ . ) and nt$ ($ . ), which represented . % and . % of the total ed-associated cost, respectively. to investigate the effect of age on ed medical expenditure, treatment-associated cost and drug-associated cost were calculated for the different age strata (figure ). treatmentassociated cost markedly increased with age, and the increase in cost due to age was estimated at % per year (p < . , tested by simple linear regression). although drug-associated cost also significantly increased with age, the difference was noted only in patients older than years (measured by posthoc anova). the international quality indicator project (iqip) of the center for performance science (cps) compares the performance of various indicators of healthcare. data are supplied by individual organizations and aggregated by cps. in , facilities, including international (non-us) facilities, were included in the aggregated, quarterly report. the hospitals located outside of the united states were in europe (united kingdom, belgium, netherlands, germany, austria, and portugal) and asia (taiwan and singapore). according to the acute-care indicators report for the fourth quarter of , aggregated descriptive statistics showed that unscheduled returns to the ed within hours and hours represented . % and . % of ed visits in the united states, . % and . % of visits in europe, and . % and . % of visits in asia. interestingly, these indicators of unscheduled revisits in ed were positively associated with the amount of ed utilization. the reported denominators (ie, ed visitors per hospital) were approximately , , , , and , cases per month in the united states, asia, and europe, respectively. according to data from the us national hospital ambulatory medical care survey (nhamcs), children (< years) and seniors ( + years) represented % and % of all in an analysis of the category of injury/poisoning, young and middle-aged adults were the majority of those treated in eds for injuries ( . % and . % in the age groups of - and - years, respectively). in taiwanese eds, the number of patients diagnosed with multiple co-morbidities (> major diagnostic categories) markedly increased with age, and treatment of the elderly figure . the cost of treatment was significantly positively associated with age (p < . , simple linear regression). the cost of medication also increased with age (p < . , simple linear regression), but the difference was significant only between patients aged - years and those aged years (examined by anova post-hoc test) table . medical expenditure in emergency departments in taiwan taiwan a survey performed at community hospitals in the us state of michigan revealed that for all emergency department visits, the average direct cost was $ . ; furthermore, the average direct costs were $ . for non-urgent visits, $ . for semi-urgent visits, and $ . for urgent visits. as compared with the results of the above studies, the average cost of ed treatment in taiwan was found to be much lower: nt$ ($ . ). taiwan's health insurance program, which began in , is a single-insurer system with a cost containment policy that mandates a fixed co-payment by the insured person for ambulatory medical services. this policy probably resulted in the increase in daily ed utilization ( % from to ). the lower medical cost for ed treatment in taiwan reflects the fact that a lower percentage of total medical insurance expenditure was spent on emergency medical care. data from the national health insurance of taiwan on annual total medical insurance costs and ed-associated costs indicate that the percentage of the total nhi expenditure that was spent on nhi medical emergency care was . % in each of the years from to and . % in . in another retrospective study using data from the us state of oregon's medicaid program, monthly ed-associated expenditures averaged $ . ( % confidence interval, . to . ) per person, representing . % of total medical expenditure. the average national health expenditure (nhe) per capita was $ in usa and only $ in taiwan. if nhe is compared to gross domestic product (gdp), the nhe/gdp ratio was lower in taiwan ( . %) than in the united states ( . %), germany ( . %), france ( . %), portugal ( . %), netherlands ( . %), united kingdom ( . %), and even japan ( . %) in . taken together, these findings show that although the number of ed visits in taiwan is high, the cost of ed treatment is lower than in other countries. in australia, a retrospective analysis of , probabilistically linked emergency hospital admissions and death records showed that hospital and ed overcrowding was associated with increased mortality. commonly studied causes of crowding included nonurgent visits, "frequentflyer" patients, influenza season, inadequate staffing, inpatient boarding, and hospital bed shortages. commonly studied effects of crowding included patient mortality, transport delays, treatment delays, ambulance diversion, patient elopement, and financial hardship. commonly studied solutions of crowding included additional personnel, observation units, hospital bed access, nonurgent referrals, ambulance diversion, destination control, crowding measures, and queuing theory. a consideration of these options from the latest systematic review would be helpful in assisting the government of taiwan's efforts to initiate essential studies, organize all associated facilities, and formulate a comprehensive policy for ems. this study did possess some limitations. first, the study used a database that was developed from the nhi database in taiwan, within which all medical data (including final diagnoses, treatments, and medications) were entered by medical personnel and payments for all procedures were determined by the medical facilities. the accuracy of diagnosis and quality of medical services was monitored by nhib, but there was no additional confirmation of these data. another limitation of the study was that fewer subjects were available for sampling in , because ed visits decreased by % to % during the sars epidemic, a situation that persisted for months after the end of the epidemic. , finally, the value of the taiwanese currency fluctuated considerably during the years from to , which makes it more difficult to interpret the currency conversions we have utilized. the principal diagnoses for patients visiting eds varied by age. in addition, overloading of the ed system in taiwan is still evident, possibly because of the low cost of an ed visit. implementing the widespread primary care reforms necessary to meaningfully reduce ed utilization will be complex and expansive, although they are likely to benefit both patients and the health system. complicated complaints and multiple diagnoses occurred more frequently in the elderly, and this should be considered when policymakers plan changes to taiwan's emergency system and resource allocation. strategies to improve continuity of care may result in lower ed use and reduced health care costs. such strategies might prove superior to current managed care policies that attempt to control costs by denying access to emergency care. recently, a group-visit model has been studied and deemed effective in improving patient and physician satisfaction, quality of care, quality of life, and in decreasing visits to emergency departments and specialists. therefore, we believe that additional public education regarding preventive medicine and increased activities geared toward community health promotion would prove suitable and effective in decreasing ed crowding in taiwan. emergency department overcrowding in the united states: an emerging threat to patient safety and public health emergency department overcrowding and ambulance diversion: the impact and potential solutions of extended boarding of admitted patients in the emergency department frequent overcrowding in u.s. emergency departments frequency, determinants and impact of overcrowding in emergency departments in canada: a national survey ambulatory medical care utilization estimates for older adults in the emergency department: a systematic review of patterns of use, adverse outcomes, and effectiveness of interventions the epidemiology of emergency medical services use by older adults: an analysis of the national hospital ambulatory medical care survey the globalization of emergency medicine and its importance for public health health and national health insurance annual statistics information service, doh, taiwan: medical services report health and national health insurance annual statistics information service, doh, taiwan: trend of statistics of nhi health and national health insurance annual statistics information service, doh, taiwan: medical annual report taiwan joint commission on hospital accreditation: taiwan quality indicator project: acute care quarterly analysis report th quarter . indicator a : unscheduled returns to the ed national academy of sciences. the future of emergency care in the united states health system national hospital ambulatory medical care survey: emergency department summary epidemiologic patterns of injuries treated in ambulatory care settings continuity of primary care and emergency department utilization among elderly people effect of population aging on emergency department speed and efficiency: a historical perspective from a district general hospital in the uk the cost of an emergency department visit and its relationship to emergency department volume the cost of visits to emergency departments how much does emergency department use affect the cost of medicaid programs? doh, taiwan: nhe and nhe/gdp report the association between hospital overcrowding and mortality among patients admitted via western australian emergency departments systematic review of emergency department crowding: causes, effects, and solutions impact of a severe acute respiratory syndrome outbreak in the emergency department: an experience in taiwan declining emergency department visits and costs during the severe acute respiratory syndrome (sars) outbreak rising utilization of us emergency departments: maybe it is time to stop blaming the patients the effect of continuity of care on emergency department use group visits: a qualitative review of current research acknowledgment this study was supported by the grants from the taoyuan general hospital, department of health, executive yuan, taiwan (doh -ho- ). key: cord- -ewx xhrb authors: rudge, james w.; hanvoravongchai, piya; krumkamp, ralf; chavez, irwin; adisasmito, wiku; ngoc chau, pham; phommasak, bounlay; putthasri, weerasak; shih, chin-shui; stein, mart; timen, aura; touch, sok; reintjes, ralf; coker, richard title: health system resource gaps and associated mortality from pandemic influenza across six asian territories date: - - journal: plos one doi: . /journal.pone. sha: doc_id: cord_uid: ewx xhrb background: southeast asia has been the focus of considerable investment in pandemic influenza preparedness. given the wide variation in socio-economic conditions, health system capacity across the region is likely to impact to varying degrees on pandemic mitigation operations. we aimed to estimate and compare the resource gaps, and potential mortalities associated with those gaps, for responding to pandemic influenza within and between six territories in asia. methods and findings: we collected health system resource data from cambodia, indonesia (jakarta and bali), lao pdr, taiwan, thailand and vietnam. we applied a mathematical transmission model to simulate a “mild-to-moderate” pandemic influenza scenario to estimate resource needs, gaps, and attributable mortalities at province level within each territory. the results show that wide variations exist in resource capacities between and within the six territories, with substantial mortalities predicted as a result of resource gaps (referred to here as “avoidable” mortalities), particularly in poorer areas. severe nationwide shortages of mechanical ventilators were estimated to be a major cause of avoidable mortalities in all territories except taiwan. other resources (oseltamivir, hospital beds and human resources) are inequitably distributed within countries. estimates of resource gaps and avoidable mortalities were highly sensitive to model parameters defining the transmissibility and clinical severity of the pandemic scenario. however, geographic patterns observed within and across territories remained similar for the range of parameter values explored. conclusions: the findings have important implications for where (both geographically and in terms of which resource types) investment is most needed, and the potential impact of resource mobilization for mitigating the disease burden of an influenza pandemic. effective mobilization of resources across administrative boundaries could go some way towards minimizing avoidable deaths. recent experience from the -h n pandemic highlights how health system capacities, even in developed countries, can be stretched by relatively mild pandemic scenarios [ ] [ ] [ ] . indeed, the vast majority of previous health system analyses in relation to pandemic influenza have focused on developed countries [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , while the capacity of health systems in low and middle income countries remains largely unstudied. paradoxically, understanding outbreak response capacity in low and middle-income countries is arguably of greater importance than that in developed countries, not only because health systems are weaker [ ] , but also because many of these countries are in regions where the risk of emerging infectious diseases is highest [ ] . moreover, these countries may suffer disproportionately because of associations between morbidity, pandemic influenza and poverty [ ] . proposed strategies for pandemic preparedness in many countries frequently focus on development and acquisition of pandemic vaccines and stockpiling and distribution of antiviral drugs [ ] [ ] . in the southeast asia region, while surveillance and outbreak response capacities have been strengthened in hope of early detection and control of outbreaks, there has been much less investment into preparing health systems for pandemic mitigation [ ] . modeling studies have been used to inform optimum intervention strategies for responding to pandemic influenza, but often neglect to take into account feasibility of health systems to implement such a response and the potential impact of resource shortages on the pandemic burden. investigation of health system capacity in east and southeast asia is of particular interest, not only given the fertile conditions for the emergence and spread of new diseases [ , ] , but also the wide socio-economic inequalities within the region, and focus of investment by the international community into pandemic influenza preparedness [ ] . resource gaps for a pandemic response are likely to be wide and vary greatly between and within countries in asia [ ] . but exactly how wide are these gaps, what are the consequences of the gaps in terms of the pandemic disease burden, and to what extent could these consequences be mitigated by improving resource allocation and mobilization? to address these questions, we conducted a health systems analysis across six asian countries and territories with widely varying socioeconomic conditions: cambodia, indonesia, lao pdr, taiwan, thailand and vietnam. in this analysis, mathematical modeling and health system resource data collected across the six territories were used to estimate and compare, within and across countries, the resource gaps, and potential consequences of those gaps in terms of expected mortalities, for a hypothetical pandemic influenza scenario. this study was conducted as part of the asiaflucap project (www.asiaflucap.org), the overall aim of which is to conduct health systems analyses to support capacity development for responding to pandemic influenza across six countries and territories in asia, specifically: cambodia, indonesia, lao pdr, taiwan, thailand and vietnam. for this comparative analysis we focus on four key health system resources: antiviral drugs (specifically oseltamivir), hospital beds, mechanical ventilators and healthcare workers (doctors and nurses), chosen due to their critical importance for responding to pandemic influenza. these resources, along with over other resource items relating to health system infrastructure, equipment, materials, and human resources, were selected through a systematic literature review and a delphi consensus process by a panel of experts, as described in [ ] . quantities of these resource items were enumerated during march to september through questionnaires administered to hospitals and health offices in all districts of each of the six study countries (except indonesia, where data were collected only from districts in jakarta and bali due to the vast geographic scale of the country). additional questionnaires were sent to ministries of health to capture central stockpiles. we received % response rates from hospitals and district health offices in cambodia. overall response rates from district health offices were more than % in viet nam and indonesia (jakarta and bali), % in lao pdr, % in taiwan, and % in thailand. the response rates for hospital questionnaires were slightly lower at % for indonesia and vietnam, % for lao pdr, and approximately % for thailand and taiwan. data from the questionnaires were double-entered into an excel database. missing values, due to non-responses or incomplete questionnaires, were extrapolated using linear prediction models, specific to each country and resource item, based on a number of district characteristics such as total number of hospital beds or public hospital beds, population size, and geographic location (region/province). for oseltamivir and ventilators, two-step models were used to first estimate the likelihood of having any oseltamivir or ventilators, and then to predict the number of these items. extrapolation of missing data was carried out in stata version . in order to estimate health system resource needs and gaps for a pandemic influenza scenario, we used a mathematical model previously developed as part of the asiaflucap project to simulate the transmission dynamics of a pandemic influenza outbreak [ ] . full details and equations of the model can be found in [ ] , and are summarized in text s . briefly, the model is based on a deterministic seir (susceptible-exposed-infectious-recovered/removed) model described by differential equations tracking number of people in each compartment over time. given that the primary aim of this analysis was to provide relative estimates of resource gaps within and across countries, rather than to accurately simulate the spread of pandemic influenza throughout each country, the model structure was kept relatively simple, with homogeneous mixing patterns and no age-structure assumed within the modeled population. however, novel complexity is incorporated through making parameters describing the clinical course of infected individuals conditional upon the availability of certain key health system resources (antivirals, beds, and ventilators). thus we could obtain relative indications of the consequences of resource shortages on the pandemic disease burden, specifically in terms of ''avoidable deaths'', which we define as deaths that would not have occurred in the presence of sufficient resources. the infectious compartment of the model was subdivided into three groups based on clinical severity: asymptomatic, mild and severe infections. all asymptomatically and mildly infected patients were assumed to recover, while severe cases were at risk of death and were assumed to need antiviral treatment and hospitalized care, although whether they received either of these depended upon the availability of oseltamivir and hospital beds, respectively. treatment with antivirals and hospitalization were assumed to reduce the infectious period and the probability of death for severe cases. furthermore, a proportion of severe cases are assumed to require mechanical ventilation, which they will receive as long as ventilators are available, otherwise these cases would die. the model parameters describing transmissibility and clinical severity were chosen based on data from the -h n pandemic, with a basic reproduction number of . [ ] [ ] . under the parameter values chosen (see table s and [ ] ), in a population with sufficient resources (i.e. when there are no shortages of oseltamivir, hospital beds, or ventilators), the scenario predicts an overall attack rate of . %, a clinical attack rate of . %, a peak prevalence (of symptomatic cases) of . %, and a case fatality rate of . %. in the absence of any resources, the case fatality rate is substantially higher at . %, while attack rates and peak prevalence remain very similar. estimating resource needs, gaps, and associated mortality in our baseline scenario, resource gaps were estimated assuming that % of ''general'' hospital resources (beds, ventilators and human resources) are available for care of pandemic influenza cases, with the remaining % required for maintaining essential healthcare services, as in a previous pilot study for thailand [ ] , and based on previous reports [ ] [ ] . we also assumed that, in the event of a pandemic all available oseltamivir doses would be dedicated to severe influenza cases. these assumptions regarding resource spare capacity and oseltamivir usage were relaxed in a multivariate uncertainty analysis (described below). the resource data were aggregated at provincial level for all countries except taiwan, where they were aggregated at county level, and indonesia, where the data were kept at district level. (counties in taiwan and districts in indonesia are of comparable population size to the provinces of the other four countries.) we then ran the model separately for each province (lao pdr, cambodia, thailand, vietnam), county (taiwan) and district (indonesia), with the appropriate resources for each of these administrative areas, assuming a closed population and that resources could not be shared between these areas in a timely manner. for the purposes of narrative flow, we henceforth use the term ''province'' for counties in taiwan. all simulations started with one mild case entering a completely susceptible population. in addition to running the model with the available resources, based on the survey data, we also ran the model with unlimited resources, in order to calculate resource needs, and thus also the resource gaps (or indeed surpluses) by comparing with the resource availability data. the needed number of hospital beds, ventilators and humans resources were estimated from the peak number of cases requiring hospitalization and ventilation, while the needed number of oseltamivir doses was calculated from total number of severe cases occurring over the duration of the outbreak (full details on assumptions of resource depletion rates are detailed in [ ] , and summarized in text s ). by comparing the number of deaths predicted by simulations with sufficient resources with those from simulations using actual resource data, we also estimated the number of deaths due to resource gaps, which we term as ''avoidable deaths''. a multivariate uncertainty analysis was conducted to approximate uncertainty surrounding avoidable deaths in light of uncertainty in resource spare capacity and effectiveness, which may vary between settings. specifically, the proportion of ''general'' healthcare resources within each province/district that would be available to care for pandemic influenza patients was allowed to vary between - %, and parameters describing the effectiveness of each resource for reducing the risk of death in cases requiring those resources were allowed to vary independently between a wide range of - %. we also explored the impact of relaxing the assumption that oseltamivir administration is restricted to severe influenza cases, by allowing between - % of mild cases to be treated. one hundred combinations of values were chosen randomly from these ranges using latin hypercube sampling, and simulations were run using each combination. the medians, interquartile ranges (iqr) and th percentile ranges of model outcomes were then calculated across the simulations. since the aim of this study was to compare resource capacities across geographic areas and resource types, rather than to evaluate how transmission dynamics may vary across geographic areas, epidemiological parameters of the model were kept fixed in the multivariate uncertainty analysis to ensure comparability of resource capacity outcomes. however, due to the unpredictability of pandemic scenarios, we also explored model outcomes for a range of values for r and for the severe clinical attack rate in a separate univariate sensitivity analysis. the model was coded and run in r version . . , using the ''simecol'' package [ ] with the runge-kutta th order algorithm for numerical integration of the differential equations. arcgis version was used to map the calculated resource gaps and avoidable mortalities at provincial level. figure presents the geographical distribution of estimated resource gaps across provinces (or districts in the case of indonesia) in each study country for the modeled pandemic influenza scenario, under our baseline assumptions and point estimates for parameter values. the corresponding statistical distributions of resource capacities across areas within each country can be found in figure s . a summary of overall resource gaps for each country is presented in table . there was substantial variation in resource gaps both between and within countries, and across resources types (figures and s ) . overall, the biggest gaps were generally seen in cambodia and lao pdr, particularly when standardized by population size, with almost all provinces in these countries displaying gaps in all resources, with the exception of nurses which were estimated to be sufficient in approximately half of the provinces in these countries. in contrast, relatively few provinces in taiwan were estimated to have gaps, at least in general health system resources (beds, ventilators, and human resources), with quantities of these resources often considerably above those predicted to be needed for this scenario. nevertheless, almost half of provinces in taiwan were predicted to have insufficient oseltamivir supplies to treat all severe cases (although it should be noted that the results in figures and s do not account for central stockpiles which might be mobilized in the event of a pandemic, as discussed later). thailand, indonesia and vietnam generally displayed a more mixed picture. results were comparable between vietnam and indonesia, with relatively few provinces of vietnam ( ? %) and only one district of jakarta (and none in bali), estimated to have insufficient oseltamivir to treat all severe cases, with supplies of this antiviral drug comparably high across most other areas in these countries. healthcare workers were also predicted to be mostly sufficient in vietnam, with only ? % and ? % of provinces predicted to have a shortage of doctors and nurses, respectively, for this scenario. however, gaps in hospital beds were observed in over half of provinces in vietnam and districts of jakarta and bali, and all of these provinces displayed a shortage of mechanical ventilators. indeed, of all the resources, the largest gaps were observed in ventilators across all countries except taiwan (table ) . thailand had the second highest number of ventilators (absolute and per capita) after taiwan, but a shortage of this resource was nevertheless predicted in over % of thai provinces. a very heterogeneous pattern was observed in thailand, with around % of provinces showing a shortage of hospital beds and oseltamivir, while many other provinces showed a clear ''surplus'' of the latter. meanwhile, a shortage of medical doctors was predicted in over % of thai provinces, with gaps in doctors comparable to those lao pdr and cambodia ( table ). the number of nurses in thai provinces was estimated to be somewhat more sufficient, however. a fairly distinct geographical pattern of resource gaps was evident in thailand, particularly for oseltamivir and ventilators, with north-eastern (and some southern) provinces showing shortages more comparable with those in neighboring lao pdr and cambodia than with other thai provinces ( figure ). it should be noted that estimates of gaps in beds, ventilators and human resources were highly dependent on the spare capacity of resources assumed to be available to care for pandemic influenza patients. for example, if spare capacity was assumed to be %, rather than %, then even in taiwan most areas would suffer gaps in these resources for the modeled scenario. furthermore, use of oseltamivir on even a fairly small proportion ( %) of mild cases, resulted in much faster depletion of this resource, such that all countries are predicted to experience a shortage of oseltamivir for treating all severe cases. the geographic distribution of avoidable deaths, estimated by calculating the number of deaths that would be prevented by filling all resource gaps in each province, and standardized by population size, is presented in figure . (a corresponding map showing absolute numbers of estimated avoidable death is given in figure s .) figure shows estimated avoidable death rates attributable to gaps in each resource type (antivirals, beds and ventilators) aggregated across all provinces in each country, and accounting for uncertainty in resource effectiveness and spare capacity. avoidable deaths for a given resource gap were estimated by calculating the number of deaths that would be prevented by filling that resource gap only. figures and highlight how resource gaps could have a substantial impact on mortality rates during an influenza pandemic. a combination of the large population size and shortage of ventilators results in the estimation that, out of the five countries for which nationwide data were collected, vietnam would have the highest total number of avoidable deaths. however, the results for jakarta and bali suggest that indonesia would have the highest avoidable death toll if the data is extrapolated across the entire population of this country. when standardized by population size, the highest rates of avoidable deaths were estimated in cambodia and lao pdr, accounting for over half of all pandemic-associated mortalities in these countries. the median avoidable death rates for these countries were over times higher than that for taiwan, where a relatively low proportion (median: . %, iqr: . - . %) of total deaths was estimated to be due to resource gaps. almost all avoidable deaths in taiwan were predicted to be due to local shortages of oseltamivir. in all other countries shortages of ventilators were estimated to be the biggest cause of avoidable deaths (figure ). in indonesia, lao pdr, and vietnam, this result was largely robust to uncertainty surrounding resource effectiveness and spare capacity. for cambodia and thailand, however, the uncertainty analysis suggested that gaps in oseltamivir might also be a main cause of avoidable deaths (figure ). when adding an additional layer of uncertainty to the model assumptions, by allowing for up to % of mild cases to be treated with oseltamivir, the increased shortages of the latter further increased uncertainty surrounding the relative importance of gaps in oseltamivir ( figure s ). given such uncertainties and the sensitivity of results to model assumptions, the proportion of mortalities that can be attributed to gaps in specific resources should be interpreted with some caution. a clear negative correlation was observed between estimated avoidable mortality rates and gdp per capita at country level ( figure a ). total funds per capita committed by donors towards avian and human influenza for each country, up to december [ ] were positively correlated with avoidable mortality rates ( figure b ). within many countries it was evident that, while at least some provinces displayed resources gaps, other provinces were estimated to have more than sufficient resources for responding to the modeled scenario, with an overall ''surplus'' of some resources in several countries (table ) . furthermore, central stockpiles of oseltamivir were present in all countries from which data on this could be obtained. thus we also investigated the proportion of avoidable deaths that might be averted in each country if the total available resources were equitably distributed across provinces according to provincial population size ( figure ). when accounting for central stockpiles of oseltamivir, the overall supply of this drug was estimated to be sufficient to treat all severe cases in all countries (table ) . thus it was estimated that, in each country (except for vietnam, and jakarta and bali, where provincial supplies of oseltamivir are already relatively high), effective mobilization of oseltamivir across administrative areas could potentially avert a significant proportion of the avoidable deaths estimated under current resource distributions (up to % of avoidable mortalities in taiwan; figure ). the (less feasible) scenario of redistributing available beds and ventilators according to provincial need within each country was generally estimated to have less of an impact on the number of avoidable deaths, compared to mobilization of oseltamivir ( figure ). in the case of ventilators, this highlights how the large numbers of deaths attributed to gaps in this resource (figure ) are mostly due to overall nationwide shortages of ventilators, rather than an inequitable distribution of ventilators within most countries. in thailand, however, if all ventilators were distributed in proportion to provincial population sizes, the model predicts around % (iqr: - %) fewer avoidable deaths than the number predicted under the observed ventilator distribution. estimates of resource gaps, and thus also avoidable mortalities, were very sensitive to the severity of the modeled pandemic scenario in relation to transmissibility and proportion of cases requiring hospitalization ( figure s ) . a sensitivity analysis showed that under more severe (yet still plausible) pandemic scenarios, even taiwan could experience substantial deaths due to shortages of hospital resources ( figure s a and s c) . furthermore, as the severity of the scenario increased, so too did the proportion of avoidable deaths that were attributable to gaps in hospital bed capacity (shown for cambodia in figure s b and s d) . it is important to note, however, that for the ranges of values explored for the basic reproduction number and the proportion of cases that become severely ill, consistent patterns were observed when comparing relative magnitudes of avoidable mortality rates across countries (and also across provinces within countries). our results indicate that health system resource gaps for responding to a mild to moderate pandemic influenza scenario are wide and vary greatly, both within and between countries in southeast asia, and that these gaps could have a profound impact on pandemic-associated mortalities. our estimates of resource gaps and avoidable mortality rates at country level show a clear association with national gdp. this result is consistent with a previous analysis of data from the influenza pandemic, which found that per capita income explained a large proportion of the variation in mortality across countries during the pandemic period [ ] . moreover, extrapolation of these mortality rates to the world population suggested that around % of deaths from pandemic influenza would occur in developing countries [ ] . our results suggest that, due to inequitable distribution of resources, the variation in pandemic burden is likely to be profound within, as well as between, countries. countries which have experienced the highest burden of highly pathogenic avian influenza (h n ), namely vietnam and indonesia, appear to be most prepared in terms of the availability and geographical distribution of oseltamivir. in the other study countries, we estimated that central stockpiles of oseltamivir would be sufficient to cover any provincial gaps for treating all severe cases from the modeled scenario, and thus mobilization of this resource could potentially avert a large number of avoidable mortalities in these countries. indeed, in all countries except vietnam, we estimated that optimum mobilization of resources across administrative boundaries could save more than % of avoidable deaths. while timely mobilization of resources may be possible in taiwan, with its small geographical size and relatively developed infrastructure, the feasibility of this scenario is questionable in the poorer, and larger, countries of the mekong region, where it might be prudent to disburse central stockpiles of antiviral drugs to provincial and district health facilities prior to an outbreak. gaps in mechanical ventilators were predicted to be a major cause of avoidable deaths, with almost all provinces across all countries estimated to have severe shortages of this of this resource, with the exception of taiwan and some thai provinces. this pattern likely reflects the relatively high cost and human resource skills associated with acquisition and operation of ventilators, and highlights the importance of developing robust triage criteria as part of pandemic preparedness plans to ensure that this resource is allocated to the patients who are most likely benefit [ ] [ ] . a previous analysis similarly suggested that a dire shortage of mechanical ventilators would be a major limiting factor in responding to a pandemic influenza outbreak in the united states [ ] . we found particularly wide variation in the availability of ventilators, and indeed other hospital resources, in thailand, where our results suggest that inequitable distribution of health system resources [ ] , rather than simply an overall nationwide shortage, could lead to a high number of avoidable deaths from pandemic influenza. of course, hospital equipment such as beds and ventilators are useless unless sufficient and qualified human resources are available to treat influenza patients, and our results suggest that gaps in healthcare workers would also be an important limiting factor for responding to pandemic influenza in many countries, particularly for cambodia, lao pdr and thailand. it is encouraging that total donor funds committed to avian and human influenza broadly correspond to avoidable mortality rates estimated at country level. a recent paper on financial and technical assistance from the international ministerial conference on animal and pandemic influenza (imcapi) reports that over % of total donor funding committed towards avian and human influenza worldwide between and was allocated towards ''human health and pandemic preparedness'' (with other funds committed towards sectors such as animal health; monitoring, information, and internal coordination; and information, education and communication) [ ] . however, the extent to which these funds have been, or will be, allocated towards mitigating the resource gaps identified in our study is unknown to us and beyond the scope of this analysis. this study is subject to several limitations, many of which relate to assumptions that were necessary for the modeled scenario. for example, in our baseline scenario we assumed that % of hospital capacity, across all provinces and countries, would be available to care for the surge of patients with influenza infections. in reality, surge capacity is likely to vary substantially between and within countries (and over time), but few data on this are available. robust analytical frameworks are urgently needed to define and measure health system surge capacity in order to inform analyses of resource gaps for emergency response scenarios. the effectiveness of resources such as antiviral drugs, ventilators, and general hospital care for improving the survival rates among severe influenza cases is also surrounded by considerable uncertainty and may vary between settings. our results show that, even if epidemiological parameters describing transmission and pathogenicity are kept constant, uncertainties in spare capacity and resource effectiveness lead to considerable uncertainties in estimates of avoidable mortalities rates. nevertheless, the distributions of model outputs from our multivariate uncertainty analysis still showed some significant differences when compared across countries and across resource types (figures and ) . furthermore, it seems likely that spare capacity and resource effectiveness would be higher in more resource-rich settings, which would only strengthen the findings of this study in terms of the geographic distribution of resource gaps and avoidable mortalities. estimates of resource gaps and avoidable mortality rates were also very sensitive to parameters describing pandemic severity, although similar patterns were observed across geographic areas for the range of values explored. however, the same cannot be said for the relative importance of gaps in different resource types. thus, although our results generally suggest that shortages of ventilators could be a major cause of avoidable deaths in low-and middle-income countries in southeast asia, investment in this resource should not necessarily be prioritized over other healthcare resources. a natural extension of this study would be to investigate the cost-effectiveness of investing different types of health systems resources for mitigating the burden of an influenza pandemic. however, more data on the effectiveness of different resources for managing severe influenza cases is needed before such assessments can be made. other limitations relate to the simplicity of the model structure. we assumed homogenous mixing and a constant basic reproduction number across all populations. in reality, heterogeneities in factors such as age-structure, geographic structure, population density, human behavior, and the underlying health of the population are all likely to play a role in transmission dynamics and burden of influenza. a previous modeling analysis, for example, has shown that higher levels of population heterogeneities, such as in age and spatial structuring of contacts, result in lower overall attack rates and peak prevalence for a given basic reproduction number [ ] . however, there is a lack of data on such heterogeneities and how they might affect patterns of pandemic progression for our study region. ongoing studies, such as contact pattern surveys in asia similar to those undertaken in europe [ ] , are attempting to rectify this. another limitation is that the resource data were collected between may and september , which includes the first wave of the h n - pandemic; thus some resource data (particularly for antiviral stockpiles) may be influenced by the time point within this period at which the data were recorded. given the above caveats, it is important to emphasize that we do not advocate these results to be accurate quantitative reflections of resources shortages or deaths that are likely to occur in any given pandemic scenario. rather, they highlight the scale of health system inequalities within and across countries in asia, and the considerable impact such inequalities could have on the pandemic disease burden. by indicating the relative disparities in resource availability within and across countries, and the potential consequences of resource shortages, these results could help guide investment decisions in scaling up resources to mitigate the burden figure . estimated impact of resource mobilization/redistribution across provinces on avoidable mortality rates within each territory. data were calculated by estimating the number of avoidable deaths if available resources (including central stockpiles for oseltamivir) within each territory were geographically distributed in proportion to provincial population size, and comparing with the total number of avoidable deaths predicted given actual resource distribution. boxplots show medians, interquartile ranges, and th percentile ranges derived from a multivariate uncertainty analysis. data are aggregated across provinces for cambodia, lao pdr, thailand, vietnam, and across counties for taiwan. data for indonesia are aggregated across districts of jakarta and bali only. doi: . /journal.pone. .g of future pandemics. as many of these resources have a generic healthcare function beyond pandemic influenza, they may also be useful to guide health system strengthening. figure s variation in estimated resource capacities across provinces within each territory for the modeled pandemic scenario. (docx) figure s geographical distribution of estimated avoidable deaths due to resource gaps for a modeled pandemic influenza scenario. modelling the impact of an influenza a/h n pandemic on critical care demand from early pathogenicity data: the case for sentinel reporting the experiences of health care workers employed in an australian intensive care unit during the h n influenza pandemic of : a phenomenological study predicting spread of new pandemic swine-origin influenza a (h n ) in local mid-size city: evaluation of hospital bed shortage and effectiveness of vaccination pandemic influenza-implications for critical care resources in australia and new zealand modeling the critical care demand and antibiotics resources needed during the fall wave of influenza a(h n ) pandemic. plos curr influenza modelling the impact of an influenza pandemic on critical care services in england pandemic influenza and hospital resources modeling hospital response to mild and severe influenza pandemic scenarios under normal and expanded capacities ability of regional hospitals to meet projected avian flu pandemic surge capacity requirements effects of interventions on the demand for hospital services in an influenza pandemic: a sensitivity analysis flusurge-a tool to estimate demand for hospital services during the next pandemic influenza major issues and challenges of influenza pandemic preparedness in developing countries global trends in emerging infectious diseases estimation of potential global pandemic influenza mortality on the basis of vital registry data from the - pandemic: a quantitative analysis preparing for the next pandemic strategies for containing an emerging influenza pandemic in southeast asia pandemic influenza preparedness and health systems challenges in asia: results from rapid analyses in asian countries emerging infectious diseases in southeast asia: regional challenges to control responses to avian influenza and state of pandemic readiness capacity of thailand to contain an emerging influenza pandemic health system resource needs in se asia for pandemic influenza: systematic review and delphi consensus study health service resource needs for pandemic influenza in developing countries: a linked transmission dynamics, interventions and resource demand model estimated epidemiologic parameters and morbidity associated with pandemic h n influenza the transmissibility and control of pandemic influenza a (h n ) virus surge capacity associated with restrictions on nonurgent hospital utilization and expected admissions during an influenza pandemic: lessons from the toronto severe acute respiratory syndrome outbreak hospital emergency surge capacity: an empiric new york statewide study simecol: an object-oriented framework for ecological modeling in r international ministerial conference on animal and pandemic influenza: international financial and technical assistance (draft) concept of operations for triage of mechanical ventilation in an epidemic simple triage scoring system predicting death and the need for critical care resources for use during epidemics emergency response planning in hospitals capacity in thai public hospitals and the production of care for poor and nonpoor patients epidemic patch models applied to pandemic influenza: contact matrix, stochasticity, robustness of predictions social contacts and mixing patterns relevant to the spread of infectious diseases the asiaflucap project is coordinated by the london school of hygiene and tropical medicine with collaborators from the hamburg university of we are grateful to the many collaborators within this project consortium for their contribution towards resource characterization, data collection, and discussions at consortium meetings. these include: key: cord- -j n a m authors: hsieh, ying-hen title: ascertaining the – hiv type crf _bc outbreak among injecting drug users in taiwan date: - - journal: int j infect dis doi: . /j.ijid. . . sha: doc_id: cord_uid: j n a m objective: to ascertain the explosive – outbreak of hiv- crf _bc among intravenous drug users (idu) in taiwan, which more than doubled the total number of reported hiv cases in less than years, resulting in a -fold increase in cumulative idu/hiv cases and a -fold increase in previously seldom-reported female idu/hiv cases. methods: a mathematical model was utilized to fit the monthly case data, in order to estimate the turning points (peak incidence) and the reproduction number r of the outbreak. furthermore, correlation analysis was carried out to assess the correlation between infections among the male and female idus. results: model fit revealed a two-wave epidemic during april –march . the larger second wave started shortly after may and peaked in october before gradually subsiding. r was estimated to be . ( . – . ) and . ( . – . ) for the two respective waves. the time series of monthly differences in male and female case data were found to be most significantly correlated at lag (i.e., r > . ) with r = . and . , respectively in each direction. the granger causality test indicated that the male time series caused the corresponding female time series with a lag of months or less. conclusions: the modeling results revealed the presence of a small first wave in , before an explosion of cases after may . furthermore, a harm reduction program implemented in august contributed to the downturn in the epidemic after october. correlation results also suggest that the upsurge in male hiv cases led to the subsequent drastic surge in female cases. in taiwan, where active hiv/aids surveillance has been in place since , with . - . million annual screening tests and free antiretroviral therapy (art) introduced since , [ ] [ ] [ ] [ ] during this time-period, an outbreak of hiv- crf _bc infections among idus, including many previously seldom-seen female idu hiv-infected cases, resulted in more reported cases than all reported hiv cases among all risk groups combined in the previous years since , when the first aids case was reported. it has been speculated that the source of this outbreak was a drugtrafficking route to taiwan from yunnan province via southeast china, guangxi province, and hong kong, [ ] [ ] [ ] from where a substantial amount of heroin was being smuggled into taiwan. moreover, five idus from southern taiwan were diagnosed as the country's first hiv- -seropositive cases infected with crf _bc in . it has been reported that the percentage of persons receiving a diagnosis of aids within months of diagnosis of hiv infection dropped suddenly from % in to . % in , during the time when most of the newly diagnosed cases came from the idu population, which implies that the detected idu cases were in the early stage of hiv infection. it has also been reported that % of objective: to ascertain the explosive - outbreak of hiv- crf _bc among intravenous drug users (idu) in taiwan, which more than doubled the total number of reported hiv cases in less than years, resulting in a -fold increase in cumulative idu/hiv cases and a -fold increase in previously seldom-reported female idu/hiv cases. methods: a mathematical model was utilized to fit the monthly case data, in order to estimate the turning points (peak incidence) and the reproduction number r of the outbreak. furthermore, correlation analysis was carried out to assess the correlation between infections among the male and female idus. results: model fit revealed a two-wave epidemic during april -march . the larger second wave started shortly after may and peaked in october before gradually subsiding. r was estimated to be . ( . - . ) and . ( . - . ) for the two respective waves. the time series of monthly differences in male and female case data were found to be most significantly correlated at lag (i.e., r > . ) with r = . and . , respectively in each direction. the granger causality test indicated that the male time series caused the corresponding female time series with a lag of months or less. conclusions: the modeling results revealed the presence of a small first wave in , before an explosion of cases after may . furthermore, a harm reduction program implemented in august contributed to the downturn in the epidemic after october. correlation results also suggest that the upsurge in male hiv cases led to the subsequent drastic surge in female cases. ß international society for infectious diseases. published by elsevier ltd. all rights reserved. hiv cases infected through idu diagnosed in - were infected with hiv subtype crf _bc, which is totally different from the previously common subtype b and subtype crf _ae in taiwan. as is typical of underreporting of hiv/aids among many hardto-count high-risk populations for hiv/aids, , there is a significant discrepancy between reported and estimated hiv/aids cases in the idu group because of the difficulty reaching idus. in taiwan, where needle-sharing or apparatus-sharing behaviors have been found to be common among idus, the majority of newly diagnosed hiv/idus were detected through mandatory inmate screening upon entry to correctional facilities. however, mandatory hiv screening of persons under police custody due to violation of the narcotics control act since late could also have partially contributed to the sharp increase in detection. in response to the outbreak in idus, a harm reduction program, which involved a needle-syringe program (nsp) and substitution treatment, was implemented by the taiwanese government in august as an intervention to the rapidly increasing hiv epidemic since . there has been a steady drop in hiv incidence among idus in recent years, down from being the major mode of hiv transmission in taiwan in [ ] [ ] [ ] to below that of homosexual and heterosexual transmissions since , but still significantly higher than its pre- level. a recent molecular epidemiology study after the crf _bc outbreak in taiwan concluded that while the percentage of crf _bc among all hiv infections decreased from to , the percentage of subtype b actually increased. however, many questions remain regarding this sudden outbreak among the idu population. in this study the reported hiv/idu case data and a simple mathematical model, the richards model, [ ] [ ] [ ] were used to investigate the temporal progression of this epidemic among idus in taiwan. in particular, the total case data are fit to the model, as well as the male and female case datasets separately, in order to ascertain the epidemic. correlation analysis was performed in an attempt to determine the relationship between the male and female idus. the data used here were extracted from the monthly reported hiv case data between april and march , for a total of months, made available by the taiwan centers for disease control and prevention (tcdc) on the tcdc website. the data are provided for each risk group/factor and gender. however, the hiv/ idu case data by gender are only available after august , the fifth month of the dataset. in what follows, for ease of illustration in the tables and figures, the months are numbered, namely, april is month and march is month . the richards model, a logistic-type mathematical model was used in this study. the explicit solution of the richards model is of the form: where c(t) is the cumulative number of deaths at week t and the prime ' ' denotes the time rate of change. k is the final outbreak size over a single wave of outbreak, r is the per capita growth rate of the cumulative case number, a is the exponent of deviation of the cumulative case curve, and t i is the turning point of the epidemic (which signifies the moment of upturn or downturn for the increase in the cumulative case number). the basic premise of the richards model is that the incidence curve of a single wave of infections consists of a single peak of high incidence, resulting in an s-shaped cumulative case curve and a single turning point (or the inflection point of the cumulative case curve) of the outbreak. this turning point t i , which is defined as the point in time at which the rate of accumulation changes from increasing to decreasing, or vice versa, can easily be pinpointed via the richards model. when more than one wave of infection occurs, a variation of the s-shaped richards model is proposed, which makes the distinction between two types of turning points. other than the first turning point ending the initial exponential growth of the cumulative case number, a second type of turning point is present in a multi-wave epidemic where the growth rate of the cumulative case number begins to increase again, signifying the beginning of the next wave. for further illustrations, the readers are referred to hsieh and cheng and hsieh and chen, in which the incidence curves for the great toronto area severe acute respiratory syndrome (sars) and the taiwan dengue outbreaks containing two peaks (or two turning points of the first type) and one valley (or a turning point of second type) are investigated. for the computation of the basic reproduction number r , the formula r = exp (rt) was used, where t is the generation interval of the disease or the average interval from onset of one individual to the onset of his/her contacts. it has been shown mathematically that, given the growth rate r, the expression r = exp (rt) provides an upper bound for the basic reproduction number, regardless of the assumed distribution of the generation interval. we noted that in this instance, the estimate obtained is not the basic reproduction number, but the effective reproduction number r, since in taiwan hiv is endemic among the idu population and multiple intervention measures have already been in place for some years. the model parameters of epidemiological importance are k, r, and the turning point t i of the epidemic. the cumulative death data can be fitted to the richards model to obtain estimates of these model parameters, using any standard software with a least-squares approximation tool, e.g., sas, matlab, etc. more applications of the richards model on other infectious disease outbreaks such as dengue can also be found in hsieh and chen and hsieh and stefan. we first examined whether the times series were 'stationary', in order to avoid spurious regression, which could possibly result in a biased and inconsistent estimator. a stationary time series means that its statistical characteristics do not change in time. in the event of a non-stationary time series, it can be suitably transformed to achieve stationarity. the augmented dickey-fuller (adf) test was employed to verify if the random variables were indeed stationary series. three equations were used to test if the series process has a non-stationary character: . without drift and trend terms: . both drift and trend terms: the null hypothesis is non-stationary or unit root, i.e. to determine the correlation between the epidemic among the male and female idus through their time series of monthly case numbers, a distributed lag model (dlm) was employed to describe the relationship between the male and female time series. a dlm is a regression model that includes current and lagged values of one or more explanatory variables. this model allows the determination of what the effects are for a change in a time series. the resulting correlation coefficient, r, is a useful measure of linear strength between two random variables. the mathematical formula for computing r is: where n is the number of pairs of data. the value of r is such that À r + . the '+' and 'À' signs are used for positive linear correlations and negative linear correlations, respectively. if there is no linear correlation or a weak linear correlation, r is close to . a value near zero means that there is a random, nonlinear relationship between the two variables. 'jrj . ' means 'low correlation', ' . < jrj . ' means 'moderate correlation', and 'jrj > . ' means 'high correlation'. in other words, a correlation greater than . is generally described as strong, whereas a correlation less than . is generally described as weak. the granger approach is used to ascertain how much of the current values of time series y can be explained by past values or some lagged values of time series y. the commonly used software eviews was developed originally by economists for use in economics applications, but can also be useful in other statistical applications. eviews version . (http://www.eviews.com/) was used to analyze the data. in general, it is better to use more lags rather than fewer lags, since the theory is couched in terms of the relevance of all past information. it is advisable to pick a lag length, l, which corresponds to the reasonable beliefs about the longest time over which one of the variables could help to predict the other. eviews performs bivariate regressions of the form: for all possible pairs of series in the group. the reported f-statistics are the wald statistics for the joint hypothesis: the null hypothesis is that series x does not granger-cause series y in the first regression and that y does not granger-cause x in the second regression. the monthly time series data of reported hiv cases for male idus, female idus, and all idus in taiwan were fit to the richards model as in figure and table the effective reproduction number r was computed for each wave. however, it is unclear what the generational interval is for hiv. it has been proposed that the rates of partner change for homosexuals and heterosexuals tend to be of the order of year, but it is unclear what the rate of needle-syringe sharing is among idus, [ ] [ ] [ ] although it is most likely of shorter length than that of sexual transmission of hiv. due to the lack of a reliable estimate for the hiv generation time among idus in the literature, a generational interval of or months was assumed, based on an estimate of doubling time for aids cases among idus in the northeastern usa early in the epidemic. it should be noted that the main purpose for estimating r in this study was to compare the transmissibility estimated using different datasets and to ascertain the relative temporal change in transmissibility that occurred in each wave of infection during the course of the epidemic. to table , where the time series of monthly reported cases and the difference of two successive monthly reported cases were found to be stationary for both males and females. note that we use 'male' and 'female' to denote the respective time series of monthly reported male and female hiv cases, and ' male' and ' female' to denote the respective time series of differences of monthly male and female hiv cases. next, the correlation between the monthly reported case data (male and female) and monthly differences in case data ( male and female) were analyzed. the correlation coefficient r is a useful measure of the linear strength between two random variables. applying a univariate model of y = b + bx t À lag + e t for 'x causes y' (or x ! y) with lag, male ! female and male ! female were found to be most significantly correlated (i.e., r > . ) with r = . and . with lag , respectively. the correlation plots for the correlation are given in figure , which indicates the most significant correlations between the male reported cases and female reported cases, as well as their differences, are consistently at lag (in red). the granger causality test was subsequently carried out between the time series of male and female and between the time series of male and female for time lags up to months. test results, also given in table with the causal direction for each pair indicated with an arrow, indicate that both male time series caused the corresponding female time series after a lag of months. the timelines of the epidemic for all cases, as well as for the male and female case numbers, are illustrated in figure , indicating good agreement among estimates of temporal progression of the epidemic using the three datasets, and pinpointing may as the month that separated the two waves obtained from all three datasets. it is further concluded that the turning points for the first of these two waves differ slightly at . ), respectively, for the total, male, and female case data (see table ( + . ) , for all cases, males, and females, respectively. it is interesting to note that in a recent study, phylogenetic tree analysis of hiv-infected inmates with an idu history in taiwan was employed to demonstrate that there were two waves of hiv- crf _bc infection from mainland china to taiwan. although no timeline of the two waves was available from the molecular study, it does corroborate our modeling results. the estimates for r indicate that the transmissibility of hiv among the idu population increased from the first wave to the second wave according to all three datasets, culminating in a peak around october , when a downward trend ensued. it is interesting to note that the harm reduction program that was implemented by the taiwanese government in august could have impacted the downturn in case numbers after october, as revealed by our modeling results. however, only a trial harm reduction program, which included a needle-syringe program (nsp) and substitution treatment in four counties, was established at that time. after year of the pilot study, data indicated that the hiv incidence in cities with an nsp decreased from . to . per persons compared to an incidence increase from . to . per persons in cities without an nsp. subsequently, the harm reduction program was expanded to the whole of taiwan in july . therefore, the country-wide downturn in case numbers after october may only be partially attributable to the harm reduction program. r for females was higher than that of males in the first wave, but lower in the second wave and ending earlier in june , perhaps reflecting the more rapid initial increase in female incidence in the early stages of the epidemic. however, this drastic upsurge in female hiv-infected idus was relatively more difficult to sustain in the second wave, as indicated by the shorter length of this wave when compared to that of the males. therefore the epidemic impacted female idus more drastically initially, but the overall magnitude of infection was still less than that of the males, which was the group most affected by the epidemic. correlation analysis of the time series of male and female cases indicates that the outbreak among female idus was most likely driven by the infections among male idus, who were far more numerous at the beginning of the epidemic. in the granger causality test, the lag length corresponds to the longest time over which one of the variables could help to predict the other. therefore, the minimum p-value at a lag of months for both the time series of case numbers and the first differences of the time series suggests that the strongest causality relationship, of male infections causing female infections, was within months, a rather immediate relationship that led to the sudden upsurge in reported female hiv/idu cases shortly after the upsurge of the male idu cases in early . it also indicates that there is likely some needle-sharing or apparatus-sharing among and between male and female idus, although one cannot rule out the possibility of sexual contact between the male and female idus, since one study in taiwan found that . % of the hiv-infected idus participating in the study were heterosexual. unfortunately no data on any relationships that might exist between the reported cases were available. the study further demonstrates how quickly a disease traditionally endemic in a male population can develop into an epidemic in the female population given appropriate circumstances; hence transmission across gender is an important aspect of disease surveillance. in summary, the abrupt outbreak among idus in taiwan in - , which was caused by the recently introduced crf _bc recombinant, led to two waves of infection with increasing transmissibility as measured by the effective reproduction number r during each wave, suggesting the presence of a small first wave in before the explosion of cases after may . this further demonstrates the future potential of real-time modeling and analysis of disease data as part of a disease surveillance system, which could conceivably detect and alert the authorities of a possible herald wave before the arrival of a major outbreak. the waves ended by march , which could be attributable to a timely and effective harm reduction program implemented in august ; this has been essential in preventing further occurrences of wide-spread infections among idus in taiwan since . furthermore, the infections among male idus led to the epidemic among the female idus, a population that had previously been mostly devoid of hiv infections. the limitation of this modeling study arises mainly from the nature of the hiv surveillance data, which typically consists of a longer period of time due to the long hiv incubation period, and hence is highly dependent on temporal changes in testing, reporting, and interventions over the years. in this study, the data that were used spanned a period of roughly years, during which time the explosive outbreak among idus emerged; this subsequently led to interventions that included wider testing of idus in taiwan and the harm reduction program. moreover, while the simple mathematical model that was employed was able to reveal the temporal progression, culmination, and conclusion of the outbreak, it was unable to further pinpoint the exact impact of these intervention measures on the outbreak, which would require much more detailed data on the reported cases as well as a far more complicated mathematical model. hiv- crf _bc infections, injecting drug users hiv- in taiwan molecular epidemiology of hiv- infection and full-length genomic analysis of circulating recombinant form _bc strains from injecting drug users in taiwan the changing epidemiology of prevalent diagnosed hiv infections in taiwan disease control and prevention. hiv/aids database timeline of the hiv epidemic among the idu population in taiwan diseases% &% prevention/issues% of% hiv-aids/statistics% of% hiv-aids/download% hiv-aids% data.htm a recent outbreak of human immunodeficiency virus type infection in southern china was initiated by two highly homogeneous, geographically separated strains, circulating recombinant form ae and a novel bc recombinant asia and africa: on different trajectories? the lack of epidemiological link between the hiv type infections in hong kong and mainland china empirical bayes approach to estimate the number of hiv-infected individuals in hidden and elusive populations ascertaining hiv underreporting in low prevalence countries using the approximate ratio of underreporting surveillance of hiv type recent infection and molecular epidemiology among different risk behaviors between and after the hiv type crf _bc outbreak in taiwan a flexible growth function for empirical use severe acute respiratory syndrome epidemic in asia real-time forecast of multi-wave epidemic outbreaks turning points, reproduction number, and impact of climatological events on multi-wave dengue outbreaks how generation intervals shape the relationship between growth rates and reproductive numbers intervention measures, turning point, and reproduction number for dengue testing for unit roots in autoregressive moving average models of unknown order investigating causal relations by econometric models and crossspectral methods epidemiological parameters of hiv transmission needles that kill: modeling human immunodeficiency virus transmission via shared drug injection equipment in shooting galleries rm. drugs, sex and hiv: a mathematical model for new york city population dynamics of hiv- inferred from gene sequences molecular epidemiology of hiv- subtype b, crf _ae, and crf _bc infection among injection drug users in taiwan oral presentation epidemic modeling in real time: novel a (h n ) influenza outbreak in canada yhh is supported by grants nsc - -b- - -my and - -m- - from the national science council of taiwan. the author is grateful to the reviewers for their constructive and insightful comments, which significantly improved this manuscript.conflict of interest: no competing interest declared. key: cord- -i nh k e authors: song, jae-hoon; huh, kyungmin; chung, doo ryeon title: community-acquired pneumonia in the asia-pacific region date: - - journal: semin respir crit care med doi: . /s- - sha: doc_id: cord_uid: i nh k e community-acquired pneumonia (cap) is an important cause of mortality and morbidity worldwide. aging population, dense urbanization, and poor access to health care make the asia-pacific region vulnerable to cap. the high incidence of cap poses a significant health and economic burden in this region. common etiologic agents in other global regions including streptococcus pneumoniae, mycoplasma pneumoniae, haemophilus influenzae, chlamydophila pneumoniae, staphylococcus aureus, and respiratory viruses are also the most prevalent pathogens in the asia-pacific region. but the higher incidence of klebsiella pneumoniae and the presence of burkholderia pseudomallei are unique to the region. the high prevalence of antimicrobial resistance in s. pneumoniae and m. pneumoniae has been raising the need for more prudent use of antibiotics. emergence and spread of community-acquired methicillin-resistant s. aureus deserve attention, while the risk has not reached significant level yet in cases of cap. given a clinical and socioeconomic importance of cap, further effort to better understand the epidemiology and impact of cap is warranted in the asia-pacific region. the asia-pacific region in this article includes east asia, southeast asia, south asia, and oceania. asia-pacific is home to more than . billion people, which is "nearly percent of the world's population." while collectively categorized as asia-pacific, considerable diversity exists. seven of the world's most populous countries are located in this region, as well as some of the world's smallest countries. some have leading economies of the world, while some are struggling to meet the most basic needs of their people. despite its large heterogeneity, the region shares some distinct characteristics. population growth rate is declining ( . % per year), infant mortality rate is still high ( deaths per , live births), proportion of older adults are growing ( . % of population are aged and above), a large population is living in urban areas ( %), and some of the world's largest megacities are located in asia-pacific. these characteristics are associated with the high burden of community-acquired pneumonia (cap) in this region, probably taking considerable toll on its population, economy, and societies. information on the epidemiology of cap in this region is limited by multiple hurdles: poor accessibility to health care, , lower utilization of microbiologic diagnosis, lack of surveillance systems, and considerable heterogeneity among different geographic areas. aging population, high population density, and high use of antibiotics are likely to result in increased incidence of cap, in particular by less susceptible pathogens. in this review, we will describe the epidemiology, etiology, antimicrobial resistance, preventive measures, and outcomes of cap in the asia-pacific region. community-acquired pneumonia in the asia-pacific region song et al. overall incidences of pneumonia and pneumonia-attributed mortality rates were recently estimated from a multicenter prospective surveillance in japan from to . the estimated annual incidence rates of adult community-onset pneumonia, hospitalization, and inhospital deaths were , , , and per , person-years, respectively. the overall estimated annual number of adult cap cases in the entire japanese population was , , ; importantly, . % were years old. a prospective study in one japanese city (kochi) from may to april cited an incidence of per , person years; . % of cases were years old. more attention was given to the geriatric population in the latter study, in which annual incidence of cap in older adults ( years) was estimated to be , per , . an asian country that showed similar socioeconomic and ethnic characteristics to japan would be south korea. although the exact nationwide overall incidence of cap in korea has not been reported, hospitalization rate was reported to be similar ( per , ). this study confirmed the significantly larger burden of cap in the elderly population by estimating that hospitalization rate in people years of age was , per , population. several reports have been published on the disease burden of cap in thailand, including both urban and rural areas. the hospitalization rate due to cap was reported to be to per , people in thailand, which was lower than those of japan and south korea. , because these studies were limited by low utilization of chest x-rays and variable access to health care, the estimates might not reflect the whole picture of cap in thailand. reports on the pacific island countries are scarce, but two studies from new zealand reported the overall incidence in adults and hospitalization rate. estimated incidences of cap in all adults and those years of age in new zealand were and , per , , respectively. another study estimated that pneumonia hospitalization rate was per , . several studies on the burden of cap among children in southeast asia have also been published. a surveillance in rural villages on lombok island, indonesia, in to reported the incidence, hospitalization rate, and mortality among young children ( year) as , , , , and , per , child-years, respectively. another interview survey in the philippines revealed similar incidence rates: , cases of pneumonia, , admissions, and deaths per , children each year. the burden of cap was much smaller in taiwan ( , pneumonia cases per , ) and new zealand ( hospitalizations per , ). rudan et al conducted an estimation of the global incidence of childhood pneumonia, in which the annual incidences in southeast asia and western pacific regions were estimated to be , and , per , children, respectively. when specific demographic groups were studied for cap, a larger burden was almost always observed in older adults, , , , , those residing in rural areas, [ ] [ ] [ ] and minority ethnicity. , most studies on the epidemiology of cap in the asia-pacific region are from either nationwide mortality statistics or surveillance in geographically limited areas. differences in case definitions and potential underreporting due to limited accessibility to health care undermine the effort to measure the burden of cap. further studies on the epidemiology of cap are warranted in the asia-pacific region based on more coordinated plans and resources. distribution of etiologic agents of cap is the most important information for the selection of appropriate antibiotics. it has been known that major identifiable pathogens of cap include streptococcus pneumoniae, haemophilus influenzae, mycoplasma pneumoniae, chlamydophila pneumoniae, and legionella spp. [ ] [ ] [ ] the last three have been referred to as "atypical pathogens," the importance of which has been the subject of considerable debate. despite the importance of this subject, the majority of the data on the etiology of cap have been reported from the u.s. and european countries. but, the number of studies from the asia-pacific region is recently increasing; they are summarized in ►table . the most comprehensive data were reported by the asian network for surveillance of resistant pathogens (ansorp) in . in this study, a total of cases with cap were collected from seven countries (south korea, china and hong kong sar, india, singapore, vietnam, taiwan, and the philippines). streptococcus pneumoniae was the most common isolate, which comprised . % of identified pathogens. pneumococcus was followed by klebsiella pneumoniae ( . %), h. influenzae ( . %), c. pneumoniae ( . %), and m. pneumoniae ( . %). the overall distribution of etiologic pathogens from this study was comparable to those from western countries. [ ] [ ] [ ] [ ] streptococcus pneumoniae was the most frequent pathogen identified in other studies from japan, [ ] [ ] [ ] [ ] [ ] south korea, , taiwan, , australia, and new zealand. however, the proportion of pneumococcus showed considerable variability, from % , , - to %. the broad range seen in these studies could be attributed to variable detection rate in addition to the actual difference in the pathogen distribution. with regard to atypical pathogens, some reports from china, [ ] [ ] [ ] taiwan, , and thailand reported a relatively more important role of these pathogens in cap. some pathogens are worth attention due to their unique importance in the asia-pacific region. klebsiella pneumoniae, which is relatively uncommon in other regions, contributes to larger cases of cap in southeast asia. this is especially evident in studies from taiwan, , , malaysia, , thailand, india, and the philippines (all > % of total cap cases), which showed a stark contrast to east asian countries (usually %). another important pathogen in this region is burkholderia pseudomallei, which is endemic in southeast asia and often results in severe infections. it was detected in % of hospitalized cap patients in malaysia and in % of patients with severe cap in thailand. in another study from singapore, which also focused on the patients who required intensive care unit admission, b. pseudomallei was isolated from % of the cases. there have been only small number of surveillance studies in which the burden of viral infections in cap were reported. we could find studies for our review, which are community-acquired pneumonia in the asia-pacific region song et al. summarized in ►table . the prevalence of respiratory virus varied from . to %. most of the studies used polymerase chain reaction (pcr) for the detection of virus, but serologic tests were applied in some reports. methods used for the detection seems to result in variable results, as different studies from same countries often showed vastly different detection rates. proportion of viral pathogens among cap was only . % in an earlier report from japan that used serologic test, but virus was identified in % among , patients in a recent study from japan using pcr. in adult population, influenza a and b viruses seem to predominate, comprising to % of pathogens detected including bacteria. , , , , , , rhinovirus, which is increasingly identified as etiologic agents of cap in adults, was the second most commonly detected virus ( - %). multiple limitations hinder the effort to elucidate the etiologic agents of cap, including suboptimal quality of respiratory specimens, difficulty to culture certain species of bacteria, interpretation of commensal bacteria detected in patients with cap, ambiguous results of serologic tests, and methods for detection of virus. pcr, often performed in multiplex, enabled sensitive and accurate detection of respiratory pathogens, and recent studies using this technique are broadening our understanding of the pathogens causing cap. there are a couple of specific pathogens of cap that are unique or notable in the asia-pacific region with regard to the incidence, antimicrobial resistance, clinical features, or clinical outcomes. the importance of s. pneumoniae as a major pathogen causing cap remains unchallenged in the asia-pacific region, as discussed previously. furthermore, the high prevalence rate of antimicrobial resistance in pneumococci in this region is a very serious threat to public health. important data on the antimicrobial resistance of s. pneumoniae in the asia-pacific are summarized in ►table . the most prominent resistance issue is macrolide resistance. two surveillance studies on pneumococcus conducted by ansorp in the early s revealed that about half of the isolates were resistant to erythromycin. community-acquired pneumonia in the asia-pacific region song et al. table antimicrobial resistance or nonsusceptibility rates (%) of streptococcus pneumoniae in the asia-pacific region community-acquired pneumonia in the asia-pacific region song et al. since the macrolide mic level in pneumococci from some asian countries is too high to be achieved by increased dose of macrolides, single empiric therapy with macrolides for the treatment of cap is generally not recommended. , high resistance rates of pneumococcus to penicillin had raised concerns in the asia-pacific region. , but after subsequent reports showing comparable clinical outcomes in infections caused by s. pneumoniae with mic . mg/l and those with . to mg/l, - the penicillin mic breakpoint for resistance in pneumococcus was revised from to mg/l in nonmeningeal isolates by the clinical and laboratory standards institute in . since the mic breakpoints used for the determination of penicillin resistance varied by studies, we selected the data using penicillin mic breakpoint of mg/l as resistance in ►table to compare the temporal trend of penicillin resistance. aforementioned ansorp studies reported that to % of the pneumococcus isolates in this region were resistant to penicillin. , like macrolide resistance, higher penicillin-resistance rates were observed in east asian countries, while those in southeast and south asian countries were considerably lower. the most comprehensive multinational surveillance study based on revised criteria had been conducted by ansorp in to , which revealed that the resistance rate according to the revised mic breakpoint ( mg/l) was only . %. it indicates that the resistance of pneumococci to penicillin is not a serious threat, at least in nonmeningeal infections treated with intravenous antibiotics. fluoroquinolone resistance has been reported to be < % in most countries. , , , [ ] [ ] [ ] [ ] [ ] the protekt international surveillance study also showed the low resistance rates (< %) in all countries except hong kong ( . %), which was likely to due to the dissemination of fluoroquinolone-resistant variant of the spain f- clone. spread of unrelated resistant clone was also reported from taiwan. widespread vaccination against pneumococci has significantly affected the incidence of pneumococcal diseases, serotype distribution, and antimicrobial resistance. introduction of the -and -valent pneumococcal conjugate vaccine (pcv- and pcv- ) led to dramatic reduction of pneumococcal infections in the united states. as serotypes included in pcv- are often associated with penicillin and multidrug resistance, the incidence of antibiotic-resistant invasive pneumococcal infections has also declined. however, there have been reports of the emergence of pneumococcal infections by nonvaccine types, especially a, which is often multidrugresistant. [ ] [ ] [ ] two recent studies on adults from japan during to reported that pcv- serotypes, especially b, decreased from . to . %. , some nonvaccine serotypes emerged, but genotypic penicillin resistance rate declined. nonetheless, the notable emergence of invasive pneumococcal infections caused by a was reported in taiwan, which was associated with reduced susceptibility to β-lactams. serotype a was also the most prominent non-pcv- serotype in the latest ansorp study, comprising . % of isolates, while . % showed pcv- serotypes. the majority of serotype a isolates were erythromycin-resistant ( . %) and multidrug-resistant ( . %). most prevalent clone among serotype a was st ( . %), which was found in hong kong, india, south korea, malaysia, saudi arabia, and taiwan. high prevalence of serotype a with multidrug resistance, even in countries with low vaccination rate, needs to be carefully evaluated. atypical pathogens: mycoplasma pneumoniae, chlamydophila pneumoniae, and legionella species the most comprehensive study on the role of atypical pathogens in the asia-pacific region was reported by ngeow et al in a multicenter surveillance study on the prevalence of atypical pneumonia in the early s. they used serology and pcr to detect m. pneumoniae, c. pneumoniae, and l. pneumophila from , patients in countries (malaysia, thailand, china, the philippines, taiwan, south korea, singapore, and indonesia). these three atypical pathogens were associated with . % of cap cases in this study, with m. pneumoniae, c. pneumoniae, and l. pneumophila detected in . , . , and . % of patients, respectively. the ansorp study also showed that atypical pathogens account for . % of the cases in which serologic tests were performed. but c. pneumoniae ( . %) and m. pneumoniae ( . %) were detected in the comparable proportion of cap patients in this study. studies from individual countries reveal considerable differences in the burden of atypical pathogens within the region. in general, studies from japan , , , , and south korea have reported lower proportion of atypical pathogens in cap, accounting for less than % in cap cases (►table ). however, studies from china, [ ] [ ] [ ] taiwan, , and thailand showed the larger role of atypical pathogens. in a multicenter prospective study conducted at centers in seven chinese cities, atypical pathogens accounted for . % of the cases with cap when fourfold increase in titers of antibodies were defined as serologic evidence of the infection: m. pneumoniae ( . %) was the single most prevalent pathogen, followed by s. pneumoniae ( . %), h. influenzae ( . %), and c. pneumoniae ( . %). legionella pneumophila was detected in only . % of the patients, which is in accordance with other studies in asia. , other studies from china, including one which used pcr, have reported the similar proportion of atypical pathogens (m. pneumoniae: %; c. pneumoniae: - %). , another report from hong kong on , adult patients with cap requiring hospitalization showed . % for m. pneumoniae, but still two atypical pathogens accounted for % of the patients in whom the etiologic agents were identified. two studies from taiwan, which included adult cap patients who were hospitalized, reported that the serologic evidence of m. pneumoniae and c. pneumoniae infection was found in . to . % and in . to . %, respectively. , similar distribution and higher prevalence in mild cap was also shown in a multicenter, prospective study from thailand in to . a more recent study at seven centers in bangkok ( - ) using both pcr and serology reported comparable results. despite the existence of many studies on atypical pneumonia in this region, our understanding of the exact role of these pathogens is still inadequate. the diagnosis of cap caused by atypical pathogens still mostly relies on the serologic tests, which requires serial testing and often yields equivocal results. further studies using molecular techniques can improve the correct understanding about the epidemiology of atypical pathogens. the most notable issue concerning m. pnuemoniae is the emergence of resistance to macrolides. as m. pnuemoniae harbors intrinsic resistance to β-lactams, most guidelines for the treatment of cap recommend the inclusion of macrolides as empirical treatment regimen when the coverage for atypical pathogens are required. , , , , but increased use of macrolides resulted in the emergence of erythromycin-resistant m. pneumoniae in the asia-pacific region. after the first report of macrolide-resistant m. pneumoniae in japan from patients in , the resistance rate in japan increased further to approximately % in to . macrolide-resistance strains were subsequently reported in china, [ ] [ ] [ ] south korea, and taiwan. reports from beijing and shanghai revealed remarkable resistance rates of % ( / ) and % ( / ), respectively. in the latter study, all strains isolated in and were resistant to macrolides. a korean study with isolates during to showed a similar picture; there were no resistant strains in , but the resistance rate surged from . % in to . % in . a recent survey from hong kong reported the resistance rate of . % ( / ) in and showed that the macrolide resistance was associated with increasing resistance in multilocus variable-number tandem-repeat analysis type - - - . a report from northern taiwan showed that . % of m. pneumoniae isolates were resistant to macrolides. in contrast, only one strain was resistant among specimens from sydney, australia. previous reports on the macrolide-resistant m. pneumoniae have been concentrated in three east asian countries: japan, china, and south korea. the vast majority of macrolideresistant m. pneumoniae strains found in asia harbor point mutations on a or a in s rrna gene. mutations on a or a result in a high level of resistance to various macrolides, but do not affect the susceptibility to doxycycline or fluoroquinolones. information on the current status in other countries within the asia-pacific region is not available. furthermore, the presence of a considerable regional difference in resistance rates within a single country has been reported. additional studies and enhanced sur-veillance are urgently warranted to clarify this issue. the clinical course of macrolide-resistant m. pneumoniae was reported to be prolonged; the duration of fever was to . days longer and cough persisted for more than days longer compared to patients with macrolide-susceptible m. pneumoniae infection. , [ ] [ ] [ ] efficacy of macrolide was reduced to . % in cases with resistant strains compared with . % in cases caused by susceptible strains. treatment with broad-spectrum tetracyclines (minocycline and doxycycline) or fluoroquinolones has been suggested, and two small-scale studies reported that minocycline or doxycycline was superior to fluoroquinolone in terms of the duration of fever after the initiation of treatment. , both classes of antibiotics have safety concerns in children (tooth discoloration and joint/cartilage toxicity, respectively), however, in whom m. pneumoniae infections are most prevalent. use of fluoroquinolones is further complicated by its tendency to accelerate the emergence of antimicrobial resistance and the relatively high prevalence of tuberculosis in the region. as m. pneumoniae infections are often mild and selflimited, the conservative use of alternative agents other than macrolides only in severe or persistent cases was suggested. klebsiella pneumoniae accounts for approximately % of cap cases in the ansorp study, while it is infrequently found in the europe and americas. [ ] [ ] [ ] [ ] even within the asian-pacific regions, australia, vietnam, and east asian countries report smaller incidence at %, , , , , [ ] [ ] [ ] [ ] , while a recent report from south korea showed a higher frequency of k. pneumoniae in elderly patients. high burden of cap caused by k. pneumoniae has been mostly seen in taiwan ( - %), , thailand ( . %), india ( %), the philippines ( %), and malaysia ( . - . %). , , , in a worldwide study on k. pneumoniae bacteremia, only % of community-acquired k. pneumoniae bacteremia were caused by cap in the europe and americas. in contrast, cap was responsible for % of k. pneumoniae bacteremia in taiwan, which made cap the leading cause of bloodstream infection by this pathogen. according to a clinical study from taiwan, evaluating clinical outcome of bacteremic cap caused by k. pneumoniae ( patients) and s. pneumoniae ( patients), mortality rate was significantly higher in patients with k. pneumoniae pneumonia ( . vs. . %). high mortality rate was also reported in another study from cambodia ( . %). among strains of k. pneumoniae tested for antimicrobial susceptibility in the ansorp study, all but one were susceptible to ceftriaxone. more recent data from taiwan and japan also suggest low resistance rate of community-acquired k. pneumoniae in this region, but further surveillance is warranted. , period is usually to days, but latency for decades has been reported. clinical manifestations have a broad spectrum, from asymptomatic infections to fulminant illness leading to death. approximately half of the patients with melioidosis present with pneumonia, which makes pulmonary infection the most common clinical presentation. among aforementioned studies, six reported the incidence of pneumonia caused by b. pseudomallei (►table ). malaysian study that used multiplex pcr for pathogen detection from adult patients reported that b. pseudomallei accounted for % of cap. in this study, % were positive by pcr alone and only % were culture positive. among patients with cap from northern thailand, b. pseudomallei was identified in %, which is slightly less frequent than s. pneumoniae ( . %) but more frequent than k. pneumoniae ( . %). the annual incidence of bacteremic melioidosis was reported to be . and . cases per , persons in two thailand provinces. a study on the etiology of severe cap in singapore between and revealed that b. pseudomallei was identified in cases among patients. the presence of endemic melioidosis has been also reported from northern australia, [ ] [ ] [ ] [ ] cambodia, , hong kong, india, taiwan, and southern china. melioidosis has been associated with poor outcomes in multiple studies. a retrospective review from royal darwin hospital in australia reported that its mortality rate in to was %, although it was reduced to % in to . mortality rate of % was reported from the aforementioned northern thailand hospital between and . also, in a case series of patients with imported melioidosis from south korea, overall mortality rate was . %. ceftazidime, sometimes in combination with cotrimoxazole, has been the treatment of choice during the initial intensive phase. burkholderia pseudomallei is highly susceptible to carbapenems in vitro, and imipenem or meropenem showed comparative outcomes to ceftazidime. , after to weeks of initial intensive therapy, subsequent antimicrobial therapy for eradication of the bacteria should be followed using the combination of cotrimoxazole, doxycycline, and chloramphenicol for longer than months. staphylococcus aureus is not a common etiologic agent of cap, as it accounts for less than % of cases. , , in the asia-pacific region, s. aureus has also been found in similar proportion, although there was a report of higher incidence of s. aureus in . % of cap cases in japan (►table ). one of the remarkable issues regarding s. aureus is the emergence of community-associated methicillin-resistant s. aureus (ca-mrsa) with varying clinical syndromes and different strains during the last decade. most common presentation of ca-mrsa infections is skin and soft-tissue infection, but ca-mrsa can also cause severe cap presenting as necrotizing pneumonia. [ ] [ ] [ ] since the emergence of ca-mrsa in western australia in the early s, numerous reports on small number of cases have been published from countries in the asia-pacific region. [ ] [ ] [ ] [ ] [ ] but data on the prevalence of ca-mrsa causing cap are lacking. a retrospective study from south korea reported that s. aureus was isolated from . % of cases with pathogens identified, and among them, twothirds ( / ) were mrsa. mrsa accounted for . % of the cases with cap in a taiwanese multicenter study. however, both studies did not examine the genotypic and phenotypic characteristics of mrsa isolates. in a report from south korea that studied the community-onset sequence type mrsa-sccmec type iv infection, the predominant ca-mrsa clone in the country, showed that pneumonia was the focus of infection in % of the cases. there have been insufficient data on the exact incidence of cap caused by ca-mrsa in this region. ca-mrsa pneumonia is often associated with poor clinical outcome, which emphasizes the importance of early appropriate treatment. therefore, further study on the epidemiology of ca-mrsa pneumonia in the asia-pacific region is of critical importance. studies published since on the mortality caused by cap in the asia-pacific region are summarized in ►table . reported mortality rates varied between . and %, depending on the country, study population, and hospitalization. but with some exceptions, mortality rates were between and %, while a recent study showed moderately improved outcomes compared with a previous review. although it is difficult to draw a conclusion from these limited data, countries with more advanced economy seem to show better outcomes with regard to pneumonia-specific mortality. older age, - comorbidities, , nursing home residence, and poor performance status , were associated with worse outcome, as in other regions of the world. a relatively small number of studies on the economic burden of cap have been performed in the asia-pacific region. a multicenter study from korea over a decade estimated that the mean direct medical cost was us$ , per case, with no difference among age and risk groups. in new zealand, the direct medical cost was estimated at us$ per episode, which would translate into the national cost of us$ . million. the total annual cost, which includes direct and indirect medical cost and loss of productivity, was us$ . million. chen et al conducted a study to evaluate the cost benefits of pneumococcal vaccination and, in the process, estimated the national cost of cap in the elderly to be us$ million each year. another study on the cost of cap in china reported the median cost for hospitalization to be us $ . . because direct and indirect costs caused by the medical condition are determined by multiple socioeconomic factors, direct comparison of the cost between countries is not appropriate. but the published data invariably revealed that the economic burden of cap is quite significant, especially in countries with limited resources. the asia-pacific region shows its own landscape of cap with regard to the incidence, etiologic pathogens, antimicrobial resistance, clinical outcomes, and socioeconomic burden of the disease, reflecting the diversity of the region. since data on major issues of cap need to be further collected in many countries in the region, appropriate and continuous surveillance of cap is strongly warranted given the clinical and socioeconomic importance of the disease. all authors have nothing to declare. this study was partly supported by a grant from the korean health technology r&d project, ministry of health & welfare, republic of korea (grant no. hi c ) , and partly by the asia pacific foundation for infectious diseases. united nations economic and social commission for asia and the pacific (unescap) the global burden of disease: update. world health organization a comparison of population-based pneumonia surveillance and health-seeking behavior in two provinces in rural thailand a household survey on morbidity and treatment of acute respiratory infections in communities in vietnam an asian study on the prevalence of atypical respiratory pathogens in community-acquired pneumonia hospitalization of aboriginal and non-aboriginal patients for respiratory tract diseases in western australia, - community-acquired pneumonia in the asia-pacific region song et al. this document was downloaded for personal use only. unauthorized distribution is strictly prohibited major causes of death among men and women in china acute respiratory illness incidence and death among children under two years of age on lombok island, indonesia adult pneumonia study group-japan (apsg-j). the burden and etiology of communityonset pneumonia in the aging japanese population: a multicenter prospective study high incidence of community-acquired pneumonia among rapidly aging population in japan: a prospective hospital-based surveillance economic cost of communityacquired pneumonia in new zealand adults māori have a much higher incidence of community-acquired pneumonia and pneumococcal pneumonia than non-māori: findings from two new zealand hospitals hospitalization for pneumonia in children in auckland incidence of acute respiratory infections in children months to years of age in periurban communities in karachi, pakistan incidence and risk factors of childhood pneumonia-like episodes in biliran island, philippines -a community-based study trends in pneumonia and influenza-associated hospitalizations in south korea trends in the leading causes of death in korea epidemiology and etiology of childhood pneumonia mortality trends of elderly people in taiwan from to epidemiology and impacts of children hospitalized with pneumonia from to in taiwan burden of adult pneumonia in thailand: a nationwide hospital admission data epidemiology of radiographically-confirmed and bacteremic pneumonia in rural thailand infectious disease mortality rates the incidence of pneumonia in rural thailand pneumonia surveillance in thailand: current practice and future needs burden of acute lower respiratory infection in children in thailand in : have we achieved the national target in under-five morbidity and mortality asian network for surveillance of resistant pathogens study group. epidemiology and clinical outcomes of community-acquired pneumonia in adult patients in asian countries: a prospective study by the asian network for surveillance of resistant pathogens infectious diseases society of america/american thoracic society consensus guidelines on the management of community-acquired pneumonia in adults community-acquired pneumonia community-acquired pneumonia requiring hospitalization among u.s. adults comprehensive molecular testing for respiratory pathogens in community-acquired pneumonia microbial aetiology of community-acquired pneumonia and its relation to severity etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods etiology of community-acquired pneumonia in hospitalized patients: a -year prospective study in japan community-acquired pneumonia in japan: a prospective ambulatory and hospitalized patient study etiology of community-acquired pneumonia requiring hospitalization in japan usefulness of the japanese respiratory society guidelines for community pneumonia: a retrospective analysis of community-acquired pneumonia between and in a general hospital a -year prospective study of a urinary antigen-detection test for streptococcus pneumoniae in community-acquired pneumonia: utility and clinical impact on the reported etiology atypical pathogens as etiologic agents in hospitalized patients with community-acquired pneumonia in korea: a prospective multi-center study the difference in clinical presentations between healthcare-associated and communityacquired pneumonia in university-affiliated hospital in korea etiology of community acquired pneumonia among adult patients requiring hospitalization in taiwan a prospective etiologic study of community-acquired pneumonia in taiwan australian cap study collaboration. the etiology of community-acquired pneumonia in australia: why penicillin plus doxycycline or a macrolide is the most appropriate therapy community-acquired pneumonia in christchurch and waikato - : microbiology and epidemiology impact of infectious etiology on the outcome of taiwanese patients hospitalized with community acquired pneumonia community-acquired pneumonia in the asia-pacific region song et al prospective multicenter study of the causative organisms of communityacquired pneumonia in adults in japan community-acquired pneumonia in shanghai, china: microbial etiology and implications for empirical therapy in a prospective study of patients causative agent distribution and antibiotic therapy assessment among adult patients with community acquired pneumonia in chinese urban population different microbiological and clinical aspects of lower respiratory tract infections between china and european/american countries community-acquired pneumonia in southeast asia: the microbial differences between ambulatory and hospitalized patients antimicrobial drug-resistant microbes associated with hospitalized community-acquired and healthcare-associated pneumonia: a multi-center study in taiwan the use of multiplex real-time pcr improves the detection of the bacterial etiology of community acquired pneumonia pulmonary tuberculosis presenting as community-acquired pneumonia pisprasert v. etiologies and treatment outcomes in patients hospitalized with community-acquired pneumonia (cap) at srinagarind hospital microbiological profile and drug sensitivity pattern among community acquired pneumonia patients in tertiary care centre in mangalore clinical features of communityacquired pneumonia treated at srinagarind hospital aetiology and outcome of severe community-acquired pneumonia in singapore viruses and gramnegative bacilli dominate the etiology of community-acquired pneumonia in indonesia, a cohort study the incidence and aetiology of hospitalised community-acquired pneumonia among vietnamese adults: a prospective surveillance in central vietnam respiratory viral detection in children and adults: comparing asymptomatic controls and patients with community-acquired pneumonia clinical and economic burden of community-acquired pneumonia amongst adults in the asia-pacific region high prevalence of antimicrobial resistance among clinical streptococcus pneumoniae isolates in asia (an ansorp study) regional trends in betalactam, macrolide, fluoroquinolone and telithromycin resistance among streptococcus pneumoniae isolates - surveillance of invasive pneumococcal disease in colombo, sri lanka treatment guidelines for community-acquired pneumonia in korea: an evidence-based approach to appropriate antimicrobial therapy japanese respiratory society. the jrs guidelines for the management of community-acquired pneumonia in adults: an update and new recommendations high incidence of multidrug-resistant streptococcus pneumoniae in south korea clinical outcomes of pneumococcal pneumonia caused by antibiotic-resistant strains in asian countries: a study by the asian network for surveillance of resistant pathogens clinical characteristics of pneumonia caused by penicillin resistant and sensitive streptococcus pneumoniae in japan risk factors and clinical outcomes of penicillin resistant s. pneumoniae community-acquired pneumonia in khon kaen effects of new penicillin susceptibility breakpoints for streptococcus pneumoniae-united states changing trends in antimicrobial resistance and serotypes of streptococcus pneumoniae isolates in asian countries: an asian network for surveillance of resistant pathogens (ansorp) study antimicrobial susceptibility of respiratory tract pathogens in japan during protekt years - ( - ) antimicrobial susceptibility and serotype distribution of streptococcus pneumoniae isolated from patients with community-acquired pneumonia and molecular analysis of multidrug-resistant serotype f and f strains in japan antimicrobial susceptibilities of streptococcus pneumoniae isolated from adult patients with community-acquired pneumonia in japan circulation of international clones of levofloxacin non-susceptible streptococcus pneumoniae in taiwan capsular serotypes and antimicrobial susceptibilities of streptococcus pneumoniae causing invasive pneumococcal disease from - with an emphasis on serotype a in bacteraemic pneumonia and empyema and β-lactam resistance worldwide incidence, molecular epidemiology and mutations implicated in fluoroquinolone-resistant streptococcus pneumoniae: data from the global protekt surveillance programme increasing resistance of streptococcus pneumoniae to fluoroquinolones: results of a seminars in respiratory community-acquired pneumonia in the asia-pacific region song et al. this document was downloaded for personal use only. unauthorized distribution is strictly prohibited hong kong multicentre study in active bacterial core surveillance of the emerging infections program network. effect of introduction of the pneumococcal conjugate vaccine on drugresistant streptococcus pneumoniae emergence of streptococcus pneumoniae serotypes a, c, and f and serogroup in cleveland, ohio, in relation to introduction of the protein-conjugated pneumococcal vaccine emergence of a as virulent and multidrug resistant pneumococcus in massachusetts following universal immunization of infants with pneumococcal conjugate vaccine increased penicillin nonsusceptibility of nonvaccineserotype invasive pneumococci other than serotypes a and a in post- -valent conjugate vaccine era invasive pneumococcal diseases surveillance study group. serotype changes and drug resistance in invasive pneumococcal diseases in adults after vaccinations in children distribution and annual changes in streptococcus pneumoniae serotypes in adult japanese patients with pneumonia predominance of st among streptococcus pneumoniae serotype a isolates from asian countries antimicrobial therapy in community-acquired pneumonia among emergency patients in a university hospital in japan role of 'atypical pathogens' among adult hospitalized patients with community-acquired pneumonia prevalence and clinical presentations of atypical pathogens infection in community acquired pneumonia in thailand comparison of laboratory diagnostic procedures for detection of mycoplasma pneumoniae in community outbreaks pneumonia guidelines committee of the bts standards of care committee. bts guidelines for the management of community acquired pneumonia in adults: update medical foundation in memory of dr. deh-lin cheng; foundation of professor wei-chuan hsieh for infectious diseases research and education; cy lee's research foundation for pediatric infectious diseases and vaccines. guidelines on antimicrobial therapy of pneumonia in adults in taiwan, revised characteristics of macrolideresistant mycoplasma pneumoniae strains isolated from patients and induced with erythromycin in vitro characterization and molecular analysis of macrolide-resistant mycoplasma pneumoniae clinical isolates obtained in japan mycoplasma pneumoniae isolated from patients with respiratory infection in kanagawa prefecture in - : emergence of macrolide-resistant strains macrolide-resistant mycoplasma pneumoniae: characteristics of isolates and clinical aspects of community-acquired pneumonia antimicrobial susceptibility of mycoplasma pneumoniae isolates and molecular analysis of macrolide-resistant strains from molecular mechanisms of macrolide resistance in clinical isolates of mycoplasma pneumoniae from china high prevalence of macrolide resistance in mycoplasma pneumoniae isolates from adult and adolescent patients with respiratory tract infection in china macrolide resistance of mycoplasma pneumoniae macrolide-resistant mycoplasma pneumoniae in children in taiwan emergence of macrolide-resistant mycoplasma pneumoniae in hong kong is linked to increasing macrolide resistance in multilocus variable-number tandemrepeat analysis type - - - molecular characterizations of pcrpositive mycoplasma pneumoniae specimens collected from australia and china regional differences in prevalence of macrolide resistance among pediatric mycoplasma pneumoniae infections in hokkaido clinical evaluation of macrolide-resistant mycoplasma pneumoniae a comparative clinical study of macrolide-sensitive and macrolide-resistant mycoplasma pneumoniae infections in pediatric patients characterization of macrolide resistance of mycoplasma pneumoniae in children in shenzhen, china rapid effectiveness of minocycline or doxycycline against macrolide-resistant mycoplasma pneumoniae infection in a outbreak among japanese children therapeutic efficacy of macrolides, minocycline, and tosufloxacin against macrolideresistant mycoplasma pneumoniae pneumonia in pediatric patients macrolide-resistant mycoplasma pneumoniae: its role in respiratory infection community-acquired pneumonia in the central desert and northwestern tropics of australia adult community-acquired pneumonia in malaysia: prediction of mortality from severity assessment on admission community-acquired pneumonia in patients requiring hospitalization community-acquired klebsiella pneumoniae bacteremia: global differences in clinical patterns bacteremic communityacquired pneumonia due to klebsiella pneumoniae: clinical and microbiological characteristics in taiwan klebsiella pneumoniae related community-acquired acute lower respiratory infections in cambodia: clinical characteristics and treatment molecular epidemiological characteristics of klebsiella pneumoniae associated with bacteremia among patients with pneumonia respiratory infections unique to asia melioidosis: an important cause of pneumonia in residents of and travellers returned from endemic regions the epidemiology and clinical spectrum of melioidosis: cases from the year darwin prospective study cutaneous melioidosis in the tropical top end of australia: a prospective study and review of the literature economic burden of bacteremic melioidosis in eastern and northeastern, thailand the - outbreak of melioidosis in the northern territory of australia: clinical aspects fatal human melioidosis in southeastern queensland endemic melioidosis in tropical northern australia: a -year prospective study and review of the literature the epidemiology of melioidosis in australia and papua new guinea acute lower respiratory infections in year -old hospitalized patients in cambodia, a low-income tropical country: clinical characteristics and pathogenic etiology pulmonary melioidosis in cambodia: a prospective study first report of septicaemic melioidosis in hong kong emerging clinico-epidemiological trends in melioidosis: analysis of cases from western coastal india bacteremic melioidosis in southern taiwan: clinical characteristics and outcome melioidosis in hainan, china: a restrospective study melioidosis causing critical illness: a review of years of experience from the royal darwin hospital icu clinical manifestation of pulmonary melioidosis in adults imported melioidosis in south korea: a case series with a literature review comparison of imipenem and ceftazidime as therapy for severe melioidosis outcomes of patients with melioidosis treated with meropenem interventions for treating melioidosis molecular epidemiology of communityassociated meticillin-resistant staphylococcus aureus in asia severe community-onset pneumonia in healthy adults caused by methicillin-resistant staphylococcus aureus carrying the panton-valentine leukocidin genes association between staphylococcus aureus strains carrying gene for panton-valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients pneumonia caused by methicillin-resistant staphylococcus aureus methicillin-resistant staphylococcus aureus in western australia, - fatal bacteraemic pneumonia due to community-acquired methicillin-resistant staphylococcus aureus clinical features and molecular characteristics of invasive community-acquired methicillin-resistant staphylococcus aureus infections in taiwanese children pediatric pneumonia death caused by community-acquired methicillin-resistant staphylococcus aureus community-acquired, methicillinresistant staphylococcus aureus isolated from children with community-onset pneumonia in china post-influenza pneumonia caused by the usa community-associated methicillin-resistant staphylococcus aureus in korea clinical predictors of communitygenotype st -methicillin-resistant staphylococcus aureus-sccmec type iv in patients with community-onset s. aureus infection ansorp study group. spread of methicillin-resistant staphylococcus aureus between the community and the hospitals in asian countries: an ansorp study life-threatening hemoptysis in adults with community-acquired pneumonia due to panton-valentine leukocidin-secreting staphylococcus aureus clinical and economic burden of invasive pneumococcal disease in adults: a multicenter hospitalbased study disease burden of pneumonia in korean adults aged over years stratified by age and underlying diseases the risk factors for mortality of community-acquired pneumonia in japan cost benefits of targeting the pneumococcal vaccination program to the elderly population in taiwan community-acquired pneumonia in the asia-pacific region song et this document was downloaded for personal use only. unauthorized distribution is strictly prohibited potential for cost-savings in the care of hospitalized low-risk community-acquired pneumonia patients in china detection of viral and bacterial pathogens in hospitalized children with acute respiratory illnesses prevalence and correlation of infectious agents in hospitalized children with acute respiratory tract infections in central china detection of viruses and atypical bacteria associated with acute respiratory infection of children in hubei the aetiology of community associated pneumonia in children in nanjing, china and aetiological patterns associated with age and season epidemiology, clinical characteristics and antimicrobial resistance patterns of community-acquired pneumonia in hospitalized children in singapore incidence and etiology of acute lower respiratory tract infections in hospitalized children younger than years in rural thailand burden of pneumonia and meningitis caused by streptococcus pneumoniae in china among children under years of age: a systematic literature review ibis study group indiaclen network. invasive pneumococcal disease associated with high case fatality in india the incidence of pediatric invasive pneumococcal disease in chiba prefecture capsular serotype and antibiotic resistance of streptococcus pneumoniae isolates in malaysia virolainen a; arivac consortium. low incidence of antibiotic resistance among invasive and nasopharyngeal isolates of streptococcus pneumoniae from children in rural philippines between and invasive pneumococcal infections: a clinical and microbiological analysis of patients in taiwan characterization of invasive isolates of streptococcus pneumoniae among taiwanese children prevalence and clinical significance of community-acquired penicillin-resistant pneumococcal pneumonia in thailand decreased streptococcus pneumoniae susceptibility to oral antibiotics among children in rural vietnam: a community study mortality of communityacquired pneumonia in korea: assessed with the pneumonia severity index and the curb- score none. key: cord- -cc e x authors: jang, t.-n; yeh, d.y; shen, s.-h; huang, c.-h; jiang, j.-s; kao, s.-j title: severe acute respiratory syndrome in taiwan: analysis of epidemiological characteristics in cases date: - - journal: j infect doi: . /j.jinf. . . sha: doc_id: cord_uid: cc e x objectives. to describe the clinical characteristics and outcomes of patients with severe acute respiratory syndrome (sars). methods. between march and june ' , patients with probable sars seen at shin kong wu ho-su memorial hospital, taipei, were analysed. results. presenting symptoms included fever ( %), cough ( . %), chills or rigor ( . %), and shortness of breath ( . %). mean days to defervescence were . ± . days, but fever recurred in patients ( . %) at . ± . days. common laboratory features included lymphopenia ( . %), thrombocytopenia ( . %) and elevated c-reactive protein (crp), lactate dehydrogenase (ldh), and aspartate aminotransferase (ast) ( . , . , . %, respectively). all patients except one had initial abnormal chest radiographs and ( . %) had radiological worsening at . ± . days. nine patients ( . %) subsequently required mechanical ventilation with four deaths ( . %). most patients with clinical deterioration responded to pulse corticosteroid therapy ( out of ) but six complicated with nosocomial infections. the risk factors associated with severe disease were presence of diarrhoea, high peak ldh and crp, high ast and creatine kinase on admission and high peak values. conclusions. prudent corticosteroid use, vigilant microbiological surveillance and appropriate antibiotics coverage are the key to successful treatment. province, people's republic of china, that has continued since november , was reported to have infected people and caused deaths. this outbreak received no international attention until february , when a nephrologist from guangdong province became ill during a one-day stay on the ninth floor of a hong kong hotel. twelve other guests became infected including staying on the same floor. these hotel guests subsequently became the index patients who transported the disease to vietnam, singapore, canada, ireland, and the united states. the primary mode of transmission of sars appears to be by the airborne spread of large droplets. as the illness has spread, the condition has been particularly prevalent among healthcare workers and their household members. many cases progressed rapidly and often resulted in acute respiratory distress syndrome (ards). , the syndrome was designated as 'severe acute respiratory syndrome' (sars) in march . , as of july , , a total of cases resulting in deaths (a case-fatality proportion of . %) have been reported from more than countries globally. taiwan has a population of over million. the development of sars became a real concern in taiwan because of the extensive business ties and inter-country travel that exist between taiwan, hong kong, and especially mainland china, which appears to be the origin of sars. the first probable sars patient in taiwan returned from china via hong kong early in the global outbreak in february . for more than a month, the daily incidence cases remained in the single digits until a nosocomial outbreak occurred in a municipal hospital (hospital a) in taipei on april , . as of july , probable cases and deaths have been reported in taiwan. we analyse the clinical, laboratory, and radiological features of patients with probable sars who were seen at the shin kong wu ho-su memorial hospital (skmh) in taipei, taiwan. in addition, we also report the probable index case for the sars outbreak in taiwan. skmh is an -bed teaching hospital in the city of taipei, taiwan. between march and june , patients who were suspected of having sars were admitted to the isolation rooms. fiftythree of these patients were subsequently excluded after other explanations for their fever and abnormal chest x-rays were found. the remaining patients fulfilled the world health organization (who) criteria of 'probable sars' infection. routine microbiological tests were performed to exclude other causative pathogens, and reversetranscriptase-polymerase-chain-reaction (rt-pcr) of oropharyngeal swabs were done for sarsassociated coronavirus in each case as described elsewhere. initial treatment included amoxicil-lin/clavulanic acid or ceftriaxone and clarithromycin to target common pathogens causing community-acquired pneumonia, according to current recommendations. , oral ribavirin ( . g followed by - mg daily) or intravenous ribavirin ( mg q h) for severe cases was also administered. corticosteroid therapy included intravenous hydrocortisone ( mg four times daily) in mild cases, and methylprednisolone ( - mg/kg/day) in moderate cases. daily pulsed administration of . - . g of methylprednisolone for two to three days was carried out for those patients with persistent high fever, radiological worsening, increasing shortness of breath, or oxygen desaturation. in severe cases, and depending on the attending physician's judgment, human immunoglobulin could be administered intravenously ( gm/kg/day for days). we compared risk factors associated with complicated and uncomplicated diseases. the wilcoxon test was used to compare distributions of continuous variables. categorical variables were compared using the chi-square or fisher's exact test, as appropriate. data are reported as meansŝ tandard deviation (sd) unless otherwise specified. all p values were -tailed; p , : was considered statistically significant. for the analysis, the spss software package, version . (spss inc., chicago, usa) was used for the analysis. the demographic profiles and comorbidities of the cases are shown in table . their median and mean ages were and . years, respectively, with a range of - years. the female-to-male ratio was . : . six of the patients ( . %) had comorbidities that included cardiovascular diseases ðn ¼ Þ; diabetes mellitus ðn ¼ Þ; and chronic pulmonary disease ðn ¼ Þ: among the patients, ( . %) had been to hospitals with known sars outbreak, ( . %) were healthcare workers, ( . %) were household contacts, ( . %) were unknown, ( . %) had recently traveled to mainland china or hong kong, and ( . %) had social contact with sars patients. one of these patients is the first native sars case without a contact history in taiwan. she was referred from hospital a on april and may have been the index case of the hospital a outbreak. here we briefly describe her history. a previously healthy -year-old housewife was transferred to skmh from hospital a on april , on suspicion of sars. she displayed a persistent fever accompanied by chills and a dry cough for days, and had become dyspnoeic days prior to transfer. she denied any previous hospital visits or recent travel outside of taiwan. the patient recollected a -hour train journey to taipei days prior, when she was in close proximity to a female who had a persistent cough. the patient went to the emergency room of hospital a in the morning of april , . a chest x-ray showed extensive bilateral lower lung infiltrates ( fig. , panel a). soon after arrival in our hospital, she required % oxygen through a non-rebreathing mask to maintain her oxygen saturation. a second chest x-ray taken in the afternoon showed progressive changes ( fig. , panel b) . by that evening, the patient developed progressive tachypnea and had to be intubated. the sputum gram-stain obtained after intubation showed many inflammatory cells without visible bacteria (fig. ) . she was treated with empiric antibiotics, ribavirin and corticosteroids. on the eighth hospital day, her fever subsided, and her oropharyngeal swab came back positive for sars-associated coronavirus by rt-pcr. on the same day, her husband and son were admitted to other hospitals in taipei due to fever and pulmonary infiltrates. both subsequently proved positive for coronavirus by rt-pcr. on april , the patient was extubated. the relative frequencies of all reported symptoms at the time of admission are shown in table all patients except one had abnormal chest radiographs on presentation; ( . %) had unilateral focal involvement, and ( . %) had either unilateral multifocal or bilateral involvement. the initial radiographic changes were indistinguishable from those associated with other causes of bronchopneumonia. radiological worsening was noted in patients ( . %) at a mean of . ^ . days. overall, patients ( . %) progressed to diffuse ground-glass appearance. sars-associated coronavirus rna was detected in oropharyngeal swabs by rt-pcr in ( . %) of patients at initial presentation. routine microbiological investigation for known viruses and bacteria was negative in most cases except three patients who had evidence of coinfection with mycoplasma, legionella, and streptococcus pneumoniae, respectively. all patients received empirical antibiotic therapy during the course of their hospitalization. ribavirin was begun at a mean of . ^ . (range - ) days after onset of illness to all patients. the mean duration of treatment with ribavirin was . ^ . days (median: days). all patients received oral the sars epidemic started in asia, with the majority of cases occurring in china and the asian-pacific region. prior to the nosocomial outbreak at 'hospital a', most cases of sars in taiwan had been restricted to imported cases from sarsaffected regions. only probable cases were detected in the first month. however, when seven cases of sars were reported among healthcare workers at hospital a on april , , the incidence of sars cases in taiwan increased dramatically. the index patient was a laundry worker who lived in the basement of hospital a and was often in the emergency room chatting with the staff. he noted the onset of fever and diarrhoea on april . the source of infection for the index patient remained unclear because hospital a admitted no known sars patients prior to the incident except for our reported case, who was treated in the emergency department of hospital a for a few hours prior to transferring. the possibility of transmission via incidental contact at the emergency room or indirect contact through laundry items cannot be excluded. success in controlling sars relies on early identification of suspect cases, proper isolation, and meticulous infection control measures. recognition of a native case without a prior contact history plays an important role in controlling an outbreak, especially when no local transmission is reported. the important clues in our reported case included rapid progressive chest x-ray changes and lack of identifiable bacterial pathogen from the initial sputum gram-stain. even though the health authority initially excluded the case patient, she was kept in a negative-pressure isolation room, and her family was quarantined. these precautions proved to be prudent, since a positive coronavirus rt-pcr result was obtained one week later. because of our aggressive infection control policy, there was no sars outbreak at our hospital. we found the initial clinical features of our sars patients to be similar to those recently reported by lee et al. in a cohort of sars patients in hong kong, with the exceptions of a higher occurrence of cough in our patient population ( . % vs. . %), less frequent occurrence of myalgia ( . % vs. . %), and of headache ( % vs. . %). in addition, we also found that . % of our cases had recurrence of fever in the second week of illness. this is similar to that described by peiris et al. where of patients ( %) exhibited recurrent fevers after initial improvement. in the present study, shortness of breath and diarrhoea typically developed at the end of the first week of illness. this finding is also consistent with the report by peiris et al. common laboratory results on presentation included lymphopenia, thrombocytopenia, and elevated crp, ldh and aspartate aminotransferase. with the exception of crp, these findings have been noted elsewhere. , , since the crp elevation resulting from most common viral infections is not as pronounced as in sars, crp is a reasonable candidate marker to distinguish sars from other viral infections early in the infectious process. in the present study, the vast majority of cases ( . %) displayed abnormal chest radiographs on presentation, and a majority of cases ( . %) had radiological worsening during the first week of hospitalisation (mean onset . days). a similar trend has been described by peiris et al. with % of cases exhibiting radiological worsening at a mean of . days. since the initial presentation of sars is quite non-specific, early diagnosis largely relies on known history of potential exposure to the infection. however, once the disease develops into an epidemic, contact history becomes unreliable. clinicians must maintain a high index of suspicion since several features of the clinical presentation may be the important clues to differentiate sars from other infectious diseases. the discovery that a novel coronavirus is the probable cause of sars , , provides a dramatic example of an emerging coronavirus disease in humans. sars-associated coronavirus fulfills koch's postulates for an infectious microbiological disease. rt-pcr assay is the most rapid method for the laboratory diagnosis of sars-associated coronavirus infection. according to a recent cohort study in hong kong, viral rna detection in the nasopharyngeal aspirate has a sensitivity of only % at presentation, but testing of multiple nasopharyngeal and faecal samples increased the sensitivity of the rt-pcr assay. in our study, sars-associated coronavirus rna was detected in oropharyngeal swabs by rt-pcr in ( . %) of patients at initial presentation. the percentage of patients in our cohort who required mechanical ventilation ( %) is much higher than the . % reported by lee et al. in a cohort of sars patients in hong kong. the different clinical courses may be related to different strains of coronavirus infection. recent reports of intubation rates of % ( of patients in hong kong), and % (six of patients in singapore) are more similar to our cases. our mortality rate was . % ( / ) overall and . % in complicated cases. these figures are much higher than those reported from canada ( . %), but comparable to a recent report from singapore with an overall mortality rate of . % ( of patients) and . % ( of patients) in complicated cases. the low canadian mortality rate may be partly due to short-term outcomes, which did not reflect the real mortality after long-term follow-up. at this time, no effective treatment is known for this infection. empirical treatment with a combination of high-dose corticosteroid and ribavirin has been advocated in certain areas. , , the rationale behind this approach is to reduce both the viral load and the inflammatory response generated by the infection. all of our patients received ribavirin without obvious therapeutic response, and . % of the patients became anaemic. this finding is consistent with booth et al. who described that % of their patients experienced a decrease in the haemoglobin level of g/dl or greater after ribavirin use. large-dose corticosteroid became the de facto mainstay of our treatment protocol. most of our patients with clinical deterioration responded to pulse corticosteroid therapy ( out of ), including four out of five patients with repeated episodes of deterioration who were successfully rescued by two or more courses of pulse steroid. recently, a report from guangzhou by zhao et al. also supported this approach. however, the use of large-dose corticosteroid is associated with the high attendant risk of infection. six patients developed several episodes of nosocomial infections in our cohort. we emphasize that appropriate antibiotics coverage and careful microbiological surveillance with judicious corticosteroid use are the key to successful treatment of these patients. univariate analyses showed that the presence of diarrhoea, high peak ldh and crp values, high aspartate aminotransferase and ck on admission and high peak values were associated with adverse outcomes. rigorous multivariate analysis could not be meaningfully performed, however, given the small sample size in our series. age and comorbidities were also not associated with an adverse outcome in our series as observed elsewhere. , , , this may also reflect our sample size. further reports involving larger patient populations will be necessary to clarify our understanding of the risk factors and optimal treatment of sars. world health organization, severe acute respiratory syndrome (sars) update: outbreak of severe acute respiratory syndrome-worldwide outbreak of severe acute respiratory syndrome-worldwide a major outbreak of severe acute respiratory syndrome in hong kong severe acute respiratory syndrome (sars)-multi-country outbreak outbreak of severe acute respiratory syndrome-worldwide world health organization. cumulative number of reported probable cases of sars control measures for severe acute respiratory syndrome (sars) in taiwan severe acute respiratory syndrome-taiwan world health organization. case definitions for surveillance of severe acute respiratory syndrome (sars) a novel coronavirus associated with severe acute respiratory syndrome practice guidelines for the management of community-acquired pneumonia in adults guidelines for the management of adults with community-acquired pneumonia: diagnosis, assessment of severity, antimicrobial therapy, and prevention selected nonparametric techniques update -taiwan, china: sars transmission interrupted in last outbreak area clinical progression and viral load in a community outbreak of coronavirusassociated sars pneumonia: a prospective study identification of severe acute respiratory syndrome in canada a cluster of cases of severe acute respiratory syndrome in hong kong identification of a novel coronavirus in patients with severe acute respiratory syndrome coronavirus as a possible cause of severe acute respiratory syndrome koch's postulates fulfilled for sars virus coronavirus genomic-sequence variations and the epidemiology of the severe acute respiratory syndrome severe acute respiratory syndrome in singapore: clinical features of index patient and initial contacts clinical features and short-term outcomes of patients with sars in the greater toronto area acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome development of a standard treatment protocol for severe acute respiratory syndrome the use of corticosteroids in sars description and clinical treatment of an early outbreak of severe acute respiratory syndrome (sars) in guangzhou, pr china short term outcome and risk factors for adverse clinical outcomes in adults with severe acute respiratory syndrome (sars) we thank the entire staff who worked on the sars ward of shin kong wu ho-su memorial hospital. key: cord- - zawygq authors: hsu, yu-chen; chen, yu-ling; wei, han-ning; yang, yu-wen; chen, ying-hwei title: risk and outbreak communication: lessons from taiwan's experiences in the post-sars era date: - - journal: health secur doi: . /hs. . sha: doc_id: cord_uid: zawygq in addition to the impact of a disease itself, public reaction could be considered another outbreak to be controlled during an epidemic. taiwan's experience with sars in highlighted the critical role played by the media during crisis communication. after the sars outbreak, taiwan's centers for disease control (taiwan cdc) followed the who outbreak communication guidelines on trust, early announcements, transparency, informing the public, and planning, in order to reform its risk communication systems. this article describes the risk communication framework in taiwan, which has been used to respond to the - influenza epidemics, ebola in west africa ( - ), and mers-cov in south korea ( ) during the post-sars era. many communication strategies, ranging from traditional media to social and new media, have been implemented to improve transparency in public communication and promote civic engagement. taiwan cdc will continue to maintain the strengths of its risk communication systems and resolve challenges as they emerge through active evaluation and monitoring of public opinion to advance taiwan's capacity in outbreak communication and control. moreover, taiwan cdc will continue to implement the ihr ( ) and to promote a global community working together to fight shared risks and to reach the goal of “one world, one health.” r isk communication before and during an outbreak continues to be an issue of great concern for public health researchers and practitioners globally. risk communication is an interactive process of exchanging information and opinion on risk among risk assessors, risk managers, and other interested parties. , it is an integral part of any public health emergency response, as it allows people at risk to understand the threat and adopt protec-tive behaviors. in order to respond to the communication challenges posed by the severe acute respiratory syndrome (sars) epidemic in , the world health organization (who) developed guidelines on outbreak communication. among the best practices outlined for effective communication were building trust, making timely announcements, maintaining transparency, informing but not inflaming the public, and planning in advance. in addition, who emphasized that risk communication is one of the core functions that who member states must fulfill as signatories to the international health regulations (ihr) ( ) . risk communication is also a component of global and country preparedness for an influenza pandemic, as part of the pandemic influenza preparedness (pip) framework. therefore, states parties should have risk communication capacity as measured by the ihr ( ) joint external evaluation tool published by who in . one of the most serious public health crises taiwan has faced was the sars outbreak in , which resulted in cases and deaths. from this experience, we learned that public panic could be another outbreak to be controlled during an epidemic. in the early stage of the sars outbreak, events led to massive social panic in taiwan. first, the demand for face masks surged, creating a shortage in the market, and the problem was compounded by certain retailers hoarding their supplies and waiting for the price to rise. this led to public discontent with the way the government handled the situation and caused significant political fallout. the government was under public pressure to take a more forceful stand, but it overreacted by carrying out the most intensive quarantine campaign in the world at that time. during the sars epidemic, taiwan had a total of confirmed cases, yet , people were put under home quarantine. this means that people were quarantined for every confirmed case-a ratio times that of hong kong and times that of beijing. the overreaction on the part of the government, the panic buying of masks on the part of the public, and their distrust of the authorities were all, in part, consequences of a communication breakdown during the early stages of sars. in order to communicate with the public, the government required airtime from all television channels to screen public service announcements on sars, times a day, minutes per session. the announcements were delivered by the minister of health and another prominent expert, who focused on teaching people how to protect themselves against sars on individual and community levels. the government was able to get its full message across without distortion or omission, and the public was given direct access to the latest updates and recommendations from the government. these announcements served ''to inform but not to inflame'' the public, which was a key risk communication principle. the above measures also helped close the information gap between the government and the public-a gap that should have been filled by a responsible media. taiwan's experience with sars highlighted the critical role played by the media during the crisis communication process. the government made it a priority to establish a more constructive relationship with the media after sars. here we describe the risk communication framework in taiwan, which has been used in response to the - influenza epidemics, the ebola outbreak in west africa ( - ), and mers-cov in south korea ( ) during the post-sars era. we also discuss the system's strengths and challenges. after the sars outbreak, taiwan's centers for disease control (cdc) followed the who outbreak communication guidelines-on trust, announcing early, transparency, informing the public, and planning-to reform its risk communication systems. since , a / toll-free hotline has been operating to consult with and educate the public about potential epidemics in a timely manner. the call center was contracted out to one of the largest phone companies in taiwan to provide service in languages (mandarin chinese, taiwanese, hakka, and english). taiwan cdc has provided materials and training to help customer service staff answer questions. if the staff are unable to answer a question, the call will be transferred to taiwan cdc staff for further assistance. in addition, the toll-free hotline has become a part of the national communicable disease surveillance system to detect and control any suspected infectious event with the potential of causing outbreaks in taiwan. we also use it as a monitor or an indicator of the level of anxiety and panic before and during an outbreak. taiwan has built a comprehensive information network for infectious disease surveillance and reporting. combined databases, such as the national health insurance data and taiwan cdc's data warehouse for infectious disease surveillance and warning, are routinely used for decision making, risk communication, and epidemic control purposes. since , a national policy of government open data has further guided health authorities' communication strategies to enhance the transparency and integration of information from diverse resources. in so doing, citizens are provided with increased resources to make well-informed health decisions for themselves and for the wider community through civic participation. for example, people now have easy electronic access to government datasets for information on groups of infectious diseases topics. all of this information is easy to read, free to use, in open document format, and free for value-added analysis. a weekly press conference is held to communicate the latest information on communicable diseases to reporters, with a well-trained spokesperson from taiwan cdc fielding questions from the journalists. in addition to the regular press conferences, during a particular pandemic period special briefing sessions have been organized to update reporters about epidemic situations and what the government is doing risk and outbreak communication to prepare for it. this has helped reporters become more informed about the evolution of the public health situation at hand so that, should a pandemic occur, they would be able to produce more accurate and constructive reports. after the sars outbreak, the government revised the communicable disease control act to make inaccurate reporting by the media a punishable offense to increase their accountability. a daily meeting is held in the early morning to review and discuss public opinion as reflected in the media, including both mass media and social media (eg, bbs, ptt, facebook). in addition, public attitudes are evaluated and analyzed monthly and yearly to provide a reference for improving the strategies of risk communication as well as infectious disease prevention and control. about . % of the population in taiwan accesses information from the newspaper, whereas around . % of the population accesses news and information from the internet. taking into consideration the media use preferences of the citizens, taiwan cdc has used both traditional media (ie, newspaper, tv, radio) and new media (ie, youtube, facebook, line, instagram) to disseminate information since . furthermore, different channels are selected depending on the type of infectious disease and primary audience under consideration. for instance, information on the enterovirus epidemics is disseminated via websites and magazines frequently browsed by parents, while information regarding the prevention and control of hiv/aids has been published on websites or dating apps targeted at the lgbtq community. in order to better prepare for the next emergency, the government has strengthened its risk communication systems and established a national health command center (nhcc) as a flexible response mechanism for internal and partner communication and coordination in the post-sars era. while nonemergency communication between government agencies is currently carried out on an ad hoc basis in taiwan, under the mechanism of national preparedness and response as mandated by the disaster prevention and protection act, these communication efforts may become more formalized and streamlined in the future to improve inter-organizational collaboration and coordination during emergencies. risk communication has been an integral part of taiwan's pandemic influenza preparedness plan. the objectives of risk communication in response to influenza pandemics are to: ( ) urge the public to protect themselves, ( ) enhance public compliance with recommended control measures, ( ) eliminate discrimination against patients and their contacts, and ( ) deal with public panic. taiwan cdc has operated a public relations office since to manage risk communicationrelated issues. the risk communication and response to major (emerging) infectious diseases operating standards was issued to strengthen the quality and reliability of influenza pandemic strategies. therefore, taiwan was able to effectively respond to the h n pandemic in , the h n avian influenza in , and annually to seasonal influenza. in response to the h n pandemic, taiwan cdc held press conferences almost every day, and sometimes twice a day, to provide updates on international travel alerts and the global epidemic situation to the public. in addition to publishing press releases via websites, social media, and text messages, the hotline was quickly deployed to communicate with the public. the number of incoming calls to the toll-free hotline increased dramatically, with a peak at around , calls in a single day, which was indicative of the degree of public panic. however, a crisis occurred when a doctor's son died month after he was vaccinated with a locally manufactured h n influenza vaccine in . the doctor believed there was a causal link between the immunization and his son's death. media coverage of this event prompted more adverse reactions to be reported and triggered a wave of public distrust in vaccine safety and government authorities. this incident eventually brought the vaccination program to a complete stop. no matter how hard health officials tried to explain and reassure, the public remained skeptical about h n vaccination, even after the case's autopsy revealed other likely causes of death. from this incident, taiwan cdc recognized the importance of communicating with medical professionals and opinion leaders in responding to adverse events when carrying out vaccination campaigns. since then, taiwan cdc has held several consultation meetings to exchange opinions on vaccination strategies with these stakeholders. effort has also been made to constantly update healthcare workers on epidemic situations and infectious disease control strategies and guidelines, so that they are able to help the government prevent and control pandemics. when the outbreak of human infections with an emerging avian influenza virus (h n ) occurred in mainland china in early , inter-and intra-organizational communication in and between government agencies was carried out to control avian influenza virus transmission to humans at poultry farms or wet markets. as a result, taiwan cdc coordinated with the animal health authorities and local governments to ban vendors from slaughtering and selling live poultry at traditional markets, which has successfully protected people from avian influenza infections since . this was a successful case of communication and engagement across multiple sectors. in response to the threat of - seasonal influenza, the government has provided million doses of influenza vaccine for the citizens in taiwan. a professional website and blog for promoting influenza immunization were launched in october . in order to analyze the efficiency of risk communication on influenza vaccination, taiwan cdc has monitored the toll-free hotline to identify topics that are of most concern to the public (eg, who are the target population, where to get the shot, adverse event reporting). furthermore, taiwan cdc has disseminated information regarding the influenza vaccination program and preventive measures through websites such as facebook, line, instragram, tumblr, and banner. online opinion monitoring has also been conducted on websites, forums, message boards, and opinion leaders' facebook pages every day to evaluate public attitudes toward the flu shot. taiwan cdc has honed in on popular online discussion platforms (eg, mobile , eyny, ck ) and social media (eg, ptt, facebook, lineq). this has enabled taiwan cdc to stay on top of public opinion in order to address popular concerns and adjust the direction of its public campaign in a timely fashion. when data analysis reveals rumors or misinformation, press releases are quickly issued to provide clarification. moreover, these releases are shared with relevant authorities to facilitate the communication of consistent messages by different government agencies. taiwan cdc's official website also has a designated area for dispelling rumors, which are countered by accurate information. the abovementioned risk communication practices are centered around dynamic listening and rumor management, and they have helped the government successfully promote communicable disease prevention and control as well as vaccination in taiwan. in response to the large-scale ebola outbreak that started in west africa in and the mers outbreak in south korea in , the objectives of risk communication were to: ( ) advise the people who had gone to, or would visit, ebola-and mers-affected areas to take precautions, and ( ) raise the vigilance of the general public. additionally, citizens who were interested in monitoring their own health, who wanted to report a suspected case, or who were in need of medical attention after coming from an affected area and developing symptoms were advised to call the / hotline for further consultation and assistance. there were no confirmed cases of ebola or mers in taiwan, so the purpose of risk communication was to control the infectious diseases outside of the borders and to detect any imported case early to avoid community spread. several risk communication strategies were implemented, including: ( ) issuing travel notices and releasing news to remind citizens going abroad to have greater vigilance, ( ) providing travelers with updated information and health education materials at airports and travel clinics to remind them about disease prevention when visiting affected areas, and ( ) displaying posters or scrolling texts at quarantine stations of the international seaports and airports. rumor monitoring and verification is another critical instrument for reducing public panic when responding to public health emergencies of international concern. during the mers pandemic in south korea, taiwan cdc's monitoring system intercepted a self-posted message on facebook. this facebook member claimed that his friend was quarantined in south korea and petitioned for help from the government. concerned that this was possibly misinformation, taiwan cdc immediately commented on the message, reminding the member not to disseminate misinformation. in addition, the toll-free hotline received a call from the same person reporting the same event, so taiwan cdc was able to get his contact details and reached out to him to get more information regarding the case quarantined in south korea. after verification with the government of south korea, the event was confirmed as a rumor. taiwan cdc issued a press release to the public to clarify this rumor to reduce social panic. the media environment in taiwan is considered one of the freest and most saturated in asia. as of december , , the percentage of internet users had reached . % of the population. in such a dynamic environment, the authorities have continued to learn from their experiences in working with the media to communicate the risk posed by sars in , h n in , h n in , and seasonal influenza in - . the risk communication systems in taiwan were established and reformed after the sars outbreak. a closer relationship with the media has been developed according to the who principles of building trust, making timely announcements, maintaining transparency, informing but not inflaming the public, and planning in advance. the toll-free hotline has also become a critical component of the national communicable diseases surveillance systems for early detection and timely response to the threat of emerging infectious diseases. several countries, such as australia, china, and singapore, have launched similar call centers. while their call centers cover all healthcare-related emergencies, they are not an integral part of the national surveillance systems to detect and respond to emerging infectious disease outbreaks. furthermore, the risk communication systems in taiwan have capitalized on new media platforms to communicate with the public since . digital communication has also helped the taiwan cdc monitor and verify rumors in response to the mers pandemic in south korea. risk communication for public health emergencies has never been an easy process. the public continues to have trust issues when it comes to official information, and rumor control remains a challenge. additionally, extra manpower and funding support have remained a challenge for implementing effective risk communication principles in risk and outbreak communication response to a public health emergency of international concern (pheic), especially in this era of exponentially increasing numbers of new media channels. the government of taiwan has demonstrated considerable improvement in its risk communication practices during public health emergencies since the sars outbreak in . many communication strategies, ranging from traditional media to social and new media strategies, have been implemented to improve transparency in public communication and promote civic engagement. according to the who, the ultimate purpose of risk communication is to enable people at risk to make informed decisions to protect themselves and their loved ones from harm. the taiwan cdc will continue to maintain the strengths of its risk communication systems and resolve challenges as they emerge through active evaluation and monitoring of public opinion to advance taiwan's capacity in outbreak communication and control. moreover, the taiwan cdc will continue to implement the ihr ( ) and to promote a global community working together to fight the shared risk and to reach the goal of ''one world, one health.'' infectious-disease-threats-registration- ?utm_ source=hmd+email+list&utm_campaign=f e a- . . +fmt+workshop+registration&utm_medium=email&utm_ term= _ e-f e a- &mc_cid=f e a&mc_eid=bf e b world health organization. food safety: risk communication world health organization world health organization. who outbreak communication guidelines world health organization joint external evaluation tool: international health regulations quarantine for sars risk communication during the sars outbreak in taiwan: what did we do and what have we learned? new media is not the promised land but a perilous journey for newspaper industry. big data group influenza pandemic strategic plan usage and population statistics: taiwan free australian health advice and information you can count on chinese center for disease control and prevention. management of health hotline useful contact numbers we would like to thank dr. steve hsu-sung kuo, former director-general of the taiwan cdc, for his advice and insights on taiwan's response to the sars outbreak, the h n influenza pandemic, the ebola outbreak in west africa, and mers-cov in south korea. we would also like to thank dr. nancy chen for editorial help on the manuscript. key: cord- -q f vh authors: lin, che-huei; lin, ya-wen; wang, jong-yi; lin, ming-hung title: the pharmaceutical practice of mask distribution by pharmacists in taiwan’s community pharmacies under the mask real-name system, in response to the covid- outbreak date: - - journal: cost eff resour alloc doi: . /s - - - sha: doc_id: cord_uid: q f vh background: pharmacists hold to their promise to foster, implement and promote the health of the population and to prevent disease, given their knowledge, skills, and proximity to the locals. the objective of this study was to foster equality and cost-effectiveness in the distribution and sale of masks to all taiwanese citizens, in response to the covid- pandemic. methods: all special community pharmacies participating in the nhi (national health insurance) served as mask-selling sites. access to masks by citizens was determined and controlled, based on the weekly rationing of the number of purchasable masks per citizen and the last digit of their nhi card number. masks were available on different weekdays for holders of cards ending with odd and even numbers, except on sundays, when everyone was eligible to buy a mask. results: implementing the program has provided equal access to masks for all citizens across taiwan. it has stabilized the pricing of masks and mitigated the public’s anxiety of a perceived likely market shortage. conclusion: the community pharmacy-based approach to the distribution of prevention face masks to citizens represents a new and innovative engagement of pharmacists in public health promotion and protection initiatives. community pharmacies can greatly improve the efficiency, reliability, and cost-saving of the distribution of public health resources to local communities, especially in the face of an epidemic. at the core of founding an informed public health management strategy, there should be an emphasis on the need to engage and empower individuals and communities to assure their own health, and that of others, while mitigating and responding to the public health risks and related exposure within the population [ ] . this is a defining component of the typical health services utilization process and the behavior of all members of society, despite their entry point into the health system [ ] . the community pharmacy-based program for the 'mask real-name system' demonstrated the potential competitive value that is inherent in pharmacists who cost effectiveness and resource allocation *correspondence: lmh.roger@msa.hinet.net † wang jong yi and lin ming hung contributed equally to this work department of pharmacy and master program, tajen university, pintung , taiwan full list of author information is available at the end of the article enhance the distribution-related outcomes of scarce public health management resources to target populations and communities. specifically, the active involvement of pharmacists across taiwan in the implementation of public health promotion and disease control efforts is associated with optimizing the outcomes, by enhancing the management of such efforts for the cost-effectiveness and reliability of their reach and impact on society [ , ] . the prospects for realizing and sustaining a healthy population cannot be assumed where there is no system-wide commitment to embrace and promote wellinformed, value-laden public health and protection strategies by all the relevant stakeholders in public health. at the core of the fundamental features of an informed public health management strategy, there should be an emphasis on the need to engage and empower individuals and communities to assure their own health and that of others, while mitigating and responding to the public health risks and related exposure in the population [ ] . national public health efforts, especially in the wake of a pandemic, can be overwhelming to health systems, in terms of the costs and implementation technicalities, among other challenges. to this end, the critical value of investing in innovative population health management strategies, as a safeguard for assuring the sustainable competitive performance of the health system of a country, cannot be over-emphasized. pharmacists boast that they have the knowledge, skills, professional expertise and proximity advantage that are needed to facilitate and contribute value-laden outcomes related to the implementation of the health promotion and disease prevention efforts by the government [ ] . they are a defining component of the typical health services utilization process and behavior by all members of the society, despite their entry point into the health system [ ] . in taiwan, community pharmacies have proved to be an invaluable resource for the government in helping to implement various health promotion initiatives. from their active involvement in the recovery of residual medicines, discarded medicines, and aids syringe recycling, to anti-drug education and campaigns in primary schools and community drug safety workshops, as well as smoking cessation and advocating the preventation of the betel nut hazard, community pharmacies play an important role in the promotion of public health prevention and treatment in taiwan (additional file ). during the continuous spread of the novel coronavirus epidemic, which started in february , and its related effect on fueling the global phenomenon of chaotic mask purchases, the taiwanese people were seen lining up overnight to buy masks, which caused panic and a crisis throughout the country. the taiwan government quickly announced a ban on the export of masks ( feb ) and the national mask factories were requisitioned to distribute them uniformly [ ] . at the same time, the government announced the implementation of the "mask real-name system" policy for face mask distribution to individuals and families across the nation (additional file ). this policy was the outcome of a high-profile meeting of government officials from the epidemic prevention bureau and the center for disease control (cdc) of taiwan, experts from the taiwan pharmacists association, as well as representatives from the chunghwa post, concerning the feasibility of the "mask real-name system "amidst the fight against the ongoing covid- pandemic. by march ( month after the implementation), the federation of taiwan pharmacists associations, based on the sale of masks in pharmacies in all the counties and cities, found that adults currently use three, and children use five, masks per week, and each pharmacy receives customers per day. in fact, the national mask coverage rate is merely %, on average (statistics of the federation of taiwan pharmacists associations, march ). since april , when the 'mask real-name system' was put into operation, community pharmacies across taiwan have seen a total of , , customers buying masks under the real-name system per week, and a total of , , customers ( customers per day) per month. in addition, according to statistics from the national health insurance administration of the ministry of health and welfare, . million people have bought masks since the mask real-name system began on february . as of april , % (about . million people) have purchased masks from the internet and physical stores, % (about . million people) have only used the internet (including supermarkets) to buy masks, and % (about . million people) have bought masks from physical channels, such as community pharmacies or health clinics (source: ministry of health and welfare). given their proven performance record as being a reliable resource for helping to implement public health promotion initiatives by the taiwanese government, community pharmacies were enlisted to assist in the distribution of face masks to citizens across the country. the objectives were to foster the efficiency, reliability, and cost-effectiveness in the distribution process and to enhance the equality and fairness of access by all taiwanese citizens to face masks. the taiwanese government is on record as having the highest coverage rate ( %) for national health insurance (nhi) and the most comprehensive health insurance database in the world. in total, the special community pharmacies participating in the nhi were according to the announcement of the ministry of economic affairs, the cost of raw materials for masks rose to % in april , and climbed to % in may. however, the ministry of health and welfare stipulated that the price of masks sold to the public by community pharmacies should be nt$ per mask (the price of masks before the pandemic was about nt$ per mask). besides, all mask factories were dispatched to produce masks. since february , when the mask real-name system was launched, the central epidemic command center announced further, on july , , that the mask real-name system would be extended to december , . at the same time, from june , the ministry of health and welfare announced that some masks can be freely traded in supermarkets. however, the selling price varied greatly from nt$ to nt$ per mask, while the price of masks under the real-name system was controlled by the government at nt$ per mask. in addition, to mitigate chaotic mask-purchasing behavior and the related risk of prompting undue face mask shortages in the market, as well as the possibility of creating a public panic and a crisis across the nation, the distribution and sale of face masks to citizens via community pharmacies was based on a rationing system [ ] . the ration for the number of face masks available for purchase at the start of the program was two face masks per week for each adult and child in the country, but on february , the number was increased to four masks per week per individual, for both adults and children. to purchase masks, individuals needed to take their health insurance card to the community pharmacy and swipe it for the purchase, and the data were uploaded to the nhi cloud system to automatically check whether the masks were being bought repeatedly. the system also displayed the available inventory of the purchases. there was also an ongoing effort by the government, in collaboration with non-governmental organizations (ngos), to develop a "mask map" app to provide details concerning the location of nearby pharmacies and the available inventory. the ministry of health and welfare requires the department of social welfare of local county and city governments to cooperate with the department of health and to manage a list for the physically disabled and the elderly who live alone, and the ministry of health was required to visit and distribute the masks, together with the social workers. village officials may carry out the above affairs on behalf of the ministry of health. the implementation of the program required the collaboration of pharmacists serving within community pharmacies, the finance personnel, information technologists, as well as the producers and distributors of face masks in the nation. the eligible buyers were determined by using the value of the last digit on the nhi card number of each individual and the data of their purchase history from the nhi database. these policy provisions were meant to mitigate the possibility of individuals engaging in multiple mask purchases. pharmacists in the community pharmacies determined and informed the local residents on the availability of masks and the specific times that they could make their purchases. in making this determination, pharmacists had to consider the available mask inventory levels, relative to the demand for masks by health care personnel within their local communities, as well as the timing when the majority, if not all, of the locals were available to make the purchases. the involvement of community pharmacists in selling prevention masks greatly enhanced the control of the distribution of face masks in markets across the nation. notably, this approach to the distribution and sale of masks mitigated the free-market approach to sales, by ensuring that masks were only available for sale to citizens through registered community pharmacies. this eliminated the chaos of having rising market prices, as it offered government authorities the upper-hand in setting and enforcing the mask prices. it was also an effective way of alleviating public anxiety about a likely mask shortage. above all, it provided a competitive means for safeguarding the healthcare system from undue mask shortages, by prioritizing the demands of the healthcare personnel mask during allocation. furthermore, details on the travel history of individuals were also filtered through the nhi cloud system, which, in turn, helped to improve the identification of subjects requiring isolation and those violating the isolation mandates of the taiwanese government in the fight against the covid- pandemic. the community pharmacy-based approach to the distribution and sale of prevention face masks to citizens for the ongoing covid- pandemic has proven to be a new and innovative engagement of pharmacists in contributing to the efficient, reliable, equitable, and costeffective implementation of public health promotion and protection initiatives by the government. by providing the increased electronic tracking and reporting of face mask sales in the various communities across the nation, community pharmacies provide the nhi with an informed and reliable mechanism for mitigating chaotic incidents in the distribution, selling, and purchasing of masks across the country [ ] . this approach provides a quick way of securing and reporting data to be used for the government's planning and decisions on the production and distribution of face masks to meet the underlying objective of safeguarding equal access to pandemic prevention resources by all citizens across the nation. in particular, this approach is valuable for enhancing costsavings by the nhi, as it eliminates the arbitrary setting of mask prices by vendors in the marketplace. the "mask real-name system . " program is based on the revision of the tax filing software of the ministry of finance. it features a stable system and immediate online operation. however, this system needs to be equipped with a card reader to read the health insurance card and it can only operate on a computer, which is inconvenient for mobile phone users and it cannot, therefore, be popularized among the public. to make it accessible for all people, the government immediately introduced the mobile phone app, in order to connect with the national health insurance system. to avoid long night-queues to purchase masks, the "mask real-name system . " has changed the "queuing system" into a "registration system", with the aim of dispersing people, reducing the pressure load on the computer system, and preventing people from queuing up to buy masks. the taiwanese government has been engaged in multiple steps from mask exports, to production, pricing to rationing. such engagement in the real-name system has brought many benefits. the price of masks is stable and people can obtain masks at a lower price than in other countries, thus avoiding the epidemic prevention gap caused by the inequality between the wealthy and the poor. in addition, the government's capital and manpower, such as the army's support for mask production, have also been key in increasing the mask production capacity. therefore, the implementation of the real-name system allows people to acquire a certain number of masks on a regular basis, which effectively reduces the crowds. some of the shortcomings and difficulties faced by the selling of real-name masks in community pharmacies are as follows: ( ) community pharmacies need to pack and sell the masks. each pharmacy needs to handle an average of masks per day. in addition to the daily pharmacy sales, the community pharmacies are required to employ more people; ( ) in some community pharmacies, one person is responsible for the whole pharmacy business, and some pharmacists are either in a poor physical condition, pregnant, or unable to provide services for long periods of time, due to family factors, or age; ( ) the taiwanese government has extended the mask real-name system till the end of december . pharmacists in community pharmacies are generally exhausted, both physically and mentally, because of irrational people who come to buy masks, so they often suffer abuse and their personal safety is threatened. however, the planned economical mode of the government will definitely stifle the mechanisms and advantages of the free market. under the government pricing control, people can obtain masks at cheaper prices. in addition, a fixed quota seems to be equal for everyone, and it does not reflect the differences in personal and family needs. for example, medical personnel or business sales personnel actually do need a different number of masks every week. it is not feasible to adjust the rations, so as to quantify the differences in lifestyles. moreover, it may also lead to ethnic opposition, occupational discrimination, and other related issues. furthermore, given that the program is integrated with the nhi database, and hence, the electronic health and medical records of patients across the nation, it allows pharmacists in community pharmacies to assist in the tracking and filling of signed prescriptions for local patients with chronic diseases. in particular, it promises to improve the coordination of supplies for critical medicines and related pharmaceuticals to community pharmacies, which is critical for reducing the number of people going to a hospital for non-critical or avoidable healthcare concerns. moreover, given their professional knowledge and skills, pharmacists serving in community pharmacies can also provide professional drug consultation services to locals [ ] . all of this has the ultimate value of helping to reduce the number of people having to visit hospitals across the country, which, in turn, reduces the undue spread of covid- , by mitigating unnecessary travel and overcrowding in hospitals. this is a critical measure for safeguarding the sustainability of the national health system in the successful fight against pandemics. as taiwan is fighting 'covid- ' , we use the advantages of a complete nhi information system and unite it with community pharmacists, in order to penetrate each community. the pharmaceutical practice of community pharmacists distributing masks to real-name buyers, in response to the covid- pandemic, is an innovative public health management program that optimizes the value-based exploitation of pharmacists, community pharmacy networks (taiwan telcom vpn), and available technology to allow for an efficient, cost-effective, reliable, and equitable population reach. this program, therefore, enables pharmacists to impact the effective management of population health by collaborating with the government and companies to ensure that there are sufficient mask supplies and well-coordinated sales to citizens across the country. given the technology-centric nature of the program, it provides assurance to pharmacists engaging in population health management initiatives of a competitive return on value (additional files and ). pharmaceutical care, health promotion, and disease prevention. in: the pharmacist guide to implementing pharmaceutical care engaging with in-need rural patient populations through public health partnerships role of the pharmacist in reducing healthcare costs: current insights effect of a virtual pharmacy review program: a population health case study taiwan plans to donate , hospital masks to us per week. washington examiner community pharmacists in taiwan at the frontline against the novel coronavirus pandemic: gatekeepers for the rationing of personal protective equipment nity-pharm acist s-taiwa n-front line-again st-novel -coron aviru s-pande mic-gatek eeper s-ratio ning# supplementary information accompanies this paper at https ://doi. org/ . /s - - - . springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. not applicable. not applicable. not applicable. we have read the policy of journal and the authors of this study have no conflict of interest involved. key: cord- - zrmsw f authors: liu, ming-der; chan, ta-chien; wan, cho-hua; lin, hsiu-ping; tung, tsung-hua; hu, fu-chang; king, chwan-chuen title: changing risk awareness and personal protection measures for low to high pathogenic avian influenza in live-poultry markets in taiwan, to date: - - journal: bmc infect dis doi: . /s - - - sha: doc_id: cord_uid: zrmsw f background: outbreaks of low and high pathogenic avian influenza (lpai, hpai) h n in chickens have occurred in taiwan since and , respectively. fully understanding the different awareness, attitudes and protective behaviors adopted by workers in live-poultry markets (lpmws) and local community residents (crs) to face the challenges of lpai and hpai is very important to minimize viral adaptations to human populations. methods: a structural questionnaire containing information on respondents’ occupation, personal risk awareness, attitudes toward different policies, and preventative measures was administered. the two-stage survey (before and after hpai h n outbreaks) was conducted from to , including: ( ) lpmws and crs at lpms from different geographical areas of taiwan after the government announced outbreaks of lpai h n during – , and ( ) lpmws and crs at two lpms in central taiwan after the hpai h n outbreaks in . the chi-squared test and logistic regression were applied for univariate and multivariate analyses, respectively. results: before hpai-h n outbreaks, higher educated respondents demonstrated greater risk awareness and concerns regarding ai. however, lpm-workers protected themselves less from ai viruses (aivs) and had lower acceptance of human or avian influenza vaccines. most importantly, the participants who opposed (versus agreed with) the policy on banning live-poultry slaughtering at lpms reported lower awareness of government prevention and control policies [odds ratio (or): . , % confidence interval (ci): . – . ] or practiced preventive measures (or: . , % ci: . – . ). after hpai-h n outbreaks, the risk awareness about ai in central taiwan significantly increased [lpai to hpai lpmws: . to . %, p < . ; crs: . to . %, p < . ] and lpmws’ belief in the effectiveness of vaccination to prevent human or avian influenza virus infection strikingly decreased ( . to . %, p < . ). conclusions: risk awareness depends on high or low pathogenicity of aivs, working in lpms, levels of education, age, and proximity to the sites of severe ai outbreaks. regardless of novel lpai or hpai virus reassortants that pose public health risks, prompt and clear risk communication focusing on both correct information about aivs and the most appropriate preventive measures are important for effective prevention of human infection. electronic supplementary material: the online version of this article (doi: . /s - - - ) contains supplementary material, which is available to authorized users. since the first occurrence of hpai h n human cases in hong kong in , the public health threat of high pathogenic avian influenza (hpai) has been a major global issue [ ] . exposure to live poultry was significantly associated with symptomatic or fatal cases of h n [ ] . as a result, hong kong government officials rapidly closed live-poultry markets (lpms), and slaughtered more than . million chickens around the end of [ ] , thus successfully controlling the outbreak [ ] . however, hpai h n viruses reappeared in , spread across continents, and sickened patients from to march , [ ] . the overall case fatality rate was . % ( / ). close contact with poultry is an important risk factor in h n infection [ , ] . in southeast asia, infections have mostly occurred in lpms, where activities such as slaughtering, removal of feathers, customers touching chickens, transportation, and cleaning poultry waste occur very frequently [ , ] . importantly, most of the low pathogenic avian influenza (lpai) h n viruses, which caused human infections in different parts of china since february of [ ] , had high viral sequence identities to the h n viruses isolated from wet poultry markets [ ] . this was quite different from the avian influenza (ai) outbreaks in europe and africa, which occurred mostly in poultry farms where migratory birds played an important role [ ] . therefore, exposure to ai viruses (aivs) in lpms in asia has been highly risky [ ] . the increasing number of fatal cases due to h n infections prompted the government of hong kong to initiate policies forbidding the slaughtering of live chickens or other poultry in wet markets [ ] . the awareness of ai has been documented to affect a persons' self-protection behaviors [ ] and live poultry purchases [ ] . it is important for mass media (such as television channels) to provide correct information to enhance the receivers' knowledge and risk awareness [ ] . an individual's level of education [ ] , occupation (such as being poultry workers) [ , ] , and the residential area's experiences with ai outbreaks [ , ] may all affect a person's perception of the risk of ai and their subsequent use of adequate personal protective equipment [ ] . thus, understanding all possible factors associated with risk awareness, attitudes, and practice of prevention measures (rap), as well as differences in risk perception of outbreaks due to lpai versus hpai viruses between the live-poultry market workers (lpmws) and community residents (crs) are all important for providing further education and implementing public health policies on preventing ai infection. taiwan, with close proximity to these asian ai epidemic and endemic centers, has many lpms which could be potential sources of ai virus maintenance for emerging novel influenza reassortant viruses. the first ai outbreak of h n in taiwan started in december , and subsequently these lpai h n viruses spread island-wide [ ] . although a policy to stamp them out was implemented from through , this virus subtype remained in circulation for many years. in october , another outbreak of h n occurred in kaohsiung (located in southern taiwan), and a molecular analysis of the cleavage site of ha of the isolated virus indicated that it was high pathogenic. as the chicken pathogenicity index (intravenous pathogenicity index, ivpi) of the specimens collected for the second time was below . (ivpi = . ), the government officials announced and reported it as an outbreak of lpai to the world organization for animal health (oie) (http://www.oie.int/) [ , ] . in fact, both of these lpai and hpai h n viruses are particularly unique, as they consist of reassortants of six internal segments derived from local taiwan lpai h n viruses, but the ha and na segments had the highest viral sequence identities with the mexican-like h n viruses [ , ] . after the first hpai h n outbreak was officially announced on march , , about , and , chickens were culled in changhua and tainan counties in central taiwan, respectively during february-march [ ] . the elevation from lpai h n to hpai h n viruses in recent years in taiwan provides a great opportunity to investigate whether the rap of high-risk populations of those working in lpms versus local crs were different when facing the greater challenges of hpai h n viruses compared to the past lpai h n ones. therefore, the specific aims of this study were: ( ) to investigate the factors associated with high and low levels of rap among lpmws and crs in outbreak areas throughout taiwan immediately following the announcement by the government on outbreaks of lpai h n ; ( ) to compare the differences in the factors associated with rap after the outbreaks of these ai viruses with low versus high pathogenicity; and ( ) to identify the different sources of information regarding the outbreaks of hpai-h n in chickens in central taiwan among lpmws and crs as well as to compare their willingness to take preventive measures against lpai-h n and the other important emerging infectious diseases. to the best of our knowledge, this is the first study to investigate public health awareness of both lpai and hpai of the same subtype viruses. moreover, our findings could help public health administrators in areas or countries with lpai to better prepare for possible subsequent hpai outbreaks or minimize the numbers of human infections with either lpai or hpai viruses. to fully understand the differences in local responses after the outbreaks of lpai and hpai of h n viruses in taiwan, we conducted two-stage surveys including: ( ) stage i: after the outbreaks caused by lapi h n viruses from january to january , and ( ) stage ii: after the outbreaks caused by hpai h n viruses from february to march . in the first-stage survey (before hpai h n outbreaks), representative lpms were selected across taiwan, including two markets each in northern, central, and southern taiwan, and five markets in eastern taiwan as illustrated in fig. . to increase the sample size for the areas with lpai h n outbreaks, which is the most neglected and important issue to be addressed, we covered all the major lpms in the outbreak areas and asked as many people as possible to answer the questions at each study site. since the outbreaks of lapi h n occurred in different years in various geographical areas, surveys were initiated in the wet markets in different time periods, right after the occurrence of outbreaks, including northern taiwan (january to june ), central taiwan (april to august ), eastern taiwan (february to may ), and southern taiwan (january ). after the outbreaks of hpai h n , which were restricted to changhwa county in central taiwan between february and march , the second-stage survey was conducted in the two lpms situated in the outbreak county (shown in fig. ) with a smaller sample size from late june to early july . for better comparison of the outcome measures between the two studied populations -( ) live-poultry market workers (lpmws) as a "high-risk group" and ( ) community residents (crs) as a "low-risk group", we used convenience sampling among these two groups for each of the study areas. the crs, who were buyers but did not sell or touch any live poultry, were sampled from visitors who shopped at the same lpms or visited the closest convenience stores (such as - stores) at the same time as we asked lpmws. a structural questionnaire was designed to investigate: ( ) ai awareness, ( ) knowledge of government policies, and ( ) protection measures used. to achieve the study objective, the team members who designed and reviewed the questionnaire included infectious disease physicians, infectious disease epidemiologists, scholars experienced in knowledge, attitude and practice (kap) of diseases, field workers who frequently went to lpm to take poultry specimens, and administrators in lpms. the questionnaire included items such as demographic information, job duties, prevention measures, personal perceptions, the impact of china's ai outbreaks on taiwan, attitudes toward different policies such as killing poultry at lpms, and potential confounding variables (age, gender, educational level, and living area) [additional file : appendix , additional file : appendix ]. we did a pilot test on both study groups in different geographical areas to assure full understanding and reliability. after a comprehensive review by questionnaire design team members, the wording of the questionnaire was revised and simplified to maximize the response rates. there were five main questions measuring risk awareness, attitudes and personal protection measures (rap) [additional file : appendix ] . in addition to these five main questions, questions on the awareness of hpai h n outbreaks in and risk perception in lpai-h n , hpai-h n and other important infectious diseases in taiwan [such as severe acute respiratory syndrome (sars)] were also included in the questionnaire of the second surveys for better comparison. most questions were multiple choice, with a comprehensive range of choices or differential scales or rankings [additional file : appendix ] . however, the second main question on possible future outbreaks of human cases of infection with aivs in taiwan was measured by the likert scale. the questionnaire was administered by well-trained interviewers. for better assessment of the exposure levels, the lpm workers were further classified into three risk groups, based on their occupational exposures. the "high-risk group" included butchers and sellers of raw chicken or duck meat. the "moderate-risk group" covered sellers of cooked chicken or duck meet, beef, mutton, pork, and other raw meat sellers. the "low-risk group" included other workers. regarding the risk levels among the market workers, the results showed that workers in all these three risk groups were located significantly more in northern taiwan than in the rest of taiwan (p = . , table ). we then focused on the comparisons of all possible factors that may be associated with rap; in particular, the differences on each question between lpmws and crs based on their occupation were analyzed. only statistically significant differences between these two study groups are presented in tables and , with the covariate of "occupation" adjusted in multivariate analyses. demographic characteristics (including age, gender, living area and education level) were summarized as frequencies and percentages. in order to analyze the respondents' answers, we classified their responses on rap measures into a binary scale (positive and negative perception of the questions) and used a chi-square test and logistic regression for univariate and multivariate analyses, respectively. additional file : appendix is the summary for all the assigned "positives" as " s" and "negatives" as " s" as a binary scale. for univariate analysis, a chi-squared test was used to compare differences in categorical variables [such as age: - , - and≧ (elderly)] and outcome of kap measures between lpmws and crs. the outcome variables, explanatory variables, as well as the model performance for data analyses in this study are all summarized in additional file : appendix . the comparison of perception changes before and after chicken h n outbreaks in central taiwan was analyzed by two-proportion z-test (table ) . for multivariate analysis, we pooled lpmws and crs together and then analyzed the outcome measures for each question. then, logistic regression with stepwise selection of variables was used for estimating the adjusted odds ratios (or) of explanatory factors and their % confidence intervals ( % ci) after adjusting for important confounding variables such as age [ ] , gender, residential area (northern, southern, central and eastern taiwan), education level, and occupation (i.e., lpmworkers and community residents), plus the other outcome variables in addition to the asked rap questions for both lpai and hpai surveys in tables and , respectively. for example, the last question, on effectiveness of vaccines, and the variables from all other questions in the same rap table such as impact of china on taiwan were entered for better assessment. for the best statistical performance, both age and education were entered as continuous variables. only significant variables (p < . ) were included in our final model. therefore, we controlled for the regional differences in each analyses of both the st-and nd-stage surveys. to ensure the validity of our results, basic model-fitting techniques for ( ) variable selection, ( ) goodness-of-fit (gof) assessment, and ( ) regression diagnostics were all used in our regression analyses. the statistical analysis was performed using sas . . (sas institute, cary, nc, u.s.a.). variables with p-value less than . were considered statistically significant. cox & snell r-square and nagelkerke r-square were applied and the results listed in additional file : appendix . the study and its consent procedures were approved by the ethical committee of national taiwan university hospital (approval number: rc). respondents were informed of the purpose of the study, while oral consent was obtained before anonymous questionnaires were administered. due to concern for privacy of the chinese signatures of names, written informed consent was not collected. whenever the respondents did not agree to join the study, the interviewers respected their opinions and did not continue for those cases. for the respondents aged less than years, the interviewers first got the agreement of their parents or guardians. otherwise, the interviewers dropped these cases. in other words, all the successfully collected questionnaires were agreed to verbally by the adult respondents themselves or children's parents or guardians. in addition, our data were fully de-identified to protect the respondents' privacy, and only group data were used for further analyses and statistical tests. both surveys recruited lpmws and crs. the response rates for high-, moderate-, and low-risk groups of lpmws and crs in the stage i survey were %, %, %, and %, respectively. such rates for lpmws and crs in the stage ii survey were % and %, respectively. the response rates for lpm workers after the hpai h n outbreaks were lower than those after the lpai h n outbreaks. in the first-stage survey after the lpai h n outbreaks but before the hpai h n outbreaks, a total of questionnaires were administered, including to lpmws and to crs (table ). in stage i, there were significant differences in gender and education, but the results were comparable across age and geographical distributions, without statistical differences between these two groups [ tables and ]. however, workers in the wet markets had a significantly higher proportion of males [ . % ( / )] as compared to the crs [ . % ( / )] (p < . ). overall, the crs had higher levels of education than the lpmws (p < . ). in the second stage survey (after the outbreaks of hpai h n in central taiwan), respondents ( lpmws and crs) completed the questionnaires. in this subgroup (table ) , the lpmws were significantly less educated (p < . ) and older [mean ± standard deviation (s.d.) of age (by years): . ± . vs. . ± . , p < . )] than those crs of the same local areas with hpai outbreaks. factors associated with risk awareness, attitude and preventive measures of ai before the outbreaks of hpai h n firstly, we analyzed possible factors influencing the awareness of ai in stage i before the outbreaks of hpai h n in taiwan (table ). as to the impact of china on taiwan (question of table ), the respondents with higher levels of education thought that the external outbreaks of ai in poultry or in human cases in china would affect taiwan (or: . , % ci: . - . ), whereas those who opposed the ban on live poultry slaughter in taiwan's traditional markets did not believe in such an influence (or: . , % ci: . - . ). next, the risk awareness regarding the impact of domestic ai outbreaks was assessed (question of table ) . besides level of education, respondents' age and residential area also influenced their risk awareness of human infection of ai in taiwan after the local lpai outbreaks. the older participants (or, . ; % ci, . - . ) and those living in central taiwan (or, . ; % ci, . - . ), where the population density of chickens is the highest and outbreaks of lpai-h n frequently occurred, were less likely to think that taiwan residents would get infection with aivs. however, the respondents living in the h n epidemic site of kaohsiung county in southern taiwan in january with different awareness of ai (after the controversial judgment on the causing agents as lpai or hpai viruses in the outbreak) compared with those in other areas, perceived that people in taiwan would become more likely to be infected with aivs (or: . , % ci: . - . ). since the government announced the new policy of "ten no's, five needs" in (additional file : appendix ) after many outbreaks of lpai h n , we then investigated the factors associated with knowing this policy and a possible future ban on slaughtering live poultry in traditional markets (question of table ). the results showed that greater percentages of respondents with higher levels of education or living in central or eastern taiwan knew the contents of the new government policy on ai than those in other areas (central taiwan in stage i, the mean, median, and range of age for crs were . ± . , . , and - , respectively whereas those for live poultry market workers (lpmws) were . ± . , . , and - , respectively. we used a chi-square test for the statistical analyses in table . there was no significant difference between these two groups [ table ] the data within the percentages of community residents related to the different demographical variables in the stage i survey served as the reference group in this tables and §high risk: butcher, raw chicken/duck sellers. moderate risk: sellers of cooked chicken/duck, beef, pork, mutton, and/or other raw meat. low risk: market cleaners, administrative officers, and those selling flowers, dry goods, vegetables and fruits. *p-value < . . ; % ci, . - . ), the respondents from eastern taiwan, where fewer outbreaks were reported (or, . ; % ci, . - . ), and those without opinions on the banning of poultry slaughtering (or, . ; % ci, . - . ), were all less motivated than those in the comparison groups to implement self-protection measures against aivs. by contrast, both respondents who believed human cases of ai would appear in taiwan (or: . , % ci: . - . ) and those who were also more aware about the new policy"ten no's, five needs" (or: . , % ci: . - . ) had more willingness to engage in self-protection against aivs. in other words, the study subjects' awareness of risk on ai in taiwan and attitude in supporting or opposing government policies were associated with their taking subsequent personal prevention and control measures. on regarding the perceptions on effectiveness of influenza vaccines (question of table factors associated with risk awareness, attitude and preventive measures after the outbreaks of hpai h n the results of the risk awareness, attitudes about, and protective behaviors against ai after the outbreak of hpai h n in taiwan are summarized in table . the older respondents were less likely to believe that taiwan would be affected by the influenza outbreaks in mainland china (or: . , % ci: . - . , question ). again, the impact of outbreaks of ai abroad as well as in taiwan was further explored (questions and table ). the risk awareness of ai causing serious disease and even death was evaluated (question of table ). crs of areas with documented chicken hpai h n outbreaks had higher awareness of ai leading to severe human clinical cases or fatalities (or: . , % ci: . - . ) than crs of other areas. these respondents with greater alertness of the ai severity not only had better knowledge of the new "ten no's, five needs" policy (or, . ; % ci, . - . ) but also were more likely to take preventive measures against aivs (or, . ; % ci, . - . ). after the government declared the outbreaks of hpai h n in taiwan in , we found protective behaviors and shopping habits were different between lpmws and crs. among the respondents, % of them washed their hands frequently ( / ) and . % of them ( / , with missing values) reported the intention to wear facemasks to protect themselves once ai outbreaks occur (table ). in this study, we did not differentiate surgical masks from cloth masks in our questionnaire on "facemasks". however, most of the public can easily buy surgical masks in convenience stores or drug stores. even among the crs, high percentages of them intended to change their shopping behaviors such as avoiding both live-poultry markets ( / , . %) and poultry purchases ( / , . %). comparing the perception differences before and after the outbreaks of chicken hpai h n among the study participants only in central taiwan, our results revealed significant increases in the proportion of both lpmws and crs who perceived taiwanese will be infected by aivs (table ) . after the occurrence of domestic hpai h n outbreaks, the lpmws' risk perception on the possibility of ai epidemics in mainland china affecting taiwan significantly decreased ( . to . %, p < . ), but their risk awareness on the likelihood of people in central taiwan being infected with aivs strikingly increased (from . to . %, p < . ). however, the lpmws' belief that vaccines are capable of preventing human or avian influenza virus infection strikingly decreased ( . to . %, p < . ). after the incident of hpai-h n outbreaks in central taiwan, we asked participants whether they knew that hpai outbreaks had occurred there. among those who knew about the hpai h n outbreaks, lpmws had significantly paid more attention to the ai outbreaks than crs [ . % ( / ) vs. . % ( / ), p = . ] ( table ). detailed analysis of the sources of information on these hpai outbreaks (table ) showed that the major channel for receiving information on the outbreaks for both groups was television broadcasts (lpmws vs cr: . % vs . %, p = . ), followed by the internet and relatives or friends for crs ( %) and newspapers for lpmws ( . %). however, seeking information through newspapers, internet and radio broadcasts was statistically more common among the crs than the lpmws (newspapers: . % vs. . %, p < . ; internet: . % vs. . %, p < . ; radio: . % vs. . %, p < . ). comparing the respondents' risk perception of lpai h n , hpai h n and other important emerging infectious diseases (eids) versus the old disease of tuberculosis (table ), severe acute respiratory syndrome (sars) was perceived as the most risky infectious disease by the respondents, while hpai h n was thought much more important than lpai h n , particularly among market workers (hpai vs lpai for lpmws: . % vs . %, p < . ; for crs: . % vs . %, p < . ). global epidemiology of ai has focused mostly on human cases after the outbreaks of hpai [ , ] , with little attention to lpai. to our knowledge, this is the first study to compare the differences in risk awareness, attitude and personal protection practice (rap) right after the outbreaks of both lpai and hpai of the same virus subtype. we have the following five major findings that may help future global efforts to prevent novel ai viruses (aivs) with pandemic threat to human populations. first, risk awareness, positive attitudes and taking preventive measures depend on several factors, including high or low pathogenicity of aivs (hpaivs or lpaivs), working in lpms, level of education, age, proximity to the sites of severe ai outbreaks, knowledge of ai outbreaks in neighboring countries or areas (e.g., mainland china or hong kong), the level of understanding of important knowledge on aivs, and learning preventive measures through various channels of mass media. second, table . lpmws were significantly older than crs (p < . ) *p-value < . . the data within the percentages of community residents related to the different demographical variables in the stage ii survey served as the reference group in this table a our government officials initiated the pilot study of phase h n avian influenza vaccine trial for animal-related workers in . at that time, the acceptance rate was quite low. therefore, the data of the reported "acceptance of avian influenza vaccine between live-poultry market workers and community residents" were thus compared only after the nd survey in table respondents with higher risk perception (concerning human ai infections in taiwan) before hpai outbreaks had not only more awareness about the ai outbreaks in mainland china affecting taiwan, but also better attitudes toward meeting domestic needs (endorsing the government's new policy on ai, and supporting a ban on slaughtering live poultry in markets). third, participants' better attitudes towards ai prevention and control were associated with higher motivation to practice self-protection measures, even in preventing lpaivs. fourth, individuals with lower educational levels, the lpm workers with high exposure to aivs, and the respondents living in areas with low frequency of ai outbreaks had a lower risk awareness of aivs, particularly lpaivs that might be transmitted to humans. fifth, the respondents' risk awareness and protective behaviors during the periods of lpai h n outbreaks strikingly rose after experiencing the outbreaks of hpai h n . all these together suggest that neglecting health education and precautions in lpms might facilitate adaptation of the virus in human populations, particularly the silent spreading of lpaivs. among all the factors associated with rap related to human infection of aivs, the pathogenicity of ai virus is crucially important, particularly in those areas or countries with no prior experience of hpai outbreaks. however, most past studies have targeted poultry workers as the high risk population due to exposure to possible hpaivs of h and h in sick or dead poultry [ ] , neglecting the dynamic changes of aivs from lpaivs to hpaivs. our study showed that risk perceptions changed significantly for both market workers and the general population after hpai outbreaks in taiwan. the increased pathogenicity of h n aivs may have caused the study subjects to feel nervous, as they faced the outbreaks of sars in and the novel h n influenza pandemic in , thus raising risk perceptions. lower risk perception in these high-risk populations is a general problem in different parts of the world, including taiwan [ ] , italy, thailand and china [ ] . this shows that high-exposure workers need more appropriate information on aivs to complement the information through mass media, which is usually obtained after rather than before outbreaks. generally, lpmws before the outbreaks of hpai in this study also had a lower perception of taiwanese ai risk than local residents (question in table ), so they did not adopt any preventive measures to avoid aiv infection, and did not believe the seasonal influenza vaccination was effective for preventing human or avian influenza. live-poultry markets, the major interface areas between poultry and humans offering conditions for sustainability, amplification, reassortment and cross-species we used logistic regression for the statistical analyses in this live-poultry market workers as the control group transmission of aivs, from h n hpaivs in [ ] to the most recent h n lpaivs in - , have been involved in many human-acquired aiv infections [ ] . most importantly, chickens sold in traditional lpms can transmit aivs to humans through respiratory transmission [ ] . interestingly, the older participants, who had more traditional thinking, and those living in central taiwan, where the density of layer-chickens ranks the highest and outbreaks of lpai-h n occurred more frequently than other areas, had lower risk awareness of aivs. by contrast, the respondents who lived in the epidemic site of kaohsiung county in southern taiwan, where the cleavage site of hemagglutinin (ha) was identified as hpaivs in , had higher perceptions than residents in other areas (or: . ) that people in taiwan would become infected with aivs. after the outbreaks of chicken hpai h n , the lpmws still had a lower belief in the effectiveness of vaccination to prevent human or avian influenza virus infection, regardless of their job duties. furthermore, compliance with and understanding of the government policy raised the individual's risk perception from lpaivs to hpaivs, while other measures of risk awareness had fewer differences among these two surveys, except for the reduction in risk perception on possible ai outbreaks in mainland china affecting taiwan among lpmws in central taiwan. such a striking decrease can be explained by the occurrence of the local hpai outbreaks instead of the imported infections. in other words, attitudes became positive and preventive measures were reported to be taken when they faced the threat of hpaivs. this may have been influenced by we used chi-square test for the statistical analyses in table the data within the percentages of community residents related to the different preventive measures served as the reference group in this this survey was implemented during late june-july , after the outbreak of hpai h n data in the two columns of "before hpai for live-poultry market workers" (lpmws) and "before hpai for community residents" (crs) served as two reference groups of lpmws and crs, respectively n number of participants who answered that specific question *p-value < . *, using a two-proportion z-test mass media or the experience of getting a voluntary h n ai vaccine. therefore, our study demonstrated that the perception of ai risk was elevated as the pathogenicity of aivs changed from low to high. these results emphasize the public health significance of educating high-risk populations, starting from lpaivs with capability to donate viral gene segments for generating novel reassortant viruses that may increase infectivity to humans, like h n and h n in china [ , ] and h n [ , ] and h n [ ] in taiwan. three important policies for ai prevention and control measures are closure of lpms, practicing personal protective measures (ppm), and receiving influenza vaccines before flu seasons. in general, numerous lpms are widely distributed in urban areas that might facilitate avian-tohuman and subsequent human-to-human transmissions of novel influenza viruses, unlike poultry farms, which are more frequently located in rural areas. such geographical differences between the urban and rural areas affected the awareness of ai in turkey [ ] and in china [ ] . in the past, closure of lpms has been implemented after the confirmation of severe or fatal human cases of h n and h n [ ] . however, the virus may still reemerge after temporary closure. therefore, market shutdown is not the most effective long-term measure, especially as the stakeholders are not likely to support it. the most likely approaches are: ( ) weekly and monthly off-market days (such as mondays and chinese festivals in taiwan) for cleaning and interrupting viral transmission, ( ) banning the slaughter of live poultry, ( ) practicing ppm, and ( ) receiving influenza vaccines. in fact, the lpmws with lower education in this study did adopt the latter three prevention measures less frequently. on the other hand, more highly educated participants believed that the outbreaks of ai in china would affect taiwanese, and thus supported the ban on slaughtering live poultry in markets. a ban on slaughtering live poultry in the market, first proposed in hong kong [ ] , has been implemented by the revised food commerce law [ ] . in , a woman in beijing without prior contact with live birds was infected with aivs after purchasing live poultry in a traditional market [ ] , implying that lpms are one of the sources of aiv infection. furthermore, most of the severe human h n cases in - also acquired their infections through contact with poultry or visiting wet markets [ ] . although the taiwan government initiated the implementation of the policy to ban slaughtering live poultry in lpms on april st, (e.g., after the h n outbreak in kaohsiung with controversial answers on viral pathogenicity), this was postponed, then reinstated on may , due to the occurrence of the first imported h n case in taiwan. in this study, lesseducated, high-risk groups had lower rap. therefore, enhancing surveillance of aivs in avian hosts as well as humans in lpms [ ] , timely epidemiologic data analyses and prompt risk communication with evidencebased data support, focusing on changing the minds of lower-educated, high-risk groups, will be very helpful to quickly control novel influenza viruses, thus minimizing the occurrence of potential pandemics. the data within the percentages of community residents related to the sources or channels of information served as the reference group in this ppms are particularly useful for reducing the risk of acquiring or transmitting emerging respiratory infections before the availability of commercial vaccines [ ] . education is the most cost-effective approach to deliver the correct knowledge and ways to prevent aiv infections and future epidemics. highly educated persons who had better access to the information on ai from television, newspapers and the internet in this study had higher risk perception of ai, similar to the findings in china [ ] and afghanistan [ ] . most importantly, strict compliance with personal protective equipment (ppe) requirements must be reinforced to manage the outbreaks of ai, regardless of the pathogenicity of the virus [ , ] . incomplete use of ppe was also associated with conjunctivitis and influenza-like illness after the outbreak of lpai h n in norfolk, england [ ] . generally, compliance with most ppe requirements tends to be suboptimal for the highly exposed groups [ ] . similarly, taiwanese lpm-workers generally feel that wearing ppe is uncomfortable, and they have not gotten used to it. the low risk perception accompanying such poor ppe usage needs to be guided with solid examples to finally achieve behavioral change. our study subjects who had higher risk perception of ai and who were more aware about the government's new policy had more motivation to use self-protection for preventing aivs. therefore, it is necessary to improve public awareness about the government's prevention policy and also educate different target groups with various approaches, based on educational levels, job duties, and residential areas. identifying populations with low acceptance rates of influenza vaccine is important before developing and implementing vaccination programs, particularly as the acceptance of influenza vaccines has become quite low in recent years in many parts of the world [ , ] . we found that market workers and the respondents living in taiwan (except the hpai h n outbreak sites in southern taiwan) did not believe that any influenza vaccine provided effective protection against aivs. a significant drop was observed in the perception of the vaccine effectiveness in preventing "avian influenza" after the impact of hpai compared to lpai h n outbreaks for both lpmws ( . % vs . %) and crs ( . % vs %). in addition, respondents who did not believe in the external influence of outbreaks of ai in mainland china, as well as those who paid no attention to domestic policy in taiwan, and those who found no need to protect themselves against aiv infection did not trust the effectiveness of any influenza vaccine for humans or poultry. to solve this problem, risk communication on sources of the risk as well as scientific data supporting safety becomes very important. additionally, easy access of high-risk populations to ai vaccines (similar to the established system for seasonal influenza vaccination of schoolchildren and the elderly in taiwan, supported by a well-established public health infrastructure), a feasible plan on resources allocation, and the available ai vaccine inducing higher immunogenicity through better innate immunity [ , ] all together, with systematic approaches, will reduce human infections of aivs. there are three major limitations of this study. first, there is a possibility of selection bias caused by the willingness of respondents to reply to the questions in the survey, even though we covered most of the live poultry markets affected by the outbreaks, and the lpmws' response rates were - % and % after the outbreaks of lpai h n and hpai h n , respectively. in addition, the nd-stage survey was conducted only in central taiwan, where the scale of layer chickens was the largest. second, our results may show reduced rap because more study subjects of lpms in the st-stage survey came from northern taiwan, where large-scale wholesale broiler chickens and ducks coming from different parts of taiwan are sold with better management and hygienic standards, whereas high densities of poultry farms are located in central and southern taiwan. third, the study subjects of the st and nd surveys were different and not comparable, and those results indicate only association rather than causation, because of the crosssectional study design. the outbreaks of lpai h n were larger in scale, and occurred much more frequently and in more places than those of hpai h n . to protect participants' privacy, we did not collect personal identification data, and therefore could not follow up on the respondents in the initial survey. future research should focus on the most effective methods and contents for risk communication in order to target different risk groups. risk perception problems on lpaivs need to be explored in relation to the scale, breeding style, types, and sanitation of poultry farms and different kinds of lpms, particularly in areas with limited resources and expertise. in addition, behavioral research is worth doing to direct the best prevention and control policies, considering the acceptance of influenza vaccination and acceptable behavior change in high-risk groups versus the general public. based on our findings, we sincerely recommend that health agencies enhance additional routine two-way risk communication with friendly interpersonal guidance for live-poultry market workers, poultry butchers and farmers, and related high-risk groups, particularly before outbreaks of ai. in addition, to minimize political concerns, fatal human cases after infection with aiv, including lpaivs of h n and h n [ ] in other countries can serve as solid examples for education, using easily influenza a (h n ) in hong kong: an overview case-control study of risk factors for avian influenza a (h n ) disease, hong kong chickens killed in hong kong to combat flu outbreak of avian influenza a(h n ) virus infection in hong kong in cumulative number of confirmed human cases for avian influenza a(h n ) reported to who risk of influenza a (h n ) infection among poultry workers, hong kong, - epidemiology of cases of h n virus infection in indonesia genetic analysis of avian influenza a viruses isolated from domestic waterfowl in live-bird markets of hanoi, vietnam, preceding fatal h n human infections in predicting the global spread of h n avian influenza epidemiology of human infections with avian influenza a(h n ) virus in china human infections with the emerging avian influenza a h n virus from wet market poultry: clinical analysis and characterisation of viral genome human avian influenza a (h n ) virus infection in china avian influenza and ban on overnight poultry storage in live poultry markets, hong kong knowledge, attitudes, practices and emotional reactions among residents of avian influenza (h n ) hit communities in vietnam avian influenza risk perception and live poultry purchase in knowledge, attitudes and practices (kap) relating to avian influenza in urban and rural areas of china relationships among trust in messages, risk perception, and risk reduction preferences based upon avian influenza in taiwan knowledge, attitudes, and practices of avian influenza, poultry workers knowledge, attitudes and practices related to avian influenza among poultry workers in nepal: a cross sectional study an exploration of how perceptions of the risk of avian influenza in poultry relate to urbanization in vietnam personal protective equipment and risk for avian influenza (h n ) the virulence variation in a h n low pathogenic avian influenza virus after passage in -day-old chicken embryonic eggs isolation and characterization of potentially pathogenic h n influenza virus from a chicken in taiwan in a low pathogenic h n influenza virus isolated in taiwan acquired high pathogenicity by consecutive passages in chickens isolation and characterization of potentially pathogenic h n influenza virus from a chicken in taiwan emergence and evolution of avian h n influenza viruses in chickens in taiwan the china post news staff: h n avian flu strikes taiwan: coa biased odds ratios from dichotomization of age global epidemiology of human infections with highly pathogenic avian influenza a (h n ) viruses molecular epidemiology of influenza a (h n ) viruses, bangladesh protecting poultry workers from exposure to avian influenza viruses spatial and temporal analysis of human infection with avian influenza a(h n ) virus in china infectivity and transmissibility of h n avian influenza virus in chickens and wild terrestrial birds infectivity, transmission, and pathology of human-isolated h n influenza virus in ferrets and pigs emergence in china of human disease due to avian influenza a(h n )-cause for concern? human infection with avian influenza a h n virus: an epidemiological analysis knowledge and anticipated attitudes of the community about bird flu outbreak in turkey knowledge, attitudes and practices (kap) relating to avian influenza in urban and rural areas of china global alert to avian influenza virus infection: from h n to h n hong kong places curbs on market poultry physical interventions to interrupt or reduce the spread of respiratory viruses attitudes, and practices regarding avian influenza (h n ) avoiding the risk of infection when working with poultry that is suspected of having h or h notifiable avian influenza effectiveness of personal protective equipment and oseltamivir prophylaxis during avian influenza a (h n ) epidemic, the netherlands self-reported use of personal protective equipment among chinese critical care clinicians during h n influenza pandemic barriers to vaccinating the elderly with h n vaccine why do i need it? i am not at risk! public perceptions towards the pandemic (h n ) vaccine ns -truncated live attenuated virus vaccine provides robust protection to aged mice from viral challenge live attenuated influenza viruses containing ns truncations as vaccine candidates against h n highly pathogenic avian influenza human influenza: one health, one world submit your next manuscript to biomed central and take full advantage of: • convenient online submission • thorough peer review • no space constraints or color figure charges • immediate publication on acceptance • inclusion in pubmed, cas, scopus and google scholar • research which is freely available for redistribution submit your manuscript at www we would like to thank ms. wei-ru chen and ms. ju-feng wang at the institute of epidemiology and preventive medicine, college of public health, national taiwan university and students at st. mary's junior college of medicine, nursing and management, central taiwan university of science and technology, taiwan shoufu university, and hungkuang university for their help on field interviews and collecting questionnaires. in addition, we like to express our sincere gratitude to dr. muh-yong yen at taipei city hospital, dr. john allen at the duke-national university of singapore (duke-nus), ms. wen-wen wang, and administrators in live-poultry markets for their sincere assistance in questionnaire design and evaluation, statistical consultation, administrative support, and coordination in live-poultry markets, respectively. understandable wordings and movies to demonstrate the danger of aerosol transmission of aivs. above all, the policy on banning the slaughter of live poultry at lpms supported by incentives of tax reduction or free health care or certification to win customers' trust, as well as active virological and serological surveillance with random sampling in poultry farms and markets, could be the most efficient way to reduce cross-species transmission. in conclusion, person-to-person risk communication to high-risk groups using more acceptable and attractive approaches and effective public policies on "one health" [ ] , and post-policy evaluation with international comparison will be helpful to promote global health. additional file : appendix . additional file : appendix .additional file : appendix . the authors declare that they have no competing interests.authors' contributions mdl, hpl, tht and cck carried out the survey and designed the questionnaires. mdl, ctc, chw, cck drafted the manuscript. ctc, fch performed the statistical analysis. chw helped interpret the findings from the perspective of veterinary epidemiology. cck conceived of the study, participated in its design and coordination, and helped to revise the manuscript. all authors read and approved the final manuscript. key: cord- -fotolimq authors: sytwu, huey-kang title: expeditious responses to covid- crisis: from governmental management to laboratory approach date: - - journal: biomed j doi: . /j.bj. . . sha: doc_id: cord_uid: fotolimq nan on the basis of recently published literatures about covid- in biomedical journal, we are bringing together this collection of news, short communication, reviews and original articles and highlighting the prompt, direct responses of the taiwanese government in managing this crisis and several thorough reviews and fundamental research on covid- . taiwan is so close to mainland china and was expected to have a very high incidence and number of covid- cases in . however, given a painful experience and lesion learnt from sars years ago, the taiwanese government has been on constant alert and ready to promptly respond to this pandemic arising from china. at the beginning of the covid- outbreak, the national health command center (nhcc) of taiwan, unifying a central command system that is composed of the central epidemic command center (cecc), the biological pathogen disaster command center, the central medical emergency operations center and the counter-bioterrorism command center, rapidly established several critical and timely actions including border control from the air and sea in early january, big data-and technology-based identification of cases, systematic quarantine of suspected cases, proactive case finding, resource allocation, daily press conference and extensive public education, negotiation with other countries and regions, formulation of policies for schools, childcare and nursing homes, and relief to businesses [ ] . apparently, the cecc effectively coordinated different efforts by various ministries, including the ministries of transportation, economics, labor, education, and environmental protection to comprehensively counteract the emerging public health crisis, allowing taiwan to manage the outbreak exceptionally well. in addition to these strategies mentioned above, the commander of j o u r n a l p r e -p r o o f cecc requested national health research institutes (nhri), the only mission-oriented medical and health research center in taiwan, to take the responsibility in coordinating clinical resources and provide a national technology platform for covid- research. in order to develop rapid diagnostic reagents or new drugs, high quality human samples with comprehensive clinical data for testing and verification prior to real clinical application are extremely critical. those bio-specimens are also essential for the basic research and epidemiological analyses. within two weeks, the nhri biobank completed all the ethical and regulatory processes, and the national biobank consortium of taiwan (nbct), also operated by nhri, started to recruit patients and collect their blood samples [ ] . meanwhile, the taiwanese government made several endeavors to improve the current practice of epidemiological investigation by introducing new technologies in digital platform and knowledge graphs [ ] . contact tracing is an important control measure to contain the spread, especially in the early stage of an infectious disease outbreak. in this issue, a swift development of an e-outbreak platform that provides a semi-structured, multifaceted and computer-aided questionnaire to reinforce disease control and contact tracing was described by chen and his colleagues. furthermore, dr. seak presented very proactive strategies implemented by lin-kou chang gung memorial hospital (lcgmh) to effectively prevent spread of covid- among healthcare workers of emergency department (ed) during outbreak [ ] . lcgmh is one of the largest hospitals in the world and the nearest tertiary hospital to taiwan taoyuan international airport, the largest and busiest airport in taiwan. its ed, with approximately , visits per month, is also one of the largest and busiest eds in the world. during the covid- outbreak, they have successfully managed to maintain a "zero-infection" rate among their ed healthcare workers through various, systematic approaches including a clear flowchart with route planning, strict infection control policies and regulation of medical equipment, and team-based segregation in the workplace. the meticulous implementation of these strategies in lcgmh is certainly the key to contribute the successful management against covid- . in this special issue of the biomedical journal, we collected three review articles by drs. shih, chauhan and chi et al., respectively [ ] [ ] [ ] . dr. shih and her colleagues provide a very comprehensive review on the basic properties, potential origin, and evolution of the novel human coronavirus. these virology-based knowledge and viewpoints will be critical for the studies of pathogenicity, antiviral designs, and vaccine development against this highly pathogenic and transmitted virus. dr. chauhan provides an update on a rapidly evolving global pandemic. facing the tremendous threat of emerging and re-emerging infectious diseases, governments all around the world should be well aware that more investments in public health, climate change countermeasures, a global health surveillance system, an effective research into identifying pathogens, subsequent treatment, vaccine development and effective health delivery systems are needed. dr. chi and her colleagues also provide a quick review on covid- , putting emphases on the necessity of urgent development of accurate diagnostic methods, effective treatments, and potential vaccines. apparently, strong, extensive international coordination and collaboration among research institutes, pharmaceutical companies, regulators, and governments are all needed to achieve this goal. given a fact that the highly pathogenic viruses need to be operated in a high level of biosafety containment, it severely hinders the developmental process of drugs, therapeutic antibodies and vaccines. to shorten the timeframe, the pseudoviral systems have been widely applied to verify the potential efficacy and/or immunogenicity of vaccines against those emerging and re-emerging viruses. here dr. wang and her colleagues quickly developed two pseudoviral systems for emerging sars coronavirus (sars-cov- ) and re-emerging avian influenza virus h subtypes which can be handled in biosafety level- facility, facilitating the process in vaccine development in taiwan [ ] . in this issue, dr. ojcius and his colleagues provide an interesting hypothesis that improving oral health could decrease the severity of covid- symptoms and reduce the associated morbidity as well [ ] . on the basis that improving oral health in people of any age effectively reduces their risk of developing non-oral systemic diseases such as diabetes, heart and lung diseases, which have been reported to exacerbate the pathogenesis of sars-cov- infection, the association between oral health and severity of covid- symptoms seems logical. however, more in-depth research is needed to demonstrate its causal relation. with the rapid emergence of new virus strains, there is an urgent requirement for the development of the novel and effective antiviral drugs for the treatment of covid- . in this special issue, drs. dubey presented a computational approach to identify the potential flavones inhibitor narcissoside that binds to coronavirus for the treatment of covid- [ ] . structure-based drug design with molecular docking approach has been a promising technique to expeditiously discover potential inhibitors and has become one of the mainstream practices in modern drug discovery. another quick-to-be-identified cure for covid- will be based on the artificial intelligence (ai) technology. dr. ke and his colleagues have fully taken advantage of this ai-based approach and identified marketed drugs with strong activities against feline infectious peritonitis (fip) coronavirus [ ] . these potential candidates are currently screened by sars-cov- assay system. furthermore, dr. lee and her research team presented another strategy by the repurposing of existing drugs approved for other indications as antiviral agents for sars-cov- [ ] . strikingly, j o u r n a l p r e -p r o o f out of drugs or pharmacologically active compounds screened were found to be active against both fip coronavirus and hcov-oc , with ec values ranging from nm to µm, providing the feasibility of an "immediate" use for covid- patients, in case their anti-sars-cov- activity has been confirmed. all the information collected in this special issue would improve our understanding of the unique features of covid- and enhance our control strategies in the future. response to covid- in taiwan: big data analytics, new technology, and proactive testing rapid establishment of a covid- biobank in nhri by national biobank consortium of taiwan development of a semi-structured, multifaceted, computer-aided questionnaire for outbreak investigation: e-outbreak platform rapid responses in the emergency department of linkou chang gung memorial hospital, taiwan effectively prevents spread of covid- among healthcare workers of emergency department during outbreak: lessons learnt from sars covid- : the first documented coronavirus pandemic in history comprehensive review of coronavirus disease (covid- ) fighting covid- : a quick review of diagnoses, therapies, and vaccines assessing the application of a pseudovirus system for emerging sars-cov- and re-emerging avian influenza virus h subtypes in vaccine development is there an association between oral health and severity of covid- complications? computation screening of narcissoside a glycosyloxyflavone for potential novel coronavirus (covid- ) inhibitor artificial intelligence approach fighting covid- with repurposing drugs repurposing old drugs as antiviral agents for coronaviruses key: cord- -fcdmbo c authors: chang, yuhsuan; chien, chuang-rei; shen, li-fang title: telecommuting during the coronavirus pandemic: future time orientation as a mediator between proactive coping and perceived work productivity in two cultural samples date: - - journal: pers individ dif doi: . /j.paid. . sha: doc_id: cord_uid: fcdmbo c this study examines the relationship between proactive coping, future time orientation, and perceived work productivity during the coronavirus (covid- ) pandemic, based on the work-from-home experience of employees in taiwan and the united states (u.s.). it draws on the conservation of resources (cor) theory, which posits that proactive coping and future time orientation are crucial personal resources that affect the capacity of an individual to adapt to stressful situations. the results show that in the relationship between proactive coping and perceived work productivity, future time orientation acts as a full mediator in taiwan and a partial mediator in the u.s. the study extends the application of the cor theory to the context of the covid- pandemic and offers important insights that will enable professionals to assess the role of proactive coping and future time orientation in their productivity evaluations of working tasks and to design appropriate training sessions. working tasks and to design appropriate training sessions. as of the beginning of , the covid- pandemic has resulted in unexpected changes to the lives of people across the globe (world health organization, ) . with no effective treatments or vaccines available yet for this novel disease, governments and companies have ordered workers to work from home in order to remain safe. salari et al. ( ) report that the prevalence of stress in the general population has reached . % as a direct result of the pandemic. the duration of the pandemic is difficult to predict, and people face many uncertainties in their daily lives as well as multiple challenges in the workplace. the pandemic poses a threat to both mental and physical health, and individuals across the globe have sought out proactive responses in an attempt to minimize the potential damage (chater, ). one such response is the adjustment to modified work arrangements, such telecommuting. in the past two decades, telecommuting usually refers to remote work arrangement that enables employees to perform job tasks at home on a voluntary basis (e.g., apgar, ) . however, they have now been forced to do so at short notice because of the covid- pandemic. a survey conducted by the organization for economic cooperation and development (oecd, ) reported that knowledge-intensive industries (e.g., technology) were more likely to adapt to covid- pandemic. compared with telecommuting in earlier years, a variety of advanced digital technology (e.g., business app with full functions of completing job tasks) tools is widely available for teleworkers. the oecd ( ) also reports that limited access to child-care support, social isolation, and family-work boundary violations have all caused teleworkers to suffer work productivity difficulties at both the individual and organizational levels during this global crisis. as a result, employees have had to be largely self-reliant in their efforts to overcome challenges and maintain a desirable level of work productivity. for example, teleworkers are learning new ways to connect with colleagues and clients for effective communication and must manage potential distractions at home in order to remain focused on their work (oecd, ) . this implies that differences in workers' personal approaches to managing unexpected changes and coping with uncertainty may result in different productivity outcomes. thus, the aim of this study is to examine how an individual's personal resources contribute to work productivity during this unique crisis period. the application of the conservation of resources (cor) theory (hobfoll, ) would provide us with a useful framework for understanding the importance of resources to an individual in the context of the covid- pandemic. the cor theory posits that people with sufficient resources are less vulnerable to stressors. of the different types of resources identified within the cor theory, personal resources are perhaps the most relevant in the context of this pandemic, considering the limitation of access to other resources imposed by national regulations regarding social distancing and quarantining (cdc, ) . moreover, because of the difficulty in controlling the unexpected spread of the covid- virus, companies and governments have had to change work policies frequently. hence, personal resources for coping with the challenges and j o u r n a l p r e -p r o o f distress caused by the pandemic may have a significant effect on the ability of workers to remain productive at work. previous studies have mostly examined personal resources (e.g., self-esteem) in jobrelated situations such as burnout (e.g., toker & biron, ) , an approach which is less applicable in the covid- context. in this study, we focus on proactive coping and future time orientation because these two factors are highly relevant resources for individuals facing uncertain and stressful situations. for example, in the case of the h n pandemic, taha matheson, cronin, and anisman ( ) found that the manner in which an individual copes with stress significantly affects the adjustment outcomes. moreover, bolotova and hachaturova ( ) suggest that time orientation is a crucial resource in an individual's mental organization that is linked to the capacity to cope under stress. thus, we shall discuss these two personal resources within the framework of the cor theory. alongside a number of different coping mechanisms, proactive coping is defined as an effort to create resources that are beneficial to manage stressors and future challenges in a way that facilitates personal growth (aspinwall & taylor, ) . unlike problem-focused or emotion-focused coping, which seek to resolve stressful situations or to reduce an individual's negative emotions toward stressors (folkman & lazarus, ) , proactive coping reflects a growth-oriented mentality when dealing with the potential challenges of ambiguous and stressful situations, which fits better in the context of covid- . research has shown that proactive coping is linked to positive work outcomes and that proactive employees are more likely to report higher work performance, compared with reactive employees (dubrin, ; ersen, & bilgiç, ) . for example, rueter and schwarzer ( ) find that employees who adopt a j o u r n a l p r e -p r o o f proactive coping approach are better able to prioritize job assignments, delegate tasks, manage deadlines, and seek managerial support, each of which is an important job competency skills, and together lead to higher job performance. in the cor theory, proactive coping can be viewed as an individual's personal resource that promotes effective adaptation, such as maintaining work productivity during challenging times. since individuals with higher proactive coping abilities are considered to possess more work-related skills and are able to adjust better to changes, we hypothesize that they have higher work productivity despite the challenges posed by the covid- pandemic (hypothesis ). future time orientation reflects a person's desire to achieve goals and to use time effectively to prepare for future encounters, which itself induces the accumulation of resources (aspinwall & taylor, ; zimbardo & boyd, ) . when people face uncertainty, their conceptualization of time may determine their reactions. for example, nuttin and lens ( ) conclude that time orientation forms a mental foundation for cognitive functioning that activates a person's subsequent actions or plans. in the context of the covid- pandemic, which has made many aspects of the future uncertain, people understandably may tend to focus on present difficulties and spend time engaging in non-work-related activities due to various distractions. however, the positive effort associated with proactively approaching distress will itself create additional new resources according to the cor theory (hobfoll, ) . that is, with proactive coping, an individual's time orientation is directed toward the evaluation of behaviors for their future implications. accordingly, this study hypothesizes proactive coping to be positively associated with future time orientation (hypothesis ). of the different types of time orientations, future time orientation has been the most widely examined in career research and theories (walker & tracey, ) . it has also been associated with positive work and learning outcomes (dubrin, ). simons, vansteenkiste, lens and lacante ( ) demonstrate that people with a future time orientation tend to be better equipped to delay gratification because they envision the future consequences of current behaviors. from the cor theory, one's future time orientation (i.e., personal resources) results in higher performance (i.e., positive adaptation to stressors) through the implementation of tasks that are associated with positive future outcomes. thus, we hypothesize that future time orientation will be positively associated with higher work productivity (hypothesis ), and will serve as a mediator between proactive coping and perceived work productivity (hypothesis ). this study investigates the relationship between proactive coping, future time orientation, and perceived work productivity, based on the work-from-home experiences of two samples of employees during the covid- pandemic. higher levels of proactive coping are hypothesized as being associated with higher levels of future time orientation as well as perceived work productivity. the mediating effect of future time orientation between proactive coping and work productivity is examined using bootstrapping methods. since the study evaluates the application of the cor theory in the covid- context, we collected data from both eastern and western country samples to account for cultural differences that may affect the examined variables. hofstede ( ) reports that the individualism-collectivism spectrum exerts a significant influence on individuals' social behavior, while jennings ( ) finds that cultural differences may contribute to the different ways in which people cope with covid- . for example, in a collectivistic culture, people may be more willing to comply with governmental policy in j o u r n a l p r e -p r o o f journal pre-proof consideration of the well-being of others. according to wang, ng, and brook ( ), taiwan is a prime example of a society in which individuals largely comply with governmental regulations and place societal safety ahead of their personal needs; thus, taiwan represents the collectivistic culture sample in this study. in contrast, the u.s. is characterized by an individualistic culture, according to the reporting score (i.e., out of ) on the individualistic scale in hofstede's study (hofstede, ) . we collected two samples to examine our hypotheses. all participants were recruited to complete an online survey through digital platforms (e.g., facebook, line, and amazon m-turk). the survey questions were designed to obtain information about the employees' work-fromhome experiences, proactive coping, and future time orientation during the covid- pandemic. the data was collected from may to june for the taiwanese sample and from june to july for the u.s. sample. in taiwan, social distancing and other restrictions were implemented in january , and daily increases in infections were low at the time of the data collection. in the u.s., the trend in covid- cases varied across states, with the number of infections increasing during the data collection period. before completing the survey, all participants were informed that their responses were anonymous, and confidentiality was assured. the demographic information for both samples is reported in table . personal resources are measured in the form of proactive coping and future time orientation. it is worth noting that a mandarin language version of the survey was used for the taiwanese respondents. to ensure measurement equivalence, we performed the conventional j o u r n a l p r e -p r o o f procedure of translation and reverse back-translation (brislin, ) and confirmatory factor analysis (cfa) for construct validity. . . proactive coping. we used greenglass, schwarzer, jakubiec, fiksenbaum, and taubert's ( ) proactive coping inventory (pci) to measure proactive coping. wu, chen, and yao ( ) conducted a cultural validation of the pci in the chinese population and reported a factor structure similar to that of greenglass et al. ( ) . examples of response statements indicate proactive coping include: "i am a take charge person," and "i always find a way to work around obstacles; nothing stops me." all items are measured on a seven-point likert scale. j o u r n a l p r e -p r o o f before proceeding to the formal analysis, we performed data screening to ascertain the missing data, which was found to be insignificant. for this reason, we assume that the items missing are random and have therefore used a mean substitution with missing value (cheung, ) . next, to ensure construct validity, we conducted a confirmatory factor analysis (cfa) of the main variables in both samples. in the taiwan sample, the three-factor model had an appropriate fit index (χ [ ] = . , comparative fit index = . , non-normed fit index = . , standardized root mean residual = . , root mean square error of approximation = . ). in the us sample, we adopted items of proactive coping and all three reversed items were subsequently deleted following cfa. previous work by schriesheim, eisenbach, and hill ( ) and woods ( ) note that reverse items often suffer from careless responding and affect reliability estimates as well as factor structures. accordingly, the us sample data showed appropriate fit index (χ [ ] = . , comparative fit index = . , non-normed fit index = . , standardized root mean residual = . , root mean square error of approximation = . ). in sum, the performance of the three-factor model was significantly greater than that of alternative models (see table ) based on the values of chi-square in the both samples, representing construct distinctiveness without common method variance concerns (podsakoff, mackenzie, lee, & podsakoff, ) . next, means, standard deviations, and correlations for the taiwan and usa samples are presented in table . for both samples, positive correlations were significantly reported among examined variables and control variables were included in the hypothesis testing. to understand the differences between the main variables in the taiwan and the u.s. samples, two correlation coefficients were also examined before hypothesis analyses. hypothesis predicted a positive j o u r n a l p r e -p r o o f association between proactive coping and self-perceived productivity, and the result was positive and significant in the taiwan sample and the usa sample ( = . , p < . ; = . , p < . ). hypothesis predicted that proactive coping is positively associated with future time orientation, and the association was also positive and significant in both samples ( = . , p < . ; = . , p < . ). hypothesis posited that future time orientation is positively correlated with selfperceived productivity, and the association was positive and significant in both samples ( = . , p < . ; = . , p < . ). (please see table ) to test the mediating effect of hypothesis , we used the process macro (model ; hayes, ) and a bootstrapping analysis with , bootstrap samples to estimate the % confidence interval. for the taiwan sample, the indirect effect index was . , and the % confidence interval of the index was . - . , which did not include zero. for the us sample, the indirect effect index was . , and the % confidence interval of the index was . - . , which did not include zero. therefore, in both samples, proactive coping had a positive, indirect effect on self-perceived productivity through its positive influence on future time orientation. however, future time orientation served as a full mediator in taiwan's sample but a parietal mediator in the us sample with different standardized coefficient strengths (please figure and ). the current study investigates the relationships of proactive coping, future time orientation, and perceived work productivity in the work-from-home experiences of employees during the covid- pandemic, and tests for the mediating effect of future time orientation. the results suggest that future time orientation is a mediator of proactive coping and perceived work j o u r n a l p r e -p r o o f journal pre-proof productivity in both samples; however, the strength of the mediating effect varies. first, hypothesis , which posited that proactive coping positively predicts perceived work productivity, is supported. this is consistent with previous research that demonstrates that individuals' proactive work styles are generally associated with positive career outcomes (cai et al., ; seibert, et al., ) . this finding is supportive of the cor theory in that stressful events do not necessarily lead to detrimental outcomes and individuals with higher proactive coping abilities are more likely to regard these challenges as opportunities and do not consider them as merely a loss of resources. this suggests that individuals with higher proactive coping abilities not only react to stressors, but also seek to manage resources actively for the purpose of implementing tasks efficiently, even during the covid- pandemic. second, hypothesis , which predicted that proactive coping is positively related to future time orientation, is also supported and is consistent with findings elsewhere in the literature (e.g., zambianchi & bitti, ) . however, this result contradicts aspinwall's ( ) finding that future time orientation explains individual differences in proactive coping. we argue that future time orientation can be either a "state" (e.g., depending on the contexts) or "trait" construct (e.g., stable personality characteristics) (steyer, schmitt, & eid, ) . as zimbardo and boyd ( ) have reported, an individual's time orientation is adaptable, and most people can change their temporal orientation in various contexts or according to life experiences. in this study, proactive coping represents a take-charge and growth-oriented mindset that can activate future time orientation in an individual with concrete selfmentalization. for example, an individual can direct cognitive attention to finish the assigned work for a future benefit; thus, future time orientation is conceptualized as a "state" construct during covid- . journal pre-proof third, hypothesis , which posits that future time orientation is related to perceived work productivity, is supported. this finding is consistent with those in previous studies regarding the link between future time orientation and desirable work outcomes. for example, kooij, kanfer, betts, and rudolph ( ) conducted a meta-analysis review and reported that future time orientation is positively associated with major work consequences. thus, an individual's capacity to consider the future represents the use of cognitive resources to focus on work behaviors that will be beneficial in the future (andre, van vianen, peetsma, & oort, ), which in turn positively influences work productivity. finally, hypothesis , which predicted a mediating effect between proactive coping and perceived work productivity through future time orientation, is supported. this result is consistent with findings made by other scholars about the role of future time orientation as a crucial mediator between individual predecessors and behavioral consequences (e.g., henry, zacher, & desmette, ) . such a role may be involved in a protective mechanism against disruptive work behaviors (carvalho, ). however, the strength of the mediation differed between the two samples. for an eastern culture such as that of taiwan, proactive coping is closely linked to future time orientation, which serves as a stronger mechanism between proactive coping and perceived work productivity. as in other asian countries, taiwan has a collectivist culture that highly values long-term planning for an improved future (tian & heppner, ) . in the context of such a culture faced with covid- , individuals tend to possess a "we" mentality, which reflects psychological togetherness toward a common goal to overcome challenges and aim for a better tomorrow. for example, self-health management instructions during the covid- pandemic have been proactive in taiwan (taiwan centers for disease control, ) and people are well informed about what to do in medical, social, j o u r n a l p r e -p r o o f and schooling situations. thus, proactive coping and future time orientation may be strengthened in such an environment, which explains the higher effects reported compared to cultures that are more individual-oriented. this study extends the current understanding about the relationship between proactive coping, future time orientation, and perceived work productivity during the covid- pandemic. theoretically, the results of this study are consistent with the principles of the cor theory (hobfoll, ; ) and expand the context in which cor theory may be applied. in particular, the study demonstrates the importance of improving our understanding through further study of time orientation during uncertain situations. while hobfoll, halbesleben, neveu, and westman ( ) report that the role of time in the cor theory is often limited to time allocation for resources or the timing of resources, this study makes a significant theoretical contribution by showing that time orientation alone can be a personal resource and act as a mediator in the link between resources and positive adaptation. one practical implication of the results of this study is that programs that target the proactive coping and future time orientation of individuals can be viewed as beneficial strategies for increasing the affected individuals' personal resources. as concluded by bodem, ridder, kuijer, and bensing ( ) , proactive coping can be conceptualized as a set of competencies that serve as transferable skills for designing relevant interventions. during the covid- pandemic, organizations can offer updated information and telework guidelines to their employees (e.g., how to report work progress effectively via digital technology). such measures will increase employee visualization of upcoming adjustments, thereby promoting proactive coping by employees. the employees can in this way be directed toward goal j o u r n a l p r e -p r o o f management and remain proactive during telework rather than passively working alone. the study results are also of practical relevance to psychologists and professionals, who will be able to review proactive coping and future time orientation in the context of work assignments and incorporate them into future employee training sessions. this study is not without its limitations, despite its theoretical and practical contributions. first, its broad conclusions are drawn from a limited sample of single countries (taiwan and the u.s.) that are chosen to represent eastern and western cultures, respectively. moreover, the two countries have reported significantly different numbers of covid- infections and related deaths during the pandemic (who, ). thus, the cultural context variable seems to be confounded by socio-demographic differences as well as differences in the dynamic of the pandemic itself. it would therefore be essential for future research to examine proactive coping and future time orientation in relation to telecommuting productivity in other culturally diverse populations, as well as in those countries that have been affected differently by j o u r n a l p r e -p r o o f j o u r n a l p r e -p r o o f note. n = in taiwan and n= in the u.s. internal consistency reliabilities are in parentheses. taiwan's correlational data was reported below the diagonal and the us correlational data was reported above the diagonal. *p < . . **p < . . j o u r n a l p r e -p r o o f a multidimensional research instrument future time perspective: a systematic review and meta-analysis process: a versatile computational tool for observed variable mediation, moderation, and conditional process modeling future time perspective in the work context: a systematic review of quantitative studies conservation of resources: a new attempt at conceptualizing stress social and psychological resources and adaptation conservation of resources in the organizational context: the reality of resources and their consequences covid- , teleworking, and productivity future time perspective and motivation: theory and research method productivity gains from teleworking in the post covid- era: how can public policies make it happen? the less is more: the -item zimbardo time perspective inventory common method biases in behavioral research: a critical review of the literature and recommended remedies manage stress at work through preventive and proactive coping. handbook of principles of organizational behavior: indispensable knowledge for evidence-based management, second prevalence of stress, anxiety, depression among the general population during the covid- pandemic: a systematic review and meta-analysis. globalization, and health the effect of negation and polar opposite item reversals on questionnaire reliability and validity: an experimental investigation self-regulatory processes in the adoption and maintenance of health behaviors. the role of optimism, goals, and threats proactive personality and career success placing motivation and future time perspective theory in a temporal perspective latent state-trait theory and research in personality and individual differences intolerance of uncertainty, appraisals, coping, and anxiety: the case of the h n the development and validation of a chinese proactive coping inventory among chinese college students conceptualization, methodology, data collection, data analyses, visualization, and result writing -editing conceptualization, data collection and methodology j o u r n a l p r e key: cord- - c z authors: tsai, shin-han; tsang, chiu-man; wu, hsueh-ru; lu, li-hua; pai, yung-chia; olsen, mark; chiu, wen-ta title: transporting patient with suspected sars date: - - journal: emerg infect dis doi: . / . sha: doc_id: cord_uid: c z nan to the editor: the severe acute respiratory syndrome (sars) outbreak in taiwan can be traced back to a taiwanese businessman who returned from mainland china to taiwan in march ( ) . in may , several outer islands belonging to taiwan reported sars, and on june , , penghu army hospital reported a year-old man with suspected sars. the patient complained of shortness of breath and a dry cough. he had visited a person with confirmed sars days earlier. he had a temperature of . °c and leukocyte count of , cells/µl, and his chest x-ray showed infiltration in both lower lobes. because medical facilities are limited on these islands, the department of health authorized the national aeromedical consultation center (nacc), a physician-based -hour control center that coordinates all aeromedical transport of critically ill or injured patients within taiwan, to coordinate transporting these patients to designated sars hospitals in taipei. the nacc dispatched an aircraft (fokker ) with a specialized team of two flight physicians, one flight paramedic, and a piu (portable isolation unit) on board. during the flight, the medical crew prepared equipment and dressed themselves in three layers of personal protective equipment. on arrival at penghu, only essential equipment was taken into the hospital. one physician took the piu into the isolation room. the rest of the crew and equipment remained in the pre-isolation room. the patient was briefed about the transport and given mg of metoclopramide to prevent motion sickness. he was asked to get into the piu. a pulse oximeter was attached to his finger and placed inside the piu so that it could be read from the outside. a ther-mohydrometer was also placed inside the unit. the patient was given a squeeze-bottle of water, and the unit was sealed and inflated. when leaving the pre-isolation room, the physician and the piu were sprayed with a sodium hypochloride solution before the first layer of personal protective equipment was removed. at the exit, the entire medical crew removed a layer of personal protective equipment after being sprayed with sodium hypochloride solution. the team returned to the airport for the flight back to taiwan. no other personnel or family member was allowed to accompany the patient on the flight. the patient remained stable and calm throughout the flight. his oxygen saturation remained %- % with heart rate of to beats per minute. humidity was maintained at % and temperature at °c. on arrival, the team proceeded to the isolation ward. the physician accompanied the patient into the isolation room; the patient was released from the piu and transferred to the receiving medical team. on exiting the isolation room, the empty piu and the medical team were sprayed with sodium hypochloride. all equipment was sprayed and put into biohazard bags. the medical team then discarded the last layer of impermeable clothing. the piu was left in biohazard bags for hours before being sprayed with water and air-dried. after the assignment, the medical crew self-documented their temperature twice daily for days. all staff remained asymptomatic with normal body temperatures during this period. the patient's temperature remained normal, and results of a polymerase chain reaction of throat swab were negative for sars-associated coronavirus (sars-cov). he was discharged on june , . when the sars outbreak occurred in taiwan, many medical and ambu-lance personnel were exposed to sars-cov while transporting or caring for patients with suspected sars. as sars was an emerging infectious disease, the mechanism of transmission was still unclear. although one report by christopher and eitzen ( ) suggested the value of an aeromedical team to evacuate patients with suspected lethal, infectious diseases, limited evidence supported a safer means of transportation that would possibly reduce transmission of sars to persons taking part in the mission. when the sars epidemic spread to remote islands, aircraft companies refused to transport patients with a case of suspected sars unless certain precautions were implemented. smaller aircraft used on domestic routes in taiwan do not meet the standards set for transporting sars patients ( , ) , which prompted the design of the piu, an airtight polyvinyl chloride bag with a oneway inlet valve and an exhalation valve. the valves were modified by incorporating hepa filters on both sides of the valves and then connecting a ventilator with an oxygen source to the inlet valve. the respiratory rate and tidal volume are set, depending on weight and oxygen requirements of the patient. by regulating the exhalation valve, the minimum pressure inside the bag can be manipulated to keep it from collapsing, since the bag has no internal or external frame. the piu has some limitations. no physical contact with the patient is possible after the piu is sealed and inflated. very strict criteria on the suitability of a patient to be transported are followed. any patient who is unconscious, uncooperative, or whose condition may deteriorate is not transportable in this unit. because of possible discomfort, a maximum total transport time of to hours is suggested. this time frame works well in taiwan; all locations in the country, including the outer islands, are within a -hour limit. the use of piu during the sars crisis had a number of positive effects in taiwan. it enabled the safe transport of sars patients between hospitals by air and road and decreased the risk of cross-infecting transport personnel. the anxiety of transport personnel was decreased, as was the fear felt by the population of the outer islands. in addition, the credibility of the local health authorities was improved among the general population in taiwan. to the editor: an outbreak of severe acute respiratory syndrome (sars) occurred from february to may in hong kong, china, singapore, and canada. according to the world health organization, , people were infected in hong kong; of these were healthcare workers. a total of persons died from sars, constituting a death rate of % ( ). evidence suggests that persons infected with sars recovered physically, but sars is associated with social and psychological problems poorly understood by the scientific community. a survey in a convalescent hospital in hong kong showed that approximately % of recovered sars patients showed anxiety ( ) , and approximately % were fearful ( ) . approximately % of the rehabilitated patients showed some negative psychological effects ( ), which included insomnia and depression. some patients with serious cases could not rid themselves of the memories of fighting sars, and these memories disrupted their daily activities. these psychosocial problems may be due to the complications of sars medications, such as ribavirin and corticosteroid. persons who took these drugs had hair loss, major memory loss, impaired concentration, and depression. a medical practitioner in hong kong who recovered from sars attempted suicide because complications from drugs made him unable to earn his living ( ). in addition to sars patients themselves, an estimated % of family members of sars patients had psychological problems, including feelings of depression or stigmatization ( ). they had difficulties sleeping, and some children who had lost parents cried continuously. some children also felt embarrassed to be a member of a sars family ( ). the spouse of one healthcare worker who died from sars attempted suicide at her workplace ( ). the loss of parents who were sars patients also impaired the growth of their children ( ). a study conducted in china ( ) reported that negative sars-related information increased persons' perception of their risk and led to irrational nervousness or fear. although data from systematic studies of sars do not exist, evidence suggests that this disease has psychosocial consequences for sars patients, their families, and society. while biomedical scientists must continue their efforts to clarify the genetic makeup of the sars coronavirus, look for new medications, and develop vaccines ( - ), the social and psychological aspects of sars should not be overlooked. since nearly all resources are devoted to biomedical research and medical treatment, psychosocial problems of sars patients and their families are largely ignored. our review of the literature using the isi web of knowledge on january , , substantiated this observation. to date, no systematic study examining psychosocial consequences of sars has been published in scientific journals. a systematic exploration of how sars negatively affects patients' air evacuation under high-level biosafety containment: the aeromedical isolation team interim guidance: air medical transport for severe acute respiratory syndromes (sars) patients interim domestic infection control precautions for aerosol-generating procedures on patients with severe acute respiratory syndromes (sars) key: cord- - gzdu authors: liou, shwu-ru; liu, hsiu-chen; tsai, hsiu-min; chu, tsui-ping; cheng, ching-yu title: relationships between disaster nursing competence, anticipatory disaster stress and motivation for disaster engagement date: - - journal: int j disaster risk reduct doi: . /j.ijdrr. . sha: doc_id: cord_uid: gzdu nurses are the largest group of healthcare providers and are often the first line responders to a disaster event. nurses' disaster competence, motivation for disaster engagement, and factors that impact their motivation to respond to disaster events need to be understood. the purposes of the study were to determine the predictive relationships between taiwanese nurses' disaster competence, anticipatory disaster stress, and motivation for disaster engagement. a cross-sectional design was used to analyze data collected between august and december from eight hospitals in southern taiwan. ninety participants who met the recruitment criteria completed and returned questionnaires with an . % response rate. data collection involved administering the disaster nursing competence questionnaire, anticipatory disaster stress questionnaire, and the motivation of disaster engagement questionnaire. the results indicated that anticipatory disaster stress was positively correlated with disaster competence and motivation for disaster engagement. disaster competence and willingness to join a hospital disaster rescue predicts an individuals' motivation for disaster engagement. the results of the study add to the understanding of factors that correlate with nurses' motivation to participate in disaster events. by understanding these factors, the government and healthcare administrators can design disaster education plans and other strategies to improve taiwanese nurses’ motivation to engage in disaster events. natural and man-made disasters are increasing in frequency and severity worldwide over the past decade. examples of major disasters in taiwan include the severe acute respiratory syndrome (sars) outbreak in , the kaohsiung massive gas explosions in , and the taiwan water park blast in . these disasters have resulted in many injuries and fatalities, as well as economic losses, serious environmental disruption, and lasting psychological trauma among survivors [ , ] . according to the world disasters report [ ] , there were recorded disasters from to , and . % of these reported disasters occurred in asian countries. asians accounted for the largest number of people affected by these disasters. in fact, the percentage of disasters occurring in asia was % in the - decade, and it increased to % in the - decade [ ] . likewise, the frequency and intensity of disaster events in taiwan have noticeably increased in recent years. in , the center for research on the epidemiology of disasters reported that taiwan was one of the top countries in terms of disaster mortality that year [ ] . these statistics amplify the importance of sound disaster training and preparation so that nurses can respond effectively and appropriately during a disaster event in taiwan. in taiwan, during disaster incidents, nurses are expected, with limited resources, to attend and work in chaotic disaster sites to quickly provide nursing care to a growing number of survivors. in light of this, issues about the current level of competence, skills, and experience in disaster preparedness and response among nurses have been valued and emphasized [ , ] . studies focused on disaster nursing in taiwan and other countries revealed that existing preparedness for and competence in disaster response among hospital personnel including nurses is less than optimal [ ] [ ] [ ] and is often fragmented, or not available at all [ ] . moreover, they may not be ready to face future disasters because of an inadequate disaster competence such as a lack of awareness of the roles and skills needed when encountering disaster events [ ] [ ] [ ] [ ] [ ] [ ] . high levels of psychological and emotional stress are frequently reported in emergency or disaster responders [ , ] . studies found that nurses felt psychologically unprepared when asked to engage in disaster events [ , ] because the events might exceed their capacity to function well, or they worried about their personal loss or their families' welfare during disaster relief [ , ] . additionally, nurses had less desire to report to work during an emergency or disaster event, although most strongly believed that they are responsible for working during such situations [ , ] . moreover, few nurses were motivated to engage in practical preparation and obtain the experience required to deploy in response to a disaster event [ , ] . in one study, some nurses openly commented that they were frustrated and were not motivated to engage in disaster trainings because of their heavy workloads and lack of time for attending educational programs [ ] . yet, other surveys reported that many hospitals or service organizations do not frequently conduct exercises to determine their level of preparedness for disaster management, which may be due to the economic burden of undergoing training exercises [ ] . therefore, it is critical to understand how to help disaster nurses overcome personal stress and assist others, such as colleagues and survivors, to effectively cope with stress as well [ ] . nurses are the largest group among the healthcare provider workforce and play an important role during the emergent phase of a disaster and throughout the phases of disaster preparedness and recovery [ ] . therefore, disaster competence and preparedness among nurses is necessary to effectively manage unpredictable events. however, the exploration of nurses' perspectives on disaster nursing remains limited in taiwan. therefore, the purposes of the study were to determine the level of and relationships between taiwanese nurses' disaster competence, anticipatory disaster stress, and motivation for disaster engagement. the motivation for engagement in disaster events can be explained by the self-determination theory developed by deci and ryan [ ] . the theory suggests that people are often moved to act by two types of motivation: intrinsic or extrinsic. the theory also proposes that three basic psychological needs-competence, autonomy, and relatedness-are important for self-growth and must be met for healthy functioning, promoting intrinsic motivation, engagement behavior, and maintaining motivation over a period of time [ , ] . competence refers to the mastery of experiences in the practical world. an individual's perceived competence can enhance their motivation for an action only when it is accompanied by a sense of autonomy and relatedness within an organization [ ] . in addition to the psychological needs that influence motivation, personnel involved in disaster events are prone to exhibiting psychological problems and distress [ ] . for nurses, psychological distress may affect their commitment to attend or remain at a disaster situation site [ , , ] . therefore, we proposed that anticipatory disaster stress and disaster competence are factors in nurses' motivation to engage in disaster events. this study used a cross-sectional design to understand factors related to nurses' motivation to engage in disaster events. using convenience sampling, nurses who: (a) had a registered nursing license; (b) were employed full-time by hospitals for more than one year; and (c) were willing to sign an agreement to complete questionnaires; were invited to participate in the study. before data collection, the sample size was calculated using g*power (version . ) with two-tailed, α level of . , and an estimation that the effect size for correlation between measured variables was at least medium (r ¼ . ). eighty-eight participants were needed to achieve a power of . . more nurses were invited to participate in the study because of possible incompletion rates. nurses distributed over eight hospitals in southern taiwan responded to our invitation to participate in the study. ninety nurses returned completed questionnaires with an . % response rate. the study was approved by the institutional review board (irb b ) before recruitment began. a packet containing a cover letter, questionnaires, informed consent, and two addressed-andstamped envelopes were mailed to nurses who were interested in participating in the study. the cover letter described the purposes of the study, the participants' rights and confidentiality. they could complete the study surveys at any place they felt comfortable with. they could decline or stop participation in the study whenever they felt uncomfortable. participants were asked to send back the signed informed consent and questionnaires separately by using the two addressed-andstamped envelopes if they agreed to participate in the study. on average, surveys were completed in less than min. data were collected between august and december of . there was no disaster in taiwan or any neighboring countries that might have influenced the participants' responses during the data collection period. demographic survey. we designed the participant information sheet based on the self-determination theory that individual differences are important factors that may influence individuals' motivation to engage in actions. in this study, individual differences are defined as a nurse's personal characteristics that may influence their preparedness and motivation to engage in disaster events, such as gender, age, seniority in the hospital, educational level, hospital type, work unit, and job title. the disaster nursing competence questionnaire (dncq). the dncq developed by the research team, based on a literature review, contains items used to measure nurses' perceived competence level when responding to disaster events. on a -point likert scale ranging from (not familiar) to (very familiar), a higher score indicates a higher level of disaster nursing competence. in the study, cronbach's alpha for the dncq was . . the principal component analysis for the validity showed that . % of the variance of the disaster nursing competence could be explained by the dncq. anticipatory disaster stress questionnaire (adsq). the anticipatory disaster stress questionnaire was developed by the research team according to literature reviews and consists of items used to measure nurses' anticipation of stressors when encountering disaster events. using a -point likert scale scored from (strongly disagree) to (strongly agree), a higher score indicates greater perceived stress while facing disaster events. in the study, cronbach's alpha for the adsq was . . the principal component analysis showed that . % of the variance of the anticipatory disaster stress could be explained by the adsq. motivation for disaster engagement questionnaire (mdeq). the mdeq, developed by the research team, was used to measure nurses' motivation to engage in disaster events or preparedness activities. with three items on a five-point likert scale (ranging from to ), a higher score indicates a higher level of motivation to participate in disaster events. in this study, cronbach's alpha for the mdeq was . . principal component analysis showed that . % of the variance of the motivation in disaster engagement could be explained by the mdeq. data were analyzed with the use of spss version . . demographic information, levels of disaster competence, anticipatory disaster stress, and motivation for engagement in a disaster event were analyzed with descriptive statistics such as frequency, mean, and standard deviation. before inferential analyses of the data, the normality of all variables was examined using the shapiro-wilk test. results showed that the dncq and adsq were normally distributed, whereas mdeq was not normally distributed. relationships between measured variables were examined using the pearson correlation when the variables were normally distributed, and the spearman correlation was used when variables were not normally distributed. the reliability of the scales was tested using cronbach's alpha coefficients, and the validity was tested with principal component analysis. hierarchical regression was applied to understand the predicting relationship of individual differences, disaster competence, and anticipatory stress on motivation for engagement in disaster events. the mean age of the nurses was . (sd ¼ . ) years. on average, they worked . months ( . years, sd ¼ . ) as a nurse and . months ( . years, sd ¼ . ) in their current hospital. most participants were females ( . %). while . % of them had an associate's degree, . % had a bachelor's degree ( . % were in the fouryear bachelor program and . % were in the two-year rn-bsn program), and . % had a master's degree. seventy-eight nurses worked as registered nurses ( . %) or nurse specialists ( . %), and . % worked in the emergency room (er) or intensive care unit (icu) in nonmedical centers or regional hospitals ( . %). over the past years, more than half of nurses attended either in-service education or conferences about disaster nursing ( . %) and attended disaster practices held by their hospital ( . %). most hospitals where the participants worked held massive disaster courses ( . %) and practices ( . %) every year. only . % of the participants had attended a disaster field rescue; . % had attended disaster management at their hospital; and only . % had attended care management of disaster aftermaths. more than half of the participants agreed ( . %) or strongly agreed ( . %) to join a hospital disaster rescue if they were asked, while . % disagreed and . % strongly disagreed to join a disaster rescue. the levels of disaster nursing competence, anticipatory disaster stress, and motivation of disaster engagement among participants were presented in table . the mdeq, dncq and adsq were significantly inter-correlated (r ranged from . to . ). the dncq was correlated with a greater number of times attending onsite practices, number of times attending in-service education or conferences about disaster nursing, number of times participating in care management of disaster aftermaths and stress of managing a disaster in hospital. the adsq was correlated with the number of times attaining onsite practices held by hospital in the past years, number of times attending in-service education or conferences about disaster nursing and the stress caused by managing a disaster in hospital. the mdeq was correlated with the number of times attending in-service education or conferences about disaster nursing and the stress caused by managing a disaster in hospital. however, effect sizes of all these correlations were low to moderate. most of the demographic variables had no statistically significant impact on nurses' disaster competence, anticipatory disaster stress, or their motivation for disaster engagement. as shown in table , participants who attended the in-service education or conferences about disaster nursing in the past years had higher scores on the dncq. participants who completed graduate school had lower scores on the adsq compared to those with an associate's or bachelor's degree. those who were more willing to join hospital disaster rescues had higher levels of adsq and mdeq than those who were less willing to participate. those who had never attended care management of disaster aftermaths had higher scores on the mdeq. because the number of times attending in-service education/conferences and stress caused by managing a disaster in hospital were correlated with the mdeq, and the mdeq differed by whether nurses attended care management of disaster aftermaths beforehand and their willingness to join hospital disaster rescues, these four variables were entered in the first set of regression analysis. as shown in table , regression analysis showed that attendance of disaster aftermath care management was included in the model and % of the variance of the mdeq could be explained (f ¼ . , p < . ). this study aimed to explore the relationships between disaster competence, anticipatory disaster stress, and motivation for disaster engagement among hospital nurses in taiwan. in addition, the factors associated with the motivation for engagement in disaster events among nurses were identified. we found that hospital nurses' level of disaster competence was not high. our findings were similar to previous studies that reported a low level of self-reported familiarity with preparedness among nurses for large-scale emergency or disaster events [ , , ] . this finding implies that most hospital nurses may not be ready or confident in their abilities to respond to disaster events. contrary to prior studies which revealed that work unit or specialty, work experiences, educational level, and gender were associated with disaster competence [ , ] , our analysis did not support such findings. rather, we found that nurses who exhibited higher competence had attended in-service education or conferences about disaster nursing. interestingly, most hospitals held massive disaster courses or practices every year; however, nurses' attendance rates to these educational offerings were not high. in addition, although the participation rates of field drills were high, nurses did not perceive that they were competent in disaster management. this situation is similar to williams et al.'s article which reviewed studies and found that the effects of disaster training on health care workers' knowledge and skills in disaster response were inconclusive. the authors suggested that hospitals should urgently examine and find the most appropriate methods for disaster preparedness practices for nurses in order to augment the authentic efficiency of the training [ ] . the psychosocial problems faced by nurses involved in disaster events are of much concern. researchers indicated that nurses may be unprepared educationally and psychologically for disaster relief [ ] . one study that was conducted to determine the international research priorities for disaster nursing found that psychosocial aspects ranked the highest [ ] . however, in our study, the level of anticipatory disaster stress was not high. this finding is different from prior concerns that the mdeq was used to measure motivation of disaster engagement, adsq was for anticipatory disaster stress, and dncq was for disaster nursing competence. *p < . , **p < . (two-tailed). nurses often reported that disaster events exceeded their ability to function and caused imbalances between professional duties and personal stress, such as their families' safety and personal loss [ , , ] . since most nurses in our study did not have any experience in disaster field rescue and also did not attend disaster management at their hospital, it may be hard for them to imagine how stressful it would be to participate in a real disaster management situation. this may be the reason for the finding of a low level of anticipatory disaster stress. additionally, although the level of anticipatory disaster stress was not high, only . % of nurses agreed or strongly agreed to join their hospital's disaster rescue when they were asked to do so. further analysis found that the participants who strongly agreed to join a hospital disaster rescue had significantly higher stress levels than nurses who did not agree to participate in a disaster relief. somehow, anticipatory disaster stress existed, but only for nurses who have motivation to attend disaster events in the future. in the study, the degree of nurses' motivation for disaster engagement was not high. the results correspond to the earlier studies, which indicated that few nurses intended to report for work during disasters [ , , ] ; moreover, few nurses have the motivation to engage in practical preparation and obtain experiences in response to a disaster event [ ] . specifically, we found that nurses who had attended care management of disaster aftermaths had lower motivation for disaster engagement. the fear of being incapable of managing disaster aftermaths and the worry that no one can take care of their family or children when they cannot get out of their duty might have made them reluctant to attend field rescue or care management of disaster aftermaths [ , ] . former surveys reported that nurses did not feel supported or motivated to engage in disaster preparedness because of their heavy workloads, and the hospitals in which they were employed did not regularly conduct exercises to prepare them for disaster management [ , , ] . although hospitals in taiwan held disaster education or practice every year, nurses reported being physically and mentally exhausted by their heavy daily workload on top of having difficulty in finding the time to participate in educational programs that were not directly work-related. therefore, as shown by a previous study that showed a perceived well-ordered organizational climate can arouse individuals' motivation and consequently cause emergent behaviors [ ] , a perception of being supported by the work environment is a meaningful motivational factor in healthcare workers' decision to work during a disaster. interestingly, the study found that nurses who were more competent in disaster nursing felt more stress. this situation might be because nurses may believe that they will never be competent enough when facing an unpredictable disaster. additionally, disaster competence and anticipatory disaster stress were significantly and positively correlated with nurses' motivation to engage in disaster events. however, both disaster competence and anticipatory disaster stress could not predict motivation to engage in disaster events. the self-determination theory proposes that competence is one of the significant factors influencing individuals' motivation in engagement behaviors [ ] . and, other studies pointed out that individuals would move toward activities and took on responsibilities or challenges when they felt more confident in their disaster competence and knowledge [ , , , ] . in our study, nurses' did not perceive high level of disaster competence and therefore might not be motivated to participate in disaster management. the sampling method in the study is convenience sampling. participants were only invited from eight regional hospitals in southern taiwan. these reasons may have caused a selection bias in sampling. in addition, . % of our participants were emergency or intensive care nurses although they might be the first line nurses to manage disaster events. therefore, the generalizability of the study findings to all taiwanese nurses is limited. because the study used a cross-sectional design, the findings cannot establish a causal relationship between variables. the findings of this study contribute to the body of knowledge regarding motivation for disaster engagement among hospital nurses and furnish implications for nursing administration, practice, education and research. we have recommendations for policy, research, practice and education. the study indicated that the rates of attending in-service education, disaster field rescue, and care management of disaster aftermaths among hospital nurses were not high. nurses' disaster competence and motivation for disaster engagement were not high as well. these findings highlight the necessity of further research to explore nurses' concerns and needs in-depth when they participate in disaster-related activities. the results of the further research can offer information for healthcare administrators to make more practical policies to enhance nurses' disaster competence and further increase nurses' motivation to participate in these activities. the study found that even though hospitals held disaster courses and trainings every year, nurses had a worryingly low level of disaster competence, which correlated with their low motivation to participate in disaster rescue. providing realistic disaster training using simulations, tabletop exercises [ , ] , and virtual reality/augmented reality/mixed reality exercises may improve individuals' interests and understanding about disaster situations and disaster knowledge and skills. this would further increase nurses' confidence in disaster management. the insufficiency of disaster competence among nurses revealed in the study emphasizes the important role of nursing educators in preparing nursing students with the knowledge and skills for disaster management. disaster nursing is a generally neglected topic in nursing education. in most nursing schools in taiwan, disaster nursing is taught as one or two units in courses of public health nursing (required course) or emergency nursing (elective course). it is urgent for nursing schools to develop a stand-alone disaster course for both undergraduate and graduate programs to increase nurses' awareness of disaster and prepare table predictive relationship of dncq and adsq with mdeq. step step for future nurses who are competence in disaster management. this study sheds some light to provide a better understanding that the degree of disaster competence may impact the motivation for disaster engagement among hospital nurses in taiwan. it appears that disaster competence and stress play an important role for nurses when encountering disaster. this situation should alert hospital administrators to reexamine the appropriateness of their training programs and their nurses' needs when it comes to training for disaster preparedness. stress management and counseling programs also need to be provided. the best and suitable methods for disaster practice to augment the authentic efficiency of training and to promote nurses' motivation for disaster engagement should be further explored and developed. this work was supported by the chang gung memorial research program in taiwan (cmrpf g ). no conflict of interest has been declared by the authors. resilience in the face of disaster: prevalence and longitudinal course of mental disorders following hurricane ike the effectiveness of disaster training for health care workers: a systematic review international federation of red cross and red crescent societies annual disaster statistical review world health organization (who) & international council of nurses (icn) australian nurses volunteering for the sumatra-andaman earthquake and tsunami of : a review of experience and analysis of data collected by the tsunami volunteer hotline readiness of hospital nurses for disaster responsed in taiwan: a cross-sectional study managing multiple-casualty incidents: a rural medical preparedness training assessment disaster preparedness among nurses: a systematic review of literature disaster nursing knowledge in earthquake response and relief among nepalese nurses working in government and nongovernment sector knowledge of disaster preparedness among nurses at two tertiary care hospitals in lahore nurses' competencies in disaster nursing: implications for curriculum development and public health israeli nurses' intention to report for work in emergency or disaster chinese nurses' relief experiences following two earthquakes: implications for disaster education and policy development disaster nursing skills, knowledge and attitudes required in earthquake relief: implications for nursing education arab, nurses' requirements for relief and casualty support in disasters: a qualitative studies public health emergencies: nurses' recommendations for effective actions nurses' experiences of ethical preparedness for public health emergencies and healthcare disasters: a of qualitative evidence disaster nursing skills, knowledge and attitudes required in earthquake relief: implications for nursing education enabling a disaster-resilient workforce: attending to individual stress and collective trauma willingness to respond in a disaster: a pediatric nurse practitioner national survey realities of rural emergency medical services disaster preparedness nurses' competencies in disaster nursing: implications for curriculum development and public health the what and why of goal pursuits: human needs and the selfdetermination of behavior self-determination theory and the facilitation of intrinsic motivation, social development, and well-being impact of organizational climate on organizational commitment and perceived organizational performance: empirical evidence from public hospitals who will be there? ethics, the law, and a nurse's duty to respond in a disaster resiliency of accomplished critical care nurses in a natural disaster analysis of texas nurses' preparedness and perceived competence in managing disasters disaster preparedness in philippine nurses readiness of hospital nurses for disaster responses in taiwan: a cross-sectional study necessity for disaster-related nursing competency training of emergency nurses in china a grounded theory study of 'turning into a strong nurse': earthquake experiences and perspectives on disaster nursing education what are the research needs for the field of disaster nursing? an international delphi study schr€ oder-b€ ack, nurses' roles, knowledge and experience in national disaster preparedness and emergency response: a literature review nurses' willingness and readiness to report for duty in a disaster relationship, motivation and organizational climate: a case of sustainability residents' disaster preparedness after the meinong taiwan earthquake: a test of protection motivation theory australasian emergency nurses' willingness to attend work in a disaster: a survey disaster preparedness among nurses: a systematic review of literature evaluation of a tabletop emergency preparedness exercise for pharmacy students supplementary data to this article can be found online at https://doi. org/ . /j.ijdrr. . . key: cord- - l fyl authors: cheng, hao-yuan; li, shu-ying; yang, chin-hui title: initial rapid and proactive response for the covid- outbreak — taiwan's experience date: - - journal: j formos med assoc doi: . /j.jfma. . . sha: doc_id: cord_uid: l fyl nan on december , , taiwan centers for disease control (taiwan cdc) detected the news about an outbreak of atypical pneumonia with unknown etiology in wuhan, hubei province, china, from social media. it was soon confirmed by the chinese government on the same day. one week later, the chinese government announced the pathogen was a novel coronavirus, formally named severe acute respiratory syndrome coronavirus- (sars-cov- ) afterwards. by february , , the number of confirmed coronavirus disease (covid- ) cases in china reached almost , , with about deaths. the outbreak affected more than countries around the world with over , cases and deaths, only two months after the virus was discovered. the first case of covid- in taiwan was detected on january . by february , there were , suspected cases reported, and covid- cases were laboratory-confirmed, including ( %) locally-acquired cases. only cases ( %) have wuhan-related travel history. at the early stage of the outbreak, the strategy in taiwan had three pillars: real-time surveillance with rapid risk assessment, border control and quarantine, and laboratory capacity building. before the outbreak, taiwan cdc has established comprehensive surveillance systems that included laboratory and social media surveillance. once the outbreak was detected by social media surveillance, our surveillance team continued collecting outbreak news from social media, government reports, and official press releases to monitor the progress in china on a daily basis and periodically updating rapid risk assessment to provincial level for decision making. considering the huge flow of cross-strait travelers (up to one hundred thousand travelers per day), risk assessments need to be tailored to the subnation level, so policymakers could modify travel restriction and quarantine measures with limited impacts. in this way, taiwan step by step expanded travel restrictions over a month for wuhan at first, later extended to hubei, guangdong, zhejiang, and finally, china, including hong kong and macau (fig. ) . the travel alerts were aligned with public health response as well. taiwan cdc initiated onboard inspection for direct flights from wuhan on december , . any passengers presenting with fever or respiratory symptoms at the entry fever screening sites of international ports would be referred to designated hospitals for evaluation. according to the different risk of covid- importation from individual countries, passengers were required to conduct home quarantine or self-health monitoring for days. these measures were adjusted rapidly based on intelligence gathered. for example, travelers returned from south korea and italy were home-quarantined starting february and , respectively, because of worsening local outbreaks. to strengthen response preparedness and ensure coordination of different government agencies, we listed covid- as a notifiable disease, named "severe pneumonia with novel pathogen", on january and activated the central epidemic command center (cecc) on january . cecc then announced several policies in response to the worsening outbreak in china, including border control and home quarantine requirement for travelers from affected countries and areas; export ban of surgical masks and n respirators to secure the domestic use; strengthening the preparedness of communicable disease control medical network for patient isolation and clinical management; and risk communication with the public through daily press and social media such as line app and facebook. from lessons learned in responding to other emerging diseases such as sars and avian influenza, we believe that laboratory capacity for rapid diagnosis is pivotal to outbreak response. after china released the whole genome sequence of sars-cov- on january , taiwan cdc's national reference laboratory immediately set up the real-time reverse transcription-polymerase chain reaction (rt-pcr) test for the virus. , the laboratory protocol and reagents, including primers, probes, and positive control, were then distributed to designated laboratories. to expand laboratory capacity, taiwan cdc started a capacity building program via the national laboratory diagnostic network after cecc was activated. by february , taiwan had laboratories that could perform up to molecular diagnostic tests for sars-cov- a day. the first death, also the first patient without exact infection source in taiwan at the beginning, was confirmed on february . at the meantime, the majority of covid- cases in surrounding countries also changed from importation to local transmission. therefore, taiwan cdc modified the original case definition of suspected covid- to include patients with undiagnosed pneumonia, regardless of travel history. the diagnostic capacity was also scaled up to tests/day by recruiting more laboratories and streamlining the testing algorithm. because of this enhanced community surveillance, we detected four local clusters of covid- cases in the following two weeks (fig. ) . when the number of the local clusters increased, widespread community transmission might be just around the corner. cecc already charted the next steps in covid- figure the number of confirmed covid- cases in taiwan by reporting date, january efebruary and the implementation of disease control measures. a novel coronavirus from patients with pneumonia in china world health organization first case of coronavirus disease (covid- ) pneumonia in taiwan real-time surveillance of infectious diseases: taiwan's experience response to covid- in taiwan: big data analysis, new technology, and proactive testing taiwan's public health national laboratory system: success in influenza diagnosis and surveillance detection of novel coronavirus ( -ncov) by real-time rt-pcr novel coronavirus genome. virological the authors have no conflicts of interest relevant to this article. key: cord- -vqs s p authors: lai, chih-cheng; lin, sheng-hsiang; sheng, wang-huei; hsueh, po-ren title: decrease in the incidence of meticillin-resistant staphylococcus aureus nosocomial bloodstream infections in taiwan date: - - journal: int j antimicrob agents doi: . /j.ijantimicag. . . sha: doc_id: cord_uid: vqs s p nan competing interests: fgdr and gdp have been speakers or advisory board members for pfizer; vmr has received funding from pfizer. all other authors declare no competing interests. ethical approval: ethical approval was given by the ethical committee of s. giovanni battista-molinette hospital. sir, in the recent review of the global epidemiology of meticillinresistant staphylococcus aureus (mrsa) by stefani et al. [ ] , they showed that mrsa remains highly prevalent in hospitals, especially in america, asia and malta. in contrast, the prevalence of hospital-acquired mrsa has declined in austria, france, ireland, the uk and greece [ ] . however, another recent study that enrolled hospitals in europe, north america and south america over a -year period ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) demonstrated that the incidence of nosocomial bloodstream infections (bsis) was increasing and that the increased incidence was mainly due to antibiotic-resistant bacteria (arb), including mrsa [ ] . in that study, the mrsa incidence density (events per patient-days) increased from . to . with an annual increase of % in seven arbendemic hospitals [ ] . in taiwan, the annual report of the taiwan nosocomial infections surveillance system by the department of health of taiwan showed that s. aureus was among the top three common pathogens causing bsis in intensive care units, and more than % of s. aureus isolates were mrsa in . these differences in mrsa incidence density may be due to geographical variation and their findings [ , ] might not be generalised to other places, such as asia. we therefore retrospectively assessed the trend in incidence of nosocomial mrsa bsis at an arb-endemic medical centre in taiwan. this study was conducted at national taiwan university hospital (ntuh), a -bed, academically affiliated medical centre providing both primary and tertiary care in northern taiwan. the number of annual patient-days at the hospital increased from in to in . to determine the temporal trend in nosocomial bsis due to mrsa at ntuh, data on disk diffusion susceptibilities of s. aureus to oxacillin among isolates recovered from to were retrieved from annual summary documents. definitions of nosocomial infections followed national nosocomial infections surveillance guidelines [ ] . isolates of each species from each patient recovered within days were considered as a single isolate. susceptibility testing for s. aureus followed clinical and laboratory standards institute (clsi) guidelines [ ] . staphylococcus aureus atcc was used as a control strain for routine disk susceptibility testing [ ] . meticillin resistance among the s. aureus isolates was routinely screened for by measuring the growth of each isolate on a trypticase soy agar plate containing mg/l oxacillin plus % nacl at • c in ambient air for h [ ] . the test was used for dichotomous variables. the test for trend was used to assess temporal trends in incidence densities, and poisson regression was used to determine yearly change in incidence density as a percentage with % confidence intervals (cis). data were analysed using spss v. . (spss inc., chicago, il) and r v. . . . during the study period, a total of nosocomial bsis were identified. of these bsis, infections were caused by s. aureus, . % of which (n = ) were due to mrsa. during the period - , the incidence density of all nosocomial bsis increased from . to . per patient-days (p < . ), with an annual increase of . % ( % ci . - . %). the secular trends in incidence density of nosocomial mrsa and meticillinsusceptible s. aureus bsis are shown in fig. . for mrsa, the incidence density significantly decreased from . to . per patient-days, with an annual decrease of . % ( % ci . - . %) over the -year study period (p < . ). in addition, the ratio of mrsa isolates to all s. aureus isolates obtained from patients with nosocomial bsis decreased from . % in to . % in (p = . ). in this study, we found that the incidence of nosocomial mrsa bsis decreased even though there was an increase in the incidence of all nosocomial bsis in taiwan. therefore, the total burden of nosocomial bsis is most likely attributable to pathogens other than mrsa. this finding contrasts sharply with that reported by ammerlann et al. [ ] but is consistent with some european countries [ ] . in response to the severe acute respiratory syndrome (sars) epidemic in , the infection prevention and control programme at ntuh was upgraded to include hand hygiene, antibiotic control policies, and an annual, intensive, project-based control programme. implementation of these measures is one of the main reasons for the decrease in mrsa infections during the study period. in fact, the impact of these policies has been demonstrated to be directly associated with the decrease in rates of bsis at ntuh [ ] . in conclusion, these results show that the incidence of mrsa nosocomial bsis decreased during the period - at ntuh and that the infection control measures at this hospital most likely played a major role in protecting against mrsa infections. funding: no funding sources. competing interests: none declared. ethical approval: not required. asap ecmo: antibiotic, sedative and analgesic pharmacokinetics during extracorporeal membrane oxygenation: a multi-centre study to optimise drug therapy during ecmo pharmacokinetics and intrapulmonary concentrations of linezolid administered to critically ill patients with ventilator-associated pneumonia clinical pharmacokinetic/pharmacodynamic profile of linezolid in severely ill intensive care unit patients therapeutic drug monitoring of linezolid: a retrospective monocentric analysis meticillin-resistant staphylococcus aureus (mrsa): global epidemiology and harmonisation of typing methods secular trends in nosocomial bloodstream infections: antibiotic-resistant bacteria increase the total burden of infection cdc/nhsn surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting performance standards for antimicrobial susceptibility testing; nineteenth informational supplement. document m -s secular trends of healthcare-associated infections at a teaching hospital in taiwan tropheryma whipplei endocarditis relapses after treatment with trimethoprim/sulfamethoxazole sir, tropheryma whipplei is involved in classic whipple's disease (wd), a chronic infection characterised by histological involvement of the small bowel [ ] . the main manifestations are arthralgias and diarrhoea, but infective endocarditis is sometimes present [ ] . one year or shorter treatment with oral trimethoprim/sulfamethoxazole preceded by weeks of ceftriaxone is recommended by some authors [ ] . however, t. whipplei is naturally resistant to trimethoprim, and acquired resistance to sulfonamides has been reported [ ] . here we report two more cases that relapsed following trimethoprim/sulfamethoxazole therapy.in , a -year-old man was hospitalised for weight loss, diarrhoea, abdominal pain and anaemia. he was diagnosed with wd based on positive periodic acid-schiff (pas) staining on a small bowel biopsy. the patient received oral trimethoprim/sulfamethoxazole ( / mg/day) for months. four years after the cessation of antibiotics, the patient was hospitalised because of progressive dyspnoea and weight loss. transoesophageal echocardiography showed aortic valve vegetation and an altered mitral valve. blood cultures were negative. both removed valves were positive with pas staining and specific pcr, allowing for the diagnosis of t. whipplei endocarditis. the entire folp sequence was obtained but did not show mutations previously reported to be associated with resistance [ ] . a small bowel biopsy was positive for pas staining and specific immunohistochemistry (fig. a) . saliva and skin biopsy were both positive for t. whipplei with specific pcr. treatment was initiated with oral doxycycline ( mg/day), hydroxychloroquine ( mg/day) and trimethoprim/sulfamethoxazole ( / mg/day). the patient was unfortunately lost to follow-up.in , a -year-old man was hospitalised for arthralgias, weight loss and lymphadenopathy. he was diagnosed with wd based on positive pas staining and specific immunohistochemistry on a small bowel biopsy. he had aortic and mitral insufficiencies, which were thought to be degenerative. treatment with intravenous ceftriaxone ( g/day for weeks) followed by trimethoprim/sulfamethoxazole ( / mg/day) was initiated, with rapid clinical improvement. six months after the initiation of this regimen the patient developed dyspnoea and underwent replacement of his aortic and mitral valves. both valves were positive with pas staining and specific immunohistochemistry (fig. b) . specific pcr was positive for the mitral valve. only a partial sequence of folp was obtained. none of the mutations that were previously reported in the t. whipplei folp sequence were detected [ ] . the antibiotic regimen was switched to doxycycline ( mg/day) and hydroxychloroquine ( mg/day) for years, with clinical improvement, followed by lifelong doxycycline ( mg/day), and the patient is currently apparently cured.management of patients with classic wd is still difficult and patients may relapse as endocarditis. there is an ongoing controversy on the use of trimethoprim/sulfamethoxazole for wd [ ] . in fact, it was used empirically in sporadic cases until genomic analysis and biological assays found that trimethoprim is not key: cord- -gm p op authors: tzeng, nian-sheng; chung, chi-hsiang; chang, chuan-chia; chang, hsin-an; kao, yu-chen; chang, shan-yueh; chien, wu-chien title: what could we learn from sars when facing the mental health issues related to the covid- outbreak? a nationwide cohort study in taiwan date: - - journal: transl psychiatry doi: . /s - - -y sha: doc_id: cord_uid: gm p op there were several studies about the psychiatric and mental health issues related to the severe adult respiratory syndrome (sars) outbreak in , however, the association between sars and the overall risk of psychiatric disorders and suicides has, as yet, to be studied in taiwan. the aim of this study is to examine as to whether sars is associated with the risk of psychiatric disorders and suicide. a total of patients with sars and controls without sars ( : ) matched for sex, age, insurance premium, comorbidities, residential regions, level of medical care, and index date were selected between february and june , from the inpatient database taiwan’s national health insurance research database. during the -year follow-up, in which in the sars cohort and in the control group developed psychiatric disorders or suicide ( . vs. . per , person-years). fine and gray’s survival analysis revealed that the sars cohort was associated with an increased risk of psychiatric disorders and suicide, and the adjusted subdistribution hr (shr) was . ( % ci: . – . , p < . ) for psychiatric disorders and suicide. the sars cohort was associated with anxiety, depression, sleep disorders, posttraumatic stress disorder/acute stress disorder (ptsd/asd), and suicide. the sensitivity analysis revealed that the sars group was associated with anxiety, depression, sleep disorders, ptsd/asd, and suicide after the individuals with a diagnosis of psychiatric disorders and suicide were excluded within the first year, and with anxiety, depression, and sleep disorders, while those in the first five years were excluded. in conclusion, sars was associated with the increased risk of psychiatric disorders and suicide. the coronavirus disease (covid- ) outbreak not only causes deaths and adverse consequences on the physical health , , but also induces a global mental health crisis, including psychiatric morbidity and suicide, in the patients, the health care professionals, and the general population [ ] [ ] [ ] . in the meantime, in may , the covid- pandemic seems not, as yet, to be ameliorated . it is too early to reach a conclusion about the overall impact on the mental health in the country or global levels from the limited empirical data. there are several differences between covid- and severe adult respiratory syndrome (sars) in the death rates and range of transmission rates , for example, in regard of the case numbers, sars was just not comparable to covid- . furthermore, the complexities of covid- , such as variety of symptoms, multiple organ involvements have not been seen in sars. on the other hand, the severe sequela in sars patients, especially the lung fibrosis, may be not common in covid- , . however, they are similar in several ways: first, they were caused by two similar, but different, coronaviruses. second, the infections have caused the large-scale influences in society , . since the understanding of the mental health issues are urgent, we believe that we could learn some experiences from the sars-related mental health issues, including the psychiatric disorders and suicide. an outbreak of sars caused by a novel coronavirus severely affected taiwan in , and the first confirmed diagnosis of sars was on february , , and the last diagnosis on june , . through this endemic outbreak, there were patients diagnosed with sars and died among these patients and there were also sars outbreaks in china, singapore, and toronto, canada, at about the same time . there were several studies about the psychiatric and mental health issues related to this sars outbreak. one report from taiwan of about cases has found that most of the psychiatric diagnoses in the consultation services were adjustments disorder, organic hallucinosis, and organic manic disorder during the acute phase treatment . in a hong kong study, the post-sars cumulative incidence of psychiatric disorders was . % in a cohort with patients, and the prevalence of psychiatric disorders at months after the sars was . %, in which one-fourth of the patients had posttraumatic stress disorder (ptsd), and . % had a depressive disorder . other studies about sars-related mental health issues were conducted in the doctors , nurses [ ] [ ] [ ] , and overall hospital workers . in addition, even though several studies have warned of a potential rise of suicides in the covid- , , there were limited reports on the topic of post-sars suicides , . therefore, a nationwide, populationbased, long-term study on the topic for psychiatric disorders and suicides for the patients with sars is yet to be conducted. apart from the psychosocial stressors related to sars or covid- , , the cytokine storms and other immunological factors might also contribute to the postinfection psychiatric morbidity . in addition, the longterm adverse health outcomes for the sars survivors could also be a risk factor for the psychiatric morbidity . therefore, we hypothesized that sars is associated with an increased risk in the development of psychiatric disorders and suicide, and we conducted this nationwide, population-based, cohort study so as to investigate the association between sars and the psychiatric disorders and suicide, using the national health insurance research database (nhird), a claims database retrieved from the whole population of taiwan. the national health insurance (nhi) program is a mandatory and universal health insurance program in taiwan, which has been has been operative since , that covered contracts with % of the medical providers with approximately million beneficiaries, or more than % of the population . the details of this program were documented in several previous studies [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the nhird contains comprehensive and detailed data regarding the total outpatients and inpatients. an inpatient dataset in - was selected from the nhird, with individual diagnoses coded by the international classification of disease, ninth revision, clinical modification (icd- -cm). this study was conducted in accordance with the code of ethics of the world medical association (declaration of helsinki). the institutional review board of the tri-service general hospital approved this study and waived the need of individual consents since all the identification data were encrypted in the nhird (irb: tsghirb no. b- - ). this is a retrospective matched-cohort research using the inpatient dataset between january , , and december , . each patient with sars was required to receive a diagnosis in an inpatient setting with the icd codes as . and . . a : sex-matched, age-matched, insurance premium-matched, comorbidities-matched, locationmatched, level of care-matched, and index date-matched controls were randomly selected for each patient with sars. the exclusion criteria for the cohorts were with unknown sex and individuals diagnosed with psychiatric disorders or pneumonia and influenza (icd- -cm codes: - ) before the index date. the index date was defined as the time when the individuals were first diagnosed as sars within the one-year study period (fig. ). all of the sars participants and controls were followed from the index date until the onset of psychiatric disorders, including anxiety disorders, depression, bipolar disorders, sleep disorders, ptsd, eating disorders, substance use related disorder, dementia, psychotic disorders, and suicide, death, withdrawal from the nhi program, or the end of . the icd codes of psychiatric disorders and suicide are as listed in table s . in taiwan the covariates include sociodemographic characteristics and comorbidities. sociodemographic characteristics included sex, age ( - , - , ≧ years), education (< years; ≧ years), monthly insured premiums, urbanization levels, regions of residence, and levels of medical care. the monthly insured premiums have been divided into three categories in new taiwan dollars [nt$]: < , , , - , , ≥ , . the urbanization level was defined by population and certain indicators of the city's level of development. level urbanization was defined as having a population greater than , , people. level urbanization was defined as having a population between , and , , . urbanization levels and were defined as having a population between , and , and less than , , respectively . the charlson comorbidity index (cci) is one of the most widely used comorbidity indexs , , which consists of conditions , including myocardial infarction, congestive heart failure, peripheral vascular disease, dementia, cerebrovascular disease, chronic lung disease, connective tissue disease, ulcer, chronic liver disease, diabetes, hemiplegia, moderate or severe kidney disease, diabetes with end organ damage, tumor, leukemia, lymphoma, moderate or severe liver disease, malignant tumor, metastasis, and acquired immune deficiency syndrome (aids). we used the cci to quantify the comorbidities since it could predict the inhospital mortality or outcome in patients with severe adults respiratory infection (sari) and other infections [ ] [ ] [ ] . the spss software version (spss inc., chicago, illinois, usa) was used to conduct the statistical analyses. the pearson chi-square test was used for the analysis of the categorical data. continuous variables presented as the mean (±sd), were analyzed using the two-sample t test. to investigate the risk of psychiatric disorders and suicide for patients with and without sars, the fine and gray's model was used to conduct the competing risk analysis to calculate the subdistribution hazard ratios (shrs) and % confidence intervals (cis), adjusting for sociodemographic characteristics, and comorbidities. the value-added module, including the competing risks survival analysis, in the spss was used to conduct fine and gray's survival analysis (https://www.asiaanalytics.com.tw/en/product/ p-asia-analytics- .jsp). the kaplan-meier method was used to determine the difference in the risk of psychiatric disorders and suicide for the patients with sars and the control cohorts using the log-rank test. a p value < . was considered statistically significant. study cohort characteristics table shows the sex, age, education, monthly insured premiums, urbanization levels, regions of residence, comorbidities, and levels of medical care in the patients with or without sars. when compared to the controls, patients with sars have had no significant difference in the covariates. kaplan-meier curves for the cumulative incidence of psychiatric disorders in patients with psychiatric disorders and suicide in total, patients were diagnosed with sars during the study period. during the follow-up period, in the sars group (n = ) and in the control group (n = ) developed psychiatric disorders or suicide ( . vs. . per , person-years). figure reveals that the difference between the two cohorts in the psychiatric disorders and suicide were significant (long-rank test, p < . ). the mean time from the index date to the diagnosis of psychiatric disorders and suicide after diagnosis was . (sd = . ) years. the mean years to the developed psychiatric disorders and suicide in patients with sars were . (sd = . ) years, which was earlier than patients without sars ( . [sd = . ] years) (table s ) . subdistribution hazard ratio analysis of psychiatric disorders and suicide in the patients with sars table shows the factors of sars, using fine and gray's survival analysis, of the factors associated with the risk of psychiatric disorders and suicide. the crude shr was . ( % ci: . - . , p < . ), and after adjusting for sex, age, education, monthly insured premiums, urbanization levels, regions of residence, comorbidities, and levels of medical care, the adjusted shr was . ( % ci: . - . , p < . ) for psychiatric disorders and suicide. sars patients aged - years, ≧ years, with the cci score ≧ , and care from the medical centers and regional hospitals, were associated with an increased risk for psychiatric disorders and suicide. male patients with sars were associated with a decreased risk for psychiatric disorders and suicide, in comparison to the female patients. subgroup analysis of psychiatric disorders and suicide in the sars cohort and controls table s shows that the sars cohort was associated with a higher risk of psychiatric disorders than the control group, regardless of sex, age, marital status, education years, comorbidities, monthly insured premiums, residences, urbanization, and levels of care, with one exception being the insured premiums of ≧nt$ , . sensitivity test for analysis of the risk of psychiatric disorders and suicide in the patients with sars patients with sars were associated with an increased risk in overall psychiatric disorders, anxiety disorders, depressive disorders, sleep disorders, ptsd, and suicide, when compared to the control group. the shr's of these psychiatric the sensitivity analysis revealed that the sars cohort was associated with anxiety, depression, sleep disorders, ptsd/asd, and suicide after the individuals with a diagnosis of psychiatric disorders and suicide were excluded within the first year, and with anxiety, depression, and sleep disorders, while those in the first five years were excluded (table ). in this study, we have several noteworthy findings: first, the sars cohort had a . -fold increased risk of overall psychiatric disorders when compared to the control cohort. compared with previous reports about the association between sars and psychiatric disorders, such as a case series , or a smaller sample size study , this study was based on a nationwide, population-based claims database, with a larger sample size, in a long-duration follow-up. even though one meta-analysis, combining sars, mers, and covid- studies, has been comprised of cases of acute phase sars , this study has a longer follow-up for the risk of developing psychiatric disorders. to the best of our knowledge, this is the first study on the association between sars and increased risk in developing psychiatric disorders and suicide, in a -year follow-up, from a nationwide, population-based database. second, we investigated the risk of different psychiatric diagnoses in the sars patients, and we found that sars was associated with anxiety, depression, sleep disorders, ptsd/asd, and suicide, which is similar to the findings of the association between severe coronavirus infections and ptsd , , anxiety , and depressive disorders , . however, we found that the risk of psychiatric disorders could be increased even in a long term follow-up of years, not just a shorter term of up to -month of follow-up , in this study. third, to resolve the influences of protopathic bias, we conducted the sensitivity analysis: the sars cohort was associated with anxiety, depression, sleep disorders, ptsd/ asd, and suicide after the individuals with a diagnosis of psychiatric disorders and suicide were excluded within the first year, and with anxiety, depression, and sleep disorders, while those in the first five years were excluded. by conducting this analysis, we could avoid the protopathic bias, that arises when the initiation of the exposure occurs in response to an undiagnosed disease under study outcome . fourth, in this study, we could also point out that the risk of development of pstd was not beyond the first five years. in addition, the mean years to developed psychiatric disorders and suicide in patients with sars were . (sd = . ) years. therefore, this finding could serve as an important reminder for the clinicians caring the sars survivors in monitoring their mental conditions in the first - years, especially for ptsd/asd. furthermore, we found that the sars cohort was at a particularly high risk of ptsd/asd: the sars cohort had a -fold increased risk of ptsd/asd and a -fold increased risk of ptsd/ asd even after excluding the psychiatric disorders within the first year. this finding is similar to several studies on the topic of the association between severe coronavirus infections and ptsd, up to one-third to one-fourth of the patients of the severe coronavirus infections , . fifth, suicide after the sars outbreak was a critical issue, and previous studies on this topic have investigated the potential increased suicide risk in the elderly , and the ed visitors , during and after the sars outbreak. this study might be the first study about the suicides of the sars survivors. as aforementioned, the association between sars and suicide was statistically significant even after excluding suicide within the first year, but not significant after excluding suicide within the first five years. therefore, the careful evaluation in the suicide risk is important in the following years after sars. the underlying mechanisms for the risk of psychiatric disorders remained unclear. one of the possible reasons for the increased risk of psychiatric disorders and suicide might well be related to the psychological impact for the patients, general stress, and the negative psychological effects are increased in the sars patients, particularly among the infected health care workers , , such as stress from the quarantine and isolation, fear of uncertainty and death, impaired health after severe viral infections, economic burden after sars, and even negative feelings for the sars-related information [ ] [ ] [ ] . furthermore, one previous study found that the elevated levels of the monocyte chemoattractant protein- (mcp- ), transforming growth factor beta- (tgfβ- ), interleukin- beta (il- β), and interleukin- (il- ) in the sars-covinfected angiotensin-converting enzyme (ace +) cells in the sars patients . the increased levels of these cytokine might not only result in acute lung injury, but also be associated with psychiatric disorders, such as depressive disorders, bipolar, or anxiety disorders , . in this study, patients aged - years or ≧ years, and a higher cci score of ≧ , and the level of care from the medical centers and regional hospitals, were associated with the risk of psychiatric disorders and suicide. this finding hints that patients with older ages, and more severe physical morbidities in the sars patients, could also contribute to the risk of psychiatric disorders. nonetheless, further studies are needed to investigate the underlying mechanisms for the development of psychiatric disorders in the sars survivors. this study has several strengths: first, we used the lhid, which has a large sample size in this study. second, sars was diagnosed by the serology test and being a notifiable disease it needed to be reported to the health authority in taiwan (https://www.cdc.gov.tw/en), third, we have conducted a long-term follow-up of years of the development of psychiatric disorders after the sars outbreak in . this could serve as a lesson for us to learn from sars when facing the challenge of psychiatric disorders from covid- : the mental health issues in covid- might not be only from the acute-phase of delirium , , depression, and acute trauma-related psychiatric disorders such as asd or acute ptsd . a longterm follow-up of psychiatric disorders for covid- survivors would be important. this study has several limitations that warrant consideration. first, similar to previous studies using the nhird on infectious, parasitic, or inflammatory diseases - , since the severity, weakness severity, laboratory parameters, or lung function examinations in sars patients were not recorded in the nhird. second, other factors, such as genetic, psychosocial, and environmental factors, were not included in the dataset. third, ascertainment bias is possible if the patients who were treated for sars were more medically attentive so that they also sought treatment for psychiatric conditions. fourth, this study contained only small number of cases, and thus there are very few numbers of ptsd and suicide, which all happened within five years after sars. furthermore, for other psychiatric cases, nearly one third of the cases happened within one year, and up to two thirds reported with five years both in the sars and control cohorts, only one occurred after ten years in sars group ( table ) . considering the new occurrence of psychiatric disorders, the difference was not so significant between two cohorts after nine years in the study period. therefore, most of the attention should be paid to psychiatric disorders that developed within ten years of the onset of sars. after all, the small numbers of sars cases limit the generalization of the sars experiences to the diagnosis and treatment of psychiatric consequences of covid- treatment. finally, the nhird does not contain the information for the sars patients' family members and the health workers who take care of them. we need further studies to investigate the post-sars psychiatric morbidity in the long-term follow-up. this study found that sars was associated with the increased risk of psychiatric disorders and suicide in a long-term follow-up study of years. this is also a reminder for the clinicians that psychiatric morbidity is an important issue in the patients with severe coronavirus infections, such as covid- . the coronavirus disease (covid- ) pandemic covid- , child and adolescent mental healthcroatian (in)experience anxiety regarding contracting covid- related to interoceptive anxiety sensations: the moderating role of disgust propensity and sensitivity prevalence of depression, anxiety, and insomnia among healthcare workers during the covid- pandemic: a systematic review and meta-analysis world health organization. summary of probable sars cases with onset of illness from the impacts on health, society, and economy of sars and h n outbreaks in china: a case comparison study covid- outbreak: migration, effects on society, global environment and prevention psychiatric complications in patients with severe acute respiratory syndrome (sars) during the acute treatment phase: a series of cases long-term psychiatric morbidities among sars survivors psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the covid- pandemic psychiatric morbidity among emergency department doctors and nurses after the sars outbreak facing sars: psychological impacts on sars team nurses and psychiatric services in a taiwan general hospital prevalence of psychiatric morbidity and psychological adaptation of the nurses in a structured sars caring unit during outbreak: a prospective and periodic assessment study in taiwan prevalence of psychiatric disorders among toronto hospital workers one to two years after the sars outbreak can we expect an increased suicide rate due to covid- ? uncomfortably numb: suicide and the psychological undercurrent of covid- elderly suicide and the sars epidemic in hong kong impact of severe acute respiratory syndrome (sars) outbreaks on the use of emergency department medical resources factors associated with psychosis among patients with severe acute respiratory syndrome: a case-control study coping responses of emergency physicians and nurses to the severe acute respiratory syndrome outbreak impact of sars-cov- infection on neurodegenerative and neuropsychiatric diseases: a delayed pandemic? neurología (english edition long-term psychological and occupational effects of providing hospital healthcare during sars outbreak taiwan's healthcare report is weight control surgery associated with increased risk of newly onset psychiatric disorders? a population-based, matched cohort study in taiwan sex and age differences in the association between anxiety disorders and narcolepsy: a nationwide population-based case control study increased risk of dementia in patients with genital warts: a nationwide cohort study in taiwan stimulants associated with reduced risk of hospitalization for motor vehicle accident injury in patients with obstructive sleep apnea-a nationwide cohort study are anticholinergic medications associated with increased risk of dementia and behavioral and psychological symptoms of dementia? a nationwide -year follow-up cohort study in taiwan association between traumatic spinal cord injury and affective and other psychiatric disorders-a nationwide cohort study and effects of rehabilitation therapies association between child abuse exposure and the risk of psychiatric disorders: a nationwide cohort study in taiwan no association between human immunodeficiency virus infections and dementia: a nationwide cohort study in taiwan psychiatric disorders after traumatic brain injury: a nationwide population-based cohort study and the effects of rehabilitation therapies the newly diagnosed amnestic disorders and dementia: a nationwide, cohort study in taiwan new users of herbal medicine containing aristolochic acids and the risk of dementia in the elderly-a nationwide, population-based study in taiwan increased risk of major depression in the three years following a femoral neck fracture-a national population-based follow-up study a new method of classifying prognostic comorbidity in longitudinal studies: development and validation how to measure comorbidity. a critical review of available methods validation of a combined comorbidity index the updated charlson comorbidity index is a useful predictor of mortality in patients with staphylococcus aureus bacteraemia charlson comorbidity index (cci): an independent predictor of outcomes in clostridium difficile infection (cdi): charlson comorbidity index scores and in-hospital prognosis in severe acute respiratory infections patients the problem of "protopathic bias" in case-control studies a revisit on older adults suicides and severe acute respiratory syndrome (sars) epidemic in hong kong stress and psychological impact on sars patients during the outbreak the psychological impact of sars: a matter of heart and mind psychological impact of the sars outbreak on a singaporean rehabilitation department expression of elevated levels of pro-inflammatory cytokines in sars-cov-infected ace + cells in sars patients: relation to the acute lung injury and pathogenesis of sars peripheral alterations in cytokine and chemokine levels after antidepressant drug treatment for major depressive disorder: systematic review and meta-analysis bipolar disorder and immune dysfunction: epidemiological findings, proposed pathophysiology and clinical implications neurological manifestations and complications of covid- : a literature review covid- : icu delirium management during sars-cov- pandemic are we facing a crashing wave of neuropsychiatric sequelae of covid- ? neuropsychiatric symptoms and potential immunologic mechanisms anti-herpetic medications and reduced risk of dementia in patients with herpes simplex virus infections-a nationwide, population-based cohort study in taiwan the association between scabies and myasthenia gravis: a nationwide population-based cohort study increased risk of bipolar disorder in patients with scabies: a nationwide population-based matched-cohort study increased risk of psychiatric disorders in allergic diseases: a nationwide, population-based, cohort study. front are chronic periodontitis and gingivitis associated with dementia? a nationwide, retrospective, matched-cohort study in taiwan the authors would like to thank the medical affairs bureau, the ministry of defense of taiwan (mab- - ), and the tri-service general hospital research foundation (tsgh-c - , tsghc - , tsgh-c - , and tsgh-b- - ). these funding agencies did not influence the study design, data collection and analysis, decision to publish, or preparation of the manuscript. we also appreciate taiwan key: cord- -oci t authors: chen, yu-wen; huang, yhu-chering; ho, tai-hua; huang, chung-guei; tsao, kuo-chien; lin, tzou-yien title: viral etiology of bronchiolitis among pediatric inpatients in northern taiwan with emphasis on newly identified respiratory viruses date: - - journal: j microbiol immunol infect doi: . /j.jmii. . . sha: doc_id: cord_uid: oci t purpose: viral etiology of bronchiolitis in children in taiwan has been fragmentary. we conducted a prospective study to figure out the viral epidemiology of bronchiolitis in taiwan. materials and methods: from january to march , a total of children with bronchiolitis, aged < years, hospitalized in chang gung children’s hospital were randomly selected for viral etiology investigation. nasopharyngeal aspirates were obtained from each case and sent for viral detection by tissue culture, antigen test, and polymerase chain reaction. results: a total of viruses were detected from children. positive viral etiology was identified in ( %) children. mixed viral pathogens were found in cases ( %). respiratory syncytial virus (rsv) was the most common pathogen and was identified in . % of the cases. human bocavirus (hbov) was the second most common identified virus (in . %), followed by human metapneumovirus (hmpv), rhinovirus, influenza viruses, and coronavirus oc . in terms of clinical characteristics, no significant difference was found among the children with bronchiolitis either caused by different single or mixed viral infection. conclusion: rsv was the most common etiologic agent for children with bronchiolitis in taiwan. newly identified viruses, including hmpv and hbov, were also among the common causative agents. clinical characteristics were not significantly different among the children with bronchiolitis caused by different viruses. bronchiolitis is the most common lower respiratory tract infection and a major cause of hospitalization in infants around the world. it is characterized by acute inflammation, edema, and necrosis of epithelial cells lining small airways; increased mucus production; and bronchospasm. clinical symptoms and signs of bronchiolitis typically include rhinitis, tachypnea, wheezing, cough, crackles, use of accessory muscles, and/or nasal flaring. , with the development of molecular techniques and the availability of monoclonal antibodies for numerous viral species, detection of viral respiratory agents has been markedly improved in the past decades. these advances allowed re-evaluation of the role of various respiratory viruses in the pathogenesis of acute bronchiolitis. however, it is not infrequently seen that no causative agent can be identified in patients with bronchiolitis. respiratory syncytial virus (rsv) is the most frequently identified agent responsible for bronchiolitis worldwide. , however, many other respiratory viruses may also cause bronchiolitis. until now, viral etiology of bronchiolitis in children in taiwan has been limited, particularly the newly identified viruses, including human metapneumovirus (hmpv), human bocavirus (hbov), and human coronavirus (hcov) nl- . , therefore, we conducted a prospective study to figure out the viral epidemiology of bronchiolitis among pediatric inpatients in taiwan. the study was approved by the institutional review board of chang gung memorial hospital, and informed consent was obtained from parents or legal guardians of the children. from january to march , children (aged < months) with the initial diagnosis of acute bronchiolitis, hospitalized in chang gung children's hospital situated in northern taiwan, were eligible for this study, and up to three cases per week were randomly selected for viral etiology investigation. nasopharyngeal aspirates were collected prospectively from all patients within e days after hospital admission. the diagnosis of acute bronchiolitis was made by an acute onset of respiratory distress with cough, tachypnea, retraction, and expiratory wheezes, often accompanied by rales. patients with underlying chronic diseases, including cerebral palsy with bedridden status, tracheostomy, congenital heart disease, chronic pulmonary disease, and immunodeficiency, were excluded. medical records were reviewed for detailed demographic, clinical, and laboratory data; radiographic images; and underlying conditions of the patients. all the clinical symptoms and signs were recorded on a standardized form while the patients were hospitalized. all the specimens were processed, and then nucleic acids (including dna and rna) were extracted by commercial kits and kept in a refrigerator at e c for further analysis. all specimens were sent for viral detection by conventional viral culture, immunofluorescent antigen detection for rsv, and multiplex reverse transcriptionpolymerase chain reaction (rt-pcr) for six viruses, including rhinovirus (rv), hmpv, hcov- e, hcov-oc , nl- , and hbov. sample preparation for virus culture and immunofluorescence nasopharyngeal aspirates were mixed with sterilized phosphate-buffered saline (pbs) followed by vigorous vortex. then the cell suspension was centrifuged at rpm for minutes to get the cell pellet. finally, the supernatant was discarded and pbs was added to resuspend the cells again. the procedures were repeated for three times. after the third time wash, the cell pellet was resuspended in viral transport medium and treated with antibiotics for minutes. specimens of cell suspension prepared as described above were inoculated into mk , mrc- , and mdck cells and incubated at c for weeks. cytopathic effect (cpe) of all culture tubes was checked every days. for cpepositive tubes, a screening kit of immunofluorescence assay for respiratory virus (chemicon inc., temecula, california, usa) was used for further examination of respiratory virus infection. only the respiratory viruses identified, including rsv, parainfluenza (piv)- , piv- , piv- , adenovirus, influenza viruses a and b, were regarded as pathogens. the cell suspension ( ml) was added to a slide and fixed in acetone for minutes. monoclonal antibody that conjugated fluorescein isothiocyanate (fitc) to rsv was used to detect rsv antigen. it is designed to amplify conserved region of each virus target. sequence of primer for each virus target is given in supplementary table . viral rnas were extracted from ml respiratory specimens using qiamp viral rna kit (qiagen, chatsworth, ca, usa), and reverse transcription reactions were performed for complementary dna synthesis using superscripttm iii one-step rt-pcr kit (invitrogen, carlsbad, ca, usa). each reaction included the following components: . m probe, . m primer, . l of  abi mater mixture (containing . mmol/l deoxyribonucleotide triphosphate (dntp) and . mmol/l mgso ), and ml of specimen rna extract or control. the final reaction volume was adjusted to ml with pcrgrade water, and rt-pcr amplification was performed using the following conditions: an initial cdna step at c for minutes, followed by at c for minutes, and cycles at c for seconds, at c for seconds, and at c for seconds. rt-pcr products of hcov-nl and hbov for positive control were kindly provided by professor patrick c.y. woo (hong kong university). one-way analysis of variance and student t test were used for the comparison of continuous variables. the c test was used to analyze categorical independent variables. results for continuous data were expressed as mean ae sd. a p value of < . was considered statistically significant. all analyses were performed using the spss version . for windows. a total of children were included in this study. the median age of the children was months, ranging from . to months, and ( %) were male. clinical characteristics of the patients are described in table . in our study, / ( . %) children received antibiotic treatment during hospitalization mostly due to secondary bacterial infection such as acute sinusitis, acute otitis media, or pneumonia. a total of viruses were detected from children, but viruses, including cytomegalovirus in seven and enterovirus in five, were regarded as nonpathogenic agents and excluded from analysis in this study. at least one viral pathogen was identified in children ( %), of whom single viral pathogen was detected in ( %) and at least two viruses were detected in ( %). rsv was the most common virus identified and accounted for ( . %) cases, followed by hbov in ( . %), hmpv in ( . %), and rv in ( . %) (fig. ) . cpe was observed in one case, but the virus species could not be identified. all specimens were negative for cov- e or influenza virus b. of the rsv-positive children, ( . %) had coinfection with other viruses. monthly distribution of the viruses identified during the study period is illustrated in fig. . the incidence of rsv infection peaked in april , march , and november . the incidence of hmpv detection peaked in april , while that of hbov peaked in august . we could not evaluate the differences in incidence of other viruses due to the small case numbers. bronchiolitis due to single viral infection was identified in patients, of whom rsv was detected in ( %), hbov in six ( %), hmpv in six ( %), and rv in seven ( %). clinical characteristics of these patients are given in table . no significant differences were observed in terms of sex, age, radiographic findings, duration of fever, length of hospital stay, antibiotic treatment, leukocyte count, and serum c-reactive protein level. multiple viral infections were found in cases ( %). rsv was the most common virus encountered in mixed infections, followed by hbov, hmpv, and rv. the detailed incidence rate of mixed viral infection is listed in table . in addition, clinical characteristics of the children with rsvmixed infection are described in table . clinical manifestations of children with rsv-mixed infection were similar to those with single viral infection, and no significant differences were found among the different groups. to our knowledge, this is the first comprehensive viral etiology study of hospitalized pediatric patients with bronchiolitis, including newly identified respiratory viruses, in taiwan. results from the present study showed that rsv, hmpv, and hbov were the most common viral pathogens for acute lower respiratory tract infection among hospitalized children, less than years of age, in northern taiwan.we demonstrated again that rsv remained the major pathogen in infants with bronchiolitis. , by thecombination of virus isolation and antigen test, rsv was detected in % of the patients in the current study. rsv bronchiolitis followed the biennial seasonal pattern of taiwan, with peaks during the spring and the fall (april , march , and november ), which were consistent with those previously reported from taiwan. this this study was strengthened by the use of rt-pcr assays in combination with virus culture and immunofluorescent assay to detect respiratory viruses, including the newly identified viruses (hmpv, hbov, and hcov-nl ) and other viruses (rv, hcov-oc , and hcov- e), which may be responsible for bronchiolitis but not identified by routine virus tissue culture. with these technologies, we were allowed to detect up to different viruses (groups) and could also explain a higher viral detection rate ( %) in the present study. in % of the patients, viruses other than rsv were identified; after rsv, the most frequently detected viruses included hbov, hmpv, and rv. the prevalence rate for hbov ( . %) was the highest so far reported among infants hospitalized for bronchiolitis. , , calvo et alreported an incidence rate of . % for hbov detection and midulla et al a rate of . %. the role of these respiratory agents in causing single or multiple viral infections in bronchiolitis has not yet been thoroughly studied. these findings suggest that many other respiratory viruses, in addition to rsv, may also cause acute bronchiolitis. in the present study, clinical characteristics of children with bronchiolitis due to different viral etiologies seemed similar, regardless of whether the infection was caused by single or multiple viruses. in our study, we also observed no statistical significance in clinical characteristics between children with bronchiolitis caused by different single viral infection. however, a trend related to older age in hbovinfected children than in rsv-infected was observed in previous studies. , , the proportion of rv infections ( . %) in taiwan is slightly lower than that reported from the usa ( %) and spain ( . %), , but higher than that from italy ( . %). the prevalence rate of hmpv ( . %) in this study was higher than in most previous reports ( . e %), , , except in the report byxepapadaki et al ( %) . multiple viral infections were present in one-fourth of the patients with positive respiratory viral detection. in agreement with previous studies, coinfection of hbov and hmpv with other viruses was very common. , , , the role of viral coinfection is still unclear, and the controversies regarding their severities were found in the literature. e in this study, clinical manifestations of children with rsvmixed infection were similar to those with single viral infections. although the combination of pcr method with other technologies was used, the causative viral agents remained undetected for one-fifth of the patients, which was in agreement with previous studies. , , the negative results may be due to technical problems related to sample collection, processing, and storage, or due to that bronchiolitis may be caused by unidentified viruses. in this study, we did find a specimen with cpe in the virus culture, but the viral pathogen could not be identified. there were several limitations in the present study. first, a relatively small sample size made it difficult to compare among children with different viral etiologies. second,the severity score of bronchiolitis could not be calculated to evaluate the disease severity of patients because oxygen saturation data were not detected for most patients and oxygen supplement such as o hood was routinely provided for children hospitalized with bronchiolitis in our hospital. third, we included only those inpatients who may affect the true prevalence rate of the viral etiology of bronchiolitis, since not all patients with bronchiolitis needed hospitalization. in conclusion, although rsv remains the major viral pathogen for bronchiolitis, more than half of bronchiolitis are associated with other respiratory viruses, including newly identified viruses such as hmpv and hbov. molecular diagnostic methods such as rt-pcr provide a rapid, sensitive, and specific approach to improve the etiological diagnosis for bronchiolitis, which enables to prompt a more appropriate and rapid management. further studies are needed to identify new viruses implicated in childhood bronchiolitis. all authors declare that they have no conflicts of interest related to the material discussed in this article. american academy of pediatrics subcommittee on diagnosis and management of bronchiolitis. diagnosis and management of bronchiolitis epidemiology of respiratory syncytial virus infection among paediatric inpatients in northern taiwan variation in timing of respiratory syncytial virus outbreaks: lessons from national surveillance the association of newly identified respiratory viruses with lower respiratory tract infections in korean children detection of new respiratory viruses in hospitalized infants with bronchiolitis: a three-year prospective study respiratory syncytial virus: a continuing culprit and conundrum epidemiology of respiratory syncytial virus infection in northern taiwan, e dseasonality, clinical characteristics, and disease burden etiology of bronchiolitis in a hospitalized pediatric population: prospective multicenter study respiratory syncytial virus, human bocavirus and rhinovirus bronchiolitis in infants human metapneumovirus infections in hospitalised infants in spain prospective multicenter study of the viral etiology of bronchiolitis in the emergency department human metapneumovirus as a causative agent of acute bronchiolitis in infants high prevalence of human bocavirus detected in young children with severe acute lower respiratory tract disease by use of a standard pcr protocol and a novel real-time pcr protocol association of respiratory picornaviruses with acute bronchiolitis in french infants differential detection of rhinoviruses and enteroviruses rna sequences associated with classical immunofluorescence assay detection of respiratory virus antigens in nasopharyngeal swabs from infants with bronchiolitis association of rhinovirus infection with increased disease severity in acute bronchiolitis high rate of viral identification and coinfections in infants with acute bronchiolitis viral etiology of acute lower respiratory tract infections in hospitalized young children in northern taiwan this study was supported by a grant from chang gung memorial hospital (cmrpg - ). supplementary data related to this article can be found online at http://dx.doi.org/ . /j.jmii. . . . key: cord- - pnl s authors: sun, haiyan; gao, min; cui, dawei title: molecular characteristics of the vp region of enterovirus strains in china date: - - journal: gut pathog doi: . /s - - - sha: doc_id: cord_uid: pnl s background: enterovirus (ev ) is the most commonly implicated causative agent of severe outbreaks of paediatric hand, foot, and mouth disease (hfmd).vp protein, a capsid protein of ev , is responsible for the genotype of the virus and is essential for vaccine development and effectiveness. however, the genotypes of ev isolates in china are still not completely clear. methods: the vp gene sequences of ev virus strains from china, excluding repetitive sequences and known ev genotypes as reference strains, between and were obtained from genbank. phylogenetic tree, amino acid homology, genetic variation and genotype analyses of the ev vp protein were performed with mega . software. results: the amino acid identity was found to be . %– % among the ev strains, . %– % compared with vaccine strain h , and . %– % compared with vaccine strains fy vp or fy- k-b. since , the prevalent strains of ev were mainly of the c genotype. among these, the c a subgenotype was predominant, followed by the c b subgenotype; other subgenotypes appeared sporadically between and in mainland china. the b genotype was the main genotype in taiwan, and the epidemic strains were constantly changing. some amino acid variations in vp of ev occurred with high frequencies, including a t ( . %), h q ( . %), a s ( . %), s t ( . %), v i ( . %), n d ( . %), and e k ( . %). conclusion: the c genotype of ev in china matches the vaccine and should effectively control ev . however, the efficacy of the vaccine is partially affected by the continuous change in epidemic strains in taiwan. these results suggest that the genetic characteristics of the ev -vp region should be continuously monitored, which is critical for epidemic control and vaccine design to prevent ev infection in children. caused by ev infection have been widely prevalent in china since [ ] . for example, hfmd pandemics in linyi city, shandong province, and guangdong, anhui province, in resulted in tens of thousands of childhood infections and death among dozens of children [ , ] . ev belongs to the enterovirus genus of the rna virus family. ev can be clustered into three genotypes according to nucleotide differences in the vp region, including genotype a (brcr) with only one member, b and c. in contrast, genotypes b and c are divided into five subgenotypes, b -b and c -c , respectively, and genotype c is further subdivided into c a and c b [ ] [ ] [ ] . in china, genotypec is the main epidemic strain; c b was the predominant epidemic genotype from to and the c a subgenotype after in mainland china, though taiwan strains continue to circulate, including c , b and b genotypes [ ] [ ] [ ] [ ] [ ] [ ] [ ] . phase iii clinical trials of vaccines from three companies in china have been completed, and the genotypes of their vaccine strains are all c a subgenotypes [ ] . the vaccine research and development center of national institutes of health in taiwan has also developed an fi-ev vaccine based on the b subtype (ev vac), which can cause a robust cross-neutralizing antibody reaction against different ev gene subtypes, such as b , b , b and c a [ , ] . nonetheless, there are many reports on recombination between different genotypes of ev [ ] [ ] [ ] [ ] , suggesting that ev has high variability and recombination ability, which may lead to the production of new pathogenic strains. therefore, genome monitoring of ev epidemic strains is of great significance for the prevention and control of ev epidemics and can guide the application of the ev vaccine to a certain extent. in this study, the vp sequences of all ev viruses registered in gen-bank in china from to were collected, and the molecular characteristics of genes were analysed using bioinformatics software to provide a scientific basis for the prevention and control of hfmd epidemics. (h , fy vp , and fy- k-b) and known genotypes of ev strains were considered reference sequences, as presented in table . the complete vp sequence of ev strains was compared by molecular evolutionary genetics analysis (mega) version . [ ] . in brief, a phylogenetic tree of the ev vp gene was constructed by the adjacency method (neighbour-joining, n-j) with bootstrap replications. homology and variation of ev strain vp gene sequences were analysed by mega . . a phylogenetic tree of the vp amino acid sequence was constructed with ev isolates from china and reference strains (fig. ) . amino acid identity among the ev strains is . %- %, . %- % compared with vaccine strain h and . %- % compared with vaccine strains fy vp or fy- k-b. among the ev strains, the c genotype accounted for most of the ev strains, and the c a subgenotype was the most common. moreover, b , c b and c were found to be important genotypes of ev ; other subgenotypes appeared sporadically. among the strains, the first strains isolated from china in were all of the b genotype, after which different genotypes/subgenotypes were detected in china. from to , there was a small epidemic peak of c -genotype ev in . between and , the b genotype was the predominant strain of ev . most ev strains between and were of the c genotype, and from to , the c a subgenotype was the most common epidemic strain. b and c b genotypes also accounted for a certain proportion (table and fig. ) . next, the ev strains isolated from china, including mainland china, hong kong, and taiwan, were further analysed to explore their genotypic distribution in different years. the results indicated that from to , the c a subgenotype was absolutely the predominant strain of ev , followed by the c b subgenotype; other subgenotypes appeared sporadically in mainland china. moreover, among the strains isolated from hong kong, there were c a-subgenotype strains table and fig. . however, the epidemic strains of ev in taiwan from to are quite different from those in mainland china. overall, epidemic strains are not predominantly represented by a single subgenotype but are constantly changing. the first strains isolated in taiwan in were all of the b genotype. in , c was the predominant ev genotype in taiwan. from to , to , and to , the epidemic strains in taiwan evolved mainly into b -genotype ev strains. additionally, c a was an important genotype between and (table and fig. ). analysis of common amino acid variation sites in the ev vp region showed that of the strains, residue was the major common site, with a total variation rate of . %; a t was the most common variant, accounting for . %. moreover, . % of strains from mainland china, including hong kong, exhibited this variation; . % of strains from taiwan also exhibited this variation. there was a total mutation rate of . % at amino acid position in the vp region. the frequency of the h q variation was detected to be . %, of which mainland china, including hong kong, exhibited . %; taiwan exhibited . %. furthermore, % of the ev strains harboured an h r mutation. the mutation rates of a s, s t, v i, n d and e k were . %, . %, . %, . % and . %, respectively. among the common sites of amino acid variation in the ev vp region, the most common was residue , with five types of amino acid variation, among which the a s mutation was the most common (table ). it has been reported that since , the major ev strains in mainland china basically belong to the c genotype [ , ] . the immune effectiveness of inactivated vaccines mostly depends on the antigenic correlation between epidemic strains and vaccine strains, which are often best for preventing infection of the same subtype virus but are inferior against different subtypes [ ] . recent studies have also shown that the ev vaccine (especially in children who receive doses) can effectively prevent and control childhood ev -associated hfmd but has no protective effect against coxsackievirus (cv) a (cva- ) or cva , and there is no explanation for the effectiveness of other subtypes of ev (excluding c a subtypes) [ ] . these studies show that vaccine research and development for ev combined with cva and cva and other multivalent vaccines might better prevent ev infection. interestingly, this study found that the ev epidemic strains in taiwan were mainly of the b genotype, which was different from those in mainland china; ev epidemic strains are also constantly changing, which is consistent with a previous report [ ] . according to a human phase clinical trial on adults in , the fi-ev vaccine (ev vac) based on the b genotype from taiwan is safe and induces a high titre of neutralizing antibodies against ev ; it was also highly effective against b , b , and c a strains. however, the titres of neutralizing antibodies against c b and cva were low in % of volunteers, and virus-neutralizing antibodies against the c genotype were not detected in % of vaccine recipients [ , ] . these studies indicate that it is necessary to h, histidine; q, glutamine; r, arginine; n, asparagine; d, aspartic acid; s, serine; g, glycine; e, glutamic acid; k, lysine; a, alanine; l, leucine; v, valine; i, isoleucine; f, phenylalanine; t, threonine; p, proline strengthen the monitoring of ev genotypes; new multivalent and effective vaccines that can cover local strains should be designed and applied according to the genotypes of the local predominant ev epidemic strains to ensure that the vaccine is more accurate in controlling hfmd epidemics. some studies have shown that the h q mutation in the vp protein of ev can lead to a decrease in the adsorption capacity of the c genotype to host cells [ ] [ ] [ ] . the amino acid at position of . % of the strains isolated in china is h (histidine), which suggests that most of the viruses have strong adsorption capacity to host cells. furthermore, h q was detected in . % of all ev strains in taiwan, significantly more prevalent than that in mainland china and hong kong ( . %), suggesting that the adsorption capacity of some strains in taiwan to host cells is weak in comparison with that of strains in mainland china. studies have shown that the a t ev vp variant is closely related to the occurrence of severe hfmd and that the neurological symptoms caused by ev infection are significantly increased when the amino acid at position of vp is a (alanine); in contrast, there is low neurotoxicity when the amino acid is t (threonine) [ , ] . in this study, . % ( strains) of the virus strains were found to contain an a (alanine), suggesting that most of these ev viruses have high neurotoxicity. moreover, . % ( strains) of the strains in mainland china (including hong kong) and . % ( strains) of those in taiwan contain a t (threonine), suggesting low neurotoxicity. it remains to be further studied whether new mutations such as a v (valine)/d (aspartic acid)/i (isoleucine) mutations will cause the emergence of severe hfmd. ev can infect human lymphocytes by binding to its receptor molecule p-selectin glycoprotein ligand- (psgl- ). when e (glutamic acid) at position in vp is mutated to g (glycine) or q (glutamine), the virus binds psgl- more readily, whereas its psgl- -binding ability is weakened or lost when e is present [ ] . in this study, the amino acid at position in most strains was found to be e, with an e g/q mutation rate of . %, suggesting that the emergence of this mutation may result in a virus that is more likely to infect human lymphocytes. it has been reported that the e k mutation may increase the hydrophobicity of vp , making it easy for large compounds to enter and interfere with receptor binding, suggesting that e k mutant viruses are sensitive to larger compounds [ ] . other studies have shown that e g and n d mutations are associated with increased virulence of ev and may increase the risk of neurological complications but that i v mutations reduce the risk of neurological complications [ ] [ ] [ ] . in this study, the e k, e g, n d and i v mutation rates were . %, . %, . % and . %, respectively. these findings indicate that these mutations may play an important role in the pathogenicity of mild and severe ev -associated hfmd. humans are the only natural host and source of ev . indeed, ev cannot infect rodents, which is due mainly to the incompatibility between the virus and rodent cells, and the different expression of its scavenger receptor in humans and rodents [ ] [ ] [ ] . however, some studies have found that simultaneous substitution of k e, e a and l f in vp of ev can result in infection in mice [ ] . our study showed that among strains, the mutation frequencies of k e, e a and l f were . %, . % and . %, respectively; however, no strain with all three mutations was found. these findings indicate that humans are still the only host of ev in china; nevertheless, the existence of individual mutations does not rule out the emergence over time of strains that can infect other mammals. therefore, it is important to closely monitor mutation of the key sites of the ev vp protein. ev is the most important pathogen causing severe hfmd in children, which can lead to irreversible sequelae or death, and it is a serious threat to their health [ , ] . at present, there is no specific treatment for ev infection. the development and marketing of an inactivated ev vaccine in china is crucial for the prevention of hfmd caused by ev infection [ , [ ] [ ] [ ] . phase iii clinical trials of the ev inactivated vaccine approved in china in have shown protective effectiveness against ev -associated hfmd of more than % [ , [ ] [ ] [ ] . however, according to molecular epidemiological studies of ev , ev gene mutations occur frequently, leading to genetic diversity [ ] [ ] [ ] [ ] ] . these studies suggest that there is still a need for strengthening surveillance of ev genotypes and the development of new ev vaccines. this study had a retrospective design, and there are some limitations. first, the ev vp gene sequences from china analysed in this study were downloaded from the genbank database but were not tested by us. due to time constraints, only the vp region was analysed and studied. in future studies, we will conduct research on the complete genome sequence of ev in china. second, the chinese ev vp strains registered in genbank do not cover all provinces in the country, and the data for some years are missing; thus, some isolates of other genotypes may have been unavailable. third, it is not clear whether some variations in the amino acid residues found in the study are related to the severity of disease or the route of transmission. in summary, the prevalent strains of ev belong mainly to the c genotype. the c a subgenotype was predominant, the c b subgenotype was the second most prevalent, whereas other subgenotypes appeared sporadically in mainland china. the b genotype was the dominant genotype in taiwan, and the epidemic strain is continuously changing. moreover, variation in key positions of the ev vp region is very important for the development of severe hfmd. taken together, the findings indicate that the genetic characteristics of the ev vp region should be continuously monitored, which is essential for the prevention and control of ev -associated hfmd in children and ev vaccine design. enterovirus outbreak in the people's republic of china in hand, foot, and mouth disease in china: patterns of spread and transmissibility hand, foot, and mouth disease in china, - : an epidemiological study virology, epidemiology, pathogenesis, and control of enterovirus ev infection induces neurodegeneration via activating tlr signaling and il- production severe paediatric conditions linked with ev-a and ev-d , france clinical features, diagnosis, and management of enterovirus therapeutic and prevention strategies against human enterovirus infection an epidemic of enterovirus infection in taiwan. taiwan enterovirus epidemic working group genetic analysis of enterovirus isolated from fatal and non-fatal cases of hand, foot and mouth disease during an epidemic in taiwan epidemic hand, foot and mouth disease caused by human enterovirus molecular epidemiology of enterovirus in peninsular malaysia population dynamics and genetic diversity of c strains of human enterovirus in mainland china retrospective seroepidemiology indicated that human enterovirus and coxsackievirus a circulated wildly in central and southern china before large-scale outbreaks from change of major genotype of enterovirus in outbreaks of hand-foot-and-mouth disease in taiwan between and genetic analysis of the vp region of enterovirus reveals the emergence of genotype a in central china evolutionary trajectory of the vp gene of human enterovirus genogroup b and c viruses an emerging recombinant human enterovirus responsible for the outbreak of hand foot and mouth disease in fuyang city of china enterovirus infection and neurological complications the persistent circulation of enterovirus in people's republic of china: causing emerging nationwide epidemics since identification of a c subgenogroup strain of enterovirus in a retrospective study in shandong province, china, from to molecular epidemiology of human enterovirus associated with aseptic meningitis in human enterovirus epidemics: what's next? epidemiology of enterovirus infections in taiwan mutations in the non-structural protein region contribute to intra-genotypic evolution of enterovirus review of enterovirus vaccines ):e . • fast, convenient online submission • thorough peer review by experienced researchers in your field • rapid publication on acceptance • support for research data, including large and complex data types • gold open access which fosters wider collaboration and increased citations maximum visibility for your research: over m website views per year • at bmc molecular epidemiology of human enterovirus in the united kingdom from to appearance of intratypic recombination of enterovirus in taiwan from detection of recombination breakpoints in the genomes of human enterovirus strains isolated in the netherlands in epidemic and non-epidemic years the association of recombination events in the founding and emergence of subgenogroup evolutionary lineages of human enterovirus complete genome characterization of the dengue outbreak in xishuangbanna, a border city of china complete genome analysis of the c subgenotype strains of enterovirus : predominant recombination c viruses persistently circulating in china for years effectiveness of ev-a vaccination in prevention of paediatric hand, foot, and mouth disease associated with ev-a virus infection requiring hospitalisation in henan, china, - : a test-negative case-control study epidemiology and etiology of hand, foot, and mouth disease in fujian province a novel finding for enterovirus virulence from the capsid protein vp of ev circulating in mainland china patterns of polymorphism and divergence in the vp gene of enterovirus circulating in the asia-pacific region between and enterovirus a vp variation a t decreases the central nervous system infectivity via attenuation of interactions between vp and vimentin in vitro and in vivo enterovirus binding to psgl- on leukocytes: vp - acts as a molecular switch to control receptor interaction antiviral activity of pyridyl imidazolidinones against enterovirus variants molecular epidemiology analysis of enterovirus strains the variations of vp protein might be associated with nervous system symptoms caused by enterovirus infection amino acid variation at vp - of enterovirus determines attachment receptor usage and neurovirulence in human scavenger receptor b transgenic mice cooperative effect of the vp amino acids e, a and f in the productive infection of mouse cell lines by enterovirus (bs strain) a novel murine model expressing a chimeric mscarb /hscarb receptor is highly susceptible to oral infection with clinical isolates of enterovirus an infectious clone of enterovirus (ev ) that is capable of infecting neonatal immune competent mice without adaptive mutations efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus vaccine in children in china: a multicentre, randomised, double-blind, placebo-controlled, phase trial ev vaccine, a new tool to control outbreaks of hand, foot and mouth disease (hfmd) epidemiology of hand, foot and mouth disease in china an inactivated enterovirus vaccine in healthy children efficacy, safety, and immunogenicity of an enterovirus vaccine in china immunogenicity, safety, and lot consistency of a novel inactivated enterovirus vaccine in chinese children aged to months molecular comparison and evolutionary analyses of vp nucleotide sequences of new african human enterovirus isolates reveal a wide genetic diversity the authors acknowledge all of the clinical staff throughout china who provided the vp protein-encoding region gene sequences and information concerning the ev strains used in this study. we gratefully acknowledge american journal experts (aje) (verification code: b- fe -f e - c- ) and (verification code: ca - -ded -fed - f a) for providing english language editing services for our manuscript twice.authors' contributions dc participated in the design of the study. dc, hs and mg performed the data collection and statistical analysis, and dc and hs drafted the manuscript. all authors read and approved the final manuscript. key: cord- -owmcxq e authors: lin, yu-kai; chang, chin-kuo; li, ming-hsu; wu, yu-chung; wang, yu-chun title: high-temperature indices associated with mortality and outpatient visits: characterizing the association with elevated temperature()() date: - - journal: sci total environ doi: . /j.scitotenv. . . sha: doc_id: cord_uid: owmcxq e this study aimed to identify optimal high-temperature indices to predict risks of all-cause mortality and outpatient visits for subtropical islanders in warm seasons (may to october). eight high-temperature indices, including three single measurements (average, maximum and minimum temperature) and five composite indices (heat index, humidex, temperature humidity index, apparent temperature and wet-bulb globe temperature), and their standardized z scores, were used in distributed lag non-linear models. cumulative -day (lag zero to seven days) relative risks (rrs) and % confidence intervals were estimated, and standardized deviations above the medium (i.e., at . th and . th percentile, respectively), by comparing with z scores for the lowest risks of mortality and outpatient visits as references. analyses were performed for taipei in north, central taiwan and southern taiwan. results showed that standardized z-values of high-temperature indices associated with the lowest health risk were approximately in taipei and central taiwan, and − in southern taiwan. as the apparent temperature was at z = , the cumulative -day mortality risk increased significantly, by % in taipei and % in southern taiwan, but not in central taiwan. the maximum temperature displayed consistently a high correlation with all-cause outpatient visits at z = ; with the cumulative -day rrs for outpatient visits increased by %, %, and % in the three corresponding areas. in conclusion, this study has demonstrated methods to compare multiple high-temperature indices associated with all-cause mortality and outpatient visits for population residing in a subtropical island. apparent temperature is an optimal indicator for predicting all-cause mortality risk, and maximum temperature is recommended to associate with outpatient visits. the impact of heat varied with study areas, evaluated health outcomes, and high-temperature indices. the increased extreme heat is associated with stronger risk for all-cause mortality than for outpatient visits. the association between temperature and mortality has been depicted with u-, v-, or j-shaped curves among various climate regions (curriero et al., ; gouveia et al., ; mcmichael et al., ) . the climate in recent decades is characterized with increased frequency and intensity of extreme temperatures (meehl and tebaldi, ) . health effects of global warming are now considered a critical issue (anderson and bell, ; kovats and hajat, ; kovats and kristie, ; o'neill and ebi, ) . most studies used ambient temperatures (i.e., average, maximum, and minimum temperature) to evaluate heat-related health effects (hajat et al., ; kim et al., ; knowlton et al., ; kovats et al., ; lin et al., ; yu et al., ; wang et al., ) . however, other weather indicators, such as relative humidity (rh), wind speed (ws), water science of the total environment - ( ) [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] abbreviations: aic, akaike's information criterion; at, apparent temperature; ci, confidence interval; cwb, central weather bureau; dlnm, distributed lag non-linear model; flu, influenza; hi, heat index; nhri, national health research institute; pm , particulate matter less than μm in aerodynamic diameter; rr, relative risk; rh, relative humidity; tcdc, taiwan centers for disease control; thi, temperature humidity index; tepa, taiwan environmental protection administration; wbgt, wet-bulb globe temperature; ws, wind speed; wvp, water vapor pressure. ☆ authors' contribution: all the authors participated in this study and contributed remarkable part of it. yk lin, ck chang, mh li and yc wang designed the study methods and obtained the research data. yc wang and yc wu performed statistical analyses. yk lin, ck chang and yc wang drafted and finalized the manuscript. all the authors have read and approved the final version of the manuscript. ☆☆ conflicts of interest: all the authors declare that this study involves no conflict of interest. vapor pressure (wvp) and thermal radiation, also affect the perception of temperature to humans. several composite indices, including heat index (hi) (hartz et al., ; metzger et al., ) , apparent temperature (at) (anderson and bell, ; chung et al., ), humidex (smoyer-tomic and rainham, ) and wet-bulb globe temperature (wbgt) (epstein and moran, ; kjellstrom et al., ) , have been used to evaluate health events associated with heat waves or extremely high temperatures. various high-temperature indices and approaches have been used to assess the association between mortality and heat waves or high temperature. but, no study has determined which index is optimal to predict mortality (hajat et al., ; vaneckova et al., ; . anderson et al. have indicated that, after adjusting for humidity, the temperature-mortality associations are not significantly different among using average, maximum and apparent temperature metrics (anderson and bell, ). barnett et al. ( ) suggested that no temperature index can be considered optimal because all indices are highly correlated with temperature measurements. the applied temperature measurement should be chosen according to practical concerns, i.e. the measure may provide comprehensive information (barnett et al., ) . thus, studies addressing the determination of an optimal high-temperature index to predict health outcomes were still far from being conclusive. most studies on the high temperature (i.e., heat wave) impact focus on mortality, and only some consider morbidity ye et al., ) . moreover, most studies on heat effects are performed in areas with temperate climate rather than subtropical climate (basu, ; kovats and kristie, ; ye et al., ) . therefore, the present study was to report high-temperature indices optimal to evaluate the all-cause mortality and outpatient visits associated with temperatures in taiwan, a subtropical island, located on the west of the pacific ocean. we evaluated models among eight standardized high-temperature indices: average, maximum, and minimum temperature, hi, temperature humidity index (thi), humidex, at, and wbgt. relative risks of all-cause mortality and outpatient visits associated with these indices were evaluated for three areas, taipei in the north, central taiwan and southern taiwan. data used in this study included vital statistics obtained from the department of health (doh), universal health insurance claims data from the national health research institute (nhri), daily meteorological data from the central weather bureau (cwb), and daily air pollution monitoring data from the taiwan environmental protection administration (tepa), all from to . data representative for population structure, climate and air pollution in taiwan were collected from three major metropolitan areas: taipei, central taiwan (taichung, zhanghua and nantou), and southern taiwan (kaohsiung and pingtung), comprising . % of the total million population in taiwan. daily area-specific all-cause deaths (icd codes - ) were retrieved from the vital statistics dataset with underlying cause of death coded with the th revision of international classification of diseases (icd- ). the nhri has established a cohort of one million residents to represent all insured residents in taiwan with their electronic reimbursement claim records accessible for research purposes. disease diagnoses were coded with the th revision of international classification of diseases with clinical modification (icd- -cm). daily area-specific all-cause outpatient visits (icd cm - ) were retrieved from the electronic records. cwb provided -hour data from real-time weather monitoring stations in taiwan central weather bureau ( ) . weather conditions measured using three stations in taipei, four stations in central taiwan and four stations in southern taiwan were available for determining daily mean, maximum, and minimum temperatures, rh, dew point temperature, wvp, and ws. the tepa established air quality monitoring network in with stationary monitoring stations throughout the island (taiwan environmental protection administration, ; taiwan governmental information office, ) . concentrations of ambient air pollutants, including particulate matter smaller than μm in aerodynamic diameter (pm ), nitrogen dioxides (no ) and ozone (o ), were measured and recorded hourly at each station. we analyzed daily levels of pm , o , and no , monitored by , and general ambient environment stations in taipei, central taiwan, and southern taiwan, respectively. locations of the weather and ambient environment stations are shown in fig. . the eight high-temperature indices used in this study including single temperature measurements and composite temperature indices that have been widely used in heat-health association studies are detailed in table . briefly, average, maximum, and minimum temperatures were monitored hourly at the regional representative weather stations. the hi based on dry bulb temperature and rh was used in environments with temperatures above °f ( . °c) and with rh above % (steadman, ) . the humidex developed by environment canada was used as the measure of subjectively perceived temperature and humidity (masterton and richardson, ) . to assess the temperature perception in study population (rosenberg et al., ) , we used the taiwan cwb adopted thi index. it is similar to the thermal discomfort index developed by the u.s. weather bureau, widely used in europe as well to assess heat discomfort (pantavou et al., ) . the at was used as an alternative measure of perceived temperature, which combines several environmental and physiological variables, including temperature, clothing cover, physical activity, ws and wvp (steadman, ) . the wbgt developed by the american conference of governmental industrial hygienists was used to estimate heat stress in the working environment. data analyses first transformed the study area (c)-specific temperature index x i (i = - for eight different high-temperature indices) on day (t) into a standardized value (z i, t c ) based on the following equation: where μ i c is the mean and σ i c is the standard deviation for hightemperature index i in warm seasons of - . locally weighted least square regression smoother (loess) was used to test each high-temperature index (original measurements and their standardized values -z score) for associations with allcause mortality and outpatient visits. the span was set to , and degree was set to under lag day (present day). for each high-temperature index, data analysis further calculated area-specific cumulative -day (from lag to lag days) relative risks (rr) and % confidence intervals (ci) to determine associations with daily deaths and outpatient visits, using distributed lag nonlinear model (dlnm) (armstrong, ; gasparrini et al., ) . the model used to measure expected deaths and outpatient visits at day (t) in each area (c) would be: where y t c is the expected deaths or outpatient visits for area c on day t. a linear relationship was assumed between deaths and outpatient visits, and air pollutants -pm , o , and no with zero thresholds and -day lag maximum. the x j, t c represents the air pollutants (j = - for pm , o , and no ) for area c on day t; ns(t i, t c or z i, t c , ; lag, ) are natural cubic splines of measurements or z-scores for each hightemperature index i = - . five degrees of freedom (df) for hightemperature indices and z-score were set, and the effect was accumulated for days (lag to days) under df lag stratification (also set as natural cubic splines). the smoother term of time ("time" in the model) was set to df per warm seasons. moreover, year was treated as an extra categorical variable in models to control for annual variation in health outcomes (e.g. the sudden drop of outpatient visits due to epidemic of severe acute respiratory syndrome in ). other covariates, such as daily deaths and outpatient visits due to pneumonia and influenza (flu t c , icd cm codes - ), public holiday and day of the week (dow) were also included in the models for adjustment. we used the akaike's information criterion (aic) to measure the relative goodness of fit of statistical models. a lower aic value indicates a better model fit (akaike, ) . because values and ranges of the high-temperature index varied dramatically, and we were unable to report the risk estimates per degree change under natural cubic spline function for high-temperature indices. the area-specific cumulative -day relative risks for deaths and outpatient visits were reported at standardized deviations of and above mean (i.e., at . th and . th percentile, respectively), and were compared with the standardized score of the lowest health risk for each high-temperature index. basically, the standardized score for the lowest health risk was inspected from each plot of standardized high-temperature index-health association. this method was similar to estimate relative risks of various temperature indices at the th, th, th, th, th, and . th percentiles, which had been used previously in the australian study (vaneckova et al., ) . data management and all statistical analyses were performed using sas version . (sas institute inc., cary, nc, usa) and statistical environment r . . table depicts the descriptive statistics for climatic factors, hightemperature indices and air pollutants in the three study areas during may-october in - . both the highest and lowest average temperatures appeared in taipei. average rh ranged from % to %, and average ws ranged from . to . m/s in study areas. air pollutant concentrations were similar among areas except that average pm and o concentrations were higher in southern taiwan. the correlation coefficients between each pairs of the eight hightemperature indices ranged from . to . , the lowest correlation was between maximum and minimum temperature, and the higher correlations were among the composite high-temperature (r = . to . ) (data not shown). fig. shows the association between high-temperature indices (lag day) and daily all-cause deaths measured using loess. the high-temperature indices varied among areas, with wider ranges for original high-temperature indices in taipei. after standardization for these indices, the regression lines showed a similar pattern of association for z scores ranged within ± standard deviation. a u-shaped temperature-mortality association was observed in taipei. an observed positive linear relationship between mortality and high temperatures was identified in southern taiwan. no significant association with high temperature was detected in central taiwan. fig. shows the association between high-temperature indices and outpatient visits on lag day measured using loess. there were larger variations at z scores lower than − (i.e., extremely low percentiles in warm seasons). in contrast with all-cause mortality, the outpatient visits were not significantly associated with extreme high temperatures in any of the study areas. the aic values among various models for associations between high-temperature indices and all-cause models were similar (table ) . based on the selection criteria for modeling, at was the most optimal index in taipei and southern taiwan, but humidex or wbgt was most optimal in central taiwan. supplemental figures - show the cumulative -day relatively risk of all-cause mortality associated with high-temperature indices and their transformed standardized values. the lowest mortality risks were identified at z = for taipei and central taiwan, and at z= − for southern taiwan. therefore, these transformed standardized scores were used as reference values in further analyses. at the transformed high-temperature index of z= ( . th percentile of high-temperature indices), the mortality risk approximately increased by %, % and % in taipei, central taiwan and southern taiwan, respectively. as of z= ( . th percentile of hightemperature indices) for at, the cumulative relative risks for mortality significantly increased by % in taipei and by % in southern taiwan. there was no significant increase in central taiwan. comparing the risk estimates for the eight high-temperature indices, the rrs were similar at z = , but the risk estimates at z= were higher for composite high-temperature indices than for single high-temperature indices. compared with the association with mortality, there was a greater variation in relationships between selected high-temperature indices and all-cause outpatient visits (table ). based on aic values, the maximum temperature was the most optimal predictor among associations between outpatient visits and temperatures. the lowest outpatient visit risk was observed at z = in taipei and central taiwan, but at z = − in southern taiwan . thus, these standardized scores were used as reference values for further analyses. at z = , the cumulative -day relative risks for outpatient visits increased by approximately %, %, and % in taipei, central taiwan and southern taiwan, respectively. at z = , the estimated cumulative relative risks for these three areas decreased dramatically and were no longer statistically significant. associations between high-temperature indices and mortality and outpatient visits differ among areas and enable to further compare the capacity of prediction. the index of temperature measurement used in the study is as simple as possible. for example, daily average temperature is a simple indicator that the general population can easily understand. average temperature is the most common measurement used for studying the impact of temperature on health outcomes. however, to account for the changes in temperature perceived by humans, recent studies have introduced comprehensive weather variables as composite high-temperature indices such as hi, at, humidex and wbgt to study the temperature-related health outcomes (anderson and bell, ; chung et al., ; epstein and moran, ; kjellstrom et al., ; smoyer-tomic and rainham, ) . the present study evaluated whether all-cause mortality and outpatient visits are associated with the eight high-temperature indices in warm seasons for population in a subtropical island. we found that the association may vary by the study area, evaluated health outcomes and selected high-temperature indices. apparent temperature is the most optimal high-temperature index associated with all-cause mortality. however, the eight temperature indices performed similarly in models fitting for predicting all-cause mortality. besides, the maximum temperature is consistently the most optimal high-temperature index for predicting all-cause outpatient visits. temperature indices vary based on demographic and geographic status. a korean study suggested that hi and mean temperature performed comparably for predicting mortality (kim et al., ) . a toronto study concluded that humidex and at are both effective for predicting excess mortality associated with hot and humid weather (smoyer-tomic and rainham, ) . some research teams have used at as the high-temperature index of interest and have found note: tavg.: daily average temperature; tmax.: daily maximum temperature; tmin.: daily minimum temperature; hi: heat index; thi: temperature humidity index; at: apparent temperature; wbgt: wet-bulb globe temperature; s.d.: standard deviation; and aic represents akaike's information criterion values. ⁎ z score of high-temperature indices for lowest predicted all-cause deaths in loess regression (fig. ) . ⁎⁎ high-temperature indices' value with lowest mortality risk in dlnm model. ⁎⁎⁎ risk estimated based on reference equals to z = in taipei and central taiwan, and z = − in southern taiwan (supplement figs. - ). significant association between temperature and mortality (chung et al., ). on the other hand, a study conducted in new york city showed that maximum hi is a better goodness of fit than maximum, minimum or average temperature in estimating the mortality risk during hot weather (metzger et al., ) . a chinese study showed that, based on model fitting, the mean temperature was a better predictor of mortality than maximum and minimum temperatures . yu et al. revealed that mean temperature was an accurate index of all-cause death in brisbane, australia . in contrast, anderson et al. reported that temperature-related mortality assessments did not significantly differ among average, maximum and apparent temperature metrics. they found that the association with apparent temperature is nearly identical to that with the mean daily temperature after controlling for humidity (anderson and bell, ). vaneckova et al. also found that average temperature and composite high-temperature indices perform similarly in estimating mortality risk (vaneckova et al., ) . likewise, all high-temperature indices are significantly associated with mortality in this study because temperature indices are highly correlated with each other. the cumulative mortality risks associated with the composite indices are also relatively similar. in subtropical regions, the consistent high temperature and humidity, and other weather characteristics such as ws and wvp result in a relatively smaller effect on perceived temperature. barnett et al. ( ) have concluded that no high-temperature index can be considered superior to others, because an optimal high-temperature index is also associated with age groups, seasons, and areas analyzed. they suggest selecting high-temperature index based on practical concerns such as the accessibility of climate measurements, public familiarity with the index, and data available (barnett et al., ) . in terms of morbidity, some studies have reported that hi is an optimal heat index for predicting inpatient cares and heat-related dispatches (hartz et al., ; semenza et al., ) . the mean apparent temperature is also an indicator that may well predict hospital admissions for several diseases in nine california counties (green et al., ) . however, khalaj et al. found that emergency hospital admissions were more likely correlated with maximum temperature (khalaj et al., ) . our study found similar results that maximum temperature is an optimal high-temperature index for predicting heat-related outpatient visits. the weather associated morbidity may be different between clinical visits and emergency room visits. the choice of high-temperature indices may thus produce subtle differences in assessing possible health-related effects of heat. this study also showed that the optimal high-temperature index for predicting mortality is different from predicting outpatient visits. no standard methodology has been developed to evaluate the capacity of high-temperature indices for predicting health effects. a common choice is to measure the change in relative risk of mortality associated with one degree temperature increase or decrease. however, this approach complicates comparisons among different hightemperature indices with different scales and ranges. in this study, we standardize the indices to unify the measurement scale and improve the capacity of prediction. most studies assume a linear association between temperatures and health outcomes, which might not be plausible with practical data (metzger et al., ) . armstrong et al. ( ) found that a linear relationship seems to fit well above the threshold temperature without controlling other climate status. although, some evidences have shown non-linearity association as the temperature is above ⁎ z score of high-temperature indices for lowest predicted all-cause outpatient visits in loess regression (fig. ) . ⁎⁎ high-temperature indices' value with lowest outpatient visit risk in dlnm model. ⁎⁎⁎ risk estimated based on dlnm set as centered value equals to z = in taipei and central taiwan, and z = − in southern taiwan . the thresholds, with quadratic or larger relationships at the highest temperatures. the present study proposed an alternative method to estimate the cumulative rr using dlmn and presented non-linear associations between high temperature indices and mortality, and outpatient visits as well. standardization assures the comparability among various high-temperature indices (armstrong et al., ) . the cumulative -day rrs of health outcomes vary among high temperatures. in summary, our study observes higher cumulative rrs for mortality than for outpatient visits in association with high temperature. the area-specific rrs of mortality associated with observed and standardized high-temperature indices are clearly non-linear with index values (supplemental figs. - ) . the corresponding rrs of outpatient visits are more fluctuated and inconsistent . these findings support the study in england that high temperatures have a larger effect on mortality than on morbidity (kovats et al., ) . we found the mortality risk increased dramatically as standardized high-temperature indices increased from z = to . nonetheless, the standardized high-temperature indices have higher rrs at z = than at z = for all-cause outpatient visits. a possible explanation is that people who have mild illness may take immediate action in response to remit the symptoms. they may stay in air conditioned environment or drink more fluids against the outdoor high temperature. an island located in a subtropical region, separated from the asian continent, with an area of km wide and km long, the weather in taiwan varied from north to south. therefore, the health risks associated with these high-temperature indices are evaluated only for the population residing in the area-specific environment. studies with similar methodologies are thus suggested for populations located in different climates. in addition, this study also found that the risks associated with heat are significant in taipei and southern taiwan rather than in central taiwan. compared with the other two areas, central taiwan has lower income and higher portion of the elders (directorate-general of budget, accounting and statistics, executive yuan, r.o.c. (taiwan), ). however, due to limited detail information for social economics, this study may not conclude any effects related with these factors. interactions among these variables are recommended to assess in future study. moreover, this ecological study focused only on all-cause mortality and outpatient visits. further studies of temperature effects on human physical responses, clinical symptoms of heat exposure, and identification of the most vulnerable groups are needed to establish a comprehensive heat wave warning system in the future. the associations between high temperature and all-cause mortality and outpatient visits varied by region, health outcomes and selected high-temperature indices. apparent temperature is the most optimal among high-temperature indices for predicting all-cause mortality. maximum temperature is highly correlated with all-cause outpatient visits. standardized high-temperature indices provided an effective platform for comparing these indices on heat related health association study. supplementary data to this article can be found online at http:// dx.doi.org/ . /j.scitotenv. . . . information theory and an extension of the maximum likelihood principle. nd international symposium on information theory weather-related mortality: how heat, cold, and heat waves affect mortality in the united states heat waves in the united states: mortality risk during heat waves and effect modification by heat wave characteristics in u models for the relationship between ambient temperature and daily mortality association of mortality with high temperatures in a temperate climate: england and wales what measure of temperature is the best predictor of mortality? high ambient temperature and mortality: a review of epidemiologic studies from ambient temperature and mortality: an international study in four capital cities of east asia temperature and mortality in cities of the eastern united states national statistics. available at calculation of the to climate normals for canada thermal comfort and the heat stress indices distributed lag non-linear models socioeconomic differentials in the temperaturemortality relationship in sao paulo, brazil the effect of temperature on hospital admissions in nine california counties the impact of temperature on mortality in tianjin, china: a case-crossover design with a distributed lag nonlinear model. environ heat-health warning systems: a comparison of the predictive capacity of different approaches to identifying dangerously hot days climate and heat-related emergencies in the health impacts of heat waves in five regions of high temperature, heat index, and mortality in major cities in south korea workplace heat stress, health and productivity -an increasing challenge for low and middle-income countries during climate change projecting heat-related mortality impacts under a changing climate in the new york city region heat stress and public health: a critical review heatwaves and public health in europe contrasting patterns of mortality and hospital admissions during hot weather and heat waves in greater london mortality risk associated with temperature and prolonged temperature extremes in elderly populations in taiwan humidex: a method of quantifying human discomfort due to excessive heat and humidity international study of temperature, heat and urban mortality: the 'isothurm' project prevention of thermal injuries during distance running -position stand more intense, more frequent, and longer lasting heat waves in the st century summer heat and mortality in new york city: how hot is too hot? temperature extremes and health: impacts of climate variability and change in the united states evaluating thermal comfort conditions and health responses during an extremely hot summer in athens human and animal biometeorology excess hospital admissions during the july heat wave in chicago beating the heat: development and evaluation of a canadian hot weather health-response plan the assessment of sultriness. part i: a temperature-humidity index based on human physiology and clothing science a universal scale of apparent temperature the central weather bureau online information taiwan air quality monitoring network taiwan governmental information office. the republic of china year book : chapter . environmental protection do biometeorological indices improve modeling outcomes of heat-related mortality? associating emergency room visits with first and prolonged extreme temperature event in taiwan: a population-based cohort study ambient temperature and morbidity: a review of epidemiological evidence is the association between temperature and mortality modified by age, gender and socio-economic status? the effect of various temperature indicators on different mortality categories in a subtropical city of brisbane we appreciate the authorities of department of health, taiwan national health research institute, taiwan environmental protection administration, and taiwan central weather bureau for providing research data. interpretations and conclusions herein do not represent those of these agencies. dr. fung-chang sung and ted knoy are appreciated for their editorial assistance. this study was supported in part by taiwan national science council (nsc - -b- - , nsc - -m- - and nsc - -e- - ), the china medical university hospital ( ms ), and the taiwan department of health (doh -td-b- - , doh -td-c- - ). key: cord- - fth xl authors: huang, yhu-chering; lien, rey-in; su, lin-hui; chou, yi-hong; lin, tzou-yien title: successful control of methicillin-resistant staphylococcus aureus in endemic neonatal intensive care units—a -year campaign date: - - journal: plos one doi: . /journal.pone. sha: doc_id: cord_uid: fth xl background: methicillin-resistant staphylococcus aureus (mrsa) is among the most important nosocomial pathogens in the intensive care unit (icu) worldwide, including taiwan. since , our neonatal icus (nicus) had become endemic for mrsa. methodology/principal findings: to control mrsa spread in our nicus, we implemented a series of infection control measures stepwise, including reinforcement of hand hygiene since january , augmentation of aseptic care over the insertion site of central venous catheter since july , introduction of alcohol-based handrubs since april , surveillance culture for mrsa and cohort care for the colonized patients between march and february , and surveillance culture with subsequent decolonization of mrsa between august and july . after implementation of these measures, mrsa healthcare-associated infection (hai) density reduced by %, from . episodes per patient-days in to . episodes per patient-days in ; mrsa bloodstream infection reduced from cases in to only one case in . compared to those obtained during the period of surveillance culture without decolonization, both rates of mrsa colonization ( . % vs. %, p< . ) and infection ( . % vs. %, p< . ) decreased significantly during the period of surveillance and decolonization. molecular analysis of the clinical isolates during the study period showed that the endemic clone, which dominated between and , almost disappeared in , while the community clones increased significantly in – . conclusion/significance: through infection control measures, mrsa hais can be successfully controlled, even in areas with high levels of endemic mrsa infections such as our nicus. methicillin-resistant staphylococcus aureus (mrsa) is among the most important pathogens of bacteremia in the intensive care units (icu). nowadays, mrsa becomes endemic in most hospitals around the world [ , ] and accounts for - % of all healthcareassociated s. aureus infections. colonized patients are the major reservoirs of mrsa in hospitals. colonizing strains may serve as endogenous sources for overt clinical infections or may spread to other patients [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . to reduce and control healthcare-associated infections (hais) caused by mrsa, a ''search and destroy'' strategy, which first detects the patients with mrsa colonization and then decolonizes the mrsa with certain antimicrobial agents, was recently proposed and implemented in some hospitals of different countries, with inconsistent effects [ ] [ ] [ ] [ ] [ ] . in taiwan, mrsa was first documented in early s and rapidly increased in s [ ] . in , methicillin resistance had been identified in - % of all s. aureus isolates in major hospitals of taiwan [ ] . in our neonatal icus (nicus), s. aureus is the leading pathogen of hais and mrsa represented majority of all the s. aureus isolates since . between and , the prevalence of s. aureus among the hais increased significantly from . % in , . % in , to . % in . the percentage of mrsa among s. aureus isolates also rose significantly from . % in , . % in , to . % in [ ] . apparently, our nicus were endemic for mrsa. we then implemented a series of infection control interventions stepwise in our nicus to try to reduce hais caused by mrsa. after a -year campaign, mrsa hais was successfully controlled temporarily with the implementation of the strategy of ''search and destroy''. here, we report our experiences for mrsa control in the nicus. chang gung children's hospital is a university-affiliated teaching hospital, situated in northern taiwan, that provides a range of care, from primary to tertiary care, and is a part of chang gung memorial hospital (cgmh). there are three nicus, distributed on floors, in this children's hospital. currently, there are and beds in nicu- , and nicu- , respectively. nicu- included two areas, level -iii beds in area and non-level-iii beds in area (special care nurseries). all the healthcareassociated infections (hais) in three nicus from to were prospectively collected and recorded according to the standard definition of hais [ ] . the study included the institution's healthcare infection data, which were routinely collected and reported by the institution's infection control committee, and was also among the institution's quality-improvement programs proposed by the institution's infection control committee. since active surveillance for mrsa control is considered to be quality improvement, irb approval was not required to be included when application for the grants and thus the study was not reviewed by the institutional review board (irb) of chang gung memorial hospital at that time and informed consent could be waived [ ] . since , a series of infection control interventions were implemented stepwise in our nicus to try to reduce healthcareassociated infections caused by mrsa (table ) . we firstly reenforced hand washing before and after contact with the infants hospitalized in nicus since january by increasing infection control education of, increasing infection control practitioner's audits of, and feedback of hais data to the health care workers (hcws) working in nicus. from a case-control study conducted in , we found that the presence of skin infection at onset was one of the risk factors for mrsa bacteremia in these infants [ ] . standardized operation procedures for the insertion and the continuous care of peripherally inserted central venous catheter (picc) were revised, aiming to accelerate the placement process (by a designated team) and to improve the aseptic care over the insertion site. briefly, after successful insertion, % povidineiodine containing alcohol ( %) was applied to the insertion site, normal saline used to decolorize, and the area was covered by a transparent dressing (''tegaderm''). nurses checked the insertion site frequently and changed the dressing every days. the picc lines were not impregnated with antibacterial or antiseptic agents and antibiotic lock prophylaxis was not used. the strategy commenced in july . from march to february , screening for mrsa carriage among the hospitalized infants at nicu- and - was conducted [ ] , which was supported by the research grants. during the nicus stay, specimens from the nares, postauricular areas, axillae, and umbilicus were obtained weekly and sent for detection of mrsa. the infants with mrsa colonization, if identified, were separated from non-colonized infants and placed in a segregated area of the units, and cohort care by designated nurses was implemented. almost at he same time, the outbreak of severe acute respiratory syndrome (sars) occurred in taiwan, and alcohol-based handrubs were introduced into the hospital in april and were used in these nicus thereafter. from august to july , we implemented the ''search and destroy'' strategy into nicu- and - , which was also supported by the research grants. from the previous surveillance study [ ] , we learned that nearly % of the colonized infants are detected within the first weeks of admission and sampling of both nares and umbilicus is adequate for surveillance cultures in this population. hence, during this period, only specimens from both nares and umbilicus were obtained, within hours of admission and then weekly for two weeks ( times in total). in addition to placing the colonizing infants in a segregated area and cohort care, decolonization procedures with topical mupirocin ointment application to nares and umbilical area were administered twice daily for five consecutive days if they still stayed in the nicus. if an infant with mrsa colonization had mrsa clinical isolates, the clinical isolates as well as the colonized isolates were genotyped and compared. mrsa isolates recovered from clinical diagnostic samples (beyond surveillance culture specimens) submitted to the clinical microbiologic laboratory were regarded as clinical isolates. in accordance with the standard definition of hais [ ] , any infant with clinical isolates of mrsa who was receiving antimicrobial therapy was categorized as experiencing an episode of infection. however, from august to october , no active surveillance for mrsa was conducted in these nicus since no research grants supported. surveillance cultures for health care workers (hcws) were performed, during surveillance periods, and specimens were obtained from the nares of hcws working in both units. intranasal mupirocin treatment was applied to the nares of each hcw with mrsa colonization. specimens for surveillance culture were obtained with a cotton swab, placed in a transport medium (venturi transystem), and then processed in the microbiology laboratory within hours. identification of mrsa was confirmed according to national committee for clinical laboratory standards guidelines [ ] . except for year , mrsa clinical isolates from the hospitalized infants at these nicus between and were collected and selected for genotyping analysis. for those years with more than clinical mrsa isolates collected ( isolates in [ , ] , which are also displayed in this study. colonized isolates from the infants and hcws were also molecularly characterized. the molecular methods included pulsed-field gel electrophoresis (pfge) with smai digestion, staphylococcal chromosomal cassette (sccmec) typing, and multilocus sequence type (mlst). in addition, the presence of panton-valentine leukocidin (pvl) genes was also examined. all the procedures were described previously [ ] [ ] [ ] [ ] [ ] [ ] . the genotypes of pfge were designated, as in our previous studies [ ] [ ] [ ] [ ] [ ] , in alphabetical order; any new type, if identified, was designated consecutively. pfge patterns with , -band differences from an existing genotype were defined as subtypes of that genotype and were labeled with arabic number suffixes. two isolates were considered to be indistinguishable, related, or distinct if they had the same subtype, the same genotype, or a different type, respectively. we compared mrsa colonization and subsequent infection between the infants with and without topical mupirocin traetment by means of x (continuity-adjusted) or student's t tests. relative risk and/or odds ratios (ors) were calculated with % confidence intervals (cis). healthcare-associated infection density and mrsa hai density from to were analyzed by mantel-haenszel chi-square test. statistical analyses of the data were performed with epiinfo, version (centers for disease control and prevention, atlanta, ga) and sas for windows, version . (sas institute, cary, nc). through these infection control measures, hais in these nicus caused by mrsa as well as by all bacterial pathogens decreased gradually and significantly from to ( the results of surveillance culture without decolonization were published previously [ ] and are summarized in table . briefly, mrsa colonization was detected for % of infants surveyed during their nicu stay and was noted for % of infants with mrsa infections. previous colonization was detected in episodes ( %) of mrsa infections; colonized and clinical isolates were indistinguishable in episodes ( %). during the period of surveillance and decolonization, mrsa colonization was detected for . % of infants surveyed. of the infants with colonization, intranasal mupirocin ointment was administered to infants who still stayed in the nicus. followup cultures were obtained from infants and showed positive in two infants. second course of intranasal mupirocin ointment was administered in both infants and subsequently eradicated mrsa in both cases. one of them developed mrsa sepsis before the second course of therapy was commenced. all isolates ( clinical and colonized isolates) from this case were genetically indistinguishably. in addition to this case, additional mrsa infected cases were identified, without previous colonization. five ( . %) of health care workers were colonized with mrsa. the comparison between the two periods is shown in table and significant difference was noted in terms of rates of infection, colonization and colonization with subsequent infection. however, no significant difference was noted in terms of rates of mrsa non-colonized but with infection and colonization of health care workers. the detailed molecular characteristics of mrsa isolates are shown in table . from the clinical isolates analyzed, a total of pulsotypes were identified. there were two major clones and characterized as sequence type (st) (or its single locus variant)/pulsotype a (hungary clone)/sccmec iii or iiia/pvlnegative, accounting for % of the isolates, and st /pulsotype c/sccmec iv/pvl-negative, accounting for %. the former clone was dominant (. % of the isolates) from to , became weakened ( % of the isolates) in , reached zero in , and then resurged in ( % of the isolates). the latter clone remained steady (around %) during the study period, ( ) ( ) belonged to the linage of st . in contrast, most colonized isolates from hcws, regardless of during which period, belonged to the clone of st /pulsotype c/sccmec iv/pvl-negative. the present study demonstrates that through infection control measures, hais caused by mrsa can be successfully controlled temporarily, even in high level mrsa endemic neonatal intensive care units. in the current study, mrsa hai density was reduced by %; ha bloodstream infection caused by mrsa was reduced from cases per year to only one case per year. with the reduction of hai caused by mrsa, the ha infection density decreased proportionally and significantly. it appears that zero ha mrsa bacteremia in nicus is not infeasible, even in mrsa endemic units like ours, if effective infection control measures are implemented and executed strictly. during the study period, neither the manpower of nursing staff nor the bed occupation rate (more than %) in our nicus was changed. the reduction of mrsa infection was gradual and significantly; it appeared to occur prominently for two specific time periods, from to and from to . for the first time period, we revised the standardized operation procedure for insertion and continuous care of peripherally inserted central venous catheter (picc). this strategy was based on our findings from the case-control study that the presence of skin infection at onset was associated with mrsa bacteremia in these infants. augmentation of aseptic procedure and care of the insertion of central venous catheter (cvc) has been documented to be able to reduce the incidence of catheter-related bacteremia [ ] and seemed to be somewhat effective in our nicus. conducting the strategy of surveillance culture with subsequent decolonization of mrsa carriage in two of three nicus was the major change of infection control measures in the second time point in the current study. compared to those during the period of surveillance culture without decolonization, both mrsa colonization rate and mrsa infection rate among the nicu infants decreased significantly. in contrast, the rate of mrsa infection among the non-colonized infants was similar during both periods; even, mrsa ha infection rate increased slightly in when the strategy of ''search and destroy'' was discontinued since the supported grant was due. (afterwards, another project with a cross-over design was granted and conducted since november ) altogether, these findings seemed to suggest that topical mupirocin treatment may effectively decolonize mrsa carriage in these infants and reduce the subsequent mrsa infection. though the susceptibility test of mrsa isolates to mupirocin was not performed in this series, we believe that most isolates were susceptible to mupirocin since this medication, though licensed, had not been used in taiwan for years. however, since no control group (only historical control) was included and not every infant with mrsa colonization received topical mupirocin therapy in the current study, further studies are needed to elucidate this issue [ ] [ ] [ ] [ ] . compared to adult icus, patients admitted to nicus are relatively ''simple''. most infants hospitalize immediately after birth and a substantial proportion of the infants are inborn. in addition, vertical transmission of mrsa is infrequently seen in newborns. therefore, most infants do not have mrsa colonization on admission to nicus. then, if the hcws working in and the environmental objects in nicus are free form mrsa, the hospitalized infants would not acquire mrsa colonization and/or infection during their nicu stay. in the current study, between and , nasal mrsa carriage rate among hcws working in our nicus ranged from . % to % for surveys [ ] . but no survey for environmental objects was conducted during the study period. however, the condition would not change, even though mrsa may be introduced into the units anytime, if each hcw can perform hand hygiene exactly and strictly. these may partly explain why the ''search and destroy'' strategy can be effective in our nicus but not so effective reported from adult icus otherwise [ ] . from the molecular analysis of mrsa isolates, we found that the epidemic as well as endemic clone, st /pulsotype a (hungary or brazilian clone), dominated between and in our nicus, even accounting for % of the clinical and colonized isolates in certain years. this clone was almost eradicated, not identified from any clinical isolate, from our nicus in ; however, it still accounted for % of the colonized isolates during - . this clone returned and identified from clinical isolates again in and persisted in (data not shown here) but accounted for less than % of the clinical isolates. the clone, st /pulsotype a, had prevailed in our hospital (cgmh) and even the whole island between and , accounting for % to % of clinical isolates from different hospitals islandwide [ , [ ] [ ] [ ] [ ] . however, the predominance was decreasing during - in our hospital (cgmh) [ ] , so was in our nicus in the current study almost at the same time. in contrast, the clone of st /pulsotype c/sccmec iv/ pvl-negative accounted for one-fourth of the clinical isolates and remained relatively steady throughout the study period. the clone accounted for most colonized mrsa isolates from healthy children [ ] as well as a substantial proportion of communityassociated mrsa infection in taiwan [ , , [ ] [ ] [ ] and thus was categorized as a community strain recently. more than % of colonized isolates from hcws working in these nicus also belonged to this clone during the study period, suggesting that they might acquire mrsa colonization in the community rather than in the hospital. in addition, two other community clones, also belonging to st linage, emerged and increased markedly during - . it has been reported that community-associated mrsa strains spread into the hospital and even successfully replaced the original hospital strains [ , ] . the changing molecular epidemiology needs more surveillance and its clinical implication and significance needs more observations. results from the surveillance culture, we reported previously [ ] , indicated that preceding or concurrent colonization was detected for . % of the infants with mrsa infection, and the clinical isolates were indistinguishable with the colonized isolates in . % of the episodes, on the basis of molecular evidence. these strongly suggest the association between mrsa colonization and subsequent infection and indirectly suggest that to reduce mrsa infection in the infants hospitalized in nicus, active surveillance with subsequent decolonization of mrsa is mandatory. as the issue which disinfectants or antimicrobials, topical or systemic administration, are effective deserve further studies. methicillin-resistant staphylococcus aureus change in the epidemiology of methicillin-resistant staphylococcus aureus in intensive care units in us hospitals risk and outcome of nosocomial staphylococcus aureus bacteraemia in nasal carriers versus non-carriers methicillinresistant staphylococcus aureus (mrsa) nares colonization at hospital admission and its effect on subsequent mrsa infection natural history of community-acquired methicillin-resistant staphylococcus aureus colonization and infection in soldiers the significance of nasal carriage of staphylococcus aureus and the incidence of postoperative wound infection risk of methicillin-resistant staphylococcus aureus infection after previous infection or colonization nasal carriage of staphylococcus aureus as a major risk factor for wound infections after cardiac surgery colonization with methicillin-resistant staphylococcus aureus in icu patients: morbidity, mortality, and glycopeptide use mrsa colonization and the risk of mrsa bacteraemia in hospitalized patients with chronic ulcers nasal carriage as a source of staphylococcus aureus bacteremia seven year experience with a surveillance program to reduce methicillin-resistant staphylococcus aureus colonization in a neonatal intensive care unit impact of routine intensive care unit surveillance cultures and resultant barrier precautions on hospital-wide methicillin-resistant staphylococcus aureus bacteremia universal screening for methicillin-resistant staphylococcus aureus at hospital admission and nosocomial infection in surgical patients universal surveillance for methicillin-resistant staphylococcus aureus in affiliated hospitals methicillin-resistant staphylococcus aureus control in an intensive care unit: a year analysis methicillin-resistant staphylococcus aureus infection current status of antimicrobial resistance in taiwan methicillinresistant staphylococcus aureus bacteremia in neonatal intensive care units: analysis of episodes cdc definitions for nosocomial infections active surveillance cultures and contact precautions for control of multidrug-resistant organisms: ethical considerations methicillin-resistant staphylococcus aureus in neonatal intensive care units: genotyping analysis and casecontrol study methicillin-resistant staphylococcus aureus colonization and its association with infection among infants hospitalized in neonatal intensive care units performance standard for antimicrobial disk susceptibility tests molecular surveillance of methicillin-resistant staphylococcus aureus in neonatal intensive care units molecular epidemiology of clinical isolates of methicillin-resistant staphylococcus aureus in taiwan prevalence of methicillin-resistant staphylococcus aureus nasal colonization among taiwanese children comparative molecular analysis of community-associated and healthcare-associated methicillin-resistant staphylococcus aureus isolates from children in northern taiwan clinical features and molecular characteristics of invasive community-acquired methicillinresistant staphylococcus aureus infections in taiwanese children multilocus sequence typing for characterization of methicillin-resistant and methicillinsusceptible clones of staphylococcus aureus is bloodstream infection preventable among premature infants? a tale of two cities treatment of staphylococcus aureus colonization and prophylaxis for infection with topical intranasal mupirocin: an evidencebased review randomized, placebo-controlled, double-blind trial to evaluate the efficacy of mupirocin for eradicating carriage of methicillin-resistant staphylococcus aureus mupirocinbased decolonization of staphylococcus aureus carrier in residents of long-term care facilities: a randomized, double-blind, placebo-controlled trial intranasal mupirocin to prevent postoperative staphylococcus aureus infections longitudinal analysis of methicillin-resistant staphylococcus aureus isolates at a teaching hospital in taiwan frequent recovery of a single clonal type of multidrug-resistant staphylococcus aureus from patients in two hospitals in taiwan and china changing molecular epidemiology of methicillin-resistant staphylococcus aureus bloodstream isolates from a teaching hospital in northern taiwan change in the molecular epidemiology of methicillin-resistant staphylococcus aureus bloodstream infections in taiwan epidemiological typing of community-acquired methicillin-resistant staphylococcus aureus isolates from children in taiwan successful multiresistant community-associated methicillin-resistant staphylococcus aureus lineage from taipei, taiwan, that carries either the novel staphylococcal chromosome cassette mec (sccmec) type v t or sccmec type iv comparison of both clinical features and mortality risk associated with bacteremia due to methicillin-resistant staphylococcus aureus and methicillin-sensitive s. aureus hospital transmission of community-acquired methicillin-resistant staphylococcus aureus among postpartum women community strain of methicillin-resistant staphylococcus aureus involved in a hospital outbreak the authors thank all the colleagues working in the neonatal intensive care units for their support and cooperation and the infection control team for their data collection and cooperation. key: cord- -lyj tua authors: chen, yu-ju; chiang, po-jung; cheng, yu-hsin; huang, chun-wei; kao, hui-yun; chang, chih-kai; huang, hsun-miao; liu, pei-yin; wang, jen-hsin; chih, yi-chien; chou, shu-mei; yang, chin-hui; chen, chang-hsun title: stockpile model of personal protective equipment in taiwan date: - - journal: health secur doi: . /hs. . sha: doc_id: cord_uid: lyj tua the taiwan centers for disease control (taiwan cdc) has established a -tier personal protective equipment (ppe) stockpiling framework that could maintain a minimum stockpile for the surge demand of ppe in the early stage of a pandemic. however, ppe stockpiling efforts must contend with increasing storage fees and expiration problems. in , the taiwan cdc initiated a stockpile replacement model in order to optimize the ppe stockpiling efficiency, ensure a minimum stockpile, use the government's limited funds more effectively, and achieve the goal of sustainable management. this stockpile replacement model employs a first-in-first-out principle in which the oldest stock in the central government stockpile is regularly replaced and replenished with the same amount of new and qualified products, ensuring the availability and maintenance of the minimum stockpiles. in addition, a joint electronic procurement platform has been established for merchandising the replaced ppe to local health authorities and medical and other institutions for their routine or epidemic use. in this article, we describe the ppe stockpile model in taiwan, including the -tier stockpiling framework, the operational model, the components of the replacement system, implementation outcomes, epidemic supports, and the challenges and prospects of this model. t he severe acute respiratory syndrome (sars) outbreak in had a severe impact on taiwan's health security systems. at the time, medical masks (including surgical masks and n respirators) and coveralls were in short supply, resulting in fear, decreased confi-dence, and decreased willingness to work among frontline healthcare workers. , in addition, the insufficient supply of medical masks in the retail markets triggered panic buying by the public. consequently, the communicable disease control act in taiwan was amended, and a -tier stockpiling framework of personal protective equipment (ppe) was established in . based on the act, the central government, local health authorities, and medical institutions are required to maintain a minimum stockpile of ppe (including surgical masks, n respirators, and coveralls) to ensure a sufficient supply for epidemic prevention and frontline healthcare personnel during the early phase of an epidemic. however, during nonepidemic periods, the use of ppe from the central government inventory was relatively limited; thus, most of the ppe remained unused and expired and needed to be destroyed. to solve this issue, the taiwan cdc, which is responsible for the management of the national stockpile system, developed a concept of stockpile replacement incorporated with a public-private partnership, including public sectors and private contractors, and employing the principles of logistics, supply chain management, commercial marketing, and relevant laws and regulations. [ ] [ ] [ ] [ ] [ ] in this article, the national stockpile systems in the us, canada, australia, and singapore are briefly introduced, and the stockpile model with a replacement mechanism in taiwan is described and evaluated. the experience described may serve as a reference for improving the national stockpile system of other countries. to counter potential biological and chemical threats, some countries formulate and provide funds for medical countermeasure (mcm) stockpiles, such as the strategic national stockpile (sns) in the united states, the national emergency stockpile system (ness) in canada, the national medicine stockpile (nms) in australia, and the rotation system in singapore. these systems are prepared to provide medicine (antiviral drugs, chemical antidotes, and antibiotics), vaccines, medical materials, ppe, and lifemaintaining equipment. multiple stockpiles and releasing models were adopted in the sns system, including self-managed inventory, vendormanaged inventory, and just-in-time procurement and supply. the stockpile includes vaccines, antiviral drugs, and ppe. the sns serves as a national repository for state and local public health authorities to support and resupply materials. it also supports multi-state and national emergencies, such as large-scale pandemics and natural disasters. the sns has developed the chempack (chemical hazards emergency medical pack) plan to assist local governments in stockpiling antitoxin drugs in advance for an immediate response to terrorist attacks. in addition, state and local governments must develop plans for rapidly receiving and allocating mcms from the sns to the areas in need. there are numerous and various products in the sns, but only some medicines can be rotated before expiration. in addition, some drugs are candidates for the food and drug administration's shelf life extension program to extend their validity period. however, the financial problems of refreshing the rest of the large amount of the stockpile continues to be a significant issue for the sns. since the canadian government has developed a national emergency strategic stockpile (ness) for providing health and social service supplies during an emergency. there are federal warehouses for stockpiling mcms with a -hour response capability. in addition, the ness contains a variety of mcms, including medical equipment and ppe, pharmaceuticals (antiviral agents, antibiotics, chemical and biological antidotes), social service supplies (generators, cots, blankets, flashlights), and units or kits (mini-clinics, reception center kits, etc). these supplies have been distributed domestically and internationally in response to a variety of public health events and emergencies. after the sars outbreak, the canadian government established a surge supply system of antiviral agents, antibiotics, and ppe (masks, face shields, gloves, gowns). however, at present, a significant proportion of the supplies and equipment in the stockpile is nearly out-of-date and not in accordance with current medical standards or practices. therefore, the canadian government is working on new strategies to solve the issue of the high maintenance cost. for instance, the ''mini-clinics'' program was designed as a concept of portable, modular, and flexible medical emergency response delivery. this pre-positioning of ''mini-clinics'' aims to supplement existing medical care facilities that might be overwhelmed in a disaster. the national medical stockpile (nms) system was established in , providing a strategic stockpile of medicines, vaccines, antidotes, and ppe available for the national response to public health emergencies. in , the australian government had developed a range of strategies to improve the efficiency of stockpile management. two key strategies are: ( ) the development of a fully costed model for shelf-life extension, and ( ) the examination of options for stock cycling or rotation. the advantages of stock cycling or rotation are to minimize waste and storage and disposal costs and to reduce the need for regular replenishment. currently, the australian department of health is implementing the policy of stock rotation through suppliers for some antibiotics and p respirators, and a % to % rotation rate of p respirators was made possible. however, it is estimated that the savings for p respirators and antibiotic rotation over years would be less than %. the ministry of health (moh) in singapore has procured sufficient ppe to maintain a -to -month minimum stock chen et al for their national hospitals and clinics. the ppe includes surgical masks, gloves, gowns, and n respirators. the moh has made contracts with third-party logistics providers ( pl) for ppe management, storage, and delivery. the stockpile is rotated by national hospitals and clinics with the contractors' assistance. once they receive a request, the contractors inform pl to deliver ppe. when the ppe stockpiles are lower than % of the baseline stock, the contractors resupply directly to the warehouse. during the early phase of an epidemic, the demand for ppe increases dramatically. however, manufacturers and suppliers often cannot meet the surge demand because of difficulties in material preparation, insufficient production capacity, and global panic buying. the discrepancy between the supply and demand directly affects protection measures for the frontline healthcare and epidemic prevention workers, causing fear and reduced workplace efficiency. after the sars epidemic, the taiwan cdc proposed ''a strategy plan for ppe minimum stockpile'' and established the -tier stockpiling framework-a central health authority (managed by the taiwan cdc), local health authorities, and medical institutions-to effectively respond to emergent demands and spread the risk of stockpiling. we have also formulated a minimum stockpile for each tier, taking into consideration: ( ) the protective properties of ppe; ( ) the consumption of ppe during nonepidemic and epidemic periods; ( ) the production capacity of the manufacturers; ( ) potential alternatives; and ( ) the lead time. in addition, the amount of ppe required for nationwide medical care, border quarantine, and epidemic prevention during the early phase of an outbreak was estimated. in , the nationwide minimum stockpile of ppe included million n respirators, . million coveralls, and million surgical masks. in , the nationwide minimum stockpile was adjusted to million n respirators, , coveralls, and million surgical masks, with half of them stockpiled in medical institutions and a quarter of them in the central and local health authorities, respectively. after the h n influenza epidemic in , the authority and the amount among tiers were reviewed and formalized. the stockpile in the central health authority is for nationwide epidemic control and emergency dispatch; the stockpile in local health authorities fulfills local public health and epidemic control needs; and the medical institutions have to assess and store their own minimum stockpile for -day epidemic use. at the same time, the nationwide minimum stockpile was adjusted to . million n respirators, , coveralls, and million surgical masks, and the minimum stockpile of the central health authority (taiwan cdc) is , n respirators, , coveralls, and million surgical masks (table ). in addition, million surgical masks were stockpiled by taiwan cdc for public needs and price stabilization. previously, the taiwan cdc adopted a traditional way to stockpile ppe in central inventory, with large purchases and then storage until use. usage during nonepidemic periods was quite low compared to the inventory level. to solve the issue of low consumption and having a mostly out-of-date ppe stockpile in the central health authority during nonepidemic periods, while maintaining the minimum stockpile, the taiwan cdc reviewed and evaluated different stockpile models in other countries and developed a replacement model for ppe stockpile management. the operational principles and outcomes of the ppe stock replacement model in taiwan are described below. since the taiwan cdc has initiated the procurement of surgical masks, n respirators, and coveralls, using a replacement model. in this model, the central health authority is regarded as a large reservoir of stocks, and the local health authority and medical institutions are regarded as small reservoirs. the concept is to combine the replacement of the large reservoir with the consumption of small reservoirs. the oldest stockpile of the large reservoir is regularly replaced and immediately replenished with the same amount of ppe by private contractors. meanwhile, the removed stock is circulated into small reservoirs for routine and emergency demand through the joint electronic procurement platform run by the contractors. through this replacement model, the stockpile continuously flows through the large reservoir to small reservoirs, and we ensure the ppe stockpile in the central health authority is available in appropriate quantities and within the expiry date. this replacement system involves cooperation between private contractors and the public sector. the private contractors play an important role in maintaining inventory, replacing the oldest stock, acquiring new and qualified products for replenishment in the central health authority, establishing the joint electronic procurement platform, and responding to the procurement requests of other institutions. the validity period of the released items from the central stockpile is about ½ years on average, and that of the replenished new products is years. during nonepidemic periods, rotating ppe stock to the market through the main components of the ppe stockpiling system in the central health authority are warehouse management, stockpile replacement, and joint procurement, which are all carried out by private contractors. first, for warehouse management, the private contractor must provide exclusive storage space, adequate temperature and humidity control, and security management. to ensure the quality of storage, regular inventory checks are conducted by the taiwan cdc. second, according to the warehouse management principle of first-in-first-out, the contractor replaces a certain amount of the oldest ppe stock every year and subsequently replenishes with the same amount of new and qualified products into the central stockpile. the quantities of annual replacement and replenishment of surgical masks, n respirators, and coveralls in the central stockpile are million, , , and , , respectively, which accounts for about one-third of the central stockpile. in addition, to ensure the surge capacity during epidemic periods, the contractors must guarantee to provide million surgical masks, , n respirators, and , coveralls within days in response to an emergency request from the taiwan cdc. third, for joint procurement, contractors built an electronic platform for receiving and processing orders from local health authorities and medical or other institutions. the platform also provides order statistics, information about warehouse environment monitoring, historical replacement records, and other information for the taiwan cdc. in addition, the n respirator contractor provides a variety of brands and sizes as well as fitting-test services for users to achieve the optimum protection of n respirators. in this replacement model, the taiwan cdc adopted a more economical and efficient way to refresh the stockpile, in which we pay the private contractors only a ''service fee'' instead of new products purchasing cost. the service fee includes the manual and computational process the contractors need to refresh the stockpile, which is less than the original purchasing cost because the contractors could further sell the replaced stockpile to domestic institutions through the joint e-purchasing platform or to other countries through their own channels of distribution. for example, the service fee for surgical mask replacement is only % of the original purchasing cost, and the total savings for surgical masks amounts to nt$ . million during the -year contract. the service fee for n respirators is only % of the original price; therefore, it is estimated that a total of nt$ . million is saved over a -year contract. for coveralls, the service fee is about % of the original price, and a total of nt$ . million is saved over a -year contract. the total savings from the procurement projects with the replacement model is nt$ . million ( table ) . during the h n epidemic in , the replaced surgical masks were all sold to domestic institutions via the joint epurchasing platform (compared to around % domestic requests and % overseas sales in a nonepidemic period), demonstrating that this model could indeed play a modulating role in material supply and successfully ease the surge demand in an emergency. in addition, the taiwan cdc actively participated in international cooperation and humanitarian aid by donating , coveralls and , surgical masks from the stockpiling system to west african countries during the ebola epidemic in . in response to the avian flu epidemic in in taiwan, the taiwan cdc also immediately provided , coveralls, , n respirators, and , surgical masks to support the taiwan bureau of animal and plant health inspection and quarantine (baphiq) as emergency supplies. through these epidemic events, we have demonstrated our stockpile system to be a reliable and useful tool for domestic emergency response and international cooperation. in this replacement model, the replaced stockpile is designed for market sales, and therefore the success of these procurement projects depends on the market acceptability, market circulation, and contractors' sales channels. at present, the replaced surgical masks are distributed to domestic or overseas institutions, while n respirators and coveralls are sold for medical protection and mostly industrial safety in taiwan. in addition, although the contractors make sure of the annual ppe replacement and replenishment and guarantee the surge capacity in an emergency situation, the factories manufacturing surgical masks, n respirators, and coveralls in these contracts are mainly located on mainland china, in southeast asia, and in other countries. it may prove difficult to quickly obtain the ppe from these manufacturers overseas if a global large-scale epidemic occurs in which every country attempts to make a large purchase. recently, the ministry of economic affairs in taiwan has supported domestic production of surgical masks and n respirators for emergency demand. support for domestic production of coveralls might depend on further cost-effectiveness evaluation and discussion among various government departments. the taiwan cdc established a -tier framework for the national stockpile in and implemented a replacement model for ppe in . this replacement model has been proven to be more economical and efficient over traditional purchasing practices as a way to renew the central stockpile, and it could also serve as emergency support in an epidemic situation and the basis of international cooperation. in the future, we will continuously improve our system by reviewing the operational outcomes of these contracts and evaluating the potential needs for different categories of ppe in response to various infectious diseases. severe acute respiratory syndrome-taiwan sars in healthcare facilities study on rational inventory level and supply chain model of national material stocks for the infectious disease with focus on personal protection equipment ?treeid= acd c fc &nowtreeid= b eacc b c &tid= d bae . accessed personal protective equipment management integrated research plan ?treeid= acd c fc &nowtreeid= b ea cc b c &tid= af de e cf. accessed november the establishment of the best resource allocation model of national personal protective equipment challenges and capacity building of public administrators in the view of cooperation governance new model of public-private cooperation in epidemic prevention materials ninth cross-strait conference on public administration (cscpa ) pandemic readiness and response plan for influenza and other acute respiratory diseases management of the national medical stockpile ?treeid= be &nowtreeid= ce f d c fda &tid= b b f f e. accessed influenza pandemic strategic plan key: cord- -vdiaexbw authors: kshetri, nir title: china date: journal: the statesman&#x ;s yearbook doi: . / - - - - _ sha: doc_id: cord_uid: vdiaexbw nan upon soviet assistance for economic development. a soviet-style five-year plan was put into action in , but the relationship with moscow was already showing signs of strain. by the end of the s the soviet union and china were rivals, spurring the chinese arms race. chinese research into atomic weapons culminated in the testing of the first chinese atomic bomb in . mao introduced rapid collectivization of farms in . the plan was not met with universal approval in the communist party but its implementation demonstrated mao's authority over the fortunes of the nation. in he launched the doctrine of letting a 'hundred flowers bloom', encouraging intellectual debate. however, the new freedoms took a turn mao did not expect and led to the questioning of the role of the party. strict controls were reimposed and free-thinkers were sent to work in the countryside to be 're-educated'. in may mao launched another ill-fated policy, the great leap forward. to promote rapid industrialization and socialism, the collectives were reorganized into larger units. neither the resources nor trained personnel were available for this huge task. backyard blast furnaces were set up to increase production of iron and steel. the great leap forward was a disaster. it is believed that m. died from famine. soviet advice against the project was ignored and a breakdown in relations with moscow came in , when soviet assistance was withdrawn. a rapprochement with the united states was achieved in the early s. having published his 'thoughts' in the 'little red book' (as it is known in the west) in , mao set the cultural revolution in motion. militant students were organized into groups of red guards to attack the party hierarchy. anyone perceived to lack enthusiasm for mao zedong thought was denounced. thousands died as the students lost control and the army was eventually called in to restore order. after mao's death in the gang of four, led by mao's widow jiang qing, attempted to seize power. these hard-liners were denounced and arrested. china effectively came under the control of deng xiaoping. deng pursued economic reform. the country was opened to western investment. special economic zones and 'open cities' were designated and private enterprise gradually returned. improved standards of living and a thriving economy increased expectations for civil liberties. the demand for political change climaxed in demonstrations by workers and students in april , following the funeral of communist party leader hu yaobang. in beijing where demonstrators peacefully occupied tiananmen square, they were evicted by the military who opened fire, killing more than , . hard-liners took control of the government, and martial law was imposed from may to jan. . since the leadership has concentrated on economic development. hong kong was returned to china from british rule in (for the background, see page ) and macao from portuguese rule in . the late s saw a cautious extension of civil liberties but chinese citizens are still denied most basic political rights. beijing was chosen for the olympic games. china's treatment of tibet came under the international spotlight in the build-up to the games, following violent protests in tibet's capital city, lhasa. the arrest by japan of a chinese trawler in disputed waters in marked the beginning of heightened tensions between the two nations in the east and south china seas. in china became the world's second largest national economy. in nov. the communist party congress selected xi jinping to succeed hu jintao as president from march . in sept. that year, former leadership hopeful bo xilai received a life sentence for corruption in one of china's highest-profile trials in decades. in oct. the government announced the end of the country's one-child policy. a month later, the presidents of china and taiwan met for talks-the first time that leaders from the respective territories had met since . on the economic front, gdp growth in was at its lowest level for a quarter of a century. china is bounded in the north by russia and mongolia; east by north korea, the yellow sea and the east china sea, with hong kong and macao as enclaves on the southeast coast; south by vietnam, laos, myanmar, india, bhutan and nepal; west by india, pakistan, afghanistan, tajikistan, kyrgyzstan and kazakhstan. the total area (including taiwan, hong kong and macao) is estimated at , , sq. km ( , , sq. miles). a law of feb. claimed the spratly, paracel and diaoyutasi islands. an agreement of sept. at prime ministerial level settled sino-indian border disputes which had first emerged in the war of . china's sixth national census was held on nov. . the total population of the provinces, autonomous regions and municipalities and of servicemen on the mainland was , , , ( , , females, representing Á %); density, per sq. km. china's population in represented % of the world's total population. the population rose by , , (or Á %) since the census in . there were , , urban residents, accounting for Á % of the population; compared to the census, the proportion of urban residents rose by Á % (reflecting the increasing migration from the countryside to towns and cities since the economy was opened up in the late s). population estimate, dec. : , , , . china has a fast-growing ageing population. whereas in only Á % of the population was aged or over and by this had increased to Á %, by it is expected to rise to Á %. long-term projections suggest that in as much as Á % of the population will be or older. the population is expected to peak at Á m. around and then begin to decline to such an extent that by around it will be back to the level. china is set to lose its status as the world's most populous country to india in about . the un gives a projected population for of , Á m. regulations restricting married couples to a single child, a policy enforced by compulsory abortions and economic sanctions, were widely ignored, and it was admitted in that the population target of , m. by would have to be revised to , m. from peasant couples were permitted a second child after four years if the first born was a girl, a measure to combat infanticide. in china started to implement a more widespread gradual relaxation of the one-child policy. in dec. the standing committee of the national people's congress (npc) approved a resolution allowing couples to have two children if either parent was an only child. the one-child policy was formally abandoned altogether from jan. . an estimated m. persons of chinese origin lived abroad in . a number of widely divergent varieties of chinese are spoken. the official 'modern standard chinese' is based on the dialect of north china. mandarin in one form or another is spoken by m. people in china, or around % of the population of mainland china. the wu language and its dialects has some m. native speakers and cantonese m. around m. people in china cannot speak mandarin. the ideographic writing system of 'characters' is uniform throughout the country, and has undergone systematic simplification. in a phonetic alphabet (pinyin) was devised to transcribe the characters, and in this was officially adopted for use in all texts in the roman alphabet. the previous transcription scheme (wade) is still used in taiwan and hong kong. mainland china is administratively divided into provinces, five autonomous regions (originally entirely or largely inhabited by ethnic minorities, though in some regions now outnumbered by han immigrants) and four government-controlled municipalities. these are in turn divided into prefectures, cities (of which are at prefecture level and at county level), , counties and urban districts. population of largest cities in : shanghai, Á m.; beijing (peking), Á m.; shenzhen, Á m.; guangzhou (canton), Á m.; tianjin, Á m.; dongguan, Á m.; wuhan, Á m.; foshan, Á m.; chengdu, Á m.; chongqing, Á m.; nanjing, Á m.; shenyang, Á m.; xian, Á m.; hangzhou, Á m.; haerbin, Á m.; suzhou, Á m.; dalian, Á m.; zhengzhou, Á m.; shantou, Á m.; jinan, Á m.; qingdao, Á m.; changchun, Á m.; kunming, Á m.; changsha, Á m.; taiyuan, Á m.; xiamen, Á m.; hefei, Á m.; urumqi (wulumuqi), Á m.; fuzhou, Á m.; shijiazhuang, Á m.; wuxi, Á m.; zhongshan, Á m.; wenzhou, Á m.; nanning, Á m.; ningbo, Á m.; guiyang, Á m.; lanzhou, Á m.; zibo, Á m.; changzhou, Á m.; nanchang, Á m.; xuzhou, Á m.; tangshan, Á m. china has ethnic groups. according to the census , , , people ( Á %) were of han nationality and , , ( Á %) were from national minorities (including zhuang, manchu, hui, miao, uighur, yi, tujia, mongolian and tibetan) . compared with the census, the han population increased by , , ( Á %), while the ethnic minorities increased by , , ( Á %). non-han populations predominate in the autonomous regions, most notably in tibet where tibetans account for around % of the population. chang tibet relations between tibet and china's central government have fluctuated over the question of tibetan independence. the borders were opened for trade with neighbouring countries in . in a buddhist seminary opened in lhasa, the regional capital, with students, and monasteries and shrines have since been renovated and reopened. there were some , monks and nuns in . in tibetan was reinstated as a 'major official language', competence in which is required of all administrative officials. in the then chinese president, jiang zemin, said he was prepared to meet the dalai lama provided he acknowledged chinese sovereignty over tibet and taiwan. in sept. direct contact between the exiled government and china was re-established after a nine-year gap. however, in march anti-chinese protests in lhasa ended in violence, with dozens reportedly killed by the chinese authorities, and in oct. that year the dalai lama stated he had lost hope of reaching agreement with china on tibet's status. in april he announced his retirement from active politics in favour of lobsang sangay, who had been elected to lead the tibetan government-in-exile. in july , shortly after us president obama had received the dalai lama in washington, china's soon-to-be president, xi jinping, pledged to 'smash' attempts to destabilize tibet. by feb. there had been over reported cases of self-immolation by tibetans protesting against chinese rule. the estimated population of tibet at the end of had risen to Á m. from Á m. at the census. the average population density was Á persons per sq. km in , although the majority of residents live in the southern and eastern parts of the region. birth rate (per , ), , Á ; death rate, Á . population of lhasa, the capital, in was , . about % of the population is engaged in the dominant industries of farming and animal husbandry. in the total sown area was , ha. output in : total grain crops, , tonnes; vegetables, , tonnes. in there were Á m. sheep and goats and Á m. cattle and yaks. tibet has over , mineral ore fields. mining, particularly of copper and gold, has expanded rapidly since when the railway came to tibet. cement production, : Á m. tonnes. electricity consumption totalled Á bn. kwh in . in there were , km of roads ( , km in most of china has a temperate climate but, with such a large country, extending far inland and embracing a wide range of latitude as well as containing large areas at high altitude, many parts experience extremes of climate, especially in winter. most rain falls during the summer, from may to sept., though amounts decrease inland. monthly average temperatures and annual rainfall ( ): beijing (peking), jan. Á f (- Á c), july Á f ( Á c). annual rainfall Á " ( mm). chongqing, jan. Á f ( Á c), july Á f ( Á c). annual rainfall Á " ( , mm). shanghai, jan. Á f ( Á c), july Á f ( Á c). annual rainfall Á " ( , mm). tianjin, jan. Á f (- Á c), july Á f ( Á c). annual rainfall Á " ( mm). on -in , and (currently in force) . the latter was partially amended in , , , and , endorsing the principles of a socialist market economy and of private ownership. the unicameral national people's congress is the highest organ of state power. usually meeting for one session a year, it can amend the constitution and nominally elects and has power to remove from office the highest officers of state. there are a maximum of , members of the congress, who are elected to serve five-year terms by municipal, regional and provincial people's congresses. - yang shangkun - jiang zemin - hu jintao -xi jinping prime ministers since . - zhou enlai - hua guofeng - zhao ziyang - li peng - zhu rongji wen jiabao -li keqiang elections of delegates to the th national people's congress were held between oct. and feb. by municipal, regional and provincial people's congresses. at its annual session in march the congress re-elected xi jinping as president and elected wang qishan as vice-president. president xi jinping succeeded hu jintao as president in march at the th national people's congress. tipped for the role since his appointment as secretary general of the chinese communist party (ccp) and chairman of the central military commission in nov. , xi pursued a strong style of authoritarian rule at home and a proactive and muscular foreign policy in his first term. in oct. the ccp gave him the title of 'core' leader, a significant honorific bracketing him with mao zedong and deng xiaoping among previous party figures although conferring no absolute powers. then, at its five-yearly congress in oct. , the party voted to enshrine his name and ideology in the chinese state constitution. he was subsequently re-elected in march and parliament also voted to abolish presidential term limits in a major shift from precedent. xi jinping was born on june in beijing, the son of one of the first generation of communist leaders. he joined the ccp in and, after graduating from tsinghua university in with a degree in chemical engineering, he became secretary to the vice-premier and secretary-general of the central military commission. xi became the zhengding county committee deputy secretary in hebei province in and the following year was promoted to secretary. in he was made deputy mayor of xiamen city, fujian province. having undertaken various party roles in the province, he became deputy governor of fujian in and governor a year later. in he moved to zhejiang province and made his first inroads into national politics when he was named a member of the th central committee. from - he was party secretary of fujian, overseeing economic growth averaging % a year and earning a reputation as an opponent of corruption. in march xi transferred to shanghai to take the role of party secretary following the dismissal of the incumbent on corruption charges. his appointment to such an important regional post was seen as a vote of confidence from the central government and he became a member of the politburo standing committee at the th party congress in oct. . he was also made a high-ranking member of the central secretariat. on march he was elected vice-president at the th national people's congress and took on a number of high profile portfolios including the presidency of the central party school. he was also beijing's senior representative for hong kong and ahead of his presidency, xi said little about his policy ambitions. there was hope abroad and at home that he would champion political and social reform and attempt to deal with corruption and a widening wealth gap between rich and poor and between urban and rural communities. he also faced the conundrum of how to provide adequate health care to a rapidly ageing population. in jan. the prospect of greater transparency and accountability under his leadership was undermined when the authorities began criminal proceedings against anti-corruption campaigners calling for public disclosure of officials' assets. this coincided with a report by a us investigative organization claiming that relatives of some of china's top political and military figures, including xi's brother-in-law, held secret offshore financial holdings. in other social and political affairs the ccp announced plans in nov. to ease china's one-child policy (which was subsequently abandoned following an announcement in oct. , with effect from ) and to abolish the system of 're-education through labour' camps, while a party plenum called-for the first time-for markets to play a 'decisive' role in the allocation of resources. meanwhile, in xi was confronted by domestic political opposition in the form of militant attacks by ethnic uighur separatists from xinjiang region and, from sept. that year, by widespread pro-democracy and autonomy protests in hong kong. on the economic front, china's previously frenetic annual rate of growth slowed markedly in , reflecting a slump in factory production and concerns over depressed oil prices, and again in to its lowest since . it also heralded severe stock market turbulence into despite emergency government measures, which had negative reverberations throughout the world economy. nevertheless, recognizing china's rise as a global economic power, the imf in nov. voted to add the yuan as the fifth member of its special drawing rights (sdr) currency basket alongside the us dollar, japanese yen, british pound and the euro. in foreign affairs, regional concerns over china's territorial and military intentions were raised in nov. by the government's declaration of a new 'air defence identification zone' over a swathe of the east china sea including disputed islands claimed by japan and south korea. there has also been friction, regionally and with the usa, over china's sovereignty claims and land reclamation operations on islands in the south china sea, although in july an international legal tribunal ruled in favour of a challenge by the philippines to china's sovereignty assertions-a verdict beijing vowed to ignore. further afield, xi has meanwhile undertaken numerous official visits abroad, as well as attending multilateral forums, for diplomatic, trading and investment purposes. and, while in singapore in nov. , xi and president ma ying-jeou of taiwan held the first direct talks between leaders of the two estranged governments since their split in . more recently, in xi aimed to extend china's economic and military co-operation with russia and also sought to defuse tensions with india over a simmering border dispute at an informal summit with prime minister narendra modi. meanwhile, friction with the usa escalated markedly over disputed trading and commercial practices, with both countries imposing punitive trade tariffs. li keqiang took office as premier of the state council, a role equivalent to prime minister, in march , succeeding wen jiabao. he was re-elected in march . li keqiang was born on july in dingyuan county, anhui province. following graduation from high school in , he joined the ccp and in he graduated in law from peking university, serving as head of the students' federation from - . he went on to earn a master's degree and doctorate in economics and headed the university's communist youth league of china (cylc) committee. over the following two decades he rose through the cylc ranks, joining the secretariat of its central committee in the s and serving as its first secretary in the s. at this time he built up his power base and forged close ties with hu jintao, a fellow cylc committee member and future chinese president. in li became deputy party secretary for henan province and a year later was appointed henan's governor. in dec. he was named party secretary for liaoning province where he spearheaded a major coastal infrastructure project, the ' points and one line' highway development. in this template was adopted at the national level to rejuvenate industrial northeast china. he also oversaw the rehousing of Á m. shanty-town residents into new apartment blocks over a three-year period. li advanced to national level politics when he was elected to the politburo standing committee in oct. . he was appointed vice-premier of the state council in march , leading a medical reform programme aimed at creating an accessible public health care service. he also chaired an affordable housing programme and introduced tax reform plans. in nov. li was re-elected as a member of the politburo standing committee and on march became premier of the state council at the th national people's congress. regarded as the steward of the chinese economy, li has aimed to focus on securing china's long-term expansion and on the further provision of basic national health care, affordable housing, employment growth, regional development and cleaner energy. however, global confidence in china's economy has been shaken since as the country's growth momentum has slowed amid apparent policy differences and blunders, prompting rumours that li was being increasingly sidelined in the governing hierarchy. he was nevertheless re-elected to the politburo standing committee in oct. and to the premiership in march . having sought assurances that a recently revised us-mexico-canada trade agreement would not stop canada from signing deals with other countries, li met with canadian prime minister justin trudeau in nov. at an international summit in singapore with the aim of pursuing negotiations on a bilateral free trade pact. the chinese president is chairman of the state and party's military commissions. china is divided into seven military regions. the military commander also commands the air, naval and civilian militia forces assigned to each region. china's armed forces (pla: 'people's liberation army'), totalling nearly Á m. in including the paramilitary people's armed police (pap) and Á m. excluding the pap, are the largest of any country. however, active armed personnel numbers have halved since . moreover, in president xi laid out plans to reform the army structure-replacing an organization based on seven regions with one based on five 'theatre commands'-and reduce the number of military personnel by a further , . conscription is compulsory, but for organizational reasons, is selective: only some % of potential recruits are called up. service is for two years. a military academy to train senior officers in modern warfare was established in . defence expenditure in was us$ , m. (equivalent to us$ per capita). china's military spending more than trebled between and . defence spending in represented Á % of gdp, although the share has actually declined since . only the usa spent more on defence in , but china's defence expenditure totalled around a fifth of that of the usa. in march it was announced that the defence budget would rise by Á % to us$ bn. following increases of Á %, Á % and Á % in the previous three years. china is the world's third largest exporter of arms after the usa and russia, with Á % of the global major weapons total over the period - . in the period - it had only been the eighth largest exporter. as at may china had , personnel serving in un peacekeeping operations (the largest contingent of any of the five permanent members of the un security council and more than the other four combined). having carried out its first test in , there have been tests in all at lop nur, in xinjiang (the last in ). the nuclear arsenal consisted of approximately operational warheads in jan. according to the stockholm international peace research institute. china has been helping pakistan with its nuclear efforts. the army (the pla groundforce) is divided into main and local forces. main forces, administered by the seven military regions in which they are stationed, but commanded by the ministry of defence, are available for operation anywhere and are better equipped. local forces concentrate on the defence of their own regions. ground forces are divided into infantry, armour, artillery, air defence, aviation, engineering, chemical defence and communications service arms. there are also specialized units for electronic counter-measures, reconnaissance and mapping. in there were group armies covering seven military regions. they included: armoured divisions and brigades; mechanized infantry divisions, brigades and regiments; motorized infantry divisions and brigades; nine special operations units; artillery divisions and brigades; amphibious brigades and divisions; two mountain brigades; aviation brigades and regiments; and two guard divisions. total strength in was Á m. including some , conscripts. reserve forces are undergoing major reorganization on a provincial basis but are estimated to number some , . there is a paramilitary people's armed police force estimated at , under pla command. in nov. the naval arm of the pla included submarines, of which three were strategic (two jin-class and one xia-class) and tactical. by mid- two more jin-class nuclear-powered ballistic missile submarines had entered service. surface combatant forces in nov. included destroyers and frigates. sea trials of china's first aircraft carrier, liaoning (a former soviet warship purchased from ukraine), began in aug. . it entered service in sept. and was initially only used for training before being declared 'combat ready' in nov. . work on china's first domestically-built aircraft carrier began in . it was launched in april and is expected to be operational by . there is a land-based naval air force of about combat-capable aircraft, primarily for defensive and anti-submarine service. the force includes h- strategic bombers and jh- fighters. the naval arm is split into a north sea fleet, an east sea fleet and a south sea fleet. in naval personnel were estimated at , , including , in the naval air force and , conscripts. the pla air force organizes its command through seven military region air forces. the air force has an estimated , combat-capable aircraft. equipment includes j- (mig- ) interceptors (known in the west as 'fishbed'), h- chinese-built copies of tu- strategic bombers, q- fighter-bombers (evolved from the mig- and known in the west as 'fantan'), su- fighters supplied by russia (known in the west as 'flanker'), j- chinese-designed and produced fighters (known in the west as 'firebird') and j- locally-developed fighters (known in the west as 'finback'). total strength ( ) was , . in agriculture accounted for Á % of gdp, industry Á % and services Á %. industry was the largest contributor until , while services only overtook agriculture as the second largest sector in . in the late s agriculture was the largest contributor towards gdp. china's economic performance has been marked by high rates of growth for over three decades. annual gdp increases in the early s consistently exceeded % until the global financial crisis. china also holds the world's largest foreign exchange reserves, at more than us$ Á trn. in april , although they have been falling since as the central bank strives to boost the currency in the face of large capital outflows. it is among the top recipients of foreign direct investment (fdi) and is the world's largest producer and consumer of coal. in china made the transition from net receiver of foreign aid to net donor and has established itself as a key player in africa's economic development, becoming the largest export partner of sub-saharan africa in . according to the world bank, china's cumulative fdi stock in africa totalled nearly us$ Á bn. in , up from us$ Á bn. in . in china overtook japan to become the world's second largest economy after the usa. new sectors like e-commerce and online financial services are gaining momentum in an economy long dominated by export-oriented sectors. rising trade tensions between the usa and china, however, pose a threat to longer-term prospects. the first steps from a centrally-planned towards a more market-oriented economy were taken by deng xiaoping in the late s. he opened the economy to foreign trade and investment, decentralized industrial management and allowed private sector development. in china became a member of the world trade organization, establishing trade relations with many countries. private entrepreneurs and foreign investors have played an important role in developing the manufacturing sector, china's principal growth engine. even before the economy was heavily skewed towards manufacturing, but following the market-oriented transition output increased significantly. during this period there was a structural shift away from large state-owned enterprises (soes), although these still remain an important part of the economy. between and the government oversaw reform of soes, with many poorly performing businesses privatized or liquidated. stronger firms were restructured and often listed on the stock market. many more recent enterprises are labour-intensive as distinct from the capitalintensive soes. growth has been fuelled by low added value and labourintensive exports. however, chinese firms are predicted to become increasingly competitive with higher added value producers, such as south korea. although the global financial crisis reduced the rate of growth and inbound fdi, china's recovery was among the earliest. gdp growth averaged Á % in the second quarter of , up from a two-decade low of Á % in the first quarter of that year. fdi also recovered rapidly, averaging Á % of gdp annually between and . growth was rooted in a stimulus package of trn. yuan (us$ bn. or % of gdp), including fiscal spending and interest rate cuts, as well as an expansionary monetary policy. central government committed Á trn. yuan, with the rest coming from local government, banks and soes. although exports declined by around % in , other countries fared worse and china's share of world exports increased to nearly Á % in (up from % in ), making it the world's largest merchandise provider. gdp growth in stood at more than % but moderated between and , reflecting the global economic slowdown and diminishing dividends from past reforms. in aug. a devaluation of the yuan sent the shanghai stock exchange plummeting by nearly %, which was swiftly followed by a surge in capital outflows. the stock market meltdown lasted until feb. , with trading halted altogether for two days in jan. that year. nonetheless, the shanghai exchange subsequently began a recovery and had stabilized (at around , points) by feb. . despite stock market turbulence, the property market, which constitutes a quarter of china's gdp and is vital to the banking sector (as it accounts for a substantial amount of its collateral), remained buoyant. gdp growth declined to Á % in (the slowest rate in years) and fell again to Á % in as china attempted to reduce its reliance on exports, increase domestic consumption and develop its service sector. however, china remains one of the fastest growing major economies in the world, recording expansions of Á % and Á % in and , respectively, driven by exports and robust domestic household consumption. in may , for the first time since , the credit rating agency moody's downgraded china's sovereign rating. inflation was Á % in , up from Á % in , while public debt was measured by the government at Á % of gdp (although there is wide-held suspicion that the real figure is significantly higher). corporate debt reached % of gdp in , with household debt-although still low-rising by % of gdp over the preceding five years. president xi jinping has targeted spending cuts and aims to curb loans to bloated soes. rapid economic advance has brought with it a number of challenges that threaten future growth. notably, china's cost advantage has been undermined in recent years by rising wages and transportation costs, as well as weak global demand. other concerns include rising property costs, high levels of local government debt, lack of enforcement of intellectual property rights, endemic corruption at government level and credit and investment dependence, while total social financing-a broad measure of total credit-increased by % of gdp between and early . the stimulus package implemented by the government to boost growth increased total debt levels to more than double the value of gdp in . according to the imf, an increase in consumer demand and a reduced dependence on exports and investment are keys to achieving stable long-term economic expansion. china's th five-year plan (covering - ) aims to promote domestic consumption and to support innovation and entrepreneurship within a framework of balanced and sustainable development. efforts to promote domestic consumption have seen exports' share of gdp falling from % in to Á % in and a lower investment contribution to gdp. trade frictions are predicted to disproportionately affect smaller firms that are less able to squeeze profit margins to accommodate tariff hikes, as well as those geographical regions most reliant on exports. the continued decline in commodity prices coupled with china's economic slowdown has had knock-on effects for commodity-exporting nations, such as brazil, indonesia and argentina, given that china consumes about half of the world's steel, aluminium and nickel. inefficient production and outmoded equipment have meanwhile led to significant environmental problems, especially in the north of the country. air pollution, soil erosion and a declining water table are of particular concern. china has become the world's largest consumer of coal and second largest consumer of oil after the usa. the government aims to diversify its energy sources, relying less on coal and more on nuclear and alternative energy sources. there has been heavy investment in hydro-power, including the three gorges dam. since , m. people have been lifted out of poverty, yet china still has the second largest number of poor in the world after india. the world bank estimates that Á m. people lived below the national poverty line at the end of (equivalent to income less than us$ per day), located mainly in remote and resource-poor regions and particularly in the west and the interior. nonetheless, some progress has been made, with Á % of the rural population living below the poverty line in compared to Á % in . a large gap remains between living standards of the urban and rural communities, between urban zones on the chinese coast and the interior and western parts of the country, and between the urban middle classes and those who have not been able to profit from the growth of recent decades. china also faces the growing burden of an ageing population. those aged and over accounted for Á % of the total population in , up from Á % in . the currency is called renminbi (i.e. people's currency). the unit of currency is the yuan (cny) which is divided into ten jiao, the jiao being divided into ten fen. the yuan was floated to reflect market forces on jan. while remaining state-controlled. for years the people's bank of china maintained the yuan at about Á to the us dollar, allowing it to fluctuate but only by a fraction of % in closely supervised trading. in july it was revalued and pegged against a 'market basket' of currencies the central parities of which were determined every night. in july , after three years of sharp appreciation, it was repegged at around Á yuan to the dollar, leading to claims from some international observers that it was being kept unfairly low to boost exports. in june the government announced that the yuan would be allowed to move freely against the dollar as long as a rise or fall does not exceed Á % within a single day. in aug. the yuan was devalued by a total of Á % on three consecutive days. in aug. total money supply was , Á bn. yuan, gold reserves were Á m. troy oz and foreign exchange reserves us$ , Á bn. (us$ Á bn. in ). china's reserves are the highest of any country, having overtaken those of japan in . inflation rates (based on imf statistics): Á % - Á % Á % Á % Á % Á % Á % Á % Á % Á % china's economy overheated in the early s, leading to inflation rates of Á % in , Á % in and Á % in of the total revenues in central government accounted for , Á bn. yuan and local governments , Á bn. yuan. tax revenues came to , Á bn. yuan in (including domestic vat , Á bn. yuan and corporate income tax , Á bn. yuan) and non-tax revenues , Á bn. yuan. of the total expenditure in central government accounted for , Á bn. yuan and local governments , Á bn. yuan. the leading items of expenditure in were education ( , Á bn. yuan) and social safety net and employment effort ( , Á bn. yuan). the standard rate of vat is %. performance gdp totalled us$ , Á bn. in , the second highest behind the usa. china's share of world gdp has risen from % in to % in . it replaced japan as the second largest economy in . it is forecast that around china will overtake the usa to become the world's largest economy. as recently as the us economy was around eight times larger than china's. real gdp growth rates (based on imf statistics): supervising the country's banks and other deposit-taking financial institutions from the central bank. legislation in permitted the establishment of commercial banks; credit co-operatives may be transformed into banks, mainly to provide credit to small businesses. there were , rural credit co-operatives at the end of . insurance is handled by the people's insurance company. the industrial and commercial bank of china is the world's largest bank by assets (us$ , bn. as at dec. ). savings deposits in various forms in all banking institutions totalled , Á bn. yuan in ; loans amounted to , Á bn. yuan. there are stock exchanges in the shenzhen special economic zone and in shanghai. a securities trading system linking six cities (securities automated quotations system) was inaugurated in for trading in government bonds. china received a record us$ Á bn. worth of foreign direct investment in , up from us$ Á bn. in . external debt totalled us$ , m. in (up from us$ , m. in ) and represented Á % of gni. china's carbon dioxide emissions from the consumption of energy in accounted for Á % of the world total (making it the biggest emissions producer, having overtaken the usa in ) and were equivalent to Á tonnes per capita (up from Á tonnes per capita in ). carbon dioxide emissions have more than doubled since . an environmental performance index compiled in ranked china th of countries, with Á %. the index examined various factors in nine areas-agriculture, air quality, biodiversity and habitat, climate and energy, fisheries, forests, health impacts, water and sanitation, and water resources. pollution is estimated to cost china about % of gdp annually. installed generating capacity in was an estimated , m. kw, compared with m. kw in . in electricity output was , , gwh, up from , , gwh in . consumption per capita was , kwh in . rapidly increasing demand has meant that more than half of china's provinces have had to ration power. sources of electricity in as percentage of total production: thermal, Á %; hydro-electric power, Á %; wind. Á % (china is one of the world's largest producers of wind power); and nuclear, Á %. in there were nuclear reactors in use and under construction. generating electricity is not centralized; local units range between and mw of output. in dec. china formally broke up its state power monopoly, creating instead five generating and two transmission firms. the three gorges dam project on the yangtze river was launched in and is intended to produce abundant hydro-electricity (as well as helping flood control). the first three , -kw generators in service at the project's hydro-power station began commercial operation in july . the original specification was completed in oct. , although six more generators have been added in the meantime (bringing the total to ). the final two generators become operational in july , giving the dam an overall capacity of Á gw. china surpassed germany in terms of solar generating capacity in , with Á gw at the end of the year. on-shore oil reserves are found mainly in the northeast (particularly the daqing and liaohe fields) and northwest. there are off-shore fields in the continental shelves of east china. oil production was a record Á m. tonnes in and was Á m. tonnes in . china is the second largest consumer of oil after the usa. ever-growing demand has meant that increasing amounts of oil are having to be imported. a -km pipeline from skovorodino in russia to daqing in the northeast of china was inaugurated in jan. , allowing china to increase significantly its imports of oil from the world's second largest producer. the , -km turkmenistan-china gas pipeline, bringing natural gas to xinjiang in china via kazakhstan and uzbekistan, was inaugurated in dec. . this connects with china's second west-east gas pipeline. only the usa imports more oil. domestic production now accounts for only % of consumption, compared to nearly % in . proven reserves in were Á bn. bbls. the largest natural gas reserves are located in the western and northcentral regions. production was a record Á bn. cu. metres in -up from Á bn. cu. metres in -with proven reserves of Á trn. cu. metres in . china is the second largest producer of wind power after the usa, with Á bn. kwh in . in total installed capacity amounted to , mw, the highest of any country and Á % of the world total. china is one of the world's leading mineral producing and consuming countries. recoverable deposits of coal in totalled Á bn. tonnes, mainly distributed in north china (particularly shanxi province and the inner mongolia autonomous region). coal production was , m. tonnes in . annual coal production has increased every year since . growing domestic demand nonetheless meant that china became a net importer of coal in . iron ore reserves were Á bn. tonnes in . deposits are abundant in the anthracite field of shanxi, in hebei and in shandong, and are found in conjunction with coal and worked in the northeast. production in was , m. tonnes, making china the world's largest iron ore producer. it is also the largest consumer, at around % of the global total in . tin ore is plentiful in yunnan, where the tin-mining industry has long existed. tin production was , tonnes in . china is a major producer of wolfram (tungsten ore). there is mining of wolfram in hunan, guangdong and yunnan. output of other minerals (in , tonnes) in : salt, , ; bauxite, , ; aluminium, , ; zinc, , ; lead, , ; copper, , . there are also reserves of diamond, nickel, barite, bismuth, graphite, gypsum, mercury, molybdenum, silver, salt, phosphate ore and sylvite. gold production, : tonnes. china surpassed south africa as the world's leading gold producer in , since when its output has increased every year. agriculture accounted for approximately % of gdp in , compared to over % in at the time of the birth of the people's republic of china and over % in . in sown areas for major crops were (in m. ha.): corn, Á ; rice, Á ; wheat, Á ; soybeans, Á ; tubers, Á ; rapeseed, Á . intensive agriculture and horticulture have been practised for millennia. present-day policy aims to avert the traditional threats from floods and droughts by soil conservancy, afforestation, irrigation and drainage projects, and to increase the 'high stable yields' areas by introducing fertilizers, pesticides and improved crops. in aug. more than m. ha., notably in the yangtze valley, were under water as china experienced its worst flooding since the s. the flood season claimed over , lives. 'township and village enterprises' in agriculture comprise enterprises previously run by the communes of the maoist era, co-operatives run by rural labourers and individual firms of a certain size. there were , state farms in with Á m. employees. net per capita annual income of rural households, : , yuan. in there were an estimated Á m. ha. of arable land and Á m. ha. of permanent cropland; Á m. ha. were equipped for irrigation. there were Á m. large/medium-sized tractors in and Á m. small tractors. china is the world's leading producer of a number of agricultural crops. production of major products (in m. tonnes), (unless otherwise indicated): corn, Á ; rice, Á ; wheat, Á ; sugarcane, Á ; potatoes ( estimate livestock, (unless otherwise indicated): pigs, , , ; sheep, , , ; goats, , , ; cattle and buffaloes, , , ; horses, , , ; chickens ( estimate), Á bn.; ducks ( estimate), m. china has more pigs, goats, sheep, horses and chickens than any other country. it is also home to nearly two-thirds of the world's ducks. meat production in was estimated at Á m. tonnes; milk, Á m. tonnes; eggs, Á m. tonnes; honey, , tonnes. china is the world's leading producer of meat, eggs and honey. gale, fred, (ed.) china's food and agriculture: issues for the st century. powell, s. g., agricultural reform in china: from communes to commodity economy, - . forestry in the area under forests was Á m. ha., or % of the total land area. the average annual increase in forest cover of , , ha. between and was the highest of any country in the world. total roundwood production in was Á m. cu. metres, making china the world's third largest timber producer ( Á % of the world total in ). it is the highest consumer of roundwood; timber consumption in totalled Á m. cu. metres. it is also the world's leading importer of roundwood, accounting for Á % of world timber imports in . total catch, : , , tonnes, of which , , tonnes were from marine waters. china's annual catch is the largest in the world, and currently accounts for approximately % of the world total. in the annual catch had been just Á m. tonnes. china's aquaculture production is also the largest in the world, at , , tonnes in . imports of fishery commodities in were valued at us$ , m. (the third highest behind japan and the usa); exports were the most of any country, at us$ , m. china's fishery commodities exports in represented approximately % of the global total. in , the first phase of the south-to-north water diversion project opened, with a second phase opening a year later. the scheme, which by provided beijing with a third of its total supply, was estimated to have cost almost us$ bn., with a third phase still to be completed. the leading companies by market capitalization in china in march were alibaba, an e-commerce and data company (us$ Á bn.); tencent holdings, an investment holding company (us$ Á bn.); and icbc, the world's largest commercial bank (us$ Á bn.). in nov. petrochina was briefly the world's largest company after its flotation on the shanghai stock market, with a market capitalization in excess of us$ trn., although its rank has since fallen considerably. industry accounted for Á % of gdp in . cottage industries persist into the st century. industrial output grew by Á % in . modern industrial development began with the manufacture of cotton textiles and the establishment of silk filatures, steel plants, flour mills and match factories. in there were , industrial enterprises with an annual revenue of more than m. yuan. of these enterprises, , were domestically funded, , were foreign funded and , were dependent on funds from hong kong, macao and taiwan. there were , state-owned industrial enterprises in total. output of major products, unless otherwise indicated (in tonnes): cement, , Á m.; rolled steel, , Á m.; crude steel, Á m.; pig iron, Á m.; gas oil and diesel oil ( ), Á m.; gasoline, Á m.; paper and paperboard, Á m.; sulphuric acid, Á m.; chemical fertilizers, Á m.; fuel oil ( ), Á m.; yarn, Á m.; refined sugar, Á m. also produced in : cloth, , m. metres; beer, , Á m. litres; , Á m. mobile phones; Á m. notebook pcs; Á m. colour tv sets; Á m. air conditioners; Á m. home refrigerators; Á m. washing machines; Á m. bicycles; Á m. cameras; Á m. motorcycles. china is the world's leading cement, steel and pig iron manufacturer; since output of cement has trebled, and production of crude steel has increased sixfold and of pig iron fivefold (although in pig iron production fell for the first time in more than years, as did crude steel production in ). china overtook japan as the world's largest producer of motor vehicles in , and in produced Á m. cars and Á m. commercial vehicles. the employed population at the census was Á m. ( Á m. female). by it had risen to Á m. ( Á m. more than in ), of whom Á m. worked in rural areas ( Á m. fewer than in ) and Á m. in urban areas ( Á m. more than in ). in china's registered urban jobless was Á %, with Á m. registered unemployed in the country's cities. with china's fast-growing ageing population, according to the united nations the working-age population began to decline in . in china had , private industrial enterprises. it was not until the late s that the private sector even came into existence in china. the average annual wage of people working in urban units in was , yuan. china's labour law stipulates a five-day working week with no more than eight hours a day and no more than hours a week. minimum working age was fixed at in . strikes over pay have become ever more frequent in china, particularly at foreign-owned facilities. china had Á m. people living in slavery according to the walk free foundation's global slavery index, the second highest total of any country. there are five special economic zones at shenzhen, xiamen, zhuhai, shantou and hainan in which concessions are made to foreign businessmen. the pudong new area in shanghai is also designated a special development area. since joint ventures with foreign firms have been permitted. a law of april reduced taxation on joint ventures to %. there is no maximum limit on the foreign share of the holdings; the minimum limit is %. in china is the second largest trading nation in the world, accounting for Á % of global merchandise imports by value in and Á % of global merchandise exports (up from Á % when it joined the wto in ). it was the second largest importer in behind the usa and the largest exporter. as recently as the usa's total trade in goods was more than twice that of china. it overtook germany as the largest exporter of goods in . its trade surplus in goods is the highest of any country. however, it has the world's highest trade deficit in services. in imports of services totalled us$ bn. but exports only us$ bn. main imports in (in us$ bn.): machinery and transport equipment, Á ; non-edible raw materials, Á ; mineral fuels, lubricants and related materials, Á ; chemicals, Á . major exports in (in us$ bn.): machinery and transport equipment, , Á ; miscellaneous manufactured goods, Á ; light textile industrial products, rubber products, minerals and metallurgical products, Á ; chemicals, Á . the main trading partners were as follows in (in us$ m.): the total road length in was , , km, including , km of expressways (of which there had not been any as recently as the mid- s); , m. tonnes of freight and , m. persons were transported by road that year. the number of civilian motor vehicles was Á m. in , including Á m. passenger vehicles and Á m. trucks (more than double the number in , when there were Á m. civilian vehicles overall including Á m. passenger vehicles and Á m. trucks). china is the world's fastest-growing car market. there were , traffic accidents in , with , fatalities. in in jan. there were , ships of gt or over registered, totalling Á m. gt. of the , vessels registered, were bulk carriers, general cargo ships, oil tankers, container ships, passenger ships and liquid gas tankers. mainland china's busiest port in was ningbo-zhoushan (handling Á m. tonnes of cargo), followed by shanghai ( Á m. tonnes), tianjin ( Á tonnes), guangzhou (canton) ( Á m. tonnes) and qingdao ( Á m. tonnes). shanghai overtook singapore to become the world's busiest container port in and handled Á m. teus (twenty-foot equivalent units) in . shenzhen, mainland china's second busiest port for container traffic and the world's fourth busiest in , handled Á m. teus. hong kong handled Á m. teus in . in jan. the first legal direct shipping links between the chinese mainland and taiwanese islands in more than years were inaugurated. inland waterways totalled , km in ; , Á m. tonnes of freight and Á m. passengers were carried. in june the three gorges reservoir on the chang jiang river, the largest water control project in the world, reached sufficient depth to support the resumption of passenger and cargo shipping. in out of countries analysed in the fragile states index-a list published jointly by the fund for peace and foreign policy magazine-china was ranked the th most vulnerable to conflict or collapse. the index is based on indicators of state vulnerability across social, political and economic categories. six new codes of law (including criminal and electoral) came into force in , to regularize the legal unorthodoxy of previous years. there is no provision for habeas corpus. as well as treason and murder the death penalty may be used for rape, embezzlement, smuggling, fraud, theft, drug-dealing, bribery and robbery with violence. amendments to the criminal law in and reduced the number of capital crimes-which include both violent and non-violent offences-from to and further to . china does not divulge figures on its use of the death penalty, but amnesty international reports that china executes thousands of people annually and is the world's top executioner. nevertheless, western analysts believe that the number of executions now is around a fifth of the yearly total in the s. 'people's courts' are divided into some higher, intermediate and , basiclevel courts, and headed by the supreme people's court. the latter, the highest state judicial organ, tries cases, hears appeals and supervises the people's courts. it is responsible to the national people's congress and its standing committee. people's courts are composed of a president, vicepresidents, judges and 'people's assessors' who are the equivalent of jurors. 'people's conciliation committees' are charged with settling minor disputes. there are also special military courts. procuratorial powers and functions are exercised by the supreme people's procuracy and local procuracies. in march the national people's congress passed legislation developing aspects of the general principles of civil law, with effect from oct. . among its provisions was the extension of legitimate rights and interests from chinese citizens only to anyone conducting civil activities in the country. in addition, the statute of limitation was increased from two to three years. the number of sentenced prisoners in mid- was , , ( per , of national population). china was ranked th of countries for criminal justice and th for civil justice in the world justice project rule of law index, which provides data on how the rule of law is experienced by the general public across eight categories. an educational reform of brought in compulsory nine-year education consisting of six years of primary schooling and three years of secondary schooling, to replace a previous five-year system. in mainland china the population census revealed the following levels of educational attainment: Á m. people had finished university education; Á m. had received senior secondary education; Á m. had received junior secondary education; and Á m. had had primary education. Á m. people over years of age or Á % of the population were illiterate, although this compared favourably with a Á % rate of illiteracy in the census and a Á % rate in . in adult literacy was estimated at Á %; youth literacy in was Á %. in there were , kindergartens with Á m. children and Á m. full-time teachers; , regular primary schools with Á m. pupils and Á m. full-time teachers; , secondary schools (including: , senior secondary; , junior secondary; , specialized; , vocational; and , technical) with Á m. pupils and Á m. full-time teachers. there were also , pupils at , special education schools. institutes of higher education, including universities, numbered , in , with Á m. undergraduates and Á m. postgraduate level students, and Á m. full-time teaching staff. china has more than private universities, almost all of which have been established since the mid- s. a national system of student loans was established in . the number of chinese students studying abroad went up from , in to , in ; it rose above , in and , in , and by exceeded , , making china the largest source of overseas students in the world. chinese students account for a fifth of all international students in tertiary education in the oecd, but fewer than half return to china after finishing their studies. the number of chinese undergraduate students in american universities in - was times as many as in - , rising from , to , in the space of seven years. there is an academy of sciences with provincial branches. an academy of social sciences was established in . in national government expenditure on education came to , , m. yuan and accounted for Á % of national government spending. medical treatment is free only for certain groups of employees, but where costs are incurred they are partly borne by the patient's employing organization. in there were , health institutions throughout china, including , hospitals, , local health centres, , centres for disease control and prevention, and , specialized prevention and treatment centres. china's first aids case was reported in . at the end of there were , reported cases of people living with hiv/aids. the number of deaths of people who had been living with hiv/aids in was , . in the first half of china was struck by an epidemic of a pneumoniatype virus identified as sars (severe acute respiratory syndrome). the virus was first detected in southern china and was subsequently reported in over other countries. according to the ministry of health, by the time the outbreak had been contained a total of , cases had been reported on the chinese mainland; , patients were cured and discharged from hospital, and died. in water: at what cost? the state of the world's water , wateraid reported that Á % of the population does not have access to safe water. china ranked as the country with the second largest number of people living without access to safe water ( Á m. in ). in an estimated Á % of adult males and Á % of adult females smoked in china. a study from the same year estimated that chinese males smoke one-third of all the world's cigarettes. in there were , social welfare enterprises with Á m. beds. numbers (in , ) of beneficiaries of relief funds in : urban residents receiving minimum living allowance, , ; rural residents receiving minimum living allowance, , ; persons receiving traditional relief, ; persons in rural households entitled to the 'five guarantees' (food, clothing, medical care, housing and burial expenses), , . the official retirement age for men is and for women (or in the case of civil servants and professionals). the government accords legality to five religions only: buddhism, islam, protestantism, roman catholicism and taoism. confucianism, buddhism and taoism have long been practised. confucianism has no ecclesiastical organization and appears rather as a philosophy of ethics and government. taoism-of chinese origin-copied buddhist ceremonial soon after the arrival of buddhism two millennia ago. buddhism in return adopted many taoist beliefs and practices. a more tolerant attitude towards religion had emerged by , and the government's bureau of religious affairs (since renamed the state administration for religious affairs) was reactivated. ceremonies of reverence to ancestors have been observed by the whole population regardless of philosophical or religious beliefs. a new quasi-religious movement, falun gong, was founded in , but has since been banned by the authorities. the movement has claimed some m. adherents, although the chinese government has disputed this. muslims are found in every province of china, being most numerous in the ningxia-hui autonomous region, yunnan, shaanxi, gansu, hebei, henan, shandong, sichuan, xinjiang and shanxi. roman catholicism has had a footing in china for more than three centuries. two christian organizations-the chinese patriotic catholic association, which declared its independence from rome in , and the protestant three-self patriotic movement-are sanctioned by the chinese government. according to estimates (by the state-approved xinhua news agency, the chinese academy of social sciences and the state administration for religious affairs) there were m. buddhists (more than in any other country), m. christians and more than m. muslims in the country in . other official figures indicate that there are Á m. catholics, although unofficial estimates are much higher. the number of christians in china is generally thought to be far higher than official numbers indicate, with so-called 'house churches' becoming ever more popular. some analysts estimate that there are as many as m. christians overall. legislation of prohibits foreign nationals from setting up religious organizations. johnson, ian, the souls of china: the return of religion after mao. china and provides habitat for a number of rare animal species, kulangsu, a historic international settlement ( ), a tiny island located on the estuary of the chiu-lung river, qinghai hoh xil ( ), the largest and highest plateau in the world, and fanjingshan ( ), an island of metamorphic rock in guizhou province. shared with kazakhstan and kyrgyzstan, silk roads: the routes network of chang'an-tianshan corridor ( ) is a , -km section of the extensive silk roads network stretching from chang'an/ luoyang to the zhetysu region in present-day kazakhstan. china has two news agencies: xinhua (new china) news agency (the nation's official agency) and china news service. in there were , newspapers and , magazines; , m. copies of newspapers and , m. copies of magazines were published. in there were fewer than newspapers. the communist party newspaper, renmin ribao (people's daily), had an average daily circulation of Á m. in . the most widely read newspaper is cankao xiaoxi, with an average daily circulation of Á m. in . china has the second highest circulation of daily newspapers after india, with an estimated average daily total of Á m. in . as of sept. it was also home to the world's two most visited online news sites: xinhua news agency ( Á m. unique desktop users per month) and people's daily online ( Á m.). in the world press freedom index compiled by reporters without borders, china ranked rd out of countries. in , , m. volumes of books were produced. in tourist numbers totalled Á m. china was the fourth most visited destination in after france, the usa and spain. income from tourists in was us$ Á bn., ranking it third behind the usa and spain. expenditure by chinese travellers outside of mainland china for was us$ Á bn., the most of any country and more than double the next largest expenditure (that of us tourists). in both german and us travellers abroad had spent more than those from china. the lunar new year, also known as the 'spring festival', is a time of great excitement for the chinese people. the climate is sub-tropical, tending towards temperate for nearly half the year, the winter being cool and dry and the summer hot and humid, may to sept. being the wettest months. normal temperatures are jan. f ( Á c), july f ( Á c). annual rainfall " ( , Á mm). hong kong used to be administered by the hong kong government. the governor was the head of government and presided over the executive council, which advised the governor on all important matters. the last british governor was chris patten. in oct. the executive council consisted of three ex officio members and ten appointed members, of whom one was an official member. the chief functions of the legislative council were to enact laws, control public expenditure and put questions to the administration on matters of public interest. the legislative council elected in sept. was, for the first time, constituted solely by election. it comprised members, of whom were elected from geographical constituencies, from functional constituencies encompassing all eligible persons in a workforce of Á m., and ten from an election committee formed by members of district boards. a president was elected from and by the members. at the elections on sept. turnout for the geographical seats was Á %, and for the functional seats ( of which were contested), Á %. the democratic party and its allies gained seats, the liberal party and the pro-beijing democratic alliance . the remaining seats went to independents. on dec. the selection committee selected a provisional legislature which began its activities in jan. while the legislative council was still functioning. in jan. the provisional legislature started its work by enacting legislation which would be applicable to the hong kong special administrative region and compatible with the basic law. constitutionally hong kong is a special administrative region of the people's republic of china. the basic law enables hong kong to retain a high degree of autonomy. it provides that the legislative, judicial and administrative systems which were previously in operation are to remain in place. the special administrative region government is also empowered to decide on hong kong's monetary and economic policies independent of china. in july the first-past-the-post system of returning members from geographical constituencies to the legislative council was replaced by proportional representation. there were directly elected seats out of for the first elections to the legislative council following hong kong's return to chinese sovereignty, increasing in accordance with the basic law to for the election with indirectly elected. in the sept. legislative council election (and that of sept. ) of the seats were directly elected. for the election in sept. the number of seats was increased to , with directly elected and indirectly elected by functional constituencies. there were also five new functional constituency seats nominated by elected district council members. the chief executive is chosen by a beijing-backed , -member election committee ( prior to the march election), although it has been stated that universal suffrage is the ultimate aim. in a timetable was announced for hong kong to directly elect its chief executive in and its legislative council in . however, beijing insisted that only approved candidates would be allowed to stand in , prompting mass pro-democracy rallies in the territory in and formal rejection of the plan by the legislative council in june . beijing nevertheless refused to countenance amendments. in july a new accountability or 'ministerial' system was introduced, under which the chief executive nominates for appointment policy secretaries, who report directly to the chief executive. the chief executive is aided by the executive council, consisting of the three senior secretaries of department (the chief secretary, the financial secretary and the secretary for justice) and eleven other secretaries plus five non-officials. hong kong used to be administered by the hong kong government. the governor was the head of government and presided over the executive council, which advised the governor on all important matters. the last british governor was chris patten. in oct. the executive council consisted of three ex officio members and ten appointed members, of whom one was an official member. the chief functions of the legislative council were to enact laws, control public expenditure and put questions to the administration on matters of public interest. the legislative council elected in sept. was, for the first time, constituted solely by election. it comprised members, of whom were elected from geographical constituencies, from functional constituencies encompassing all eligible persons in a workforce of Á m., and ten from an election committee formed by members of district boards. a president was elected from and by the members. at the elections on sept. turnout for the geographical seats was Á %, and for the functional seats ( of which were contested), Á %. the democratic party and its allies gained seats, the liberal party and the pro-beijing democratic alliance . the remaining seats went to independents. overview hong kong has one of the world's most open economies and is an internationally important financial centre. the territory's economic rise was founded on its role as an international trade emporium, acting as a conduit for china's burgeoning exports. mainland china, the usa and japan are hong kong's major export partners, accounting for Á %, Á % and Á % of exports respectively in . the island is dependent on imports of food and other resources. in it imported % of goods from mainland china, % from taiwan and % from japan. in and the economy grew strongly on the back of a rise in chinese tourism, healthy global demand for exports and improving domestic consumer confidence. however, the global financial crisis saw the economy shrink by Á % in before rebounding with a Á % increase the following year. between and annual growth averaged Á %, supported by strong external demand. student-led pro-democracy protests in the latter months of caused major disruption in several key business districts and threatened to weaken the local economy in the short term. foreign direct investment levels have been high, averaging % of gdp between and according to world bank data, and the world economic forum ranked hong kong as the ninth most competitive economy in the world in its report. the government aims to tackle a housing shortage by providing , new housing units by the mid- s. the unit of currency is the hong kong dollar (hkd) of cents. it has been pegged since at a rate of hk$ Á to the us dollar. banknotes are issued by the hongkong and shanghai banking corporation and the standard chartered bank, and, from may , the bank of china. total money supply was hk$ , m. in july . in aug. gold reserves were , troy oz and foreign exchange reserves were us$ , m. inflation rates (based on imf statistics): environment hong kong's carbon dioxide emissions from the consumption of energy in were the equivalent of Á tonnes per capita. installed capacity was Á m. kw in . production in was Á bn. kwh. hong kong is a net importer of electricity. consumption in was Á bn. kwh. the local agricultural industry is directed towards the production of high quality fresh food through intensive land use and modern farming techniques. out of the territory's total land area of , sq. km, only sq. km is currently farmed. in local production accounted for % of live poultry consumed, % of live pigs and % of fresh vegetables. the gross value of local agricultural production totalled hk$ , m. in , with pig production valued at hk$ m., poultry production (including eggs) at hk$ m., and vegetable and flower production at hk$ m. in the total catch was , tonnes, exclusively from marine waters. the leading companies by market capitalization in hong kong in march were: china mobile, a telecommunications company (us$ Á bn.); aia group, a life insurance company (us$ Á bn.); and cnooc, an integrated oil company (us$ Á bn.). industry is mainly service-oriented. in june there were , establishments employing , , persons in service industries and , establishments employing , persons in manufacturing industries. establishment statistics by service type (and persons engaged) were mainly: import/export trade and wholesale, , ( , ); retail, , ( , ); social and personal services, , ( , ) ; professional and business services, , ( , ); financing and insurance, , ( , ); accommodation and food services, , ( , ); real estate, , ( , ) . in the size of the labour force (synonymous with the economically active population) was , , ( , , females). the persons engaged in june included , , people in wholesale, retail and import/ export trades, accommodation and food services, , in finance, insurance, real estate, professional and business services, , in the civil service, , in manufacturing and , in construction sites (manual workers only). a minimum wage of hk$ per hour was introduced for the first time on may . unemployment stood at Á % in the period sept.-dec. . in the total value of imports was hk$ , , m. and total exports hk$ , , m. the main suppliers of imports in were mainland china ( Á %), japan ( Á %), taiwan ( Á %), singapore ( Á %) and usa ( Á %). in , Á % of total exports went to mainland china, Á % to the usa, Á % to japan, Á % to germany and Á % to the united kingdom. the chief import items in were: electrical machinery, apparatus and appliances, etc. ( Á %); telecommunications, sound recording and reproducing equipment ( Á %); office machines and automatic data processing machines ( Á %); articles of apparel and clothing accessories ( Á %). the main exports in were: electrical machinery, apparatus and appliances, etc. ( Á %); telecommunications, sound recording and reproducing equipment ( Á %); office machines and automatic data processing machines ( Á %); articles of apparel and clothing accessories ( Á %). in there were , km of roads, over % of which were in the new territories. there are road tunnels, including three under victoria harbour. in there were , private cars, , goods vehicles, , buses and coaches, and , motorcycles and mopeds. there were , road accidents in , of which were fatal. a total of Á m. tonnes of cargo were transported by road in . a km bridge (the world's longest sea bridge) linking hong kong, zhuhai in guangdong province in mainland china and macao opened in oct. following a number of delays. hong kong was ranked fourth for its road infrastructure in the world economic forum's global competitiveness report - . hong kong's railways are run by the mtr corporation limited (mtrcl), a public listed company of which the government is the majority shareholder. the mtr system comprises nine railway lines serving hong kong island, kowloon and the new territories. its km network has stations and carries an average of Á m. passengers each day. mtr lines carried , m. passengers in . in addition, a light rail network ( Á km and stops) serves the local communities of tuen mun, yuen long and tin shui wai in the new territories; , passengers travel daily on the system. a high speed rail service between hong kong and guangzhou on the mainland opened in sept. . the electric tramway on the northern state of hong kong island commenced operating in and has a total track length of km. the peak tram, a funicular railway connecting the peak district with the lower levels in victoria, has a track length of Á km and two tramcars (each with a capacity of passengers per trip). it carries an average of , passengers daily. the airport express line ( Á km) opened in and is also operated by the mtrcl. it carried Á m. passengers in . in june it was estimated that Á m. passenger journeys were made daily on public transport (including local railways, buses, etc.). in the world economic forum's global competitiveness report - hong kong ranked third for quality of rail infrastructure. the new hong kong international airport (generally known as chek lap kok), built on reclaimed land off lantau island to the west of hong kong, was opened on july to replace the old hong kong international airport at kai tak, which was situated on the north shore of kowloon bay. more than airlines now operate scheduled services to and from hong kong. in cathay pacific airways, the largest hong kong-based airline, operated approximately , passenger and cargo services to destinations in countries and territories around the world. cathay pacific carried , , passengers and Á m. tonnes of cargo in . dragonair, a cathay pacific subsidiary, provided scheduled services to cities in mainland china and asia in . in air hong kong, an all-cargo operator, provided scheduled services to bangkok, beijing, ho chi minh city, manila, nagoya, osaka, penang (via bangkok), seoul, shanghai, singapore, taipei and tokyo. hong kong international airport handled more international freight in than any other airport. in , , aircraft arrived and departed and m. passengers and Á m. tonnes of freight were carried on aircraft. hong kong was second, behind only singapore, in the rankings for air transport infrastructure in the world economic forum's global competitiveness report - . the port of hong kong handled Á m. teus (twenty-foot equivalent units) in , making it the world's third busiest container port after shanghai and singapore. the kwai chung container port has berths with , metres of quay backed by ha. of cargo handling area. at the end of there were , ships ( , ocean-going) of , , gt registered in hong kong. in , , ocean-going vessels, , river cargo vessels and , river passenger vessels arrived at the port of hong kong. a total of m. tonnes of freight were handled in . hong kong was ranked third in the world economic forum's global competitiveness report - for the quality of its port facilities. in there were , , main (fixed) telephone lines (equivalent to Á per , population). the local fixed telecommunications network services (ftns) market in hong kong was liberalized in . there were , , mobile phone subscriptions in (equivalent to , Á per , population), up from , , in ( , Á per , population). the number of subscriptions doubled between and . the internet market has also seen huge growth. in there were , , wireless broadband subscriptions ( Á per , population) and , , fixed broadband subscriptions ( Á per , population). the number of fixed broadband subscriptions has been declining since as more people have wireless subscriptions instead. in march there were Á m. facebook users. the external telecommunications services market has been fully liberalized since jan. , and the external telecommunications facilities market was also liberalized starting from jan. . in the adult literacy rate was Á % ( Á % in ). universal basic education is available to all children aged from six to years. in around three-quarters of the ordinary secondary day schools teaching has been in cantonese since - , with about a quarter of ordinary secondary day schools still using english. in there were , pupils in kindergartens, , in primary schools (including international schools) and , in secondary schools (including international schools). the estimated total government expenditure on education in - was hk$ Á bn. ( Á % of total government spending and Á % of gdp). in - : Á % of total government spending and Á % of gdp. according to the oecd's pisa (programme for international student assessment) study, -year-olds in hong kong rank second among oecd and other major countries and cities in mathematics and reading, and ninth in science. the three-yearly study compares educational achievement of pupils in over countries. the department of health (dh) is the government's health adviser and regulatory authority. the hospital authority (ha) is an independent body responsible for the management of all public hospitals. in there were , registered doctors, equivalent to Á doctors per , population. in there were , dentists, , nurses and , midwives. the total number of hospital beds in was , , including , beds in public hospitals under the ha and , beds in private hospitals. the bed-population ratio was Á beds per thousand population. the chinese medicine ordinance was passed by the legislative council in july to establish a statutory framework to accord a professional status for chinese medicine practitioners and ensure safety, quality and efficacy of chinese medicine. in there were , registered chinese medicine practitioners. total expenditure on health in - amounted to hk$ , m., an increase of Á % over that in - . the hong kong act of provided for hong kong ordinances to replace english laws in specified fields. the courts of justice comprise the court of final appeal (inaugurated july ), which hears appeals on civil and criminal matters from the high court; the high court (consisting of the court of appeal and the court of first instance); the lands tribunal, which determines on statutory claims for compensation over land and certain landlord and tenant matters; the district court (which includes the family court); the magistracies (including the juvenile court); the coroner's court; the labour tribunal, which provides a quick and inexpensive method of settling disputes between employers and employees; the small claims tribunal, which deals with monetary claims involving amounts not exceeding hk$ , ; and the obscene articles tribunal. while the high court has unlimited jurisdiction in both civil and criminal matters, the district court has limited jurisdiction. the maximum term of imprisonment it may impose is seven years. magistracies exercise criminal jurisdiction over a wide range of offences, and the powers of punishment are generally restricted to a maximum of two years' imprisonment or a fine of hk$ , . after being in abeyance for years, the death penalty was abolished in . , crimes were reported in , of which , were violent crimes. , people were arrested in , of whom , were for violent crimes. the population in penal institutions was , at dec. ( per , population). social welfare programmes include social security, family services, child care, services for the elderly, medical social services, youth and community work, probation, and corrections and rehabilitation. non-governmental organizations are subsidized by public funds. the government gives non-contributory cash assistance to needy families, unemployed able-bodied adults, the severely disabled and the elderly. caseload as at aug. totalled , . victims of natural disasters, crimes of violence and traffic accidents are financially assisted. estimated recurrent government expenditure on social welfare for - was hk$ Á bn. in there were daily newspapers, of which were paid-for and four free. the newspapers with the highest circulation figures are all chinese-language papers-oriental daily news, apple daily and the sun. the english-language paper with the highest circulation is the south china morning post. circulation of dailies (including free papers) in was Á m. ( Á m. paid-for and Á m. free). there were a record , , visitor arrivals in . expenditure associated to inbound tourism totalled hk$ , Á m. in . the macao special administrative region, which lies at the mouth of the pearl river, comprises a peninsula ( Á sq. km) connected by a narrow isthmus to the people's republic of china, on which is built the city of santa nome de deus de macao, the islands of taipa ( Á sq. km), linked to macao by three bridges, colôane ( Á sq. km) linked to taipa by a -km causeway, and cotai, a strip of reclaimed land between colôane and taipa ( Á km). the total area of macao in was Á sq. km. additional land continues to be reclaimed from the sea. the population at the census was , ( , females); density, , people per sq. km. according to un estimates, the entire population lived in urban areas in . the official languages are chinese and portuguese, with the majority speaking the cantonese dialect. only about , people speak portuguese as their first language. the un gives a projected population for of , . in , , foreigners were legally registered for residency in macao. there were , legal immigrants from mainland china. social statistics : births, , ( Á per , population); deaths, , ( Á ); marriages, , ( Á ); divorces, , ( Á ). infant mortality, , Á per , live births. life expectancy at birth , Á years. sub-tropical tending towards temperate, with an average temperature of Á c. the number of rainy days is around a third of the year. average annual rainfall varies from - " ( , - , mm) . it is very humid from may to sept. macao's constitution is the 'basic law', promulgated by china's national people's congress on march and in effect since dec. . it is a special administrative region (sar) of the people's republic of china, and is directly under the central people's government while enjoying a high degree of autonomy. the legislative assembly has seats of which are directly elected, indirectly elected by functional constituencies and seven appointed by the chief executive. at the elections held on sept. the macau-guangdong union won two of elected seats with Á % of votes cast and the union for development two with Á %. ten other parties won a single seat each. turnout was Á %. fernando chui sai-on was re-elected chief executive for a second term on aug. , receiving out of votes in the election committee. chief executive: fernando chui sai-on; b. (sworn in dec. and re-elected in aug. . government website: http://www.gov.mo the gaming sector is of major importance to the economy of macao. it accounted for Á % of total gdp in and provides billions of dollars in taxes. in , Á % of the workforce was employed in gaming. in gross gaming revenue totalled us$ , m. (nearly double the figure) . however, revenues were down slightly on the total. macao overtook nevada as the world's largest gaming market in . macao's traditional manufacturing industries virtually disappeared following the transfer of much of the textile industry to the chinese mainland and, in , the termination of the multifibre arrangement, which had governed international textile trade flows for three decades. the unit of currency is the pataca (mop) of avos, which is tied to the hong kong dollar at parity. inflation was Á % in and Á % in . foreign exchange reserves were us$ , m. in . total money supply was , m. patacas in . in revenues totalled , m. patacas; expenditures, , m. patacas. revenues from gaming tax accounted for Á % of total revenue in ; current expenditure accounted for Á % of expenditure. real gdp growth was just Á % in but then rose to Á % in and Á % in . more recently the economy contracted by Á % in before growing by Á % in . total gdp in was us$ Á bn. environment macao's carbon dioxide emissions from the consumption of energy in were the equivalent of Á tonnes per capita. installed capacity was Á m. kw in ; production, Á bn. kwh. macao imported , m. kwh of electricity in . oil and gas , , litres of fuel oil were imported in . the catch in was estimated at , tonnes. although the economy is based on gaming and tourism there is a light industrial base of textiles and garments. in the number of manufacturing establishments was (food products and beverages, ; textiles and wearing apparel, ; publishing, printing and reproduction of recorded media, ). in a total of , people were in employment, including , ( Á %) in gaming and junket activities (up from , in ); , ( Á %), hotels, restaurants and similar activities; , ( Á %), construction; , ( Á %), wholesale and retail trade, repair of motor vehicles, motorcycles and personal and household goods; , ( Á %), real estate and business activities; , ( Á %), public administration and social security. employment in was Á % of the labour force; unemployment rate stood at Á %. in imports (c.i.f.) were valued at us$ , Á m., of which the main products were telecommunications, sound recording and reproducing equipment; petroleum and petroleum products; and gold, silverware, jewellery and articles of precious materials. in the chief import sources (in us$ m.) were: mainland china ( , Á ); hong kong ( Á ); japan ( Á ). exports (f.o.b.) were valued at us$ Á m., of which the leading products were articles of apparel and clothing accessories; gold, silverware, jewellery and articles of precious materials; and petroleum oils and oils obtained from bituminous minerals. in the main export markets (in us$ m.) were: hong kong ( Á ); usa ( Á ); mainland china ( Á ). in there were km of roads. in there were , passenger cars in use ( cars per , inhabitants), , buses and coaches, , trucks and , motorcycles. there were fatalities in road accidents in . a km bridge (the world's longest sea bridge) linking macao, zhuhai in guangdong province in mainland china and hong kong opened in oct. following a number of delays. an international airport opened in dec. . in macau international airport handled , , passengers and , tonnes of freight (including transit cargo). in air macau flew to bangkok, beijing, changsha, chengdu, chongqing, da nang, hangzhou, hefei, kaohsiung, nanjing, nanning, ningbo, osaka, quanzhou, seoul, shanghai, shenyang, taipei, taiyuan, tokyo, wenzhou, xiamen and zhengzhou. regular services connect macao with hong kong, km to the northeast. in there were , landline telephone subscriptions (equivalent to Á per , inhabitants) and , , mobile phone subscriptions (or , Á per , inhabitants). in , Á % of households had internet access. in march there were , facebook users. there are a judicial district court, a criminal court and an administrative court with magistrates in all. in there were , crimes, of which , were against property. there were persons in prison in dec. . there are both public and private schools. in - there were schools and colleges. number of students in the - academic year (with number of teachers): pre-primary, , ( ); primary, , ( , ); secondary, , ( , ). in - there were four special education schools with pupils and teachers. there were ten higher education institutions with student enrolment of , . in there were institutions offering vocational training courses, in which participants totalled , . expenditure on education came to Á % of gdp in and Á % of total government spending in . in there were doctors, dentists and nurses working in primary health care, and doctors, dentists and , nurses working in hospitals. in there were , hospital beds; there were Á doctors per , population. in there were an estimated , folk religionists and , buddhists according to the pew research center's forum on religion & public life. a further , people were religiously unaffiliated. there are also small numbers of catholics. the historic centre of macao was inscribed on the unesco world heritage list in . in there were daily newspapers (nine in chinese, three in portuguese and two in english) and weekly newspapers (ten in chinese and one in portuguese). tourism is one of the mainstays of the economy. in there were Á m. tourists (of which Á m. were from mainland china, Á m. from hong kong and Á m. from taiwan), up from Á m. in and Á m. in . visitor spending in totalled , m. patacas. the government-run macao international music festival featuring a wide range of chinese and western music takes place in oct.-nov. in july president lee teng-hui repudiated taiwan's -year-old 'one china' policy-the pretence of a common goal of unification-arguing that taiwan and china should maintain equal 'state to state' relations. this was a rejection of beijing's view that taiwan is no more than a renegade chinese province which must be reunited with the mainland, by force if necessary. in the presidential election of march chen shui-bian, leader of the democratic progressive party, was elected, together with annette lu hsiu-lien as his vice president. both supported independence although chen shui-bian made friendly gestures towards china and distanced himself from colleagues who wanted an immediate declaration of independence. following his wife's indictment on embezzlement charges in nov. , president chen survived three parliamentary attempts to impeach him. he was succeeded as president in by ma ying-jeou of the nationalist party. in sept. chen shui-bian received a life sentence (later reduced to a -year term) after being found guilty of multiple counts of corruption. china and taiwan signed a free trade agreement in june , which was considered a significant thawing of relations. nonetheless, tensions remained, particularly in relation to disputed sovereignty over several islands in the east china sea. in jan. ma ying-jeou was re-elected to the presidency but the election in jan. was won by tsai ing-wen, whose democratic progressive party won the most seats in legislative polls at the same timethe first occasion that the nationalist party has not been the largest party in government since . the climate is subtropical in the north and tropical in the south. the typhoon season extends from july to sept. the average monthly temperatures of jan. and july in taipei are Á f ( Á c) and Á f ( Á c) respectively, and average annual rainfall is Á " ( , Á mm). kaohsiung's average monthly temperatures of jan. and july are Á f ( Á c) and Á f ( Á c) respectively, and average annual rainfall is Á " ( , Á mm). the roc constitution is based on the principles of nationalism, democracy and social wellbeing formulated by dr sun yat-sen, the founding father of the republic of china. the roc government is divided into three main levels: central, provincial/municipal and county/city, each of which has welldefined powers. the central government consists of the office of the president, the national assembly, which is specially elected only for constitutional amendment, and five governing branches called 'yuan', namely the executive yuan, the legislative yuan, the judicial yuan, the examination yuan and the control yuan. beginning with the elections to the seventh legislative yuan held on jan. the legislative yuan has members (formerly ). of the members are elected under the first-past-the-post system in singlemember constituencies, are filled by proportional representation in accordance with a nationwide party vote and six are reserved for aboriginal candidates. since the president has been directly elected. since a resolution on the impeachment of the president or vice president is no longer to be instituted by the control yuan but rather by the legislative yuan. the legislative yuan has the power to pass a no-confidence vote against the premier of the executive yuan, while the president of the republic has the power to dissolve the legislative yuan. the premier of the executive yuan is directly appointed by the president of the republic. in dec. a law came into effect allowing for referendums to be held. professional force-a process that was originally scheduled to start in and end in but has been delayed owing to low recruitment levels. defence expenditure in totalled us$ , m. (us$ per capita), representing Á % of gdp. the republic of china army conducts ground combat missions as well as air support and airborne special operations. it was estimated to number about , personnel in , with reserves numbering Á m. its principal role is to defend against a possible amphibious assault from the chinese mainland by the people's liberation army. in addition there are paramilitary forces totalling , personnel. navy personnel in totalled , , with , reservists. the forces consist of four submarines, four cruisers and frigates. there are also missile craft for patrol and coastal defence, mine-laying vehicles and amphibious landing craft. in the air force numbered , personnel with , reservists. there were combat-capable aircraft in the same year including f- es, f- s and mirage - s. taiwan has made a successful transition from an agricultural economy to one based on high-tech electronics. economic growth averaged % per year over three decades from the s, driven primarily by high value-added manufacturing and exports, especially in electronics and computers. government-owned enterprises, including banks, have been privatized. though largely escaping the impact of the asian financial crisis, the economy went into recession in with the first year of negative growth ever recorded and unemployment reaching record highs. strong export performance stimulated a recovery, with annual gdp growth above % from - . inflation has been consistently low and unemployment, which fell below % in , has averaged between and % since the turn of the century. owing to its heavy dependence on exports, taiwan suffered a severe downturn as a result of the global financial crisis in . major export industries such as semiconductors and memory chips declined, unemployment reached its highest levels since and, in , the economy again went into recession. a us$ Á bn. stimulus package boosted recovery and in the economy recorded its highest growth rate for nearly three decades, at Á %. however, growth subsequently cooled owing to lower demand from developed nations, averaging Á % per year between and . tourism has grown in importance, with over Á m. visitors in constituting taiwan's highest annual number to date. an ageing population and high savings rates threaten to constrain domestic demand in the future. the unit of currency is the new taiwan dollar (twd) of cents. gold reserves were Á m. oz in dec. . there was inflation of Á % in and Á % in . foreign exchange reserves were us$ Á bn. in dec. . in general government revenues totalled nt$ , , m. and expenditures nt$ , , m. tax revenue accounted for Á % of revenues in ; education, science and culture accounted for Á % of expenditures, economic development Á % and general administration Á %. vat is %. taiwan sustained rapid economic growth at an annual rate of Á % from up to . the rate slipped to Á % in the s and Á % in ; taiwan suffered from the asian financial crisis, though less than its neighbours. in global economic sluggishness and the events of sept. in the usa severely affected taiwan's economy, which contracted by Á %. subsequent economic recovery led to growth of Á % in and Á % in . there was negative growth of Á % in but again the economy bounced back, and grew by Á % in and Á % in . the central bank of the republic of china (taiwan), reactivated in , regulates the money supply, manages foreign exchange and issues currency. the governor is yang chin-long. the bank of taiwan is the largest commercial bank and the fiscal agent of the government. there are seven domestic banks, commercial banks and foreign banks. there are two stock exchanges in taipei. taiwan's carbon dioxide emissions from the consumption of energy in were the equivalent of Á tonnes per capita. output of electricity in was Á m. mwh; total installed capacity was , mw. there were six units in three nuclear power stations in . crude oil production in was , bbls; natural gas, m. cu. metres. taiwan imports most of the oil and natural gas that it consumes. in the cultivated area was , ha., of which , ha. were paddy fields. rice production totalled , , tonnes. livestock production was valued at nt$ , m., accounting for % of taiwan's total agricultural production value. forest area, : , , ha. forest reserves: trees, , , cu. metres; bamboo, , m. poles. timber production, , cu. metres. the catch in was , tonnes, almost exclusively from sea fishing. the largest companies in taiwan by market capitalization in march were: taiwan semiconductor manufacturing (us$ Á bn.); hon hai precision industry, an electronics manufacturer (us$ Á bn.); and chunghwa telecom (us$ Á bn.). output (in tonnes) in : crude steel; Á m.; cement, Á m.; cotton fabrics, Á m. sq. metres; integrated circuit packages, Á trn. units; global positioning system (gps) sets, Á bn. units. in the average total labour force was Á m., of whom Á m. were employed. of the employed population, Á % worked in manufacturing; Á % in wholesale and retail trade; Á % in construction; Á % in accommodation and food services; Á % in education; Á % in agriculture, forestry and fisheries. the unemployment rate was Á %. in there were , km of roads. in , Á m. passenger cars, , buses and coaches, Á m. lorries and vans, and Á m. motorcycles and mopeds were in use. , m. passengers and m. tonnes of freight were transported in . there were , fatalities in road accidents in . in freight traffic amounted to Á m. tonnes and passenger traffic to m. total route length was , km. there are metro systems in taipei (opened in ) , kaohsiung (opened in ) and taoyuan (opened in ). there are currently two international airports: taiwan taoyuan international airport at taoyuan near taipei, maritime transportation is vital to the trade-oriented economy of taiwan. in jan. there were ships of gt or over registered, totalling Á m. gt. of the vessels registered, were general cargo ships, bulk carriers, container ships, oil tankers and nine passenger ships. there are six international ports: kaohsiung, keelung, taichung, hualien, anping and suao. the first three are container centres, kaohsiung handling Á m. -ft equivalent units in , making it the world's th busiest container port in terms of number of containers handled. suao port is an auxiliary port to keelung. in jan. the first legal direct shipping links between taiwanese islands and the chinese mainland in more than years were inaugurated. in there were , , landline telephone subscribers ( Á per , inhabitants). taiwan's biggest telecommunications firm, the stateowned chunghwa telecom, lost its fixed-line monopoly in aug. . in there were , , mobile phone subscriptions, equivalent to , Á per , persons. in there were Á mobile broadband subscriptions per inhabitants and Á fixed broadband subscriptions per inhabitants. in march there were Á m. facebook users. the judicial yuan is the supreme judicial organ of state. comprising grand justices, since these have been nominated and, with the consent of the legislative yuan, appointed by the president of the republic. the grand justices hold meetings to interpret the constitution and unify the interpretation of laws and orders. there are three levels of judiciary: district courts and their branches deal with civil and criminal cases in the first instance; high courts and their branches deal with appeals against judgments of district courts; the supreme court reviews judgments by the lower courts. there is also the supreme administrative court, high administrative courts and a commission on the disciplinary sanctions of public functionaries. criminal cases relating to rebellion, treason and offences against friendly relations with foreign states are handled by high courts as the courts of first instance. the death penalty is still in force. there were no executions in but there was one in . the population in penal institutions in april was , ( per , of national population). since there has been compulsory education for six to -year-olds with free tuition. the illiteracy rate dropped from Á % in to Á % by . there were , primary schools, , secondary schools and vocational schools in ; and universities, colleges and junior colleges. in - there were , , pupils with , teaching staff at elementary schools; , pupils and , teaching staff at junior high schools; , pupils and , teaching staff at senior high schools; and , students and , teaching staff at senior vocational schools. there were , , students in universities and colleges in - with , academic staff. in there were , physicians (one for every persons), , doctors of chinese medicine, , nurses, , dentists and assistants, and , pharmacists and assistants. in there were , medical facilities serving , persons per facility; there were , beds and Á beds per , persons. in cancers, heart diseases, cerebrovascular diseases, diabetes and accidents were the first five leading causes of death. a universal health insurance scheme came into force in as an extension to social insurance plans that cover only % of taiwan's population. premium shares among the government, employer and insured are varied according to the insured statuses. by the end of , Á m. people or % of the population were covered by the national health insurance programme. according to estimates by the pew research center's forum on religion & public life, Á % of the population in were folk religionists, Á % were buddhists and Á % christians. the remainder of the population was either religiously unaffiliated or followed other religions, including taoism. there were daily newspapers in with a circulation of Á m. and non-dailies with a circulation of Á m. the biggest circulation dailies are the liberty times and apple daily. in there were , , international visitors. receipts totalled us$ , m. the pop festival, spring scream, is held in april in kenting. xinjiang tianshan ( ), a mountainous site comprising four components covering , ha. and an important habitat for endemic and relic flora species, the grand canal ( ), a vast waterway system running from beijing to zhejiang, tusi sites ( ), the remains of tribal domains whose leaders were appointed by the central government as 'tusi', hereditary rulers of their regions from the th to the early th century, located in southwest china prime minister and president of the executive yuan: su tseng-chang vice premier: chen chi-mai. there are ministries under the executive yuan: culture; economic affairs; education; finance; foreign affairs; health and welfare; interior; justice; labour; national defence; science and technology minister of culture: cheng li-chiun examples include the mongolian and tibetan affairs commission; the mainland affairs council; the fair trade commission; the public construction commission; and the financial supervisory commission. some of these are headed by ministers without portfolio (see above). other commissions, councils and agencies are headed by: council of agriculture: chen chi-chung mainland affairs council: chen ming-tong. national communications commission: chan ting-i. ocean affairs council: lee chung-wei. overseas community affairs council: wu hsin-hsing. directorate general of personnel administration: shih ning-jye. transitional justice commission (acting): yang tsui. veterans' affairs council: chiu kuo-cheng china in world history chinese politics in the age of deng xiaoping china and the global political economy china: the rise of xi jinping the cambridge encyclopaedia of china the cambridge history of china. vols the politics of hong kong's reversion to china the european union and china the chinese economy under transition china this century the tragedy of liberation: a history of the chinese revolution china: a modern history china's deep reform: domestic politics in transition chinese capitalism deng xiaoping and the making of modern china the great chinese revolution - the politics of eu-china economic relations china's second continent: how a million migrants are building a new empire in africa china in transition: communism, capitalism and democracy sowing the seeds of democracy in china: political reform in the deng xiaoping era historical dictionary of the chinese cultural revolution how the chinese economy works the rise of modern china china: a macro history tombstone: the untold story of mao's great famine china's economy: what everyone needs to know all under heaven: a complete history of china chinese politics in the hu jintao era: new leaders, new challenges the people's republic of amnesia: tiananmen revisited chinese foreign policy in a changing world chinese economy in the s the politics of china: sixty years of the people's republic of china the party: the secret world of china's communist rulers. .-asia's reckoning: china, japan and the fate of us power in the pacific century china's war with japan, - : the struggle for survival social and political development in post-reform china age of ambition: chasing fortune, truth and faith in the new china a revolutionary life at the crossroads of post-communist modernisation: russia and china in comparative perspective a history of china wealth and power: china's long march to the twenty-first century mao's road to power: revolutionary writings - . vols china goes global: the partial power the chinese century: the rising chinese economy and its impact on the global economy, the balance of power, and your job the china-pakistan axis: asia's new geopolitics the chan's great continent: china in western minds eldest son, zhou enlai and the making of modern china china in the xi jinping era india's and china's recent experience with reform and growth critical issues in contemporary china making china strong tide players: the movers and shakers of a rising china other more specialized titles are listed under territory and popula-tion; tibet; agriculture . commissioner: ning jizhe information: the census and statistics department is responsible for the preparation and collation of government statistics. these statistics are published mainly in the hong kong monthly digest of statistics. the department also publishes monthly trade statistics, economic indicators and an annual review of overseas trade hong kong's transitions the politics of hong kong's reversion to china the end of hong kong: the secret diplomacy of imperial retreat the hong kong story the final years of british hong kong: the discourse of colonial withdrawal last post: the end of empire in the far east the politics of democratization in hong kong historical dictionary of hong kong and macau china: a political history of the british crown colony's transfer to chinese rule managing china's sovereignty in hong kong and taiwan macau, the imaginary city: culture and society, to the present taiwan statistical yearbook of the republic of china. annual. the republic of china yearbook. annual. taiwan statistical data book. annual. annual review of government administration the other taiwan: to the present day historical dictionary of taiwan national identity and status in international society taiwan's political re-alignment and diplomatic challenges managing china's sovereignty in hong kong and taiwan the shadow of china: political developments in taiwan since . national library: national central library key: cord- -gd phncm authors: chuo, hsin-you title: theme park visitors’ responses to the sars outbreak in taiwan date: - - journal: nan doi: . /s - ( ) - sha: doc_id: cord_uid: gd phncm the purpose of this study is to examine empirically different characteristics between theme park visitors who did and did not visit theme parks during the sars outbreak period in taiwan. the data consisting of , respondents were obtained from visitors to the five leading theme parks. discriminant analysis was used to analyze respondents’ characteristics such as age, benefit sought, product involvement, and risk perception to examine significant differences between the two categories of respondents. results of this study showed that younger or more frequent visitors more likely continued to visit theme parks during the sars outbreak. besides, visitors who continued to visit theme parks perceived greater infectious risk than those who did not visit theme parks during the sars outbreak. severe acute respiratory syndrome (sars), caused by the previously unrecognized coronavirus (sars-cov), is a highly contagious febrile respiratory illness and also associated with a high mortality rate. it is the first severe and readily transmissible new disease to emerge in the st century. dr. carl urbani, a advances in hospitality and leisure, volume , - copyright r by elsevier ltd. all rights of reproduction in any form reserved issn: - /doi: . /s - ( ) - world health organization (who) epidemiologist working in vietnam, submitted a report to the wto, an affiliation of the united nations, and identified/named this unknown disease ''sars'' initially in march for the cases with the onset in february of (who, a , however, the health authority in china named the disease ''atypical pneumonia'' (or feidian, the shortened version of its full chinese name) instead (wang, ) . the first cases of sars are now known to have emerged in mid-november in guangdong province, china. on february , , an infected medical doctor (dr. liu) left guangdong province and visited hong kong for attending a wedding reception. dr. liu stayed at the metropole hotel in hong kong and infected a number of tourists from several parts of the world (who, b) . subsequently, the disease began spreading around the world along international air travel routes. a few days later, hospitals in hong kong, vietnam, and singapore began reporting cases. by late february , sars was considered an emerging disease (who, a) . from sars' appearance in november to july , , when the who declared that owing to the outbreak more than , individuals were infected by and victims died from the disease (who, c) . most sars cases have occurred in mainland china, hong kong, taiwan, and canada. mainland china reported the largest number of sars infections ( , ) and deaths ( ), followed by hong kong ( , ; ) and taiwan ( ; ) (cdc, ; who, c) . consequently, sars caused considerable social disruption and public anxiety, even in area well beyond the outbreak sites (who, d) . in terms of the number of sars infections and deaths, the severity of the outbreak might seem to be overstated and people's responses might look like over-reacting. in contrast to tuberculosis ( , people infected and , dead per year), or car accidents ( , people injured and killed in the first months of ), sars killed ''only'' patients in taiwan (chen, jang, & kim, ) . accordingly, some scholars (e.g., chen et al., ; mckercher & chon, ) point out that people were over-reacting to the sars epidemic and tourism suffered unnecessary damage. however, it seems more interesting and necessary to realize factors out of the cumulative number of fatal cases that caused an enormous panic -which subsequently resulted in the over-reactions. the sars epidemic has been characterized by its rapid spread. hsieh, chen, and hsu ( ) synthesize official reports and describe the rapid spread of the sars outbreak in taiwan in detail. the who reported , probable sars cases with deaths worldwide on april , ; china, hong kong, singapore, vietnam, and toronto, canada, had the most cases. taiwan, meanwhile, had probable cases and no deaths. seventyeight percent of the cases were imported. the growth of the numbers of sars infections seemed to be a typical minor outbreak at that time. on that day, a new cluster of seven infections in hoping hospital in taipei was reported and it started a chain of local transmissions that cumulated in probable cases and deaths in the following two weeks. by mid-may, the numbers grew to probable cases and deaths. subsequently, by june , it expanded into probable cases and deaths. in a period of less than one month, more than a sixfold increase in the numbers of sars infections and victims was erupted rapidly in taiwan. the rapid increase rates of reported probable sars case-patients and deaths undoubtedly would cause a panic nationwide in taiwan. in addition to the rapid increase rate of reported probable sars casepatients, the nationwide panic in taiwan might also be resulted from a sense of the endless and uncontrolled expansion of the outbreak. as the disease was spreading so rapidly, the health authority in taiwan enforced many stringent measures in order to contain the outbreak. in addition to thermal scanning arrivals from abroad to check for signs of fever induced by sars, hsieh et al. ( ) indicate two of the most important stressed measures. one measure was reporting, admitting, and hospitalizing all susceptible patients. the other was the house quarantine of people either those with contacts to the suspected case-patients or arrivals from the affected areas abroad. however, on the first hand, hospitals in taiwan were initially unprepared for and unprotected from the sars disease. the patient quarantine rooms, personal protective equipments for health care workers, and general infection control, etc., which had been improved and well prepared professionally later (esswein et al., ) , were relatively insufficient at the beginning of the outbreak. since frequent unprotected or inadequately protected patient-to-health care worker interactions and grouping large numbers of ill persons can greatly amplify intrahospital transmission (gopalakrishna et al., ) , almost percent of all traceable infections in taiwan occurred in hospital settings (hsieh et al., ) . it caused inevitably a panic among all medical professions on the frontline in the battle against sars. on the other hand, the home quarantine of a number of susceptible people was frequently broken (hsieh et al., ) . just as the acquired immune deficiency syndrome (aids), it cannot be considered quarantineable not only because of medical but also because of ethical and legal issues (gensini, yacoub, & conti, ) . accordingly, a sense of uncontrollability was emerged publicly at the beginning of the sars outbreak. furthermore, the local sensationalist media accelerated and amplified the resulted panic from the sense of uncontrollability successfully by focusing their attention on some intrahospital transmission and out-of-supervised quarantine cases. this phenomenon was consistent with mason, grabowski, and du's ( , p. ) description of the global media that the media were much less interested in providing accurate information and more concerned with selling copies of their publication through sensationalist but inaccurate stories. aside from the domestic factors, i.e., the rapid increase rate of sarsinfected cases and a sense of out-of-control, it should be noted that there was an international factor as well. the international factor played a significant role in the enforcement of not only a nationwide panic in taiwan but also a worldwide panic to the sars epidemic. in order to minimize the global spread of sars, the who issued a series of specific travel advisories -recommending travelers to postpone all but essential travel to designated areas where the risk of exposure to sars was considered high -against hong kong, china, toronto, and taiwan, respectively from april to may and especially a ''general travel advisory'' to potential travelers on march , (who, d . the travel advisories did trigger a chain reaction of public anxiety even in areas well beyond the outbreak sites. the announcements were unprecedented in the who's almost -year history, for this was the first time that the organization had issued advisories for specific geographical areas due to an outbreak of an epidemic (wttc, ) . although the recommendations were respectively removed by the who from all the designated areas to which they had applied as the sars outbreak was successfully curtailed in late june, the hospitality and tourism industry in asia had been severely hit by the outbreak of the sars epidemic. while it must be praised for the who's substantial actions in controlling the sars outbreak, strong criticism from authorities of the ''off-limits'' areas, tourism industry, and scholars was directed at the organization. mckercher and chon ( ) indicate that the who's travel advisories criticism was instrumental in triggering the almost complete eradication of tourism in asia. based on the costs of canceled travel and decreased investment in asia, the economic costs have been estimated ranging from us$ , million to us$ , (who, d) . it is even estimated to produce costs that might rival the asian financial crisis of the mid- s (de lisle, ) . lakshmanan ( ) (as cited by mckercher & chon, ) well describes the very unusual feature of the sars outbreak by a statement that ''a panic spread faster than the disease itself.'' most likely, it was partly contributed by the participation of the global media as a role of accelerators and amplifiers in the spread of the worldwide panic. since the who publicized its message about sars and travel warning by using the global media, however, it could not write word-for-word the article or website commentary, the organization could hardly control the tone or precise nature of any media communication. accordingly, mason et al. ( ) point out that the way the who's global health alert was reported by the world's media is also likely to have contributed to the feeling of worldwide panic. tourism industry is still threatened by the possibility of the recurrence of the infectious disease since the who has warned that sars might recur. besides, there will be new biological threats whether sars reappears or not. therefore, during the post-outbreak period, one of the most significant recovery efforts that marketing managers in the tourism industry can make is to know what kind of customers continued to patronize their services during the outbreak period. from customers' different patronage decisions in response to the sars outbreak, they can learn valuable lessons and develop a plague survival strategy for possible emerging epidemic outbreaks in the future. particularly, if customers who continued to patronize a hospitality/ tourism service during the sars outbreak can be distinguished and identified from those who did not, marketing managers may be able to increase their efforts to attract the most potential customers in case the sars or similar biological crises emerge someday. drawing on insights from crisis management literature, not only the proactive, strategic, holistic approaches to the issue of crises have been proposed and discussed (e.g., ritchie, ) , but generic or specific models for analyzing and developing management strategies have also been proposed (e.g., faulkner, ; huang & min, ) . aside from the underlying efforts, various crisis cases have been explored, investigated, analyzed, and discussed. chen ( ) examined asian outbound travelers' consumption patterns after the asian economic crisis and provided marketing strategies for international tourism practitioners. blake and sinclair ( ) examined policy responses to the september terrorist attacks in the united states and suggested some ways of handling the situation to policymakers. page, yeoman, munro, connell, & walker ( ) illustrated complex issues associated with a flu pandemic qualitatively via a case study of scenario planning exercise. to the impacts of the sars outbreak, a number of researchers devoted efforts to the formulation of proactive and recovery management in the tourism industry. while some (e.g., chen et al., ; dombey, ; mckercher & chon, ; pine & mckercher, ) revealed the impacts of the sars effects on diverse aspects of the managerial functions, on various sectors of the industry, and/or on different geographical areas, some others (e.g., chien & law, ; henderson & ng, ; tse, so, & sin, ) suggested substantial processes to set up contingency and recovery arrangements for hotel and restaurant management specifically. the purpose of this study is to examine empirically different characteristics between theme park visitors who did and did not visit theme parks during the sars outbreak period in taiwan. significant differences between the two categories of respondents on their characteristics such as age, patronage frequency in the last year, benefit sought, product involvement, and risk perception were examined. accordingly, the following four research questions were developed: . can a significant discriminant function be developed to interpret the differences between respondents who did and did not visit theme parks during the sars outbreak period in taiwan on the basis of their personal characteristics? . which characteristics contribute to most of the inter-group differences? . how accurately can respondents be classified into the two categories by the developed discriminant function? . what marketing implications can be derived from theme park visitors' different patronage decisions in response to the sars outbreak? the target population for this study was visitors to the five leading theme parks in taiwan (i.e., jenfusan, leofoo, yamay, formosan aboriginal culture village, and window on china). quota sampling technique was employed to select elements of the research sample from the sampling population based on the official report (tourism bureau, ) on annual attendance to domestic theme parks in taiwan in . in order to minimize respondents' recall errors, the field survey for data collection was conducted during the period between june and july in since the who extended its travel recommendation to include taiwan on may and removed it from the list of postpone-travel areas on june . junior students from a local university were trained as interviewers for data collection. interviewers stationed near the exit gates of the five parks invited departing visitors to participate in this study. all subjects were selected based on their willingness to volunteer their personal information on site. a structured-undisguised questionnaire was developed for data collection. in addition to the information of respondents' general demographics, their patronage frequency in the last year and whether they visited theme parks in the period of the sars outbreak, the question content also consisted of scale items to measure ''benefit sought,'' ''product involvement,'' and ''risk perception.'' ten individual benefit scale items were derived from pearce's ( ) leisure ladder model for theme park visitors. respondents were asked to rate each of the benefit items from '' '' to '' '' to indicate the extent to which the benefit motivated them to make the current visits. in the specific interests of this study, mcquarrie and munson's ( ) eight scale items for the measurement of consumers' ''enduring involvement'' with a product were modified to measure respondents' product involvement with theme parks in this study. the ''many factors'' described in the seventh scale item ''i usually take many factors into account before purchasing this product'' were replaced by ''admission fee'' and ''the distance a theme park is from my home,'' respectively. as a result, nine involvement measure items with a five-point likert scale were designed in the questionnaire. finally, respondents were asked to subjectively estimate the probability a person will be infected with sars in each of the three given scenarios, respectively. the given scenarios were: ( ) right now in the theme parks which they had just departed from; ( ) participating in outdoor recreational activities if the who should again extend its postpone-travel recommendation to include taiwan; and ( ) visiting a theme park in the same period of time described in the second scenario. respondents were asked to rate the sars-infected possibility in each of the scenarios in terms of percentage (from '' '' to '' ''). in order to develop a meaningful discriminant function, possible correlations between respondents' personal characteristics had to be avoided or eliminated first. accordingly, variables representing each of the respondents' personal characteristics were condensed into factors by the technique of principal components analysis. internal consistency reliability of the variables contained in each of the factors was assessed. a value of cronbach's alpha coefficient greater than . generally indicates satisfactory internal consistency reliability (malhotra, ) . mean of respondents' ratings to consistent variables contained in each of the factors served as the input score of the factor in the process of discriminant analysis. thus, on the one hand, whether or not the respondents visited theme parks during the sars outbreak was adopted to be the dependant (criterion) variable; on the other, respondents' age, their patronage frequency in the last year, and the factors condensed from scale items of respondents' risk perception, benefit sought, and product involvement were adopted to be the independent variables (predictors) in the developing discriminant function. the significance and validity of the function were assessed based on wilks' l test and the percentage of cases correctly classified, respectively. spss was utilized for data processing and the level of significance of . was accepted for all statistic tests in this study. by using quota sampling technique, a research sample consisting of , respondents was obtained from visitors to the five leading theme parks. table shows that the distribution patterns of the respondents' demographics were consistent with the practical observation of theme park visitors' characteristics in the real world. respondents' age ranged from to years, with the mean age of . years (s.d. ¼ . ). they had been to the five theme parks ranging from to times and for an average of . times (s.d. ¼ . ) in the last year. the correlation matrices of the benefit and involvement scale items in the procedure of principal components analysis were examined by bartlett's test of sphericity. to the benefit scale items, the approximate w statistic was . with degrees of freedom, which is of . significance. besides, the value of the kmo statistic (. ) was also large (>. ). to the involvement scale items, the approximate w statistic was . with degrees of freedom, which is also of . significance and the value of the kmo statistic was . . therefore, the procedure of principal components analysis was considered an appropriate technique for analyzing the data in this study. in order to differentiate between the two categories of respondents, a discriminant function was developed in this study. at first, seven independent variables for the subsequent discriminant analysis were identified through the analytical procedures of principal components analysis and cronbach's alpha test. tables and show the results of principal components analysis. ten benefit scale items and nine involvement scale items were condensed into two benefit factors and two involvement factors, were examined to ensure satisfactory internal consistency reliability and then accepted into the discriminant analysis. as a result, the developed standard canonical discriminant function was: where if di>. , classify individual i as belonging to ''visitors who did visit theme parks during the sars outbreak''; otherwise classify individual i as belonging to the other category. the eigenvalue associated with this function is . , and it accounts for percent of the explained variance. the canonical correlation associated with this function is . . it indicates that the variance in the dependent variable is not largely explained by this model. however, the wilks' l associated with the function is . , which transforms to a w of . with degrees of freedom. this is significant beyond the . level. in other words, the discriminant function is statistically significant. therefore, it is meaningful to interpret the results of the discriminant analysis. table shows the primary results of the discriminant analysis. the significance of the univariate f ratios indicates that when the independent variables are considered individually, only the respondents' age, their patronage frequency, and risk perception were significant predictors in discriminating between the groups. besides, the pooled within-groups correlation matrix indicates low correlations between the independent variables. in this case, multicollinearity was unlikely to be a problem. given low intercorrelations between the independent variables in table , independent variables with relatively large standardized coefficients contribute more to the discriminating power of the function, as compared with independent variables with smaller coefficients. therefore, respondents' age and their patronage frequency in the last year contribute to most, while respondents' risk perception also contributes to some, of the inter-group differences. the signs of the coefficients associated with the significant predictors suggest that younger age and more experience in visiting theme parks were more likely to result in the respondents visiting theme parks during the sars outbreak. meanwhile, individuals who visited theme parks during the sars outbreak were also associated with higher risk perception. table shows the classification results based on the developed discriminant function. the percentage of cases correctly classified is . percent. the function seems to be of deficient validity if one expects the function to distinguish individuals who had been to theme parks during the sars outbreak from those who had not, since the predictability of the function is only percent greater than that obtained by chance (i.e., / ¼ . or percent). generally speaking, in this study, a statistically significant discriminant function was successfully developed to interpret the differences between respondents who did and did not visit theme parks during the sars outbreak period in taiwan on the basis of their personal characteristics. among the seven adopted characteristics, respondents' age and their patronage frequency in the last year contributed to most of the inter-group differences. moreover, individuals who visited theme parks during the sars outbreak were also associated with higher risk perception. substantial marketing implications can be explored based on the results of the discriminant analysis, although the function seems to be of deficient validity in terms of predictability. first of all, in case the sars or similar biological crises emerge in the future, younger and/or frequent consumers should be the focused targets of theme park managers' primary marketing efforts because they are more likely to continue to visit theme parks during the period of epidemic outbreak. accordingly, a plague survival strategy can be developed with the goal of attracting consumers from the targets. since the benefits sought by theme park visitors played only a trivial role in their patronage decisions during the sars outbreak, contents of the promotion projects may not be associated with or restricted to particular benefits of visiting theme parks. instead, a series of sales promotions, such as special promotional prices for the admission of large teen groups, cross-promotions with firms providing other products or services to young consumers, or discounted season passes for potential heavy-users, may help theme parks survive the period of epidemic outbreak. one of the results of this study indicates that individuals who continued visiting theme parks during the sars outbreak were associated with higher risk perception in comparison with those who did not visit theme parks. it is interesting to note that grobe and douthitt ( ) also obtained similar findings from their research regarding milk consumers' risk perception of the recombinant (synthetic) bovine growth hormone (rbgh). their findings indicated that consumers who purchase more milk perceive a greater risk than those who purchase less (p. ). however, they did not explain the findings of their research. in fact, the theme park visitors' continued patronage or the milk purchasers' greater consumption resulted in, rather than resulted from, their greater risk perception. in detail, the consistent theme park patronage during the sars outbreak and milk consumption under the purchasers' psychological resistance to the rbgh injection seem to be caused by individuals' relatively inelastic demands for theme parks or milk. in order to build lasting customer relationships, managers should compensate the customers with inelastic demands for their consistent patronage rather than take advantage of them since there are usually a couple of brands or selections for a particular product. therefore, in case the sars or similar biological crises emerge in the future, the present seems to be the perfect time to build up a valuable database consisting of the customers with inelastic demands for particular hospitality and tourism services. thus, service providers may continuously benefit from the database. the finding that visitors' risk perception of the sars infection did not largely contribute to their patronage decisions during the sars outbreak provides indirect evidence that theme park visitors' ''risk attitude'' dominated their ''risk perception'' in their risk response behavior to the sars epidemic. pennings, wansink, and meulenberg ( ) proposed that the behavior of consumers in a crisis situation can be explained by a combination of risk perception and risk attitude. whereas risk attitude deals with consumers' interpretation of the content of the risk, the seriousness of adverse consequences, or the extent of risk aversion toward a particular crisis, risk perception instead deals with consumers' interpretation of the chance of being exposed to the content of the risk. since individuals with greater risk perception were the ones who continued to visit theme parks while those with lower risk perception tended to avoid the patronage, risk perception does not seem to be the dominant motivator of theme park visitors. suppose that risk attitude is the true motivator behind theme park visitors' responses to the sars outbreak. in such a case, pennings et al. suggest that even if the probabilities of being exposed to the risk are small, effectively communicating these probabilities will have little influence on consumer behavior. instead, marketers will have to focus on ways to eliminate the risk. chien and law ( ) suggested substantial processes to minimize hotel employees and guests' possibility of sars infection and to contain the potential spread of viruses on the hotel property. the processes can also be well utilized by other businesses or services in the hospitality and tourism industry. in addition to actually implementing the processes of risk elimination, it is equally important that management should make efforts to let the potential consumers know and let the customers see, smell, hear, and feel the processes of risk elimination on the property. based on the findings and limitations of this study, several recommendations for further research can be drawn. first, the roles that both risk perception and risk attitude play in people's responses to severe epidemics or similar biological crises can be further explored. extended from the existing related literature, the following research might be expected to establish a theoretical model -consisting risk perception, risk attitude, and other significant variables -of people's responses to disease outbreaks. second, although the significant role of the media in the sars outbreak has been well discussed in mason et al. ( ) in terms of the amount of media attention given to the outbreak along the five stages of hall's ( ) ''issue-attention cycle,'' given a strong averse risk attitude toward particular epidemics or pandemics, issues regarding how and what the media can communicate effectively to the public to have significant influence on their responses to the disease outbreak can be further investigated by the following research. however, it might be even more important to know how to allure or encourage the media to cease rather than amplify social panic by the above approaches. the singapore case -a well-trusted institute (e.g., tourist board) coordinates related media and tourism sectors to establish a taskforce and working with the national health authority to produce guidelines and to have a hold over the social panic -indicated in henderson ( ) might not work applicably in elsewhere, however, it did provide a sample of possible domestic problem-solving mechanism. based on the basic framework, a possible international cooperation mechanism might be further discussed and developed. it is clear that the international hospitality and tourism industry will always benefit from researchers' continuing efforts to confront any possible emerging industry crises in the future. the efforts provide effective suggestions to either the management practitioners or the public policymakers during and after a certain crisis emergence in the industry. tourism crisis management: us response to use of quarantine to prevent transmission of severe acute respiratory syndrome: taiwan examining asian outbound travelers' consumption patterns after the asian economic crisis the impact of the sars outbreak on taiwanese hotel stock performance: an event-study approach the impact of the severe acute respiratory syndrome on hotels: a case study of hong kong atypical pneumonia and ambivalent law and politics: sars and the response to sars in china the effects of sars on the chinese tourism industry environmental and occupational health response to sars towards a framework for tourism disaster management the concept of quarantine in history: from plague to sars sars transmission and hospital containment consumer acceptance of recombinant bovine growth hormone: interplay between beliefs and perceived risks travel safety and the media: the significance of the issue-attention cycle managing a health-related crisis: severe acute respiratory syndrome (sars) in singapore responding to crisis: severe acute respiratory syndrome (sars) and hotels in singapore sars outbreak earthquake devastation and recovery in tourism: the taiwan case hong kong's fear of sars spreading faster than the disease itself: % residents wearing surgical masks marketing research: an applied orientation severe acute respiratory syndrome, tourism and the media the over-reaction to sars and the collapse of asian tourism a revised product involvement inventory: improved usability and validity a case study of best practice-visit scotland's prepared response to an influenza pandemic fundamentals of tourist motivation a note on modeling consumer reactions to a crisis: the case of the mad cow disease the impact of sars on hong kong's tourism industry chaos, crises and disasters: a strategic approach to crisis management in the tourism industry report on tourism statistics crisis management and recovery: how restaurants in hong kong responded to sars china's response to sars severe acute respiratory syndrome (sars): status of the outbreak and lessons for the immediate future severe acute respiratory syndrome (sars): report by the secretariat (provisional agenda item . , eb / ) singapore and vietnam reports). london: world travel and tourism council this study reveals that younger or more frequent visitors more likely continued to visit theme parks during the sars outbreak period. in addition to the substantial suggestions on possible adjustments of marketing mix, some implications can be emerged from the findings and discussion of this study. it should be firstly noted that, during a plague outbreak, the impact against tourism industry is primarily generated by the panic resulted from the plague rather than by the plague itself. the dominant determinant in the formulation of the plague-resulted panic tends to be the magnitude of people's aversion (risk attitude) to the plague rather than the perceived possibility to be infected by the plague (risk perception). by the back-up of the media, the scale and spread of possible emerged panic tends to be amplified and accelerated extensively. if a panic has been prevailed, it might be an inevitable outcome that people tend to over-react in their responses to a plague outbreak. people's over-reactions might be represented by decreasing the amount of consumption or even the collapse of regional tourism. according to the subsequence of a plague-outbreak crisis emerging from the discovery and identification of an epidemic to possible damages suffered by tourism industry, several critical points between different stages of the crisis progression can be found. in terms of crisis management, if the critical points can be well monitored and managed, the situation will be substantially better off. key: cord- -kenstpja authors: nan title: china date: journal: the statesman&#x ;s yearbook doi: . / - - - - _ sha: doc_id: cord_uid: kenstpja nan yuan dynasty in , swept into southern china. the mongol yuan dynasty adopted chinese ways but was overthrown by a nationalist uprising in , led by hongwu ( - ), a former beggar who established the ming dynasty. the ming empire collapsed in a peasants' revolt in . the capital, beijing (peking), was only km from the great wall and vulnerable to attack from the north. within months the peasants' leader was swept aside by the manchus, whose qing dynasty ruled china until . preoccupied with threats from the north, china neglected its southern coastal frontier. the portuguese, who landed on the chinese coast in , were followed by the dutch in and the english in . the qing empire expanded into mongolia, tibet, vietnam and kazakhstan. but by the th century, under pressure from rural revolts ignited by crippling taxation and poverty, the qing dynasty was crumbling. two opium wars ( - ; - ) forced china to allow the import of opium from india into china, while britain, france, germany and other european states gained concessions in 'treaty ports' that virtually came under foreign rule. the taiping rebellion ( - ) set up a revolutionary egalitarian state in southern china. the european powers intervened to crush the rebellion and in british and french forces invaded beijing and burnt the imperial palace. further trading concessions were demanded. a weakened china was defeated by japan in and lost both taiwan and korea. the xenophobic boxer rebellion, led by a secret society called the fists of righteous harmony, broke out in . the guangxu emperor attempted modernization in the hundred days reform, but was taken captive by the conservative dowager empress cixi who harnessed the boxer rebellion to her own ends. the rebellion was put down by european troops in . china was then divided into zones of influence between the major european states and japan. with imperial authority weakened, much of the country was ripe for rebellion. in the kuomintang (guomintang or nationalist movement) of sun yet-sen (sun zhong shan; - ) overthrew the imperial system. the authoritarian yuan shih-kai ruled as president from to . following the overthrow of yuan, china disintegrated into warlord anarchy. in sun founded a republic in southern china but the north remained beyond his control. reorganizing the nationalist party on soviet lines, sun co-operated with the communists to re-establish national unity. but rivalry between the two parties increased, particularly after the death of sun in . after sun's death the nationalist movement was taken over by his ally chiang kai-shek (jiang jie shi; - . as commander in chief of the nationalist army from , chiang's power grew. in april his campaign to suppress the chinese communist party saw thousands of communists slaughtered. the survivors fled to the far western province of jiangxi. in chiang's army entered beijing. with the greater part of the country under chiang's rule, he made nanjing the capital. in the communists were forced to retreat from jiangxi province. led by mao zedong (mao tse-tung; - they trekked for more than a year on the , -mile long march, eventually taking refuge in shaanxi province. in the japanese invaded manchuria. by they had seized beijing and most of coastal china. the nationalists and communists finally co-operated against the invader but struggled against the superior japanese forces. during the second world war , a nationalist government ruled unoccupied china ineffectually from a temporary capital in chongqing. at the end of the war, nationalist-communist co-operation was short-lived. the soviet union sponsored the communist party, which marched into manchuria in , beginning a civil war that lasted until . although the nationalist forces of chiang kai-shek received support from some western countries, particularly the united states, the communists were victorious. on oct. mao declared the people's republic of china in beijing. chiang fled with the remains of his nationalist forces to taiwan, where he established a government that claimed to be a continuation of the republic of china. at first recognized as the government of china by most western countries, taiwan kept china's security council seat at the united nations until . chiang's authoritarian regime was periodically challenged by red china, which bombed taiwan's small offshore islands near the mainland. in the s and s, taiwan gradually lost recognition as the legitimate government and in the usa recognized the people's republic of china. in china invaded tibet, independent since . chinese rule quickly alienated the tibetans who rebelled in . the tibetan religious leader, the dalai lama, was forced to flee to india. since then, the settlement of large numbers of ethnic chinese in the main cities of tibet has threatened to swamp tibetan culture. during the s and s china was involved in a number of border disputes and wars in neighbouring states. the communists posted 'volunteers' to fight alongside communist north korea during the korean war . there were clashes on the soviet border in the s and the indian border in the s, when china occupied some indian territory. from the establishment of the people's republic of china, communist china and the soviet union were allies. communist china initially depended upon soviet assistance for economic development. a soviet-style five-year plan was put into action in , but the relationship with moscow was already showing signs of strain. by the end of the s the soviet union and china were rivals, spurring the chinese arms race. chinese research into atomic weapons culminated in the testing of the first chinese atomic bomb in . mao introduced rapid collectivization of farms in . the plan was not met with universal approval in the communist party but its implementation demonstrated mao's authority over the fortunes of the nation. in he launched the doctrine of letting a 'hundred flowers bloom', encouraging intellectual debate. however, the new freedoms took a turn mao did not expect and led to the questioning of the role of the party. strict controls were reimposed and free-thinkers were sent to work in the countryside to be 're-educated'. in may mao launched another ill-fated policy, the great leap forward. to promote rapid industrialization and socialism, the collectives were reorganized into larger units. neither the resources nor trained personnel were available for this huge task. backyard blast furnaces were set up to increase production of iron and steel. the great leap forward was a disaster. it is believed that m. died from famine. soviet advice against the project was ignored and a breakdown in relations with moscow came in , when soviet assistance was withdrawn. a rapprochement with the united states was achieved in the early s. having published his 'thoughts' in the 'little red book' in , mao set the cultural revolution in motion. militant students were organized into groups of red guards to attack the party hierarchy. anyone perceived to lack enthusiasm for mao zedong thought was denounced. thousands died as the students lost control and the army was eventually called in to restore order. after mao's death in the gang of four, led by mao's widow jiang qing, attempted to seize power. these hard-liners were denounced and arrested. china effectively came under the control of deng xiaoping. deng pursued economic reform. the country was opened to western investment. special economic zones and 'open cities' were designated and private enterprise gradually returned. improved standards of living and a thriving economy increased expectations for civil liberties. the demand for political change climaxed in demonstrations by workers and students in april , following the funeral of communist party leader hu yaobang. in beijing where demonstrators peacefully occupied tiananmen square, they were evicted by the military who opened fire, killing more than , . hard-liners took control of the government, and martial law was imposed from may to jan. . since the leadership has concentrated on economic development. hong kong was returned to china from british rule in (for the background, see page ) and macao from portuguese rule in . the late s saw a cautious extension of civil liberties but chinese citizens are still denied most basic political rights. beijing was chosen for the olympic games. china's treatment of tibet came under the international spotlight in the build-up to the games, following violent protests in tibet's capital city, lhasa. the arrest by japan of a chinese trawler in disputed waters in marked the beginning of heightened tensions between the two nations in the east and south china seas. in china became the world's second largest national economy. in nov. the communist party congress selected xi jinping to succeed hu jintao as president from march . in sept. that year, former leadership hopeful bo xilai received a life sentence for corruption in one of china's highest-profile trials in decades. in oct. the government announced the end of the country's one-child policy. a month later, the presidents of china and taiwan met for talks-the first time that leaders from the respective territories had met since . on the economic front, gdp growth in was at its lowest level for a quarter of a century. china is bounded in the north by russia and mongolia; east by north korea, the yellow sea and the east china sea, with hong kong and macao as enclaves on the southeast coast; south by vietnam, laos, myanmar, india, bhutan and nepal; west by india, pakistan, afghanistan, tajikistan, kyrgyzstan and kazakhstan. the total area (including taiwan, hong kong and macao) is estimated at , , sq. km ( , , sq. miles). a law of feb. claimed the spratly, paracel and diaoyutasi islands. an agreement of sept. at prime ministerial level settled sino-indian border disputes which had first emerged in the war of . china's sixth national census was held on nov. . the total population of the provinces, autonomous regions and municipalities and of servicemen on the mainland was , , , ( , , females, representing · %); density, per sq. km. china's population in represented % of the world's total population. the population rose by , , (or · %) since the census in . there were , , urban residents, accounting for · % of the population; compared to the census, the proportion of urban residents rose by · % (reflecting the increasing migration from the countryside to towns and cities since the economy was opened up in the late s). population estimate, dec. : , , , . china has a fast-growing ageing population. whereas in only · % of the population was aged or over and by this had increased to · %, by it is expected to rise to · %. long-term projections suggest that in as much as · % of the population will be or older. the population is expected to peak at · m. around and then begin to decline to such an extent that by around it will be back to the level. china is set to lose its status as the world's most populous country to india in about . the un gives a projected population for of , · m. regulations restricting married couples to a single child, a policy enforced by compulsory abortions and economic sanctions, were widely ignored, and it was admitted in that the population target of , m. by would have to be revised to , m. from peasant couples were permitted a second child after four years if the first born was a girl, a measure to combat infanticide. in china started to implement a more widespread gradual relaxation of the one-child policy. in dec. the standing committee of the national people's congress (npc) approved a resolution allowing couples to have two children if either parent was an only child. the one-child policy was formally abandoned altogether from jan. . an estimated m. persons of chinese origin lived abroad in . a number of widely divergent varieties of chinese are spoken. the official 'modern standard chinese' is based on the dialect of north china. mandarin in one form or another is spoken by m. people in china, or around % of the population of mainland china. the wu language and its dialects has some m. native speakers and cantonese m. around m. people in china cannot speak mandarin. the ideographic writing system of 'characters' is uniform throughout the country, and has undergone systematic simplification. in a phonetic alphabet (pinyin) was devised to transcribe the characters, and in this was officially adopted for use in all texts in the roman alphabet. the previous transcription scheme (wade) is still used in taiwan and hong kong. mainland china is administratively divided into provinces, five autonomous regions (originally entirely or largely inhabited by ethnic minorities, though in some regions now outnumbered by han immigrants) and four government-controlled municipalities. these are in turn divided into prefectures, cities (of which are at prefecture level and at county level), , counties and urban districts. tianjin, · m.; dongguan, · m.; wuhan, · m.; foshan, · m.; chengdu, · m.; chongqing, · m.; nanjing, · m.; shenyang, · m.; xian, · m.; hangzhou, · m.; haerbin, · m.; suzhou, · m.; dalian, · m.; zhengzhou, · m.; shantou, · m.; jinan, · m.; qingdao, · m.; changchun, · m.; kunming, · m.; changsha, · m.; taiyuan, · m.; xiamen, · m.; hefei, · m.; urumqi (wulumuqi), · m.; fuzhou, · m.; shijiazhuang, · m.; wuxi, · m.; zhongshan, · m.; wenzhou, · m.; nanning, · m.; ningbo, · m.; guiyang, · m.; lanzhou, · m.; zibo, · m.; changzhou, · m.; nanchang, · m.; xuzhou, · m about % of the population is engaged in the dominant industries of farming and animal husbandry. in the total sown area was , ha. output in : total grain crops, , tonnes; vegetables, , tonnes. in there were · m. sheep and goats and · m. cattle and yaks. tibet has over , mineral ore fields. mining, particularly of copper and gold, has expanded rapidly since when the railway came to tibet. cement production, : · m. tonnes. electricity consumption totalled · bn. kwh in . in there were , km of roads ( , km in ) . there are airports at lhasa, bangda and nyingchi providing external links. in , , foreign tourists visited tibet. in july a , -km railway linking lhasa with the town of golmud opened. it is the highest railway in the world. direct services have subsequently been introduced between lhasa and a number of major chinese cities, including beijing and shanghai. an extension from lhasa to shigatse, tibet's second largest city, became operational in aug. . in tibet had primary schools (with , pupils) and secondary schools of which were senior secondary schools (with , pupils), junior secondary schools (with , pupils) and eight whole secondary schools. there were also six vocational secondary schools in ( , pupils). tibet has six higher education institutes (the largest of which is tibet university), with , enrolled students in total in . the illiteracy rate of people aged and above was · % in . in there were , medical personnel (including , doctors) and , medical institutions, with a total of , beds. births, , , , ; deaths, , , . birth rate (per , population), · ; death rate, · . in the birth rate rose for the first time since . there were , , marriages and , , divorces in . in the marriage rate was · per , population and the divorce rate a record high · per , . the divorce rate has doubled since . in april parliament passed revisions to the marriage law prohibiting bigamy and cohabitation outside marriage. the suicide rate in china in was · per , population. life expectancy at birth, , was · years for men and · years for women. infant mortality, , per , live births. china has made some of the best progress in recent years in reducing child mortality. the number of deaths per , live births among children under five was reduced from in to in . fertility rate, , · births per woman (compared to over in the mid- s). annual population growth rate, - , · %. according to the world bank, the number of people living in poverty (less than us$ · a day) at purchasing power parity declined from m. in to m. in . most of china has a temperate climate but, with such a large country, extending far inland and embracing a wide range of latitude as well as containing large areas at high altitude, many parts experience extremes of climate, especially in winter. most rain falls during the summer, from may to sept., though amounts decrease inland. monthly average temperatures and annual rainfall ( ): beijing (peking), jan. · °f (- · °c), july · °f ( · °c). annual rainfall · " ( mm). chongqing, jan. · °f ( · °c), july · °f ( · °c). annual rainfall · " ( , mm). shanghai, jan. · °f ( · °c), july · °f ( · °c). annual rainfall · " ( , mm). tianjin, jan. · °f (- · °c), july · °f ( · °c). annual rainfall · " ( mm). on sept. the chinese people's political consultative conference met in beijing, convened by the chinese communist party. the conference adopted a 'common programme' of articles and the 'organic law of the central people's government' ( articles). both became the basis of the constitution adopted on sept. by the st national people's congress, the supreme legislative body. the consultative conference continued to exist after as an advisory body. three further constitutions have been promulgated under communist rule-in communist rule-in , communist rule-in and . the latter was partially amended in , , and , endorsing the principles of a socialist market economy and of private ownership. the unicameral national people's congress is the highest organ of state power. usually meeting for one session a year, it can amend the constitution and nominally elects and has power to remove from office the highest officers of state. there are a maximum of , members of the congress, who are elected to serve five-year terms by municipal, regional and provincial people's congresses. , xi pursued a strong style of authoritarian rule at home and a proactive and muscular foreign policy in his first term. in oct. the ccp gave him the title of 'core' leader, a significant honorific bracketing him with mao zedong and deng xiaoping among previous party figures although conferring no absolute powers. then, at its five-yearly congress in oct. , the party voted to enshrine his name and ideology in the chinese state constitution. he was subsequently re-elected in march and parliament also voted to abolish presidential term limits in a major shift from precedent. xi jinping was born on june in beijing, the son of one of the first generation of communist leaders. he joined the ccp in and, after graduating from tsinghua university in with a degree in chemical engineering, he became secretary to the vice-premier and secretary-general of the central military commission. xi became the zhengding county committee deputy secretary in hebei province in and the following year was promoted to secretary. in he was made deputy mayor of xiamen city, fujian province. having undertaken various party roles in the province, he became deputy governor of fujian in and governor a year later. in he moved to zhejiang province and made his first inroads into national politics when he was named a member of the th central committee. from - he was party secretary of fujian, overseeing economic growth averaging % a year and earning a reputation as an opponent of corruption. in march xi transferred to shanghai to take the role of party secretary following the dismissal of the incumbent on corruption charges. his appointment to such an important regional post was seen as a vote of confidence from the central government and he became a member of the politburo standing committee at the th party congress in oct. . he was also made a high-ranking member of the central secretariat. on march he was elected vice-president at the th national people's congress and took on a number of high profile portfolios including the presidency of the central party school. he was also beijing's senior representative for hong kong and ahead of his presidency, xi said little about his policy ambitions. there was hope abroad and at home that he would champion political and social reform and attempt to deal with corruption and a widening wealth gap between rich and poor and between urban and rural communities. he also faced the conundrum of how to provide adequate healthcare to a rapidly ageing population. in jan. the prospect of greater transparency and accountability under his leadership was undermined when the authorities began criminal proceedings against anti-corruption campaigners calling for public disclosure of officials' assets. this coincided with a report by a us investigative organization claiming that relatives of some of china's top political and military figures, including xi's brother-in-law, held secret offshore financial holdings. in other social and political affairs the ccp announced plans in nov. to ease china's one-child policy (which was subsequently abandoned following an announcement in oct. , with effect from ) and to abolish the system of 'reeducation through labour' camps, while a party plenum calledfor the first time-for markets to play a 'decisive' role in the allocation of resources. meanwhile, in xi was confronted by domestic political opposition in the form of militant attacks by ethnic uighur separatists from xinjiang region and, from sept. that year, by widespread pro-democracy and autonomy protests in hong kong. on the economic front, china's previously frenetic annual rate of growth slowed markedly in , reflecting a slump in factory production and concerns over depressed oil prices, and again in to its lowest since . it also heralded severe stock market turbulence into despite emergency government measures, which had negative reverberations throughout the world economy. nevertheless, recognizing china's rise as a global economic power, the imf in nov. voted to add the yuan as the fifth member of its special drawing rights (sdr) currency basket alongside the us dollar, japanese yen, british pound and the euro. in foreign affairs, regional concerns over china's territorial and military intentions were raised in nov. by the government's declaration of a new 'air defence identification zone' over a swathe of the east china sea including disputed islands claimed by japan and south korea. there has also been friction, regionally and with the usa, over china's sovereignty claims and land reclamation operations on islands in the south china sea, although in july an international legal tribunal ruled in favour of a challenge by the philippines to china's sovereignty assertions-a verdict beijing vowed to ignore. further afield, xi has meanwhile undertaken numerous official visits abroad, as well as attending multilateral forums, for diplomatic, trading and investment purposes. and, while in singapore in nov. , xi and president ma ying-jeou of taiwan held the first direct talks between leaders of the two estranged governments since their split in . most recently, xi urged greater trade co-operation with the usa during his first encounter with the new us president, donald trump, in april , while also increasing economic and military cooperation with russia. li keqiang took office as premier of the state council, a role equivalent to prime minister, in march , succeeding wen jiabao. he was re-elected in march . li keqiang was born on july in dingyuan county, anhui province. following graduation from high school in , he joined the ccp and in he graduated in law from peking university, serving as head of the students' federation from - . he went on to earn a master's degree and doctorate in economics and headed the university's communist youth league of china (cylc) committee. over the following two decades he rose through the cylc ranks, joining the secretariat of its central committee in the s and serving as its first secretary in the s. at this time he built up his power base and forged close ties with hu jintao, a fellow cylc committee member and future chinese president. in li became deputy party secretary for henan province and a year later was appointed henan's governor. in dec. he was named party secretary for liaoning province where he spearheaded a major coastal infrastructure project, the ' points and one line' highway development. in this template was adopted at the national level to rejuvenate industrial northeast china. he also oversaw the rehousing of · m. shanty-town residents into new apartment blocks over a three-year period. li advanced to national level politics when he was elected to the politburo standing committee in oct. . he was appointed vice-premier of the state council in march , leading a medical reform programme aimed at creating an accessible public healthcare service. he also chaired an affordable housing programme and introduced tax reform plans. in nov. li was re-elected as a member of the politburo standing committee and on march became premier of the state council at the th national people's congress. regarded as the steward of the chinese economy, li was expected to focus on securing china's long-term expansion and on the further provision of basic national healthcare, affordable housing, employment growth, regional development and cleaner energy. however, global confidence in china's economy has been shaken since as the country's growth momentum has slowed amid apparent policy differences and blunders, prompting rumours that li was being increasingly sidelined in the governing hierarchy. he was nevertheless re-elected to the politburo standing committee in oct. and to the premiership in march . the chinese president is chairman of the state and party's military commissions. china is divided into seven military regions. the military commander also commands the air, naval and civilian militia forces assigned to each region. china's armed forces (pla: 'people's liberation army'), totalling nearly · m. in including the paramilitary people's armed police (pap) and · m. excluding the pap, are the largest of any country. however, active armed personnel numbers have halved since . moreover, in president xi laid out plans to reform the army structure-replacing an organization based on seven regions with one based on five 'theatre commands'-and reduce the number of military personnel by a further , . conscription is compulsory, but for organizational reasons, is selective: only some % of potential recruits are called up. service is for two years. a military academy to train senior officers in modern warfare was established in . defence expenditure in was us$ , m. (equivalent to us$ per capita). china's military spending more than trebled during the s. defence spending in represented · % of gdp. only the usa spent more on defence in , but china's defence expenditure totalled around a fifth of that of the usa. in march it was announced that the defence budget would rise by · % to us$ bn. following increases of · %, · % and · % in the previous three years. china is the world's third largest exporter of arms after the usa and russia, with · % of the global major weapons total over the period - . in the period - it had only been the eighth largest exporter. as at may china had , personnel serving in un peacekeeping operations (the largest contingent of any of the five permanent members of the un security council and more than the other four combined). having carried out its first test in , there have been tests in all at lop nur, in xinjiang (the last in ). the nuclear arsenal consisted of approximately operational warheads in jan. according to the stockholm international peace research institute. china has been helping pakistan with its nuclear efforts. the army (pla: 'people's liberation army') is divided into main and local forces. main forces, administered by the seven military regions in which they are stationed, but commanded by the ministry of defence, are available for operation anywhere and are better equipped. local forces concentrate on the defence of their own regions. ground forces are divided into infantry, armour, artillery, air defence, aviation, engineering, chemical defence and communications service arms. there are also specialized units for electronic counter-measures, reconnaissance and mapping. in there were group armies covering seven military regions. they included: armoured divisions and brigades; mechanized infantry divisions, brigades and regiments; motorized infantry divisions and brigades; nine special operations units; artillery divisions and brigades; amphibious brigades and divisions; two mountain brigades; aviation brigades and regiments; and two guard divisions. total strength in was · m. including some , conscripts. reserve forces are undergoing major reorganization on a provincial basis but are estimated to number some , . there is a paramilitary people's armed police force estimated at , under pla command. in nov. the naval arm of the pla included submarines, of which three were strategic (two jin-class and one xia-class) and tactical. by mid- two more jin-class nuclear-powered ballistic missile submarines had entered service. surface combatant forces in nov. included destroyers and frigates. sea trials of china's first aircraft carrier, liaoning (a former soviet warship purchased from ukraine), began in aug. . it entered service in sept. and was initially only used for training before being declared 'combat ready' in nov. . work on china's first domestically-built aircraft carrier began in . it was launched in april and is expected to be operational by . there is a land-based naval air force of about combatcapable aircraft, primarily for defensive and anti-submarine service. the force includes h- strategic bombers and jh- fighters. the naval arm is split into a north sea fleet, an east sea fleet and a south sea fleet. in naval personnel were estimated at , , including , in the naval air force and , conscripts. the people's liberation army air force organizes its command through seven military region air forces. the air force has an estimated , combat-capable aircraft. equipment includes j- (mig- ) interceptors (known in the west as 'fishbed'), h- chinese-built copies of tu- strategic bombers, q- fighterbombers (evolved from the mig- and known in the west as 'fantan'), su- fighters supplied by russia (known in the west as 'flanker'), j- chinese-designed and produced fighters (known in the west as 'firebird') and j- locally-developed fighters (known in the west as 'finback'). total strength ( ) was , . in agriculture accounted for · % of gdp, industry · % and services · %. industry was the largest contributor until , while services only overtook agriculture as the second largest sector in . in the late s agriculture was the largest contributor towards gdp. china's economic performance has been marked by high rates of growth for over three decades. annual gdp increases in the early s consistently exceeded % until the global financial crisis. china also holds the world's largest foreign exchange reserves, at more than us$ · trn. in april , although they have been falling since as the central bank strives to boost the currency in the face of large capital outflows. it is among the top recipients of foreign direct investment (fdi) and is the world's largest producer and consumer of coal. in china made the transition from net receiver of foreign aid to net donor and has established itself as a key player in africa's economic development, becoming the largest export partner of sub-saharan africa in . according to the world bank, china's cumulative fdi stock in africa totalled nearly us$ · bn. in , up from us$ · bn. in . in china overtook japan to become the world's second largest economy after the usa. the first steps from a centrally-planned towards a more market-oriented economy were taken by deng xiaoping in the late s. he opened the economy to foreign trade and investment, decentralized industrial management and allowed private sector development. in china became a member of the world trade organization, establishing trade relations with many countries. private entrepreneurs and foreign investors have played an important role in developing the manufacturing sector, china's principal growth engine. even before the economy was heavily skewed towards manufacturing, but following the market-oriented transition output increased significantly. during this period there was a structural shift away from large state-owned enterprises (soes), although these still remain an important part of the economy. between and the government oversaw reform of soes, with many poorly performing businesses privatized or liquidated. stronger firms were restructured and often listed on the stock market. many more recent enterprises are labourintensive as distinct from the capital-intensive soes. growth has been fuelled by low added value and labour-intensive exports. however, chinese firms are predicted to become increasingly competitive with higher added value producers, such as south korea. although the global financial crisis reduced the rate of growth and inbound fdi, china's recovery was among the earliest. gdp growth averaged · % in the second quarter of , up from a two-decade low of · % in the first quarter of that year. fdi also recovered rapidly, averaging · % of gdp annually between and . growth was rooted in a stimulus package of trn. yuan (us$ bn. or % of gdp), including fiscal spending and interest rate cuts, as well as an expansionary monetary policy. central government committed · trn. yuan, with the rest coming from local government, banks and soes. although exports declined by around % in , other countries fared worse and china's share of world exports increased to nearly · % in (up from % in ), making it the world's largest merchandise provider. gdp growth in stood at more than % but moderated between and , reflecting the global economic slowdown and diminishing dividends from past reforms. in aug. a devaluation of the yuan sent the shanghai stock exchange plummeting by nearly %, which was swiftly followed by a surge in capital outflows. the stock market meltdown lasted until feb. , with trading halted altogether for two days in jan. that year. nonetheless, the shanghai exchange subsequently began a recovery and had stabilized (at around , points) by feb. . despite stock market turbulence, the property market, which constitutes a quarter of china's gdp and is vital to the banking sector (as it accounts for a substantial amount of its collateral), remained buoyant. gdp growth declined to · % in (the slowest rate in years) and fell again to · % in as china attempted to reduce its reliance on exports, increase domestic consumption and develop its service sector. the economy then grew by · % in . rapid economic advance has brought with it a number of challenges that threaten future growth. notably, china's cost advantage has been undermined in recent years by rising wages and transportation costs, as well as weak global demand. other concerns include rising property costs, high levels of local government debt, lack of enforcement of intellectual property rights, endemic corruption at government level and credit and investment dependence, while total social financing-a broad measure of total credit-increased by % of gdp between and early . the stimulus package implemented by the government to boost growth increased total debt levels to more than double the value of gdp in . according to the imf, an increase in consumer demand and a reduced dependence on exports and investment are keys to achieving stable long-term economic expansion. china's th five-year plan (covering - ) aims to promote domestic consumption and to support innovation and entrepreneurship within a framework of balanced and sustainable development. efforts to promote domestic consumption have seen exports' share of gdp falling from % in to · % in and a lower investment contribution to gdp. the continued decline in commodity prices coupled with china's economic slowdown has had knock-on effects for commodityexporting nations, such as brazil, indonesia and argentina, given that china consumes about half of the world's steel, aluminium and nickel. inefficient production and outmoded equipment have meanwhile led to significant environmental problems, especially in the north of the country. air pollution, soil erosion and a declining water table are of particular concern. china has become the world's largest consumer of coal and second largest consumer of oil after the usa. the government aims to diversify its energy sources, relying less on coal and more on nuclear and alternative energy sources. there has been heavy investment in hydro-power, including the three gorges dam. since , m. people have been lifted out of poverty, yet china still has the second largest number of poor in the world after india. the world bank estimates that · m. people lived below the national poverty line at the end of (equivalent to income less than us$ per day), located mainly in remote and resource-poor regions and particularly in the west and the interior. nonetheless, some progress has been made, with · % of the rural population living below the poverty line in compared to · % in . growing inequality between urban and rural regions, particularly in terms of educational opportunities, needs to be addressed, however. china also faces the growing burden of an ageing population. those aged and over accounted for · % of the total population in , up from · % in . the currency is called renminbi (i.e. people's currency). the unit of currency is the yuan (cny) which is divided into ten jiao, the jiao being divided into ten fen. the yuan was floated to reflect market forces on jan. while remaining state-controlled. for years the people's bank of china maintained the yuan at about · to the us dollar, allowing it to fluctuate but only by a fraction of % in closely supervised trading. in july it was revalued and pegged against a 'market basket' of currencies the central parities of which were determined every night. in july , after three years of sharp appreciation, it was repegged at around · yuan to the dollar, leading to claims from some international observers that it was being kept unfairly low to boost exports. in june the government announced that the yuan would be allowed to move freely against the dollar as long as a rise or fall does not exceed · % within a single day. in aug. the yuan was devalued by a total of · % on three consecutive days. in aug. total money supply was , · bn. yuan, gold reserves were · m. troy oz and foreign exchange reserves us$ , · bn. (us$ · bn. in of the total revenues in central government accounted for , · bn. yuan and local governments , · bn. yuan. tax revenues came to , · bn. yuan in (including domestic vat , · bn. yuan and corporate income tax , · bn. yuan) and non-tax revenues , · bn. yuan. of the total expenditure in central government accounted for , · bn. yuan and local governments , · bn. yuan. the leading items of expenditure in were education ( , · bn. yuan) and social safety net and employment effort ( , · bn. yuan). the standard rate of vat is %. savings deposits in various forms in all banking institutions totalled , · bn. yuan in ; loans amounted to , · bn. yuan. there are stock exchanges in the shenzhen special economic zone and in shanghai. a securities trading system linking six cities (securities automated quotations system) was inaugurated in for trading in government bonds. china received a record us$ · bn. worth of foreign direct investment in , up from us$ · bn. in . external debt totalled us$ , m. in (up from us$ , m. in ) and represented · % of gni. china's carbon dioxide emissions from the consumption and flaring of fossil fuels in accounted for · % of the world total (making it the biggest emissions producer, having overtaken the usa in ) and were equivalent to · tonnes per capita (up from · tonnes per capita in ). an environmental performance index compiled in ranked china th of countries, with · %. the index examined various factors in nine areas-agriculture, air quality, biodiversity and habitat, climate and energy, fisheries, forests, health impacts, water and sanitation, and water resources. pollution is estimated to cost china about % of gdp annually. installed generating capacity in was an estimated , m. kw, compared with m. kw in . in electricity output was , , gwh, up from , , gwh in . consumption per capita was , kwh in . rapidly increasing demand has meant that more than half of china's provinces have had to ration power. sources of electricity in as percentage of total production: thermal, · %; hydro-electric power, · %; wind. · % (china is one of the world's largest producers of wind power); and nuclear, · %. in there were nuclear reactors in use and under construction. generating electricity is not centralized; local units range between and mw of output. in dec. china formally broke up its state power monopoly, creating instead five generating and two transmission firms. the three gorges dam project on the yangtze river was launched in and is intended to produce abundant hydro-electricity (as well as helping flood control). the first three , -kw generators in service at the project's hydro-power station began commercial operation in july . the original specification was completed in oct. , although six more generators have been added in the meantime (bringing the total to ). the final two generators become operational in july , giving the dam an overall capacity of · gw. china surpassed germany in terms of solar generating capacity in , with · gw at the end of the year. on-shore oil reserves are found mainly in the northeast (particularly the daqing and liaohe fields) and northwest. there are off-shore fields in the continental shelves of east china. oil production was a record · m. tonnes in . china is the second largest consumer of oil after the usa. ever-growing demand has meant that increasing amounts of oil are having to be imported. a -km pipeline from skovorodino in russia to daqing in the northeast of china was inaugurated in jan. , allowing china to increase significantly its imports of oil from the world's second largest producer. the , -km turkmenistan-china gas pipeline, bringing natural gas to xinjiang in china via kazakhstan and uzbekistan, was inaugurated in dec. . this connects with china's second west-east gas pipeline. only the usa imports more oil. domestic production now accounts for only % of consumption, compared to nearly % in . proven reserves in were · bn. bbls. the largest natural gas reserves are located in the western and north-central regions. production was a record · bn. cu. metres in -up from · bn. cu. metres in -with proven reserves of · trn. cu. metres in . china is the second largest producer of wind power after the usa, with · bn. kwh in . in total installed capacity amounted to , mw, the highest of any country and · % of the world total. china is one of the world's leading mineral producing and consuming countries. recoverable deposits of coal in totalled · bn. tonnes, mainly distributed in north china (particularly shanxi province and the inner mongolia autonomous region). coal production was , m. tonnes in . annual coal production has increased every year since . growing domestic demand nonetheless meant that china became a net importer of coal in . iron ore reserves were · bn. tonnes in . deposits are abundant in the anthracite field of shanxi, in hebei and in shandong, and are found in conjunction with coal and worked in the northeast. production in was , m. tonnes, making china the world's largest iron ore producer. it is also the largest consumer, at around % of the global total in . tin ore is plentiful in yunnan, where the tin-mining industry has long existed. tin production was , tonnes in . china is a major producer of wolfram (tungsten ore). there is mining of wolfram in hunan, guangdong and yunnan. output of other minerals (in , tonnes) in : salt, , ; bauxite, , ; aluminium, , ; zinc, , ; lead, , ; copper, , . there are also reserves of diamond, nickel, barite, bismuth, graphite, gypsum, mercury, molybdenum, silver, salt, phosphate ore and sylvite. gold production, : tonnes. china surpassed south africa as the world's leading gold producer in , since when its output has increased every year. agriculture accounted for approximately % of gdp in , compared to over % in at the time of the birth of the people's republic of china and over % in . in sown areas for major crops were (in m. ha.): corn, · ; rice, · ; wheat, · ; soybeans, · ; tubers, · ; rapeseed, · . intensive agriculture and horticulture have been practised for millennia. present-day policy aims to avert the traditional threats from floods and droughts by soil conservancy, afforestation, irrigation and drainage projects, and to increase the 'high stable yields' areas by introducing fertilizers, pesticides and improved crops. in aug. more than m. ha., notably in the yangtze valley, were under water as china experienced its worst flooding since the s. the flood season claimed over , lives. 'township and village enterprises' in agriculture comprise enterprises previously run by the communes of the maoist era, cooperatives run by rural labourers and individual firms of a certain size. there were , state farms in with · m. employees. net per capita annual income of rural households, : , yuan. in there were an estimated · m. ha. of arable land and · m. ha. of permanent cropland; · m. ha. were equipped for irrigation. there were · m. large/medium-sized tractors in and · m. small tractors. china is the world's leading producer of a number of agricultural crops. production of major products (in m. , - . forestry in the area under forests was · m. ha., or % of the total land area. the average annual increase in forest cover of , , ha. between and was the highest of any country in the world. total roundwood production in was · m. cu. metres, making china the world's third largest timber producer ( · % of the world total in ). it is the highest consumer of roundwood; timber consumption in totalled · m. cu. metres. it is also the world's leading importer of roundwood, accounting for · % of world timber imports in . output of major products, unless otherwise indicated (in tonnes): cement, , · m.; rolled steel, , · m.; crude steel, · m.; pig iron, · m.; gas oil and diesel oil ( ), · m.; gasoline, · m.; paper and paperboard, · m.; sulphuric acid, · m.; chemical fertilizers, · m.; fuel oil ( ), · m.; yarn, · m.; refined sugar, · m. also produced in : cloth, , m. metres; beer, , · m. litres; , · m. mobile phones; · m. notebook pcs; · m. colour tv sets; · m. air conditioners; · m. home refrigerators; · m. washing machines; · m. bicycles; · m. cameras; · m. motorcycles. china is the world's leading cement, steel and pig iron manufacturer; since output of cement has doubled and production of crude steel and pig iron has quadrupled (although in both crude steel and pig iron production fell for the first time in years). china overtook japan as the world's largest producer of motor vehicles in , and in produced · m. cars and · m. commercial vehicles. the employed population at the census was · m. ( · m. female). by it had risen to · m. ( · m. more than in ), of whom · m. worked in rural areas ( · m. fewer than in ) and · m. in urban areas ( · m. more than in ). in china's registered urban jobless was · %, with · m. registered unemployed in the country's cities. with china's fast-growing ageing population, according to the united nations the working-age population began to decline in . in china had , private industrial enterprises. it was not until the late s that the private sector even came into existence in china. the average annual wage of people working in urban units in was , yuan. china's labour law stipulates a five-day working week with no more than eight hours a day and no more than hours a week. minimum working age was fixed at in . strikes over pay have become ever more frequent in china, particularly at foreign-owned facilities. china had · m. people living in slavery according to the walk free foundation's global slavery index, the second highest total of any country. there are five special economic zones at shenzhen, xiamen, zhuhai, shantou and hainan in which concessions are made to foreign businessmen. the pudong new area in shanghai is also designated a special development area. since joint ventures with foreign firms have been permitted. a law of april reduced taxation on joint ventures to %. there is no maximum limit on the foreign share of the holdings; the minimum limit is %. in china is the second largest trading nation in the world, accounting for · % of global merchandise imports by value in and · % of global merchandise exports (up from · % when it joined the wto in ). it was the second largest importer in behind the usa and the largest exporter. as recently as the usa's total trade in goods was more than twice that of china. it overtook germany as the largest exporter of goods in . its trade surplus in goods is the highest of any country. however, it has the world's highest trade deficit in services. in imports of services totalled us$ bn. but exports only us$ bn. main imports in (in us$ bn.): machinery and transport equipment, · ; non-edible raw materials, · ; mineral fuels, lubricants and related materials, · ; chemicals, · . major exports in (in us$ bn.): machinery and transport equipment, , · ; miscellaneous manufactured goods, · ; light textile industrial products, rubber products, minerals and metallurgical products, · ; chemicals, · . the main trading partners were as follows in (in us$ m.): the total road length in was , , km, including , km of expressways (of which there had not been any as recently as the mid- s); , m. tonnes of freight and , m. persons were transported by road that year. the number of civilian motor vehicles was · m. in , including · m. passenger vehicles and · m. trucks (more than double the number in , when there were · m. civilian vehicles overall including · m. passenger vehicles and · m. trucks). china is the world's fastest-growing car market. there were , traffic accidents in , with , fatalities. in in jan. there were , ships of gt or over registered, totalling · m. gt. of the , vessels registered, were bulk carriers, general cargo ships, oil tankers, container ships, passenger ships and liquid gas tankers. mainland china's busiest port in was ningbo-zhoushan (handling · m. tonnes of cargo), followed by shanghai ( · m. tonnes), tianjin ( · tonnes), guangzhou (canton) ( · m. tonnes) and qingdao ( · m. tonnes). shanghai overtook singapore to become the world's busiest container port in and handled · m. teus (twenty-foot equivalent units) in . shenzhen, mainland china's second busiest port for container traffic and the world's fourth busiest in , handled · m. teus. hong kong handled · m. teus in . in jan. the first legal direct shipping links between the chinese mainland and taiwanese islands in more than years were inaugurated. inland waterways totalled , km in ; , · m. tonnes of freight and · m. passengers were carried. in june the three gorges reservoir on the chang jiang river, the largest water control project in the world, reached sufficient depth to support the resumption of passenger and cargo shipping. out of countries analysed in the fragile states index-a list published jointly by the fund for peace and foreign policy magazine-china was ranked the th most vulnerable to conflict or collapse. the index is based on indicators of state vulnerability across social, political and economic categories. six new codes of law (including criminal and electoral) came into force in , to regularize the legal unorthodoxy of previous years. there is no provision for habeas corpus. as well as treason and murder the death penalty may be used for rape, embezzlement, smuggling, fraud, theft, drug-dealing, bribery and robbery with violence. amendments to the criminal law in and reduced the number of capital crimes-which include both violent and non-violent offences-from to and further to . china does not divulge figures on its use of the death penalty, but amnesty international reported that in china executed thousands of people and was the world's top executioner. nevertheless, western analysts believe that the number of executions now is around a fifth of the yearly total in the s. 'people's courts' are divided into some higher, intermediate and , basic-level courts, and headed by the supreme people's court. the latter, the highest state judicial organ, tries cases, hears appeals and supervises the people's courts. it is responsible to the national people's congress and its standing committee. people's courts are composed of a president, vice-presidents, judges and 'people's assessors' who are the equivalent of jurors. 'people's conciliation committees' are charged with settling minor disputes. there are also special military courts. procuratorial powers and functions are exercised by the supreme people's procuracy and local procuracies. in march the national people's congress passed legislation developing aspects of the general principles of civil law, with effect from oct. . among its provisions was the extension of legitimate rights and interests from chinese citizens only to anyone conducting civil activities in the country. in addition, the statute of limitation was increased from two to three years. the number of sentenced prisoners in mid- was , , ( per , of national population). china was ranked th of countries for criminal justice and th for civil justice in the world justice project rule of law index, which provides data on how the rule of law is experienced by the general public across eight categories. an educational reform of brought in compulsory nine-year education consisting of six years of primary schooling and three years of secondary schooling, to replace a previous five-year system. in mainland china the population census revealed the following levels of educational attainment: · m. people had finished university education; · m. had received senior secondary education; · m. had received junior secondary education; and · m. had had primary education. · m. people over years of age or · % of the population were illiterate, although this compared favourably with a · % rate of illiteracy in the census and a · % rate in . in adult literacy was estimated at · %; youth literacy in was · %. in there were , kindergartens with · m. children and · m. full-time teachers; , regular primary schools with · m. pupils and · m. full-time teachers; , secondary schools (including: , senior secondary; , junior secondary; , specialized; , vocational; and , technical) with · m. pupils and · m. full-time teachers. there were also , pupils at , special education schools. institutes of higher education, including universities, numbered , in , with · m. undergraduates and · m. postgraduate level students, and · m. full-time teaching staff. china has more than private universities, almost all of which have been established since the mid- s. a national system of student loans was established in . the number of chinese students studying abroad went up from , in to , in ; it rose above , in and , in , and by exceeded , , making china the largest source of overseas students in the world. chinese students account for a fifth of all international students in tertiary education in the oecd, but fewer than half return to china after finishing their studies. the number of chinese undergraduate students in american universities in - was times as many as in - , rising from , to , in the space of seven years. there is an academy of sciences with provincial branches. an academy of social sciences was established in . in national government expenditure on education came to , , m. yuan and accounted for · % of national government spending. medical treatment is free only for certain groups of employees, but where costs are incurred they are partly borne by the patient's employing organization. in there were , health institutions throughout china, including , hospitals, , local health centres, , centres for disease control and prevention, and , specialized prevention and treatment centres. china's first aids case was reported in . at the end of there were , reported cases of people living with hiv/ aids. the number of deaths of people who had been living with hiv/aids in was , . in the first half of china was struck by an epidemic of a pneumonia-type virus identified as sars (severe acute respiratory syndrome). the virus was first detected in southern china and was subsequently reported in over other countries. according to the ministry of health, by the time the outbreak had been contained a total of , cases had been reported on the chinese mainland; , patients were cured and discharged from hospital, and died. in water: at what cost? the state of the world's water , wateraid reported that · % of the population does not have access to safe water. china ranked as the country with the second largest number of people living without access to safe water ( · m. in ). in an estimated · % of adult males and · % of adult females smoked in china. a study from the same year estimated that chinese males smoke one-third of all the world's cigarettes. in there were , social welfare enterprises with · m. beds. numbers (in , ) of beneficiaries of relief funds in : urban residents receiving minimum living allowance, , ; rural residents receiving minimum living allowance, , ; persons receiving traditional relief, ; persons in rural households entitled to the 'five guarantees' (food, clothing, medical care, housing and burial expenses), , . the official retirement age for men is and for women (or in the case of civil servants and professionals). the government accords legality to five religions only: buddhism, islam, protestantism, roman catholicism and taoism. confucianism, buddhism and taoism have long been practised. confucianism has no ecclesiastical organization and appears rather as a philosophy of ethics and government. taoism-of chinese origin-copied buddhist ceremonial soon after the arrival of buddhism two millennia ago. buddhism in return adopted many taoist beliefs and practices. a more tolerant attitude towards religion had emerged by , and the government's bureau of religious affairs (since renamed the state administration for religious affairs) was reactivated. ceremonies of reverence to ancestors have been observed by the whole population regardless of philosophical or religious beliefs. a new quasi-religious movement, falun gong, was founded in , but has since been banned by the authorities. the movement has claimed some m. adherents, although the chinese government has disputed this. muslims are found in every province of china, being most numerous in the ningxia-hui autonomous region, yunnan, shaanxi, gansu, hebei, henan, shandong, sichuan, xinjiang and shanxi. roman catholicism has had a footing in china for more than three centuries. two christian organizations-the chinese patriotic catholic association, which declared its independence from rome in , and the protestant three-self patriotic movement-are sanctioned by the chinese government. according to estimates (by the state-approved xinhua news agency, the chinese academy of social sciences and the state administration for religious affairs) there were m. buddhists (more than in any other country), m. christians and more than m. muslims in the country in . other official figures indicate that there are · m. catholics, although unofficial estimates are much higher. the number of christians in china is generally thought to be far higher than official numbers indicate, with socalled 'house churches' becoming ever more popular. some analysts estimate that there are as many as m. christians overall. legislation of prohibits foreign nationals from setting up religious organizations. in , , m. volumes of books were produced. in tourist numbers totalled · m. the world tourism organization predicts that china will overtake france as the world's most visited destination by . it was the third most visited destination in after france and the usa. income from tourists in was us$ · bn., ranking it fourth behind the usa, spain and france. expenditure by chinese travellers outside of mainland china for was us$ · bn., the most of any country. in both german and us travellers abroad had spent more than those from china. the lunar new year, also known as the 'spring festival', is a time of great excitement for the chinese people. constituencies encompassing all eligible persons in a workforce of · m., and ten from an election committee formed by members of district boards. a president was elected from and by the members. at the elections on sept. turnout for the geographical seats was · %, and for the functional seats ( of which were contested), · %. the democratic party and its allies gained seats, the liberal party and the pro-beijing democratic alliance . the remaining seats went to independents. on dec. the selection committee selected a provisional legislature which began its activities in jan. while the legislative council was still functioning. in jan. the provisional legislature started its work by enacting legislation which would be applicable to the hong kong special administrative region and compatible with the basic law. constitutionally hong kong is a special administrative region of the people's republic of china. the basic law enables hong kong to retain a high degree of autonomy. it provides that the legislative, judicial and administrative systems which were previously in operation are to remain in place. the special administrative region government is also empowered to decide on hong kong's monetary and economic policies independent of china. in july the first-past-the-post system of returning members from geographical constituencies to the legislative council was replaced by proportional representation. there were directly elected seats out of for the first elections to the legislative council following hong kong's return to chinese sovereignty, increasing in accordance with the basic law to for the election with indirectly elected. in the sept. legislative council election (and that of sept. ) of the seats were directly elected. for the election in sept. the number of seats was increased to , with directly elected and indirectly elected by functional constituencies. there were also five new functional constituency seats nominated by elected district council members. the chief executive is chosen by a beijing-backed , -member election committee ( prior to the march election), although it has been stated that universal suffrage is the ultimate aim. in a timetable was announced for hong kong to directly elect its chief executive in and its legislative council in . however, beijing insisted that only approved candidates would be allowed to stand in , prompting mass pro-democracy rallies in the territory in and formal rejection of the plan by the legislative council in june . beijing nevertheless refused to countenance amendments. in july a new accountability or 'ministerial' system was introduced, under which the chief executive nominates for appointment policy secretaries, who report directly to the chief executive. the chief executive is aided by the executive council, consisting of the three senior secretaries of department (the chief secretary, the financial secretary and the secretary for justice) and eleven other secretaries plus five non-officials. according to the anti-corruption organization transparency international, hong kong ranked equal th in the world in a survey of the countries and regions with the least corruption in business and government. it received out of in the annual index. overview hong kong has one of the world's most open economies and is an internationally important financial centre. the territory's economic rise was founded on its role as an international trade emporium, acting as a conduit for china's burgeoning exports. mainland china, the usa and japan are hong kong's major export partners, accounting for · %, · % and · % of exports respectively in . the island is dependent on imports of food and other resources. in it imported % of goods from mainland china, % from taiwan and % from japan. in and the economy grew strongly on the back of a rise in chinese tourism, healthy global demand for exports and improving domestic consumer confidence. however, the global financial crisis saw the economy shrink by · % in before rebounding with a · % increase the following year. between and annual growth averaged · %, supported by strong external demand. student-led pro-democracy protests in the latter months of caused major disruption in several key business districts and threatened to weaken the local economy in the short term. foreign direct investment levels have been high, averaging % of gdp between and according to world bank data, and the world economic forum ranked hong kong as the ninth most competitive economy in the world in its report. the government aims to tackle a housing shortage by providing , new housing units by the mid- s. the unit of currency is the hong kong dollar (hkd) of cents. it has been pegged since at a rate of hk$ · to the us dollar. banknotes are issued by the hongkong and shanghai banking corporation and the standard chartered bank, and, from may , the bank of china. total money supply was hk$ , m. in july . in aug. gold reserves were , troy oz and foreign exchange reserves were us$ , m. inflation rates (based on imf statistics): in - revenue totalled hk$ · bn. and expenditure hk$ · bn. earnings and profits taxes accounted for · % of revenues in - and indirect taxes · %; education accounted for · % of expenditures and social welfare · %. hong kong's carbon dioxide emissions from the consumption of energy in were the equivalent of · tonnes per capita. installed capacity was · m. kw in . production in was · bn. kwh. hong kong is a net importer of electricity. consumption in was · bn. kwh. the local agricultural industry is directed towards the production of high quality fresh food through intensive land use and modern farming techniques. out of the territory's total land area of , sq. km, only sq. km is currently farmed. in local production accounted for % of live poultry consumed, % of live pigs and % of fresh vegetables. the gross value of local agricultural production totalled hk$ , m. in , with pig production valued at hk$ m., poultry production (including eggs) at hk$ m., and vegetable and flower production at hk$ m. in the total catch was , tonnes, exclusively from marine waters. the leading companies by market capitalization in hong kong in may were: china mobile, a telecommunications company (us$ · bn.); aia group, a life insurance company (us$ · bn.); and cnooc, an integrated oil company (us$ · bn.). industry is mainly service-oriented. in june there were , establishments employing , , persons in service industries and , establishments employing , persons in manufacturing industries. establishment statistics by service type (and persons engaged) were mainly: import/export trade and wholesale, , ( , ); retail, , ( , ) ; social and personal services, , ( , ) ; professional and business services, , ( , ); financing and insurance, , ( , ); accommodation and food services, , ( , ); real estate, , ( , ) . in the size of the labour force (synonymous with the economically active population) was , , ( , , females). the persons engaged in june included , , people in wholesale, retail and import/export trades, accommodation and food services, , in finance, insurance, real estate, professional and business services, , in the civil service, , in manufacturing and , in construction sites (manual workers only). a minimum wage of hk$ per hour was introduced for the first time on may . unemployment stood at · % in the period sept.-dec. . in the total value of imports was hk$ , , m. and total exports hk$ , , m. the main suppliers of imports in were mainland china ( · %), japan ( · %), taiwan ( · %), singapore ( · %) and usa ( · %). in , · % of total exports went to mainland china, · % to the usa, · % to japan, · % to germany and · % to the united kingdom. the chief import items in were: electrical machinery, apparatus and appliances, etc. ( · %); telecommunications, sound recording and reproducing equipment ( · %); office machines and automatic data processing machines ( · %); articles of apparel and clothing accessories ( · %). the main exports in were: electrical machinery, apparatus and appliances, etc. ( · %); telecommunications, sound recording and reproducing equipment ( · %); office machines and automatic data processing machines ( · %); articles of apparel and clothing accessories ( · %). in there were , km of roads, over % of which were in the new territories. there are road tunnels, including three under victoria harbour. in there were , private cars, , goods vehicles, , buses and coaches, and , motorcycles and mopeds. there were , road accidents in , of which were fatal. a total of · m. tonnes of cargo were transported by road in . a -km bridge linking hong kong, zhuhai in guangdong province in mainland china and macao has been built and was scheduled to open in july following a number of delays. hong kong was ranked fourth for its road infrastructure in the world economic forum's global competitiveness report - . hong kong's railways are run by the mtr corporation limited (mtrcl), a public listed company of which the government is the majority shareholder. the mtr system comprises nine railway lines serving hong kong island, kowloon and the new territories. its -km network has stations and carries an average of · m. passengers each day. mtr lines carried , m. passengers in . in addition, a light rail network ( · km and stops) serves the local communities of tuen mun, yuen long and tin shui wai in the new territories; , passengers travel daily on the system. a high speed rail service between hong kong and guangzhou on the mainland is scheduled to open in late . the electric tramway on the northern state of hong kong island commenced operating in and has a total track length of km. the peak tram, a funicular railway connecting the peak district with the lower levels in victoria, has a track length of · km and two tramcars (each with a capacity of passengers per trip). it carries an average of , passengers daily. the airport express line ( · km) opened in and is also operated by the mtrcl. it carried · m. passengers in . in june it was estimated that · m. passenger journeys were made daily on public transport (including local railways, buses, etc.). in the world economic forum's global competitiveness report - hong kong ranked third for quality of rail infrastructure. the new hong kong international airport (generally known as chek lap kok), built on reclaimed land off lantau island to the west of hong kong, was opened on july to replace the old hong kong international airport at kai tak, which was situated on the north shore of kowloon bay. more than airlines now operate scheduled services to and from hong kong. in cathay pacific airways, the largest hong kong-based airline, operated approximately , passenger and cargo services to destinations in countries and territories around the world. cathay pacific carried , , passengers and · m. tonnes of cargo in . dragonair, a cathay pacific subsidiary, provided scheduled services to cities in mainland china and asia in . in air hong kong, an all-cargo operator, provided scheduled services to bangkok, beijing, ho chi minh city, manila, nagoya, osaka, penang (via bangkok), seoul, shanghai, singapore, taipei and tokyo. hong kong international airport handled more international freight in than any other airport. in , , aircraft arrived and departed and m. passengers and · m. tonnes of freight were carried on aircraft. hong kong was second, behind only singapore, in the rankings for air transport infrastructure in the world economic forum's global competitiveness report - . the port of hong kong handled · m. teus (twenty-foot equivalent units) in , making it the world's third busiest container port after shanghai and singapore. the kwai chung container port has berths with , metres of quay backed by ha. of cargo handling area. at the end of there were , ships ( , ocean-going) of , , gt registered in hong kong. in , , ocean-going vessels, , river cargo vessels and , river passenger vessels arrived at the port of hong kong. a total of m. tonnes of freight were handled in . hong kong was ranked third in the world economic forum's global competitiveness report - for the quality of its port facilities. in there were , , main (fixed) telephone lines (equivalent to · per , population). the local fixed telecommunications network services (ftns) market in hong kong was liberalized in . there were , , mobile phone subscriptions in (equivalent to , · per , population), up from , , in ( , · per , population). the number of subscriptions doubled between and . the internet market has also seen huge growth. in there were , , wireless broadband subscriptions ( · per , population) and , , fixed broadband subscriptions ( · per , population). the number of fixed broadband subscriptions has been declining since as more people have wireless subscriptions instead. in march there were · m. facebook users. the external telecommunications services market has been fully liberalized since jan. , and the external telecommunications facilities market was also liberalized starting from jan. . the hong kong act of provided for hong kong ordinances to replace english laws in specified fields. the courts of justice comprise the court of final appeal (inaugurated july ), which hears appeals on civil and criminal matters from the high court; the high court (consisting of the court of appeal and the court of first instance); the lands tribunal, which determines on statutory claims for compensation over land and certain landlord and tenant matters; the district court (which includes the family court); the magistracies (including the juvenile court); the coroner's court; the labour tribunal, which provides a quick and inexpensive method of settling disputes between employers and employees; the small claims tribunal, which deals with monetary claims involving amounts not exceeding hk$ , ; and the obscene articles tribunal. while the high court has unlimited jurisdiction in both civil and criminal matters, the district court has limited jurisdiction. the maximum term of imprisonment it may impose is seven years. magistracies exercise criminal jurisdiction over a wide range of offences, and the powers of punishment are generally restricted to a maximum of two years' imprisonment or a fine of hk$ , . after being in abeyance for years, the death penalty was abolished in . , crimes were reported in , of which , were violent crimes. , people were arrested in , of whom , were for violent crimes. the population in penal institutions was , at dec. ( per , population). in the adult literacy rate was · % ( · % in ). universal basic education is available to all children aged from six to years. in around three-quarters of the ordinary secondary day schools teaching has been in cantonese since - , with about a quarter of ordinary secondary day schools still using english. in there were , pupils in kindergartens, , in primary schools (including international schools) and , in secondary schools (including international schools). the estimated total government expenditure on education in - was hk$ · bn. ( · % of total government spending and · % of gdp). in - : · % of total government spending and · % of gdp. according to the oecd's pisa (programme for international student assessment) study, -year-olds in hong kong rank second among oecd and other major countries and cities in mathematics and reading, and ninth in science. the three-yearly study compares educational achievement of pupils in over countries. the department of health (dh) is the government's health adviser and regulatory authority. the hospital authority (ha) is an independent body responsible for the management of all public hospitals. in there were , registered doctors, equivalent to · doctors per , population. in there were , dentists, , nurses and , midwives. the total number of hospital beds in was , , including , beds in public hospitals under the ha and , beds in private hospitals. the bed-population ratio was · beds per thousand population. the chinese medicine ordinance was passed by the legislative council in july to establish a statutory framework to accord a professional status for chinese medicine practitioners and ensure safety, quality and efficacy of chinese medicine. in there were , registered chinese medicine practitioners. total expenditure on health in - amounted to hk$ , m., an increase of · % over that in - . social welfare programmes include social security, family services, child care, services for the elderly, medical social services, youth and community work, probation, and corrections and rehabilitation. non-governmental organizations are subsidized by public funds. the government gives non-contributory cash assistance to needy families, unemployed able-bodied adults, the severely disabled and the elderly. caseload as at aug. totalled , . victims of natural disasters, crimes of violence and traffic accidents are financially assisted. estimated recurrent government expenditure on social welfare for - was hk$ · bn. sub-tropical tending towards temperate, with an average temperature of · °c. the number of rainy days is around a third of the year. average annual rainfall varies from - " ( , - , mm) . it is very humid from may to sept. macao's constitution is the 'basic law', promulgated by china's national people's congress on march and in effect since dec. . it is a special administrative region (sar) of the people's republic of china, and is directly under the central people's government while enjoying a high degree of autonomy. the legislative assembly has seats of which are directly elected, indirectly elected by functional constituencies and seven appointed by the chief executive. at the elections held on sept. the macau-guangdong union won two of elected seats with · % of votes cast and the union for development two with · %. ten other parties won a single seat each. turnout was · %. fernando chui sai-on was re-elected chief executive for a second term on aug. , receiving out of votes in the election committee. the economy grew by an average · % per year from - , driven mainly by the gaming sector and the ongoing construction of a number of casino resorts. however, it went into recession from following china's crackdown on government corruption. macao's traditional manufacturing industries virtually disappeared following the transfer of much of the textile industry to the chinese mainland and, in , the termination of the multifibre arrangement, which had governed international textile trade flows for three decades. the unit of currency is the pataca (mop) of avos, which is tied to the hong kong dollar at parity. inflation was · % in and · % in . foreign exchange reserves were us$ , m. in . total money supply was , m. patacas in . in revenues totalled , m. patacas; expenditures, , m. patacas. revenues from gaming tax accounted for · % of total revenue in ; current expenditure accounted for · % of expenditure. real gdp growth was just · % in but then rose to · % in and · % in . more recently the economy contracted by · % in and then by · % in -the lowest rate for any advanced economy that year-owing to a decline in tourism and gaming revenues. total gdp in was us$ · bn. there are two note-issuing banks in macao-the macao branch of the bank of china and the macao branch of the banco nacional ultramarino. the monetary authority of macao functions as a central bank (chairman, teng lin seng). commercial business is handled ( ) by banks, nine of which are local and foreign. total deposits, (including non-resident deposits), , · m. patacas. there are no foreign exchange controls within macao. macao's carbon dioxide emissions from the consumption of energy in were the equivalent of · tonnes per capita. installed capacity was · m. kw in ; production, · bn. kwh. macao imported , m. kwh of electricity in . oil and gas , , litres of fuel oil were imported in . the catch in was estimated at , tonnes. although the economy is based on gaming and tourism there is a light industrial base of textiles and garments. in the number of manufacturing establishments was (food products and beverages, ; textiles and wearing apparel, ; publishing, printing and reproduction of recorded media, ). in a total of , people were in employment, including , ( · %) in gaming and junket activities (up from , in ); , ( · %), hotels, restaurants and similar activities; , ( · %), construction; , ( · %), wholesale and retail trade, repair of motor vehicles, motorcycles and personal and household goods; , ( · %), real estate and business activities; , ( · %), public administration and social security. employment in was · % of the labour force; unemployment rate stood at · %. in imports (c.i.f.) were valued at us$ , · m., of which the main products were telecommunications, sound recording and reproducing equipment; petroleum and petroleum products; and gold, silverware, jewellery and articles of precious materials. in the chief import sources (in us$ m.) were: mainland china ( , · ); hong kong ( · ); japan ( · ). exports (f.o.b.) were valued at us$ · m., of which the leading products were articles of apparel and clothing accessories; gold, silverware, jewellery and articles of precious materials; and petroleum oils and oils obtained from bituminous minerals. in the main export markets (in us$ m.) were: hong kong ( · ); usa ( · ); mainland china ( · ). in there were km of roads. in there were , landline telephone subscriptions (equivalent to · per , inhabitants) and , , mobile phone subscriptions (or , · per , inhabitants). in , · % of households had internet access. in march there were , facebook users. there are a judicial district court, a criminal court and an administrative court with magistrates in all. in there were , crimes, of which , were against property. there were persons in prison in dec. . there are both public and private schools. in - there were schools and colleges. number of students in the - academic year (with number of teachers): pre-primary, , ( ); primary, , ( , ); secondary, , ( , ). in - there were four special education schools with pupils and teachers. there were ten higher education institutions with student enrolment of , . in there were institutions offering vocational training courses, in which participants totalled , . expenditure on education came to · % of gdp in and · % of total government spending in . in there were doctors, dentists and nurses working in primary health care, and doctors, dentists and , nurses working in hospitals. in there were , hospital beds; there were · doctors per , population. in there were an estimated , folk religionists and , buddhists according to the pew research center's forum on religion & public life. a further , people were religiously unaffiliated. there are also small numbers of catholics. the historic centre of macao was inscribed on the unesco world heritage list in . in there were daily newspapers (nine in chinese, three in portuguese and two in english) and weekly newspapers (ten in chinese and one in portuguese). tourism is one of the mainstays of the economy. in there were · m. tourists (of which · m. were from mainland china, · m. from hong kong and · m. from taiwan), up from · m. in and · m. in . visitor spending in totalled , m. patacas. the government-run macao international music festival featuring a wide range of chinese and western music takes place in oct.-nov. in sept. chen shui-bian received a life sentence (later reduced to a -year term) after being found guilty of multiple counts of corruption. china and taiwan signed a free trade agreement in june , which was considered a significant thawing of relations. nonetheless, tensions remained, particularly in relation to disputed sovereignty over several islands in the east china sea. in jan. ma ying-jeou was re-elected to the presidency but the election in jan. was won by tsai ing-wen, whose democratic progressive party won the most seats in legislative polls at the same time-the first occasion that the nationalist party has not been the largest party in government since . beginning with the elections to the seventh legislative yuan held on jan. the legislative yuan has members (formerly ). of the members are elected under the first-past-thepost system in single-member constituencies, are filled by proportional representation in accordance with a nationwide party vote and six are reserved for aboriginal candidates. since the president has been directly elected. since a resolution on the impeachment of the president or vice president is no longer to be instituted by the control yuan but rather by the legislative yuan. the legislative yuan has the power to pass a no-confidence vote against the premier of the executive yuan, while the president of the republic has the power to dissolve the legislative yuan. the premier of the executive yuan is directly appointed by the president of the republic. in dec. a law came into effect allowing for referendums to be held. national anthem 'san min chu i' ('the three principles of the people'); words by dr sun yat-sen, tune by cheng mao-yun. conscription was reduced from months to months in . the government has announced its intention to move towards a volunteer professional force-a process that was originally scheduled to start in and end in but was delayed owing to low recruitment levels. in dec. the defence minister announced that conscription would officially cease in . defence expenditure in totalled us$ , m. (us$ per capita), representing · % of gdp. the republic of china army conducts ground combat missions as well as air support and airborne special operations. it was estimated to number about , personnel in , with reserves numbering · m. its principal role is to defend against a possible amphibious assault from the chinese mainland by the people's liberation army. in addition there are paramilitary forces totalling , personnel. navy personnel in totalled , , with , reservists. the forces consist of four submarines, four cruisers and frigates. there are also missile craft for patrol and coastal defence, mine-laying vehicles and amphibious landing craft. in the air force numbered , personnel with , reservists. there were combat-capable aircraft in the same year including f- es, f- s and mirage - s. by a treaty of dec. the usa pledged to defend taiwan, but this treaty lapsed one year after the usa established diplomatic relations with the people's republic of china on jan. . in april the taiwan relations act was passed by the us congress to maintain commercial, cultural and other relations between usa and taiwan through the american institute in taiwan and its taiwan counterpart, the co-ordination council for north american affairs in the usa, which were accorded quasi-diplomatic status in . the people's republic took over the china seat in the un from taiwan on oct. . in may taiwan ended its formal state of war with the people's republic. taiwan became a member of the world trade organization on jan. . in feb. taiwan had formal diplomatic ties with countries. in aug. , of the diplomatic allies sponsored an unsuccessful proposal for taiwan to join the un. taiwan has made a successful transition from an agricultural economy to one based on high-tech electronics. economic growth averaged % per year over three decades from the s, driven primarily by high value-added manufacturing and exports, especially in electronics and computers. government-owned enterprises, including banks, have been privatized. though largely escaping the impact of the asian financial crisis, the economy went into recession in with the first year of negative growth ever recorded and unemployment reaching record highs. strong export performance stimulated a recovery, with annual gdp growth above % from - . inflation has been consistently low and unemployment, which fell below % in , has averaged between and % since the turn of the century. owing to its heavy dependence on exports, taiwan suffered a severe downturn as a result of the global financial crisis in . major export industries such as semiconductors and memory chips declined, unemployment reached its highest levels since and, in , the economy again went into recession. a us$ · bn. stimulus package boosted recovery and in the economy recorded its highest growth rate for nearly three decades, at · %. however, growth subsequently cooled owing to lower demand from developed nations, averaging · % per year between and . tourism has grown in importance, with over · m. visitors in constituting taiwan's highest annual number to date. an ageing population and high savings rates threaten to constrain domestic demand in the future. the unit of currency is the new taiwan dollar (twd) of cents. gold reserves were · m. oz in dec. . there was inflation of · % in but deflation of · % in . foreign exchange reserves were us$ · bn. in dec. . in general government revenues totalled nt$ , , m. and expenditures nt$ , , m. tax revenue accounted for · % of revenues in ; education, science and culture accounted for · % of expenditures, economic development · % and general administration · %. taiwan sustained rapid economic growth at an annual rate of · % from up to . the rate slipped to · % in the s and · % in ; taiwan suffered from the asian financial crisis, though less than its neighbours. in global economic sluggishness and the events of sept. in the usa severely affected taiwan's economy, which contracted by · %. subsequent economic recovery led to growth of · % in and · % in . there was negative growth of · % in but again the economy bounced back, and grew by · % in , · % in and · % in . the central bank of the republic of china (taiwan), reactivated in , regulates the money supply, manages foreign exchange and issues currency. the governor is yang chin-long. the bank of taiwan is the largest commercial bank and the fiscal agent of the government. there are seven domestic banks, commercial banks and foreign banks. there are two stock exchanges in taipei. taiwan's carbon dioxide emissions from the consumption of energy in were the equivalent of · tonnes per capita. output of electricity in was · m. mwh; total installed capacity was , mw. there were six units in three nuclear power stations in . crude oil production in was , bbls; natural gas, m. cu. metres. taiwan imports most of the oil and natural gas that it consumes. in the cultivated area was , ha., of which , ha. were paddy fields. rice production totalled , , tonnes. livestock production was valued at nt$ , m., accounting for % of taiwan's total agricultural production value. forest area, : , , ha. forest reserves: trees, , , cu. metres; bamboo, , m. poles. timber production, , cu. metres. the catch in was , tonnes, almost exclusively from sea fishing. the first three are container centres, kaohsiung handling · m. -ft equivalent units in , making it the world's th busiest container port in terms of number of containers handled. suao port is an auxiliary port to keelung. in jan. the first legal direct shipping links between taiwanese islands and the chinese mainland in more than years were inaugurated. in there were , , landline telephone subscribers ( · per , inhabitants). taiwan's biggest telecommunications firm, the state-owned chunghwa telecom, lost its fixed-line monopoly in aug. . in there were , , mobile phone subscriptions, equivalent to , · per , persons. in there were · mobile broadband subscriptions per inhabitants and · fixed broadband subscriptions per inhabitants. in march there were · m. facebook users. the judicial yuan is the supreme judicial organ of state. comprising grand justices, since these have been nominated and, with the consent of the legislative yuan, appointed by the president of the republic. the grand justices hold meetings to interpret the constitution and unify the interpretation of laws and orders. there are three levels of judiciary: district courts and their branches deal with civil and criminal cases in the first instance; high courts and their branches deal with appeals against judgments of district courts; the supreme court reviews judgments by the lower courts. there is also the supreme administrative court, high administrative courts and a commission on the disciplinary sanctions of public functionaries. criminal cases relating to rebellion, treason and offences against friendly relations with foreign states are handled by high courts as the courts of first instance. the death penalty is still in force. there was one execution in but none in . the population in penal institutions in april was , ( per , of national population). since there has been compulsory education for six to year-olds with free tuition. the illiteracy rate dropped from · % in to · % by . there were , primary schools, , secondary schools and vocational schools in ; and universities, colleges and junior colleges. in - there were , , pupils with , teaching staff at elementary schools; , pupils and , teaching staff at junior high schools; , pupils and , teaching staff at senior high schools; and , students and , teaching staff at senior vocational schools. there were , , students in universities and colleges in - with , academic staff. in there were , physicians (one for every persons), , doctors of chinese medicine, , nurses, , dentists and assistants, and , pharmacists and assistants. in there were , medical facilities serving , persons per facility; there were , beds and · beds per , persons. in cancers, heart diseases, cerebrovascular diseases, diabetes and accidents were the first five leading causes of death. a universal health insurance scheme came into force in as an extension to social insurance plans that cover only % of taiwan's population. premium shares among the government, employer and insured are varied according to the insured statuses. by the end of , · m. people or % of the population were covered by the national health insurance programme. according to estimates by the pew research center's forum on religion & public life, · % of the population in were folk religionists, · % were buddhists and · % christians. the remainder of the population was either religiously unaffiliated or followed other religions, including taoism. there were daily newspapers in with a circulation of · m. and non-dailies with a circulation of · m. the biggest circulation dailies are the liberty times and apple daily. in there were , , international visitors. receipts totalled us$ , m. the pop festival, spring scream, is held in april in kenting. china in world history chinese politics in the age of deng xiaoping china and the global political economy china: the rise of xi jinping the cambridge encyclopaedia of china the cambridge history of china. vols the politics of hong kong's reversion to china the chinese economy under transition china this century the tragedy of liberation: a history of the chinese revolution china: a modern history china's deep reform: domestic politics in transition chinese capitalism deng xiaoping and the making of modern china the great chinese revolution - the politics of eu-china economic relations china's second continent: how a million migrants are building a new empire in africa china in transition: communism, capitalism and democracy sowing the seeds of democracy in china: political reform in the deng xiaoping era historical dictionary of the chinese cultural revolution the rise of modern china china: a macro history tombstone: the untold story of mao's great famine china's economy: what everyone needs to know all under heaven: a complete history of china chinese politics in the hu jintao era: new leaders, new challenges the people's republic of amnesia: tiananmen revisited chinese foreign policy in a changing world chinese economy in the s the politics of china: sixty years of the people's republic of china the party: the secret world of china's communist rulers. .-asia's reckoning: china, japan and the fate of us power in the pacific century china's war with japan, - : the struggle for survival social and political development in post-reform china age of ambition: chasing fortune, truth and faith in the new china a revolutionary life at the crossroads of post-communist modernisation: russia and china in comparative perspective a history of china wealth and power: china's long march to the twenty-first century mao's road to power: revolutionary writings - . vols china goes global: the partial power the chinese century: the rising chinese economy and its impact on the global economy, the balance of power, and your job the china-pakistan axis: asia's new geopolitics the chan's great continent: china in western minds eldest son, zhou enlai and the making of modern china india's and china's recent experience with reform and growth critical issues in contemporary china making china strong other more specialized titles are listed under territory and population; tibet; agriculture further reading statistical information: the census and statistics department is responsible for the preparation and collation of government statistics. these statistics are published mainly in the hong kong monthly digest of statistics. the department also publishes monthly trade statistics, economic indicators and an annual review of overseas trade hong kong's transitions the politics of hong kong's reversion to china the end of hong kong: the secret diplomacy of imperial retreat the hong kong story the final years of british hong kong: the discourse of colonial withdrawal last post: the end of empire in the far east the politics of democratization in hong kong historical dictionary of hong kong and macau china: a political history of the british crown colony's transfer to chinese rule managing china's sovereignty in hong kong and taiwan the democratic progressive party won seats ( constituency and proportional); the nationalist party, ( constituency and proportional); the new power party, ; the people first party, ; the non-partisan solidarity union, ; ind., . current government president: tsai ing-wen; b. (nationalist party/kuomintang foreign affairs; health and welfare; interior; justice; labour; national defence; science and technology national defence: yen de-fa. science and technology: chen liang-gee. transportation and communications: ho chen-tan tang feng; lo ping-cheng coast guard administration: lee chung-wei. environmental protection administration: lee ying-yuan. fair trade commission: huang mei-ying. financial supervisory commission: koo lihsiung. hakka affairs council: lee yung-te. council of indigenous peoples: icyang parod. mainland affairs council: chen ming-tong. national communications commission: chan ting-i. overseas community affairs council: wu hsin-hsing. directorate general of personnel administration: shih ning-jye. veterans' affairs council: lee shying-jow hon hai precision industry, an electronics manufacturer (us$ · bn.); and chunghwa telecom (us$ · bn metres; integrated circuit packages, · trn. units; global positioning system (gps) sets, · bn. units. labour in the average total labour force was · m., of whom · m. were employed. of the employed population, · % worked in manufacturing · % in construction; · % in accommodation and food services buses and coaches, · m. lorries and vans, and · m. motorcycles and mopeds were in use. , m. passengers and m. tonnes of freight were transported in . there were , fatalities in road accidents in . rail in freight traffic amounted to · m. tonnes and passenger traffic to m. total route length was , km. there are metro systems in taipei civil aviation there are currently two international airports: taiwan taoyuan international airport at taoyuan near taipei, and kaohsiung international in the south there were ships of gt or over registered, totalling · m. gt. of the vessels registered, were general cargo ships, bulk carriers, container ships, oil tankers and nine passenger ships. there are six international ports statistical yearbook of the republic of china. annual. the republic of china yearbook. annual. taiwan statistical data book. annual. annual review of government administration the other taiwan: to the present day historical dictionary of taiwan national identity and status in international society managing china's sovereignty in hong kong and taiwan the shadow of china: political developments in taiwan since national statistics website the climate is subtropical in the north and tropical in the south. the typhoon season extends from july to sept. the average monthly temperatures of jan. and july in taipei are · °f ( · °c) and · °f ( · °c) respectively, and average annual rainfall is · " ( , · mm). kaohsiung's average monthly temperatures of jan. and july are · °f ( · °c) and · °f ( · °c) respectively, and average annual rainfall is · " ( , · mm). the roc constitution is based on the principles of nationalism, democracy and social wellbeing formulated by dr sun yat-sen, the founding father of the republic of china. the roc government is divided into three main levels: central, provincial/ municipal and county/city, each of which has well-defined powers.the central government consists of the office of the president, the national assembly, which is specially elected only for constitutional amendment, and five governing branches called 'yuan', namely the executive yuan, the legislative yuan, the judicial yuan, the examination yuan and the control yuan. key: cord- - oynmvt authors: tsai, jong‐rung; yang, chih‐jen; huang, wei‐ling; chen, yen‐hsu title: decline in invasive pneumococcus diseases while combating the covid‐ pandemic in taiwan date: - - journal: kaohsiung j med sci doi: . /kjm . sha: doc_id: cord_uid: oynmvt nan according to the taiwan cdc, there has been a marked decline in invasive pneumococcus disease since february compared with cases in the past years (figure ). streptococcus pneumoniae can spread through droplets in the air as with covid- , and s pneumoniae may enter and remain in the nose and throat. the incubation period of s pneumoniae is about to days, after which it can invade the lungs, blood, sinuses, middle ear, or brain, potentially leading to a severe and fatal infection. "invasive pneumococcal disease" is defined as an infection confirmed by the isolation of s pneumoniae from a normally sterile site, such as blood, cerebrospinal fluid, and pleural, joint, or peritoneal fluid. invasive pneumococcus is a notifiable disease, and it must be reported to the taiwan cdc within week. we believe that the reduction in invasive pneumococcus disease has been influenced by the current preventive strategies for covid- in taiwan. chih-jen yang wei-ling huang covid- : face masks and human-to-human transmission. influenza other respir viruses effectiveness of masks and respirators against respiratory infections in healthcare workers: a systematic review and meta-analysis rational use of face masks in the covid- pandemic upper respiratory tract colonization with streptococcus pneumoniae in adults a visual review of the human pathogen streptococcus pneumoniae key: cord- -v jryi authors: sun, ya-yen; rodriguez, ariel; wu, jih-hwa; chuang, shu-tzu title: why hotel rooms were not full during a hallmark sporting event: the world games experience date: - - journal: tour manag doi: . /j.tourman. . . sha: doc_id: cord_uid: v jryi hosting mega- and hallmark-events is perceived as an important vehicle for tourism development. however, in the case of the world games, the first international hallmark sporting event in taiwan, the volume of hotel occupancies and revenue fell short of expectations, despite years of planning and an investment of us$ million. this study set out to investigate this phenomenon by adopting semi-structured interviews to gather opinions from key stakeholders regarding their business operation and societal conditions. factors contributing to the lower than expected revenue included inefficient collaboration among stakeholders, a substantial displacement effect to regional hotel competitors, and the unfriendly local atmosphere associated with the fear of h n , typhoon morakot, and controversial political events. to mitigate inefficiencies from stakeholder collaborations, the study results suggest greater equality in terms of responsibility, information distribution, and risk sharing is needed among the broader tourism industry, the event planning association, and the event supervising authority. in addition, business strategies should take into account taiwan, an island destination, and current tourism characteristics to counter the displacement effects of loyal and potential customers. large-scale, high-profile sporting events have increasingly been positioned as critical components when aspiring for international recognition as well as generating significant social, cultural, and economic benefits for a region. in particular, hosting mega-and hallmark events is perceived as an important vehicle for tourism development because it facilitates an increase in tourist numbers, the generation of a positive destination image, and the development of areas (fourie & santana-gallego, ; getz, ) . according to teigland ( ) , the tourism demand pattern of special events follows two forms: a "new plateau" scenario and a "back to normal" alternative. the former represents increased tourist volume after the hosting of mega-events because of increased awareness of the destination, improved attractions and infrastructure, and an extensive transportation system established during the hosting, from which the destination builds up its competitiveness among other tourist destinations. the "back to normal" scenario, on the other hand, implies that a big tourism boom is realized during the event period; however, the demand related to tourism services and goods reverts to pre-event levels after the occasion is completed. a bell-shaped curve of the tourist flow over time is thus observed. the main factor that determines the reduction of tourist demand is a decreased destination awareness among potential tourists when media attention switches to other upcoming events. in response to the economic importance of tourism development with special events, academic research on this topic has flourished. this research line can be divided into two categories. the first research direction emphasizes the economic impact analysis associated with the expenditure of participants using empirical numbers to demonstrate the contribution of sales, personal income, and value added generated by the event. the applications include mega-events (such as the olympics or fifa world cup), hallmark events (such as the commonwealth games and world games) and small-scale regional sports competitions (connell & page, ; daniels, ; daniels, backman, & backman, ; daniels & norman, ; dwyer, forsyth, & spurr, ; gratton, dobson, & shibli, ; gratton, shibli, & coleman, ; jones & munday, ; lee & taylor, ; manzenreiter, ; preuss, ; ryan & lockyer, ; wilson, ) . from teigland's ( ) perspective, this type of quantitative practice is used to measure the magnitude of the economic peak during the once-only impulse of a sporting event, as these studies capture a snapshot of economic changes on-site during a relatively short period. the second type of research focuses on long-term economic changes from a local, regional, and national perspective with the aim of verifying whether hosting special events can effectively stimulate regional economic changes over a long-term period. this research line addresses only mega-event scenarios by performing econometric analysis on time-series data of tourist numbers, tourism industry performances, gross domestic product, or employment figures. the main purpose is to provide evidence as to whether the growth path of a host region differs from that of other reference cities (baade & matheson, ; fourie & santana-gallego, ; hagn & maennig, ; kirkup & major, ; manzenreiter, ; preuss, ; solberg & preuss, ; szymanski, ; teigland, ) . this type of research is equivalent to examining which condition, a "new plateau" scenario or a "back to normal" alternative, is observed based on teigland's ( ) typology. the commonality of both study lines generally acknowledges a tourism demand peak during the event; however, the magnitude of visitor influx or the level of "big tourist boom" was inconsistent in various ex-post impact reports. by using visitor numbers or hotel occupancy as measurement variables, the following studies presented a less optimistic result regarding short-term tourism impacts during the event. du plessis and maennig ( ) indicated that the total number of attendees at the fifa world cup (wc) was only one-third of the most conservative ex-ante expectation. porsche and maennig ( ) argued that the tourism, employment, and income effects of the wc were not realized and the greatest outcome of this event was the "feel-good" effect. manzenreiter ( ) showed that monthly foreign visitor numbers to japan during the wc were no different to other months in the same year for the host country. allmers and maennig ( ) , using monthly overnight non-resident stay data, demonstrated that the wc did not produce any statistically significant effects on local hotel suppliers. porter and fletcher ( ) pointed out that, during the summer olympics, the occupancy rate in atlanta rose slightly ( . %). similarly, teigland ( ) indicated that the winter olympic games was a disappointment for several hotels in the host regions, especially for hotels located approximately e min away from the city center because a strong concentration effect was observed in which visitors occupied hotels that were close to the event venues. this type of general pessimism is also supported for other major sporting events, as matheson and baade ( ) and porter ( ) reported insignificant visitor spending and hotel occupancy rates during the us super bowls. of course, there is supporting evidence regarding short-term positive, significant, and satisfactory tourism effects, including the montreal olympics (whitson & horne, ) , the world cup (baade & matheson, ) , the flora london marathon (gratton, shibli, & coleman, ) , the summer olympic games (drayton, ) , and the winter olympic games (porter & fletcher, ) . although the literature has demonstrated two possible, significant and insignificant, short-term tourism effects associated with large sporting events, every host country strives to prepare itself for the greatest opportunity to attract large tourist numbers and spending. hosting the world games (wg), the first international hallmark sporting event in taiwan, was no different in seeking the same objective. however, despite years of preparation, heightened media attention, and investments of us$ million, the ex-post analysis for the wg revealed that the local accommodation sector did not achieve a satisfactory performance with regard to hotel receipts and occupancy rates, nor was an enduring short-term accommodation demand observed afterward. this pattern of the wg was consistent to the literature on the insignificant tourism effects associated with major sporting events, signaling that a "big tourist boom" scenario was not realized. several reasons have been attributed to insignificant tourism demand in the literature, including displacement effects, financial crisis, the scale of events, the development level of the host country, and whether the event is held during the off-season (baade & matheson, ; fourie & santana-gallego, ; manzenreiter, ) . however, because each region embraces different economic relationships and unique interactions of stakeholders, case studies of individual scenarios shall be adopted and elaborated to provide an insight into factors that may help to address the unsatisfactory tourism performances and lay out the interconnected components (d' angella & go, ; solberg & preuss, ) . therefore, the purpose of this paper is to explore factors that may help to address this unexpected short-term soft occupancy rate in the host city by interviewing representatives of the local business sector and municipal government. the study contributes to the literature by deviating from the research agenda of the previous studies, which generally analyzed highly aggregated econometric data without direct contacts with business enterprises. through industry and event organizer interviews combined with secondary information, this study provides insights specifically into the accommodation phenomenon. additionally, the context focuses only on hallmark sporting occasions instead of mega-events, as the former type is the prime target for small economic entities to compete for the right of hosting. aim of this study is to assist planners of similar future events to improve their forecasting efforts, decisions, and concepts. the reminder of this paper is as follows: section presents background information regarding the world games and the ex-post analysis of the accommodation sector during the event; sections and discuss the process and the results of personal interviews with representatives of the local business sector and municipal governments, while section provides implications and then concludes with discussion. context. since , the world games (wg), which is held at quadrennial intervals, has provided an international competition stage for major and popular sports that are excluded from the olympic games, such as cannon polo, sumo wrestling, and bowling. the first wg in santa clara in included sports with participating athletes, and it gradually expanded to sports and athletes in duisburg in . the wg is held under the auspices of the international world games association (iwga), which comprises international sports federations, and receives support from the international olympic committees (international world games association, ) . although the world games have only been held times, they are regarded as the largest multi-sport event outside the olympic games and have received increasing attention (wu & chu, ) . kaohsiung city, the second largest city in taiwan, started its planning and bidding process in to compete for the right to host the th world games in against other bidders from rotterdam, budapest, birmingham, cleveland, and houston (kaohsiung organizing committee, ). in june , the official announcement from the iwga declared that kaohsiung city had won the bid and the host region received a considerable amount of national publicity because this opportunity represented the first international multi-sport event ever held in taiwan. this event was scheduled for july e , and offered a diverse program with the greatest number of competing sports in the history of the wg. for the host government, this represented an excellent opportunity to market the national brand name and generate significant social, cultural, and economic benefits for the region. one major objective in hosting the wg was to revitalize the image of kaohsiung and attract significant visitor numbers and spending during and after the event (wu & chu, ) . a high tourism volume was eagerly anticipated because the host region was anxious to transform its economic base from traditional manufacturing production to service and tourism economics. to cope with this special event, the central government and the taiwan tourism bureau laid out a series of campaigns to promote tourism and attract foreign visitors. an investment of us$ million on world-wide tourism promotional campaigns and activities was implemented in and . this marketing campaign aimed to attract over . million tourists to taiwan in , where two major sporting events, the world games in kaohsiung and the deaflympics in taipei, were highly regarded (international world games association, ; the china post, ) . process. the preparation committee and coordination committee for the world games was established in , entitled the kaohsiung organizing committee (koc), a temporary, nongovernmental foundation. this organization was supervised by a board of directors, including the city mayor and appointed officials. although the koc was positioned as a non-governmental agency, among their full-time employees, % of the staff were kaohsiung city government employees who were temporarily transferred from their original posts to this agency to assist in all the administration details. in addition, the koc was entrusted with a total budget of us$ million dollars, including the construction of a main stadium ($ . million), event operation ($ . million), venue renovation ($ . million), and broadcasting service fees ($ . million) (kaohsiung organizing committee, ). taiwan's central government and the local city government provided % and % of the funding respectively. hotel capacity. one of the obligations for hosting wg is to cover all the lodging and local transportation expenses for the iwga committee representatives, wg athletes, referees, and staff members. to arrange complimentary accommodation for all wg participants, the koc chose to use existing hotel facilities in kaohsiung city, instead of school or athlete dormitories. to accommodate the large volume of guests, koc contracted with tourism hotels, general hotels, and publicly owned accommodation facilities in kaohsiung city. the tourism hotels are -or -star hotels, serving mainly inbound visitors and high-end domestic tourists (taiwan tourism bureau, e ) . the general hotels were small-scale hotels with a main market focus on group travelers based on discounted prices. the accommodation providers that cooperated with the koc were the main stakeholders in the region for room capacity and service quality, and were members of the kaohsiung hotel association. the contracted room prices were predetermined by the koc as follows: us$ , us$ , and us$ per night, differentiated based on the quality of the hotel facility. each hotel was first evaluated by the koc for qualification, and the business then determined the number of rooms that they reserved for the koc during the -week period. in the end, the government contract ensured that accommodation establishments in total provided a capacity of beds per day. the ex-post economic impact study estimated that the wg attracted wg participants and , travel parties of spectators with a total spending of us$ million to kaohsiung city (sun, ) . domestic tourists contributed % of total spending, followed by local residents ( %), world games participants ( %), and international tourists ( %). simply using these demand-side figures to determine the success of catalyzing tourism development is difficult and subjective. because the sales and capacity utilization of the tourism industry sector can serve as a good proxy to reflect optimal visitor volumes (bonn & dai, ; brannas & nordstrom, ; solberg & preuss, ; stynes & white, ) , these indicators were used in this study as a measurement basis. the performance of the local accommodation sector was first compared with the national data so that the lodging effect associated with the wg could be contrasted with other areas that did not host any high-publicity events. the historical data indicated that tourism hotels and general hotels in kaohsiung generally exhibited superior performance than the national average for monthly occupancy (fig. ). in particular, during april and may , -star hotels in kaohsiung had an excellent season, reaching over % occupancy, and performed %w % higher than the national average (taiwan tourism bureau, e ). however, this trend did not continue. for the month of the wg in july, the occupancy rate of kaohsiung tourism hotels was %, and the general hotels reported % occupancy, which was only % and % higher than the national average respectively. the hotel demand of the wg did not fit the profile of a bell-shaped demand curve proposed by teigland ( ) . after the event, occupancy in the kaohsiung area continued to drop and reached its lowest point in september, during which the performance was inferior to the national average. compared with the data, the monthly sales of the tourism hotels decreased by % from october to november , indicating a weak tourism demand immediately following the event (taiwan tourism bureau, e ). although the tourism hotel occupancy rate did not demonstrate a peak in july, the local room price rose considerably during that month, from an average of us$ . per night in june to us$ per night in july ( % increase) (fig. ) . the high room price and relatively low occupancy rate compensated for each other so that total sales of kaohsiung tourism hotels during the wg, us$ . million, were similar to the sales level of other periods. from a monthly perspective, the two best performance periods for hotel revenue in were january and december, reaching over us$ million. neither of the good months had factors directly linked to the hosting of the world games. the contribution of room nights and hotel revenue by wg participants and spectators for july were isolated and compared. the contribution of the wg spectators to the city hotels in july was estimated to be % whereas wg participants contributed %. in terms of lodging sales, the total accommodation spending of the wg spectators was estimated to be us$ . million, accounting for % of local monthly sales. owing to a lower contract price, the koc covered the us$ . million lodging expenses of the wg participants, which constituted only % of the monthly room revenue in the host city (sun, ) . to conclude, the local hotel sector exhibited a relatively high room price pattern, a soft occupancy rate, and an ordinary room revenue intake during the month of the world games. to explore the factors associated with this observation, key stakeholders, including members of the local lodging sector and the koc, were interviewed independently to obtain insights regarding their business operation and the related administration details. the interview process is described in the following section. on-site semi-structured interviews were conducted with local hotel managers and the koc. the sampling frame of hotels was obtained with the assistance of the kaohsiung city government, providing a list of contracted hotels that offered accommodation services to the wg athletes, staff, vips, and media. these hotels were selected as our samples because they cooperated closely with the city government and their business was greatly affected by the staging of this event. in addition, these providers were the key stakeholders in the region for room capacity. the kaohsiung city government assisted with data collection by issuing an official letter to the hotels month after the wg to request these businesses to participate in the interview. individual companies were later contacted by phone to inform them of the study purposes, inquire as to their willingness to participate, and to set up the appointment. twenty hotels, including tourism hotels and general hotels, agreed to be interviewed during october and november . the face-to-face interview adopted the semi-structured format and two main questions were raised: "is the hosting of the world games beneficial to the hotel business?" and "what is the importance of the world games on future tourism development in kaohsiung city?". the interviewee in this study was either the marketing department director or room division manager, and had the knowledge and seniority to answer the interview questions regarding the hotel's operation before, during, and shortly after the wg. the interviews averaged approximately . h each and were summarized using field notes. the second stage of this study was to arrange a personal interview with the koc/kaohsiung tourism bureau. the timing was arranged after the hotel interviews were completed to communicate the problems that were raised by the private sector to the governing authorities. after each interview, interview scripts were coded and then categorized into main themes, such as the contract issue and the turn away of group visitors. texts under the same theme were merged together across interviewed hotels to support each other's opinions. we further summarize these common themes into five major factors. during the interview process, some hotel managers supplied their occupancy rates and room revenue to support their opinions, which were later cross-checked against the data provided by the koc. in addition, secondary data from governmental statistics, newspapers, and other study reports were studied and are cited in this paper to further validate stakeholders' opinions and draw out content and meaning. based on the observation of the researchers, the interview results reflect a high level of credibility based on the cooperative and candid attitude of the managers and the consistency of their descriptions of business with secondary data. hotel managers all perceived the wg as a positive stimulus to kaohsiung city tourism development from a long-term perspective. the transformation of the city image, the marketing of the city brand name, and the improvement in basic infrastructure were deemed to be strong advantages to attract a diverse array of visitors in the future. in particular, the newly built us$ million world games stadium was highly regarded as an effective venue to host large events in kaohsiung city. compared with the deaflympics in taipei, hotel managers indicated that wg received greater praise and positive publicity, demonstrating that local government had the ability to stage a large-scale activity. this perspective was further confirmed by the endorsement of the iwga officials in claiming this event as the "the best world games ever" (international world games association, ). however, for the short-term operation, hotel managers all stated that the wg generated only a modest one-time peak in demand and did not maintain a steady tourism volume afterward; at least, the effect was not observed during the -month period after the wg (augustenovember, ). fifteen hotels ( %) indicated that room sales during the event were lower than expected, whereas only one hotel indicated a % sales increase during july compared with typical monthly revenue. four hotel managers ( %) declined to comment on that issue directly. hotel managers provided various factors that may help to address this unsatisfactory sales figure during and shortly after the event period. their opinions are summarized in the following. the majority of hotel managers indicated that the rooms contracted with the koc for wg participants were poorly utilized. among the reserved beds per day (defined as a room block) across hotels, on average, % of the capacity was not used and each hotel suffered a different level of low occupancy for their contracted rooms. ten hotels reported that less than half the reserved rooms were used, and the worst scenario involving two hotels reported that % and % of the reserved rooms remained empty during the -week period. the original motivation of these businesses to participate in the koc contract, in addition to raising the awareness of brand name among wg participants, was to guarantee particular amount of room sales during the event period because hotel managers all optimistically expected the contracted rooms would be highly utilized. in reality, the total number of wg guests and their overall length of stay were much lower than the koc had previously anticipated. this resulted in low occupancy of reserved rooms. in addition, under the contract with the city government, the unoccupied rooms were not able to be released during the event and the loss of sales was not compensated by the government either. many managers said that they understood that % occupancy was unfeasible, but that an occupancy of % from the wg guests and athletes was very disappointing because they did not receive any compensation from the government for any unused reserved rooms. from the koc perspective, the discrepancy between their estimated numbers and the real occupancies of the wg guests was caused by a technical problem with the iwga registration system. the technical problem delayed the registration process, and the final list of participants and guests that were scheduled to check in to the local hotels was not available until a few days prior to the opening ceremony. this delay meant that the koc was unable to determine the exact number of rooms required per night. bounded by the contract, % of the reserved hotel rooms (¼ , bed-nights in weeks) remained empty and unpaid for during the event period. several hotel managers indicated that a substantial displacement effect in location for potential and regular hotel guests during the wg was a crucial factor for the low hotel occupancy rate during the event. this pattern was verified by the fact that star hotels in tai-nai and kaohsiung county, approximately mine h driving distance away, reported a % and % increase in occupancy from june to july , respectively, whereas the tourism hotels in kaohsiung only reported a % increase in occupancy for the same period (taiwan tourism bureau, e ) . based on managers' opinions, a number of customers were discouraged to stay locally mainly because regional service providers had offered a much more attractive room price, around us$ eus$ , which were %e % cheaper than those in the host city. in addition, kaohsiung hotels experienced a % price increase during the wg event, whereas the tourism hotels in tai-nai and kaohsiung county only increased their room prices by % and % from the previous month. from the perspective of the accommodation sector in kaohsiung city, an elevated room price was a normal business practice because local hotels all expected that the wg would generate an influx of domestic and international visitors who were willing to pay premium prices to be part of this event. members of the kaohsiung hotel association had a mutual agreement that the high-season room price would be charged during the event period, especially as they felt that july was already a popular travel season for families during the summer break irrespective of the highly anticipated wg spectators. the iwga policy on wg admission tickets also contributed to the displacement effect. from the start of the preparation stage, the iwga did not permit any package deal that combined wg tickets with local tourism amenities, such as accommodation, transportation, or souvenir discounts. their position was that each wg event bore a prestigious image, serving as an excellent attraction in itself. therefore, all event spectators purchased wg tickets independently through a nationwide convenience store network, disregarding their choices of lodging and transportation. not being able to promote local accommodation services with wg tickets meant that there was no incentive for visitors to stay locally. these aforementioned factors together led to switching behavior of tourists during the event, which resulted in good revenue for hotels located about min away at the expense of low occupancies of hotels in the host city. the combined factors of reserving a large number of rooms for the koc and charging high prices during the event period led to the loss of group customers. the process of working with local travel agencies who channel package tourists to the hotels requires confirmation of rooms and prices e months prior to the event. in hoping for a large volume of individual customers willing to pay premium prices, the hotel managers indicated that they turned down several business opportunities with local travel agencies. this practice, especially for general hotels, which primarily based their business on group tourists, drove away loyal customers and hampered cooperation with travel agencies that bring in largevolume package tours. many group customers, arranged by travel agencies, therefore shifted their lodging choices to regional cities. a number of managers suspected that the low demand was partially caused by the fear of a possible pandemic outbreak. the risk of a wide-spread h n influenza outbreak in taiwan and other asian countries since may has deterred certain groups from traveling domestically and internationally (lee, song, bendle, kim, & han, ) . the number of friends and relatives that might have come along with the athletes to taiwan was greatly reduced, resulting in a much lower numbers than hotel managers had previously anticipated. although cases of large-scale infection had not been reported in taiwan, the information on the contagious nature reminded people of the previous outbreak of severe acute respiratory syndrome (sars) in asia in , which resulted in medical cases and deaths in taiwan alone (world health organization, ) . the fear of a possible h n outbreak echoed the previous memory of sars and reduced people's willingness to travel. no-one, except one hotel manager, claimed that the hosting of the wg generated consistent short-term tourist demand. after the world games, monthly room sales in kaohsiung from august to october plunged to the lowest point of the year, which validated the opinions of most managers. the reasons for the low occupancy after the wg were complicated by severe weather conditions and controversial political events in the hosting city. two weeks after the closing ceremony, southern taiwan was devastated by the powerful typhoon morakot on august , , which was the deadliest typhoon to affect taiwan in recorded history. the typhoon caused the most severe flood of the past years, and resulted in the deaths of people, missing people, and more than damaged bridges, which disrupted the transportation network for the rural areas in southern taiwan (central weather bureau, ) . this destruction led to a negative destination image for kaohsiung city and deterred domestic travel to the area even though all tourism services and attractions were fully functional and accessible in the city (ko, ) . in addition to the weather factor, the visit of a political figure, the dalai lama, to kaohsiung city from august to september , , and the public screening of the controversial kadeer film "the ten conditions of love" during mid-october , both of which were administered by the local government, triggered heated political disputes. both the dalai lama and kadeer were regarded by the chinese government as instigating rebellion, and any international recognition given to them would trigger retaliation as these events were perceived by the chinese government as interference in domestic affairs. the controversy surrounding both events was reported to have hindered the cross-straits relationship as well as bilateral tourism volume between taiwan and mainland china (mcdonald, ) . strong rebukes of kaohsiung city by mainland china were observed through the cancellation of official business visits and diversion of chinese leisure travelers to other regions in taiwan without stopping in the city. hotel managers agreed that these two events led to reduced demand from chinese tourists who had been an important and emerging market segment for kaohsiung. the aforementioned factors, their influences, and consequences on hotel revenue are further summarized in the framework of stakeholders, island characteristics, and social and natural factors ( table ). the three major stakeholders identified in this study are the kaohsiung organizing committee (koc), the international world games association (iwga), and kaohsiung hotel businesses, each inheriting the role of event planning, event supervision, and service provision. in addition to the administered policies and business strategies, the characteristics of the island economy, and complex social and natural factors contributed to unsatisfactory hotel revenue and occupancies. it is important to note that the results from this study do not imply a simple causal relationship between the hosting of a hallmark event and short-term insignificant tourism demand. the short-term effect of the wg may have been positive, but because of these external uncontrolled natural and social factors, demand for tourism services was pushed down. without the counterfactuals, we only attempt to capture the factors relevant to the observed phenomenon, but warn against any direct inference or generalization to other events. although there is no perfect recipe for initiating a tourism demand peak, two important implications emerged from this case study as lessons to be learned. in the tourism literature, the general stakeholder theory calls for broad involvement in tourism networks from diverse bodies and firms so that management, planning, and marketing can be efficient and effective in building up destination competitiveness (d 'angella & go, ; jamal & getz, ; sheehan & ritchie, ) . the same logic, that is, a collaborative and inclusionary consensus-building practice, applies to all stakeholders that host a successful large event. the shared capital for a sustainable strategy, as proposed by healey ( ) , can be differentiated as social capital (trust, flows of communication, and willingness to exchange ideas), intellectual capital (mutual understanding), and political capital (formal or informal agreements and implementation of projects). the interaction among the koc, iwga, and local business sectors had experienced various social, intellectual, and political dynamics, which allowed us to trace their cooperation patterns in response to the hosting of the wg. the in-depth observation of these three stakeholders on their responsibility, power status, and communication revealed an unbalanced pattern. when the koc was entrusted with the responsibility for arranging complimentary lodging services for all wg participants, the agency decided to enter into contract with the local accommodation sector. the initial planning was offered as goodwill for the regional economy because it was assumed to guarantee an ensured amount of sales to local businesses. this concept was originally welcomed by small-scale general hotels and further embraced by -star tourism hotels when the koc and city government officials provided repeated and friendly invitations for them to join the project. the social and intellectual capitals, at that stage, were firmly established when both bodies exchanged trust and mutually agreed that provision of high-quality accommodation services with a large capacity was the core objective of the project. at that moment, the hotel sector trusted the arrangement of the koc and optimistically believed the contracted rooms would be utilized and this cooperation would benefit business greatly in terms of revenue generation and brand name promotion. however, the balance of cooperation between both parties was first hampered by the formal contract agreement, the political capital, which imposed the following rules: ( ) businesses must reserve a certain number of rooms during the event and no reselling was allowed if not occupied; ( ) businesses must accept a room price that was predetermined by the koc; ( ) no payment will be granted if the contracted rooms are not used. the last rule was against a typical booking requirement as most hotels would ask for advance payment and a penalty would apply if customers did not show up. one driving factor for the koc to impose such an atypical restriction was that all of the operations of the wg were % government funded. this required the koc to comply with the taiwan government procurement act by paying only for products or services that were transacted (ministry of justice, ). for rooms that were not used by wg participants, the transaction was not realized and, under these circumstances, the koc was unable to make final payments. this political agreement between both parties was in favor of the koc and transferred the operational risk from the government to the local business owners by asking the businesses to bear the revenue losses for any no-shows or shorter stays. under this condition, the koc was able to reserve a more than sufficient number of hotel rooms without concerns for the possible penalty for unoccupied units. consequently, this put the koc in a safe position because any last-minute wg athletes or vips would be guaranteed a room, especially when the iwga was not able to deliver the final list of guests on time because of technical problems with the registration system. the social capital, flow of information and communication, at this stage, started to demonstrate an unbalanced pattern as the iwga and koc were not able to synchronize the information on exact checking-in of guests and their length of stay to the businesses in advance, creating vulnerability for the hotel owners as they were not in direct control of occupancy. since the opening ceremony, the trust between the koc and hotels began to deteriorate, especially for those that faced a larger percentage of empty reserved rooms. the disappointing hotel revenue caused arguments between the two parties and threatened the mutual trust and possibility of future cooperation. the goodwill of the koc, that is, providing the room contracts to local hotel businesses, triggered a chain reaction in which the hotel businesses turned down reservations for group customers e months prior to the event, raised the room price because they expected individual customers to pay premium prices for limited room capacity, and then suffered revenue losses due to empty reserved rooms and the turning away of group and potential customers. before we comment further on this contracting and risk issue, the accommodation system and policies of the fifa world cup are presented first to provide parallel perspectives. in contrast to the wg, for which the accommodation policy was fully controlled by the government-oriented koc, the wc had mandated private match event services as its exclusive official accommodation, ticketing, and information technology service provider. match is % share-owned by a uk company, byrom plc, and has also been the official supplier of accommodation for the six previous world cups (rose, ) . the inclusion of such an official accommodation service provider generates a capacity to the following: ( ) involve various hotel operators, ranging from hotel chains and universities to small, medium, and micro-enterprises (smme) with fifa accreditation for the guarantee of quality; ( ) offer package deals that combined accommodation, entertainment, and air travel to ensure high attendance at the tournament; and ( ) provide free marketing displays for the hotels on the fifa website, which helped to gain extensive international exposure (cornelissen, ) . although match was praised for its inclusion of smme, match's policy created financial burdens on the accommodation providers because it forcefully stipulated the fifa room prices as "the june room rate plus a percent mark-up" for business operators, and a % commission fee was required on top of the net payable fifa wc rate (darkey & horn, ; jago, dwyer, lipman, van lill, & vorster, ; rose, ) . the strict accommodation provision agreements led to an outcry from the industry as they complained that the rate was artificially too low, and they felt that match had taken the cream of the accommodation crop as match's profit would be diverted to a uk-based company. the comparison of the wc and the wg on their accommodation arrangement process in table points out two perspectives as lessons to be learned for taiwan. first, the development of package deals, combining ticketing, accommodation, air travel, and entertainment services, is necessary to provide a strong incentive to ensure high attendance and spending at the tournament. the success of this type of tour package signals a means to diversify revenue income for the hotel because they can benefit from the provision of associated recreational services. this premise, however, requires close cooperation among the koc, iwga, and the local hotel industry to create an image of the "official suppliers". we observed that the koc website advertised local hotels disregarding whether they have cooperated with the koc. in other words, no marketing advantages were created solely for those businesses that were contracted. therefore, one way to assist these partners is to arrange marketing campaigns and price discounts to foster the exclusiveness and competitive advantages of these operators under the banner of the "official world games accommodation service provider". this would contribute to their brand name promotion in addition to revenue generation. second, from the wg experience, the strict contract agreement and inefficient capacity control of wg participants shall be evaluated. although limited by the taiwan government procurement act, paying only for services that are transacted, it is recommended that the room price policy should consider the probability of noshows or shorter stays, and raise the contracted room rate proportionally, instead of being arbitrarily determined by the koc alone. in the example of the wg, approximately one-third of the reserved rooms were unoccupied, suggesting that the official room rate set by the koc could be raised upward of at least %. with brand name promotion, revenue diversification, and contract price adjustment, the cooperation among the koc, iwga, and local hotel entities would represent one step toward a fair status in terms of responsibility, information distribution, revenue generation, and risk sharing. because the world games was the first international hallmark event for taiwan and kaohsiung city, the local business sectors had no previous experience to draw on. their current business strategies did not adequately adjust to the characteristics of a small island economy in response to large events, rendering their operation at a disadvantage. observation of the wg indicated a high percentage of day trips ( %) and a strong displacement effect among individual and group customers to the nearby counties. these customers preferred to commute to the city center instead of staying locally (sun, ) . for the first factor, it is crucial for the hotel industry to recognize that taiwanese event spectators are currently dominated by local residents, followed by regional domestic visitors and very limited numbers of international travelers. based on a study of four major cultural festivals in taiwan, local residents accounted for %e % of total event participants, whereas international travelers comprised less than % (outdoor recreation association, ) . although the wg was a larger scale event with intensive international media exposure, its spectators still conformed to this pattern, showing relative percentages of %, %, and % from local residents, domestic visitors, and international visitors on party trips (sun, ) . in terms of the displacement effect, it has been cited by many researchers as a key factor in leading to less optimistic visitor numbers during the event (baade & matheson, ; du plessis & maennig, ; fourie, siebrits, & spronk, ; manzenreiter, ; porter, ) . this concept was first raised by crompton ( crompton ( , , as the hosting of a sporting event may drive away potential visitors who may otherwise have come to the community. in the observation of the authors, the crowding-out effect of the wg did not completely drive spectators away (to cancel their visit), but it reduced their willingness to stay locally and shortened their length of stay in the host region. the displacement of tourism is not only observed between cities (regions) but also over time in this instance. from the location perspective, contrary to some literature indicating a strong concentration effect on demand for staying close to the sporting venues (drayton, ; teigland, ) , in the case of the wg, accommodation located about min away was perceived as a good alternative to stay overnight for some spectators. this displacement effect by location can be explained by the island and tourism characteristics of taiwan. the small and highly populated country has an extensive transportation network of high-speed rail, public transportation, and highway systems, allowing travelers to bear relatively cheap switching costs in terms of time and monetary expenses (huang & tai, ) . in addition, the pricing practice of hotels located around min away from the host city remained relatively constant and cost-effective during the event period, thereby offering a strong "pull factor" in relation to centrally located hotels. from the temporal perspective, the crowding-out effect applies to group visitors whose reservations were declined by the local hotel industry e months in advance. this was attributed mainly to a self-defeating expectation pattern, that is, the adverse impact on actual demand of exaggerated prices based on the ex-ante anticipation of massive tourist arrivals, which was also reported previously from the world cup in south africa (du plessis & maennig, ) . in contrast to individual travelers, group customers follow a pre-determined itinerary, and it is difficult to rearrange their accommodation choice once determined. in other words, if accommodation operators observe that their occupancy is less than expected, it is less likely that they can re-secure group customers even if discounted prices are offered. therefore, the refusal of group customers must be approached with caution as it is against the practice of risk-aversion. this study supports the fact that hotel businesses in taiwan faced immature market demand from international visitors, along with a substantial number of "day trippers", and a displacement effect caused by the price disparity during a hallmark sporting event. in coping with these factors, business operation should acknowledge that a high-season room price strategy should be adopted cautiously in taiwan during the event period. although local hotels only raised their room rates by % during the month of the wg, which is far from the price gouging phenomenon reported in the related literature, the optimistic expectation of all wg spectators paying for premium prices in kaohsiung is still challenged. thus, it is necessary to allow a flexible yield management strategy to adjust room price based on unoccupied units over time. in addition, the yield management strategy should simultaneously consider the room inventory allocation in relation to customer segments. the retention of loyal patrons or group customers should be maintained and targeted because this core market provides an ensured amount of sales and revenue intake, serving as a safety net in securing minimum business revenue, even if they produce a less profitable yield. last and most importantly, offering travel deals that combine accommodation services with exclusive event tickets, complimentary transportation, or souvenirs should be strongly promoted from the business operation itself. these exclusive and quota-limited travel deals should demonstrate the value of staying locally to counter the price advantage of regional hotel competitors. the world games was significant for taiwan because it was the first of its kind and scale to be staged. however, the magnitude of tourism demand on the hotel sector during the event was less than expected and the short-term post-event effect was not enduring, resulting in relatively soft occupancies and revenue intakes. this study clarified the factors that contributed to these outcomes from the major stakeholders and the broader tourism system. factors contributing to this observation include the imbalanced cooperation among stakeholders on information distribution, legal agreements, and risk sharing; a displacement effect among loyal and potential customers because of the strong price advantage of nearby competitors; the unfriendly atmosphere of the external environment associated with the fear of h n , the lethal typhoon, and controversial political events. apart from the uncontrollable natural and social factors, practical lessons have been drawn from this world games experience. first, a hierarchical top-down structure between the event supervising authority, the event organizer, and the broader tourism industry should be avoided. this imbalance of power has been criticized at the fifa world cup (darkey & horn, ; rose, ) , and the dominance of the international sports federation and the government organizing committee has also been identified in this example. this is where the future host country should be cautious about. second, a community must host events that fit their capabilities to benefit from sports tourism (maclaurin & matthews, ) . one type of capacity lies in the ability to recognize the island and tourism characteristics in shaping their pricing and reservation strategy. for taiwan, adopting a proper fee strategy, retaining a proportion of group customers, and offering travel deals for exclusive admission tickets or transportation would assist the local businesses to counter the displacement effects of loyal hotel demands to regional competitors. the information provided in this study demonstrated the complexity of catalyzing strong tourism demand during a hallmark sporting event. the interaction of stakeholders, the consequence of policy, and the influences of the societal environment should be carefully considered as each experience, based on different contexts, provides a foundation for shaping the next successful event. lastly, although economic impact analysis (eia) is a standard evaluation tool and is widely applied to understand the economic influences of event hosting (porter & fletcher, ) , eia only yields estimates on sales, income, jobs, and value added. these figures simply reveal the partial information of event impacts. therefore, combining the quantitative economic impact results with qualitative stakeholder opinions will help the planning organization and local businesses to develop a clear perspective in the bidding for and hosting of hallmark sporting events. dr. ya-yen sun is an assistant professor at the national cheng kung university, taiwan. her reach area is on the economic impact evaluation associated with tourism development using the inputeoutput model. the empirical cases that she has worked with included economic impact studies of us. national park service visitor consumption, taiwan national tourism policy e doubling tourists arrivals plans, world games, and chinese visitors to taiwan by cross-strait ferry services. in addition to empirical works, her research has involved with theoretical perspectives of the standard inputeoutput model, the methodology of visitor expenditure studies, and the characteristics of tourism industries. dr. ariel rodríguez has been an assistant professor for the past four years in the school of community resources and development at arizona state university (asu), phoenix, arizona, usa. his research focuses on the positive development of youth within a leisure context. his areas of expertise include leisure, programming, active transportation safety, positive youth development, quality of life, and "latino" populations. he has published in numerous outlets including social indicators research, journal of park and recreation administration, and the journal of school health. he has also given presentations in national conferences such as world leisure and aahperd. dr. jih-hwa wu is a professor of public affairs management institute in national sun yat-sen university in taiwan dr. shu-tzu chuang is an assistant professor at the national university of kaohsiung, taiwan. her research area is on the tourism impacts and ecotourism development on the taiwan rural areas using the quantity and quality methods. the empirical cases that she has worked with included ecotourism constructed in taiwan, the residents' perspective of rural tourism and agri-tourism, the relationship of emotional labor and leisure coping strategy. in addition to empirical works, her research has involved with theoretical perspectives of the poststructuralism, the methodology of ecotourism research, and the characteristics of tourism industries. dr. chuang also received the best paper award in the asia-pacific tourism association th annual conference in . economic impacts of the fifa soccer world cups in france tale of two cities' collaborative tourism marketing: towards a theory of destination stakeholder assessment the quest for the cup: assessing the economic impact of the world cup using hotel capacity to estimate direct economic impact: a study of the southwest airlines gasparilla pirate fest tourist accommodation effects of festivals evaluating the economic and spatial effects of an event: the case of the world medical and health games sport, mega-events and urban tourism: exploring the patterns, constraints and prospects of the world cup economic impact analysis of sports facilities and events: eleven sources of misapplication economic impact studies: instruments for political shenanigans central place theory and sport tourism impacts supplementing event economic impact results with perspectives from host community business and opinion leaders estimating the economic impacts of seven regular sport tourism events homing in(n) on the economic benefits of fifa world cup: opportunities for and misgivings of bed-and-breakfast operators in gauteng sydney hotels suffer decreased food & beverage revenue and displacement of loyal guests during olympics but double average room rate the fifa world cup high-frequency data economics: effects on international tourism and awareness for south africa assessing the economic impacts of events: a computable general equilibrium approach the impacts of mega-events: the case of expo' e lisbon the impact of mega-sport events on tourist arrivals tourist displacement in two south african sport mega-events event tourism: definition, evolution, and research the economic importance of major sports events: a case-study of six events the economics of sport tourism at major sports events the economic impact of major sport events: a review of ten event in the uk large sport events and unemployment: the case of the soccer world cup in germany consensus-building across difficult divisions: new approaches to collaborative strategy making. planning practice and research the impact of high speed railway on travel industry in south taiwan. city development, e . international world games association optimising the potential of mega-events: an overview collaboration theory and community tourism planning evaluating the economic benefits from tourism spending through input-output frameworks: issues and cases the th world games doctoral foundation paper: the reliability of economic impact studies of the olympic games: a post-games study of sydney and considerations for london the study of the world games for the effect on city marketing in kaohsiung. city development the impact of nonpharmaceutical interventions for h n influenza on travel intentions: a model of goal-directed behavior critical reflections on the economic impact assessment of a mega-event: the case of dalai lama visit adds to taiwan leader's troubles. the new york times olympic games and the lodging industry: lessons from sydney for vancouver and other host cities. paper presented at the ttra canada annual conference the 'benefits' of hosting: japanese experiences from the padding required: assessing the economic impact of the super bowl the feel-good effect at mega sport events e recommendations for public and private administration informed by the experience of the fifa world cup mega-sports events as municipal investments: a critique of impact analysis the economic impact of the olympic games: ex ante predictions and ex poste reality the conceptualization and measurement of mega sport event legacies assessing the impact of hallmark events: conceptual and research issues fifa's 'official' suppliers: shadowy tenders and conflicts of interest at match an economic impact case study: the south pacific masters destination stakeholders exploring identity and salience major sport events and long-term tourism impacts reflections on measuring recreation and travel spending visitor consumption of world games. city development the economic impact of the world cup the operating report of international tourist hotels in taiwan monthly report on hotel operations in taiwan mega-events and impacts on tourism; the predictions and realities of the lillehammer olympics underestimated costs and overestimated benefits? comparing the outcomes of sports mega-events in canada and japan the economic import of local sport events: significant, limited or otherwise? a case study of four swimming events. managing leisure, , e . world health organization the world games; changed the visage of kaohsiung assistances from the kaohsiung organizing committee and kaohsiung tourism bureau are highly appreciated. financial support from the taiwan national science council under nsc - -h- - -ss is gratefully acknowledged. key: cord- -gmx p j authors: shen, gwan-han; tsao, thomas chang-yao; kao, shang-jyh; lee, jen-jyh; chen, yen-hsu; hsieh, wei-chung; hsu, gwo-jong; hsu, yen-tao; huang, ching-tai; lau, yeu-jun; tsao, shih-ming; hsueh, po-ren title: does empirical treatment of community-acquired pneumonia with fluoroquinolones delay tuberculosis treatment and result in fluoroquinolone resistance in mycobacterium tuberculosis? controversies and solutions date: - - journal: international journal of antimicrobial agents doi: . /j.ijantimicag. . . sha: doc_id: cord_uid: gmx p j abstract the role of fluoroquinolones (fqs) as empirical therapy for community-acquired pneumonia (cap) remains controversial in countries with high tuberculosis (tb) endemicity owing to the possibility of delayed tb diagnosis and treatment and the emergence of fq resistance in mycobacterium tuberculosis. although the rates of macrolide-resistant streptococcus pneumoniae and amoxicillin/clavulanic acid-resistant haemophilus influenzae have risen to alarming levels, the rates of respiratory fq (rfq) resistance amongst these isolates remain relatively low. it is reported that ca. – % of cap cases are re-diagnosed as pulmonary tb in asian countries. a longer duration (≥ days) of symptoms, a history of night sweats, lack of fever (> °c), infection involving the upper lobe, presence of cavitary infiltrates, opacity in the lower lung without the presence of air, low total white blood cell count and the presence of lymphopenia are predictive of pulmonary tb. amongst patients with cap who reside in tb-endemic countries who are suspected of having tb, imaging studies as well as aggressive microbiological investigations need to be performed early on. previous exposure to a fq for > days in patients with tb is associated with the emergence of fq-resistant m. tuberculosis isolates. however, rates of m. tuberculosis isolates with fq resistance are significantly higher amongst multidrug-resistant m. tuberculosis isolates than amongst susceptible isolates. consequently, in taiwan and also in other countries with tb endemicity, a short-course ( -day) regimen of a rfq is still recommended for empirical therapy for cap patients if the patient is at low risk for tb. the role of fluoroquinolones (fqs) as empirical therapy for community-acquired pneumonia (cap) remains controversial in countries with high tuberculosis (tb) endemicity owing to the possibility of delayed tb diagnosis and treatment and the emergence of fq resistance in mycobacterium tuberculosis. although the rates of macrolide-resistant streptococcus pneumoniae and amoxicillin/clavulanic acidresistant haemophilus influenzae have risen to alarming levels, the rates of respiratory fq (rfq) resistance amongst these isolates remain relatively low. it is reported that ca. - % of cap cases are re-diagnosed as pulmonary tb in asian countries. a longer duration (≥ days) of symptoms, a history of night sweats, lack of fever (> • c), infection involving the upper lobe, presence of cavitary infiltrates, opacity in the lower lung without the presence of air, low total white blood cell count and the presence of lymphopenia are predictive of pulmonary tb. amongst patients with cap who reside in tb-endemic countries who are suspected of having tb, imaging studies as well as aggressive microbiological investigations need to be performed early on. previous exposure to a fq for > days in patients with tb is associated with the emergence of fq-resistant m. tuberculosis isolates. however, rates of m. tuberculosis isolates with fq resistance are significantly higher amongst multidrug-resistant m. tuberculosis isolates than amongst susceptible isolates. consequently, in taiwan and also in other countries with tb endemicity, a short-course ( -day) regimen of a rfq is still recommended for empirical therapy for cap patients if the patient is at low risk for tb. © elsevier b.v. and the international society of chemotherapy. all rights reserved. community-acquired pneumonia (cap) is one of the leading causes of death worldwide. the mortality rate has increased agents if urine cultures are positive for pneumococcal antigen, and macrolide-or tetracycline-related agents if urine cultures are negative for pathogens. however, the rate of penicillin, macrolide and tetracycline resistance amongst s. pneumoniae isolates is high in taiwan [ ] . the antibiotic options for inpatients with cap are ␤-lactams or respiratory fluoroquinolones (rfqs) (levofloxacin, moxifloxacin and gemifloxacin). in the intensive care unit (icu), a ␤-lactam antibiotic combined with a macrolide or with a fluoroquinolone (fq) is appropriate [ ] [ ] [ ] . however, the increasing resistance of key pathogens to ␤-lactam antibiotics poses great challenges to physicians in taiwan. rfqs can be used in the treatment of cap in outpatients [ ] , inpatients and patients in the icu. rfqs have been shown to have excellent activity against key causative pathogens of cap as well as atypical pathogens; however, use of rfqs for empirical treatment of cap might mask the diagnosis of tuberculosis (tb), leading to delayed treatment and fq resistance amongst subsequently isolated mycobacterium tuberculosis strains. this article briefly reviews the common microbial causes of cap, the resistance rates amongst key pathogens, and the proper administration of fqs in the treatment of cap. the incidence of and mortality associated with tb and the status of multidrug-resistant m. tuberculosis (mdr-tb) in taiwan are also described. in addition, we review the controversies surrounding the empirical use of fqs to treat patients with cap, treatment options for patients with a delayed tb diagnosis, and the emergence of fq resistance amongst m. tuberculosis isolates. lauderdale et al. collected isolates from patients from december to april in taiwan and found that the most common cause of cap amongst adult patients in taiwan was s. pneumoniae ( %), followed by atypical pathogens (mycoplasma pneumoniae, chlamydophila pneumoniae and legionella pneumophila), h. influenzae and klebsiella pneumoniae [ ] . the aetiology of cap was undetermined in ca. % of cap cases [ , ] . staphylococcus aureus was the causative pathogen in % of cap cases, and the overall mortality rate of patients with cap was . % [ ] . lin et al. found that amongst all s. pneumoniae strains that caused bacteraemia, only . % were susceptible to penicillin, . % to erythromycin, % to tetracycline and . % to clindamycin [ ] . however, . % were susceptible to cefotaxime, . % to levofloxacin and . % to moxifloxacin. amongst nonbacteraemic strains, only . % were susceptible to penicillin, % to erythromycin, % to tetracycline and % to clindamycin. however, the rates of susceptibility amongst s. pneumoniae isolates to cefotaxime, levofloxacin and moxifloxacin were each % [ ] . the rate of non-susceptibility of s. pneumoniae to levofloxacin in a medical centre in taiwan was . % in , peaked at . % in and then gradually decreased to % in [ ] . for moxifloxacin, the non-susceptible rate was . % in , % in and then gradually decreased to % in and . hsieh et al. also showed that the prevalence of fq-resistant s. pneumoniae isolates in taiwan was low, even though fqs are widely used in that country [ ] . amongst the fq-non-susceptible isolates in that study, serotype v ( %) was the most common, followed by f ( . %), f ( . %) and f ( . %) [ ] . these serotypes are all vaccine-type s. pneumoniae. fig. shows the proportion of levofloxacin resistance amongst s. pneumoniae isolated from major teaching hospitals located in different parts of taiwan in . the majority ( - %) of the s. pneumoniae isolates were susceptible to levofloxacin [ ] . the susceptibility rate of h. influenzae to amoxicillin/clavulanic acid (amc) decreased markedly from % in to % in in a medical centre in taiwan [ ] . amc should be administered with caution to patients with cap. in addition, jean and hsueh showed that the rate of extended-spectrum ␤-lactamase (esbl)producing k. pneumoniae strains in taiwan was % [ ] . wang et al. found that the resistance rates to amc, cefuroxime, cefaclor, ceftazidime, ceftriaxone and levofloxacin amongst k. pneumoniae isolates associated with community-acquired respiratory tract infection were all ≤ % [ ] . amongst community-acquired meticillin-resistant s. aureus (ca-mrsa) isolated in a medical centre in taiwan, % were susceptible to levofloxacin and moxifloxacin [ ] . regarding atypical pathogens in taiwan, the rates of susceptibility to levofloxacin were reported to be . % for m. pneumoniae, . % for c. pneumoniae and % for l. pneumophila [ ] . in taiwan, patients with cap who were previously healthy and have not used antibiotics in the months prior to disease onset are normally given a macrolide or doxycycline as outpatient treatment [ ] . however, the rates of non-susceptibility to penicillin and erythromycin amongst clinical isolates of s. pneumoniae have increased markedly in recent years [ ] . therefore, caution should be exercised before administering macrolides for cap unless atypical pathogens are highly suspected. for patients with co-morbidities, a rfq or a ␤-lactam antibiotic plus macrolide is suggested [ ] . for inpatients with co-morbidities, especially in the icu, a ␤-lactam antibiotic plus either azithromycin or a fq is suggested [ ] [ ] [ ] . for atypical pathogens, fqs are as effective as macrolides. the length of stay in hospital and the time to clinical stability favour the use of fqs [ ] . drago et al. showed that the combination of levofloxacin with ceftriaxone produced the highest rate of synergy ( %), mainly against macrolide-resistant isolates, whereas clarithromycin combined with amc was shown to be antagonistic in % of isolates [ ] . no antagonism was noted between fq and ␤-lactam antibiotics [ ] . the prevalence of levofloxacin-resistant s. pneumoniae increased markedly during the period - in hong kong, especially amongst the elderly [ ] . the most common aetiology of levofloxacin resistance was suboptimal use of a fq in which small doses ( - mg) of ofloxacin and levofloxacin were administered two or three times daily. accordingly, appropriate doses of a rfq (levofloxacin, mg/day; moxifloxacin, mg/day; and gemifloxacin, mg/day) are recommended [ ] [ ] [ ] . the incidence of tb was cases per population in , but decreased to cases per population in because of the severe acute respiratory syndrome (sars) outbreak (fig. ) . in , the incidence rebounded to cases per population ( new cases) [ ] . in , the taiwan centers for disease control (cdc) performed a 'stop tb program' to try to reduce the incidence by one-half. from to the tb incidence rate decreased from to per population and the mortality rate decreased from . to per population (fig. ) . the overall number of patients who died decreased from in to in . the long-term trend in tb mortality also decreased from per population in to per in . fig. demonstrates the proportions of tb amongst patients initially diagnosed as having cap in different countries. the rates ranged from - % in taiwan to % in india [ , , , ] . the majority (> %) of those patients with cap due to tb were of advanced age (> years) and had various co-morbidities [ ] . the taiwan cdc reported that there was a marked difference in antimicrobial resistance rates between patients with incident tb and patients with recurrent tb [ ] ; the rates of resistance were, respectively, % and % to isoniazid, % and % to rifampicin, % and % to ethambutol, % and % to streptomycin and % and % to any first-line drug during - (http://www.cdc.gov.tw). the rates of resistance to first-line drugs tended to decrease during - except for the rate of resistance to streptomycin, which remained stable. the rate of incident mdr-tb was % in . the rate of resistance to any drug class as well as the incidence of mdr-tb also showed a downward trend during that decade [ ] . during the period - , the fq resistance rate amongst non-mdr-tb isolates in taiwan was . %, that amongst isolates from patients with previous anti-tb treatment was . % and that amongst mdr-tb isolates was . % [ ] . wang et al. evaluated fq susceptibility as well as genetic mutations amongst isolates from patients who had been exposed to fqs from january to december [ ] . they found that multiple drug resistance had the strongest correlation with fq resistance ( % of isolates) [ ] . neither previous use of fqs nor the duration of fq exposure was correlated with fq susceptibility. amongst the fq-resistant isolates, . % had a gyra mutation (d g and a v) and . % had a gyrb mutation (n ) [ ] . amongst the mdr-tb isolates from taiwan reported by yu et al., . % were resistant to ofloxacin [ ] . the rate of extensively drug-resistant tb (xdr-tb) was . % in ( / isolates) and . % in ( / isolates) [ ] . according to the annual report from taiwan cdc, the rate of fq-resistant mdr-tb isolates was . % ( / ) from july to march (http://www.cdc.gov.tw). in total, mdr-tb isolates were also resistant to capreomycin, amikacin or kanamycin. the rate of xdr-tb amongst mdr-tb isolates was . %. nearly all fq-resistant m. tuberculosis isolates were found amongst mdr-tb isolates (fig. ) [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the most common sites from which fq-resistant m. tuberculosis isolates were obtained were the genitourinary tract ( . %), pulmonary tract ( . %) and pleural cavity ( . %) [ ] . dooley et al. was the first to point out the possibility that empirical treatment with a fq might delay the diagnosis of tb [ ] . amongst patients who received empirical fq treatment, the median time between symptom onset and receipt of anti-tb medication was days compared with a median time of days amongst those who did not receive fqs [ , ] . however, the sample size in their study was small. of the patients who did not receive fqs, received anti-tb therapy and patients did not receive antibiotic treatment. the initial acid-fast bacillus smear was positive in of those patients. tb was suspected in at least one-half of the patients who did not receive fqs, so antibiotics were not prescribed and anti-tb treatment was given directly. interestingly, of those patients who received fq monotherapy, % experienced improvement in the symptoms of tb, and clinical improvement occurred an average of days after the initiation of therapy. other studies have also reported that the delay in initiation of anti-tb medication was longer amongst patients who received fqs than amongst patients who did not receive fq-based antibiotics ( . ± . days vs. . ± . days; p = . ) [ ] [ ] [ ] . median healthcare delay for patients who received antibiotics for non-tb diagnoses/indications prior to tb diagnosis was days versus days (p < . ) for patients who had initially received tb therapy [ ] . not only did administration of a fq result in a delayed diagnosis of tb (median days), but administration of other antibiotics (such as ␤-lactams, macrolides or carbapenems) had a similar effect (median days). in the study by golub et al., only % of patients initially diagnosed as having pneumonia had a chest radiograph [ ] . interestingly, % of the chest radiographs suggested a diagnosis of tb; however, the patients were still subsequently prescribed empirical antibiotics. more importantly, both antibiotic use and not having a chest radiograph taken during the first healthcare visit were independently related to longer healthcare delays in the overall cohort. mathur et al. showed that ca. - % of active tb patients were given an incorrect diagnosis at the initial presentation, mainly because of atypical radiographic manifestations [ ] . a study from malaysia clearly demonstrated that a duration of symptoms of > weeks before hospital admission [odds ratio (or) = . ; p < . ), history of night sweats (p = . ), a chest radiograph showing upper lobe involvement (p = . ) or cavitary infiltrates (p = . ), a total white blood cell count of ≤ × /l on admission (p = . ) and lymphopenia (p = . )] was significantly associated with culturepositive pulmonary tb (fig. ) [ ] . in addition, lower lung field tb (llftb) is difficult to differentiate from pneumonia and is often fig. . clinical and laboratory predictors of patients with tuberculosis who were initially diagnosed as having community-acquired pneumonia [ ] . cxr, chest radiography; wbc, white blood cell count. misdiagnosed because of atypical findings on chest radiographs [ , ] . in taiwan, ca. % of pulmonary tb patients have llftb [ ] . multivariate analysis conducted by lin et al. showed that prolonged duration of symptoms ≥ days (or = . ; p = . ), lack of fever > • c (or = . ; p = . ) and the absence of air bronchograms (or = . ; p = . ) were significant predictors of llftb in patients with llf pneumonia [ ] . a calculated probability of > . [ ] . park et al. evaluated the impact of short-term exposure to fq on ofloxacin resistance in human immunodeficiency virus (hiv)-negative patients with tb and found that the rate of ofloxacin-resistant m. tuberculosis was low and that most cases of ofloxacin resistance were associated with mdr-tb [ ] . they also found that the frequency of ofloxacin-resistant m. tuberculosis was low amongst patients who were exposed to fqs for a short period of time [ ] . these findings favour the application of fqs in the regimen for cap or tb in patients with shorter disease durations. in taiwan, only - % of patients with cap receive a final diagnosis of tb. it is important to differentiate between cap and tb in the initial presentation. if the lesion is located in the upper lung field, clinical specimen collection or rapid nucleic acid amplification could shorten the delay to tb diagnosis rather than restrict the empirical treatment with fqs in cap. if the lesion is in the lower lobe, risk factors including advanced age, prolonged duration of the lesion, lack of fever and absence of air bronchograms should raise the suspicion of llftb. although use of fqs in taiwan is high, the incidence of tb, the mortality rate associated with tb and the rate of drug resistance have decreased. the rate of fq resistance in s. pneumoniae is low and the rate of susceptibility to fqs is high amongst h. influenzae, k. pneumoniae (including esbl-producing strains), atypical pathogens and ca-mrsa in taiwan. because of the high incidence of cap caused by atypical pathogens in taiwan, coverage of atypical pneumonia must be considered in the empirical treatment of cap both in outpatients and inpatients. macrolides should be used with caution because of high rates of resistance to that antimicrobial class in s. pneumoniae. fqs have a good synergistic effect with other antimicrobial agents, with the exception of a macrolide combined with a ␤-lactam, which might show some antagonist properties. empirical treatment of cap with a fq might mask active tb, delay treatment and contribute to the development of fq resistance. fq resistance in m. tuberculosis is related to fq duration and the timing of exposure. exposure to a fq for > days and exposure for > days before tb diagnosis were both shown to be associated with a significant risk of developing fq resistance. consequently, in taiwan as well as in other countries with endemicity of tb, a short-course ( -day) regimen of a fq (levofloxacin, moxifloxacin and gemifloxacin) is still recommended for empirical therapy for cap patients if the patient is at low risk for tb. furthermore, fq resistance is less likely to occur amongst m. tuberculosis strains isolated from patients with short-term exposure (< days) to fq. funding: no funding sources. competing interests: none declared. ethical approval: not required. infectious diseases society of america/american thoracic society consensus guidelines on the management of community-acquired pneumonia in adults guidelines for the management of adult lower respiratory tract infections taiwan society of pulmonary and critical medicine; medical foundation in memory of dr. deh-lin cheng; foundation of professor wei-chuan hsieh for infectious diseases research and education s research foundation for pediatric infectious diseases and vaccines. guidelines on antimicrobial therapy of pneumonia in adults in taiwan, revised antimicrobial drug resistance in taiwan fluoroquinolones in the management of communityacquired pneumonia in primary care etiology of community acquired pneumonia among adult patients requiring hospitalization in taiwan a prospective etiologic study of community-acquired pneumonia in taiwan outcomes of hospitalized patients with bacteraemic and non-bacteraemic community-acquired pneumonia caused by streptococcus pneumoniae circulation of international clones of levofloxacin non-susceptible streptococcus pneumoniae in taiwan national survey of invasive pneumococcal diseases in taiwan under partial pcv vaccination in : emergence of serotype a with high invasive potential alarmingly decreasing rates of amoxicillin-clavulanate susceptibility among clinical isolates of haemophilus influenzae from antimicrobial susceptibility of bacterial pathogens associated with community-acquired respiratory tract infections in asia: report from the community-acquired respiratory tract infection pathogen surveillance (cartips) study in vitro activity of nemonoxacin (tg- ), a novel non-fluorinated quinolone, against clinical isolates of staphylococcus aureus, enterococci and streptococcus pneumoniae with various resistance phenotypes in taiwan efficacy and safety of nemonoxacin versus levofloxacin for community-acquired pneumonia macrolides versus quinolones in legionella pneumonia: results from the community-acquired pneumonia organization international study comparative evaluation of synergy of combinations of ␤-lactams with fluoroquinolones or a macrolide in streptococcus pneumoniae decreasing prevalence of levofloxacin-resistant streptococcus pneumoniae in hong kong trends in tuberculosis in taiwan pulmonary tuberculosis presenting as community-acquired pneumonia fluoroquinolones should not be the first-line antibiotics to treat community-acquired pneumonia in areas of tuberculosis endemicity extensively drug-resistant tuberculosis differences in drug resistance profiles of mycobacterium tuberculosis isolates causing pulmonary and extrapulmonary tuberculosis in a medical centre in taiwan extensively drug-resistant mycobacterium tuberculosis during a trend of decreasing drug resistance from through at a medical center in taiwan fluoroquinolone resistance in mycobacterium tuberculosis isolates: associated genetic mutations and relationship to antimicrobial exposure fluoroquinolone-resistant tuberculosis at a medical centre in taiwan, - trends in fluoroquinolone resistance of mycobacterium tuberculosis complex in a taiwanese medical centre: - empiric treatment of community-acquired pneumonia with fluoroquinolones, and delays in the treatment of tuberculosis fluoroquinolones are associated with delayed treatment and resistance in tuberculosis: a systematic review and meta-analysis impact of fluoroquinolones on the diagnosis of pulmonary tuberculosis initially treated as bacterial pneumonia empirical treatment with a fluoroquinolone delays the treatment for tuberculosis and is associated with a poor prognosis in endemic areas impact of empiric antibiotics and chest radiograph on delays in the diagnosis of tuberculosis delayed diagnosis of pulmonary tuberculosis in city hospitals the value of roentgenographic and fiber bronchoscopic findings in predicting outcome of adults with lower lung field tuberculosis factors changing the manifestation of pulmonary tuberculosis unilateral lower lung field opacities on chest radiography: a comparison of the clinical manifestations of tuberculosis and pneumonia low rate of fluoroquinolone resistance in mycobacterium tuberculosis isolates from northern tanzania impact of short-term exposure to fluoroquinolones on ofloxacin resistance in hiv-negative patients with tuberculosis key: cord- -kfjujs z authors: huang, yu-tung; lee, yue-chune; hsiao, chun-ju title: hospitalization for ambulatory-care-sensitive conditions in taiwan following the sars outbreak: a population-based interrupted time series study date: - - journal: journal of the formosan medical association doi: . /s - ( ) - sha: doc_id: cord_uid: kfjujs z background/purpose in , the severe acute respiratory syndrome (sars) outbreak resulted in probable cases and deaths in countries. the purpose of this study was to explore the effect of the sars outbreak on hospitalization for chronic ambulatory-care-sensitive conditions (acscs) in taiwan. methods we applied a population-based interrupted time series study design and used the time series auto-regressive integrated moving-average model to compare the actual and predicted admission rates of seven selected chronic acscs. the analyses were based on national health insurance hospital inpatient claims data from to . results the impact of sars on acscs after the outbreak varied among seven selected chronic conditions. hospitalization for respiratory conditions was significantly lower than the predicted values, whereas hospitalization for diabetes was significantly higher than the predicted values after the outbreak. conclusion admission rates for most acscs, except for diabetes, did not change in the post-sars period. the reductions in outpatient utilization during the sars outbreak did not appear to affect adversely admissions for most acscs. during the sars outbreak in taiwan. among the different types of health care, inpatient care had the greatest reduction ( . %) in utilization, followed by ambulatory care ( . %) . similar trends were also observed in the greater toronto area , and hong kong. , within ambulatory care, the reduction in utilization was greatest for minor acute diseases and modest for chronic conditions. , health service utilization for lifethreatening diseases was nearly unaffected. , although a sars outbreak has not recurred, other potential infectious diseases such as pandemic influenza or avian flu may emerge in the future. to guide preparation and planning, it is necessary to investigate the potential health impact of decreased service utilization caused by disruption to the health care system during major outbreaks. ambulatory-care-sensitive conditions (acscs) are those for which timely and adequate outpatient care can prevent future hospitalization. these conditions have been used widely to measure access to and performance of primary care, and can be used to identify areas for improving access and quality in health care delivery. [ ] [ ] [ ] , therefore, in this study, we used these conditions as indicators to examine whether the decreased access to primary health care caused by sars, which has been reported in previous studies, , , had an impact on population health, as measured by hospitalization for chronic acscs. the specific aim of this study was to explore the effect of the sars outbreak on hospitalization for chronic acscs after the sars outbreak. the following reasons provided explanations on why we excluded acute hospitalization for acscs: . health services utilizations of acute conditions were not significantly affected by sars during the outbreak. , . acute conditions, in general, are more life-threatening. hospitalization related to inappropriate primary care might have occurred immediately following the event, and not a few months later. . patients with chronic conditions, particularly the less severe ones, are more likely to delay ambulatory care during the sars outbreak. , therefore, we only included chronic conditions in this study. the study finding might be of interest particularly to health policy makers and those in health services that are responsible for the preparation and planning for a major outbreak of infectious disease. this was an exploratory study. we applied a population-based interrupted time series design to compare the actual with predicted hospitalization for acscs after the sars outbreak, to identify conditions with increased hospitalization that might have been caused by untimely or inappropriate primary care during the sars outbreak. the national health insurance (nhi) claims data during - were used to estimate the trends in hospitalization for acscs before the sars outbreak, and to generate the predicted value in . the interrupted time series design allowed us to take into account any underlying trends or seasonal influences prior to the sars outbreak, and then quantify accurately the subsequent impact of sars. any changes in the trends that occurred after the outbreak were assumed to have been caused by the outbreak. monthly admission rates for each acsc were calculated throughout the study period based on the claims data from january to december . to provide a reference, we included a non-acsc condition, appendicitis, in this study as a comparison. besides, because of our inability to obtain databases that link individual inpatient and outpatient data, we provided the aggregate statistics of outpatient utilization of acscs for reference. the data source for this study was the "inpatient expenditures by admissions (dd)" and "systematic sampling data of outpatient (scd)" datasets provided by the bureau of the nhi, department of health, and managed by national health research institutes. the dd dataset included each inpatient claim of every nhi beneficiary in taiwan from to ; whereas, the scd dataset included . % systematic samples of all outpatient claims during the same period. nhi is a universal health insurance program, which covers about % of the population. therefore, almost all hospital admissions are recorded in the nhi claims database. we used encrypted beneficiaries' identification (id) number and encrypted hospitals' id number to link the data and to ensure that each claim only appeared once in the analyses. since the first sars case was identified on march , in taiwan, the epidemic increased at the end of april, and reached its peak in may and june of . taiwan was removed finally from the list of sars-affected countries by the world health organization (who) on july , . therefore, we defined april-june as the sars outbreak period and january-march as the pre-sars period. we then defined two post-sars periods: the first months after the outbreak (july-september) was post-sars- period, and the following months (october-december) was the post-sars- period. hospitalization for acscs has been used widely as a marker of access and quality of care. [ ] [ ] [ ] , the agency for healthcare research and quality (ahrq) has defined a list of acscs. ten of these are chronic conditions, including uncontrolled diabetes without complications, diabetes short-term complications, diabetes long-term complications, diabetes-related lower-extremity amputation, pediatric asthma, adult asthma, hypertension, chronic obstructive pulmonary disease (copd), angina without procedure, and congestive heart failure. one is birth outcome (low birth weight) and five are acute conditions (bacterial pneumonia, dehydration, urinary tract infection, perforated appendix, and pediatric gastroenteritis). we only included chronic conditions as indicators in this study because they were more likely to be affected by sars than acute conditions. however, among the chronic conditions, we also excluded long-term diabetes complications and lower-extremity amputation among diabetic patients because the incidence of these conditions is low, and a longer study period would have been required to observe these outcomes. furthermore, the ahrq guidelines for acscs states that the indicator for uncontrolled diabetes is designed to be combined with diabetes short-term complications. accordingly, for diabetes, we only included a combined diabetes measure that comprised uncontrolled diabetes without complications and diabetes short-term complications. as a result, we included seven acscs in this study. all the indicators were identified by the principal diagnoses listed on the ahrq pqis version . , revision and coded by the international classification on diseases, ninth revision, clinical modification (icd- -cm). first, we used the monthly hospitalization rates for each condition between january and december to fit the time series auto-regressive integrated moving-average (arima) model. arima models are fitted to time series data to better understand the underlying trends in the data and to predict data points in the future. the ljung-box q-statistic was used to check whether lack-of-fit existed in these models. predicted monthly hospitalization rates for each selected condition in were obtained subsequently from the arima models. we then compared the actual monthly hospitalization rates and the predicted rates with the % ci. we considered the differences between the actual and predicted monthly rate as significant if the actual hospitalization rate of a given condition was beyond the % ci of the predicted rate. all analyses were performed using spss version . (spss inc., chicago, il, usa) for windows. a total of , hospitalizations were observed for the seven selected acscs during four time periods (pre-sars, sars, post-sars- and post-sars- ) in . table displays the actual number of hospitalizations for each selected acsc and appendicitis, as well as the percentage changes in the number of hospitalizations from to . among the seven acscs, copd had the most hospital admissions, with approximately , patients. all the hospitalizations for selected acscs were reduced in the sars period compared with those in , most notably among circulatory and respiratory conditions. the hospitalizations for most conditions were still reduced in the post-sars- period, with the exception of diabetes and hypertension, which increased more than %, when compared with the numbers in , during the post-sars- period. for appendicitis, the admission numbers had stable reductions in pre-and post-sars periods. as well as acscs, the number of appendicitis admissions decreased substantially in the sars period. table also presents the number of outpatient visits for each selected acsc, and the patterns for outpatient visits were similar to those for acsc admissions in the sars period. however, for diabetes, the reduction in outpatient visits was much more than the reduction in the admissions. table presents the predicted hospitalization rates, the associated % ci obtained from the arima model, and the differences between the actual and predicted hospitalization rates among the four periods. during the pre-sars period, admission rates for all conditions did not differ significantly from their predictive values. however, during the sars period, admission rates for pediatric asthma, copd, and angina without procedure were reduced by . , . , and . per , population per month, and were significantly (p < . ) different from their respective predictive values. in general, the actual hospitalization rates for respiratory and circulatory conditions were lower than the predicted rates in the post-sars periods. the admission rates for all respiratory conditions were lower compared with their predictive values in the post-sars periods; however, the differences were significant only in the post-sars- period. yet they were higher than the predicted rates for hypertension (during post-sars- ) and diabetic conditions. the diabetes admission rates increased by . per , population per month, which was significant (p < . ) in the post-sars- period. compared with the acscs, the admission rate for appendicitis remained insignificant during all study periods. figures - display the monthly trends in hospitalization rates for the seven selected acscs, with predicted values and % ci indicated for and . during the sars period, the actual hospitalization rates for all selected acscs were significantly lower than the lower boundary of the % ci of the predicted rates for at least month, except for diabetes. the differences in hospitalization rates for respiratory conditions during the post-sars- period, shown in figure , were also significant for at least month. yet, only the differences in pediatric asthma remained significant in two of the three months during the post-sars- period. in figure , the actual hospitalization rates for the three circulatory conditions all fell within the range of the % ci of their predicted values in both post-sars periods. figure shows that the actual admission rates for diabetes also fell within the % ci during both post-sars periods. nonetheless, the actual admission rates for diabetes were significantly higher than the predicted rates and exceeded the upper limit of the % ci at the end of . we found that the actual hospitalization rates for six selected acscs, particularly respiratory conditions, were significantly lower than their predicted rates for at least month during the sars period. this trend remained significant only in respiratory conditions during the post-sars- period. the admission rates for two conditions, hypertension and diabetes, were higher than the predicted rates during either of the post-sars periods, but the differences were significant only for diabetes in the post-sars- period. in contrast, no significant change in admission rates for the reference condition appendicitis was observed during the entire study period. the reduction in hospitalization rate was most profound among respiratory conditions and was consistent with previous findings during the sars period. these trends continued to be significant in the post-sars- period. since sars is associated with the respiratory system, people with respiratory conditions were more likely to avoid hospital contact compared with people with other conditions. the health belief model can be used to explain such behavior, when people may have evaluated the perceived susceptibility and benefit before taking a health-related action. in addition, people were more cautious about their health during the sars outbreak and took all means available to prevent respiratory infection (e.g. wearing masks and avoiding public gatherings). another explanation is that the who warning about the return of sars may have provided a booster effect during the post-sars- period and even in the post-sars- period. our study indicated that the actual admission rates for diabetes were significantly higher than the predicted values during the post-sars- period. diabetic patients might have worse access to care because several hospitals discontinued their emergency and routine services, or mailed the medications to patients during the sars outbreak. , since medication alone is not sufficient for diabetes, it is possible that some difference between actual and predicted admission rates for diabetes during the post-sars- period resulted from under-use of regular or effective care during the sars outbreak. we found that outpatient utilization reduced by . % in sars period. if we take the increased trend for diabetes in the pre-sars period into consideration, the actual reduction was as high as . %, and was ranked the second among all the acscs in our study. this might support partially our above explanation and explains why the admission rates for other acscs were not elevated significantly after the sars outbreak. however, we were unable to examine the relationship between outpatient and inpatient utilization directly, to provide further evidence, because the nhi outpatient database provided by nhri is sampled based on outpatient visits rather than individuals; thus, we were unable to obtain meaningful individual samples in the present study. previous studies have shown that hospitalization rates declined during the sars period in taiwan, , and have found no significant changes in mortality, readmission, and complication rates for critically ill patients in toronto. , however, the present study is possibly the first to explore the possible impact of sars on hospital admissions in the post-sars period in taiwan, by focusing on specific conditions such as acscs. in addition, the application of the population-based interrupted time series design, using a non-acsc condition for comparison, did allow us to take into account the underlying trends and seasonal effect of the admission rates, and rule out other possible contemporary influences present during the study period. besides, the ljung-box q-statistic enabled us to select the best-fitting arima models, which was indicated by the fact that most of the actual values in the pre-sars periods were within the % ci of the predicted values. this study however has some limitations that warrant discussion. first, we did not compare the changes in acsc admissions among areas with different impacts of sars. this was because almost every area in taiwan was in a state of alert during the sars outbreak, and many hospitals suspended emergency, outpatient, inpatient or all services during that time, even hospitals in areas without any probable sars cases, such as greater chiayi area, taitung and yilan counties. second, we were unable to evaluate the impact of sars after because nhi introduced many interventions in , including: reduction of outpatient and increase of inpatient budgets; implementation of hospital self-management/hospital center of excellence initiative; revision on nhi fee schedules; and the launch of family physicians initiatives. it would be inappropriate to relate the changes between the post-sars period and to the impact of sars. besides, the accuracy of the predictions from the time-series model would be greatly reduced for a longer period. third, we did not conduct a simple correlation analysis between aggregate outpatient and inpatient statistics, because the health seeking behavior might have varied among conditions with different severity and likelihood of acquiring sars at health facilities (e.g. patients with respiratory diseases were more likely than others to acquire sars). in conclusion, we found that the impact of sars on hospital admission rates after the sars outbreak varied among different conditions. it had a negative and significant impact on respiratory conditions in the first post-sars period, no significant impact on circulatory conditions, and a positive impact on diabetes conditions during the second post-sars period. in addition, the admission rates for most acscs, except for diabetes, did not change in the post-sars period. the reductions in outpatient utilization during the sars outbreak did not appear to affect adversely admissions for most acscs. access to health care in america impact of socioeconomic status on hospital use in new york city agency for health research and quality. ahrq quality indicators-guide to prevention quality indicators: hospital admission for ambulatory care sensitive conditions summary of probable sars cases with onset of illness from the impact of the sars epidemic on the utilization of medical services: sars and the fear of sars impact of sars on healthcare utilization by disease categories: implications for delivery of healthcare services hospice utilization during the sars outbreak in taiwan the impact of the sars outbreak on an urban emergency department in taiwan impact of an outbreak of severe acute respiratory syndrome on a hospital in taiwan, roc impact of severe acute respiratory syndrome (sars) outbreaks on the use of emergency department medical resources the impact of sars on a tertiary care pediatric emergency department effect of widespread restrictions on the use of hospital services during an outbreak of severe acute respiratory syndrome update on emerging infections: news from the centers for disease control and infection the public's response to severe acute respiratory syndrome in toronto and the united states the role of primary care in preventing ambulatory care sensitive conditions hospitalization for ambulatory care-sensitive conditions: a method for comparative access and quality studies using routinely collected statistics severe acute respiratory syndrome-taiwan time series analysis: forecasting and control, rd edition on a measure of lack of fit in time series models the health belief model: a decade later journey through an epidemic: some observations of contrasting public health responses to sars will the sars epidemic recur? sars in taiwan: an overview and lessons learned use of quarantine to prevent transmission of severe acute respiratory syndrome-taiwan population mortality during the outbreak of severe acute respiratory syndrome in toronto health impact of hospital restrictions on seriously ill hospitalized patients: lessons from the toronto sars outbreak we thank the nhri in taiwan for providing the data. however, the authors take full responsibility for the article. this study was self-funded, and none of the authors have any conflict of interest in connection with this manuscript. key: cord- - r gc authors: chan, ta-chien; hsiao, chuhsing kate; lee, chang-chun; chiang, po-huang; kao, chuan-liang; liu, chung-ming; king, chwan-chuen title: the impact of matching vaccine strains and post-sars public health efforts on reducing influenza-associated mortality among the elderly date: - - journal: plos one doi: . /journal.pone. sha: doc_id: cord_uid: r gc public health administrators do not have effective models to predict excess influenza-associated mortality and monitor viral changes associated with it. this study evaluated the effect of matching/mismatching vaccine strains, type/subtype pattern changes in taiwan's influenza viruses, and the impact of post-sars (severe acute respiratory syndrome) public health efforts on excess influenza-associated mortalities among the elderly. a negative binomial model was developed to estimate taiwan's monthly influenza-associated mortality among the elderly. we calculated three winter and annual excess influenza-associated mortalities [pneumonia and influenza (p&i), respiratory and circulatory, and all-cause] from the – through the – influenza seasons. obtaining influenza virus sequences from the months/years in which death from p&i was excessive, we investigated molecular variation in vaccine-mismatched influenza viruses by comparing hemagglutinin (ha ) of the circulating and vaccine strains. we found that the higher the isolation rate of a (h n ) and vaccine-mismatched influenza viruses, the greater the monthly p&i mortality. however, this significant positive association became negative for higher matching of a (h n ) and public health efforts with post-sars effect. mean excess p&i mortality for winters was significantly higher before than after that year [mean ± s.d.: . ± . vs. . ± . , p = . ]. further analysis revealed that vaccine-matched circulating influenza a viruses were significantly associated with lower excess p&i mortality during post-sars winters (i.e., – ) than during pre-sars winters [ . ± . vs. . ± . , p = . ]. stratification of these vaccine-matching and post-sars effect showed substantial trends toward lower elderly excess p&i mortalities in winters with either mismatching vaccines during the post-sars period or matching vaccines during the pre-sars period. importantly, all three excess mortalities were at their highest in may, , when inter-hospital nosocomial infections were peaking. furthermore, vaccine-mismatched h n viruses circulating in the years with high excess p&i mortality exhibited both a lower amino acid identity percentage of ha between vaccine and circulating strains and a higher numbers of variations at epitope b. our model can help future decision makers to estimate excess p&i mortality effectively, select and test virus strains for antigenic variation, and evaluate public health strategy effectiveness. increased influenza vaccination coverage for the elderly, one of the highest risk groups for influenza-related deaths [ ] , has prevented influenza-related complications and deaths, based on studies from to [ ] . in taiwan, elderly populations (aged $ years) have received free influenza vaccination since . vaccine coverage rates have increased from . % in to . % in . despite similar expansions in coverage, pneumonia and influenza (p&i) mortality among the elderly have continued to rise in italy [ ] and the united states [ , ] . such findings contribute to the current international debate on the influenza vaccine's effectiveness in preventing elderly influenzaassociated deaths. to examine this issue, we investigated the impact of potential vaccination mismatches with co-circulating viral strains of influenza virus types/subtypes, and public health efforts after the outbreak of sars on vaccination effectiveness in subtropical regions like taiwan. routine virological surveillance has been crucial for early detection of influenza viral changes [ ] . understanding epidemiological pattern changes of influenza in taiwan, located geographically close to several past influenza pandemic epicenters in china and southeast asia, has larger implications for global virological surveillance. taiwan's dominant circulating a(h n ), a(h n ), and b wild-type influenza virus strains appeared about one to two years earlier than selected vaccine strains recommended by world health organization (who) for the northern hemisphere, implying that taiwan has the potential to play a key role in early pandemic and epidemic detection and control [ , ] . the aims of this study were: ( ) to evaluate the effectiveness of matching or mismatching influenza vaccine strains on influenzaassociated mortality, ( ) to assess whether public health improvements during the post-sars period might have decreased elderly mortality, and ( ) to investigate molecular variation among vaccine-mismatched influenza viruses that may be associated with increased excess influenza-associated mortality. data was collected on taiwan's annual and monthly influenzaassociated mortality rates for the elderly population, monthly meteorological conditions (obtained from taiwan's central weather bureau), annual influenza vaccine strains (collected from the who) [ ] , dominant types/subtypes of influenza viruses for winter epidemic seasons, and monthly influenza isolation rates [compiled from the centers for disease control in taiwan (taiwan-cdc)] for the - through - influenza seasons. rates of both winter and annual influenza-associated excess mortality among the elderly were calculated. winters periods were designated as december st to february th of the following year. annual periods were marked as beginning on october st and concluding on september th of the following year. the elderly population was calculated as the average of two mid-years' elderly population (acquired from the census database of the ministry of the interior). monthly isolation rates of influenza virus types/subtypes for each studied year were obtained from the virological surveillance database of contract laboratories and compiled by taiwan-cdc ( figure s ) [ ] . wild-type, dominant circulating influenza virus strains were also collected from the contract laboratories, as designated by taiwan-cdc and the literature [ ] . comparisons between influenza vaccine strains and taiwan's dominant influenza epidemic strains are summarized in table s . to better evaluate influenza's disease burden, we used influenzaassociated mortality rates that were calculated under broad definitions [ ] . using international classification of diseases, ninth revision (icd- ) codes and clinical data obtained from taiwan's department of health, mortality was divided into three categories: ( ) pneumonia and influenza (p&i, icd- : - ), ( ) respiratory and circulatory (r&c, icd- : - ), and ( ) all-cause deaths (icd- : - ) with the exclusion of non-natural deaths. we developed a negative binomial regression model and added two variables of vaccine match/mismatch and pre/post-sars effect for multivariate analyses with a modification of a thompson-like model [ ] , because of dispersed distributions of the three influenza-associated mortality rates (variance/mean . ). explanatory variables for the above three outcome measures include monthly meteorological parameters (monthly means of temperature and humidity), annual periodic cycle (i.e., sine/cosine function of seasonal periodicity), monthly virus isolation rates for different subtypes/types of influenza viruses [a (h n ) or a (h n ) or b], matching status of different vaccine strains for each subtype/type in each of the studied years, post-sars effect, and linear temporal monthly trends. matching status for each subtype/ type of influenza viruses was defined as the consistency between the nomenclature of the vaccine strain and the nomenclature of that season's dominant wild-type strain in taiwan. if no wild-type subtype was isolated for a certain year, the status of the flu vaccine was thus coded as ''matching'' for that subtype/type and year. to assess whether the public health effort after the unique outbreak of sars in taiwan might also play a role in mortality, the indicator variable ''post-sars effect'' was applied to the period beginning october (the first month of the influenza season) till after the conclusion of the outbreak in june . model selection was based on akaike's information criterion (aic) and likelihood ratio test [ ] . when modeling p&i mortality, both mean temperature and relative humidity were found to be without statistical significance and were thus excluded from the full model (table ) . the model was implemented by sas (version . ; sas institute inc, cary, nc). the final model for ''influenza-associated deaths'' was devised as follows: winter and annual influenza-associated excess elderly mortalities to evaluate the impact of influenza vaccination and/or post-sars effect on influenza-associated elderly mortalities, we listed both variables in table . excess mortality ( % confidence interval) was calculated for each winter and year. these excess deaths were assessed by calculating the difference between observed data and expected baselines that were derived from the negative binomial model ( figure s ). when we modeled vaccinematching status and post-sars effect, we coded data as '' 's'' or '' 's'' depending on the actual data for each year. ''post-sars'' was defined as all months after october . after calculating residual deaths for each month, we replaced negative residuals (e.g. observed values less than the expected value) with zero and summed up excess deaths for each influenza season. winter (or annual) excess mortality rates were calculated based on each winter's (or annual) total excess deaths divided by mid-year mean populations. in other words, we assessed temporal differences between each winter's monthly observed influenza-associated deaths and monthly expected value [obtained from our multivariate modeled deaths (baseline)], and then divided these monthly differences by the mid-year mean population for two years to calculate the actual excess mortality rate in each winter for statistical comparison among the three time periods (prior to sars, during sars, and post-sars) ( table , table s ). the mean values for each winter's excess mortality before and after sars were evaluated by independent t-test. to better understand why - exhibited the highest winter and annual excess p&i mortality rates, ha sequences of the epidemic influenza virus a (h n ) fujian strain (a/ fujian/ / (h n )), vaccine strains (red squared symbol) from to , and other taiwanese h n isolates (circular symbol) from to were gathered from the national center for biotechnology information (ncbi) for genetic comparison. we then constructed a phylogenetic tree of ha amino acids among taiwanese a (h n ) virus strains using the neighbor-joining method. this tree was bootstrapped , times with mega . software [ ] . percentages of amino acid sequence identity in the ha between dominant wild-type circulating and vaccine strains were calculated for vaccine-mismatched influenza a(h n ) viruses isolated from months and years ( - , - , and - ) with high annual/monthly influenza-associated excess p&i mortality. the numbers and percentages of amino acid difference at specific epitope locations of ha that have been documented in literature [ ] were further analyzed for vaccine-mismatched influenza a (h n ) viruses isolated from these three years. temporal patterns of influenza-associated mortality rates indicate that taiwan's elderly p&i mortalities have been increasing since the beginning of the - influenza season despite significant increases in vaccine coverage ( figure s a ). as described in figure , the mean p&i mortality rate, [ ] . these increasing patterns were consistent throughout the study period among the three oldest age groups ( - , - , and +) ( figure s b ). in addition to this temporal pattern, seasonal cycles (cosine and sine function in table ) were also found to be significant (p, . ) for all three influenza-associated mortality rates (except for the cosine function for r&c). furthermore, the corresponding coefficients in table 's model demonstrate the considerable reduction in elderly p&i mortality in years with either matching vaccines or post-sars effect. temporal patterns of monthly isolation rates for human influenza viruses in taiwan are displayed in figure s . during the study period, a (h n ) and b were the dominant type/subtypes of influenza viruses. regarding to vaccine matching rate, a (h n ) was the most frequently matched subtype ( . %, / ) in eight epidemic seasons. a (h n ) had the second highest ( . %, / ) and b had the worst ( %, / ). using multivariate negative binomial regression models, we found that four significant variables -the monthly isolation rate of table . estimated coefficients ( " b), standard errors (se) and p-values (p) of three fitted negative binomial models for influenzaassociated deaths: ( ) pneumonia and influenza (p&i), ( ) respiratory and circulatory, and ( ) all-cause in taiwan, from october to september , respectively. ( ) p&i deaths ( ) respiratory and circulatory deaths ( ) all-cause deaths influenza a (h n ), vaccine mismatch with a (h n ), linear temporal trends, and sine function -were all positively correlated with annual p&i deaths (p, . , table ). in contrast, post-sars effect and cosine function were negatively correlated with annual p&i mortality (p, . ). influenza a (h n )'s monthly isolation rate and sine function, as well as vaccine mismatch for influenza b, were positively correlated with r&c deaths (p, . ). mean temperature and relative humidity were both negatively correlated with r&c deaths (p, . ). values for observed and estimated deaths were proximate for all three influenza-associated mortality models (as illustrated in figure s ). , excess p&i mortality rates ( . per , ) were - times higher than rates for the same months in prior years and about times higher than rates for the four months preceding the outbreak (table s ). in may , when interhospital nosocomial infection was the most severe, the three influenza-associated excess mortality rates of p&i ( . per , ), r&c, and all-cause ranked the highest throughout the studied months. after june , excess p&i mortalities in july and august declined dramatically to per , ( figure s ). . stratification analysis. totally, four of the eight studied years showed increased winter excess influenza-associated mortalities (" / , ) plus one higher excess mortality in march, ( . / , ), and five of them had vaccinemismatches. of the latter five, three occurred in the pre-sars period ( - , - , and - ) and the remaining two happened in the post-sars period ( - and - ) . to examine the winter seasons' excess mortality in those years with vaccine-matched versus vaccine-mismatched strains before and after sars, we first reviewed the data on vaccine-matches or not during the pre-sars years only (e.g. without effect of sars). then, we focused on vaccine-mismatches table . annual and winter excess mortality rates of influenza-associated deaths (per , ) among the elderly (" years). in summary, stratification of these two variables showed substantial trends toward lower excess p&i mortality during: ( ) influenza vaccine-matched winters during the pre-sars period (without post-sars effect), and ( ) figure s ). during the - flu season, a/sydney/ / (h n ) and a/ moscow/ / (h n ) were the dominant circulating strains affecting taiwan while a/sydney/ / -like was the vaccine strain and provided inadequate protection against a/moscow/ / . as shown in table s , five variations were identified at known epitopes [ ] , including two variations (y s, s r) at (table s ). most notably, we discovered one variation at the undefined epitope (position , i l) previously identified by shih et al. [ ] , and three new variations (positions of a s, i l, y h, figure s (table s ). we also observed that the excess mortality in - 's winter was much lower than in - . this can be supported by higher identity percentage between vaccine and circulating strains, and a lower number of variations at epitope b. this is the first study to analyze the impact of the dominant types/subtypes of influenza viruses, the matching status of influenza vaccine strains, and the sars outbreak on three influenza-associated mortality rates among the elderly in taiwan. the study is unprecedented in its molecular-level investigation of vaccine-mismatched influenza viruses associated with excess mortality. while the limitations of our data prevent us from drawing definitive conclusions about these potential factors, we did observe five associations that merit discussion. first, higher a (h n ) subtype isolation rates were associated with increased influenza-associated mortality. second, lower p&i mortality rates were observed when circulating strains of influenza viruses were vaccine-matched. third, increased influenza p&i excess mortality was associated with vaccine-mismatched circulating influenza h n and b viruses with fewer amino acid identities. fourth, influenza disease burden after the sars outbreak (i.e. with post-sars effect) was significantly lower than before this sars outbreak. lastly, patterns of taiwan's influenza types/subtypes became more diversified after when mini links with china facilitated open travel exchanges [ ] . co-circulation of h n subtype with h n subtype or b type viruses resulted in higher p&i mortality than any subtype/type acting alone. our observations suggest that improvements in public education and public health efforts (as a result of post-sars effects and better vaccine matching) may have contributed to a reduction in p&i mortality. this trend would be further supported if mortality reductions persist in the presence of adequately sustained prevention measures. our study suggests that the future deployment of epidemiological measures such as virological surveillance (obtaining more specimens), timely molecular analysis of viral isolates and their accompanying vaccine strains, and identification of vaccinemismatched strains would support public health efforts to minimize complications and deaths. we recommend that public health resources be allocated to include both pharmaceutical [ ] and non-pharmaceutical interventions [ ] for minimizing elderly deaths whenever vaccine-mismatched h n viruses are dominant. daily syndromic surveillance data integrated with virological surveillance information and statistical methods for detecting abnormal signals and trends can provide timely information for identifying the occurrence of vaccine-mismatched or novel influenza viruses. these efforts can jump-start prevention at the initial phase of an epidemic, when there is a higher risk of humanto-human transmission (e.g., increased epidemic/pandemic potential of newly emerged influenza viruses). as outbreaks of emerging infectious diseases (eid) and novel influenza viruses continue to increase [ ] , we believe our results will help countries have not affected by sars to evaluate the effectiveness of their preventive and/or control measures for reducing influenza disease burdens (including vaccination programs for the current influenza h n pandemic in - ). in addition to determining the effectiveness of vaccine strains in a given flu season, variant epitopes on the surface of the virus may also result in varying immunological responses. certain epitope variants might be less effective at stimulating the development of b-cell humoral immunity or interfere with the ability of cytotoxic t-lymphocytes to recognize epitopes presented by hla class i proteins on the surface of infected cells [ ] . analysis of data from pre-sars winters-before the initiation of public health intervention efforts prompted by sars-may provide more clues as to the impact of vaccine-mismatched influenza viruses on excess mortality. in addition, taiwan's vaccine-mismatched influenza viruses appeared prior to the introduction of who's recommended vaccine strain [ ] . therefore, it is explainable why we observed higher excess p&i mortality during pre-sars vaccinemismatches than post-sars. the mismatched a (h n ) fujian strain which appeared in and circulated for several months may have steadily increased the population's herd immunity leading up to - . lower influenza-associated excess mortality during the winter of - , particularly in comparison to - , may also be attributed to a higher identity percentage between vaccine strains and circulating strains, a lower number of variations at epitope b, the development of herd immunity, and the post-sars effect. these two vaccinemismatching examples suggest that both quantitative and qualitative variations of amino acids, as well as the locations and epitopes involved, are important considerations when monitoring vaccine-mismatched influenza viruses. antigenic differences thus need to be identified efficiently by serological testing for isolated influenza viruses with high monthly/weekly excess p&i mortality [ ] . our results suggest that timely identification of vaccinemismatched circulating influenza viruses and their antigenic variations is crucial for effective evidence-based public health planning and preparedness. from january -october , documented vaccine effectiveness (ve) was % for preventing pneumonia deaths (when b was mismatched) and % for preventing all-cause deaths among the elderly in taiwan [ ] . matched vaccines reached a ve as high as % for preventing influenza among healthy adults [ ] . this ve declined to % when vaccines mismatched with circulating influenza viruses. we can surmise from past data that the ve for mismatched vaccines would be even lower for elderly populations because of their weakened immune responses [ ] . the variation of ve across different countries may be attributed to different age distributions, variable influenza vaccination coverage rates [ ] , and variation in post-sars effects. these variations may account for the higher overall p&i mortality and excess p&i mortality rates observed in italy and u.s compared to taiwan. the sars outbreak posed a significant challenge to taiwan's health care system but also had the potentially beneficial effect of educating the public about the need for seeking health care earlier [ ] and protective behaviors [ , ] . public education measures and behavioral changes prompted by the sars outbreak may have contributed to the ensuing decline in excess p&i mortality in taiwan and other sars-affected countries/areas [ , ] . although our observation periods were not long, the evidence suggests that the sars outbreak not only spurred behavioral change among taiwanese citizens [ ] but also prompted government officials to reform the infectious disease surveillance system [ ] as well as policies for hospital management [ ] and infection control [ ] in taiwan these changes, in combination with increasing awareness of infectious diseases among physicians, may have contributed to the sustained post-sars effect that we propose had a significant impact on taiwan's elderly p&i mortality rates. three studies in taiwan [ ] , in wuhan city of hubei province in mainland china [ ] and in hong kong [ ] support the claim that public health efforts were sustained after the sars epidemic. interestingly, influenzaassociated mortalities in taiwan, southern china and hong kong in the post-sars period were all lower than in the pre-sars period (personal communication in the march - , misms oceania regional influenza meeting and workshop in melbourne, australia). moreover, many public health measures taken in response to sars-including advising sick students to stay at home, teaching coughing etiquette, providing hand-cleaning facilities in front of elevators and at building entrances, closing classes if more than three influenza-like illnesses occur in one class, and vaccinating high-risk populations-all had been applied during the influenza h n pandemic. the effectiveness of these public health efforts is supported by the lower total number of p&i mortalities observed during the - winter season (ending february , ) than in previous years [ ] . in addition, we found that people had a greater understanding of health protection measures during the - pandemic influenza in sars-affected areas/countries such as taiwan and hong kong [ ] . this protective effect may have contributed to the lower numbers of p&i deaths in - compared to seasonal influenza in - and to the reduction in total laboratory-confirmed pandemic influenza h n deaths in taiwan ( deaths from july , to may , )) and hong kong ( deaths from july , to april , ) [ ] . this study has five major limitations. first, taiwan's monthly influenza virus isolation rates prior to were not comprehensive. second, weekly and monthly matching statuses were not available. third, the benefit of vaccination may be underestimated because older elderly populations are at higher risk of developing severe complications and deaths [ ] . fourth, the unknown temporality of vaccinations and the presence of many possible uncontrolled confounders (such as variations in age-specific attack rates, prior accumulated immunity, socioeconomic conditions, nutrition factors, public health efforts, and viral characteristics of individual influenza viruses including infectivity, pathogenicity, transmissibility and virulence) could not be fully accounted for in this retrospective ecological study. causal effects cannot be determined with certainty from observational studies comparing these groups (e.g., vaccine-matched versus vaccine-mismatched groups or pre-sars versus post-sars groups in this study). additionally, uncontrolled confounders at the individual level are a major limitation of an ecological study design. fifth, accounting for epitope variations in a (h n ) viruses will require more amino acid sequencing and serological data of the ha over the course of several years. enhanced virological surveillance in asia, where mostly past pandemic influenza viruses have originated [ , ] , is urgently needed because most new wild-type influenza virus strains have appeared much earlier in taiwan and south-east asia [ ] than in who-recommended vaccine strains [ , ] . furthermore, viral changes and co-circulating subtypes/types have been documented in the later periods of influenza epidemics [ ] . antigenic distance between the vaccine and circulating strains can be best measured by serologically testing simultaneously for vaccine strains and - local influenza isolates obtained from various time intervals of the same year (in which excess influenzaassociated mortality is identified). unfortunately, we did not have enough monthly retrospective samples to incorporate serological results into the model during the study period. the major limitation of this study was a lack of long-term data that prevents us from drawing definitive conclusions. however, we have illustrated possible associations between the observed reduction in p&i mortality and vaccine match on the one hand, and the post-sars effect on the other hand. our model is sufficiently flexible to apply to different scenarios in various countries. for minimizing a country's/global influenza disease burden, further studies will be required to validate the interpretations of our results that we have suggested. international collaboration on an integrated clinical, epidemiological, and virological/serological influenza surveillance system will be necessary to monitor for potential increases in clinical severity as well as viral sequence and antigenic changes in any parts of the world. this study points to a number of possible directions for improving influenza vaccination policy and provides a means for public health officials to monitor for possible occurrences of vaccine-mismatched influenza viruses at the population level. moreover, our study attempts to lay a foundation for a molecular explanation of influenza-associated deaths that integrates macrolevel mortality data with micro-level amino acid sequence identity percentage. we hope that our findings can prompt the discovery of better and more effective mechanisms for selecting strains for future serological testing. in the future, we hope to collect more data domestically and internationally in order to reevaluate and refine our recommendations. public health professionals in sarsaffected countries can also examine the post-sars impact and vaccine-mismatched effect using data sets from their countries. a concerted effort to obtain more evidence can bring the international community closer to devising more effective guidelines for the global control of next pandemic influenza. future research efforts should include: ( ) weekly/daily monitoring of influenza viral sequences, antigenic changes of the ha [ ] , and excess influenza-associated mortality; ( ) an evaluation of vaccine efficacy through measurement of antigenic distances [ , ] , and b-and t-cell epitopes [ ] ; and ( ) improvements in influenza vaccines through enhancement of innate immunity [ , , ] . figure s the d structure of the three newly undefined epitopes of human influenza a (h n ) viruses during the three vaccine-mismatched influenza seasons in taiwan, taiwan, - prevention and control of influenza: recommendations of the advisory committee on immunization practices (acip) vaccines for preventing influenza in the elderly influenzarelated mortality in the italian elderly: no decline associated with increasing vaccination coverage mortality associated with influenza and respiratory syncytial virus in the united states impact of influenza vaccination on seasonal mortality in the us elderly population seasonal trends of viral respiratory tract infections in the tropics the global circulation of seasonal influenza a (h n ) viruses influenza in taiwan: seasonality and vaccine strain match world health organization. who recommendations for influenza vaccine composition molecular characterization of the ha gene of influenza type b viruses simultaneous amino acid substitutions at antigenic sites drive influenza a hemagglutinin evolution cabinet expands mini links with mainland exploration of the emergence of the victoria lineage of influenza b virus increasing appearance of reassortant influenza b virus in taiwan from to process of standardized antiserum and antigen of human influenza viruses in taiwan mortality from pandemic a/h n influenza in england: public health surveillance study nonpharmaceutical interventions implemented by us cities during the - influenza pandemic global trends in emerging infectious diseases t-cell tolerance for variability in an hla class i-presented influenza a virus epitope laboratorybased surveillance and molecular epidemiology of influenza virus in taiwan mapping the antigenic and genetic evolution of influenza virus impact of influenza vaccination on major cause-specific mortality vaccines for preventing influenza in healthy adults antibody response to influenza vaccination in the elderly: a quantitative review international data base (idb) impact of sars on healthcare utilization by disease categories: implications for delivery of healthcare services factors influencing the wearing of facemasks to prevent the severe acute respiratory syndrome among adult chinese in hong kong severe acute respiratory syndrome epidemic and change of people's health behavior in china handwashing practice and the use of personal protective equipment among medical students after the sars epidemic in hong kong taipei's use of a multi-channel mass risk communication program to rapidly reverse an epidemic of highly communicable disease establishing a nationwide emergency department-based syndromic surveillance system for better public health responses in taiwan the reform of the hospital accreditation system in taiwan the impact of sars on hospital performance influenza express in taiwan -week widespread public misconception in the early phase of the h n influenza epidemic flu pandemic by country complications of viral influenza influenza vaccine strain selection and recent studies on the global migration of seasonal influenza viruses influenza vaccine strain selection and recent studies on the global migration of seasonal influenza viruses vaccination and antigenic drift in influenza influenza virus antigenic variation, host antibody production and new approach to control epidemics on the use of hemagglutinationinhibition for influenza surveillance: surveillance data are predictive of influenza vaccine effectiveness on the use of hemagglutination-inhibition for influenza surveillance: surveillance data are predictive of influenza vaccine effectiveness influenza virus ctl epitopes, remarkably conserved and remarkably variable influenza a viruses with truncated ns as modified live virus vaccines: pilot studies of safety and efficacy in horses live attenuated influenza viruses containing ns truncations as vaccine candidates against h n highly pathogenic avian influenza influenza b virus ns -truncated mutants: live-attenuated vaccine approach the authors appreciate the laboratory surveillance efforts of taiwan's virological surveillance contract laboratories and taiwan-cdc. we would also like to express our gratitude to ms. peggy lee, mr. andres su, and mr. james steed for their help in editing this paper in english. we are also grateful to dr. chi-tai fang for his critical viewpoints and the department of health -national taiwan university (ntu) infectious diseases research and education center for their administrative support. key: cord- -n ywei t authors: keck, frédéric title: avian preparedness: simulations of bird diseases and reverse scenarios of extinction in hong kong, taiwan, and singapore date: - - journal: j r anthropol inst doi: . / - . sha: doc_id: cord_uid: n ywei t this article describes relations between humans, animals, artefacts, and pathogens in simulations of disasters, taking bird diseases in three chinese sentinel posts as ethnographic cases. drawing on distinctions between simulation, ritual, and play, it shows that the engagement of actors in the imaginary of simulations, which they describe as ‘realism’, reflectively reverses the oppositions between humans and nonhumans, active and passive, fiction and reality that shape ordinary life. borrowing from the anthropology of hunting societies, it argues that simulations of bird diseases, considered as signs of future species extinction, rely on cynegetic techniques of power, in which humans and animals symmetrically shift perspectives, and not only on pastoralist techniques, in which humans are above the population they monitor and sometimes sacrifice. of action, simulations can be described as ritual performances displaying relations between humans and nonhumans in extraordinary settings. this article starts from observed simulations of an avian influenza pandemic in china. influenza viruses emerging from birds have been considered as potentially causing future pandemics, because birds (particularly waterfowl in south china) have been identified as the reservoir in which flu viruses mutate before spreading successfully between humans (shortridge & stuart-harris ) . among other techniques such as early warning systems and stockpiling vaccines, preparing for the next pandemics therefore involves simulating the transmission of pathogens from birds to humans (caduff ; lakoff ) . arguing that a human pandemic is a symmetrical threat to the extinction of a bird species, i then consider another bird disease for which chinese experts organize simulations: botulism. this disease, which doesn't affect humans, is considered a potential disaster for black-faced spoonbills because it kills migratory birds when they concentrate in wetlands on their flyways (wilson : ) . bringing together simulations of avian influenza and botulism, this article questions the ethnography of simulation from the perspective of animal studies. how does preparedness transform relations between humans and birds? what does it mean to include birds, and more generally animals, in exercises simulating coming disasters? how does the description of animals as victims of disasters transform them into actors of simulations (keck & ticktin ) ? i will show that animals become, in a paradoxical way, 'passive actors' when they carry the signs of diseases that can potentially affect humans. techniques of preparedness have been included in the set of tools for global health initiatives, either in humanitarian actions or in biosecurity interventions, which have shaped contemporary affects and anticipations of the future (adams, murphy & clarke ; lakoff ) . global health has been extended to animals and the environmentan approach called 'one world, one health' -thus requiring an interspecies approach towards the ethical issues involved (hinchliffe ) . one of the most debated questions in the anthropology of pandemic preparedness is the adequacy of the notion of sacrifice to describe how some populations are separated from others and killed or left to die for the sake of public health. in exercises of triage, some patients are prioritized over others through the framework of urgency (nguyen ; redfield ) . in the management of human populations, migrant workers are considered as a threat by educated experts using viral connectivity as a metaphor of modernity (macphail ; mason ) . in the management of zoonotic pathogens, the notion of sacrifice seems even more obvious, since animals are massively killed to eradicate the reservoir of emerging infectious diseases; and in the management of wild animals, some individuals are sacrificed to protect the species (van dooren ). other descriptions, however, have been proposed of the entangled relations between animals and humans in the 'hotspots' or 'sentinel devices' where emerging pathogens connect them in productive ways (brown & kelly ; fearnley ; keck & lakoff ; lezaun & porter ; lowe ) . while sacrifice separates some living beings from others to eradicate pathogens, sentinels instantiate relations between living beings through the anticipation of future pathogens. simulations of bird diseases shift perspectives between humans and animals through the use of fiction. to support this argument, i rely on the anthropology of hunting societies, by contrast with pastoral societies. while public health relies on pastoral techniques of power combining sacrifice and surveillance to contain the threats coming from outside in a population (foucault ) , the 'one world, one health' approach uses techniques from birdwatchers and wildlife managers to monitor data about changing relations between humans and animals. whereas pastoral techniques are asymmetrical, relying on the pastor's superior gaze over the flock manifested by sacrifice, cynegetic techniques are symmetrical, as hunters and prey constantly change perspectives when displayed in rituals (chamayou ) . most analyses of simulation have placed it in a genealogy starting with the cold war, using notions of ritual, performance, and play (davis ; galison ; gusterson ; lakoff ; masco ) . but they don't take the perspective of animals because they consider simulations as pastoral techniques of biopower, therefore bypassing what the anthropology of hunting societies shows about ritual action. in this article, i define a cynegetic practice of simulation that is always mixed with forms of planning, combining two different forms of anticipation. i call 'avian preparedness' this mix of cynegetic becoming-animal and pastoralist care for populations initiated by microbiologists, considered both as 'virus hunters' (perrey ) and as 'microbe farmers' (caduff : ) . to analyse simulations of bird diseases, i combine the notion of reverse scenario (schull ) with the notion of reflexive ritual. pandemic or extinction scenarios, i argue, connect humans and animals in realistic ways to play on the imagination of what could happen if a pathogen emerges. using animal reservoirs as mirrors in which anxieties about pandemics are reflected, humans exchange their perspectives with animals in an imagined future where their relations are reversed. simulations can thus be situated in an anthropological space between play and ritual. roberte hamayon ( : ) has called 'simulation' the way shamans in mongolian hunting societies imitate the movements of animals in a ritualized setting to prepare for the uncertainties of hunting. in an article entitled 'dissimulation and simulation as forms of religious reflexivity' , michael houseman proposes to move away from a definition of ritual as a collective action based on a shared secret to study 'the emergent properties of ritual simulation generally ' ( : ) . he draws on two cases taken from hunting societies of central africa, one in which male novices are symbolically killed and the other in which a goat is actually sacrificed. he asks: how do participants come to believe in a series of speeches and actions -the novice's death and the goat's consent to sacrifice -that are obviously false? he answers that ritual action creates an extraordinary space of reflexivity with regard to the ordinary relations that constitute the group. while the ritual for male novices is a 'dissimulation' , in which the relations between initiated and uninitiated are constantly reversed in such a way that the moment of death becomes uncertain, the ritual of goat sacrifice, says houseman, is a simulation of consent, in which the silencing of the goat through the consumption of herbs mimics the consent of male hunters to their initiation. the ritual is reflexive in the sense that it stages the condition of the ritual itself -the secrecy known by initiators and unknown by the initiatedthrough the manipulations of daily relations between humans and nonhumans, whose asymmetries are reflected as in a mirror. similarly, i suggest that we call 'reverse scenarios' the ritual performances by which simulators reflect playfully on the relations between humans and birds in the imagination of a disease that could affect them both. simulations, i argue, are far more than mere 'rehearsals' of a pandemic drama: they are catalysts in the transformation of human/nonhuman relations into asymmetrical biopolitical and ontological processes. to support this argument, i will describe three ethnographic cases in hong kong, taiwan, and singapore. these three territories have competed at the global level since the sars crisis in to be the best 'sentinel posts' where pandemic pathogens coming from china can be detected (abraham ) . as hubs for the intense circulation of persons and commodities in asia, but also as repositories of chinese traditional relations between humans and birds, they have prepared for the catastrophic effects of a bird flu outbreak. but while the hong kong government regularly culls its poultry and sends warning signals from the chinese border, taiwan and singapore rarely had to cull their poultry and rather invested in scenarios for the simulation of pandemic. taiwan, on the other side, shares with hong kong the monitoring of black-faced spoonbills, considered as one of asia's most threatened and charismatic species. this article thus connects the rationalities of preparedness with the economies of human/animal relations in three different but interconnected settings. it will examine indoor and outdoor simulations of avian influenza in singapore and hong kong, and compare them with simulations of botulism in taiwan. however, my analysis is not restricted to simulations of bird diseases in east asia, but highlights general traits of disaster simulation as a technique of preparedness. by looking at the relations between humans and birds in these three contexts through their common exposure to emerging pathogens, this article also analyses the relations between national states in asia as they have to manage a common disaster. since simulations of bird diseases connect relations at different scales, from the microbiological to the biopolitical, this article combines science studies, ethnography of rituals, and political economy through an anthropology of 'more-than-human' relations (helmreich & kirksey ; kohn ; sagan ) . in july , i was visiting gavin smith, who was then an associate professor at the duke graduate medical school of the national university of singapore (nus). i had known gavin in hong kong while he was working in the state key laboratory of emerging infectious diseases at the department of microbiology of the university of hong kong. born in australia, gavin had studied botany and ecology at the university of melbourne, and then moved to hong kong for a ph.d. in molecular systematics. gavin had first analysed the genome of fungi, then of the sars coronavirus, then of bird flu viruses. he described this development of his research as a reduction of the size of the living beings he was sequencing, and a refinement of the data and results he could produce. gavin and his team relied strongly on the collaboration between the state key laboratory of emerging infectious diseases and the university of shantou. this university had been created by the hong kong tycoon li ka-shing, who opened it in in his native guangdong, with the approval and administrative support of the chinese authorities. it provided the state key laboratory of emerging infectious diseases with samples collected in poultry markets in fujian province, thus offering a real-time surveillance of influenza strains emerging in this 'epicentre' of pandemic flu. but after the publications of gavin's team showed the role of the chinese poultry industry in the emergence of these new strains (smith et al. ) , the guangdong authorities had severely restricted hong kong virologists' access to these samples. gavin then moved to singapore in , where he had more freedom to continue his fundamental research, and more funding from international institutions. he had shifted from the sentinel post, where the new strains of avian influenza emerged, such as the h n virus in (keck ) , to a place where he could simulate the evolution of flu viruses in high-tech computers. there was no need to be close to the site where viruses emerge, he explained to me, as he could simulate viral emergence through the use of genetic data banks. singapore was then considered the new 'pole of excellence' for biological research. the small city-state founded by lee kwan yew in at the end of the malay peninsula had converted its industrial and financial power, owing to its position on the commercial trade routes between east and west, into an economy of knowledge and information, with high investment in biotechnologies (ong ; ) . the nus graduate medical school was located just next to the ministry of health and the singapore general hospital, in the centre of the city. it had been created in to train high-tech medical leaders on the model of the duke university school of medicine in north carolina. the programme in emerging infectious diseases, for which gavin had been hired to work, was headed by wang linfa, who was also leading a team on bat viruses at the australian animal health laboratory in geelong. his programme was running projects for the surveillance of emerging infectious diseases, particularly influenza and other respiratory diseases, in singapore and the rest of southeast asia. gavin's career took a meaningful turn when his team published two major articles at the height of the h n pandemic. the first one, entitled 'dating the emergence of pandemic influenza viruses' , was published just after the emergence of the h n virus in mexico in april . it showed that genetic components of the h n pandemic virus circulated among pigs and humans as early as , thus challenging the commonly held view that spanish flu jumped from birds to humans in . in the context of the new h n 'swine flu' , this article stressed the need for intensified surveillance of pigs to detect emerging flu viruses before they become pandemic. 'if future pandemics arise in this manner' , gavin and his team concluded, 'this interval may provide the best opportunity for health authorities to intervene to mitigate the effects of a pandemic or even to abort its emergence' (smith, bahl, vijaykrishna, et al. : ) . this conclusion was immediately reinforced by gavin's team's second publication, entitled 'origins and evolutionary genomics of the swine-origin h n influenza a epidemic' , published in nature at the end of , in which they showed that a 'twin' virus bearing the same genetic sequence as the pandemic h n had been identified in pigs in hong kong in . gavin's conclusion was not that the asian swine industry was to blame for the emergence of h n , but that there was a better surveillance of the animal reservoir for influenza viruses (waterfowl and pigs) in hong kong than in the united states. the team's paper ended, 'despite widespread influenza surveillance in humans, the lack of systematic swine surveillance allowed for the undetected persistence and evolution of this potentially pandemic strain for many years' (smith, vijaykrishna, bahl, et al. : . in july , i took a course at the hong kong university pasteur research centre in bioinformatics, during which gavin and his team partners, vijay and justin, explained to virology students how to obtain this kind of result. bioinformatics is a method to analyse the massive amount of biological data available on the web -particularly through the website of the us national center for biotechnology information, genbank -with the help of dedicated software. this software, called blast (basic local alignment search tool) or msa (multiple sequence analysis), calculates the probability that genetic sequences derive from one another. such a procedure, called alignment, aims at approximating the real descent relationships between viruses through a calculation of the optimal 'tree of life' , based on the darwinian hypothesis that life expands in a rational manner to maximize fitness capacities (mackenzie ) . for gavin and his team, however, bioinformatics was not only about probability calculation. in the construction of a phylogenetic tree, biological knowledge is necessary because some correlations proposed by the computer make no sense in an evolutionary perspective, as they can be due to errors in sequencing or genetic deletion. to decide which correlations to take into account and which to consider as irrelevant, virologists use other software (such as bootstrap, jukes cantor, or tamura) providing the probability of correlations based on a given scenario. as for other techniques of preparedness, probability is not enough to simulate a coming disaster: it requires a work of imagination (lakoff ) . peter galison has shown that computer simulation emerged in the field of particle physics as a 'subculture' among experimenters and theoreticians under the 'monte carlo' programme funded by nasa in the s to simulate a nuclear explosion. simulation replaces experimentation when the data needed for the theory are too numerous and complex to be processed with traditional instruments, creating a 'trading zone' in which different professional groups share a common language or 'pidgin' (galison : ) . similarly, bioinformatics produces new images shared by microbiologists, computer scientists, and public health executives in the anticipation of epidemics. software such as bootstrap can be considered as an accessory or decoy to trap the live bird viruses through the sequences that have been stored in genbank. gavin opened the course with a simulation of the work his team had done a few months before on the h n virus, presented as a desktop exercise of what to do when a new virus emerges. 'imagine we've received this new sequence from atlanta. paste it to blast, and take as much information as possible. make a tree so big you can never print it on a sheet of paper: it will be good starting material before reducing the inquiry' . gavin and his team explained that in contrast to other virologists working on flu viruses, they had decided to use the eight segments of the virus's rna, not just the two segments that shape the h and n proteins, usually considered to be the most significant markers of antigen evolution. they could thus build eight parallel evolutionary trees which, by their similarities, gave an indication of the real evolution of the whole flu virus. there was nothing secret in the images of pandemic viruses built by these microbiologists, unlike simulations of nuclear explosions built indoors by particle physicists (gusterson ) : all the phylogenetic trees produced by gavin and his team were publicly available on websites. drawing back the 'molecular clock' based on the estimated kinship relations between viruses, virologists could see the branches where evolutionary ruptures occur and pathogens jump from one species to another, such as the emergence of the h n pandemic in and . following continuities between genetic sequences, they exhibited the discontinuities between evolutionary niches. gavin said that when a virus jumps from one species to another, it inaugurates a new set of lines, as the 'immunity pressure' of the environment creates an 'evolutionary bottleneck' in which this mutation can replicate. drawing back these lines then lead him to what he named 'the most recent common ancestor' . 'i love those trees' , he added. the amount of information provided in a single image was correlated to the unity of an evolutionary hypothesis drawing this information back to a common ancestor. historians of science have shown the power of evolutionary trees in the books through which darwinism came to be accepted as a new worldview (bredekamp ; helmreich ), and their reframing in global health under the notion of an animal reservoir in which emerging pathogens spill over from animals to humans (king ; lynteris ) . but i was mostly intrigued by the way gavin and his team turned sequences into images through an anticipatory mode of reasoning that i call 'reverse scenario' . natasha schull proposes the term in her work with on-line gamblers, to describe the way they 'cope with the necessarily uncertain futures of any hand by returning them to a point in the past and confronting them with a branching diversity of outcomes that might have emerged from it' ( : ). it applies well to the practices of 'virus hunters' who use 'reverse engineering' to reconstruct potentially pandemic pathogens such as the h n virus (caduff : ; napier : ) . just as a gambler speculates how much he could have won if he had played this or that card, gavin imagines what could have happened if the h n virus had been detected in pigs prior to or . virus sequencing allows him to trace potential connections between birds, pigs, and humans, and to imagine other futures of cross-species transmission. yet we don't know how birds (and pigs) are actually involved in the construction of pandemic scenarios, because we don't see how virologists take virus samples from birds. we thus need to turn from desktop simulations to 'real-ground' exercises organized by public health officials and birdwatchers. after my visit to gavin smith at nus duke graduate medical school, i went to a nearby building to meet jeffery cutter at the singapore ministry of health. trained as an epidemiologist, jeffery cutter was the director of the communicable diseases division of the ministry of health, co-ordinating preparedness for emerging infectious diseases in singapore. 'there are million passengers every year at singapore changi airport' , he told me, 'so there is a high probability that emerging infectious diseases will come to singapore. we need to be prepared' . during the sars crisis in , he said, people were infected by the new coronavirus, with thirty-three deaths. they were all treated at the tan tock seng hospital, which had been designated by the government as an isolation hospital for sars patients. at the peak of the crisis, all schools in the country were closed for ten days, and home quarantine was established for more than , people known to have come into close contact with a sars-infected person. prime minister goh chok tong said publicly that sars could possibly become the worst crisis singapore had faced since independence. when a journalist asked him if he was being alarmist, goh responded: 'well, i think i'm being realistic because we do not quite know how this will develop. this is a global problem and we are at the early stage of the disease' (zolli ) . jeffery cutter introduced me to yoong cheong wong, head of the emergency preparedness & response division at the ministry of health. mr wong was a former policeman in charge of organizing exercises for emerging infectious diseases in hospitals. the first national exercise for influenza in singapore was organized in , after the first cases of human-to-human transmission of h n were suspected in thailand. called 'sparrowhawk' , it was organized in two stages: a table-top discussion and assessment of pandemic response plans among six hospitals in the country between april and june; and a practical exercise on - july, in which the six designated hospitals had to manage potential patients and share information about their circulation. mr wong explained that a thousand people were involved in the real-ground drill, mostly volunteers from grassroots organizations and nurses from training institutions. while patients moved from one hospital to another, some hospitals assessed the behaviour of others and gradually raised the number of casualties. the main question, according to mr wong, was: 'if there are casualties in one hospital, which resources do they need?' the goal of these exercises is officially the identification of unplanned gaps in coordination between the actors who manage epidemics. but the actual criticism of planners most often focuses on the drills' lack of realism. 'we try our best to do it as real as possible' , said mr wong, 'but everyone knew it was just an exercise' . to explain the improvement between 'sparrowhawk' exercises in and in singapore, an official leaflet notes, 'the exercises were activated unannounced to inject greater realism. the ministry of health emergency medical staff turned up without prior justification at the general ward of the exercise hospital and "triggered" the simulated case of human infection with avian influenza' (unsic : ) . realism, in this case, came from the fact that people were surprised, and yet they knew that they were faking the epidemic. what does it mean for a simulation to be realistic? here the notion of 'reverse scenario' is useful. just as microbiologists imagine what could have happened if viruses had been stopped in their animal reservoir, public health planners imagine what would happen if contagious patients were stopped before entering hospitals. but in both cases, death is not performed in the scenario. by contrast, another type of exercise conducted in singapore was very real. on july , the agriculture and veterinary authority (ava) organized a drill in one of the poultry slaughterhouses on the border with malaysia. there are no authorized poultry farms on the territory and only five chicken farms for eggs, which constrains singapore to import and slaughter million live chickens from malaysia every year. malaysian farmers need to be licensed by the ava to import their poultry to singapore, and are always regarded with suspicion by border authorities. and yet no case of h n has been found in singapore. i was able to watch the drill on-line because it was streamed widely on a number of websites. the name, 'exercise gallus vii' , referred to the fact that it was the seventh avian influenza exercise conducted by the ava since . it took place in the biggest of the ten slaughterhouses in singapore run by soonly food processing industry, which processed , chickens daily, providing per cent of the fresh chicken meat in singapore (asia one ). the scenario for the exercise was the following: , chickens had been infected with h n and should be killed and destroyed, according to emergency response plans. about employees of the slaughterhouse, mostly indians, had to be screened for their temperature, take an antiviral drug, and then wear personal protective equipment (boots, cap, mask, glasses, gloves) on the back of which their name was written. the 'affected' chickens were placed in green cages on belts, immersed in water, and electrocuted. their cadavers were then placed inside two layers of biohazard bags to be incinerated. dr yap him ho, director of the quarantine and inspection group, declared on television, 'to make sure that ava is prepared for any incursion, the main thing we want to do for this exercise is to train our officers, as well as the other parties that are involved in the contingency planning, to be familiar with the steps of the procedures' (straits times ). although much could be said on the paternalistic ethnic, gender, class, and age divides that structured these exercises, i want to focus on the distinction between humans and animals. while the simulation at the clinic was animated by a sense of urgency and scarcity of resources confronted with a fake pandemic, the simulation at the slaughterhouse was quietly following the procedures in actually killing false positive chickens. i was also intrigued by the fact that while the hong kong government organized many such exercises on the human side, they had never simulated bird flu in poultry farms, because outbreaks occurred regularly in farms on its territory. while singapore authorities actually killed poultry for a disease that remained virtual, hong kong authorities simulated the transmission of bird flu from chickens to humans because it was already circulating among birds. although avian influenza kills birds as well as humans, the reverse scenario of a pandemic represents massive death in a different mode for humans and for birds, depending on past experiences of pathogens crossing borders between species. i now turn to the simulation of bird flu in hong kong. on november , hong kong co-ordinated a desktop exercise called 'great wall' which simulated a virtual cluster of three human infections with h n in a family returning to hong kong and macau after their visit to a poultry market in mainland china. the goal of the exercise was 'to synchronize the three systems of pandemic preparedness to engender an effective response among them' (unsic : ) . the exercise opened with a ceremony attended by the vice-minister of the chinese ministry of health, wang longde. it was considered as a success in creating good relations between mainland china and the former british and portuguese colonies. while the sars coronavirus had caused a division between china and the former colonies in because of beijing's reluctance to share information (abraham ) , 'great wall' unified the country against an imagined enemy, pandemic avian influenza, but it instantiated ruptures between humans and birds. in january , after long discussions with the centre for health protection, i was allowed to participate in an exercise in a hong kong hospital. the centre for health protection was created by the department of health after the sars crisis to anticipate outbreaks similar to sars through active surveillance and communication (leung & bacon-shone ) . within this centre, the emergency response branch, headed by a police officer, was in charge of writing scenarios and organizing simulations. twice a year, a field exercise was held in hong kong, with observers from china and overseas, bearing the name of natural entities: maple, cypress, chestnut, redwood, eagle, jadeite, and so on. there was no epidemic simulation in hong kong in because the emergency response branch considered the management of the h n virus in the spring and autumn to be a 'real-life exercise' . 'exercise redwood' took place in the clinic of shau kei wan, located in the workingclass district of hong kong island. the following scenario was distributed to the participants and posted at major public buildings. confirmed human cases of bird flu had been reported in hong kong's neighbouring countries, as well as a rising trend in patient attendance with influenza-like illness in hong kong hospitals. live poultry had tested positive for avian influenza in hong kong's markets and were then culled at farms and markets. a member of the staff participating in the culling was reported to carry the h n virus, as was an -year-old boy who had played with live poultry. four clinics were designated in hong kong for triage. only the final part of the scenario was held in shau kei wan; the first part was meant to provide a plausible context. the official purpose of the simulation was to co-ordinate hospital services in the management of patients with influenza-like illness. eighty actors playing patients came in through the front door of the hospital and were sent to different departments depending on their symptoms (pulmonary conditions, tuberculosis, etc.). twenty 'players' treated them in the services, and two 'simulators' communicated with other hospitals on a hotline. those who were diagnosed with h n were evacuated by ambulance through the back door of the hospital, where the media took pictures. the head of the department of health gave a press conference after visiting the hospital, but the journalists asked him about new bacteria found in a private jacuzzi, not about the exercise itself. the drill's success was not questioned; it was successful because it had been held. the scenario was designed in such a way that no surprising event could happen: the only reality that came up was the bacteria in the jacuzzi, not the virus in bird markets. all the actors i saw looked young and relaxed, wearing blue caps and casual clothes. their symptoms were described on a tag they wore around their necks, indicating their name, address, nationality, sex, and age. these cards were red or green depending on whether they had bird flu or only influenza-like symptoms. they did not have to fake illness; their only role was to move to the designated departments. in another exercise organized by the centre for health protection, a plane was evacuated because a patient had been found with influenza-like symptoms; those who sat next to the patient received a red tag, and those who sat at a good distance received a yellow tag. what was remarkable in 'exercise redwood' was the absence of tension or anxiety in the medical staff's behaviour. although humanitarian ngos consider triage to be an ethical issue when a higher number of patients is met with limited resources (nguyen ; redfield ) , the medical staff of the shau kei wan clinic only separated symptomatic and asymptomatic patients to avoid the spread of the disease. the tension of the situationwho would be considered a spreader, who would receive treatment first -was delegated to objects: tags and caps. people were reduced to bearers of signs that circulated fluidly in the hospital under the gaze of the media. while the medical staff of the hospital played their own role, the actors playing patients with influenza-like illness came from a humanitarian association, the auxiliary medical service (ams). this association, created in to deal with the influx of chinese refugees, was registered in under the security department of the hong kong government. its , members are trained for disaster management in hong kong and outside. one of them described it to me as 'after-work entertainment' , 'a place to meet other singles'; it is an elite association where similar people express and share moral values. during their own exercises, performed every month, they train how to rescue victims of car accidents or fires. they simulate heartbeats on dummies with fake hearts. 'patients cannot fake the heart rate or the respiratory rhythm' , said the organizer, 'so they have tags' . tags have an indirect realistic effect, while dummies can actually simulate the heartbeat of an injured victim. members of the ams, who describe their own exercises as significant moments in the life of the association, were frustrated by 'exercise redwood' . from their perspective, there is a sharp difference between regular accident rescue exercises and extraordinary epidemic evacuation drills that co-ordinate several departments. one of the actors said he felt 'passive' , playing on the ambivalence of the term: as we had experienced sars in , we all can forecast how we would behave in another similar situation, like avian flu. being a citizen, we are quite passive; i believe that we should follow the guidelines and the government's advice so as to prevent ourselves from getting affected. but in the exercise, we were being passive. it can be said, consequently, that when they simulate patients in an epidemic exercise, members of the ams literally act as if they were dummies. there is thus a fundamental distinction in the real-ground exercises between actors and players. while actors are passive, reduced to the objects that 'act' or 'speak for them' , players and simulators introduce uncertainty by the way they combine these objects in the scenario. if actors have to appear 'real' to produce good images in the media, the simulators play on the fictional possibilities of the scenario. the distinction between simulators and actors in real-ground simulations runs parallel to the distinction between virologists and public health planners in desktop exercises: while actors and planners only follow their roles in the exercise, simulators and virologists explore the potentialities of reverse scenarios. another example shows how real-ground exercises combine the virtual and the actual as desktop simulation does. in an exercise called 'jadeite' , organized in january , members of the emergency response branch were simulating the evacuation of a residential building on computers, and the scenario specified that they had to evacuate the simulation room to a 'fallback room' . the simulation room, from which the vulnerability of vital infrastructures in hong kong was virtually assessed, thus came to be seen itself as a material environment under threat. the head of the emergency response branch who described this exercise to me said it was 'more fun than a movie' , as if images had suddenly burst through the screen. in this reversal of the scenario, simulators became actors, and fiction reality. neither a ritual performance nor a scientific model of prediction, the simulation was, for this former policeman, a game he enjoyed playing. animals take part in simulations in a general category that can be called 'passive actors' . if there was no need to simulate the culling of poultry because it regularly happened in hong kong markets, simulators for the evacuation of residential buildings in hong kong planned that some residents were accompanied by pets that should be handled with care by the agriculture department, because their reaction to the evacuation was unknown, just as simulators of the evacuation of planes planned how to handle 'reluctant potential patients' . the real opposition in simulations is thus not between humans and animals but between poultry, handled as commodities that can be destroyed, ordinary citizens and pets, considered as 'passive actors' that should be handled with care, and simulators, changing the rules of the game. more than sharp ontological distinctions between fiction and reality or between animals and humans, there is a virtual gradient of actors in the anticipation of massive death produced by simulation. the use of accessories and animals in simulations of disasters is indeed an essential part of their 'realism' . tracy davis has shown that people coming from the world of theatre were hired by cold war experts to implement scenarios of nuclear blast through the design of accessories. simulation designers were, therefore, less concerned with the participation of the public than with the realism of the objects. after an exercise organized in coventry in , prime minister winston churchill complained about the high degree of realism of the simulations, which he considered a waste of public money. 'who thought of the blood-stained old woman with the birdcage? i hope there is not going to be any more of this sort of thing at government expense' (quoted in davis : ) . women were the main targets of civil defence after the second world war, as they had been the targets of public health campaigns against microbes at the beginning of the twentieth century, because they were in charge of the household with children and pets. animals were portrayed as good accessories of nuclear blast simulations not only because they were good laboratory models (masco : ) , but also because they were part of a familiar landscape disrupted by an extraordinary event. the extraordinary context of the simulation thus provides the opportunity to display a series of apparent contradictions: people become objects; animals become people; actors turn out to be passive; fiction enters into reality. this capacity to displace oppositions in an extraordinary context through reverse scenarios brings simulations close to rituals. however, if simulations can be considered as rituals of public health administration, justifying the work of virus hunters who sound the alarm about future pandemics, it doesn't mean that there is a secret worldview shared by simulators (gusterson ) . rather, simulations display openly contradictions that public health administrations have to solve, often by the use of sacrifice in operations of culling (of infected poultry) or triage (of suspected patients). they create a tension between two techniques of power: those of biologists and simulators who follow viruses as they mutate between species, which i describe as cynegetic, and those of public health officials who have to protect some populations against others, which i call pastoral. to support this hypothesis, i will now turn to simulations organized by birdwatchers. can we say that birdwatchers take the perspectives of threatened wild birds as virologists take the perspective of poultry infected with flu viruses? how do humans in charge of the protection of animals cope with the oppositions we have seen in reverse scenarios of pandemics? birdwatchers have been involved in the surveillance of the avian reservoir of influenza viruses. public health and agriculture authorities realized that they could not follow the mutations of flu viruses in wild birds, and collaborated with birdwatching associations to monitor potential cases in wild bird reserves and natural environments. in hong kong and taiwan, birdwatching practices, a privilege of british and american expatriates until the s, have become popular among chinese middle classes with the development of a leisure society, the commercialization of camera equipment, and the awareness of the vulnerability of the environment (choy ) . birdwatching has taken the form of a 'citizen science' with the opening of websites where amateurs post their observations and experts turn them into statistical data. every year, bird races offer opportunities for birdwatchers to compete in observing the highest number of birds on a designated territory. thus, birdwatching practices, like simulations, have virtual and actual aspects, orientated by the imagination of a disaster: the extinction of bird species. in hong kong and taiwan, the introduction of birdwatching was linked to techniques of preparedness and concerns for biosecurity. the main wild bird reserve in hong kong, mai po, is situated on the estuary of the pearl river delta and on the border with mainland china. after , british officers used to sit there with their binoculars to trace chinese refugees or to signal an attack by the chinese army, and took this opportunity to inventory the more than bird species in hong kong. hong kong and taiwan were part of the migratory animal pathological survey, a programme of surveillance of pathogens carried by birds (particularly japanese encephalitis). through this programme, british and american ornithologists trained chinese workers to band birds and collect samples. transforming birds into data and following the evolution of their numbers has been a way to simulate threats coming from birds since the second world war (keck ) . methods derived from us wildlife management have changed the perception of birds in the last twenty years in taiwan and hong kong, with the introduction of the concept of the flyway. species that fly from japan and korea to australia, along what came to be called the east asian-australian flyway, have been shown to have declined owing to the urbanization and development of the chinese coast. climate change is also supposed to damage the places where wild birds feed and roost on their migratory routes. among the bird species affected by these changes, one of the most charismatic is the black-faced spoonbill, a waterbird breeding in japan and korea in the summer and migrating to south china in the winter. in the s, the number of these birds was estimated to be , , but thanks to the conservation efforts shared by the countries to which they migrate, it increased to , at the end of the s. wetlands have been developed in hong kong, taiwan, and fujian as shelters on their flyways. images of spoonbills abound in schools, environmental agencies, and natural reserves, often portrayed as funny birds smiling to the public. to understand how reverse scenarios of disasters enter the management of spoonbills in china, we have to go beyond these anthropomorphic images, and look at how they actually perform in simulations. in the winter of - , seventy-three black-faced spoonbills were found dead from botulism in taijiang national park. the wild bird society of tainan consequently organized a campaign to vaccinate spoonbills against botulism, and used decoys to train their staff on how to safely handle the birds. since then, drills have been regularly organized for bird protectors to learn how to manipulate fake spoonbills with caution. these decoys are also used to attract spoonbills for gps monitoring. carved in wood and painted in black and white, they are posted in the wetlands close to traps. decoys are different from images of spoonbills on posters: wildlife managers interact with them as if they were alive, because of their accurate mimicking. the use of decoys is a traditional feature of bird hunting. by contrast with lures, which attract birds based on their appetites, decoys attribute intentions to prey (schaeffer : ) . in england, duck decoys take the form of pondside wooden houses into which ducks are attracted by a fake dog, because hunters have observed that ducks swim towards the dog to signal that it has been seen. in the same way, the fake spoonbill is used as a decoy because it creates a situation of communication with the bird. but at the same time, the fake spoonbill is used as a dummy by birders who train to manipulate spoonbills in risky situations, as in epidemic simulations. the use of spoonbill decoys mixes hunting techniques and pastoral techniques because decoys are considered both as intentional agents and as objects that should be manipulated with care. this hypothesis was confirmed on april when the wild bird federation of tainan led me to a site where three black-faced spoonbills had been trapped -a very rare event, which i was considered lucky to have witnessed. birdwatchers had found shelter in a taoist temple on the banks of the marshes, and they turned on some buddhist music to soothe the birds. with very calm gestures, a man equipped with gloves and a mask sewed a gps satellite tracking device around the waist of the spoonbill, while a woman held it gently but firmly. five other birdwatchers watched them with amusement, taking pictures and making comments on the bird's reactions. the man explained to me that he had to be cautious because it was a young spoonbill, so the weight of the satellite tracking device had to be imposed on its body in such a way that it would not hamper its growth or unbalance its flight. how to build techniques of monitoring that do not kill animals considered as indexes of the fate of their species is a major concern for wildlife managers, who often talk about the sacrifice of individual animals when they die as the result of an improper monitoring device (benson ) . but taiwanese birdwatchers focused the discussion on how to properly release these birds so that they would not be sacrificed but become sentinels of a threatened species. the release of birds is a major ritual concern in south china, known as fangsheng (literally 'let live'). this practice finds its roots in aristocratic practices of opening the cages of birds who sang well, and was codified in taoist rituals as a specific sequence of releasing a live animal; but it has developed massively in recent centuries with its qualification by buddhists as a practice of compassion that increases the 'merits' (gongde) of those who release live animals (handlin smith ) . in hong kong and taiwan, buddhist associations entered into discussion with birdwatching societies because many birds were found dead after they were bought in bird markets and released in surrounding natural parks. these associations had to warn through posters that releasing birds could cause the death of birds, because they were released in an improper environment, and the death of humans, since some of the birds found dead after the release carried avian flu (severinghaus & chi ) . consequently, when they released a bird equipped with gps that they had learned to manipulate through the use of decoys, taiwanese birdwatchers inserted a ritual sequence into a simulation practice. while the ritual introduced the bird into a cycle of life and death, the simulation used the decoy to produce signs of future threats for birds and humans. the black-faced spoonbills were released in the taijiang national park with the hope that they would fly over to hong kong or the fujian coast, where their signals could be captured. it should be noted that the taiwan straits are also the sites of military exercises or drills through which threats coming from china are mitigated. to prepare for an attack from the people's republic of china, the taiwanese centers for disease control was organizing exercises simulating the use of bioweapons in a public space, such as sars, smallpox, and avian flu virus (rollet : ) . the release of a black-faced spoonbill in the same chinese straits mimics and reverses the scenario of an avian flu outbreak from china. instead of carrying information on the potential war between two long-term enemies, it produces signals on the changes of bird habitats that concern birds as well as humans. while in the public health simulations birds are considered as carriers of infectious diseases, birdwatchers' simulations frame them as living beings with which humans share pathogens as signs of communication. another practice with birds in taiwan clarifies by contrast their role in simulations. according to peta, more than a million pigeons are released every day from boats in the taiwan straits by pigeon-racing clubs, and only per cent survive to come back to their shelter. huge amounts of money (an estimated us$ billion) are spent in bets on those which will return, welcomed as heroes if they are first, killed if they are too slow. this is neither a ritual nor a simulation but a gambling practice through which birds crossing the sea between china and taiwan are qualified as political signifiers. the reverse scenario of the game, producing strange identifications between humans and birds, tells the story of a pigeon successfully returning home while others fail and die in the taiwan straits. releasing a bird in taiwan can thus appear as a simulation when it is embedded in the framework of an environmental flyway, as a ritual when it mobilizes a cosmological view of the circulation of souls between humans and animals, or as a game when it is organized on the border separating two competing territories. simulation, ritual, and play are three frameworks to mitigate the uncertainties of catching and releasing a potentially sick bird. i have considered three stages where bird diseases are simulated: computer simulations of avian influenza by microbiologists; outdoor performances of pandemic influenza by public health administrations; and exercises of manipulating threatened birds by birdwatchers. these three types of simulation displace the problem of sacrifice: that is, the definition of those who deserve to live and those who will die. microbiological surveillance of viruses moves away from the site of emergence where birds are killed to prevent the spread of pathogens to humans, and traces continuities between humans and animals as a reservoir where viruses silently mutate. simulations of epidemics don't address the problem of triage between humans in a situation of exception, but rather configure new relations between humans and animals through accessories in a performance. exercises of vaccinating and releasing potentially sick birds don't raise the issue of how many birds can die for the sake of the species, but rather reflect on how to handle a bird with care in a political environment where they carry signals of threat. in the reverse scenarios of simulations, birds appear not as sources of infection that must be eradicated, but as sentinels with which humans can communicate to imagine potential futures. simulations, therefore, should be analysed not only as a pastoral technique of power, as ways to mobilize populations under a common threat in which some are sacrificed for the sake of others, but also as a cynegetic technique of power, creating relations of identification between humans and animals around a perceived uncertainty at the borders between species. in the world of databased science and transparency of communication, simulations of bird diseases imply playing like animals or with animals to anticipate the (im)possibility of a mass extinction, thus mobilizing elementary forms of identification. in the cases i have considered, the question of the realism of exercises is a way to draw attention to the circulation of objects that recast relations between humans and birds by simulating the diseases they share. the use of computer software, accessories, and decoys in the three types of simulations i have analysed blurs the sharp opposition between humans and nonhumans. these objects can be considered as decoys because they carry the intentions that humans attribute to animals and shift their perception from inanimate objects to living beings. while scenarios of bird-generated epidemics play on the asymmetries between humans and birds, the horizon of the simulation (the extinction of the human or of a bird species) integrates them as common actors of a game. simulations can thus be considered as reflexive rituals because they display the uncertainties of the beings they play with and help to mitigate their threats. framing simulation as an operation unfolding between the spheres of mimetic play and reflexive ritual, and at the same time performing a series of subject-object reversals, i have argued for the need to approach this key apparatus of preparedness through a lens that allows for the mixing of pastoral and cynegetic techniques. what i have called in this article 'avian preparedness' takes place in a long history of simulating bird movements, from classical divination by roman augurs to medieval bird hunting and modern birdwatching. the specificity of contemporary forms of anticipation through sentinels, simulation, or stockpiling is that the distinction between cynegetic techniques of preparedness, taking the perspectives of birds on future threats through imagination and communication, and pastoral techniques of prevention, protecting human or nonhuman populations from external dangers through risk calculation, has become more difficult to make and yet more urgent. this article has argued for such a distinction, while opening the stage for future analyses of simulations as forms of play and ritual. this research was made possible by a project on simulations of disasters headed by sandrine revet at sciences po paris in - . i am grateful to her and to marc elie and guillaume lachenal for the discussions we had on simulations, as well as to the four anonymous reviewers and the editors of the jrai, who helped me improve the writing of this article. this approach was launched in by the wildlife conservation society, and then endorsed by the international organizations for human and animal health (http://www.oneworldonehealth.org/, accessed february ). contrary to other viruses such as smallpox, flu viruses don't have their genetic information encoded in dna (a double-stranded helix of nucleic acid) but in rna (a single-stranded ribonucleic acid). this explains why they mutate more randomly. anonymous interview by email after a questionnaire sent to the ams, february . http://www.peta.org/action/action-alerts/first-ever-taiwan-raid-police-bust-pigeon-racers/ (accessed february ). twenty-first century plague: the story of sars anticipation: technoscience, life, affect, temporality rehearsing for the plague: citizens, security, and simulation ava holds culling exercise in poultry slaughterhouse wired wilderness: technologies of tracking and the making of modern wildlife darwins korallen: frühe evolutionsmodelle und die tradition der naturgeschichte material proximities and hotspots: towards an anthropology of viral hemorrhagic fevers the pandemic perhaps: dramatic events in a public culture of danger manhunts: a philosophical history ecologies of comparison: an ethnography of endangerment in hong kong stages of emergency: cold war nuclear civil defense wild goose chase: the displacement of influenza research in the fields of poyang lake, china omnes et singulatim: towards a criticism of political reason image and logic: a material culture of microphysics nuclear rites: a weapons laboratory at the end of the cold war chicago: hau books. handlin smith, j.f. . liberating animals in ming-qing china: buddhist inspiration and elite imagination alien ocean: anthropological voyages in microbial seas more than one world, more than one health: re-configuring interspecies health dissimulation and simulation as modes of religious reflexivity une sentinelle sanitaire aux frontières du vivant: les experts de la grippe aviaireà hong kong security, disease, commerce: ideologies of postcolonial global health how forests think: toward an anthropology beyond the human preparing for the next emergency hong kong's health system: reflections, perspectives and visions containment and competition: transgenic animals in the one health agenda viral clouds: becoming h n in indonesia zoonotic diagrams: mastering and unsettling human-animal relations bringing sequences to life: how bioinformatics corporealizes sequence data viral network: a pathography of the h n influenza pandemic the nuclear borderlands: the manhattan project in post-cold war new mexico infectious change: reinventing chinese public health after an epidemic the age of immunology: conceiving a future in an alienating world the republic of therapy: triage and sovereignty in west africa's time of aids fungible life: experiment in the asian city of life un ethnologue chez les chasseurs de virus: enquête en guyane française a small world': ethnography of a natural disaster simulation in lima dimensions identitaire, sécuritaire et sociétale de la politiqueétrangère de taiwan dans le domaine de la lutte contre les maladies infectieuses the human is more than human: interspecies communities and the new 'facts of life'. cultural anthropology website pourquoi la fiction? paris: seuil the gaming of chance: online poker software and the potentialization of uncertainty ritual and its consequences: an essay on the limits of sincerity prayer animal release in taiwan an influenza epicentre? models, simulations and their objects dating the emergence of pandemic influenza viruses emergence and predominance of an h n influenza variant in china origins and evolutionary genomics of the swine-origin h n influenza a epidemic culling exercise. razor tv simulation exercises on influenza pandemic responses in the asia-pacific region flight ways: life and loss at the edge of extinction seeking refuge: birds and landscapes of the pacific flyway learning from sars. andrewzolli.com cet article décrit les relations entre humains, animaux, artefacts et pathogènes dans les simulations de désastres, en considérant les maladies qui affectent les oiseaux dans trois territoires sentinelles aux frontières de la chine comme des cas ethnographiques. en s'appuyant sur les distinctions entre la simulation, le ritual et le jeu, il montre que l'engagement des acteurs dans l'imaginaire des simulations, qu'ils décrivent sous le terme de « réalisme », renverse réflexivement les oppositions entre les humains and les non-humains, l'actif et le passif, la fiction et la réalité qui organisent la vie quotidienne. en empruntant les concepts de l'anthropologie des sociétés de chasseurs, il montre que les simulations de maladies aviaires, lorsqu'elles sont perçues comme des signes d'une potentielle extinction d'espèce, recourentà des techniques de pouvoir cynégétiques, dans lesquelles des humains et des animauxéchangent symétriquement leurs perspectives, et pas seulementà des techniques pastoralistes, dans lesquelles les humains sont au-dessus de la population qu'ils surveillent et parfois sacrifient.frédéric keck is a researcher at the laboratoire d'anthropologie sociale (collège de france, ehess, cnrs, psl). he has conducted research on the history of social anthropology and on the contemporary management of animal diseases, and headed the research department of the musée du quai branly.laboratoire d 'anthropologie sociale, rue cardinal lemoine, paris, key: cord- - j axjd authors: chen, ying-chu title: system dynamics evaluation of household water use behavior and associated greenhouse gas emissions and environmental costs: a case study of taipei city date: - - journal: journal of water process engineering doi: . /j.jwpe. . sha: doc_id: cord_uid: j axjd abstract taiwan is an island surrounded by sea and only % of its freshwater usage is for domestic applications. a system dynamic model was developed to investigate interactions between household water use behaviors (toilet flushing, clothes washing, bathing/showering, and cleaning) and associated greenhouse gas emissions and environmental costs. six hundred and fifty face-to-face interviews were conducted in districts of taipei. the results showed that the respondents’ individual attributes were not significantly related to water use behaviors. the highest volume of water was used for cleaning ( . %), followed by clothes washing ( . %), bathing/showering ( . %), and toilet flushing ( . %). five water management scenarios with %– % reductions in water volume from different water use behaviors were simulated. the maximum reduction in water use ( . t) was found in the fifth scenario ( % reduction), which reflected the priority the respondents gave to save water if its price increased. . % of respondents had water saving appliances; . % and . % of the appliances were toilets and shower heads, respectively. the environmental cost of ghg emissions associated with water use behavior was us$ . /t, causing an % increase in water price. a better understanding of household water use behaviors is needed to develop bottom-up strategies or measures for sustainable water management. water saving measures or strategies would lead to targets being met in a short time. there are more than , islands in the world, accounting for one sixth of the global land area [ ] and more than million people live on these islands [ ] . small islands comprising over one sixth of the global land area are facing struggles associated with global climate change. taiwan has a population of . million and an average gdp of us$ , /capita in [ ] . the unique topographical and geological characteristics in taiwan affect water availability, water use and conservation. about two thirds of the island is mountainous, which means that water flows into the ocean quickly and cannot easily be stored. total rainfall is hugely different in the dry and wet seasons (november to april and may to october, respectively), leading to water shortages in the dry season. in addition, extreme events such as typhoons increase the deposition of sand and rock in rivers and reservoirs, gradually reducing their storage volumes and increasing water turbidity. furthermore, the groundwater in southern taiwan has been over-pumped for years due to the development of agricultural and aquacultural industries. domestic use accounts for only % of freshwater usage, with industry and agriculture accounting for % and % respectively [ ] . taiwan is already struggling to meet the growing demand for water, particularly in summer. the residential water demand will continue to grow due to urbanization. households are high consumers of water and are therefore important sites for water conservation [ , ] . domestic water consumption in most developed countries is higher than the or l/d specified as being sufficient to fully meet household water requirements [ ] . it ranges from as low as l/capita/d in the netherlands [ ] , to l/ capita/d in the uk [ ] , l/capita/d in taiwan [ ] , and l/ capita/d in the usa [ ] . researchers have investigated household water consumption by types of appliance [ ] , and behavior [ ] . previous findings confirm that attributes including gender [ ] , age [ ] , education [ ] , and income [ ] significantly affect household water consumption. women are more likely to participate in environmental behavior and activism such as water resources conservation. age is inversely related to environmental concern; in other words, younger people are more likely to engage in environmental behaviors [ ] . however, chenoweth et al. [ ] reported that older water users were slightly more likely to consider water saving options. people with a higher level of education often consume more water [ ] . in one study, as income level increased, so did reported participation in water conservation [ ] . household water use can help make water consumption a key indicator of human behavior [ ] . water saving behavior can be sorted into similar groups based on location (indoor or outdoor), and behavior type (efficiency, curtailment or maintenance) [ ] . however, water use behavior has not been fully assessed even though it can lead to considerable reductions in water consumption [ ] . household water use is frequently assessed by questionnaire or established models. yu et al. [ ] used a face-to-face interview method to estimate residential water use associated with three types of behavior: bathing, cooking, and cleaning. they found a strong correlation between water use and energy consumption. chenoweth et al. [ ] investigated the links between household water consumption and wellbeing in southern england via a household survey. the results showed that actual water use appears to be unlinked to willingness to adopt water saving measures. wolter [ ] conducted a survey in oregon and found that environmental concern and sociodemographic attributes predicted water conservation behaviors. daioglou et al. [ ] modeled domestic water demand at the end-use level and indicated that cooking was the main end-use function. other functions, such as space heating and cooling appliances, become more important. ren et al. [ ] developed a tool to predict energy consumption at the end-use level and related greenhouse gas (ghg) emissions of australian households. researchers further compared energy-related ghg emissions from the water systems of various cities without analyzing the behavior of endusers [ ] [ ] [ ] . the pumping, treatment and distribution processes in water systems are the major contributors to ghg emissions [ ] . ghg emissions is a prominent environmental indicator that primarily determines the sustainability of urban water systems. studies have indicated that water conservation at the household level is one of the effective ways to reduce ghg emissions originating from water systems journal of water process engineering ( ) [ ] . system dynamics (sd) modeling has been used to evaluate environmental and water systems at various scales. the sd model, introduced by jay forrester in the s, is a well-established methodology for understanding, visualizing and analyzing complex dynamic feedback systems [ ] . it attempts to quantify qualitative aspects without altering the accuracy of the original statement, providing a much more explicit basis for communication [ ] . sd models are useful for considering dynamic interrelationship among variables within social and economic systems [ ] . water resources (quantity and quality) are integrated with five sectors that drive industrial growth: population, agriculture, economy, nonrenewable resources, and persistent pollution [ ] . an sd model was used to increase public understanding of the value of water conservation in las vegas [ ] . the results of sd model simulations show that water scarcity, unlike other limitations such as nonrenewable resources and persistent pollution, results in severe problems within a short time of its occurrence [ ] . qi and chang [ ] proposed an sd model based on a coupled modeling structure that takes into account the interactions among economic and social dimensions, offering a realistic platform for practical use. a reservoir balance sd model was developed and presented for the pedra 'e othoni reservoir in italy to assess resilience to climate and development changes [ ] . an sd model to evaluate the water-energy-food nexus at the household scale was developed by hussien et al. [ ] . the model successfully estimated a water-energy-food demand and the impact of change in user behavior, diet, income, family size, and climate. more work is needed to develop systematic and detailed approaches to assess household water use in terms of ghg emissions and environmental costs. the aim of this study was to develop an integrated sd model addressing the interactions between household water use and ghg emissions at the household scale. taking taipei city as a case study, the model captures more water use behaviors including toilet flushing, clothes washing, bathing/showering, and cleaning than previous studies. the number of water saving appliances and the priority given to saving water with different appliances were also innovatively evaluated in this study. the potential ghg emissions were internalized into environmental costs to reflect increases in the water price. the price of water has a direct influence on household water use [ , ] unlike tax [ ] . otherwise, water has been considered as a natural resource with little economic and utilization values [ ] . this kind of research is needed to better understand household behaviors regarding the use of potable water. globally, emissions of ghg can be mitigated by taking a bottom-up approach. taipei city, which has a high water quality standard (total coliform < cfu/ml, turbidity < . ntu, heavy metal and nitrite nitrogen are none detected [ ] ), was taken as a case study. the city has districts ( fig. ) and . million residents with us$ , /captia gdp on average [ ] . ghg emissions from the water supply system have been evaluated in several published studies as noted in the introduction. this study focused on ghg emissions caused by different household water use behaviors. respondents were asked to complete a questionnaire about their water use. the results of the questionnaire were incorporated into an sd model. the water quality in households reached the government's quality standard with little variation and therefore is not discussed in this study. face-to-face surveys can be clearly structured, flexible and adaptable [ ] . in this study, at least questionnaires were required when applying a convenience sampling method with a % confidence interval. therefore, six hundred and fifty face-to-face interviews were conducted during the spring vacation (april to april ) of in different districts of taipei city. the questionnaire, which could be completed within min, consisted of three sections. the first section collected information about the houses owned by the respondents, such as age and floor area. it was based on a survey of hong kong residents [ ] . the second section contained seventeen questions about the respondents' water use behavior. the questions were designed with reference to shan et al. [ ] and covered frequencies of bathing/showering, drinking water, and cleaning. the number of water saving appliances (e.g., low-flow taps and/or shower heads, dual-flush toilet) was also recorded. the respondents were also asked about the priority they would give to saving water if the water price increased. the final section elicited the respondents' socio-economic information, such as gender, income, age, and education. an sd model is constructed from building blocks (variables) and includes four main components: stocks, flows, connectors, and converters (fig. ) . stock variables, symbolized by rectangles, are the state variables and they represent the accumulation water in the system. flow variables, symbolized by valves, are the rate of change in stock variables and they represent those activities and decision functions that fill up or drain the stocks. converters, represented by circles, are intermediate variables used for miscellaneous calculations. finally, the connectors, represented by simple arrows, are information links representing the cause and effects within the model. an example relating to household water volume is as follows. the overall volume of water used for clothes washing depends on the water volume used each time and the frequency of clothes washing (fig. ) . the mathematical mapping of an sd stock-flow diagram occurs via a system of differential equations, which are solved numerically in the simulation. the specifications of the sd model are shown in table s . six equations were modeled using stella software in this study. the year was taken as the base time and -year simulations (from to ) with a step size time variable of year were modeled. household water use in taiwan can be divided into five major categories: toilet flushing, clothes washing, bathing/showering, cleaning, and other uses [ ] . the categories of cleaning and other uses were frequently confused by respondents in pretests of the survey and were integrated in this study. the detailed calculations of water volume are described below. the formulae to calculate water use volume was based on yu et al. [ ] and redesigned as follows: where v flush is water volume used for toilet flushing (l/y), f fα and f fβ are the frequency of toilet flushing (times/capita/d), q fα and q fβ are the water volume of toilet flushing (l/times), α is the percentage of households that own water saving toilets, β is the percentage of households without water saving toilets, equal to − α , p is the population of taipei city, equal to , , in [ ] , and is the conversion factor from year to day. where v cloth is water volume used for clothes washing (l/y), f c is the frequency of clothes washing (times/capita/d), and q c is the water volume of clothes washing (l/times). clothes washing is not classified with/without water saving appliances by the government in . where v bath is bath/shower volume (l/y, with or without water saving appliances), f sα and f sβ are the frequency of taking a shower (times/ capita/d). q , sα and q sβ are the water volume of taking a shower (l/ times), f b is the frequency of taking a bath (times/capita/d), and q b is the water volume of taking a bath (l/times). clean clean other ( ) where v clean and v other are water volume for cleaning and other purposes, respectively (l/y). therefore, ghg emissions from household water use can be calculated as follows: where v i is water volume and i can stand for toilet flushing, clothes washing, bathing/showering, or cleaning (l/y). one ton of tap water has been reported to produce . kg co -eq ghgs in [ ] ; therefore, the converting factor is × − . t co -eq/l/y in this study. the ghg calculations are mainly used to represent environmental costs as monetary values. the environmental costs (ec ghg , us$) of ghg emissions can be calculated as follows [ ] : where pi t is the carbon price at year t (us$/t co -eq). for the year of , the carbon price announced by the european union emission trading scheme (eu ets) was . eur/t co -eq (equal to . us$/t co -eq) [ ] . qcf t is the ghg emission from unit water volume each year (t co -eq/y), and r is the discount rate of . % [ ] . therefore, the water price in terms of the environmental costs of ghgs is as follows: where pv is the operating and maintenance costs (us$) and a is the external profits of the water department. currently, the operating and maintenance costs in taiwan are us$ . /t and basic external profits for the water company should be % [ ] . it is known that water saving measures and/or appliances can reduce water usage by %- % [ ] . therefore, this study simulated five different water management scenarios (fig. ) : %, %, % and % reductions in water volume from different water use behaviors, and a scenario to reduce % water volume in which respondents gave priority to saving water if the water price increased. an effective water management system must be accepted by the public [ ] . the randomly sampled people resided in different districts of taipei city. among the questionnaires, ( %) were suitable for analysis; % were excluded due to non-responses. as shown in table , % of the sample was male and % was female; . % of the respondents had four family members (i.e., two children in the family); . % of the respondents were educated to college level; and . % were aged between and . the monthly income of half of the respondents ranged from us$ to us$ , . the respondents' individual attributes (gender, age, education, and income) were cross-analyzed with their water use behaviors. it is interesting that % of the respondents said they took less than s to wash their hands, − min for cleaning, and − min to take a bath/ shower. the unicef [ ] suggests to scrub all surfaces of the hands for at least s to protect against coronavirus (covid- ) which was successfully controlled in taiwan. the promotion of population's awareness of hand washing will still provide the greatest benefit to mitigate the pandemic [ ] . male respondents took shorter showers than female respondents in this study. high school students took longer baths/showers than college students did, confirming the finding of yu et al. [ ] that older people use less bathing water. respondents with an income level between us$ and us$ would take − min shower, versus other respondents ( − min). the water used for clothes washing and shower is greater for lower-income areas [ ] . in other words, higher levels of income demonstrated more engagement in water conservation behaviors [ , ] . rosinger et al. [ ] found that income was linearly associated with tap water consumption among us citizens; however, the individual attributes were not significantly related to water use behaviors in this study. in this study, . % of water volume was used for cleaning, followed by clothes washing ( . %), bathing/showering ( . %), and toilet flushing ( . %) (fig. ) . in the netherlands, a population survey indicated that the main end uses of household water were showering ( %), toilet flushing ( %), and clothes washing ( %) [ ] . an analysis of the north american residential end uses of water study indicated that the top three indoor end uses of water were toilet flushing ( . %), clothes washing ( . %), and showering ( . %) [ ] . the amount of water for lawn and landscape irrigation is rapidly increasing in the us and is estimated at a total of billion gallons per day nationwide [ ] . average water end use consumption in australia has been reported as showering ( %), outdoor uses ( . %), taps ( . %), clothes washing ( . %), and toilet flushing ( . %) [ ] . garden watering and showering are two of the largest contributors to water use in households in australia [ ] . in poland, water used for showering and clothes washing accounts for % and % of total household water use, respectively [ ] . showering is the greatest consumer of domestic water in portugal, accounting for % of total water consumption [ ] . taiwan's water resources agency [ ] found that toilet flushing ( %), clothes washing ( %), and bathing/ showering ( %) were the highest contributors to household water use (fig. ) . in this study, the volume of water used for toilet flushing had reduced to %, perhaps because of an increase in the use of water saving appliances during the past years. other water use behaviors were increased. as shown in table , . % of respondents had water saving appliances; . % and . % of the appliances were toilets and shower heads, respectively. asian countries, like korea, japan and taiwan, had - % water saving toilets; however, other europe countries had higher percentage of using water saving toilet [ ] . a saving of l can be made each time a water saving toilet is used. most respondents reported using l and l each time for clothes washing and bathing, respectively. family size and seasons were positive related to frequency of clothes washing [ ] . taking a shower with or without a water saving shower head would save ca. - % water compared to bathing. showering frequency rather than duration played a dominant role in use of water for bathing [ ] . the participants in this study used . l/d for cleaning. the average volume of water used for cleaning was . l/d in taiwan in the past years [ ] . water use efficiency can be significantly increased by the installation of more efficient water use devices [ ] . for example, solar hot water systems are marketed to households on the basis of reduced energy costs through reduced ghg emissions [ ] . some households adopt water saving appliances and practices to continue their high consumption habits [ , ] . kenway [ ] found that behavioral changes play a vital role in water savings and ghg emissions. different water use behaviors will have their own best water saving scenarios. as shown in fig. , the highest reduction in water volume ( . t) was reached in the fifth scenario, which reflected the priority respondents gave to saving water if the price increased. the - % water volume reduction from different water use behaviors would only reduce water use by . t (first scenario) to . t (fourth scenario). the water volume reduces very fast in the first years ( - ) and stays steady in the following years, showing that water saving measures or strategies would lead to targets being met in a short time (fig. ). the reduction in water used by toilet flushing was highest in the fourth scenario, in which . t was saved during the study period. the reduction in water used for clothes washing was lower in the fifth scenario ( . t) than in the fourth scenario ( . t). the volume of water used for clothes washing may be limited by the size of washing machines that only work when there is a full load. other water use behaviors would be related to the targets for water use reduction. the volume of water used for bathing/showering and cleaning would reduce by . - . and . - . t, respectively, in the different scenarios. shove's [ ] work on changes in showering practices in the uk over time is particularly important. domestic water saving may be increased through economic incentives, technical improvements, or policy instruments and regulations [ ] . in sum, establishing water saving targets for different water use behavior depending on water prices would be more efficient than a single target, which is frequently applied by the government. as water reuse systems are less efficient than conventional water supply systems [ ] this option is not suggested in this study. the environmental cost of ghg emissions from water use behavior was us$ . /t in . the direct and indirect costs of water management in taiwan are ca. us$ . /t and us$ . /t, respectively [ ] . the direct costs are incurred by purifying, treating, supplying, and managing water resources. the indirect costs include employee training, disaster losses, retirement, and interest. the water price would be increased to us$ . /t (according to eq.( )) after monetizing the environmental costs of ghg emissions (us$ . /t). an % increase was accepted by respondents in this study if the government keeps providing clean and safe water resources in taiwan. the majority ( %) of survey respondents are willing to pay - % of the household monthly water bill for reliable water service in banda aceh, indonesia [ ] . houtven et al. [ ] suggested that households are willing to pay approximately us$ - per month for improvements in water access. expenditure on water in taiwan was the third from last when water price was divided by gdp for different countries [ ] . facing a price increase, households will generally adjust their consumption by reducing it. renwick and archibald [ ] found that marginal water price had a strong effect on the number of water-efficient devices in households. however, some people would be willing to pay extra not to compromise their daily showering rituals [ ] . the water price should be increased to reflect environmental costs, not only ghg emissions but also the costs of protection/conservation. the costs of water scarcity could reach % of gdp in some regions [ ] . pricing has been found to be a cost-effective tool for promoting water conservation [ ] . in addition, environmental education and attitudinal change might be more effective in influencing water use [ ] . it is advisable to educate general public the importance/advantage of water and alterative water resources [ ] . taiwan is a small island surrounded by sea. domestic water use accounts for only % of total freshwater usage in taiwan. ghg emissions from water systems have received attention as a prominent environmental indicator in recent years. an integrated sd model addressing the interactions between household water use and ghg emissions was therefore developed in this study. taking taipei city as a case study, the model captures different behaviors including toilet flushing, clothes washing, bathing/showering, and cleaning. potential ghg emissions were represented as environmental costs to reflect an increase in water price. a total of face-to-face interviews were conducted during the spring vacation (april to april ) of in districts of taipei city. the results revealed that the respondents' individual attributes were not significantly related to water use behaviors. the largest volume of water ( . %) was used for cleaning, followed by clothes washing ( . %), bathing/showering ( . %), and toilet flushing ( . %). five different water management scenarios with - % reductions in water volume from different water use behaviors were modeled. it is appropriate to establish water saving targets within years. the maximum reduction in water use ( . t) was found in the fifth scenario, which reflected the priority respondents gave to saving water if the water price increased. the environmental cost of ghg emissions associated with water use behavior was us$ . /t, causing an % cost increase, which was acceptable to the respondents in this study. further research of this kind is needed to better understand household behaviors regarding the application of water saving strategies or measures. the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. % res-a challenge for island sustainable development climate-smart technologies: integrating renewable energy efficiency in mitigation and adaptation responses the current and future development of water resources utilization in taiwan using individual householder survey responses to predict household environmental outcomes: the cases of recycling and water conservation residential water and energy nexus for conservation and management: a case study of tianjin water consumption and subjective wellbeing: an analysis of british households the water cycle from source to tap, vereniging van waterbedrigven in delving into water: performance of the water companies in england and wales - to - water resources agency, technologies for saving household water manual estimated use of water in the united states in alarming visual display monitors affecting shower end use water and energy conservation in australian residential households assessment of household water use efficiency using performance indices water conservation awareness and practices in households receiving improved water supply: a gender-based analysis predication of urban residential end-use water demands by integrating known and unknown water demand drivers at multiple scales ii: model application and validation representing in-home and out-of-home energy consumption behavior in beijing from income and housing wealth inequalities to emissions inequality: carbon emissions of households in china attitude-behavior consistency in household water consumption water and related electrical energy use in urban households: influence of individual attributes in beijing a methodology for synthetic household water consumption data generation it's what you do and where you do it: perceived similarity in household water saving behaviours model projections for household energy use in developing countries a model for predicting household end-use energy consumption and greenhouse gas emissions in australia understanding the water-energy-carbon nexus in urban water utilities: comparison of four city case studies and the relevant influencing factors evaluating the energy and carbon reductions resulting from resource-efficient household stock water-related energy in households: a model designed to understand the current state and simulate possible measures socidemographic patterns of household water-use costs in puerto rico study of the inter-relationship between water use and energy conservation for a building a system dynamics model for evaluating the alternative of type in construction and demolition waste recycling center-the case of chongqing policies, decisions and information sources for modeling a prototype system dynamic model for assessing the sustainability of construction projects world water dynamics: global modelling of water resources a system dynamics model to facilitate public understanding of water management options in las vegas, nevada world continental modelling for water resources using system dynamics system dynamics modelling for municipal water demand estimation in an urban region under uncertain economic impacts operational resilience of reservoirs to climate change, agricultural demand, and tourism: a case study from sardinia an integrated model to evaluate water-energyfood nexus at a household scale demand side management policies for residential water use: who bears the conservation burden? household water use behavior: an integrated model assessing the impact of full cost recovery of water services on european households enhancing domestic water conservation behavior: a review of empirical studies on influencing tactics comparison table of water quality standards and national water quality standards online, face-to-face and telephone surveys: comparing different sampling methods in wine consumer research water supplies department, residential water consumption behavior survey household water consumption: insight from a survey in greece and poland carbon footprint accounting in support of city water supply infrastructure siting decision making: a case study in ningbo eu carbon price falls below € , carbon pricing using smart meters for household water consumption feedback: knowns and unknowns integrated solid waste management: a life cycle inventory unicef, everything you need to know about washing your hands to protect against coronavirus (covid- ) google searches for the keywords of "waste hands" predict the speed of national spread of covid- outbreak among countries gold coast domestic water end use study delving deeper: exploring the influence of psychosocial wellness on water conservation behavior understanding the blue water footprint of households in china from a perspective of consumption expenditure disparities in plain, tap and bottled water consumption among us adults: national health and nutrition examination survey (nhanes) residential end uses of water, awwa research foundation and american water works association south east queensland residential end use study: final report changing household water consumption practices after drought in three australian cities water resources agency, indicators for saving household water household adoption of energy and water-efficient appliance: an analysis of attitudes, labelling and complementary green behaviours in selected oecd countries understanding australian household water-related energy use and identifying physical and human characteristics of major end uses effects of feedback information on the household consumption of water and electricity: a case study in colombia energy use in the provision of urban water in australia and new zealand, csiro: water for a healthy country national research flagship cleanliness and convenience: the social organization of normality energy consumptions and associated greenhouse gas emissions in operation phases of urban water reuse systems in korea domestic water supply, residential water use bahaviour, and household willingness to pay: the case of banda aceh, indonesia after ten years since the indian ocean tsunami what are households willing to pay for improved water access? results from a meta-analysis average water price loading in the world demand-side management policies for residential water use: who bares the conservation burden? land econ high and dry: climate change, water, and the economy modeling residential water demand: an approach based on household demand systems analysis of social attitude to the new end use of recycled water for household laundry in australia by the regression models the authors thank the ministry of science and technology of the republic of china for financial support (most - -m- - ). the authors further thank the anonymous reviewers for their invaluable comments and suggestions. supplementary material related to this article can be found, in the online version, at doi:https://doi.org/ . /j.jwpe. . . key: cord- - u xe authors: hsu, chih-cheng; chen, ted; chang, mei; chang, yu-kang title: confidence in controlling a sars outbreak: experiences of public health nurses in managing home quarantine measures in taiwan date: - - journal: am j infect control doi: . /j.ajic. . . sha: doc_id: cord_uid: u xe background: taiwan experienced one of the most serious outbreaks of severe acute respiratory syndrome (sars) during the epidemic. public health nurses faced unprecedented challenges in implementing an extensive quarantine policy to prevent disease spread. their professional confidence, however, was shattered during the sars crisis. this paper assesses factors related to public health nurses' confidence in managing community sars control programs. methods: in may , we sent structured questionnaires to all health centers in taiwan and asked the public health nurses responsible for epidemic control to complete. a total of completed surveys were returned for a response rate of . %. descriptive methods and logistic regression were used to analyze the data. results: most public health nurses ( . %) expressed a general lack of confidence in handling the sars epidemic. confidence was significantly associated with perceived epidemic severity (or, . ; % ci: . - . ), daily epidemic updates (or, . ; % ci: . - . ), and number of cases in the community (or, . ; % ci: . - . ). conclusion: nurses' individual risk perception and prompt update of epidemic information significantly affect levels of professional confidence, a key factor influencing quarantine implementation success. strategies to promote productive interagency collaboration and advocate participatory policy making involving health workers at all levels are needed to control effectively infectious disease outbreaks. the global spread of severe acute respiratory syndrome (sars) in was a prelude to other emerging infectious diseases in the st century. recent outbreaks of h n avian influenza in asia continue to remind the world of the threat of periodic and unpredictable recurrences of pandemic contagion. since the beginning of the sars outbreak, many scientists have worked to characterize the coronavirus, , trace epidemic patterns, and synthesize potential vaccines to prevent further outbreaks. , however, the global experience of managing sars has revealed that reducing contact between people by implementing quarantine measures is as important as discovering effective remedies. , taiwan reported probable sars cases and sars-related deaths during the outbreak in , making it one of the most serious sars epidemic areas in the world , figure shows the chronology of the sars epidemic in taiwan. facing this unprecedented outbreak, the taiwan government began implementation of compulsory home quarantine on march to stop community transmission. individuals who were suspected to have been infected with sars were quarantined at home (or in special facilities) for to days. in those months of the epidemic period, , individuals were quarantined in taiwan. this includes , people who had close contact with sars patients and , travelers who came to taiwan from world health organization (who)-designated sars-affected areas. , public health administration in taiwan is organized at levels: national, city/county, and township. generally speaking, national health policies are often formulated in the national department of health (doh) with participation of city/county health bureau officials. the health centers (or health stations, as they are called) are the local agencies situated in the townships. the major responsibility of health centers is to implement public health protocols developed at the national and city/ county levels. the directors of health centers are usually licensed physicians. public health nurses are usually the supporting staff who carry out program assignments. the public health operation in taiwan is managed under this clear chain of command. under this system, taiwan eradicated malaria infection in the s, succeeded in having % of all married women aged to years practice contraception in the s, and dropped % of hepatitis b carriers in the s. public health nurses working at the local health centers played a key role in achieving public health success in taiwan. however, the public health nurses were unprepared in at the time of the sars crisis. sars hit taiwan in march . in response to the outbreak, the doh created an emergency operation office and appointed an anti-sars task force commander to direct a comprehensive national sars control program. home quarantine was ordered for all suspected sars cases. health centers at all localities were asked to implement the home quarantine policy. local public health nurses were not invited to participate in the national sars control policy making but were requested to carry out the mission. during the quarantine period, public health nurses were requested to undertake several public health measures, which included conducting initial registration, maintaining daily temperature records, disposing of personal trash, and providing social support and advice on medical care to those with a fever or sars-related symptoms. success in quarantine management was considered a crucial factor in the successful control of sars. however, it was soon evident that public health nurses' lack of experience in managing community quarantine and their fear of being infected with sars presented a major challenge. this study was designed to understand better the challenges and threats facing public health nurses responsible for implementing sars quarantine procedures. the results will be valuable for developing better strategies for controlling the rapid spread of infectious diseases such as sars. an attitudinal questionnaire was developed by researchers in may at the peak of the taiwan sars epidemic. questionnaire items were designed on the basis of the working experience of a panel of public health nurses. the questionnaire went through a content validation process. six experts from public health or community nursing fields served as the expert panel in checking the validity of questionnaire items. the drafted questionnaire was piloted for understandability among public health nurses in northern taiwan. moreover, within week after the questionnaires were returned, the researchers randomly selected and phoned respondents (approximately % of the total) to check the reliability of their written answers. the test/retest reliability for this questionnaire was high (pearson correlation coefficients for continuous variables: . - . ; spearman rank correlation coefficients for categorical variables: . - . ). one section of the questionnaire was designed to collect baseline information, including ( ) demographics, ( ) number of quarantined cases managed and responsibilities within the previous week (itemizing quarantine-related extra workload), and ( ) the date the nurses predicted sars epidemic would end. another section (using categorical scales) asked about sars-related operations that included the frequency of ( ) epidemic information updated in the health center, ( ) sars-related training courses received, and ( ) assistance of community volunteers on quarantine measures. the third section contained questions (using -point likert scale: the worst to the best) about the effectiveness of the nurse's institution in managing the sars epidemic, including the nurse's assessment of ( ) the institutional functioning on community home quarantine, ( ) the quality of training received for controlling infectious disease outbreaks, and ( ) the adequacy of support (for both manpower and financing) received from superior health agencies force commander said the epidemic situation was stable and advised people to return to their routine. (e) who removed taiwan from its list of areas to which travelers were advised to avoid for all but essential travel. (doh or city/county health bureaus). in the fourth section of the questionnaire (also using -point likert scale), the nurses were asked to assess the severity of the epidemic, the public's awareness of the epidemic situation, the public's fear of sars, and the public's compliance with official quarantine measures. finally, the nurses were asked to list major difficulties they encountered in managing the sars epidemic. the main island of taiwan has a total of health centers. on may , , questionnaire was mailed to each of the health centers to be completed by the head nurse or the nurse in charge of sars epidemic control. a reminder letter was sent week later to nonresponding centers. a total of completed surveys were returned for a response rate of . %. logistic regression was used to identify variables associated with the nurses' lack of confidence in sars control. nurses who estimated that the sars epidemic would not be declared ''ended'' by the who until mid-september or later (the who declared taiwan sars free on july ) were categorized as ''less confident.'' logistic regression also identified variables associated with public compliance of official anti-sars measures. variables in univariate models that exerted a significant effect were subjected to multivariate logistics to assess significance level. statistical analyses were performed using sas . (sas institute inc., cary, nc). all reported p values were -sided; p , . was considered statistically significant. table , approximately half ( %) of the respondents were to years of age, one third ( %) to years, and % older than years. most respondents ( %) had at least years of experience working in a health center. approximately % of respondents believed the sars outbreak would be controlled by mid-july; the remainder of the respondents believed control would not occur until mid-september ( %), mid-december, or later ( %). many public health nurses encountered difficulties while performing sars-related duties. they expressed dissatisfaction with the shortage of protective equipment such as n masks and gloves ( %), public resistance to following protection measures ( %), poor interagency communication ( %), and lack of standard operating procedures ( %). as shown in table , nurses' perceptions of epidemic severity were negatively associated with confidence that the epidemic could be controlled (or, . ; % ci: . - . ). nurses in health centers receiving fewer epidemic updates were more likely to doubt the effectiveness of epidemic control measures (or, . ; % ci: . - . ). nurses working in areas with relatively fewer probable sars cases were less confident in control efforts (or, . ; % ci: . - . ). several factors contributed to the public's lack of cooperation with sars-related home quarantine measures (table ). according to the nurses, people were less likely to cooperate with quarantine measures when ( ) they were less knowledgeable about sars (or, . ; % ci: . - . ), ( ) they expressed less fear of sars (or, . ; % ci: . - . ), ( ) the health centers were not functioning well (or, . ; % ci: . - . ), and ( ) the health centers received inadequate manpower or financial support from higher health authorities (or, . ; % ci: . - . ). this study is the only study reporting on the assessment of frontline nurses' reactions to home quarantines implemented by most health centers in taiwan during the sars outbreak. survey respondents were mainly head nurses with more than years of health center experience and were very familiar with their organizations, clients, communities, and issues surrounding quarantine operations. furthermore, because they were required to interact directly with quarantined persons, they had the best opportunity to understand the community's response to the sars outbreak. also, because the survey was conducted just after the sars epidemic had peaked, the related experiences were fresh in their minds, and recall bias would have been minimal. therefore, this report can be a valuable reference for the control and management of sars-like contagious disease outbreaks. the who removed taiwan from its list of sarsinfected areas on july , ; however, even at the beginning of june, many taiwanese, including public health officials and lay people, remained pessimistic about the success of sars control measures. as shown in table , most public health nurses ( . %) believed that the outbreak would not end until mid-september or even later. there was at least a -month difference between frontline nurses' estimates and the actual timing of the epidemic's end, indicating a low confidence level on the part of the nurses. this is serious because the pessimistic attitudes of nurses could affect the morale of quarantined subjects, people in the community, and, eventually, the success of the sars control program. why did public health nurses lack confidence in implementing the anti-sars program? as shown in table , individual risk perception, working environment of the health centers, and epidemic severity in the community were contributing factors. during the sars epidemic, the taiwan government made efforts, via media announcements, to assure the public that the situation was under control. from may , all major television channels broadcast daily the ''sars front-line'' program on the evening news. the premier and the commander of the anti-sars task force also repeatedly delivered public announcements that said the outbreak would soon be over. [ ] [ ] [ ] however, these optimistic public announcements were not always trusted by frontline nurses. the daily epidemic reports received by the nurses always seemed to be outdated. as the severity of the epidemic lessened day by day, the outdated data that showed a more severe phase of epidemic were counterproductive to boosting nurses' trust in the government's optimistic announcements. it appears that providing public health nurses with rapidly updated information is of utmost importance. results also show that risk communication at the time of infectious disease outbreak should be based on timely, rapidly updated, and evidence-based data to supplement routine government announcements. we determined whether nurse confidence in epidemic control measures was a function of extra hours and activities required for managing the epidemic. results indicated that lower confidence levels were associated with fewer cases in the community (table ) . without an immediate threat, health centers in counties/cities with few sars cases might not have fully mobilized their community resources to prepare the public or their nurses for sars prevention and control measures. because the national media broadcasted sensationally on the severity of sars epidemics, public health nurses without sufficient preparation and support might have been more vulnerable to rumors and speculation about negative aspects of the outbreak such as mortality rate, resulting in a loss of confidence in organized efforts to control the sars epidemic. another factor contributing to nurses' low confidence may be related to their lack of opportunity to participate in the formation of national policy, which they are asked to implement at the local level. according to the aforementioned traditional chain of command in the taiwanese public health bureaucracy, when the sars policy was developed, standard procedures for field operations were decided by the national office. without having policy fine-tuned with input from frontline nurses, this top-down policy could not promptly respond to local needs that changed rapidly according to the disastrous nature of sars contingencies. it is obvious that the long-established champion of the taiwanese public health system needs an effective feedback mechanism to renovate its response to newly emerging infectious outbreaks. a platform that encourages participatory decision making involving health professionals at all levels should be critically emphasized in developing a national policy to control sars-like outbreaks of pandemic contagion. frontline nurses reported that one of the most frustrating experiences during the sars epidemic was the reluctance of people to follow quarantine guidelines. this was independent of local epidemic severity but significantly related to people's cognitive preparedness and the efficiency of interagency collaborations (table ) . quarantine restricts the movement of people who can potentially expose others to a disease. , how to implement effectively a community-wide quarantine therefore presents a major challenge to health agencies. table shows that people who were less knowledgeable about the sars outbreak and those who expressed little fear of infection were less compliant in following anti-sars measures. in the future, more efforts should be placed on educating people to increase their health knowledge and beliefs, especially about risk susceptibility and severity, and belief in the benefits of taking health actions. , moreover, effective community health education programs that emphasize community-based participatory research and education should be considered. , from a national perspective, a comprehensive sars control strategy should also be developed that would streamline communication and resource sharing among health agencies at all levels. in summary, public health nurses' confidence in the control of a sars outbreak and people's compliance with quarantine measures are major factors that can affect the success of a sars-control program. other important determinants to a successful program include effective risk communication, participatory policy making that involves health workers at all levels, and intergovernmental collaboration at national and local levels. factors critical to sars management are similar to those for crisis management of avian influenza outbreaks and of the results of terrorist acts. [ ] [ ] [ ] [ ] lessons learned in this study can serve as useful guidelines to prevent and manage emerging infectious disease outbreaks. sars: unprecedented global response to a newly emerging disease avian influenza and pandemics sars virus: the beginning of the unraveling of a new coronavirus sars: beginning to understand a new virus a double epidemic model for the sars propagation current concepts in sars treatment treatment of sars with human interferons evaluation of control measures implemented in the severe acute respiratory syndrome outbreak in beijing preventive strategies to keep saudi arabia sars-free information below was mainly re-classified according to the current sars definition and test results in laboratory from who. center for disease control taiwan basars%ac%db%c %f %b %ea%b t/%a x%c wsars%ac% control measures for severe acute respiratory syndrome (sars) in taiwan use of quarantine to prevent transmission of severe acute respiratory syndrome-taiwan health care system in a transitional society: a taiwan experience. a conference speech delivered at the international research foundation for development sars: a perspective from a school of nursing in hong kong china: sars transmission interrupted in last outbreak area who estimated that the taiwan epidemic situation might be under control in six to seven weeks the premier said that the outbreak would be over by the end of the chief commander of anti-sars project in taiwan said it did not need seven weeks to control the outbreak efficiency of quarantine during an epidemic of severe acute respiratory syndrome community based participatory research: a promising approach for increasing epidemiology's relevance in the st century community-based participatory research: an approach to intervention research with a native american community who views on perspectives in health informatics introduction to community empowerment, participatory education, and health the public and effective risk communication communicating risk: wireless and hardwired public reliance on risk communication channels in the wake of a cryptosporidium outbreak bioterrorism risk communication policy key: cord- -nh s maw authors: shen, ching-fen; wang, shih-min; chi, hsin; huang, yi-chuan; huang, li-min; huang, yhu-chering; lin, hsiao-chuan; ho, yu-huai; hsiung, chao a.; liu, ching-chuan title: the potential role of pneumococcal conjugate vaccine in reducing acute respiratory inflammation in community-acquired pneumococcal pneumonia date: - - journal: j biomed sci doi: . /s - - - sha: doc_id: cord_uid: nh s maw background: pneumococcal conjugate vaccine (pcv) reduces both invasive pneumococcal disease (ipd) and other pneumococcal infections worldwide. we investigated the impact of stepwise implementation of childhood pcv programs on the prevalence of pneumococcal pneumonia, severity of acute inflammation, and associations between breakthrough pneumonia and pneumococcal serotypes in taiwan. methods: in total, children diagnosed with community-acquired pneumococcal pneumonia were enrolled between january and december . results: proportions of pneumococcal vaccinations increased each year in age-stratified groups with pcv ( . %) as the majority, followed by pcv ( . %). the proportion of pneumococcal pneumonia decreased each year in age-stratified groups, especially in – year group. serotype a is the leading serotype either in vaccinated ( . %) or unvaccinated patients ( . %). in particular, vaccinated patients had significantly higher lowest wbc, lower neutrophils, lower lymphocytes and lower crp values than non-vaccinated patients (p < . ). after stratifying patients by breakthrough infection, those with breakthrough pneumococcal infection with vaccine coverage serotypes had more severe pneumonia disease (p < . ). conclusion: systematic childhood pneumococcal vaccination reduced the prevalence of community-acquired pneumococcal pneumonia, especially in – year group. serotype a was the major serotype for all vaccine types in patients with pneumococcal pneumonia and severity of acute inflammatory response was reduced in vaccinated patients. bacteremic pneumococcal pneumonia is a major global health problem with a deleterious impact on patients' lives, presenting a management challenge to clinicians because of its complications, especially in children and older adults [ , ] . pneumococcal disease is the primary cause of childhood morbidity and mortality worldwide, resulting in . to . million deaths each year in children younger than age years [ ] . childhood community-acquired pneumonia is most often attributed to streptococcus pneumoniae, and the greatest incidence of invasive pneumococcal infection (ipd) is observed in children younger than age [ ] . many countries have had reductions in ipds since after the introduction of pneumococcal conjugate vaccine (pcv), specifically -valent conjugate pneumococcal vaccine (pcv ) containing seven serotypes [ ] [ ] [ ] [ ] . universal vaccination with pcv also resulted in a % reduction in pneumococcal disease in children aged - and a % reduction in hospitalization of children age under age [ ] . a recent review and meta-analysis reported that systematic childhood pcv immunization programs provided widespread protection against ipd and reduced cases by % within years [ ] . taiwan began an ipd surveillance program in october , requiring every hospital to report ipd cases of all ages and to send s. pneumoniae isolates to the taiwan centers for disease control (taiwan cdc) [ ] . the highest burden of ipd in taiwan occurs in children younger than age , particularly those aged - years, among whom the incidence was . per , population per year between and [ ] . the serotype a became most prevalent in and was the dominant ipd serotype in taiwanese infants and children between and [ , ] . during july and february , the taiwan cdc introduced a series of public-funded pcv programs targeting different groups of children at high-risk for ipd, including children younger than years of age with certain medical conditions susceptible to ipd, or those who were born into families with low or middle income. a nationwide stepwise catch-up program for -valent pcv (pcv ) was then launched in march , targeting children aged - years [ ] ; the age-range was then expanded in to cover children aged - years, and a systematic pcv program introduced in january provided routine two-plus-one immunization for all infants [ ] . despite early and appropriate antibiotic treatment, mortality associated with community-acquired pneumonia (cap) still remains high [ ] , especially in patients with underlying clinical illness. approximately % of patients hospitalized for cap match the criteria for severe cap, with more patients presenting with septic shock and need for mechanical ventilation. the mortality rate of severe cap can be as high as % [ ] . progression to septic shock is believed to be caused by excessive or uncontrolled local and systemic pro-inflammatory response [ ] . a stronger inflammatory response is associated with treatment failure and mortality [ ] . specific pneumococcal serotypes are associated with different clinical patterns of pneumococcal disease, classified according to their capacity to cause invasive disease [ ] . serotypes , and f are highly invasive serotypes associated with invasive disease in younger adults, but with low mortality rates. in contrast, serotypes , f and f possess relatively low invasive potential, affecting older adult patients with comorbidities and increasing case-fatality rates [ ] [ ] [ ] [ ] . among all pneumococcal disease, pneumococcal pneumonia serotypes are associated with the greatest severity and highest mortality rates [ , ] . however, to the best of our knowledge, no previous studies have addressed the relationship between pcv, acute inflammation, respiratory failure, and associations with pneumococcal serotypes. therefore, the overall purpose of the present study was to investigate the impact of stepwise implementation of pneumococcal conjugate vaccine (pcv) on epidemiological change in pneumococcal cap, including: ) potential reduction in the prevalence of pneumococcal pneumonia, ) whether or not childhood pcv vaccination affects the severity of acute inflammation in those who develop pneumococcal pneumonia, and ) whether breakthrough pneumococcal pneumonia is associated with specific pneumococcal serotypes or not. children and adolescents under years of age who had been diagnosed with cap were recruited prospectively between january and december from the taiwan pediatric infectious diseases alliance (tpida), a collaborative consortium of pediatric institutes in nine major medical centers in taiwan. tpida contained pediatric infectious disease departments of tertiary medical centers, including national taiwan university hospital (taipei city, taiwan); mackay memorial hospital (taipei city, taiwan); chang gung memorial hospital (linkou, taiwan); china medical university hospital (taichung city, taiwan); national cheng kung university hospital (tainan city, taiwan), kaohsiung chang gung memorial hospital (kaohsiung city, taiwan), and buddhist tzu chi general hospital (hualien, taiwan). tpida conducted nationwide surveillance of childhood cap from jan. to jan. . cap was defined as acute lung parenchymal change and pulmonary infiltrates on chest x-ray with associated clinical symptoms or sign of respiratory tract infection. patients' demographic data, clinical manifestations and chest radiographic characteristics were recorded. the protocol of this study was reviewed and approved by the institutional review board (irb) of each hospital in tpida, and was also approved by the irb of national cheng kung university hospital (ncku) (no. hr- - ). signed informed consent to participate in the study was obtained from each included patient or the patient's parents or guardian. multiplex pcr of pleural effusion was performed to identify respiratory bacterial pathogens, including s. pneumoniae, moraxella catarrhalis, haemophilus influenzae, staphylococcus aureus. serum samples were tested for the presence of antibodies to m. pneumoniae by using the igm-specific mycoplasma immuno-card, an enzyme immunoassay from meridian bioscience (cincinnati, oh, usa), and the m. pneumoniae igg/ igm antibody test system (fti-serodia-myco ii test; fujirebio inc., taipei, taiwan) following the manufacturers' instructions. the serotypes of pneumococcal isolates were identified by a multiplex polymerase chain reaction (pcr) method as described in previous studies [ , ] . nineteen different serotypes were determined by sequential multiplex pcr reactions: reaction includes serotypes a/b, v, b/c, c, f, reaction includes serotypes , , a, f, reaction includes , , , a, reaction includes a, f, f and reaction includes serotype , , f. the serotypes not included in the multiplex pcr reactions were defined as non-typed serotypes. pneumococcal pneumonia was divided into two groups by the following definitions [ ] . definitive pneumococcal pneumonia ( patients) was defined by either s. pneumoniae isolated from sterile body sites, major blood or pleural effusion, or positive pneumococcal pcr [ , ] from pleural effusion [ ] . probable pneumococcal pneumonia ( patients) was defined by positive urine or pleural effusion pneumococcal antigen reaction without isolating pneumococci or positive pcr result. descriptive analyses of numerical variables are presented as mean and standard deviation (mean ± sd), and categorical variables are presented as frequency and percentage. student's t test was used for analyzing normal distribution of continuous variables between groups; mann-whitney u test was used for un-normal distribution of continuous variables between groups. chi-square test and fisher's exact test were used for analyzing categorical variables. logistic regression analysis was used to evaluate associations between definitive pneumococcal pneumonia and vaccine type. all test hypotheses were evaluated using two-tailed t tests. a p-value of< . was considered statistical significance. all statistical analyses were performed using sas . software (sas institute inc., cary, nc, usa.). the flowchart of study sample recruitment is shown in fig. table ) . after stratifying by age groups (< years, - years and - years), the proportion of pneumococcal vaccinations increased year by year in each group ( table ). the proportions of vaccinations increased more in children age under years old compared with those age - years (table and fig. ). the proportion of pneumococcal pneumonia decreased in the - years group from to compared with the proportion in the < years or - years groups (fig. ) . the distribution of different types of pneumococcal vaccination by year is shown in table . of note, patients received pcv vaccine and received ppv in ; and patients received pcv in . however, these patients who received pcv conjugate vaccine were given pcv boosters after . pcv is the major type of pneumococcal vaccine ( . %) among all vaccinated patients, followed by pcv ( . %). pcv was predominant during ( . to . %), but it was replaced by pcv after ( . % in , . % in , % in ). this clearly demonstrates the impact of national stepwise implementation of pcv into the routine childhood vaccination schedule. the distribution of serotypes was similar between vaccinated patients and non-vaccinated patients with pneumococcal pneumonia (table ) . serotype a is the leading serotype either in vaccinated ( . %) or unvaccinated patients ( . %), followed by serotype (vaccinated: . %; unvaccinated: . %). univariate analysis (table ) revealed that pleural fluid aspiration, chest catheter use, icu admission, and days in icu were lower in vaccinated patients compared to non-vaccinated patients, but the difference was not statistically significant (p > . ). however, vaccinated patients had significantly higher lowest wbc, lower neutrophils, lower lymphocytes and lower crp values than non-vaccinated patients (all p value < . ). when looking into the specific pneumococcal vaccines received, patients receiving either pcv or pcv had significantly lower crp values than those who did not receive any pneumococcal vaccine, while patients receiving pcv had the lowest crp value ( . ± . mg/dl vs . ± . mg/dl in non-vaccinated patients, p value = . ). patients who received pcv pneumococcal vaccine had significantly higher wbc, lower bandemia, lower neutrophils, lower lymphocytes, higher eosinophils and lower crp values than those who did not receive any pneumococcal vaccine (all p value < . ). patients who received any pneumococcal vaccine and had definitive pneumococcal pneumonia were divided into subgroups of vaccine coverage breakthrough infection and non-vaccine type infection according to pneumococcal serotypes (table ) . those with breakthrough pneumococcal infection with vaccine coverage serotypes had more severe pneumonia, including higher risk of chest catheter use, video-assisted thoracoscopic surgery, and any one to three complications compared with non-vaccine serotypes (all p value < . ). breakthrough infection with vaccine coverage serotypes also presented with lower hb level, higher eosinophils, and higher crp than the non-vaccine serotype group (all p value< . ). results of this study clearly demonstrated that implementing a systematic immunization program to administer pneumococcal vaccine to infants and children reduces the prevalence of pneumococcal pneumonia in the community. during the study period, serotype a was the major serotype in patients with pneumococcal pneumonia who had received any type of vaccine in taiwan. serotypes are a crucial element in determining the severity of pneumonia and inflammation in patients with pneumococcal pneumonia. the severity of acute inflammatory response was reduced in vaccinated patients with pneumococcal pneumonia compared with that in unvaccinated patients. to date, our study is the first report discussing the attenuation effect on inflammatory response in breakthrough pneumococcal infection. other than pneumococcal infection, the influenza vaccine had been reported to reduce symptoms severity among patients with influenza a/h n disease (vaccine failures) [ ] . hence, in the present study, the evidence of vaccine reducing the systemic inflammation in breakthrough ipd still supports the universal use of pcv in children, providing additional value regardless of vaccine failure. results of previous studies are largely compatible with results of the present study. a national case-control study of the effectiveness of pcv against ipd (conducted by the taiwan cdc) demonstrated a vaccine effectiveness of % for an age-appropriate pcv program [ ] . also, in the same program, effectiveness against serotype a was %, while effectiveness of at least dose of pcv, including either pcv , pcv , or pcv , declined from % within months of the last dose of pcv to % after years. this indicates that protection was decreasing over time, either because of the waning protective antibody or vaccine serotypes gradually being replaced by other non-vaccine serotypes. however, the effectiveness of catch-up programs is evidenced primarily by changes in ipd incidence over time at the population level, but not at the individual level [ , ] . similarly, high effectiveness was shown against vaccinetype ipd in a randomized controlled trial of pcv efficacy in american-indian children when the first pcv dose was given at < months of age and as a catch-up after - months [ ] . however, the modifying effect of age may be a concern for vaccine effectiveness analysis [ ] . in addition to ipd, some reports had addressed the influence of pneumococcal vaccine on non-ipd pneumococcal infection, especially pneumonia and otitis media. conjugate pneumococcal vaccination (either pcv or pcv ) had significantly reduced pneumonia in children with congenital heart disease in mexico (vaccinated, . % vs. unvaccinated . %, p < . ) [ ] . in the united states, pneumococcal pneumonia requiring hospitalization significantly decreased in children after pcv introduction. although complicated pneumococcal pneumonia had decreased steadily after pcv introduction, the need for intensive care, mechanical ventilation, and invasive procedure remained unchanged. among those with breakthrough pneumococcal pneumonia, pcv serotypes a and were still responsible for half of cases in the post-vaccine era [ ] . recent meta-analysis also indicated that pcv and pcv had a significant impact in reducing hospitalizations for pneumonia, particularly in children aged < months and for radiologically confirmed disease. in children younger than months, the reduction in hospitalization rates was % ( %ci: - %, p-value< . ) and % ( %ci: - %, p < . ) for clinically and radiologically confirmed pneumonia, respectively, after the introduction of pcvs [ ] . in the present study, a protective effect was observed in a catch-up program targeting children aged to years starting from with a stepwise national catchup immunization program. although the proportion of pneumococcal pneumonia among all-cause pneumonia declined in , it resurged in , then declined further to % in . the case numbers of all-cause pneumonia and pneumococcal pneumonia indicate that both of these diseases have been decreasing since . however, vaccine use in taiwan prior to was different. public-funded [ ] . public-funded pcv was only available to children in mountainous areas for short time and the use in private markets was also much less compared to the use of pcv and pcv . vaccine use is much different in taiwan from the universal use of pcv in other countries such as canada, and explains why only patients with previous pcv vaccination are included in the present study [ , ] . our study also clearly demonstrate that the use of pcv has shifted to pcv since , especially in children younger than age years. pcv was the most common pneumococcal vaccine used in children (above %) before , but was completely replaced by pcv in . at the same time, the vaccine coverage rate reached % in children younger than age years, and . % in children aged ~ years. since the incidence of community acquired pneumonia is highest among children younger than years, the implementation of the vaccine program was apparently aimed at the target population. results of the present study have shown that this vaccine policy not only decreased invasive pneumococcal disease (ipd), but also decreased non-invasive pneumococcal disease (esp. pneumococcal pneumonia). as for the surge of pneumococcal pneumonia cases in , several things need to be clarified. first, according to the cdc report conducted by wei et al. [ ] , the ipd incidence decreased significantly in the - years old group, from . cases per , person-years in - to . per , person-year in . the ipd incidence decreased from . cases per , in to . cases per , person-years among children year of age in . the reduction in cases contributed majorly to the decrease of serotype a. this reveals that the stepwise introduction helps to decrease the incidence of ipd among target age groups [ ] . however, in the study conducted by cho et al. [ ] , pneumococcal isolates were collected, including both invasive and non-invasive strains, during ~ in northern taiwan, and the number of pneumococcal isolates in was higher than those in or . looking more closely at cases in , most of the pneumococcal isolates came from non-ipd cases ( . %) [ ] . therefore, we may conclude that the implementation of pcv stepwise vaccination policy decreased both ipd and non-invasive pneumococcal disease. nevertheless, the secular trend of overall pneumococcal disease, including both invasive and non-invasive disease, may fluctuate during the transitional period. in the present study, patients receiving more types of pcv appears to have more of an impact on reducing the prevalence of pneumococcal pneumonia than patients receiving only one type of vaccine ( supplementary fig. ) . also, the major vaccine-types received by patients with pneumococcal pneumonia were pcv and pcv ( table ) . a possible explanation for these findings may be that non-pcv /pcv -covered serotypes, such as a, emerged gradually and that protection against pneumococcal pneumonia may decline with the changing epidemiology of nonvaccine serotypes. other authors have suggested that this epidemiological trend may influence estimations of vaccine effectiveness [ , ] . therefore, children who received more types of pcv appear to increase the covered serotypes (such as a), resulting in lower prevalence of pneumococcal pneumonia. pcv was found to provide significant protection for most vaccine serotypes, but serotype-specific correlates of protection still appear to vary widely [ ] . associations between serotypespecific igg concentrations after pcv priming during infancy and long-term clinical protection against vaccine serotypes and non-vaccine serotypes requires further study. in the present series, an acute inflammation was found in children infected by serotypes contained in pcv , represented mainly by serotypes a and . these findings are similar to those of previous studies that describe how serotypes a, , and f were independently associated with respiratory symptoms, including the development of hypoxemic respiratory failure, multi-lobar involvement and the need for mechanical ventilation in adults [ ] . however, to the best of our knowledge, no previous studies have addressed the relationship between pneumococcal vaccine and pulmonary or systemic inflammation. our results show that serotypes a and were the main serotypes of all vaccine types, and that the severity of systemic inflammation was reduced in patients receiving pcv more than in those receiving pcv . however, the specific serotypes associated with development of respiratory failure do not have a well-defined pathophysiological explanation. other studies have shown that the features of the polysaccharide capsule of pneumococcus appear to foster higher resistance to neutrophil activity in the lungs and this allows bacterial growth in the lungs to persist; consequently, the result is prolonged and greater immune response and lung injury are characteristic of serotypes a, , and f [ , - ] . moreover, based on the adhesions they express, the various pneumococcus serotypes differ in their ability to adhere to the respiratory epithelium, resulting in different levels of virulence of serotype-dependent strains [ , ] . experimental studies in animal models also have shown that pneumococcal serotypes differ in properties such as resistance to phagocytosis, ability to penetrate into tissues and capacity to activate the inflammatory response [ ] . taken together, the results of these studies provide strong evidence supporting our finding that pcv vaccines may reduce the severity of acute inflammation in children with pneumococcal pneumonia attributed to serotypes a, , and f . results of the present study show that patients who received pneumococcal vaccine have higher lowest wbc, and lower neutrophil counts and crp levels compared to non-vaccinated patients, and this difference was even more prominent in those receiving pcv vaccine. this is likely due to the fact that pcv works by eliciting an igg (and igg ) response to polysaccharide. meanwhile, it also triggers a stronger immune response because polysaccharides coexpressed with carrier proteins interact better with major histocompatibility complex and mediate cognate cd + t-cell help for polysaccharide-specific bcell activation. this mechanism enhances immunogenicity and supports more rapid and robust production of antibodies and the establishment of t-celldependent immunological memory [ ] . as for the differences in wbc and neutrophils between vaccinated and non-vaccinated patients observed in the present study, we speculate that this could be explained by the modulated immune response after vaccination. in previous studies, relative leukopenia was found to be a major risk factor for mortality in pneumococcal bacteremia [ ] . actually, in fulminant pneumococcal infection, the host fails to evoke adequate immune response to contain the bacteria, even after producing more neutrophils for phagocytosis, but the total white cell counts are still rapidly consumed. in the present study, we demonstrated that with prior pneumococcal immunization, the vaccinated hosts primed with pre-existing antibody and cellular immunity responded better to breakthrough infection. this study has several limitations. first, there is a small number of patients who initially received ppv or ppv vaccination ( in , and in ) and subsequently, received - doses of pcv boosters. however, we have justified that this was due to the change in public funding policy, and further, the proportion was very minor relative to those who received pcv or pcv vaccine; therefore the influence of prior ppv or ppv vaccination on the current analysis was considered very limited. also, we could not evaluate the vaccine effectiveness of each pcv because a larger number of normal healthy children would be needed as a control group for comparison. thirdly, subjects in this study were actively recruited from medical center patients with pneumonia, so results for vaccine effectiveness are necessarily limited. the recruitment of more severe cases and not including all pneumonia cases may also represent selection bias. future studies must broaden the sources of pneumonia cases to enhance the reference of research results. the present study confirms that routine childhood pneumococcal vaccination reduces the prevalence of community-acquired pneumococcal pneumonia. results also confirmed that pneumococcus serotypes are associated with the severity of pneumonia and systemic inflammation in patients with pneumococcal pneumonia. serotype a was the major serotype in patients with pneumococcal pneumonia during the study period. interestingly, the degree of acute systemic inflammatory response was much more reduced in vaccinated patients than unvaccinated patients. dr. ching-fen shen and ching-chuan liu are the guarantor of the content of this manuscript, had full access to all of the data in the study and take responsibility for the integrity of the data. dr. ching-fen shen, shih-min wang, and ching-chuan liu contributed to the study conception and design, collection of data, data analysis and interpretation, critical review of the manuscript, and approval of the final version to be published. dr. hsin chi, yi-chuan huang, and li-min huang contributed to the data analysis, critical review of the manuscript, and approval of the final version to be published. yhu-chering huang, hsiao-chuan lin, yu-huai ho, and chao a. hsiung contributed to the collection of data, data analysis and interpretation, critical review of the manuscript, and approval of the final version to be published. taiwan pediatric infectious disease alliance had provided the critical review of the manuscript and approval of the final version to be published. the author(s) read and approved the final manuscript. the data used to support the findings of this study are included within the article. ethics approval and consent to participate the protocol of this study was reviewed and approved by the institutional review board (irb) of each hospital in tpida, and was also approved by the irb of national cheng kung university hospital (ncku) (no. hr- - ). the written informed consents were obtained from all participating patients prior to clinical data. the patients' guardians got the informed consents form principal investigator and the written informed consents were delivered to the study co-ordinators form patients' guardians. the submission of this manuscript has been approved by all authors. the patients have provided consent for publication: "the individuals in this manuscript have given written informed consent to publish these case details". streptococcus pneumoniae: epidemiology, risk factors, and strategies for prevention estimating the burden of pneumococcal pneumonia among adults: a systematic review and metaanalysis of diagnostic techniques progress in introduction of pneumococcal conjugate vaccine--worldwide burden of disease caused by streptococcus pneumoniae in children younger than years: global estimates rapid reduction in invasive pneumococcal disease after introduction of pcv into the national immunization plan in israel early impact of sequential introduction of -valent and -valent pneumococcal conjugate vaccine on ipd in israeli children < years: an active prospective nationwide surveillance pneumococcal conjugated vaccines: impact of pcv- and new achievements in the postvaccine era geographic variation in invasive pneumococcal disease following pneumococcal conjugate vaccine introduction in the united states indirect effects of childhood pneumococcal conjugate vaccination on invasive pneumococcal disease: a systematic review and meta-analysis national surveillance of invasive pneumococcal diseases in taiwan pediatric invasive pneumococcal disease in taiwan following a national catch-up program with the -valent pneumococcal conjugate vaccine taiwan centers for disease control. pneumococcal conjugate vaccination program for children risk factors for -day mortality in patients with pneumonia who receive appropriate initial antibiotics: an observational cohort study epidemiology and outcome of severe pneumococcal pneumonia admitted to intensive care unit: a multicenter study septic shock systemic cytokine levels in community-acquired pneumonia and their association with disease severity temporal and geographic stability of the serogroup-specific invasive disease potential of streptococcus pneumoniae in children impact of the emergence of non-vaccine pneumococcal serotypes on the clinical presentation and outcome of adults with invasive pneumococcal pneumonia invasive pneumococcal disease among adults: associations among serotypes, disease characteristics, and outcome clonal and capsular types decide whether pneumococci will act as a primary or opportunistic pathogen pneumococcal serotypes and mortality following invasive pneumococcal disease: a population-based cohort study association of serotype with risk of death due to pneumococcal pneumonia: a meta-analysis realtime pcr is more sensitive than multiplex pcr for diagnosis and serotyping in children with culture negative pneumococcal invasive disease sequential multiplex pcr approach for determining capsular serotypes of streptococcus pneumoniae isolates increase in fitness of streptococcus pneumoniae is associated with the severity of necrotizing pneumonia vaccine-associated reduction in symptom severity among patients with influenza a/h n disease effectiveness of pneumococcal conjugate vaccines of different valences against invasive pneumococcal disease among children in taiwan: a nationwide study impact of + pneumococcal conjugate vaccine program in the province of quebec prompt effect of replacing the -valent pneumococcal conjugate vaccine with the -valent vaccine on the epidemiology of invasive pneumococcal disease in norway efficacy and safety of seven-valent conjugate pneumococcal vaccine in american indian children: group randomised trial pneumococcal conjugate vaccine and pneumonia prevention in children with congenital heart disease pneumococcal pneumonia requiring hospitalization in us children in the -valent pneumococcal conjugate vaccine era the impact of -valent and -valent pneumococcal conjugate vaccines on hospitalization for pneumonia in children: a systematic review and metaanalysis decline in the incidence of invasive pneumococcal disease at a medical center in taiwan the shifting epidemiology and serotype distribution of invasive pneumococcal disease in ontario, canada limited impact of pneumococcal vaccines on invasive pneumococcal disease in nunavik (quebec) pneumococcal disease and use of pneumococcal vaccines in taiwan redistribution of streptococcus pneumoniae serotypes after nationwide -valent pneumococcal conjugate vaccine program in children in northern taiwan effect of the -valent pneumococcal conjugate vaccine on invasive pneumococcal disease in england and wales years after its introduction: an observational cohort study restraining the pneumococcus serotype-specific effectiveness and correlates of protection for the -valent pneumococcal conjugate vaccine: a postlicensure indirect cohort study pneumococcal vaccination strategies. an update and perspective serotypespecific mortality from invasive streptococcus pneumoniae disease revisited publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we thank ms. yi-hsuan chang and ms. hui-feng lee for the collection of clinical cases. we also thank all members of taiwan pediatric infectious disease alliance for their assistance. supplementary information accompanies this paper at https://doi.org/ . /s - - - . the authors declare that they have no competing interests. key: cord- -wjapj w authors: liou, je-liang; hsu, pei-chun; wu, pei-ing title: the effect of china's open-door tourism policy on taiwan: promoting or suppressing tourism from other countries to taiwan? date: - - journal: tour manag doi: . /j.tourman. . sha: doc_id: cord_uid: wjapj w this study employs an extended gravity model to analyse the complementarity or competitiveness relationship of the number of inbound tourists and corresponding tourism revenue between china and other nations under the implementation of china's open-door tourism policy to taiwan in . a simulation for – demonstrates the sustained impact of this policy. the results show that the number of tourists to taiwan from china reached its peak in at % and will decrease to % by . the corresponding tourism revenue will decrease from % to % over the same period. the results also show that if the number of tourists from china remains above , , the number of tourists from japan, hong kong, australasia, north america, and europe will still increase. however, the number of tourists from south korea and south and southeast asia will increase continuously regardless of tourists from china, even far below , . tourists who travel from different regions or nations generate economic revenues for destination nations. thus, travel and tourism play important roles in the economic development of some nations, such as fiji (aresh, umar, & aryan, ; eilat & einav, ) . fiji, one of the nations in the pacific region, is a typical tourism nation for tourists from australia, new zealand, the us, canada, the uk, and japan. the national income for fiji is not as large as that of other nations. thus, revenue from tourism is relatively more important than it is for other nations. the tourism revenue for fiji reached % of its gdp in (eilat & einav, ) . similarly, tourism revenue accounted for approximately % of total government revenue in for the maldives (statistics & research section, ministry of tourism, maldives, ) . in , the world tourism organization of the united nations (henceforth unwto) predicted that the total number of tourists will reach . billion by and that tourism will be one of the major sources of revenue for developing nations (unwto ( ) ). data by unwto ( a) also indicate that tourism in asia and the pacific region contributes % of the total tourism revenues of all nations. the development of tourism directly benefits revenues and employment opportunities in the tourism sector and indirectly encourages improvement and investment in new infrastructure and the reformation of (world economic forum (wef), , ) public transportation networks for destination nations. tax revenues are thus expected to increase. tourism not only benefits the revenue of a nation as a whole but also has specific benefits for a city or a region within a nation (neuts, ; tang & abosedra, ) . the strong positive connection between tourism and employment opportunities is even more significant in ecotourism (laterra et al., ) . to determine the relative advantage of each nation's tourism attraction, the travel & tourism competitiveness index (ttci) was constructed by the world economic forum (wef, (wef, , (wef, , (wef, , (wef, , (wef, , (wef, , (wef, , . the ttci is a comprehensive index to calculate each nation's travel and tourism competitiveness. because the ttci is a composite index, it is difficult to identify the performance of any specific factor of a sub-index or certain category of the index for a specific nation (hanafiah & hemdi, ; joshi, poudyal, & larson, ; weaver, kwek, & wang, ) . thus, if a certain factor is prominent or important, it must be calculated individually. studies by song and li ( ) have determined the influence of the relative commodity price level on travel and tourism. other studies have indicated that factors such as the security of the travelling spot, gourmet food, and scenic views are crucial for tourism decisions (cîrstea, ; enright & table total number of tourists from the major nations to taiwan, taiwan, - year the other four inbound nations are india, thailand, the philippines, and vietnam. we were unable to obtain data on the daily expenditures of these four nations. to be consistent with the presentation for the total daily expenditures in the follow-up analyses, the presentation for the total number of tourists combines these four nations into one group. newton, ) . marti and puertas ( ) noted that in europe, the tourism industry is important for reducing poverty and regional differences. tourism increases revenues for destination nations. durbarry and sinclair ( ) studied tourism demand in france and concluded that italy, spain, and great britain (henceforth gb) accounted for % of outbound tourists to france. their study further indicated that from to , the number of tourists to gb decreased by %, and tourism revenue for the nation decreased by %. in contrast, the number of tourists to italy and spain increased by % and %, respectively, and their tourism revenue increased by % and %, respectively. this evidence not only shows the consistent change between the number of inbound tourists and the amount of tourism revenue but also demonstrates tourism competition among nations. thus, each nation uses different ways to attract tourists (harb & bassil, ; kozak, kim, & chon, ; mar� akov� a, dyr, & tuzimek, ; unwto, ) . the unwto has compiled a complete tourist record for each nation since (world tourism organization unwto, ). the record shows that the total number of tourists visiting taiwan was approximately . million in and million in (world tourism organization unwto, ). the number of tourists over years increased by approximately . million, with an average annual increase of , tourists. previously, japan had the largest share of inbound tourists in taiwan. tourists from the united states (henceforth the us) were ranked second. however, this situation changed in . the number of inbound tourists from japan decreased, as did the share of total inbound tourists. a similar situation was observed for inbound tourists from the us. the unwto began recording data on tourists from china to taiwan in . in , there were only , tourists to taiwan. before , only chinese living overseas, studying abroad, with permanent residency in other nations, or transferring to other nations for business purposes were allowed to travel to taiwan. there was clearly a change in . prior to , the total number of tourists from china was approximately . million, accounting for . % of the total number of inbound tourists to taiwan. this number exceeds the number of tourists from many other nations, including japan and the us, in terms of both the number and the share. this situation reversed in , when the number of tourists from china decreased dramatically from its highest level of . million in to . million in and further decreased to . million in . the reason for this significant variation was the implementation of china's open-door tourism policy to taiwan (hereafter open-door policy) in . in , the number of tourists allowed to visit taiwan was relaxed, but it was tightened in when the ruling party of the central government in taiwan changed. thus, this policy has highly political connotations. it is quite different from regular tourism policies that are designed to limit or attract tourists based on tourists' personal qualifications. theoretically and ideally, increasing the number of inbound tourists from any nation should have a positive impact on taiwan's economy. it is generally believed that an increase in the number of tourists will create more employment opportunities in the travel industry, generate more revenue from the tourism sector, and provide frequent cultural exchanges among nations (ap & crompton, ; kwek & lee; omkar, poudyal, & larson, ) . however, these positive impacts may not occur if the number of inbound tourists is less than that stipulated by policies implemented by other nations. that is, if there is a tremendous increase in the number of inbound tourists or a large number of tourists pour into taiwan and tourism revenue increases due to the open-door policy, a decline could occur in the number of tourists and tourism revenues. the changes in the number of chinese tourists to taiwan stated above from to and to are obvious evidence. in a broad sense, the open-door policy can be categorized as a tourism policy under the ttci categories. however, when the implementation of such a policy is imposed by other nations, it affects the nature of tourism as an action of free movement. for tourists, the selection of destinations is not a free choice but should be approved by home nations. for destination nations, this causes the potential number of inbound tourists and potential tourism revenue to become highly uncertain. as such, improvement in any facility or other factor might not be useful for engaging inbound tourists. this uncertainty could make tourism either change or remain the same for destination nations. for instance, tourists and the associated tourism revenues from other nations might decline due to an increase in the number of tourists from china. specifically, if the number of inbound tourists declines, this will reduce travel expenditures, and the overall tourism revenue in taiwan will decrease. however, this pessimistic situation may not occur. an increase in the number of tourists from china might attract more tourists from other nations. the purpose of this study is to employ an extended gravity model (egm) to explore the relationship between the change in the number of inbound tourists and the corresponding tourism revenue from china and from visitors from other major nations to taiwan in - under china's open-door policy to taiwan. to the best of our knowledge, this study is the first to analyse the change in the number of tourists to taiwan and tourism revenue under the open-door policy. the innovation of this study is that a policy factor imposed by a nation other than taiwan is included in the egm. this factor means that the number of tourists to taiwan is basically controlled by other nations. the analysis in this study not only empirically allows us to identify the impact of a particular factor in the egm but also scientifically provides deeper insight into tourism management in the egm. the simulation for - observes the sustained impact in the number of tourists visiting taiwan and the change in tourism revenue for different nations under this policy. the remainder of this paper is arranged in four sections. the second section presents the egm for inbound tourists to taiwan proposed in this study. the third section indicates the selection of variables and data sources used in the empirical analyses. the fourth section presents the results and discussion. the final section proposes a conclusion. according to the world tourism barometer prepared by the unwto ( ), world tourism can be classified into five regions: europe, america, asia, the pacific islands, and the middle east. in , the total number of tourists in asia and the pacific island regions was only . million, but this number dramatically increased to million in . these regions had a rapidly increasing tourism market. approximately . million tourists from taiwan to japan in accounted for . % of the total outbound tourists from taiwan. japan was ranked fourth in the world and first in the asia pacific region as a tourist destination. among the reasons that tourists selected japan as a destination, the "attitude of the population towards foreign visitors" and "convenience of ground transportation" were ranked highest. in , japan attracted approximately . million tourists from around the world (world tourism organization unwto, ). in terms of inbound tourism in taiwan, the tourism sector started in . in the early stage, inbound tourists were mainly from the us. a large number of tourists came from japan in . to attract more tourists to taiwan, the ministry of foreign affairs in taiwan made visas free in for tourists from france, gb, germany, spain, italy, the netherlands, austria, belgium, portugal, switzerland, singapore, japan, the us, canada, new zealand, and australia. the total number of tourists was approximately . million in and increased to more than million in . there has been a significant increase in the number of tourists to taiwan in the past years. the largest number of tourists comes from japan, with . million tourists in and approximately . million in , accounting for . % and . %, respectively, of the total number of inbound tourists. the share of inbound tourists from the us was . % in and was still higher than % ( . %) in . data from the world tourism organization unwto, show that tourists who came to taiwan in - were from nations. however, only a few tourists came from many of these nations, and there was no variation over the years. tourists mainly come from nations, which are the nations used in our analyses: australia, canada, china, france, germany, gb, hong kong, indonesia, india, italy, japan, south korea, malaysia, new zealand, singapore, thailand, the netherlands, the us, the philippines, and vietnam. the unwto began recording the number of tourists visiting taiwan from china in . there are no data available from the unwto in the number of tourists from china visiting taiwan before the open-door policy (i.e., before ). as a result, data on the number of inbound tourists from china during - must be obtained from other sources. the data obtained from the mainland affairs council, republic of china, taiwan ( ) and from the ministry of the interior national immigration agency, republic of china, taiwan ( ) are the data used in this study. table provides the number of inbound tourists to taiwan for the abovementioned nations and a group of other nations in - . table shows that the number of tourists from china constituted approximately . % of the total tourists visiting taiwan in and slightly increased to . % in . in the same period, tourists from japan constituted . % of tourists in and . % in . before china's open-door policy, the highest share of tourists visiting taiwan were from japan. the share of tourists from japan and china was basically stable. however, the implementation of the opendoor policy in significantly increased the number of tourists from china, which represented the largest share of inbound tourists in at . %, the second year after the implementation of the policy. in , the total number of tourists from china reached . million and constituted . % of tourists. in contrast, the share of tourists from japan significantly dropped to . %. this policy has completely changed the composition of inbound tourists in taiwan. various waves of the open-door policy have been implemented since . the first wave began for people from provinces with tour groups in and out of taiwan. the second wave extended to provinces in . the policy was further extended to provinces in . people from beijing, shanghai, and xiamen were allowed to travel to taiwan individually in , with a total quota of tourists per city per day. the quota was extended to tourists per day for each city, and people from tianjin, chongqing, nanjing, guangzhou, hangchow, and chengdu were included on the list. the quota for each city was further extended to tourists per day in and to tourists per day in . the wef identified three categories of factors regarding tourism competitiveness for each nation in . these categories are international openness and price competitiveness in relation to the sustainability of travel and tourism development, the availability and quality of all types of transportation, and the number of natural spots and areas as well as cultural, and known heritage sites (unwto, ). one more category, the tourism environment, which includes business security, health and human resource-related factors, was added by the wef in . from to , although the overall ranking of taiwan increased compared to the rest of the asia pacific region and taiwan was ranked among the top of nations, the overall tourism performance for taiwan as measured by the ttci was unimpressive. however, from to , some individual indexes, such as the primary educational enrolment rate, lack of malaria incidence, hiv prevalence, purchasing power parity, and fixed telephone lines, were ranked in the top during this period. mobile network coverage was ranked number one globally in . the gravity model is a commonly used model for issues related to immigration activities such as international trade or transportation in travel. marti and puertas ( ) used a gravity model with the ttci to examine the competitiveness of tourists in the euro-mediterranean region. the performance of the ttci is used as a tourism industry development guideline for many developing nations, although some indices have been adjusted to fit nations' unique concerns (lall, ) . cîrstea ( ) used the ttci to analyse the most competitive nations, including france, germany, the us, japan, and singapore, and concluded that these nations were not a homogenous group. that is, differences exist among the nations, and each nation has its own advantages. in addition to considering traditional variables (i.e., the gdp, population, and distance between sites), bikker ( ) extended the traditional gravity model to include variables that have special or particular meaning for sites (i.e., nations) and called it the extended gravity model (egm). the estimation of the egm can determine factors that influence international trade, and the model can be applied to tourism. park and jang ( ) used the egm to analyse nations from to and found that the major factors were not only the gdp, population, and distance but also natural and cultural resources, infrastructure for tourism, price competitiveness, and political and policy factors (e.g., the process of applying for a visa). certain types of infrastructure, such as public transportation, have been included in the gravity model (e.g., khadaroo and seetanah's study, ) to study their effect on tourists. moreover, both economic and non-economic factors affect tourism. vietze ( ) noted that a common culture, such as the same or a similar language, was a decisive factor for the selection of visiting nations. climate factors may also affect tourism demand (cohen & cooper, ; lorde, li, & airey, ; yingsha, li, & wu, ) . past literature shows that the application of the egm to tourism issues mainly addresses the identification of the major factors that influence travel and tourism decisions. moreover, the application of the egm in past studies has been used to explore the competitiveness among various nations. these nations usually have their own advantages and disadvantages in attracting different types of tourists in different tourism industry development periods. thus, the nations used for comparison are those with similar levels of incomes or in close geographical locations, such as travel among developed nations or among nations in the euro-mediterranean region. under these circumstances, the analysis can reduce the impact of two essential factors in the gravity model, income and distance, to their minimum. the effect of other particular factors that attract tourists can thus be presented clearly from the egm analysis. furthermore, past research has used the egm to analyse the attraction of each tourism destination to different nations. there is no study in the current literature that utilizes the egm to analyse a policy factor imposed by other nations with an impact on the destination nation. thus, a policy factor imposed by china that influences inbound tourists to taiwan is included in the egm employed in this study. moreover, typical factors of the gravity model, the gdp and population of visiting nations and the destination nation and the distance between visiting nations and the destination nation are included. the model is extended to contain factors s ij;t evaluated by the wef for various years that have been deemed to have relatively prominent performance for taiwan since . in this study, tourist ij;t is the total number of tourists from nation or region i to destination nation or region j in year t. the income and population for the visiting nation and the destination nation in certain time periods are c gdp i; t , t gdp j;t and c pop i;t , t pop j;t , respectively. distance ij is the distance between each the number of tourists visiting taiwan from these nations constitutes % of the total number of tourists visiting taiwan, according to the unwto ( ). visiting nation or region i and the destination nation or region j. normally, the distance between the two will not change; thus, the distance will not vary over time t. when more provinces are approved to travel in groups or individually to taiwan under the open-door policy, there will potentially be more tourists visiting taiwan. thus, the actual number of tourists from china in a specific time period is touristchina t , a policy factor mentioned above, used as a proxy for the degree of openness of this policy. the estimated coefficient of touristchina t measures the competitiveness or complementarity of tourists from china with those from all other nations. the general egm used in this study is presented in eq. ( ): to observe the impacts of the open-door policy on the number of tourists and tourism revenue from other nations, the magnitude of the variable (touristchina t ) indicates the degree of openness. since the observation focuses on china's policy and its impact on all other nations visiting taiwan, the population and gdp for taiwan vary by year. moreover, under the same conditions, distance is a key factor for the selection of tourist destinations. normally, a short distance between the visiting nation and the destination nation is considered more advantageous than a long distance between the two nations (kozak et al., ; nicolau & mas, ) . the other extended variables used in the egm include english as the official and/or national language in the visiting nation (language i ). the relative advantage indices for taiwan presented in the ttci include "malaria incidence," "primary education enrolment rate," and "purchasing power parity." however, the above indices used in the ttci are for universal comparison purposes. as compulsory education in taiwan is junior high school (grade or in some nations) and approximately % of junior high school pupils continue their education to senior high school, the use of senior high school is difficult to compare over time. therefore, the "university rate" (university rate) is used for this variable. however, the results of the preliminary test indicate that this variable is highly correlated with taiwan's gdp. thus, university rate is dropped from further analysis. as with purchasing power parity, the consumer price index (cpi) is used specifically for this variable (arsad & johor, ; craigwell, ; morley, ) . malaria has not been a problem in taiwan for decades. one recent outbreak of infectious disease involved severe acute respiratory syndrome (sars), which occurred in and lasted until in taiwan. a dummy variable is set as for the period - and for others to detect whether the sars outbreak influenced the number of inbound tourists. the notations, definitions, and mean values of all variables used in the estimation are listed in table . once all the variables are prepared, the specific functional form of double log is set for the egm in this study as in eq. ( ). we assume that the impact of tourists from china is not in a single direction, and the total effect on the number of tourists from other nations is a combination of the linear and square terms of the number of tourists from china lnðtouristchinaÞ. thus, the quadratic form allows us to consider the possible existence of nonlinearities in the effect of the number of tourists from china. although the combination of nations and time periods is typical for panel data, this analysis can theoretically be achieved using a fixed-effect or random-effect model. however, some variables, such as distance lnðdistanceÞ and language (language), will not change for any nation over time. thus, the fixed-effect model is not appropriate when these variables are included (liu, lai, & chen, ; prehn, brümmer, & glauben, ) . as such, the random effect model is favoured under such circumstances. the estimated coefficients from the random effect model for eq. ( ) are listed in table . the results of the estimation show that except for the population in taiwan (lnðt popÞ), lnðt cpiÞ, and sars, all other variables are significant at different significance levels. moreover, the effects of these significant variables on the number of tourists from the nations to taiwan are consistent with our expectations. there are fewer tourists to taiwan from the farthest nations. nations with high gdps have more outbound tourists visiting taiwan, and tourists from countries where english is the official and/or national language visit taiwan more often than those from other countries. the effect for the dummy variable of language (language) and the outbreak of sars (sars) is the magnitude of the corresponding estimated coefficient. because all other variables are taken as the natural logarithm, the effect of each variable on the this situation occurs frequently in the gravity model. it normally involves variables that are constant throughout the years. thus, the distance proxy variable between two nations, a typical variable used in the gravity model, has no variation throughout the years. due to this drawback, the fixed-effect model is not appropriate for this application. number of tourists from the nations means that a % change in a certain variable will result in a certain percentage change for the number of total tourists from the nations other than china (ln tourist). although the double log form can be used to compute the elasticity for the variable of lnðtouristchinaÞ, it is not the purpose here. the main purpose of this study is to observe the effect for every unit (person) change of tourists from china on the unit change of tourists from other nations. thus, the marginal effect is computed by taking the derivate of total tourists from other nations (tourist) to tourists from china (touristchina). to observe the impact of a one-unit change of tourists from china on the change of tourists from other nations or regions, the marginal effect (me t ) plays a role. this effect is shown in the estimation of eq. ( ), which accounts for all related factors that influence the number of tourists from all nations except those from china and the interaction between tourists from china and those from the other nations. as a result, the marginal effect is computed as eq. ( ): ½ : þ ð * : Þ*lnðtouristchinaÞ t �: ( ) thus, tourist i;t represents the average number of tourists from any specific nation or region of interest. the sign of the marginal effect is determined by the negative part and the positive part of eq. ( ). the turning point is the number of tourists from china, which reaches a threshold that switches the impact from positive to negative or vice versa. that is, when the number of tourists from china is above , , the increase of tourists from china will concurrently increase the number of tourists from other nations or regions. in contrast, when the number of tourists from china is below , , tourists from china increase under this ceiling, and tourists from other nations or regions will competitively increase. the following analyses are employed to determine the impact of a change in the number of tourists from china on the number of tourists from the seven nations, areas, or regions. the selection of the nations or areas represents the highest share of tourists among all nations, such as japan, until or countries that had a significant increase in the number of tourists in recent years, such as south korea and hong kong. the other nations are classified according to their geographical location. the regions are australasia, including australia and new zealand; north america, including canada and the us; europe, including france, gb, germany, italy, and the netherlands; and south and southeast asia, including india, indonesia, malaysia, the philippines, singapore, thailand, and vietnam. the marginal effect of every change in the number of tourists from china on the number of tourists from each nation, area, or region can be computed by ( ) based on the mean number of tourists from each nation, area or region, tourist i;t , in the last three years ( ) ( ) ( ) . the results are presented in part b of table . the marginal effects for japan, south korea, hong kong, australasia, north america, europe, south and southeast asia are . , . , . , . , . , . , and . , respectively. the results indicate that the number of tourists from japan will increase . for each additional tourist from china. the explanation for the other marginal effects is the same. the positive marginal effect implies that there is no competitiveness between tourists from china and those from any other nation, area, or region stated above. this is because the variable representing the number of tourists from china (lnðtouristchinaÞ) has negative linear and positive square terms. the turning point for this curve is , tourists from china. when the number of tourists from china falls below this number, the number of tourists from the above seven nations or regions will also decrease. without considering the effect of china, the actual rate of the increase (decrease) of the number of tourists from each nation or region i for the last three years can be computed by taking the average rate between and (denoted as γ i; ). the results are presented in part a of table . table shows the significant decrease in the number of tourists from china in and . thus, it is crucial to determine the potential impact on the number of tourists from other nations or regions due to this noticeable decline in the number of tourists from china over the next few years. this can be accomplished by simulating the number of tourists from the above seven nations and regions. the increase in the rate of tourism between two different years has higher variation than the average rates for the change in the number of tourists for successive years, - . the use of the average rate provides a relatively reliable tourist change rate. thus, it is assumed that the rate of increase (decrease) in the number of tourists for each nation or region has the same rate as in - , γ i; . eq. ( ) source: data on the average rate of increase in tourism in - were computed based on data obtained from the unwto ( ). numbers with *, **, and *** indicate that the estimated coefficients are significantly different from zero at the %, %, and % significance levels, respectively. note: a the numbers in parentheses are the standard deviations of the corresponding estimated coefficients. other individual nations or regions is positive and has high variation. the highest increase rate is for south korea, and south and southeast asia is ranked second. the lowest increase rate for tourists visiting taiwan is for hong kong. due to the extreme decrease of tourists from china, the total number of tourists from china has a share of . % of the simulated rate for each nation or region. this share is far below the . % in shown in table . this means that tourists visiting taiwan mainly come from nations or regions other than china, with an increase in the rate of tourism for each nation or region. the simulation can also be accomplished by accounting for the marginal effect at the - level based on a change in the number of tourists from china. thus, the simulated number of tourists for each nation or region is computed as in eq. ( )-( ) and eq. ( )-( ): ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) , and data on the length of stay were obtained from the taiwan statistics database of the taiwan tourism bureau ( ). the results of the simulation for total tourism revenue considering the average rate of increase in tourists and table under the corresponding marginal effect of each nation or region. the actual number of tourists from china in is the highest on record. the average simulated numbers of tourists from all nations and regions for - are shown in table for reference. the share of inbound tourists from china in was approximately %, and that of the remaining seven nations was %. the situation reverses in - , when the number of tourists from china continues to decrease and accounts for only %, whereas the share of the other seven nations or regions increases to more than %. the discrepancy between the actual number of tourists from the other seven nations and regions is shown in figs. - . all the figures show that most of the simulated total numbers of tourists from each nation and region have similar patterns, with two exceptions. that is, the simulation of the total number of tourists based upon the average increase (decrease) rate of - is higher than the number simulated by the marginal effect of each nation or region from the change in the number of tourists from china for the coming four years, - . furthermore, all figures demonstrate that the influence of tourists from china through marginal effects on the other nations or regions can be divided into two groups. one group includes the total number of tourists visiting taiwan from japan, hong kong, australasia, some nations in europe, and nations in north america, and the other group includes south korea and various nations in the south and southeast asia regions. the dotted line in each figure shows that the number of tourists from the first group of nations or regions is affected to different degrees by a decline in the number of tourists from china depending upon the curvature of the line. the number of tourists from south korea and the south and southeast asia regions will continue to increase and will not be affected by a decline in the number of tourists from china. regardless of whether there is an increase or decrease in the number of tourists from any nation or region, we are concerned with determining whether tourism revenue might change. to compute the tourism revenue for the next years simulated by either method, data for daily expenditures and length of stay are required. these data were obtained from the taiwantourism bureau, republic of china (taiwan) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) , and the taiwan statistics database of the taiwan tourism bureau ( ) . data on daily expenditures were obtained from a routine survey, and data on the length of stay were included in a long-term record compiled by the taiwan tourism bureau. table lists the last three years of data on daily expenditures and length of stay. the weighted daily expenditure is computed for each region composed of more than nations. the daily expenditure deflated by the cpi is computed for china and the other seven nations and regions for the last years ( - ). we then compute the average of three years of daily expenditures, as shown in table . the annual tourism revenue for a specific nation can be obtained by multiplying the daily expenditures, length of stay, and total number of tourists in a year. each component must be calculated before the corresponding tourism revenue is computed for the simulated years, - . we assume that the daily expenditures are inflated at the same rate as - . the inflated daily expenditures are shown in part b of table . similar to the length of stay, it is assumed that tourists from china and from the seven other nations and regions stay as long as the average days for the - period, which is shown in table . total tourism revenues for china and the other seven nations and regions are then calculated by multiplying part b for and part c in table and the simulated number of tourists and by considering the average rate of increase for the period - , which is shown in part a of table . a similar procedure is used to calculate tourism revenue for the simulated number of tourists, accounting for the average marginal effect of - , which is shown in part b of table . the simulated tourism revenue results for china and all other nations and regions are shown in table . the results show that the tourism revenue from china in the coming four years represents only % of the total tourism revenue of taiwan. the amount is million us$ less than that in and million us$ less than the average for the period - . these results indicate that tourism revenue from china is consistently declining due to the noticeable decrease in the number of tourists. however, the simulated tourism revenue from the other seven nations and regions for - is million us$ higher than that in and million us$ higher than the average for the - period. although the number of tourists for most of the nations and regions is concurrently declining because of the interaction through marginal effects in the decrease in the number of tourists from china, the number of tourists from south korea and south and southeast asia will continuously increase in the next four years. this increase in the number of tourists will lead to an increase in the corresponding tourism revenue from south korea and south and southeast asia. the results shown in table are used in fig. to compare the number of tourists from china and the share in its high peak year, , and all four simulated years, - , with those from all other sovereign nations and regions. a similar comparison can be conducted for tourism revenue and its corresponding share to total tourism revenue in the same year for the nations and regions. we find that the actual total number of tourists from china decreases rapidly from its highest point in - (the year for which the most recent data are available) by approximately %. if the number of tourists from china continues to decline (as the simulated results indicate it will), the share of tourists from china will decrease to % by . the corresponding tourism revenue will then drop from % of total tourism revenue in taiwan in to % in . however, this decline will decrease the number of tourists travelling to taiwan from some nations and regions but will increase the number of tourists from south korea and many nations from south and southeast asia. that is, the negative effect of suppressing both the number of tourists and tourism revenue from some nations and regions is offset by the positive effect of promoting tourists and tourism revenue from other nations. the open-door policy implemented by china in significantly increased the number of tourists from china who visit taiwan. in , the number of tourists from china reached its highest level and its largest share, %, of all tourists to taiwan. however, this policy factor, which has highly political connotations, switched its direction when the ruling party in taiwan changed in . this policy promoted a large number of tourists to taiwan. it is important to identify the impact of this policy when operated in opposite directions by china. the impact will reveal not only the number of inbound tourists through competitiveness or complementarity between china and the other major nations visiting taiwan but also the amount of tourism revenue. simulation is employed to observe the impact of manipulating the open-door policy for - . the results show that if the number of tourists from china is above , , then the number of tourists from the other individual nations or groups of nations will increase. it seems optimistic to have a larger number of tourists from the other nations when there are more tourists from china under its open-door policy to taiwan. however, taiwan will inevitably be faced with fewer tourists from all other nations (i.e., japan, hong kong, australasia (new zealand and australia), north america (canada and the us), and europe (france, germany, gb, italy, and the netherlands)) as china reduces its number of tourists. among the major nations visiting taiwan, only tourists from south korea and from south and southeast asia will consistently increase regardless of whether the number of tourists from china is more or less than , . similar results are found for the change pattern of tourism revenue. it is difficult for taiwan to expect good intentions from china that will allow more tourists to visit taiwan and will complementarily bring more tourists from other nations. the results clearly indicate that taiwan must identify the reason for the increase in tourists from all other nations. to minimize the impact of china's open-door policy on the number of tourists from all other nations (regions), the best strategy for taiwan is to promote different factors to attract tourists from nations other than china. if the current preparation and arrangement of travel and tourism facilities is specifically designed or developed for china due to its large number of inbound tourists, then other nations have the opportunity to use them only incidentally. this makes other nations a spillover beneficiary of travel to taiwan. this is not an effective way of developing the tourism industry for taiwan in the long term. because inbound tourists from different nations have different preferences and tastes for tourism facilities and installations, such as hotels, motels, and public transportation, the preparation of different types of hardware and software facilities suitable for tourists from different nations around the world is essential. relying on a policy imposed by other nations to bring taiwan an abundant number of tourists is an unwise and passive decision. the development and improvement of travel and tourism facilities for tourists from different nations is a constructive way to produce a competitive relationship for the number of tourists and tourism revenue between china and other nations. there are some limitations of the methodological perspective in this study. first, the distance between the capital of taiwan and that of a specific country is a proxy variable of travel cost and is constant over time; thus, the model used here, like most other gravity model applications, cannot take into account the effect of travel cost variation for travel and tourism to different destinations. if data for flight routes to different destinations are available, the travel costs from the gasoline use of aircrafts travelling at different times to different nations might replace the current constant distance variable between the capitals of nations. if this is possible, the creation of this variable requires high demands for data. second, the estimated coefficients of variables in the conventional gravity model only present the mean effects for tourist numbers and fail to capture out-of-average differentiations. an advanced method, such as quantile regression, is a possible solution to this problem and could be used in future research. je-liang liou, pei-chun hsu, and pei-ing wu have brainstorm to come out with this topic. je-liang liou contributes all the software management regarding the estimations. pei-chun hsu then develops her specialty in all the computation of number of tourists and the associated tourism revenue of each nation and/or region for all the scenarios simulated in this study. pei-ing wu frames each section of this manuscript and writes the draft for the full manuscript. the meaningful analyzed contents, such as design of the simulation scenarios and the utilization of the estimation outcomes, are certainly from the frequent back and forth discussion among three authors. pei-chun hsu has a degree in business administration and another degree in agricultural economics. her major work is in administration at the accounting office at national taiwan university (ntu). this work involves accounting and auditing budget control. before joining the accounting office at ntu, she worked in the industrial part of a semi-conductor in charge of financial affairs and negotiations with all types of firms. this study aligns with her focus on managing tourism revenue computation and arranging various types of computation. pei-ing wu is a full professor of the department of agricultural economics, national taiwan university (ntu), and has taught at ntu for nearly years. dr. wu has completed many studies in environmental evaluation with various types of environmental goods and services. her other specialties include natural resource economics, consumer economics, quantitative methods, consumer economics, and research methodology. she has published more than journal articles and book chapters on these topics in both mandarin and english. she is also an author or co-author of several books on her specialties. each year, she conducts at least one project. the implementation of these projects leads to good connections and interactions with graduate students. developing and testing a tourism impact scale fiji's tourism demand: the ardl approach to cointegration estimating european tourism demand for malaysia an international trade flow model with substitution: an extension of the gravity model travel & tourism competitiveness: a study of world's top economic competitive countries language and tourism tourism competitiveness in small island developing states. world institute for development research market shares analysis: the case of french tourism demand determinants of international tourism: a three-dimensional panel data analysis tourism destination competitiveness: a quantitative approach tourism core and created resources: assessment on travel and tourism competitiveness index (ttci) ranking and tourism performance gravity analysis of tourism flows and the 'multilateral resistance to tourism'. current issues in tourism the influence of sociopolitical, natural, and cultural factors on international tourism growth: a cross country panel analysis the role of transport infrastructure in international tourism development: a gravity model approach competitiveness of overseas pleasure destinations: a comparison study based on choice sets intracultural variance of chinese tourists in destination image project: case of queensland competitiveness indices and developing countries: an economic evaluation of the global competitiveness report how are jobs and ecosystem services linked at the local scale? trade effects of regional trade agreements on taiwan: an empirical study using gravity model modeling caribbean tourism demand: an augmented gravity approach statistics: preliminary statistics of cross-strait economic relations factors of tourism's competitiveness in the european union countries determinants of tourist arrivals in european mediterranean countries: analysis of competitiveness statistics: . foreign residents by nationality the use of cpi for tourism prices in demand modelling tourism and urban economic growth: a panel analysis of german cities the influence of distance and prices on the choice of tourist destinations: the moderating role of motivations the influence of sociopolitical, natural, and cultural factors on international tourism growth: a cross country panel analysis an extended gravity model: applying destination competitiveness gravity model estimation: fixed effects vs. random intercept poisson pseudo-maximum likelihood tourism demand modelling and forecasting: a review of recent research tourism yearbook inbound visitors: length of stay small sample evidence of the tourism-led growth hypothesis in lebanon annual survey report on visitors expenditure and trends in taiwan cultural effects on inbound tourism into the usa: a gravity approach cultural connectedness and visitor segmentation in diaspora chinese tourism the travel & tourism competitiveness report the global competitiveness report the global competitiveness report the global competitiveness report the global competitiveness report the global competitiveness report - the global competitiveness report the global competitiveness report the global competitiveness report the global competitiveness report the global competitiveness report why tourism? geneva: world tourism organization. available at: . (accessed why tourism? geneva: world tourism organization world tourism barometer. geneva: world tourism organization yearbook of tourism statistics dataset the impacts of cultural values on bilateral international tourist flows: a panel data gravity model liou's specialties include resource & environmental economics and production economics. his research interests include cost-benefit analysis (cba); non-market evaluation, efficiency and performance measurement; and ghg policy assessment. dr. liou has published more than academic articles (in mandarin and english) we sincerely appreciate the generous and kind offer for the data used in this study by world tourism organization (unwto) and taiwan tourism bureau, republic of china (taiwan). without the support of these data, the accomplishment of this study will not be possible. nation or region total tourism revenue from nations or regions key: cord- -ghmqd yv authors: wang, peng-wei; ko, nai-ying; chang, yu-ping; wu, chia-fen; lu, wei-hsin; yen, cheng-fang title: subjective deterioration of physical and psychological health during the covid- pandemic in taiwan: their association with the adoption of protective behaviors and mental health problems date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: ghmqd yv this study aimed to determine the proportion of individuals who reported the deterioration of physical and psychological health during the coronavirus disease (covid- ) pandemic in taiwan. moreover, the related factors of deterioration of physical and psychological health and the association between deterioration of health and adoption of protective behavior against covid- and mental health problems were also examined. we recruited participants via a facebook advertisement. we determined the subjective physical and psychological health states, cognitive and affective construct of health belief, perceived social support, mental health problems, adoption of protective behavior and demographic characteristics among respondents ( women and men; mean age: . years with standard deviation . years). in total, . % and . % of respondents reported deteriorated physical and psychological health during the covid- pandemic, respectively. participants with higher perceived harm from covid- compared with severe acute respiratory syndrome (sars) were more likely to report the subjective deterioration of physical and psychological health, whereas respondents who were older and perceived a higher level of social support were less likely to report a deterioration of physical and psychological health. the subjective deterioration of psychological health was significantly associated with avoiding crowded places and wearing a mask. both subjective deteriorations of physical and psychological health positively related to general anxiety. the coronavirus disease (covid- ) pandemic has been raging globally. as a novel respiratory infectious disease that is highly contagious, the covid- pandemic has impacted int. j. environ. res. public health , , of physical [ ] and mental health [ , ] , the economy [ ] , education [ ] , quality of life [ ] , occupations [ ] , and the interpersonal relationships [ ] of humans. the first covid- case in taiwan was confirmed on january [ ] . due to proactive containment and comprehensive contact tracing, the number of covid- cases in taiwan has remained lower than in other countries [ ] . by august , taiwan had tested , individuals. a total of confirmed cases were identified, of which were domestic and had died [ ] . therefore, taiwan did not impose a social lockdown. however, the pandemic has impacted the economy and unemployment rate profoundly [ ] . in - , taiwan experienced a major outbreak of severe acute respiratory syndrome (sars). the covid- outbreak rekindled memories of sars and caused fear among the people of taiwan. covid- is a threat to the physical health of both infected individuals and the general public. a study in canada found that % of the population was very or extremely concerned about the impact of covid- to their health [ ] . an online-based study on the general public in china found that % of the participants experienced physical pain or discomfort on the euroqol- d evaluating health-related quality of life [ ] . the psychological health of the public has also been deeply affected by the covid- pandemic. a review study found that both specific populations such as children, elderly, and medical personnel and the general population were harmed psychologically by imposition of strict isolation during the covid- pandemic [ ] . the covid- pandemic might also threaten individual bodily integrity and autonomy and subsequently result in psychiatric comorbidity representing as atypical pictures, such as functional movement disorders [ ] . these studies examined the cross-sectional status of physical and psychological health among people during the covid- pandemic. given that covid- has impacted human lives rapidly and unprecedentedly, examining the deterioration of physical and psychological health since the pandemic began may provide insights into changes in health status during the covid- pandemic. several individual and environmental factors may correlate with the physical and psychological health problems evident during the covid- pandemic, such as pre-existing physical and mental health conditions [ , , [ ] [ ] [ ] , low income [ , ] , and experiencing the profound influence of the pandemic on daily activities [ , , ] . determining the modifiable factors predicting the deterioration of physical and psychological health during the covid- pandemic may provide evidence to develop prevention and intervention programs for the public affected by the covid- pandemic. the health belief model (hbm) can serve as a theoretical basis for determining the predictors of deteriorating physical and psychological health during the covid- pandemic. the hbm proposes cognitive and affective constructs that predict whether an individual will adopt health-promoting behaviors. these include perceived susceptibility to and severity of a health problem, perceived benefits of and barriers to engaging in recommended action, and the belief in one's ability to successfully perform a behavior [ , ] . several studies have examined the association of cognitive and affective constructs of health beliefs with physical and psychological health during the covid- pandemic. for example, perceived high vulnerability for contracting covid- [ , ] , perceived low survival likelihood [ ] , anxiety regarding contracting covid- [ ] , and the distress caused by the uncertainty of the endpoint of the covid- pandemic [ ] predict physical and psychological health during the covid- pandemic. however, hbm-based assessment is inadequate. liao et al. [ ] proposed cognitive and affective constructs of health beliefs concerning the risk of contracting ( ) influenza a/h n in and ( ) respiratory infectious diseases in future epidemics or pandemics. these can be used to examine the cognitive and affective constructs of health beliefs predicting physical and psychological health during the covid- pandemic. studies have found that levels of social support were significantly associated with self-efficacy and sleep quality and negatively associated with the degree of anxiety and stress among medical staff in china who were treating patients with covid- [ ] . however, the association between perceived social support and deteriorating physical health has not been well examined. studies on the association between demographic characteristics and physical and psychological health during the covid- pandemic have revealed mixed results. one study found that aging individuals had a higher risk of physical pain or discomfort and depression or anxiety [ ] , whereas other studies have found that young people were more likely to report mental health problems during the covid- pandemic [ , , ] . moreover, several studies have confirmed that women are more likely to report poor mental health during the covid- pandemic than men are [ , , , ] ; however, gender difference in determining physical health during the covid- pandemic has not been examined. further study is needed to examine whether demographic factors relate to the deterioration of physical and psychological health during the covid- pandemic. adopting protective behaviors, such as avoiding crowded places, washing hands frequently, and wearing a mask, are essential to prevent contracting covid- and staying healthy. a two-wave study in china indicated that precautionary measures, such as maintaining hand hygiene and wearing a mask, were associated with a lower psychological impact from the outbreak and lower levels of stress, anxiety, and depression in both the initial stage of the covid- outbreak [ ] and four weeks later [ ] . however, studies on people during the sars epidemic have reported that respondents with a moderate level of anxiety were most likely to take comprehensive precautionary measures against the infection [ ] . moreover, the use of personal protective equipment increases the discomfort level and causes difficulties in communication [ ] . there is a need of further research into the roles played by deteriorating physical and psychological health in the adoption of protective behaviors against covid- . physical symptoms and poor self-rated health status were significantly associated with a higher incidence of post-traumatic stress disorder and symptoms of stress, anxiety, and depression [ ] . both sleep problems [ ] and suicidal ideation [ ] are serious mental health problems in the era of covid- . it is reasonable to hypothesize that the deterioration of psychological health is significantly associated with sleep problems and suicidal ideation that have become more prevalent during the covid- pandemic, whether the deterioration of physical health is significantly associated with sleep problems and suicidal ideation bears further exploration. this study had three aims: ( ) to determine the proportion of individuals who reported the deterioration of physical and psychological health during the covid- pandemic in taiwan, ( ) to examine the association between cognitive and affective constructs of health beliefs and demographic characteristics and the subjective deterioration of physical and psychological health, and ( ) to examine the association between subjective deterioration of physical and psychological health and adoption of protective behavior against covid- and mental health problems. the current investigation was based on the dataset of the survey of health behaviors during the covid- pandemic in taiwan, which was comprehensively described elsewhere [ ] . briefly, a facebook advertisement was deployed between april and april . we targeted the advertisement to facebook users by location (taiwan) and language (chinese), where facebook's advertising algorithm determined which users to show our advertisement to. facebook users who were years or older and resided in taiwan were eligible for this study. participants reached the research questionnaire website through the facebook advertisement, which was composed of a headline, main text, pop-up banner, and weblink. a total of respondents completed the research questionnaire; of them, respondents were excluded due to missing data on any variable or being younger than . data from respondents were analyzed. figure demonstrates the flowchart of study design. the institutional review board (irb) of kaohsiung medical university hospital that is responsible for ethical review approved this study (kmuhirb-exempt(i) ). as participation was voluntary and survey responses were anonymous, written informed consent was waived based on the approval of irb. the participants were given no incentive for participation. we provided links to taiwan centers for disease control, kaohsiung medical university hospital, and medical college of national cheng kung university for participants to learn more about covid- at the end of the online questionnaire. the analyses of information sources [ ] , sexual behaviors [ ] , and sleep and suicidality [ ] using the dataset have been published elsewhere. facebook advertisement was deployed between april and april . we targeted the advertisement to facebook users by location (taiwan) and language (chinese), where facebook's advertising algorithm determined which users to show our advertisement to. facebook users who were years or older and resided in taiwan were eligible for this study. participants reached the research questionnaire website through the facebook advertisement, which was composed of a headline, main text, pop-up banner, and weblink. a total of respondents completed the research questionnaire; of them, respondents were excluded due to missing data on any variable or being younger than . data from respondents were analyzed. figure demonstrates the flowchart of study design. the institutional review board (irb) of kaohsiung medical university hospital that is responsible for ethical review approved this study (kmuhirb-exempt(i) ). as participation was voluntary and survey responses were anonymous, written informed consent was waived based on the approval of irb. the participants were given no incentive for participation. we provided links to taiwan centers for disease control, kaohsiung medical university hospital, and medical college of national cheng kung university for participants to learn more about covid- at the end of the online questionnaire. the analyses of information sources [ ] , sexual behaviors [ ] , and sleep and suicidality [ ] using the dataset have been published elsewhere. the four-item self-perceived health questionnaire was developed by ko et al. [ ] to evaluate the physical and psychological health of the public during the sars epidemic. for this study, the four questions were modified to evaluate the self-rated physical and psychological health of the respondent compared with those of other people before the covid- outbreak and during the week before filling out the questionnaire ("how is the state of your physical/psychological health compared with other people before the covid- pandemic/in the recent week?"). the questions are listed in table s . the rating for each question ranged from (much worse), (mildly worse), (the same), (mildly better), and (much better). then, the self-reported physical and psychological health states were compared between before and during the covid- pandemic. respondents whose self-rated physical health score in the preceding week was lower than that before the covid- outbreak were classified as having a deterioration of physical health during the covid- pandemic. the respondents whose self-rated physical health score in the preceding week was the same as or higher than that before the covid- outbreak were classified as having no deterioration respondents completed the research questionnaire respondents who were years or older and resided in taiwan completed the questionnaire without missing data data from respondents were analyzed respondents were excluded due to missing data or being younger than the four-item self-perceived health questionnaire was developed by ko et al. [ ] to evaluate the physical and psychological health of the public during the sars epidemic. for this study, the four questions were modified to evaluate the self-rated physical and psychological health of the respondent compared with those of other people before the covid- outbreak and during the week before filling out the questionnaire ("how is the state of your physical/psychological health compared with other people before the covid- pandemic/in the recent week?"). the questions are listed in table s . the rating for each question ranged from (much worse), (mildly worse), (the same), (mildly better), and (much better). then, the self-reported physical and psychological health states were compared between before and during the covid- pandemic. respondents whose self-rated physical health score in the preceding week was lower than that before the covid- outbreak were classified as having a deterioration of physical health during the covid- pandemic. the respondents whose self-rated physical health score in the preceding week was the same as or higher than that before the covid- outbreak were classified as having no deterioration in physical health. the respondents with or without a deterioration of psychological health during the covid- pandemic were classified according to the same rules. we examined the cognitive and affective constructs of health beliefs in the context of covid- , according to the particularization of the hbm to respiratory infectious disease pandemics [ ] . the four cognitive constructs included perceived relative susceptibility to covid- ("what do you think are your chances of contracting covid- over the next month compared with others outside your family?"), perceived severity of covid- relative to sars ("how serious is covid- relative to sars?"), sufficiency of knowledge and information about covid- ("do you think you have sufficient knowledge and information on covid- ?"), and perceived self-confidence in coping with covid- ("how confident are you that you can cope well with covid- ?"). the affective construct included worry about covid- ("please rate how worried you are toward covid- "). the questions, response scales, and dichotomous scales for statistical analysis are listed in table s . three questions developed in the study of tardy [ ] were used to assess the levels of perceived social support from families, friends, and colleagues during the preceding week ("in the past days, were you satisfied with the support from your ( ) family, ( ) friends, and ( ) colleagues or classmates?). the questions and response scales are listed in table s . the total score for the three questions indicates the level of perceived social support. higher scores represent higher perceived social support. the internal reliability (cronbach's α) of the measure was . in this study. as the scores of perceived social support were not normally distributed (skewness = − . , kurtosis = − . , p of kolmogorov-smirnoff test < . ), we used the median score of as the cutoff, and respondents whose score of perceived social support was lower than and whose score was or higher were classified as the groups of low and high perceived social support, respectively. we assessed whether the participants avoided crowded places, washed their hands more often, or wore a mask more often in the preceding week to protect themselves from contracting covid- ("in the past week, did you ( ) avoid going to crowded places, ( ) wash your hands more often, and ( ) wear a mask more often?") [ ] . the questions, response scales, and dichotomous scales for statistical analysis are listed in table s . respondents' level of general anxiety was assessed with the previously validated state-anxiety scale of the chinese version of state-trait anxiety inventory (c-stai), wherein respondents rate their feelings in response to general statements (for example, "i feel rested") [ , , ] . a previous study found that the state-anxiety scale of c-stai had a high internal consistency (cronbach's alpha = . , split-half reliability = . ) and high item-total correlations (r = . - . ) [ ] . two questions adopted from the revised -item brief symptom rating scale were used to assess sleep problems ("in the past week, did you have sleep problems?") and suicidal ideation ("in the past week, did you ever have suicidal thoughts?") in the preceding week [ , ] . previous studies confirmed that both questions had acceptable test-retest reliability (paired sample correlation coefficients = . - . ) and significant correlations with suicidal risk in general population (p < . ) [ , ] . the questions, response scales, and dichotomous scales for statistical analysis are listed in table s . data on gender (women vs. men), age, and education level (university qualifications or above vs. high school qualifications or below) were collected. as age was not normally distributed (skewness = . , kurtosis = − . , p of kolmogorov-smirnoff test < . ), we used the median age int. j. environ. res. public health , , of ( years old) as the cutoff, and respondents who were younger than and who were or older were classified as the younger and older groups, respectively. data analysis was performed using spss . statistical software (spss inc., chicago, il, usa). demographic characteristics, cognitive and affective constructs of health beliefs related to covid- , and perceived social support were compared between respondents who did or did not exhibit a subjective deterioration in physical and psychological health during the covid- pandemic using univariate logistic regression with the crude odds ratio (cor). furthermore, all potential predictive variables identified from the first step were eligible for inclusion in the multivariate logistic regression models with an adjusted odds ratio (aor) to determine the independent predictors of the subjective deterioration of physical and psychological health. the association between the deterioration of physical and psychological health and adoption of protective behaviors against covid- (avoiding crowded places, washing hands, and wearing a mask) and mental health problems (general anxiety, sleep problems, and suicidal ideation) was examined using multivariate logistic regression after controlling for the effects of gender, age, and educational level. moreover, p values, odds ratios (ors), and % confidence intervals (cis) of or were used to indicate significance. a two-tailed p value of < . indicated statistical significance. we also used the standard criteria proposed by baron and kenny [ ] to examine whether the associations of the deteriorated physical and psychological health and related factors (cognitive and affective constructs of health beliefs, perceived social support, adoption of protective behaviors, and mental health problems) were moderated by demographic characteristics that were significantly associated with the deterioration of physical and psychological health. the interactions (demographic characteristics × related factors) were selected into the logistic regression analysis to examine the moderating effects. data from respondents ( women and men) were analyzed. the mean age was . years (standard deviation [sd] = . years; range: - ), ( . %) participants were classified as the older group, and ( . %) participants had university qualifications or above. the mean scores for worry and self-confidence were . (sd = . ; range: - ) and . (sd = . ; range: - ), respectively. regarding the cognitive and affective constructs of health beliefs related to covid- , ( . %) respondents reported high perceived susceptibility to covid- ; moreover, ( . %) perceived that covid- was more harmful than sars, ( . %) reported having sufficient knowledge and information about covid- , ( . %) reported having high confidence in coping with covid- , and ( . %) reported having a high degree of worry about covid- . the mean level of perceived social support was . (sd = . ; range: - ), and ( . %) participants were classified as the group of high perceived social support. table shows the proportions of the respondents with various levels of subjective physical and psychological health and changes in health from before to during the covid- pandemic. most of the respondents reported their health the same as other people before (physical: . %; psychological: . %) and during the covid- pandemic (physical: . %; psychological: . %). regarding the changes in health from before to during the covid- pandemic, . % and . % of the respondents reported no change in physical and psychological health, respectively. of those who had changes in physical and psychological health, most reported mild deterioration (physical: . %; psychological: . %) or improvement (physical: . %; psychological: . %). in total, ( . %) and ( . %) respondents reported that their physical and psychological health deteriorated during the covid- pandemic, respectively. table presents the results of the univariate logistic regression model examining the associations between demographic characteristics, cognitive and affective constructs of health beliefs related to covid- , perceived social support, and the subjective deterioration of physical and psychological health. participants who reported higher perceived harm with respect to covid- than to sars all variables that were significantly associated with the subjective deterioration of physical and psychological health during the covid- pandemic in the univariate logistic regression model were included in the multivariate logistic regression models ( table ). the results indicate that participants with higher perceived harm from covid- compared with sars (b = . , aor = . , % ci: . - . , p = . ) and sufficient knowledge and information about covid- (b = . , aor = . , % ci: . - . , p = . ) were more likely to report the subjective deterioration of physical health during the covid- pandemic because both b values were larger than zero. the moderating effects of age on the associations between perceived harm of covid- relative to sars, sufficiency of knowledge and information about covid- , confidence in coping with covid- , and perceived social support with the deterioration of physical health were further examined based on the criteria proposed by baron and kenny ( ) . the results demonstrate that the interaction between age and sufficiency of knowledge and information about covid- was significantly associated with the deterioration of physical health (b = − . , aor = . , % ci: . - . , p = . ), indicating that age moderated the association between the deterioration of physical health and sufficiency of knowledge and information about covid- . further analysis found that the significant association between the deterioration of physical health and sufficient knowledge and information about covid- existed only in younger respondents (b = . , aor = . , % ci: . - . , p = . ) but not in older ones (b = . , aor = . , % ci: . - . , p = . ). the moderating effects of gender and age on the associations between perceived harm of covid- relative to sars, worry about covid- , and perceived social support with the deterioration of psychological health were also examined. the results demonstrate that the interactions between age and other factors were not significantly associated with the deterioration of psychological health, indicating that age did not moderate the associations between the deterioration of psychological health and other factors. regarding the adoption of protective behaviors against covid- , respondents ( . %) reported avoiding crowded places, ( . %) washed hands more often, and ( . %) wore a mask more often. table demonstrates the results from examining the association between the deterioration of physical and psychological health and the adoption of protective behaviors against covid- . the results indicate that after controlling for the effects of demographic characteristics, the subjective deterioration of psychological health was associated with more adoption of two protective behaviors, including avoiding crowded places (b = . , aor = . , % ci: . - . , p = . ) and wearing a mask (b = . , aor = . , % ci: . - . , p = . ). the interactions between demographic characteristics and the deterioration of psychological health were not significantly associated with avoiding crowded places, indicating that demographic characteristics did not moderate the associations between the deterioration of psychological health and avoiding crowded places. no significant association was found between the deterioration of physical health and adoption of protective behaviors against covid- . regarding mental health problems, respondents ( . %) had a high level of general anxiety, ( . %) had sleep problems, and ( . %) had suicidal ideation. the results from examining the association between the deterioration of physical and psychological health and mental health problems are shown in table . the results show that after controlling for the effects of demographic characteristics, the deterioration of both physical and psychological health was associated with more general anxiety (physical: b = . , aor = . , % ci: . - . , p < . ; psychological: b = . , aor = . , % ci: . - . , p < . ). the deterioration of psychological health and not physical health was associated with more sleep problems (b = . , aor = . , % ci: . - . , p = . ). the interactions between gender and the deterioration of physical and psychological health were not significantly associated with general anxiety. the interaction between age and the deterioration of psychological health was not significantly associated with sleep problems. the results indicate that neither gender nor age moderated the association between the deterioration of health and general anxiety and sleep problems. the deterioration of physical or psychological health was not significantly associated with suicidal ideation. before discussing the results, some issues related to the method of recruiting participants using the facebook advertisement warrants discussion first. recruiting participants through facebook can deliver large numbers of participants quickly, cheaply, and with minimal effort as compared with mail and phone recruitment [ ] . facebook is a platform that provides the opportunity to assess the general public during fast-moving infectious disease outbreaks. however, facebook users may not be representative of the population. a review of a study that recruited respondents through facebook reported a bias in favor of women, young adults, and people with higher education and incomes [ ] . the gender disproportion of the respondents also existed in the present study. to control the effect of gender, gender was used as the covariate when we examined the associations between the deterioration of health and the adoption of protective behaviors and mental health problems. moreover, the present study examined the moderating effects of gender. however, the nonrepresentation of the population in the study should be cautiously considered, and is a consequence of using social media to recruit the participants. this study found that . % and . % of respondents reported experiencing a deterioration of physical and psychological health during the covid- pandemic, respectively. according to the statistics of the national health insurance administration, taiwan, the numbers of patients visiting health care facilities during the period of april to june in reduced . % when compared with the same period in [ ] . people with chronic illnesses may worry about contracting covid- in hospitals and doctor's offices and therefore not seek medical assistance and delay treatment. people with anxiety may interpret changes in perceived bodily sensations as symptoms of being ill, related or unrelated to covid- , and complain of deteriorating physical and psychological health [ ] . although taiwan was not placed under lockdown, people may have reduced outdoor activities or stopped routine exercise due to the worry of contracting covid- and the burden of physical and psychological health problems may have therefore increased [ ] . the results of this study indicate that in addition to monitoring health states of people who are quarantined or have contracted covid- , it is necessary for the governments and health professionals to early detect health problems of and timely deliver medical assistance to the public in the pandemic. introducing novel methods of clinical interaction, such as telemedicine and the use of electronic devices for covid- education, self-assessment, and maintenance of a symptom diary may assist in overcoming the mounting challenges of the covid- pandemic [ , ] . health promotion strategies directed at adopting or maintaining positive health-related behaviors should be utilized to address the increase in psychological distress during the pandemic [ ] . moreover, promoting community-supported interventions for stress and anxiety due to covid- is recommended [ ] . this study found that the perceived harm from covid- , more than that from sars, was significantly associated with the subjective deterioration of physical and psychological health during the covid- pandemic. the perceived risk of contracting covid- may cause stress, which may compromise physical and psychological health [ ] . the public evaluates the risk of covid- relative to sars based on the information they receive from the media and social networks. this study also found that self-rated knowledge and information about covid- were positively associated with the deterioration of physical health. the provision of timely and accurate information on covid- is fundamental to mitigating the disease [ ] and for rationally understanding covid- . moreover, high confidence in coping with covid- was negatively associated with deterioration of physical health. helping build confidence to successfully cope with the pandemic by delivering information through traditional and social media should be a priority for governments and health professionals. however, controlling misinformation on covid- remains a challenge. this study found that perceived social support was negatively associated with the deterioration of physical and psychological health. good social interactions not only provide emotional support but also daily necessities, which may contribute to the maintenance of physical and psychological health. for example, social support can increase individual capacity to maintain health behaviors [ ] . a study on women's sport practice in spain found that brothers/sisters, best friends and workmates encourage women to practice exercise; in particular, the presence of supportive friends increases with age [ ] . social support may be attenuated due to social distancing according to the health policy requirement and the fear of contracting covid- . social support can be offered through telecommunication instead of physical contact to those who have been quarantined to prevent mental health problems. the governments should take an initiative to provide support for those who were socially isolated before the pandemic. this study found that the respondents who reported deteriorated psychological health were more likely to avoid crowded places and wear masks. the results of previous studies were mixed. a study in cyprus found that higher anxiety was positively associated with the adoption of measures related to personal hygiene, whereas higher depression was negatively associated with higher compliance with precautionary measures [ ] . a study in china during the initial outbreak of covid- demonstrated that the adoption of precautionary measures was associated with a lower psychological impact from the outbreak of covid- and lower levels of stress, anxiety, and depression [ , ] . another study in china found that people's perceptions that the outbreak can be controlled by protective behaviors were associated with lower prevalence of depression and anxiety [ ] . the results of the present and previous studies indicate that there might be factors such as the timing of survey, severity of the pandemic and definition of psychological health influencing the association between psychological health and adoption of protective behaviors. this study found that the deterioration of both physical and psychological health was significantly associated with general anxiety and that of psychological health with sleep problems. general anxiety is closely connected to dysfunction of interoception, which can disturb the process by which the nervous system senses, interprets, and integrates signals originating from within the body, providing a moment-by-moment mapping of the body's internal landscape across conscious and unconscious levels [ ] . somatic discomfort, such as increased muscle ache and heart rate, and psychological discomfort, such as excessive worry and irritability were also the core symptoms of generalized anxiety disorder [ ] . therefore, general anxiety and the perception of deteriorating health may occur together. moreover, the present study found that deteriorated psychological health was significantly associated with sleep problems. sleep disturbance is the core symptom of several mental disorders; for example, depression and anxiety disorders [ ] . sleep problems may be used as an indicator of psychological health and may warrant psychological intervention during the covid- pandemic. the present study has some limitations in addition to the gender nonrepresentation of the participants recruited by the facebook advisement. first, there might be recall bias for the health state before the covid- outbreak. second, the cross-sectional design of this study limited causal inference between changes in health state and related factors. third, some factors such as chronic diseases that might influence deteriorated health in the covid- pandemic were not examined in the present study. fourth, the psychometric measures used in the present study for evaluating perceived social support warrants further examination. this facebook-based online study on the general public in taiwan found that . % and . % of respondents reported deteriorated physical and psychological health during the covid- pandemic, respectively. both subjective deteriorations of physical and psychological health positively related to general anxiety. the results indicate that the physical and psychological health of the public, but not only those who were contracted with covid- , should be focus of health professionals' concern. the present study identified several health belief constructs, social support and demographic characteristics that were significantly associated with deteriorated physical and psychological health. these factors can be used to screen for the individuals who need intervention for physical and psychological health problems. the subjective deterioration of psychological health was significantly associated with avoiding crowded places and wearing a mask. further study is needed to examine the mechanism accounting for the association and provide reference for developing strategies to promote adoption of protective behaviors against respiratory infectious diseases. funding: this research did not receive any specific grant from funding agencies in the public, commercial, or nonprofit sectors. the authors declare no conflict of interest. the outbreak of covid- coronavirus and its impact on global mental health preventing suicide in the context of the covid- pandemic the socio-economic implications of the coronavirus pandemic (covid- ): a review covid- -related school closings and risk of weight gain among children impact of the covid- pandemic on mental health and quality of life among local residents in liaoning province, china: a cross-sectional study the traumatic impact of job loss and job search in the aftermath of covid- regulation and trust: -month follow-up study on covid- mortality in european countries a new reportable disease is born: taiwan centers for disease control's response to emerging zika virus infection initial rapid and proactive response for the covid- outbreak-taiwan's experience accounting and statistics, executive yuan health-related concerns and precautions during the covid- pandemic: a comparison of canadians with and without underlying health conditions evaluation of health-related quality of life using eq- d in china during the covid- pandemic mental health effects of covid- pandemia: a review of clinical and psychological traits functional movement disorders in a patient with covid- the psychological impact of preexisting mental and physical health conditions during the covid- pandemic understanding the perceived mental health of canadians during the covid- pandemic depression, anxiety and stress during covid- : associations with changes in physical activity, sleep, tobacco and alcohol use in australian adults the impact of physical activity on psychological health during covid- pandemic in italy covid- pandemic and its impact on mental health of healthcare professionals social learning theory and the health belief model fear and the -ncov outbreak immediate psychological responses and associated factors during the initial stage of the coronavirus disease (covid- ) epidemic among the general population in china the psychological impact of quarantine and how to reduce it: rapid review of the evidence anxiety, worry and cognitive risk estimate in relation to protective behaviors during the influenza a/h n pandemic in hong kong: ten cross-sectional surveys the effects of social support on sleep quality of medical staff treating patients with coronavirus disease (covid- ) in january and february in china generalized anxiety disorder, depressive symptoms and sleep quality during covid- outbreak in china: a web-based cross-sectional survey factors associated with mental health outcomes among health care workers exposed to coronavirus disease a longitudinal study on the mental health of general population during the covid- epidemic in china the impact of community psychological responses on outbreak control for severe acute respiratory syndrome in hong kong human factors considerations in using personal protective equipment in the covid- pandemic context: a bi-national survey study aggregated covid- suicide incidences in india: fear of covid- infection is the prominent causative factor covid- -related information sources and their relationships with confidence of people in coping with covid- : a facebook survey study in taiwan (preprint) changes in sex life among people in taiwan during the covid- pandemic: the roles of risk perception, general anxiety, and demographic characteristics covid- -related factors associated with sleep disturbance and suicidal thoughts among the taiwanese public: a facebook survey psychosocial impact among the public of the severe acute respiratory syndrome epidemic in taiwan social support measurement reliability and factorial structure of the chinese version of the state-trait anxiety inventory state trait anxiety inventory: a test manual/test form predictive validity of a five-item symptom checklist to screen psychiatric morbidity and suicide ideation in general population and psychiatric settings development and verification of validity and reliability of a short screening instrument to identify psychiatric morbidity the moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations social media divide: characteristics of emerging adults who do not use social network websites the use of facebook in recruiting participants for health research purposes: a systematic review social isolation during the covid- pandemic can increase physical inactivity and the global burden of cardiovascular disease using ehealth to support covid- education, self-assessment, and symptom monitoring in the netherlands: observational study covid- related stress exacerbates common physical and mental pathologies and affects treatment (review) infodemic" and emerging issues through a data lens: the case of china theoretical explanations for maintenance of behaviour change: a systematic review of behaviour theories estudio de la relación del entorno psicosocial en la práctica deportiva de la mujer prevalence and predictors of anxiety and depression symptoms during the covid- pandemic and compliance with precautionary measures: age and sex matter public behavior change, perceptions, depression, and anxiety in relation to the covid- outbreak © by the authors key: cord- - t q w authors: liu, keh-sen; yu, tsung-fu; wu, hsing-ju; lin, chun-yi title: the impact of global budgeting in taiwan on inpatients with unexplained fever date: - - journal: medicine (baltimore) doi: . /md. sha: doc_id: cord_uid: t q w unexplained fever is one of the most common and difficult diagnostic problems faced daily by clinicians. this study evaluated the differences in health service utilization, health care expenditures, and quality of care provided to patients with unexplained fever before and after global budget (gb) implementation in taiwan. the national health insurance research database was used for analyzing the health care expenditures and quality of care before and after implementation of the gb system. patients diagnosed as having unexplained fever during – were recruited; their – and – data were considered baseline and postintervention data, respectively. data of patients with unexplained fever were analyzed. the mean lengths of stay (loss) before and after gb system implementation were . ± . days and . ± . days, respectively. the mean costs of different health care expenditures before and after implementation of the gb system were as follows: the mean diagnostic, drug, therapy, and total costs increased respectively from new taiwan dollar (nt$) . ± nt$ . , nt$ . ± nt$ . , nt$ . ± nt$ . , and nt$ , . ± nt$ , . before gb system implementation to nt$ . ± nt$ . , nt$ . ± nt$ . , nt$ . ± nt$ . , and nt$ , . ± nt$ , . after implementation. the mean rates of revisiting the emergency department within days and readmission within days increased respectively from . % ± . % and . % ± . % before implementation to . % ± . % and . % ± . % after implementation. gb significantly increased los and incremental total costs for patients with unexplained fever; but improved the quality of care. unexplained fever represents as one of the most common and difficult diagnostic problems encountered daily by clinicians; it is a febrile illness without an initially obvious etiology. [ , ] when unexplained fever prolongs despite intensive evaluation and diagnostic testing, clinicians refer to it as fever of unknown origin (fuo). [ ] earlier, fuo was defined as a fever of ≥ . °c lasting for ≥ weeks with undiagnosed etiology even after week of intensive hospital testing. [ ] physicians specializing in infectious diseases have redefined fuo as the fever of ≥ . °c lasting for ≥ weeks with undiagnosed etiology after days of in-hospital testing or during ≥ outpatient visits. [ ] [ ] [ ] for pediatric fuo, the generally accepted definition is, a fever lasting - weeks without positive preliminary investigations or without a diagnosis after three outpatient clinic visits. [ , ] fuo can be divided into following four general categories based on the etiology of fever: infection, rheumatic-inflammatory, neoplastic, or miscellaneous. [ ] infectious diseases account for approximately one-third of fuo. the most common infections associated with fuo are miliary tuberculosis (tb), q fever, and brucellosis, followed by human immunodeficiency virus (hiv); cytomegalovirus (cmv); epstein-barr virus; intra-abdominal, pelvic, intranephric and perinephric abscess; typhoid or enteric fever; toxoplasmosis; and extrapulmonary tb. notably, in % of the hiv patients, fuo is results from secondary infection, rather than from the hiv infection. [ ] furthermore, rheumatologic and inflammatory disorders, such as rheumatoid arthritis, systemic lupus erythematosus, giant cell/temporal arteritis, adult still disease, periarteritis nodosa, and microscopic polyangiitis, account for another one-third of fuos. [ ] moreover, fuos due to neoplasms and malignancies account for % of all fuos; of them, renal cell carcinoma and lymphoma are the most common neoplasms, followed by acute myeloid leukemia and myeloproliferative disorders. [ ] the remaining causes of fuo are miscellaneous disorders, including drug fevers, liver cirrhosis, crohn disease, and subacute thyroiditis. [ ] fuo, a challenge for physicians to diagnose and manage currently, represents approximately % of hospital admissions, with morbidity caused by prolonged hospital stay, and mortality rates accounting %- %. furthermore, fuo is associated with repeated invasive investigations, presumptive treatment, and a high impact on health care systems due to unnecessary and additional laboratory tests and medications. [ , ] over causes for fuo have been reported. [ ] relatively few infectious diseases have the potential to cause prolonged fever; therefore, patients with prolonged and perplexing fevers, in whom the infection has been ruled out, pose a diagnostic challenge. [ ] moreover, fever is one of the most common reasons for outpatient visits of children and visits to emergency department (ed). [ ] difficulty in diagnosing fuo also makes its treatment difficult. empirical antibiotics cannot be indicated unless the patient with fuo is neutropenic. in addition, empiric glucocorticoids cannot be indicated without a strong evidence of rheumatologic disease. [ ] recurrent fuo, which is a strong independent predictor of unestablished diagnosis, represents %- % of the cases in large series. in addition, a final diagnosis can be established in only % of patients with recurrent fuo. [ ] [ ] [ ] [ ] [ ] [ ] [ ] a comprehensive and careful history-taking as well as examination by physician and exhaustive laboratory testing have are required for a focused diagnostic evaluation of fuo. [ ] the diagnostic approaches for fuo include medical historytaking, physical examination, laboratory tests, and imaging studies. the etiologies of fever may be approached in terms of their height, fever pattern, and duration. most studies have stressed on the significance of a complete history and comprehensive physical examination. in case of infectious fuo, fever is often accompanied by chills, night sweating, weight loss without loss of appetite, rigors, exudative tonsillitis, or splenomegaly. in general, the longer the fuo remains undiagnosed, the more likely it is to have a noninfectious etiology. [ ] a patient presenting with b-symptoms and significant weight loss might have a neoplasm or malignancy as the cause of the fuo. by contrast, joint involvement may indicate rheumatologic disorders. [ , ] laboratory testing includes complete blood count, three sets of blood cultures, erythrocyte sedimentation rate, complete metabolic panel, urinalysis, urine culture, tuberculin skin test, and tests for biomarkers (such as antinuclear antibodies, rheumatoid factor, cmv immunoglobulin m, hiv antibodies, and heterophile antibodies) in children and young adults. moreover, imaging techniques include chest radiography, computed tomography (ct), and radionuclide scanning. [ ] fuo is associated with broad differential diagnosis leading to a wide range of potential diagnostic and therapeutic costs. however, little is known regarding the hospitalization costs for patients with fuo. recent studies have reported high hospitalization charges for fuo (us$ , -us$ , ). [ , ] the national health insurance (nhi) program, the backbone of the health care system in taiwan, is the major source of health financing and covers % of the population of taiwan. national health care expenditure in taiwan increased from . % in to . % in of the gross national product. the nhi operated on a fee-for-service (ffs) basis and as a result health care spending increased by approximately % from to . to prevent unlimited and rapid growth of spending on health care, the bureau of nhi (bnhi) implemented the global budget (gb) system to modify the ffs mechanism in . the gb in taiwan is an overall spending target, designed to limit the volume of service and its total price. [ ] [ ] [ ] [ ] [ ] here, we evaluated the differences in health service utilization, health care expenditures, and quality of care among patients with unexplained fever before and after gb system implementation by using nhi research database (nhird) data. this was a pre-post comparison study. the study was based in part on data from nhird provided by bnhi, department of health and managed by the national health research institutes (nhri). the database contains the registration files and original claims data for reimbursement. the nhird is provided to scientists in taiwan for research purposes. each year, the bnhi collects data from the nhi program and sorts it into data files. these data files are de-identified by scrambling the identification codes of both patients and medical facilities and then sent to nhri to form the original files contained in the nhird. [ ] based on the registration files and original claims data in the nhird, specific data subsets can be re-constructed for research purposes. the registration datasets, systemic sampling inpatient expenditures by admissions (dd file) and systemic sampling ambulatory care expenditures by visits (cd file) were used in this study. the interpretation and conclusions contained herein do not represent those of bnhi, the department of health, or nhri. [ ] . . systemic sampling cd and dd files . % of the ambulatory care expenditures, by visit, cd file extracted by systematic sampling method on a monthly basis, together with the related records in details of ambulatory care orders form the systematic sampling cd file. % of the inpatient expenditures, by admission, dd file extracted by systematic sampling method on a monthly basis, together with the related records in details of inpatient orders form the systematic sampling dd file. [ ] a total of one million cases of systemic sampling dataset were used in this study. taiwan . it has been reported that sars had an impact on health care utilization. [ ] therefore, data from was not used in this study. a score of was added when the subjects had co-morbid myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, connective tissue disease, peptic ulcer disease, mild liver disease, or diabetes without end-organ damage. a score of was added when the subjects had co-morbid hemiplegia, moderate or severe renal disease, diabetes with end-organ damage, tumor without metastases, leukemia, or lymphoma. a score of was added when the subjects had co-morbid moderate or severe liver disease. a score of was added when the subjects had co-morbid metastatic solid tumors or acquired immunodeficiency syndrome. the total score was obtained by adding the relative weight of all comorbidities. for each decade > years of age, a score of is added to the sum of the abovementioned scores. [ ] [ ] [ ] [ ] in taiwan, health insurance premiums are calculated as a percentage of an individual's monthly salary. there were seven income levels in this study, levels ∼ [ ] (table s , http://links. lww.com/md/d ). the nhird encrypts patient personal information to protect privacy and provides researchers with anonymous identification numbers associated with relevant claims information, including sex, date of birth, medical services received, and prescriptions. patient consent is not required to access the nhird. this study was approved by the institutional review board (irb) of china medical university (cmu-rec- - ). the irb specifically waived the consent requirement. all data and related metadata were deposited in an appropriate public repository. the data on the study population that were obtained from the nhird (http://w .nhri.org.tw/nhird// date_ .html) are maintained in the nhird (http://nhird.nhri. org.tw/). the nhri is a nonprofit foundation established by the government. data are described as mean ± standard deviation. the t test was used to compare the differences in mean values. multilevel and generalized linear model were employed to determine the impact of several independent variables. multilevel and generalized linear model were employed to determine the impact of several independent variables on los, diagnostic costs, drug costs, therapy costs, total costs, the risk of revisiting the ed within days, and the risk of being readmitted within days after discharge. there were two nested levels in this study: hospital accreditation levels and regional levels. there are three accreditation hospital levels in taiwan: medical centers, regional hospitals, and local hospitals. taiwan is divided into six geographical areas that include taipei city, northern taiwan, central taiwan, southern taiwan, kaoshiung, and eastern taiwan. the independent variables evaluated in this study included pre-post gb, age, gender, income state index, charlson comorbidity index, the three hospital levels, and the six geographic areas in taiwan. all statistical analyses were performed using the statistical package stata for windows (version . ). a p-value of . was considered to represent statistical significance. data on patients with unexplained fever ( pre-and post-gb) were analyzed in this study. the mean ages of subjects before and after gb were . ± . years and . ± . years, respectively. in the pre-budget group, % of subjects were male and in the post-budget group, % of subjects were male. the mean income state indexes before and after gb were . ± . and . ± . , respectively. the mean charlson comorbidity index before and after gb were . ± . and . ± . , respectively. there were no significant differences in age, male to female ratio, or income state index before and after implementation of the gb system (p = . , p = . , p = . ). however, there was a significant difference in charlson comorbidity index before and after gb (p = . ) ( table ) . the mean los before adoption of the gb was . ± . days and the mean los after implementation of the system was . ± . days. the mean diagnostic costs before and after the gb system went into effect were nt$ , . ± . and nt $ , . ± . , respectively. the mean drug costs increased from nt$ , . ± , . at baseline to nt$ , . ± , . after adoption of the gb system. the mean therapy costs before and after gb were nt$ . ± . and nt $ , . ± . , respectively. the mean total costs increased from nt$ , . ± , . at baseline to nt$ , . ± , . after the system went into effect. the mean -day ed revisiting rate decreased from . % ± . % at baseline to . % ± . % after adoption of the gb system. the mean -day readmission rates before and after gb were . % ± . % and . % ± . %, respectively. there were significant differences in los, diagnostic costs, therapy costs, total costs, -day ed revisiting rate, and -day readmission rate before and after implementation of the gb system among patients with www.md-journal.com unexplained fever (p = . , p = . , p < . , p = . , p = . , p = . , respectively). there was no significant difference in drug costs before and after the gb among patients with unexplained fever (p = . ) ( table ) . a generalized linear poisson model was used for clustered count data analysis. [ ] the poisson regression model was fitted using option irr (incidence-rate ratio) to obtain exponential estimates. the gb system did not have a significant impact on los (irr = . , p = . ). in addition, gender was not a significant predictor of los (irr = . , p = . ). there was a significantly positive correlation between age, charlson comorbidity index, and los (irr = . , p = . ; irr = . , p < . , respectively). there was no significant correlation between income state index and los (irr = . , p = . ). los did not differ significantly between patients treated at medical centers and those treated at local hospitals (irr = . , p = . ). however, patients treated at regional hospitals had a significantly shorter los than those treated at medical centers (irr = . , p = . ). compared with hospitals in taipei (table ) . a generalized linear model was used for analysis. because diagnostic costs were skewed to the right, data were converted to log base for statistical analysis. the gb system had a significantly positive impact on diagnostic costs (b = . , p = . ). neither gender nor income state index was significantly correlated with diagnostic costs (b = . , p = . ; b = . , p = . , respectively). there was a significantly negative correlation between age and diagnostic costs (b = À . , p = . ), and a significantly positive correlation between charlson comorbidity index and diagnostic costs (b = . , p < . ). there were no significant differences in diagnostic costs between regional hospitals and medical centers or local hospitals and medical centers (b = . , p = . ; b = . , p = . , respectively). compared with hospitals in taipei city, there were no significant differences in diagnostic costs among hospitals located in northern taiwan, central taiwan, southern taiwan, kaoshiung city, or eastern taiwan (b = . , p = . ; b = . , p = . ; b = . , p = . ; b = À . , p = . ; b = À . , p = . , respectively) ( table ). taiwan) % % table the impact of several independent variables on los in the patients with unexplained fever (generalized linear poisson model). a generalized linear model was used for analysis. because drug costs were skewed to the right, data were converted to log base for statistical analysis. gb had a significantly negative impact on drug costs (b = À . , p = . ). there was a significantly positive correlation between age and drug costs (b = . , p = . ), but there was no significant correlation between gender, income state index or charlson comorbidity index and drug costs (b = À . , p = . ; b = À . , p = . ; b = . , p = . , respectively). there were no significant differences in drug costs between regional hospitals and medical centers or local hospitals and medical centers (b = À . , p = . ; b = . , p = . , respectively). compared with hospitals in taipei city, there were no significant differences in drug costs among hospitals in northern taiwan, central taiwan, southern taiwan, kaoshiung city, or eastern taiwan (b = . , p = . ; b = . , p = . ; b = . , p = . ; b = . , p = . ; b = À . , p = . , respectively) ( table ). a generalized linear model was used for analysis. because the therapy costs were skewed to the right, data were converted to log base for statistical analysis. gb had a significantly positive impact on therapy costs (b = . , p = . ). there was no significant correlation between gender or income state index and therapy costs (b = À . , p = . ; b = À . , p = . , respectively). there was a significantly negative correlation between age and therapy costs (b = À . , p < . ) and a significantly positive correlation between charlson comorbidity index and therapy costs (b = . , p < . ). there were no significant differences in therapy costs between regional hospitals and medical centers or local hospitals and medical centers (b = À . , p = . ; b = . , p = . , respectively). compared with hospitals in taipei city, there were no significant differences in therapy costs among hospitals in northern taiwan, central taiwan, southern taiwan, kaoshiung city, or eastern taiwan (b = . , p = . ; b = À . , p = . ; b = À . , p = . ; b = À . , p = . ; b = À . , p = . , respectively) ( table ) . a generalized linear model was used for analysis. because the total costs were skewed to the right, data were converted to log base for statistical analysis. gb had a significantly positive impact on total costs (b = . , p = . ). there was no significant correlation between gender, age or income state index and total costs (b = . , p = . ; b = À . , p = . ; b = . , p = . , respectively), but there was a significantly positive correlation between charlson comorbidity index and total costs (b = . , p = . ). there were no significant differences in total costs between regional hospitals and medical centers or local hospitals and medical centers (b = . , p = . ; b = . , p = . , respectively). compared with hospitals in taipei city, there were no significant differences in total costs among hospitals in northern taiwan, central taiwan, southern taiwan, kaoshiung city, or eastern taiwan (b = . , p = . ; b = . , p = . ; b = . , p = . ; b = . , p = . ; b = À . , p = . , respectively) ( table ) . table the impact of several independent variables on diagnostic costs, drug costs and therapy costs in the patients with unexplained fever (generalized linear model). table the impact of several independent variables on total costs in the patients with unexplained fever (generalized linear model). a generalized linear binary regression model was used for analysis. gb did not have a significant impact on the risk of revisiting the ed within days (or = . ; p = . ). there was no significant correlation between age, gender, income state index or charlson comorbidity index and the risk of revisiting the ed within days (or = . , p = . ; or = . , p = . ; or = . , p = . ; or = . , p = . , respectively). in addition, there were no significant differences in the risk of revisiting the ed within days between regional hospitals and medical centers or between local hospitals and medical centers (or = . , p = . ; or = . , p = . , respectively). compared with hospitals in taipei city, there were no significant differences in the risk of revisiting the ed within days among hospitals in northern taiwan, central taiwan, southern taiwan, kaoshiung city, or eastern taiwan (or = . , p = . ; or = . , p = . ; or = . , p = . ; or = . , p = . ; or = . , p = . , respectively) ( table ). a generalized linear binary regression model was used for analysis. gb did not have a significant impact on the risk of being readmitted within days (or = . ; p = . ). there were no significant correlations between age, gender, income state index, or charlson comorbidity index and the risk of readmission within days (or = . , p = . ; or = . , p = . ; or = . , p = . ; or = . , p = . , respectively). no significant differences in the risk of readmission within days were noted between regional hospitals and medical centers or between local hospitals and medical centers (or = . , p = . ; or = . , p = . , respectively). compared with hospitals in taipei city, there were no significant differences in the risk of being readmitted within days among hospitals in northern taiwan, central taiwan, southern taiwan, kaoshiung city, or eastern taiwan (or = . , p = . ; or = . , p = . ; or = . eÀ , p = . ; or = . , p = . ; or = . , p = . , respectively) ( table ). unexplained fever imposes additional burden on both the nhi system and patients. however, studies on hospitalization costs for patients with unexplained fever are limited. in this study, we investigated the impact of the gb system for patients with unexplained fever in taiwan. the gb system was associated with significantly longer los of the patients with unexplained fever. after adjustments for other covariates, age and charlson comorbidity index were independent los predictors. gb did not significantly affect los in patients with unexplained fever. patients with unexplained fever in regional hospitals had a significantly shorter los than patients in medical centers. fuo is diagnosed less frequently in adults than in children; however, adult patients are more likely to be admitted and have longer loss. [ ] the mean age of patients with unexplained fever in medical centers was . ± . years, whereas that of patients with idiopathic fever in regional hospitals was . ± . years. the mean charlson comorbidity indexes in medical centers and regional hospitals were . ± . and . ± . , respectively. thus, the younger the age and the fewer the comorbidities, the shorter may be the loss in patients with unexplained fever in the regional hospitals. infections are the main causes of fuo in children, [ , , , ] including the children in taiwan. [ , ] notably, a significant proportion of pediatric patients, accounting approximately %- %, remain undiagnosed. [ , , , ] however, in adults, the number of undiagnosed cases has been demonstrated to be more common than that of the infectious etiology cases. [ , ] as fluorodeoxyglucose positron emission tomography (fdg-pet)/ct emerged in the end of th century, [ ] it was applied for the diagnosis of fuo. compared to conventional scintigraphic techniques, fdg-pet/ct has following advantages: higher resolution and higher sensitivity for anatomic localization of infectious, inflammatory, or neoplastic processes. [ ] the workup of patients with fuo demonstrated that the diagnostic performance of f-fdg-pet/ct is superior to ga singlephoton emission computed tomography (spect)/ct. [ ] furthermore, previous studies have suggested that using fdg-pet/ ct shortened the diagnostic work-up for fuo. [ , ] a metaanalysis reported that pet and pet/ct had successfully localized the source of fever in % and % of the patients with classic fuo, respectively, after a series of unsuccessful investigations. [ ] the major drawbacks are cost and accessibility; fdg-pet/ct costed £ , compared with £ for a chest-abdomen-pelvis table the impact of several independent variables on the risk of revisiting ed within days and the risk of re-admission within days among the patients with unexplained fever (generalized binary linear model). risk of re-admission within days ct. however, this could be offset by earlier definitive treatment due to higher diagnostic sensitivity, which could reduce los with an average of £ per day. [ ] therefore, fdg-pet/ct can aid in diagnosing fuo, particularly when diagnostic clues are absent. diagnostic, therapy, and total costs incurred for treating patients with unexplained fever significantly increased after gb system implementation. after adjustments for other covariates, the gb system and charlson comorbidity index was found to be positively correlated with increased diagnostic, therapy, and total costs. the increase in health care expenditures from . % to . % significantly exceeded the . % growth in consumer price index for the same period in taiwan (table s , http://links. lww.com/md/d ). the possible reasons for the higher costs include longer loss, additional comorbidities, and higher proportion of older individuals in the study population after gb system implementation (table ) . moreover, salaries of physicians in taiwan are calculated more or less on the basis of ffs. therefore, physicians demonstrate a natural proclivity to maximize medical services to maximize their income; and the gb system does not provide an incentive for physicians to reduce the volume of medical care. health care expenditures incurred by patients with unexplained fever did not differ between hospitals with different accreditation levels or in different geographic areas in taiwan. the risks of revisiting the ed within days and readmission within days significantly decreased after implementation of the gb system, which suggested that the quality of care was improved. however, after controlling other covariates, the gb was not associated with reduced risks of revisiting the ed within days or readmission within days. furthermore, none of the tested variables were independent predictors of revisiting the ed within days or being readmitted within days for patients with unexplained fever. a possible reason this observation are the regulations for evaluating the quality of care in hospitals in taiwan. bnhi has developed a series of plans structured to improve the quality of care while keeping costs under control. the plans offer incentives to health care providers by paying them based on clinical outcomes to care for overall wellbeing of patients. the risks of revisiting the ed within days and readmission within days are the two indicators used by bnhi to measure the quality of care. these two indicators are linked to the reimbursement rate at each hospital. the amount of reimbursement is reduced if the quality of care is determined to be poor. to safeguard against being penalized, all hospitals in taiwan have made concerted efforts to reduce the -day ed revisiting and -day readmission rates. in this study, no difference in the risks of revisiting the ed within days or readmission within days between hospitals with different accreditation levels or between different geographic areas of taiwan was noted. this research has some limitations. first, the nhird data did not provide detailed information of patients regarding factors, such as their lifestyle, habits, socioeconomic status, and family history; all of which are possible confounding factors in this study. second, the nhi claims registries are primarily used for administrative billing alone and thus are not verified for scientific purposes. the laboratory data and information regarding symptoms of patients were lacking, and therefore, discussion of these factors in relation to the gb system is not possible. furthermore, because of the anonymity of the identification numbers, obtaining additional information by directly contacting the patients was not possible. the accuracy of medical coding in the claims data may affect the data validity. however, the diagnosis data in the nhird are highly reliable. the insurance system has mechanisms to monitor the insurance claims. third, the conclusions derived from a cohort study are generally of lower methodological quality than those from randomized trials because a cohort study is subject to several biases and the necessary adjustments for confounding factors are required. despite the meticulous design of this study and adequate control of confounding factors, biases associated with possibly unmeasured or unknown confounding factors can occur. gb significantly increased los and incremental diagnostic, therapeutic, and total costs; however, the quality of care improved for patients with unexplained fever. a similar health policy can be applied in other countries to benefit more patients with unexplained fever. table age stratification of unexplained fever patients before and after implementation of global budget (gb). post gb (%) fever of unexplained origin: report on cases unexplained fever and chronic fatigue: abnormal circadian temperature pattern fever of unknown origin: an evidence-based review fever of unknown origin: focused diagnostic approach based on clinical clues from the history, physical examination, and laboratory tests fever of unknown origin-reexamined and redefined fever of unknown origin: the evolving definition fever of unknown origin in children fever of unknown origin in children: a systematic review fever of unknown origin: clinical overview of classic and current concepts imaging of infectious diseases using [ f] fluorodeoxyglucose pet a comprehensive evidence-based approach to fever of unknown origin fever of unknown origin approach to neonates and young infants with fever without a source who are at risk for severe bacterial infection treasure island (fl): statpearls a prospective multicenter study on fever of unknown origin: the yield of a structured diagnostic protocol recurrent or episodic fever of unknown origin. review of cases and survey of the literature abrupt onset of papulovesicular lesions: diagnostic features and outcome fever of unknown origin (fuo). i a. prospective multicenter study of patients with fuo, using fixed epidemiologic entry criteria. the netherlands fuo study group fever of unknown origin (fuo): report on patients in a dutch university hospital fever of unknown origin in the s. an update of the diagnostic spectrum from prolonged febrile illness to fever of unknown origin: the challenge continues fever of unknown origin. an algorithmic approach evaluation of prolonged and recurrent unexplained fevers fever of unknown origin etiology and resource use of fever of unknown origin in hospitalized children fever of unknown origin: a retrospective review of pediatric patients from an urban does universal health insurance make health care unaffordable? lessons from taiwan a -year experience with universal health insurance in taiwan: measuring changes in health and health disparity providers' responses to global budgeting in taiwan: what were the initial effects? about national health insurance, global budget payment scheme the effects of the global budget system on cost containment and the quality of care: experience in taiwan introduction to the national health insurance research database (nhird) impact of sars on healthcare utilization by disease categories: implications for delivery of healthcare services comorbidity negatively influences prognosis in patients with extrahepatic cholangiocarcinoma charlson comorbidity index using administrative database in incident pd patients prognostic impact of charlson comorbidity index obtained from medical records and claims data on -year mortality and length of stay in gastric cancer patients introduction of national health insurance premium level multilevel and longitudinal modeling using stata outcomes in patients with an emergency department diagnosis of fever of unknown origin pediatric fever of unknown origin clinical approach to fever of unknown origin in children clinical analysis of fever of unknown origin in children: a -year experience in a northern taiwan medical center fever of unknown origin or fever of too many origins? imaging infection and inflammation. diagnostic nuclear medicine radiolabeled compounds in diagnosis of infectious and inflammatory disease the efficacy of ( )f-fdg pet/ct and ( )ga spect/ct in diagnosing fever of unknown origin fever of unknown origin: the value of fdg-pet/ct nuclear imaging for classic fever of unknown origin: meta-analysis diagnostic yield of fdg-pet/ ct in fever of unknown origin: a systematic review, meta-analysis, and delphi exercise key: cord- -x faz x authors: lee, hong-hsi; lin, sheng-hsuan title: effects of covid- prevention measures on other common infections, taiwan date: - - journal: emerg infect dis doi: . /eid . sha: doc_id: cord_uid: x faz x to determine whether policies to limit transmission of severe acute respiratory syndrome coronavirus (sars-cov- ) hinder spread of other infectious diseases, we analyzed the national health insurance database in taiwan. rates of other infections were significantly lower after sars-cov- prevention measures were announced. this finding can be applied to cost-effectiveness of sars-cov- prevention. d rawing from experience with the severe acute respiratory syndrome epidemic in , the taiwan government has established a central command system for a quick response to epidemics arising from china ( ) . since the first confirmed case of coronavirus disease in taiwan was reported, taiwan officials acted immediately with regard to border control, public health education (mask wearing and handwashing), ensuring adequate medical equipment, and early suspension of classes. these policies may not only reduce the spread of severe acute respiratory syndrome coronavirus (sars-cov- ) but may also have similar effects on spread of other infectious diseases ( , ). using nationwide weekly surveillance data ( ), we compared the activity of common infections during - with the timeline of actions and policies implemented to protect against spread of sars-cov- in taiwan. the taiwan national infectious disease statistics system ( ) from the taiwan centers for disease control monitors emergency and outpatient visits for patients with acute infections, diagnosed according to clinical manifestations and laboratory results in hospitals (covering . % of emergency visits), through the national health insurance database and reports weekly statistical data. using these data, we compared the number of outpatient visits for influenza, pneumonia, enterovirus infection, and scarlet fever and the number of confirmed cases of severe complicated influenza in the - influenza season (week in through week in ; , , cases) versus the same data for the previous influenza seasons ( , , total cases). to estimate the change in outpatient visits or confirmed case numbers (hereafter called activity) after the covid- outbreak (weeks - in ), we used a difference-in-difference regression model. the model included a categorical variable for each week, a categorical variable for each year, and the interaction variables for each week after the outbreak and for the - season. because of concerns about the covid- pandemic, during the first quarter of , the overall number of hospital visits in taiwan dropped by %. we conducted a sensitivity analysis by multiplying /( - . ) times the number of cases for the selected diseases during these periods. institutional board review was not required because we used only deidentified, secondary statistical data for this study. overall infection activity was lower during the - season than during the previous seasons. for the - season, activities of all diseases notably decreased after weeks - (figure) . according to the difference-in-difference analysis, activities of influenza and severe complicated influenza were significantly lower after week during the - season than during the previous seasons. comparing the - season with the previous seasons, outpatient pneumonia activity was lower after week , enterovirus activity after week , and scarlet fever activity after week (table; figure) . in taiwan, infection rates for selected diseases were lower in than in previous seasons. this observation correlates with implementation of actions and policies against covid- , such as early vigilance and taking proactive measures to prevent droplet and contact transmission in public and at schools. the effect of social distancing in taiwan was unclear because related measures were not officially announced until the covid- pandemic started subsiding in early april ( ). these policies potentially have indirect effects on noninfectious diseases associated with acute viral infections, such as myocardial infarction and ischemic stroke ( , ) . by comparing the cost of sars-cov- prevention and the effect on the economy and health during the pandemic in taiwan and other areas, we could evaluate the cost-effectiveness of these measures and use this information to develop policies for future disease control. to determine whether policies to limit transmission of severe acute respiratory syndrome coronavirus (sars-cov- ) hinder spread of other infectious diseases, we analyzed the national health insurance database in taiwan. rates of other infections were significantly lower after sars-cov- prevention measures were announced. this finding can be applied to cost-effectiveness of sars-cov- prevention. dr. lee is a postdoctoral fellow in the department of radiology, new york university school of medicine. his research focuses on retrieving microstructural information of the human brain via diffusion magnetic resonance imaging techniques, segmentation and analysis of microscopy data in the brain white matter, monte carlo simulation of diffusion in realistic tissue microgeometry, and the medical imaging processing pipeline. response to covid- in taiwan: big data analytics, new technology, and proactive testing seasonal influenza activity during the sars-cov- outbreak in japan collateral benefit of covid- control measures on influenza activity taiwan centers for disease control. taiwan national infectious disease statistics system applying the lessons of influenza to coronavirus during a time of uncertainty inflammation and infections as risk factors for ischemic stroke p ertussis (whooping cough) is a highly contagious disease caused by the gram-negative bacterium bordetella pertussis. vaccination is an effective method to prevent and control pertussis, but in many countries, pertussis incidence remains despite high vaccination coverage. macrolides are commonly used to treat pertussis, but macrolide-resistant b. pertussis (mrbp) strains have been observed in mainland china and iran ( ) ( ) ( ) ( ) . in china, mrbp is isolated with increasing frequency ( . %- . %) and has been since the early s ( , ) . most mrbp isolates from china have a homogeneous a g mutation in each of the copies of the s rrna gene, which is associated with macrolide resistance ( , , ) . in contrast, mrbp is rare in iran; the a g mutation is not identified in the iran mrbp isolate ( ) . china has several reports of mrbp, but our knowledge about these bacteria in other countries in asia is limited.to survey mrbp in vietnam, which neighbors china, we performed a retrospective analysis of stored dna samples from nasopharyngeal swabs collected during - from patients with pertussis in northern vietnam (median age months [range days- years]; patients in , in , and key: cord- -h r jpy authors: wang, tsung-hsi; wei, kuo-chen; jiang, donald dah-shyong; chiu, chan-hsian; chang, shan-chwen; wang, jung-der title: unexplained deaths and critical illnesses of suspected infectious cause, taiwan, – date: - - journal: emerg infect dis doi: . /eid . sha: doc_id: cord_uid: h r jpy we report years’ surveillance data from the taiwan centers for disease control on unexplained deaths and critical illnesses suspected of being caused by infection. a total of cases were reported; the incidence rate was . per , person-years; and infectious causes were identified for cases ( %). i n , the outbreak of severe acute respiratory syndrome (sars) demonstrated that the world has become a global village in which human risk for exposure to different kinds of biological hazards is increased through frequent travel and commercial activities ( ) ( ) ( ) ( ) ( ) . historically, emerging diseases occur abruptly in outbreaks of unknown cause. although various efforts have been proposed and conducted to analyze secondary data periodically ( ) ( ) ( ) ( ) , they generally provide information for the less urgent decision making in health policy and may not be in time for infectious disease control. thus, a task force is needed to provide timely and accurate diagnosis for early control of any potential epidemic infection, especially in a newly developed country like taiwan, where the healthcare resources may not be evenly distributed and autopsy for diagnosis is not widely accepted culturally. in , the taiwan centers for disease control collaborated with academic institutions, medical examiners, local health authorities, and experts from different fi elds to establish a nationwide surveillance center for outbreak and unexplained death investigation due to unknown infectious causes (counex) (figure) . this effort was to build local health authorities, hospitals, or clinics report suspected infection-related cases through the "notifiable infectious disease surveillance system," "syndromic surveillance system," and toll-free notification hotline figure. flow of information and decision making for reported cases of unexplained death or critical illness. *if unexplained infectious causes were suspected, counex mobilized an investigation team including experts, fi eld epidemiology training program members, public health workers from the local branch of taiwan centers for disease control (tcdc), and public health authorities to proceed with further fi eld investigation. tcdc was in charge of the investigation. †cases were categorized into > of the following clinical syndromes: acute neurologic (encephalitis, meningitis), acute respiratory (pneumonia), acute hemorrhagic, acute diarrhea, acute jaundice (hepatitis), acute heart (myocarditis, pericarditis, endocarditis), and acute kidney-related. for every reported case, counex investigators usually selected diagnostic tests relevant to a particular syndrome (www.cdc.gov.tw). additional tests were prescribed if needed. the hospital laboratories were requested to save all remaining clinical specimens, including biopsy specimens, obtained from clinical management and send them to our reference laboratories, if indicated. ‡if an autopsy was performed, whenever possible tissue specimens were examined by pathologists of tcdc-designated medical centers and the forensic department of the ministry of justice to ensure the accuracy of the fi nal diagnosis. specimens were also sent for microbiologic cultures and tests as well as toxicologic examination for trace toxic chemicals, if needed. §all laboratory results and clinical, epidemiologic, and pathologic data were sent to the expert committee to determine if the etiologic agent could fully or most likely explain the disease. otherwise, cases were categorized as unexplained. in general, histopathogic examination was the major evidence for determining cause. if casepatients could not be autopsied within hours of death, laboratory results would be the most useful information for identifi cation of cause of death. taiwan's capacity for detecting and responding to uncommon and unrecognized pathogens, which was conceptually the same as that of the study of hajjeh et al. ( ) . we defi ned the surveillance case-patient as a previously healthy resident who died or was admitted to a hospital with a lifethreatening illness possibly caused by infection of unidentifi ed etiology. usually the death occurred within days of the patient's admission. patients were excluded if the cause of death was noninfectious. a life-threatening illness was defi ned as any illness requiring admission to an intensive care unit or reported as being critical. an infectious disease is generally suspected if the case-patient has > of the characteristics such as fever, leukocytosis, histopathologic evidence of an acute infectious process or more specifi c symptom patterns, or infection precipitating adult respiratory distress syndrome, renal failure, or sepsis. a total of cases were reported during - , for an annual average rate of . cases per , persons. the annual incidence rates varied by year and among branches of taiwan centers for disease control (table) . the highest rate was in the eastern branch, where surveillance was conducted in a well-defi ned population of ≈ , persons. ninety-fi ve ( %) of the case-patients died. for ( %) of those who died, an autopsy was performed, a rate much higher than the national autopsy rate of < % ( ). the mean age of case-patients was . years. the incidence rates varied by age group; it was highest in those - years of age, followed by those < - years, and then - years, with . , . , and . per , person-years, respectively. men had a higher incidence rate than women ( . vs. . per , person-years). approximately % of case-patients and % of patients with cases of infection had a history of animal contact; % of case-patients and % of infection casepatients had a history of travel outside taiwan within the previous months. the most common initial syndromes were acute respiratory ( %), acute neurologic ( %), and acute diarrhea-related syndrome ( %). initially, patients had acute heart-related syndrome, and had acute kidney-related syndrome; both of these syndromes had a % case-fatality rate. the online appendix table ( www.cdc.gov/eid/ content/ / / -appt.htm) lists all the infectious pathogens and noninfectious causes identifi ed among fatal cases. one third were related to bacterial infection and one fourth to viral infection; remained unclassifi ed. the proportion of explained cases was lower among patients who survived ( %) than that among patients who died ( %). the proportion of explained cases was also higher for patients who underwent autopsy ( %) than for nonautopsied patients ( %) but not statistically signifi cantly so. explained cases were similar to unexplained cases in terms of patient age and interval between dates of disease onset and report (median . and . days, for explained and unexplained cases, respectively). although the overall case-fatality rate was %, patients were more likely to die if they had multiple organ system involvement. we have established the infrastructure needed to detect critical and fatal cases of unknown causes; such a surveillance system is essential to identify early potential infectious threats in a period of globalization and increasing travel between countries. the contributions of our surveillance system are demonstrated by early detection and control of at least outbreaks of serious viral diseases: hantavirus pulmonary syndrome, rabies, and sars. in , a family cluster occurred in huanlian city; dyspnea, cough, leukopenia, and pulmonary edema developed in both parents, who died. their -year-old daughter was also ill, but she survived. counex quickly intervened, and hantavirus pulmonary syndrome was confi rmed by positive serologic test results, which led to an early control of local rodents and spread of the disease. taiwan has been free of human and animal rabies since . however in , a -year-old woman from mainland people's republic of china was admitted to a hospital because of diffi culty in swallowing, fear of wind (aerophobia), and numbness of the arms. her condition was reported to the surveillance system as suspected rabies. our emerging infectious diseases • www.cdc.gov/eid • vol. , no. , october ( ) and approximately the midpoint of this study period, included all people in the age groups under surveillance at the various sites and were used to calculate the incidence rate. personnel quickly confi rmed the diagnosis by reverse transcription-pcr and dna sequence analysis of the samples from cerebrospinal fl uid, saliva, and trachea while the patient was still alive ( ) . the patient had been bitten by a domesticated dog in mainland china months earlier. during the sars outbreak in , the surveillance system received reports of cases; autopsies were performed on patients. as a result, the correlation between clinical course and pulmonary pathology at different stages of the disease was possible, and corroborative evidence for control measures was provided ( ) . had the surveillance system for unexplained death and critical illness not functioned normally during these outbreaks, more people in taiwan would have been ill and died from the diseases because of the high population density on this island. this system was particularly useful for infection control at remote regions with limited resources. most physicians in the rural eastern part of the country have less access to consultation and referral to other specialties in medical centers and teaching hospitals. thus, they rely more on this kind of surveillance system for early detection of potential infectious threats. this was especially important for acute unexpected deaths, as was demonstrated by a higher incidence and autopsy rates in eastern taiwan. throughout this project, we have increased the autopsy rate and established a population-based bank of specimens for future research. this collection could provide a better opportunity for corroboration or refutation of any previous diagnosis of infectious disease. this improved decision making in regard to control of infections was demonstrated in november , when infl uenza virus (h n ) was diagnosed in a patient who had a previous misdiagnosis of sars ( ) . because emerging and reemerging infectious diseases may quickly travel between different countries, the system is becoming more crucial for early detection and control of potential health hazards. the system depends on close cooperation among different disciplines and staff from different agencies. thus, education, empowerment, and good feedback incentives should be continually offered to keep this system sustainable. this work was supported in part by taiwan centers for disease control grant no. doh -dc- . dr t.-h. wang is the head of the public relations offi ce of taiwan cdc. she was the previous coordinator of counex and conducted investigations for infectious disease outbreaks. her research interests include governmental strategic planning and for-mulation and evaluation of response measures for public health disasters. control measures for severe acute respiratory syndrome (sars) in taiwan update: outbreak of severe acute respiratory syndrome⎯worldwide severe acute respiratory syndrome-singapore evidence of airborne transmission of the severe acute respiratory syndrome virus optimizing severe acute respiratory syndrome response strategies: lessons learned from quarantine addressing emerging infectious disease threats: a prevention strategy for the united states. atlanta: us department of health and human services unexplained deaths due to possibly infectious causes in the united states: defi ning the problem and designing surveillance and laboratory approaches. the unexplained deaths working group the role of postmortem examination in medical education retrospective validation of the prospective surveillance of unexplained illness and death due to potentially infectious causes surveillance for unexplained deaths and critical illnesses due to possibly infectious causes institute of forensic medicine. mobilization of forensive medicine business molecular-biological analysis of the fi rst imported rabies case in taiwan evolution of pulmonary pathology in severe acute respiratory syndrome fatal infection with infl uenza a (h n ) virus in china all material published in emerging infectious diseases is in the public domain and may be used and reprinted without special permission; proper citation, however, is required.use of trade names is for identifi cation only and does not imply endorsement by the public health service or by the u.s. department of health and human services. key: cord- - myoqms authors: song, yann-huei title: cross–strait interactions on the south china sea issues: a need for cbms date: - - journal: marine policy doi: . /j.marpol. . . sha: doc_id: cord_uid: myoqms abstract recent developments in the south china sea (scs) and the actions expected to be taken by china and member states of asean in accordance with the declaration on the conduct of parties in the scs have the potential to further marginalize taiwan's role in any serious discussion on scs issues and then deprive taiwan of its legitimate rights and interest in the area. these developments will also force taiwan to respond by taking more active actions for the sole purpose of safeguarding its sovereignty and maritime jurisdiction in the scs. this article discusses a number of possible confidence-building measures that could be considered for adoption by china to help engage taiwan in the regional security dialogue process and enable taiwan to participate in the planned joint co-operative activities in the scs. the co-operative actions taken in the scs area could enhance mutual trust between the two sides of the taiwan strait. taiwan is one of the six parties directly involved in sovereignty and maritime jurisdictional disputes in the south china sea (scs). coast guard personnel from taiwan are now stationed on the largest island in the spratly island chain, taiping-dao (itu aba island), and the pratas islands. despite this fact, taiwan has been excluded from the discussions on the code of conduct in the scs, mainly because of china's opposition and the adherence to the so-called ''one china'' policy by member states of the association of southeast asian nations (asean). taiwan has also been barred from participating in the track one regional security dialogue processes, such as the asean regional forum (arf), which address security issues, including the scs territorial disputes, confidence building measures (cbms), and preventive diplomacy in the asia-pacific region. recent developments in the scs and the actions expected to be taken by china and member states of asean in accordance with the declaration on the conduct of parties in the south china sea (scscop declaration) have the potential to further marginalize taiwan's role in any serious discussion on scs issues and then deprive of taiwan's legitimate rights and interest in the area. the development will also force taiwan to respond by taking more active actions for the sole purpose of safeguarding its sovereignty and maritime jurisdiction in the scs. on november , , the china national offshore oil corporation (cnooc) and the philippine national oil company agreed to jointly look for oil and gas in the scs. a committee will be set up by the two companies to help select parts of the waters in the scs area where exploration for oil may be carried out. they also agreed to a program to ''review, assess and evaluate relevant geological, geophysical and other technical data available to determine the oil and gas potential in the area''. this joint project is one of the most recent examples that exclude taiwan from participation in the proposed cooperative activities in the scs. taiwan cannot but respond to the recent developments in the area by taking counter-actions. on august , , taiwan's interior minister yu cheng-hsien, on behalf of premier yu shy-kun, traveled to taiping-dao to reaffirm the nation's sovereignty over the spratly islands. in late october , taiwan's coast guard personnel stationed on taiping-dao drove vietnamese fishing vessels away in the waters near the island. it can be expected that more actions will be taken by taiwan if both china and member states of the asean keep ignoring taiwan's territorial claims and fail to respect its legitimate right in the scs area. taiwan's being excluded continuously from the regional security dialogue on the scs issues and the failure of the parties concerned to invite taiwan to participate in any of the proposed joint co-operative activities in the disputed areas that are also claimed by taiwan have the potential to destabilize the overall situation in the scs. the cross-strait relations and foreign relations between taiwan and member states of asean will also likely be affected. china is holding the key to taiwan's involvement in the regional security dialogue process on the scs issues and its participation in any of the proposed co-operative activities in the spratly area between china and the asean based on the guidelines underlined in the scscop declaration. it is suggested that china should consider the utility of taking a ''win-win-win-win'' approach to deal with the territorial and jurisdictional disputes in the scs. it is believed that china, by adopting the approach, will gain (win), taiwan likewise (win), and the asean will also benefit from it (win). in the end, all parties concerned and the region as a whole will win. not only will this approach help realize china's policy goal of ''setting aside sovereignty disputes, jointly develop the resources'' in the scs, but also help promote peace, stability and prosperity in the region. the cross-strait relations could also be improved. the purpose of this paper is to discuss a number of possible cbms that could be considered for adoption by china to help engage taiwan in the regional security dialogue process and enable taiwan to participate in the planned joint co-operative activities in the scs. this paper begins with a short review of the asean-china relations, focusing in particular on the result of their consultations over the scs issues. after that, the impact of the recent development in the scs and the actions to be taken following the signing of the scscop declaration between china and member states of asean on taiwan's scs policy and its sovereign right and maritime interest in the scs will be assessed. then, the paper moves to review the cross-strait interactions on the scs issues in the period of time between and . finally, possible cbms will be identified and discussed. mainly in response to the serious disputes between china and the philippines over mischief reef, the foreign minister of the asean issued a statement on the recent developments in the scs on march , , in which they asked inter alia all parties concerned to refrain from taking actions that destabilize the region article in press ''chinese, philippine firms join forces to look for oil in south china sea,'' agence france presse, november , (lexisnexis on-line search, page not available). ''taiwanese interior minister returns from inspection tour to spratly islands,'' bbc monitoring international reports, august , (lexisnexis on-line search, page not available). the vietnamese name of the island is dao ba binh. ''vietnam warns taiwan over spratly islands,'' channel news asia, november , (lexisnexis on-line search, page not available). the philippines discovered in february that china had built octagonal structures on mischief reef of the spratly archipelago. the reef's chinese name is meiji jiao; the filipino name is panganiban; and the vietnamese calls it vanh khan. china and vietnam also engaged in armed conflicts in the dispute over the ownership of the paracel and spratly islands in the scs in and , respectively. in response to china's enactment of its territorial sea law on february , , in which china reaffirms its sovereignty over the paracel islands, the spratly islands, and other island in the scs, and to china's signing a contract with the denver-based us oil corporation crestone on may , to explore oil and gas potential in the spratly area, the foreign ministers of the member countries of the asean issued the asean declaration on the south china sea on july , , which urged all parties concerned to exercise restraint with view to creating a positive climate for the eventual resolution of all disputes. the declaration also asked the countries having directly interests in the area to explore the possibility of co-operation in the scs relating to the safety of maritime navigation and communication, protection against pollution of the marine environment, coordination of search and rescue operations, efforts towards combating piracy and armed robbery as well as collaboration in the campaign against illicit trafficking in drugs. in addition, the declaration commended all parties concerned to apply the principles contained in the treaty of amity and cooperation in southeast asia as the basis for establishing a code of international conduct over the scs. for the text of the declaration, visit website of asean at: http://www.aseansec.org/ .htm and http://www.aseansec.org/ .htm. and to undertake co-operative activities in the scs area. the united states also responded to the increasing tensions in the scs by issuing a strong official statement on the scs on may , , which inter alia urged all claimants to exercise restraint, to avoid destabilizing actions, and to intensify diplomatic efforts which address issues related to competing territorial and jurisdictional claims in the scs [ ] . on july , , vietnam became the seventh member state of the asean. china's scs policy during the second half of the s had been influenced to a large extent by the actions taken by the united states, the asean, admission of vietnam to the organization, and the increasing importance of asean market to china's foreign trade development. it is observed that china began to calculate carefully the costs it had to bear and the benefits it could gain between the policy options of taking a much more aggressive stand, such as occupying new reefs or constructing new structures on the islands it occupies in the scs area, or undertaking co-operative activities with the member states of the asean in the future. the increasing us involvement in the scs area through strengthening military co-operation with member states of the asean, such as the philippines, singapore, and thailand, and the increasing frequency of joint military exercises conducted at sea between the united states and member states of the asean, which was interpreted by the chinese scholars and officials as a change of us scs policy, moving from a position of neutral to active concerns, are believed to have important impacts on the direction of china's scs policy. the development pushed the chinese policy makers to move further toward adopting a diplomatic co-operative approach when the scs issues are to be tackled with. the asian financial crisis of - reinforced this policy choice of china. in , china and the asean issued a joint statement, in which the two sides reaffirmed the principles of peaceful settlement of disputes in the scs, agreed to resolve their disputes in the scs through friendly consultations and negotiations in accordance with universally recognized international law, including the united nations convention on the law of the sea, and agreed that the concerned countries should exercise self-restraint and to explore ways for cooperation in the scs. on december , , at the informal asean-china summit, zhu rongji, premier of china, stated that china would continue to render support to and co-operate with member states of asean in regional and international organizations such as the arf, the un, and others. he also said that china would increase multilateral and bilateral security dialogue and consultations and made joint efforts for the establishment of a new just and reasonable international political, economic and security order. as far as the scs issues are concerned, the chinese premier stressed that china will, as always, adhere to the principles and spirit of the china-asean joint statement signed in and resolve its differences and disputes with asean countries through friendly consultations and peaceful means. china appreciated the purposes and spirit of the treaty of amity and cooperation in southeast asia and will continue to support asean in its efforts to establish a zone of peace, freedom and neutrality and a southeast asia nuclear weapon free zone. a joint statement between china and vietnam was signed in beijing on february , , in which the two sides agreed to settle territorial disputes through peaceful means and consultations. before reaching a final settlement of the disputes, the two sides agreed to strive for maritime co-operation in areas such as marine environmental protection, marine scientific research, and others. the normal development of foreign relations between china and vietnam should not be affected by any existing differences over the ownership of the islands in the scs [ ] . in , china signed a joint statement on comprehensive co-operation with indonesia (may ), the philippines (may ), and vietnam (december ), respectively. the three statements share one common goal, namely enhancing bilateral relations between china and the member state of asean, and then moving toward the establishment of a comprehensive co-operative framework as well as setting the direction of co-operation between the two sides for the st century. at the th asean summit and the th asean+ (china, japan, and south korea) summit, held in the signing of the scscop declaration, in particular, attracted great attention, which was described as ''a major leap for peace'' and would lead to an eventual adoption of a regional code of conduct in the scs. it was also believed that the signing of the declaration would help build up trust, enhance co-operation, reduce tensions between china and member states of the asean, and thus promote peace and stability in the scs area and the asia-pacific. the scscop declaration contains several important cbms, including: holding dialogues and exchange of views between defense and military officials; ensuring just and humane treatment of all persons who are either in danger of in distress; and notifying on a voluntary basis other parties concerned of any impending joint/ combined military exercises conducted in the spratly/ scs region. in addition, china and member states of the asean agreed to explore or undertake cooperative activities in the scs area, which may include marine environment protection, marine scientific research, safety of navigation and communication at sea, search and rescue operation, and combating transnational crimes. on august , , a senior officials meeting between china and the asean was held in wuyishan mountain, fujian province, china, in which they agreed that the two sides will strictly follow the guidelines underlined in the scscop declaration to jointly maintain regional stability. on august , , china and the philippines, on the occasion of an official goodwill visit to manila by china's top legislator wu bangguo, issued a joint communique´, in which they welcomed the signing of the scscop declaration and expressed their readiness to press ahead with follow-up actions for continued progress. a proposal was submitted by wu bangguo to the philippines to jointly explore oil resources in the scs area. on october , , china acceded to the treaty of amity and cooperation in southeast asia. on the same day, asean and china also issued a joint declaration on strategic partnership for peace and prosperity, in which the two sides agreed, inter alia, to ''[i]mplement the declaration of the conduct of parties in the south china sea, discuss and plan the way, areas and projects of follow-up actions''. this was followed by a news report, in which his majesty the sultan and yang di-pertuan of brunei darussalam stated that asean looks forward to implementing cooperative activities outlined in the scscop declaration, especially in cbms. china also expressed its willingness to accede to the protocol to the treaty on the southeast asia nuclear weapons free zone in the future. the closer relationships between china and member states of the asean, together with china's recent rise in regional and global prominence in geostrategic, political, economic, social and cultural terms make china become more patient when it comes to the handling of the territorial and maritime jurisdictional disputes in the scs. china is now not only becoming supportive to a regional code of conduct in the scs, but also willing to take actions to speed up the process of developing the code. the main purpose is to help facilitate joint use and prevent military clashes in the scs area. china has not changed its essential position on sovereignty over the islands in the scs, but it seems that on this matter, beijing is taking a longer view with a sense that time is on china's side. at present, joint development of oil and gas reserves is put on the top of its scs policy agenda, given the fact that china the recent developments in the scs and the tendency to exclude taiwan one step further from cooperative activities to be carried out in the areas also claimed by taiwan make it more difficult for taiwan to accomplish the goals explicitly stated the policy of the republic of china towards the scs, which include ''firmly safeguarding [taiwan's] sovereignty in the south china sea, enhancing the development and management of [the resources in the scs], actively promoting cooperation [with the countries concerned] in the scs, peacefully handling the disputes in the scs, and protecting the ecological environment of the scs [ ] ''. without taiwan's consent and participation, taiwan's sovereignty, sovereign rights, and maritime jurisdiction in the scs will be encroached upon by other claimants, provided that the co-operative activities or joint development projects are to be carried out in the areas also claimed by taiwan. taiwan's participation in the regional security, political, economic, or technical talks on the scs issues will also be affected by the recent agreements done between the member states of asean and china, and the follow-up activities. as a result, taiwan will be further marginalized in any serious consultations or negotiations over the scs issues in the future. the recent development in the scs will also turn taiwan's policy regarding ''temporarily shelving the sovereignty disputes in order to explore ways of jointly developing, managing and policing the scs'' into empty words, with no possibility of being implemented. taiwan will continuously be excluded from the regional dialogue over the adoption of a code of conduct in the scs. on the other hand, if indeed the co-operative activities were carried out in the areas also claimed by taiwan, and thereafter oil reserves for example were found, taiwan would be forced to take actions to defend its sovereignty and maritime interests in the scs. under this circumstance, taiwan would encounter another policy dilemma. the actions taken against china or member states of asean in the scs would have profound impact on the future development of crossstrait relations and its policy goal of enhancing foreign relations with member states of asean. paragraph of the scscop declaration provides that ''[t]he parties concerned undertake to resolve their territorial and jurisdictional disputes by peaceful means, y through friendly consultations and negotiations by sovereign states directly concerned, in accordance with universally recognized principles of international law y (emphasis added)''. it is believed that the wording was included in the declaration mainly for the purpose of excluding taiwan and other international organizations from participating in the process that deals with scs issues. given the fact that member states of asean are adhering to the so-called ''one china'' principle, it is also unlikely for taiwan to enter into official talks with countries such as vietnam, the philippines, and malaysia to explore the possibility of jointly developing resources in the scs. as a result, one of the policy choices for taiwan is to find means and ways to participate in the future talks and co-operative activities on the scs issues. a flexible arrangement for taiwan's involvement in the track one scs talks and participation in the future planned or agreed co-operative projects in the scs could possibly be made only after obtaining china's consent, directly or indirectly. in a background briefing to members of the legislative yuan shortly after china and vietnam engaged in armed conflicts in the waters near the disputed chigua jiao (johnson reef) of the spratly islands in march , taiwan's defense minister cheng wei-yuan reportedly said that taiwan, if asked by china to help defend the islands from a third party attack, would respond affirmatively. his statement was then confirmed by taiwan's ministry of foreign affairs [ ] . it was also reported in december that the pla navy had the intention to co-operate with taiwan's navy to defend the spratly islands. the naval conflict between china and vietnam in the spratly islands opened the window of opportunity for the cross-strait, nongovernmental dialogue on the scs issues, in which ideas of cross-strait co-operation in the scs in areas such as fisheries, marine environmental protection, marine scientific research, drug trafficking, underwater shipwreck salvage, and marine archaeology were proposed and discussed. the possibility for the cross-strait co-operation in the scs area was enhanced by a symposium on scs issues, which was organized by the ministry of interiors and national sun yet-san university, and held in taipei, taiwan in january . one of the major policy recommendations made at the end of the conference was that, based on the common position taken by the chinese regimes across the two sides of the taiwan strait, cross-strait co-operative relationship should be developed to jointly safeguard the sovereignty, jurisdiction, and interests in the scs. it is believed that the ''one china'' principle adhered to by the then kmt for a copy of the policy guidelines, see [ ] . vietnamese name is: da gac ma. united daily (taipei, in chinese), december , , p. . see records of the symposium on scs issues, january , , p. . government in the early s and taiwan's proposal to jointly defend the scs islands with beijing were the two major reasons that help explain why china did not oppose taiwan's participation in the indonesian-sponsored, canadian-funded informal workshop on managing potential conflicts in the south china sea held in bandung, indonesia in july (the second scs workshop). both taipei and beijing agreed to attend the second scs workshop on the same condition that the question of sovereignty over the islands in the scs should not be raised at the meeting. in july , seven representatives from china and four from taiwan attended the second scs workshop. the majority of the chinese participants were governmental officials, in particular, from the ministry of foreign affairs. two of the taiwanese participants were professors teaching at national taiwan university. the other two came from taiwan's de-facto embassy ''taipei economic and trade office'' in jakarta. the participants at the workshop agreed to recommend to the relevant governments to explore areas of co-operation in the scs, which include cooperation to promote safety of navigation and communications, to coordinate search and rescue to combat piracy and armed robbery, to promote the rational utilization of living resources, to protect and preserve the marine environment, to conduct marine scientific research, and to eliminate illicit traffic in drugs in the scs. since july , both taiwan and china have continued sending representatives to attend the scs workshop and its relevant meetings on legal matters, marine scientific research, marine environmental protection, shipping and safety of navigation, resource assessment, and others in the scs. scientists from china and taiwan also participated in the anambas expedition, which is the first joint co-operative project on marine biodiversity implemented in the scs area in , participated and funded by countries in the scs area. in september , nine participants from china and seven from taiwan attended the th scs workshop held in medan, indonesia. table lists the workshop and its relevant technical and group of experts meetings that were held between and . it is expected that scientists from china and taiwan will also participate in the exercise palawan in april , which is the second agreed biodiversity project to be funded and participated by countries in the scs area without financial support from the ''outsiders''. both taiwan and china agreed that the workshop process should continue to function to develop and promote co-operation in the scs. it was also discussed between and among the taiwanese and chinese participants at the informal gathering when attending the workshop or its relevant meetings that taiwan and china should exchange views on the scs issues or reach understanding before attending the workshop meetings. but it is totally wrong to say that there had no conflicts between taiwan and china at the scs workshop. on the contrary, the use of taiwan's official or preferred names (in particular the republic of china or taiwan) and taiwan's right to host technical working group meetings or group of experts meetings under the workshop framework have always been the source of conflict between the taiwanese and chinese participants over the past years. participants from china at the workshop took actions to delete any wording found in the documents delivered or circulated during the meeting, or written in the draft version of the final statement of the meeting, which they worried would have policy implications for recognizing taiwan as a sovereign country or not consistent with the ''one china'' principle. for taiwan, the participation in the scs workshop has also created a policy dilemma. on the one hand, taiwan is concerned very much about the discussion on the scs issues per se, and is therefore willing to co-operate with china and other claimants in accordance with its scs policy position, that is, ''setting aside the territorial disputes, and jointly developing the scs resources''. on the other hand, taiwan intends to use the scs workshop as a diplomatic platform to promote its international legal status recognized as a country, instead of being treated as another special administrative district like ''hong kong'', and to strengthen its foreign relations with member states of the asean. the ''one china'' problem made it very difficult for the workshop process to be formalized or establish a permanent secretariat. but it should also be noted that the scs workshop is the only regional dialogue mechanism dealing specifically with the scs issues, where scholars and governmental officials from both taiwan and china can meet regularly and exchange views on a variety of scs issues even though in their personal capacity. given that fact that taiwan has been excluded from the track one security dialogue mechanisms in the region that also discuss the scs issues, the scs workshop and its relevant technical/group of experts meetings have become the very few international occasions where taiwan's voice and its concerns over the scs issues can be raised and heard. in addition to the scs workshop, scholars and governmental officials from taiwan and china had also met at a number of cross-strait informal talks on the scs issues between and as shown in table . taiwanese and chinese scholars as well as governmental officials met and exchange views on a variety of scs issues at these academic symposia. the first cross-strait academia symposium on the scs issues was held in haikou, hainan, china in september . most of the participants were chinese scholars, but four representatives from taiwan were also invited to attend the meeting. around papers on a variety of issues related to the scs were presented. among them, zhao enbo, the then section chief of office of laws and regulations at the state oceanic administration, presented a paper entitled ''prospects for cross-strait cooperation in the spratly islands'' in which he called upon both sides of the taiwan strait to promote cooperation in the areas of marine scientific research, marine weather forecasting, marine fisheries, search and rescue at sea, and even military co-operation such as conducting alternative naval patrols in the spratly archipelago area. he listed three bases for the proposed cross-strait cooperation in the scs: ( ) the consensus on the ownership of the spratly islands; ( ) common actions taken against other claimants in the scs; and ( ) the efforts made to safeguard the sovereignty of the spratly islands. in addition, he stressed that any implementation of the cross-strait co-operation on the scs issues must be guided by the principle of ''peaceful re-unification, and one country two systems''. hu chizi, a participant from taiwan, called for crossstrait co-operation to develop fisheries resources in the spratly islands by setting up a fisheries base on itu aba island [ ] . in june , the cross-strait and oversea chinese academic symposium was organized by the chinese international law association and held at soochow university in taipei, taiwan. the goal of the symposium, as stated in the invitation letter, was to establish consensus on the scs issues between the chinese people who are living in the two sides of the taiwan strait, and to help protect their rights in the scs area. ten scholars came from mainland china, each of them presented a paper on different topics related to the scs, including china's legal claim, historical evidence, archaeology, marine environmental protection, marine scientific research, research institutions, assessment and exploitation of oil and gas resources, marine fisheries, and shipping and navigation. it was understood that both taiwan and china at that time considered the need to strengthen the cross-strait co-operation in the scs area. under the guidelines for national unification, that was adopted by taiwan's executive yuan council (cabinet) on march , , the principle of one china should be applied to the cross-strait interactions on the scs issues. as stated clearly in one of the four principles listed in the guidelines, ''both the mainland and taiwan areas are parts of chinese territory. helping to bring about national unification should be the common responsibility of all chinese people''. in addition, under taiwan's scs policy guidelines, adopted in april , one of the policy implementing actions to be taken is to support the guidelines for national unification by studying and setting up relevant policy and plans, and studying the matters relevant to the scs issues that involve both sides of the taiwan strait [ ] . at the cross-strait and oversea chinese academic symposium, lin chin-tz, a senior researcher from xiamen university, proposed to consider the possibility of cross-strait co-operation on compiling the historical literature in relation to the scs, inviting scholars to participate in the joint compilation project, and exchange data or research findings/results [ ] . wang henjei, a professor from the central national university, called for setting up a general academic structure to be in charge of the responsibility for coordinating the scs research works done by scholars in taiwan, china, macau, and hong kong [ ] . du bilan, the chinese participant from the state oceanic administration, proposed to organize a cross-strait co-operative research project on environmental and ecological studies in the scs [ ] . du shu, a senior engineer from the cnooc, stated at the end of his paper that ''the chinese people of both sides of the taiwan strait have [ ] [ ] [ ] common interests and position on the issues related to the spratly islands, and therefore can fully co-operate to make contribution in safeguarding the legitimate rights and benefits of the chinese people in the waters surrounding the spratly islands [ ] .'' yu mainyu, a research fellow at the nanhai aquaculture research institute, called for setting up a coordinating mechanism between the two sides of the taiwan strait to manage fisheries resources in the scs [ ] . ideas for cross-strait co-operation in the scs had also been raised by the taiwanese participants. the cross-strait and oversea chinese academic symposium was followed by the hainan and nanhai academic symposium, organized by the department of history, national chengchi university and held in taipei on - october . originally there were participants from different cities of mainland who were invited and planned to attend the symposium. suddenly the organizing committee was informed that all of the invited chinese participants decided to cancel their trip to taiwan. the main reason for the cancellation obviously was president lee teng-hui's visit to cornell university in the united states in june . after the visit, the cross-strait relations deteriorated. the tension in the taiwan strait area was escalated and reached to the peak in march , when china decided to ''test-fire'' its missiles in the water areas near taiwan's two largest sea ports, keelung in the north and kaohsiung in the south, to intimidate taiwan and therefore influence the outcome of the presidential election. the deteriorating relations between taiwan and china made it impossible for the cross-strait exchange of views on the scs issues to be continued. while the chinese participants could not attend the symposium on the scs issues, they sent their papers on different subjects in relation to the hainan and scs issues to the organizing committee in advance, possibly before the final decision made by their authority to cancel the trip. however, it is worthwhile to read the paper prepared by zhao enbo, the then section chief of office of laws and regulations at the state oceanic administration. he stated in the paper that in recent years, at a series of local meetings, and academic symposia held in mainland and taiwan surrounding the spratly islands issues, experts and scholars from the two sides of the taiwan strait have had a wider contact, and reached a consensus on many issues, which laid the foundation for the crossstrait co-operation to take concrete actions in the spratly islands. it is assumed that the timing for the two sides of the taiwan strait to adopt jointly concrete actions has become matured, with the needed conditions [ ] . he then proposed that china and taiwan could begin with co-operation in joint oil and gas exploration activities and then the development of fisheries resources in the spratly area. the taiwanese participants, in particular, professor fu kuen-chen of national taiwan university, urged that the common position taken by the two sides of the taiwan strait should be actively utilized, and that china and taiwan should co-operate ''equally'' on the following issues: ( ) to study how those countries surrounding the semi-enclosed sea could proceed to co-operation in accordance with article of the united nations convention on the law of the sea; ( ) to study and sort out the content of china's preferential rights in the ushaped historic waters within the scs; ( ) to delimit and announce the archipelagic waters in the paracel islands and spratly islands and control the foreign passage through the waters; ( ) to decide and draw the identical base points and baselines off the chinese coasts; ( ) to collect, preserve, and publish those historical evidence found in taiwan, china, france, and japan; ( ) to conduct underwater shipwreck and archaeological works in the waters surrounding the paracel islands and spratly islands; ( ) to conduct joint marine scientific investigating activities; ( ) to exchange weather information and research; ( ) to draw and exchange satellite images and sea charts; and ( ) to conduct survey of fisheries resources [ ] . the items for crossstrait co-operation were proposed in the crossstrait scs symposium held in taipei at soochow university. he also listed the following possible areas for cross-strait co-operation: ( ) china and taiwan conduct joint oil and gas exploration activities in the waters of the scs where are not disputed by the neighboring countries; ( ) the development of marine tourism on the paracel islands and spratly islands and their surrounding water areas; ( ) the establishment of a military warning system in the spratly islands; or ( ) the establishment of a oil pollution prevention warning cooperative mechanism [ , p. ] . after years of suspension, the cross-strait exchange of views on the scs issues resumed in november . surprisingly, the statement on ''special state-to-state relations'' made by president lee in july to define the cross-strait relations, unlike his trip to the united states in , did not affect the decision of the chinese state oceanic administration and the hainan scs research institute to hold a cross-strait scs academic symposium in haikou, hainan in november . several taiwanese scholars and one former rear admiral were invited to attend the meeting entitled ''academic symposium: the scs in the st century: retrospect and prospect. these taiwanese participants are active advocators of cross-strait co-operation in the scs area. for instance, zhao guochai, a professor from national chengchi university, suggested in his paper that both sides of the taiwan strait should not take counteractions to negate other's claim and interests because of the same position taken on the scs issues. taiwan and china should make every endeavor to safeguard the territorial integrity and legitimate rights in the scs so that foreign countries would not have the opportunity to take advantage of the conflict between taipei and beijing and thus obtain the benefits in the scs from the cross-strait confrontation [ ] . at the meeting, the chinese participants, such as wang peiyun, chief-editor of china offshore oil report, and shu danfu, deputy secretary-general of kwangsi southeast asian research center, called for cross-strait co-operation on the scs issues. wang peiyun pointed out in his paper that while there exist differences between the two sides of the taiwan strait, china and taiwan do have common language and common interests in the spratly islands. china would obtain advantages in the spratly islands if china and taiwan could co-operate. shu danfu also urged to utilize the cross-strait consensus on the spratly issues and then develop co-operation to protect the rights and interests of the chinese people. at the meeting, for the first time, a paper prepared by ma yin of shanghai asean research center examined the shift of taiwan's scs policy. ma yin listed three changes she observed: ( ) president lee's government is taking a position not to co-operate with china on the spratly issues; ( ) taiwan gives up the sovereignty claims in the historical waters within the scs; and ( ) taiwan intends to invite the united states and japan to involve in the scs issues. she interpreted the changes as taiwan's strategy to split china, move to independence, and to break the international political myth of ''one china''. therefore, she suggested that china should take actions to disclose and criticize president lee's ''two states statement'', and prevent his goal of splitting china from becoming a reality. in addition, china should urge taiwanese authority to consider and respect the interest of the chinese people and insist on the principle of ''one china''. in december , the cross-strait exchange and co-operation on scs issues academic symposium, organized by state oceanic administration and hainan scs research institute, was held in sanya, hainan. around scholars and governmental officials attended the meeting, but only three from taiwan. gao zhiguo, director of the institute of ocean development and strategy institute, suggested to increase academic exchange and to promote cross-strait co-operation to safeguard rights and interest in the scs. wang peiyun, chief-editor of the chinese offshore oil report, called for cross-strait joint development of scs resources, in particular oil and gas [ ] . one of the taiwanese participants delivered a paper entitle ''on the scs policy of taiwan's new government,' in which the author compared the positions on the scs policy taken by the kmt government and the dpp government in taiwan. the organizer of the symposium decided not to distribute the paper to the chinese participants because of political consideration, such as the use of official names of the country and governmental officials used by the taiwanese participant in his paper. one important discussion at the cross-strait exchange and co-operation on scs issues academic symposium needs to be mentioned before moving to the review of the discussion at the symposium held in taiwan in november . at the sanya scs meeting, the chinese participants raised their great concerns over taiwan's move to replace its marines stationed on the taiping dao (itu aba) with personnel from the coast guard administration. according to a report prepared by the institute of ocean development and strategy institute, which is under china's state oceanic administration, the taiwanese move was interpreted as another practice of president lee's ''two states statement''. it is also believed that the move was taken for the strategic purpose of differentiating taiwan scs policy from china's and was an important indicator of taiwan's adjustment of its security strategy. it is also stated in the report that taiwan's move in the spratly islands would have the potential to make the situation in the scs more complicated and to weaken china's overall safeguarding strength in the scs area. in december , the cross-strait scs issues exchange and co-operation academic dialogue meeting was held in tao-yuan, taiwan. around taiwanese and chinese scholars and governmental officials attended the meeting. one of the major issues discussed was cross-strait co-operation on the scs issues. it was proposed in a paper prepared by taiwanese participant chung-young chang, professor at central police university, that at the non-governmental level, the two sides of the taiwan strait may ( ) study the possibility of setting up a permanent, institutional co-operative mechanism and exchange channel to help ordinate those research institutions, universities or graduate schools that are involving in the scs research; ( ) encourage the private research article in press ''let the chinese people in the st century understand [the importance] of the spratly islands,'' paper presented at the meeting, in chinese. ''spratly disputes and the policy measures that should be adopted by our government,'' paper presented at the meeting, in chinese. ''the changing attitudes of taiwanese authority on the spratly islands and its impact on the situation of the scs,'' paper presented at the meeting, in chinese. institutions, public interest groups, or professional associations to conduct the scs-related research; and ( ) encourage and assist the relevant industries or private institutions to co-operate and jointly to conduct investigation, exploration, and development of the scs resources [ ] . at the governmental level, he suggested, the agencies of the two sides of the taiwan strait in charge of marine affairs and the scs issues ( ) should go through academic units, research institutions or associations to establish the cross-strait linkage, working relations; ( ) should consider establishing a joint patrol mechanism in the scs to help maintain safety of navigation at sea, maintain fisheries order, protect marine ecological conservation, and prevent smuggling, drug trafficking, and illegal activities at sea; and ( ) should provide funds, through foundations or academic institutions, to support and encourage the proceeding of the cross-strait co-operative project on the scs issues and to help increase the awareness of the people on the importance of the scs issues [ , p. ] . lee guochang, a chinese research fellow from china's social sciences academy, chen hungyu, a taiwanese professor from national chengchi university, zhou zhonghai, a chinese professor from china politics and law university, and wen-chen lin, a taiwanese professor from natonal sun yat-sen university, made the similar remarks at the meeting. however, before setting up the co-operative mechanism, lee guochang suggested, the two sides of the taiwan should consider the areas and scope of the co-operation and exchange of views. the scientific research and economic development areas should be included in the cross-strait co-operation. but more importantly, communication is first needed [ ] . chen hungyu pointed out that at this current stage, there are difficulties for the cross-strait co-operation on the scs issues at the governmental level [ ] . zhou chonghai stated in his paper that the objective for the cross-strait co-operation is to promote peaceful reunification and to safeguard national rights and interests. the basis for this cooperation is ''one country two systems, and peaceful unification''. he listed the following possible direction, scope and concrete items for the cross-strait cooperation on the scs issues: ( ) to ensure china's ownership over the islands in the scs area in accordance with international law; ( ) to discuss and prove the status of the scs in accordance with international law and international law on recognition; ( ) to empower china's rights and fulfill its obligations in the scs in accordance with the united nations convention on the law of the sea; ( ) to proceed with research and co-operation on the fisheries preservation, protection, development and utilization in the scs area; ( ) to proceed with co-operation on marine scientific research; and ( ) to study the possibility of joint exploitation of oil resources in the scs. the approach taken should include three steps: making the co-operative plan, setting up a co-operative fund, and then establishing a coordination mechanism [ ] . the consensus reached at the cross-strait scs issues exchange and co-operation academic dialogue meeting on the possibility of setting up a cross-strait scs forum was further discussed at a special meeting held in haikou, hainan province, china on october , . two representatives from taiwan were invited to attend the meeting. it is clear that the idea of setting up a cross-strait scs forum had been approved before by the chinese government in beijing, since a copy of draft by-law for the cross-strait scs forum was prepared for discussions at the special meeting. in fact, the main purpose of the meeting, as decided by the host hainan scs research institute, was to adopt the by-law that will govern the operation of the cross-strait scs forum if established. under the by-law, the official name of the forum is: cross-strait non-governmental academic forum on the scs issues,'' abbreviated as ''cross-strait scs forum''. the goal of the forum is ''to safeguard the territorial integrity and maritime interests of the chinese people in the scs, to integrate, develop and expand the power of the cross-strait in studying the scs issues, to promote the cross-strait academic exchange and cooperation, to increase the depth and width of the research on safeguarding scs rights and interests, and to co-ordinate the positions and claims of the academic institutions against foreign countries on the scs issues. a secretariat will be set up, respectively, in taiwan and china to be responsible for communication matters between the two sides. the secretariat is also in charge of issuing news release, organizing the forum's preparatory meetings, coordinating with the countersecretariat across the strait to draft or amend the by-law, and to raise funds for the forum activities. the forum meetings will be held alternatively in hainan and taiwan without fixed dates. the two secretariats, after obtaining the permission from the authors, could either respectively or jointly publish the papers delivered at the meeting. the two secretariats of the forum may accept financial support from contributors to cover the expenses for daily administrative works and hosting of academic symposia, but no conditions considered inconsistent with the goals of setting up the cross-strait scs forum should be attached for the financial contributions. due to the fact that the two taiwanese representatives were not instructed to talk about the adoption of the by-law, in addition to several political and administrative concerns raised by taiwan's counter- institute, national chengchi university thereafter, the idea for setting up the cross-strait scs forum remains a matter to be discussed between the two sides of the taiwan strait at other meetings. over the past years, as mentioned in the review done earlier, quite a few new and old ideas that advocated the cross-strait co-operation on the scs issues have indeed been raised by scholars from taiwan and china, in particular, at the cross-strait scs academic symposia held in two sides of the taiwan strait. however, it is noticed that most of the recommended items for the co-operation fall in the category of ''low politics'', which call for cross-strait cooperation in the areas of marine scientific research, marine environmental protection, combating piracy, armed robbery, and illegal activities at sea, exploration and development of natural resources, and other technical and functional matters. table summarizes the areas for the cross-strait co-operation on the scs issues that have been proposed over the last decade or so. table demonstrates that no items for the crossstrait co-operation on the scs issues are considered ''high politics'' matters. the taiwanese scholars and governmental officials have been asking for participation in the regional track one security dialogue mechanisms that also deal with the scs issues. but china insists on the exclusion of taiwan from the process because of the concern over the risk of helping upgrade taiwan's international status. china, for instance, has been blocking taiwan's involvement in the process of developing a regional code of conduct in the scs. even though it is a track two dialogue mechanism, china has been adopting the same strategy to block taiwan's proposal for hosting technical or group of expert meetings on technical matters such as shipping and safety of navigation in the scs. in fact, taiwan is the only participating party in the scs workshop process that has never had the chance to host twg or gem meetings (see table ). why so? again, because china is worried about the risk of upgrading or strengthening the diplomatic relations between taiwan and member states of the asean, which is interpreted by the policy makers in beijing as a violation of the principle of ''one china''. there is no possibility for the proposed areas of scs co-operation being accepted if they are considered not abiding by the principle of ''one country, two systems'' or ''one china, joint development''. indeed there exist several major obstacles to the implementation of the cross-strait cooperation in the scs, which are unlikely to be overcome in the near future. as pointed out by professor steven kuan-tshy yu, the insistence on the principle of ''one china'' by china and taiwan's being forced to adopt a strategy of ''pragmatic diplomacy'' to counter china's diplomatic blockade are the main barriers to any ideas of crossstrait co-operation in the scs [ ] . from the perspective of taiwan, if taipei co-operates closely with beijing government in the scs, its foreign policy goal of improving diplomatic relations with member states of the asean would then be jeopardized. professor hung-yu chen listed a number of obstacles to the improvement of cross-strait relations and the implementation of co-operative projects in the scs area, which include: ( ) ideological differences between the two sides; ( ) limitation on contact between the taiwanese and chinese officials; ( ) china's political and military intervention in taiwan's domestic politics and presidential election; ( ) china's misinterpretation of the consensus reached between beijing and taipei in singapore in ; ( ) china's successful attempt to prevent taiwan from attending the apec summit held in shanghai in october ; ( ) the co-operation on scs issues involving the sensitive issue of sovereignty; and ( ) actions taken by china to prevent taiwan from participating in the regional and international security dialogues [ ] . chung-young chang also stated in his paper presented at the cross-trait scs issues exchange and co-operation academic dialogue meeting that if taiwan adopts a position identical with china's, it would not only alienate its bilateral diplomatic relations from the member states of the asean, but also imply taiwan's acquiesce in the principle of ''one china'', which, as a result, would make its sovereign status and independent entity subject to doubt [ ] . wen-chen lin argued that china's military threat against taiwan is the major obstacle to the cross-strait co-operation in the scs. china's diplomatic suppression also makes it impossible for taiwan to trust china on the scs issues. how can taiwan co-operate with china if beijing continues to impose embargo against taiwan's proposal to host twg or ge meetings within the track two framework of scs workshop? [ ] . kuen-chen fu called for a cross-strait co-operation on the scs issues based on equality and listed the following difficulties in the crossstrait co-operation on the scs issues: ( ) shortage of financial support from the governments in taiwan and china; ( ) taiwan's being discriminated by china without fair treatment; and ( ) both taiwan and china are concerned about the reaction of the member states of asean to the cross-strait co-operation in the scs [ ] . the shift from a direct and indirect confrontation to co-operation between china and member states of the asean on the scs issues has the potential to alleviate taiwan's concern that its move toward a closer crossstrait co-operation in the scs area would jeopardize its foreign policy goal of improving bilateral relations with the member states of the asean and the association as a whole. but, on the contrary, it can be argued that the development of a closer cross-strait co-operative relationship between taipei and beijing could also help improve taiwan's bilateral relations with the member states of the asean. as a result of improvement of the cross-strait relations in the scs, taiwan might be invited to participate in the proposed joint projects between china and member states of the asean based on the guidelines underlined in the scscop declaration, provided that flexible arrangements are found and accepted by the parties concerned. in addition, the rising power and influence of china in total brunei cambodia indonesia laos malaysia china philippines singapore taiwan thailand vietnam total a a special scs meeting on funds was held in jakarta in august . the international affairs in general and in the scs area in particular would have the impact of discouraging member states of the asean to take actions that challenge the principle of ''one china''. as a result, it would become less necessary for china to apply the ''one china'' principle to the cross-strait relations and its foreign relations with member states of the asean in a rigid manner as it did before. in short, a win-winwin-win approach should be considered seriously for adoption by the chinese policy makers, in particular if the cross-strait co-operation in the scs are at issues. flexible arrangements and other creative measures, reflected in the practice of international governmental organizations such as apec, wto, wcpfc, and others, could be followed to help promote cross-strait co-operation in the scs area. as a matter of fact, taipei and beijing has been cooperating on the issue of oil and gas exploration in the taiwan strait and northern part of the scs area since the early s. in december , for instance, authorities in hainan province of china proposed joint exploitation of natural resources in the scs with taiwan. in addition, some investors from taiwan also proposed the establishment of a ''south china sea development funds'' for joint fishing and crude oil exploration in the area of the sea not involved in sovereignty disputes with vietnam and other member states of the asean. in october , two state-run oil companies from china and taiwan met in singapore to discuss the possibility of joint oil exploration in the east china sea and scs. in july , taiwan and china finally agreed their first ever upstream joint venture with the signing in taipei of a -year exploration and surveying accord for acreage in the scs [ ] . in , it was also reported that china national offshore oil corporation (cnooc) and taiwan's chinese petroleum corporation (cpc) would begin a joint oilexploration project in the scs in august of that year. in may , taiwan's cpc and china's cnooc agreed to postpone their joint wildcat drilling program in the scs block as severe acute respiratory syndrome (sars) continued to ravage the greater china region [ ] . in addition to the cross-strait co-operation on oil exploration, the two sides have also been co-operating on the maritime safety measures. in november , the taipei-based china rescue association and its mainland counterpart, the china marine rescue center, agreed to set up a hotline to facilitate marine rescue work in the taiwan strait. under the agreement, when marine accidents occur, involving vessels from taiwan and china, the vessels in distress and the rescuing vessels may use the hotline to ask for help and request permission to enter the waters and harbors of the other side. it was also reported in february that the border defense corps of fujian province of china would explore channels with taiwan for jointly maintaining cross-strait security and co-operation. allen, a senior associate in the cbm project at the henry l. stimson center, concluded in his study of military cbms across the taiwan strait that ''it is unlikely there will be any significant movement toward military cbms across the taiwan strait until there is movement on political issues [ ] ''. this is also true for the movement of cross-strait co-operation in the scs area. as pointed out by allen, two of the most important cbms in the cross-strait relations are: ( ) the unilateral declaration made by beijing, promising not to use force to reunify taiwan with the mainland; and ( ) the announcement made by taiwan not to declare independence [ , p. ]. while president chen shui-bian made his ''four nos'' commitments during his inaugural speech, pledging that during his term in office, he would not declare independence, not change the national title, not push for the inclusion of the socalled ''state-to-state'' description in the constitution, and not promote a referendum to change the status quo in regards to the question of independence or unification, china has never renounced its policy to use force against taiwan. it should be noted that the ''four nos'' commitments were made under the pre-condition of ''rapprochement, co-operation and peace''. but clearly the policy makers in beijing do not trust president chen. the recent move made by china to block taiwan's efforts to join the world health organization (who) in may generated a series of counter-measures adopted by taiwan, in particular, advocating a ''referendum'' to join the who and revising its constitution. the recent developments in taiwan have sparked new tension in the cross-strait relations. under the current situation, it seems remote for the realization of the establishment of a closer relationship between taiwan and china on the scs issues. however, it is likely that the cross-strait relations would move toward a different direction when the presidential election ends in march . while it is still subject to debates, it seems that the chance for the cross-strait co-operation on the scs issues would be bigger if the pan-blue camp wins the election. if the pan-green camp wins the election, however, the possibility for adopting cbms between taiwan and china in the scs area can never be ruled out either, given the fact that president chen might renew his call for rapprochement and co-operation with china. accordingly, the following declaration, communications, transparency, and constraint cbms are listed for consideration by the policy makers in beijing and taipei: * exchange of visits by scholars and retired military officer to the occupied pratas islands (taiwan), paracel islands (china) , and spratly islands (taiwan and china) in the scs. * declaration of not use of force or not threat to use force against each either in the scs area. * exchange of monitoring information on activities taken by other claimants in the area of the sea in the scs that are also claimed by taiwan and china. * setting up hotlines or notification mechanism to assist stationed military and coast guard personnel in the occupied islands and fishermen operating in the claimed waters in maritime rescue. * pre-notification, on voluntary basis, of the military exercises to be conducted in the scs area. * avoidance of entering the waters or flying over the zones in the scs, that are considered by each other as sensitive in terms of security and military defense. * inviting national security academics and retired military personnel to attend the cross-strait scs conferences held either in taiwan or china for discussions on scs issues. * dispatching national security academics and military personnel to attend international meetings on the scs issues. * setting up a cross-strait scs academic forum that is based on the principle of equality. * organizing friendship sports games on the occupied spratly islands in the scs. * conducting cross-strait anti-piracy, anti-maritime terrorism, and search and rescue joint exercises in the scs areas. * encouraging member states of the asean to invite taiwanese scholars and governmental officials to attend regional track one or track two scs dialogues; at the same time, discouraging taiwan's attempt to take advantage of the chance to participate to achieve other political and diplomatic goals. * making a flexible arrangement to allow taiwan to participate in the process of developing a regional code of conduct in the scs. * finding a way to enable taiwan to participate in the joint projects to be implemented in the scs in accordance with the guidelines underlined in the scscop. it is possible for taiwan and china, in and the years that follow to move toward strengthening the cross-strait co-operation on the scs issues. the cooperative actions taken in the scs area could enhance mutual trust between the two sides of the taiwan strait. if china and member states of the asean can reach agreements to move from confrontation to co-operation in the scs area, there are more reasons to believe that taiwan and china should do the same thing. the cbms suggested in the paper are welcomed to be considered seriously by the policy makers of the two sides of the taiwan strait. it is believed that the adoption of the proposed cbms will not only help improve the crossstrait relations, but also assist in maintaining stability and peace in the taiwan strait and the scs areas. all of the people in the region would benefit from the adoption of the proposed ''win-win-win-win approach'' by china as urged in this paper. hainan proposes economic cooperation with roc cross-strait cooperation 'a long way off' after china-taiwan talks hotline to facilitate rescue work in taiwan strait fujian seeks taiean coopearation on fighting crimes at sea the statement can be found in us interest in southeast asia, hearing before the subcommittee on international economic policy and trade and the subcommittee on asia and the pacific of the committee of international relations, house of representatives, th congress compilation of the literature on the south china sea issues policy of the republic of china towards the south china sea chinese); for the discussion of the event, graver jw. china's push through the south china sea: the interaction of bureaucratic and national interests an analysis of the current situation in the scs, its prospects policy of the republic of china towards the south china sea. appendix : policy guidelines for the south china sea thoughts on how to proceed to historical evidence research and compilation on the scs islands the scs sovereign, historical research: archaeological works in the paracel islands and spratly islands marine environmental protection, the exploration of cross-strait co-operation assessment, development and utilization of the oil and gas resources in the spratly of the scs current situation of fisheries resources in the scs, prospects for management current situation, analysis of prospect the legal status of the scs, the possibility of cross-strait equal co-operation analyzing the sovereignty disputes over the spratly islands in accordance with the modern law of the sea the situation, mission in the scs at the turn of the century. papers presented at the meeting promote ocean culture, consolidate the cross-strait joint power to establish a cross-strait co-operative, exchange mechanism and fixed channel on the scs issues taiwan and scs islands over the past years possible direction and areas for the cross-strait cooperation on the scs issues possible direction, scope and concrete items in the cross-strait co-operation on the scs issues case study of pragmatic diplomacy, the crossstrait relations: comparing the position and policy taken by the two sides of the taiwan strait on the sovereignty issues in the scs. paper presented at the symposium on pragmatic diplomacy and cross-strait relations, organized by the department of political science possible co-operative direction, areas of the cross-strait in the scs issues. prepared for the dialogue and co-operation of the cross-strait on the scs issues possible co-operative direction and areas of the cross-strait in the scs issues. prepared for the dialogue and co-operation of the cross-strait on the scs issues possible co-operative direction and areas of the cross-strait in the scs issues. prepared for the dialogue and co-operation of the cross-strait on the scs issues the legal status of the scs and the possibility of cross-strait co-operation on equal footing. paper presented at the hainan and nanhai academic symposium taiwan plan to explore s. china sea taiwan and china sign historic upstream deal. platt's oilgram news taiwan postpone drilling jv on sars fears investigating confidence-building measures in the asia-pacific region key: cord- - ctp bem authors: liou, bo-huang; duh, ruay-wang; lin, yi-tsung; yang lauderdale, tsai-ling; fung, chang-phone title: a multicenter surveillance of antimicrobial resistance in serratia marcescens in taiwan date: - - journal: j microbiol immunol infect doi: . /j.jmii. . . sha: doc_id: cord_uid: ctp bem background: serratia marcescens is an important nosocomial pathogen and the characteristic property of resistance conferred by extended-spectrum beta-lactamase or a novel ampc cephalosporinase was not unusual in taiwan. this study investigated the trends in antimicrobial resistance in s. marcescens from a nationwide surveillance in taiwan. materials and methods: s. marcescens isolates were collected biennially between and from medical centers and regional hospitals throughout taiwan, as part of the taiwan surveillance of antimicrobial resistance program. minimal inhibitory concentrations were determined by the clinical and laboratory standards institute reference broth microdilution method. results: a total of nonduplicate s. marcescens isolates were collected, mostly from respiratory samples ( , . %), followed by the urinary tract samples ( , . %). overall, . % isolates were susceptible to imipenem, . % to ceftazidime, . % to minocycline, . % to amikacin, . % to cefepime, . % to aztreonam, . % to ceftriaxone, . % to levofloxacin, . % to ciprofloxacin, . % to trimethoprim/sulfamethoxazole (tmp/smx), and . % to gentamicin. a significantly increased susceptibility rate after was observed for the following antibiotics: amikacin ( . % vs. . %), gentamicin ( . % vs. . %), ciprofloxacin ( . % vs. . %), ceftriaxone ( . % vs. . %), cefepime ( . % vs. . %), aztreonam ( . % vs. . %), and tmp/smx ( . % vs. . %). conclusion: in this -year study, the susceptibility of s. marcescens to ceftazidime and imipenem remained consistently high in taiwan. s. marcescens isolates demonstrated relatively higher resistance to ciprofloxacin and levofloxacin, and therefore continued surveillance of antimicrobial resistance, especially for fluoroquinolone, is warranted. serratia species are identified as aerobic, motile gramnegative rods, which occupy various habitats (mainly water, plants, and soil). human infections by members of the genus serratia were not well recognized until the latter half of the th century. serratia marcescens accounts for the majority of isolates and appears to be a pathogen capable of causing a wide spectrum of clinical diseases, including wound infections, urinary tract infections, pneumonia, central nervous system infections such as meningitis, and bloodstream infections. e although s. marcescens is a rare cause of communityacquired infections, it has emerged as an important nosocomial pathogen that has been cultured from a variety of sources, including disinfectants, e pressure transducers, bronchoscopes, and multidose medication vials. factors such as debilitating clinical condition, lengthy ward stay, exposure to medical interventions, and increased frequency and intensity of direct contact with staff hands predispose patients to s. marcescens infection. s. marcescens isolates account for . % of nosocomial urinary tract infection and resulted in . % fatality in a single institute in taiwan. although s. marcescens has a relatively low virulence, it often causes nosocomial infections in severely immunocompromised or critically ill patients. , the mortality rate of s. marcescens bacteremia was approximately e % in previous studies. , s. marcescens is usually resistant to ampicillin, amoxicillin, amoxicillin/clavulanate, ampicillin/sulbactam, narrow-spectrum cephalosporins, cefuroxime, cephamycins, nitrofurantoin, and colistin. , e s. marcescens also harbors a chromosomal ampc gene that can extend resistance to several more b-lactam antibiotics. in a nationwide surveillance of antimicrobial resistance from taiwan in , over half ( %) of s. marcescens were resistant to ciprofloxacin, %, %, and % were resistant to cefotaxime, aztreonam, and cefepime, respectively. however, many studies in recent years suggested that the occurrence of extended-spectrum beta-lactamase (esbl)producing isolates of s. marcescens was not unusual in taiwan. , , e in addition, an institutional prolonged spread of clonally related s. marcescens isolates with a novel ampc cephalosporinase (s ) that confers a phenotype of resistance to cefotaxime was identified. therefore, continuous and extensive surveillance of the antimicrobial resistance among s. marcescens isolates is necessary in taiwan. the aim of this study was to investigate the trends in antimicrobial resistance in s. marcescens from a nationwide surveillance in taiwan. isolate collection and identification s. marcescens isolates were collected biennially between and , corresponding to periods iiievii of the taiwan surveillance of antimicrobial resistance (tsar) program, from medical centers and regional hospitals throughout taiwan. in were collected between july and september from the same hospitals, except that isolates in were from hospitals. , these hospitals comprised medical centers and regional hospitals, which are located in all four regions of taiwan, namely seven, eight, eight, and three hospitals in the north, central, south, and east regions, respectively. details of the collection process of the tsar program have been described previously. , , each isolate was subcultured onto the appropriate agar plates (bbl; becton dickinson microbiology systems, cockeysville, md, usa) to check for purity. s. marcescens was identified by standard conventional biochemical tests followed by confirmation with the vitek gram-negative identification plus cards (biomérieux vitek, hazelwood, mo, usa), and analytical profile index (api) e or api gn (biomérieux, marcy-l'etoile, france). antimicrobial susceptibility was determined by the reference broth microdilution method using freshly prepared cation-adjusted müellerehinton broth and following the criteria proposed by the clinical and laboratory standards institute (clsi). minimum inhibitory concentration (mic) interpretive criteria were defined by the clsi guidelines for all drugs except tigecycline, for which the u.s. food and drug administration breakpoints were used. all analyses were performed with spss version . (spss inc., chicago, il, usa). significance of differences in frequencies and proportions were tested by pearson c test, and p . was considered to be statically significant. a total of nonduplicate s. marcescens isolates were identified and tested for susceptibility during the -year study period of e . table summarizes the source breakdown of the isolates from each run of tsar. isolates were mostly recovered from respiratory samples ( isolates, . %), followed by the urinary tract ( , . %), and blood ( , . %). most isolates ( , . %) were from inpatients, including ( . %) from the intensive care unit (icu) and ( . %) from non-icu patients. isolates from northern taiwan comprised the largest proportion ( , . %). among the isolates whose patient age was known, the mean age was . ae . years and . % were from those aged ! years. the in vitro susceptibilities, mic , mic (mic at which % and % of isolates were inhibited), and mic range of the isolates to various antimicrobial agents are shown in table . overall, . % of isolates were susceptible to imipenem, . % to ceftazidime, . % to piperacillin/ tazobactam, . % to levofloxacin, . % to ciprofloxacin, . % to trimethoprim/sulfamethoxazole (tmp/smx), and . % to gentamicin according to the clsi criteria. by contrast, susceptibility of % for each round of tsar was observed for ampicillin, amoxicillin/clavulanate, cefazolin, cefoxitin, cefuroxime, and tetracycline. the mic and mic of tigecycline were . mg/ml and mg/ml, respectively. the susceptibility rate of s. marcescens from different patient locations was compared (table ) . isolates from the icu had higher rates of nonsusceptibility than isolates from other locations for amikacin, gentamicin, ciprofloxacin, levofloxacin, ceftazidime, cefepime, and tmp/smx, but the differences were not significant. the susceptibility rate to ciprofloxacin/levofloxacin was lower in northern taiwan than other regions (p z . and p z . , respectively). fig. illustrates the comparison of susceptibility rate for selected antibiotics from different specimen sources. we found that isolates from urine had the lowest susceptibility rate for the various antibiotics. isolates from urine were significantly less susceptible than those from nonurine sources for amikacin ( a others: one from ascites, one from joints, two from bile, four from ears, seven from catheter tips, four from eyes/conjunctiva/ corneas, one from urethra, and one from discharge. b included six isolates from respiratory care center/respiratory care ward. er z emergency room; icu z intensive care unit; opd z outpatient department; tsar z taiwan surveillance of antimicrobial resistance program. data are presented as n (%). in the present study, we examined trends in susceptibility to multiple antibiotics for nonduplicate clinical s. marcescens isolates in taiwan between and . the results show that the activities of ceftazidime and imipenem have remained consistently high over the years. susceptibilities of % for each round of tsar were observed for ampicillin, amoxicillin/clavulanate, cefazolin, cefoxitin, cefuroxime, and tetracycline. fluoroquinolones showed less activity against s. marcescens than other blactams. in taiwan, the occurrence of ctx-m- esbl-producing isolates of s. marcescens was not unusual, , , e and the novel ampc cephalosporinase (s ) was reported previously. the distinctive property of resistance to cefotaxime but not ceftazidime was due to ctx-m- esbl and srtlike ampc such as s conferring the same phenotype of resistance to cefotaxime. the antibiogram-based method to simplify the screening of potential esbl-producing populations among s. marcescens isolates has also been reported recently. although the molecular characteristics of isolates were lacking in the current study, the higher susceptibility of ceftazidime than ceftriaxone corresponded to the previous studies, , , e and further underlined the need to establish practical guidelines for esbl screening, confirmation, and reporting for chromosomal ampc producers in taiwan. in the tigecycline evaluation and surveillance trial study, isolates of s. marcescens collected globally between and with susceptibilities ! % were observed for amikacin, levofloxacin, ceftazidime, cefepime, imipenem, meropenem, piperacillin/tazobactam, and tigecycline. a similar study conducted by hawser et al collected clinical isolates of s. marcescens throughout the asiaepacific region between and and demonstrated constantly high susceptibility to levofloxacin ( e %). a characteristic finding in the present study was the much lower susceptibility to levofloxacin and ceftriaxone compared with the global data. susceptibility to levofloxacin in the current study was only tested between and , but susceptibility to ciprofloxacin was tested throughout the study period. the much lower susceptibility to ciprofloxacin suggests that resistance to fluoroquinolones is the major concern surrounding drugresistant s. marcescens in taiwan. the susceptibility rate to ceftriaxone was e % between and in the asiaepacific region, which is consistent with our findings. hawser et al also demonstrated a decline in susceptibility to minocycline (decreased to e % in e ) and tigecycline in s. marcescens. by contrast, susceptibility to minocycline and tigecycline tested in in the present study showed higher susceptibility rates of . % and . %, respectively. shih et al found that % of s. marcescens blood isolates in e were sensitive to ceftazidime, but only % were sensitive to ciprofloxacin, % to levofloxacin, and % to tmp/smx in a single institute in taiwan. the high susceptibility rate of ceftazidime is consistent with the current study. a previous nationwide surveillance of antimicrobial resistance among enterobacteriaceae at the icus of major teaching hospitals in taiwan in reported low susceptibility of s. marcescens to ciprofloxacin ( %) and levofloxacin ( %). despite_enref_ the present study showing increased susceptibilities to ciprofloxacin ( . %) and levofloxacin ( . %) compared with previous results in taiwan, the resistance to fluoroquinolones continues to be a problem in taiwan. examination of trends in antimicrobial susceptibility has revealed higher resistant rates for amikacin, gentamicin, ciprofloxacin, ceftriaxone, cefepime, aztreonam, and tmp/ smx prior to than those after that date. the higher proportion of isolates recovered from urine between and may have influenced the results. the significantly higher proportion of isolates recovered from urine between and ( . %) than that after ( . %, p < . ) may have influenced the results. the reasons why isolates from urine had the lowest susceptibility rate for the various antibiotics cannot be clearly defined. it might imply that we should put more focus on the resistance pattern in the urinary isolates. in addition, after the emergence of severe acute respiratory syndrome in , the reinforcement of prevention of health care-associated infection in hospitals resulted in a more cautious approach to intervention with antimicrobials as a part of the infection control policy. the trends in total consumption of aminoglycosides, extended-spectrum cephalosporins, and fluoroquinolones significantly increased prior to and remained stable after in the hospital-wide investigation. , the reduced consumption of antibiotics in taiwan may explain the observation of greater susceptibility after in the present study. we recognize a number of potential biases in the present study. the first limitation concerns the specimen types. isolates from the urinary tract showed higher resistance rates to many antibiotics than those from other sites; therefore, the higher percentage of urine specimen prior to may result in lower overall susceptibility in this period. second, < % of isolates were collected from eastern taiwan and the data are likely to have underestimated the events occurring in this region. third, we did not analyze the resistant mechanism due to the lack of molecular method such as multiplex polymerase chain reaction screening of ampc genes in these s. marcescens isolates. finally, given the limited clinical information from this surveillance, we cannot exactly determine the clinical significance of these isolates. in conclusion, the results of this study suggest that the susceptibility of s. marcescens to ceftazidime and imipenem in taiwan remained consistently high over the study period. s. marcescens isolates from taiwan demonstrated relatively higher resistance to ciprofloxacin and levofloxacin than other b-lactams, and continued surveillance of antimicrobial resistance in s. marcescens, especially for fluoroquinolones, is warranted. tsar is ongoing in taiwan involving clinically important bacteria. the longitudinal surveillance study will continue to provide key information related to antimicrobial resistance over time. the authors declare that they have no conflicts of interest. serratia infections: from military experiments to current practice serratia marcescens: historical perspective and clinical review population-based laboratory surveillance for serratia species isolates in a large canadian health region epidemiology and antimicrobial susceptibility profiles of gramnegative bacteria causing urinary tract infections in the asia-pacific region: e results from the study for monitoring antimicrobial resistance trends (smart) nosocomial urinary tract infection with serratia marcescens: an epidemiologic study serratia marcescens meningitis: epidemiology, prognostic factors and treatment outcomes an outbreak of serratia marcescens infections related to contaminated chlorhexidine serratia marcescens outbreak associated with extrinsic contamination of % chlorxylenol soap hand washing soap as a source of neonatal serratia marcescens outbreak epidemic bloodstream infections associated with pressure transducers: a persistent problem an outbreak of serratia marcescens traced to a contaminated bronchoscope serratia liquefaciens bloodstream infections from contamination of epoetin alfa at a hemodialysis center independent prognostic factors for fatality in patients with urinary tract infection caused by serratia marcescens serratia marcescens bacteremia: clinical features and antimicrobial susceptibilities of the isolates serratia marcescens bacteremia at a medical center in southern taiwan: high prevalence of cefotaxime resistance natural antibiotic susceptibility of strains of serratia marcescens and the s. liquefaciens complex: s. liquefaciens sensu stricto, s. proteamaculans and s. grimesii confirmation of extended-spectrum beta-lactamase-producing serratia marcescens: preliminary report from taiwan survey of ctx-m- extended-spectrum beta-lactamase (esbl) among cefotaxime-resistant serratia marcescens at a medical center in middle taiwan the status of antimicrobial resistance in taiwan among gram-negative pathogens: the taiwan surveillance of antimicrobial resistance (tsar) program clinical experiences of the infections caused by extended-spectrum beta-lactamase-producing serratia marcescens at a medical center in taiwan extended-spectrum beta-lactamases in taiwan: epidemiology, detection, treatment and infection control screening extended-spectrum beta-lactamase production in enterobacter cloacae and serratia marcescens using antibiogrambased methods institutional spread of clonally related serratia marcescens isolates with a novel ampc cephalosporinase (s ): a -year experience in taiwan emergence of extensively drug-resistant acinetobacter baumannii complex over years: nationwide data from the taiwan surveillance of antimicrobial resistance (tsar) program meca-positive staphylococcus aureus with low-level oxacillin mic in taiwan performance standards for antimicrobial susceptibility testing; twentieth informational supplement. clsi document m -s . wayne: clinical and laboratory standards institute in vitro activity of tigecycline and comparator agents against a global collection of gram-negative and gram-positive organisms: tigecycline evaluation and surveillance trial trending years of in vitro activity of tigecycline and comparators against gram-positive and gram-negative pathogens from the asia-pacific region: tigecycline evaluation surveillance trial (test) nationwide surveillance of antimicrobial resistance among enterobacteriaceae in intensive care units in taiwan correlation between antibiotic consumption and resistance of gram-negative bacteria causing healthcare-associated infections at a university hospital in taiwan from implementation and outcomes of a hospital-wide computerised antimicrobial stewardship programme in a large medical centre in taiwan we express our sincere appreciation to the hospitals that participated in the tsar program. this project was supported by an intramural grant from the national health research institutes (nhri) (grant nos. id- -pp- and id- -pp- ) and yen tjing ling medical foundation (grant no. ci- - ). we thank the technical staff at nhri for their assistance in identification and antimicrobial susceptibility testing. key: cord- -dybchjfl authors: chang, ko; pan, chao‐ying; lu, po‐liang title: sentinel surveillance at airports: experience of dengue and covid‐ prevention in taiwan date: - - journal: kaohsiung j med sci doi: . /kjm . sha: doc_id: cord_uid: dybchjfl nan these findings revealed that sentinel surveillance at airports detected . % to % of dengue cases and . % of imported covid- cases in taiwan, even though a high number of passengers were screened and the positive rate of symptomatic passengers was low. in addition to sentinel surveillance, other interventions at airports such as onboard quarantine announcements and home quarantine notices delivered to each passenger highlight the multidisciplinary measures at national gates required to effectively prevent the spread of sars-cov- , especially during the containment stage of pandemic control. transmission of the severe acute respiratory syndrome on aircraft epidemiologic and clinical characteristics of hospitalized patients with covid- in zhejiang, china: a retrospective, multi-centre case series airport sentinel surveillance and entry quarantine for dengue infections following a fever screening program in taiwan phylogenetic study of dengue- virus in taiwan with sequence analysis of the core gene key: cord- - yao a authors: chiang, wen-chu; ko, patrick chow-in; wang, hui-chih; yang, chi-wei; shih, fuh-yuan; hsiung, kuang-hua; ma, matthew huei-ming title: ems in taiwan: past, present, and future() date: - - journal: resuscitation doi: . /j.resuscitation. . . sha: doc_id: cord_uid: yao a taiwan is a small island country located in east asia. from around modern concepts of the ems were imported and supported by legislation. considerable progress has since been made towards the construction of an effective pre-hospital care system. this article introduces the current status of the ems in taiwan, including the systems, response configurations, funding, personnel, medical directorship, and outcome research. the features and problems of in-hospital emergency care are also discussed. key areas for further development in the country vary depending on regional differences in available resource and population density. an analysis of the strength, weakness, opportunity, and threats of the evolving ems in taiwan could be an example for other countries where the ems is undergoing a similar process of development and optimisation. taiwan is a small island country located in east asia. from around modern concepts of the ems were imported and supported by legislation. considerable progress has since been made towards the construction of an effective pre-hospital care system. this article introduces the current status of the ems in taiwan, including the systems, response configurations, funding, personnel, medical directorship, and outcome research. the features and problems of in-hospital emergency care are also discussed. key areas for further development in the country vary depending on regional differences in available resource and population density. an analysis of the strength, weakness, opportunity, and threats of the evolving ems in taiwan could be an example for other countries where the ems is undergoing a similar process of development and optimisation. © elsevier ireland ltd. all rights reserved. taiwan, previously named formosa (meaning beautiful island) by a portuguese explorer in , is a country consisting of a main island and some smaller islands located in east asia off the southeastern coast of china. the main island is km long and km wide, slightly larger than the combined areas of massachusetts and connecticut, or a little smaller than the netherlands. the population of taiwan was estimated at almost million in july , spread across a land area of , km , making it the th most densely populated country in the world. in fact, the population density should be even higher than estimated because of the topographic character of taiwan. a central mountain range geographically bisects taiwan from north to south which results in two-thirds of the island being covered by forested peaks. most of the population is distributed in four cities (taipei, kaohsiung, taichung, and tainan), as shown in fig. . the uneven population distribution has led to disparities in regional resourcing and has influenced the level of development of the local emergency medical service (ems) system. in the s, a basic ems system (mainly transporting sick and injured patients to hospital by ambulance) was started in taiwan. the system was delegated to police stations with neither well-coordinated communication to the hospital nor well-trained providers in pre-hospital care. although some efforts were made, the situation did not alter for the better until . in that year a formal emergency medical technician (emt) training curriculum was initiated by pioneers of emergency medicine who had studied ems abroad. this initiative was supported by the society of emergency and critical care medicine in taiwan. the year marked the beginning of modern ems in taiwan when a lot of important concepts of ems were put into legislation, the emergency medical service act. the law designated pre-hospital care as a function of fire administration at the central and local level. it also regulated essential ambulance equipment and permitted emts acting as physician surrogates to provide different levels of care based on their levels of certification. in , emergency medicine was recognized as an autonomous medical speciality by the department of health (doh) in taiwan. this landmark facilitated the further development of the ems. over the last eight years, taiwan's ems has undergone rapid development, including the implementation of off-line medical direction, establishment of national disaster response teams, and the introduction of automatic external defibrillators (aed) by emts. enabling the ems to provide fire service based advanced life support (als). new initiatives are close to introduction. these include medical directorship, public-access aed programs, and a nationwide standard for computerized reporting of out-of-hospital cardiac arrests (ohca) and major trauma. the pre-hospital care system in taiwan can be categorized into governmental or privately supported services. the governmental services are all fire-based with three levels of care providers (emt-i, emt-ii, emt-p), and are activated by a universal access number ( ). in some cities, hospital-based als teams, consisting of a physician and a nurse, participated in pre-hospital care of the critically ill but this was temporary and gradually shifted to a fire service based response soon after the introduction of qualified emt-ps into the system. however, due to the limited number of emt-ps, complete pre-hospital als only exists in some urban areas. the primary responsibility of the governmental ems system is to deliver sick and injured patients to hospital and not for secondary transportation (i.e. between hospitals or back home). in contrast to the free governmental service, the private service charges patients. most only have emt- or emt- crews in their ambulances and they play a complementary role to the governmental service by providing inter-hospital transport. for sicker patients, a physician or nurse from the transferring hospital is also required to staff the ambulance. as a local custom, privately supported ambulances also transport dying patients home from hospital because many people wish to pass away at home. the public demand for the ems is increasing. the latest data from the national fire agency (nfa) in the ministry of the interior shows a % annual increase in ems demand over the last ten years. the annual ems call volume was , in , which is equivalent to . calls per , persons per day, or approximately half of the number of ems calls seen in the united states. according to an evaluation carried out in urban taipei, the als demand was estimated at around - % of ems calls , and the average response times were . - . min, , with mean call-to-first shock times for cardiac arrest of . min. in a rural area, the average response time was found to be longer, up to . min. a bypass policy for major trauma or severe illness (e.g. stroke or acute coronary syndrome) is recommended by academic societies but not fully implemented because of insufficient coordination and uncertain accountability between the jurisdiction of the doh and nfa. land ambulances are the main transport mode in the taiwan ems. aero-medical and helicopter transport is limited to emergency events with poor access (i.e. major incidents, off-shore island inhabitants or transplant organ procurement), and requires interagency coordination. a few private companies provide efficient aero-medical evacuation but at a much higher cost. the main funding of ems operations is from general taxation. there is another important resource for public ems in taiwan: donations from taoism or buddhism temples. in many jurisdictions, ambulances are funded by donations from buddhism or taoism temples, as indeed is most ems equipment. this is in line with their obligation to charity. in return, ambulances and equipment bear the names and logos of the temples or charities to honor their contributions. in , there were a total of emts in governmental firestations in taiwan, responsible for fires and pre-hospital care. over % of them were at emt- or emt- level. in july there were only emt-ps (paramedics) across the country, and most were employed in urban areas. since the development of the ems system in taiwan was modelled on the north american paradigm, the pre-hospital care providers and their training program resemble those of their north american counterparts. the national standard training program of emt- is h to ensure competency in vital sign measurement, basic life support (bls) skills and aed operation. the curriculum of emt- level requires h of training and, in addition to the emt- material, includes ecg monitoring, application of the laryngeal mask and pasg (pneumatic anti-shock garment), and some medications, e.g. oral glucose water or intravenous saline. in addition to firemen, volunteers and crews of private ambulance companies are also required to certify as emt- s and emt- s. for entry to the emt-p course (the highest level of pre-hospital care provider), most entrants are selected from the best members of the fire-based emt- course because at present training costs are completely supported by the government. the duration of the curriculum for emt-p is h. the course content is extended to important concepts of medicine, advanced airway management, advanced cardiac life support, pre-hospital trauma life support, paediatric advanced life support, disaster man-agement, and hazmat procedures (hazard identification, action plan, zoning, managing the accident, assistance and termination). they are also required to perform two internships during the training: to practice medical skills under the tutelage of registered nurses and physicians in a tertiary emergency department and to participate in ambulance runs with experienced paramedics in the field. finally, after almost nine months of training, they must pass the examination approved by doh to get the licence. all emt levels are required to recertify by attending approved refresher courses within a prescribed period of time. in , the emergency medical service act of taiwan provided implementation of medical oversight for pre-hospital carers at all levels. physicians on the medical consulting committees (required by law) are responsible for the standards of patient care, including establishment of pre-hospital medical protocols and assistance in education of emts. however, a lack of specific tasking and full-time positions in the fire department for medical directors has resulted in the medical oversight remaining incomplete in terms of protocol revision, quality assurance, system design, and direct medical oversight. the situation improved after july when the amended emergency medical service act stipulated that local fire departments appoint an identifiable physician for medical oversight. ems dispatch in taiwan is performed by experienced fire fighters. however, there are neither formal training courses nor certification available for ems dispatchers. moreover, the standard dispatcher protocol and decision-making steps for delivering als or bls are not well-established in many systems. therefore, appropriate dispatch performance on als cases was only %, and over triage (i.e. dispatching an als team to a bls scene) was very common. besides, the numbers of dispatcher-assisted bystander cpr in ohca were also low according to data acquired in metropolitan taipei. these drawbacks indicate that a standard als dispatch protocol and dispatcher training programs should be established in taiwan. an advantage of the taiwan ems is that the system is still growing and receiving considerable attention from the public and government. during this developing process, ems researchers potentially have the chance to exam the effectiveness and outcome of many newly implemented strategies, such as als performance on cpr quality, [ ] [ ] [ ] [ ] [ ] their effect on outcome of ohca and costeffectiveness analysis. , since taiwan is located at the western pacific seismic belt near mainland china, researchers also have opportunities to evaluate the ems response to catastrophic events like earthquakes or public health emergencies like sars (severe acute respiratory syndrome). [ ] [ ] [ ] this type of research can be used to optimize the pre-hospital care system with data derived from relevant local events. to date most studies have been carried out only in metropolitan taipei. lacking a universal, well-established infrastructure in the ems, data collection for quality assurance and outcome research at the national scale remains currently unavailable. in each jurisdiction, there is an ems advisory committee for the planning and integration of pre-hospital and in-hospital emergency department care. hospital eds that are determined as capable of receiving ambulance patients are designated as ems response hospitals by law. before transporting patients to a hospital ed, ems personnel will contact the nearest ed by radio. when the destination ed is overwhelmed, ems patients may be re-directed to other nearby eds. since emergency medicine was approved as a medical specialty in taiwan, the predominant workforce in the ed are emergency physicians. based on hospital accreditation in taiwan, both doctors and nurses working in the ed are required to certify in acls, atls, or equivalent trauma training courses. some tertiary hospitals are allowed to accept registered residency and rotating trainees including student nurses and emts. the major problem of eds in taiwan is of significant overcrowding, especially among many tertiary hospitals. two systemic causes contribute to this condition: the limited patient flow and undeveloped interfacility transfer rules. under the national insurance of health (nih) for all inhabitants, the medical cost for users is relatively low in taiwan compared to other developed countries. people can seek medical care in any level of hospital they wish, with little difference in cost. political and cultural considerations make the attendance/triage of patients with non-serious problems to suitable eds impossible. solutions for overcrowding are proposed and include creation of a large holding unit, pre-established rules for admission, priority-setting and active interfacility transfer. many evidence-based life-saving strategies for severely sick patients including hypothermia for post-resuscitation care or early goal directed therapy for severe sepsis have been started in some hospitals. although restricted financial resources and overcrowded eds limit the practices above, there is a paradoxical phenomenon of the use of ecmo (extra-corporeal membrane oxygenation) in resuscitation in taiwan. one of the most notable features of tertiary eds is the widespread use of e-cpr (ecmointegrated cardiopulmonary resuscitation) for cardiac arrest and its effects on outcome. the intervention initially arose from a scientific interest in one medical centre, ntuh (national taiwan university hospital), but is now popular in many hospitals because of initial favorable outcome data, patient demands, and payments form the nih. diversity in population density and its geographical distribution heavily influence the distinct blueprints of taiwan ems development in the future. it can be divided into three models: the metropolitan, the outskirt, and the rural system, as shown in fig. . in the metropolitan model (areas marked a), both ems personnel and hospital capacity are abundant. the goal should focus on the full implementation of more evidence-based advanced prehospital interventions and area wide disaster preparedness, and improving the precision of pre-hospital triage and transport. in the rural model (areas marked c), where pre-hospital and in-hospital ems resources are limited, the emphasis should be placed on shortening the ems response time and provision of good quality bls-d care. the local public safety agencies should consider emergency healthcare services as a primary responsibility, not a role secondary to fire fighting or policing. the government should develop aero-medical capability to reduce the time to definite care for critically ill patients in these areas. public education on awareness of severe illness and bystander cpr is also helpful. for the outskirt model (areas marked b), regionalized care for conditions such as trauma or stroke should be facilitated. ems personnel should distribute the patient flow efficiently, including following the bypass rules, even cross-district, and streamlining the interfacility transfer network. beyond all regional aims above, there are two important tasks that must be emphasized in all regions. first and foremost, a universal well-established infrastructure for quality assurance is of paramount importance for the ems in taiwan so that the quality of care and the outcomes of many new integrated interventions in the ems can be evaluated. another priority would be to coordinate various components in the ems. historical events show that coordinating services across county lines is particularly challenging. ems personnel should also promote cooperation in solving problems arising from incidents that cross jurisdictional lines, such as near municipal and county border areas. the ems is unique in straddling medical care, public safety and public health. being a young system in taiwan, the ems has gained momentum in the last decade. the strength of the system is that the development process provides opportunities to integrate new interventions and to evaluate their outcomes. the weaknesses are an immature data collection system for quality assurance and insufficient coordination in the leadership of government healthcare between the doh and nfa. the geographic and demographic characteristics such as frequent natural disasters, public health emergencies and an aging population provide an opportunity to create an efficient system. ems personnel need to be able to show the benefits of their work in terms of improved patient outcomes and patient satisfaction. this will gain the respect and support of other health professionals and make the system a sustainable one. all authors declared no potential conflicts of interest in this report. central intelligence agency, us government emergency physician and the emergency medical service ministry of the interior, taiwan the demand for prehospital advanced life support and the appropriateness of dispatch in taipei ems characteristics in an asian metropolis impact of community-wide deployment of biphasic waveform automated external defibrillators on out-ofhospital cardiac arrest in taipei study of patients arriving by ambulance in taipei city three years' experience of emergency medical services in ilan county evaluation of emergency medical dispatch in out-ofhospital cardiac arrest in taipei comprehensive evaluation for quality of prehospital cpr video-recording and time-motion analyses of manual versus mechanical cardiopulmonary resuscitation during ambulance transport machine and operator performance analysis of automated external defibrillator utilization evaluating the quality of prehospital cardiopulmonary resuscitation by reviewing automated external defibrillator records and survival for out-of-hospital witnessed arrests better adherence to the guidelines during cardiopulmonary resuscitation through the provision of audio-prompts outcomes from out-of-hospital cardiac arrest in metropolitan taipei: does an advanced life support service make a difference? cost-effectiveness of different advanced life support providers for victims of out-of-hospital cardiac arrests improving surge capacity for biothreats: experience from taiwan emergency medical services utilization during an outbreak of severe acute respiratory syndrome (sars) and the incidence of sars-associated coronavirus infection among emergency medical technicians facing an outbreak of highly transmissible disease: problems in emergency department response ed overcrowding in taiwan: facts and strategies cardiopulmonary resuscitation with assisted extracorporeal life-support versus conventional cardiopulmonary resuscitation in adults with in-hospital cardiac arrest: an observational study and propensity analysis the part of the future models of ems design in this work was supported by grants from department of health, taiwan: doh -td-h- - and doh -td- - . key: cord- -jvhgrsbm authors: phan, huy p.; ngu, bing h.; chen, si chi; wu, lijuing; lin, wei-wen; hsu, chao-sheng title: introducing the study of life and death education to support the importance of positive psychology: an integrated model of philosophical beliefs, religious faith, and spirituality date: - - journal: front psychol doi: . /fpsyg. . sha: doc_id: cord_uid: jvhgrsbm life education, also known as life and death education, is an important subject in taiwan with institutions (e.g., high school) offering degree programs and courses that focus on quality learning and implementation of life education. what is interesting from the perspective of taiwanese education is that the teaching of life education also incorporates a number of eastern-derived and conceptualized tenets, for example, buddhist teaching and the importance of spiritual wisdom. this premise contends then that life education in taiwan, in general, is concerned with the promotion, fulfillment, and cherishing of quality life experiences (e.g., personal contentment, happiness). one example of life education, which resonates with other spiritual beliefs and religious faiths (e.g., hinduism), is related to spiritual cultivation and the enlightenment of life wisdom. our own teaching of the subject, likewise, places emphasis on the goal of teaching students to seek meaningful understanding of and appreciation for three major, interrelated components of life education: life wisdom, life practice, and life care. it has been acknowledged, to a certain degree, that life education has made meaningful contributions, such as the creation and facilitation of a civil, vibrant society, and that many taiwanese individuals show dignity, respect for elders, and reverence for spiritual and religious faiths. for example, aside from high-quality hospice care, many taiwanese engage in different types of benevolent acts (e.g., providing spiritual advice to someone who is dying), where possible. life education is a beneficial subject for teaching and learning as its theoretical understanding may help individuals cope with pathologies and negative conditions and life experiences. one negative life experience, in this case, is the ultimate fate of humankind: death. approaching death and/or the onset of grief is something that we all have to experience. how does one approach death? it is not easy feat, and of course, grief for a loved one is personal, and some of us struggle with this. we contend that spiritual cultivation and enlightenment, arising from life education, may assist us with the topic of death (e.g., the possibility of transcendence beyond the realm of life). more importantly however, from our own teaching experiences and research development, we strongly believe and rationalize that the subject of life education could, indeed, coincide with and support the paradigm of positive psychology (seligman, , ; seligman and csíkszentmihályi, ). forming the premise of the present conceptual analysis article, we propose that a person’s “spiritual and enlightened self,” reflecting the convergence of three major aspects of life education (i.e., philosophical reflection, enrichment of personal well-being, and spiritual cultivation), would result in the initiation and creation of a number of virtues and positive characteristics, for example, having a positive outlook in life, having a perceived sense of spirituality, showing compassion, forgiveness, etc. these virtues and quality characteristics, from our philosophical reasoning, are equivalent to those qualities that the paradigm of positive psychology advocates for. in summary, we conceptualize that the subject of life education, from the perspective of taiwanese education, may intertwine with the paradigm of positive psychology. a person’s spiritual and enlightened self, or his/her “holistic self,” from our rationalization, is the ultimate optimal life experience that he/she may have, enabling him/her to address the gamut of life conditions and experiences. the distinctive nature of life education in this case, as a point of summary, is that it incorporates spiritual beliefs and religious faiths (e.g., buddhist faith), encouraging a person to seek nature and divine–human relationships, as well as to contemplate and to explore the complex nature of his/her inner self. the notion of buddhist samsâra, for example, as “evidence” of spirituality, entailing the endless cycle of birth, rebirth, and redeath, may provide a person with hope into the afterlife. such esoteric discourse, we contend, is positive and optimistic, allowing individuals to discard the dividing line between life and death. life education, also known as life and death education, has gained vast interests both in terms of teaching and research development. specifically, with reference to the case of taiwan and its education systems, life education is taught in schools and universities, as well as applied in society in the form of educational and social programs. what is significant, however, with reference to taiwanese education, is that the teaching and learning of life education also incorporate eastern-derived theoretical tenets of buddhism (yeshe and rinpoche, ; sheng yen, ) , confucianism (yao, ; havens, ) , and spirituality (carmody et al., ; lazaridou and pentaris, ) . the teaching of buddhist meditation (e.g., a focus on enlightenment), for example, has been incorporated to emphasize the salient nature of the study of life education-that life education is concerned with exploration of death, which is inevitable, and the fulfillment of a cherished life. how can a person overcome grief and accept that a close relative has moved on from this physical world? how does life wisdom assist a person in his daily functioning? are immortality and the notion of transcendence beyond death a possibility? these questions, we contend, are significant, which the study of life education makes attempts to address. death, grief, negative outlook, and maladaptive life experience are inevitable. overcoming these life deficiencies, obstacles, and difficulties is an important quest, which we believe the study of life education (shi, ; huang, ; chen, ) could assist. indeed, aside from life education, we acknowledge that the paradigm of positive psychology (gilham and seligman, ; seligman, ; seligman and csíkszentmihályi, ) could also play a prominent role in helping to alleviate suffering, helplessness, grief, negative life conditions, etc. our existing research inquiries into the effect of positive psychology have resulted in the development of a psychological concept that we termed as "personal resolve" (e.g., phan et al., phan et al., , phan et al., , c . despite our emphasis on educational processes, we contend that personal resolve, briefly defined as "person's mental resolute and "unwavering focus" to stay on task without any uncertainty or reservation to achieve optimal best" (phan et al., c, p. ) , could feature and assist individuals to overcome barriers, negative life experiences, etc. an interesting question, though, is whether we could integrate the study of life education and the paradigm of positive psychology into a holistic framework for research development and/or implementation. to date, to our knowledge, no researchers have yet made this attempt to unify the two theoretical orientations into one coherent model. this inquiry, we contend, is significant for the purpose of cross-cultural contribution, especially when we consider the uniqueness of eastern epistemologies and philosophical reasoning. recently, we published an article in frontiers in psychology (phan et al., a) , where we focused, in particular, on the unification of positive psychology (gilham and seligman, ; seligman, ; seligman and csíkszentmihályi, ) and mindfulness from the perspective of buddhism (hanh, ; loden, ; sheng yen, ) . from this account, a focus on life and death education from the perspective of taiwanese education is insightful in terms of elucidation of theoretical understanding of the relationship between the two orientations. it is interesting to note that taiwan places strong emphasis on the study of life education. it is a subject that is taught in school and university. indeed, many scholars, government officials, and teachers would attest that the study of life education has played a central role in transforming taiwanese society into what it is today-civil, democratic, robust, and stable. one clear example, in this case, is the recent covid- coronavirus pandemic where taiwan had only seven cases of death (note: dated as of june , ) (source: https: //www.worldometers.info/coronavirus/#countries). in a similar vein, high-quality service of hospice care for senior citizens in taiwan is commendable. some taiwanese, for example, serve as hospice care volunteers to provide religious and spiritual advice. given its importance, we have devoted a complete chapter in our forthcoming book on the subject of life and death education. the history of life education in taiwan, which we covered in detailed in this chapter, is quite interestingfor example, in part, it arose from the study of thanatology (fonseca and testoni, ; doka, ; meagher and balk, ; chapple et al., ) , or death education, from the united states and other western countries. to understand and appreciate the nature of life education, it is important for us to identify the chinese characters of " , " which translate to mean "life education." the term life education has been in use since , when taiwan started to promote various life education programs for secondary school teaching and learning (ministry of education taiwan, , . likewise, and interestingly, the ministry of education, taiwan, dedicated as the year of life education in acknowledgment and recognition of its significance and relevance to individuals, families, and the community. the national taipei university of education, where four of the authors work, has also established the life education and health promotion institute, which serves to promote life and death education. other institutions have similar programs and courses that promote the cultivation of life and death education. despite our brief mentioning so far, it is noteworthy to ask the question of what life education is about. we contend that this question does not have a definitive, consistent answer as the study of life education is relatively broad in scope. our attempt to provide a balanced definition and description of life education, from historical accounts (e.g., evolution of life education with the introduction of a seminal paper by professor song-yuan huang (huang, ) , titled: "death education: a controversial subject in school health education"), has resulted in the following: that life education is concerned with "spiritual and personal cultivation, " via different means (e.g., formal learning of a subject titled "spiritual cultivation" in university) in order to elicit appreciation and meaningful understanding of life and death (chen, (chen, , . in this analysis, life education is a formal process of delivery of knowledge that could, in effect, assist in the promotion, fulfillment, and cherishing of quality life experiences. from this account, it is noted that life education in taiwan is a valuable subject matter that could educate taiwanese citizens to appreciate and live productive life. it is important to note, however, that life education is not simply concerned with the nature of life. death is also a topic of discussion within the teaching of life education (huang, ) , hence why life education is also known as life and death education. for many taiwanese and asians, in general, death is a taboo topic that is often not talked about. this point is interesting as life and death are on the opposite ends of a spectrum. life is perceived as being positive (e.g., celebration, joy), whereas, in contrast, death is negative (e.g., sorrow, grief). any person for that matter would choose life, and not death, for studying in school and/or university. death, of course, is inevitable and is the ultimate fate that we all have to face. grief, sorrow, and despair, upon death of a loved one, are personal experiences that require assistance, counseling, and resolution. in this sense, life education, complementing with the teaching of buddhism (hanh, ; loden, ; sheng yen, ) , may assist and counsel taiwanese to confront and face death with sense of dignity, serenity, and respect (fu, ) . for example, the notion of buddhist samsâra may provide understanding into the possibility of "personal transcendence" beyond death itself. an interesting question that is often asked within the context of life education is the following: what is life? this question, similar to that of life education, does not have a straightforward answer. death, in contrast, is perhaps more easily definedfor example, we can define death as simply the permanent ceasing of a person or a biological organism. life, however, is more complex and may entail different interpretations and theoretical approaches-philosophical, scientific, theological, and metaphysical speculation. from a general point of view, though, we could say that the nature of life is concerned with a person's fulfillment of his/her purposes and goals in life, which are structured and timed for different periods in life (e.g., as part of life, the fulfillment of a goal to attend university). one taiwanese scholar, tsai ( ) , proposes that life in itself is not a passive "pathway"; rather, there are dynamic and proactive operations and contextual influences that ultimately portray unique, differing pathways for each person. one person's pathway, unique in its depiction, is likely to differ from other individuals' pathways. in this discussion of tsai's ( ) in summary, from the two aforementioned points of view, it is noted that life is made up of different life course trajectories. in a person's lifetime, he/she may possess and manifest different life course trajectories-for example, a life trajectory as a spouse vs. a life trajectory as an employee at a local bank. we anticipate that different life course trajectories are complementary with each other, despite their uniqueness (e.g., a spouse vs. an employee). in a similar vein, of course, there are underlying operational mechanisms or principles (tsai, ) that may contribute to assist and facilitate in the achievement of different life course trajectories. in the course of a person's life as a university student, say, he/she may rely on the process of optimization (phan et al., (phan et al., , a (phan et al., , b as an operational mechanism to assist with his/her schooling experiences. in a similar vein, another person's life trajectory as a senior citizen may consist of his/her social relatedness to others. the preceding sections have highlighted the nature of life and briefly, likewise, the importance of death and its aftermath. life education, as detailed, has a number of purposes that are related to both life and education. the goals of life education in this sense are unambiguous, focusing on meaningful appreciation for quality life experiences and in-depth understanding of deathrelated matters (e.g., the coping of grief). in our recent writing, surmising other scholars' discussions (huang, ; chen, chen, , , we purport that the main goal of life education is to educate, cultivate, and enrich a person's knowledge and ability so that he/she is able to (i) continuously refine the daily practice and wisdom of life, (ii) initiate the importance of care (e.g., looking out for others), and (iii) live a meaningful life through different stages. we surmise that the goal of life education, likewise, is to empower individuals with personal belief and resolute to accept death and/or to overcome death-related matters (e.g., sorrow). for example, the teaching of buddhism (yeshe and rinpoche, ; sheng yen, ) , situated within the framework of life education places consistent emphasis on spiritual cultivation (chen, (chen, , , which in this case encourages a person to seek meaningful understanding into the transcendence of oneself toward an ultimate, better self, and the transformation of the complexity of life experiences (i.e., positive and negative) into some form of unity. this emphasis of spiritual cultivation, likewise, considers the incorporation of mystical and esoteric sentiments such as a person's quest to strive for "awakening" or enlightenment experiences, and to offer hope into the possibility of the afterlife. the significance of life education is reflected by the objectives and subject contents that different courses and educational programs offer. in the course of a person's life, there are three aspects for consideration in development: i. the wisdom of life: it is important for a person, from birth to death, to continuously reflect on his/her acquired knowledge and experiences, which could help refine understanding into the meaning of life wisdom (e.g., "why is it important for us, as a nation, to offer free health care?"). ii. the caring of life: life wisdom, as we briefly described, may cultivate an appropriate mindset, which could emphasize the importance of empathy, compassion, mercy, and love toward oneself and toward others. these attributes, in turn, may motivate and compel a person to show love and care for others. iii. the practice of life: it is a noteworthy feat for a person to live a meaningful life with the main purpose of contemplation, refinement, and improvement. meaningful practice of life, in this case, may consist of voluntary community service (e.g., helping out at church on saturday). from this understanding, it can be seen that with reference to life, there are three distinctive elements that are of significant value: wisdom, care, and practice. as we explore next, wisdom, care, and practice are inseparable and may, in fact, unite the two contrasting topics: life and death. thus, as a point of summation, we could say that the main goal of life education is to explore the true meaning and nature of the wisdom, caring, and practice of life. in a course of study at university, for example, an educator may choose to include subject contents that focus on and/or reflect the importance of wisdom, care, and practice of life. at the same time, of course, subject contents via whole-class teaching, individual learning, and/or collaborative may also entail the study and understanding of death-related matters-for example, the coping of sorrow using faith in buddhism as a possible means (phan et al., b (phan et al., , a . research into the positive effect of life education in taiwan, over the years, has focused on different aspects of developmentfor example: empirical establishment, application, theorization, and conceptualization (e.g., tsai, ; huang, ; chen, ; tsai et al., tsai et al., , tsai et al., , . for example, recently, we conducted an empirical study that consisted of taiwanese undergraduate students from public and private universities, where our focus of inquiry delved into the empirical validation of a concept that we developed, termed as "appreciation and the valuing of life." for us, appreciation and the valuing of life, as a psychosocial concept, is defined as a person's gratitude, respect, and cherishing of life and/or toward others in society (e.g., "i appreciate bau-yi for who she is, regardless of her poor upbringing"). importantly, however, we conceptualized and reasoned that acquired knowledge of the subject of life education could assist in the development of the concept of appreciation and the valuing of life. moreover, as shown in figure , we postulate that personal experience of appreciation and the valuing of life could act as a potent antecedent of future outcomes. using likert-scale measures and the statistical technique of structural equation modeling (loehlin, ; kline, ) , we found evidence to substantiate our hypothesized a priori modelfor example, appreciation and the valuing of life positively predicted the concepts of daily functioning (β = . , p < . ), personal experience (β = . , p < . ), willingness to help others in society (β = . , p < . ), and happiness (i.e., positive emotions) (β = . , p < . ). this study overall, we contend, is significant as it underlines the potency of the study of life education-that meaningful understanding life education, in this case, could yield in the development of perception and personal experience of appreciation and the valuing of life. aside from empirical research, we have noted that many scholars, educators, government officials, etc. have also made concerted efforts to advance the study of life education. one interesting line of inquiry has involved advancement into the nexus between research and application. this emphasis, in this case, focuses on the successful transformation of theoretical tenets of life education into practice. for example, in , a buddhist master, master xiao yun, used "enlightenment education" as a philosophical foundation to establish huafan university, currently located in new taipei city, taiwan. master yun advocated the use of humanistic education (e.g., the study of self-actualization) to enrich a person's mindset. master xiao yun, in particular, believed in the integration of both humanities and technological advances and that, likewise, there was a need to acknowledge and recognize the importance of compassion and wisdom. to promote this thinking, huafan university offered a unit, titled "enlightenment wisdom and life, " which was compulsory for enrolment. this enlightenment education is based on the theoretical premise of enlightenment, taking into consideration both chinese culture and buddhist teaching. specifically, reflecting our previous mentioning, this unit incorporates contemporary pedagogical practices and places emphasis on the integration of both humanities and technological frontiers in psychology | www.frontiersin.org advances, as well as the promotion of compassion and wisdom (shi, ) . it was hoped at the time that enlightenment education, focusing on the cultivation of compassion and life wisdom (e.g., caring for another person), would bring peace and happiness to taiwanese society. other institutions in taiwan, similar to huafan university, have also made attempts to highlight and promote the importance of life education. for example, from our observations and professional experiences, we note that there are pastoral care programs, courses and degree programs, extracurricular and social activities, and campus events that place emphasis on religious and spiritual cultivation, the enrichment of personal well-being, and the proactive caring for others (chen, ) . one notable goal from these positive initiatives is to educate and to encourage students to practice care, love, compassion, and life wisdom (e.g., looking out for friend in time of needs). at huafan university, even to this day, there are weekly classes on buddhist meditation practice and mindfulness that are intended to cultivate spirituality and beliefs in religious sentiments (e.g., the seeking of understanding of transcendence). the main premise of the present conceptual article is to consider the possibility that life education, in general, could coincide with and/or support and substantiate the paradigm of positive psychology (gilham and seligman, ; seligman, ; seligman and csíkszentmihályi, ) . as we briefly mentioned in the preceding sections, we recently published a conceptualanalysis article, titled "advancing the study of positive psychology: the use of a multifaceted structure of mindfulness for development, " which explored the interrelationship between buddhist mindfulness (hanh, ; loden, ; sheng yen, ) and positive psychology. this conceptual analysis is poignant as it acknowledges the possibility that both western and eastern epistemologies and philosophical rationales (e.g., psychological thoughts vs. spirituality) could combine into a holistic framework, which would then provide detailed information about the proactivity of human agency (bandura, (bandura, , . the advent of technologies and globalization has encouraged social dialogues and, importantly, the sharing of knowledge, ideas, opinions, and viewpoints across cultures. our cross-institutional research collaborations over the past years, for example, have resulted in our propagation of meaningful and interesting cross-cultural discussions of topical themes, such as subjective well-being, optimal best, and personal fulfillment. how does life education, from the perspective of taiwanese education, fit in with the teaching of positive psychology? an alternative question that we could inquire, likewise, is whether and/or to what extent positive psychology would fit in and support the teaching of life education. this attempt to integrate the two theoretical frameworks is innovative as it would add credence to the prominence of positive psychology as a driver of life's proactivity and, by the same token, the promotion of the teaching of life education in school, college, and society. positive psychology, in brief, explores life conditions and experiences both in terms of negativities (e.g., the remedy of pathologies and maladaptive functioning) and positivities (e.g., the encouragement and promotion of enriched life conditions) (gable and haidt, ) . this theorization of positive psychology (gable and haidt, ) largely arises from the work of seligman, csikszentmihalyi, and peterson, who seek to understand the psychological well-being and optimal functioning of people (quick, ) . from the literature, seligman and csikszentmihalyi (seligman and csíkszentmihályi, ) have been credited with coining the term "positive psychology." according to sheldon et al. ( ) , positive psychology is defined as: "the scientific study of optimal human functioning. it aims to discover and promote the factors that allow individuals and communities to thrive. the positive psychology movement represents a new commitment on the part of research psychologists to focus attention upon the resources of psychological health, thereby going beyond prior emphases upon disease and disorder". this definition, as reflected in pawelski's ( ) comprehensive review of this topic, suggests that positive psychology incorporates and emphasizes personal characteristics, such as internal drive, character building, human strength, and family and civic virtue. from this emphasis, the study of positive psychology may entail the "building of the most positive qualities of an individual" (seligman, , p. ) and "on building of what makes life most worth living" (seligman, , p. ) . seligman and csíkszentmihályi's ( ) published work, likewise, emphasizes the science of positive psychology may exist on three levels-subjective, individually, and institutional: "the field of positive psychology at the subjective level is about valued subjective experiences: well-being, contentment, and satisfaction (in the past); hope and optimism (for the future); and flow and happiness (in the present). at the individual level, it is about positive individual traits: the capacity for love and vocation, courage, interpersonal skill, aesthetic sensibility, perseverance, forgiveness, originality, future mindedness, spirituality, high talent, and wisdom. at the group level, it is about the civic virtues and the institutions that move individuals toward better citizenship: responsibility, nurturance, altruism, civility, moderation, tolerance, and work ethic" (p. ). interestingly, ancient greek philosophers refer to the concept of "eudaimonia, " which is translated to connote good spirit, happiness, and a state of flourishing. psychologists in early as the s, likewise, recognized the need to examine the virtue of strength-based approaches to prevent and treat a person's mental illness. in the area of human motivation (franken, ) , likewise, maslow's ( a maslow's ( , humanistic theory describes the importance of self-fulfillment of inner psychological needs. maslow ( b) argued that the science of psychology has been far more successful on addressing the negatives than improving the positives. it has revealed man's and woman's shortcomings, his/her illness, and his/her sins, but little about his/her potentialities, his/her virtues, his/her achievable aspirations, or his/her full psychological height (maslow, b, p. ) . indeed, positive psychology has been and is difficult to define because of its nature and broad scope of psychological domains (donaldson et al., ) . over the years, of course, there have been different theories proposed to explain and/or to reflect the tenets of positive psychology-for example, phan et al.'s ( ) framework of achievement bests, seligman's ( ) perma model (i.e., positive emotions, engagement, relationship, meaning and accomplishment), keyes's ( ) continuum of psychological well-being, and peterson and seligman's ( ) character strengths and virtues framework. in their seminal writing, seligman and csíkszentmihályi ( ) defined positive psychology as "the combination of valued subjective experiences, which could contribute to the optimal experience of well-being." this testament, based on our analysis, may incorporate reflection of a person's past (e.g., achievement), as well as his/her hope and optimism for the future (e.g., positive emotions), and flow and happiness in the present moment (e.g., engagement and meaning) (phan et al., a) . this personal experience, indeed, attests to a continuation of time: past, present, and future. at an individual level, it is operationalized through positive individual traits such as the capacity for love, vocation, courage, interpersonal skill, aesthetic sensibility, perseverance, forgiveness, originality, future mindedness, spirituality, high talent, and wisdom. at the community or the organization level, in contrast, positive psychology is concerned with civic virtues and the goal of institutions to move individuals toward better citizenship, responsibility, nurturance, altruism, civility, moderation, tolerance, and work ethic (seligman and csíkszentmihályi, ) . as noted from the preceding section, positive psychology may act to negate pathologies and maladaptive states of functioning (e.g., continuing failures in mathematics learning) and, in contrast, to also promote positive life conditions and experiences (e.g., enjoyment in seeking mastery in music composition). the theory of optimization (e.g., fraillon, ; phan et al., phan et al., , a , b , recently developed to coincide with the paradigm of positive psychology, interestingly places more emphasis on positive life experiences and adaptive outcomes-for example, the achievement of optimal best (liem et al., ; phan et al., ) . this focus of development (i.e., a focus on the achievement of optimal functioning) is beneficial and insightful as it seeks to promote the importance of positive life conditions and different types of adaptive outcomes. it is a central feat of human agency that individuals in society strive to achieve their optimal bests and flourish in life. in terms of schooling, for example, what is it that could encourage a student to strife for optimal best in gymnastic? in a similar vein, in a non-academic sense, what could we do to cultivate optimal health? optimal best, also known as optimal functioning, is an important hallmark of positive psychology (seligman and csíkszentmihályi, ; fraillon, ; phan et al., a) and, by the same token, is an antithesis of pessimism, procrastination, a state of demotivation, and suboptimal functioning. optimal best, as the term connotes, is concerned with successful accomplishment and/or fulfillment of a state of functioning (e.g., cognitive functioning) that, in this case, reflects the maximization of a person's capability (fraillon, ; phan et al., a) . in terms of diversity, for example, achievement of optimal best may involve the following: • academic learning, for example, a student's optimal cognitive functioning in essay composition, where he is able to write a , -word essay and subsequently receiving an a + grade. • personal well-being in a workplace environment, for example, a bank employee's optimal state of resilience, personal resolve, and motivation to overcome difficulties and achieving exceptional kpis. • health functioning on a daily basis, for example, a senior citizen's optimal state of health despite her recent temporary illness from the covid- pandemic. • professional sports performance (e.g., european football), for example, a football player's optimal physical and creative ability to score goals in the / season. the above examples emphasize the general nature of optimal best for different life contexts. optimal best, which fraillon ( ) also terms as "notional best, " is a point of reference by which a person strives to achieve. "what is my optimal best?" indeed is a phrase that one may commonly use as a source of aspiration and motivation to succeed. in their recent article, phan et al. ( a) provided a comprehensive overview and conceptual analysis of this concept of optimal best. according to the authors, determination of optimal best in a subject matter (e.g., a football player's optimal physical and creative ability), denoted as "l , " requires some form of "benchmarking" or referencing from a current level of best practice, denoted as "l ." interestingly, from their conceptualization, phan et al. ( a) argued that the difference between l and l , denoted as (l -l ) , would represent and define a person's state of flourishing. from this account, we contend that a person's experience of flourishing, (l -l ) , entails some positive, enriched quantitative and/or qualitative change. importantly, however, phan and his colleagues' research work of optimal best is seminal and innovative for their emphasis on the process of optimization-that is, what is it that governs and causes a person to achieve optimal best? positive psychology does not simply focus on optimal functioning, nor does it entail the masking of negative life conditions and experiences (pawelski, ) . indeed, helplessness, sorrow, depression, continuing failures, and despair are some notable pathologies and negative life conditions, which we contend are noteworthy for consideration and addressing. in brief, the taboo subject of death itself is something that we all have to confront. it is the ultimate fate of humankind: the ceasing of life itself. in life, there are many personal situations, circumstances, events, experiences, etc. that are ongoing and/or repetitive, allowing us to recall and inform others-for example, ". . .it was like this for me when the covid- coronavirus pandemic happened. . ., " and ". . .i really enjoyed the music concert the other day. . .." death, however, is not an experience, situation, events, etc. that we can recall and repeat to someone (e.g., ". . .. for me, death was like . . ."). interestingly, there is an article by jennie dear (september , ) published in the atlantic (titled "what it feels like to die") that seeks to clarify the question of what it feels like to die. by all accounts, dr. james hallenbeck, a palliative care specialist at stanford university, compares dying to blackholes-"we can see the effect of black holes, but it is extremely difficult, if not impossible, to look inside them. they exert an increasingly strong gravitational pull the closer one gets to them. as one passes the 'event horizon, ' apparently the laws of physics begin to change" (source: https://www.theatlantic.com/health/archive/ / /what-it-feels-like-to-die/ /). dear's (september , ) article and personal account of death is interesting as it makes attempts to understand death. of course, the article does not completely elucidate the complex nature of death in terms of the emergence of onset experience (e.g., one's onset experience as he/she approaches death), grief, suffering, etc. despite this caveat, the article does, in part, support the use of positive psychology, as a form of remedy, to address death and other related negative aspects of life (e.g., a person's experience of trauma). moreover, as an interesting premise from dear's (september , ) article, we contend that the subject of life education in itself could coincide with the paradigm of positive psychology (seligman, (seligman, , seligman and csíkszentmihályi, ) and serve as an important remedy. that life education, in this sense, could play a prominent role in helping to alleviate negative emotions, feelings, and experiences and, by contrast, improve and enhance positive life characteristics (e.g., a state of personal resolve). from this account, we posit that life education (chen, (chen, , huang, ) , as a subject, could act as an informational source, which then would help to facilitate in the achievement of optimal best, academically and non-academically. let us now consider this possibility in detail in terms of the focus of theoretical orientation. by all accounts, we acknowledge that life education is not the only subject and/or theory that could coincide with the paradigm of positive psychology (seligman, (seligman, , seligman and csíkszentmihályi, ) and/or that it is the only framework, which could facilitate a person's achievement of optimal best. our examination of the literature, for example, has indicated that there are a number of notable theories that may successfully explain the achievement of optimal best: academic buoyancy (e.g., martin et al., ; collie et al., ) , personal thriving (e.g., su et al., ; wiese et al., ) , and academic striving (e.g., phan and ngu, ; phan et al., c) . what is unique, though, from our proposition, is that the study of life education may delve into the premise of philosophical psychology, spiritual psychology, and religious psychology. its scope, as we indicated earlier on, is more broader than just the teaching of theories pertaining to the different stages of human development (e.g., stage of cognitive development) (inhelder and piaget, / ; erikson, ) . life education from the perspective of taiwanese education is quite unique in terms of its theoretical premise, which we contend may coincide with other religious faiths, cultural practices and values, and philosophical beliefs, for example, christianity (davis, ; knitter, ; van der merwe, ) , hinduism (warrier, ; srivastava and barmola, ; goswami, ) , and islam (nasr, (nasr, / bonab et al., ; marzband et al., ) . in this analysis, as a point of prominence, life education's focus is more philosophical, spiritual, and personal, delving into a person's inner self and his/her relationship with nature, others in society, and some form of "divine being" (e.g., buddha). at its core, perhaps, is the fact that the teaching of life education makes a concerted attempt to promote and facilitate the enrichment of personal well-being via means of what we term as "divine-human relationships" (bonab et al., ) . enrichment of subjective well-being (e.g., a person's experience of optimal health well-being) is positive and, in this case, reflects one of the theoretical tenets of positive psychology (seligman, (seligman, , seligman and csíkszentmihályi, ) , namely, to encourage and promote positive life experiences and conditions (i.e., in this case, to encourage and promote optimal health wellbeing). of particular interest, from our point of view, is that life education shares a point of commonality with other religious faiths and philosophical beliefs (e.g., saksena, ; jones, ; kourie and ruthenberg, ; marzband et al., ) in terms of emphasis in acknowledgment of the importance of nature and its intimate association with life, inclination and human attachment to some form of divine being (e.g., the importance of god), and the seeking of spiritual cultivation and connectedness between personal and transpersonal realms (nasr, (nasr, / bonab et al., ) . this theoretical contention, interestingly, suggests that life education espouses the importance in unity of the spirit, the mind, and the body in both worldly and nonworldly esoteric contexts. it is evident that there is consensus among researchers' conceptualizations and established findings (e.g., saksena, ; jones, ; koenig, ; marzband et al., ; wagani and colucci, ; villani et al., ) , which showcase the positive impact of religious faith, spiritual cultivation, and personal enlightenment toward the optimization of one's personal wellbeing. bonab et al.'s ( ) theoretical overview of islamic spirituality, for example, is interesting as it highlights the relationship between personal religious commitment and mental health and coping ability (miller and thoresen, ) . in this analysis, a person's perceived positive relation with god is likely to enhance his/her coping and mental health condition (galanter et al., ; pargament, ; belavich and pargament, ) . testament of appreciation of spirituality, likewise, has also been found to make a profound impact on a person's wellbeing. in a recent study in north india, interestingly, wagani and colucci ( ) explored an important "negative" aspect of positive psychology with reference to hindu faith-in this case, the remedy and prevention of pathologies and maladaptive experiences. the authors found that spirituality (e.g., defined as "the improvement and knowledge of oneself. spirituality. . . defined as a way to know oneself, the inner self, or the soul": wagani and colucci, , p. ) positively impacted on a student's well-being and, more importantly, served as a protective measure against suicidal tendency. as we have acknowledged earlier, the subject of life education is not new to taiwan and has, in fact, been credited elsewhere in terms of theoretical development. what is novel, though, is that taiwan has placed strong emphasis on the application of life education theories into practice. how can life education assist individuals to appreciate their sense of self-worth? how can life education negate a person's perception of life dissatisfaction? how does life education complement a person's emphasis on a need to have financial wealth? these questions are authentic and have life-related relevance, emphasizing the importance of theoretical understanding into the multiple purposes of life, personal reflection, and philosophical reasoning, all of which account for the goals of life education. that life education, specific to the case of taiwan, is concerned with a focus on enrichment of personal well-being, appreciation for life and the fulfillment of life qualities, and the development of coping mechanisms to deal with life matters. our quest is to consider a coinciding support for positive psychology from the study of life education. how does the subject of life education, from the perspective of taiwanese education, support and/or coincide with the theoretical tenets of positive psychology? this consideration acknowledges, from our viewpoint, the perspective and understanding that life education, in general, is positive and/or that it entails positive life characteristics for development (e.g., emphasizes the importance of positive emotional well-being). on this point, we concur and strongly believe that life education, in terms of its proposed theoretical tenets (e.g., a focus on the development of life wisdom, which may consist understanding of spiritual cultivation), is a positive subject that may soundly support the paradigm of positive psychology. this testament, indeed, is the hallmark of this conceptual analysis article. let us now explore three major components of life education, which we consider as being prevalent to supporting our seminal postulation-that the subject of life education is closely aligned with and in support of the paradigm of positive psychology (seligman, (seligman, , seligman and csíkszentmihályi, ) . our proposition, drawn from professional teaching practices and existing theoretical and research development, posits that life wisdom (i.e., acquired knowledge pertaining to the importance of spirituality), personal daily engagement of life practices (e.g., engagement in meditation), and one's willingness to show care for others in society, in general, produce a number of positive life qualities, for example, a person's positive outlook in life. in a similar vein too, from our point of view, taiwanese life education studies (chen, (chen, , huang, ) also facilitate and enhance the following: philosophical reflection: personal reflection, we contend, encourages a person to internalize and to reflect on daily happenings in a philosophical manner in order to attain meaningful understanding. the main premise, in this case, is for a person to philosophically reflect and reason why things in life happen and why they are the way they are. buddhist meditation, resulting in calmness and serenity of the mind (loden, ; phan et al., a) may, in this sense, enable the person to reflect from "within the mind" and to provide sound philosophical reasoning. as an example, consider the case of social stigma and its subsequent effect (major and o'brien, ; frost, ) that an adolescent is experiencing. philosophical reflection, in this analysis, would encourage a person to seek understanding from all sides, not necessarily for the purpose of resolution for this social mishap. this act, in turn, formulates evidence of life wisdom, which a person may refer to and use for other contexts. spiritual cultivation: spiritual cultivation, also known as the cultivation of spiritual mind, seeks to enlighten a person in a religious and/or spiritual sense. specifically, with reference to the incorporation of buddhist teaching (yeshe and rinpoche, ; sheng yen, ) , taiwanese scholars and students alike believe that spiritual cultivation, via means of acquired knowledge (e.g., buddhist scripture) and meditation practice, would enable a person to attain meaningful understanding and appreciation of esoteric matters, such as the possibility of transcendence beyond the realm of death itself, unexplained phenomena of this physical world, and the true meaning of satori (phan and ngu, ; phan et al., a) , that is, the achievement of perfection and/or tranquility. spiritual cultivation, indeed, is a form of teaching, both formal and informal, which may serve to enlighten a person's view and mindset of the world in a positive manner. for example, compassion, love, and willingness to forgive are all evidence of the success of spiritual cultivation. enrichment of personal well-being: enrichment of personal well-being reflects the nature of life care in which a person may show love, care, and compassion for oneself and for others in the community. enrichment of personal well-being may reflect a person's mindset, as well as his/her physical being. importantly, however, enriched personal well-being may espouse the development and acquired experience of a "spiritual self "-in this case, the perception in experience of calmness, serenity, peace, and harmony with reference to the surrounding. moreover, research development and the study of life education (e.g., chen, chen, , chen, ) in taiwan posit that spiritual cultivation (e.g., the teaching of satori) could assist and encourage individuals to show willingness in care, love, and wisdom for others' well-being. taiwan is relatively advanced in terms of quality services of hospice care to senior citizens. one of the authors of this article, for example, works as a volunteer on weekends and afterhours to look after senior citizens. his personal account, as he describes, entails spiritual advice, which may consist of buddhist chanting and reading of buddhist scriptures. from our rationale, we contend that philosophical reflection, spiritual cultivation and enlightenment, and a person's enriched well-being are positive experiences and characteristics that may arise from the study of life education. by all accounts, we acknowledge that this viewpoint and rationalization may resonate elsewhere with other religious faiths, teaching subjects, cultural practices, etc. indeed, as attested from the extensive literature, religious faiths such as christianity (davis, ; knitter, ; van der merwe, ) , hinduism (warrier, ; srivastava and barmola, ; goswami, ) , and islam (nasr, (nasr, / bonab et al., ; marzband et al., ) also explore the importance of spiritual cultivation and life enlightenment. for example, as we briefly referenced, hindu faith places emphasis on a need for a person to "know and live in the highest self, the divine, the all-embracing unity, and to raise life in all its parts to the divinest possible values" (goswami, , p. ) . what is poignant, however, is that taiwanese society and education systems place self-awareness and prominence on these elements, all of which are quality characteristics that coincide with positive psychology (seligman, (seligman, , seligman and csíkszentmihályi, ) . drawing from the preceding section, our proposition considers the extent to which life education would yield quality life characteristics that, in turn, support the paradigm of positive psychology (seligman, (seligman, , seligman and csíkszentmihályi, ) . positive psychology, in a general sense, entails the promotion of optimal best, academically [e.g., optimal cognitive achievement (e.g., mastery) in algebra] and non-academically (e.g., optimal emotional well-being despite one's obstacle). we rationalize that, in this instance, spiritual cultivation and enlightenment, philosophical reflection, and enriched well-being, all of which are positive qualities, would naturally converge, resulting in the development of life-relevant characteristics, which are shown in figure and summarized in table . our rationalization for the support of positive psychology (seligman, (seligman, , seligman and csíkszentmihályi, ) from the study of life education (e.g., chen, chen, , chen, ) is shown in figure . foremost from figure is our conceptualization, shown as a venn diagram, which depicts a point of convergence (i.e., denoted as 'x") between three described components-spiritual cultivation and enlightenment, philosophical reflection, and enriched well-being. in particular, we propose that life education would create a specific form of knowledge, understanding, and personal experience that we term as "spiritual and enlightened self." a person's spiritual and enlightened self is religious and spiritual and, from our proposition, may emphasize his/her intimate connectedness with some form of divine being and/or divinity. this point about spirituality and enlightenment, in a general sense, is not novel and has been noted to resonate with other religious faiths. for example, aside from islam faith, hindu faith, etc., christian spirituality also recognizes the importance of a "dynamic divine-human dialogue-between the divine and the spiritual person" (van der merwe, , p. ). what is of consistency, perhaps, is that a perceived sense of spirituality could give rise to a person's "eureka moment" of awakening, or enlightenment (schneiders, ; knitter, ) , resulting in his/her experience of connectedness with nature, people, and divinity (van der merwe, ). what do the characteristics, or "virtues, " in table , as we conceptualize, actually represent? our rationale, in this analysis, posits the following: that the study of life education, focusing . perceived sense of spirituality acquired knowledge and manifestation of spiritual belief-for example, a person's striving to appreciate and/or to engage in the practice of tranquility. a person's willingness to show love, empathy, and care for others in society, regardless of their ethnicity, race, social standing, political affiliation, etc. a person's willingness to be non-judgmental and to forgive others for their deeds, regardless of subsequent effects. forgiveness, in this sense, reflects a person's magnanimous state . social relatedness social relatedness is more than just evidence of proactive social interactions between individuals. it is also about empathetic thoughts and acts, such as offering friendship to a person who is in need . enlightened the word "enlightened" arises from personal understanding and/or, perhaps, experience of enlightenment, or nirvana. this emphasis identifies the beatitude of life, both in the physical sense and the esoteric sense . open-mindedness a person's understanding, acknowledgment, and acceptance that anything in this physical world is possible. this description, in particular, reflects a person's state of inquisitiveness to understand about the world . benevolence a person's disposition to engage in charitable acts and to show kindness and good will to others in the community. benevolence, in this case, may also reflect sacrifice and willingness to go beyond of what is expected . resolute personal resolute, a concept recently developed, emphasizes a person's unwaivered focus, concentration, and mental fortitude, which may then account for his/her state of decisiveness in a particular context. on the teaching of philosophical reflection, the cultivation of spirituality, and the enrichment of personal well-being would give rise to the "creation" of a holistic entity-a person's spiritual and enlightened self. when a person experiences spirituality and feels enlightened or awakened) (i.e., his/her holistic self), he/she is likely to exhibit different types of life characteristics and virtues such as having a positive outlook about life, being compassionate and showing forgiveness, etc. by all accounts, these positive life characteristics (e.g., a positive outlook) are comparable with those established elsewhere, especially in relation to other theoretical perspectives, cultural viewpoints, religious faiths, and customary practices. for example, our description of the positive characteristic of "positive outlook in life" (i.e., a person's inclination to be positive about life, regardless of his/her current situations, etc.) has been referenced in existing research development pertaining to the subject of future time orientation (e.g., wallace, ; nuttin, ; mehta et al., ) in the field of psychology. a positive future time orientation at school, according to research evidence, would result in an improvement in academic performance. in a similar vein, a person's experience and manifestation of compassion is welldocumented with other religious faiths, for example, islam (i.e., the concept of rahmah) (engineer, ; taib, ; nasir, ) and christianity (cornelius, ; godlaski, ; zylla, ) . holistic self, from our proposition, is a virtuous and magnanimous entity that arises from the study of life education. this consideration of a person's holistic self is personal for us, drawing from our own teaching experiences, existing theoretical understanding, and ongoing research development. a person's holistic self, we contend, reflects his/her state of liveliness, awakening, and spirituality, yielding a number of virtues and life qualities (e.g., indication of compassion) that largely support the paradigm of positive psychology (seligman, (seligman, , seligman and csíkszentmihályi, ) in helping to address different types of pathologies and/or the achievement of optimal best. let us consider a negative condition of death and how a person would overcome this fate. death as a topic is dark, negative, and something that not many of us would like to discuss and/or talk about. death is the ultimate destruction of life. for a person who is approaching death, it is a daunting and suffering experience. by the same token, for a close relative of someone who is dying, this "confrontation" of death is also a daunting experience, for example, the self-cognizance of grief, denial, and pain. how would positive psychology and, more importantly, a person's holistic self-address this fundamental topic? likewise, how would life education assist someone who is approaching death, and/or the close relative who is experiencing the onset of grief, etc.? referring to our previous discussion, an acquired spiritual and enlightened self (i.e., a person's holistic self) in this case may provide relevant information (e.g., meaningful understanding of life wisdom) and experiences (e.g., realization that everything in life is aesthetic) (loden, ; phan et al., a) , which could assist a person to confront and cope with death. buddhist faith, in particular, could encourage and instill the following comparable beliefs and/or perceptions: i. the spiritual belief of samsāra, that is, the endless cycle of birth, rebirth, and redeath. that is, in this case, every rebirth is temporary and impermanent. upon death, a person is reborn elsewhere in accordance with his/her own karma. hence, from this spiritual belief, those who are approaching death may view death with a sense of encouragement, hope, and optimism, knowing that this is simply a cycle of life and death. ii. the spiritual belief that the nature of life and death is aesthetic and that negativity, pain, suffering, etc. are part of the norm and subjective, depending on a person's resolve, outlook, open-mindedness, etc. this emphasis connotes, in particular, the importance of enlightenment, which would potentially allow a person in this case to achieve the everlasting the beatitude of life. ii. the spiritual belief into the esoteric nature of life and death, which may involve the possibility of transcendence beyond the realm of the physical world. in other words, spiritual cultivation may allow a person to view death as not being the ultimate end, but rather as a dividing line that separates one physical world life cycle from that of another cycle. in contrast to death, pathologies, and other forms of maladaptive functioning, likewise, a person's acquired holistic self is also able to facilitate the achievement of optimal best (fraillon, ; liem et al., ; phan et al., b) and the experience of flourishing (diener et al., ; seligman, ; phan et al., a) . our consideration in this matter connotes that virtues (e.g., compassion) and quality characteristics (e.g., having a positive outlook), in this case, may reflect a person's optimal "individual experience." in other words, a person's achievement and/or experience of spirituality and enlightenment is more than just perceived evidence of positivity; rather, we rationalize that development of the holistic self is the ultimate optimal achievement or fulfillment that a person may experience. this optimal personal experience of spirituality and enlightenment, enabling a person to feel connected with god or some divine being (nasr, (nasr, / bonab et al., ; goswami, ; van der merwe, ), is of an exceptional level, which many of us may not achieve. the study of death education in taiwan is extremely prominent. over the past four decades, institutions have offered degree programs and courses that emphasize the importance of life education. one unique aspect of life education in taiwan has been the incorporation of specific eastern-derived epistemologies, philosophical and religious beliefs, and cultural practices. this uniqueness has led to the conceptualization and meaningful understanding that life education, in general, is concerned with enrichment of life qualities, cultivation of spiritual wisdom, and the pursuing of personal contentment and happiness. the main premise in this case is that aside from social stability and financial wealth, the notion of having a spiritual, fulfilling life is a noteworthy feat for development. hence, on a daily basis, many taiwanese engage in buddhist meditation and other forms of meditation, as well as partaking in charitable acts and short courses, which would facilitate in the achievement and fulfillment of life qualities. our premise, as explored in the preceding sections, is to consider the extent to which life education, from the perspective of taiwanese education, could coincide with and/or support the study of positive psychology (seligman, (seligman, , seligman and csíkszentmihályi, ) . this consideration is innovative as it emphasizes the potential nexus in terms of epistemologies, philosophical reasoning, and theoretical psychology between western and eastern contexts. the study of life education in taiwan, for example, is interesting, delving into the complex nature of three interrelated elements that, in this sense, incorporate eastern-derived epistemologies (e.g., buddhist spirituality): life wisdom, life practice, and life care. our concerted effort, in this analysis, led to the proposition of a theoretical-conceptual model for continuing research development. the proposed point of convergence, labeled as "x" in figure , is significant, highlighting a person's spiritual and enlightened self. this point of convergence, which we termed as spiritual wisdom and life enlightenment, is positive and, more importantly, would form part of a person's holistic development (forbes, ; hare, ) . overall, then, what is the main premise of our conceptual analysis article and, more importantly, our proposition? for us, as scholars, we have a collective interest to seek understanding into the proactivity of human agency-for example, does having a positive mindset assist a person to flourish, and/or to cope with an impending health problem? from the "western" literature, we note that the paradigm of positive psychology (seligman, (seligman, , seligman and csíkszentmihályi, ) has been effective in assisting individuals with their wellbeing experiences (e.g., facilitating positive emotional wellbeing, via means of resilience). our viewpoint, largely derived from teaching and research development, likewise, considers the use of life education theories (huang, ; chen, ; huang, ) to gauge into and facilitate the proactivity of human agency. in this case, we hope that researchers, educators, organizations, etc. will consider the use of life education and, in particular, our proposition (e.g., a person's holistic self) to encourage and promote quality life experiences. quality life experiences for a person, in this case, may entail the following: (i) to appreciate and value life, regardless of personal hardship, socioeconomic standing, obstacles, etc.; (ii) to seek meaningful daily understanding, insights, and experiences about life and to live a meaningful life; and (iii) to plan and to have positive future outlooks about life, including death and other liferelated negativities. our intent, as scholars of education and psychology, is to seek innovative and new frontiers in theory and research development, which may then assist students and educators alike in their learning and teaching experiences. a focus on the seeking of life wisdom, spiritual cultivation (e.g., endeavor and/or perceived connectedness with some divine being), and experience of enlightenment (e.g., personal feeling of contentment and inner peace) is a noteworthy feat for consideration, especially in terms of applicability, practicality, and continuing research development. foremost, from the present article, we encourage readers to capitalize on our research proposition of life education and to consider other inquiries for development. our future goal, interestingly, is to use theoretical psychology and philosophical reasoning to unify comparable theories (e.g., life education, mindfulness, positive psychology) and cross-cultural viewpoints into an overarching framework for understanding-namely, to date, we have inquired into the process of optimization, the nature of holistic psychology, the multifaceted nature of mindfulness and the potential interrelationship between mindfulness and positive psychology, and of course life education and positive psychology. of particular interest for us, in this case, is to develop and propose a unified theoretical model that could explain a person's holistic development in terms of his/her subjective well-being (e.g., emotional well-being), cognition, morality, and social relationship. is this feat of developing a unified model possible, and/or can we develop a theoretical model of human agency (e.g., a person's achievement of optimal best in a particular domain of functioning) that could successfully take into account different philosophical beliefs, religious faiths, theoretical perspectives, etc.? theoretical psychology, philosophical reasoning, epistemologies, etc. are interesting "academic strategies" and/or approaches that we could use to develop new innovative theories and conceptualizations. like any proposed theory or theoretical model for that matter, however, it is important that we are able to scientifically validate a particular line of inquiry, theoretical model, conceptual framework, etc. for example, in terms of quantitative research, it is perceived as being straightforward to investigate, say, a one-factor (e.g., brown and ryan, ; chadwick et al., ) , a two-factor (e.g., cardaciotto et al., ; davis et al., ) , and/or a more complex factorial structure of mindfulness (e.g., a four-factor model: baer et al., ; feldman et al., ) using likert-scale inventories with confirmatory factor analysis techniques (kline, ; byrne, ) . in a similar vein, despite modest empirical development at present, it is possible to explore and empirically validate the nature of subjective well-being (diener et al., (diener et al., , wiese et al., ) . we acknowledge that our discussion in this article is theoretical and that, at present, there is only limited empirical evidence (e.g., figure ) to support its premise. in this sense, it is not always feasible and/or achievable to validate an inquiry, especially when it is esoteric and non-scientific in nature. for example, in accordance with our previous discussion, we contend that it is somewhat unachievable to design an appropriate methodological design for usage, which could measure, assess, and validate different types of esoteric experiences (e.g., "tranquility, " "enlightenment, " "samsāra"). in this analysis, we are extremely constrained in our quest to validate the experience of and the concept of transcendence-that is, the possibility of life transcending beyond death. how would we scientifically determine whether this notion of postdeath experience is plausible? one interesting topic and/or line of inquiry in the social sciences is related to methodological design (bordens and abbott, ; gravetter and forzano, ; babbie, ) , which a researcher could use to investigate and validate a particular concept, relationship, etc. for example, as a question for consideration, would a two-group experimental design (e.g., control group vs. experimental group) be the course for usage in terms of validating the negative impact of cognitive load imposition (sweller et al., ; sweller, ) ? in our research development (phan et al., a) and, in particular, our recent conceptual-analysis article (phan et al., a) , we introduced a term, coined as "methodological appropriateness." methodological appropriateness, in brief, is concerned with a researcher's consideration of the appropriateness (or inappropriateness) and adequacy (or inadequacy) of a methodological design that he/she would use to validate a concept, association, etc. methodological appropriateness, from our point of view, may explain limitations, as well as the ineffectiveness, inconsistency, and inaccuracy of established findings of empirical research. poignant to this discussion, though, is the fact that the topic of methodological appropriateness (phan et al., a (phan et al., , a is also associated with conceptualizations and theorizations drawn from philosophical reasoning, theoretical psychology, and non-scientific intuitions. in other words, it is still plausible for researchers to consider the relevance and applicability of methodological appropriateness for esoteric and non-scientific matters. from the above, we contend there are a number of caveats that are worthy for continuing research development. foremost, in this analysis, is the "scientific" validation of our proposed conceptualization, as shown in figure . with reference to figure , there are two notable issues for researchers to consider: i. develop likert-scale measures [e.g., ( ) not true at all, ( ) neutral, ( ) complete true], other forms, which could assist in the measurement and assessment of positive life characteristics, such as a perceived sense of spirituality (e.g., likert-scale rating of item: "i often experience a sense of spirituality for the unknown"), forgiveness (e.g., likert-scale rating of item: "i am a forgiving person"), benevolence (e.g., likert-scale rating of item: "i find it fulfilling to help others in the community"), etc. ii. develop a comparable framework, which we could perhaps use to cross-validate the described theoretical model as depicted in figure . researchers often use this methodological approach to cross-validate and establish psychometric properties of a likert-scale measure. in a similar vein, as one of our reviewers recently pointed out, our conceptualization of the spiritual and enlightened self may have relevance and applicability to the western context. in other words, in addition to buddhist teaching (yeshe and rinpoche, ; sheng yen, ) , it is plausible for us to consider the impact of other cultural and religious faiths, which could also initiate, instill, and facilitate a person's spiritual belief regarding life [e.g., christianity (davis, ; knitter, ; van der merwe, ) , hinduism (warrier, ; srivastava and barmola, ; goswami, ) , islam (nasr, (nasr, / bonab et al., ; marzband et al., ), etc.] . in a similar vein, resonating with the focus of our conceptual analysis, we contend that support for the study of positive psychology (gilham and seligman, ; seligman, ; seligman and csíkszentmihályi, ) could involve other cultural practices, religious faiths, and theoretical understanding. an important question then for consideration is whether and/or to what extent there is a central point of commonality between different cultural practices, religious faiths, and theoretical understanding, which in turn could support the paradigm of positive psychology and/or the teaching of life education. in this sense, is it plausible for us to establish some form of "convergence" in terms of commonalities of theoretical understanding between, say, christianity, buddhism, and islam? how does this convergence point, in particular, assist a person to appreciate, value, and/or understand the true meaning of life? by all accounts, we contend the possibility that there are contrasting and diverse viewpoints, resulting in dissimilarity and inconsistency with reference to the study of life education. for example, in terms of life wisdom, we note that hinduism also places emphasis on the notion of moksha, or the freeing of the samsāric cycle altogether (warrier, ) . spiritual enlightenment, the personal striving for inner discipline, and one's detachment from the external world at large may all assist a person to free himself/herself from the endless cycle of birth, death, and rebirth. social sciences research, as we mentioned, places emphasis on the topic of methodological appropriateness and the use of different methodological data collection techniques to gather evidence. some subject matters are relatively straightforward, relying on quantitative methodological approaches and robust statistical analyses. it is sound and possible, from our point of view, for researchers to consider their own teaching practices, professional and personal experiences, personal reflections and interpretations of life, and social interactions as "anecdotal evidence, " which could provide insights and theoretical understanding into the study of life education. for example, documenting our own experiences of meditation and teaching of mindfulness (hanh, ; chen, ; phan et al., a) has helped us to appreciate the importance of spirituality and the meaning of life wisdom as opposed to cognitive intelligence in a subject matter. continuing practice of buddhist meditation, in this sense, has encouraged and motivated us to engage in benevolent acts. by the same token, our anecdotal experiences, in tandem with our existing research and personal intuitions, have enabled us to develop different conceptualizations and theorizations of positive psychology (e.g., the theory of optimization) (phan et al., (phan et al., , a . researchers may adopt our lead and take a similar pathway, sharing with the academic community personal practices, experiences (e.g., esoteric experience), intuitions, etc. that could, likewise, assist in theoretical understanding of life education. having said this, however, we acknowledge that personal anecdotal evidence is non-scientific and contentious in nature, raising the question of validity, acceptance, and generalization. to a certain degree, the same point of acknowledgment also lends itself to the study of positive psychology, which has received relatively modest scientific evidence to date. on this basis, we encourage researchers to consider pathways, conceptualizations, methodological designs, etc. that could, similarly, help validate the paradigm of positive psychology. in this analysis, taking our cue, it is plausible to consider the establishment of "proxy" evidence that could affirm the prevalence of positive psychology. hp and bn were responsible for the literature search and writeup of this article. hp, bn, sc, lw, wl, and ch contributed equally to the conceptualization and theoretical contribution of the article. the basics of social research, th edn assessment of mindfulness by selfreport: the kentucky inventory of mindfulness skills social foundations of thought and action: a social cognitive theory self-efficacy: the exercise of control the role of attachment in predicting spiritual coping with a loved one in surgery attachment to god in islamic spirituality research design and methods: a process approach, th edn the benefits of being present: mindfulness and its role in psychological well-being structural equation modeling with mplus: basic concepts, applications, and programming the assessment of present-moment awareness and acceptance: the philadelphia mindfulness scale mindfulness, spirituality, and health-related symptoms responding mindfully to unpleasant thoughts and images: reliability and validity of the southampton mindfulness questionnaire (smq). br the body of knowledge in thanatology: an outline research on the experiment and reflection of the education of awareness: taking the course of 'wareness and life'of hua fan university as an example the fusion of life and health-spiritual education oriental humanities, mindfulness and life education. paper presented at the life education symposium overview and reflection on the -year national education life education curriculum constructing campus culture with life education: taking the education of huafan university as an example academic buoyancy, student's achievement, and the linking role of control: a cross-lagged analysis of high school students the motivation and limits of compassion development and preliminary validation of a trait version of the toronto mindfulness scale the simplicity of spiritual enlightenment what it feels like to die new measures of well-being new well-being measures: short scales to assess flourishing and positive and negative feelings historical and contemporary perspectives on dying happiness, excellence, and optimal human functioning revisited: examining the peer-reviewed literature linked to positive psychology the concept of compassion in islam mindfulness and emotion regulation: the development and initial validation of the cognitive and affective mindfulness scale-revised the emergence of thanatology and current practice in death education holistic education: an analysis of its ideas and nature. brandon, vt: foundation for edcational renewal measuring student well-being in the context of australian schooling: discussion paper (e. ministerial council on education, training and youth affairs ed.). carlton south: the australian council for research human motivation, th edn social stigma and its consequence for the socially stigmatized the dignity of death and the dignity of life: from dying psychiatry to modern life and death what (and why) is positive psychology? rev the "moonies": a psychological study of conversion and membership in a contemporary religious sect footsteps on the road to a positive psychology on compassion spiritual dimensions of indian culture research methods for the behavioral sciences miracle of mindfulness holistic education: an interpretation for teachers in the ib programmes confucianism as humanism new orientation of life education in the st century: spiritual awakening, classic study and environmental education health promotion and health education the growth of logical thinking from childhood to adolescence judaism, spirituality, and disability the mental health continuum: from languishing to flourishing in life principles and practice of structural equation modeling without buddha i could not be a christian religion, spirituality, and health: the research and clinical implications contemporary christian spirituality: a worldly embodiment mindfulness and spirituality: therapeutic perspectives personal best goals and academic and social functioning: a longitudinal perspective meditations on the path to enlightenment latent variable models: an introduction to factor, path, and structural equation analysis, th edn the social psychology of stigma academic buoyancy and psychological risk: exploring reciprocal relationships a concept analysis of spiritual care based on islamic sources spiritual nutrition from the islamic point of view motivation and personality personality and motivation toward a psychology of being handbook of thanatology future time perspectives of adolescents in india and the united states spirituality and health elective subjects in ordinary senior middle schools: outline of life education curriculum. taipei: ministry of education: committee for curriculum development of general senior middle schools reflection on compassion in islam and malay sufi identity islamic spirituality: foundations the future time perspective in human motivation and learning the psychology of religion and coping defining the 'positive' in positive psychology: part i. a descriptive analysis character strengths and virtues teaching, learning and psychology optimization: an attempt to establish empirical evidence for theoretical and practical purposes advancing the study of positive psychology: the use of a multifaceted structure of mindfulness for development future time perspective and the achievement of optimal best validating newly developed 'optimizing' concepts: the importance of personal resolve, effective functioning, and academic striving understanding levels of best practice: an empirical development introducing the concept of optimal best: theoretical and methodological contributions achieving optimal best: instructional efficiency and the use of cognitive load theory in mathematical problem solving optimization: in-depth examination and proposition the importance of mindfulness in the achievement of optimal best: conceptualization for research development doing what works in brief therapy: a strategic solution focused approach essays on indian philosophy theology and spirituality: strangers, rivals, or partners? horizons the president's address flourish: positive psychology and positive interventions. paper presented at the the tanner lectures on human values at the university of michigan positive psychology: an introduction positive psychology manifesto the dharma drum lineage of chan buddhism: inheriting the past and inspiring the future. taipei: the sheng yen education foundation enlightenment education, rd edn rituals in hinduism as related to spirituality the development and validation of the comprehensive inventory of thriving (cit) and the brief inventory of thriving (bit) human cognitive architecture: why some instructional procedures work and others do not cognitive load theory the central role of compassion in muslim ethics nursing students' relationships among meaning in life, well-being, and positive beliefs a cross-sectional survey study simulated directed-learning in life-education intervention on the meaning of life, positive beliefs, and well-being among nursing students: a quasiexperimental study the effectiveness of a health promotion intervention on the meaning of life, positive beliefs, and well-being among undergraduate nursing students: one-group experimental study life and philosophy of life: definition and clarification the characterisation of the spiritual christian: in conversation with god according to corinthians the role of spirituality and religiosity in aubjective well-being of individuals with different religious status spirituality and wellbeing in the context of a study on suicide prevention in north india future time perspective in schizophrenia faith guides for higher education: a guide to hinduism measuring thriving across nations: examining the measurement equivalence of the comprehensive inventory of thriving (cit) and the brief inventory of thriving (bit) an introduction to confucianism wisdom energy: basic buddhist teachings inhabiting compassion: a pastoral theological paradigm we would like to extend our appreciation and gratitude to the editor and the two reviewers for their insightful comments. hp would also like to express his appreciation to the university of new england, armidale, australia for allowing him to undertake his sabbatical, which led to the preparation and writeup of this article. a special thank you to the national taipei university of education and, in particular, the department of education (especially, sc, lw, and wl) for hosting the first author's sabbatical. the authors declare that the research was conducted in the key: cord- -a s di g authors: su, sheng-fang; han, yueh-ying title: how taiwan, a non-who member, takes actions in response to covid- date: - - journal: journal of global health doi: . /jogh. . sha: doc_id: cord_uid: a s di g nan o n march , the world health organization (who) declared that the coronavirus disease (co-vid- ) outbreak could be characterized as a pandemic [ ] . meanwhile, covid- has spread rapidly from wuhan, china to numbers of countries in asia, the middle east, and europe. as of march , more than counties, territories or areas had reported covid- cases with a total of confirmed cases and deaths globally [ , ] . while covid- is raging worldwide [ ] , taiwan [ ] -a non-who member, located km from china with more than of its million citizens working there, and with almost three million chinese visitors in , which was predicted to be one of the countries that was most affected by the virus, has defied the expectation to have only confirmed cases ( imported, indigenous, panshi how taiwan, a non-who member, takes actions in response to covid- fast combat support ship) and deaths as of april [ ]. how taiwan emerged as self-reliant from the experiences of severe acute respiratory syndrome (sars) and h n pandemic, has become a successful example during the covid- pandemic. this article describes the measures that taiwan took to prevent the spread of the novel coronavirus. on december , epidemic prevention physicians of the taiwan centers for disease control (cdc) were alerted by seven cases with suspected atypical pneumonia from wuhan, china of whom all had exposure history to the huanan seafood market of wuhan. immediately on that day ( december, ) taiwan cdc sent an email to who international health regulations (ihr): "news resources today indicate that at least seven atypical pneumonia cases were reported in wuhan, china. their health authorities replied to the media that the cases were believed not sars; however, the samples are still under examination, and the cases have been isolated for treatment" [ ]. in response to potential pneumonia outbreak in wuhan, taiwanese government immediately activated enhanced border control and quarantine measures based on the possibility of human-to-human transmission assumption on december, . the success of taiwan for anti-epidemic measures included: quick response and efficient management, central production and distribution of masks/medical supplies, quarantine/isolation regulations with tracking contacts technology, and coordination between government, medical workers, public health professionals, and the whole taiwanese society. in preparedness to potential influenza outbreak to formulate the first phase of prevention strategies [ ] . in addition to the existing measure of onboard quarantine inspection, including fever screening of arriving passengers, suspected cases screening through history of travelling, occupation, contact and cluster (tocc) inquiring, and health assessments conducting, all health care facilities should reinforce reporting severe cases of pneumonia among people who arrive in taiwan from wuhan. all health care workers should strictly adhere to standard precautions for preventing nosocomial infection, wearing n respirators as required while performing invasive medical procedures such as intubation and tracheostomy [ , ]. to minimize the threat of the outbreak, on january , the taiwan cdc activated the central epidemic command center (cecc) for severe special infectious pneumonia that composed of government agencies and medical experts/specialists to take charge of the domestic epidemic prevention and control, and to coordinate resources from across ministries and private stakeholders [ , , ] . since then, the cecc convened a daily press conference to update the latest epidemic, prevention measures and health guidelines. such efforts included reporting criteria of all pneumonia cases, testing and quarantine procedures, preparation of pharmaceutical and medical supplies, capacity ensuring of isolation wards, and public health education (mask wearing, temperature checking, hand washing, avoiding eyes, nose, and mouth touching, environmental disinfection, etc.). following identifying the first imported covid- case returning from wuhan on january , cecc raised travel notice level for wuhan, china to level warning. the confirmed case was treated in a negative pressure ward at the hospital, the close contacts were traced and the quarantined individuals were electronically monitored. in light of the ongoing outbreak, cecc has introduced guidelines for high-risk individuals regarding ) self-health management (reported cases who have tested negative and met criteria for being released from isolation, or people under "covid- community-based surveillance), ) -day home quarantine (with travel history), and ) -day home isolation (who had contact with confirmed cases), and provided quarantine sites with free meals and a us$ compensation per day during the -day period. furthermore, on february an electronic health declaration system was established for returning travelers, allowing updated health care services. starting from march, home quarantine measures have been expanded to include arriving passengers from all countries. taiwan designated response and isolation hospitals, as well as regional hospitals or medical centers for treatment of confirmed cases, to establish the communicable disease control medical network (cdcmn) [ ]. according to the communicable disease control act, the taiwan cdc classified covid- as a category communicable disease on january. people who meet the epidemiological criteria within days: ) history of traveling or living abroad, or contact with symptomatic (fever or other respiratory tract infection symptoms) individuals returning from abroad; ) history of close contact with symptomatic suspected or confirmed case(s); ) history of cluster related to confirmed cases are required to report to the cdc and placed for laboratory diagnosis. furthermore, starting april, patients with pneumonia are required to be reported and subjected to testing. a total of medical facilities were designated for collecting specimens. the laboratory testing capacity in taiwan has reached laboratories for cases per day. as of may, cases have been tested and were excluded (as negative) with laboratory-confirmed cases. people with three negative testing results were able to be released from isolation [ ]. the community surveillance system has been implemented since february for travelers to scan the qr code with a health declaration and home quarantine e-system (entry quarantine system). people in -day home isolation were contacted twice a day by local health agencies to follow their health status. in collaboration with telecom companies, taiwan launched an electronic security monitoring system to cellphone track people subjected to home quarantine/isolation [ , ] . the responsible civil affair bureau worker could receive a notification via sms when the phone signal disappears, allowing the police to per-form the location check. violators could be fined or forcibly placed to the designated sites. taiwan central and local governments provided consultation and support services for the assistance of transport arrangements, medical care arrangements and household services. isolation hospitals, hotels and transportation arrangements for epidemic prevention were designated for home quarantined/isolated individuals. a special act for prevention, relief and revitalization measures for severe pneumonia with novel pathogens was adopted on february to respond to the coming crisis [ ]. to evacuate taiwanese in wuhan, cecc deployed a thorough onboard quarantine procedure. individuals with symptoms were sent to negative pressure isolation wards directly upon arrival. all other evacuees were sent to designated quarantine sites by designated transport vehicles and placed under -day period of quarantine with their luggage disinfected. all related staff and health care workers participated in the charter plane operation wore personal protective equipment. different from the stigmatization in the west, the less negative perception of wearing a face mask in taiwan (and eastern asia) has contributed to the "first line of defense" of covid- [ ] . for taiwanese, it has become a cultural norm to wear a face mask due to various reasons, including: a courtesy to others when feeling sick, to keep face warm in winter, and as a protection from vehicle exhaust or air pollution. it is not implication for crime and security in the society. more importantly, from the sars outbreak in , taiwanese government and citizens have learned how viral respiratory diseases can inflict and realized the impact of wearing a mask on reducing the risk of disease transmission, adopting mask wearing for covid- was implemented quickly. people in taiwan wear masks when taking mass transportation (metro, trains, buses and taxis), and going into the crowded public places. in addition, taiwanese acknowledge scientific-based evidence, respect experts' recommendations, and follow government' s policies at the preparedness phase of the pandemic. the whole community voluntarily partnering with the government to create a network of databases with transparent information is another key to the success of "testing, tracing and isolating" strategy for fighting covid- [ ] . the taiwanese government has been collaborating with developers and citizens to develop strategies and solutions at the online town hall (https://info. vtaiwan.tw/), where people can participate in the dialogue and the process of policy making and therefore, inspire the trust. the consensus of sharing digital data temporarily and of understanding how it is used have kept the virus from spreading in the community. taiwan though excluded from membership in the who stands out in the covid- pandemic as an example of successful prevention and outbreak control [ ] [ ] [ ] . as of may, while covid- affected over countries with a total of confirmed cases and deaths worldwide [ ] , taiwanese society maintained routine daily life without long-term nationwide school closures or bushiness shutdown. taiwan's baseball league was the first professional game to open the season on april. given its effective actions and managements, taiwan had the capability to donate up to million masks to the us, europe, and diplomatic allies, and collaboratively work with the world [ , ] . it is the time to rethink how the world is tightly connected. taiwan' s model of fighting covid- set an example of how to effectively prevent or better response to the next public health crisis. coronavirus disease (covid- ) situation report covid- dashboard by the center for systems science and engineering (csse) at johns hopkins university (jhu) covid- -a timeline of the coronavirus outbreak as government fumbled their coronavirus response, these four got it right. here' s how how my country prevented a major outbreak of covid- taiwan health minister: covid- outbreak underscores importance of taiwan' s inclusion in who. ipoli-tics it' s taiwan. bloomberg opinion asia may have been right about coronavirus and face masks, and the rest of the world is coming around. cnn. available we thank dr chien-jen chen, dr huei-wen chen and mr. nathan peluso for their constructive suggestions, and the ministry of science and technology for the support. authorship contributions: all authors contributed to writing and conceptualizing the manuscript. the authors have completed the icmje unified competing interest form (available upon request from the corresponding author) and declare no conflicts of interest. key: cord- - tb uha authors: chen, ming-hsiang title: the economy, tourism growth and corporate performance in the taiwanese hotel industry date: - - journal: tour manag doi: . /j.tourman. . . sha: doc_id: cord_uid: tb uha this study investigates the impact of economy and tourism growth on the corporate performance of tourist hotels in taiwan. the indicators of corporate performance under consideration are occupancy rate (opr), return on assets (roa), return on equity (roe), stock return, and the overall financial performance measured by a comprehensive score (a combined measure of asset management, profitability, short-term solvency or liquidity and long-term solvency based on factor analysis). the effects of changes in the state of economy (real gdp growth rate, [formula: see text]) and tourism growth (growth rate of total foreign tourist arrivals, [formula: see text]) on the corporate performance of tourist hotels are then examined via panel regression tests. test results show that both [formula: see text] and [formula: see text] are significant explanatory factors of opr, but only [formula: see text] can strongly explain roa and roe. however, neither [formula: see text] nor [formula: see text] have a significant influence on hotel stock performance. further, the economic factor [formula: see text] is slightly more crucial than the industry factor [formula: see text] in describing the overall financial performance in the taiwanese hotel industry. empirical findings offer valuable information for government tourism policymakers and tourist hotel owners and managers. the economy is the environment in which all firms operate (bodie, kane, & marcus, ) . thus, the prospects of a firm are closely tied to the state of the economy (or economic climate). in other words, changes in corporate performance are closely related to expansion and contraction of the business cycle. bodie et al. ( ) argued that the economic climate might have a greater impact on profits than the firm's performance within its industry. the corporate performance in the hotel industry may also rely on economic conditions. the hotel industry is viewed as a cyclical industry, an industry that is highly sensitive to the state of the economy (bodie et al., ) . the reason is that the hotel companies tend to have higher fixed costs (costs that all firms incur regardless of their production levels) than variable costs (costs that increase or decrease as the firm produces more or less). with high fixed costs, hotel companies are very sensitive to business conditions because in economic downturns, hotel firms cannot reduce costs as output falls in response to falling sales. hotel profits will hence swing more widely with sales because costs do not move to offset revenue variability (i.e. small swings in business conditions can have profound effects on profitability of hotels). as graham and harris ( ) noted, due to their high fixed costs, hotels require maintaining high revenue to survive and generate adequate profit. in addition to economic condition, tourism expansion or tourism growth can also have a strong influence on the corporate performance of hotel companies. on the one hand, the expansion of tourism industry or activities directly enhances the development of hotel industry by increasing the occupancy rate and hence sales revenue. on the other hand, tourism development can significantly improve business environment, which has an indirect effect on the corporate performance of hotel firms. previous empirical studies have supported that tourism expansion can boost economic development (balaguer & cantavella-jorda, ; dritsakis, ; fayissa, nsiah, & tadasse, ; gunduz & hatemi-j, ; kim, chen, & jang, ; lee & chang, ; proenca & soukiazis, ) . chen ( b) showed that improved economic conditions caused by tourism expansion could raise corporate earnings and strengthen the financial performance of tourism-related firms. in other words, the expansion of tourism is expected to promote the corporate performance of hotel companies. this study investigates the impact of the state of economy and tourism growth on the corporate performance of tourist hotels in taiwan. to measure corporate performance, the majority of previous studies used return on assets/return on equity (athanasoglou, brissimis, & delis, ) or stock returns (barro, ; beckers, grinold, rudd, & stefek, ; chen, b; chen, kim, & kim, ; fama & french, ) . ross, westerfield, and jordan ( ) stated that return on assets (roa) and return on equity (roe) indicate the profitability of companies, which may fail to measure the company's overall performance. moreover, although stock price has been widely used as an indicator for corporate performance (chen, b; heiman, ) , it might be easily twisted by expectations of irrational investors about future corporate earnings. that is, if investors are not rational, investors' perceptions about market riskiness will be biased and a firm's stock price would not reflect the true financial performance. specifically, this study makes the following contributions to the tourism literature. first, various indicators of corporate performance are used to test the effects of economic condition and tourism growth on corporate performance in the tourist hotel industry. the indicators of corporate performance under consideration are occupancy rate, roa, roe, stock return, and a comprehensive score. the occupancy rate is a common performance measure of sales revenue in the hotel industry. as mentioned, roa and roe measure profitability of hotel companies, whereas stock price can evaluate hotel stock performance. in addition, we follow boubakri, cosset, fischer, and guedhami ( ) , kesner ( ) , liu and hung ( ) and otchere and chan ( ) to use several accounting/financial ratios to calculate a comprehensive measure, or score, of corporate performance that can represent the overall financial performance of hotel companies. six accounting ratios, including debt-equity ratio, total asset turnover, current ratio, quick ratio, roa, and roe, are used to calculate a comprehensive score based on factor analysis. the comprehensive score thus combines measures of asset management (total asset turnover), profitability (roa and roe), short-term solvency or liquidity (current ratio and quick ratio) and long-term solvency (debt-equity ratio). in consequence, this study enables us to evaluate the impact of economic condition and tourism expansion on the corporate performance of tourist hotels in terms of not only their sales revenue, profitability and stock performance but also the overall financial performance. empirical findings can provide tourism policymakers and hotel business managers with some practical managerial implications. second, this paper considers the possible impact of some unexpected crises related to the hotel and tourism industry into consideration. some empirical studies reported that events such as the earthquake on september , the terrorist attacks of september in the us, and the outbreak of severe acute respiratory syndrome (sars) in march , significantly damaged financial performance of hotel companies in taiwan (chen, jang, & kim, ; chen & kim, in press; chen et al., ) . the dummy variables of crisis events are incorporated into test regressions to control for their potential effects on interactions between the corporate performance of hotel firms and the two factors (economy and tourism growth). lastly, this study can offer a comparative examination on whether the economic factor or the industry factor exerts a greater impact on different dimensions of corporate performance in the tourist hotel industry. changes in the economy can be viewed as the economic factor, whereas the expansion of the market for foreign tourism, proxied by the growth of foreign tourist arrivals, can be used as the industry-specific factor. as bodie et al. ( ) have argued, compared to the industry factor, the state of the economy might have a greater influence on a firm's performance. it would be interesting to see if the effect of the economic factor on corporate performance of hotel firms is as strong as that of industry factor. the remainder of the paper is organized as follows. section reviews the empirical research efforts in the literature. section describes the data and variables. section presents the panel regression models and test results. discussions and conclusion with some managerial implications are shown in section . since the business success of hotel companies is assumed to be tightly related to the economy, it makes sense to analyze the influence of the state of the aggregate economy on corporate performance in the hotel industry. however, there is relatively little examination of the association between business conditions and corporate performance of hotel companies in the hospitality and tourism literature. choi, olsen, kwansa, and tse ( ) developed a model of the business cycle for the u.s. hotel industry. the hotel industry cycle is defined as the fluctuation in the total receipts of the entire hotel industry. the hotel industry cycle model demonstrated the growth of the hotel industry by showing that the hotel industry grew rapidly every four or five years during the years from to . the hotel industry cycle model could provide valuable guidelines for practitioners and researchers in the hotel industry. for instance, the average expansion period was about three years, while the average contraction period was about two years. moreover, the hotel industry led general business cycle troughs (peaks) by an average of . ( . ) years. choi ( ) employed an economic indicator system to project the growth and turning points of the us hotel industry. he identified leading, coincident and lagging indicators in the study based on a comprehensive literature review as well as the national bureau of economic research turning point criteria and statistical correlation method. as he noted, the performance of the economic indicator system illustrated the system's great potential as a forecasting method. another stream of research work focused on the significance of the key economic variables that can be used to summarize the state of the economy in explaining financial performance (stock return) of hotel firms (barrows & naka, ; chen, a chen, , c chen et al., ) . barrows and naka ( ) investigated whether five selected economic variables (the expected inflation rate, money supply, domestic consumption, term structure of the interest rate, and industrial production) could determine the returns of u.s. hospitality stocks. they found that the expected inflation rate, growth rates of money supply and domestic consumption had a significant impact on hospitality stock returns. chen et al. ( ) tested the impact of a set of economic variables and non-economic events on hotel stock returns in taiwan. they observed that money supply growth rates and changes in unemployment rates are two influential economic factors of taiwanese hotel stock returns. in addition, not only economic variables but also non-economic events, including wars, presidential elections, natural disasters, sports mega-events, and terrorist attacks, could have a strong effect on hotel stock returns. similarly, a significant influence of economic and non-economic factors on hotel stock performance was found in china (chen, c) . chen ( a) studied the relationship between hotel stock returns and monetary conditions. by examining the performance of taiwanese hotel stocks under two monetary policy environments, he showed that hotel stocks had a higher mean return and rewardto-risk ratio during expansive monetary periods. chen ( b) argued that a sound (poor) business environment should lead to a growth (decrease) in sales and earnings, and consequently strengthen (weaken) the performance of business firms. in other words, corporate earnings are expected to rise (fall) when the economy is expanding (contracting), resulting in strong (sluggish) business performance. accordingly, he studied interactions between business conditions and stock performance of tourism companies in china and taiwan. gross domestic product (gdp) and stock price were used as proxies of business conditions and financial performance of tourism firms, respectively. empirical results revealed a long-run link between business conditions and stock performance of tourism firms. further, the improved business conditions could enhance the stock performance of tourism firms and financial success of tourism firms could improve business development. tang and jang ( ) examined the cointegration and causality between sales of four tourism-related industries (airlines, casinos, hotels, and restaurants) and economic growth in the u.s. test results indicated no cointegration between gdp and sales of all four tourism industries, i.e. there was no long-run link between gdp and industry sales. however, gdp growth could lead to sales growth of all four industries and industry sales failed to cause gdp growth in the short run. while the development of tourism industry is expected to have a directly beneficial impact on hotels, it can affect the hotel industry via its ability to enhance the state of economy, thus strengthening the corporate performance of hotels. empirical studies supported that tourism expansion can improve economic condition (balaguer & cantavella-jorda, ; dritsakis, ; gunduz & hatemi-j, ; kim et al., ) . balaguer and cantavella-jorda ( ) proposed a tourism-led growth hypothesis that tourism expansion was a significant factor in the development of the spanish economy. empirical results based on cointegration and causality tests supported the hypothesis. cointegration tests revealed a long-term relationship between tourism receipts and gross domestic product, and causality test results indicated that tourism expansion can cause economic development. dritsakis ( ) examined whether tourism could serve as a long-term economic growth factor in greece. such a relationship between tourism receipts and gdp was detected. moreover, there was a bi-directional causality between growth in gross domestic product and tourism receipts. in other words, growth in tourism receipts and gdp growth could promote each other. gunduz and hatemi-j ( ) stated that turkey, like many developing countries, gave priority to tourism as a part of its economic growth strategy. they tested the tourism-led growth hypothesis by examining whether tourism expansion had contributed to turkey's economic growth. test results showed that tourism development could lead to economic growth and thus validated the applicability of the tourism-led growth hypothesis to turkey. kim et al. ( ) studied the causal relationship between tourism expansion (proxied by growth in the number of total foreign tourist arrivals) and economic growth (gdp growth) in taiwan. the results based on cointegration and causality tests illustrated a long-run equilibrium link and a bi-directional causality between the two factors. in other words, an expanding economy could lead to the expansion of tourism while the increase in the number of foreign visitors to taiwan could promote economic growth. similarly, the spending of international tourists had a positive impact on the economic growth of african countries (fayissa et al., ) and tourism contributed significantly to the improvement of the standard of living in four southern european countries (greece, italy, portugal and spain) (proenca & soukiazis, ) . lee and chang ( ) re-examined the long-run comovements and causal links between tourism development and economic growth for oecd and non-oecd countries (including those in asia, latin america and sub-saharan africa) using a heterogeneous panel cointegration technique. they found a cointegrated relationship between gdp and tourism development on the global scale, after allowing for the heterogeneous country effect. in addition, tourism development exerted a greater effect on gdp in non-oecd countries than in oecd countries. in the long run, tourism development could cause economic growth in oecd countries and the two factors reinforced each other in non-oecd countries. in addition, chen, kim, and liao ( ) noted that the tourism industry has experienced a significant growth since the taiwanese government changed the weekend policy in and foreign institutional holdings on stocks of tourism companies have escalated since then. they explained that foreign institutional investors increased their holdings on tourism stocks because they anticipated a positive influence of weekend policy changes on earnings of tourism companies and are optimistic about the future corporate performance in the tourism industry. they further showed that the increasing foreign institutional holdings could not only enhance tourism stock performance, but also decrease the risk of tourism stock returns. to sum up, tourism growth can promote business and boost corporate sales and earnings, thus strengthening the financial performance of hotel firms. the variable of total foreign tourist arrivals (tourism expansion) is hence expected to have an impact on corporate performance in the hotel industry. however, chen ( a) compared the impact of economic variables and tourism expansion factor on hotel stock returns in taiwan. test results indicated that the tourism expansion factor had a positive but not statistically significant effect on hotel stock performance. chen ( c) found that the tourism expansion variable could not satisfactorily explain hotel stock returns in china, either. chen and kim (in press) argued that tourism expansion had a more direct impact on tourism firms' earnings than on their stock performance. relatively, not many research papers studied the impact of noneconomic forces on financial performance in the tourism industry. sales earnings of taiwanese hotel firms were found to been significantly harmed by the earthquake in taiwan on september , and by the sars outbreak in march (chen & kim, in press ). illustrated the adverse influence of the sars outbreak in on taiwanese hotel stock prices. stock prices of publicly traded hotel companies in taiwan plunged during the sars outbreak. in addition to the sars outbreak, several other crises related to the hospitality industry seriously damaged hospitality stock performance. chen et al. ( ) showed that the earthquake on september , and the terrorist attacks of september , in the u.s. substantially deteriorated hotel stock performance in taiwan. since those crises had a significant influence on financial performance of hotel companies in taiwan, this study takes those non-economic events into consideration when regression tests are performed. thus, when examining the impact of economy and tourism development on corporate performance in the tourist hotel industry, we use dummy variables of crisis events to control for the potential effects of those crises on interactions between the corporate performance of tourist hotels and the two factors. the hotel companies covered in this study need to have complete data on all accounting or financial variables over the -year period from to . according to this criterion, we selected five publicly traded hotels: ambassador hotel, first hotel, grant formosa regent taipei, hotel holiday garden, and leofoo corporation. all five hotels are tourist hotels whose stocks are traded on the taiwan stock exchange. all data used in the study are taken from the database of the taiwan economic journal (tej) from the second quarter of to the first quarter of ( quarters). occupancy rate (opr). opr is the percentage of occupancy and calculated as the number of rooms occupied divided by the number available. it is one of the commonly used performance measures of revenue in the hotel industry (gray & liguori, ) . return on assets (roa). roa, computed as net income divided by total assets, is a measure of profit per dollar of assets: net income total assets  %: ( ) roa reflects the ability of a firm's management to generate profits from the firm's assets (athanasoglou et al., ) . kang and stulz ( ) stated that investors prefer firms with high roa because it is an indication of management efficiency. roa is also commonly used to measure corporate performance (capon, farley, & hoenig, ; gonzalez-hermosillo, pazarbasioglu, & billings, ; hall & weiss, ; kesner, ; persons, ; thomson, ) . return on equity (roe). roe is defined as the net income divided by total equity and a measure of a firm's efficiency at generating profits from every dollar of shareholders' equity: roe is also widely used to measure profitability of companies (athanasoglou et al., ; capon et al., ; chathoth & olsen, ; kesner, ) . moreover, liu and hung ( ) argued that roa and roe can measure both profitability and earnings quality of companies. stock return (sr). the stock return is the capital gains (or loss), i.e. the percentage change in the price of the stock divided by the initial price: where stock price is the closing price at the end of each quarter. as heiman ( ) noted, although there are several indicators of a company's financial success, the company's stock price is considered to be the most important. stock return has been generally used as an indicator for corporate performance (barro, ; beckers et al., ; chen, b; chen et al., ; fama & french, ) . the overall financial performance (score). as mentioned, this study uses a comprehensive score to measure the overall financial performance of hotels. the overall financial performance or comprehensive score combines measures of asset management (total asset turnover), profitability (roa and roe), short-term solvency or liquidity (current ratio and quick ratio) and long-term solvency (debt-equity ratio). it takes two steps to calculate the variable of score. the first step is the selection of related accounting/financial ratios. following boubakri et al. ( ) , kesner ( ) , liu and hung ( ) , and otchere and chan ( ), we use several accounting/ financial ratios to calculate the comprehensive score (score). the accounting ratios selected in the study need to meet two criteria. the accounting ratios have to have complete data from the second quarter of to the first quarter of . moreover, the selected accounting variables can represent six dimensions of corporate performance: capital adequacy, asset quality, management, earnings, liquidity, and sensitivity to market risks (persons, ; thomson, ) . accordingly, six accounting ratios are selected in the study: debt-equity ratio, total asset turnover, current ratio, return on assets, return on equity and quick ratio. the quarterly data of six financial ratios are also obtained from the tej database. total asset turnover (tat) measures how efficiently a company uses its assets to generate sales (weygandt, kieso, & kimmel, ) : total asset turnover, the proxy of management capability, can measure the operating efficiency that the board of directors and senior managers command total assets (gonzalez-hermosillo et al., ; persons, ) . gu and kim ( ) suggested that a high level of operational efficiency leads to an increase in profit. current ratio (cr) is a widely used measure for evaluating a company's liquidity and short-term debt-paying ability (weygandt et al., ) : according to kallberg and parkinson ( ) , corporate liquidity can be used to access the management of the firm's assets. kim, mauer, and sherman ( ) stated that the relationship between the liquid asset holdings and the firm's growth opportunities might be positive. myers ( ) argued that maintaining high liquidity might help in reducing the financial distress. however, high liquidity might also indicate that available resources are not wisely invested, which may increase the investors' risk perception (borde, ) . quick ratio (qr) is a measure of a company's immediate shortterm liquidity (weygandt et al., ) : the quick ratio also represents the liquidity of companies. according to ross et al. ( ) , inventory is often the least liquid current asset. they indicated that book value is not a very reliable measure of market values because it fails to take the quality of the inventory into consideration. relatively large inventories are often a sign of problems with short-term liquidity. it is important for firms to maintain the optimal liquidity reserve for contingent use. debt-equity ratio (de) is also called leverage ratio and used to examine the firm's long-run ability to meet its obligations or financial leverage (ross et al., ) : liu and hung ( ) used this variable as the proxy of capital adequacy to measure if companies maintain ample capital to monitor their own risk. barton and gordon ( ) noted, if the environmental conditions are favorable for firm's growth, firms will use more equity and less debt to fund their growth. the pecking order theory also suggests that well-performing firms in terms of their profitability are likely to be less leveraged (morck, shleifer, & vishny, ) . second, after selecting six accounting ratios, we compute the final comprehensive score based on the factor analysis (choi & chu, ; chu & choi, ; hair, anderson, tatham, & black, ; pitt & jeantrout, ; west, ) . using factor analysis enables us to create correlated variable composites from the original six financial ratios and identify a smaller set of factors that can explain most of the variances among the ratios (chu & choi, ) . through the method of factor analysis, we can better understand the underlying structure of the data. accordingly, a principal component factor analysis with varimax rotation is performed to extract from the six hotel financial ratios into a set of simplified composite hotel performance factors. whether a financial ratio should be included in a factor is decided by the factor loadings, eigenvalues and the percentage of variance explained (hair et al., ) . hair et al. ( ) suggest that factors are considered significant and retain only if they have an eigenvalue equal to or greater than , and a factor loading equals to or greater than . . as matter of fact, all factors included in the study have a factor loading above . . we repeat the same procedure to extract factors from six financial ratios for every quarter. note that although there are different extracted factors in each quarter, the extracted factors can explain more than % of the total variance for each quarter. after the factor analysis, we obtain the extracted factors that represent corporate performance of hotel companies and the corresponding factor score of each hotel for each quarter. the corresponding factor score of each hotel multiplies the weight of each factor and then sum up to get the quarterly comprehensive scores of hotel performance. in consequence, the comprehensive scores of hotel companies are computed as: where score i is the comprehensive score of corporate performance for the ith hotel company, s i is the corresponding factor score of the ith hotel company and w i is the weight or ratio of the variation explained by each factor divided by the variation explained by all factors: where w i is the weight of the ith factor, e i is the variation explained by the ith factor and k is the number of factors. gross domestic product (gdp), the measure of the economy's total production and services, is used as the proxy for economic condition. real gdp growth therefore represents changes in economic condition (athanasoglou et al., ; bikker & hu, ; chen, b; kim et al., ) . the growth rate of real gdp (dgdp) is computed as: the hotel industry, as a cyclical industry, is very sensitive to the economy. shifts in economic condition can have a great impact on the success of hotel firms. a business expansion (contraction) can strengthen (weaken) corporate earnings and profit, which in turn can improve (worsen) corporate performance of hotel companies. we therefore anticipate that the hotel industry has a better corporate performance in better economic times. accordingly, it is hypothesized that corporate performance of hotel companies is positively related to economic growth. the growth rate of total foreign tourist arrivals ðdtaÞ is used to represent tourism growth or expansion (chen, a (chen, , c kim et al., ; wang & godbey, ) and calculated as: tourism expansion can lift the occupancy rate and earnings and enhance the financial performance of hotel companies. in addition, as empirical studies have shown, tourism expansion can boost economic development (balaguer & cantavella-jorda, ; dritsakis, ; gunduz & hatemi-j, ; kim et al., ) and the improved economy caused by tourism expansion can raise sales and corporate earnings. high tourism arrivals growth is expected to have a favorable impact on corporate performance of hotel firms. consequently, corporate performance of hotel companies is hypothesized to be positively related to tourism growth. the internal factor, the variable of firm size (size), is used as a control variable. size is measured by the natural logarithm of the average total assets. this data of hotel firm size are also taken from the tej financial database. in addition, the possible influences of some recent unexpected crisis events related to the hotel industry are also incorporated into the test regressions. as mentioned, the crisis events under consideration in the study are the earthquake of september , (the earthquake), the terrorist attacks of september , in the u.s. (the terrorist attacks) and the outbreak of sars on april , (the sars outbreak). table displays the correlation coefficient values among the five dependent variables and the exploratory variables over the entire sample period. as shown in table , opr is significantly correlated with dgdp, whereas opr, roa and roe are highly correlated with dta. however, hotel stock return (sr) is not significantly correlated with either dgdp or dta. the overall performance (score) appeared to be strongly correlated with both dgdp and dta. moreover, high correlation between dgdp and dta indicates that economic growth and tourism development are highly correlated. this is consistent with the empirical finding in kim et al. ( ) . they show that the growing inflow of foreign visitors to taiwan promotes economic development and an expanding economy leads to tourism expansion. to examine the impact of economic condition and tourism growth on corporate performance of hotel companies, we perform panel regression tests using a balanced panel data of five hotel companies spanning the period from to . baltagi ( ) and hsiao ( ) argued that panel data methodology can control for an individual firm's heterogeneity, reduce problems associated with multicollinearity and estimation bias and specify the time-varying relation between dependent and independent variables. moreover, when performing panel regression tests, we also consider three estimation methods: pooled ordinary least square (ols), fixed effects and random effects. accordingly, the following panel regression tests are performed: where d , d and dsars denotes the dummy variable of the earthquake (september ), the terrorist attacks in the us (september ), the sars outbreak (april ) respectively. all dummy variables take the value of during the corresponding quarter on the event date and otherwise. before running panel regression tests, we use the unit root test to examine the stationary of all variables. to avoid the spurious regression, we have to confirm that all variables are stationary. the panel unit root tests of breitung ( ) and im, pesaran, and shin ( ) are executed to examine the stationary of all variables. results of both tests indicate that dgdp, dta, opr, roa, roe, sr, score and size are all stationary (see table ). linear panel data regression test can be estimated using three methods: pooled ordinary least square (ols), the fixed effects method and the random effects method (dimitrios, ) . the pooled ols method estimates a common constant for all crosssections. that is, there are no differences between the estimated cross-sections. the constant is treated as section-specific in the fixed effects method. the difference between the fixed effects method and random effects method is that the constants of the random effects method for each section are random parameters. the fixed effects estimator is also called the least squares dummy variables estimator because the fixed effects method includes a dummy variable for each hotel to allow for different constants for each hotel. consider the following model: we can re-write the model in the matrix notation as: i ¼ ; /n, t ¼ ; /t; the dummy variable allows us to take different group-specific estimates for each of the constants for every different section. n is the number of hotels. t andkrepresent the time periods and the number of the independent variables, respectively. in this study, n is equal to (hotels), t is and kis . consequently, there are sample observations ( hotels times quarters) available for the panel regression test. we also need to test whether fixed effects (i.e. different constants for each group) should be appropriate in the model before assessing the validity of the fixed effects method. hence, f-test is used to determine whether the pooled ols is more appropriate than the fixed effect model. the null hypothesis is that all the constants (the respective intercepts of hotels) are the same, and therefore the common constant method is applicable: the f-statistic is: ðnt À n À kÞ wfðn À ; nt À n À kÞ; where r fe is the coefficient of determination of the fixed effects model, r cc is the coefficient of determination of the common constant model, n represents the number of hotel firms. if f-statistic is larger than f-test critical value, we then reject the null hypothesis, implying that the fixed effects method is more appropriate than the pooled ols. results of the f-test in table ( dta ¼ growth rate of total foreign tourist arrivals; size ¼ the natural logarithm of the average total assets. *significance at the % level. **significance at the % level. ***significance at the % level. the random effects model suggests that the intercepts a of different hotels are random and independently drawn from population. random effects model focuses on arbitrary individuals that have certain characteristics and allows us to make inference with respect to the population characteristics. based on the random effects model, the matrix notation can be written as: where a is the random intercept, m is the error term of the random intercept, mwiidð ; s m Þ. the hausman test is used to determine if the fixed or random effects should be considered. the null hypothesis is that m and x are uncorrelated and thus random effects are consistent and efficient (dimitrios, ; maddala, ) : the test statistic is: where b h fe is the estimator of the fixed effects model, b h re is the estimator of the random effects model. if the test statistic is large (i.e. the difference between the two estimators is significant), we can reject the null hypothesis that the random effects model is consistent, suggesting that the fixed effects model is more appropriate. the hausman ( ) test results (see panel b in table ) illustrate that panel regressions based on eqs. - , and are significant at the % level. hence, the fixed effects model is used to perform panel regressions for eqs. - and . empirical results of panel regression tests based on eqs. - are summarized in tables - , respectively. panel regression test results in table show that coefficients of dgdp and dta are positive and statistically significant at the % and % level respectively, implying that dgdp and dta have a significant impact on opr. this is consistent with the correlation coefficient values reported in table that opr is highly correlated with dgdp and dta. the explanatory power (adjusted r value) of dgdp and dta on opr is relatively high at about % (see panel b) and % (see panel c), respectively. these results indicate that dgdp and dta are strong explanatory factors of opr. the link between opr and size is found to be significantly positive, suggesting that tourist hotels with larger size enjoy higher occupancy rate. it is also found that the negative coefficients of the dummy variables of d and dsars are statistically significant at the % level. tables and , has a positive impact on roa and roe and its effect (the coefficient of dta) is statistically significant at the % level. this supports the correlation coefficient values in table that both roa and roe are correlated with dta. the overall explanatory power of dta on roa and roe is also high at about % and % (see panel b in both tables), respectively. while dgdp exhibits a positive influence on both roa and roe, its influence is not statistically strong. in addition, size is found to be negatively related to roa and roe. among three dummy variables, only dsars has a significantly negative impact on roe. test results in table reveal that dta and dgdp have a positive effect on sr, but their effects are not statistically significant. the low adjusted r value of pooled ols regression implies the goodnessof-fit for the estimated regression equation is poor and the two independent variables explain very little proportion of variation in hotel stock returns. the overall adjusted r value is also relatively low at %. it is also found that there is no strong relationship between size and sr. dsars and d have a significantly negative influence on sr. tests results presented in table illustrate that the coefficients of dgdp and dta are positive and statistically significant at the % and % level, respectively. the findings indicate that a better economic condition and tourism development can improve the overall corporate performance of tourist hotels. the overall explanatory power of dgdp and dta on the comprehensive score is opr (regression equation ( )) . [ . ]*** fixed effects roa (regression equation ( )) . [ . ]*** fixed effects roe (regression equation ( )) . [ . ]*** fixed effects score (regression equation ( )) . [ . ]*** fixed effects note: *, **, and *** indicate that the null hypothesis can be rejected at the %, % and % level, respectively. about % (see panel b) and % (see panel c), respectively. moreover, size, d and dsars are negatively related to score. this study examines the impact of economic and industry factors on corporate performance of tourist hotels in taiwan. the economic factor is changes in the economy (real gdp growth rate, dgdp), whereas tourism expansion (the growth rate of foreign tourist arrivals, dta) is used as the industry-specific factor. the indicators of corporate performance of hotels under consideration include occupancy rate (opr), return on assets (roa), return on equity (roe), stock return and a comprehensive score. opr is a common performance measure of sales revenue in the hotel industry. roa and roe measure the profitability of hotel companies, whereas stock return can evaluate hotel stock performance. based on factor analysis approach, six accounting ratios (total asset turnover, return on assets, return on equity, current ratio, quick ratio and debt-equity ratio) are used to compute a comprehensive score that can measure the overall financial performance rather than just sales revenue, profitability and stock performance. the comprehensive score combines measures of asset management (total asset turnover), profitability (roa and roe), short-term solvency or liquidity (current ratio and quick ratio) and long-term solvency (debt-equity ratio). the effects of dgdp and dta on corporate performance in the tourist hotel industry are then scrutinized via panel regression tests. panel regression test results reveal that both economic and industry factors have a positive and significant effect on occupancy rate of taiwanese tourist hotels. the results imply that tourist hotels can enjoy a better occupancy rate when the economy is expanding and the foreign tourist market is growing. in contrast, the hotel occupancy will suffer if the economy is in recession and tourism interest in taiwan is low. compared to the economic factor, the industry factor explains more variation in occupancy rate. changes in the state of economy can account for % of variation in occupancy rate, whereas tourism expansion describes even as high as % of variation in occupancy rate. in other words, the sales revenue of tourist hotels relies heavily on the development of foreign tourist markets and economic conditions. these results also support the assumption that the growth of total foreign tourist arrivals should have a direct and beneficial influence on corporate performance of tourism-related companies. both economic and industry factors are found to have a positive impact on hotels' roa and roe, but only the influence of tourism expansion is statistically significant. that is, the profitability of tourist hotels in taiwan is more closely related to the industry factor rather than economic factor, and the development of foreign tourist market displays a greater impact on the profitability of tourist hotels. in specific, tourism expansion can account for more than % and % of variation in roa and roe of tourist hotels, respectively. while shifts in economic condition can strongly affect sales revenue of tourist hotels, they exhibits no substantial influence on the profitability. stock performance of tourist hotels, however, is found to be not significantly linked to changes in both economic condition and inflow of foreign tourists. the insignificant impact of economic and tourism growth on hotel stock returns might be attributable to a time-varying discount rate caused by investors' changing perceptions about the riskiness of cash flows. note that variations in stock prices, according to the basic stock valuation model, reflect changes in both expected cash flows and the discount factor (perceived riskiness of a stock's cash flows). while the booming economy and especially strong tourism expansion can impact hotel stock prices majorly through their influences on sales revenue of tourist hotels as illustrated above, investors' changing perceptions about the riskiness of cash flows can lead to changes in the discount rate (or the time-varying discount rate). hence, the time-varying discount rate, caused by investors' changing perceptions about the riskiness of cash flows, can break the tie between hotel stock returns and the two factors, regardless of how good the state of economy and how successful tourism development can be in improving earnings performance. in addition, both economic and industry factors are positive and significant explanatory variables of the overall financial performance of tourist hotels. this indicates that a better economic climate and tourist market development can improve the financial health of tourist hotels. moreover, the economic factor can explain a slightly more percentage of variation in the overall financial performance of tourist hotels than the industry factor. the economic growth factor accounts for about % and the tourism expansion factor accounts for about %. nonetheless, the proportion of variation in the overall financial performance explained by both factors is relatively small, compared to those of variation in occupancy rate and profitability. among three unexpected crisis events dummy variables, the sars outbreak had the most serious impact on corporate performance in the tourist hotel industry. the sars outbreak significantly reduced the occupancy rate, profitability, stock performance and the performance of tourist hotels. the terrorist attacks in the us seriously damaged the occupancy rate, stock performance and performance. in comparison, the earthquake only hurt the hotel stock returns. since crises greatly reduced the occupancy rate (i.e. earnings revenue or expected cash flows of tourist hotels), investors' perceived riskiness of cash flows of hotel stocks would increase. hence, a plunge in expected cash flows and a surge in the discount factor caused poor hotel stock returns. these results are generally consistent with findings in chen et al. ( ) and . there are several explanations for the relatively weaker influence of the earthquake on hotel performance. first, while the earthquake substantially damaged the taichung area (the middle of the taiwan island), all five publicly traded tourist hotels are located in the taipei area (the northern part of the island). thus the event had no significant effect on occupancy rate, profitability and performance. second, the earthquake was considered as a local crisis, one that did not seriously damage the foreign tourism market. this is supported by the statistics. the growth rate of foreign tourist arrivals was À . % in the third quarter of (when the earthquake struck), which is relatively small compared to À . % and À . % for the corresponding quarter of the terrorist attacks in the us and the sars outbreak. since the growth rate of foreign tourist arrivals has a substantial influence on corporate performance of tourist hotels, it explains why the damage of the earthquake and the sars outbreak is the least and the most serious, respectively. empirical findings also offer valuable information and implications for government, tourism policymakers, tourist hotel owners, and managers in taiwan. first, although the internal factor, hotel size, can have a positive impact on occupancy rate, it is negatively related to profitability and the performance of tourist hotels. in other words, large tourist hotels generate better sales, but worse corporate performance in terms of profitability. the poor profitability and the corporate performance of tourist hotels may be attributed to the following reasons. net profit is equal to total revenues minus total cost. large tourist hotels enjoy high occupancy and hence sales revenue, but low profitability. apparently, they need to focus on the issue of cost control. further, according to the agency theory, it may become harder for hotel owners to monitor and control managers' abnormal behavior as hotel companies grow (pi & timme, ) . adams and buckle ( ) argue that large organizations can inhibit financial performance because of diseconomies of scale, resource misallocation, and the failure of managers to exploit output efficiencies. chen and soo ( ) also state that hotel companies provide many services that tourists demand. those services include accommodation, food, beverages and laundry, swimming pools, and conference facilities. the quality of these services, not hotel size, might be a more important factor in ensuring corporate performance in the tourist hotel industry. second, this study demonstrates that the corporate performance in the tourist hotel industry is closely related to the state of economy and especially to tourism growth. moreover, economic growth is highly correlated with tourism development. this supports the findings in kim et al. ( ) , who found a long-term association between economic growth and tourism expansion and a bi-directional causality between tourism and economic growth in taiwan. in other words, economic development and tourism growth can promote each other. since both economic growth and tourism expansion can have a significant impact on the corporate performance of tourist hotels, it is appropriate for the taiwanese government to use a long-term tourism strategic plan to develop the tourism market, thus stimulating the economy and corporate performance in the tourist hotel industry. in particular, since taking office in may , the taiwanese president ma ying-jeou has actively advocated stronger economic ties with china (taiwan tourism bureau, ). one of his policies was to re-open direct flights between taiwan and china, which had been banned since . taiwan and china signed the agreement to restore regular direct flights between the two regions on june , and direct flights resumed on july , . currently, up to chinese tourists a day are allowed to visit taiwan and the number may increase from to after may . this phenomenon of tourism growth is expected to improve the taiwanese economy and the corporate performance of local hotel companies. for example, it is estimated that chinese visitors per day would bring at least billion taiwanese dollars (us $ . billion) a year for local restaurants, hotels, bus companies and tour agents and moreover, approximately , jobs could be created, reducing domestic unemployment rate by one percent (asiaone, ) . third, the occupancy rate, return on assets and return on equity of tourist hotels rely on the development of foreign tourist markets in taiwan. this implies that tourism authorities and hotel business managers need to be aware that the sales revenue and profitability in the tourist hotel industry would suffer during periods of instable or low demand for tourism. to solve this problem, tourism policymakers and hotel managers can use the practical findings in jang and chen ( ) as guidelines for diversification or risk management in the taiwanese tourism market. they used the financial portfolio theory to show how taiwan can obtain optimal foreign tourist market mixes by minimizing variability in foreign tourist arrivals. finally, while the economic factor explains a very high proportion of sales ( %) and the industry factor explains a very high proportion of sales ( %) and profitability ( - %), the two factors together can only account for a relatively small percentage (about %) of the overall financial performance of tourist hotels. this suggests that a large proportion of the overall financial performance of tourist hotels is still unexplained and affected by other factors. note that both economic condition and tourism growth are external factors for the hotel industry. the development of the local economy and tourism market may depend on the development of the global economy and local government policies and efforts. hotel owners and managers, instead, could concentrate on some internal factors or issues, such as cost control, the service quality, managerial efficiency, production productivity and human resource management. whether those internal factors can explain the overall financial performance of tourist hotels deserves further examination. the determinants of corporate financial performance in the bermuda insurance market taiwan tourism sector eyeing china boost bank-specific, industryspecific and macroeconomic determinants of bank profitability tourism as a long-run economic growth factor: the spanish case econometric analysis of panel fata the stock market and investment use of macroeconomic variables to evaluate selected hospitality stock returns in the us corporate strategy: useful perspective for the study of capital structure the relative common factors across the european equity markets cyclical patterns in profits, provisioning and lending of banks and procyclicality of the new basel capital requirements essentials of investments risk diversity across restaurants privatization and bank performance in developing countries nonstationary panels, panel cointegration, and dynamic panel determinants of firm performance does corporate growth really matter in the restaurant industry? hotel stock performance and monetary conditions interactions between business conditions and financial performance of tourism firms: evidence from china and taiwan macro and non-macro explanatory factors of chinese hotel stock returns the impact of sars outbreak on taiwanese hotel stock returns: an event study approach tourism expansion and corporate earnings in the tourism industry the impact of macroeconomic and nonmacroeconomic forces on hotel stock returns the impact of government weekend policy changes and foreign institutional holdings on weekly effect of tourism stock performance cost structure and productivity growth of the taiwanese international tourist hotels developing an economic indicator system (a forecasting technique) for the hotel industry determinants of hotel guests' satisfaction and repeat patronage in the hong kong hotel industry forecasting industry turning points: the us hotel industry cycle model an importance-performance analysis of hotel selection factors in the hong kong hotel industry: a comparison of business and leisure travelers applied econometrics: a modern approach using eviews and microfit tourism as a long-run economic growth factor: an empirical investigation for greece using causality analysis dividend yields and expected stock returns impact of tourism on economic growth and development in africa determinants of banking system fragility: a case study of mexico development of a profit planning framework in an international hotel chain: a case study hotel and motel management and operations casino firms' risk features and their beta determinants is the tourism-led growth hypothesis valid for turkey? multivariate data analysis firm size and profitability specification tests in econometrics effects of key issues on the financial performance of hospitality firms analysis of panel data testing unit roots in heterogeneous panels financial portfolio approach to optimal tourist market mixes corporate liquidity: management and measurement why is there a home bias? an analysis of foreign portfolio equity ownership in japan directors stock ownership and organization performance: an investigation of fortune companies tourism expansion and economic development: the case of taiwan the determinants of corporate liquidity: theory and evidence tourism development and economic growth: a closer look at panels. tourism management services and the long-term profitability in taiwan's banks introduction to econometrics management ownership and market valuation: an empirical analysis determinants of corporate borrowing intra-industry effects of bank privatization: a clinical analysis of the privatization of the commonwealth bank of australia using financial information to differentiate failed vs. surviving finance companies in thailand: an application for emerging economies corporate control and bank efficiency management of customer expectations in service firms: a study and a checklist tourism as an economic growth factor: a case study for southern european countries essentials of corporate finance current state of taiwan tourism since initiation of taiwan-china direct flights the tourism-economy causality in the united states: a sub-industry level examination predicting bank failures in the s. economic review -federal reserve bank of cleveland a normative approach to tourism growth to the year a factor-analytic approach to bank condition financial accounting financial support provided by the national science council of taiwan (grant no.: nsc - -h- - -) is gratefully acknowledged. i wish to thank the editor, professor chris ryan, and three anonymous referees for their constructive comments. key: cord- - vy md authors: fang, li-qun; sun, yu; zhao, guo-ping; liu, li-juan; jiang, zhe-jun; fan, zheng-wei; wang, jing-xue; ji, yang; ma, mai-juan; teng, juan; zhu, yan; yu, ping; li, kai; tian, ying-jie; cao, wu-chun title: travel-related infections in mainland china, – : an active surveillance study date: - - journal: lancet public health doi: . /s - ( ) - sha: doc_id: cord_uid: vy md background: transmission of infection through international travel is a growing health issue, and the frequency of imported infection is increasing in china. we aimed to quantify the total number of infections imported into mainland china by arriving travellers. methods: we actively surveyed arriving travellers at all international entry–exit ports in mainland china. suspected cases were detected through fever screening, medical inspection, self-declaration, and reporting by on-board staff. participants completed a standardised questionnaire with questions about demographics, their travel itinerary (including detailed information about all countries or regions visited), and clinical manifestations. nasopharyngeal swabs, sputum samples, faecal samples, vomitus, blood, and serum were collected as appropriate for diagnoses. diagnosis was made by specific laboratory tests according to the national technical guidelines. infections were classified as respiratory, gastrointestinal, vector-borne, blood-transmitted and sex-transmitted, or mucocutaneous. we divided arriving travellers into two groups: travellers coming from countries other than china, and travellers coming from hong kong, macau, and taiwan. we integrated surveillance data for – , calculated incidences of travel-related infections, and compared the frequency of infections among subgroups. findings: between jan , , and dec , , cases were identified among arriving travellers—an overall incidence of · per million. pathogens were detected in participants: respiratory ( cases), ten gastrointestinal ( cases), seven vector-borne ( cases), seven blood-transmitted and sex-transmitted ( cases), and three mucocutaneous ( cases). both the overall number and incidence of infection were more than five times higher in than in . case numbers and incidences also varied substantially by province, autonomous region, and municipality. overall, ( %) infections were detected by fever screening, but ( %) blood-transmitted and sex-transmitted infections were identified through medical inspection. ( %) cases of respiratory infection and ( %) of gastrointestinal infections were in tourists. tuberculosis, hepatitis a virus, vector-borne, and blood-transmitted and sex-transmitted infections were common among chinese labourers who worked abroad. dengue and malaria were most commonly diagnosed in travellers arriving from africa. ( %) of the cases arriving from hong kong, macau, or taiwan were respiratory infections. hand, foot, and mouth disease accounted for · % of infections in travellers from hong kong, macau, or taiwan and · % of infections in international travellers. interpretation: this report is the first to characterise the profile of travel-related infections among arriving travellers in mainland china. our findings should increase public awareness of the potential risk of imported infections, and help health-care providers to make evidence-based health recommendations to travellers. funding: the natural science foundation of china. the number of international travellers has more than doubled worldwide during the past two decades, from million in to · billion in . this rapid increase in cross-border travelling has become the main driver of the global spread of infections, as exemplified by international transmission of severe acute respira tory syndrome, dengue, influenza a (h n ), and zika virus. [ ] [ ] [ ] [ ] timely identification of infections among arriving travellers can help to alert the medical and public health communities of outbreak threats before they affect the general population of that country. surveillance of travel-related infections is important for global public health as international travel continues to increase worldwide. , china has become the world's fourth most popular destination in terms of arrivals, with million tourists in , and has inevitably been affected by travelrelated infections. malaria and dengue have been introduced by arriving travellers from countries where those diseases are endemic. [ ] [ ] [ ] an outbreak of chikungunya virus caused by infected travellers has been recorded in main land china, and zika virus, yellow fever, and rift valley fever have all been imported within the past years. [ ] [ ] [ ] [ ] in response to the increasing risk of imported infections, the general administration of quality supervision, inspection and quarantine of the people's republic of china (aqsiq) obliged all air and surface ports to do active surveillance of infections among arriving travellers. systematic surveillance began in to reduce risk of autochthonous transmission and help to inform evidence-based advice for travellers. we integrated the data from all entry-exit ports in mainland china to characterise travel-related infections, define the demographic features of imported cases, identify risk groups and exposure countries or regions, and assess the effectiveness of surveillance for further improvement. we did an active surveillance study of all travel-related infections from jan , , to dec , , at all international entry-exit ports to mainland china, comprising airports, water (sea and river) ports, and land (highway and railway) entry-exit stations (appendix p ). we also gathered data for the total number of people arriving in each of the provinces, five autonomous regions, and four municipalities of mainland china. all patient data were anonymised. because this study constituted public health surveillance rather than research in human beings, ethical approval from institutional review boards was not required. participants or their guardians provided written informed consent for collection of biological samples (appendix p ). people who were suspected of having an infection but who did not consent to collection of samples were made known to local centres for disease control and prevention for potential further follow-up. active surveillance was done among all arriving travellers at a quarantine station before they passed through customs at each entry-exit port. suspected cases were detected through four approaches: fever screening, medical inspection, self-declaration, and reporting by on-board staff (appendix p ). all people with suspected infections were quarantined according to who's international health regulations and the rules for the implementation of frontier health and quarantine law of the people's republic of china. participants completed a standardised questionnaire with questions about demographics, their travel itinerary (including detailed information about all countries or regions visited), and clinical manifestations. infections were diagnosed by laboratory testing at the international travel health-care centre of each provincial entry-exit inspection or the quarantine bureau, per the surveillance technical scheme developed by aqsiq. quarantine officers at entry-exit ports suggested which tests should be done on the basis of clinical manifestations in each suspected patient. they collected nasopharyngeal swabs, sputum samples, faecal samples, vomitus, blood, or serum samples as appropriate for diagnoses. according to core capacity requirements for surveillance and response in who's international health regulations and the frontier health and quarantine law of china, aqsiq listed required and recommended infectious diseases for causative testing. , diagnosed infections were classified as respiratory, gastrointestinal, vector-borne, blood-transmitted and sex-transmitted, or mucocutaneous according to standard clinical practice evidence before this study we searched pubmed and isi web of science with the terms "travel" and "infection" or "infectious disease", and "global spread" and "infection" or "infectious disease" for work published in any language between jan , , and oct , . we noted that previous studies mainly focused on surveillance of post-travel illness, which was usually based on clinician-based surveillance systems-eg, geosentinel, which tracks infectious diseases and other adverse health outcomes related to travel. several identified studies were about the epidemiological features of imported malaria or about febrile illnesses or hiv infection at one port of china. we did not find any studies of active surveillance for various infections among arriving travellers at all entry-exit ports throughout mainland china. to the best of our knowledge, our report is the first to characterise the spectrum of travel-related infections, and reveals variety in frequency of each infection by traveller type, exposure country or region, and arrival provinces of mainland china in - , representing the pattern of travel-associated infections during travel. our findings imply that health-care providers should make evidence-based health recommendations to travellers before travel, and do destination-specific medical assessments of arriving travellers when they are ill, based on our estimates of the incidence of infections. active surveillance at entry ports can identify imported cases with emerging or re-emerging infections to prevent or at least postpone local transmission. in addition to entry surveillance upon arrival, follow-up surveillance (especially contact tracing of highly communicable infections) is needed to better understand the whole profile of travel-related infections. overall, our findings should help to increase public health awareness about the potential risk of imported infections to mainland china. see online for appendix in china (appendix pp [ ] [ ] . patients with infections were informed of their diagnosis, and recommended for treatment. we also informed local centres for disease control and prevention of each case, and close contacts were informed for prevention and quarantine, if necessary, according to who's international health regulations and the frontier health and quarantine law of china. we excluded people without specific diagnoses, people with ambiguous itineraries, and those whose final diagnosis had been identified before travelling. we used epidata . to establish a structured database. each case was geo-referenced to a world map with arcgis (esri, redlands, ca, usa) according to the exposure location where patients might have been infected. the exposure location was defined as the country or region that the participant travelled from. for travellers who visited several destinations, exposure location was established according to their itinerary on the basis of incubation period or known patterns of endemicity. arriving travellers were classified into two groups: travellers coming from countries other than china, and travellers coming from hong kong, macau, and taiwan descriptive statistics were calculated for all variables. continuous variables were summarised as median and range. we estimated the annual incidence of each infection at national and provincial levels. proportions were calculated according to various categories. we constructed graphs to show distribution patterns of proportion among different subgroups, and created thematic maps according to entry province and exposure countries. the study funder had no role in study design; data collection, analysis, or interpretation; or writing of the report. w-cc and l-qf had full access to all data in the study, and had final responsibility for the decision to submit for publication. of inner mongolia ( ) heilongjiang ( ) jilin ( ) liaoning ( ) types of pathogens were detected in participants: respiratory pathogens ( cases), ten gastrointestinal pathogens ( cases), seven vector-borne pathogens ( cases), seven blood-transmitted and sex-transmitted pathogens ( cases), and three mucocutaneous pathogens ( cases; figure a) . the most frequent respiratory infection was influenza virus, followed by rhinovirus ( figure a) . dengue was the most common vector-borne disease, hepatitis b virus infection was the most common blood-transmitted and sex-transmitted infection, and hand, foot, and mouth disease was the most common mucocutaneous infection ( figure a) . ( %) respiratory infections, ( %) gastrointestinal infections, ( %) vector-borne infections, and ( %) of the cases of hand, foot, and mouth disease were detected by fever screening (figure b). ( %) of participants arrived from a different country ( countries represented), whereas ( %) came from hong kong, macau, or taiwan. the types and distribution of infection differed substantially between these two groups (figure ). ( %) of the cases arriving from hong kong, macau, or taiwan were respiratory infections. influenza was the most common infection in both groups, accounting for ( %) cases in the international group and ( %) cases in the hong kong, macau, and taiwan group ( figure ) . however, hepatitis b and c virus infections, syphilis, hiv, malaria, and dengue were substantially more common in the international group, whereas respiratory infections with rhinovirus, para influenza virus and metapneumovirus, and hand, foot, and mouth disease were more common in travellers from hong kong, macau, and taiwan ( figure ) . in the international travel group, infection was acquired in the western pacific region by ( %) people, in the south-east asia region by ( %), in the european taiwan region by ( %), in the american region by ( %), in the african region by ( %), and in the eastern mediterranean region by ( %). influenza accounted for more than two-thirds of cases among travellers who acquired infections in the western pacific, south-east asia, european, american, and eastern mediterranean regions (appendix p ). people with gastrointestinal infections mainly travelled from countries in the south-east asia and western pacific regions ( figure b ). vector-borne diseases, including dengue and malaria, were predominantly diagnosed among travellers from countries in western and central africa and the south-east asia region (figure c). cases with mucocutaneous infections mostly come from countries in the western pacific region and eastern europe (figure ). we noted seasonal patterns of travel-related infections, which differed between the international travellers (infection peak in november and december) and those who travelled from hong kong, macau, or taiwan (respiratory infections peak in february and june, mucocutaneous infection peak in may and july; appendix p ). to our knowledge, ours is the first multicentre study of travel-related infections among travellers arriving in mainland china. we characterised the range of travel-related infections, and showed how they varied by traveller type, exposure country or region, and province of arrival to mainland china. our findings, which are based on surveillance data for infections among travellers who arrived at the entry-exit ports to the mainland, are helpful for increasing public health awareness about the potential risk of imported infections. most previous studies about this topic in mainland china explored the epidemiological features of imported malaria, or febrile illnesses or hiv infection at a single entry-exit port. , , [ ] [ ] [ ] [ ] by comparison with geosentinel, a clinician-based global surveillance system that tracks infectious diseases and other adverse health outcomes related to travel, we actively surveyed infections among travellers upon arrival in mainland china. this method enabled us not only to profile imported infections, identify risk groups, and formulate optimum advice for travellers (as done previously on the basis of data from geosentinel or its linked european surveillance network, eurotravnet), [ ] [ ] [ ] but also to estimate the incidence of each infection by using the total number of arrivals as denominator. additionally, active surveillance of arriving travellers enables timely identification of imported infections, allowing for alerting of public health authorities of threats before autochthonous transmission. both case numbers and incidence of infection have increased over time among travellers arriving in mainland china (table) . this increase probably reflects the worldwide epidemic trend of infectious diseases. improvements in diagnostic procedures and rapid tests might have also contributed to the increase. case numbers and incidence varied greatly between the provinces, autonomous regions, and municipalities (figure ), which implies that each province should optimise a unique strategy for surveillance of, and response to, specific infections. the diagnostics used in our study were based on the surveillance technical scheme developed by aqsiq, whereby diagnosis was based on recommended specific laboratory tests. accordingly, we classified diagnosis according to the main transmission route of each infection: respiratory, gastrointestinal, vector-borne, blood-trans mitted and sex-transmitted, and mucocutaneous. over four-fifths of respiratory infections and about two-thirds of vector-borne and mucocutaneous infections were detected by fever screening (table), suggesting that fever screening is essential to identification of febrile patients. our findings also suggest that medical inspection should be sustained to identify people with mucocutaneous infections other than hand, foot, and mouth disease or blood-transmitted and sex-transmitted infections, which are often associated with obvious clinical manifestations such as rashes, vomiting, and jaundice (appendix pp - ). additionally, on-board staff should be encouraged to report patients they suspect of being infected for timely identification. chinese labourers (ie, chinese people who work overseas, mostly in the manufacturing, construction, forestry, fishing, transportation, and catering industries, although some are highly skilled workers) abroad seemed prone to tuberculosis, hepatitis a virus infection, vectorborne infections, and blood-transmitted and sextransmitted infections (figure c). pre-travel advice to labourers should focus on such public health threats. additionally, we suggest that on-site health education and primary health care should be provided to chinese labourers in the countries where they work. rubella, acute conjunctivitis, and herpes zoster virus infections were frequently detected in sailors (figure c), suggesting that close contact and working in humid environments are risk factors for transmission of these infections. although the infection profiles of international travellers and travellers from hong kong, macau, and taiwan differed substantially, influenza was the most common infection in both groups (figure ). our findings show the epidemic pattern of influenza in different global regions, and imply that vaccination should be considered if travelling to a region where influenza transmission is ongoing. people with blood-transmitted and sextransmitted diseases were mostly male labourers and sailors (table). although the reasons for high risk in these populations were unclear, our study shows the sociodemographic characteristics of people with these diseases arriving in mainland china, which were significantly associated with travel-associated sexually transmitted infections in data gathered by geosentinel travel medicine clinics worldwide. further research is required to investigate effective intervention measures. dengue and malaria were frequent among international travellers arriving from africa (appendix p ). imported dengue has caused autochthonic transmission in new areas of china, europe, and the usa. [ ] [ ] [ ] [ ] in our study, we also noted the arrival of patients with zika virus, yellow fever virus, and rift valley fever to mainland china since february, . [ ] [ ] [ ] [ ] governments and the public health community should be aware of these new threats to prevent possible local epidemics. in travellers from hong kong, macau, and taiwan, the incidence of hand, foot, and mouth disease was high (figure ). we could not establish where these travellers were infected, because they usually travel frequently to and from mainland china. detailed data about itineraries should be collected to help to clarify the infection exposure site. the warm and humid climate in hong kong, macau, taiwan, and southern china could favour transmission of hand, foot, and mouth disease. fortunately, a vaccine against the ev , the most prevalent virus strain, is commercially available and has a good protective effect. we mapped travel-related infections globally to show differences in terms of exposure country and region ( figure ) . health-care professionals should be aware of the specific risks to travellers, and should provide targeted pre-travel consultations. accordingly, countryspecific or region-specific vaccination and prophylaxis are strongly recommended to reduce the burden of travel-related infections. our study had several limitations. because our findings were based on surveillance of travellers when entering mainland china, most cases had clinical manifestations of disease upon arrival (appendix pp - ). patients who were infected but did not develop symptoms until after arrival were not included in our study. thus, the frequency of travel-related infections are underestimated. by contrast, for infections such as tuberculosis, hepatitis b and c virus infections, hiv, and syphilis, which have long latent or incubation periods, the location of acquisition is difficult to establish. for example, chinese citizens who travelled overseas and were diagnosed upon arrival back to mainland china could have acquired the infection before travelling. thus, the frequency of such infection in arriving travellers could have been overestimated. although we estimated the overall incidence of each infection, would could not calculate the numerical risk for travellers coming from a particular country or region because of the lack of denominator data. furthermore, we could not compare the demographic characteristics of the people with an infection to those without an infection, because demographic data were not collected for all arriving travellers. in conclusion, our findings suggest that health-care providers should provide evidence-based health recommendations to travellers before travel and should do destination-specific medical assessments of arriving travellers who are ill. active surveillance at entry-exit ports can help with timely identification of people with emerging or re-emerging infections to prevent or at least postpone local transmission. , in addition to entry surveillance, follow-up surveillance-especially contact tracing of highly communicable infections-will be necessary to understand the entire profile of travel-related infections. we declare no competing interests. world tourism organization. unwto tourism highlights transmission of the severe acute respiratory syndrome on aircraft global spread and persistence of dengue spread of a novel influenza a (h n ) virus via global airline transportation potential for zika virus introduction and transmission in resource-limited countries in africa and the asia-pacific region: a modelling study approach to fever in the returning traveler surveillance for travel-related disease-geosentinel surveillance system epidemiologic features of overseas imported malaria in the people's republic of china plasmodium falciparum malaria importation from africa to china and its mortality: an analysis of driving factors the changing epidemiology of dengue in china, - : a descriptive analysis of years of nationwide surveillance data isolation, identification and genomic characterization of the asian lineage zika virus imported to china zika virus in a traveler returning to china from caracas yellow fever virus: increasing imported cases in china rift valley fever virus imported into china from angola basic technical scheme for the active surveillance and medical response for infectious diseases at entry-exit ports the state council of the people's republic of china. rules for the implementation of frontier health and quarantine law of the people's republic of china trends of imported malaria in china - : analysis of surveillance data the epidemiology of plasmodium vivax and plasmodium falciparum malaria in china surveillance of mosquito-borne infectious diseases in febrile travelers entering china via shenzhen ports, china hiv- prevalence and subtype/recombinant distribution among travelers entering china from vietnam at the hekou port in the yunnan province defining infections in international travellers through the geosentinel surveillance network spectrum of disease and relation to place of exposure among ill returned travelers geosentinel surveillance of illness in returned travelers travel-associated infection presenting in europe ( - ): an analysis of eurotravnet longitudinal, surveillance data, and evaluation of the effect of the pre-travel consultation who. emergencies: disease outbreaks global circulation patterns of seasonal influenza viruses vary with antigenic drift latitudinal patterns of travel among returned travelers with influenza: results from the geosentinel surveillance network, - travel-associated sexually transmitted infections: an observational cross-sectional study of the geosentinel surveillance database climate and the timing of imported cases as determinants of the dengue outbreak in guangzhou, : evidence from a mathematical model autochthonous dengue fever in croatia first two autochthonous dengue virus infections in metropolitan france efficacy, safety, and immunogenicity of an enterovirus vaccine in china entry screening to delay local transmission of pandemic influenza a (h n ) effectiveness of screening for ebola at airports we thank the medical inspection officers, on-board staff, and laboratory-test personnel who contributed to the detection, epidemiological investigation, and diagnosis of all suspected infections. key: cord- -o i hy authors: holliday, ian; tam, wai-keung title: e-health in the east asian tigers date: - - journal: int j med inform doi: . /j.ijmedinf. . . sha: doc_id: cord_uid: o i hy objective: the article analyzes e-health progress in east asia's leading tiger economies: japan, hong kong, singapore, south korea and taiwan. it describes five main dimensions of e-health provision in the tigers: policymaking, regulation, provision, funding and physician-patient relations. methods: we conducted a series of fieldwork interviews and analyzed key healthcare websites. results and conclusion: our main finding is that the development of e-health in the region is less advanced than might be expected. our explanation focuses on institutional, cultural and financial factors. the application of information technology (it) to public sector operations sometimes captured in the notion of e-government is starting to have an impact on developed healthcare systems the world over. as time goes by, that impact is expected to become even more pronounced. ''the consensus seems to be that new information technologies will significantly affect almost every aspect of health care,'' wrote blumenthal [ ] . in this article, we examine the progress of e-health in the five leading economies of east asia: japan, hong kong, singapore, south korea and taiwan. each seeks to place itself at the forefront of the information revolution and has high levels of internet access and usage. each also has a sophisticated healthcare system dedicated to securing maximum healthcare benefit at minimal cost. by standard outcome indicators, these systems all have very good records. the tigers, therefore, form a cluster in which e-health might be expected to be notably advanced. however, our finding is that although some progress is being made, it remains limited. it is also variable across the five societies. the article begins by reviewing some of the literature on e-health taking from it a series of critical dimensions and issues. it then briefly analyzes the two relevant contextual aspects of the east asian tigers: their participation in the information age and the nature of their healthcare systems. on these bases, it examines their e-health progress, focusing on the major themes unearthed in the contemporary literature. finding limitations and variations, it concludes by thinking through possible explanatory factors, focusing on institutional, cultural and financial issues. much of the existing e-health literature has been developed in the context of the united states, reflecting both us leadership in the information age and the continuing search for solutions to us healthcare problems. five main themes are prominent. four of the five address distinct dimensions of the broad policy and management framework for healthcare, examining internet impacts on policymaking, regulation, provision and funding. the fifth theme looks inside the healthcare sector and inside the surgery, at the implications of the internet for physician-patient relations. eventually, this may have policy significance, but for now, it is best treated separately. the major argument made about healthcare policymaking is that the us government has been slow to engage with the numerous issues generated by the it revolution [ ] . the core features of that revolution, notably enhanced information flows, increased networking possibilities and novel commercial opportunities, are now well documented [ ] . however, it is said that in us healthcare, most policy actors in both congress and the executive branch continue to focus on pre-information age agendas. although, the bush administration has started to address these concerns, the result remains something of a lack of internet-related policy activity and only a limited number of perspectives on the internet's potential to transform the us healthcare system. clearly structural features of the us system, including fragmentation both of government and of the healthcare sector, play key roles. looking at the narrower sphere of regulation, concerns are expressed about the failure of regulatory agencies to keep pace with internet-related developments. goldsmith notes that the internet generates many potential regulatory problems, ranging from licensing e-health practitioners to monitoring information quality in a virtual world with no boundaries [ ] . fried et al. detail some of the obstacles placed in the way of e-health by existing regulations, holding that individuals and organizations must navigate a maze of rules and codes, old and new, if they wish to implement fresh ideas and approaches [ ] . kassirer's prediction is that the courts will play a role when substandard medical advice provided through web sites or e-mail yields poor medical outcomes. he believes that courts will be especially important when professional advice is given without a direct patient encounter, or when state lines are crossed [ ] . some regulatory issues are us-specific, but many have much wider relevance. partly building on the regulatory theme, analysts have also debated the limitations currently imposed on healthcare provision through the internet. kleinke argues that the internet will not contribute to a solution to the administrative redundancies, economic inefficiencies, and quality problems that have long plagued the us healthcare system. instead, it will exacerbate the cost and utilization problems of a system in which patients demand more, physicians are legally and economically motivated to supply more, and public and private purchasers are expected to pay the bills [ ] . goldsmith holds that the challenges of standardizing coding and formats for clinical information, and protecting patient privacy, will hinder the realization of network computing potentials in healthcare [ ] . the problems to which these and other authors point are structural. economic, organizational, legal, regulatory, and cultural conflicts rooted in the us healthcare system are all barriers to e-healthcare provision. further problems are found in the sphere of healthcare funding. shortliffe criticizes congress for focusing on short-term benefits, arguing that research investment for e-health must be balanced between basic and applied analyses [ ] . robinson examines the effect of distinct forms of capital on the development of the healthcare internet. in the late s, venture capital flooded into the ehealth sector, rising dramatically from us$ million in early to us$ million in late . in the same period, e-health firms went public, raising us$ . billion at their initial public offerings. however, the technology-sector crash in late hit the e-health sector especially hard, prompting an extended period of consolidation between e-health and more conventional firms [ ] . us funding problems thus relate to both the public and the private sectors. finally, analysts have looked inside the surgery at physician-patient relations. existing survey data show that citizens make considerable use of the internet for healthcare information and services, mostly of a generic kind [ ] . indeed, anderson reports that in , % of us adults with internet access did so [ ] . as more patients go online, increasing numbers will turn up in surgeries with internet-fueled questions and concerns. meeting the growing expectations of these individuals will be a significant challenge for physicians [ ] . assessing the likely impact, kassirer argues that the internet will change the physician-patient relationship in unpredictable ways, with some aspects of electronic communication strengthening the bond, and others undermining it [ ] . goldsmith believes patients have most to gain from the emergence of the internet, arguing that it will rebalance the steeply asymmetrical medical knowledge held by patients and physicians [ ] . using information gained through internet searches, patients can now open their dialogues with physicians at a much higher level than before, and thereby gain leverage in the care process. ball and lillis also discuss the potential challenges the internet presents to physicians. as internet searches often generate as many questions as answers, physicians are likely to find themselves under increased workload pressures [ ] . the variable quality of healthcare information accessed through online searches [ ] , a matter that is being actively addressed by bodies such as the health on the net foundation (www.hon.ch) and the internet healthcare coalition [ ] , can only reinforce those pressures. zupko and toth hold that physicians sometimes encounter a form of cultural shock when confronted by well-informed patients [ ] . it is therefore perhaps not surprising that an april survey found that physicians are much more reluctant than patients to use the internet for healthcare interactions. while % of patients wanted to exchange e-mail with their doctors, only about % of doctors actually did so. physician-patient confidentiality, time concerns and increased exposure to malpractice liability were cited as primary reasons for doctors' wariness [ ] . in the face of this mounting speculation and evidence, lumpkin is sanguine, however, contending that the physician-patient encounter is little changed, despite widespread internet usage in healthcare [ ] . though focused on the us, the existing e-health literature generates key themes for an analysis of progress in other parts of the world, including the east asian tigers. however, before exploring those themes, we first present some basic contextual information about our five societies. two features of the east asian tigers are particularly relevant to this analysis: their participation in the information age and the nature of the healthcare systems in which their application of it needs to be assessed. in this section, we examine both features. looking at broad social participation, it was exploited more rapidly in the five east asian tigers than in any other global cluster. for many years, the nielsen//netratings global internet index has ranked all five societies in the top worldwide for personal computer (pc) connections and internet access and usage. the four smaller societies, hong kong, singapore, south korea and taiwan, are particularly advanced. furthermore, the severe acute respiratory syndrome (sars) crisis that hit the region in spring gave a major boost both to internet usage in general, and to e-health in particular [ ] . in hong kong, for instance, the number of active internet users increased by % from february to april , before falling back by % from april to june . the overall increase was %. also at the start of , the time spent online by hong kong people first increased by % and then fell back by %, registering an overall increase of % [ ] . consistent with the image of economic and social dynamism, they have projected for many years now, the east asian tigers are among the most advanced it societies on earth. to some extent, this strong it orientation is the product of developmental state strategies. with the partial exception of hong kong, the east asian tigers have long placed considerable faith in stateled growth strategies. furthermore, for many years they have frequently focused those strategies on it and it-related sectors. in japan, in the s, the fabled ministry of international trade and industry targeted supercomputers and the fifth generation as a major development project [ ] . despite a long period of economic stagnation in the s, the japanese it industry remains a significant global force. in singapore in the s, the state took the lead in nurturing wafer fabrication, the most sophisticated ''front end'' of the semiconductor industry. chartered semiconductor manufacturing, established by the government in , is now the third largest silicon foundry in the world. in south korea, in the early s, the state reorganized the public-sector telecommunications system by closing inefficient firms and allocating profitable segments to major chaebol like samsung and goldstar, enabling them to establish specialized chip businesses. by the early s, samsung had become the world's number one producer of dynamic random access memories for pcs and workstations. in taiwan since the s, the ministry of economic affairs and the state-controlled electronics research service organization have played crucial roles in developing the semiconductor industry. today, it is the fourth largest in the world, and firms within it have entered into strategic alliances with leading industry players in the west [ ] . even in hong kong, where a developmental state took longer to emerge, the government is currently overseeing the construction of a flagship cyberport, intended to host a strategic cluster of companies and professional talents, specializing in it applications, information services and multimedia content creation, and designed to project a hi-tech international digital city image. the east asian tigers are also leading players in the development of e-government. the un/aspa benchmarking survey of all un member states placed singapore at number (a long way behind the us, but only fractionally behind australia and new zealand), south korea at number and japan at number . all three states featured in the top category of high e-government capacity. the survey did not assess hong kong and taiwan, neither of which is a un member state. the report noted that singapore ''demonstrated a balanced and citizen-centric e-government program, while possessing the benefits of a high technological infrastructure and human capital measures''. it held that south korea ''made perhaps the most dramatic advances in its e-government program by successfully implementing several new online transaction features''. it was more critical of japan, arguing that it had ''yet to live up to its rather significant potential''. ''japan's e-government program has not yet reached a comparable level of sophistication as that of the regional leaders due primarily to achieving only a limited interactive presence among national government websites'' [ ] . a january analysis of e-government in east and southeast asia reached similar conclusions, identifying the five tigers as regional leaders [ ] . accenture's survey looked at only two of the five east asian jurisdictions analyzed here. it ranked singapore number in the world after canada, and japan number [ ] . looked at from many different perspectives, then, the east asian tigers are leading participants in the emergent information age. healthcare systems in the tigers share a basic orientation, but are otherwise quite varied. the orientation is best termed productivist, in that in each society social policy has usually been subordinate to economic objectives. while the governments of all five tigers certainly get involved in social policy, they usually do so either for economic reasons or after they have made provision for their various economic goals. the main stimuli to this strong focus on economic development were, in all cases, the devastation brought by the second world war, and the uncertainties of the international order constructed thereafter [ ] . this shared orientation has fed into healthcare policy in three main ways [ ] . in japan and its two former colonies, south korea and taiwan, healthcare was initially left chiefly to the market. only once economic policy was on track and a measure of growth had already been attained, did these societies turn their attention to planning their healthcare systems. in doing so, they concerned themselves chiefly with healthcare finance, creating social insurance systems by gradualist means. now, in all of these societies, the health insurance scheme is universal in aspiration and near universal in fact. across all three societies, healthcare provision remains privatesector-driven, with the state performing a chiefly regulatory role. traditional medicines are significant in all three societies and covered by national health insurance schemes [ ] . however, they are not consistently brought within the planning frame. in hong kong, until the early s, the colonial government took a strictly reactive and incremental approach to healthcare. its major interventions focused on subventing charitable organizations in the healthcare business, though in time, it also built hospitals and delivered care directly through them. throughout, government activity was funded out of general government revenue. the major and to date, only step change came in , with the formation of the hong kong hospital authority (hkha). this imposed state control and state funding on the secondary sector and gave hong kong a miniature version of the british national health service. however, there has never been any attempt to bring primary care within the planned healthcare system. only in , was traditional chinese medicine subjected to anything more than minimal government regulation [ ] . in singapore, the early post-war experience was similar to that of hong kong. here, however, separate initiatives were taken in the spheres of provision and funding. in , much provision was integrated at the secondary care level through creation of the state-run hospital corporation of singapore. this body subsequently sought to drive private-sector disciplines into state provision through ''corporatization''. in , in an attempt to generate integrated pathways of care, it was broken into two territorial clusters focused on the secondary sector but also having primary and tertiary elements. however, as most of the primary sector remained outside the state sector, the extent of integration was limited; in singapore, the state provides % of secondary care but only % of primary care. on the funding side, singapore in created a compulsory savings system, medisave, within the wider central provident fund scheme. it added the insurance schemes medishield and medishield plus in and and created a basic social safety net, medifund, in . these various schemes partially fund secondary care provision. there is also some direct state subsidy. funding of primary care takes place mainly through out-of-pocket expenses. the traditional sector stands outside all state planning and, as in hong kong, has only recently been brought within the regulatory framework. these healthcare systems have enviable records. not only did they make a rapid post-war transition from the contagious disease characteristic of thirdworld countries to the chronic disease characteristic of first-world societies, but also they register very favorable health outcomes as measured by standard input and outcome indicators (table ) . healthcare systems in the east asian tigers thus share a productivist orientation and strong performance. they exhibit varied state roles, with much healthcare activity lying outside the public sector and some of it falling beyond the planning horizon. in japan, south korea and taiwan, state involvement is extensive in finance but limited in provision. in hong kong, the government both funds and directly provides care in the secondary sector, but not elsewhere. in singapore, the state provides a large amount of secondary and some primary care. the funding regime is complex, comprising direct state subsidy, forced individual saving, state-run and private-sector insurance, and out-of-pocket expense. in all five tigers, both the public and private sectors play important roles and face clear incentives to take an interest in harnessing the internet for healthcare gain. note: taiwan data are from . sources: [ ] . against the dual backdrop of sophisticated it societies that make extensive use of the internet and cost-effective healthcare systems driven in variable ways by actors from the public and private sectors, we now turn to a survey of e-health in the east asian tigers. to frame the survey, we begin by providing a brief descriptive overview of the major state-run healthcare websites in the region. we then structure our analysis using the five main analytical spheres that dominate the existing e-health literature: policymaking, regulation, provision, funding and physician-patient relations. all ministries or departments of health in the east asian tigers have their own website. throughout the region, the major quasi-autonomous state agencies, such as the national health insurance agencies in japan, south korea and taiwan, the hkha in hong kong and the two big healthcare clusters in singapore, also have sites. here, we look only at the main government healthcare sites ( table ) . the overall quality is high. all have clickable links to organizational objectives and tasks. most also offer detailed information about subsidiary divisions. all contain links to the government homepage and related healthcare sites so that visitors can conduct further searches and collect additional information. all provide feedback channels. in singapore, the ministry of health (moh) offers online feedback opportunities. in taiwan, citizens can make online appointments with the director of the department of health (doh). in japan, the ministry of health, labour and welfare (mhlw) uses e-mail to solicit however, within this generally strong showing, there are also significant differences, with japan's mhlw and to a lesser extent, hong kong's hwfb lagging behind their regional counterparts in key respects. firstly, the mhlw fails to provide contact details for named officials on its website. this is standard practice in the other four tigers. singapore's moh, for example, gives address, telephone number and e-mail details for key officials. secondly, while healthcare professionals and officials in singapore, south korea and taiwan can communicate with each other through the internet, their counterparts in japan and hong kong cannot. thirdly, the range of options available to users is more restricted in japan and hong kong than in the other three tigers. in south korea, for instance, it has played a role in the surveillance system for communicable disease since . through electronic data interchange and regional database management systems, notifying and reporting systems have been computerized, and an electronic record of all notified and reported cases is kept. using the super-highway communication network, physicians and public health centers can access the notifying and reporting system, disweb, anywhere and anytime through the internet (http://dis.mohw.go.kr). in singapore, the moh site within the government's ecitizen portal enables healthcare professionals to download application forms for license renewal, approval to perform a pregnancy termination, and so on. the policymaking strand of the e-health literature castigates us policymakers for being slow to grasp the potential of the internet. such a charge is less easy to sustain in the east asian tigers, though again experience is variable. singapore and taiwan are the regional leaders. singapore's ecitizen portal addresses many aspects of citizen interaction with government, with healthcare being a prominent theme. the internet is used to reinforce the public health messages that have been disseminated by the singaporean government through other media for many years. behind the scenes, e-mail links pervade the healthcare system and enhance the cohesiveness of policy networks. in a controlled city state, those networks are in any case very tight. in taiwan, the doh in launched an ambitious e-health project, with a timeline stretching to . the health information network that is central to this initiative has a backbone funded by central government and permits local users in both the public and private sectors to participate on a self-paying basis. drawing on us experience, it seeks to promote electronic medical records, based on a smart card system, so that information can flow to all parts of the healthcare sector. a healthcare certification authority, created in , oversees promotion of this initiative. in the other three tigers, progress is less impressive. japan launched an e-japan strategy in january , designed to make it ''the world's most advanced it nation within years'' [ ] . the strategy had an explicit e-government strand. in september , the mhlw followed up by issuing a ''grand design'' for promotion of it in the healthcare sector. the aim was to computerize the entire sector by and to introduce an electronic medical record system covering % of clinics and % of hospitals with plus beds by . progress towards targets appears to be on track. however, japanese performance in the e-health domain is poor by regional standards. hong kong is also quite slow to place healthcare online. the hwfb site contains standard bureaucratic information, such as current policy initiatives and recent speeches, plus public health information that has been developed particularly since the sars crisis. here, the major networking initiative is being taken by the dominant public-sector delivery agency, the hkha. while its primary focus is provision, the networking links being created among hospitals are likely to have policy consequences. as in singapore, e-mail links also bolster ties within policy networks that are already quite cohesive. south korea is making an aggressive attempt to exploit the internet across all areas of government, but in the healthcare sphere, currently remains an average performer. turning to regulation, three main issues are raised in the literature. the first is that e-health generates a number of regulatory problems. the second is that excessive regulation may impede e-health progress. the third is that the courts are likely to have to step in when administrative regulation fails. in the east asian tigers, regulation is clearly a major concern and an evident constraint on ehealth development, often for good reason. one instance is limitations placed on consultations, which in all five tigers quite properly mandate face-toface physician-patient contact before any specific healthcare information or advice can be given. for the foreseeable future, online consultation, though technically feasible, is likely to be restricted by professional concerns. another instance is limitations placed on information sharing and exchange, which in all the tigers are again very properly re- stricted by privacy considerations. however, there is some variation in regional regulatory practice. in singapore, patients requiring repeat prescriptions can place an order online and have the medications delivered to their homes. only after months, do they have to return to the healthcare system to consult a physician. elsewhere, this practice is illegal. in japan, physicians are prohibited from answering specific questions about healthcare or disease by e-mail or telephone. regarding provision, assessments in the us literature are mainly negative. on the one hand, the argument is made that it cannot be expected to solve structural problems in healthcare systems. on the other, barriers even to less ambitious networking initiatives are held to be substantial. these are fair points, but they should not be allowed to obscure the real progress being made by healthcare systems around the world, and in our case in east asia. among the five tigers, taiwan's healthcare websites, both public and private, provide the most comprehensive services to patients. singapore ranks second, and hong kong third. japan and south korea are somewhat behind the regional pace. an overview is given in table . in taiwan, the doh operates a taiwan e-hospital site to provide free online medical advice to patients (http://taiwanedoctor.doh.gov.tw/). currently, medical practitioners and nutritionists from public hospitals form a consulting team to answer questions about specialties. patients seeking general medical advice can send questions to a particular practitioner and receive feedback online or by e-mail. in the private sector, a number of hospitals, such as the chang gung memorial hospital, have online question-and-answer services for patients. the kingnet second opinion webhospital (www.webhospital.org.tw) and the taiwan physician's net (www.doctor.com.tw) are two prominent sites providing free online medical advice to patients. established by kingnet entertainment (www.kingnet.com.tw) in , the webhospital has some voluntary physicians answering questions from the public. the taiwan physician's net brings together about physicians, whose information and advice are posted on the web. apart from getting online medical advice, patients can search for a particular physician and visit his or her office for treatment. in taiwan, patients can also make medical appointments online with many public and private hospitals. looking to the future, the doh is planning to develop a medical information exchange center to promote information sharing and enhance treatment quality. in singapore, health is one of a number of cluster points within the ecitizen site. to date, the internet is mainly used to provide general healthcare information, with the healthcare portal containing comprehensive information about healthcare providers, the healthcare establishment, healthy lifestyles and public health issues such as sars. many searches are possible. the site also allows individuals to submit complaints and feedback. only a few transactions can be undertaken online. as in taiwan, appointments can be made and altered online. through singapore's e-pharmacy services, recurrent prescription items can be ordered online and delivered throughout the island. in one of its two main healthcare clusters, patients can register online and access summary medical records. inside the healthcare system, information flows are starting to change as polyclinics and gps gain access to hospital records online. the likelihood is that enhanced integration of the public and private sectors will result. in hong kong, the hkha, which oversees almost the entire secondary sector, is currently introducing online networking in hospitals. its clinical management system is an integrated clinical workstation giving clinicians access to departmental information and patient records. it will soon develop into a longitudinal electronic patient record within the public hospital system, enabling records to be accessed by many parties simultaneously anywhere, anytime. the system will also actively support clinical decisions by offering alerts, reminders, links to medical knowledge and other aids. it is expected to play an important role in reducing medical errors and improving the quality of patient care. over the next years, the hkha is planning to create a hong kong health information infrastructure, with the aim of networking all healthcare providers in the public, private and social welfare sectors. it also intends to build an electronic medical record for every hong kong resident and provide citizens with an electronic gateway to healthcare information and evidence-based medicine [ ] . these initia-tives are likely to enhance information flows within the public healthcare system. compared with taiwan and singapore, however, hong kong lags behind in developing internet services for patients. individuals cannot register and access summary medical records online. lacking an e-pharmacy service, the hong kong system does not allow recurrent prescription items to be ordered online. japan and south korea are falling behind their regional counterparts in providing online health services to patients. their official health websites do not deliver any electronic service to individual patients. with the exception of initiatives taken by a small number of private hospitals in south korea, like the yonsei eye and ent hospital, neither public nor private hospitals in these two tigers allow patients to register online. however, in , japan's mhlw established telemedicine networks to provide specialized care to people in remote areas. the government will provide us$ million a year to form networks consisting of one large hospital and three clinics working together to supervise patients. each patient will be equipped at home with a computer that can monitor heart rate, blood pressure and other indicators, as well as a phone capable of transmitting video. they will be linked to physicians through an isdn digital phone connection, thus enabling physicians to diagnose illness by electronically transmitted data. from june , the mhlw started to establish such networks a year, so that all districts will have at least one by [ ] . in , south korea's semipublic seoul national university hospital founded ezhospital, which is business-oriented instead of patient-oriented. with three main business elements, education (content services), e-trading and system integration, ezhospital is starting to alter purchasing arrangements for both medical and non-medical supplies. as the south korean system is highly fragmented, the purchasing consortia that can be built through the internet could one day become significant. at present, however, e-purchasing is at an early stage of development. analyses of e-health funding focus on one main issue, the short-termism of us initiatives. in this domain, it is difficult to reach an overall assessment of the tigers' performance. on the one hand, their developmental state orientations make the general climate for it industrial emergence very different from the climate found in the us. in this regard, the tigers look to the long term in a systematic fashion that has no us equivalent. on the other hand, it is hard to find evidence that the tigers are investing heavily in e-health applications. moreover, because the private sector plays such a large regional role in healthcare, as it does in the us, many of the relevant initiatives fall outside the state sector and are hard to capture. there are undoubtedly many small commercial initiatives in east asia as, again, there are in the us. furthermore, like other commercial websites, private healthcare sites throughout the region rely heavily on advertising and sale of products for income. to take just two taiwanese instances, the kingnet webhospital and the taiwan physician's net offer online sales not only of healthrelated products, but also of cinema tickets. the very fragmented nature of private-sector healthcare operations throughout the tigers means that few summary assessments can be made. looking finally at physician-patient relations, the existing literature contains variable forecasts of unpredictable change, little change, and so on. however, there is a clear belief that patients have most to gain from e-health and physicians correspondingly have most to lose. in general, physicians in the tigers have tended to be wary of exploiting the internet for patient interactions. this partly reflects the tight regulatory climate in which many find themselves, with many modes of physician-patient contact outlawed. it may also reflect a certain reluctance on the part of both physicians and patients to engage in the informalities of online contact. until recently, then, the emergence of virtual physician-patient relations was highly limited. since the spring sars crisis, however, the pattern may have started to change. although it is too early to register the longterm impact of the crisis, it is clear that during the sars outbreak, many individuals sought to shift to online interactions with healthcare professionals. the fear of visiting surgeries and, in particular, hospitals that gripped the region in has certainly not disappeared and seems likely to provide a lasting stimulus to virtual delivery of healthcare. furthermore, the generic healthcare information found in great abundance on english-language websites is paralleled on regional websites operating in chinese, japanese and korean. there is also some official encouragement for patients to migrate to e-health. in may , hong-jen chang, ceo and president of taiwan's bureau of national health insurance, argued at an oecd forum that e-health could make a major contribution in informing patients. as evidence, he cited taiwanese experience in confronting hiv/aids and the role of the internet in educating patients about the disease. in the long run, he contended, patients equipped with information gained from online searches ''will translate into quality improvement and efficiency gains for the system'' [ ] . overall, east asian societies retain many traditional features, which generate some resistance to change in established modes of physician-patient contact. nevertheless, there are also factors operating in the opposite direction. one long-term impact of the sars crisis seems likely to be heightened caution about visiting healthcare facilities, for fear of contracting infectious disease, and a consequent boost for e-health. the east asian tigers form the most wired cluster of societies found anywhere in the world. moreover, they have long had a developmentalist orientation that has seen their states become involved in many aspects of economic and social development. in the sphere of e-health, however, their performance is strong at the level of basic web provision, but otherwise not particularly advanced. on the whole, their health ministries or departments have good sites covering all the fundamentals of online provision. outside central government agencies, they often have a wealth of additional sites in the public and private sectors. beyond that, they do not make pioneering use of the internet in healthcare. there are many possible reasons for this slightly disappointing performance, some of which apply to all of the tigers and others which are specific to a particular society. in japan, the structural problems that mired the economy in stagnation for more than a decade from the early s also form part of the explanation for its sluggish e-health performance. a notable feature of the japanese healthcare system is the considerable power of the japan medical association and its extensive links to the liberal democratic party that has governed the country for almost all of the post-war period. in hong kong, the sovereignty transfer was quite disruptive, and only several years on is the political system taking a settled shape on the developmental state model. looking beyond the specific circumstances of individual tigers, however, the major explanatory factors appear to be institutional, cultural and financial. institutionally, east asian healthcare systems tend to be highly fragmented, notably in japan, south korea and taiwan. in consequence, policymakers in healthcare ministries and departments have rather few levers that they can use to direct change. in the e-health sphere, they can quite easily construct official government websites, but generating reform in the wider healthcare system is more difficult and depends on their success in building consortia of interest among many private-sector actors. in part, they seek to do this by offering ring-fenced seed money for specified development projects. in part, they resort to exhortation, calling on all members of society to engage in the project of securing and maintaining regional and/or global leadership in the information age. in these many respects, the east asian tigers have a great deal in common with the us. in the additional domain of culture, they differ from the us. while capitalism is certainly a dynamic force in east asia as in north america, it also co-exists with still vibrant cultural underpinnings. the confucian heritage that characterizes all five east asian tigers has many complex strands. among them is considerable respect for authority, hierarchy, status and so on. in the medical sphere, one consequence is that doctors tend still to be accorded considerable professional status. this may make it difficult for full commercialization to take place and for the market drive that characterizes ehealth in the us to work its way through the system. finally, the financial dimensions of healthcare in the east asian tigers should not be overlooked. these are healthcare systems that deliver the excellent outcomes already mentioned at a fraction of the cost registered in the us and, indeed, in most developed societies. as a proportion of gdp, east asian tigers spend between and % on healthcare, with most coming in at around %. this is far below the us figure of - %, and also below the highincome country standard of almost %. one result of the tigers' success in holding down healthcare costs is that the incentive to experiment with new initiatives is reduced. clearly, there still are some incentives, but they are not as strong as in the us. e-health in the east asian tigers remains at an early stage of development. all have attained a good basic standard, but few are engaged in pathbreaking initiatives. alongside institutional factors that are similar to those found in the us, cultural and financial factors help to explain this rather unsatisfactory level of performance. doctors in a wired world: can professionalism survive connectivity? milbank q the internet promise, the policy reality the information age: economy, society and culture. vol. ii. the power of identity the information age: economy, society and culture. vol. i. the rise of the network society the information age: economy, society and culture. vol. iii. end of millennium how will the internet change our health system? ehealth: technologic revolution meets regulatory constraint patients, physicians and the internet com: the failed promise of the healthcare internet networking health: learning from others, taking the lead financing the healthcare internet rethinking communication in the e-health era consumers of e-health: patterns of use and barriers the impact of cyberhealthcare on the physician-patient relationship e-health: transforming the physician/patient relationship health care web sites: are they reliable? internet healthcare coalition, e-health quality partners named exclusive education and outreach affiliate of the internet healthcare coalition physicians get on line, aspen publishers doctor-patient e-mail slow to develop, international herald tribune nielsen//netratings, internet provided vital information and alternative access to shopping, banking and education for people in hong kong as sars took hold online shopping and banking sites soared in popularity as people in hong kong shunned the crowds sars stimulates ongoing growth in internet usage in hong kong divided sun: miti and the breakdown of japanese high-tech industrial policy tiger technology: the creation of a semiconductor industry in east asia united nations/american society for public administration building e-government in east and southeast asia: regional rhetoric and national inaction high performance, maximum value productivist welfare capitalism: social policy in east asia welfare capitalism in east asia: social policy in the tiger economies traditional medicines in modern societies: an exploration of integrationist options through east asian experience agenda-setting for the regulation of traditional chinese medicine in hong kong networking health: dawning of the e-health era. paper presented to apami-mic conference at the hong kong convention and exhibition centre e-health and the informed patient, paper presented to oecd forum taiwan council of economic planning and development, taiwan statistical data book world development indicators the work described in this article was substantially supported by a grant from the research grants council of the hong kong special administrative region, china [project no. cityu / h]. initial seed funding was provided by the governance in asia research centre, city university of hong kong.we are grateful for the research support we received. we thank academics, officials and practitioners in east asia for talking to us about e-health. the usual disclaimer applies. key: cord- -ybouh cw authors: huang, irving yi‐feng title: fighting against covid‐ through government initiatives and collaborative governance: taiwan experience date: - - journal: public adm rev doi: . /puar. sha: doc_id: cord_uid: ybouh cw taiwan is situated less than km from the first covid‐ outbreak state, china, and has millions of international visitors yearly. taiwan's collective efforts to block and eliminate the invisible enemy (covid‐ ) from the island, have resulted in relatively low infection and death numbers, and were hailed as a successful anomaly amid the global pandemic. in this review, i pinpoint some background on the systems and organizations that helped taiwan streamline a task force (command center) in a timely manner to launch related initiatives, mobilize the public, and engage private resources to implement the strategies and policies which were further enhanced by collaborative behaviors and volunteers. also, even subject to similar threatening conditions such as cruise ship stopover and numerous foreign immigrant workers, there were no outbreaks of community infection in taiwan similar to singapore, japan, etc. taiwan's successful measures offer good example for future comparative studies. this article is protected by copyright. all rights reserved. in three months, the coronavirus originated from wuhan, china and spread rapidly to the entire world. according to who statistics, on may th , there were , , confirmed cases, , deaths worldwide (who, ) . taiwan, in the meantime, fared relative well compared to other regions and countries. as of may th , taiwan recorded cases and deaths (tcdc, a) . for a country of more than million people living on a mountainous island the size of maryland, usa with only % inhabitable lands, the odds of preventing the spread of a highly infectious disease are not very promising. favorable conditions and successful strategies are behind this anomaly. regarding blocking infectious diseases, taiwan underwent a similar crisis in in the severe acute respiratory syndrome (sars) epidemic which caused probable (k.-t. chen et al., ) . during sars, one of the major urban hospitals (ho-ping hospital) was locked down to avoid outbreaks and thousands of people were quarantined. after losing a number of frontline workers, this smaller scale epidemic was finally contained over a few months with minimal casualties. for taiwan's center for disease control (tcdc), sars was both a warning and rehearsal to test the public health capacities and reactions. from the reviews and experiences, taiwan envisioned a better structure for a command center and developed some sops to deal with possible future epidemics. taiwan is an open society where information can be used or abused and where government can be trusted or opposed, all at the same time. during the sars period, there were panics and missteps that led to uneasiness and uncertainly. however, overall, good judgement based on knowledge dictated the pace and direction in battling this infectious disease. to be sure, government agencies play a leading role in mobilizing all possible resources. positive perceptions such as "transparency" and "authority" toward them are even more critical in soliciting public support during a pandemic. in this new round of a covid- battle, both "transparency" and "authority" were assumed generally in the society. moreover, a degree of "social capital" (i.e. people in taiwan tend to trust public institutions) facilitated policy implementation during a public health crisis. this can be seen in the active civic engagement and public participation throughout the crisis. citizens were willing to trust and help each other, dedicating themselves to maintaining a safe and healthy society. the following, will review some of the conditions and practices that highlight the positive interplay between government initiatives and public supports in taiwan. the government setting national healthcare insurance system the national health insurance (nhi) covers almost everyone in taiwan. nhi is government-implemented social insurance, and has the ministry of health and welfare as its competent authority. (nhia, , ) . the government's original intention in providing the nhi program was to provide health security to all citizens via a mutual assist system. the system was designed to ensure that everyone enjoyed equal rights to healthcare. the inclusion of different groups in the program means that all citizens have equal rights to access medical services when they get sick, are injured, or give birth. with the integrated circuit (ic) health card, every patient can check clinic records thru the nhi app. this system became a tool to help the government distribute masks through pharmacies to citizens all over taiwan, and also helped trace citizens' travel records. after sars, a number of the prominent public health leaders such as dr. chen chienjen (an epidemiologist served as the minister of health then and vice president in ) and dr. kuo shu-song (director of cdc in ) realized that not "whether" but "when" the large scale infectious disease will threat taiwan. they suggested preventive hoarding of first response equipment and medicines (such as tamiflu). to streamline leadership and avoid confusion, they advocated setting up the national health command center (nhcc) in . nhcc is to respond to large outbreaks swiftly and acts as the nerve center to mobilize resources, coordinate personnel and advice guidelines during pandemics. this mission-oriented ad hoc system includes the central epidemic command center (cecc), the biological pathogen disaster command center, the counter-bioterrorism command center and the central medical emergency operations center. this joint framework serves as a comprehensive platform for preventing epidemics. its legal foundation is based on the communicable disease control act and the enforcement regulations governing the central epidemics command center. on january , , the tcdc announced the activation of the cecc for severe special infectious pneumonia. the tcdc director-general chou chih-haw(周志浩) was appointed as the commander in order to integrate resources across government agencies and further protect the health of the taiwanese public from the outbreak. a cross-agency command center meeting and an expert consultation meeting were held that day. (tcdc, b). it's was a level- emergency establishment. wuhan city, china was shut down starting from am on january , indicating increasing coronavirus infections, the cecc announced that starting from january the outbreak level for the wuhan pneumonia was escalated to level and that minister of ministry of health and welfare chen shih-chung (陳時中) would act as the commander. (tcdc, c). on feb. , premier su tseng-chang announced that he accepted health and welfare minister chen shih-chung's recommendation to upgrade the cecc to a level- facility in light of the mounting, global urgency to contain the novel coronavirus disease . minister chen continued as commander. the premier explicitly instructed all agencies concerned to maintain the highest vigilance as the government continued to combat the outbreak, provide economic relief, and stimulate local industries. a cabinet meeting was conducted to propose an economic relief act, which was passed by the congress on feb. , . according to the preparedness and contingency planning in response to covid- epidemic, the cecc was gradually upgraded as table shows. according to the authorization of enforcement regulations governing the central epidemics command center, the cecc commanding officer has the unified authority to command, supervise, and coordinate government organizations at various levels, public enterprises, reserved servicemen's organizations, and non-governmental organizations to implement disease control matters. when necessary, support of the army may be coordinated. the commanding officer may instruct government organizations at various levels to requisition, expropriate, and integrate resources, facilities, or manpower of organizations (institutions) concerned. the center may invite one deputy minister or designated representative of each ministry/council/commission concerned to be member of the center. the cecc hosted a daily press conference to announce further information of confirmed cases, infection sources, and related treatments. representatives from related ministries were also required to attend and provide necessary explanations. it demonstrated a transparent operation and government decision process, including a q&a briefing, which helped to stabilize the public and clarify the rumors and fake news. the cecc/cdc produced many one-minute programs to play on cable tv channels almost every hour for public health education. these included how to wear a mask, how to wash hands completely, how to keep proper social distance, etc. they invited all specialties of physicians to explain how to avoid virus infection including how to reduce stress and anxiety caused by quarantine. figure details the structural response of the government. taiwan is a unitary state. the central government is responsible for policy formulation and the local governments for implementation. according to the communicable disease control act, local governments are in charge of the following responsibilities: .develop implementation plans and implement those plans according to the communicable disease control policies and plans formulated by the central government and locality-specific disease control practices. also report to the central competent authority for reference. .implement various communicable disease control measures in the locality including immunization, prevention of communicable diseases, epidemiological surveillance, case reporting, investigations, laboratory testing, management, drills, mobilization by level, training, pharmaceutical, device and protective equipment stockpile, and houseisolation. .conduct quarantine of local ports. .implement matters instructed or commissioned by the central government. .other matters that shall be implemented by local competent authorities. by january , the taiwan cdc began monitoring all individuals who had travelled to wuhan within fourteen days and exhibited a fever or symptoms of upper respiratory tract infections. these people were screened for known pathogens, including sars and middle east respiratory syndrome (mers), and those tested positive were quarantined (wang, ng, & brook, ). as of march, persons directly returning to taiwan from most of europe, plus persons who transferred through china, hong kong, macau, and dubai, had to quarantine in-home for days (new york times, ). as of march, the only foreign nationals permitted into the country (those holding alien resident certificates (arc cards) or those on urgent diplomatic, business, or other special missions) could rent a room in a public quarantine center (mofa, ). on march, the cecc raised the global travel notice to level , and taiwanese citizens were advised to avoid all nonessential travel (tcdc, e). the local governments cooperated with the cecc to ensure the quarantine. based on these and later border controls, the cecc required all travelers arriving in taiwan to be quarantined for days and their information to be passed to local governments. next, street-level officers in district governments visited those quarantined to make sure that they were healthy, were abiding by the requirement, and were also provided with an anti-virus pack including masks and disinfectant alcohol. those quarantined were fined if they went outside. the district government was responsible for monitoring them by tracking their cellphones. the police also worked to find the quarantined who went outside or even tried to escape the quarantine. on march , the cecc announced that the covid- outbreak had become a global pandemic and that the number of imported cases continued to rise. in order to stop the spread of covid- through air transport, the cecc announced that the transit of airline passengers through taiwan was suspended from : taipei standard time (gmt+ ) on march (tuesday) until april , in order to decrease the cross-border movement of people and to reduce the risk of disease transmission (tcdc, d). in order to curb panic buying and the hoarding of face masks in taiwan, the cecc announced on february that a name-based rationing system for face masks would be launched on february . this would ensure universal access to face masks as well as fairness and transparency of resources allocation (tcdc, f). people were able to get a mask on alternate days depending on the odd or even last digit of their ic health card, and the number available to each was rationed. one of the innovative ways to help the general public get masks is through an online order system. the cecc announced on march that an online ordering mechanism would be added, on march , to the name-based rationing system for face masks. the purpose of this new mechanism was to better ensure even distribution. it made distribution of face masks more convenient for people such as office workers and students who lacked the time to go to the pharmacies and public health center distribution spots, where there were sometimes long lines. the cecc announced social distancing measures on april to encourage the general public, in phases, to maintain social etiquette and observe social distancing. this thereby further reduced the risk of community transmission of covid- , which continued to spread across the globe. these measures sought to protect people's rights while bolstering epidemic prevention and control efforts, which could be undermined by infected people who did not seek medical help or were asymptomatic (tcdc, g). in addition to very few covid- cases were found in taiwan, only cases were due to community transmission, plus another from panshi fast supply war ship. this was in contrast to the significant number of imported cases, either early on from wuhan or later from student's and travelers returning from around the world. because of the low infection and death rates, the high standards and professionalism of the healthcare system and workers, and the nhi scheme, taiwanese abroad generally felt that they wanted to be back home. their return also made quarantining and social distancing very important the mandatory rules specified separate social distancing standards for restaurants, school campuses, offices, mass transport, supermarkets, other commercial sites, locations with long lines of waiting people, and special institutions such as long-term care facilities and prisons. during the continuing covid- outbreak, social distancing is to be followed in order to prevent community transmission and protect oneself and others. public participation and acceptance have been a crucial factor, and fines and charges for disobedience have been very few. this is an exceptional example of democratic concern for the public good. on april th , the cecc announced that a line bot system, called disease containment expert, developed jointly by the cecc, line taiwan and htc corporation's healthcare unit deepq would be officially launched for use on april to track people in home quarantine. the cecc also added a new function to the current sms (short message service) reporting mechanism, allowing those in home quarantine/isolation to report their health status via sms (tcdc, h). with the line bot system, those in home quarantine can voluntarily report their health status to the disease prevention staff every day and obtain information concerning disease prevention. those in home quarantine can use the line bot system by clicking a link, sent to them via sms, to add the disease containment expert to the friend list on line and then complete the identity verification process. in addition to information on disease prevention and health status reporting, the system also sends home quarantine related details and notes to users two days before the end of the home quarantine period to remind them to conduct an additional -day period of self-health management. in addition to the line bot system, on april , the cecc began to send sms messages every day to track the health status of those in home quarantine and home isolation the quarantined and isolated people can directly reply to the messages to report their health conditions. no less important in effecting government policies are public collaboration and voluntary assistance. highly demanded masks were originally collected and distributed by government through all of the existing manufacturers. backed by government funds, the factories soon expanded their capacities and made up to million masks per day. the government also sent soldiers to the factories to work to speed up production. under the coordination of the taiwan pharmacy association, all the masks were mailed to local pharmacies that allocated certain hours to sell masks without fees to the general public. to help with "social distancing", many of the popular gathering places such as "night markets" organized patrollers to control the flow of crowds. from the beginning and depending on the sources of entry back to taiwan or the likelihood of being infected, different levels of "quarantine" were mandated to different people. thanks to flexible manpower and voluntary assistance, the implementation and effectiveness of these quarantines were assured with low social cost. those designated as "stay-home-isolation" or "stay-home-quarantine", they were not supposed to leave their residence for days. not only were their health conditions monitored by health workers or borough chiefs twice a day, their whereabouts were reported by whistle blowers or building managers when they went out of bounds. also, there were tens of thousands of volunteers who provided food to people who were under quarantine and checked their conditions on site. even though fewer infected people means fewer people need to be quarantined, these volunteers help to lower the likelihood that covid- spread out in the community. in a "collaborative governance" model, the critical elements include cooperation between the central and local governments, coordination with the ngos and major associations, and mobilization of corporate resources to provide essential goods. despite the inherent mistrust for public management in a democracy, taiwan shows that, once people realized they are "at war" amid a pandemic, cross-sector collaborative governance can be applied successfully in a large scale crisis. from the perspective of emergency management, the government has responsibility to take necessary actions to avoid or reduce damage and look for resources from possible stakeholders. in taiwan experience, government initiatives and collaboration from other sectors worked together to prevent the spread. based on the above description, we can conclude that the government initiatives and collaborative governance model for fighting in taiwan is as shown in figure . this article is protected by copyright. all rights reserved. it was a combination of well-implemented measures to block, track, and isolate possible sources of infection along with high public compliance that helped taiwan have an outstanding "report card" in the global wave of covid- . taiwan was also extremely lucky in that, in some of the potential cases, it miraculously escaped community outbreaks. these includes: the late blocking in the taiwanese islands that are off the chinese mainland of their throngs of chinese visitors; the disembarking of the diamond princess in taiwan with , visitors roaming around northern taiwan; the hundreds of thousands of foreign immigrant labors work in taiwan, etc. but, unlike japan, singapore and other countries which developed community transmitted infections after similar situations, taiwan remained unscathed. if we add in the factor that there was a "lack of large scale tests" in taiwan, such good fortune begs a question: does a higher proportion of taiwanese have an "antibody" in the first place? this is a puzzle that requires further epidemiological study. how various factors played their role in in fighting of the pandemic will remain to be studied in related fields in the future. whether in a "control group" or "experiment group", taiwan's experience will provide evidence that contributes to our understanding of this public health crisis. source: tcdc ( i). note: division of work among ministries mandated by the communicable disease control act .ministry of interior: matters concerning the control of entry and exit, assistance in supervising local governments in the implementation of public services such as in-house isolation. .ministry of foreign affairs: matters concerning liaison with foreign governments and international organizations, issuance of visas to foreign passport holders. .ministry of finance: matters concerning lease of state properties for use. .ministry of education: matters concerning promotion and education of disease control for students and school personnel, and surveillance and control of communicable diseases among them. .ministry of justice: matters concerning surveillance and control of communicable diseases among inmates in correctional centers. .ministry of economic affairs: matters concerning supply of protective equipment, and control of industry-specific ports. .ministry of transportation and communication: matters concerning control of airports and commercial seaports, service requisition of transport facilities. .mainland affairs council: matters concerning the coordination of policies governing contacts between people of the taiwan area and people of the mainland china area, or hong kong and macau. .environmental protection administration: matters concerning the sanitation and disinfection of public environment, and disposal of wastes. .council of agriculture: matters concerning the control of communicable diseases common to humans and animals, and control of fishing harbors. .ministry of labor: matters concerning occupational safety and health, and protection of workers' rights. .national communication commission: matters concerning the management and release of news, dissemination of government orders, and designating radio and television media for broadcast. .ocean affairs council and coast guard administration: matters concerning the seizure of smuggling of vectors of communicable diseases at sea areas, sea coasts, river mouths and non-commercial ports, and illegal entry and exit across the national borders. .other relevant organizations: implementing relevant matters necessary to the control of communicable diseases. . taiwan sars in taiwan: an overview and lessons learned nt$ billion budget to cope with coronavirus clears legislature virus outbreak: masks required for train passengers virus outbreak: fines authorized for unmasked riders virus outbreak: legislature raises relief budget ceiling. taipei times faq: taiwan's -day quarantine requirements - national health insurance annual report. taipei: national health insurance administration, ministry of health and welfare new york times. . coronavirus travel restrictions, across the globe. the new york times taiwan centers for disease control, tcdc. a. covid- (sars-cov- infection taiwan cdc announces activation of central epidemic command center (cecc) for severe special infectious pneumonia to comprehensively prevent novel coronavirus pneumonia outbreak in china and ensure health of taiwanese public in response to wuhan pneumonia outbreak, central epidemic command center (cecc) raises outbreak level for wuhan pneumonia to level and continues to maintain prevention efforts during the chinese new year holiday and ensure health of taiwanese public taiwan centers for disease control, tcdc. d. taiwan to ban airline passenger transits through the country starting tcdc. e. cecc raises travel notice for all this article is protected by copyright. all rights reserved.accepted article countries to level : warning; advises against all nonessential travel. (mar. , key: cord- - uvbfp c authors: li, dian-jeng; ko, nai-ying; chen, yi-lung; wang, peng-wei; chang, yu-ping; yen, cheng-fang; lu, wei-hsin title: covid- -related factors associated with sleep disturbance and suicidal thoughts among the taiwanese public: a facebook survey date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: uvbfp c coronavirus disease (covid- ) pandemic has impacted many aspects of people’s lives all over the world. this facebook survey study aimed to investigate the covid- -related factors that were associated with sleep disturbance and suicidal thoughts among members of the public during the covid- pandemic in taiwan. the online survey recruited participants through a facebook advertisement. their self-reported experience of sleep disturbance and suicidal thoughts in the previous week were collected along with a number of covid- -related factors, including level of worry, change in social interaction and daily lives, any academic/occupational interference, levels of social and specific support, and self-reported physical health. in total, . % of the participants reported sleep disturbance, and . % reported having suicidal thoughts in the previous week. multiple covid- -related factors were associated with sleep disturbance and suicidal thoughts in the covid- pandemic. increased worry about covid- , more severe impact of covid- on social interaction, lower perceived social support, more severe academic/occupational interference due to covid- , lower covid- -specified support, and poorer self-reported physical health were significantly associated with sleep disturbance. less handwashing, lower perceived social support, lower covid- -specified support, poorer self-reported physical health, and younger age were significantly associated with suicidal thoughts. further investigation is needed to understand the changes in mental health among the public since the mitigation of the covid- pandemic. coronavirus disease (covid- ) is a novel infectious disease that emerged in wuhan, china at the end of and rapidly spread worldwide [ ] . as the threat increased, the world health organization (who) declared the outbreak of covid- a global public health emergency on the january and it was declared a pandemic on the march . the covid- pandemic is severely affecting people's daily lives all over the world, including their health, economic wellbeing and social interactions [ ] . social distancing, self-isolation, and travel restrictions have resulted in a massive decrease in productivity across all economic sectors, which has had severe lockdown effects and placed a heavy burden on society, such as the decline in global stock markets and overload of healthcare services [ ] . people in taiwan also suffered from threats of covid- . the taiwan centers for disease control (taiwan cdc) identified the risk of the covid- pandemic and delivered necessary policy quickly at the end of january . according to the situation report of taiwan cdc [ ] , cases were infected with covid- at june th. of the confirmed cases, there have been seven deaths, and patients have been released from isolation. most of the morality was associated with elderly and chronic systemic disease. healthcare workers followed the order of authorities to increase the intensity of infection control, such as forced wearing of masks, taking body temperatures, and limitations for visitors in hospitals. due to limited cases of infection, the intense care facilities were sufficient. the relatively minimal proportion of less confident individuals may result from timely border control, application of big data analytics, and experienced teams of officials [ ] . in addition to the socio-economic burden that covid- has caused, the pandemic may also have hazardous effects on the public's mental health. several studies had addressed the psychological impact of covid- . a web-based survey reported that the overall prevalence of anxiety symptoms, depressive symptoms, and poor sleep quality were . %, . %, and . %, respectively, among the public affected by the covid- outbreak in china [ ] . another study recruited subjects reported that a considerable proportion of participants reported symptoms of depression ( . %), anxiety ( . %), insomnia ( . %), and distress ( . %) [ ] . it is important to examine covid- -related factors that affect mental health during the covid- pandemic. studies predicting factors associated with mental health problems will enhance understanding and help develop timely prevention and intervention strategies to enhance public mental health during covid- pandemics [ ] . it was reported that nurses, women, frontline health care workers, and those working in wuhan, china were significantly associated with more severe degrees of depression and anxiety symptoms than other health care workers [ ] . another covid- study indicated that female gender, student status, specific physical symptoms (e.g., myalgia or dizziness), and poor self-rated health status were significantly associated with higher levels of stress, anxiety, and depression [ ] . in addition, individuals with frequent social media exposure were positively associated with higher odds of anxiety than lower exposed ones during the covid- pandemic [ ]. although previous studies explored the high prevalence of psychological distress for the public during the covid- pandemic, it was still insufficient for investigations regarding the risk factors associated with mental health problems, such as social support. an egyptian population-based study demonstrated that only . % of individuals had increased support from friends, while . % of them reported increased support from family members during the covid- pandemic [ ] . however, whether social support can buffer the negative effects of social isolation and changes in daily lives during the covid- pandemic warrants further study. in addition, seldom covid- related studies discussed suicide, which is an unneglectable issue due to elevated psychological distress [ ] . therefore, the aim of the current study focused on the impact of covid- on daily lives and how varying levels of support may affects people's mental wellbeing, such as level of sleep disturbance and suicidal thoughts. participants were recruited through a facebook advertisement from april to , . facebook users were eligible for this study if they were ≥ years old and living in taiwan. the facebook advertisement included a headline, main text, pop-up banner, and link to the research website and questionnaire. the advertisement was designed to appear in the facebook users' "news feeds," which is a continually updated list of posts from advertisers and the user's connections (such as friends and the facebook groups that they have joined). our advertisement only targeted users' news feeds, as opposed to other facebook advertising locations (e.g., the right column), because news feed advertisements are most effective in recruiting research participants [ ] . the advertisement was targeted to facebook users by location (taiwan) and language (chinese), and facebook's advertising algorithm determined which users to show our advertisement to. to ensure that health care workers were recruited, the facebook advertisement was also posted link to line (a direct messaging app) and facebook groups joined by healthcare workers. this study was approved by the institutional review board (irb) of kaohsiung medical university hospital (approval no. kmuhirb-exempt (i) ). as participation was voluntary and survey responses were anonymous, the irb ruled that this study did not require informed consent. the study participants were given no incentive or reward for their participation. the links were provided regarding the covid- information by the taiwan cdc, kaohsiung medical university hospital, and medical college of national cheng kung university so participants could learn more about covid- . the sleep disturbance and suicidal thoughts of participants were assessed with the question on a -point likert scale, with scores ranging from (never) to (extremely severe). participants who rated the items of sleep disturbance and suicidal thoughts > were classified as having sleep disturbance or suicidal thoughts, respectively [ ] . the details of this and following questionnaires are provided as supplemental data (tables s -s ). the participants' gender (female, male, or transgender), age, and education level (high school or below vs. college or above) were collected. moreover, whether the participants were healthcare workers was also identified. the five-item questionnaire developed by liao and colleagues to assess individuals' level of worry about h n [ ] was applied to assess the severity of participants current worry about covid- . participants responded to them with four -point and one -point likert scale. cronbach's α was . . a higher total score of the five questions indicated more severe worry about covid- (table s ). with reference to a previous study, seven questions were developed to evaluate the changes to participants daily lives due to covid- [ ] . the responses were transformed into ("no" or "yes, but not due to covid- ") and ("yes, due to covid- "). cronbach's α of the questionnaire was . (table s ). four questions were developed to assess the impact of covid- on social interaction. the responses were transformed into ("no" or "yes, but not due to covid- ") and ("yes, due to covid- "). cronbach's α was . . higher total scores for the four questions represented covid- having a more severe impact on the individual's social interactions (table s ). the academic/occupational interference was evaluated by the covid- pandemic with one question. participants responded to the question on a -point likert scale ranging from (entirely no interference) to (extreme interference) (table s ). three questions were used to measure the level of perceived social support. the responses to these three items were graded on a -point likert scale, with scores ranging from (entirely disappointed) to (extremely satisfied). cronbach's α was . . a higher total score represented a higher level of perceived social support. the participants' level of covid- -specified support was estimated with five questions. the responses to the questions were graded on a -point likert scale, ranging from (entirely insufficient), (mild insufficient), and (sufficient). cronbach's α was . . a higher total score represented higher satisfaction with the level of covid- -specified support (table s ). two questions from the self-perceived health questionnaire developed by ko and colleagues [ ] were used to assess the level of self-reported physical health. the level of self-reported physical health was a -likert scale rated from (much worse) to (much better). cronbach's α was . . a higher total score indicated better self-reported physical health (table s ). descriptive analysis was used to summarize the variables. univariate logistic regression with crude odds ratios (cor) was used to identify potential covid- -related factors associated with sleep disturbance and suicidal thoughts. furthermore, all potential predictive variables identified from the first step were eligible for inclusion in the forward stepwise logistic regression models with adjusted odds ratios (aor) to determine the independent predictors for sleep disturbance and suicidal thoughts. all tests were examined using a two-tailed test with the alpha level set at < . . all data were processed using spss version . for windows (spss inc., chicago, il, usa). initially, there were respondents who filled in the online questionnaire. after excluding those respondents with missing values (n = ) and those aged below years (n = ), the data of participants ( females, males, and transgender) were entered for analysis. the mean age of the participants was . ± . years. a summary of the remaining characteristics for all participants are listed in tables and . a total of ( . %) participants reported sleep disturbance, and ( . %) reported having suicidal thoughts in the past week (table ) . tables and show the results of the univariate logistic regression. the results demonstrated that current sleep disturbance was significantly associated with several factors, including younger age (cor = . ; p = . ), more severe worry about covid- (cor = . ; p < . ), more severe impact of covid- on social interaction (cor = . ; p = . ), lower perceived social support (cor = . ; p < . ), lower self-reported physical health (cor = . ; p < . ), higher academic/occupational interference (cor = . ; p < . ), lower covid- -specified support (cor = . ; p < . ), and more household disinfection (cor = . ; p = . ). table shows the results of the forward stepwise logistic regression. the results indicated that more severe worry about covid- (aor = . ; p = . ), more severe impact of covid- on social interaction (aor = . ; p = . ), lower perceived social support (or = . ; p < . ), poorer self-reported physical health (aor = . ; p < . ), more severe impact of covid- on academic/occupational interference (aor = . ; p = . ), and lower covid- -specified support (or = . ; p = . ) remained significant independent predictors associated with sleep disturbance. for suicidal thoughts, the univariate logistic regression indicated several potential factors that could predict suicidal thoughts, including a younger age (cor = . ; p < . ), being transgender (cor = . ; p = . ), being non-healthcare workers (cor = . ; p < . ), more severe worry about covid- (cor = . ; p = . ), lower perceived social support (cor = . ; p < . ), poorer self-reported physical health (cor = . ; p < . ), lower covid- -specified support (cor = . ; p < . ), and less handwashing (cor = . ; p = . ) (tables and ). the results of the forward stepwise logistic regression demonstrated that younger age (aor = . ; p < . ), less handwashing (aor = . ; p = . ), lower perceived social support (aor = . ; p < . ), poorer self-reported physical health (aor = . ; p < . ), and lower covid- -specified support (or = . ; p < . ) remained significant independent predictors of suicidal thoughts (table ). the findings of the current study were discussed initially with the primary outcome, including sleep and suicidal thoughts. then several independent predictors associated with sleep disturbance and suicidal thoughts were discussed. the current study was conducted using an online survey, which has been reported to be a promising method for evaluating how the general public understand and perceive a fast-moving infectious disease outbreak [ ] . in the current study, the rate of sleep disturbance in the previous week was . %, which was much higher than the result of a population-based investigation in taiwan using the same question to assess sleep disturbance (up to . %) [ ] . the rate of suicidal thoughts reached . % in the previous week, which was also higher than the findings of a previous survey in taiwan using the same question to assess suicidal thoughts ( . %) [ ] . in addition, increased worry about covid- , more severe impact of covid- on social interaction, lower perceived social support, more severe academic/occupational interference due to covid- , lower covid- -specified support, and poorer self-reported physical health were significantly associated with sleep disturbance. less handwashing, lower perceived social support, lower covid- -specified support, poorer self-reported physical health, and younger age were significantly associated with suicidal thoughts. the present study found that a high level of worry about covid- was significantly associated with sleep disturbance. previous study indicated that degree of worry was significantly associated with psychological distress measured by general health questionnaire- during a/h n influenza [ ] . another study regarding middle east respiratory syndrome (mers) reported that individuals with very high stress in daily life had higher levels of worry than those who reported having little stress [ ] . people with significant psychological distress may suffer from sleep disturbance. in addition, it had been reported that misinformation about covid- has been proliferating on social media [ , ] . owing to the significant association between worry about covid- and sleep disturbance, whether misinformation on social media may deepen people's worry about covid- warrants further investigation. social distancing is one of the main protective behaviors against contracting covid- [ ] . moreover, previous studies have found that the severe acute respiratory syndrome (sars) outbreak changed social interaction because of the fear of contracting the disease among the public [ ] and due to healthcare workers being stigmatized [ ] . the present study found a significant association between changes in social interaction due to covid- and sleep disturbance, but not significant for suicidal thoughts. instead, the present study found that lower perceived social support and specific support against covid- were both independent predictors for sleep disturbance and suicidal thoughts. previous research has found that perceived support from a family member, friends, and medical staff were associated with mental health during the sars pandemic [ ] , and also that insufficient social support was a risk factor for depression, anxiety, and sleep problems among healthcare workers in the covid- pandemic [ ] . the results of this and previous studies demonstrate the importance of sufficient social support and specific support against infective respiratory diseases during a pandemic. social distancing may hamper physical, social interaction; however, social support can be offered by telecommunication. governments should provide support for those who are socially isolated before the pandemic and for those who are quarantined due to infection during the pandemic to help prevent mental health problems. to prevent the spread of covid- , authorities all over the world announced stay-at-home and school-closure orders, which interfere with people's academic/occupational performance. the present study found that the higher the academic/occupational interference by covid- the higher the predicted sleep disturbance. although academic and occupational activities may be restored as the risk of covid- is mitigated, it takes time and consistent policies to restore economic prosperity. the unemployment rate increased because of the enormous impact of covid- on the global economy. research has found that the unemployment rate increased in parallel with the prevalence of depressive and anxiety disorders [ ] . academic and occupational interference by the covid- pandemic and the negative effect this has on health should be monitored not only during but also after the pandemic. the daily lives of the public have changed due to the adoption of protective behaviors against contracting covid- and searching for information on covid- . the present study found that less handwashing was significantly associated with suicidal thoughts in the multiple logistic regression. handwashing is the most recommended behavior by the who to protect individuals from contracting covid- [ ] . however, people who had suicidal thoughts might not have the motivation to adopt the experts' recommendation of hand washing. this association may be influenced by level of depression. previous study revealed the association between depression prevalence rates and poor health habits [ ] . in addition, people with mental illnesses have a greater vulnerability to serious complications from covid- due to cognitive impairment, little awareness of risk, and diminished efforts regarding personal protection [ ] . early intervention for mentally ill individuals during the covid- pandemic is crucial for preventing a possible loophole for infection control. the present study found that poorer self-reported physical health was significantly associated with sleep disturbance and suicidal thoughts. several possible etiologies may account for this association. first, poorer physical health, such as chronic diseases or impaired physical function, may directly increase psychological distress [ ] . second, people might stop seeing the doctors because they were worried about contracting covid- and the treatment for physical problems might be delayed. both anticipatory anxiety about and actual occurrence of exacerbated illnesses may result in sleep disturbance and suicidal thoughts. third, poorer physical health may result in reduced physical activities, which was reported to be associated with higher psychological distress [ ] . fourth, sleep disturbance may worsen physical health [ ] . moreover, people with suicidal thoughts were likely to have depressive disorders, which were significantly associated with physical health problems [ ] . although the cross-sectional study design limited the ability to determine the causal relationship between self-reported physical health, sleep disturbance, and suicidal thoughts, health professionals should encourage the public to continuously enhance physical health in addition to detecting the symptoms of covid- infection. younger age was an independent predictor for suicidal thoughts as determined by multivariate logistic regression. it was also potentially associated with sleep disturbance. a recent study in china also demonstrated that younger subjects were at high risk of mental illnesses, such as general anxiety disorder during the covid- pandemic [ ] . moreover, the present study found that non-healthcare workers and transgender people were potentially more likely to have suicidal thoughts than healthcare workers and females, respectively, as determined by univariate logistic regression. however, these associations became insignificant in the multiple logistic regression. the study in china found that healthcare workers were at high risk for poor sleep quality during the covid- pandemic [ ] , whereas the present study did not find more severe sleep disturbance in healthcare workers compared with non-healthcare workers. given that the covid- epidemic in china was much more severe than in taiwan [ ] , we suggest that varying healthcare burdens across the covid- pandemic may account for the discrepancy between the results of the present and other studies. transgender people were reported to have higher rates of depression, suicidal thoughts, and other mental illnesses compared with other genders [ ] . the psychological impact of infectious disease pandemics on gender minorities should not be neglected. the present study has several limitations. first, although recruiting participants through the internet is a promising research method for targeting the general public, possible selection bias exists for those who are not netizens. hence, a paper-and-pencil test and advertisements posted on public area may recruit participants who rarely surf the internet. second, the cross-sectional design of this study during acute pandemic stage limited causal inference and the presence of sufficient information at follow-up. a prospective follow up study may further explore the causality between variables and change of measurements with time, especially during plateau or remission stage. third, this study was conducted during the period of covid- mitigation but not during period when covid- first emerged in taiwan. therefore, the initial impact of covid- cannot be identified. finally, sleep pattern and suicidal thoughts were only measured by a single question, which may limit the implication of the current study. formal questionnaires such as the pittsburgh sleep quality index may provide comprehensive assessment for sleep problems. the present study identified several covid- -related predictors for sleep disturbance and suicidal thoughts among people during the covid- pandemic. this massively undesirable effect on mental health deserves more attention and support from authorities during the covid- pandemic. for instance, a lower support system was associated with higher risk of sleep disturbance and suicidal thoughts, indicating the importance of timely support during pandemics. in addition, the significant association between less handwashing and suicidal thoughts demonstrated the possibility that individuals with suicidal thoughts may have poor coping strategies of infection control. hence, intervention to those with mental health problems during the covid- outbreak is necessary to enhance their coping with the threats of infection, which may decrease the risk of poor infection control. the study provides information that could aid timely intervention in the mental health of the public. moreover, sleep disturbance and suicidal thoughts may occur not only during the covid- pandemic but also during the restoration period. further investigation is needed to fill the limitations of the current study. the prospective study with follow up at different stages of the pandemic can help us better understand the changes of association between mental health and multi-dimensional factors. moreover, studies with multiple recruiting sources and detailed questionnaires of mental health problems can further extend the application of the findings of the current study. supplementary materials: the following are available online at http://www.mdpi.com/ - / / / /s , table s : sleep disturbance and suicidal thoughts; table s : worry about covid- ; table s : impact of the covid- pandemic on participants' daily lives; table s : impact of the covid- pandemic on social interaction; table s : academic/occupational interference by the covid- pandemic; table s : perceived social support and covid- -specified support; table s : self-reported physical health. the authors declare no conflict of interest. a novel coronavirus outbreak of global health concern covid- outbreak: migration, effects on society, global environment and prevention the socio-economic implications of the coronavirus and covid- pandemic: a review covid- press releases d-dimer and tat measurement in patients with deep venous thrombosis: utility in diagnosis and judgement of anticoagulant treatment effectiveness generalized anxiety disorder, depressive symptoms and sleep quality during covid- outbreak in china: a web-based cross-sectional survey factors associated with mental health outcomes among health care workers exposed to coronavirus disease timely mental health care for the novel coronavirus outbreak is urgently needed immediate psychological responses and associated factors during the initial stage of the coronavirus disease (covid- ) epidemic among the general population in china mental health problems and social media exposure during covid- outbreak impact of the covid- pandemic on mental health and social support among adult egyptians suicide risk and prevention during the covid- pandemic facebook recruitment of young adult smokers for a cessation trial: methods, metrics, and lessons learned predictive validity of a five-item symptom checklist to screen psychiatric morbidity and suicide ideation in general population and psychiatric settings anxiety, worry and cognitive risk estimate in relation to protective behaviors during the influenza a/h n pandemic in hong kong: ten cross-sectional surveys psychosocial impact among the public of the severe acute respiratory syndrome epidemic in taiwan use of rapid online surveys to assess people's perceptions during infectious disease outbreaks: a cross-sectional survey on covid- general hospital staff worries, perceived sufficiency of information and associated psychological distress during the a/h n influenza pandemic worry experienced during the middle east respiratory syndrome (mers) pandemic in korea covid- related misinformation on social media: a qualitative study from iran misinformation of covid- on the internet: infodemiology study. jmir public health world health organization. coronavirus disease (covid- ) advice for public public health measures to control the spread of the severe acute respiratory syndrome during the outbreak in toronto survey of stress reactions among health care workers involved with the sars outbreak social support and psychological adjustment to sars: the mediating role of self-care self-efficacy mental health status and coping strategy of medical workers in china during the covid- outbreak changing trends in the prevalence of common mental disorders in taiwan: a -year repeated cross-sectional survey personal health habits and symptoms of depression at the community level patients with mental health disorders in the covid- epidemic depression, anxiety, perceived stress, and their changes predict greater decline in physical health functioning over months among patients with coronary heart disease physical activity and anxiety: a perspective from the world health survey why sleep is important for health: a psychoneuroimmunology perspective depression and physical health multimorbidity: primary data and country-wide meta-analysis of population data from people across low-and middle-income countries this article is an open access article distributed under the terms and conditions of the creative commons attribution (cc by) license key: cord- -c c op authors: cheng, yung-hsiang; chang, yu-hern; lu, i.j. title: urban transportation energy and carbon dioxide emission reduction strategies() date: - - journal: appl energy doi: . /j.apenergy. . . sha: doc_id: cord_uid: c c op sustainability is an urban development priority. thus, energy and carbon dioxide emission reduction is becoming more significant in the sustainability of urban transportation systems. however, urban transportation systems are complex and involve social, economic, and environmental aspects. we present solutions for a sustainable urban transportation system by establishing a simplified system dynamics model with a timeframe of years (from to ) to simulate the effects of urban transportation management policies and to explore their potential in reducing vehicular fuel consumption and mitigating co( ) emissions. kaohsiung city was selected as a case study because it is the second largest metropolis in taiwan and is an important industrial center. three policies are examined in the study including fuel tax, motorcycle parking management, and free bus service. simulation results indicate that both the fuel tax and motorcycle parking management policies are suggested as potentially the most effective methods for restraining the growth of the number of private vehicles, the amount of fuel consumption, and co( ) emissions. we also conducted a synthetic policy consisting of all policies which outperforms the three individual policies. the conclusions of this study can assist urban transport planners in designing appropriate urban transport management strategies and can assist transport operation agencies in creating operational strategies to reduce their energy consumption and co( ) emissions. the proposed approach should be generalized in other cities to develop an appropriate model to understand the various effects of policies on energy and co( ) emissions. sustainability is an urban development priority. thus, energy and carbon dioxide emission reduction is becoming more significant in the sustainability of urban transportation systems. however, urban transportation systems are complex and involve social, economic, and environmental aspects. we present solutions for a sustainable urban transportation system by establishing a simplified system dynamics model with a timeframe of years (from to ) to simulate the effects of urban transportation management policies and to explore their potential in reducing vehicular fuel consumption and mitigating co emissions. kaohsiung city was selected as a case study because it is the second largest metropolis in taiwan and is an important industrial center. three policies are examined in the study including fuel tax, motorcycle parking management, and free bus service. simulation results indicate that both the fuel tax and motorcycle parking management policies are suggested as potentially the most effective methods for restraining the growth of the number of private vehicles, the amount of fuel consumption, and co emissions. we also conducted a synthetic policy consisting of all policies which outperforms the three individual policies. the conclusions of this study can assist urban transport planners in designing appropriate urban transport management strategies and can assist transport operation agencies in creating operational strategies to reduce their energy consumption and co emissions. the proposed approach should be generalized in other cities to develop an appropriate model to understand the various effects of policies on energy and co emissions. Ó elsevier ltd. all rights reserved. sustainable development has become a worldwide priority. sustainable development is viewed as the development that meets the current needs without compromising the ability of future generations to meet their own needs [ ] . the transportation sector is important as it relates to sustainability because this sector supports the economy and most social activities and has substantial environmental impact [ ] . thus, a well-established urban transportation system should not only harmonize economic growth with land-use planning and promote the use of public transit systems but also conserve resources and be environmentally friendly [ ] [ ] [ ] . according to key world energy statistics [ ] , the aggregate energy demand of the global transport system increased from % in to % in . the world energy outlook [ ] reported that the transportation sector will account for % of the growth in petroleum consumption between and . this finding indicates that the increasing use of motor vehicles will accelerate resource exhaustion and global warming, despite its promotion of road transportation mobility. in taiwan, the road transportation system not only facilitates the mobility of people and goods over space and time but also is essential for the industrial and economic development of taiwan's trade-oriented economy. according to taiwan's statistical abstract of transportation and communications [ ] , the number of registered vehicles in taiwan rose from . million in to . million in september . this rise was a consequence of the increase in individual disposable income, the opening of the first national north-south expressway in , and the subsequent improvement of the highway infrastructure: a second national north-south expressway, a west coast highway, and an east-west highway, among others. along with the rapid growth of the number of motor vehicles, energy consumption in the road transportation sector reached the equivalent of , kl of oil in , which was . times higher than that in , and accounted for . % of aggregate transport fuel demand. the amount of co emitted in the road transportation system increased at an annual rate of . % per annum, from . million tons in to an estimated . million tons in . under the pressure of global warming and significant great fluctuations in fuel prices, we face issues related to humanity-oriented transportation, energy conservation, and co mitigation, which have already become important topics in transportation planning and management. the ministry of transportation and communications (motc) in taiwan had invested nt$ billion from to to reduce the number of private vehicles driven and the amount of fuel consumption and co emissions through the use of public transportation promotion programs. many academic works focused on co emission and energy consumption in the urban system context [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . however, interactions between various transportation subsystems are not considered. moreover, a systematic approach covering more aspects of the urban air pollution problem is still lacking to examine the effects of various transport policies. an urban transportation system is complex and involves a variety of social, economic, and environmental issues. interpreting the inherent mechanisms of the system and capturing the dynamic behavior of the components with analytical methods, such as decomposition analysis, grey theory, least-squares regression, and geometric average method, are not easy because the database is limited and because these subsystems are interlinked and dependent on each other. system dynamics (sd) provide a simulation platform to analyze a large-scale and complex socioeconomic system with multiple variables that change over time. with the aid of an sd model, we selected kaohsiung as a case study to explore the effects of variations in demographics, fuel prices, and economic growth rate, among other factors, on the number of vehicles, fuel consumption, and energy-related co emissions. in addition, we developed three scenarios based on the possible policies that could be adopted by the city government to simulate their potential both for reducing the vehicular fuel consumption and for mitigating co emissions in kaohsiung. sd, which is based on systems theory, is a method for analyzing complex management problems with cause-effect relationships among different systems. industrial dynamics [ ] was the first book to illustrate the influence of organizational structure, policies, and action delays on industrial activity. an urban dynamics model was then constructed to show the effects of the interactions among business, housing, and people on the growth pattern of a city. finally, a large and complex socioeconomic simulation system, i.e., world dynamics, was developed [ ] . the world socioeconomic system might collapse if actions are not taken to slow population growth and the continuous and unrestrained exploitation of natural resources. in recent years, the sd model has been widely used to analyze agricultural systems [ , ] , environmental management and planning [ , ] , industrial sectors [ ] [ ] [ ] [ ] [ ] [ ] [ ] , strategy planning and decision making [ ] [ ] [ ] , transportation systems [ ] [ ] [ ] [ ] [ ] , ] , urban planning [ ] [ ] [ ] [ ] [ ] , waste management [ ] [ ] [ ] [ ] [ ] , and water resources and lake eutrophication [ ] [ ] [ ] [ ] . the transport mode for distributing goods in germany was explored with the aid of an sd model [ ] . in addition, policy interventions such as infrastructure investments, and carbon tax were simulated to examine their effects on energy savings, co reduction, public expenditure, and economic development. an sd model was used to evaluate the influence of the traditional supply chain and the vendor-managed inventory system on the performance of a firm's supply chain [ ] ; to examine the effects of policy scenarios on traffic volume, modal share, energy conservation, and co mitigation [ ] ; and to investigate how incorporated systems, such as population, economy, transportation demand, transportation supply, and the vehicular emission of nitrous oxides, affect the dynamic development of urban transportation systems under five policy interventions on vehicle ownership [ ] . an sd model was developed to explore the interrelationships among population, economy, housing, transport, and urban land in hong kong; the long-term constraints of and potentials for urban development yielded by the study were offered as policy suggestions for city planning [ ] . previous relevant studies rarely considered interactions among various transportation subsystems simultaneously with co emission and energy consumption. although certain developed countries, such as the united states, the united kingdom, and members of the european union, have focused on improving fuel efficiency using advanced technologies [ , ] , few studies have developed a practical sd approach for urban planners to further assess the effect of urban transportation policies on energy consumption and co emission. this study examines three main urban transportation policies in our proposed model: fuel tax, motorcycle parking management, and free bus service. prior studies mainly investigate the effect of a particular policy, such as fuel tax in europe and the us [ ] ; parking management policies in china [ ] ; and free bus policy in japan, belgium, and england [ ] [ ] [ ] . a limited number of studies analyze the effect of these policies on energy consumption and co emission reduction simultaneously and compare the respective policy with the synthetic policy to compare the policy effectiveness. our study aims to fill this research gap by developing a systematic and simplified analytical tool that can help urban planners to evaluate the influence of various transportation policies on energy consumption and co emission reduction. briefly, an sd model describes the information, structural boundaries, strategies, and action delay inside the system structure through a feedback process. a quantitative simulation is performed to study the dynamic behavior of the interaction of interrelated components inside the system structure. the sd model analyzes a complex system with multiple variables that change over time and determines how the system is affected by the implementation of specific policies [ ] . in addition, kummerow [ ] revealed that the sd model not only relatively easily incorporates qualitative mental and written information as well as quantitative data but also can be used when the database is insufficient to support statistical forecasting analysis. thus, the sd model is an appropriate approach to display the inherent behavior and influences inside the system structure despite multidirectional dynamic interactions and the fact that life is infinitely more complicated and difficult than we can effectively simulate [ , , , , , ] . although an sd model is an appropriate approach to simulate a complex and multidirectional dynamic system by constructing mathematic functions, it is a subjective and time-consuming operation. the causal relationships of the sd model are based on the subjective judgment of the operator, reference suggestions, data availability, and information acquisition. thus, the simulation result will change if the operator adopts different stock and flow variables. in addition, error analysis based on historical statistical data should be evaluated to ensure that the forecasted results are accurate and efficient and that the causal relationships used are reasonable. an sd model contains two parts. the first part is a causal-loop diagram that describes an idea, both conceptually and as a set of simplified cause-effect relationships between the different systems developed during model construction. the second part is a stock-flow diagram that represents the quantitative relationships among variables. a more detailed description follows. the relationships of real urban transportation systems are not likely to be simple, but the sd model offers an opportunity to show how interrelated variables in a system affect one another by arrows. a plus or minus sign indicates the direction of the variations between two variables: the ''+'' sign indicates that a change in one variable causes another variable to change in the same direction, and the ''À'' sign indicates that one variable causes another to change in the opposite direction. fig. shows the causal-loop of the sd model for an urban transportation system (more explanation is described in section ). a stock-flow diagram has four components: stock, flow, auxiliary variables, and arrows (appendix a). the stock variables are represented by labeled rectangles, e.g., ''individual disposable income'' and ''urban population.'' each stock variable accumulates all the values that flow into and out of it (indicated by the thick heavy arrows pointing from and to the stock variables, such as ''increases in individual disposable income'') and reflects the condition within a system at a specific point in time. stock variables can be changed only through flows. thus, the value of the stock variable is controlled by the pipes (the thick heavy arrows with a valve in the center and a cloud symbol at the end) pointing into or out of the stock variable. a flow variable refers to the rate of changes over a certain interval of time. an auxiliary variable is an intermediate variable used to show the informational transformation process, the environmental parameter values, or the systematic test functions or values. the causal relationship between variables is depicted by the curved blue arrows. the city of kaohsiung in southwestern taiwan comprises an area of , ha ( . square miles or . square kilometers). kaohsiung city is the second largest metropolis in taiwan and offers air, land, rail, and sea transportation. air and sea transport traffic determines the industrial structure share and the scope of city development. the kaohsiung harbor is an important transport point for the taiwan straits and the bashi channel. the kaohsiung international airport has airlines flying worldwide through air routes. kaohsiung is not only important for the import and export businesses in taiwan but also taiwan's industrial center because of the predominance of the international harbor and airport. heavy industries, such as steel-making, refining, shipbuilding, and those involved in the manufacture of petrochemicals and cement, as well as two export-processing zones in kaohsiung and neighboring nantse have significantly accelerated the diversity of local industrial activities and turned kaohsiung into the most important industrial and commercial center in southern taiwan. the population of kaohsiung rose from . million in to . million in . with the urbanization and internationalization of kaohsiung, individual disposable income has also increased: in , it was . % higher than in , with an average annual growth rate of . %. the number of motor vehicles in the city grew at an annual rate of . % over the past years, reaching . million in . among the . million vehicles, . % and . % represent the number of private cars and the number of motorcycles, respectively. the percentages of light trucks, heavy trucks, and city buses were . %, . %, and . %, respectively. vehicle ownership rates for private cars and motorcycles were and vehicles for every people. in this study, the sd model includes seven subsystems: urban population, individual disposable income, private cars, motorcycles, light trucks, heavy trucks, and city buses (appendix a). the size of the human population is the foundation of a city's development, and issues such as the growth rate in the number of motor vehicles, vehicular energy consumption, and co emissions are derivatives of the interaction between human population and economic activities. based on this assumption, the subsystem of the transportation mode and the related variables [i.e., vehicle kilometers of travel (vkt), vehicular fuel efficiency, transfer ratio among modes, emission coefficient, and other factors] were added to the model after the dynamic behavior of urban population and individual disposable income had been determined. furthermore, using commercial simulation software (vensim ; ventana systems, inc., harvard, ma), the causal relationships between the various components within the system were simulated from to . vensim is herein used to develop, analyze, and package highquality dynamic feedback models. models are constructed graphically or in a text editor. features include dynamic functions, subscripting (arrays), monte carlo sensitivity analysis, optimization, data handling, application interfaces, and more options. vensim is an interactive software environment that allows the development, exploration, analysis, and optimization of simulation models [ ] . fig. shows the causal-loop of the sd model for the urban transportation system. economic growth increases the number of motor vehicles and attracts more migrants from other cities. the amount of energy requirement and co emission will rise as the number of motor vehicles increases. however, the increase in the amount of co will reduce the growth rate of the urban population. simultaneously, the number of motor vehicles will decrease with the reduction of urban population. economic development affects population, wherein economic growth leads to an increased number of vehicles [ ] . therefore, we assume that economic growth positively affects the number of motor vehicles and population growth. moreover, fuel use can positively influence co emission [ ] . we thus assume that energy consumption can positively affect environmental issues (co emission). the number of private vehicles and buses positively affects traffic congestion and energy consumption [ ] . we assume that the number of city buses and the number of motor vehicles both positively affect traffic density and energy consumption. in addition, the tax policy on fuel can reduce the fuel consumption of motor vehicles, leading to reduced co emissions [ ] . traffic density is also a significant and robust predictor of habitant survival, more so than ambient air quality [ ] . we assume the association between traffic density and co emission as well as the existence of the negative effect of traffic density on population growth. in fig. , the p values of each variable are less than . , which indicates statistical significance. in kaohsiung, one out of two residents own motorcycles, whereas one out of three residents own cars. these residents are accustomed to the convenience, independence, and flexibility that are provided by private vehicles. energy consumption and co emission issues are mainly derived from private vehicles. therefore, we mainly focused on the influence of private vehicles in our case. less than % of the population uses the taxi service because of the higher charge compared with other forms of transportation [ ] . moreover, the uber platform service is not currently allowed to be officially operated by the authority, and this service is thus less popular in kaohsiung. road motor vehicles account for the relative large co emission and energy consumption ( . %) compared with the metro system that, having its own electrification system, supplies electric power for movement without a local fuel supply [ ] . therefore, the other possible variables, including vehicle technology, emission legislation, and automobile park age, are not currently emergent in this stage for kaohsiung and can be further examined in future studies. contributions of our study include the use of a systematic approach to examine energy and co emission reduction by implementing various transport policies in the urban transportation context. adopting this proposed approach is useful in other cities, and their specific features should be considered to develop an appropriate model to understand the various effects of policies. we considered two equations to explain the effects of individual disposable income and an economically active population on the number of motorcycles in the main text. linear least-squares regression analysis was performed to reflect the effects of individual disposable income and an economically active population on the variation of private cars and the sd model is an approach to understand the behavior of complex systems over time. sd can estimate fuel price while considering the time effect. therefore, we used delay i to consider this time effect. this delay function can be used in the equation as with normal sd modeling. this function is frequently used in sd for modeling postponed effects. we adopted the delay function to model the effect of fuel price on the relationship between the decrease in private car use and the increase in fuel price. the postponed effects of fuel price are considered in our model by using the delay function. the decrease in private car use is associated with the increased fuel price that can be estimated by the following formula: decrease in private car use ¼ private cars  ð : %= : % à ðfuel price À delay i ðfuel price; ; ÞÞ=delay i ðfuel price; ; ÞÞ; where . % is the probability that the number of private cars that will decrease when fuel prices increase by . % the size of the human population not only reflects the scale of urban development but also drives the transport demand. the size of the urban population was selected as a stock variable, and natural changes in the population and changes caused by social migration were selected as flow variables because the size of the human population is affected by both natural changes in the population and changes caused by social migration. the formulation of the natural changes in the population is expressed as the product of the human population and the natural population ratio per year, where the natural population ratio is adopted from the statistical yearbook of kaohsiung city [ ] . in addition, individual disposable income, traffic density, and aggregate co emissions were considered in this study to control the variations in social migration. economic performance is an important index for evaluating the competitiveness of a city. if individual disposable income grows, then the number of migrants and the number of motor vehicles increase; otherwise, these values decrease. therefore, individual disposable income was chosen as a stock variable dependent on the growth ratio of the gdp [ ] . furthermore, the prediction of the global insight database [ ] on the future gdp growth ratio of taiwan was reduced by . % to avoid an overestimate. several studies have indicated that the number of motor vehicles, as well as the number of new vehicles purchased, is closely associated with economic growth and population [ ] [ ] [ ] [ ] [ ] . we analyzed this subsystem to evaluate the effect of the changes in the level of the individual disposable income and in the size of the economically active population on the variation of the number of private cars. according to the survey of motc, the number of private cars driven decreased by . % after fuel prices increased by . %. thus, the effect of fuel prices on the variations of automobile use was also considered because of the rise in the price of crude oil, which has almost doubled since the beginning of . the auxiliary variable energy consumption by private cars was calculated by multiplying the number of private cars, vkt, and the inverse of the average vehicular fuel efficiency (km/l), where the value of vkt and fuel efficiency were obtained from the taiwan emissions database system (teds) . . estimations of energy-related co emissions were determined by the product of vehicular energy consumption and its emissions coefficient, published by the intergovernmental panel on climate change (ipcc). the reason for the omission of electric vehicles in the model is that the electric vehicle technology in taiwan is currently in the early stages. moreover, the central and city government did not provide strong incentives, including direct subsidies, fiscal reduction, and regulatory policy, to increase the use of electric vehicles. in terms of user perspectives, short driving range and slow speed of electric vehicles lead to the less popularity of electric vehicles in taiwan. even when considering improvements in the fuel economy of vehicles, we observe that the dense traffic in kaohsiung requires the car to stop and go frequently. thus, fuel economy improvements of vehicles are not significant in the local context. therefore, the policy imposing fuel tax seems to remain useful in kaohsiung. the kaohsiung mass rapid transit (kmrt) system opened for service in . the system not only provided a new lifestyle for citizens but also reduced the number of private vehicles used for commuting to work. to reflect the influence of the kmrt on vehicular fuel consumption, the transit system was also incorporated into this subsystem. specifically, the decrease in the number of commuters who switched from using private cars to using the kmrt was estimated by combining the average number of passengers carried by the kmrt, the average number of kilometers per passenger trip, the average number of occupants per automobile, and the transfer ratio. thus, the effect on vehicular energy consumption was calculated by multiplying the decrease in private car use and the average vehicular fuel efficiency of private cars. motorcycles accounted for . % of the . million registered vehicles in kaohsiung in ; motorcycles provide greater mobility and are less expensive than other types of motor vehicles. in this study, the increase in the number of motorcycles was primarily driven by individual disposable income and the size of the economically active population [ ] [ ] [ ] [ ] . as mentioned previously, fluctuations in fuel prices affect the number of private vehicles driven and the distances that they are driven. hence, the effect of fuel prices on mode choice and mode transfer was further incorporated into the model through the operation of flow variables: mode transfer from private cars and the decrease in motorcycle use by fuel price increase (appendix a). in addition, the formulation of vehicular fuel consumption and associated co emissions derived from the number of motorcycles was the same as that from the number of private cars, but the average occupancy rate (the number of passengers per motorcycle) and the transfer ratio between the kmrt and motorcycles were different. as the world's thirteenth ( ) largest international port and the largest industrial center in taiwan, the city of kaohsiung is important both for freight transportation and for industrial and commercial activities. many cargos and freight need to be transported to the northern metropolitan areas because kaohsiung is located in the south of taiwan and is a harbor city. after exiting the harbor, some heavy trucks need to pass the city area to the highway system. this phenomenon is reason for the consideration of heavy-duty trucks in our model. the dynamic behavior of this subsystem is analyzed through the operation of a stock variable: the number of heavy trucks; a flow variable: the increase in the number of heavy trucks; and two auxiliary variables: the effect of gdp on heavy truck function and the growth ratio of gdp. the growth of freight transport demand is primarily a consequence of the growth of economic activity [ ] [ ] [ ] [ ] ] . hence, the growth of gdp was selected as the motivational factor in this study to reflect the variation in the number of heavy trucks. the auxiliary variable effect of gdp on the heavy truck function was constructed based on the concept of a table function, which is a graphical tool that captures the causal and non-linear relationship between two variables. business activities and commercial services, such as food markets, street vendors, bazaars, superstores, cargo carriers, and other such entities, are closely linked with the number of light trucks. thus, gdp growth rate was selected as an auxiliary variable to reflect the effect of economic development. in this subsystem, the number of light trucks was defined as a stock variable, and the change in the number of light trucks was defined as a flow variable inspired by the growth of the gdp by constructing a table function. the formula used to calculate the aggregate energy demand of light trucks was the same as the one used for heavy trucks. despite the . % modal share of the city buses, they were incorporated into the model to reflect a complete picture of the transportation system in kaohsiung city. in this subsystem, the number of city buses was selected as a stock variable, and its value is influenced by the flow variable the annual change in the number of city buses. the historical value of auxiliary variables and the government-set target determined the number of city buses through the feedback loops. to improve the quality of the city bus service, the city bus operation agencies added buses since by adjusting the frequency and routes of city buses, releasing government-run routes to private enterprises, enhancing realtime bus information, and upgrading the service quality. . discussion of analytical results to detect the effectiveness of the proposed model, the simulation results were validated by comparing the estimated values with their historical trends [ , , , , , ] . the examined variables included urban population, individual disposable income, motorcycles, private cars, light trucks, and heavy trucks (tables and ). the model developed in this study appears to be reasonable because the relative errors were all less than % [ ] . the behavior analyzed using the reference model was simulated from to based on existing socioeconomic conditions and policies. the decline in the natural population of taiwan for the past years has lowered the growth rate of the urban population. a decreasing natural population is both the current and the future trend in most developed countries. our simulation predicted that in , the population of kaohsiung would gradually decline to . million, , fewer than today's population (table ). global insight projected that the annual economic growth rate of taiwan in would be . % higher than it is in . however, in the next years, the growth rate of the gdp of taiwan is expected to be lower than those during the past two decades. given this slowdown in economic activity, individual disposable income will grow at only a moderate rate. for example, our simulation predicts that the annual growth rate of individual disposable income from to will be . %, which is lower than previous rates. our simulation also predicts that this income will reach nt$ , in ( us dollar = nt$). the simulation indicated that the number of motorcycles will increase by , vehicles between and , which is a growth rate of . % per year. this growth in the number of motorcycles and private cars is attributed to the size of the economically active population, the level of individual disposable income, and the variation of fuel prices. similarly, the simulation estimated that the number of private cars in will be , , a decrease of . % over years. economic weaknesses will also cause a slow growth rate ( . %) in the number of heavy trucks until , when , of such vehicles will show an increase of . % compared with the number in . the effect of a lower gdp growth rate on the number of light trucks will be limited because they are used for daily commodity exchanges and business transactions. the simulation showed that the number of light trucks will have grown an average of . % per year and will have reached , vehicles in . after , the aggregate energy consumed by motor vehicles will increase by . % until . the aggregate increase in co emissions will be nearly , metric tons between and , which is . % higher than the emission level in . most of our simulated results have an estimation error lower than % except for rare cases. therefore, the prediction capability of our model is acceptable [ ] . the reason for the main percentage errors concentrated between and may be the severe acute respiratory syndrome (sars) outbreak in taiwan between and . sars caused widespread social disruption and economic losses, and its economic effect has been considerable in taiwan. moreover, after taiwan's first experience of party alternation in , the government system experienced instability in the early stages that led to the negative effect on economic propensity and motor-vehicle growth. these major unusual events caused the disturbance in our model predictions during this period. we failed to fully understand the real effect of co emission and energy use reduction under various transportation policies because the data were limited. to demonstrate the accuracy of our proposed model, a comparison is performed between real data from to and the estimated number of motor vehicles in the reference model during the same period, after a free bus policy was implemented in . the deviation between simulated data and real data is within %, which is reasonable [ ] . the reason for the reduced population in can be that the increasing labor costs have encouraged numerous manufacturers to leave kaohsiung, which has reduced the number of residents in the city. among all strategies for sustainable transport policy, the implementation of programs including those that encourage the use of the public transportation system using benefits, such as subsidies, free transfers, or transfer discounts, and deterrents (e.g., restraining the use of private vehicles by parking management and levying taxes on fuel oil), is mostly discussed and encouraged in taiwan. furthermore, the taiwanese government is considering an additional nt$ . per liter tax on fuel prices to reflect social justice and the user-pays principle and to restrain the use of private vehicles. thus, based on the various assumptions and the past trends of the variables in the reference model, the policies including fuel tax, motorcycle parking management, free bus service, and synthetic policy are discussed in this study to explore their energy-saving and co -emission-reducing potential (see tables and ) . we analyzed three scenarios considering including low, medium, and high oil price in our revised paper (see tables - ). we used the average oil price to represent the medium price; high oil price can be estimated by the average oil price plus one standard deviation of oil price. lastly, low oil price can be estimated by the average oil price minus one standard deviation of oil price. this study examines the appropriate urban transportation policies that mitigate a global warming effect mainly from co emission. nitrous oxides (nox), hydrocarbons (hc), co, and soot emissions affect the health of urban populations. however, due to data limitation, we assume that the relationship between co emission and nox, hc, co, and soot emissions is of proportional equivalence. the estimated nox, hc, co, and soot emissions are included in. the detailed study regarding the precise toxicity of the emissions in the model can be further examined in future we simulated the scenario of a fuel tax because the increase in oil price not only influences the transportation mode choice but also reduces the amount of vehicular energy consumption. therefore, oil price is a relatively direct and efficient incentive for inducing consumers to reduce private vehicle use, which lowers fuel consumption and co emissions. currently, a fixed fuel tax is levied per year according to the engine capacity of vehicles in taiwan. an additional nt$ per liter of fuel tax will also be considered in the next years. in our simulation, once the tax was included in the prices of gasoline and oil and levied according to the amount of fuel used, the numbers of motorcycles and automobiles used in kaohsiung were both predicted to decrease. overall, the number of vehicles in is estimated to be . million (fig. ) , which is . % lower than the base. this reduction in the number of motor vehicles caused by the increase in fuel prices will lead to changes in the modal shares of the means of transport. under this policy, the projected growth of vehicular energy consumption varies from , kl to , kl from to . during the same period, motor-vehicle co emissions are expected to increase by , metric tons. compared with the reference model, the energy requirements and co emissions in are predicted to be . % and . % lower, respectively. the increase in the price of crude oil will not only reduce fuel consumption but will also force a transformation in traffic modes. as seen in the reference model, the number of motorcycles in kaohsiung increased because of the prior rise in fuel prices. since , the kaohsiung city government has planned a system of six regional transit centers, which are areas composed of two major and four subsidiary transit stations that link the kmrt and the shuttle bus terminals in kaohsiung into a -min access metropolitan circle. under these measures, the number of passengers carried by mass transit increased by about million. in , the taipei city government introduced a successful parking management program that prohibits motorcycles from being parked on sidewalks and in building arcades, requires payment for roadside motorcycle parking, and offers a parking-information inquiry system. the ownership of motorcycles in kaohsiung city is . %, the highest in taiwan. from the success of this policy, kaohsiung introduced a similar system to other popular centers such as night markets, train stations, and department stores since april to reduce motorcycle use. in this study, the rate of shifting from motorcycles to the kmrt, city buses, and bicycles was based on a survey made by the taipei parking management office, because the motorcycle parking management system in kaohsiung is still under implementation (fig. ) . the number of motor vehicles driven in kaohsiung will sharply decrease when the city introduces and enforces its parking management policy. our simulation estimated that the number of motor vehicles will decline to . million at the end of , which is . % fewer than in the reference model. concurrently, fuel consumption and co emissions will be . % and . % lower than in the base model. in this scenario, the simulation assumed a % increase in bus ridership if both free bus service and discounted tickets for kmrt transfers from the subway to the bus were extensively implemented to the other weekdays. the simulation outcome indicates that the number of vehicles in kaohsiung city will decrease by . % (fig. ) . in , the number of motor vehicles will reach . million, whereas the vehicular fuel requirement will decrease by only . %. by , the need for vehicular fuel will increase by , kl. the change in energy consumption will also imply the estimated increase of co emissions to be . million metric tons in , which is . million more than in . to evaluate the maximum potential for vehicular fuel and co reduction, the interventions act together as a package of measure, which is also considered in this study. according to the simulation, the results indicate that the number of vehicles in kaohsiung city will decrease to . million vehicles in , which is . % lower than the base model (fig. ). in terms of the variation in vehicular fuel requirement, the variable will increase slightly from , kl to , kl from to . compared with the value at the end of , the value is . % lower than that in the reference model. the growth patterns of co emission and energy demand are similar because the variation of co levels is directly related to energy consumption. thus, the contribution of aggregate co emission will be . million metric tons until , which is lower by . million metric tons than the emission amount in the base model. from the observations of the forecasted patterns, the aggregate co emission needs to be reduced by about . million metric tons compared with the emission level in . this result implies the difficulties and urgency of co mitigation in kaohsiung city, despite the synthetic policy being considered in the sd model. furthermore, we simulated the scenario of a fuel tax because the increase in oil prices not only influences the mode choice but also reduces the amount of vehicular energy consumption. therefore, oil price is a relatively direct and efficient incentive for inducing consumers to reduce private vehicle use, which lowers fuel consumption and co emissions. despite the limited effect of the separate policies of motorcycle parking management and free bus service on reducing vehicular fuel consumption, the government was able to reduce the number of private vehicles in use and promote the use of the public-transit system. thus, we suggest that all three policies can be implemented simultaneously to restrain the growth of the number of private vehicles, motor-vehicle fuel consumption, and co emissions in kaohsiung. with regard the effect of various policies, the number of motor vehicles, co emission, and emergency consumption significantly decreased between and , and the reason can probably be the global financial crisis during this period because this negative influence caused the slowdown of economic development (see figs. - ). the sd model is not only able to analyze a system with many interrelated variables but is also able to describe its dynamic trends based on a limited information set. by using a simplified sd model, which we constructed to analyze issues of urban population, disposable income, number of motor vehicles, vehicular energy consumption, and co emissions, we conclude that the fuel tax policy is the most effective method to reduce vehicular fuel consumption and co emissions. this policy is even more effective than the motorcycle parking management and free bus service policies. according to the investigation of the motc of taiwan, the fluctuations in fuel prices affect the number of private vehicles driven and the distances they are driven. for instance, the use of private cars and motorcycles decreased by . % and . %, but the rate of transfer from driving private cars to driving motorcycles was . % when the average price of gasoline increased by . %. the simulation of a fuel tax also suggests that the increase in fuel prices will lead to changes in the modal shares of the means of transport. the number of motor vehicles in kaohsiung will decline by . % in , with a . % decrease in the actual number of registered motor vehicles in the city between and . the fuel tax will also cause a considerable reduction in the growth rates of vehicular fuel use and co emissions. the motorcycle parking management policy will also cause a . % decrease in the number of motor vehicles by , as well as . % and . % reductions in fuel demand and co emissions, respectively. an extensively implemented free bus service will reduce the number of motor vehicles and the fuel requirement by only . % and . %, respectively. furthermore, the maximum potential of vehicular fuel consumption and co reduction is suggested in the scenario of all the interventions acting together as a package of measure. in , the aggregate vehicular energy requirement and co emission will reach , kl and . million metric tons, respectively, which suggests a . % and a . % decrease in energy requirement and co emission compared with the reference model. simulation results indicate that both the fuel tax and motorcycle parking management policies are suggested as potentially the most effective methods for restraining the growth of the number of private vehicles, the amount of fuel consumption, and co emissions. we conducted a synthetic policy consisting of all policies which outperforms the three individual policies. compared with other countries, taiwan is densely populated (its average population density is persons/sq. km. of ) and has limited energy resources. in terms of energy consumption, the taiwanese economy is sensitive to oil price variations because the country lacks conventional energy resources and is highly dependent on energy imports (nearly % of total energy consumption). similar to the case of south korea, road transportation in taiwan accounts for more than % of co emission of the transport sector [ ] . taiwan is not yet a member of the united nations framework convention on climate change. the country's co emission increased significantly over the past two decades, making taiwan the rd largest co emitter in the world [ ] . taiwan's transportation sector accounted for % of the country's co emission in . taiwan, which is newly transformed from a developing country to a developed country [ ] , pursues economic development even with limited energy resources. therefore, finding a compromise between economic development and energy consumption as well as co emission is a critical issue for taiwan. many transferable lessons can be learned from taiwan's experience and can be a useful reference for countries with analogous characteristics such as economic development pattern, high population density, and high energy dependence. with respect to generalizability of the proposed model, this study proposes policies to restrain the use of private vehicles, for example, by increasing fuel tax and launching a strict motorcycle parking management strategy. this study also examines the policy of providing free bus service from the perspective of increasing public transportation service supply and enhancing service quality to decrease urban transportation energy consumption and co emission. in this study, we present the example of kaohsiung, a city that is highly dependent on using private vehicles (i.e., every two residents have one motorcycle, and every three residents have one private car). the lessons from kaohsiung are applicable to other cities with similar population density, urban environment, and economic development pattern, especially asian cities, such as bangkok, kuala lumpur, and ho chi minh, which are characterized by high popularity of motorcycles and limited public transportation services. the proposed sd model examines the factors, including the influence of gdp evolution, population growth, and individual disposable income, on urban transportation energy consumption and co emission of various urban transportation systems simultaneously. the model also considers the interactions among these factors over time to assess the effectiveness of various urban transportation policies. cities can modify our proposed approach according to their specific urban environment, economic development pattern, and public transportation service level to derive an appropriate model to understand the influence of urban transportation policies on energy consumption and co emission. the sd model can also be applied to other programs such as urban planning, low emission vehicles, speed limits, high occupancy vehicle control lanes, strengthening energy conservation standards for new vehicles, and other aspects of transportation are certainly considerable. they provide a helpful reference for city governments in urban development planning and setting policies associated with transport-related energy policies. the cost of implementing a free bus policy needs a certain amount to subsidize the ticket price of passengers. in , the central government provided . million us dollars to kaohsiung to implement a free bus policy for two months. the motorcycle parking management and fuel tax policies need the extra administration and resources to pay the costs. compared with the latter policies, implementing a free bus policy seems to be a more costly policy. among the three proposed policies, the fuel tax policy seems to be the most cost effective. the information with respect the cost of implementing different policy measures is useful for the urban planner and the decision maker. however, due to the data limitation, the precise cost-benefit analysis of various scenarios can be implemented in the future studies. system in kaohsiung city classification notation/data source environmental sustainability: a definition for environmental professionals defining and measuring progress towards a sustainable transport system. trb sustainable transportation indicators (sti) discussion paper sustainable transport: analysis frameworks energy and exergy efficiencies in turkish transportation sector the importance of decoupling between freight transport and economic growth key world energy statistics world energy outlook . international energy agency taiwan's statistical abstract of transportation and communications. ministry of transportation and communications r.o.c estimating fuel demand elasticities to evaluate co emissions: panel data evidence for the lisbon metropolitan area scenario-based co emissions reduction potential and energy use in republic of korea's passenger vehicle fleet assessing greenhouse gas and related air pollutant emissions from road traffic counts: a case study for mauritius regional disparity of urban passenger transport associated ghg (greenhouse gas) emissions in china: a review strategies and instruments for low-carbon urban transport: an international review on trends and effects land use policies and transport emissions: modeling the impact of trip speed, vehicle characteristics and residential location a dynamic modeling approach to highway sustainability: strategies to reduce overall impact an integrated approach to improving fossil fuel emissions scenarios with urban ecosystem studies effect of resource allocation policies on urban transport diversity synthesising carbon emission for mega-cities: a static spatial microsimulation of transport co from urban travel in beijing industrial dynamics world dynamics environmental sustainability in an agricultural development project: a system dynamics approach drought adaptation policy development and assessment in east africa using hydrologic and system dynamics modeling an exploration of dynamical systems modeling as a decision tool for environmental policy application of system dynamics in environmental risk management of project management for external stakeholders long-term perspectives on world metal use -a system dynamics model aggregate analysis of manufacturing systems using system dynamics and anp application of a system dynamics approach for assessment and mitigation of co emissions from the cement industry elucidating the industrial cluster effect from a system dynamics perspective an integrated system dynamics model for strategic capacity planning in closed-loop recycling networks: a dynamic analysis for the paper industry system dynamics modelling of a production and inventory system for remanufacturing to evaluate system improvement strategies reducing carbon emissions in china: industrial structural upgrade based on system dynamics strategy support models the role of system dynamics in project management analyzing price and product strategies with a comprehensive system dynamics model -a case study from the capital goods industry the control of goods transportation growth by modal share re-planning: the role of a carbon tax the impact of transportation disruptions on supply chain performance a system dynamics model of co mitigation in china's intercity passenger transport system dynamics model of urban transportation system and its application a system dynamics model for the sustainable land use planning and development a system dynamics modeling for urban air pollution: a case study of tehran, iran urban ecosystems, energetic, hierarchies, and ecological economics of taipei metropolis spatial dynamic modeling and urban land use transformation: a simulation approach to assessing the costs of urban sprawl energetic mechanisms and development of an urban landscape system energy management in lucknow city towards greening the us residential building stock: a system dynamics approach application of system dynamics and fuzzy logic to forecasting of municipal solid waste forecasting municipal solid waste generation in a fastgrowing urban region with system dynamics modeling modeling of urban solid waste management system: the case of dhaka city a system dynamics approach for hospital waste management a system dynamics model for determining the waste disposal charging fee in construction system dynamics of euthrophication processes in lakes a system dynamics approach for regional environmental planning and management: a study for the lake erhai basin water resources planning based on complex system dynamics: a case study of tianjin city managing water in complex systems: an integrated water resources model for saskatchewan a review on global fuel economy standards, labels and technologies in the transportation sector a study of fuel efficiency and emission policy impact on optimal vehicle design decisions distributional effects of taxing transport fuel what does a one-month free bus ticket do to habitual drivers? an experimental analysis of habit and attitude change the impact of ''free'' public transport: the case of brussels free bus passes, use of public transport and obesity among older people in england managerial applications of system dynamics a system dynamic model of cyclical office oversupply understanding models with vensim™ simulation with system dynamics and fuzzy reasoning of a tax policy to reduce co emissions in the residential sector traffic density as a surrogate measure of environmental exposures in studies of air pollution health effects: longterm mortality in a cohort of us veterans bureau of energy: ministry of economic affairs department of budget: accounting and statistics kaohsiung city government statistical yearbook of the interior. ministry of the interior, r.o.c vehicle ownership to : implications for energy use and emissions income's effect on car and vehicle ownership link between population and number of vehicles determinants of car ownership in rural and urban areas: a pseudopanel analysis transport scenarios in two metropolitan cities in india: delhi and mumbai reliability of territory-wide car ownership estimates in hong kong an econometric analysis of motorcycle ownership in the uk exploring the vehicle dependence behind mode choice: evidence of motorcycle dependence in taipei a multivariate cointegrating vector auto regressive model of freight transport demand: evidence from indian railways transport intensity in europe-indicators and trends towards a theory of decoupling: degrees of decoupling in the eu and the case of road traffic in finland between taiwan emission database system (teds . ). taiwan environmental protection administration decomposition and decoupling effects of carbon dioxide emission from highway transportation in taiwan epidemiological features of intestinal infection with entamoeba histolytica in taiwan the survey of fuel price increased on mode choice. ministry of transportation and communications r.o.c institute of transportation: ministry of transportation and communications r.o.c department of energy statistical report of transportation and communications. ministry of transportation and communications r.o.c research on urban housing trip and trip characteristic analysis. ministry of transportation and communications r.o.c parking practices and policies under rapid motorization: the case of china city research on kaohsiung urban housing trip and trip characteristic analysis the authors of this paper sincerely acknowledge the valuable suggestions of the editor-in-chief, professor j. yan and the three anonymous reviewers, which have immensely helped to enhance the quality of the paper over its earlier version. the authors also thank ms. yung-ching, chiu and ms. han-ning, chang for their assistance in data collection and processing. the statistical yearbook of kaohsiung city [ ] key: cord- -xuw zfn authors: chen, hui-wen; huang, yuan-pin; wang, ching-ho title: identification of taiwan and china-like recombinant avian infectious bronchitis viruses in taiwan date: - - journal: virus res doi: . /j.virusres. . . sha: doc_id: cord_uid: xuw zfn infectious bronchitis virus (ibv) infections in poultry cause great economic losses to the poultry industry worldwide. the emergence of viral variants complicates disease control. the ibv strains in taiwan were clustered into two groups, taiwan group i and taiwan group ii, based on the s gene. a variant was previously identified and showed a distinct s gene homology with other local strains. this study investigated the ′ . kb genome of eight taiwan strains isolated from to . the genes of interest were directly sequenced. sequence analyses were performed to detect any recombination event among ibvs. the results demonstrated that all of the examined viruses maintained the typical ibv genome organization as ′-s- a- b-e-m- a- b-n-utr- ′. in the phylogenetic analyses, various genes from one strain were clustered into separate groups. moreover, frequent recombination events were identified in the simplot analyses among the taiwan and china ck/ch/ldl/ i-type strains. putative crossover sites were located in the s , s , b, m genes and the intergenic region between the m and a genes. all of the recombinants showed chimeric ibv genome arrangements originated from taiwan and china-like parental strains. field ibvs in taiwan undergo genetic recombination and evolution. avian infectious bronchitis virus (ibv), with a large infectious rna genome ( . kb), belongs to the family coronaviridae, the group coronavirus. the rna molecule of the ibv is linear, singlestranded, positive sense and possesses a cap and a poly-a tail. ibvs can replicate in respiratory, alimentary and urogenital tracts in chickens of all ages, resulting in great economic losses to the poultry industry worldwide (cavanagh and naqi, ) . clinical signs associated with respiratory and enteric tracts and renal damage might be found in infected chickens (cavanagh, ) . during infection, ibv possesses a unique discontinuous transcription system, i.e. a nested set of co-terminal subgenomic mrnas sharing a common leader sequence in the end are transcribed in the presence of negative-stranded rna intermediates. the viral polymerase "jumping" possibly contributes to the high rna recombination frequency in coronaviruses (lai, ; lai and holmes, ) . the ibv genome encodes four structural proteins: spike glycoprotein (s), envelope protein (e; also known as sm), membrane glycoprotein (m), and nucleocapsid protein (n) (cavanagh and naqi, ) . the spike glycoprotein is post-translationally cleaved into s * corresponding author. tel.: + ; fax: + . e-mail address: chingho@ntu.edu.tw (c.-h. wang) . and s subunits. the s subunit anchors onto the viral outer membrane using the s subunit to form a club-shaped projection on the mature virion (cavanagh, ) . the s glycoprotein is involved in cell attachment and carries epitopes for serotype-specific hemagglutination-inhibition and virus-neutralization antibodies (cavanagh and davis, ; hodgson et al., ; ignjatovic and sapats, ; koch et al., ) . the s glycoprotein, in which two antigenic determinants were identified (koch et al., ) , may possess different secondary structures that affect the s specific antibody binding (callison et al., ) . the membrane glycoprotein is associated with virus assembling and budding (lai and holmes, ) . the nucleocapsid protein interacts with genomic rna to form the viral nucleocapsid, playing a role in viral rna synthesis and cell immunity (lai and holmes, ) . in addition, four non-structural proteins of unknown function are expressed by the polycistronic genes, gene and . virus mutants carrying truncated b genes demonstrate increased virulence and growth advantages in vitro and in ovo (shen et al., ) . the open reading frames (orfs) of a, b, a, and b encode accessory proteins not essential for ibv replication (casais et al., ; hodgson et al., ; youn et al., ) . as a signature of avian coronaviruses, ibv strains are continuously evolving through point mutations and recombination of their genomes. those variants have better adaptation or increased virulence advantageous to ib outbreaks. to date, a large number of ibv sero-or genotypes have been identified worldwide (cavanagh, / broiler taoyuan nephropathogenic tw-i / broiler taoyuan nephropathogenic tw-ii / broiler changhua nephropathogenic tw-i / spike glycoprotein gene. (bochkov et al., ; dolz et al., ; dolz et al., ; jackwood et al., ) . it was reported that slight sequence differences in the s gene probably lead to poor crossprotection (cavanagh et al., ) . viruses of different types can co-circulate within a region (capua et al., ; liu et al., ) , raising the inter-strain rna recombination frequency (bochkov et al., ; jia et al., ; lee and jackwood, ) . the wide use of live virus vaccine may also critically contribute to the genetic evolution of ibvs by acting as a heterologous rna donor template (kusters et al., ; wang et al., ) . the emergence of viral variants has complicated disease control requiring persistent ibv molecular surveys. ibv strains in taiwan were previously clustered into two groups, taiwan group i (tw-i) and taiwan group ii (tw-ii), on the basis of the s gene (wang and tsai, ) . however, a variant isolated in showed an unusually high s gene homology with china strains, but not in the n gene, suggesting an inter-strain recombination event (huang et al., ) . in this study, the . kb genomes from taiwan ibv strains were investigated to elucidate the genetic diversity of viruses. eight ibvs isolated in taiwan from to (huang et al., ) and the vaccine strain h (abic biological laboratories teva ltd., israel) were recovered for this study. the case histories of local strains are listed in table . viruses were propagated in the allantoic cavity of - -day-old specific pathogen free embryonated eggs (animal health research institute, council of agriculture, tamsui, taiwan). each egg received . - . ml inoculation. after - h incubation, allantoic fluid was collected and frozen at − • c until use. viral rna was extracted from l of virus-infected allantoic fluid using a viral nucleic acid extraction kit (geneaid biotech ltd., taipei, taiwan) following the manufacturer's protocol. previously published primers (huang and wang, ) were employed in this study to amplify the gene fragments. for sequencing the untranslated region (utr) of h , one additional forward primer was designed as -ggaacaatgcacagctggaa- from strain h -gd (genbank accession no. ay ). reverse transcriptase-polymerase chain reaction (rt-pcr) was performed with one step in a reaction volume of l containing . l of u/l realtaq dna polymerase (real biotech, taipei, taiwan dna sequencing in both strands from separate rt-pcr products was conducted by a commercial service (mission biotech). each nucleotide was determined from at least four identical results. the obtained nucleotide sequences were compiled and the amino acid sequences were deduced using dnastar software (dnastar, madison, wi). the ibv reference strains were retrieved from the genbank database with the accession number listed in table . the alignx program of the vector nti suite software table ibv reference strains included in this study. country accession numbers armidale australia dq (s -n) a vic australia dq (s -n) bj china ay (s -n) taiwan dq (s -n) / taiwan dq (s -n) / taiwan dq (s -n) beaudette usa nc (s -n) cal usa ay (s -n) cu-t usa u (s -n) de usa af (s ), ay (s ) (informax, north bethesda, ml) was used to generate multiple sequence alignments and determine the nucleotide identity. phylogenetic analyses were performed with the neighbor-joining method using mega version (tamura et al., ) . the bootstrap values were determined from replicates of the original data. the consecutive ibv nucleotide sequences from the s to n genes ( . kb) based on the multiple alignment results were introduced into similarity plots with simplot version . . (lole et al., ) . the nucleotide identity was calculated using the kimura -parameter method with a transition-transversion ratio of in each window of bp. the window was successively furthered along the alignment using a -bp increment. at least four sequences were required to initiate an analysis. the ibv sequences resulting from this study were submitted to the genbank database. the accession numbers are eu (strain / ), eu (strain / ), eu (strain / ), eu (strain / ), eu (strain / ), and eu (strain h ). fig. . phylogenetic analyses of the taiwan strains (᭹), h ( ) and reference strains for structural and non-structural protein genes of ibvs. the phylogenetic trees were constructed using the mega version by the neighbor-joining method (bootstrapping for replicates with its value > %). sequences that covered the . kb genome were determined from the taiwan ibvs and strain h . all of the examined viruses were found to maintain the typical ibv genome organization as -s- a- b-e-m- a- b-n- (data not shown). the s gene size ranged from a minimum of nucleotides (strain / ) to a maximum of nucleotides (strains / and / ). compared with other local strains, single base mutations in the end of the s and b genes from the strain / changed the genetic code from gaa to taa (glutamine → stop codon), resulting in -and -base truncated orfs, respectively. similarly, in the / , a single base t-insertion in the b gene created an early stop codon, leading to a -base truncation. however, the a, b, and n gene orf sizes were conserved among ibvs. all of the virus genomes carried an intergenic (ig) region located between the m and a genes with a size of - nucleotides. the ig region of the strain h was bases longer than that of the strain beaudette. the utr, downstream of the stop codon in the n gene, a region of and nucleotides was sequenced from local strains and h , respectively. all of the local strains shared a high sequence identity ( - %) in this region. however, only % and % identity were observed between h and its closely related m and beaudette strains, respectively. phylogenetic analyses were performed based on the nucleotide sequence alignment using each orf from the s to n genes among eight taiwan and reference strains (fig. ) . in the s gene, the taiwan strains showed the highest identity ( %) with the beaudette reference strain and the lowest ( %) with the de . the taiwan strains (except for / and / ) could be clustered into two groups, tw-i and tw-ii, based on the s gene. strains / and / were closely related (> % identity) to the china genotype vii strains (ck/ch/ldl/ i, ck/ch/ldl/ i, q , j , and t ) (liu et al., ) . in the s gene, all of the local strains were grouped with ck/ch/ldl/ i and ck/ch/ldl/ i except for the two viruses isolated before (strains / and / ). strains / and / were classified with ck/ch/ldl/ i and ck/ch/ldl/ i in the analyses of the a and b genes. the e gene analysis segregated the / into the china group. strains / and / were distributed with the china strains in the m gene analysis. the a, b and n genes analyses revealed that all of the local strains were in the same group. nucleotide sequences from the three orfs were conserved among the taiwan strains with > % homology. the . kb genome sequence (s-n gene) of six taiwan ibvs were queried in the simplot analysis. strains / , h and the china strain ck/ch/ldl/ i were used as putative parental strains when strains / , / , / , / , / (tw-i) were queried. the parental strain / was replaced with / when strain / (tw-ii) was queried. the similarity plot displays the consecutive nucleotide identity (%) among the queried strain and parental strains. strains were considered as recombinants if any crossover event took place between two putative parental strains. the breakpoint in which the parental strains have equal identity to the query strain is the predicted recom-bination site. as fig. demonstrates, crossover events between parental / or / and ck/ch/ldl/ i were detected in each plot. the recombination sites were located in the s , s , b, m genes, and the ig region between the m and a genes. each putative recombinant was schematically assembled using taiwan and china-like sequence fragments. the genomic positions of those crossover sites were indicated within the plot (numbers in red). in taiwan, field outbreaks are frequently reported despite routine vaccine use. there were originally two ibv genotypes (tw-i and tw-ii) circulating in the field wang and tsai, ) until genetic variants / (huang et al., ) and / emerged. both variants showed a high s gene homology with the proventriculus pathogenic strains j , q , t , ck/ch/ldl/ i and ck/ch/ldl/ i, belonging to the china genotype vii (liu et al., ; yu et al., ) . the . kb gene of ck/ch/ldl/ i was used as a putative parental strain. mass type viruses have been widely used as vaccine strains in taiwan. our primary concern was the possible viral recombination resulting from the co-circulation of heterologous vaccine strains in flocks. the consecutive sequence of . kb genome in strain h was obtained first in this study and served as another putative parental strain. to our surprise, six local strains experienced crossover events with the strain ck/ch/ldl/ i instead of h . thus, inter-strain recombination events had occurred between the ibvs from taiwan and china. taiwan and china are geographically separate. neither live poultry nor processed poultry products from china have been allowed to import into taiwan for years. how those recombinants arose remains unknown. a recently identified ibv isolate in korea (kr/d / ) also revealed a close relationship to the china ck/ch/ldl/ i-type strains (lee et al., ) . furthermore, the appearance of the chinalike strains in taiwan is reminiscent of the spread of the china qxibv strain in european countries (beato et al., ; domanska-blicharz et al., ) . in this case, it could be speculated that migrating birds provide the genetic sources of ibv variants in taiwan. a chicken-nephropathogenic ibv strain was identified from a non-diseased teal (anas sp.) in china (liu et al., ) . thus, the transport of ibvs over long distances by other avian species appears to be possible (cavanagh, ) . however, we still cannot overlook illegal trafficking or unapproved vaccine use in the field. all six recombinants defined in this study were inter-genotypic recombination and the "china-like" sequence substitutions took place in multiple genes. in particular, partial s gene replacement was observed in every recombinant. since coronaviruses possess different host range or cell tropism through the variance in the s gene (casais et al., ; kuo et al., ) , alterations in the antigenic characteristic in those variants could be expected. in this study, however, nearly all of the strains showed nephropathogenicity (lesions of kidney) in chickens, rather than the proventricular lesions caused by the ck/ch/ldl/ i-type strains. how a variant with a chimeric genome arrangement from heterologous strains demonstrates its tissue tropism or pathogenicity in a host is not clear. in addition, it was found that chicks challenged with virulent ck/ch/ldl/ i were incompletely protected by commercial vaccines and other heterologous strains (liu et al., ) . to effectively control the ib disease in taiwan, the protective effect of vaccines against challenges from those recombinants awaits to be investigated. to our knowledge, this is the first use of simplot for genetic analyses of ibv strains. the similarity plot can depict the genetic distance among the aligned sequences in a graphical window. in this study ibv recombinants could be defined directly from the simplot analyses, and the crossover events and corresponding genome positions were readily observed. in phylogenetic analyses, strains were deduced as recombinants if different genes from the genomes were clustered into separate phylogenetic groups. parallel results were obtained from both analyses. the emergence of ibv variants through rna recombination was previously described (brooks et al., ; jia et al., ; lee and jackwood, ; mondal and cardona, ; wang et al., ) . recombination events occurred in multiple genes. the consensus ig sequences ct(t/g)aacaa or the conserved regions around were assumed as the recombination "hot spots" in ibvs (lee and jackwood, ) . in addition, the cttttg sequence was observed adjacent to the putative recombinant junction (brooks et al., ; wang et al., ) . in this study, t-rich motifs (a/t/g)ttttg, consensus among a recombinant and its parental strains, were located upstream of several crossover sites. for instance, the motifs were found in the s gene of the / , the b gene of the / , and the ig region of the / and / . all of the recombinants experienced crossover events in the end of the s gene, indicating a possible region for template switching in viral rna synthesis. similar results were obtained from the ibv strain cu-t and cal , whose recombination sites were deduced in the and nucleotide of the s gene, respectively (jia et al., ; mondal and cardona, ) . in addition to viral recombination, point mutation is a way of virus evolution. the single base nonsense mutations resulted in truncations of the s and b genes in the taiwan strains / and / . the naturally occurring ibv strains with mutations or complete deletions in non-structural orfs a, b, a, and b revealed lower virus growth rate or titer in ovo (liu et al., ) and in vivo (mardani et al., ) . this study describes the dual viral genomes incorporation in the separated areas having no known interactions between poultry. the molecular investigation in the . kb of the ibv genome demonstrates that inter-strain recombination events contribute to the genetic diversity of the taiwan strains. field ibvs in taiwan undergo genetic recombination and evolution, which might lead to disease control difficulty. the biological and antigenic characteristics of the ibv variants await further studies. evidence of circulation of a chinese strain of infectious bronchitis virus (qxibv) in italy molecular epizootiology of avian infectious bronchitis in russia phylogenetic analysis of partial s and n gene sequences of infectious bronchitis virus isolates from italy revealed genetic diversity and recombination genes and of infectious bronchitis virus are accessory protein genes comparisons of envelope through b sequences of infectious bronchitis coronaviruses indicates recombination occurs in the envelope and membrane genes infectious bronchitis virus s gene sequence variability may affect s subunit specific antibody binding co-circulation of four types of infectious bronchitis virus ( /b, /i, b and massachusetts) gene of the avian coronavirus infectious bronchitis virus is not essential for replication recombinant avian infectious bronchitis virus expressing a heterologous spike gene demonstrates that the spike protein is a determinant of cell tropism coronavirus ibv: structural characterization of the spike protein coronaviruses in poultry and other birds coronavirus avian infectious bronchitis virus coronavirus ibv: removal of spike glycopolypeptide s by urea abolishes infectivity and haemagglutination but not attachment to cells relationship between sequence variation in the s spike protein of infectious bronchitis virus and the extent of crossprotection in vivo infectious bronchitis antigenic and molecular characterization of isolates of the italy infectious bronchitis virus genotype molecular epidemiology and evolution of avian infectious bronchitis virus in spain over a fourteen-year period new variant of ibv in poland neither the rna nor the proteins of open reading frames a and b of the coronavirus infectious bronchitis virus are essential for replication recombinant infectious bronchitis coronavirus beaudette with the spike protein gene of the pathogenic m strain remains attenuated but induces protective immunity s and n gene analysis of avian infectious bronchitis viruses in taiwan sequence changes of infectious bronchitis virus isolates in the . kb of the genome after attenuating passage in embryonated eggs identification of previously unknown antigenic epitopes on the s and n proteins of avian infectious bronchitis virus molecular and serologic characterization, pathogenicity, and protection studies with infectious bronchitis virus field isolates from california a novel variant of avian infectious bronchitis virus resulting from recombination among three different strains antigenic domains on the peplomer protein of avian infectious bronchitis virus: correlation with biological functions retargeting of coronavirus by substitution of the spike glycoprotein ectodoma: crossing the host cell species barrier sequence evidence for rna recombination in field isolates of avian coronavirus infectious bronchitis virus rna recombination in animal and plant viruses coronaviridae: the virus and their replication evidence of genetic diversity generated by recombination among avian coronavirus ibv genetic diversity of avian infectious bronchitis virus isolates in korea between detection of infectious bronchitis virus by multiplex polymerase chain reaction and sequence analysis isolation of avian infectious bronchitis coronavirus from domestic peafowl (pavo cristatus) and teal (anas) identification of the avian infectious bronchitis coronaviruses with mutations in gene evaluation of the protection conferred by commercial vaccines and attenuated heterologous isolates in china against the ck/ch/ldl/ i strain of infectious bronchitis coronavirus genetic diversity of avian infectious bronchitis coronavirus strains isolated in china between full-length human immunodeficiency virus type genomes from subtype c-infected seroconverters in india, with evidence of intersubtype recombination infectious bronchitis viruses with a novel genomic organization genotypic and phenotypic characterization of the california (cal ) variant of infectious bronchitis virus emergence of a coronavirus infectious bronchitis virus mutant with a truncated b gene: functional characterization of the b protein in pathogenesis and replication mega : molecular evolutionary genetics analysis (mega) software version . genetic grouping for the isolates of avian infectious bronchitis virus in taiwan evidence of natural recombination within the s gene of infectious bronchitis virus in vitro assembled, recombinant infectious bronchitis viruses demonstrate that the a open reading frame is not essential for replication characterization of three infectious bronchitis virus isolates from china associated with proventriculus in vaccinated chickens the financial support of the national science council and council of agriculture, executive yuan, taiwan, is greatly appreciated. key: cord- - xq dpg authors: chang, chia-chien; yang, alan h. title: weaponized interdependence: china's economic statecraft and social penetration against taiwan date: - - journal: orbis doi: . /j.orbis. . . sha: doc_id: cord_uid: xq dpg nan how do great powers utilize economic and social instruments to coerce the other countries? in this section, we elaborate the theories of economic statecraft and social penetration. economic statecraft and asymmetrical interdependence. china is not the first great power to resort to economic statecraft and societal penetration in pursuing national ambition. at the end of world war ii, the political economist albert o. hirschman published national power and the structure of foreign trade, analyzing how foreign trade could be used as an instrument of national power. the theme of hirshman's book is nazi germany's strategy to expand its trade and political influence during the s. hirschman pointed out that the gain from "seemingly harmless" trade relations can result in the dependence of the country that receives the traded goods. prior to world war ii, nazi germany had already launched "bloodless invasions," using economic carrots to penetrate the political systems and societies of hungary, bulgaria, romania, and others. nazi germany's economic practices, including the export of capital, personnel, and enterprises, had created a dense network of interests and customers with the result of rendering eastern and southeastern europe subservient to nazi germany. although hirschman was writing against the backdrop of nazi germany's economic aggression, his work has a broader implication for international relations today. hirschman elucidated that trade relations, or economic interdependence broadly defined, could be used as a means of political pressure and leverage because economic interdependence is usually asymmetrical, suggesting that in such an economic relationship one state is more dependent on the other. and political power and dominion arises out of the asymmetry. in international relations, power is the crucial "currency" of great power politics, and states compete for it among themselves. therefore, great powers constantly pursue asymmetrical economic relationships in order to create dependence and political dominance. david baldwin, senior political scientist in the woodrow wilson school at princeton, refers to such pursuit of power through economic means as economic statecraft, defined as influence attempts relying on resources which have a reasonable semblance of a market price in terms of money. economic statecraft, baldwin contends, has been practiced for centuries. and the utility of economic statecraft has been systematically underestimated. today, it is all too common for great powers to resort to economic statecraft and social penetration to further their national interests. nuclear program. the russian federation launched cyber warfare to destabilize ukraine's democratic order. moreover, russia misinformed and polarized u.s. voters by extensive propaganda and penetration of social media platforms. as a rising power, aiming at building its own order and sphere of influence, china has been engaging extensively in economic and social penetration of other countries. for instance, china banned rare earth metals exports to japan and curtailed the import of japanese autos due to the territory disputes regarding the senkaku/diaoyu island in the east china sea. china, as noted, also banned banana imports from the philippines to coerce the philippines to concede in the south china sea dispute. more important, economic globalization, the development of supply chains, and breakthroughs of network technology have jointly transformed and updated china's coercive capabilities. some liberal scholars argue that global networks create mutual dependence that decrease states' incentives to engage in conflict or coercion. however, as political scientists henry farrell at george washington university and abraham l. newman at georgetown university show, global connectivity actually creates new opportunities for great powers to coerce, manipulate, and penetrate. like hirschman's emphasis on power asymmetry in economic interdependence, farrell and newman also find that modern globalization results in asymmetrical networks, in which some states are far more connected than others. those states become the "hubs" of the global networks and have the capabilities to exploit "weaponized interdependence." specifically, those great powers can utilize their hub positions to gather information or cut off financial and information flows, discover and exploit vulnerabilities, compel policy change, and deter unwanted actions. sharp power and social penetration. financial power, hub positions in the global exchange networks, and information supply chains also enable authoritarian regimes to engage in comprehensive social penetration and manipulation of other societies. christopher walker and jessica ludwig of the national endowment for democracy analyze such phenomena through a lens of "sharp power," defined as authoritarian influence efforts to "pierce, penetrate, or perforate the information environments and societies in the targeted countries." to delegitimize democracies and other universal human-rights regimes, authoritarian regimes seek to incite and amplify existing divisions in democratic societies by manipulating or faking the information that reaches them. they also use financial incentives to induce media or civil societies in democracies to censor opinions that may be critical of those authoritarian regimes. finally, they employ new digital technologies to spread false and divisive discourse. authoritarian regimes usually exercise their sharp power through four types of social exchanges: cultural exchange programs, academic/think tank cooperation, media, and publishing. for example, china established a global network of confucius institutes all over the world to host cultural, educational, and academic exchange programs. each year, china also hosts several all-expenses-paid media and think tank conferences and exchanges with journalists and scholars worldwide. those programs and conferences, no matter how diversified they are, share one thing in common: censorship. program staff usually seek to block discussions on sensitive topics, such as taiwan, tibet, uyghurs, or other human rights issues in china. criticisms are discouraged, especially those that challenge the legitimacy of the chinese communist party (ccp). participants are expected to promote a positive image of china, as well as to praise china's social, economic, and cultural model and its achievements. of course, liberal hegemons or other democratic great powers also regularly promote their culture and political values worldwide. joseph nye uses "soft power" to describe liberal powers' pursuit of and competition for international attractiveness, legitimacy, and credibility. however, there are two qualitatively different characteristics between soft power and sharp power. first, as nye indicates, soft power rests in the ability of persuasion and voluntarism: you persuade your target to voluntarily follow your request with legitimate values or reasons. sharp power, in contrast, fundamentally rejects voluntarism. sharp power relies on the deceptive use of information and covert operations to mislead the target. in other words, sharp power is actually a type of coercive power because it eliminates the target's voluntary choices by manipulating ideas, political perceptions, electoral processes, and so on. second, openness is the prerequisite for developing soft power, while sharp power is based on opacity, censorship, and barriers to free flows of information. ultimately, soft power hinges on legitimacy, and no one can sustain legitimacy without transparency. a country is likely to lose its international legitimacy, as well as soft power, if it continues to rely on covert operations or secret diplomacy, or if its actions are opaque or have a hidden agenda. in contrast, opacity facilitates manipulation through disinformation and is thus conducive to sharp power. liberal democracies historically countered sharp power by promoting open information and transparency of state behaviors. however, information and communication technologies have created the opportunities for authoritarian regimes to exploit the openness and interdependence of global networks. today, authoritarian regimes like russia and china regularly spread fake news worldwide to sabotage democratic societies while raising barriers to fact-checking. they use international propaganda machines and cyber techniques to dump disinformation externally so as to crowd out the global information markets and drive out other news providers or media companies. at the same time, they further tighten domestic censorship. china, for instance, has launched several censorship programs, like the "great firewall" and "great cannon" among others, which guarantee that the chinese state-own news media can monopolize its domestic marketplace of information (ideas, news, knowledge, etc.). one central goal behind the use of sharp power is to delegitimize democracies, as well as to decrease democratic soft power. dictatorships manipulate the information and destabilize democratic societies in order to show that democratic institutions and values, such as freedom and universal human rights, are no better than authoritarian ones in solving domestic disputes. furthermore, they combine sharp power with economic statecraft to propagate the argument that authoritarianism (dictators often calling it "strong nation") could be an alternative model, perhaps a better one, for development. of course, authoritarian regimes may face international backlash once their sharp power operations are disclosed. however, dictators can still benefit from sharp power because it could help consolidate authoritarian grips on domestic affairs. because dictatorships impose censorship, they can block external information and shape domestic opinions about international responses. dictators may even take advantage of international pushback to stimulate domestic resentment and patriotism. in essence, the priority is to strengthen authoritarian stability by using sharp power to penetrate other societies. china has exploited global networks in a number of ways. first, as hirschman reminded us, great powers regularly seek to convert their economic might into political leverage around the world. china is no exception. with the development of global and regional connectivity, china has used its financial muscles to gain control over major natural resources and strategic locations and to influence other states' stances in disputes. china has provided a substantial amount of aid to african countries to harden its grasp on natural resources. beijing has also launched comprehensive programs of financial statecraft, known as belt and road initiatives (bri), to establish its sphere of influence in the indo-pacific region and even the whole of eurasia. china's financial prowess successfully has swayed some states' stances in many regional disputes. philippine president rodrigo duterte's recent concession on the south china sea dispute is one notable example. another salient case is china's successful effort to induce the solomon islands to end its diplomatic relationship with taiwan. second, the fundamental goal for the chinese leadership is to create a world that is safe for china's authoritarian regime. such an objective could be achieved if there are more non-democratic regimes around the world, or more countries adopting the "china model." therefore, china does not only seek to develop its repressive capacities, but also it tries to export its censorship regime-encouraging other authoritarian regimes to censor and silence domestic dissidents with the technologies and programs it supplies. china's strategy is twofold: first, it has exploited global supply chains and cross-border networks to upgrade its infrastructural power for censorship and monitoring domestic citizens. for example, china has engaged in intellectual property theft worldwide and cyber espionage to increase its information and communication technologies. it has also provided various governmental supports to develop huawei, china's largest telecommunications company and chinese "national champion" of the g industry. huawei's success and control over g network technologies have enabled the chinese government to collect and store the data of almost every chinese citizen. the government also used similar industrial policies to develop hikvision digital technology and dahua technology, chinese manufacturers and the world's two largest suppliers of video surveillance products. the monitoring capacity provided by chinese surveillance camera companies, together with huawei's big data technology, strengthen china's policing capacity and the communist party's censorship. the second fold of china's strategy is to export its censorship regime to other countries as well as surveillance hardware and data-analytics tools. china has engaged in social penetration into other societies and wielded its sharp power globally to justify the china model. for example, beijing is cultivating media elites and government ministers around the world to create a network of countries that will follow its lead on internet policy. chinese officials have held many all-expensespaid trainings, workshops, seminars, and conferences with representatives from other countries. during those events, china regularly propagates that the chinese model of censorship is helpful in combating terrorism and fake news, monitoring public opinion, china/diplomacy/article/ /us-cancels-solomon-islands-meeting-after-disappointmentit. and ensuring cyber security. several countries introduced cyber-security laws that closely mimic china's own version after their official participated in those events. finally, and much more concerning, the chinese state apparatus has been developing its "information troops" to silence or deter dissidents as well as to enforce pro-china views at home and abroad. the great majority of these troops-called by some as the " -cent army"-may not actually be part of the security apparatus, but independent operators including student volunteers at universities, communist youth league members, and government bureaucrats. according to political scientists gary king at harvard, jennifer pan at stanford, and margaret e. roberts at university of california san diego, the chinese state apparatus is involved in faking several hundred million social media accounts and posts. the chinese information troops often use social media to launch campaigns against voices or opinions that criticize the chinese government or challenge the legitimacy of the ccp. the troops constantly use fake news or specious arguments to manipulate public opinion. with help from chinese government censorship, they can easily silence dissents and "manufacture" some public consensus. then, backed by this manufactured consensus, the chinese government is able to resort to coercion against the dissenters. in january , chou tzu-yu, a taiwanese singer in the korean pop band twice, performed while holding a taiwanese national flag on a korean tv show. the chinese government and information troops directed a campaign that led to a ban on chou's presence on almost every tv show in china. and beijing demanded that chou's korean management company, jyp, refund the loss of those shows. eventually, chow was forced to bow deeply and tearfully read a scripted apology that accepted "one china" in the media. in august , china ordered the hong kongbased airline cathay pacific to suspend any staff that supports pro-democracy protests in hong kong. perhaps even more telling was china's ban on the broadcasts of the preseason games of the u.s. national basketball association (nba) due to a tweet by houston rockets general manager daryl morey that appeared to support the hong kong pro-democracy movements. although morey was soon forced to delete the tweet, the chinese government still demanded that the company remove morey from his post. when nba commissioner adam silver insisted that freedom of expression s i | is a principle not to be compromised, the chinese government and information troops launched a series of boycott campaigns against the nba. in sum, economic statecraft and social penetration have become china's common practices to further its national goal. taiwan, which is highly dependent on china for its economy, is on the frontline of china's weaponized interdependence. as indicated earlier, the reunification of taiwan is china's self-defined core interest. hence, china has been engaging in economic and social penetration into taiwanese society. china's aim toward taiwan is threefold: increasing taiwan's dependence to cultivate pro-china factions in taiwanese society, constraining taiwan's pursuit of independence and democratic values, and forcing taiwan to gradually accept china's preferred version of "one-country, two-systems." china has been taiwan's largest trading partner. in , china accounted for . percent of taiwan's foreign trade (while taiwan only accounted for about percent of china's foreign trade). china continues to be the largest destination of taiwanese foreign direct investment ( . percent in ) and the top destination for taiwanese heading overseas to work. in , , taiwanese worked in china, (including hong kong and macao), accounting for . percent of all taiwanese nationals working overseas. china is the largest single source of visitors to taiwan. in (january-october), percent of total tourists visiting taiwan were chinese citizens. these statistics indicate that the economic and social network interdependence between china and taiwan is highly asymmetrical. decades ago, hirschman depicted how nazi germany used industrial policies, market size, and technology to shape eastern and southeastern european neighbors' foreign trade relations, making them substantially dependent on the german market. those efforts contributed to the rise of germany's power over them before and during wwii. today, china is poised to establish its own sphere of influence over taiwan. just as great powers did in history, china has been engaging in the " m" approach of economic statecraft and social penetration against taiwan: money, manpower exchange, misinformation, mooching (cultivating compradors), and magnifying (propagating the "chinese dream"). roman philosopher marcus tullius cicero ( bc- bc) argued: "the sinews of war are infinite money." even during peacetime, money is one of the most crucial foundations for national power and statecraft. regarding china's economic and social statecraft, money could be broadly understood as any forms of positive inducements-providing quid pro quos to anyone for their loyalty and behaviors consistent with china's national interest. those quid pro quos include, but are not limited to, economic and societal benefits, such as granting market/profit shares, licensing, subsidies, protections, and various forms of privileges. in general, china utilizes its monetary power in three ways: positive quid pro quos, negative sanctions (or threaten to launch negative sanctions), and penetration of taiwanese companies for future collusion. positive quid pro quos. there are various examples of china using quid pro quos to gain leverage in taiwan. one of the most significant examples was the economic cooperation framework agreement (ecfa), a preferential trade agreement signed in between china and taiwan. through ecfa, china unilaterally lowered tariffs on many taiwanese agriculture goods and others. here, we find a historical parallel. in the s, as hirschman pointed out, germany supported the agricultural economies of southeastern europe by not only paying them higher prices, but also by promising them stability in both price and volume of their exports. therefore, germany cultivated vested interests in those countries, and tied the interests of existing powerful groups in their societies to relations with germany. likewise, china's quid pro quos have created powerful vested interests in taiwanese society and misperceptions about taiwan's economy and governance. for example, although the data shows that in recent years taiwan's economic situation has been relatively stable, compared with most of the countries in the region, as well as globally, still a substantial portion of taiwanese population think that the ruling party democratic progressive party (ddp) and incumbent president tsai ing-wen did not handle the economy or cross-strait relations well. although ecfa created powerful vested interests in supporting china's influence, it also provoked taiwanese societal discontent with the hollowing-out effect on taiwan provide for "national treatment" to induce taiwanese youth, enterprises, startup entrepreneurs, and blue-and white-collar workers in many sectors. taiwan-funded companies may be qualified to take part in china's key industries, such as major technological equipment, g networks, and civil aviation. in addition, the measures allow taiwanese athletes to be treated as chinese nationals when joining professional sport leagues in china. china's economic statecraft has gained success in a number of cases. in december , days after the dpp's landslide defeat in the local elections, wu paochun, an international award-winning taiwanese baker, announced that he was going to open branches of his bakery in china. however, in order to appease chinese netizens, wu issued a statement saying that he was born in "taiwan, china" and is "proud to be chinese." wu insisted that "two sides of the strait are one family" and is willing to promote economic exchanges and trade across the taiwan strait. wu also hoped that he could participate in the "measures to promote cross-strait economic and cultural ties" released by china's taiwan affairs office of the state council. china's tactics are especially effective in the entertainment industry. several taiwanese celebrities currently working in china have made supportive statements consistent with china' interests, even including the sovereignty issue. in , after the permanent court of arbitration negated china's "nine-dash line" claims to the south china sea, many chinese celebrities started to post a map of the territory that china officially claims, including the nine-dash line. the image also bears a slogan: "china: we cannot lose a single inch [of territory]" and "china's territorial sovereignty doesn't need others to arbitrate." in , then, after a taiwanese director made an independence-leaning, pro-democracy award speech at the golden horse film festival and awards (the chinese-speaking world's version of "oscars"), beijing immediately censored the broadcast of the award ceremony. this time, many taiwanese celebrities working in china immediately posted or re-tweeted that image and the slogan: "china: we cannot lose a single inch" even though taiwan has different claims on its own sovereign territory and the south china sea dispute. negative sanctions or threatening. negative sanctions are common in china's toolbox of economic statecraft. once china successfully cultivates asymmetrical networks with other states, or private actors, and makes them highly dependent on china, beijing becomes more capable of coercing them by cutting (or threatening to cut) the money flows. for example, the chinese recently suspended a program that allowed individual tourists from chinese cities to travel to taiwan, citing the current state of relations between the two sides. the scheme had been in place since under the more china-friendly administration of former president ma ying-jeou. the suspension is commonly interpreted as china's effort to dampen local support for the dpp by cooling the tourism industry in taiwan. another salient example was the "yifang fruit tea event." yifang fruit tea ( , yī fāng shuǐ shuǐ guǒ chá) is one of the famous taiwanese tea brands that has opened many shops around asia. in august , when the pro-democracy protests in hong kong escalated, one of yifang fruit tea shops in hong kong closed for a day and put up a sign that read in chinese: "stand together with hong kongers." chinese netizens were furious because it seemed like yifang fruit tea was backing pro-democracy protests in hong kong. they called for a boycott on yifang, which soon spread to other taiwanese bubble tea brands, including gong cha, heytea, coco, and a little tea. days after the boycott, yifang fruit tea issued a statement on social media in china, saying that yifang firmly supports "one country, two systems" and opposes protests and strikes in hong kong. china also constantly enacts negative sanctions in the entertainment industry. in august , china's film regulator announced that it was prohibiting the chinese movie industry from participating in taiwan's golden horse awards. in addition, a popular taiwanese youtuber lost his business in china after a video of him interviewing taiwan's president went viral. in the video, potter king, a taiwanese internet celebrity with a significant following on both sides of the taiwan strait, addressed taiwan's leader, tsai ing-wen, as "president." king's chinese distributor immediately demanded that he to take down the interview from taiwanese social media. his chinese social media accounts were also seized by the chinese distributor, who removed the video from chinese social media. later, the chinese distributor released a statement indicating that potter king's contract had been terminated. it described king's language and actions as "inappropriate," and "it strongly rebukes any actions which undermines china's dignity and sovereignty. it firmly insists 'one china' principle." china also seeks to use licensing or customs inspection to coerce taiwanese companies to accept the "one-china principle." for example, taiwanese companies need to label their goods as made in "taiwan area, china," instead of "made in taiwan" or "made in taiwan, r.o.c." when they export to china. if they do not comply, then they may face extra duties or longer inspection time. in some cases, customs agencies in china destroyed imported taiwanese products that did not have the newly required "taiwan area, china" label. illegal buyout and forced collusion. lastly, china is also launching two sophisticated monetary statecrafts to penetrate individual taiwanese companies as well as the whole industries. chinese state-owned or state-backed enterprises constantly use their enormous financial resources to lure taiwanese companies, especially those with crucial know-how, to cooperate and jointly develop business. for example, in , tsinghua unigroup ltd, a chinese state-owned technology conglomerate, planned to spend billions to acquire stakes in three taiwanese semiconductor companies. the three targets, silicon precision industries co. (spic), powertech technology inc., and chipmos technologies inc., are all leading chip packing and testing companies in the global arena. the case was controversial because tsinghua unigroup's parent company, tsinghua holding, is considered deeply connected with the chinese communist party. tsinghua holding's former communist party secretary, hu haifeng, is the son of hu jintao, the predecessor of xi jinping. tsinghua unigroup used to have strong government support; in fact, its acquisitions were far beyond its yearly revenue. because the acquisition of tsinghua unigroup raised concerns about market monopoly and national security, the taiwanese regulatory agency reviewed it carefully. in the end, the three investment plans of tsinghua unigroup failed. however, there are many cases where chinese state capital tried to enter taiwan through a third location (either hong kong or singapore) in order to circumvent taiwanese regulations. more concerning still is china's collusion strategy. once chinese state-owned enterprises (soes) acquire controlling shares of a taiwanese company, these enterprises not only want to grab the crucial know-how/technologies of that company, but they also try to leverage the newly acquired company as part of broader economic statecraft. one notable example was a case of china's economic espionage, in which a taiwanese company was charged with helping a chinese soe steal a u.s. company's intellectual property. according to the u.s. department of justice's indictment, prior to the intellectual property theft, fujian jinhua integrated circuit, co., ltd. ("fujian jinhua"), a chinese soe, did not possess dram technology. then, fujian jinhua sought help from a taiwanese individual, chen zhengkun, who previously worked for micron (the u.s. company) and became the president of a micron subsidiary in taiwan responsible for manufacturing micron's dram chips. chen resigned from micron in july and immediately began working at united microelectronics corporation ("umc"), a taiwan semiconductor foundry. while at umc, chen arranged a cooperation agreement between umc and fujian jinhua; with funding from fujian jinhua and the chinese government, umc would transfer dram technology to fujian jinhua. chen later became the president of fujian jinhua and was responsible for its dram production facility. while at umc, chen recruited taiwanese employees from micron to join him at umc. those taiwanese employees stole and brought to umc several micron trade secrets related to the design and manufacture of dram. manpower exchange is another part of china's economic and social statecraft. china is not the first great power to use its networks of manpower to cultivate external influences. in hirschman's study, anecdotal evidence shows the export of german trained and skilled labor contributed to germany's penetration into foreign countries. china is practicing similar tactics. what makes china's manpower strategy so special is its size, and how comprehensive and sophisticated china's manpower networks have become. the flows of manpower as well as other types of social exchanges create opportunities for china to not only develop the united front in the taiwanese society, but also to breed taiwanese affinity with the ccp. the chinese state apparatus has been using multiple manpower channels to make direct contacts with local people and grant benefits to them. china's statecraft used to focus on the "three middles and the youth"-the youth, small and medium enterprises, middle-and low-income classes, and the population in the middle and southern taiwan, who are traditionally considered more pro-independent. in , yu zhengsheng, the chairman of the chinese people's political consultative conference (cppcc) and member of the politburo standing committee, further unveiled that china's economic and social statecraft is going to target "one generation and on stratum" in taiwan-the younger generation and the grassroots. china has launched its social penetration operations through those channels, and two are most influential: religious networks established by local temples and quasiillegal organizations, and various "cross-strait exchange groups." traditionally, china used to manipulate these two channels to penetrate the whole taiwanese society, including both the younger generation and the grassroots. in recent years, religious networks have become china's main instrument toward the grassroots because of the political-societal role local temples play in the communities. as for the younger generation, china has become more inclined to rely on cross-strait exchange groups to tempt the taiwanese youth with travel, studying, and job opportunities. religious networks, local temples, and quasi-illegal organizations. in taiwan, temples play an important role in local lives and communities. because of their huge cash flows and unsupervised finances, temples are the foundation of taiwan's underground economy. temples also serve as a place for regular gathering and information sharing within the communities. finally, temples usually function as local charities in taiwan and may provide emergency support in natural disasters (though their roles in this regard are limited). therefore, temples tend to have important political influence over local communities and a capacity for political mobilization. because a large number of people on both sides of the taiwan strait share similar religions, the chinese state apparatus has noticed the potential to use temples and religious exchanges to win local people's heart. accordingly, the chinese state apparatus has been actively seeking local agents' help to develop cross-strait religious networks with temples in taiwan. one famous agent is the chinese unification promotion party, also known as the unionist party. the unionist party was founded in by the "white wolf" chang an-lo, formerly a key member of the bamboo union, a gang accused of engaging in organized crime. the unionist party is controversial not only because of its strong pro-unification stance, but also due to its aggressive tactics. for example, it provoked violence and attacked pro-independence demonstrators in the "sing! china" event at national taiwan university. in addition, its members were constantly seen holding chinese flags outside the taipei skyscraper to confront falun gong ( , fǎ lun gōng) members. moreover, in , during a rally in taiwan supporting pro-democracy movements in hong kong, the unionist party members threw red paint at the participants. furthermore, the unionist party held several conferences and activities in taiwan to promote the idea of unification by any means, including brute force. the unionist party also uses its networks to help chinese people more easily enter taiwan to conduct political propaganda. for example, the unionist party invited li yi, a chinese scholar, who once argued for the necessity of using force for unification, to deliver a political speech in a pro-unification conference although li's visa was only for tourism. in addition, chang wei, son of chang an-lo, runs the huaxia dadi travel service co, a shadow travel agency for chinese tourists. huaxia dadi and other shadow travel agencies have used "fake exchange proposals" to secretly and illegally help more than , chinese people enter taiwan, including chinese civil servants. according to one report in commonwealth magazine, there are three pillars of the unionist party: gangs (or former gangs), temples, and overseas taiwanese businesses. the unionist party and temples have a close cooperative relationship, and some have secured important positions in temple groups. a notable example is lin kuo-ching, a former gang member, who is now a member of the unionist party's central committee. lin serves as the honorary chairman of several temples, and has excellent relations with the taiwan mazu fellowship run by yen ching-piao. moreover, because smaller temples usually find it hard to establish channels for interaction with temples in china, they turn to the unionist party for help. in exchange, they give party members lucrative contracts for the temple's processions and rituals. now, several small and medium private temples around taiwan are said to have links with the unionist party. in sum, the unionist party, other pro-unification organizations, and taiwanese local temples jointly have created a powerful network of local political mobilization. such a network has become a major channel for the chinese state apparatus to target the grass roots in taiwan and cultivate local communities' affinity with china and the ccp. cross-strait exchange groups. the cross-strait exchange groups are another crucial element of china's social penetration efforts. for many years, the chinese government has used semi-official or puppet organizations to increase and deepen economic, social, and cultural ties between taiwan and china. the aim of those groups has been to cultivate a shared "pan-chinese" identity and to create vested interests in unification. a common strategy for those exchange groups is free tours to specific places in china. such "tours" are planned by the exchange groups, and travel expenses and accommodation are fully covered. during each tour, taiwanese participants are exposed to political propaganda. on occasion, ccp officials deliver keynote speeches. taiwanese participants are also likely to receive some benefits (or promise of benefits). last, personal networks between taiwanese and chinese are established during the interactions. those tours could increase the likelihood that participants rejoin similar tours in the future. with increased participation, powerful bonds are likely to develop between the taiwanese participants and china. those bonds may become useful tools for the chinese government to shape the identity and interest of the taiwanese participants, making them more willing to accept china's influence. previously, those exchange groups mostly focused on taiwanese adults or the elderly. recently, they have shifted their target to taiwanese youth. according to the data, every summer, more than , taiwanese students participate in such china tours. there are usually five kinds of tours. the first is theme workshops or forums. the themes include: leadership, entrepreneurship, development, technology, and chinese history and culture. such tours tend to be organized by top chinese universities and usually contain political propaganda. the second kind of tour is corporate internships. participants have the opportunity for internships in different chinese companies. their travel expenses and accommodation are covered, and they can earn stipends. participants can develop their personal networks. following the internships, participants also have chances to become full-time employees. this kind of tour can cultivate participants' material interest in china and has the potential to function as positive quid pro quos. the third kind of tours is natural and historic sites, and business parks. this kind of tour is usually the presentation of china's soft power. the fourth type of tour is academic conferences and expert workshops. because there are many high-ranking chinese universities, and those universities have more resources to hire renowned professors, this kind of tours can attract taiwanese students seeking more educational opportunities and future employment. finally, there are "art and sport exchange tours." to some extent, this kind of tour functions as the "ping pong diplomacy" between the united states and china from the s. however, such tours have powerful potential as economic and social statecraft because they target even younger generations, such as teenagers, or the athletes, who face an insecure job market in taiwan. china also resorts to sharp power to misinform the taiwanese public, manipulate the society, and sabotage taiwan democracy. china's manipulation in taiwan's politics has been carried out through different channels over years. with the development of cyber technologies, china has also been making greater effort in nurturing pro-communist media and strengthening its capability to manipulate social media in taiwan. in january , when tsai ing-wen won the presidential election, members of "diba," a forum with more than million followers on china's largest search engine baidu, called upon chinese web-users to flood prominent taiwan-related facebook pages with anti-taiwan independence comments. within hours, there were , negative comments on tsai's facebook page. "diba expedition"-an abbreviated description of the campaign-became a top trending search on china's social media weibo. another example was the rise of han kuo-yu, the kuomintang (kmt) party's presidential candidate in and mayor of kaohsiung city. han was a largely unknown name until late summer , barely four months before the mayoral election. however, han started his meteoric rise through the polls. he eventually won a landslide victory in the critical election. many people attributed han's ascendancy to his personal charisma and popularity on social media. for example, han kuo-yu's official facebook account had half a million followers at the end of the campaign. however, a careful analysis shows that china's information manipulation may have contributed to han's victory. as paul huang points out, many of han's facebook supporting groups were created, managed, and nurtured by what looks very much like a professional cyber group from china. those groups helped mobilize the support for han through many means, including using fake news to manipulate the public attitude. china's manipulation tactics and espionage are also common in taiwanese academia. an anonymous scholar from national sun yat-sen university pointed out that since , unidentified hackers have silently accessed and checked the email of more than professors of political science and international relations through several fake accounts posing as senior school administrators. the intruders' ip address has been traced back to china, hong kong, and the united states. this year, the hackers' ip addresses were highly concentrated in hong kong and were suspected of being a domain address generated by using a virtual private network (vpn). this suspicion indicates that china may have extended its cyber espionage network into the taiwanese academia and universities to increase political control by monitoring the behavior of teachers and students. another method for china to penetrate taiwan's society and politics is "mooching." the purpose of mooching is to cultivate local political agents loyal to the ccp, and to use them to undercut the capacity and authority of taiwanese government. to some extent, the strategy is similar to colonial authorities' policy toward local compradors. the mooching approach resembles the manpower exchange approach. for example, both approaches include approaching/inviting taiwan's opinion leaders, local politicians, community leaders, and key figures, such as retired ministers, exmilitary generals, religious leaders, school principals, and teachers, as well as young students to take part in cross-strait forums and various exchange programs organized by china's public and private sectors. nevertheless, these two approaches are different. first, they rely on different ways to govern cross-strait ties. the manpower exchange approach focuses on building institutionalized channels to conduct routine cross-strait interactions, while the mooching approach emphasizes developing informal networks to deal with ad hoc tasks. second, each approach has a distinct strategic goal. the manpower exchange approach seeks to shape taiwanese general public opinion toward china and the ccp, and to foster a group of constituents that can influence taiwanese politics in china's favor. in contrast, the mooching approach aims for cultivating specific pro-china agents to conduct ad hoc cross-strait affairs. a salient example is the recent taiwanese evacuation from wuhan due to the coronavirus. after the outbreak of the novel coronavirus (also commonly known as the wuhan coronavirus) in china, taiwan's government kept requesting that beijing permit the evacuation of taiwanese citizens from wuhan. however, the chinese government did not respond to taiwan's request because china stopped official communications with the incumbent government led by president tsai ing-wen since . china also continues to block taiwan's attendance at the world health organization, constricting the taiwanese government's ability to receive timely information about the coronavirus situation. beijing eventually allowed an evacuation flight due to the worsening situation. however, media reported that the chinese officials only collaborated with pro-china taiwanese businesspersons and elites when drafting flight manifests, rather than allowing taiwan's government to directly handle the evacuation. the mooching method is also widely adopted by china's local governments, enterprises, and associations when they approach young taiwanese. for example, china's universities provide young taiwanese doctorates with assistant the author interviewed a community leader in yilan county on his opinion regarding cross-strait local community interaction. he argued, "china is developing democracy at the grassroots level. wealthy and strong community organizations are important to improve their quality of life. therefore, community representatives came to taiwan to learn about the development and reinvigoration of local community and are aimed at establishing close ties between grassroots communities in china and taiwan. from their perspective, it is to facilitate natural social integration of both sides. nevertheless, with our successful experience, they shall and will thank taiwan and maintain good relationship with us." interview with a local community leader in yilan county, dec. , . huang tzu-ti, "x-defense minister of taiwan says beijing approached him," taiwan news, dec. , , https://www.taiwannews.com.tw/en/news/ . "coronavirus: beijing allows taipei to evacuate taiwanese in wuhan," the straits times, feb , , https://www.straitstimes.com/asia/east-asia/beijing-allows-taipei-to-evacuatetaiwanese-in-wuhan; and nick aspinwall, "taiwan's coronavirus response hits obstacles set by chinese government?," the diplomat, feb. , , https://thediplomat.com/ / /taiwans-coronavirus-response-hits-obstacles-set-bychinese-government/. professorships. local governments offer young entrepreneurs with funding for startups, working spaces, law services (ex. company registration service), and other business incentives. some professional associations even provide young taiwanese professionals with certificates related to their future careers. for example, young tea farmers in central taiwan are encouraged to take china's version of certification in tea art. it is easier for those with china's professional qualification certificates to seek jobs in china and to promote taiwanese tea products in chinese market. china's final approach to penetrate taiwanese society is "magnifying." similar to the misinformation approach, magnifying is also a strategy of using media to create disinformation to manipulate taiwanese public opinion, a case of china's sharp power. however, the two approaches have different missions and tactics. the goal of the misinformation approach is to delegitimize taiwan's democratic institutions and values. hence, misinformation regularly relies on fake news to amplify existing divisions, instigate social conflicts, trigger political instability, and sabotage public trust and confidence in the taiwanese government. in contrast, magnifying is designed to propagate the china model, glorify the "chinese dream," and preach the necessity of reunification of taiwan and china. therefore, the magnifying approach adopts media propaganda that exalts the success of china's development, highlights china's cultural significance, praises china's contribution to the world, and advocates the benefit and the inevitability of joining china's sphere of influence. in recent years, the chinese state apparatus and pro-china forces have targeted the southern localities of taiwan by using various media channels, such as traditional radio stations and new social media. the local radio stations in the central and southern part of taiwan traditionally were the primary local sources of everyday information in support of the pro-taiwan independence sentiments, and the audience is regarded as deep-green supporters and anti-china hot-liners. in taiwan, the key member of chinese unification promotion party hosts radio programs in the southern cities in conjunction with new social media, such as live streaming facebook fans page, to convey the pro-china ideology and disinformation to local people. the brainwashing information includes praising china's political economic development and industrial policy under the leadership of xi jinping, promoting the success of the bri globally, and advocating the cross-strait social and economic integration. some programs even argued that the people's liberation army, china's warships, missiles, and fighters circumnavigating taiwan were to defend taiwan against terrorism or other countries, including the united states and japan. these programs are to formulate a new pro-china social echo chamber in the deep-green localities of taiwan. cross-strait relations between china and taiwan used to maintain a fragile balance. however, since the global financial crisis of - , china has become more assertive in challenging international norms, pursuing national rejuvenation, and wielding its power globally. china's threatening behaviors have pushed the relationship between taipei and beijing toward the brink of crisis. in order to counter china's threat, taiwan needs to be vigilant and take necessary measures. first, taiwan must pay attention to china's economic and social penetration and cultivate the general will and commitment to defending its democracy and sovereignty. as hirschman underscored, when facing great power's threat of domination, if a small country pays greater attention to the asymmetrical relationship, and maintains a stronger commitment to defending its autonomy, the "disparity of commitment" could generate room for the smaller country to maneuver to achieve greater autonomy. taiwan's democracy is the best antibody against china's penetration. the taiwanese government as well as taiwanese people must be vigilant against china's statecraft. taiwan must be deeply committed to its democratic development and institutions. recently, taiwan passed a new cybersecurity law and enacted new penalties on fake news. the government and civil society also cooperate to form fact-checking mechanisms to curb fake news and disinformation. taiwan is initiating an "antiinfiltration law" to counter external interference in domestic affairs, such as elections and legislations. those measures are essential to assure taiwan's democratic resilience against china's threat and malicious penetration. in addition, taiwan must continue seeking, building, and strengthening relationships with democratic, like-minded allies. china's economic and social leverage arise from its hub position in global networks, in which many other countries are asymmetrically dependent on china. of course, chinese markets, resources, and civil societies are valuable assets for world development, and there are always opportunities for cooperation with china. while, it is unnecessary to cut off economic interactions with china, taiwan should pursue a diversification strategy. taiwan has sought to contribute to one cluster among the contending regional approaches in the indo-pacific region, including the u.s.-led free and open indo-pacific (foip) strategy, the ira, social media and political polarization in the united states china's unilateral sanctions weaponized interdependence: how global economic networks shape state coercion what is 'sharp power'? how sharp power threatens soft power: the right and wrong ways to respond to authoritarian influence the rise of digital authoritarianism fake news: national security in the post-truth era how the chinese government fabricates social media posts for strategic distraction, not engaged argument a -year-old pop star was forced to apologize to china for waving taiwan's flag taiwan rebukes beijing's new measures for cross-strait exchanges taipei times the social media 'war' over the south china sea you can speak whatever you want in the golden horse film festival:' from 'taiwan as an independent country' to 'china: we cannot lose a single inch china bans citizens from traveling to taiwan as individual tourists storm in a bubble teacup over taiwan firm's support for hong kong protesters absence of china a 'loss' at chinese-language 'oscars' in taiwan taiwan youtuber loses china business over tsai interview goods manufactured in taiwan and exported to china are required to be labeled 'made in taiwan, china,' source tells china's tsinghua unigroup to invest $ billion via world's biggest private placement chinese cyber-operatives boosted taiwan's insurgent candidate hackers accessed to and monitored the email accounts of political science professors of national sun yat-sen university for three years most of the participants were strongly encouraged to show their support for chinese nationalism, recognize the traditional cultural roots as the basis for the unification of the two sides of the taiwan straits the opinion leaders, including scholars, experts, and retired military officers, were invited to participate in china's state-run tv programs and expressed their support for the chinese government or the unification of the two sides of the taiwan straits, which led the chinese people to mistakenly believe that this was the mainstream opinion of taiwanese society. see, chung li-hua interview with a young tea farmer who was encouraged to take the qualification exam of tea artist in china chang mong-tsung's facebook page china provides no solution for taiwan japan's indo-pacific vision, and india's act east policy to reinforce its relationships with the like-minded countries and other democracies in the region taiwan's nsp not only seeks to build trade and investment linkages, but also pursues mutually beneficial social bonds through people-to-people centered networks since xi jinping consolidated his grip on power, the risk of china abusing its power has increased dramatically. today, the chinese government is imposing stringent rules on domestic citizens, including detention camps in xinjiang and the social credit/surveillance system for all citizens. it also has become much more aggressive in challenging democratic values and universal human rights globally. china has been using its financial and technological power to export censorship and promote authoritarianism to other countries. it has leveraged its position in global networks to penetrate other democratic societies to undermine universal values including the freedom of expression. beijing's social penetration and economic coercion pose severe challenges for democracies unpacking taiwan's presence in southeast asia: the international socialization of the new southbound policy a taiwanese vision for a free and open indo -pacific region key: cord- -niurdu t authors: chern, jimmy ps; chen, duan-rung; wen, tzai-hung title: delayed treatment of diagnosed pulmonary tuberculosis in taiwan date: - - journal: bmc public health doi: . / - - - sha: doc_id: cord_uid: niurdu t background: mycobacterium tuberculosis infection is an ongoing public health problem in taiwan. the national tuberculosis registry campaign, a case management system, was implemented in . this study examined this monitoring system to identify and characterize delayed treatment of tb patients. methods: records of all tuberculosis cases treated in taiwan from through were obtained from the national tuberculosis registry campaign. initiation of treatment more than days after diagnosis was considered a long treatment delay. results: the study included , patients. the mean day of delayed treatment was . days. most patients were treated immediately after diagnosis. the relationship between number of tb patients and days of delayed treatment after diagnosis exhibited a power-law distribution. the long tail of the power-law distribution indicated that an extreme number occur cannot be neglected. tuberculosis patients treated after an unusually long delay require close observation and follow up. conclusion: this study found that tb control is generally acceptabl in taiwan; however, delayed treatment increases the risk of transmission. improving the protocol for managing confirmed tb cases can minimize disease transmission. mycobacterium tuberculosis infection has long been a public health problem in taiwan. the annual incidence of tuberculosis in taiwan was . / , and . / , in and , respectively [ ] . in aboriginal mountainous areas, the reported incidence is even higher: . / , in . in a geographic analysis, yeh et al. reported that the incidence of tb cases in aboriginal populations in mountain areas decreased with distance from foci in mountain areas. the yeh study suggested that recent or new infections, not reactivation, explained the high incidence of tb in the general population of taiwan [ ] . a netherlands study estimated that the average patient with untreated smear-positive pulmonary tb infects more than ten patients annually during the natural course of the disease [ ] . however, identifying smear-positive tb cases through control programs and treatment with effective drug regimens can reduce the spread of infections. there-fore, timely and accurate diagnosis of tb and treatment are vital. delayed treatment can cause more infections per case [ ] . delays can be categorized as patient delays or health care system delays. identifying when delays occur and the factors related to types of delay can help tuberculosis control programs and medical providers improve diagnosis and treatment efforts [ ] . in taiwan, an aggressive case monitoring system has been in place since through the efforts of local public health administrations in cooperation with the taiwan centre for disease control (cdc). this monitoring system requires medical personnel to report all suspected and confirmed cases of tb to city or county local health bureaus. reliability of the reporting system is ensured by two policies: the no-report-no-reimbursement policy and the notification-fee policy [ ] . one policy stipulates that a medical facility failing to report a suspected case cannot receive reimbursement by the taiwan national health care system. the second policy financially rewards the medical facility for reporting suspected cases to local health administrations. this monitoring system collects data as of the dates the tb patient is diagnosed and treated. it provides a unique opportunity to study delayed treatment, defined as the length of time between initial diagnosis and initial treatment. therefore, this study identified and characterized tb cases with unusually long delays in treatment to evaluate the effectiveness of tb control in taiwan. data for all tuberculosis cases treated during - were obtained from the national tuberculosis registry campaign surveillance program. the tb surveillance program was established by the center for disease control (cdc, taiwan), taiwan department of health, and began collecting demographic, geographic, diagnostic and treatment data for all diagnosed tb cases since . this study enrolled only tb patients with sputum smear-and/ or culture-positive tb. treatment delays were measured as the time from the date of definite diagnosis (i.e., confirmation by laboratory findings) to the date of initial treatment for the disease. any treatment initiated more than seven days after diagnosis was considered delayed treatment. in taiwan, physicians are required to immediately treat patients with confirmed tb. physicians who lack sufficient expertise in treating tb must immediately refer the patient to a pulmonologist. this referral process is usually accomplished within a week. data for patients who experienced treatment delays longer than days were considered incorrectly managed and excluded from analysis. the annual distributions in days of delayed treatment were analyzed. differences between patients with tb infection were tested by independent t test and chi square test. we employed mantel-haenszel chi-square test for linear trend to examine whether the confirmed tb cases by laboratory diagnosis increased significantly over the four-year period of analysis [ ] . a p-value less than . was considered statistically significant. distribution-fitting and power function regression were performed to examine whether the days of delayed treatment was power-law distributed, which was determined by the following formula: where k represents the total days of treatment delay, and p(k) indicates the number of tb cases receiving delayed treatment. if the days of delayed treatment could be fitted by a power-law function with a high γ value (larger than ), the number of tb cases would sharply decrease, indicating that long delays are rare [ ] . most patients have experienced short delay, but a significant number of nodes have experienced a longer delayed treatment. the lotka was used to fit the power-law distribution [ ] multivariate logistic regression was employed to model the variables associated with long treatment delay. the dependent variable is a binary variable. patients with treatment initiated more than seven days after diagnosis was considered delayed treatment, coded as " ", otherwise, coded as " ". the study analyzed table ) . the distribution of treatment delays was skewed. mean treatment delay was . median and mode of treatment delay was during these years. in more than % of the patients, treatment commenced within days after laboratory-confirmed diagnosis; only . %- % had treatment delays longer than days (table ) . delayed treatment, defined as initial treatment seven or more days after diagnosis, was noted in , patients ( . % table ). the correlations between number of tb patients and days of delayed treatment after diagnosis were similar for each year ( fig. to fig. ). the days of delayed treatment of tb patients exhibited a power-law distribution with a % statistical significance, indicating that most patients were treated immediately after diagnosis. conversely, the absolute values of γ in power-functions ranged from . to . with r-square = . ( fig. to fig. ). this finding suggests that a small number of patients experienced treatment delays for a significant number of days. multivariate logistic regression results showed that gender, type of treatment facilities, and year were significantly associated with being long treatment delay. as compared to women, men were . times more likely to be in long treatment delay. patients treated in hospitals were also . times more likely to be in long treatment delay, compared to patients treated in clinics. yearly difference was also significant. the prevalence of long treatment delay in was % less than that in (the baseline), and the prevalence of long treatment delay in and were % and % respectively less than that in (as shown in table ). delayed diagnosis and treatment of active tuberculosis can be categorized as patient delay or health care system delay. in the health care system, most delays are caused by the diagnosing facility. such delays can be further categorized as delayed diagnosis or delayed treatment [ ] . regardless of cause, delayed diagnosis and treatment can be catastrophic to those exposed to infected patients [ ] , particularly medical personnel [ ] . for example, the large tb outbreak involving sixty healthcare workers in a taipei hospital was attributed to delayed diagnosis and treatment [ ] . minimizing delays in diagnosis or treatment can substantially improve tb prevention. previous studies measured patient and health care system delay [ , [ ] [ ] [ ] whereas the current study focused on treatment delays after definite diagnosis in a health care system. the intent was to focus on the severity of delays occurring. in taiwan, the the incidence of cases with definite diagnosis increased significantly during these years. mantel-haenszel chi-square for linear trend p < . . data are n, means ± sd, or n (%). number (n) of patients is given when the variable concerned is not measured in all patients. * chi-square tests p < . . incidence of laboratory-confirmed diagnoses increased gradually during these years. however, the incidence of tb remained relatively stable. the increased incidence of definite diagnosis may be attributable to improved accuracy of diagnosis by healthcare facilities. among these patients, most cases of tb infection in taiwan were males, which is consistent with previous studies. this gender difference may partly reflect epidemiological differences, including differences in exposure, infection risk, progression from infection to disease, socio-economic status, cultural factors and quality of health care received [ , [ ] [ ] [ ] [ ] [ ] [ ] . however, although a gender difference in incidence was noted, no gender difference was noted in number of days of delay after definite diagnosis. taiwan national health insurance was implemented in to provide universal health coverage. the national health insurance program provides accessibility to health care at reasonable cost [ ] . this might have increased utilization of medical care by both genders. additionally, taiwan also implemented a no-report-no-reimbursement policy in which penalizes medical facilities for not reporting possible tb cases by denying reimbursement. together, these measures may have helped improve the surveillance, diagnosis and time to treatment of tb in the overall population. however, this study revealed that more men than women experienced long delays in treatment. a study in yemen demonstrated that women were more likely than men to complete tuberculosis treatment [ ] , which suggests that women have shorter treatment delays than males and tend to receive treatment immediately after diagnosis. data are n, means ± sd, or n (%). number (n) of patients is given when the variable concerned is not measured in all patients. * chi-square test, p < . . ** t-test, p < . . however, a bangladesh study showed that women experience longer total delay, total diagnostic delay, patient delay and treatment delay (males . days, females . days) [ ] . these inconsistencies highlight the impact of different communities and cultures on gender differences in tuberculosis treatment delays. hence, a better understanding of the people and communities affected by tuberculosis is needed to provide consistent and high quality care [ ] . recent research indicates that many natural and socialeconomic phenomena, such as income, disease-related death and earthquake magnitude, follow a power-law distribution rather than a bell-curve distribution. this implies that small occurrences are common, and large instances are rare but possibly devastating [ , ] . our study also revealed a power-law distribution in tb treatment, suggesting that while most tb cases are controlled by public health authorities, the few patients who experience long delays in treatment can cause serious transmission. as can be seen in fig. to fig. , the tail of the powerlaw distribution has a much slower decay than other probability distributions, such as the poisson distribution. the probability that an extreme number will occur from a random sample cannot be neglected if we are dealing with power-law phenomena. it is worth noting that a powerlaw distribution in tb treatment, suggesting that while most tb cases are controlled by public health authorities, the few patients who experience long delays in treatment can cause serious risk for transmission [ , ] . as pastor-satorras and vespignani [ ] has revealed, in a power-law distribution, epidemics can reproduce with a considerably lower number of infected persons at each point in time, than other probability distributions. therefore, epidemics in a power-law distribution will not exhibit a threshold. it brings serious concerns for public health researchers working in the field of tuberculosis control. additionally, based on the data in this study, long delays in treatment usually occurred in hospitals (range: . % . %) rather than in primary-care clinics. the likely explanation is that not all physicians are familiar with treatment of tb, especially in hospitals with many specialists. chung et al. reported that physicians who are not pulmonologists are less effective in treating tb [ ] . we speculate that if the attending physician cannot explain the disease as convincingly as a pulmonologist, the patient may choose to visit another doctor for a second opinion or simply leave under the impression that the doctor is uncertain or is reluctant to disclose the tb findings because of the social stigma attached to the disease. to minimize treatment delays and disease transmission, the protocols for controlling tb at the hospital level must be strengthened. for example, nurses responsible for hospital tb control should be informed immediately after a laboratory diagnosis is confirmed. the nurse can contact the patient, inform primary doctor and arrange an immediate visit to a pulmonologist. nevertheless, this study bears the following limitations. first, the data analysis did not differentiate newly detected cases from relapses. second, global surveillance of drug resistance has shown that a substantial proportion of tuberculosis patients are infected with drug resistant mycobacterium tuberculosis strains [ ] . unfortunately, the possibility of multiple-drug resistant tb (mdr-tb) cannot be considered due to the lack of information in the data set. however, based on the report from chest hospital in taiwan, multidrug resistance occurred in . % of retreated tb patients, and . % of multidrug resistant isolates were found in new tb patients from january to june [ ] . a recent report in may revealed that, among patients with mdr-tb, . % ( / ) were fluoroquinolone-resistant [ ] . fluoroquinolones are widely used for the treatment of bacterial respiratory infections in taiwan. this treatment regimen of using fluoroquinolone before definite diagnosis of pulmonary tb might cause temporary symptom relief of the patient, and might eventually cause treatment delay and drug resistance [ ] . further studies are needed to examine the extent of fluoroquinolone-resistance in patients with long treatment delays. this study found that tb control is generally acceptable in taiwan; however, delayed treatment increases the risk of transmission. improving the protocol for managing confirmed tb cases can minimize disease transmission. mycobacterium tuberculosis in taiwan incidence of tuberculosis in mountain areas and surrounding townships: dose-response relationship by geographic analysis epidemiology of tuberculosis. the royal netherlands tuberculosis association patient and health care system delay in the diagnosis and treatment of tuberculosis patient and health care system delay in the start of tuberculosis treatment in norway the impact of national health insurance on the notification of tuberculosis in taiwan openepi: open source epidemiologic statistics for public health, version . . power laws, pareto distributions and zipf's law lotka: a program to fit a power law distribution to observed frequency data diagnostic and treatment delay among pulmonary tuberculosis patients in ethiopia: a cross sectional study diagnostic standards and classification of tuberculosis in adults and children tuberculosis among health care workers nosocomial transmission of mycobacterium tuberculosis found through screening for severe acute respiratory syndrome -taipei patient and health care system delay in queensland tuberculosis patients delay in tuberculosis case-finding and treatment in mwanza, tanzania patient and health system delay in the diagnosis and treatment of tuberculosis in southern taiwan the global burden of disease and risk factors in her lifetime: female morbidity and mortality in sub-saharan africa women and tuberculosis gender difference in delay to diagnosis and health care seeking behaviour in a rural area of nepal key p: women, health and development, with special reference to indian women. health policy and planning longer delay in tuberculosis diagnosis among women in vietnam the effect of universal health insurance on health care utilization in taiwan. results from a natural experiment gender and literacy: factors related to diagnostic delay and unsuccessful treatment of tuberculosis in the mountainous area of yemen gender differences in delays in diagnosis and treatment of tuberculosis the role of gender and literacy in the diagnosis and treatment of tuberculosis power-law distributions in empirical data scale-free networks epidemic spreading in scalefree networks sexual networks: implications for the transmission of sexually transmitted infections factors influencing the successful treatment of infectious pulmonary tuberculosis anti-tuberculosis drug resistance in the world report drug-resistant mycobacterium tuberculosis extensively drug-resistant tuberculosis the authors would like to thank the ministry of education of taiwan, "aiming for the top university and elite research center development plan" (no. hp ), and department of health of taiwan (doh -td-ph- ) for financial support. the pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/ - / / /pre pub key: cord- -unhg e authors: juan, hui-chun; chao, chien-ming; lai, chih-cheng; tang, hung-jen title: decline in invasive pneumococcal disease during covid- pandemic in taiwan date: - - journal: j infect doi: . /j.jinf. . . sha: doc_id: cord_uid: unhg e nan dear editor , we read with great interest lim et al's report, which showed a decreased incidence of pneumococcal disease in singapore during the first weeks in in the time of covid- . although the collateral benefit of controlling covid- for other common respiratory infectious diseases, such as influenza and tuberculosis in taiwan have been demonstrated, , the impact of the infection control and policy to prevent covid- outbreak on pneumococcal disease remained unclear. therefore, this study was conducted to determine whether the incidence of pneumococcal disease in taiwan would be decreasing as lim et al's study in singapore. in taiwan, invasive pneumococcal disease (ipd) is a notifiable disease for which reporting is mandatory for all clinicians. therefore, this study can obtain the case number of patients with ipd used data from open data website of taiwan's cdc. to compare the case number of ipd during the same period each year, we extracted the monthly cases between january and august from to . first, a total of ipd cases were reported during the first months in , by contrast, the accumulative case number within the months ranged from in to in , which were much higher than that in ( fig. a) . second, in , the case number of ipd was highest in january ( n = ) and gradually decreased with time, which was lowest in may ( n = ) ( fig. b) . in this study, we found the similar phenomena that ipd was decreasing during covid- in taiwan, like lim et al's findings in singapore. the possible explanation could be the strict performance of infection control and policy during covid- pandemic. since the first case of covid- was identified in january, a total of covid- cases were reported till now and caused seven deaths. to prevent the outbreak of covid- , taiwan authority immediately practiced many infection control measures, particularly mask wearing, hand hygiene and avoid visiting crowd area. most of these interventions can help prevent the transmission of sars-cov- via respiratory droplets and may also provide additional benefit in the controlling other respiratory infectious diseases, such as pneumococcal disease, which was demonstrated here. although many confounding factors, such as vaccine strategy or under-report of ipd during covid- pandemic were not evaluated in this study, our findings was consistent with singapore's study suggest that strictly performance of infection control and policy not only mitigate the threaten of covid- but also reduce the burden of other respiratory infections disease -invasive pneumococcal diseases. decline in pneumococcal disease incidence in the time of covid- in singapore the covid- pandemic and tuberculosis in taiwan one benefit of covid- measures in taiwan: the reduction of influenza infections and severe complications. influenza other respir viruses severe acute respiratory syndrome coronavirus (sars-cov- ) and coronavirus disease- (covid- ): the epidemic and the challenges key: cord- -qh cxp authors: tanaka, miho; kodama, satoshi; lee, ilhak; huxtable, richard; chung, yicheng title: forgoing life-sustaining treatment – a comparative analysis of regulations in japan, korea, taiwan, and england date: - - journal: bmc med ethics doi: . /s - - -w sha: doc_id: cord_uid: qh cxp background: regulations on forgoing life-sustaining treatment (lst) have developed in asian countries including japan, korea and taiwan. however, other countries are relatively unaware of these due to the language barrier. this article aims to describe and compare the relevant regulatory frameworks, using the (more familiar) situation in england as a point of reference. we undertook literature reviews to ascertain the legal and regulatory positions on forgoing lst in japan, korea, taiwan, and england. main text: findings from a literature review are first presented to describe the development of the regulatory frameworks surrounding the option of forgoing lst in each country. based on the findings from the four countries, we suggest five ethically important points, reflection on which should help to inform the further development of regulatory frameworks concerning end-of-life care in these countries and beyond. there should be reflection on: ( ) the definition of – and reasons for defining – the ‘terminal stage’ and associated criteria for making such judgements; korea and taiwan limit forgoing lst to patients in this stage, but there are risks associated with defining this too narrowly or broadly; ( ) foregoing lst for patients who are not in this stage, as is allowed in japan and england, because here too there are areas of controversy, including (in england) whether the law in this area does enough to respect the autonomy of (now) incapacitated patients; ( ) whether ‘foregoing’ lst should encompass withholding and withdrawing treatment; this is also an ethically disputed area, particularly in the asian countries we examine; ( ) the family’s role in end-of-life decision-making, particularly as, compared with england, the three asian countries traditionally place a greater emphasis on families and communities than on individuals; and ( ) decision-making with and for those incapacitated patients who lack families, surrogate decision-makers or ads. conclusion: comparison of, and reflection on, the different legal positions that obtain in japan, korea, taiwan, and england should prove informative and we particularly invite reflection on five areas, in the hope the ensuing discussions will help to establish better end-of-life regulatory frameworks in these countries and elsewhere. recently, two critical laws on end-of-life care were enacted in asia. one is the act on decisions on life-sustaining treatment for patients in hospice and palliative care or at the end of life (hereafter, lst decision act), which was enforced in early in korea [ , ] . this act permits the withdrawal of lst from patients at the end of life. the other is the patient right to autonomy act (hereafter praa) enforced in early in taiwan [ ] . much earlier, in , taiwan enacted the hospice palliative care act, which permits withdrawal of treatment from terminally ill patients at their request. the new law allows treatment withdrawal not only from terminally ill patients, but also from any patient who is in an irreversible coma, in a vegetative state, has severe dementia, or otherwise suffers from unbearable pain. in contrast to these two countries, japan has yet to pass a law on forgoing lst, even though the public discussion on the issue has been ongoing for over a decade. in , japan's ministry of health, labour and welfare (hereafter, mhlw) issued the guideline for medical decision-making process in end-of-life (terminal) care (hereafter, the process guideline); however, it does not explicitly permit or prohibit forgoing lst. in , a group of non-partisan diet members proposed a draft bill for respecting the patient's decision in end-of-life care act (provisional name; hereafter, the draft ad bill), which offers immunity to physicians if they withhold or withdraw lst in accordance with the patient's advance directive (hereafter, ad). as of , the proposed draft ad bill has yet to be submitted to the national diet. as portrayed above, regulatory developments on forgoing lst have progressed in these three countries to differing degrees. unfortunately, the nature and specifics of these remain relatively unknown to other countries, partly due to the language barrier. the legislation, guidelines, and deliberation processes are typically posted only in the native language on the websites of health ministries and parliaments of these countries, so the regulatory schemes for end-of-life care are little known beyond the particular jurisdiction, even by neighbouring asian countries. many western countries formulated public policies about forgoing lst in end-of-life care prior to most asian countries. england is one such example, along with the us and other english-speaking countries including australia and canada. looking specifically to the english legal system, professional medical organisations have long published guidance on end-of-life care, including the doctors' trade union the british medical association (hereafter, bma) and the doctors' regulator in england, the general medical council (hereafter, gmc) , , , english law primarily derives from the common law (i.e. the decisions of judges) and acts of parliament. although common law had long governed lst decisions, in the mental capacity act (hereafter, mca) came into force, which covers lst decisions for adult patients who lack "mental capacity" [ ] . comparison of the situations in korea, taiwan and japan with the situation in england is useful as it enables clarification of legal and philosophical issues pertaining to the legalisation of forgoing lst. we believe that the results of such a comparison will be valuable for critical reflection on the relevant laws and policies, in these countries and others. to this end, the present study involved a literature review to examine the laws, guidelines, and newspaper articles relevant to this issue. below, we first summarise the development of regulatory frameworks on forgoing lst in japan, korea, taiwan, and england. we then compare the regulatory frameworks on forgoing lst in each country. finally, we discuss legal and philosophical issues concerning forgoing lst that need to be addressed in order to create better regulatory frameworks for end-of-life care in asian countries and worldwide. development of regulatory frameworks with regard to forgoing lst in japan, korea, taiwan, and england japan in japan, court cases and other incidents highlighting problems associated with lst withdrawal increased the momentum for legislation. while no bill has been submitted to the national diet for deliberation, several ethical guidelines have been created. here, in order to better understand the current situation in japan, we summarise two crucial court cases and one incident regarding the forgoing of lst. the tokai case ( ) in this case, the attending physician withdrew treatment from a -year-old patient suffering from end-stage multiple myeloma at tokai university hospital. the physician then administered sedative drugs to stop the patient from stertorous breathing, followed by potassium chloride, which causes heart failure if injected undiluted. the patient subsequently died from cardiac arrest, and the attending physician was prosecuted for homicide. in march , the in the united states, beginning with california's enactment of the natural death act in , all states had enacted ad-related laws by . england comprises different legal systems; our focus will be on english law i.e. essentially the law of england and wales. see: (accessed april ). the general medical council (gmc) in england is an independent organisation and statutory regulator for the medical profession in england. its guidance applies to doctors working in all four uk countries (i.e., england, wales, scotland, and northern ireland). in addition, the gmc helps protect patients and improve medical education and practice. see: (accessed april ). yokohama district court found the attending physician guilty of murder and sentenced him to years in prison with years of suspension [ ] . in the ruling, the court not only set forth admissibility requirements for active euthanasia, but also provided admissibility criteria for forgoing lst in the obiter dictum (table ) . although the tokai case concluded at the district court level without appeal, the decision had a considerable impact on japanese society and influenced subsequent discussions, not only on active euthanasia, but also concerning the forgoing of lst. the kawasaki case ( ) in the case of kawasaki kyodo hospital, the attending physician removed the endotracheal tube from a -year-old patient upon request from the patient's family. the patient was unconscious due to hypoxic brain injury accompanied by status asthmaticus [ ] [ ] [ ] . when the physician could not alleviate the patient's heavy breathing, she ordered an assistant nurse to inject a muscle relaxant, and the patient eventually died. the doctor was later charged with homicide. the most distinctive aspect of the kawasaki case was that the disputed point in the supreme court was the illegality of treatment withdrawal. both the yokohama district court and the tokyo high court in the kawasaki case decided that treatment withdrawal was illegal because two requirements for withdrawing treatment had not been fulfilled, specifically "the physician's duty of care" and "the patient's autonomy", respectively corresponding to the first and second admissibility requirements in the court decision of the tokai case. the physician was accordingly convicted of homicide. in early , the tokyo high court sentenced the physician to year in prison with years of suspension. in , the supreme court ruled to uphold the high court ruling. the imizu incident ( ) ( ) ( ) ( ) ( ) ( ) in the imizu municipal hospital incident, two physicians withdrew artificial ventilators from seven terminally ill patients in their s to s in response to requests either from the patients or their families [ , ] . all patients died following removal of the ventilators. in , the incident made national headlines, with the hospital director apologising that his staff had undertaken "ethically problematic" treatment withdrawal. in , the police referred the physicians to public prosecutors. by the end of , however, the public prosecutors office decided not to prosecute due to insufficient evidence [ ] . both the kawasaki case and the imizu incident fuelled the fears of healthcare professionals about facing legal or social sanctions over forgoing treatment, and clarification of the legal (im)permissibility of forgoing lst became an urgent issue for the government and professional medical associations. in , soon after the high court decision on the kawasaki case and the exposé of the imizu incident, the mhlw issued the process guideline, which addressed the issue of lst withdrawal (details explained below in section ) [ ] . several professional associations also published end-oflife guidelines, including the guideline on end-of-life care in acute care and intensive care (compiled collaboratively by the japanese association for acute medicine, the japanese society of intensive care medicine, and the japanese circulation society) [ ] , the guideline on end-of-life care (japan medical association) [ ] , and the guidelines for decision making process of elderly care: focusing on the use of artificial hydration and nutrition (japan geriatrics society) [ ] . however, even after publication of the mhlw's process guideline and other professional guidelines, healthcare professionals were not sure about the legality of forgoing lst. for example, in , year after the publication of the mhlw's process guideline, the ethics committee at the kameda medical center approved the withdrawal of the artificial ventilator from a patient with motor neurone disease (mnd), but the hospital director chose not to follow the committee's advice due to legal uncertainty [ ] [ ] [ ] . , , this situation led to the drafting of an ad bill in by a group of non- . it is desirable that the patient has declared his or her wishes when forgoing treatment is considered an option. it is permissible to presume the family's will to be the patient's will, provided that the patient's family makes a deliberate decision that takes into consideration the patient's perspective. . treatments that can be forgone include all treatments considered to be curative measures, supportive measures, or lst, e.g., drug administration, chemotherapy, artificial dialysis, artificial ventilator, blood transfusion, and artificial nutrition and hydration (anh). a the term they actually use in the decision is "stop treatments (chiryo chushi)," but because there appears to be no distinction in the decision between withholding treatments and withdrawing them, we interpreted the word "stop" to mean "forgoing" on april , one of the authors (tanaka) was able to view this important report which the hospital had submitted to the shinminato district police on october , by gaining access to the official files of imizu city. als is a rare neurological disease that mainly involves nerve cells (neurons) responsible for controlling voluntary muscle movements that enable actions such as chewing, walking, and talking. currently, there is no cure for als and no effective treatment to halt, or reverse, the progression of the disease. partisan diet members. seven years later, the draft ad bill has yet to be submitted to the national diet. in korea, the boramae hospital case and the severance hospital case were critically important in shaping the public discussion and subsequent legislation on lst withdrawal. the boramae hospital case ( ) the attending physician at boramae hospital removed the artificial ventilator from a -year-old patient, who had been admitted to an intensive-care unit (icu) after a surgical operation due to massive intracranial haemorrhage, following a request from the patient's wife [ , ] . the doctor and the patient's wife were subsequently charged with homicide and prosecuted as joint offenders. the medical team in the hospital had tried to persuade the wife to continue the patient's treatment in the hospital, but she requested that the patient be discharged because of the financial burden of further hospitalisation, and the team decided to discharge the patient. less than min after leaving the hospital, the patient developed respiratory difficulties and died. expecting to be the beneficiary of a free funeral service if police were engaged, the wife reported this as an unexpected death to the police, and it led to a court case. in , the supreme court sentenced the physician to months in prison and years of probation. the court ruled that if the physicians discharged the patient at the request of the patient's wife and were aware that the reason for the wife's discharge request was the death of the patient and that discharge of the patient would lead to his death, then the physicians were guilty as accomplices to murder. this ruling came as a shock to many korean physicians. until then, proxy decisions by the patient's family had been generally accepted as essential grounds on which physicians could make difficult choices regarding treatment. however, the court decision reminded physicians of their duty to act in the best interests of the patient before complying with the will of a (potentially untrustworthy) proxy. however, physicians regarded this decision as requiring them to do their best to prevent the death of the patient [ ] . the severance hospital case ( ) a -year-old female patient at severance hospital suffered hypoxic brain damage due to severe bleeding from the pulmonary artery, which was a complication arising during bronchoscopic biopsy [ ] . she was deemed to be in a persistent vegetative state (pvs) and could not breathe sufficiently on her own. her family asked the hospital to withdraw the artificial ventilator from the patient, but the hospital refused. the family filed a lawsuit and won the case at the supreme court level. this case was different from the boramae hospital case in two respects. first, the patient was thought to be irreversibly dying. second, the court judged the family's proxy decision to be the patient's will. furthermore, the supreme court pointed out the necessity of legislation on forgoing lst that respects the right to pursue happiness, as guaranteed by the korean constitution. along with these court cases, the following significant events happened in korean society [ , ] . in , in response to the boramae trial, the korean association of medical societies (kams) proposed the kams guideline on forgoing lst. in , in response to the severance case, the kams, the korean medical association, and the korean hospital association together established a set of guidelines on forgoing lst. creation of these guidelines attracted the attention of legal and ethical professionals, policymakers, and medical professionals [ ] . several bills on withdrawing lst were submitted to the national diet from to . these developments led the government to set up consultation bodies in and to take measures to facilitate social consensus-building around these topics. the topics included whether or not treatments may be withdrawn only from terminally ill patients, whether lst (including cardiopulmonary resuscitation and artificial ventilation but not anh) may be withdrawn, and whether and to what extent physicians must respect patient autonomy. these developments culminated in the enactment in , and full enforcement in , of the hospice palliative care and lst decision act. taiwan was one of the first asian countries to create a law on forgoing lst. , , it is believed that the practice of "terminal discharge from hospital" played an important role in shaping the public discussion and subsequent legislation concerning lst. in taiwan, the term "terminal prior to this, a group of non-partisan diet members had announced a draft proposal in that would allow withdrawal of lst, but this was only an outline of a bill and was never submitted to the national diet. the outline of the draft ad bill in was made public at the end of . the initial plan allowed only terminally ill patients to withhold lst. in the strict sense, the patient was near pvs (her brain responded to external stimuli, that she has minimal consciousness) but medical professionals expected she would not survive the condition very long. the court recognised the professionals' prediction, so the court mentioned it as "irreversible dying stage". so it ruled that the hospital should respect the patient's preference. ironically she regained the respiration ability, and lived another months after the court decision. other countries include thailand and singapore. thailand enacted the national health act, b.e. in . singapore enacted the advance medical directive act in . discussion of the situation in these countries is beyond the scope of this paper. discharge" refers to the practice of allowing terminally ill patients to spend the last few hours or days with their families at home by being discharged from the hospital of their own will or their family's proxy decision. the legitimacy of such practice was recognised as part of the "discharge at patient's request," which was stipulated in the medical care act in [ , ] . since then the practice of "terminal discharge" has been widely accepted in the clinical scene in taiwan. along with the above development, the hospice movement began to take root in taiwan [ , ] . in , a substantial discussion on the need for hospices and palliative care began, and the first hospice program was set up in , followed by the creation of the first hospice unit in taiwan in [ ] . since then, several hospice wards have been established in both public and private hospitals, and many religious hospice foundations and non-profit hospice organisations have been created. as the hospice movement developed in taiwan, calls for the legalisation of forgoing lst grew amongst healthcare professionals in . the ministry of health and welfare (formerly the department of health; upgraded as mhw in ) was initially reluctant to answer such requests because the officials believed it was too early to discuss such an issue. however, as the hospice movement progressed in taiwan, the mhw indicated in that providing palliative care and withholding lst were within the realm of a doctor's "duty of care" and, therefore, not illegal. following the policy change in mhw, healthcare professionals sought legislation on do not resuscitate (dnr) orders, in order to allow patients to die naturally in hospital [ ] . as a result, the hospice and palliative care act was enacted in , legalising the withholding of lst from terminally ill patients in line with their ads (including a healthcare proxy to legally make healthcare decisions on behalf of patients) or their family's consent. the law was amended several times and now also permits lst withdrawal at the patient's or family's request, as described in more detail in section below. although the act contributes to the development of hospice in taiwan, it was criticised for not fully respecting patient self-determination for two reasons. first, the physician's duty to tell the truth, to disclose a diagnosis, or to obtain consent from the patient is not explicitly stipulated [ ] . second, even after the law was enforced, the patient's family primarily make decisions to withhold or withdraw lst [ ] . in response to these criticisms, the praa was passed at the end of and enforced in january . the law and professional guidance permit lst to be withdrawn or withheld, not only from patients who have mental capacity and have refused such treatment but also from patients who lack mental capacity. the relevant principles were initially enshrined in professional guidance and court rulings, but some have since been set down in the mca. the crucial first ruling in this area was bland, which concerned a patient who lacked the mental capacity to make decisions about his treatment at the relevant time [ , ] . the bland case ( ) anthony bland (then -yearsold) was trapped in a crush at the hillsborough football stadium disaster in sheffield (england) and later diagnosed to be in a pvs. three years passed without any improvement in his condition. he had not indicated his will concerning the treatment in advance. however, the hospital trust and bland's family came to believe that treatment withdrawal was appropriate as they perceived no benefit in treatment continuation. the hospital applied to the court, seeking a declaration that the withdrawal of bland's anh would be lawful. in , the house of lords, the then superior court, ruled that withdrawing lst is an omission, which can be justified if a responsible body of doctors hold that treatment is not in the patient's best interests [ , ] . the court ruled that future such cases involving patients in the pvs should be brought before a judge for a decision as to whether or not lst should (continue to) be provided. after the decision, bland's anh was withdrawn, and he died shortly afterwards. pvs cases involving anh were, therefore, a matter for the judges and the requirement was subsequently extended to patients in the minimally conscious state (mcs) [ ] . however, the (now) superior court, the supreme court, has recently confirmed that there is no requirement to bring such cases to court [ ] . this means that, regardless of the patient's diagnosis or the treatment to be withdrawn, decisions do not require court approval, although difficult or contested situations may still come before the judges. instead, lst decisions are generally a matter for the healthcare professionals, albeit in consultation with the incapacitated patient's loved ones. following the bland case, professional societies issued guidelines on forgoing lst. these included the bma, which published guidance on withholding and withdrawing lst in [ ] . the gmc also published guidance, entitled "withholding and withdrawing -guidance for doctors" in , which set the standards of practice expected of doctors when they consider whether to withdraw or withhold treatments that might prolong a patient's life [ ] . in , the latter was replaced with new guidance, entitled "treatment and care towards the end of life: good practice in decision making." the gmc's current guidance provides a framework for good practice regarding the provision of treatment and care to patients who are likely to die within a year [ ] . there are also more specific guidance documents, focused on (for example) decisions about cpr and, most recently, anh [ , ] . the various professional guidance encompasses not only incapacitated patients, but also patients who have "mental capacity" (or competence). the common law had long defined capacity in functional terms, i.e. the focus was on whether the patient could comprehend and retain relevant information and reach a decision [ ] . the common law had also long recognised the right of a competent adult patient to refuse lst, a position most powerfully confirmed in re b in , in which a ventilator-dependent patient had this unwanted treatment withdrawn at her request [ ] . furthermore, the common law also recognised an adult patient's right to make an ad refusing treatment they might otherwise receive in the future when incapacitated: provided that the patient was competent and informed, and their advance directive applied to the situation that later arose, their refusal had to be respected [ ] . many of these propositions were then enshrined in the mca in , thus replacing the common law [ , ] . as the parliamentary office of science and technology reported, "while healthcare practice had to operate according to these common law judgements, historically it has been guided by more paternalistic concepts of duty of care without a strong legal awareness. outside of hospitals, however, for many carers of people with learning disabilities, dementia or mental illness, concerns were expressed about the lack of legal guidance [ ] ". the mca, therefore, provided a statutory test for mental capacity and generally provided that decisions about patients who lacked capacity were to be made in their "best interests". although there is no strict legal test of best interests, the courts have increasingly emphasised the importance of respecting the patient's wishes and values [ ] . furthermore, the act also placed adsspecifically now labelled "advance decisions to refuse treatment"on a statutory footing, and for the first time provided for surrogate decision-making, through the creation of "lasting powers of attorney" (hereafter lpa). details of the law are explained below. this section compares the regulatory frameworks of the four countries regarding forgoing lst. the foci under comparison include: the legal effectiveness of advance directives; eligibility criteria for medical conditions; the definition of 'terminal phase'; and proxy decision-making by the patient's family. japan in japan, the tokyo high court ruling in the kawasaki case highlighted the need for a law or guidelines on forgoing lst, yet no relevant law has been enacted to date. the mhlw's process guideline issued in has been the most influential document in this area to date. it consists of the main body and commentary, and contains two core elements: ) respecting patient selfdetermination and ) deciding the course of care by the healthcare team (and not by the attending physician alone). the process guideline stipulates that the healthcare team shall make healthcare decisions through repeated discussions with patients and their families, with a particular emphasis on respecting the patient's will. it also specifies that if patients cannot express their will, the healthcare team shall decide the best course of care in light of the family's wishes. the guideline further states that if it is difficult for the healthcare team to decide or reach a consensus with patients or their family, a committee composed of multiple experts should be set up for consultation. in this way, the process guideline puts a significant emphasis on consensus-building among those involved in the patient's end-of-life care. interestingly, the process guideline is silent on the following two points. first, the main body of the process guideline does not define "the terminal stage" or when the patient is considered as terminal or facing the endof-life stage, even though this phrase appears in the very title of the guideline [ ] . the commentary of the guideline does state that there can be different types of terminal stages according to the patient's disease, which could include terminal cancer, chronic disease, cerebrovascular disease, and senility. the healthcare team is instructed to judge when the patient has reached the terminal stage through careful assessment of the patient's condition. however, the guideline does not provide any specific criteria that would define the terminal stage, such as "six months to live". second, it is unclear whether healthcare professionals can avoid criminal or civil liability for forgoing lst if they act according to all of these countries have a national healthcare system covering all citizens. as for differences, the three asian countries have adopted the social insurance scheme for healthcare, for which citizens of these countries must pay some healthcare costs at the time they receive care. meanwhile, england's national healthcare system is run by tax money, and people do not have to pay when they receive medical care. in japan, administrative guidelines with no legal basis have neither direct legal force in courts nor any direct effects on the rights and duties of citizens. the process guideline has no legal basis, and lack penal or administrative sanctions. however, the guideline is widely understood to express the official position of the mhlw concerning end-of-life care, and is therefore often cited in relevant literature as well as in the media. incidentally, in , the mhlw revised the title of the process guideline to "the process guideline for the medical decision-making at the last stage of life (jinsei no saisyu dankai)," because the term "end-of-life (or terminal) care (shumatuski iryo)" was not popular. however, as was the case with the original process guideline, the revised process guideline did not define the phrase "the last stage of life". the mhlw again revised the process guideline in march , both to extend it to home-based care situations, and to include the idea of acp. the guideline. after all, the process guideline is not legally binding because, although the mhlw issues it, it is not supported by any specific law. in korea, the lst decision act was passed in january , and full enforcement of the law began in february . as the name of the act implies, it allows patients with not only cancer but also other medical conditions to receive hospice and palliative care. additionally, it enables people to create ads about withdrawing lst and sets up a national online registry system for storing ads and reviewing them. physicians are granted access to the registry and are therefore able to access an ad, which can inform decision-making. the act also stipulates that a consensus between two or more family members can be regarded as the patient's will when the patient does not have an ad or cannot express his or her wishes. characteristically, the korean act gives a two-fold definition of "end-of-life". "terminal stage", which is used to define the terminal patient, is when a patient is expected to die in several months, and the provision of hospice palliative care is considered appropriate. "the end of life process" refers to situations where a patient's death is considered imminent due to rapid deterioration of his or her condition and the withdrawal of lst is offered as a choice. while clarifying the necessity of hospice care, the korean law is restricted in its application to lst decisions, because an lst decision is only applicable at the very end of a disease process. the act also provides a clause covering a physician's order on lst (life-sustaining treatment plans), which is a physician's order written after consulting a patient about her wishes about end-of-life care. the physician may (or the patient may ask the physician to) inform the patient about diagnosis, end-of-life care options, and lst options, and prepare this document. when a physician places this document in the healthcare record, it takes priority over any existing ad that purports to state the patient's preferences on lst. in a sense, this order resembles the physician order for life-sustaining treatment (polst) used in the various american states. however, the korean document is supposed to be used within hospitals, whereas polst is focused on emergency medical services. as explained above, taiwan has two laws concerning forgoing lst. the hospice and palliative care act allows withdrawing and withholding lst from a terminally ill patient who has a valid ad, which covers the relevant treatment options and designates healthcare proxies; if there is no ad, the patient's family can submit a consent form on their behalf when patients cannot express their will. the phrase "terminally ill patient" refers to a person who is diagnosed by a physician as having an incurable disease or injury and whose death is imminent based on the best available medical evidence. the praa, which was enacted in january and enforced in january , explicitly stipulated that healthcare institutions and physicians are duty-bound to tell patients about their medical conditions, treatments, procedures, medications, and prognoses in order to honour the patient's right to know. it also stipulated that, with a valid ad, lst (including anh) can be withdrawn from not only terminally ill patients but also patients in an irreversible coma, a persistent vegetative state, and from those with severe dementia or other medical conditions specified by the ordinance of the mhw [ ] . although both laws stipulate forgoing lst, the praa is complements the hospice and palliative care act by focusing on a patient's autonomy. as the praa expands the clinical conditions to non-terminally ill patients and includes anh in the range of lst, advance care planning (acp) must be conducted before any ad is made. such legal regulation of acp is new to taiwanese society because, according to the hospice and palliative care act, consensus-building among the involved parties is not a necessary condition to forgo lst. the decision of forgoing lst for terminally ill patients can be made either with a patient's ad or with their families' consent. since taiwan has little experience of acp, this has been a major focus of work since the enactment of praa in : hospital staff are being trained in this area and acp groups, which consist of a physician, a nurse, and a social worker, are being developed. after the enactment of praa in , the development of acp groups in hospital and provision of suitably knowledgeable hospital personnel has been the main tasks of the enforcement in [ ] . in england, there are many legal developments and professional guidance documents pertinent to the issue of forgoing lst, but for the sake of brevity, we focus on the critical legislation and professional guidance. first, incidentally, in , the mhlw revised the title of the process guideline to "the process guideline for the medical decision-making at the last stage of life (jinsei no saisyu dankai)," because the term "end-of-life (or terminal) care (shumatuski iryo)" was not popular. however, as was the case with the original process guideline, the revised process guideline did not define the phrase "the last stage of life". the mhlw again revised the process guideline in march , both to extend it to home-based care situations, and to include the idea of acp. the lst decision act uses the term "advance statement on life-sustaining treatment" for conventional ad. the mca focuses on decisions made about, with and for adults who lack mental capacity. like the preceding common law, the act essentially defines capacity in functional terms [ ] . if a patient has capacity, they may prepare an advance decision to refuse treatment that might otherwise be provided when she or he lacks capacity. such a decision can apply to lst, provided that the decision is written, signed and witnessed, and there is a clear statement to the effect that the decision will apply even if this will put the patient's life at risk [ ] . the mca provides immunity for physicians who withhold or withdraw treatments from their patients if they reasonably believe that an advance decision exists that is valid and applicable to the treatment in question [ ] . however, the act does not require the patient's medical condition to be terminal in order to execute the patient's ad to forgo treatments. the mca also provides for surrogate decisionmaking, through the lpa. the act also empowers the court to appoint a deputy to make decisions, for example, in cases where there is a serious and enduring lack of capacity, such as due to dementia. however, the lpa is the main means by which a patient can appoint someone to decide on his or her behalf. the mca stipulates that an attorney has the power to consent to or refuse lst if the patient has explicitly so empowered the attorney. notably, however, an lpa is required to make decisions in the best interests of the patient; as such, there is always the possibility that an attorney's decision will be challenged on this basis. indeed, for patients who lack an ad or lpa, best interests provide the test as to whether treatmentincluding lstshould be provided. the act enumerates, rather than elaborates, the factors to be balanced in a best interests decision [ ] . the law in this area had evolved considerably since bland, with the courts increasingly emphasising the holistic nature of the assessment, i.e. medical factors, which had been dominant in the ruling, were not the only consideration [ ] . the mca seeks to emphasise the breadth of the test, as have the courtsincluding the supreme court, the now superior english courtin subsequent rulings [ ] . clinicians are required to consult appropriately in determining a patient's best interests. if there is no one close to a patient to provide input into the decision, the act also provides an independent mental capacity advocate (hereafter imca) service, which can support decisionmaking by and for incapacitated patients in their best interests [ , ] . a further recent legal change concerns patients with prolonged disorders of consciousness. bland had required decisions about anh for patients in the pvs to come to court, a requirement which was later extended to patients in the mcs. although that requirement persisted for decades, recent rulings have confirmed that this is not strictly the law: as such, these cases should no longer routinely come to court, although they may do so, for example, if there is disagreement between the relevant parties about what is in the patient's best interests [ ] . the second crucial regulatory source is the gmc guidance on decision-making in end-of-life care. the gmc guidance addresses issues surrounding decisionmaking in end-of-life care and provides decision-making models for patients who can decide as well as those who lack the capacity to do so [ ] . the guideline advises physicians to provide or forgo lst when they judge that these would not be clinically appropriate for a patient. when making such judgments, physicians must weigh the benefits of treatment against the burdens and risks for the patient. furthermore, physicians should carefully take into account not only clinical considerations but also other factors relevant to the circumstances of each patient, including the patient's wishes, values, and feelings. it also emphasises the importance of acp. unlike the mca, the guidance defines the phrase, "approaching the end of life". in this last section, we will discuss the legal and philosophical issues that have emerged from the comparison of regulatory frameworks relating to forgoing lst in japan, korea, taiwan, and england. in order to bring about improvements in these frameworks, particularly concerning end-of-life care, the following five points must be addressed. first, the definition of terminal stage (or phase) can be essential when considering a regulatory framework for forgoing lst. as described in section , the lst decision act in korea and the hospice and palliative care act in taiwan permit patients to forgo treatment only in the terminal stage. it makes the definition of 'terminal stage' significant, not to mention the clinical judgement of when a particular patient is in the terminal stage. the gmc guidance also addresses decision-making for children, including neonates, and young people. further details are provided in the following guidance. the guidance defines the phrase as follows: for the purposes of this guidance, patients are 'approaching the end of life' when they are likely to die within the next months. this includes patients for whom death is imminent (expected within a few hours or days) and those with: (a) advanced, progressive, incurable conditions; (b) general frailty and co-existing conditions that mean they are expected to die within months; (c) existing conditions if they are at risk of dying from a sudden acute crisis in their condition; and (d) life-threatening acute conditions caused by sudden catastrophic events. both korean and taiwanese laws stipulate that a patient is in the terminal stage when his or her condition is diagnosed as irrecoverable and his or her death is imminent with rapid deterioration of the condition. as explained earlier, the korean act distinguishes between two phases of the terminal stage; namely, the terminal stage when patients with irrecoverable conditions are expected to die within several months, and the end-of-life stage when patients are facing imminent death with rapidly worsening conditions. the act only allows the latter patients to elect for withdrawal of lst. meanwhile, the taiwan act interprets the terminal stage more conservatively and considers terminal patients to be those who have been diagnosed as having an incurable disease or injury, and who cannot avoid death shortly based on the best available medical evidence. this definition more or less corresponds to "the end of life stage" in the korean act. regarding the kind of medical conditions to which the law applies, the korean law limits the "terminal stage" to patients with cancer, acquired immune deficiency syndrome (aids), chronic obstructive pulmonary disease (copd), and chronic hepatic disease, as well as other diseases specified by the ordinance of the mhw. patients with these conditions are eligible for hospice palliative care in the terminal stage, while no such limitation exists for patients in the dying stage who are eligible to elect for termination of lst. on the other hand, although there are similar rules about the coverage of palliative care in the taiwanese national health insurance system, the hospice and palliative care act in taiwan does not specify any health conditions for patients in the terminal stage to be eligible for forging lst. in japan, no law stipulates a definition of terminal stage. the mhlw's process guideline avoids providing a definition and only suggests several instances of medical conditions which can be considered as reaching a terminal stage, such as "when a patient's prognosis is predicted to be from a few days to - months in the case of terminal cancer". england also lacks such a stipulation; indeed, lst may be refused, withdrawn or withheld regardless of the patient's life-expectancy. the mca, for example, is not limited to patients in the terminal stage [ ] . the gmc guideline, however, states that patients are "approaching the end of life" when they are likely to die within the next months, which is broader than the korean or taiwanese criteria. we believe that the definition of terminal stage should be neither too narrow nor too wide when specifying the period within which one can choose to withdraw treatment. if the definition is too narrow and the law only applies to patients who are expected to die within a few days or even a few hours, the case for withdrawing lst might not be so compelling, for they will die in a short time in any case. that said, however, there may be clinical (and ethical) reasons for withdrawing treatment, even in such a short period, to ensure that the imposition of treatment does not adversely affect the dying process, and there may also be cultural reasons for doing so, as demonstrated by taiwan's "terminal discharge from hospital". on the other hand, if the definition is too broad, the law might apply to those with incurable diseases such as mnd, end-stage renal disease (esrd), and alzheimer's disease, who may be able to live for a relatively long period if treatmentsuch as artificial ventilation, dialysis, or gastric fistulais continued. however, expanding the definition to include patients with such conditions might give rise to concerns and confusion, particularly as such a definition would potentially include those who are early in the disease trajectory, and therefore not in the "terminal phase" as this is conventionally understood. moreover, patients who are diagnosed with such incurable diseases might feel threatened because the regulatory framework such as law or guidelines would classify them as "terminal patients" who can have their treatments withdrawn. of course, the requirement that the patient must consent might dispel any concerns these patients and their loved ones might havebut we should also be mindful that such patients might feel under pressure to "consent" [ ] . alternatively, a strict definition of the terminal stage could be avoided altogether. if the principle of autonomy or the right of self-determination is considered paramount, then perhaps we may not need to limit forgoing treatment to the terminal stage, as england's mca and taiwan's new law seem to suggest. however, if we adhere to the idea that the patient can choose to have lst withdrawn only at the terminal stage, then a defined set of clinical criteria for "terminal stage" are likely to be required. the revised law deleted these specific names of disease, and only provided the criteria of terminal stage. the revised law was enforced from march, . in the commentary for the process guideline published by the mhlw, the terminal stage is not defined but the following situations are considered as terminal stage: ) a patient's prognosis is predicted to be from a few days to - months in the case of terminal cancer; ) a patient repeats acute exacerbation of chronic disease and falls into poor prognosis; ) a patient will die within months to years as the sequelae of cerebrovascular disease or senile deterioration. likewise, the science council of japan explains in the report that depending on the disease and condition of a patient, terminal stage can be divided into an acute type (e.g., emergency medical care), a subacute type (e.g., cancer), and a chronic type (e.g., senility, vegetative state, and dementia). based on our analysis, one important lesson is that the purpose of defining the terminal stage should be clear. in particular, two relevant objectives for defining the term would be the specification of a period when retreating from aggressive treatments and focusing on palliative care is appropriate, and the determination of a period when the patient or the family can choose to withdraw lst. furthermore, it appears that policymakers and professional societies should be required not only to define the term but also to establish clinical criteria for judging when patients with various conditions are in the terminal stage. forgoing lst for non-terminal patients (e.g., patients with mnd and those in pvs) the second issue is whether to allow patients who are not in the terminal stagebut are suffering from conditions such as mnd or are in a pvsto forgo lst. such patients who are not in the terminal stage can continue living with the assistance of artificial ventilators and anh. our comparison has revealed different positions on withdrawing or withholding lst from these nonterminal patients. the korean act, for example, limits the permissibility of treatment withdrawal to the dying stage, thereby excluding non-terminal patients with pvs or mnd. taiwan's hospice and palliative care act also applies only to terminal patients. however, the newly enacted praa has a broader scope than the preceding act and allows even pvs patients to forgo lst. it should be emphasised here that mnd is not included in the four conditions stipulated in taiwan's new act. england's mca does not have any such restrictions and thus applies to both terminal and non-terminal patients. in japan, the draft ad bill does not mention specific medical conditions that would fall under the scope of the bill; presumably, however, neither the draft ad bill nor the mhlw's process guideline applies to non-terminal pvs or mnd patients. not allowing mnd patients to withdraw lst because they are not terminal seems particularly problematic in places like japan, where tracheostomy with invasive mechanical ventilation (tiv) rates for mnd patients may be the highest in the world [ ] , ranging from . to . % [ ] [ ] [ ] . even if mnd patients require artificial ventilators or anh, they can remain alive if they choose to receive these treatments. if we understand the terminal stage as an incurable and irreversible condition that, regardless of the use or withdrawal of lst, will result in death within a relatively short time [ , ] , then these mnd patients are not terminal. in japan, however, although the mnd patients' choice of withholding lst seems to be respected [ ] , detaching artificial ventilators once they have been initiated is next to impossible [ ] and physicians who detach them from mnd patients are highly likely to be prosecuted [ , ] . in such circumstances, mnd patients can choose either to receive or not to receive lst, knowing that this cannot later be withdrawn even if they desire it. in these asian countries, whether or not to allow pvs and mnd patients who are not in the terminal stage to forgo lst remains controversial. england has also struggled with the question of whether lst can be withdrawn from mcs patients. the courts initially appeared reluctant to authorise the withdrawal of anh from such patients, although they have become more willing to countenance this, at least where there is compelling evidence that the patient him-or herself would not consent to such treatment [ , ] . whether the law in this jurisdiction does enough to respect the autonomy of (now) incapacitated patients nevertheless remains a live issue [ ] . in most western countries including england, the common understanding is that there is no morally significant difference between withholding and withdrawing treatments [ , , ] . thus, withdrawing treatments is permitted in circumstances in which withholding treatments is permitted [ ] . in contrast, such a view is not necessarily the norm in asia. according to a survey of physicians who manage patients in intensive care units (icus) in countries and regions in asia, the proportion of respondents who felt that withholding and withdrawing lst were ethically dissimilar was % on average [ ] . by country or region, the largest was % in pakistan, followed by % in bangladesh, while the lowest was % in singapore, followed by % in hong kong. in japan, % responded that withholding and withdrawing were ethically dissimilar; the percentages were % in korea and % in taiwan. for example, in clinical settings in japan, the general idea is that withdrawing lst is ethically more difficult than withholding it, and that withdrawing lst is considered "unacceptable" [ , ] . legal scholars in japan are also split on the legality of withdrawing lst. for instance, according to one legal scholar, "no medical professional has been prosecuted for removing the artificial ventilator or the gastrostomy feeding tube from a terminally-ill patient" since the publication of the process guideline by the mhlw in [ , ] , implying that withdrawing lst is not illegal if one follows the protocol set by the process guideline. on the other hand, some scholars think that, whereas withholding treatment can be regarded as an instance of omission, it is difficult to view withdrawing as such, and thus claim that withdrawing and withholding treatment is not necessarily legally equivalent [ , ] . thus, while an absolute consensus exists regarding the legal status of withholding lst, differing views are held on withdrawing lst, not only among healthcare professionals but also among legal scholars. several factors may underlie the difficulty of equating withholding lst with withdrawing it. for example, a qualitative survey of emergency physicians in japan conducted between and found the following factors to be motivations for avoiding the withdrawal of artificial ventilators: ) fear of criminal prosecution and concern about unwanted media exposure; ) concern for the feelings of the patient's family; ) physicians' psychological barriers to shortening patients' lives by withdrawing lst because they regard withdrawing lst to be an act and not an omission; and ) medical factors in the acute phase of a severe condition, including the uncertainty of treatment outcome (i.e., they cannot completely deny that the patient may recover) [ ] . the fact that there is no law in japan permitting the withdrawal of lst may also be a background factor. in summary, unlike their counterparts in western countries, many healthcare professionals, as well as some legal scholars, in asian countries still find it difficult to equate withholding lst with withdrawing lst. moreover, as the above discussion suggests, it may be necessary to address the feelings of healthcare professionals adequately when considering a legal framework for endof-life care. fourth, our comparative analysis revealed that the role of the family (or, indeed, other loved ones) in england differs from those in the three asian countries. although the family plays a significant role in end-of-life decisionmaking in all three asian countries, the legal stipulations concerning their role are slightly different. in taiwan, the hospice and palliative care act stipulates the role of the family in end-of-life decision-making. the act states that patients may nominate a medical proxy in advance and that the designated family member by law may consent to forgo lst on behalf of terminally ill patients if their will cannot be expressed and no ad has been signed. the family members designated by law include (in descending order of closeness): spouses, adult children and adult grandchildren, parents, adult siblings, grandparents, great-grandparents or collateral consanguinities within the third degree, lineal relatives by affinity within the first degree. the law states that one designated family member should sign the consent form for forgoing lst. if there are disagreements concerning forgoing lst among family members, the consent of the closer family member should be prioritised following the order of closeness. in korea, the lst decision act defines two aspects of surrogate decision making, which involves family members verifying the patient's intention by witnessing (article ) and deciding for the patient (article ). the act also sets out the differing family input in each of the cases. the family members considered relevant for witnessing are: ) spouse, ) linear descendants, such as children and grandchildren, ) linear ascendants, such as parents and grandparents, and ) siblings, if there is no one corresponding to )- ). as for the witnessing, the requirement for verification is such that two family members need to witness the patient expressing his or her preferences for lst. however, the family members are different in the case of surrogate decision making, for the decision must be made by agreement of all relevant members. family members, in this case, include: ) spouses, ) lineal descendants and ascendants with one degree of kinship (i.e. parents and children,) ) lineal descendants and ascendants with two degrees of kinship (i.e. grandparents, and grandchildren) ) siblings, if there is no one corresponding to )- ). thus, the korean act and the taiwan act differ, both in how they rank family members and how the family's will is decided when there is no consensus. in japan, families have conventionally made medical decisions on behalf of patients [ , ] . the draft ad bill contains no provisions about the family's ability to forgo treatment for patients. the process guideline, however, grants this role to the family of the patient, especially when the patient is incompetent and cannot express his or her will. in that case, the family either presumes the patient's will or, when that is not possible, the healthcare team discusses with the family what will be in the patient's best interest. interestingly, the commentary of the process guideline explains that 'family' is not restricted to family members as defined by law, but can include people like trusted friends of the patient and those who have supported the patient at the end of their life. in england, the mca does not specify who may or may not be an attorney (although he or she must be an adult, i.e. of years or older). thus, unlike the three asian countries mentioned above, legally speaking, family members are not automatically authorised to make decisions about treatment on behalf of the patient who has lost his or her decision-making capacity. the legal forms of lpa list people whom the patient trusts and know well as examples of an attorney, i.e., spouses, partners, adult children, or good friends [ ] . where the patient has not made an lpa, the relevant decision-maker is still required to consult those caring for the patient or interested in his or her welfare; no limit is placed on who, precisely, should be consulted. the general rule is that, when a proxy makes decisions on behalf of the patient, it is crucial to represent the patient's prior wishes or his or her best interests. based on our analysis, we believe that the following issues regarding the role of the family need careful examination: ) whether or not family members are the best proxies or advocates for incompetent patients [ ] ; and ) whether or not there is a chance that family members may prioritise their own interests over those of the patient because they want to reduce financial or other types of burdens or even to benefit financially, for example through inheritance [ ] . in addition, there are other issues such as the definition and scope of family [ ] . , compared with england, the three asian countries traditionally place a greater emphasis on families and communities than on individuals. thus, patients will sometimes prefer to have their family and physician decide the course of their treatments rather than doing so themselves; such familybased medical decision-making is said to be an expression of filial piety [ ] [ ] [ ] [ ] [ ] . further studies will be needed to determine how a suitable framework for proxy decision-making can be established in these asian countries. decision-making in the case of a patient without family lastly, our comparative analysis found that decisionmaking with, about or for an incompetent patient who lacks family or close friends may pose a severe problem. recently, the significant increase in dementia patients has become a global issue; as of , . million people worldwide are living with dementia, and nearly million new cases emerge every year [ ] . dementia poses an enormous financial burden both on society and the individual, as well as giving rise to such issues as stigma and social isolation [ ] . in the context of endof-life decision-making, the following question is especially important: who should make, or contribute to, decisions, when patients with dementia who lack family or close friends are unable to make treatment decisions for themselves? in the three asian countries highlighted here, no specific regulatory framework covers such cases. however, japan's process guideline recommends the establishment of a committee consisting of various experts to deal with such complicated cases. in england and wales, the mca makes provision for those incapacitated adults who lack close family or friends, namely, the imca service. the purpose of the imca service is to represent and support particularly vulnerable people who have no family or friends and who lack the capacity to make important decisions about (providing, withholding, or withdrawing) serious medical treatments and changes in accommodation [ ] . clinicians must involve an imca when a decision about serious medical treatments is to be made in relation to such patients. an imca will interview or meet in private with the person who lacks mental capacity and obtain the views of professionals and anybody else who can provide information about the wishes, feelings, beliefs, or values of the person. they work to determine any alternative options, may examine relevant records, and then must write a report on their findings. the number of imca referrals regarding serious medical treatments (including withholding or withdrawing anh) was between april and march [ ] , but has been increasing every year since . among these, patients with dementia accounted for % ( referrals). the imca service of england and wales is unique among the four countries compared in this article [ ] . we suggest that when lawmakers and policymakers make regulatory frameworks concerning end-of-life care, they should discuss not only ads (including those encompassing attorneys) and proxy decision-making by the patient's family, but also make provision for cases in which people who lack ads, family, or close friends lose the capacity to make such decisions. the reason for this is that there will always be those "unbefriended patients" who cannot be helped by any of the standard legal mechanisms that protect and promote autonomy through the use of ads, family, friends, or courtappointed guardians [ ] . in such cases, establishing a service such as england's imca is one option, but the use of clinical ethics support services, such as hospitalbased committees, may be another option, as suggested by japan's process guideline. as one study has shown, ethics consultation may be useful for resolving ethical dilemmas that involve the forgoing of lst [ ] . some limitations of the present study should be noted. because our main focus was on laws and guidelines, our see (a lineal relative by affinity refers to a lineal relation of his or her spouse (such as a husband's or wife's parents or grandparents), and a spouse of his or her lineal relation (a husband or wife such as a child or a grandchild)) for different interpretations of family members in korea's and taiwan's acts. england's mca does not give such authority to family members both on decision-making and consent on behalf of individuals. findings may not fully reflect the actual practice of healthcare professionals in each of the four countries. thus, the actual practices in each country may be more similar to that in other countries, even though legal and other stipulations may suggest otherwise. furthermore, we could not compare data surrounding withdrawal of lst among these four countries due to the lack of yearround data from each [ ] [ ] [ ] [ ] . future studies should assess the actual practice(s) surrounding end-of-life care of healthcare professionals and psycho-spiritual care in end-of-life care in the four countries. additionally, in a pandemic or disaster situation such as the current covid- pandemic, ethically complex issues such as the allocation of scarce healthcare resources may adversely affect end-of-life care. future research could usefully address such situations [ ] . this study compared regulatory frameworks governing forgoing lst in japan, korea, taiwan, and england, and presented five important legal and philosophical points: ) the importance of defining the terminal stage and associated criteria for clinical judgment; ) the importance of discussions on withdrawing lst in pvs or mnd patients who are not terminal; ) the importance of (re)considering any moral and legal differences between withholding and withdrawing treatments; this is disputed particularly in asian countries; ) the importance of ascertaining the family's role in end-of-life decisionmaking; and ) the importance of devising ways to deal with incompetent patients who lack family or ads. focusing on these five points will be important for the establishment of better end-of-life regulatory frameworks for these four countries and others. abbreviations decisions on life-sustaining treatment for patients in hospice and palliative care or at the end of life right to die' program goes into effect laws & regulations database of the republic of china. patient right to autonomy act mental capacity act the hospital "the physician withdrew treatments" after switching off artificial ventilators from seven patients; they died "ethically problematic the suspicious death: the hospital in toyama prefecture "seven patients euthanized" -year-surgeon switched off artificial ventilators from patients removing artificial ventilators in the imizu municipal hospital: two physicians not prosecuted the guideline on medical decision process at the final stage of life the japanese association for acute medicine. the guideline on end-of-life care in acute care and intensive care the japan medical association. the guideline on end-of-life care the guideline on decision making process of elderly care: an adoption of anh removing an artificial ventilator: als patient requested to hospital, but the hospital director "can't answer the ripple spreads to the request for death flame of life, mind is free (living a patient - ) the law on end-of-life care: background and implication. in: presentation for international workshop: ethics at the end-of-life end-of-life care in korea: current situation biomedical ethics policy in korea: characteristics and historical development debated on end-of-life care and the legalization of "natural death" in taiwan: the practice of terminal discharge and the hospice and palliative care act the law and ethics of end-of-life care in taiwan: on the practice of terminal discharge and a criminal court case concerning the hospice and palliative care act promotion of advance care planning in taiwan palliative medicine and the hospice movement in taiwan the legislation of end-of-life care in taiwan: the passage of "patient's self-determination act london: hodder & stoughton end of life trust -v-bland [ ] wlr part death with dignity and end of life care practice direction e: applications relating to serious medical treatment withholding and withdrawing lifeprolonging medical treatment: guidance for decision making withholding and withdrawing -guidance for doctors treatment and care towards the end of life: good practice in decision making british medical association, the resuscitation council (uk) and the royal college of nursing. decisions relating to cardiopulmonary resuscitation rd edition, st revision british medical association and royal college of physicians. clinicallyassisted nutrition and hydration (canh) and adults who lack the capacity to consent: guidance for decision-making in england and wales adult: refusal of treatment re ak (medical treatment: consent) [ ] flr . . department for constitutional affairs. what is the mental capacity act ? in: mental capacity act code of practice houses of parliament, parliamentary office of science and technology. postnote no. : mental capacity and healthcare aintree university hospitals nhs foundation trust v james release: regarding the revised guideline on medical decisionmaking process at the final stage of life debates on end-of-life care and the legalization of "good death" in taiwan: the hospice and palliative care act and the patient self-determination act mental capacity act mental capacity act clarifying the best interests standard: the elaborative and enumerative strategies in public policy-making re a (male sterilisation department for constitutional affairs. what is the new independent mental capacity advocate service and how does it work? in: mental capacity act code of practice an exposition of the mental capacity act in britain: focusing on the lasting powers of attorney and the independent mental capacity advocate service - years: guidance for all doctors japan amyotrophic lateral sclerosis association "we are against the bill to refuse the treatment needed to sustain life the survey report about the end-of-life care with als patients of the als physicians in japan mechanical ventilation in amyotrophic lateral sclerosis: a cross-cultural perspective clinical features of als in japan from the registration system of intractable diseases tracheostomy with invasive ventilation for als patients: neurologists' roles in the us and japan regarding withdrawal of artificial ventilator. home health care people intractable dis some critical topics for further discussion on palliative medicine in amyotrophic lateral sclerosis (als) the yokohama district court applied inducing or aiding suicide or homicide with consent to the mother. regarding withdrawal of artificial ventilator from her child with intractable disease the place of wishes and feelings in best interests decisions: wye valley nhs trust v mr b deciding to forgo life sustaining treatment: a report on the ethical, medical, and legal issues in treatment decisions part generation of the doctrine in the united states: conditions for not receiving life sustaining treatments withdrawing and withholding life-sustaining treatments in withholding and withdrawal of lifesustaining treatments in intensive care units in asia, supplementary online content efigure attitudes of japanese and japanese-american physicians towards life-sustaining treatment end of life care and legal issues: a comparison with the united states legal issues on medical interventions in terminally ill patients the supreme court precedent: criminal case third small court precedent on kyodo hospital case: the supreme court withdrawal of mechanical ventilation from dying patients at emergency and critical care facilities in japan: a qualitative study with physicians report and recommendation of legal improvement on supporting decision making and proxy decision making in medical practice outline of a law on proxy consent regarding treatments for persons without capacity of medical consent lasting power of attorney forms the kawasaki kyodo hospital case appeal trial decision. hogaku shimpo the theory of autonomy support in the adult guardianship system in england and wales. kyoto: minerva shobo preferences for advance directives in korea cultural diversity at the end of life: issues and guidelines for family physicians family experience with difficult decisions in end of life care which factors have the greatest influence on bereaved families' willingness to execute advance directives in taiwan? cancer nurs survey of the general public's attitudes toward advance directives in japan: how to respect patients' preferences fact sheet: dementia world alzheimer report : the global impact of dementia independent mental capacity advocacy service: th annual report mental capacity act /mental capacity act code of practice unbefriended and unrepresented: better medical decision making for incapacitated patients without healthcare surrogates effect of ethics consultations on nonbeneficial life-sustaining treatments in the intensive care setting: a randomized controlled trial decision-making on withholding or withdrawing life support in the icu: a worldwide perspective end-of-life decision-making in six european countries: descriptive study euthanasie en andere medische beslissingen rond het levenseinde euthanasia laws in benelux's three countries -comparison and task the importance of addressing advance care planning and decisions about do-not-resuscitate orders during novel coronavirus (covid- ) publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we would like to thank proedit japan which provided professional english proofreading services. all authors contributed to the conception and design of this paper. mt wrote the draft of the paper and sk, il, yc and rh made changes to this draft, with the final draft being prepared by mt. all authors read and approved this final draft. this research was supported by the fondation brocher (swizterland), the sasakawa memorial health foundation (japan), the uehiro foundation on ethics and education (japan) and by the global research network program through the ministry of education of the republic of korea and the national research foundation of korea (nrf- s a a ). the funder did not play a role in the study design, in the collection, analysis and interpretation of research or in writing the manuscript. all materials that support our findings of this study are publicly available. professor richard huxtable is a member of the editorial board of bmc medical ethics and a member of various ethics committees, including that of the british medical association; the views stated in this article are those of the authors and should not be taken to represent those of any organisation with and for whom they work. other authors declare that they have no competing interests. key: cord- - e fkafa authors: jung, f.; krieger, v.; hufert, f.t.; küpper, j.-h. title: herd immunity or suppression strategy to combat covid- date: - - journal: clinical hemorheology and microcirculation doi: . /ch- sha: doc_id: cord_uid: e fkafa some months ago, severe acute respiratory syndrome coronavirus (sars-cov- ) broke out in wuhan, china, and spread rapidly around the world. some states, such as the netherlands, germany, great britain, sweden and the usa initially focused on keeping the restrictions for economy and society as low as possible. the responsible authorities were of the opinion - and still are e.g. in sweden - that it is sufficient enough to protect particularly vulnerable persons such as the elderly or people with pre-existing conditions. the idea behind this is that as soon as to percent of the population is infected with a pathogen, a so-called “herd immunity” has developed. however, the increasing numbers of deaths and modelling studies showed the expected overload of the hospitals. therefore, most countries decided for a temporary lockdown with the exception of sweden. based on the number of the total population, three times more people died from covid- in sweden ( deaths per million inhabitants) compared to germany ( deaths per million inhabitants). the comparison sweden versus taiwan is even worse because times more people died in sweden based on the number of the population ( deaths per million inhabitants). in the face of the lack of an antiviral treatment and the lack of a protective vaccine one must state taiwan has made the best out of the pandemic situation whereas sweden failed completely. each state is currently pursuing its own strategies to cope with the sars-cov- pandemic that started in december in wuhan, china. on january , the first imported case appeared in the usa and on january , sars-cov- emerged globally in many other countries including europe where first cases were reported from france [ ] [ ] [ ] [ ] . some states, such as the netherlands, germany, great britain, sweden and the usa initially focused on keeping the restrictions for economy and society as low as possible. mass gatherings were initially neither prohibited nor were there strict regulations on social distancing or hygiene rules. the responsible authorities were of the opinion -and still are e.g. in sweden -that it is sufficient enough to protect particularly vulnerable persons such as the elderly or people with pre-existing conditions. for the rest of the population, infection with the virus is certainly accepted, and even sought. the idea behind this is that as soon as to percent of the population is infected with a pathogen, a so-called "herd immunity" has developed. the procedure was as follows: the virus was taiwan (orange line) data were obtained from the following source: ecdc (https://www.ecdc.europa.eu/en/publicationsdata/download-todays-data-geographic-distribution-covid- -cases-worldwide). the data obtained from the above listed sources is put in to a context described herein with. our policy regarding the information format is prioritizing open source and free software. we therefore make all data retrieved and analyzed hereby available at corona.milliways.online. to be suppressed only by gradual measures so that enough people could become infected. the strategy was an attempt to build up herd immunity so that "enough of us who will only show mild symptoms can become immune". this was the statement of sir p. vallance, the british governments' chief scientific adviser on march , . however, after modelling studies of the epidemic by imperial college london showed the expected overload of the hospitals. as a consequence, the british government abruptly changed the strategy march and decided for a temporary lockdown. the netherlands and germany also left herd immunity strategy to cope covid- . figure shows the clear reaction of the lockdown for germany: the new infections per day in relation to the population of the respective country were continuously and significantly decreasing. sweden followed a strategy that is almost equivalent to the herd immunity. restaurants, shops and fitness studios are also open. border closures have not taken place. only secondary schools and universities have been closed. older people are advised to avoid social contacts. those who feel symptoms of a possible covid- disease should be placed in home quarantine. this figure clearly shows two findings. the course of the pandemic and the spread of the virus in those countries from day ( / / ) until day ( / / ). the course of the sars-cov- pandemic in sweden could be interpreted that a plateau has been reached. however, the further development of the situation remains to be elucidated. in any case, the swedish health authority folkhälsomyndigheten was wrong when it reported that most new cases occurred on april . that was when the curve had reached its highest point. the further course of the curve indicates an ongoing increase, although the dynamic has slowed down. however, it is possible that a plateau-phase has been reached. in contrast, fig. . cumulative case numbers of infections in sweden (blue line), germany (black line) and taiwan (orange line) in relation to mill people data were obtained from the following source: ecdc (https://www.ecdc.europa.eu/en/publicationsdata/download-todays-data-geographic-distribution-covid- -cases-worldwide). the data obtained from the above listed sources is put in to a context described herein with. our policy regarding the information format is prioritizing open source and free software. we therefore make all data retrieved and analyzed hereby available at corona.milliways.online. the cumulative graph of daily infections is still increasing in sweden while in germany almost, and more importantly in taiwan, a plateau seems to be reached since many days (see fig. ). swedens' advantages in fighting the pandemic are the high proportion of single households in large cities, the sparse population outside the conurbations around stockholm (more than a third of those infected and more than half of those dying of covid- are from the stockholm area), gothenburg and malmö, and the generally high level of prosperity. based on the number of the total population, three times more people died from covid- in sweden ( deaths per million inhabitants) compared to germany ( deaths per million inhabitants). the comparison sweden versus taiwan is even worse because times more people died in sweden based on the number of the population ( deaths per million inhabitants). the rise in the curve of normalized mortality rates for sweden is still much steeper than for germany (see fig. ), so that the mortality rate is likely to drift even further apart (unless sweden takes significant countermeasures). this shows how effective the rigorous implementation of protective measures in taiwan has been in preventing both infection and death. unlike the european countries, taiwan reacted very early [ ] ; data were obtained from the following source: ecdc (https://www.ecdc.europa.eu/en/publications-data/download-todaysdata-geographic-distribution-covid- -cases-worldwide). the data obtained from the above listed sources is put in to a context described herein with. our policy regarding the information format is prioritizing open source and free software. we therefore make all data retrieved and analyzed hereby available at corona.milliways.online. has rapidly produced and implemented a list of at least action items including border control from the air and sea, case identification (using new data and technology), quarantine of suspicious cases, proactive case finding, resource allocation (assessing and managing capacity), reassurance and education of the public while fighting misinformation, negotiation with other countries and regions, formulation of policies toward schools and childcare, and relief to businesses [ ] . these measures were so effective that only patients died from a total of confirmed infections in a population of more than million people." it is currently unclear how long immunity lasts after sars-cov- infection. there are four other corona viruses circulating in the world population causing common cold, pneumonia and bronchitis. however, not much is known about cross protection. antibodies to sars-cov- have been described to be detected up to years after infection, this might render people to be susceptible again for reinfection after three years [ ] . a time-limited sars-cov- immunity would make it necessary that reinfection occurs to keep up herd immunity and the infestation of a country may take even longer than individual immunity. however, there are no data on the clinical course of re-infected people and the impact t-cell immunity to prevent severe clinical outcome. in the face of the lack of an antiviral treatment and the lack of a protective vaccine one must state taiwan has made the best out of the pandemic situation whereas sweden failed completely. a lot of patients who survived the severe covid- are suffering from severe sequelae especially after multiple thrombotic processes in the vascular system [ ] involving lung, liver, spleen and kidney [ ] [ ] [ ] and other organs. today, prevention is the only and best tool we have to prevent severe covid- cases and unnecessary late sequelae or deaths. the motto must be prevention first, since we all have only one life. a recent simulation study by the universities of uppsala and stockhom [ ] illustrated, that if the current measures will be continued (day ), , people in sweden would die of corona virus. if social distancing were to be implemented consistently, the study shows that the figure would be just over , . rapidly increasing cumulative incidence of coronavirus disease (covid- ) in the european union/european economic area and the united kingdom first cases of coronavirus disease (covid- ) in france: surveillance, investigations and control measures potential scenarios for the progression of a covid- epidemic in the european union and the european economic area how we should respond to the coronavirus sars-cov- outbreak: a german perspective response to covid- in taiwan. big data analytics, new technology, and proactive testing duration of antibody responses after severe acute respiratory syndrome covid- -related severe hypercoagulability in patients admitted to intensive care unit for acute respiratory failure contrast enhanced ultrasonography (ceus) to detect abdominal microcir-culatory disorders in severe cases of covid- infection: first experience inflammation in deep vein thrombosis: a therapeutic target? incomplete echocardiographic recovery at months predicts long-term sequelae after intermediate-risk pulmonary embolism. a post-hoc analysis of the pulmonary embolism thrombolysis (peitho) trial intervention strategies against covid- and their estimated impact on swedish healthcare capacity key: cord- -fmnle iy authors: cheng, hao-yuan; li, shu-ying; yang, chin-hui title: safety practices and appropriate infection prevention mitigate potential staffing shortage date: - - journal: j formos med assoc doi: . /j.jfma. . . sha: doc_id: cord_uid: fmnle iy nan letter to the editor safety practices and appropriate infection prevention mitigate potential staffing shortage dear editor, in the letter from chun-yu lin et al., the authors misleadingly linked healthcare worker (hcws) travel restrictions with the preservation of human resources for the healthcare system. the healthcare system becomes overwhelmed when coronavirus disease (covid- ) spreads widely in the community. when that occurs, the highest infection risk will come from community exposure, not international travel. therefore, for hcws, universal precaution with appropriate personal protective equipment (ppe) is the most appropriate practice to prevent the transmission between hcws and their patients. the central epidemic control center had provided comprehensive guidelines for the use of appropriate ppe and corresponding infection control protocols for covid- . since march , taiwan tested > hcws for covid- ; none were infected. contact tracing study in taiwan also showed low infection risk among hcws. these data suggest that compliance with infection prevention and control measures are key to the preservation of precious healthcare workforce. because of the covid- pandemic, many countries, including taiwan, implemented border control and warned their citizens against nonessential international travel. however, travel restrictions could not sustain for long; reopening is inevitable. in time, universal quarantine for all travelers may need to be refined to preserve public health and healthcare workforce. adjusting quarantine measures by risk for individual countries or professions will be a critical issue for policymakers as we begin life under a "new normal". currently, no consensus has been reached in the use of serological tests for case investigation and contact tracing because of their poor sensitivity and specificity. most covid- patients in taiwan had been detected within one week after their symptom onset and contact tracing conducted within h. considering such good timeliness, pcr test might be sufficient for identifying patients. investigations into exposure condition had often been limited by poor patient recall. however, studies have shown that the exposure with the highest risk occurred in household contacts and the common transmission route, , providing evidence in policy-making to control outbreaks. additional behavior studies may have only marginal effects. more comprehensive behavior studies may have only marginal effects. in taiwan, we took early aggressive approaches in containing the first wave of the pandemic because so much was unknown of covid- . the more we learn from the current pandemic, the more accurate we could be in preparing for the second wave of disease. scientific-evidence-based policy development would be of great importance to minimize collateral health, societal, and economic damages. escalating infection control response to the rapidly evolving epidemiology of the coronavirus disease (covid- ) due to sars-cov- in hong kong contact tracing assessment of covid- transmission dynamics in taiwan and risk at different exposure periods before and after symptom onset epidemiology and transmission of covid- in cases and of their close contacts in shenzhen, china: a retrospective cohort study the authors have no conflicts of interest relevant to this article. key: cord- -hslnkv p authors: ke, kai-yuan; lin, yong-jun; tan, yih-chi; pan, tsung-yi; tai, li-li; lee, ching-an title: enhancing local disaster management network through developing resilient community in new taipei city, taiwan date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: hslnkv p large-scaled disaster events had increasingly occurred worldwide due to global and environmental change. evidently, disaster response cannot rely merely on the public force. in the golden hour of crisis, not only the individuals should learn to react, protect themselves, and try to help each other, but also the local school, enterprise, non-government organization (ngo), nonprofit organization (npo), and volunteer groups should collaborate to effectively deal with disaster events. new taipei city (ntpc), taiwan, was aware of the need for non-public force response and therefore developed the process of enhancing local disaster management networks through promoting the resilient community since . the concept of a resilient community is to build community-based capacity for mitigation, preparedness, response, and recovery in an all-hazards manner. this study organized the ntpc experience and presented the standard operation procedure (sop) to promote the resilient community, key obstacles, maintenance mechanism, and the successful formulation of the local disaster management network. the performance of the promotion was evaluated through a questionnaire survey and found that participants affirmed the positive effect of building community capacity through the entire process. in general, the resilient community as the center of the local disaster management work is shown promising to holistically bridge the inner/outer resources and systematically respond to disaster events. global warming and environmental changes have led to more frequent and extreme weather events and resulted in disasters of a greater magnitude worldwide. serious disaster events accompanied by significant casualties repeatedly occurred, such as the great hanshin earthquake in japan, the chi-chi earthquake in taiwan, the indian ocean earthquake and tsunami, hurricane katrina in the usa, sichuan earthquake in china, typhoon morakot in taiwan, as well as tohoku earthquake and tsunami in japan. exposure of persons and assets in all countries has increased faster than vulnerability has decreased, thus generating new risks and a steady rise in disaster-related losses, especially at the local and community level. the impact could be short, medium, and long term and appears in terms of economic, social, health, cultural, and environmental aspects [ ] . in the great hanshin earthquake, during the early stage, . % of those in danger survived by themselves, . % escaped with assistance by family members, . % by neighbors/friends, and . % by passerby [ ] . only less than . % of those in need of help were saved by the public in the great hanshin earthquake, during the early stage, . % of those in danger survived by themselves, . % escaped with assistance by family members, . % by neighbors/friends, and . % by passerby [ ] . only less than . % of those in need of help were saved by the public force. this investigation indicated that, in such a great-scaled disaster, public force usually could not timely reach all the affected areas. therefore, the community must be resilient enough to respond by themselves and help each other in the golden hour of crisis events. community resilience refers to the capacities and capabilities of a human community to "prevent, withstand, or mitigate" any traumatic event [ ] . to strengthen community resilience, not only the residents but also neighboring stakeholders, no matter the public sector or private sector, units, or individuals, should join together to form a local disaster management network. it is not easy for the community to organize such a network by itself; hence, the government must invest funding and resources to accomplish this goal. many studies have shown that to deal with disasters, whether pre-disaster [ , ] , in-disaster [ ] , or post-disaster [ ] , awareness raising [ ] and capacity building [ ] are of significant importance, especially at the community level. this study aims to present how new taipei city (ntpc) government, taiwan, integrated the resources at the local government level and enhance the local disaster management by building a significant amount of resilient community, and begins with why the promotion of resilient community is necessary and how the promotion links to the local disaster management network. the performance is assessed through a questionnaire survey. two successful cases of community operation are introduced. from the ntpc government's angle, its experience from nowhere to somewhere is investigated and key obstacles, as well as solutions, are finally identified. new taipei city, taiwan, covers an area of km with a population of million. there are districts and villages under ntpc authority. districts can be categorized into types, i.e., in the urban areas, in the rural areas, and in urban-rural areas. geologically, ntpc is extremely vulnerable to earthquakes due to the direct pass-through of active shanchiao fault from the southwest to the north-east. from a topographical perspective, % of ntpc is the mountainous area (partly covered by tatun volcano), and the entire coastline is km long, which means ntpc is prone to geohazards such as debris flows, landslides, volcano eruptions, and tsunamis. flooding is another disaster event happening frequently due to annual typhoon and torrential rain. furthermore, two nuclear power plants are situated in ntpc, implying possible nuclear hazards ( figure ). according to the report by the national fire agency, ministry of interior, taiwan [ ] , a total of , (partly) collapsed buildings, , casualties, and , citizens in need of shelter are likely to happen if a large earthquake of scale . occurred in the center of taipei basin. with such kind of catastrophic damage, the public force is unlikely to give support for all affected areas fully and timely. more assistance from private sectors or citizens is necessary, especially those in or nearby the disaster hotspots. ntpc's disaster management system can be divided into three levels, i.e., local government, district office, and community, from the top down. ntpc government was aware of the complex and hazard-prone environment, as well as the abovementioned potential damage which cannot rely on merely the government's capacity. therefore, the government thought of enhancing the local disaster management network through matching cooperation between the local units and individuals. to do so, the promotion of the resilient community was considered as the cornerstone. seven standardized steps were taken to develop a resilient community in ntpc as follows [ ] . stakeholders in the resilient community include the public sector, community residents, and at least one expert in the disaster management field. to coordinate the resilient community promotion, the start-up meeting is hosted. in the meeting, it is vital to make sure the key person in the community, usually the village chief or community committee chairman, understands the benefit of the resilient community and has the willingness to cooperate in the future activities to be hosted. to encourage community participation, it is necessary to arouse public interest through the activation workshop in which the invited expert would give the lecture on the resilient community. because not all the community had experienced a serious disaster event, the lecture material usually includes not only the concept of the resilient community but also some case studies about disaster scenarios and associated casualties in taiwan or worldwide. successful cases of resilient community operation were also delivered to construct the vision and inspire the residents' participation in future activities. all lecture materials are prepared for the layperson rather than for an expert in order to ensure the lecturer and participants are on the same page. there has to be a broader and more people-centered preventive approach to disaster risk. disaster risk reduction practices need to be multi-hazard and multi-sectoral, inclusive, and accessible to be efficient and effective [ ] . therefore, community residents are invited to jointly investigate the environment. accompanied by experts, residents learn to identify potential/historical disaster hotspots and resources, such as shelter, convenience stores, and public facilities, useful for responding to the disaster event. after the site survey, all participants will furtherly discuss associated strategies through following minor steps ( figure ): sorting photo: during the site survey, photos are taken and printed. participants are asked to sort out the photos into two categories, i.e., disasters hotspot and resource points. mapping photo: those photos sorted in the previous step are pasted on the aero map with stickers near the photo. if the photo is a disaster hotspot, its condition, such as the location and cause/effect of the potential disaster is written down on the stickers; if the photo is a resource point, its function is described. strategy discussion: with possible disaster conditions and resource points at hand, the expert will help participants discuss strategies to deal with issues from the perspective of the individual, the community, and the local government level. for example, trash sometimes jams the gutter and causes flooding; therefore at the individual level, every resident should be made aware of not dropping trashes in the gutter; at the community level, residents should team up to clean the gutter regularly especially before the flooding season; at the local government level, district office can ask the cleaning contractors to dredge the cutter or provide the community with equipment needed to clean it. local enterprises and schools can be invited to discuss their role as outer resources to help the community respond to disasters. . experience sharing: the goal of this workshop is to finalize valid strategies mainly by the community; therefore, resident representatives are asked to report the discussed strategies to all the participants and try to reach consensus. aware of not dropping trashes in the gutter; at the community level, residents should team up to clean the gutter regularly especially before the flooding season; at the local government level, district office can ask the cleaning contractors to dredge the cutter or provide the community with equipment needed to clean it. local enterprises and schools can be invited to discuss their role as outer resources to help the community respond to disasters. . experience sharing: the goal of this workshop is to finalize valid strategies mainly by the community; therefore, resident representatives are asked to report the discussed strategies to all the participants and try to reach consensus. to efficiently carry out strategies in the previous step, the resilient community response team is organized. the typical structure of the response team is shown in figure . it contains five divisions, namely, patrol, evacuation, rescue, medical, and logistics, with their general function as table . the commander, usually the village chief or community committee chairman, supervises the deputy commander and executive secretary, as well as oversees outsourcing and leads the team. the deputy commander supervises the heads of every division and the executive secretary assists the commander and the deputy commander. to efficiently carry out strategies in the previous step, the resilient community response team is organized. the typical structure of the response team is shown in figure . it contains five divisions, namely, patrol, evacuation, rescue, medical, and logistics, with their general function as table . the commander, usually the village chief or community committee chairman, supervises the deputy commander and executive secretary, as well as oversees outsourcing and leads the team. the deputy commander supervises the heads of every division and the executive secretary assists the commander and the deputy commander. aware of not dropping trashes in the gutter; at the community level, residents should team up to clean the gutter regularly especially before the flooding season; at the local government level, district office can ask the cleaning contractors to dredge the cutter or provide the community with equipment needed to clean it. local enterprises and schools can be invited to discuss their role as outer resources to help the community respond to disasters. . experience sharing: the goal of this workshop is to finalize valid strategies mainly by the community; therefore, resident representatives are asked to report the discussed strategies to all the participants and try to reach consensus. to efficiently carry out strategies in the previous step, the resilient community response team is organized. the typical structure of the response team is shown in figure . it contains five divisions, namely, patrol, evacuation, rescue, medical, and logistics, with their general function as table . the commander, usually the village chief or community committee chairman, supervises the deputy commander and executive secretary, as well as oversees outsourcing and leads the team. the deputy commander supervises the heads of every division and the executive secretary assists the commander and the deputy commander. pre-disaster in-disaster and post-disaster patrol . understanding and periodically patrolling the disaster potential area and hotspot. eliminating disaster factors in advance, such as cleaning gutters. monitoring weather and patrolling disaster potential area. if a disaster condition is spotted, send messages to the community command center and make records. setting up a cordon around a disaster point and prevent from a passerby in. tabulating and periodically updating the vulnerable residents, such as elderly, incapable people and those living in disaster potential areas. planning evacuation route. making and periodically updating the evacuation map. reminding and assisting the residents, especially the vulnerable residents, to evacuate in an emergency. making sure the evacuation route is safe and not blocked. helping traffic control in vital traffic intersection and direct the evacuating people. maintaining existing equipment and assess the need for additional equipment based on disaster type and potential in the community. being familiar with the equipment operation through periodically training. keeping smooth telecommunication by preparing walkie-talkie. preparing the equipment and applying it in a small-scaled disaster event, such as putting out a small fire with a fire extinguisher or sawing a fallen tree into pieces and removing it to avoid traffic congestion. if residents were trapped due to serious events, trying to identify their location and asking support from the authority concerned. being proficient in first aid and caring skills . periodically training residents with those medical skills. preparing items for medical purposes, such as first-aid kit and stretcher. helping injuries in need of first aid. guide outside medical resources to people in need. helping local governments open shelters and prepare living supplies. mentally comforting the refugees scared by disasters. assessing the living material, such as drinking water, food, and medical needs, required during a disaster event. tabulating and periodically updating the community response team members. helping the local government maintain shelters. helping local governments open shelters and prepare living supplies. helping refugees register when they arrive at the shelters and distributing living supplies. supporting the other four response team divisions. based on the characteristics of the potential disaster, the community action plan is suggested to include but not limited to the following items. environmental and disaster risk assessment the environmental assessment should cover the location of the community, its neighboring geography, social condition, and historical disaster hotspots. the disaster risk assessment must include disaster type the community is facing and associated risk map drawing. the community usually has no capacity of drawing such kind of risk map; therefore, it is advised to utilize some government resources. in taiwan, the national science and technology center for disaster reduction (ncdr) developed the risk map platform (https://dmap.ncdr.nat.gov.tw/) for the public to have access to risk maps of earthquake, landslide, debris flow, flooding, tsunami, and nuclear event nationwide. community response team and local disaster management network the community response team is the frontline force to deal with the disaster. according to the experience of all resilient communities promoted by the ntpc government, the general functions of the team were organized as in table . in addition to the community's strength, outer resources, such as district office, fire department, police department, school, enterprise, volunteers, ngo, and npo could be invited to formulate a local disaster management network and cooperate pre-disaster, in-disaster, and post-disaster. community resources mean the equipment such as pump, power generator, fire extinguisher, and power saw owned by the community or facility such as activity center, shelter, and community office managed by the community. however, those existent resources might not fully meet the need in terms of disaster response. the community should periodically update resources inventory and proactively assess the extra demand for resources to deal with the possible disaster. all the resources must have someone be appointed to manage. some of the duties could be assigned to the community response team member as a suggested division task in table . after the resilient community is established, the top issue is that the community sometimes does not keep on its work due to not having a sustainable operation mechanism to follow. the standard sustainable operation mechanism for the resilient community in ntpc includes the following items: ( ) regular training: it defines the courses and skill training to behold and its frequency; ( ) community disaster management database update: it includes the response team member recruitment/retirement, vulnerable residents list update, and equipment maintenance frequency; ( ) disaster processing record: the community should record the action taken pre-disaster, in-disaster, and post-disaster. it helps review the community action as well as identify defects and weak points of the plan. the community action plan was discussed and instituted by the residents and the community response team. stakeholders, such as the school, enterprise, or vulnerable individual/groups in the neighboring area, were welcome to join the discussion. the role of each stakeholder was be identified, e.g., community response team as helpers; residents and vulnerable individuals/groups as help receivers; enterprise as helpers and living material supplier; school as shelter accommodators. education and training aim to develop the knowledge and basic skills for community residents responding to disasters and specifically enhance the response team's capacity to execute their tasks. for the basic knowledge, the courses include disaster response concepts according to the community disaster characteristics. the required skills include basic first aid, such as cpr (cardiopulmonary resuscitation), heimlich maneuver, and aed (automated external defibrillator) and operation of equipment such as fire extinguishers, pumps, power saws, etc. this course is suggested to be hosted at least once per year. the community response team members could practice their tasks and skills through the war game or drill. war game helps test the validity of the action plan established in step , and the drill can further test the skills learned from step . in ntpc, not only the community response team but also stakeholders in the neighboring area, such as staff from the district office, the local fire department, school staffs, and enterprise partners are role players. table is the typical scenario designed for an earthquake drill in ntpc. a few key principles are suggested as follows: . scenarios must correspond to community characteristics in terms of single disaster or complex disaster. . self-protection skills of individuals could be exercised, such as "drop", "cover", "hold on" during the earthquake. the disaster scale should be designed properly so that the community must and could react. if the scale is too small, then no significant damage will highlight the necessity for community response; if the scale is too large, most community members might lose their capability due to casualties resulting in malfunction of the team. every division in the community response team should have the chance to familiarize themselves with their tasks and required skills. coordination and communication among the response team, stakeholders, and public/private agencies should be tested. . the community should understand the evacuation routes to the shelter as well as arrange and test the transportation for evacuation. . collaboration between the district office and the community team to open the shelter should be exercised. scenario self-protection, such as "drop", "cover", "hold on" exercise at the time of an earthquake. community response team mobilization and preparedness. preparedness for opening shelter by logistic division. the assistance of refugee evacuation to the shelter by evacuation division. patrol division surveys the area and calls for help from the rescue division upon locating damage. assistance by logistics division in shelter opening, such as registration, food sharing, and related operations. living supply may come from the enterprise. first-aiding the physically wounded people or caring for the traumatized people by medical division. rescue division puts out small-scaled fire induced by the earthquake scenario recovering the environment by the entire response team and community residents. upon completion of resilient community development, posters and videos are made showing the annual activities and joint efforts achieved by the community, government, school, and enterprise. the community response team member share experiences with those from other communities/villages who have never joined the resilient community workshop. the purpose is to not only encourage the ongoing involvement in this developed resilient community but also inspire other villages' participation shortly. to evaluate the effect and performance of promoting a resilient community, an anonymous physical questionnaire survey was conducted after we finished each resilient community for that year. the participants were informed that participation was voluntary and the participants' willingness to return the completed questionnaire indicated their consent to participate in this study. eight key questions were asked as follows: q : do you understand the disaster risk of your community after the workshop? q : do you feel developing a resilient community and building capacity is necessary? q : has your community built a feasible action plan after the workshop? q : do you understand the tasks of the response team? q : are you willing to become a member of the response team? q : have you learned basic medical skills and been capable of performing it when necessary? q : have you learned the fire-fighting skills and been capable of performing it when necessary? q : is retraining necessary for the community? q and q checked if the participants were aware of the disaster risk and management; q checked if the community action plan was built and valid; q and q checked if the participants understood the tasks they should perform while they became response team members; q and q checked if basic skills were well taught; q checked the necessity of hosting retraining courses, and is linked to the maintenance mechanism in section . . despite the eight key questions, only age and gender information were collected; therefore, no personal information of any specific individual could be exposed. table shows the age distribution of respondents who joined the workshops hosted by the ntpc government in . we kindly asked every participant to do the questionnaire for us right after the workshop; therefore, the response rate was %. from a total of participants, including males and females from communities, more than % of them were over years old, and more than % were over years old. the aging population phenomenon is very common in rural areas of ntpc which are usually prone to high disaster risks. it implies that their mobility to react to disaster events is relatively low before the promotion of a resilient community. the questionnaire was designed to confirm the contribution of promotion, and results are shown in figure . the survey has shown that, after -steps of promotion as described in section . , % of the participants realize the risks they are facing and % agree with the necessity to develop a resilient community; % believe that the action plan we helped them build is feasible; % understand the tasks of the response team and % are willing to serve the community as a team member; % and % think that they had well learned and were ready to perform basic medical skills and fire-fighting, respectively; % also thinks retraining is important for the community. overall, about % of the participants' awareness was raised and the capacity to deal with community-based disaster events the survey has shown that, after -steps of promotion as described in section . , % of the participants realize the risks they are facing and % agree with the necessity to develop a resilient community; % believe that the action plan we helped them build is feasible; % understand the tasks of the response team and % are willing to serve the community as a team member; % and % think that they had well learned and were ready to perform basic medical skills and fire-fighting, respectively; % also thinks retraining is important for the community. overall, about % of the participants' awareness was raised and the capacity to deal with community-based disaster events was established. it indicates the triumph of resilient community promotion and implies its contribution to the successful community operation introduced in the next section. two case studies are introduced to demonstrate how the established resilient community reacts pre-disaster, in-disaster, and post-disaster. those cases may not have been catastrophic events but showed how the community spontaneously mobilized after the training received through building community resilience. jiaqing village, an urban village located in zhonghe district, is the resilient community that started in . this village was prone to flooding, earthquake, and fire. after the village was trained and the community response team was organized, it progressively operates whenever there is a typhoon coming ( figure ). the village chief, as the response team commander will host a preparedness meeting and assign tasks for the team. the biggest concern is to prevent the low-lying area from flooding; therefore, team members were sent to the gutter and drainage outlet where garbage is easily accumulated. once waste was found stuck in the drainage system, the team notified the district cleaning contractor and cleaned the site together. occasionally, if the cleaning of the drainage system could not prevent the flooding from happening, the team recorded the situation for the village chief to discuss improvement measures thereafter. respectively; % also thinks retraining is important for the community. overall, about % of the participants' awareness was raised and the capacity to deal with community-based disaster events was established. it indicates the triumph of resilient community promotion and implies its contribution to the successful community operation introduced in the next section. two case studies are introduced to demonstrate how the established resilient community reacts pre-disaster, in-disaster, and post-disaster. those cases may not have been catastrophic events but showed how the community spontaneously mobilized after the training received through building community resilience. jiaqing village, an urban village located in zhonghe district, is the resilient community that started in . this village was prone to flooding, earthquake, and fire. after the village was trained and the community response team was organized, it progressively operates whenever there is a typhoon coming ( figure ). the village chief, as the response team commander will host a preparedness meeting and assign tasks for the team. the biggest concern is to prevent the low-lying area from flooding; therefore, team members were sent to the gutter and drainage outlet where garbage is easily accumulated. once waste was found stuck in the drainage system, the team notified the district cleaning contractor and cleaned the site together. occasionally, if the cleaning of the drainage system could not prevent the flooding from happening, the team recorded the situation for the village chief to discuss improvement measures thereafter. baiyun village, a mountainous village located in xizhi district, is a resilient community stated in . after six months of solid training and immediately after the community drill was performed on october , a landslide event occurred due to typhoon aere in the early morning of october. the village chief, jun-di chen, immediately assembled the community response team as well as reported the situation to the xizhi district office and ntpc fire department as soon as he was notified by the residents who spotted the event. eight team members were called in and approached baiyun village, a mountainous village located in xizhi district, is a resilient community stated in . after six months of solid training and immediately after the community drill was performed on october , a landslide event occurred due to typhoon aere in the early morning of october. the village chief, jun-di chen, immediately assembled the community response team as well as reported the situation to the xizhi district office and ntpc fire department as soon as he was notified by the residents who spotted the event. eight team members were called in and approached the disaster site to evacuate people by knocking on doors one after another. once the government forces arrived and took over the frontline, the community response team helped set up the cordon to prevent residents from entering the disaster site. the team also helped the public force establish the command post in the nearby area to monitor disaster development and timely response. finally, when the situation was under control, the response team moved to the shelters and took care of the residents who had evacuated earlier. in total, people took shelter in the baiyun activity center with no casualties reported. the resilient community developed in ntpc has by far been running for three phases as follows. most problems were identified in phase and solutions were given accordingly in phases and . ntpc has launched the resilient community since . until , only resilient communities were developed by a few ntpc departments. the speed of promotion is quite slow because the nptc government was unfamiliar with the concept of the resilient community and need help from certain universities who have associated expertise and enough manpower to host the workshops and activities described in section . . during the first phase, key factors impeding the promotion were identified as follows: in general, residents usually lack the willingness to participate in the resilient community workshop from the beginning due to three reasons. first of all, they think that if no serious disaster happened before then why would there be one in the future. next, there is already some structural protection in the community such as the dike or pumping stations/machines to prevent flooding and the retaining wall to prevent from hillslope disaster. they feel quite safe with those protection measures. finally, even if a disaster indeed happened, the government would come and help because the government must save the citizens. there are varying conditions in different communities. the community is usually prone to hillside disaster and debris flow in the rural area especially in the mountainous area; prone to earthquake and fire in the urban area especially with densely distributed old buildings; and prone to flooding in the low-lying area. therefore, there is no "one size fits all" approach for community resilience building [ ] . although the goal of the resilient community is building capacity for it, the ntpc government specifically asks the public sector such as district office and local fire department corps and branch to progressively join associated activities. therefore, a great amount of time and involvement from the community and public sectors is required. it usually takes a minimum of - months to develop a base-type resilient community and up to years to finish the complete-type resilient community. the minimum requirement for a base-type resilient community is to raise the residents' awareness and train their basic skills. for the complete-type resilient community, the steps in section . should be strictly followed and their performance tracked to ensure a fully built capacity. it would cost , to , usd to hire the expert/team to finish one complete-type resilient community. there are villages in ntpc, and the total expense would exceed million usd for all. the different authorities concerned are entitled to deal with different disaster types. for example, in ntpc, the water resources department and the agriculture department promote resilient communities prone to flooding and debris flow, respectively. it is not be a problem if the community has only a single disaster type. however, it is very common that the community has more than one disaster potential. more than one department can invest in the same community if they wanted to, resulting in the duplicate investment and waste of government resources, furthermore, harming the government's general interest. one other issue is that every department in the local government is a subordinate agency of certain authority in the central government which institute the policy to promote the resilient community. for example, the soil and water conservation bureau (swcb) under the council of agriculture supervises the agriculture department in ntpc. they focus only on debris flow and train the residents accordingly. on the other hand, the water resources agency supervises the water resources department in ntpc to build flood-proof capacity for the community. as a result, not all communities receive the same training and build the all-hazards response code. the abovementioned four obstacles account for the "integrated resilient community program" launched by the ntpc government in phase and the necessity of establishing a maintenance mechanism, as shown in the following section. the different authorities concerned are entitled to deal with different disaster types. for example, in ntpc, the water resources department and the agriculture department promote resilient communities prone to flooding and debris flow, respectively. it is not be a problem if the community has only a single disaster type. however, it is very common that the community has more than one disaster potential. more than one department can invest in the same community if they wanted to, resulting in the duplicate investment and waste of government resources, furthermore, harming the government's general interest. one other issue is that every department in the local government is a subordinate agency of certain authority in the central government which institute the policy to promote the resilient community. for example, the soil and water conservation bureau (swcb) under the council of agriculture supervises the agriculture department in ntpc. they focus only on debris flow and train the residents accordingly. on the other hand, the water resources agency supervises the water resources department in ntpc to build flood-proof capacity for the community. as a result, not all communities receive the same training and build the all-hazards response code. the abovementioned four obstacles account for the "integrated resilient community program" launched by the ntpc government in phase and the necessity of establishing a maintenance mechanism, as shown in the following section. (figure ). it ensures not only the optimal utilization of the local government's resources but also the consistent procedures for all departments to follow and promote resilient communities. in phase , the school played quite an important role in the local disaster management network. the ministry of education had initiated the campus safety program in , and the focus was on building school internal capacity until . after , schools were asked to gradually cooperate with nearby villages and communities in the context of disaster management. school and district activity centers are two major facilities in taiwan to shelter the refugees in a disaster event. the community and school must work together while opening the shelter. besides, both of them could in phase , the school played quite an important role in the local disaster management network. the ministry of education had initiated the campus safety program in , and the focus was on building school internal capacity until . after , schools were asked to gradually cooperate with nearby villages and communities in the context of disaster management. school and district activity centers are two major facilities in taiwan to shelter the refugees in a disaster event. the community and school must work together while opening the shelter. besides, both of them could collaborate in medical service, mental caring, patrolling disaster hotspots, and dealing with small-scaled disaster events if needed. such cooperation is practically valid because most students, even teachers, are from a neighboring community and therefore a tight bonding already exists. the only movement needed to enhance the link and push forward is asking both parties to attend the resilient community workshop and discuss the terms of cooperation in the context of the local disaster management network. schools, especially at the university level, can also help build resilience capacity for the community [ ] . in phases and , all of the resilient communities were promoted by the local government's departments with help from certain universities. however, building community capacity to deal with disasters is the legal duty of the district office in taiwan. to help the district office learn and promote the resilient community by itself, the community consultant team was organized by the ntpc government in . it hires experts specialized in community disaster management to train the district offices to promote the resilient community through the seven-step process. besides, the resources from enterprises were specifically introduced to the community in phase . as is well known, the key to successful enterprise disaster management is the development of business continuity planning (bcp). however, bcp functions more internally than externally. it means, with bcp, the enterprise knows how to deal with disaster by itself whether in terms of mitigation, preparedness, response, or recovery. what the ntpc government tries to achieve is to develop a cohesive local disaster management network that involves the collaboration of community, public sector, schools, and enterprises. the enterprise is the last piece to complete such a network. not all enterprises are suitable to join the network. the enterprise must meet three ntpc criteria such as positive image, enough scale, and high willingness. the ntpc government or district office will sign the mou with the enterprise after it is chosen. to build tighter bonding among stakeholders, the enterprise is invited to join the resilient community activity and discuss cooperation or action plan as mentioned in section . . . other than direct financial support to the community or public sector, there are various ways in which the enterprise can play a role in the local disaster management network. for example, the mitsui outlet park in linkou joined the drill hosted by the linkou district office and provided hot meals and medicines for nearby communities; yulon group, well known for its yulon motor co., ltd. offered xindian district office vehicles to evacuate community refugees. through helping the local government and community, the enterprise can not only fulfill corporate social responsibility (csr) but also enhance its image from the public sector's media propaganda. the maintenance of the resilient community is usually harder than its development; therefore, it is suggested to employed four measures as the ntpc government did and keep the heat on. retraining is vital as shown by the questionnaire survey (q ). various courses could be chosen from the following depending on the community's needs. tasks review of the community response team: new members will join the community response team now and then. it is of great importance to make sure each member, whether senior or newcomer, knows his/her task well. collection and reporting of disaster information: with the popularization of smartphones, more apps are available for collecting disaster information and uploading it to the cloud platform. the community should learn which technical tool is more suitable to the community and how it functions. all disaster information collected could be reserved in a community database for future review. advanced disaster response skills: basic skills such as cpr, heimlich maneuver, and fire extinguisher operation were taught while developing a resilient community. advanced skills, such as patient moving, escape from the fire scene, and responding with the tool at hand (e.g., making slippers with old newspapers; making simple toilets with paper box and plastic bag) are suggested in the retraining courses. considering the covid- pandemic in , epidemic prevention is also suggested to be included in the retraining. thereby, every trainee could be a community watcher and help spread epidemic prevention knowledge and support the government's action if necessary. the selection of skills is not limited to specific disaster types that the community is most likely to confront. the advanced skill training aims to make the community function in an all-hazards response manner. . war game: every disaster management action plan should be periodically reviewed and tested. at the community level, war game is a less costing and less time-consuming way to validate the plan compared to drill. however, the design of a proper war game is still not easy for the community. they should deeply consider the potential risk and transform it into disaster scenarios for strategy discussion. they will also have to manage inner resources and seek additional outer resources. usually, inviting experts or public sector personnel to join the war game would help the community deliver more insightful outcomes. skills training and raising awareness are compulsory for community residents to increase their chance of survival in the catastrophic disaster event. with the right tools and equipment, the core function of self-help and mutual help could be even more effective. the ntpc government supports certain funding for the community to purchase equipment upon the completion of a resilient community establishment. the community could buy the equipment according to a predefined list which includes evacuation bag, disaster prevention hood, helmet, first-aid kit, stretcher, walkie talkie, pumps, fire extinguisher, trolley, power saw, power generator, emergency ration, etc. the purchased equipment should be listed in the community action plan and be maintained regularly. the response team member must be trained to operate it. issuing the resilient community certificate to those progressively engaged in associated activities and who made solid achievements would raise the community's sense of honor and make it more likely to keep on the operation. ntpc government initiated the certificate application program in . the community receives the ntpc certificate (figure ) , and it proves the following criteria have been met: environmental risk assessment: the identification of disaster potential and associated strategies must be delivered. community disaster management database: including the identification of vulnerable people in the community, inventory of equipment, list of community residents with special skills and who can help respond to disaster, and contact list of outer resources such as police department, fire department, volunteer, school and enterprise. . community response team: including the head and crew of the five-response team divisions. it is batter if the enterprise and school can join as a support division. skill training: including basic skills introduced in section . . . drill: including the script with properly designed disaster scenarios and the actual role-playing of team divisions. ideally, after the resilient community is established, it should consistently and spontaneously operate by itself; nevertheless, this is usually not the case in reality. without the government's supervision or expert's assistance, some communities fail to keep on with the work. to avoid it, the ntpc government designed a simple performance tracking table (table ) and asks the community to fill it in whenever a disaster happens or is expected to come. the table is separated into operation types, valid not only for operation during the disaster event but also for mitigation measures on normal days. the following are some suggested actions that the community can take. . mitigation: including routine education, skill training, drill/war game, environment patrol, disaster information; . preparedness: including hosting preparedness meeting, equipment inventory, real-time weather monitoring and early warning, checking vulnerable people's condition and need, patrolling areas prone to disasters, and shelter opening preparedness; . report in: once the disaster is spotted, reporting to the community and the authority concerned for timely response, as well as to associated private sectors such as water company or power company for assistance; . response: including dealing with disasters such as removing fallen trees, fire-fighting, identifying risk area and setting up cordon; evacuating people in the high-risk area; helping public sectors such as opening shelter, traffic control, and setting up command post; taking care of wounded by first-aid, caring for, and moving patients; . recovery: including environment cleaning, recovery, and rebuilding. ideally, after the resilient community is established, it should consistently and spontaneously operate by itself; nevertheless, this is usually not the case in reality. without the government's supervision or expert's assistance, some communities fail to keep on with the work. to avoid it, the ntpc government designed a simple performance tracking table (table ) and asks the community to fill it in whenever a disaster happens or is expected to come. the table is separated into operation types, valid not only for operation during the disaster event but also for mitigation measures on normal days. the following are some suggested actions that the community can take. checking the drainage fence the water level is normal in the drainage system near jiaqing bridge as shown in table , the population is aging in ntpc rural areas. young people leave their hometown to seek more work opportunities, which leave the elders more vulnerable to disasters. the aging population is not a unique problem to taiwan. many developed countries, such as japan, italy, finland, portugal, and greece, have this kind of social problem. responding to disaster requires mobile manpower to execute the tasks as designated in table . to have more young people engage as shown in table , the population is aging in ntpc rural areas. young people leave their hometown to seek more work opportunities, which leave the elders more vulnerable to disasters. the aging population is not a unique problem to taiwan. many developed countries, such as japan, italy, finland, portugal, and greece, have this kind of social problem. responding to disaster requires mobile manpower to execute the tasks as designated in table . to have more young people engage in community-based disaster management, the government should help improve the employment market in rural areas to attract young residents' return or stay. it also implies the inseparability of disaster-related and social-economic issues in the era of public engagement in disaster management. it takes a disaster to learn a lesson. however, most people never really suffer from a medium to large scale disaster, not to mention a catastrophic one. what is taught in the resilient community workshop is the concept of self-help and mutual-help, as well as basic response skills. we never know if the residents could apply the concepts and skills perfectly during a disaster event. therefore, the retraining courses should be hosted persistently. moreover, most of the public lacks the experience of dealing with post-disaster recovery. it is time for the community to participate in pre-disaster recovery planning with the government to envision the potential damage and associated recovery work. after the entire training of a resilient community, most residents recognize its necessity and are willing to continue running it. the only problem is where the funding support comes from for consistent operation. although the ntpc government offers the community certain equipment, it is usually not enough regarding the regular operation, emergency response, and administrative works. more funding contributions from public and private sectors shall be needed. the government should put more effort into matchmaking between the needs of the communities and the resources from enterprises. extracting from ntpc experience, this research has proposed the sop to promote the resilient community, identified the key obstacles, suggested the maintenance mechanism, and shown the successful formulation of the local disaster management network. the policy to deal with disaster in ntpc is the "top-down" guidance with "bottom-up" implementation. in this manner, responsibilities and initiatives could be well balanced between residents and the government [ ] . the network involves the community, local government, district office, school, and enterprise. those network members are invited to join the workshops and associated training for collaborative learning and developing a viable joint action plan. therefore, it is expected that, during a major incident or disaster (mid), the resilient community, school and enterprise could all play a role when the local government requires flexible surge capacity (fsc). surge capacity (sc) means the ability to increase staff, stuff, structure, and system ( s) rapidly and effectively in the affected areas. fsc indicates the capability to scale up and down resources in a fast, smooth, and productive way [ ] . the community could provide manpower to help local government in many ways such as, but not limited to, evacuating vulnerable people, opening shelters, managing living supplies/materials, and identifying disaster hotspots. with that assistance, the government could focus more on addressing hardest-hit areas and situations. since this study shows a promising non-structural method to enhance the local disaster management network, any country or government willing to intensify the capacity of disaster management at the community level could follow ntpc's steps and avoid the obstacles. mitigation: including routine education, skill training, drill/war game, environment patrol, disaster information; . preparedness: including hosting preparedness meeting, equipment inventory, real-time weather monitoring and early warning, checking vulnerable people's condition and need once the disaster is spotted, reporting to the community and the authority concerned for timely response, as well as to associated private sectors such as water company or power company for assistance response: including dealing with disasters such as removing fallen trees, fire-fighting, identifying risk area and setting up cordon; evacuating people in the high-risk area; helping public sectors such as opening shelter, traffic control, and setting up command post; taking care of wounded by first-aid, caring for recovery: including environment cleaning, recovery, and rebuilding. operation process note central weather bureau issued the land waring of typhoon mitag at : garbage accumulated at the drainage fence in lane , liancheng rd. was reported to the district office, and removed by the cleaning contractor no garbage spotted in the gutter along lane the water level is normal in the drainage system near jiaqing bridge united nations office for disaster risk reduction (undrr, formally unisdr) japan association for fire science and engineering. fire investigation of southern earthquake in hyogo prefecture in , japan community capitals as community resilience to climate change: conceptual connections community advantage and individual self-efficacy promote disaster preparedness: a multilevel model among persons with disabilities applying community resilience theory to engagement with residents facing cumulative environmental exposure risks: lessons from louisiana's industrial corridor analysis of the actions and motivations of a community during the torrential rains in northern kyushu building resilience during recovery: lessons from colorado's watershed resilience pilot program. environ. manag. , , are cities aware enough? a framework for developing city awareness to climate change a typology of community flood resilience ministry of the interior. assessment of the problem and preparedness of metropolitan taipei during a large scale earthquake new taipei city fire department. resilient community operation manual understanding the operational concept of a flood-resilient urban community in jakarta, indonesia, from the perspectives of disaster risk reduction, climate change adaptation, and development agencies a case study of university involvement in community-based reconstruction: in the coventry university model. community-based reconstruction of society bottom-up citizen initiatives as emergent actors in flood risk management: mapping roles, relations and limitations flexible surge capacity-public health, public education, and disaster management this article is an open access article distributed under the terms and conditions of the creative commons attribution (cc by) license acknowledgments: this research was supported by the ministry of science and technology (most), taiwan, through project most - -m - . the authors declare no conflicts of interest.int. j. environ. res. public health , , garbage accumulated at the drainage fence in lane , liancheng rd. was reported to the district office, and removed by the cleaning contractor. no garbage spotted in the gutter along lane , liancheng rd. the water level is normal in the drainage system near jiaqing bridge. no flooding in the mrt construction site. the water level is normal in the drainage system near jiaqing bridge as shown in table , the population is aging in ntpc rural areas. young people leave their hometown to seek more work opportunities, which leave the elders more vulnerable to disasters. the aging population is not a unique problem to taiwan. many developed countries, such as japan, italy, finland, portugal, and greece, have this kind of social problem. responding to disaster requires mobile manpower to execute the tasks as designated in table as shown in table , the population is aging in ntpc rural areas. young people leave their hometown to seek more work opportunities, which leave the elders more vulnerable to disasters. the aging population is not a unique problem to taiwan. many developed countries, such as japan, italy, finland, portugal, and greece, have this kind of social problem. responding to disaster requires mobile manpower to execute the tasks as designated in table as shown in table , the population is aging in ntpc rural areas. young people leave their hometown to seek more work opportunities, which leave the elders more vulnerable to disasters. the aging population is not a unique problem to taiwan. many developed countries, such as japan, italy, finland, portugal, and greece, have this kind of social problem. responding to disaster requires mobile manpower to execute the tasks as designated in table key: cord- -vi dms authors: hanvoravongchai, piya; adisasmito, wiku; chau, pham ngoc; conseil, alexandra; de sa, joia; krumkamp, ralf; mounier-jack, sandra; phommasack, bounlay; putthasri, weerasak; shih, chin-shui; touch, sok; coker, richard title: pandemic influenza preparedness and health systems challenges in asia: results from rapid analyses in asian countries date: - - journal: bmc public health doi: . / - - - sha: doc_id: cord_uid: vi dms background: since , asia-pacific, particularly southeast asia, has received substantial attention because of the anticipation that it could be the epicentre of the next pandemic. there has been active investment but earlier review of pandemic preparedness plans in the region reveals that the translation of these strategic plans into operational plans is still lacking in some countries particularly those with low resources. the objective of this study is to understand the pandemic preparedness programmes, the health systems context, and challenges and constraints specific to the six asian countries namely cambodia, indonesia, lao pdr, taiwan, thailand, and viet nam in the prepandemic phase before the start of h n / . methods: the study relied on the systemic rapid assessment (sysra) toolkit, which evaluates priority disease programmes by taking into account the programmes, the general health system, and the wider socio-cultural and political context. the components under review were: external context; stewardship and organisational arrangements; financing, resource generation and allocation; healthcare provision; and information systems. qualitative and quantitative data were collected in the second half of based on a review of published data and interviews with key informants, exploring past and current patterns of health programme and pandemic response. results: the study shows that health systems in the six countries varied in regard to the epidemiological context, health care financing, and health service provision patterns. for pandemic preparation, all six countries have developed national governance on pandemic preparedness as well as national pandemic influenza preparedness plans and avian and human influenza (ahi) response plans. however, the governance arrangements and the nature of the plans differed. in the five developing countries, the focus was on surveillance and rapid containment of poultry related transmission while preparation for later pandemic stages was limited. the interfaces and linkages between health system contexts and pandemic preparedness programmes in these countries were explored. conclusion: health system context influences how the six countries have been preparing themselves for a pandemic. at the same time, investment in pandemic preparation in the six asian countries has contributed to improvement in health system surveillance, laboratory capacity, monitoring and evaluation and public communications. a number of suggestions for improvement were presented to strengthen the pandemic preparation and mitigation as well as to overcome some of the underlying health system constraints. background "world 'well prepared' for virus" is the title of a news article from the bbc on april , a day the world health organization (who) raised the level of influenza pandemic alert from phase to phase [ ] . the article cited a high-level who officer who commented that "the international community is better prepared than ever" to handle the potential influenza pandemic, because several years of preparation for avian flu had helped countries build up stockpiles of antiviral drugs globally. on the same day, a spokesman for the who regional office for the western pacific declared that "asia is better prepared and in a better position than others" citing experience in management of and response to the severe acute respiratory syndrome (sars) outbreak which affected the region in [ ] . having established a large antiviral stockpile and/or having experience with sars does not necessarily mean that a country is well equipped to face an influenza pandemic. preparedness is a complex phenomenon which involves many aspects, including disease surveillance, case management, command and control, and community containment [ ] . earlier studies on the completeness of national pandemic influenza preparedness plans in several regions reveal that many challenges and important gaps in preparedness remain [ ] [ ] [ ] [ ] [ ] [ ] . besides, these studies show that the level of preparedness varies hugely across and within regions. the situation in developing countries is the most worrisome as their public health infrastructure is often weak with severe shortage in financial, human, and technical resources [ , [ ] [ ] [ ] . since , asia-pacific, particularly southeast asia, has received substantial attention because of the anticipation that it could be the epicentre of the next pandemic. there has been active investment in preparedness strategy and planning in many countries by both domestic and international players. despite such strong interest and investment, a review of strategic pandemic preparedness plans in asia in and a report on regional preparedness published by the united nations system influenza coordinator (unsic) in reveals that the translation of these strategic plans into operational plans is still lacking in many countries in the region [ , ] . this paper presents the results from a rapid situation analysis (rsa) of health system and pandemic preparedness in six countries of the asia-pacific region prior to the h n / epidemic. taiwan had extensive experience with the sars outbreak, with over confirmed cases. viet nam, thailand, and indonesia also had sars cases (albeit fewer than taiwan) and, together with lao pdr and cambodia, have had human avian influenza cases. besides, endemicity of the influenza subtype h n is found in poultry in these five countries. the objectives of this rapid situation analysis are to describe the pandemic preparedness programmes and the health systems context in which these programmes have been established, and to identify challenges and constraints specific to the six countries. it is a part of a bigger project, the asiaflucap project, which aims to evaluate health system capacity in these countries in response to different phases of influenza pandemic. the study was conducted in the second half of with funding support from the european union and the rockefeller foundation. this study relies on the systemic rapid assessment (sysra) toolkit which is a systematic approach for gathering information about structures and modes of operation from complex health systems [ ] . it builds on the sysra framework, a conceptual and analytical framework initially developed by atun et al. to evaluate health systems and communicable disease control programmes [ , ] . the sysra analytical framework provides a conceptual, analytical framework and tool to evaluate health interventions that takes into account disease programmes, the general health system, and the wider sociocultural and political context. for the purpose of this study, this framework was adapted to pandemic influenza. our sysra toolkit comprises of two core elements: (i) the 'health systems element' and (ii) the 'pandemic preparedness programme element' (figure ). the health systems element focuses on structures and functionality of an overall health system (horizontal level). the 'pandemic preparedness programme element' assesses the specific pandemic influenza programme components embedded within a health system (vertical level). for each element, the components under review are: external context; stewardship and organisational arrangements; financing, resource generation and allocation; healthcare provision; and information systems. the study was conducted in the second half of . for each of the rsa modules qualitative and quantitative data were collected based on a review of published data, documentation and interviews with key informants in each country. as a first step, secondary data and documentation was reviewed and summarised for each country in order to determine what information was available and what data was lacking. afterwards, an interview team consisting of members (public health specialists) familiar with the health system and pandemic management programme in the country conducted interviews with key informants using a predefined semi-structured questionnaire, focusing especially on gaps identified in the initial literature review. the questions explored past and current patterns of health programme response, changes in pandemic response and other historical information about outbreak management. while conducting the interviews, additional qualitative and quantitative information were collected through an iterative process of information gathering. key informants were selected on the basis of their expertise in a broad range of health system and pandemic programme components. they were chosen from all administrative levels and from different institutions to provide a triangulated view of the health system and of the pandemic management programme. field visits occurred between october to december with up to key informants being interviewed in each country. no remuneration was provided to the informants. the lists of field researchers and the affiliations and roles of the key informants from each country are provided in the country case study reports available publicly accessible on the website: http://www.cdprg.org/publications. ethi-cal approval for this project was obtained from all participating countries. the scope of this study is limited to health system and health service response and preparation for pandemic influenza. non-health sector preparation and mitigation efforts are beyond the scope of this analysis. the choice of the six countries is based on an historical assessment that they would likely be at the epicentre of an influenza pandemic, the incidence of h n in poultry, and their experience with sars. the country contexts in the six study countries vary considerably. the political systems include republic (taiwan and indonesia), constitutional monarchy (thailand and cambodia), and socialist republic (vietnam and lao pdr). the level of economic development based on world bank's classification ranges from low income with high agricultural share (lao pdr, cambodia, and viet nam), middle income (thailand and indonesia) to industrialized and high income (taiwan). there is, however, similarity in that all countries enjoyed relative political stability (except recently in thailand) and continuous economic growth over the past decade preceding the current global economic crisis. health systems in the six countries vary in regard to the current health status and epidemiological profile, the level of health care resource, health financing mechanisms and health service provision patterns (table ) . • current health status and epidemiological profile taiwan shows a pattern of industrialized economies post epidemiological transition with low mortality, high life expectancy, and high disease burden from chronic diseases. in contrast to taiwan, lao pdr and cambodia have lower life expectancy with high morbidity and mortality from communicable diseases. • level of healthcare resources the level of health system resources reflects the level of economic development. taiwan has a high level of health spending and high density of hospital beds and health workforce per capita. on the other end of the spectrum, cambodia and lao pdr have low health spending and very low health facility and health workforce density. external resources are a significant source of health financing in cambodia and lao pdr. • health financing mechanisms only taiwan and thailand have universal coverage of health insurance. indonesia and viet nam have a number of health insurance schemes such as social security scheme and government employee health insurance for different sectors of the population. lao pdr and cambodia relied mainly on out-of-pocket payments with recent development of community financing. lao pdr is developing social security insurance. • health service provision health service provision patterns in the six countries are mixed. the private sector plays a major role in tai- wan. in both thailand and viet nam, the public sector has an extensive network of public health facilities. however, a significant proportion of population is increasingly using private sector health care providers such as drug stores and private clinics as their first source of health care. in indonesia, lao pdr, and cambodia, the availability of health facilities is quite limited as seen in the density of hospital beds which is at per , or less. one indicator of health service access is the proportion of skilled birth attendance. the statistics in shows that the proportion was over % in thailand and viet nam, around two-third in indonesia, nearly % in cambodia and less than % in lao pdr in . all countries in this study have experienced an outbreak of sars or avian influenza in humans ( table ) . during the sars outbreak, taiwan was severely affected with casualties. there were , nine, and two confirmed cases in vietnam, thailand and indonesia respectively [ ] . for avian and human influenza (ahi), more than human cases have been reported each in viet nam and indonesia, in thailand, eight in cambodia, and two in lao pdr. there were no ahi cases in taiwan. all six countries have developed national governance on ahi and pandemic preparedness. they all have national pandemic preparedness plans and ahi response plans. however, the governance arrangements and the nature of the plans differ across the countries. moreover, the operational procedures as well as strategic directions vary. this section presents the preparedness arrangements in regard to governance and stewardship, financial resources, other resources, and health service provision in the study period. • in all countries, the pandemic preparedness committees were headed by the president or prime minister or his/her representative. in indonesia, lao pdr, and thailand the national pandemic preparedness plans and the ahi response plans were integrated together with ahi response plan as a part of pandemic preparedness plan. the other countries had separated plans for pandemic preparedness from the ahi response plans. at the central/national level, there were three main patterns of pandemic preparedness governance. first, as in lao pdr and indonesia, a special coordination unit (national ahi coordination office (nahico) which recently changed its name to national emerging infectious diseases coordination office (neidco) in lao pdr, and national committee for ai control and pandemic preparedness (komnas) for indonesia) was established specifically to coordinate ahi and pandemic related activities as a priority programme (vertical policy approach). second, in vietnam, the governance relies on existing governance structure e.g. responsible agencies only. third, in cambodia, taiwan and thailand, pandemic preparedness is situated as part of programmes on disaster preparedness and mitigation so the preparation for pandemic is framed within the national disaster response. there was also a difference in the governance in regard to the level of responsibility. this reflects the existing governance structure and the nature of devolution of governing power in the country. in cambodia, lao pdr, taiwan, thailand, where resource allocation decisions are centralized, the budget allocation towards ahi and pandemic preparedness programmes was also decided mostly at central level. in indonesia and viet nam, central authority was important but local authorities also played crucial roles in the decision and priority setting of the level of pandemic preparedness investment in their regions. nevertheless, in all countries the operational activities of pandemic preparation at the local level were allocated to/integrated within the network of existing government bodies. • financial resource data on government and external spending for ahi and preparedness are not readily available and our best estimate shows that most countries spent around usd per capita per year or less on these activities (table ) . whereas the level of to the disease was highest in and , it declined in . funding solely or mostly originated from central budget, except in indonesia and viet nam where the local source of funding was also important, and to a lesser extent in thailand. all countries but cambodia, had discretionary budget for local level administration to use on ahi and pandemic preparation. external resources have been substantial for low income countries, particularly lao pdr and cambodia. almost the entire budget for ahi and pandemic preparedness activities in lao pdr and cambodia was provided by external donors and international organizations. indonesia also drew in a significant amount of external funding for ahi and pandemic preparedness, accounting for almost one-fourth of total budget. there was no external financial support for taiwan and less than percent in thailand. no data was available for vietnam. • other resources: human resource, vaccine, drugs, technology in all six countries, pandemic preparedness activities at the operational level relied on existing healthcare workforce in the public sector. hence human resources available for ahi are reflective of the health workforce situation in public health system. shortage of highly skilled workers was a major problem in all developing countries, especially in relation to physicians and nurses. in regard to specific knowledge and skills for pandemic influenza, additional trainings were provided to specific sections of the workforce in all countries, particularly to those working in surveillance, case detection, and infection control. most, except taiwan and viet nam, did not have a plan for surge capacity of health care workers during pandemic time. moreover, there is a question over potential absenteeism among existing workforce at the time of pandemic. all countries have strengthened their laboratory investigation capacity to prepare for the potential pandemic. all, except lao pdr, had biosafety level (bsl ) laboratory capacity and can conduct virus sequencing. these five countries were also capable of immuno-fluorescence assay (ifa) and reverse transcription-polymerase chain reaction (rt-pcr). only taiwan had the capacity to produce pre-pandemic vaccine and has a plan to increase its capacity towards pandemic vaccine production by . indonesia, thailand, viet nam had plans, or were in the process of conducting research, towards developing their pandemic vaccine production capacity. taiwan, thailand, and indonesia had local capacity to produce antiviral drugs from chemical entities. all countries had stockpiles of antivirals and personal protective equipment (ppe) but the size of the stockpiles varied across countries. in taiwan, the national stockpile was enough to treat % of population and there is a plan to increase this stockpile if necessary. the national stockpiles of thailand and indonesia covered approximately % of their population while in cambodia the national stock in phnom penh was enough for . % of the population ( , doses). we were unable to estimate the size of the stockpiles in lao pdr and viet nam from key informants or reviewed documents. in most countries, the antiviral stockpiles were located at both central level and at hospital and local health authorities. in addition to national stockpiles, there was an asean regional stockpile in singapore. • health service health service preparedness for pandemic influenza highly concentrated on surveillance and rapid containment activities in all countries but taiwan. the surveillance systems were mainly facility and community based surveillance systems where suspected cases are reported to the central level authority for further investigation and note: * only budget for adb cdc regional project; # government budget only containment. several channels for case reporting have been set up including telephone hotline, sms, email and websites. all countries except lao pdr also conducted laboratory surveillance of samples from influenza-like-illness cases. the surveillance system for pandemic influenza in the five countries with history of ahi focused on poultry related cases. when there were animal cases of avian influenza in the neighbourhood, patients with influenzalike illness with history of poultry contacts would be specially monitored. in these countries active collaboration between human and animal health sectors to conduct joint surveillance was reported. also, surveillance rapid response teams (srrts) have been set up at both central level and local level based on existing capacity, to be readily available for field investigation when there is a suspected case. in countries with shortage of qualified human resources, the surveillance and response capacity at local level remains a major challenge. only taiwan and viet nam had explicit plans for surveillance and response in time of pandemic. all countries have assigned referral hospitals to take care of ahi cases in the pre-pandemic phases. a model hospital preparedness plan has been developed in most countries to be used by their health facilities in time of pandemic. hospital surge capacity (extra beds) has been planned in all countries but lao pdr and cambodia. similar to surveillance and response, only taiwan and viet nam had an explicit staff surge capacity plan. lao pdr and taiwan had additional plans to use volunteer in time of pandemic. in regard to case management, the focus was mainly on ahi cases. clinical treatment guidelines for ahi infection have been developed in all countries. training on clinical management of ahi cases has been conducted with patient isolation and antiviral treatment as the main instruments. in all countries there was a policy to provide antiviral prophylaxis to ahi contacts. however, there was no clear rationing policy on antiviral distribution in case of pandemic. all countries (except taiwan which has not reported any case) have provided free care to all ahi patients thus far. in the five countries where human cases have been reported, most infected patients arrived at hospital after their symptoms had developed for several days. in these countries, a patient generally seeks self medication or informal/private primary-care providers as his/her first contact point and only visit public health facilities when the symptoms are severe. this is compounded by the relative lack of health care facilities in lower resource countries like cambodia and lao and the high use of private care facilities in cambodia. there were active public health education efforts in all countries. in the countries with ahi cases, most of the messages and materials were related to the handling of livestock and basic health hygiene such as hand washing, protection when sneezing/coughing. the main strategy of public health education was to focus on the prevention of avian influenza transmission (e.g. use chicken as a mascot, etc). very few messages were on pandemic influenza. a number of simulation exercises have been conducted in all six countries. most of the exercises were table-top style where relevant officers discuss and manage a hypothetical pandemic situation in a round-table manner. for example, thailand had at least one table-top exercise at the central level and in each province. viet nam has conducted many simulations for ahi preparedness at national, provincial and district level as well as at airport and borders. there were also a few regional (multi-country) table-top exercises coordinated by the world health organization and one table-top exercise by the mekong basin disease surveillance network (mbds). only indonesia and taiwan had full-scale exercises involving real field activities. indonesia's full-scale exercise in bali in april was the first of its kind in the world. taiwan's full-scale exercise at its national airport focused on its response to the arrival by plane of a suspected h n case. most exercises reveal that management and coordination between various players, including non-health sector players, constitutes a major weakness in preparedness. a criticism common to all six countries is that most simulations exercises have focused on early containment but not on pandemic preparedness in later phases. the preparation for mitigation efforts at more advanced stages of a pandemic was quite limited in most countries. they have identified various channels for risk communication to the public. however, only taiwan had clear operation procedures to sustain service provision and resource mobilization when widespread pandemic occurs. the researchers also found that knowledge/skills for pandemic preparation at local level were more limited than central level staff. the rapid analyses in six asian countries show a strong link between the health system functions and pandemic preparation. in all countries, the health system context shapes how pandemic preparedness in the country is carried out. from the rsa we found that the interfaces/linkages between health system contexts and pandemic preparedness programmes are particularly strong in three areas: governance and stewardship, resources, and service provision. the arrangements and strength of governance and stewardship of pandemic preparedness programme follow those of the general health system. in well-established health systems, pandemic preparedness is integrated within existing mechanisms, notably within the national disaster preparedness framework. in countries with a weak healthcare system, new vertical programme had to be established to manage and coordinate pandemic preparedness and response. the nature of pandemic governance also depends on the existing political context. decentralized countries have greater challenges to deal with during both outbreaks and pandemics. in a decentralized system like in indonesia, the level of political commitment could affect the level of investment in pandemic preparedness in that region/area as seen in the contrasting difference between bali and jakarta. in jakarta, where political interest on pandemic is low, the planned table-top simulation exercise was postponed because of the lack of budget while in bali, a full-scale exercise was carried out with strong support from all sectors. the political and historical context also shapes the pandemic preparedness process. for example, the political crisis in thailand in resulted in frequent changes of minister of public health and several postponements of national pandemic preparedness committee meetings. in taiwan, pandemic preparation is high on national political agenda because of its previous history of sars outbreak and casualties as well as a perceived threat of bioterrorism. the level of resource available for pandemic preparedness depends on the level of economic and health system development of the country. the amount of financial investment in preparedness activities and stockpiling of drugs and equipments is dependent on the level of budget availability. countries with low financial resource need to rely on external funding for their pandemic preparedness activities. the series of h n outbreaks which have occurred in the region since combined to the heightened global interests in averting a pandemic have allowed many low resource countries to draw in financial resources to support their preparation especially for surveillance and early detection. however, there are questions about the sustainability of these external resources given the current global economic recession and other public health priorities in donor countries themselves. such resources might also be much more difficult to mobilize during pandemic time. similarly, the shortage of highly skilled workers in the general health system has been raised as a major limitation of the preparedness planning and response in many of these countries. this situation could be even more serious in pandemic time when a number of staff may become ill with the disease and some of them may be absent due to the fear of infection. health service provision for ahi control relies primarily on the existing provider system. the main strategy used in all countries but taiwan is to focus on early detec-tion and containment. investment was made into rapid response team and surveillance mechanisms with attention to the linkages between poultry infection and human cases. this strategy may be driven by several factors. the emergence of human cases of h n may have led each of the five countries to strongly assume that outbreaks of human-to-human transmission could start within their own country. moreover, the potential threat of the h n pandemic also drew external funding whose main interest may have been to rapidly contain avian influenza outbreaks within the region, hence investment in surveillance and case detection. besides, the lack of internal resources may have yield to limited investment in pharmaceutical interventions such as antiviral and vaccine stockpiling. the who pandemic classification system into various phases could have also influenced countries into investing first in preparedness for the earlier phases and to delay preparedness for the later phases, although phases will remain fluid during a pandemic as the h n / has demonstrated. investment in pandemic preparedness activities has contributed to the strengthening of health system functions in many countries specifically in regards to surveillance, laboratory capacity, monitoring and evaluation, and public communication. regionally, there has been active cooperation through the surveillance network in the mekong basin through the mekong basin disease surveillance network (mbds). these health system functions could be useful for other diseases beyond pandemic response. however, the low investment in clinical care in relation to other health services may be a big challenge for these countries, especially if a pandemic is to expand beyond the early containment phase. the outbreak of influenza h n / and its spread globally also raises many important questions on how prepared these asian countries are for global pandemic influenza. the underlying assumption that the pandemic would start from avian influenza virus mutation within the country led to heavy investment on surveillance and case detection mechanisms in the five developing countries. these mechanisms were designed primarily for ahi with reliance on poultry contact history in the surveillance and case detection operational guidelines and unlikely to be effective for early-detection and containment of pandemic influenza now that human-to-human transmission has been observed without an animal tracer. the pandemic response strategy and the surveillance and case detection protocols in these countries need to be transformed to accommodate this changing circumstance. it is also important to translate existing pandemic response and mitigation plans into operations particu-larly at the subnational level as local administration and communities need to be active and ready for these plans to be effective. limited stockpiles of the antivirals, covering % or less of the population in all countries other than taiwan, raise the issue of drug allocation when a large-scale highimpact pandemic occurs. the world health organization recommended countries to stockpile antivirals for % of their population but this is obviously not feasible financially for many developing countries [ , ] . similarly, it is already clear with the h n / outbreak that when the pandemic vaccine is developed its availability will be limited [ ] . explicit rationing or prioritization policy for the medicines and vaccines is necessary and should be developed to avoid ethical and political conflicts that may arise [ ] [ ] [ ] . the ongoing threat of pandemic influenza with humanto-human transmission also calls for a revision/reposition of public education campaigns that were shown to be focusing on animal to human transmission in many southeast asian countries. the message requires adjustment from current emphasis on animal handling hygiene to respiratory health hygiene and when to seek medical care. the current treatment strategy to rely on a referral hospital system may also need to be adjusted towards community level surge capacity and the use of volunteers to support the system in time of pandemic. simulation exercises with phase hypothetical scenarios could be useful as a test of the level of preparedness especially with actors from non-health sector. for the preparation to be effective and sustainable, the interventions need not only focus on the influenza related activities. our study shows that health systems provide important context towards the success of the responses. the effort to strengthen pandemic preparedness should also be done in such a way that also strengthens health systems. three areas of improvement based on our findings of strong linkages between pandemic preparation and health systems in governance and stewardship, health system resource, and service provision are highlighted here. firstly, the governance and stewardship of ahi and pandemic preparedness should be integrated into the broader disaster preparedness system. taiwan benefited from more resources from higher level of economic development but comprehensive and multisectoral responses with commitment from all levels also resulted from high political interest and a systematic approach to preparedness using disaster and bioterrorism response system. national ownership of the preparedness activities is particularly important especially in low resource countries where external funding is prominent. the allocation decision of pandemic related investment should be harmonised and aligned with national systems and priorities. secondly, the scarcity of health care resources particularly in rural areas was shown to hamper the preparation for the pandemic as well as the responses to other diseases. scaling up health system capacity such as health workforce and health care infrastructure is necessary and should be decided based on evidence together with effective planning. for example, the countries can benefit from the asiaflucap project's ongoing analysis of health system resource gaps to effectively respond to pandemic. nevertheless, investment in health workforce and health care infrastructure should avoid disease-specific focus and contribute to overall system strengthening [ ] . a number of tools and proposed actions for scaling up disease specific capacity that also promote health system strengthening are increasingly available [ ] [ ] [ ] . lastly, in service provision the preparedness strategy also needs to address the prominent role of the private sector. private providers are the first contact point for health care in many countries. in many countries where the linkage of information system between public and private sector does not exist, the surveillance system may not be able to detect the cases early enough before it has already spread. treatment success could also be lower and the fatality rate could be higher if the patients present themselves late to public health care system where antiviral medicines are prescribed. the pandemic and disaster responses could also tap into the capacity of private nonprofit network and volunteers to support the scaling up of necessary responses. better planning and coordination between public and private sector health providers and is necessary and should be strengthened. this study contains a number of limitations. first, the rapid nature of the analysis was useful for simplicity, speed, and limited cost but it also limits the extent and the depth of the analyses. this limitation is alleviated by the way the questionnaires and data collection procedures were designed. published and grey literature documents were reviewed prior to and after field visits to prepare and verify the data received from the interviews. second, there are potential biases from key informants' selection. these were mitigated by including resource persons from different health system levels and sectors to allow for the triangulation of results from various sources. additionally, the data collection including interviews was carried out by both external and local experts to balance the views and to provide systematic, robust, contextual understanding. third, the scope of the analysis is limited to pandemic influenza and the health systems. other competing health care needs and priorities were assessed to a limited extent in the analysis of health care context. relative importance of those needs could influence how health systems respond to pandemic influenza, which could add to the complexity of the analysis. additionally, a pandemic could create adverse social events beyond health impacts and interrupts essential services such as food logistics or water and electricity supply systems. our study did not explore multisectoral responses or the continuity of essential services beyond the health sector, which is important and deserves further careful evaluation. additional research should be conducted to shed more light into pandemic preparation in these asian countries. a number of research activities are now going on as part of the asiaflucap project. these include the analyses of health system capacity and resource distribution in the country, scenario development for identification of resource requirements at different stages of a pandemic, and stakeholder analyses to better understand the political context and relationship between actors. future research may include the implications of pandemic preparedness on health systems e.g. financial trend, health workforce burden, the economic analyses of resource needed to fill the capacity gaps, and so on. the study in late prior to the h n / epidemic shows that the health system context influences how the six countries have been preparing themselves for a pandemic. the level and form of pandemic preparedness depend on existing health systems arrangements particularly its governance, resource, and existing service provision patterns. the political and historical context of previous epidemics shaped the priority given to pandemic preparation in a country. countries with limited domestic resources rely heavily on external funding for pandemic preparation activities. the fragmentation of health information and referral systems in some countries particularly in relation to linkage with private sector providers constitutes a challenge in synergistic pandemic response. pandemic preparation in the six asian countries has contributed to improvement in health system surveillance, laboratory capacity, monitoring and evaluation and public communications. however, preparation for pandemic mitigation in countries with low health system resources is still rather limited. with the emergence of h n / , the previous preparation in the five developing countries based on the ahi model of poultry to human transmission became less relevant. if a pandemic is to expand beyond the early containment phase it will be a big challenge for these countries whether their health system will have enough capacity to effectively respond. a number of suggestions for improvement were presented to strengthen the pandemic preparation and mitigation as well as to overcome three areas of the underlying health system constraints -governance and stewardships, resources, and service provision. the heightened public interest and awareness on the ongoing pandemic could be mobilized towards more investment in health systems. world 'well prepared' for virus afp: swine flu: asia 'better prepared' to tackle outbreak world health organization: who checklist for influenza pandemic preparedness planning pandemic influenza preparedness in the asia-pacific region how prepared is europe for pandemic influenza? analysis of national plans progress and shortcomings in european national strategic plans for pandemic influenza pandemic influenza preparedness in africa is a profound challenge for an already distressed region: analysis of national preparedness plans pandemic influenza preparedness in latin america: analysis of national strategic plans. health policy plan summary report of the sars expert committee major issues and challenges of influenza pandemic preparedness in developing countries avian and pandemic influenza: progress and problems with global health governance. global public health meeting the challenge of influenza pandemic preparedness in developing countries coordination of avian and human influenza activities. a report produced for the un system influenza coordinator a toolkit for rapid assessment of health systems and pandemic influenza preparedness and response: systemic rapid assessment toolkit (sysra). london, london school of hygiene and tropical medicine world health organization: guide to rapid assessment and response (tg-rar) a framework and toolkit for capturing the communicable disease programmes within health systems tuberculosis control as an illustrative example world health organization: summary of probable sars cases with onset of illness from uk department of health: agreements secured for pre-pandemic vaccine for the uk prioritization strategies for pandemic influenza vaccine in countries of the european union and the global health security action group: a review priority setting for pandemic influenza: an analysis of national preparedness plans antiviral resistance during pandemic influenza: implications for stockpiling and drug use overcoming health-systems constraints to achieve the millennium development goals task force on human resources for health financing: what countries can do now: twenty-nine actions to scale-up and improve the health workforce scaling up in international health: what are the key issues? health policy & planning the asiaflucap project is funded by a grant from the european commission # this paper benefits from the comments received from the participants of the ubud workshop on health system resource for pandemic preparation between - february . we are grateful to the three reviewers -mahomed patel, oscar mujica, and hitoshi oshitani -who provided extremely helpful comments to improve the manuscript. excellent administrative support from nicola lord and wasamon sabaiwan is greatly appreciated. rc has received funding from f hoffmann-la roche, various governments, and the european commission. key: cord- - h q h authors: cheng, yi-hsien; lin, yi-jun; chen, szu-chieh; you, shu-han; chen, wei-yu; hsieh, nan-hung; yang, ying-fei; liao, chung-min title: assessing health burden risk and control effect on dengue fever infection in the southern region of taiwan date: - - journal: infect drug resist doi: . /idr.s sha: doc_id: cord_uid: h q h background: the high prevalence of dengue in taiwan and the consecutive large dengue outbreaks in the period – suggest that current control interventions are suboptimal. understanding the effect of control effort is crucial to inform future control strategies. objectives: we developed a framework to measure season-based health burden risk from to . we reconstructed various intervention coverage to assess the attributable effect of dengue infection control efforts. materials and methods: a dengue–mosquito–human transmission dynamic was used to quantify the vector–host interactions and to estimate the disease epidemics. we used disability-adjusted life years (dalys) to assess health burden risk. a temperature-basic reproduction number (r( ))–dalys relationship was constructed to examine the potential impacts of temperature on health burden. finally, a health burden risk model linked a control measure model to evaluate the effect of dengue control interventions. results: we showed that r( ) and dalys peaked at °c with estimates of . and , respectively. results indicated that most dengue cases occurred in fall with estimated dalys of ( – , % ci) at % risk probability. we found that repellent spray had by far the largest control effect with an effectiveness of ~ % in all seasons. pesticide spray and container clean-up have both made important contributions to reducing prevalence/incidence. repellent, pesticide spray, container clean-up together with wolbachia infection suppress dengue outbreak by ~ %. conclusion: our presented modeling framework provides a useful tool to measure dengue health burden risk and to quantify the effect of dengue control on dengue infection prevalence and disease incidence in the southern region of taiwan. southern taiwan with relatively high temperatures and relative humidity year-round forms an ideal condition for the female mosquito (aedes aegypti)-transmitted dengue. , despite its importance, current knowledge on the nature and drivers of changing dengue infection in southern taiwan is unclear. the effect of dengue control interventions on a. aegypti infection prevalence is also poorly understood. moreover, the high prevalence of dengue in southern taiwan and the consecutive large dengue outbreaks in the period - suggest that current control strategies are suboptimal. mathematical modeling is an essential tool to address public concerns relating to an ever-expanding number of emerging diseases and to explore the importance of biological and ecological characteristics on disease transmission. , mathematical models submit your manuscript | www.dovepress.com dovepress dovepress cheng et al are useful tools in controlling infectious disease, allowing us to optimize the use of limited resources or simply to target control measures more efficiently. a variety of mathematical models have been proposed for enhancing our understanding of the interactions between the mosquito−human population dynamics and dengue transmission. [ ] [ ] [ ] [ ] [ ] [ ] for vector-borne diseases, the vectorial capacity and the basic reproduction number (r ) are usually used to characterize the critical components involved in vector-human transmission dynamics. [ ] [ ] [ ] [ ] the vectorial capacity captures key components of an insect's role in pathogen transmission, whereas r quantitatively characterizes the average number of secondary cases that are generated by a primary infectious case via the vectors in an entirely susceptible population. r is also a key epidemiological determinant that establishes threshold criteria for control practices and provides an index for the intensity of control interventions necessary to contain an outbreak. it is recognized that temperature fluctuations have significant impacts on the time when mosquitoes become infectious and consequently affect vectorial capacity, r , and disease burden. [ ] [ ] [ ] [ ] fraser et al derived a control measure model from von foerster equation-based criteria for the likely success of public control measures in containing outbreaks of infectious diseases. the r and the proportion of asymptomatic infectious (q) are two major determinants indicating whether the disease is under control. the fraser's control measure model has been applied to evaluate the control effectiveness for several infectious diseases such as severe acute respiratory syndrome (sars), hiv, smallpox, and influenza, , , but not yet for dengue. recently, the parameter of disability-adjusted life years (dalys) estimates the amount of time, ability, or activity of an individual lost because of disease-induced disability or death. these composite measures incorporate several estimates, including the incidence, prevalence, duration of a particular condition, as well as the outcome of a specific disease, either disability or premature death. hence, a daly represents year lost of healthy life. nowadays, several studies have used dalys to estimate the disease burden of dengue in various regions, including mexico, usa, southeast asia, and globally. it is estimated, on average, . (range . - . ) dalys per million population annually were lost to dengue for the period - in taiwan. in epidemic years, direct costs associated with dengue result mostly from hospitalization ( . %), followed by emergency ( . %), outpatient ( . %), and drug costs ( . %). for indirect costs, lost productivity due to death ( . %) was the dominant contributor. overall, the costs were . times higher in epidemic years than those in nonepidemic years (wilcoxon rank sum test, p< . ). taken together, the relationship among temperature, vectorial capacity, r , and disease burden in terms of dalys lost is still poorly understood in taiwan. a better understanding of the complex relationship is helpful for designing more effective public control programs. therefore, this study aims ) to explore the temperature-r -dalys relationship; ) to examine the impacts of temperature on the risk of dengue health burden in terms of dalys lost; and ) to evaluate the effectiveness of various control interventions to design more effective control strategies for achieving the optimal containment of dengue epidemics. to achieve these goals, we developed an integrated framework with a combination of a dengue-mosquito-human transmission model, probabilistic risk assessment, and multi-efficacy control model. continual daily monitoring of temperatures were adopted from the air quality monitoring network, environmental protective administration, taiwan (republic of china) (taiwan environmental protection administration). to appraise the effects of temperature variation on dengue disease burden, this study first extracted and analyzed daily minimum, maximum, and mean temperatures and further properly transformed them into monthly temperature timeseries in the period - . here the monthly minimum (t min ), maximum (t max ), and mean (t mean ) temperatures are defined as the lowest, highest, and averaged daily temperatures of a specific month. kaohsiung, located in southern taiwan with a typical tropical climate, the second largest metropolitan with dense populations, is a major dengue epidemic area with ~ > % confirmed dengue cases each year. officially notifiable data on the monthly dengue cases in kaohsiung in the period - were obtained from the centers for disease control, taiwan the previously developed dengue-mosquito-human transmission model , was adopted to describe the dynamics of vector-host interactions and to estimate the disease epidemics. the essential features of the mosquito-human transmission model are depicted in figure . there are four compartments constituting mosquito population dynamics including ) pre-adult mosquitoes composed of eggs, larvae, and pupae and ) adult mosquitoes that can be divided into susceptible (s m ), exposed but not yet infectious (e m ), and infectious dengue virus-carrying mosquitoes (i m ) based on infectious status ( figure a ). on the other hand, the susceptible-exposed infectious recovery compartmentalized disease transmission model was implemented to simulate the dengue virus transmission within human populations ( figure b ). to account for the impact of temperature on the epidemics of vector-host interactive dynamics, we selected three temperature-dependent parameters including larvae survival proportion (s l ), extrinsic incubation rate (n m ), and female mosquito death rate (μ m ) for mosquito populations based on the previously published studies to construct temperature-basic reproduction number (r ) profile. , , , a previous study has been validated with observed dengue incidence rates during - in southern taiwan, this study directly applied the validated compartmentalized mosquito-human transmission dynamic model to estimate the temperature-varied r by incorporating optimally fitted temperature-dependent and derived constant parameter estimates as , where b mh and b hm represent transmission probabilities from mosquito to human and from human to mosquito per mosquito bite, n m and n h stand for extrinsic and intrinsic incubation rates, ie, the reciprocals of mean periods in dengue viral shedding for mosquito and human, respectively, b is daily mosquito biting rate, μ m and μ h are death rates for female mosquitoes in adult stage and human, s m ( ) represents susceptible female mosquitoes that can be estimated by the product of female mosquitoes surrounding a human (m), s l , as well as total people in kaohsiung (n h ), and h h is the dengue fever recovery rate for human. note that r represents transmission potency of dengue virus in the vector-host dynamic model constituted with transmissibility of dengue from mosquito to human (r mh ) and from human to mosquito (r hm ) populations (ie, r =r mh ×r hm ). , r > indicates that dengue fever is epidemically spreading within the human populations with increasing incidences, whereas r < means the disease is dying out. an average r of implies that the disease is in endemic equilibrium. in addition, to investigate the contribution of each parameter to the variance of temperature-dependent r , uncertainty and sensitivity analyses were conducted using monte carlo (mc) simulation by a commercial software crystal ball (version . , decisionerring, inc., denver, co, usa). specifically, each parameter was defined with an optimally fitted distribution (ie, lognormal distribution) by assigning with either its mean and sd or mean and % ci values (ie, define assumption). temperature-dependent r was then assigned as the integrated forecast of each defined parameter distribution that can be estimated using eq. ( ). a total of , iterations were performed in the mc simulation through crystal ball to ensure the stability of probability distributions. a built-in function, sensitivity analysis, in crystal ball was then adopted to examine the contribution of each parameter to the variance of temperature-dependent r . this study estimated dalys lost by each confirmed dengue case in kaohsiung in the period - by using murray's equation as dce − + where d is the disability weight (d= for premature death, for perfect health), c and b are parameters from an ageweighted function, and a is the age at onset of the disease, l is the duration of the disability or years of life lost due to premature death, and r is the social discount rate used for discounting years of health life in the future. the incorporation of a discount rate in the calculation of dalys reflects a similar practice in economic analysis and gives policymakers incentives to invest society's resources in currently available health interventions for immediate benefit, though they may be less effective than from saving resources for possible future eradication programs. disabilities are then classified into six categories or grades, with each grade allocated a scalar value weighting between and . the lower the value, the less impact the disability has on a person's life. dengue cases were classified into different age groups at , , , , , - , - , - , - , - , - , - , - , - , - , - , - , - and > years, based on data collected from taiwan cdc ( ). to capture the relationship among temperature, r , and model-derived temperature-associated dalys were estimated. specifically, monthly dalys during - were estimated using eq. ( ), but only mean temperatures ranging from °c to °c paired with nonzero daly estimates were selected to establish the temperaturebasis daly relationships using the curve fitting software tablecurve d (version . , aisn software inc., mapleton, or, usa). likewise, temperature-r relationships were constructed under the same temperature range of °c- °c using tablecurve d. a three-dimensional model was then constructed to describe the temperature-r -dalys relationship. tablecurve d packages (version . , aisn software inc., mapleton, or, usa) was used to perform the model-fitting techniques. the optimal model was selected based on the least squares criterion from a set of linear and nonlinear models provided by tablecurve d packages. to better assess dengue disease burden risk based on epidemics in the period - , seasons including summer (june-august), fall (september-november), and winter (december-february) were selected since there were none or only sporadic dengue cases occurring in spring (march-may). dalys was selected to represent the health burden caused by dengue epidemics and outbreaks in the risk assessment. we applied a probabilistic risk assessment to quantify the impact of temperature on the risk of dalys during different seasons. combined with season-specific temperature and r , the dalys estimates could be further obtained by the temperature-r -dalys relationship. we then conducted a mc simulation to capture the probabilistic distribution of dalys. a total of , iterations were performed in the mc simulation through crystal ball to ensure the stability of probability distributions, and resulted in the cumulative distribution function of dalys as Ф(dalys). hence, the exceedance risk (er) profiles could be obtained by -Ф(dalys), standing for the probability that an estimated daly would exceed a specified magnitude. to effectively contain dengue disease burden, this study implemented a multi-efficacy control curve , conceived with critical elements including r , the asymptomatic infectious proportion (q), as well as efficacy for each control measure (e i ). the multi-efficacy r -q control curve can be expressed in a mathematical equation as where e i represents control efficacy of different control strategies, and h and j are integers. based on the algorithm in estimating q, , , we then defined and estimated q for dengue as where eip and iip represent extrinsic and intrinsic incubation periods in mosquitoes and humans, respectively, in that the total infectious period of dengue existing in both mosquito and human populations (ie, mean duration of dengue viral shedding) can be expressed as the summation of iip and eip. on the other hand, to achieve the optimal containment of dengue spread, this study took into account numerous combinations of control measures including life-shortening wolbachia infection (e w ), water container clean-up (e c ), pesticide spray (e s ), and repellent use (e r ). , an area under r -q control curve represents a controllable ratio (ie, dengue is under contained) whereas the above-curve area indicates an uncontrollable ratio of dengue disease relative to the total r -q rectangular area of dengue. table lists parameter values essential in estimating monthly total dalys. we assigned d as . and . and l as . and . for dengue fever and dengue hemorrhagic fever/dengue shock syndrome cases, respectively. the dalys for each age-specific category and degree of severity were multiplied by the number of cases in each year and then summed to give annual totals. the highest t max , the maximum value of the estimated total dalys may occur (figure ). we also showed that the logistic equation was capable of well describing the relationship between temperature and larvae survival percentage (s l ) (r = . , p< . , figure c ). the fitted equations with parameters (eqs. (t )-(t )) are listed in table . results showed that in the interval of °c- °c, the extrinsic incubation rate increased with temperature ( figure a ). by contrast, an opposite result was found in the female mosquito death rate, which decreased with elevated temperature between °c and °c and subsequently increased slightly after °c (figure b ). moreover, figure c reveals that the peak value of larvae survival was found to be . % at °c with an increasing phase in the interval of °c- °c with a falling phase after the peak. figure demonstrates the uncertainty and sensitivity analysis result for contribution of simultaneous variation in each parameter to the variance of temperature-derived r . biting rate (b) alone contributes positively to the overall highest r variance with a fraction of . followed by female mosquitoes surrounding a human (m) of - . , human recovery rate (h h ) of . , and similar fractional contribution of per bite transmission probability from human to mosquito and from mosquito to human (b hm and b mh ) of . . whereas the fractional contribution to the overall r variance of the rest parameters add up to ~ . . it is noticeable that this study has considered the temperature-varied disease epidemics (measured by r ), the temperature-dependent parameters submit your manuscript | www.dovepress.com dovepress dovepress cheng et al (ie, μ m , n m , and s l ) merely contribute to < . variance of r . however, the temperature-dependent parameters facilitate constructing and characterizing the temperature-r relationships of different seasons. figure presents the best-fitted results of temperature-r -dalys relationship by using three-dimensional models. the optimally fitted models and associated parameter values were listed in table . results highlighted that the r and dalys increased with temperature but turned to decline at a specific temperature. for instance, the highest estimates of r ( . ) and dalys ( . ) were found in the fall at °c and then decreased dramatically ( figure b ). compared to fall and winter, summer had the lowest dalys with the estimated range from . at °c to . at °c ( figure a ). in winter, a peak daly of . was observed at °c, and meanwhile, the r estimate was . ( figure c ). we also summarized data to obtain the overall temperature-r -dalys relationship by pooling temperature data, dalys, and r s from seasons including summer, fall, and winter ( figure d ). we found that r and dalys peaked at °c with estimates of . and . , respectively ( figure d ). to capture temperature and r variability featured dengue burden risk (dalys), we began with estimating the seasonvaried temperature and r . figure a shows temperature monthly burden of dengue fever (dalys) figure b ). figure c -f displays er profiles conceived with dalysbased dengue health burden given temperature and r variability. generally, most dengue cases occurred in the fall with a risk probability of % (er= . ) and had dalys estimates of ( % ci: - ) ( figure d and table ), whereas the least dengue cases were likely to occur in winter with dalys estimates of ( - ) ( figure e and table ). taking all seasons into consideration, dalys estimates were more likely (er= . ), likely (er= . ), and less likely (er = . ) to be ( % ci: - ), ( - ), and ( - ), respectively ( figure f and table ). among all interventions, repellent spray alone by hosts can achieve the highest control effectiveness of . %, . %, . %, and . % in all seasons, summer, fall, and winter, respectively ( figure e ). although the combination of the two (e r +e s ) and three (e r +e s +e c ) highest efficacy control measures being considered simultaneously, > % and > % control effectiveness for the fall season can be reached, respectively. in addition, in order to achieve optimum containment of dengue outbreak, we further considered a four efficacy control strategy. as shown in control effectiveness, repellent use, pesticide spray, container clean-up, together with wolbachia infection (e r +e s +e c +e w ) could suppress dengue outbreak by %- % ( figure e ). climatic factors such as rainfall and relative humidity affect the disease dynamics. the temperature had the highest contribution to the dengue variability in the regions of taiwan. the present study integrated a dengue-mosquito-human transmission model, three temperature-dependent entomological parameters (n m , μ m , and s l ), with the concept of dalys to estimate the temperature-varied r and dengue disease burden. the extrinsic incubation rate (n m ) can be an index of mosquito vector competence and is deeply dependent on temperature change. , capturing all aspects of the disease is a daunting task, but newer temperature-dependent parameters that incorporate a more holistic view of the viral ecology can be implemented as new information on transmission models. besides the three temperature-dependent parameters in the estimation of r considered in this study, the other two mosquito-related parameters (transmission probability and biting rate) depend on the temperature and seasonality as well. due to the lack of experimental data from previous studies, we applied the probabilistic approach to simulate the parameter distribution of these parameters. the simple nonlinear and logistic model could well describe the relationship of temperature and the entomological properties; even so, we can still obtain the uncertainty in our regression modeling. in addition to temperature, some climatic and environmental factors might play crucial roles to change the ecological characteristic of the mosquito population that increases the challenge in model application. therefore, we considered the uncertainty in our predicted result in the current study. alto and bettinardi assessed the temperature impact on vector competence during immature and adult stages for female mosquito aedes albopictus with blood feeding with dengue- virus infection to determine infection and disseminated infection with dengue- virus rna of mosquito. they demonstrated that adult mosquito cultured at higher temperature environment ( °c) had nearly % dissemination. however, both immature and adult stages of mosquitoes with higher rearing temperature had nearly % disseminated infection. it revealed that different rearing stages with higher temperature were associated with increased virus spread to dengue in a. abopictus. the rate of dengue- virus disseminated infection on a. aegypti was similar to a. abopictus, the temperature change on virus-disseminated infection of mosquito may be species specific. , hence, if sufficient published data are available, temperature-dependent virus dissemination should be incorporated into extrinsic incuba- our result showed that dengue has the highest transmissibility and causes health burden in the fall ( figure ), reflecting that overheated (summer) and cool (winter) temperature can relatively reduce the disease activity. in general, the dengue transmission pattern in taiwan is unique compared to other southeast asia countries that has been repeated annually: beginning with imported case from southeast asia countries in the early summer, spreading out through southern taiwan in fall, and dying out in winter because of the cold weather with temperatures dropping to below °c. the summer weather in southern taiwan is hot and wet, which provides perfect conditions for vector a. aegypti to thrive and facilitate the dengue transmission. since annual dengue cases emerge in early summer, the authorities concentrate mainy on physical and chemical interventions (eg, breeding site clean-up and pesticide spray) during summer, dengue transmission is under controlled. if the control measures are not successful, the outbreak then spreads out gradually and peaks around october. compared with the conditions in summer, the frequency and strength of dengue control measures are reduced during late fall and temperatures drop to below °c during late winter, which may lead to a little higher dengue burden in early winter compared to that in late summer. based on the epidemiological study in taiwan, hsu et al indicated that people aged - years had a relatively higher prevalence rate of dengue fever than those in the other age besides the temperature dependency in epidemics and disease burden, this study also investigated the optimal control strategies by using the different combinations of the control measures that contain dengue outbreak targeting different aspects of either host and/or vector populations. in this study, four commonly used control measures were combined for modeling the control effectiveness in different seasons. repellent spray (r) alone by hosts can achieve the higher control effectiveness of % whereas the other interventions -pesticide spray (s), water container clean-up (c), and wolbachia infection (w) can only achieve control effectiveness of %, %, and %, respectively, in all seasons. therefore, the implication for repellent spray could be expedited in an epidemic setting in the future as the primary preventive response beginning in early summer to contain further dengue outbreaks in the following seasons. although other interventions, due to lower efficacies compared with that of repellent spray, could serve as complemented and combinative interventions to prevent and contain dengue outbreaks. repellent spray alone by hosts is the highest control effectiveness. in considering the repellent product as a control measure against mosquito vectors, it is important to understand specific-repellent efficacy on the length of use , and mosquito species. two essential oils (melaleuca leucadendron and callistemon citrinus) have been demonstrated to have higher adulticidal activity with hours of exposure than with hours in a. aegypti and culex quinquefasciatus. soonwera et al found that cymbopogon citratus oil exhibited repellent activity with . % protection from bites from female a. aegypti and . % from female c. quinquefasciatus. therefore, future research should investigate the length of use and specific mosquito species to develop repellent spray formulations in the control of dengue vectors. this study provides an integrated dengue-mosquito-human transmission model and explores the temperature-r -dalys relationship for disease burden of dengue fever in southern taiwan. in the absence of detailed and robust surveillance data, our presented modeling framework provides a useful tool to measure dengue health burden risk and to quantify the effect of dengue control on a. aegypti infection prevalence and disease incidence in the southern region of taiwan. most importantly, we quantified the various control interventions to simulate the optimal containment in different seasons. these results are useful to provide the reference to understand the temperature-associated dengue prevalence and to identify priority interventions for high dengue burden regions. modelling respiratory infection control measure effects modeling control measure effects to reduce indoor transmission of pandemic h n infectious diseases of humans: dynamics and control modeling infectious diseases in humans and animals a simulation model of the epidemiology of urban dengue fever: literature analysis, model development, preliminary validation, and samples of simulation results threshold conditions for a non-autonomous epidemic system describing the population dynamics of dengue modelling the control strategies against dengue in singapore how important is vertical transmission in mosquitoes for the persistence of dengue? insights from a mathematical model dengue vector control strategies in an urban setting: an economic modelling assessment dynamics of flavivirus infection in mosquitoes estimation of the reproduction number of dengue fever from spatial epidemic data understanding the link between malaria risk and climate impact of daily temperature fluctuations on dengue virus transmission by aedes aegypti modelling the effect of temperature on transmission of dengue modeling the transmission dynamics of dengue fever: implications of temperature effects assessing dengue infection risk in the southern region of taiwan: implications for control regional response of dengue fever epidemics to interannual variation and related climate variability factors that make an infectious disease outbreak controllable quantifying the burden of disease: the technical basis for disability-adjusted life years economic and disease burden of dengue in mexico economic impact of dengue illness in the americas economic and disease burden of dengue in southeast asia the global burden of dengue: an analysis from the global burden of disease study economic cost and burden of dengue during epidemics and non-epidemic years in taiwan air quality monitoring network, environmental protective administration, executive yuan on a temporal model for the chikungunya disease: modeling, theory and numerics assessing the effects of temperature on the population of aedes aegypti, the vector of dengue modeling dynamic introduction of chikungunya virus in the united states stable introduction of a life-shortening wolbachia infection into the mosquito aedes aegypti impact of combined vector-control and vaccination strategies on transmission dynamics of dengue fever: a model-based analysis repellency of volatile oils from plants against three mosquito vectors efficacy of advanced odomos repellent cream (n, n-diethyl-benzamide) against mosquito vectors expansion of the dengue transmission area in brazil: the role of climate and cities lagged temperature effect with mosquito transmission potential explains dengue variability in southern taiwan: insights from a statistical analysis extrinsic incubation period of dengue: knowledge, backlog, and applications of temperature dependence potential for extrinsic incubation temperature to alter interplay between transmission potential and mortality of dengue-infected aedes aegypti temperature and dengue virus infection in mosquitoes: independent effects on the immature and adult stages vertical transmission of key west dengue- virus by aedes aegypti and aedes albopictus (diptera: culicidae) mosquitoes from florida larval temperature-food effects on adult mosquito infection and vertical transmission of dengue- virus infection rate of aedes aegypti mosquitoes with dengue virus depends on the interaction between temperature and mosquito genotype within-host viral dynamics of dengue serotype infection characteristic of dengue disease in taiwan: - trend and geographic analysis of the prevalence of dengue in taiwan adulticidal and repellent activities of melaleuca leucadendron (l.) and callistemon citrinus (curtis) against filarial and dengue vectors three repellent gels that contain essential oils from local malaysian plants against dengue vector mosquito repellent from thai essential oils against dengue fever mosquito (aedes aegypti (l.)) and filarial mosquito vector (culex quinquefasciatus (say)) world health organization. the global burden of disease burden of symptomatic dengue infection in children at primary school in thailand: a prospective study a model of the transmission of dengue fever with an evaluation of the impact of ultra-low volume (ulv) insecticide applications on dengue epidemics dynamic life table model for aedes aegypti (diptera: culicidae): analysis of the literature and model development clinical study on dengue fever during - epidemic at kaohsiung city, southern taiwan intervention measures, turning point, and reproduction number for dengue the interactive roles of aedes aegypti super-production and human density in dengue transmission this study was supported by the ministry of science and technology of the republic of china under grant most - -e- - -my . all authors contributed toward data analysis, drafting and critically revising the paper, and agree to be accountable for all aspects of the work. the authors report no conflicts of interest in this work. infection and drug resistance is an international, peer-reviewed openaccess journal that focuses on the optimal treatment of infection (bacterial, fungal and viral) and the development and institution of preventive strategies to minimize the development and spread of resistance. the journal is specifically concerned with the epidemiology of antibiotic resistance and the mechanisms of resistance development and diffusion in both hospitals and the community. the manuscript management system is completely online and includes a very quick and fair peerreview system, which is all easy to use. visit http://www.dovepress.com/ testimonials.php to read real quotes from published authors. health burden and control effect of dengue infection key: cord- -enq kgab authors: yu, jung-sheng; ho, chung-han; hsu, yao-chin; wang, jhi-joung; hsieh, ching-liang title: traditional chinese medicine treatments for upper respiratory tract infections/common colds in taiwan date: - - journal: eur j integr med doi: . /j.eujim. . . sha: doc_id: cord_uid: enq kgab introduction: traditional chinese medicine (tcm) has been used to treat upper respiratory tract infections/common colds (urtis) in asian countries for over years. however, chinese medicine doctors (cmds) follow the traditional treatment rules to select or administer these diverse chinese medicine formulae. the main purpose of our study was to explore data on the frequency of medication and medication habits by cmds for the treatment of urtis with chinese herbs and chinese medicine formulae. methods: the tcm treatments for patients consulting with an urtis were analyzed from the national health insurance research database using the appropriate codes from the international classification of diseases, ninth revision, clinical modification diagnoses for taiwan in . a data mining and association rules, were used to analyze co-prescriptions of tcm for patients with urtis. results: for , patients who sought the treatment of urtis, a total of , patients with urtis received tcm treatments, of these , patients sought both tcm and western medication treatments. of the urtis patients who had received a tcm treatment, % presented with an acute common cold, % had influenza, and % had acute upper respiratory infections. furthermore, . % of the sample were aged between and years, and . % were women, . % of the patients used yin-qiao-san and . % used jie-geng. yin-qiao-san and ma-xing-gan-shi-tang were the most commonly combinations of prescriptions for patients with urtis. conclusions: the patients experiencing urtis were more likely to request tcm treatment if their symptoms were mild and they were women. the chinese medicine doctors treating urtis generally followed tcm theory. a coding system for tcm diagnostic classifications could improve evaluations of tcm treatments. traditional chinese medicine (tcm) has been used to treat upper respiratory tract infections/common colds (urtis) in asian countries for over years. urtis-related symptoms, complications, treatment methods, and principles were thoroughly recorded in shanghanzabinglun, which was written by zhang zhongjing during the han dynasty in china ( - a.d.) [ ] . as part of the long-term development of urtis treatment theories, wen bing theory advocated by wu jutong was published during the qing dynasty http://dx.doi.org/ . /j.eujim. . . - /© elsevier gmbh. all rights reserved. ( - a.d.) because febrile diseases, including infectious diseases such as encephalitis, were added to the texts [ ] . to the best of our knowledge, the current principles of the tcm treatments used for diseases, such as urtis remain diverse. therefore, this study employed a database analysis to investigate the basis of chinese medicine doctors' (cmd) treatments. several reports have described how tcm treatments for urtis and related diseases, including influenza, can alleviate symptoms with fewer side effects [ , ] . the efficacy of tcm possibly results from the antibacterial and antiviral effects of the chinese herbs and formulae [ ] . many articles mention chinese herbal medicines may shorten the symptomatic phase in patients with the common cold and treat or prevent seasonal influenza. however, these articles are weak owing to the lack of high quality tcm trials. well-designed clinical trials are required [ ] [ ] [ ] . in spite of this, many extracts of medical herbs have been found to have the potential to treat urtis and prevent colds [ , ] . some chinese herbs have even been recommended as a treatment to prevent severe acute respiratory syndrome (sars) [ ] . the same chinese herbs or formulae may be used to treat many diseases, and cmds may use a single chinese herb or a mixture of herbs, depending on their experience. nevertheless, how cmds follow the treatment rules to select or administer these drugs or chinese medicine formulae remains diverse [ ] . this required further investigation. to the best of our knowledge, there are no population based pharmacoepidemiologic studies of tcm for the treatment of urtis. the main purpose of our study was to explore the data on the frequency of medication and medication habits by cmds for the treatment of urtis with chinese herbs and chinese medicine formulae. taiwan's national health insurance system was established in and covers % of inpatient and outpatient medical benefit claims for taiwan's million residents. the detailed clinical information for each patients for each visit includes the date of diagnosis, diagnostic codes, payments for consultations and prescriptions, and is contained in this claims data [ , ] . traditional chinese medicine is also covered in taiwan's national health insurance program. the prescriptions are written by cmds for treating various disorders that are recorded by the international classification of diseases, ninth revision, clinical modification (icd- -cm) codes [ ] . we used a cohort database from the nhird that comprises of a million randomly sampled individuals who were alive in . the tcm claims database for was analyzed in this study. the ambulatory file (cd ) and corresponding prescription file (oo ) were included in the tcm claims data. encrypted personal identifications were used to protect patient privacy for avoiding the possibility of the ethical violation. ethical approval and exemption was obtained from the institutional review board of chi mei medical center (irb no. -e ). urtis patients were identified from the ambulatory file (cd ) and corresponding prescription file (oo ) based on the icd- cm codes (acute nasopharyngitis [common cold]), (acute pharyngitis), (acute tonsillitis), (acute upper respiratory infections of multiple or unspecified sites), and (influenza). patients received either both western and tcm medication, or only tcm treatment or western medication in this study. the mean (standard deviation) and frequency (percentage) were presented as continuous variables and discrete variables, respectively. the frequency of each variable category according to age group and tcm prescription patterns of a single herb or herbal formulae were shown as distributions among the urtis patients. for exploring the prescription patterns of the single tcm herbal drugs or formulae among the urtis patients, a data mining method, association rule, was used to analyze individual patterns and combinations to determine the most common prescription patterns [ ] . the method of association rule was often used in large databases for finding frequent item sets which are the lists of commonly displayed together or finding the strong relationships between two items [ , ] . this method has been used extensively in various published studies using the taiwan nhird [ ] [ ] [ ] [ ] . each single herb or chinese medicine formula was set as an independent fixed prescription to estimate the support probability of all of the prescriptions in the data set containing the fixed prescription in order to measure how frequently the association rule occurred in the data set. the minimum level of support was . %. statistical software r (version . . ) and its package a rules were employed to perform all the statistical analyses. in our study, , patients sought the treatment of urtis, including; , for the western medication only, , for western medication and tcm, and , for the tcm only. a total of , ( . %) urtis patients sought the tcm treatment, which accounted for . % of the , patients underwent tcm treatment. those , urtis patients receiving tcm treatment as an outpatient, included; the common cold ( %), influenza ( %), acute upper respiratory infections of multiple or unspecified sites ( %), acute pharyngitis ( %), and acute tonsillitis ( %) (fig. ) . the results showed that the most patients who suffered from urtis mainly sought western medicine treatment. the common cold was a most common condition for patients who sought treatment of tcm treatment. the age distribution of the , patients with urtis showed that most of all ( . %) were aged between and years, and . % were between and . the use of tcm to treat urtis among women ( . %) exceeded that for men ( . %); the usage ratio for women to men was approximately . : ( table ). the main seasons of morbidity from urtis were december and january (fig. ) . the results indicated that the distribution was between and , with females more likely than males consulting for tcm if they had a urti. there were ( . %) patients who also presented with comorbidity of gastroenteritis, ( . %) with hypertension, ( . %) with allergic rhinitis, ( . %) with diabetes mellitus, and ( . %) with urinary tract infections. other comorbid conditions such as: mental disorders, cancer, chronic kidney disease, and cerebrovascular accidents for each accounted for less than % ( table ). the results showed that the most common comorbidity was gastroenteritis in these urtis patients. a total of , tcm prescriptions to treat urtis were issued in taiwan in . there were , ( . %) prescriptions for yin-qiao-san, the most popular tcm prescription, followed by , ( . %) for xin-yi-qing-fei-tang, , ( . %) for ma-xing-gan-shi-tang and , ( . %) for chuan-xiong-cha-tiao-san (table ) . jie-geng (radix platycodi) was the most popular chinese herb and was included in , ( . %) prescriptions of the total , . this was followed by yu-xing-cao (herbahouttuyniae) with , ( . %), and bei-mu (bulbus fritillaria) with , ( . %) ( table ) . overall, ( . %) prescriptions contained combinations of yin-qiao-san and ma-xing-gan-shi-tang, followed by ( . %) with yin-qiao-san and ban-lan-gen (radix isatidis) and ( . %) with yin-qiao-san and xin-yi-qing-fei-tang (table ). in summary, according to the tcm principle of clearing heat for the common cold, the tcm pattern of wind-heat was a common trend for urtis in taiwan during the yin-qiao-san, xin-yi-qing-fei-tang and ma-xing-gan-shi-tang formula, and ban-lan-gen belong to cold characteristics. this study was a database analysis of the taiwanese population who used tcm to treat urtis. a total of , patients with urtis received tcm treatment in . the primary reason for using tcm among people in taiwan was the belief that chinese herbs are natural products and, consequently, their associated side effects are less than those of western drugs [ ] . of the urtis patients, % presented with a common cold. the majority reported mild cold symptoms including nasopharyngeal inflammation [ ] , running and/or stuffy nose, oropharyngeal irritation or discomfort, cough, and fever [ ] . tcm treatment of patients with influenza, acute pharyngitis, acute tonsillitis, or acute upper respiratory infections was relatively rare. symptoms and signs of these diseases included a severe sore throat, tonsillar exudate, fever, and cervical lymphadenopathy [ , ] . our results indicated that most patients with urtis treated with tcm ranged between and years of age. people in this age group are generally healthy; thus, their urtis symptoms were milder compared to those in older or younger age groups. our results also indicated that the percentage of clinical visit for urtis female patients receiving tcm treatment was higher than for males ( . : ). this result was very similar to the reports of chen et al., who found the tcm utilization ratio was higher for females than males in taiwan between and [ ] , but the real reasons still remain unclear and need further study. in , the period with the highest frequency of tcm treatment of urtis was from october to april, and the main month of morbidity from urtis was january. during the winter and spring, the weather is colder and the incidence of urtis corresponds to the weather [ ] . although lowen et al. concluded that both cold and dry weather favor transmission of the influenza virus [ ] , and the annual influenza epidemic season is the winter [ ] , the results of this study did not provide sufficient evidence to support their conclusion because the % influenza rate in was low. the most likely connection between gastroenteritis and urtis is the common mucosal immune system for the respiratory and gastrointestinal tracts. in this immune system, secretory iga plays a critical role because it originates from the lymphoid tissue of the gastrointestinal and respiratory tracts, forming the first line of defense in these tracts [ ] . numerous patients had comorbid of hypertension. one study has reported that the coxsackie virus is related to hypertension because it can cause cardiovascular disease and myocarditis [ ] . we contend that this is unlikely because urtis development resulting from coxsackie viral infections is uncommon. a more probable suggestion is that hypertension is the underlying disease and a urtis may cause rhinitis and sinusitis, resulting in obstructive sleep apnea and a lack of oxygen, which then leads to increased blood pressure [ ] . allergic rhinitis is another type of urtis. one study reported that . % of pre-school children had a history of allergic rhinitis and often experienced urtis; they assumed that this association was because of an immunity deficiency [ ] . a large environmental study suggested that a humid climate and airborne mold could easily induce multiple respiratory tract diseases including asthma, bronchitis, respiratory infections, common colds, and allergic rhinitis [ ] . in other words, allergic rhinitis and urtis can occur concurrently because of environmental factors. in addition, these two diseases may produce several similar symptoms, such as allergic rhinitis, a sore throat, coughing for longer durations, and a runny nose because of external environmental factors [ ] . a number of chinese herbs have been used to treat urtis. tcm treatment of disease in taiwan is generally in accordance with tcm theories and the personal experience of the cmds. our results showed that yin-qiao-san was the most popular tcm formula that was used to treat urtis. yin-qiao-san first appeared in the record of wenbingtiaobian ( - a.d.) and remains a common tcm prescription for treating seasonal influenza [ ] , as well as the common cold, fever, cough, and other respiratory tract diseases [ ] . yin-qiao-san is comprised of the following herbs: jin-yin-hua (flos lonicerae), lianqiao (fructus forsythiae), niu-bang-zi (fructus arctii), jing-jie (herba schizonepetae), bo-he (herba menthae), dan-do-chi (semen sojae praeparatum), zhu-ye (herba lophatheri), lugen (rhizoma phragmitis), and gan-cao (radix glycyrrhizae). based on the theory of tcm, yin-qiao-san can be used to treat a cough or sore throat resulting from warm-heat diseases (febrile disease). one study reported that lian-qiao (fructus forsythiae) had antiviral, antibacterial, anti-inflammatory, and antioxidant effects, and that jin-yin-hua (flos lonicerae) had anti-inflammatory, anticancer, and immune-boosting effects [ ] . the second most popular chinese medicine formula for treating urtis was xin-yi-qing-fei-tang. xin-yi-qing-fei-tang is comprised of the following chinese herbs: xin-yi (flos magnoliae), bai-he (bulbus lilii), zhi-mu (rhizoma anemarrhenae), shi-gao (gypsum fibrosum), pi-pa-ye (folium eriobotryae), sheng-ma (cimicifuga foetid), mai-dong (radix ophiopogonis), zhi-zi (fructus gardeniae), huang-qin (radix scutellariae), and gan-cao. one study reported that xin-yi-qing-fei-tang was the most commonly prescribed formula for treating allergic rhinitis [ ] . xin-yi is primarily used to treat allergic rhinitis, sinusitis, and headaches in tcm. another study found that xin-yi had anti-allergic and anti-inflammatory effects, and that these effects resulted from the inhibition of histamine, prostaglandin e (pge ), platelet active factor (paf), nitric oxide (no), pro-inflammatory cytokine interleukin- ␣ (il- ␣), and tumor necrosis factor-␣ (tnf-␣) [ ] . in tcm, ma-xing-gan-shi-tang is used mainly for the treatment of urtis with a fever, cough, and yellow phlegm. the primary ingredients are the following herbs: ma-huang (herba ephedrae), xing-ren (semen armeniacae amarum), gan-cao, and shi-gao (gypsum fibrosum). an animal study found that ma-xing-gan-shi-tang was an excellent antipyretic agent because of its antiviral and t-cell regulation effects. therefore, ma-xing-gan-shi-tang can inhibit the proliferation of influenza a [ ] . jie-geng has long been employed in asian countries for the treatment of urtis, including the common cold, coughs, sputum, tonsillitis, and even asthma [ ] . furthermore, a number of studies have found that jie-geng has an immune regulatory effect and can inhibit the production of inflammatory substances, such as il- , pgd , ltc , and cox- protein, by mast cells; thus, it may reduce allergic reactions [ ] . jie-geng is also an expectorant that can prevent secondary respiratory tract infections [ ] . in tcm, yu-xing-cao is considered to have heat-clearing and detoxifying actions, although this has seldom been investigated [ ] . yu-xing-cao (herbahouttuyniae) has also been suggested to have weak antibacterial efficacy [ ] ; however, it has been employed to treat severe acute respiratory syndrome (sars) [ ] . bei-mu (bulbus fritillaria) is commonly used to treat urtis because it is an expectorant. in actuality, bei-mu is divided into zhe-beimu (bulbus fritillariae thunbergii) and chuan-beimu (bulbus fritillariae cirrhosae), and chuan-beimu is further divided into fritillaria unibracteato, fritillaria przewalskii, and fritillariadelavay [ ] . chuan-beimu is considered the best antitussive and expectorant in tcm. zhe-beimu contains a cholic acid-verticinoneester that may regulate central opioid receptors; thus, its excellent antitussive and expectorant effects are believed to be superior to those of codeine phosphate [ ] . extant studies had shown that ban-lan-gen (radix isatidis) possesses anti-helicobacter [ ] , anti-e. coli [ ] , and anti-endotoxic effects [ ] . thus, we can conclude that the common chinese herbs used to treat urtis have antitussive and/or expectorant properties. the cmd treating disease is accordance with the principles of tcm, treating cold with heat and treating heat with cold. the yin-qiao-san, xin-yi-qing-fei-tang and ma-xing-gan-shi-tang formula, and ban-lan-gen are belong to cold in character. therefore, we suggested the most common type of urtis in taiwan belonged to the tcm wind-heat pattern. although the results of this research investigated the prescription patterns of tcm for patients with urtis, there are several limitations to this study: ( ) some patients with urtis may buy chinese herbs from pharmacies by themselves, so the frequency of tcm treatment may be underestimated. however, the nhi program has the encyclopedic coverage of all population, so this selection biases may have been minimized by the large sample size; ( ) the cmd prescribes a treatment according to the patient's clinical manifestations, which is, symptoms, the color and quality of the tongue, and the various pulse formations that comprise the so-called examinations of tcm. these methods differ from the etiological diagnoses of western medicine. therefore, when selecting herbs for the treatment of disease, patient symptoms, such as appetite, thirst, and mood, play a crucial role [ ] ; ( ) the study did not use condition probability to explore the relationship between herbs and diseases and further analysis the different patterns of herb or herb combination; ( ) the study did not record the usage of western medication, so therefore, information for common polypharmacy was unavailable; ( ) the study is limited to the use tcm theory to explain the simple descriptive statistics. but the logistical regression analysis could not be carried out or that there was no statistical relationship. in the future research, developing a suitable coding system for tcm diagnostic classifications could improve evaluations of tcm and link the western medicine for increasing the efficacy of tcm. the results suggested that patients experiencing urtis requested tcm treatment if the symptoms were mild and were more likely to be women. the chinese medicine doctors treating urtis is accordance to tcm principles, such as treating cold with heat, to select the formula or herb. traditional chinese medicine and kampo: a review from the distant past for the future applying wen bing principles in acute respiratory tract infections chinese medicinal herbs for influenza: a systematic review this obscure herb works for the common cold antiviral activity in vitro of two preparations of the herbal medicinal product sinupret(r) against viruses causing respiratory infections complementary medicine for treating or preventing influenza or influenza-like illness traditional chinese medicine in the treatment of acute respiratory tract infections chinese medicinal herbs for the common cold andrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy efficacy of an extract of north american ginseng containing poly-furanosyl-pyranosylsaccharides for preventing upper respiratory tract infections: a randomized controlled trial using herbal medicine as a means of prevention experience during the sars crisis treatment effectiveness of two chinese herbal medicine formulae in upper respiratory tract infections-a randomized double-blind placebo-controlled trial taiwan's new national health insurance program: genesis and experience so far taiwan's national health insurance system: high value for the dollar. six countries, six reform models: their healthcare reform: experience of israel, the netherlands use frequency of traditional chinese medicine in taiwan evidence combination in medical data mining discovering frequent closed itemsets for association rules machine learning in action frequency and pattern of chinese herbal medicine prescriptions for urticaria in taiwan during : analysis of the national health insurance database nationwide surveillance of influenza during the pandemic ( - ) and post-pandemic prescriptions of chinese herbal medicines for insomnia in taiwan during application of frequent itemsets mining to analyze patterns of one-stop visits in taiwan knowledge, attitude and behavioral intention of chinese traditional medicine among outpatients respiratory tract infections -antibiotic prescribing: prescribing of antibiotics for self-limiting respiratory tract infections in adults and children in primary care the chinese national guidelines on diagnosis and management of cough chinese guidelines for diagnosis and treatment of influenza influenza-associated morbidity in subtropical taiwan influenza virus transmission is dependent on relative humidity and temperature iga class switch occurs in the organized nasopharynx-and gut-associated lymphoid tissue, but not in the diffuse lamina propria of airways and gut pathogen burden in essential hypertension allergic respiratory disease as a potential co-morbidity for hypertension allergic rhinitis and immunoglobulin deficiency in preschool children with frequent upper respiratory illness respiratory and allergic health effects of dampness, mold, and dampness-related agents: a review of the epidemiologic evidence othman nh. the association between pre-morbid conditions and respiratory tract manifestations amongst malaysian hajj pilgrims oseltamivir compared with the chinese traditional therapy maxingshigan-yinqiaosan in the treatment of h n influenza a randomized trial evaluation of the use of different solvents to extract the four main components of yinqiaosan and their in vitro inhibitory effects on influenza-a virus a kampo medicine, yin-chiaosan, prevents bleomycin-induced pulmonary injury in rats the prescriptions frequencies and patterns of chinese herbal medicine for allergic rhinitis in taiwan inhibitions of mast cell-derived histamine release by different flos magnoliae species in rat peritoneal mast cells anti-allergic activity of a platycodon root ethanol extract platycodin d and d increase airway mucin release in vivo and in vitro in rats and hamsters antimicrobial and antioxidant activities of cortex magnoliae officinalis and some other medicinal plants commonly used in south-east asia susceptibilities of mycoplasma hominis to herbs symptom combinations associated with outcome and therapeutic effects in a cohort of cases with sars herbological study for the beimu categorical chinese medicine on the original plants addictive evaluation of cholic acid-verticinone ester, a potential cough therapeutic agent with agonist action of opioid receptor screening test for anti-helicobacter pylori activity of traditional chinese herbal medicines thermochemical studies on the quantity -antibacterial effect relationship of four organic acids from radix isatidis on escherichia coli growth the anti-endotoxic effect of o-aminobenzoic acid from radix isatidis this study is based in part on data from the national health insurance research database provided by the bureau of national health insurance, department of health and managed by national health research institutes. the interpretation and conclusions contained here in do not represent those of bureau of national health insurance, department of health or national health research institutes. all authors were involved in the design and writing of the study, and chh conducted the statistical analysis. all authors approved the submitted version of the manuscript. no current external funding sources for this study. the authors declare that they have no conflict of interest. key: cord- - la tm authors: hsueh, po-ren; kao, chuan-liang; lee, chun-nan; chen, li-kuan; ho, mei-shang; sia, charles; de fang, xin; lynn, shugene; chang, tseng yuan; liu, shi kau; walfield, alan m.; wang, chang yi title: sars antibody test for serosurveillance date: - - journal: emerg infect dis doi: . /eid . sha: doc_id: cord_uid: la tm a peptide-based enzyme-linked immunosorbent assay (elisa) can be used for retrospective serosurveillance of severe acute respiratory syndrome (sars) by helping identify undetected chains of disease transmission. the assay was developed by epitope mapping, using synthetic peptides from the spike, membrane, and nucleocapsid protein sequences of sars-associated coronavirus. the new peptide elisa consistently detected seroconversion by week of onset of fever, and seropositivity remained through day . specificity was % on normal blood donor samples, on serum samples associated with infection by other pathogens, and on an interference panel. the peptide-based test has advantages of safety, standardization, and automation over previous immunoassays for sars. the assay was used for a retrospective survey of healthy healthcare workers in taiwan who treated sars patients. asymptomatic seroconversions were detected in two hospitals that had nosocomial disease. a peptide-based enzyme-linked immunosorbent assay (elisa) can be used for retrospective serosurveillance of severe acute respiratory syndrome (sars) by helping identify undetected chains of disease transmission. the assay was developed by epitope mapping, using synthetic peptides from the spike, membrane, and nucleocapsid protein sequences of sars-associated coronavirus. the new peptide elisa consistently detected seroconversion by week of onset of fever, and seropositivity remained through day . specificity was % on normal blood donor samples, on serum samples associated with infection by other pathogens, and on an interference panel. the peptide-based test has advantages of safety, standardization, and automation over previous immunoassays for sars. the assay was used for a retrospective survey of healthy healthcare workers in taiwan who treated sars patients. asymptomatic seroconversions were detected in two hospitals that had nosocomial disease. r etrospective surveillance for infection is an important means to screen for and interrupt undetected chains of disease transmission. such surveillance may be key to tracking the severe acute respiratory syndrome-associated coronavirus (sars-cov) because mild and asymptomatic cases of sars-cov infection that do not meet the world health organization's case definition ( ) have been identified by immunoassays ( ) ( ) ( ) , and sars-cov-like viruses have been isolated from wild mammals ( ) . sars-cov may have persisted over the summer in previously affected areas in such difficult-to-recognize reservoirs ( ) . the reemergence of sars in the city of guangzhou of the guangdong province of china in december and january ( ) is evidence that an unknown reservoir exists and signals the need for continued surveillance with laboratory testing. the current laboratory methods for identifying sars are not ideal tools for use in retrospective mass screening. reverse transcription-polymerase chain reaction (rt-pcr) for detecting viral rna is the most sensitive method for early identification of sars. however, viral load rapidly declines beginning or days after disease onset ( ) ( ) ( ) . moreover, rt-pcr requires sophisticated equipment and high laboratory quality-assurance standards ( , ) . identifying seroconversion to sars-cov by immunoassay also is a definitive criterion for laboratory determination of sars ( ) , and seroconversion is the preferred standard for retrospectively detecting sars-cov infection ( ) . sars immunoassays include the enzyme-linked immunosorbent assay (elisa) or western blot with antigen from whole virus or various recombinant proteins, a cumbersome immunofluorescence assay (ifa) using whole virus fixed on glass, and methods to determine neutralizing antibodies ( , ) . immunoglobulin (ig) g to sars-cov, detected by these immunoassays, begins to rise sharply by day after onset of symptoms. virtually all sars patients show virus-specific antibody by week , and anti-sars-cov igg persists through day ( , , ) . although any of these immunoassays can provide a definitive laboratory finding, all but the recombinant tests require biosafety level to contain the virus or are time-consuming to perform, have not been well-standardized, are of unknown specificities, and would be difficult to adapt to large-scale manufacture. improving laboratory methods for the large-scale serologic surveillance of sars, particularly in the presence of other respiratory illnesses, and standardization of diagnostic assays are key priorities for controlling sars ( ) . in this report, a standardized and rapid peptide-based sars elisa is characterized for sensitivity and specificity. beginning in april , delay in recognizing sars cases and in implementing isolation procedures led to several nosocomial clusters of sars-cov transmission in healthcare facilities in taiwan ( , ) . the results from a retrospective serologic survey by the peptide elisa of healthcare workers from facilities affected by nosocomial outbreaks are presented as a working example. we developed an elisa for sars that has synthetic peptide antigens as the solid-phase immunosorbent. over overlapping peptides, deduced from the tor sars-cov genomic sequence ( ) , were synthesized as candidate antigens from the spike (s), membrane (m), and nucleocapsid (n) proteins. candidate immunodominant s, m, and n peptides were selected and refined on the basis of serologic reactivities to a panel of serum samples from patients clinically diagnosed with sars at national taiwan university hospital in taipei and the xiaotangshan sars emergency hospital in beijing ( ) . epitope mapping by serologic validation has been described for the development of peptide-based elisa tests for hiv, hepatitis c virus, and foot-and-mouth disease virus ( ) ( ) ( ) . for the peptide-based sars elisa, wells of microtiter plates were coated with µg/ml of a mixture of the s, m, and n protein-derived peptides, and serologic reactivities were determined by a standard elisa procedure as previously described ( ) , except that the detector was horseradish peroxidase-conjugated goat anti-human igg, and the chromaphore was , ′, , ′tetramethylbenzidine (tmb). in brief, serum samples, including two normal human samples provided as nonreactive controls, were diluted : in phosphate-buffered saline with carrier proteins and preservative. the diluted serum samples were reacted to the peptide-coated microtiter wells for l h at °c. plates were washed times, reacted to the antibody conjugate, again washed times, and reacted to tmb; reactivity was then determined by a . assay results were obtained within h. results were scored on the basis of the signal/cutoff (s/c) ratio, and cutoff absorbance was determined from the mean of the two controls plus standard deviations (sd) from the distribution of normal human samples ( figure ). seroconversion panels were collected as serial serum samples from sars patients at national taiwan university hospital in the course of treatment. these panels tested positive for seroconversion by ifa ( ) and are used here to evaluate analytical sensitivity. a panel of serum samples from convalescent sars patients were provided by the center for disease control, department of health, taiwan, to evaluate diagnostic sensitivity. these serum specimens were confirmed for sars-cov infection clinically by the world health organization diagnostic criteria ( ) and serologically by whole virus-based elisa and ifa; some specimens were also confirmed by rt-pcr ( ) . samples were drawn with appropriate timing for serologic reactivity ( - weeks after onset of symptoms). a panel of , plasma samples collected from random blood donors in florida before was obtained from the gulf coast regional blood center (houston, tx) for specificity evaluation. additional specificity studies were conducted with serum that had serologic reactivities for bloodborne pathogens (hiv- , hiv- , hepatitis c virus, htlv /ii, and syphilis) obtained by united biomedical inc. before from various u.s. sources, an interference panel supplied by boston biomedica inc. (boston, ma) of serum samples with interference substances commonly found in processed clinical samples (edta, acid citrate dextrose, and citrate phosphate dextrose with adenine), and serum supplied by national taiwan university hospital from patients associated with typical and atypical respiratory pathogens other than sars-cov (influenza, rubella, cytomegalovirus, epstein-barr virus, and mycoplasma pneumoniae). serum samples were collected from healthy healthcare workers after interviews to confirm lack of signs and symptoms of sars including fever, respiratory symptoms, and diarrhea. the peptide-based elisa was evaluated for sensitivity to seroconversion on eight seroconversion panels obtained from national taiwan university hospital (figure , table ). in patient , seroconversion was detected by day with an a of . . absorbance remained at > at day . in patient , from whom blood was drawn on days , , , , and (no samples were collected from day to day ), seroconversion was apparent on day after the onset of fever. on day , the a remained > . in five of the other six seroconversion panels, from acute to convalescent phases, seropositivity was observed by days to , and by day in patient , from whom serum had not been collected from days to ( figure ). the peptide-based elisa showed an analytical sensitivity to earliest time of detection by week and for duration of detection beyond day . the seroreactivities of patients to were also evaluated by a standard ifa method ( ) for comparison. seroconversion was detected in all six patients by the ifa method within days of the peptide elisa (data not shown). the diagnostic sensitivity of the peptide elisa was % on a panel of convalescent-phase serum samples from sars patients provided as a reference panel by the center for disease control, department of health, taiwan. these sera, confirmed for sars by diagnostic and serologic criteria, displayed a mean s/c ratio of . (figure ). the specificity of the peptide-based sars elisa was tested on plasma obtained before from , random florida blood donors (gulf coast regional blood center, houston, tx). these normal plasma samples with a presumed zero seroprevalence rate gave a mean a of . ± . (sd). subsequently, the cutoff value for the peptide-based assay was set as the mean a for duplicate nonreactive controls plus . (based on sds from the mean for these , normal plasma samples). the distribution of the s/c ratio for the blood bank samples is plotted in figure with the mean s/c ratio of . . none showed positive reactivity, for a specificity on the normal samples of % ( table ) . the peptide elisa was further evaluated for specificity with a pre- collection of serum samples from patients with seropositivities for bloodborne pathogens such as hiv- , hiv , hepatitis c virus, htlv /ii, and syphilis (various u.s. sources), and with normal serum samples spiked with interference substances heparin, edta, acd, and cpda- (boston biomedica). the samples with seroreactivities for the pathogens all tested negative by the peptide-based sars elisa, as did the sera interference panel ( table ). the peptide elisa was evaluated for specificity on serum samples drawn from patients associated with typical and atypical respiratory pathogens other than sars-cov (national taiwan university hospital). these included samples from ) patients naturally infected with influenza (two sequential bleeds per influenza patient), ) patients with rubella, bacterial agent for atypical pneumonia, and ) pre-and postvaccine blood samples from patients given influenza vaccine. all samples were tested in duplicate. the sitespecific antigens of the peptide sars-cov elisa were free of cross-reactivities to the other respiratory pathogens ( table ) . a prospective study was performed to determine asymptomatic infection among primary healthcare workers in hospitals that treated sars patients. we collected serum samples from healthcare workers without symptoms, not all of whom were in direct contact with sars patients, who agreed to be tested for antibody to sars-cov at ho ping, yang ming, en chu kong, and hsin tai hospitals, approximately weeks after the outbreaks were recognized. ho ping and yang ming hospitals had admitted sars patients before the recognition of sars and before healthcare workers had implemented control measures. subsequently, these facilities experienced transmission to healthcare workers. the en chu kong and hsin tai facilities admitted patients once control measures had been implemented. neither of these hospitals recorded transmission of sars to healthcare workers. elisa detected three cases out of samples from ho ping and one case in blood samples from nursing aides at yang ming. these four positive samples, indicative of asymptomatic infection, were confirmed for seropositivity by ifa. none of the serum samples from the two hospitals without nosocomial infection displayed seroconversion. a convenient elisa to detect igg to sars-cov, based on site-specific synthetic antigens taken from the s, m, and n proteins of the virus, has high specificity. no cross-reactivity was detected in samples associated with common non-coronavirus respiratory pathogens. in addition, the lack of detectable reactivities among the , u.s. blood donors supports a specificity for the assay to distinguish sars-cov infection from infection by other human coronaviruses. the presence of anti-coronavirus antibodies among a u.s. population of this size is strongly anticipated because an incidence as high as % for oc and e respiratory infections has been observed, even among healthy young adults ( ) . the new peptide-based elisa is equivalent in sensitivity to other immunoassays for sars and can be detected after day . the synthetic antigens provide the advantages of high standardization, freedom from biohazard, and ease of scale-up production. moreover, testing by the elisa format can be readily automated for large-scale screening. the highly specific peptide-based sars antibody test is a convenient means to carry out widespread retrospective surveillance, such as that now being proposed for china to trace hotspots of persons carrying antibodies to sars-cov and to track the origins of the disease ( ) . a preliminary survey with the peptide elisa detected asymptomatic clusters of seroconversion among exposed healthcare workers in two taiwan hospitals that also had nosocomial disease. in contrast, no seroconversion was found among the exposed healthcare workers from two hospitals that had no apparent disease transmission to healthcare workers. the finding of asymptomatic seropositive persons indicates that the test will be useful in larger retrospective surveillance studies, which are needed to fully define the epidemiology and spectrum of disease. the protocol and the informed consent documents were approved by the ethics committee of medical research of the biomedical sciences, academia sinica. all participation was voluntary and was documented with written informed consent. dr. hsueh is an associate professor in the departments of laboratory medicine and internal medicine, national taiwan university hospital, national taiwan university college of medicine. his research interests include mechanisms of microbial resistance and molecular epidemiology of emerging pathogens. he is actively involved in a national research program for antimicrobial drug resistance and is a member of the sars research group of national taiwan university college of medicine and national taiwan university hospital. world health organization. case definitions of surveillance of severe acute respiratory syndrome (sars) mild severe acute respiratory syndrome asymptomatic severe acute respiratory syndrome-associated coronavirus infection early indications point to lab infection in new sars case isolation and characterization of viruses related to the sars coronavirus from animals in southern china sars-one year later update : announcement of suspected sars case in southern china; investigation of source of infection for confirmed case begins tomorrow clinical progression and viral load in a community outbreak of coronavirus-associated sars pneumonia: a prospective study detection of sars coronavirus in plasma by real-time rt-pcr serologic and molecular biologic methods for sars-associated coronavirus infection communicable disease surveillance & response. use of laboratory methods for sars diagnosis evaluation of reverse transcriptase-pcr assays for rapid diagnosis of severe acute respiratory syndrome associated with a novel coronavirus surveillance case definition for severe acute respiratory syndrome (sars) and update on sars cases-united states and worldwide the severe acute respiratory syndrome profile of specific antibodies to the sars-associated coronavirus sars laboratory workshop. summary of the discussion and recommendations of the sars laboratory workshop use of quarantine to prevent transmission of severe acute respiratory syndrome-taiwan the genome sequence of the sars-associated coronavirus peptides as diagnostic reagents for sars. united states patient application no detection of antibodies to human t-lymphotropic virus type iii by using a synthetic peptide of amino acid residues corresponding to a highly antigenic segment of gp envelope protein improved serodiagnosis of hepatitis c virus infection with synthetic peptide antigen from capsid protein differentiation of convalescent animals from those vaccinated against foot-and-mouth disease by a peptide elisa microbiologic characteristics, serologic responses, and clinical manifestations in severe acute respiratory syndrome evidence-based medicine for student health services antibodies to sars-like virus hint at repeated infections key: cord- -ed fth i authors: wong, li ping; hung, chia-chun; alias, haridah; lee, tony szu-hsien title: anxiety symptoms and preventive measures during the covid- outbreak in taiwan date: - - journal: bmc psychiatry doi: . /s - - - sha: doc_id: cord_uid: ed fth i background: it is hypothesized that anxiety and behavioral responses are intense at the beginning of an epidemic. the objective of this study was to investigate anxiety symptoms and use of preventive measures against covid- . the study also compared the association between preventive measures and anxiety symptoms during the week immediately preceding the study and those symptoms and measures at the beginning of the outbreak. methods: a cross-sectional population survey using an online questionnaire commenced on february . the study participants were residents of taiwan ages to years. the -item state version of the state–trait anxiety inventory (stai- ) was used to assess anxiety symptoms. the questions about preventive measures asked participants about their personal protection, cough etiquette, contact precautions, voluntary quarantine, and prompt reporting. multivariable logistic regression was used to determine the factors influencing an increase in the preventive measures scores. results: of a total of completed responses, a total of . % ( % confidence interval [ci] . – . ) of the respondents reported moderate to severe levels of anxiety symptoms in the past week, whereas . % ( %ci . – . ) reported moderate to severe anxiety symptoms at the beginning of the outbreak. with a higher score indicating greater anxiety, the median scores for anxiety symptoms in the past week and at the beginning of the outbreak were . (iqr [interquartile range] . – . ) and . (iqr . – . ), respectively. the median scores for the preventive measures taken in the past week and at the beginning of the outbreak were . (iqr . – . ) and . (iqr . – . ), respectively, out of a maximum score of . in the multivariable analysis, an increased anxiety symptom score from the beginning of the outbreak to the past week (adjusted or = . , %ci . – . ) was a strongly significant determinant of an increased preventive measures score in the past week compared with the score at the beginning of the outbreak. conclusions: anxiety and preventive measures scores were high and increased with the epidemic rate. higher anxiety was associated with an increased use of preventive measures against covid- . on january , a novel coronavirus was detected as the causative agent linked to cases of pneumonia reported in wuhan, china and the genome sequence was made public [ ] . subsequently, the rapid spread of the outbreak across wuhan and, at a later date, outside mainland china prompted the chinese government to take immediate action to lockdown the epicenter and several nearby cities in the province of hubei. the rapid spread of the novel coronavirus caused much anxiety and stigma and on february , the world health organization (who) declared the official name of the new coronavirus disease to be covid- [ ] . the severity and highly contagious nature of covid- have sparked concern worldwide and especially in the countries neighbouring china. the close proximity of taiwan to china, coupled with the high frequency of cross-border travel, has placed taiwan as one of the most highly threatened countries, among the other neighbouring countries in asia, in relation to a covid- outbreak. taiwan's government learned from the severe acute respiratory syndrome (sars) epidemic in , as such, the country has been on constant alert for another epidemic. the taiwanese government has raised the levels of alert and worry about a potential covid- outbreak in the country. the country has also issued an advisory warning against travel to china. at a later date, various measures were undertaken by the taiwan government to contain the spread of the covid- virus, including travel bans, and quarantine for those who had recently been to china and who had close contact with confirmed cases of covid- . despite these measures, the first case of covid- in taiwan was reported on january . on february, the number of confirmed cases in taiwan had increased to . on february, the first coronavirus death was reported in taiwan, and the total number of confirmed cases was . the first death, from a local transmission in taiwan, also marked the fifth fatality outside mainland china [ ] . taiwan has been listed by the centers for disease control (cdc) and prevention as one of the countries with an apparent community spread [ ] . the covid- outbreak threatens not only the life of those infected but also the psychological health of the affected community [ ] . the lessons learned from previous outbreaks such as ebola [ ] , sars [ ] , and the influenza a (h n ) [ , ] have led to a worldwide recognition of the importance of addressing morbidities related to mental health associated with the outbreak. the impact of such morbidities during a disease outbreak is crucial, not only because it results in a significant weakening in social and other important areas of functioning, including failure in preventive measures [ , ] , but also because excessive mental distress may have a number of biological effects, including reduced cellmediated immunity and increased inflammatory processes [ , ] . recently, a review of global evidence reported that quarantine during previous infectious disease outbreaks such as sars, ebola, h n influenza, and middle east respiratory syndrome resulted in serious psychological consequences with potentially longlasting effects [ ] . thus, it is important for the general population, in particular people who are under home quarantine or social isolation, to reduce the distress associated with the outbreak in order to maintain an optimal state of psychosocial well-being. considering the severe psychological effect of the covid- outbreak, it is tremendously important to assess the lay public's psychobehavioural response to the outbreak in order to develop and implement effective preventive and emotional regulation control strategies. an important element of outbreak management is an appropriate psychobehavioural response to preventive measures so as to minimize the spread of infection. experiences from the previous sars epidemic highlights the importance of appropriate behavioural responses in controlling an epidemic [ , ] . because of the importance of determining the level of psychological distress and understanding the psychobehavioural consequences of covid- in the general public while the epidemic is still ongoing, our main objective in this study was to investigate the anxiety symptoms caused by covid- , and use of preventive measures against covid- , among the general public. we also aimed to compare the anxiety symptoms and preventive measures during the week immediately prior to the study, while the outbreak was still on the rise, and at the time the covid- outbreak was first reported in china. we hypothesized that the preventive practices and level of anxiety in the public increased as the number of covid- cases increased. further anxiety has also been hypothesized to act as a trigger to preventive practices during disease outbreak [ ] , thus, we also investigated the influence of anxiety on the use of preventive practices. we commenced a cross-sectional, web-based anonymous survey using an online questionnaire on february . in taiwan, nearly % of the population is between the ages of and years [ ] . the legal age of adulthood in the civil code of taiwan is years. therefore, we surveyed taiwan residents years old and above. participants were informed that their participation was voluntary, and consent was implied by the completion of the questionnaire. for this online survey, consent obtained from the participants was verbal and the institutional review board has waived written (signed) consent. our survey ended on february , immediately after the report of the first death from the covid- virus in taiwan. the snowballing sampling technique was used to recruit the participants. the researchers used social networks, namely facebook and line (the most popular messaging app in taiwan) to circulate the survey link to all members on their contact lists. when participants anonymously completed the survey, they were encouraged to disseminate the survey link to all their contacts with a thank you note at the end. the questionnaire was developed in english and then translated into mandarin. local experts validated the content of the questionnaire, after which it was pilot tested. the survey consisted of three sections, which assessed ( ) demographic background, ( ) anxiety symptoms, and ( ) use of preventive measures. the survey took approximately min to complete. the -item state version of the state-trait anxiety inventory (stai- ), which assesses anxiety symptoms, was adapted from previous studies for use in this study [ , ] . the stai- has been shown to be highly correlated with the -item stai, and all internal consistency reliabilities are greater than . [ ] . the stai- has been used both as a self-administered and online questionnaires [ ] [ ] [ ] . the chinese version of the stai was used in this survey [ ] . the participants rated the frequency of experiencing six emotional states, namely being calm, tense, upset, relaxed, content, and worried, in relation to the current covid- outbreak. a -point scale was used ( = not at all, = somewhat, = moderately, = very much). the scores on the three positivelyworded items were reverse coded. the participants were asked to rate each of the anxiety symptoms during the past week (pw)-starting on february and during the beginning of the outbreak (bo)-january (the day of the wuhan lockdown) to february . the anxiety symptoms during the pw are defined as the anxiety level between february and the time of the survey. the anxiety level during the bo is defined as the anxiety symptoms experienced from the date of the wuhan lockdown ( january ) until february . the total summed scores for the pw and bo periods were prorated (multiplied by / ) in order to obtain scores that were comparable with those from the full -item stai (range from to ) [ ] . scores of or above were defined as indicating moderate to severe symptoms [ , , ] . questions assessing use of preventive measures were developed specifically for this study (additional file ). preventive measures were assessed using questions that asked the participants about their personal protection (four items), cough etiquette (four items), contact precautions (two items), voluntary quarantine (one item), and prompt reporting (one item). the response options were on a -point likert scale, with the items scored as (rarely), (occasionally), (often), and (always). the participants were asked to answer each question about the preventive measures they had carried out during the pw and during the bo. as with the anxiety levels, the preventive measures during the pw are defined as preventive measures carried out between february and the time of the survey, and preventive measures during the bo are the measures carried out from the date of the wuhan lockdown ( january ) until february . the total scores for the preventive measures for each period were obtained by summing across all the questions. the possible score ranges from to , with higher scores indicating higher use of preventive measures. the study protocol was approved by the research ethics committee of the national taiwan normal university (no. hs ). informed consent was obtained using an online consent form that the participant had to actively agree to and all participants were years old and above. this method of consent was approved by the ethics committee. the reliability of the anxiety symptoms and preventive measure scores were evaluated by assessing their internal consistency. the items for preventive measures had a reliability (cronbach's α) of . . multivariable logistic regression was used to determine the factors influencing an increase in the preventive measures score ( = increase in use of preventive measures score over time; = no increase or a decrease in use of preventive measures over time). variables that were significant by a chisquare (χ ) test were selected for multivariable logistic regression analysis and included in the model, using a simultaneous forced-entry method. odds ratios (or), % confidence intervals ( %ci), and p values were calculated for each independent variable. the model fit was assessed using the hosmer-lemeshow goodness-of-fit test [ ] . all statistical analyses were performed using the statistical package for the social sciences, version . (ibm corp., armonk, ny, usa). a p < value of less than . was considered statistically significant. of a total of complete responses, the majority were from the north district of taiwan ( . %), females ( . %), and ages - years ( . %) or - years ( . %). the great majority had either a college degree ( . %) or postgraduate degree ( . %). a summary of the characteristics of the respondents is provided in the first and second columns of table . on the whole, respondents who were older, male, whose highest educational level was a college degree and above, in the higher income group and from the south or east districts reported the lower levels of anxiety symptoms during both the pw and the bo periods. the greatest increase in the proportion of moderate to severe cases of anxiety from the pw to the bo periods was from those in the - age group ( . %; %ci . - . ), and this value was statistically significant. in contrast, there was a decrease in the proportion with moderate to severe anxiety (− . %; %ci − . - . ) among the respondents in the - age group. female participants showed a significantly higher increase in the proportion of moderate to severe cases of anxiety ( . %; %ci . - . ) than male participants ( . %; %ci . - . ). the highest increase in the proportion with moderate to severe anxiety came from respondents whose highest educational level was high school or below ( . %; %ci . - . ) and whose income was below nt$ , ( . %; %ci . - . ). increases in the proportions of moderate to severe anxiety levels were greater in respondents from the north ( . %; %ci . - . ) and central ( . %; %ci . - . ) districts than from other districts. the difference in mean stai score for the pw period ( . , sd = . ) and the bo period ( . , sd = . ) was statistically significant (wilcoxon signed rank test = . , p < . ). the median scores for anxiety symptoms during the pw and the bo periods were . (iqr . - . ) and . (iqr . - . ), respectively. the scale for both scores ranges from to . in total, ( . %; %ci . - . ) had increases in their anxiety scores from the pw to the bo periods (pw score > bo score), and ( . %; %ci . - . ) recorded a similar or lower anxiety score (pw score ≤ bo score). a summary of responses in relation to use of preventive measures during the pw and bo periods is shown in table . during the pw period, the highest proportion of use of personal protective measures was for respondents who frequently washed their hands with soap ( . %; %ci . - . ), followed by those who wore a mask ( . %; %ci . - . ). as for cough etiquette, the most commonly practised preventive measures were disposing of tissues immediately ( . %; %ci . - . ) and covering one's mouth and nose when coughing or sneezing ( . %; %ci . - . ). always performing hand hygiene was reported by a high proportion of the participants ( . %; %ci . - . ). over a third of respondents reported that they always avoided proximity with others ( . %; %ci . - . ) and avoided gathering in groups ( . %; %ci . - . ). nearly two-thirds reported that they always voluntarily quarantined themselves if they were feeling unwell ( . %; %ci . - . ), but fewer than half said they would always report promptly to health authorities if they were feeling unwell ( . %; %ci . - . ). similar findings were reported for preventive measures during the bo period, with the highest proportion reporting that they always disposed of tissues immediately after coughing and sneezing ( . %; %ci . - . ), followed by those who reported covering their mouths and noses when coughing or sneezing ( . %; %ci . - . ). the proportion who practised contact precautions was relatively low. a comparison of the proportions who always practised particular preventive measures during the pw and the bo periods shows that disposing of tissues immediately after coughing and sneezing recorded the highest increase ( . %; %ci . - . ), followed by avoiding group gatherings ( . %; %ci . - . ) and frequently washing hands ( . %; %ci . - . ). the increases were lower for using eye protection ( . %; %ci . - . ) and covering one's mouth and nose when coughing or sneezing ( . %; %ci . - . ). the difference in the mean total scores for preventive measures during the pw ( . , sd = . ) and the bo periods ( . , sd = . ) was statistically significant (wilcoxon signed rank test = . , p < . ). the median scores for preventive measures during the pw and the bo periods were . (iqr . - . ) and . (iqr . - . ), respectively. the observed total scores for use of preventive measures ranged from to for the pw period and - for the bo period. a total of ( . , %ci: . - . ) respondents had an increase in their total preventive measures scores from the pw to the bo periods, and ( . , %ci: . - . ) had similar or lower total preventive measures scores. table shows results of the univariate and multivariable analyses of the factors associated with a higher total preventive measures scores in the pw periods than in the bo period. having a higher anxiety score for the pw than for the bo period (adjusted or = . , %ci . - . ) was a strong significant determinant of an increase in the preventive measure score from the bo to the pw periods. respondents with a college-level education (adjusted or = . , % . - . ) and graduate level education or above (adjusted or = . , % . - . ) were more likely to have an increased preventive measure scores from the bo to the pw periods than those whose highest education level was high school or below. approximately weeks after the widespread news of the lockdown of the epicenter of covid- , we found the alarming result that over half ( . %) of lay members of the taiwanese public who participated in the survey had moderate to severe anxiety. the anxiety level of our study sample is similar to that reported in mainland china. a recently published study conducted in mainland china at the same time as our study reported that . % of the people in china rated the psychological impact of the outbreak as moderate or severe [ ] . those in the younger age groups, females, and those with less education and a lower income were found to report more anxiety symptoms. this provides valuable information to allow public health authorities and stakeholders to coordinate their targeted mental health interventions. similarly, other recently published studies conducted in mainland china during the covid- pandemic also found higher anxiety among females and younger people [ , ] . higher anxiety among females has been reported in sars outbreaks [ ] . this greater psychological impact of disease outbreaks on females corresponds to many psychiatric epidemiology findings, namely, that women being significantly more likely than men to develop an anxiety disorder when exposed to traumatic events [ , ] . of important note, the reason why the younger respondents in our study expressed a higher degree of anxiety is unknown, and this warrants further investigation. future studies should focus on the consequences of the infodemic of false information about covid- circulating on social media and of the social anxiety in taiwan. the huge amount of information about the novel coronavirus circulating on social media has been reported to spark anxiety, fear and panic in users [ ] . it is also noteworthy that in our study the older age group reported the lowest anxiety levels during the time of the interview and the beginning of the outbreak; however, they reported a greater increase in anxiety over time. this could perhaps be due to an increase of reporting in the news media nationwide of evidence of elderly people's elevated risk of serious illness and death from the new coronavirus. despite it being widely circulated in the news media that older adults affected by covid- likely have a higher risk of complications and mortality, and the recent large epidemiological data from the chinese centre for disease control and prevention that shows that those above years of age accounted for . % of confirmed cases in wuhan [ ] , our study's participants in the older age group appear to have a lower level of anxiety. further studies are warranted to determine whether the low anxiety stems from a lack of knowledge or the respondents being out-of-touch with current media interventions. the exponential increase in confirmed covid- cases in mainland china following the lockdown, as well as the increasing numbers of cases outside china, including in taiwan, has sparked global concern and likewise an increase in anxiety among the participants in this study. further, the advisory warning against travel, including border control from the air and sea, and daily press briefings by the ministry of health and welfare of the central epidemic command center (cecc) of taiwan [ ] perhaps also caused or exacerbated stress in the community. concurrent with the relatively low anxiety levels among those with higher education and higher incomes, the increase in anxiety was also lowest among the group with the higher socioeconomic status. the underlying reasons for these socioeconomic disparities in anxiety also warrant further investigation. since the early phase of the covid- pandemic, people in taiwan have been constantly provided health information that encourages the practice of proper handwashing, social distancing, and cough etiquette through mass media and billboards in public areas. this perhaps resulted in good preventive measures being adopted by the study participants, as evidenced by the median scores of and , out of a possible score of , for the past week and the beginning of the outbreak, respectively. further, nearly half of them reported improved preventive practices in the past week compared to the beginning of the outbreak. we also found a considerable increase in use of the preventive measures in hand washing, cough etiquette, and contact precaution, which perhaps explains why, as of february , only confirmed covid- cases have been reported in taiwan, despite it being in close geographical proximity to mainland china and having a high volume of travellers to and from mainland china prior to the outbreak. nonetheless, the findings highlight the need to improve contact precautions, since the proportion of respondents who were avoiding proximity and group gatherings was low at both the beginning of the outbreak and in the past week. multivariable analyses revealed that participants with higher education levels reported a greater increase in the use of preventive measures. a greater increase in anxiety symptoms was associated with a greater increase in preventive practices. this finding is in congruence with previous findings from the sars outbreak in hong kong where a positive dose-response gradient between anxiety level and adoption of personal protective measures was found [ ] , suggesting that the right level of anxiety, not so high as to result in a detrimental health impact, can perhaps help to stimulate practices that prevent an epidemic. the current study has several limitations. the first limitation is that the responses were based on selfreports and may be subject to self-report and recall biases. second, the online survey with snowballing sampling resulted in a sample that was lack of representativeness of the general population. in taiwan, females account for . % of the total population, and . % have completed tertiary education. high school graduates and below account for . and . %, respectively. the northern region of taiwan accounts for nearly half ( . %) of the total taiwan population [ ] . it is notable that the study had an over-representation of female and highly educated participants, and an unequal distribution of respondents among the districts of taiwan. the current total taiwanese population is estimated at , , . taipei, the capital city, and its surrounding metropolitan area are on the northern part of the island; this resulted in a large proportion of our study participants coming from the northern region. nevertheless, during the crisis period of the outbreak, the snowballing method, which uses line and facebook, the largest social media platform in taiwan, was extremely effective in achieving a wide coverage of participants. despite the limitations, the study contributes tremendously to the understanding of the psychological well-being and psychobehavioural responses of the general public in taiwan associated with covid- while the epidemic is still on-going. anxiety and the use preventive measures increased along with the increase in the covid- epidemic rate. higher anxiety was associated with greater use of preventive measures against covid- . it is of the utmost urgency that public health interventions be carried out to reach the identified groups of people with poor adherence to preventive measures. considering the extremely contagious nature of covid- , a slight lack of compliance by even a small portion of the population may have grave consequences and contribute to the continued spread of the coronavirus. the demographics disparities in psychological effects and psychobehavioural responses to the outbreak found in this study provide important information for developing and implementing targeted preventive and emotional regulation control strategies. genomic characterisation and epidemiology of novel coronavirus: implications for virus origins and receptor binding covid- ) outbreak situation report- information for travel -ncov epidemic: address mental health care to empower society impact of ebola experiences and risk perceptions on mental health in sierra leone behaviour of singaporeans during the sars outbreak: the impact of anxiety and public satisfaction with media information community psychological and behavioral responses through the first wave of the influenza a (h n ) pandemic in hong kong public perceptions, anxiety, and behaviour change in relation to the swine flu outbreak: cross sectional telephone survey longitudinal assessment of community psychobehavioral responses during and after the outbreak of severe acute respiratory syndrome in hong kong factors influencing psychological distress during a disease epidemic: data from australia's first outbreak of equine influenza the adverse effects of psychological stress on immunoregulatory balance: applications to human inflammatory diseases psychological stress and the human immune system: a meta-analytic study of years of inquiry the psychological impact of quarantine and how to reduce it: rapid review of the evidence. the lancet monitoring community responses to the sars epidemic in hong kong: from day to day a tale of two cities: community psychobehavioral surveillance and related impact on outbreak control in hong kong and singapore during the severe acute respiratory syndrome epidemic population in taiwan threat to democracy: physical and mental health impact of democracy movement in hong kong the development of a six-item short-form of the state scale of the spielberger state-trait anxiety inventory (stai) support for the reliability and validity of a six-item state anxiety scale derived from the state-trait anxiety inventory women's experiences and preferences for service delivery of non-invasive prenatal testing for aneuploidy in a public health setting: a mixed methods study women's experience with non-invasive prenatal testing and emotional well-being and satisfaction after test-results psychological and social consequences of non-invasive prenatal testing (nipt): a scoping review the chinese version of the state-trait anxiety inventory: its relationship to different measures of psychological well-being some norms and reliability data for the state-trait anxiety inventory and the zung self-rating depression scale manual for the stait-trait anxiety inventory applied logistic regression immediate psychological responses and associated factors during the initial stage of the coronavirus disease (covid- ) epidemic among the general population in china a nationwide survey of psychological distress among chinese people in the covid- epidemic: implications and policy recommendations gender differences in anxiety disorders: prevalence, course of illness, comorbidity and burden of illness sex differences in trauma and posttraumatic stress disorder: a quantitative review of years of research the impact of social media on panic during the covid- pandemic in iraqi kurdistan: online questionnaire study the epidemiological characteristics of an outbreak of novel coronavirus diseases (covid- ) in china. zhonghua liu xing bing xue za zhi= zhonghua liuxingbingxue zazhi response to covid- in taiwan: big data analytics, new technology, and proactive testing department of household registration, moi global information network, department of household affairs, ministry of the interior taiwan. statistical map of national population database the authors would like to thank all participants involved in this study.authors' contributions lpw and tshl conceived the study. cch and tshl conducted the study and collected the data. lpw and ha analysed the data. lpw wrote the manuscript. all authors have approved the manuscript. this study was supported by the national taiwan normal university. the research team is independent of the funding agencies and the funding agencies were not involved in the design, interpretation or writing of the manuscript. the datasets used and analyzed during the current study are available from the corresponding author on reasonable request. this study protocol was approved by the research ethics committee of the national taiwan normal university (no. hs ). not applicable. supplementary information accompanies this paper at https://doi.org/ . /s - - - . the authors declare that they have no competing interests. received: april accepted: july key: cord- -ffk ifwy authors: lim, christine; mcaleer, michael; min, jennifer c.h. title: armax modelling of international tourism demand date: - - journal: math comput simul doi: . /j.matcom. . . sha: doc_id: cord_uid: ffk ifwy box–jenkins ( ) models are often used to capture the autoregressive moving average of past observations of tourist arrivals from japan to taiwan and new zealand. however, other explanatory variables, such as real income in the origin country, have also affected the demand for international travel. the purpose of this paper is to use the armax model to investigate the dynamic relationship between tourism demand and real income of japan, and to compare the findings with the single-equation model. unit root tests and diagnostics are performed before estimating the income elasticity of travel demand by japan for new zealand and taiwan based on seasonally unadjusted quarterly data for ( ) to ( ). the empirical results of the armax model support the economic theory that the demand for international travel is positively related to income of the origin country. japan has long been a dominant economic power and a tourism superpower in the asia-pacific region. it has been the largest inbound market for many countries in the region, particularly in the s and the s. after some discussion of tourism movements from japan to new zealand and taiwan since and certain characteristics of the tourists in section , the rest of the paper is organised as follows. the theoretical model and unit root tests for the tourism and income time series are discussed in sections and , respectively. in section , the estimation of the single equation and armax models is presented. some concluding remarks are given in section . the eviews econometric software package [ ] is used for the data analysis and empirical estimation. japan is new zealand's largest asian tourist source market. tourist arrivals from japan had been increasing by more than % per annum from to , after which new zealand started to experience a decline in the japanese market (see fig. ). the / asian economic and financial crises, continuing economic slowdown in the japanese economy since the mid- s, sars and the appreciation of the new zealand dollar have all contributed significantly to the sharp decline in the japanese market [ ] . most japanese tourists regard new zealand as a holiday destination, as shown in fig. . as a long haul destination, it seems that new zealand is a popular destination for older japanese tourists, with % of all visitors aged years and above. according to the international visitor surveys conducted in , most japanese visitors were package travellers, and very few were repeat tourists. auckland (in the north island), followed by canterbury and queenstown (in the south island), were the most popular regions in new zealand for japanese tourists. not surprisingly, hotels were the dominant type of accommodation used by these visitors. market surveys also indicated that shopping and eating out were the most popular activities engaged in by japanese tourists [ ] . besides a decline in japanese tourist arrivals, the increase in the strength of the new zealand currency has also caused a decrease in tourist spending. average japanese tourist expenditures in new zealand decreased by more than % from to . historically, taiwan was a colony of japan from to prior to the kuomintang (kmt) party's flight to taiwan (from china) to exercise its sovereignty. during that time, only the japanese language and education were allowed to be spoken and learned by the island residents. thus, taiwan's lifestyle has been heavily influenced by the japanese culture. for instance, taiwanese and japanese enjoy similar leisure activities, such as shopping, dining, and soaking in hot springs all year around [ ] . japan is a significant inbound tourism market for taiwan in terms of tourist arrivals and tourist average daily expenditure. japanese tourists, which accounted for over % of all international tourists in taiwan, have been increasing by more than % between and [ ] . higher tourism or relative prices in taiwan due to inflation in recent years have not slowed down the flows of tourists from japan. in particular, the number of japanese visitors to taiwan has reached a new record of . million in , a double-digit growth compared with (see fig. ). however, the sars outbreak in , which was the first pandemic of the st century declared by [ ] , had a far-reaching effect on japanese inbound arrivals to taiwan to such levels the country had not experienced since . between and , more than one-third of japanese tourists to taiwan were in the and older age group. the share of japanese male tourists outnumbered their female counterparts by the ratio of approximately : . about % of japanese travelled to taiwan for pleasure, followed by business ( %), and visiting relatives and friends ( %), as shown in fig. . according to a survey conducted by [ ] , taroko, tienhsiang (one of the national parks located on the eastern side of taiwan) and the night markets were the major scenic spots for japanese tourists. the study also found that cuisine and historical relics were the major attractions for most japanese tourists. on average, their duration of stay was . nights, compared with . nights on average for all inbound visitors. the seasonal patterns of tourist arrivals from japan to new zealand and taiwan are shown in fig. . using the multiplicative ratio-to-moving average technique to estimate the monthly seasonal indices, it is not surprising that there is less seasonal variation for a short-haul destination such as taiwan. the seasonal range is . and . for taiwan and new zealand, respectively. nonetheless, the peak tourism months for the two destinations are february (for new that is, from november to march. while the intra-year movements of japanese tourists to new zealand may be related to the climatic conditions at the destination, the same argument would not seem to apply to taiwan. one of the basic goals of tourism demand modelling is to estimate income and/or price elasticities, which can then be used in developing better informed public and private policies. the focus of econometric studies is to determine the extent to which the data support a particular theory. in reviews of empirical studies on international tourism demand and its determinants, lim [ , ] argued that the most prominent and frequently used variable in these studies is income of tourist-generating countries, which affects the ability of consumers in these countries to pay for their overseas travel. more specifically, the demand for international travel is positively related to income in the origin market. the focus of econometric studies is to determine the extent to which the data support a particular theory, namely the demand for international travel is positively related to income of the origin country. we propose to use time series econometric modelling of inbound tourism based on seasonally unadjusted quarterly data for ( ) to ( ) to obtain estimates of income elasticities of travel to new zealand and taiwan by japanese residents. we assume a linear model in the variables in which the data on y , . . ., y t have been generated by y t = α + βx t + ε t , such that y t depends linearly on α and β. the other key assumptions of the classical linear regression model include ( ) homoskedasticity, or constant variance of the disturbances: var(ε t ) = σ e for all t. ( ) no serial correlation of the disturbances across periods: e(ε t ε s ) = (t / = s). ( ) explanatory variables are weakly exogenous, that is, there is zero covariance between ε t and each explanatory variable: for all t. ( ) parameter constancy: α, β and σ (> ) are fixed unknown numbers. [ ] models are often used to capture the autoregressive moving average of past observations of tourist arrivals from japan to taiwan and new zealand. while it is possible to use the autoregressive (ar) and moving average (ma) processes to capture the current pattern of tourist arrivals from a particular market based on its own past arrivals and the random error from previous periods, other explanatory variables, such as real income in the origin country, have also affected the demand for international travel. the armax model is an extension of the box-jenkins autoregressive-moving average (arma) model with explanatory exogenous variables (x). ordinary least squares (ols) is used to estimate the influence of real income on tourism demand by japan for new zealand and taiwan. specifically, we will estimate single equation and armax models to compare the estimates of the japanese income elasticity of travel demand for the two destinations. the sensitivity of tourist arrivals from japan to changes in real income will also be evaluated. as a guide to model selection, the akaike information criterion (aic) and schwarz bayesian criterion (sbc) are used to choose the model with the smallest aic and sbc values. before specifying the armax model, tests and diagnostics are performed on the estimated box-jenkins models. a graphical analysis of the seasonally unadjusted quarterly data from ( ) to ( ) suggests that the logarithm of tourist arrivals from japan to new zealand and taiwan are likely to be nonstationary (see fig. ). this result is supported by the correlogram, which displays the estimated autocorrelation and partial autocorrelation functions of the residuals. a tourist arrival series is said to be stationary if the mean, variance and covariance of the series remain constant over time. the unit root test is a formal method of testing the stationarity of a series. quarterly tourist arrivals (in logarithms) from japan to new zealand and taiwan are tested for unit roots using the augmented dickey-fuller (adf) test procedure, which is based on the following regression equation: where α t is the logarithm of tourist arrivals to new zealand or taiwan from japan at time t, t is a deterministic trend, ε t is a disturbance term of the regression which is independent and normally distributed with zero mean and constant variance. in order to test for unit roots, the hypothesis of interest is the null hypothesis of a unit root is based on the t-statistic (which has a non-standard distribution) using simulated critical values. the deterministic time trend (t) is retained (β / = ) in the test regression because the adf t-statistics with and without a trend are substantially different. as quarterly data are used, an initial lag length of is used in the adf regression to accommodate possible serial correlation in the disturbances. if the fourth lag is insignificant at the % level, the lag length is reduced sequentially until a significant lag length is obtained. the third lag is significant for both series. the adf test results indicate that the adf statistics for the tourist arrival series from japan to new zealand and taiwan (− . and − . , respectively) are both greater (that is, are less negative) than the critical value of − . at the % significance level. therefore, the null hypothesis of a unit root cannot be rejected, which implies that tourist arrivals from japan to new zealand and taiwan are nonstationary. taking the first differences of the logarithm of the tourist arrivals and applying the adf test procedure to the transformed series, a more negative test statistic (of − . at a significant lag length of for new zealand and − . at a lag length of for taiwan) than the critical value of − . are obtained. this suggests that the first difference series are stationary. individual adf tests show that the logarithm of tourist arrivals is integrated of order , i( ), whereas the first difference of the logarithm of the series follow an i( ) process, or is integrated of order . the adf test procedures are applied to the real gdp of japan (in logarithms) for the presence of unit roots. since the reported adf statistics, with and without a deterministic time trend, are substantially different from each other, the former is included in the auxiliary regression test for a unit root in log real gdp (see table ). the results of the adf tests of real gdp presented in table show that the null hypothesis of a unit root cannot be rejected at the % level, which implies that real gdp series of japan are nonstationary. however, the differenced series is stationary and follows an i( ) process, or is integrated of order , whereas the logarithm of real gdp is integrated of order , i( ). the first difference series for tourist arrivals and real gdp will be used in the empirical modelling in the next section. using a single-equation model, the influence of real income on tourism demand by japan is given as follows: where y t is the log of japanese real gdp at time t. with the inclusion of seasonal dummy variables, d t , d t and d t in the model as well as a sars dummy variable for taiwan, the following estimates are obtained by ols (with absolute t-ratios in parentheses): a t = . ( . ) deletion of the insignificant seasonal dummy variable for new zealand does not yield a significant income elasticity of travel demand. the same is also true for taiwan with the deletion of the insignificant seasonal and sars dummy variables. the armax model is used to investigate the dynamic relationship between tourism demand and real income of japan, and to compare the findings with the single-equation model. extensive discussion of armax modelling and estimation can be found in [ , ] . a simple armax(p, q) model can be expressed as a t = α + β a t− + · · · + β p a t−p + φ y t + φ y t− + ε t − θ ε t− − · · · − θ q ε t−q in this form, the model has lagged dependent and independent variables and a moving average disturbance. we assume that the errors are independently and identically distributed, with zero mean, constant variance and zero covariance. the granger causality tests also suggest no feedback from α t to y t and vice versa (see tables and ) . additional independent variables, each with its own lag structure can be included in the model. an armax(p, q) model with no additional regressors is equivalent to the arma(p, q) model: another important special case is the arx(p) model, which is an armax(p, q) model with no significant disturbance terms: the unit root tests for different available price proxies show that the latter follows an i( ) process, while the tourist arrival and real income series are integrated of order , i ( ) . before the armax model is used to estimate the relationship between income and travel demand by japan, we need to identify a plausible set of arma models. using the first difference of the log tourist arrivals from japan, various arima models have been estimated using ordinary least squares. by excluding insignificant ar and ma lags, the use of diagnostics and selection criteria would help to determine a more parsimonious model. the latter is subsequently used to undertake armax modelling and estimation of the income elasticity of travel demand by japan for new zealand and taiwan over the period - . hence, the models selected yield significant t-statistics at the % level of significance for the ar and ma coefficients, with no serial correlation at the % level, using the lagrange multiplier test for serial correlation. arima ( , , ) and arima( , , ) have been identified for new zealand, and arima( , , ) for taiwan as the optimal models. inclusion of three seasonal dummy variables in these models and a sars dummy for taiwan, the final armax models are obtained as follows, with the lowest aic and sbc values (with absolute t-ratios in parentheses): a t = . ( . the lagrange multiplier tests, lm(sc), show that the models do not have serial correlation at the % level. in this paper we have estimated single-equation models to evaluate the effect of changes in income on japanese travel demand for new zealand and taiwan over the period - . by including an income variable with a finite lag structure, the armax model is also used to estimate the income elasticity of tourism demand of japan for the same period. the tourist arrival and income variable have been tested and appropriately transformed to obtain stationarity of the data series. additional variables, namely seasonal and sars dummy variables, were also included in the estimation of the single equation and armax models. unlike the single-equation model, the armax technique is more appropriate for investigating the dynamic relationship between tourism demand and real income of japan. the model is developed in two stages, which initially requires that the box-jenkins arima models be identified and selected. the findings of the armax model support the economic theory. in contrast to the single-equation models, all the armax models show that the japanese income elasticities of travel demand are positive and significant. according to the single-equation model for taiwan, the effects of sars in had a significant but positive effect on japanese inbound travel. the latter is contrary to theory and reality. only the seasonal effect in quarter is negative and significant in both the single equation and armax models for new zealand and taiwan. future research could include the box-jenkins intervention analysis, which is a useful technique to evaluate the effects of exogenous interventions which occurred at some identifiable points in time [ ] . in this regard, intervention analysis may provide a useful stochastic modelling tool to enable an examination of the impact of the significant structural breaks on japanese travel demand for different countries. time series analysis forecasting and control intervention analysis with applications to economic and environmental problems eviews , quantitative micro software primary demand for beer in the netherlands: an application of armax model specification econometric analysis a meta-analytic review of international tourism demand a survey of tourism demand modelling practice: issues and implications taiwan: magnet for japanese tourists world health organisation, world health organisation issues emergency travel advisory world tourism organisation, tourism highlights edition the authors are grateful to the reviewer, and conference participants at the international congress on modelling and simulation, christchurch, new zealand, for helpful comments. the second author wishes to acknowledge the financial support of the australian research council. key: cord- -zhiuuwv authors: lo, yi-chun title: implementation of the ihr joint external evaluation: taiwan's experiences date: - - journal: health secur doi: . /hs. . sha: doc_id: cord_uid: zhiuuwv in february , the world health organization developed the joint external evaluation (jee) tool to independently assess country capacity to prevent, detect, and respond to public health threats as part of the international health regulations (ihr) ( ) monitoring and evaluation framework. in light of this, the taiwan government actively engaged at least government agencies or institutions and voluntarily implemented the jee. an external assessment team consisting of us subject matter experts conducted the external evaluation, including site visits, from june to july , . the results, published on october , , are useful and will be translated into actions and change in the system. based on taiwan's experiences, early stakeholder engagement and an experts' pre-jee pilot visit would contribute to a successful jee process. t he beginning of the st century has been marked by a series of epidemics and pandemics, including extensively drug-resistant tuberculosis (xdrtb) worldwide, anthrax in the united states, severe acute respiratory syndrome (sars) in east asia and canada, avian influenza [a(h n ) and a(h n )] in southeast asia and china, middle east respiratory syndrome (mers) in the middle east and south korea, ebola virus disease in west africa, and, most recently, zika virus disease in the americas. these emerging infectious diseases as a global health burden are thought to be driven, at least partly, by the emergence and spread of new pathogens; globalization of travel, food, and medicines; the rise of antimicrobial resistance; and intentional engineering or accidental release of biohazard agents. the morbidity, mortality, and economic impact of such public health threats can be enormous. for example, the ebola outbreak in west africa during - was estimated to have resulted in approximately , human cases, at least , deaths, and economic loss of more than $ billion. , in response to international public health emergencies such as sars, the world health organization (who) established the international health regulations (ihr) ( ) , which require that all countries have the capability to detect, assess, report, and respond-that is, detect potential threats through surveillance systems and laboratories, make decisions in public health emergencies, report specific diseases and any potential international public health emergencies, and respond to public health events. however, the who reported that by , fewer than % of the countries had met the ihr goals, and by , only approximately % of the countries were fully prepared to detect and respond to an outbreak. in the wake of the ebola outbreak in west africa, several high-level panel reports highlighted the pitfalls of relying solely on a government's voluntary self-assessment to measure core capacities. [ ] [ ] [ ] the panels unanimously recommended that all countries should commit to participate in regular, independent peer review or external assessment of their core capacities. in the th world health assembly in , the ihr review committee on second extensions for establishing national public health capacities and on ihr implementation recommended that countries move from exclusive self-evaluation to approaches that combine selfevaluation, peer review, and voluntary external evaluations involving a combination of domestic and independent experts. in light of this, who, in collaboration with the global health security agenda (ghsa) launched in february , developed the joint external evaluation ( jee) process and jee tool in february as part of the ihr ( ) monitoring and evaluation framework. the jee tool integrated the ghsa assessment tool, which was intended to assess country capacity to prevent, detect, and respond to public health threats independently of whether they are naturally occurring, deliberate, or accidental. countries are encouraged to request a jee mission to help them identify the most urgent needs in their health system with the expectation that the jee can help engage with stakeholders and partners to support a country's preparedness for outbreaks and health emergencies. bangladesh, ethiopia, liberia, mozambique, pakistan, tanzania, and the united states were among the first countries to have completed and published an external full assessment using the jee tool. taiwan's commitment to participation in jee taiwan had a population of . million and a nominal gross domestic product (gdp) of $ . billion in , when it was rated the world's th largest economy and the th largest economy in asia. the sars outbreak in east asia, including taiwan, and the subsequent public health threat from avian influenza, mers, and zika outbreaks in the region, have repeatedly tested taiwan's preparedness for public health emergencies and illustrated the urgent need to establish a systematic approach to prevent, detect, and respond to human and animal disease threats, particularly through multilateral and multisectoral collaboration, including domestic and international partnerships. although not a member state of the who, taiwan has demonstrated strong commitment to global health security activities. examples include actively reporting cases to the who and sharing surveillance data with the relevant countries through the national ihr focal points since , contributing funds and personal protective equipment to fight against ebola in west africa in , and conducting ebola, mers, and zika training courses for regional partners during - in cooperation with the united states through the taiwan-us global cooperation training framework (gctf). in april (before the jee tool was developed), the taiwan centers for disease control (cdc) officially announced that it would pursue an independent, external review of taiwan's core capacities using the ghsa assessment tool. during the next months, taiwan cdc established a ghsa external assessment working group in the division of planning and coordination and an agencylevel, interdepartmental ghsa external assessment task force; secured funding and high-level support from the executive yuan and ministry of health and welfare (mohw); and requested expertise and guidance from the university of pittsburgh medical center (upmc) center for health security (now the johns hopkins center for health security) to prepare for the assessment. in february , in light of the fresh release of the jee tool, which already integrated the ghsa assessment tool, taiwan cdc and the center for health security promptly decided to switch to the jee tool for this assessment. although the jee working group (formerly named the ghsa external assessment working group) remained in the division of planning and coordination of taiwan cdc, because the jee was used to assess taiwan's collected capabilities, not just those of the mohw or taiwan cdc, the interdepartmental task force was expanded to a multisectoral team that involved other government agencies, such as authorities of agriculture, defense, border control, environmental protection, and nuclear power, to address elements that were not included in the ghsa assessment tool. an external assessment team consisting of us subject matter experts from the center for health security and a former us cdc official conducted the evaluation in collaboration with the jee working group and the multisectoral team of officials from relevant agencies from the government of taiwan. the external evaluation process was planned to involve separate visits to taipei, taiwan, including a pre-self-assessment orientation visit (pilot visit) in march and the evaluation mission, which took place in june . the -day pilot visit took place in taiwan cdc's office building from march to april , . three subject matter experts from the external assessment team were on the pilot visit. on day , the experts listened to briefings on taiwan's response to ebola and zika threats, introduced the ghsa and jee mission, and explained the proposed work plan for completing the jee in taiwan. the experts also discussed with taiwan's jee working group and multisectoral team the steps that would be required to conduct the self-assessment and the external evaluation using the jee tool. on days to , the experts met individual members of the multisectoral team who were responsible for specific jee elements and discussed each of the technical and contextual questions contained in the respective sections of the jee tool. the indicators and questions listed in the jee tool were in the original english text, not translated. the language used in the conversation was english, too, with occasional assistance from local staff in translating to mandarin chinese when needed. before the discussion, individual members were instructed that, because the experts would talk them through each indicator and question to ensure full understanding, it was unnecessary for the members to answer or draft a response to the jee questions in advance. the discussion of each element generally took at least minutes, mostly involving clarification about what each question really means and how responses should be drafted. for example, elaborative answers that demonstrated real examples were preferred, rather than just yes or no answers. the members could also describe an example that came to mind and ask the experts if it was eligible for a response. although most of the time the experts' answers would be ''yes,'' the q&a process not only provided reassurance to the members who were not native english speakers but also helped engage the members in ownership of jee implementation. overall, the pilot visit was successful and well received. at the end of the pilot visit, the experts and taiwan's jee working group discussed next steps, jointly planned for work to be completed before the experts' next visit in june , and developed a proposed agenda for the next visit. after the pilot visit, the jee working group announced the launch of the jee self-assessment on april . members of the multisectoral team, supported by the respective authorities, were requested to submit point-by-point responses in english to the technical and contextual questions in the designated jee element by may , , to the jee working group. documents that served as attachments to the responses could be submitted in their original text and language, but each needed to be accompanied by a summary of content in english with the focus on its relevance to the specific jee question. the team was asked not to provide a self-scoring result. throughout the process, the jee working group facilitated communication and coordination among all departments, forwarded additional queries that were raised by the multisectoral team members to the center for health security for clarification, provided support with english translation if necessary, and compiled the self-assessment report. four high-ranking taiwan cdc officials, each responsible for to jee elements, were asked to review the reports with the team members who drafted the responses to ensure appropriateness of the content and representativeness of the report at the national level. the experts of the center for health security answered queries forwarded by the jee working group to ensure consistent understanding of each jee question. the external evaluation mission took place in taiwan cdc's office building from june to july , , comprising working days. during day to day , the schedule was broken down into jee elements, with each session lasting hours. the external assessment team reviewed the written self-assessment report and supporting documentation, interviewed the multisectoral team members who had drafted and presented the self-assessment results, and assigned scores for each of the indicators on a point scale. in each -hour discussion, the external assessment team and taiwan team members also developed consensus on taiwan's strengths, limitations, recommended priority actions, and scores for the specific jee element. to evaluate ihr capacities at different levels, the external assessment team conducted site visits to a regional health department and a regional teaching hospital in taichung city, located in central taiwan, and to the taiwan cdc's emergency operation center. on the final day, the external assessment team presented to taiwan's jee working group and multisectoral team members a summary of key findings for each assessment area as well as a summary of needs for additional supporting documentation for certain indicators. the results of the jee for taiwan were published on october , , with the full text available at the websites of both the upmc center for health security and the taiwan cdc. , on the same day, the findings of taiwan's jee were presented at an international public health symposium entitled ''assessing countries' global health security capabilities,'' convened by the center for health security in washington, dc. taiwan became the th country to publish the results of an external assessment using the jee tool. the jee process in taiwan in involved the participation of at least government agencies or institutions. the key to success in achieving such large-scale multisectoral collaborations for jee is the -month preparatory work beforehand: advocacy of the one health concept among stakeholders, sensitization of high-level political leadership across levels and agencies, and the taiwan government's strong commitment to transparency and accountability. previous self-assessment and external assessment experiences in taiwan were useful in planning and advocating for the jee. during - , taiwan conducted a selfassessment of the national ihr core capacities using the who-issued assessment tool for core capacity requirements at airports, ports, and ground crossings and the protocol for assessing national surveillance and response capacities for the ihr ( ) that were released in october and in december , respectively. to commemorate the th anniversary of sars, the government had further invited the upmc center for biosecurity to conduct an external assessment of taiwan's public health emergency preparedness in december . external assessment of ihr core capacity requirements at airports and seaports was conducted by invited australian experts in march . these experiences not only helped to engage stakeholders in uptake of regular self and external review of relevant programs, but also helped build confidence and comfort among participants in honestly demonstrating both strengths and limitations to external reviewers without need for fear of being blamed or punished. we also found the pilot visit of the external assessment experts to be extremely useful. such face-to-face conversations substantially avoided confusion and misinterpretation of certain jee questions and helped reduce anxiety among stakeholders, especially team members tasked to provide self-assessment results. the experts' reassuring emphasis on the importance of transparency, accountability, and ownership also echoed the values promoted by the taiwan government and demonstrated the professionalism of the jee process. the taiwan government is dedicated to contributing to regional and global health security. the strengths recognized through the jee might represent opportunities for taiwan to help other countries prevent, detect, and respond to public health threats. on the other hand, limitations and challenges identified through the jee highlight areas of core capacities that need prioritization for increased funding and other resource input for improvement. because the jee is expected to be repeated every to years, the public health, animal health, and science and technology authorities have jointly proposed a -year project ( - ) with an annual budget of $ . million to address strengths and limitations identified through jee with focus on elements such as antimicrobial resistance, zoonotic diseases, biosafety and biosecurity, the national laboratory system, real-time surveillance, and workforce development. multisectoral collaborations will be substantially strengthened, including participation of nongovernmental organizations. as of november , the proposal has been approved by the executive yuan, pending budget approval by the legislative yuan. the leading agency for this jee was taiwan cdc. however, in light of the multisectoral nature of the jee, taiwan cdc plans to propose to the high-level political leadership that post-jee monitoring mechanisms should be placed at an upper level, such as the homeland security office of the executive yuan, which is authorized to oversee and coordinate all relevant ministries, agencies, and institutions. an annual self-assessment using the jee tool is also recommended to help all stakeholders monitor the current status of progress of respective elements. in conclusion, implementation of the jee in taiwan has led to findings that will be readily translated into actions and changes in the system. we encourage countries that have not conducted a jee to consider and invest in this useful activity. based on taiwan's experiences, early stakeholder engagement and an experts' pre-jee pilot visit would contribute to a successful jee process. world health organization. the world health report : a safer future: global public health security in the st century the economic impact of the ebola epidemic: short-and medium-term estimates for west africa cost of the ebola epidemic. cdc website world health organization report of the review committee on second extensions for establishing national public health capacities and on ihr implementation. geneva: who report of the ebola interim assessment panel will ebola change the game? ten essential reforms before the next pandemic. the report of the harvard-lshtm independent panel on the global response to ebola the neglected dimension of global security-a framework for countering infectious-disease crises joint external evaluation tool: international health regulations taiwan's international role and the gctf taiwan centers for disease control. taiwan cdc seeks active participation in global health security agenda (ghsa) [press release ihr joint external evaluation of taiwan taiwan centers for disease control. interim ihr jee report of taiwan assessing countries' global health security capabilities: an international public health symposium convened by the upmc center for health security building core capacities at the designated points of entry according to the international health regulations : a review of the progress and prospects of taiwan taiwan's public health emergency preparedness programs years after sars key: cord- - jh w f authors: huang, shiu-feng; huang, yhu-chering; chang, feng-yee; lin, jung-chung; chiu, chun-hsiang; chen, chien-wen; wang, fu-der; chiu, yen-ling; cheng, shu-hsing; cheng, chien-yu; lin, yi-chun; chen, cheng-pin; huang, chien-hsien; liu, po-yu; lee, yuan-ti; lee, chen-hsiang; chen, yao-shen; sy, cheng-len; tseng, yu-ting; hsu, cheng-ting; tseng, chia-chun; lee, yu-lin; liu, chun-eng; sytwu, huey-kang title: rapid establishment of a covid- biobank in nhri by national biobank consortium of taiwan date: - - journal: biomed j doi: . /j.bj. . . sha: doc_id: cord_uid: jh w f by the request of the minister of health and welfare, nhri biobank was assigned to establish a covid- biobank in early feb, to collect covid- patients' blood samples for taiwan researchers and industries in an emergent way. it was set up in less than weeks and quickly opened for application. this biobank can provide applicants with biosamples, such as serum, dna and rna, and also the clinical and genomic data, so as to accelerate the covid- treatment and prevention research in taiwan. this coid- biobank already received applications. it has become a very important research resource for the covid- pandemic in taiwan, including disease mechanism, the variable human responses and epidemic preventions. a new severe pneumonia outbreak occurred in wuhan, china in december , and has rapidly spread to provinces in china and countries around the world. this respiratory illness is caused by severe acute respiratory syndrome coronavirus (sars-cov- ). [ ] the who has named it novel coronavirus ( -ncov) on jan. , . [ ] . as of may , , more than million persons with covid- infection were reported in countries and territories worldwide and resulting in , death [ ] . in order to slow down the spread of the virus, most countries have carried out limiting travel, quarantining all possible infected citizens, and cancelling large gathering activities, such as sporting events, and concerts, or even closed all of the schools, restaurants, movie theaters, etc. this covid- pandemic not just a global health crisis, but also affect the global economy system. it becomes the greatest disaster to the human kind since world war two. [ ] taiwan had experienced a severe health crisis and economic recession in due to sars. therefore, taiwan government took very quick reaction to prevent the spread of covid- in taiwan according to the previous experience dealing with sars. it turns out to be very effective. taiwan still has a low incidence and very low death rate of covid- compared with europe and usa. [ ] but the situation of covid- infection in the united states and european countries are still in the peak by mid-april, . how to treat and prevent covid- infection becomes the most important global health issues. the governments of big countries, the big pharmaceutical companies, the major scientific laboratories all have made big investment for the treatment of covid- currently. since taiwan has many academic institutes and industries good in the biotechnology and pharmaceutical fields, it is a very good time point for taiwan to develop quick diagnosis kits, new drugs and vaccines for covid- infection. therefore, after taiwan start to have covid- patients in january, , the minister of health and welfare requested national health research institutes (nhri) to take the responsibility in coordinating the research in the treatment and prevention of covid- infection in taiwan. for development of rapid diagnostic reagent or new drugs, good human sample with clinical data for testing and verification before real clinical application is very important. biosamples are also very important for the basic research and epidemiology analyses. in , the taiwan government also had organized several research projects for sars. however, the sars epidemic ended quickly in taiwan by the time when all the domestic academic laboratories were ready to work on it. there were few human samples or data collected for further research. there were no new patients in taiwan or in the world for treatment, either. thus, most of the research for sars were discontinued. the situation for covid- appears quite different. it has much more mild or even asymptomatic cases and much higher infectious rate. so it is expected that covid- will be more like influenza, difficult to be eradicated like sars. on feb. , , the th covid- case in taiwan following this request, an in-house expert panel meeting was immediately carried out on feb. , to discuss what kind of specimens to collect and what are the biosafety rules should be followed when collecting these specimens from covid- patient. the conclusion was that blood and sputum or throat swab samples are both valuable for research. blood samples could be used for serum antibody analyses, rna sequencing, and dna genetic analysis. the sputum or throat swab could be used for microbiome analysis. the collection and transportation of the specimens from covid- patient need to be in p level. handling the specimen needs to be in a p laboratory with negative pressure and within a biosafety cabinet. multiple experts of virology or infectious disease were consulted for the above issues in the following days. since this is a new virus with so many unknown characters, the collection and transportation of the airway specimens such as sputum and throat swab could have a very high risk. in addition, for rapid screening of covid- , the throat swab needs to be freshly obtained specimen, not good with the frozen specimen. therefore, only blood samples will be collected prospectively, airways specimen collection will not be done. this decision was supported by the members attending the covid- expert meeting on feb. , which is chaired by the nhri vice president huey-kang sytwu. since these human specimen will be used for diverse purposes, it would be most convenient to store the biosamples in a biobank with broad consent. however, infectious specimens should not be placed in the same space with other biobank specimens, and all biobanks in taiwan are not designed for p level. they are not willing to collect or store infectious biosamples, either. thus, nhri biobank was assigned to collect all covid- human blood biosamples, since nhri is mission oriented institutes. this is a big challenge for nhri biobank, we need to set up a new isolated laboratory in p level for storage and handling of these covid- human biosamples in a very short time, so that we could offer these precious biospecimens for developing new detection reagents or drugs for covid- as soon as possible. to achieve this goal, we need to work in directions quickly and simultaneously: ) to collect the covid- biosamples in accordance with the human biobank management act all recruitment could directly use the nhri biobank non-tumor icf without the need to apply for irb approval in each hospital. on march , we received the first covid- patient blood samples immediately. we also quickly received the first application for covid- serum samples on march and got approved in april. act [ ] nhri president liang rapidly approved the usage of a new laboratory exclusively for nhri biobank to store and handling the covid- biosamples. this laboratory needs to be of p level with negative pressure, access control and video camera inspection. in addition, it also needs to have a biosafety cabinet (bsc) for handling the covid- biosamples. two deep freezers (- ℃ and - ℃) for storage of the biosamples, a large capacity centrifuge, and a water bath for the dna and rna extraction were also necessary. all of the above equipment were purchased in an urgent way and fortunately were all available for the p laboratory in one week. for opening this p lab, and to handle the covid- human biosamples, we need to apply for the permission of nhri biosafty committee. they would check all details to see if the laboratory meet the p operating standard. this special p laboratory was completely set up and got permission to work in weeks, just before we received the first covid- human samples on march , . http://biobank.nhri.org.tw/zht/webcont!cont.action?news_id= &lab_i d=biobank. after the application form is received, it will have a scientific review first, which will be completed within weeks. then, the applicants need to provide irb approval and grant approval documents of their research to the biobank office. the application will then be discussed in the biobank ethic and governance committee conference to get final approval. since covid- specimens are quite precious, we have organized a covid- scientific committee to review all of the applications for covid- . the committee members of the biobank include specialists from different fields, including virology, vaccine, immunology, pharmaceuticals, disease control, and governmental industry office. if the application is for patient's serum, the applicants need to transport the specimen in p standard and need to have p lab for handling the specimens. since covid- patients in taiwan was few (only cases reported when the p laboratory was established), and these patients distributed diversely across taiwan. only the nation-wide biosample collection could achieve enough case number for good research and industrial application. in contrast, it will be very time consuming if the investigators want to collect enough specimens from several hospitals one by one by themselves, not to mention that they also need to apply for irb approval of each hospital first. this nhri covid- biobank will also conduct value-added analyses of the collected blood samples, including dna whole genome sequencing and rna sequencing. thus, we will not only provide biosamples, such as serum, dna and rna, but also the clinical and genomic data. by may , , this covid- biobank has collected blood samples of patients from more than hospitals across north, middle and south part of taiwan, including both covid- (+) and (-) pneumonia patients. however, since taiwan already have reported covi- cases as of may , [ ] , the current recruitment of covid- patients is still not satisfactory. the challenge of nation-wide collection is that many hospitals are reluctant to collect or transport infectious specimens or not familiar with it. we need to convince the hospital personnel that collection of the infectious biosamples according to the sop is quite safe and not difficult. we are very grateful for the doctors and the medical personnel who spent the time and effort to help collect the specimens and all of the patients who are willing to donate their blood samples for covid- research. this covid- biobank was opened to all researchers and industries for application immediately on march , . all applications will be reviewed by a scientific committee composed of specialists in the treatment or research in covid- to make sure these precious biosamples are in good hands for use. currently we already received applications from academic institutes. by the request of the minister of health and welfare, nhri biobank was assigned to establish a covid- biobank in early feb, to collect covid- patients' blood samples for taiwan researchers and industries in an emergent way. it was set up in less than weeks and quickly opened for application. this biobank can provide applicants with biosamples, such as serum, dna and rna, and also the clinical and genomic data, so as to accelerate the covid- treatment and prevention research in taiwan. this coid- biobank already received applications. it has become a very important research resource for the covid- pandemic in taiwan, including disease mechanism, the variable human responses and epidemic preventions. the species severe acute respiratory syndrome-related coronavirus: classifying -ncov and naming it sars-cov- " surveillance case definitions for human infection with novel coronavirus (ncov): interim guidance v laws and regulations database of the republic of china: human biobank management act laws and regulations database of the republic of china: communicable disease control act key: cord- - gvay i authors: hsieh, yu-chia; tsao, kuo-chien; huang, ching-tai; chang, kuang-yi; huang, yhu-chering; gong, yu-nong title: clinical characteristics of patients with laboratory-confirmed influenza a(h n )pdm during the / and / clade b/ b. / b. -predominant outbreaks date: - - journal: sci rep doi: . /s - - - sha: doc_id: cord_uid: gvay i a novel pandemic influenza a(h n )pdm virus emerged in globally, and it continues to circulate in humans. the national influenza surveillance network in taiwan identified five a(h n )pdm -predominant seasons, representing the / , / , / , / , and / outbreaks from to . independently, a retrospective cohort study (which enrolled infected patients during the five seasons) was conducted at chang gung memorial hospital to explore the risk factors associated with influenza a(h n )pdm -related complications. a phylogenetic analysis of hemagglutinin (ha) sequences showed that the circulating a(h n )pdm virus belonged to clades , , and in / ; clades , , , and in / ; clades and c in / ; clades b in / ; and b/ b. / b. in / . compared to individuals infected in non- b/ b. / b. seasons ( / , / , and / ), those infected in b/ b. / b. seasons ( / and / ) were at higher risk for influenza-related complications (adjusted odds ratio [aor]: . , % confidence interval [ci]: . – . ), pneumonia (aor: . , % ci: . – . ), mechanical ventilation (aor: . , % ci: . – . ), and acute respiratory distress syndrome (aor: . , % ci: . – . ). for the increased severity of infection during the influenza a(h n )pdm clade b/ b. / b. seasons, aspects related to the antigenic change of a(h n )pdm virus, immune response of the host, and environmental factors required further investigation. scientific reports | ( ) : | doi: . /s - - - number of severe cases and outcomes in the groups at risk and healthy young adults; these events were associated with a(h n )pdm clade b. infection , . since , the taiwan centers for disease control (cdc) has established a nationwide surveillance system requiring contract virologic laboratories to perform continuous virologic surveillance for respiratory viruses, particularly influenza and enteroviruses; this system was established after an epidemic of enterovirus in . the long-term national influenza surveillance network described the epidemiologic pattern of circulating viruses, and it has successfully identified the outbreaks of severe acute respiratory syndrome (sars)-associated coronavirus and adenovirus , . moreover, it also identified the novel h n and h n influenza viruses were significantly different between each season (table ) . a phylogenetic analysis of hemagglutinin (ha) sequences recovered in these epidemics, along with geographically diverse global influenza a(h n ) pdm viral sequences, has revealed that the sequences are members of clades , seasons versus non-clades b/ b. / b. seasons, the patients were classified into two groups. the median (interquartile range, iqr) age of patients in the b/ b. / b. season was older than that in the non b/ b. / b. seasons ( table ). the number of infected individuals aged - years was higher in b/ b. / b. seasons than that in the non-clade b/ b. / b. seasons ( table ). the rate of underlying conditions; complications, including pneumonia and acute respiratory distress syndrome (ards); icu admission; respiratory failure with mechanical ventilation; -day mortality; and in-hospital mortality in b/ b. / b. seasons were significantly higher than that in non-clade b/ b. / b. seasons ( table ). the rate of underlying conditions; complications, such as ards; icu admission; and respiratory failure with mechanical ventilation in b/ b. / b. seasons was significantly higher than that in non-clade b/ b. / b. seasons (table ) . the results of the logistic regression analysis on the risk factors associated with influenza a(h n )pdm -related complications and pneumonia are shown in table , and respiratory failure with mechanical ventilation and ards are also presented in table . in the univariate analysis, b/ b. / b. season, age ( - years), onset to presentation, underlying conditions, obesity, smoking, alcoholism, and antiviral therapy were significant risk factors of complications, pneumonia, mechanical ventilation, and ards (tables and ). in the multivariate logistic regression analysis, b/ b. / b. season, age ( - years and ≥ years), underlying conditions, and antiviral therapy were significant independent risk factors of complications, pneumonia, and mechanical ventilation (tables and ). only b/ b. / b. season and obesity were considered as significant independent risk factors of ards ( table ). the effect of b/ b. / b. season on the total number of influenza-related complications was not significant in children aged ≤ years. however, it was significantly stronger among individuals aged ≥ years (table s ). among the hospitalized patients with laboratory-confirmed influenza a(h n )pdm infection, male patients and those with underlying conditions were significantly at risk for -day mortality (overall death within the first days after hospital admission) and all-cause in-hospital mortality (overall death during hospital admission) as assessed using the multivariable cox proportional hazard model ( table ). the same analysis showed that season was not associated with an increased risk for -day and all-cause in-hospital mortality (table ). the during the / season, an unusually high hospitalization rate in adults aged - years was observed in the united states and mexico , . the increased morbidity in middle-aged adults during the / season had been attributed to the low vaccination rate in this age group . however, that hypothesis cannot explain the unusual number of severe cases because the vaccination rate had already been low during the previous years , . an interesting study has shown that up to % of middle-aged adults born between and , who had been exposed to seasonal h n viruses circulating in , had reduced serologic reactivity with the / a(h n )pdm ; notably, the / virus harbors the distinctive k q ha antigenic mutation . in the cohort of individuals born between and , ha-specific antibodies with activity against a(h n )pdm must have been produced and shaped by exposure to prior-season h n viruses (the so called "original antigenic sin") . nonetheless, the ha-specific antibodies in this cohort failed to recognize the / a(h n ) . compared to the a/california/ / vaccine virus, viruses of clade b harbor d n, k q, s t, k e, and a t substitutions in ha . viruses of subclade b. harbor further amino acid substitutions s n, s n, and i t and b. and carry amino acid substitutions v t and v i . more extensive studies must be conducted to identify the potential antigenic differences between clade b and subclade b. / b. ; such studies are expected to improve our understanding of how a(h n )pdm evolved (and continues to evolve) and how it affects and interacts with the human immune system. in the / season, the who has selected a new vaccine virus, which is the a/michigan/ / (h n )pdm -like virus (a member of the b. subclade), as the influenza vaccine virus component for the northern hemisphere. the national influenza surveillance network coordinated by the taiwan cdc was established more than years ago. policies favoring government funding for vaccines and antiviral agents have been consistent during the subsequent intervals. between and , government-funded vaccines have been administered primarily to those aged months to years, elderly individuals aged ≥ years, healthcare workers, and individuals with underlying diseases. individuals aged - years were not included in the government-funded vaccination program. elementary school children aged - years had the highest influenza vaccination rate, with coverage reaching - % annually . the present study is limited by its observational nature and the incorporation of a retrospective investigation. a potential bias may exist due to the exclusion of all cases with a(h n )pdm infection for years. nonetheless, no change was observed in terms of admission or management procedures during these outbreaks. the surveillance and reporting system in taiwan has long been established. taken together, the increased frequency of complications in / and / is unlikely due to detection bias. in addition, the major drawback of this study was the lack of documentation about the history of influenza vaccination in the records used to generate this study. however, a study by taiwan cdc has reported that % of patients with complications in the / season had not received the influenza vaccine . the vaccine coverage rate in non-elderly adults and elderly individuals would have been low during each of the outbreaks, particularly during the first wave, given that no a(h n )pdm vaccine was available in / . thus, the increased severity of influenza during the / and / seasons is unlikely to reflect a decreased rate of vaccination. the study has shown that taiwan experienced the greatest burden of influenza-related complications due to a(h n )pdm clades b/ b. / b. in the sixth year of its circulation. the reasons for the increased impact of influenza-related complications remain uncertain. aspects related to the antigenic change of a(h n )pdm virus, immune response of the host, and environmental factors required further investigation. this report shows the importance of influenza disease surveillance and requires that the influenza a(h n )pdm virus should always be considered. national influenza surveillance network. the network consists of eight regional commissioned laboratories located in the northern (n = ), central (n = ), southern (n = ), and eastern (n = ) parts of taiwan. these laboratories have steadily collected more than respiratory specimens for surveillance per year, including more than influenza virus specimens annually, all of which are sent to the taiwan cdc for the monitoring of influenza viral activity. the taiwan influenza express, a weekly online influenza surveillance report, has been published by the taiwan cdc from july to may of each year since (http://www.cdc.gov.tw/english/ submenu.aspx?treeid = ed d c bb &nowtreeid = f e d fd a) , . this report includes the total number of respiratory specimens; isolate number of influenza a(h n ), influenza a(h n ), and influenza b; and case number of laboratory-confirmed influenza cases in intensive care units (icus), a class of events that is considered a category nationally notifiable disease. however, data on weeks - are not available annually. a confirmed case involved a patient who had acute influenza-like illness (temperature ≥ °c with either cough or sore throat) and nasopharyngeal/throat or bronchoalveolar lavage samples harboring influenza a(h n )pdm virus as detected using real-time (rt) reverse-transcription polymerase chain reaction (pcr) assay or via viral culture , . for the purposes of the present study, each season was defined as extending from july of the same year to may of the following year. the annual population figures provided by the department of household registration affairs of the interior ministry were used for the calculation of the incidence of laboratory-confirmed influenza a(h n )pdm cases in the icu. , a -bed, university-affiliated teaching hospital that is located in northern taiwan and provides both primary and tertiary care. in addition, cgmh is one of the regional commissioned laboratories of the taiwan cdc. patients who had acute influenza-like illness (temperature ≥ °c with either cough or sore throat) and had influenza a(h n )pdm virus as detected using rt-pcr assay or via viral culture using respiratory specimens were included in the study. patients whose data are not available were excluded. the institutional review board of cgmht approved the study, and it was carried out in accordance with the relevant guidelines and regulations. informed consent was waived due to the study's retrospective nature. all medical records of the enrolled patients were reviewed. demographic characteristics, underlying medical conditions, clinical course, antiviral treatment (oseltamivir or zanamivir), mechanical ventilation, admission to an icu, and death were recorded using a structured questionnaire. body mass index (bmi), a measure of obesity, was calculated for patients whose height and weight data were available. obesity was defined as follows: ) body weight ≥ th percentile in children < years of age; ) bmi ≥ kg/m in patients aged between and years; and ) bmi > kg/m (chinese criteria) in patients > years . medical conditions associated with a high risk for influenza complications were defined based on those listed by the united states advisory committee on immunization practices . patients with confirmed pneumonia on radiography, acute respiratory distress syndrome (ards), acute onset of cardiovascular, neurologic condition, respiratory failure with mechanical ventilation; those who were admitted in the icu; and those who died were considered to have influenza-related complications. pneumonia on radiography was diagnosed based on the presence of a consolidation, infiltrate, or opacity . ards was defined according to the standard criteria . the primary study outcome was the occurrence of (any) influenza-related complications. the secondary study outcomes were pneumonia, mechanical ventilation, ards, -day mortality, and in-hospital mortality. genetic characterization of the virus. a total of isolated influenza a(h n )pdm virus were randomly selected for the analysis of viral hemagglutinin (ha) and neuraminidase (na) genes across the five seasons. the rna was extracted using the qiaamp viral rna mini kit (qigen, germany) according to the manufacturer's instructions. rt-pcr and primer pairs used for sequencing ha and na genes were performed, as previously described . sanger sequencing of the viral ha and na genes was performed to establish clade designation and to detect differences in amino acid . the obtained amplicons were assembled into a full-length , -bp span for ha and -bp for na using dnastar lasergene (dnastar, madison, wi). newly reported sequences in this study were deposited at the genbank database under the accession numbers shown in fig. s for ha and na genes. the evolution history was inferred by the maximum likelihood method based on the hasegawa-kishino-yano model . the percentages of replicate trees ( , replicates) are shown next to the branches in which the associated taxa clustered together in the bootstrap test. phylogenetic analysis in this study was conducted using mega . statistical analysis. continuous variables were presented as medians and interquartile ranges (iqrs); categorical variables were presented as numbers and percentages. all analyses were performed using the statistical package for the social sciences software package version . (spss inc., chicago, il, the usa). the incidence rate ratio (irr) was generated using poisson regression with % confidence intervals to compare the rates of laboratory-confirmed influenza a(h n )pdm cases in the icu per , populations across different seasons; % confidence intervals for which the upper and lower bounds did not include were considered as statistically significant. differences in categorical variables were compared using the chi-square test or a fisher's exact test. continuous variables were compared using the kruskal-wallis one-way analysis of variance test. multivariate logistic regression analysis and multivariate cox proportional hazards model were used for outcome analysis. the variables included sex, season, age group, onset to presentation, underlying condition, obesity, smoking, alcoholism, and antiviral therapy. variables with a p value < . in the univariate analysis were included in the multivariate model. the hosmer-lemeshow goodness-of-fit test was performed to assess the overall fit of the model. all statistical operations were two-tailed. p values ≤ . were considered statistically significant. world now at the start of influenza pandemic report prepared for the who annual consultation on the composition of influenza vaccine for the southern hemisphere influenza activity -united states, - season and composition of the - influenza vaccines report prepared for the who annual consultation on the composition of influenza vaccine for the southern hemisphere risk assessment of the - influenza season in thewho european region, week / to week / a major impact of the influenza seasonal epidemic on intensive care units, reunion an epidemic of enterovirus infection in taiwan. taiwan enterovirus epidemic working group community outbreak of adenovirus taiwan's public health national laboratory system: success in influenza diagnosis and surveillance new variants and age shift to high fatality groups contribute to severe successive waves in the influenza pandemic in taiwan risk factors for severe outcomes following influenza a(h n ) infection: a global pooled analysis case-control study of risk factors for hospitalization caused by pandemic (h n ) . emerg infect dis oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials return of pandemic h n influenza virus high intensive care unit admission rate for - influenza is associated with a low rate of vaccination seasonal influenza vaccination coverage among adult populations in the united states potential antigenic explanation for atypical h n infections among middle-aged adults during the - influenza season immune history shapes specificity of pandemic h n influenza antibody responses predominance of influenza a(h n )pdm virus genetic subclade b. and influenza b/victoria lineage viruses at the start of the / influenza season in europe the potential risks and impact of the start of the - influenza season in the who european region: a rapid risk assessment. influenza other respir viruses a(h n )pdm influenza infection: vaccine inefficiency clinical characteristics and -day outcomes for influenza a (h n ) complications among adults hospitalized with influenza: a comparison of seasonal influenza and the h n pandemic focused antibody response to influenza linked to antigenic drift influenza epidemic of / influenza season in taiwan real-time surveillance of infectious diseases: taiwan's experience. health secur laboratory-based surveillance and molecular epidemiology of influenza virus in taiwan risk factors for severe illness with pandemic influenza a(h n ) virus infection in china prevention and control of seasonal influenza with vaccines: recommendations of the advisory committee on immunization practices (acip), . mmwr recommendations and reports standardized interpretation of paediatric chest radiographs for the diagnosis of pneumonia in epidemiological studies the american-european consensus conference on ards. definitions, mechanisms, relevant outcomes, and clinical trial coordination amino acids transitioning of h n pdm in taiwan from dating of the human-ape splitting by a molecular clock of mitochondrial dna molecular evolutionary genetics analysis version . for bigger datasets this work was supported by a grant from national science council, taiwan, and three grants (grant cmrpg f and cmrpg f to yc hsieh, most - -b- a- -my ,nmrpg g to kc tsao) from the chang gung memorial hospital. y.c.h., c.t.h., y.c.h., and t.y.l. designed the study. k.c.t. and y.n.g. conducted the virologic characterization. y.c.h. and k.y.c. performed the statistical analysis. h.y.l. collected data. y.c.h. wrote the first draft of the manuscript, and all authors contributed to the final draft. all authors contributed to data interpretation and critically reviewed the manuscript. supplementary information accompanies this paper at https://doi.org/ . /s - - - . the authors declare no competing interests.publisher's note: springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.open access this article is licensed under a creative commons attribution . international license, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the creative commons license, and indicate if changes were made. the images or other third party material in this article are included in the article's creative commons license, unless indicated otherwise in a credit line to the material. if material is not included in the article's creative commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. to view a copy of this license, visit http://creativecommons.org/licenses/by/ . /. key: cord- -l pbw ry authors: fang, chin-yi; hu, jin-li; lou, tze-kai title: environment-adjusted total-factor energy efficiency of taiwan's service sectors date: - - journal: energy policy doi: . /j.enpol. . . sha: doc_id: cord_uid: l pbw ry this study computes the pure technical efficiency (pte) and energy-saving target of taiwan's service sectors during – by using the input-oriented data envelopment analysis (dea) approach with the assumption of a variable returns-to-scale (vrs) situation. this paper further investigates the effects of industry characteristics on the energy-saving target by applying the four-stage dea proposed by fried et al. ( ). we also calculate the pre-adjusted and environment-adjusted total-factor energy efficiency (tfee) scores in these service sectors. there are three inputs (labor, capital stock, and energy consumption) and a single output (real gdp) in the dea model. the most energy efficient service sector is finance, insurance and real estate, which has an average tfee of . and an environment-adjusted tfee (eatfee) of . . the study utilizes the panel-data, random-effects tobit regression model with the energy-saving target (est) as the dependent variable. those service industries with a larger gdp output have greater excess use of energy. the capital–labor ratio has a significantly positive effect while the time trend variable has a significantly negative impact on the est, suggesting that future new capital investment should also be accompanied with energy-saving technology in the service sectors. energy is one of the critical resources for economic development in a country as well as one of the most important input production factors for driving business growth. in accordance with the kyoto protocol, which is the international treaty to mitigate global warming, each country is required to reduce its greenhouse gas emissions down to levels. as energy consumption is the main source of carbon dioxide emissions, the energy efficiency issue has been addressed by both developed and developing economies. because taiwan is a small open and developing economy, it relies heavily on overseas supplies for its energy needs, and as a result the international economic environment has continuously impacted the country's energy prices. for example, in the percentage of taiwan's imported energy accounted for . % of total energy supplies, in contrast to . % of indigenous energy, with total energy supplies in taiwan hitting , thousands of kiloliter of oil equivalent (kloe). in the same year, taiwan's total energy domestic consumption achieved a record high of , thousands of kloe (energy statistics, ) . saving energy has thus become an extremely important issue in taiwan, with existing research studies addressing energy efficiency or productivity on the region level or country level (for example bian and yang ( ) , greening et al. ( ) , guo et al. ( ) , hu ( , ) , howarth et al. ( ) , hu and kao ( ) , shi et al. ( ) , worrell et al. ( ) ). some researches focused on the fossil fuel power plants with considering the undesirable outputs (sueyoshi and goto, ) . furthermore, the capital-labor ratio as the proxy of technology level is one of the important indicators in contents lists available at sciencedirect journal homepage: www.elsevier.com/locate/enpol energy policy the energy economics. wu ( ) proposed that the capital-labor ratio reduces inefficient energy use, because new capital utilizes energy-saving technology. however, blomberg et al. ( ) indicated that even bigger companies with high capital in sweden might have challenges to improving energy efficiency because of possible risks for production disruptions and the associated costs. however, there is a paucity of research investigating the energy issue in the service sectors as well as the impact of the capital-labor ratio toward the energy efficiency even though the relative share of services in total gross domestic production (gdp) has been increasing and accounts for nearly % in taiwan. especially, the growth rate of energy consumption in the service sectors from to is . % in contrast to the . % as of the industrial sectors in taiwan. hence, this paper's objective is to bridge the gap in the literature by measuring the energy efficiency for different subsectors under the service aggregation sectors in taiwan and to validate the hypothesis of the impact of capital-labor ratio on the energy efficiency in the service sectors. ang ( ) defined that energy efficiency is a relative concept. hu and wang ( ) indicated that other inputs (for example, labor and capital) together with energy consumption ought to be considered in assessing the energy efficiency. furthermore, hu and wang ( ) developed the index of total-factor energy efficiency (tfee) to analyze energy efficiencies of administrative regions in china during - . their paper employed data envelopment analysis (dea), using labor, capital stock, energy consumption, and total sown area of farm crops as the four inputs and real gdp as the single output in order to find the target energy input of each region in china for each particular year. a u-shape relation between an area's tfee and per capita income in the areas of china empirically confirms the scenario that energy efficiency eventually improves with economic growth. hu and kao ( ) further used constant-returns-to-scale (crs) dea by incorporating three inputs (energy, labor, and capital) and a single output (gdp) to establish the energy-saving target (est) and then measured energy-saving target ratios (estrs) for apec economies during - . the empirical results indicate a u-shape relation between per capita est and per capita gdp. estr has a positive relation with the value-added percentage of gdp of the industry sectors and a negative relation with that of the service sectors. researchers have also focused on energy efficiency in the energy and manufacturing sectors (for example blomberg et al. ( ) ), though few studies have looked at the energy efficiency of specific industrial sectors. gouyette and perelman ( ) took input-oriented dea and the malmquist index, including gdp as the single output and labor and capital inventory as two inputs, to measure efficiency and productivity of the manufacturing and service sectors for oecd countries over the - period. the results indicate that the productivity of the service sectors in oecd countries slightly increased, which is mostly caused by an increase in efficiency change. boyd and pang ( ) examined the differences in plant-level electricity and fossil fuel intensity in the glass industry. productivity differences between plants are statistically significant in explaining differences in plant energy intensity. productivity has a significantly positive impact on the energy efficiency for flat glass, but not for container glass. honma and hu ( ) used dea with the assumption of variable-return-to-scale (vrs) by incorporating three inputs (energy consumption, labor, and capital stock) and a single output (the value added in each sector) to estimate the tfee of sectors in japan during - . the empirical result presents that the tfee is relatively higher in the mining, general machinery, real estate and housing service, and the financial and insurance and service sectors in japan, in contrast to the relatively lower energy intensity for the agricultural sector, as well as the transportation and communication sector. honma and hu ( ) further computed and analyzed the tfee of industries in developed countries during - using the dea approach and by considering four inputs (labor, capital stock, intermediate inputs other than energy, and energy) and one output (the value added). the most inefficient industry is the metal industry, with an average tfee of . %. the results also identify the most efficient countries in each different time period of of - of , of - of , and of - of . shi et al. ( also used fixed asset, energy consumption, and labor as the inputs of the dea model to assess the efficiency of different regions in china. many studies have criticized energy intensity (ei), which is a commonly used indicator of energy efficiency in the past. ei stands for the energy consumption for producing every unit of real gdp within a certain time frame. renshaw ( ) and patterson ( ) suggested that ei considers only partial factors of energy consumption without embracing capital and labor factors. another critic noted that this partial factor index is inappropriate for investigating the impact of changing energy use over time (asia pacific energy research center (aperc), ). hence, the objective of this paper is three-fold. first, this paper analyzes the pure technical efficiency (pte) and assesses the energy-saving target of taiwan's service sectors by employing vrs-dea. second, the paper computes the energy-saving target ratio and tfee for each service subsector developed by hu and wang ( ) . third, this study further investigates the effects of industry characteristics on the energy-saving target by applying the four-stage dea proposed by fried et al. ( ) . we also calculate the pre-adjusted and environment-adjusted totalfactor energy efficiency (tfee) scores in these service sectors. this paper is organized as follows. the next section describes the theoretical model, which briefly introduces vrs-dea, tfee, and the four-stage dea along with the data collected and variables used. the section following that applies vrs-dea, and the four-stage dea to measure pre-adjusted tfee and environment-adjusted tfee indices on taiwan's service sectors. we also examine the hypothesis of capital-labor ratio toward the energy efficiency by applying the panel random-effects tobit regression. the final section then presents some concluding remarks and future research direction. the paper uses vrs-dea to determine the input targets for each service sector by comparing the efficiency frontier that is established by all service sectors in taiwan. the paper utilizes input-oriented measures following farrell's ( ) work. in order to control the effects of scale, this study adopts the vrs-dea model (banker et al., ) . a higher efficiency score means that the decision making units (dmus) use fewer inputs to obtain a given level of outputs (charnes et al., ) . all dmus at the same time constitute the reference set for constructing the efficiency frontier for each dmu i . banker et al. ( ) developed the so-called bcc-dea model by expanding the crs-dea model into a vrs situation as follows: λ j x k j z ; k ¼ ; :::; k; where θ is a scalar and the pte for the ith dmu, with r θ r ; there are k inputs and m outputs for each of the dmu, respectively. the ith dmu is represented by the column vectors x i and y i , and λ is an n  vector of constants. the value θ¼ indicates a point on the efficient frontier and hence presents technically efficient sectors, in accordance with farrell's ( ) definition. the frontier is a piecewise linear isoquant, determined by the observed data points of the same year. the sectors that construct the frontier are the efficient sectors among those observed sectors in that year. the weight vector λ forms a convex combination of observed inputs and outputs. the set on the frontier is the production of best practices among the observed sectors. for the ith sector, the distance (amount) from the projected point on the frontier by radial reduction without reducing the output level, ( À θ)x i , is called the 'radial adjustment'. technical efficiency reflects the ability of firms to use as little input as possible to obtain a given level of output. fried et al. ( ) introduced a four-stage dea. the management component of inefficiency is separated from the influences of the external environment, because the management level is not able to control these influences. the result is a radial measurement of managerial efficiency. it is indeed the assessment of managerial competence on running a business. the first stage calculates a dea frontier using the observable inputs and outputs according to the vrs model in eq. ( ). the summation of slack and radial adjustments is the total amount ('target') that can be reduced without decreasing the output levels. with respect to energy input, the above summation is called the 'energy-saving target' (est), and the formula is est ði;tÞ ¼ nonÀradial slack adjustment for energy ði;tÞ þradial adjustment for energy ði;tÞ ; where est (i, t) refers to the est in the ith sector and the tth year. an inefficient sector can reduce est in energy use without reducing real economic growth. the dea model suggests that the input slack and radial adjustments of any individual input for all objectives are efficient. the actual energy consumption is larger than or equal to the ideal energy input, because the actual practice is able to improve to become the best practice. efficiency is generally defined as the ratio of the value of the best practice compared to that of the actual practice. the energysaving target ratio (estr) index is therefore the ratio of the aggregate energy-saving target from eq. ( ) to actual energy consumption. the total adjustments in energy input are regarded as the inefficient portion of actual energy consumption. hu and wang ( ) where estr (i,t) refers to the estr in the ith sector and the tth year. as eq. ( ) indicates, the estr represents each sector's inefficient level of energy consumption. since the minimal value of est is zero, the value of estr lies between zero and unity. the totalfactor energy efficiency (tfee) index originally developed by hu and kao ( ) and honma and hu ( ) is related to the estr as in eq. ( ) where tfee (i, t) refers to the tfee in the ith sector and the tth year. a zero estr value means a sector is on the frontier with the best tfee (up to one) among the observed sectors and also indicates that no redundant or over-consumed energy use exists in this sector; otherwise, an inefficient sector with the value of estr larger than zero shows that energy needs to be saved at the same economic growth level. a higher estr and lower tfee imply higher energy inefficiency and a higher energy-saving amount, and vice versa. the different industry characteristics generate different impacts on the est. in order to incorporate these industry characteristics, the second stage of fried et al. ( ) used a cross-sectional tobit regression to adjust these environmental impacts. this study estimates the energy consumption equation by implementing a panel tobit regression in eq. ( ). the dependant variables are radial plus slack input movement for energy consumption; the independent variables are measures of environmental variables applicable to this particular input. the objective is to quantify the effect of external conditions on the excessive use of inputs. est ði;tÞ ¼ f ðe ði;tÞ ; β ði;tÞ ; u ði;tÞ Þ; i ¼ ; :::; n; t ¼ ; :::; t: where est ði;tÞ is the total radial plus slack movement for the energy input of service sector i on time t based on the dea results from stage ; e ði;tÞ is a vector of variables characterizing the operating environment for different service i that may affect the utilization of the input; β ði;tÞ is a vector of coefficients and u ði;tÞ is a disturbance term. the third stage uses the estimated coefficients from the abovementioned equations to predict the total input slack for each service sector based on its industry characteristic difference: est ði;tÞ ¼ f ðe ði;tÞ ; β ði;tÞ Þ; i ¼ ; :::; n; t ¼ ; :: these predictions are used to adjust the primary energy data for each service sector based on the difference between maximum predicted total energy slack and predicted total energy slack: aei ði;tÞ ¼ actual energy input ði;tÞ þ ½maxfest ði;tÞ gÀÊðest ði;tÞ je ði;tÞ Þ; i ¼ ; :::; n; t ¼ ; :::; t: this study uses the concept of using the least favorable operating environment as the basis from fried et al. ( ) . the notation aei means the adjusted energy input. this generates a new projected dataset where the inputs are adjusted for the influence of external conditions. the final stage uses the adjusted dataset to re-compute the dea model under the initial output data and adjusted input data. the result generates new radial and slack measures of inefficiency. these radial and slack scores measure the inefficiency that is attributable to environmental characteristics. adj_est ði;tÞ ¼ non À radial slack adjustment for energy ði;tÞ þradial adjustment for energy ði;tÞ after the final À stage dea; where adj_ est (i, t) refers to the adjusted est in the ith sector and the tth year after incorporating the industrial characteristics. this study yields the adjusted energy-saving target (adj_est) and adjusted energy-saving target ratio (adj_estr) in eq. ( ), incorporating the different industrial characteristics where adj_estr (i,t) refers to the adj_estr in the ith sector and the tth year. the environment-adjusted total-factor energy efficiency (eat-fee) index is related to the adj_estr as in eq. ( ): where eatfee (i,t) refers to the environment-adjusted tfee in the ith sector and the tth year. existing research studies have criticized the commonly used indicator of energy inefficiency, which is the ei, as a direct ratio of energy consumption to gdp. the ratio is only a partial factor of the energy efficiency index without considering the capital and labor inputs. hence, this paper measures energy efficiency using the tfee index by a total-factor framework, extending to include eatfee after incorporating the industry characteristic differences using the four-stage dea in order to provide more information and a more realistic comparative base to examine the de facto situation across sectors. the first major objective of this section is to derive pte and tfee in taiwan's service sectors over the - periods. service is defined as the aggregation of four service sectors in taiwan including: ( ) wholesale and retail trade sector; ( ) transportation and storage sector; ( ) lodging and catering sector; and ( ) finance, insurance and real estate sector. we apply the dea to a dataset of these service subsectors during the - periods. the paper uses three inputs (capital input, labor employment, and energy consumption) and a single output (real gdp) to assess the pte of each sector. data regarding real gdp (nt$ million) were collected from the directorate general of budget, accounting and statistics of the executive yuan in taiwan. two data inputs (capital input and labor employment) were obtained from the database of advanced retrieval and econometric modeling system (aremos) and a third data input, energy consumption, from the bureau of energy (bureau of energy, ministry of economic affairs, ). all nominal variables are transformed into real variables at the price level by taiwan's gdp deflators. the units of real gdp, labor employment, real capital, and energy consumption are nt$ million, persons, nt$ million, and millions of tons of oil equivalent (mtoe), respectively. table shows the summary statistics of these inputs and output. table presents the correlation coefficients of the input and output variables. the isotonicity property-that an output should not decrease with an increase in an input-is not violated. table , respectively. even though there is an increasing trend in terms of pte after , the result shows that there is a - % improvement in input resource savings. table also reveals that the ptes of the two sectors of finance, insurance and real estate and transportation and storage are higher than the other two sectors. the financial service sector has been apparently continuous working on business process reengineering (bpr). the financial holding companies established since have also created capital efficiency in the financial service sector. the transportation and storage sector has the second highest efficiency score among these four service sectors over the period - . the wholesale and retail trade sector obtains the lowest efficiency in the service sectors during - . this result indicates that the financial service and transportation and storage sectors have a competitive capability for using less capital, labor, and energy to yield a certain gdp. from the statistics of the directorate general of budget, accounting and statistics of the executive yuan in taiwan, total employment in the wholesale and retail trade sector is the highest among the service sectors, accounting for . million persons ( %), in contrast to . million persons ( . %) in the lodging and catering sector, and , persons ( . %) in the real estate sector. this finding shows that the wholesale and retail trade sector needs much improvement in the input of resources, especially on labor savings. the pte of the lodging and catering sector obviously deceases after . the severe acute respiratory syndrome (sars) outbreak in weakened taiwan's economy as well as its tourism industry. this event also proved that the slowdown in the economy had a great impact on lodging and catering businesses. this study further utilizes eqs. ( )-( ) to measure tfee for each service sector in table . the result of tfee presents a similar pattern with that of pte. the financial service sector has the highest tfee among the service sectors herein. particularly, energy in the financial service sector might be consumed less than in the other service sectors. honma and hu ( ) also indicated that the financial and insurance sector has the high level tfee in japan. they pointed out that the tertiary industries, except for the transportation and communication sector, have higher tfee scores in japan, which is consistent with this paper's finding. the government needs to develop financial service businesses to yield a relatively higher gdp under the given labor and energy. weber ( ) further indicated that banks have pursued cost saving effects by reducing their consumption of energy, water, and resource materials. banks also have demonstrated their environmental strategy of 'going for green' to attract more customers. the tfee in the wholesale and retail trade sector dramatically increases to a record high in . the r (recycling, reuse, and refill) policy in taiwan has resulted in obvious progress in the wholesale and retail trade sector. the popular recycle containers in hypermarkets have helped promote the concept of energy conservation, while the severe price-cutting competition among wholesalers and retailers in taiwan have also indirectly had a positive impact on the energy-saving action. the tfee of the transportation and storage sector has deteriorated since . in contrast with a gdp growth rate of % in this sector, the input resource consumption growth rate of capital and energy in this sector increased . % and %, respectively. this finding is a reminder to the management of this sector to pay attention to resource efficiency. this finding is consistent with the work in japan by honma and hu ( ) , as they indicated that the transportation and communication sector in japan had high fuel consumption. chen et al. ( ) suggested that the efficient use of energy, the introduction of non-fossil fuels, and the development of innovative technologies are essential strategies for establishing a robust renewable energy technology portfolio plan. to understand the industrial variation in est and its determinants, we compute four industrial characteristics indices, including gdp shares, labor use shares, energy consumption shares, and capital-labor ratio, by using the panel random-effects tobit regression for est in eq. ( ). metcalf ( ) indicated that energy and technology might have a substitution effect. wu ( ) used the capital-labor ratio as the proxy of the technology level and hypothesized that the capital-labor ratio reduces inefficient energy use, because new capital utilizes energy-saving technology. this study also includes a time trend variable to capture the trend of change over time. table shows that a (positive) negative coefficient on these environmental variables suggests that the environment is (un)favorable for a dmu, since it is associated with (greater) less excess use of energy. several findings can be drawn from the estimation results of the random-effects tobit regression. a gdp share variable has a significantly positive effect on the est, which indicates that those service industries with more gdp output have greater excess use of energy. the capital-labor ratio also has a significantly positive effect on the est, which is not consistent with wu's findings on regions in china. this may be because more high-tech service industries in taiwan use more energy-consuming facilities that are not so energy-efficient. blomberg et al. ( ) also indicate that even bigger companies in sweden may face significant barriers to improving energy efficiency because of possible risks for production disruptions and the associated costs. meanwhile, the medium sized companies also have the lower priority to increase the capital turnover in order to address on the energy efficiency issue (blomberg et al., ) . therefore, the service industries in taiwan should pay attention to energy efficiency of newly acquired facilities. a time trend variable has a significantly negative impact on the est and indicates less excess use of energy over - among the service industries in taiwan. table compares the tfee and environment-adjusted tfee (eatfee) for the individual services industry in taiwan. fig. indicates the comparisons of tfee and eatfee for the wholesale and retail trade sector during - . the graph illustrates that the eatfee and tfee have a similar increasing pattern for this sector, with the eatfee obviously higher than the tfee after incorporating the industrial characteristics. the gdp real growth finding suggests that there is much room for energy-saving improvement among wholesalers and retailers after incorporating the unfavorable factors (gdp, energy consumption, capital-labor ratio) compared to capital and labor. hence, this finding also offers a recommendation for wholesale and retail trade to keep up their cost savings through energy-saving actions even though there is a significant movement toward the efficient frontier for the tfee and eatfee in . fig. illustrates the comparisons of tfee and eatfee in the transportation and storage sector. the empirical results reveal a worsening trend in tfee in this sector over - . as a result of controlling for the industrial characteristics, the eatfee has decreased in the sector since and indicates that without controlling for the industrial difference, the penalty to this sector operating under favorable factors is less than the benefit to this sector operating under favorable industrial characteristics. these favorable environments (less energy consumption and lower capital-labor ratio in the transportation and storage sector) provide much benefit for the tfee of this sector. fig. illustrates that the tfee and eatfee in the lodging and catering sector have a decreasing trend in the - period. during the same period, the tfee and eatfee in this sector present a similar pattern with the transportation and storage sector. these favorable environments (less energy consumption and lower capital-labor ratio in the lodging and catering sector) note: tfee and eatfee stand for total factor of energy efficiency and environment-adjusted energy efficiency, respectively. provide much benefit for the tfee of this sector. even though taiwan's environmental law has restricted the use of nonwashable dining utensils in restaurants since , which possibly led to the slightly drop for the tfee and eatfee in the sector of lodging and catering. this finding shows that energy efficiency also needs improvement in the lodging and catering sector. fig. shows the trend of tfee and eatfee in the financial service sector in the - periods. the results show that tfee and eatfee hit the efficient frontier in the financial service sector during - . the comprehensive conclusion in the national energy conference in alleged that the energy service company (esco) establishment in taiwan had led the energy efficiency improvement for the peripheral banking and leasing business because of the increasing loan amounts for procurements of energy-saving equipment since . aside from the synergy creation in financial holding companies since , merger and acquisition activities in this sector have also promoted cost savings, capital efficiency, and cross selling to yield overall efficiency. the unfavorable industrial characteristics (second highest gdp share, second highest capital-labor ratio) benefit the tfee in this sector. being a small open economy highly dependent on imported energy, taiwan needs to put forth a lot of effort and a better policy execution on energy saving and conservation. to achieve better performance in improving energy efficiency, those service sectors with worsening and/or poor energy efficiency should receive more attention from policy makers. particularly, the taiwan tourism bureau (ttb) needs to offer incentives for lodging and catering businesses to offer green hotels or green restaurants. in order to accomplish energy-saving benefits in the lodging industry, ttb could include "green" criteria in ttb's hotel star-rating system. offering incentives to use solar water heaters and green furniture in the service sectors could also minimize the gap between the pte and tfee. Önüt and soner ( ) suggest that the lodging industry could install solar energy systems for different departments such as swimming pools and laundry. meanwhile, the hoteliers could control and repair all water related equipment as soon as possible and it was also suggested monitoring water consumption periodically. to encourage water saving programs by a permanent promotion program for employees and customers, and using low flow shower heads are the way to save the energy consumption. the financial services sector has the best performance among the four service sectors in terms of tfee and eatfee. this result is consistent with the work from honma and hu ( ) on japan's financial industries. their empirical result indicates that the tfee is relatively higher in the real estate and housing service sector as well as the financial and insurance service sector in japan. from the statistics of the directorate general of budget, accounting and statistics of the executive yuan in taiwan, total employment in the wholesale and retail trade sector is the highest among the service sectors, accounting for . million persons ( %). the tfee and eatfee in the group sector of lodging and catering show a deteriorating trend, as the severe acute respiratory syndrome (sars) in weakened taiwan's economy. in fact, the tourism industry experienced the highest stock price decline (chen et al., ) during this time. this research utilizes the vrs-dea to assess the pte, tfee, and eatfee of service sectors in taiwan over the period - . in contrast to the traditional ei, which considers only the direct ratio of energy input to gdp for assessing energy efficiency without embracing capital and labor factors, we measure tfee and eatfee by incorporating the industrial characteristics and extending the four-stage dea proposed by fried et al. ( ) , which includes inputs such as energy, labor, and capital. a better comprehensive indicator for energy efficiency provides more information for improvement and more comparative suggestions for different service subsectors. the results herein show that there is a - % potential improvement on input resource savings in taiwan's service sectors, although there is an increasing trend in terms of pte after . the pte of two sectors (the finance, insurance and real estate sector and the transportation and storage sector) is higher than that of the other two sectors. the financial service sector has been dramatically working on bpr and organizational reshuffling in order to establish financial holding companies or push mergers among financial institutions, causing consolidation synergy to gradually appear. the empirical result also indicates that tfee and eatfee of the finance, insurance and real estate sector have the highest score among all service sectors during - . both the wave of mergers and acquisitions and the establishment of financial holding companies during - helped motivate energy efficiency in the financial service arena. this result also confirms that c (cross-selling, capital-efficiency, and cost-saving) synergy in the financial service sector was created, because financial holding companies were established. at the same time, the financial institutions pursued cost savings effects by reducing their consumption of energy, water, and materials and demonstrated their environmental strategy of 'going for green' in order to attract more customers (weber, ) . the pte of the wholesale and retail trade sector is the worst, and this group sector needs a lot of improvement on input resources, especially labor savings. the pte of the lodging and catering sector had an obvious decreasing trend after . the sars outbreak in and the global financial turmoil in weakened taiwan's economy as well as its tourism industry. these events also prove that a slow economy has a great impact on lodging and catering businesses. this study further utilizes the panel-data, random-effects tobit regression model with the est as the dependent variable. those service industries with more gdp output have greater excess use of energy. the capital-labor ratio has a significantly positive effect, while the time trend variable has a significantly negative impact on the est, indicating that more high-tech service industries in taiwan use more energy-consuming facilities that may not be more energy-efficient. therefore, the service industries in taiwan should pay attention to energy efficiency of their newly acquired facilities. a time trend variable has a significantly negative impact on the est, indicating less excess use of energy over - among the service industries in taiwan. the eatfee is obviously higher than the tfee after incorporating the industrial characteristics in the wholesale and retail trade sector. this finding suggests that there is much room for energy-saving improvement among wholesalers and retailers after incorporating the unfavorable factors (gdp, energy consumption, capital-labor ratio) compared to capital and labor. hence, this finding also offers a recommendation for wholesalers and retailers to keep up their cost savings through energy-saving actions even though they show a significant achievement toward the efficient frontier for the tfee and eatfee in . the tfee of the transportation and storage sector has been decreasing since , showing that this sector has relatively high fuel consumption. this finding is consistent with the results in japan (honma and hu, ) . establishing a robust renewable energy technology portfolio plan should yield an efficient use of energy (chen et al., ) . after controlling for the industrial characteristics, the eatfee also has been decreasing in the transportation and storage sector since and indicates that without controlling for the industrial difference, the penalty to this sector for operating under favorable factors is less than the benefit to this sector for operating under favorable industrial characteristics. the tfee in the wholesale and retail trade sector dramatically increased to a record high in . the r (recycling, reuse, and refill) policy in taiwan has resulted in obvious progress for this sector. for example, popular recycle containers in hypermarkets help promote the concept of energy conservation. the most energy efficient service sector is finance, insurance and real estate. it has an average tfee of . and environment-adjusted tfee (eat-fee) of . . being a small open economy highly dependent on imported energy, taiwan has to put forth a lot of effort and a better policy execution on energy savings and conservation. in fact, taiwan's indigenous energy supply has fallen so much that it has only accounted for less than % of total energy supply since (energy statistics, bureau of energy, ministry of economic affairs) in contrast to more than % of energy supply being imported. policy makers should pay more attention to those service sectors with poor energy efficiency. for example, the taiwan tourism bureau (ttb) could offer incentives for green hotels or green restaurants in order to improve energy efficiency in the catering and lodging sector. the ttb could further combine 'green' criteria into the on-going hotel star-rating system. taiwan's government should encourage restaurateurs to measure, list, and mitigate their carbon footprint on each menu item. even though taiwan government alleges main six promotions for energy saving: "( ) promote energy saving light bulb; ( ) apply thermostat timer on water dispenser and water fountain machine; ( ) set up one degree more for the temperature in summer time and clean the filter; ( ) be sure to power off the computer, instead of idling for a while; ( ) promote unplugging the electric appliance; ( ) promote turning off the light for an hour during lunch break for governmental and regular business office buildings (bureau of energy, ministry of economic affairs)," offering financial incentives to use solar water heaters, green furniture, and other energy-saving equipment in the service sectors could also enhance energy efficiency through electricity, gas, and other energy-saving plans. the government in taiwan at the same time needs to address the issue of whether new capitals bring energy-saving technology into the rapidly expanding service sectors. according to this study's empirical findings on the service industries in taiwan, a high capital-labor ratio tends to have excess energy consumption during the period of - . hence, the replacement of old equipment and infrastructure and new capital inflow with energysaving technology are two very important issues among the service sectors in taiwan. future research can focus on assessing energy efficiency in a specific service industry, such as banking, securities, insurance, etc. measuring energy efficiency by a total-factor framework and extending it to include more input resources will enhance the comprehensiveness of energy efficiency and offer policy makers further industry structure suggestions to improve a country's overall energy efficiency. monitoring changes in economy-wide energy efficiency: from energy-gdp ratio to composite efficiency index energy efficiency indicators and potential energy savings in apec economies some models for estimating technical and scale inefficiencies in data envelopment analysis resource and environment efficiency analysis of provinces in china: a dea approach based on shannon's entropy energy efficiency and policy in swedish pulp and paper mills: a data envelopment analysis approach estimating the linkage between energy efficiency and productivity the main six promotions for energy saving measuring the efficiency of decision making units the impact of the sars outbreak on taiwanese hotel stock performance: an event-study approach renewable energy technology portfolio planning with scenario analysis: a case study for taiwan an introduction to efficiency and productivity analysis national statistics taiwan bureau of energy, ministry of economic affairs the measurement of productive efficiency incorporating the operating environment into anonparametric measure of technical efficiency productivity convergence in oecd service industries comparison of six decomposition methods: application to aggregate energy intensity for manufacturing in oecd countries evaluation of potential reductions in carbon emissions in chinese provinces based on environmental dea total-factor energy efficiency of regions in japan industry-level total-factor energy efficiency in developed countries total-factor energy efficiency for sectors in japan manufacturing energy use in eight oecd countries: decomposition the impacts of changes in output, industry structure and energy intensity efficient energy-saving targets for apec economies total-factor energy efficiency of regions in china an empirical analysis of energy intensity and its determinants at the state level energy efficiency assessment for the antalya region hotels in turkey what is energy efficiency? concepts, indicators and methodological issues energy efficiency and the slump in labour productivity in the usa chinese regional industrial energy efficiency evaluation based on a dea model of fixing non-energy inputs dea radial measurement for environmental assessment and planning: desirable procedures to evaluate fossil fuel power plants sustainability benchmarking of european banks and financial service organizations energy intensity in the iron and steel industry: a comparison of physical and economic indicators energy intensity and its determinants in china's regional economies the authors thank the chief editor and two anonymous referees of this journal for their valuable comments. financial support from the taiwan's national science council is gratefully acknowledged (nsc - -h- - and nsc - -h- - ). key: cord- -ff d authors: ko, nai-ying; lu, wei-hsin; chen, yi-lung; li, dian-jeng; chang, yu-ping; wu, chia-fen; wang, peng-wei; yen, cheng-fang title: changes in sex life among people in taiwan during the covid- pandemic: the roles of risk perception, general anxiety, and demographic characteristics date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: ff d this study used data collected from an online survey study on coronavirus disease (covid- ) in taiwan to examine changes in sex life during the pandemic and the factors affecting such changes. in total, respondents were recruited from a facebook advertisement. the survey inquired changes in sex life during the pandemic, including satisfaction with the individual’s sex life, frequency of sexual activity, frequency of sex-seeking activity, and frequency of using protection for sex. the associations of change in sex life with risk perception of covid- , general anxiety, gender, age, and sexual orientation were also examined. for each aspect of their sex life, . %– . % of respondents reported a decrease in frequency or satisfaction, and . %– . % reported an increase in frequency or satisfaction. risk perception of covid- was significantly and negatively associated with frequencies of sexual and sex-seeking activities. higher general anxiety was significantly and negatively associated with satisfaction of sex life and frequencies of sexual and sex-seeking activities. sexual minority respondents were more likely to report decreased satisfaction with sex life and frequencies of sexual activity and sex-seeking activities during covid- . health care providers should consider these factors when developing strategies for sexual wellness amid respiratory infection epidemics. covid- emerged in wuhan, china, at the end of and has been spread to over countries and territories around the world, with the total number of infected cases having risen to over , , and more than , deaths, as of july [ ] . given the geographical proximity and busy transportation between taiwan and china, taiwan was predicted to have the second highest number of covid- cases early in the outbreak [ ] . after all, taiwan experienced the severe outbreak of - severe acute respiratory syndrome (sars), which also originated from china; globally, taiwan had the third highest number of sars cases, after china and hong kong [ ] . the experience with sars made the taiwanese government and people vigilant against covid- . early since december , , taiwanese officials began to assess passengers on direct flights from wuhan for fever and pneumonia symptoms before passengers could deplane. the first covid- case in taiwan was confirmed on january [ ] . during the period from january to february , the taiwan centers for disease control rapidly produced and implemented a list of at least action items including border control, case identification, quarantine of suspicious cases, proactive case finding, resource allocation, reassurance and education of the public while fighting misinformation, negotiation with other countries and regions, formulation of policies toward schools and childcare, and relief to businesses [ ] . with proactive containment efforts and comprehensive contact tracing, the number of covid- cases in taiwan remained low, as compared with other countries that had widespread outbreaks [ ] . therefore, there was no social lockdown in taiwan. as of july , taiwan had tested a total of , persons showing confirmed cases, of which only were domestic. six patients died, and people were released from hospital after testing negative three times subsequently [ ] . the covid- pandemic results in widespread and wide-ranging concerns spanning the issues of physical morbidity and mortality [ ] , mental health [ , ] , the economy [ ] , education [ ] , and interpersonal relationships [ ] . sexual health in the context of the pandemic, however, warrants investigation [ ] . according to the world health organization, sexual health is a state of physical, mental, and social well-being in relation to sexuality [ ] ; sexuality is influenced by the interaction of biological, psychological, social, economic, political, cultural, legal, historical, religious, and spiritual factors [ ] . accordingly, it is reasonable to hypothesize that sex life would be deeply influenced by the impacts of the covid- pandemic on personal and environmental levels. regarding the personal level, all forms of in-person sexual contact carry the risk of viral transmission [ ] . people may abstain from sexual intercourse because they fear contracting covid- . the covid- pandemic may adversely influence individuals' mental and physical health [ , , ] and further compromise sex life. regarding the environmental level, the pandemic prevention measures of social distancing may jeopardize an individual's sex life. governments of many countries ordered to close down gathering spaces and promote social distancing to prevent the spread of covid- . not being able to physically meet with others may change people's sexual habits [ ] . a social atmosphere of collective anxiety about the covid- pandemic may also result in detriment of the mood to enjoy sex. conversely, yuksel and ozgor proposed people may spend more time at home during the covid- pandemic and therefore increase the frequency of sexual behaviors with their partners [ ] . a few studies have examined the effect of the covid- pandemic on sexual behaviors. a study comparing sexual behaviors among turkish women during the pandemic with - months prior to the pandemic found that sexual desire and frequency of intercourse significantly increased during the covid- pandemic, whereas quality of sexual life significantly decreased; the pandemic is associated with decreased desire for pregnancy, decreased female contraception, and increased menstrual disorders [ ] . an online study in three south-east asian countries (bangladesh, india, and nepal) found that although % of the participants reported that the lockdown affected their sexual life, there was no substantial difference in sexual activity between before and during the lockdown period of the covid- pandemic [ ] . however, the study of yuksel and ozgor focused on women and did not examine sexual behaviors in men [ ] . the sample size in the study of arafat et al. was small ( respondents) [ ] . given the importance of sexuality to health, further study is needed to examine how the covid- pandemic has changed peoples' sex life and what factors are associated with such change [ ] . risk perception of covid- may influence individuals' engagement in sexual activity during the pandemic. risk perception of covid- refers to people's intuitive evaluations of how likely they are to contract covid- [ ] . according to stage theory, risk perception acts as a trigger for precautionary action [ ] . leung et al. reported that people with higher risk perceptions of severe acute respiratory syndrome (sars) were more likely to take comprehensive precautionary measures against infection [ ] . the fear of contagion itself may reduce physical contact within couples, from simple kissing to full sexual intercourse [ ] . if the risk perception is excessive, particularly when a person is overwhelmed with negative sars-related information, it will lead to irrational fear [ ] . psychological disturbances, such as anxiety and depression, may also reduce satisfaction with an individual's sex life and increase sexual dysfunction [ , ] . the prevalence of anxiety symptoms was high among the public during the sars [ ] and covid- outbreaks [ ] . both risk perception and anxiety can result in psychological stress. stressful lifestyle is a factor that may negatively impact people's sexual desire, though the results of previous studies were mixed [ ] [ ] [ ] . given that the covid- is a novel respiratory infectious disease resulting in global impacts on human lives worldwide, additional studies are required on whether risk perception of covid- and general anxiety are significantly associated with changes in sex life during the covid- pandemic. gender and age have been found to influence the degree of sex-related quality of life. forbes et al. reported that unlike quality of life in other life domains [ ] , sex-related quality of life tends to decline with age. pinxten and lievens also noted a considerable gender gap in the propensity to engage in sexual activity [ ] , with this gender gap throughout the life course being smaller in more gender-equal societies. the roles of gender and age in changes in sex life during epidemics of novel infectious diseases, such as sars, ebola, or h n influenza, have yet to be examined. in addition to gender and age, sexual orientation should also be analyzed as an influence on changes in sex life during epidemics. a study hypothesized that in times of a pandemic when people are particularly susceptible to mental health difficulties, messaging that frames sex as being dangerous has adverse psychological effects [ ] . there is no evidence that the covid- can be transmitted via either vaginal or anal intercourse; however, there is evidence of oral-fecal transmission of the covid- and that implies that anilingus may represent a risk for infection [ ] . in this case, sexual stigma may have a negative role for sex life of sexual minority individuals [ ] . from a historical perspective, human immunodeficiency virus and acquired immunodeficiency syndrome (aids) was conceived of as a "gay plague," by analogy with the sudden, devastating epidemics of the past [ ] . considering the historical trauma of the aids epidemic, sexual minority individuals may voluntarily or involuntarily restrict their sex life. in addition to sexual stigma, sexual minority individuals may experience more severe impacts of the covid- pandemic on their daily lives. a study on men who have sex with men (msm) in the united states found that most of the participants had no change in condom access or use, many participants had adverse impacts of the covid- pandemic to general wellbeing, social interactions, money, food, drug use, and alcohol consumption; especially many reported fewer sex partners and covid- -related barriers to hiv and sexually transmitted diseases testing, pre-exposure prophylaxis access, and hiv treatment [ ] . the authors also suggested that additional studies of covid- epidemiology among sexual minority populations are needed [ ] . whether the covid- pandemic has affected the sex lives of sexual minority individuals differently than that of their heterosexual counterparts warrants further study. the online survey study on covid- in taiwan was conducted to assess the life experiences of people in taiwan during the covid- outbreak. the survey examined changes in sex life, including satisfaction with the individual's sex life, frequency of sexual activity, frequency of sex-seeking activity, and frequency of using protection for sex. the present study used data from this survey to examine three issues. first, we compared changes in sex life prior to and during the covid- pandemic. second, we examined the associations of gender, age, sexual orientation, risk perception of covid- , and general anxiety with changes in sex life. third, we determined what the moderators are in the associations between the aforementioned factors and changes in sex life. participants were recruited through a facebook advertisement from april to , . during the study period, the total number of confirmed cases contracting covid- in taiwan increased from to without no new deaths. of the newly confirmed cases, only was domestic. it indicated that this study was conducted during the period of covid- mitigation in taiwan. however, a collective covid- infection among the members of the navy serving on a three-ship fleet broke out during the period. meanwhile, the total number of infected cases all over the world massively increased to nearly , . the domestic and foreign situations intensified worry about covid- among people in taiwan. facebook users were eligible for this study if they were at least years of age and living in taiwan. the facebook advertisement included a headline, main text, pop-up banner, and link to the research questionnaire website. we designed the advertisement to appear in the facebook users' "news feeds," which is a continually updated list of updates from advertisers and the user's connections (such as friends and the facebook groups that they have joined). our advertisement was placed only in the targeted users' news feed, rather than other advertising locations (e.g., right-hand column), on facebook because news feed advertisements are most effective in recruiting research respondents [ ] . we targeted the advertisement to facebook users by location (taiwan) and language (chinese), where facebook's advertising algorithm determined which users to show our advertisement to. to ensure that sexual minority individuals were recruited, we also posted the link of the facebook advertisement to the facebook pages of three taiwanese health promotion and counseling centers for lesbian, gay, and bisexual individuals. this study was approved by the institutional review board (irb) of kaohsiung medical university hospital (kmuhirb-exempt(i) ). because participation was voluntary and survey responses were anonymous, the irb ruled that this study did not require informed consent. our study respondents were given no incentive for participation. we provided links to covid- information from the taiwan centers for disease control (taiwan cdc), kaohsiung medical university hospital, and medical college of national cheng kung university for respondents to learn more about covid- . the survey comprised the following sections. we measured four aspects of self-reported changes in sex life using four questions, which were adopted from a previous study's questionnaire on an individual's sex life [ ] . first, change in satisfaction with sex life was asked about in "compared with that before the covid- outbreak, how has your satisfaction with sex life changed in the past month?" second, change in sexual activity was asked about in "compared with that before the covid- outbreak, how has your sexual activity changed in the past month?" third, change in sex-seeking activity was asked about in "compared with that before the covid- outbreak, how has your sex-seeking activity, such as using dating apps or visiting a sex worker, changed in the past month?" fourth, change in using protection for sex was asked about in "compared with that before the covid- outbreak, how has your use of protection during sex, such as wearing a condom or taking pre-exposure prophylaxis, changed in the past month?" each question was rated as (obviously decreased), (slightly decreased), (no change), (slightly increased), and (obviously increased). to measure risk perception of covid- , we used the -item questionnaire that was developed by liao and colleagues to measure worry toward h n influenza [ ] . the first question was "if you were to develop flu-like symptoms tomorrow, you would be ___," where respondents filled in the blank with a number from (not at all worried) to (extremely worried). the second question was "in the past week, have you ever worried about getting covid- ?" this question was scored from (no, i have never thought about it) to (i worry about it all the time). the third question was "please rate the current level of your worry toward covid- ." this question was rated from (very mild) to (very severe). the fourth question was "how likely do you think it is that you will contract covid- ?" this question was scored from (never) to (certain). the fifth question was "what do you think are your chances of getting covid- over the next month compared with others outside your family?" this question was rated from (not at all) to (certain). the scores for the first two, the third, and the last two questions were divided by , , and , respectively. these five quotients were then summed to obtain a score representing the level of risk perception of covid- , with higher scores indicating greater risk perception. cronbach's α was . for this measure. general anxiety in the past week was measured using a previously validated state anxiety scale from the state-trait anxiety inventory wherein respondents rate their feelings in response to general statements; these statements inquire into feelings of being rested, contented, comfortable, relaxed, pleasant, anxious, nervous, jittery, highly strung, and over-excited and "rattled" [ ] [ ] [ ] . each question was rated as (not at all), (sometimes), (moderately so), and (very much so). statements reflecting positive feelings were reversely coded. a higher total score of the items represented greater general anxiety. the cronbach's α was . for this measure. data on sexual orientation (heterosexual, homosexual, bisexual, pansexual, asexual, or unsure), gender (female and male), and age were collected. respondents were categorized into heterosexual and sexual minority individuals. data analysis was performed using the statistical software spss (version . ; spss inc., chicago, il, usa). we noted the percentages of participants reporting no change, an increase, and a decrease for changes in each aspect of their sex life. the associations of changes in each aspect of sex life with sexual orientation, gender, age, risk perception of covid- , and general anxiety were examined using multivariate logistic regression. the p value, odds ratio (or), and % confidence interval (ci) were used to indicate significance. a two-tailed p value of < . indicated statistical significance. moreover, the moderators of the associations between sexual orientation and changes in sex life were examined based on the criteria proposed by baron and kenny [ ] . the data of sexual minority and heterosexual individuals were analyzed, with of the initial respondents excluded due to missing data. among sexual minority respondents, identified as homosexual, identified as bisexual, and identified as pansexual, asexual, or unsure. table presents descriptive statistics for demographic characteristics, risk perception of covid- , general anxiety, and changes in sex life among respondents. the mean age was . years (standard deviation [sd] = . years); and . % were female. the mean scores for risk perception of covid- and general anxiety were . (sd = . ) and . (sd = . ), respectively. as for changes in sex life, respondents reported decreases in their satisfaction with their sex life ( . %), their sexual activity ( . %), their sex-seeking activity ( . %), and their use of protection for sex ( . %) during the covid- pandemic. by contrast, respondents reported increases in their satisfaction with their sex life ( . %), their sexual activity ( . %), their sex-seeking activity ( . %), and their use of protection for sex ( . %) during the covid- pandemic. table presents the multivariate logistic regression results for the associations of changes in each aspect of sex life (dependent variables) with sexual orientation, gender, age, risk perception of covid- , and general anxiety (independent variables). the results indicated that decreased satisfaction with sex life was significantly associated with being male, being a sexual minority, and having a higher level of general anxiety; no factor was significantly associated with increased satisfaction with sex life. regarding frequency of sexual activity, decreased frequency was significantly associated with being male, being a sexual minority, having a higher risk perception of covid- , and having greater general anxiety; increased frequency was significantly associated with being male, being younger, and having a lower risk perception of covid- . regarding frequency of sex-seeking activity, decreased frequency was significantly associated with being male, being a sexual minority, having a higher risk perception of covid- , and having greater general anxiety; increased frequency was significantly associated with being male and being a sexual minority. finally, being male was significantly associated with both decreased and increased frequency of the use of protection for sex. the product interaction terms between gender, age, sexual orientation, risk perception, and general anxiety that were significantly associated with each aspect of change in sex life were selected into multiple logistic regression models to examine the moderators ( table ). the results indicated that the interaction between gender and sexual orientation was significantly associated with decreased frequencies of sexual activity and sex-seeking activity. further analysis revealed that the significant association between being sexual minority and decreased frequency of sexual activity was only true for men (or = . , % ci: . - . , p < . ) but not for women (or = . , % ci: . - . , p = . ). moreover, the significant association between being a sexual minority and decreased frequency of sex-seeking activity was only true for men (or = . , % ci: . - . , p < . ) but not for women (or = . , % ci: . - . , p = . ). most respondents reported no change in their sex life during the covid- pandemic, whereas . % reported the decrease satisfaction with their sex life, . % decreased sexual activity, . % decreased sex-seeking activity, and . % reported the increased use of protection for sex. by contrast, . % reported the increased satisfaction with their sex life, . % increased sexual activity, . % increased sex-seeking activity, and . % reported the decreased use of protection for sex. sexuality is a central aspect of human health [ ] . considering the ineffectiveness of recommendations of long-term sexual abstinence [ ] , health care providers should consider counseling people on their sexual health whenever possible to help them maintain or even improve their sexual wellness amid the covid- pandemic; in general, the human need for intimacy should be balanced with personal safety and pandemic control [ ] . further study is also warranted to understand the psychological mechanisms underlying sexuality during a pandemic. although only . % of respondents reported the decreased use of protection for sex in the present study, the increased risk of contracting covid- and sexually transmitted diseases should also be investigated in people who engage in sexual activity more but use protection less during the pandemic. the present study found that risk perception, general anxiety, gender, age, and sexual orientation related to various aspects of changes in sex life during the covid- pandemic. firstly, a higher risk perception of covid- was significantly associated with decreased frequencies of sexual activity and sex-seeking activities. because in-person sexual contact carries the risk of covid- transmission [ ] , we can hypothesize that people with a high risk perception of covid- reduce their sexual activity, whether casual or with long-term partner, as a means to protect themselves against getting covid- . however, leung et al. noted that the self-perceived likelihood of contracting or surviving sars did not predict personal protective behavior [ ] . in addition to sexual inactivity as a personal protective behavior, other reasons may also account for the association between risk perception of covid- and the decreased frequencies of sexual activity and sex-seeking activities. people who perceive a high risk of covid- tend to invest greater time and effort to learning more about pandemic prevention and using facemasks and disinfectant alcohol. moreover, as with governments in many other countries, the taiwanese government has suspended the sex industry to prevent the spread of covid- . this policy may have led people with a high risk perception of covid- to perceive having sex in general as being unsafe during the pandemic. these personal and environmental factors may have contributed to the decreased frequencies of sexual activity and sex-seeking activities during the pandemic. the present study found that higher general anxiety was significantly associated with decreased satisfaction of sex life and frequencies of sexual activity and sex-seeking activities during the covid- pandemic. greater general anxiety may result in less pleasurable sex or make sex difficult, which depresses a person's interest in sex; sexual dysfunction may further exacerbate anxiety [ ] . however, anxiety is one of most common affective responses to the respiratory infectious disease epidemics or pandemics [ ] . during the respiratory infectious disease outbreaks, social distancing and quarantine are inevitable methods to prevent spreading of the illness; however, both may precipitate anxiety [ ] . thus, health care providers should help people manage their anxiety in particular and mental health in general. a study on turkish women found that despite the increased frequency of sexual intercourse during the covid- pandemic, quality of sexual life decreased during the pandemic [ ] . the present study extends the scope of genders in participants and found that men were more likely to report a change, whether an increase or decrease, in their frequencies of sexual activity, sex-seeking activities, and use of protection for sex. a uk study also noted that men in the general population were more likely to engage in sexual activity during covid- self-isolation [ ] . both biological and socioenvironmental factors may influence sexual behaviors across genders. research on -to -year-old children found significant gender differences in sexual behavior [ ] . gender stereotypes in societies may also affect the way people behave in sexual activities [ , ] . there might be multiple etiologies accounting for gender difference in changes of sexual activities during the covid- pandemic that warrant further study. moreover, research in china has demonstrated that women tend to be more psychologically affected by the covid- outbreak with respect to stress, anxiety, depression, and posttraumatic stress symptoms [ , ] . the results of previous and present study indicated that the covid- pandemic might have various impacts on sexual activities differently compared with and psychological wellbeing, as well as that changes in sex life might not be influenced by psychological status only. younger people were noted to be at greater risk of mental illnesses, such as general anxiety disorder, during the covid- pandemic [ ] . consistent with the aforementioned study, the present study found that older respondents were less likely to have increased sexual activity during covid- pandemic [ ] . gender and age differences in sexual activity have already been noted by a taiwanese study before the pandemic; these differences include men being more likely to have multiple sexual partners and older people being more likely to have a lower frequency of sexual activity [ ] . the results of the present study demonstrate that the covid- pandemic has had differential effects on sex life across gender and age. the factors that explain the reason that men are more likely to have a pandemic-induced change in their sex life-whether an increase or decrease in the aspects analyzed in this study-should be investigated further. the present study found that sexual minority respondents were more likely to report decreased satisfaction with their sex life and decreased frequencies of sexual activity and sex-seeking activities during the pandemic; a gender difference with respect to the aforementioned frequencies was also noted. sexual minority individuals have faced the threat of hiv infection since the s [ ] , and health information pertaining to hiv prevention and treatment strategies is transferable to knowledge on covid- [ ] . thus, being more knowledgeable about pandemic prevention, sexual minority individuals may reduce their sexual activity, albeit at the expense of reducing their satisfaction with their sex life. however, the decreases in sexual activity could also be explained by sexual stigma, which sexual minority communities have experienced since the aids pandemic [ ] . recommendations for sexual abstinence during the covid- pandemic may elicit memories of the widespread stigmatization of sexual minorities during the aids crisis [ ] . such sexual stigma contributes to a hostile social environment against sexual minority individuals and makes mental health problems more likely [ ] . sexual minority individuals may reduce their sexual activity under the interpersonal strain caused by the covid- pandemic. however, a group of sexual minority individuals have increased their sex-seeking activity during the covid- pandemic. whether this is a response to the unhappy atmosphere during the pandemic warrants further study. the present study has some limitations. first, the present study did not ask participants about their current sexual relationship status or relationship quality, which are major factors affecting people's sexual satisfaction during a pandemic like covid- where people's social lives may have been curtailed. sex between intimate couples can be an activity to support psychologically fragile people living in restricted areas for longer quarantine periods [ ] . second, although recruiting respondents through facebook is a promising research method for targeting the general public during fast-moving infectious disease outbreaks [ ] , facebook users may not be representative of the population. a review of a study that recruited respondents through facebook reported a bias in favor of women, young adults, and people with higher education and incomes [ ] . third, the cross-sectional design of this study limited causal inference between changes in sex life and general anxiety. fourth, this study did not survey the various aspects of respondents' sex life before the pandemic. this study also did not follow-up on the changes in respondents' sex life during the mitigating period of the covid- pandemic. last, some factors such as physical health and self-confidence that might influence sex life in the covid- pandemic were not examined in the present study. although most respondents reported no change in their sex life during the covid- pandemic, . %- . % of respondents reported a decrease and . %- . % reported an increase in various aspects of their sex life. risk perception of covid- , general anxiety, gender, age, and sexual orientation were associated with greater change in various aspects of an individual's sex life. considering that sexuality is a central aspect of human health, human needs for intimacy should be balanced with personal safety and pandemic control [ ] . health care providers should consider the factors related to changes in sex life reported in this study when formulating strategies for maintaining sexual wellness amid respiratory infection epidemics. funding: this research did not receive any specific grant from funding agencies in the public, commercial, or nonprofit sectors. the authors declare no conflict of interest. summary of probable sars cases with onset of illness from first case of coronavirus disease (covid- ) pneumonia in taiwan response to covid- in taiwan: big data analytics, new technology, and proactive testing initial rapid and proactive response for the covid- outbreak-taiwan's experience the outbreak of covid- coronavirus and its impact on global mental health preventing suicide in the context of the covid- pandemic the socio-economic implications of the coronavirus and covid- pandemic: a review covid- -related school closings and risk of weight gain among children regulation and trust: -month follow-up study on covid- mortality in european countries sexual health in the sars-cov- era defining sexual health: report of a technical consultation on sexual health - impact of the covid- pandemic on the sexual behavior of the population. the vision of the east and the west effect of the covid- pandemic on female sexual behavior does covid- pandemic affect sexual behaviour? a cross-sectional, cross-national online survey risk perception and covid- the precaution adoption process the impact of community psychological responses on outbreak control for severe acute respiratory syndrome in hong kong rationality of cities' public perception of sars and predictive model of psychological behavior women's sexual dysfunction associated with psychiatric disorders and their treatment. women's health the burden of lower urinary tract symptoms: evaluating the effect of luts on health-related quality of life, anxiety and depression: epiluts quality of life and psychological status in survivors of severe acute respiratory syndrome at months postdischarge mental health burden for the public affected by the covid- outbreak in china: who will be the high-risk group? a report on the reproductive health of women after the massive wenchuan earthquake chronic stress and sexual function in women stress symptoms and frequency of sexual intercourse among young women sexual quality of life and aging: a prospective study of a nationally representative sample gender differences in the development of sexual excitation and inhibition through the life course: preliminary findings from a representative study in flanders the presence of sars-cov- rna in the feces of covid- patients understanding aids: historical interpretations and the limits of biomedical individualism characterizing the impact of covid- on men who have sex with men across the united states in facebook recruitment of young adult smokers for a cessation trial: methods, metrics, and lessons learned willingness to self-pay for pre-exposure prophylaxis in men who have sex with men: a national online survey in taiwan anxiety, worry and cognitive risk estimate in relation to protective behaviors during the influenza a/h n in hong kong: ten cross-sectional surveys longitudinal assessment of community psychobehavioral responses during and after the outbreak of severe acute respiratory syndrome in hong kong the moderator-mediator variables distinction in social psychological research: conceptual, strategic, and statistical consideration abstinence and abstinence-only education psychological and interpersonal dimensions of sexual function and dysfunction using social and behavioural science to support covid- pandemic response mental health status of people isolated due to middle east respiratory syndrome teachers' and parents' reports on -to -year-old children's sexual behavior-a comparison gender stereotypes multidimensional discriminative factors for unprotected sex among adolescents in southern taiwan immediate psychological responses and associated factors during the initial stage of the coronavirus disease (covid- ) epidemic among the general population in china prevalence and predictors of ptss during covid- outbreak in china hardest-hit areas: gender differences matter covid- social distancing and sexual activity in a sample of the british public men's and women's sexual behavior in taiwan: intersectional effects of cohort, gender, education, and marital status marginalization and social change processes among lesbian, gay, bisexual and transgender persons in swaziland: implications for hiv prevention social and behavioral health responses to covid- : lessons learned from four decades of an hiv pandemic journals of the plague years: documenting the history of the aids epidemic in the united states prejudice, social stress, and mental health in lesbian, gay, and bisexual populations: conceptual issues and research evidence covid- pandemic and its implications on sexual life: recommendations from the italian society of andrology use of rapid online surveys to assess people's perceptions during infectious disease outbreaks: a cross-sectional survey on covid- the use of facebook in recruiting respondents for health research purposes: a systematic review key: cord- - wqpvf authors: chiu, hsiao-hsuan; hsieh, jui-wei; wu, yi-chun; chou, jih-haw; chang, feng-yee title: building core capacities at the designated points of entry according to the international health regulations : a review of the progress and prospects in taiwan date: - - journal: glob health action doi: . /gha.v . sha: doc_id: cord_uid: wqpvf background: as designated points of entry (poes) play a critical role in preventing the transmission of international public health risks, huge efforts have been invested in taiwan to improve the core capacities specified in the international health regulations (ihr ). this article reviews how taiwan strengthened the core capacities at the taoyuan international airport (tia) and the port of kaohsiung (pok) by applying a new, practicable model. design: an ihr poe program was initiated for implementing the ihr core capacities at designated poes. the main methods of this program were ) identifying the designated poes according to the pre-determined criteria, ) identifying the competent authority for each health measure, ) building a close collaborative relationship between stakeholders from the central and poe level, ) designing three stages of systematic assessment using the assessment tool published by the world health organization (who), and ) undertaking action plans targeting the gaps identified by the assessments. results: results of the self-assessment, preliminary external assessment, and follow-up external assessment revealed a continuous progressive trend at the tia ( , , and %, respectively), and at the pok ( , , and . %, respectively). the results of the follow-up external assessment indicated that both these designated poes already conformed to the ihr requirements. these achievements were highly associated with strong collaboration, continuous empowerment, efficient resource integration, and sustained commitments. conclusions: considering that many countries had requested for an extension on the deadline to fulfill the ihr core capacity requirements, taiwan's experiences can be a source of learning for countries striving to fully implement these requirements. further, in order to broaden the scope of public health protection into promoting global security, taiwan will keep its commitments on multisectoral cooperation, human resource capacity building, and maintaining routine and emergency capacities. t aiwan, an island situated in the subtropical zone, economically relies on international trade and has long been aware about preventing the import of communicable diseases through the thriving international traffic. the point of entry (poe) plays a critical role for early detection of disease risks and the mitigation of the impact of the rapid spread of infections. therefore, border health measures have been applied at all international airports and seaports by the taiwan centers for disease control (tcdc). however, the emergence of new import infections urged taiwan to ensure the capability of responding to the pandemic at poes. as it has always been a challenge to ensure prompt mobilization of various stakeholders at poes for jointly battling a threat of an epidemic, tcdc invested substantial efforts to seek a systematic and focused approach that can develop poe capacities with the strong collaboration of stakeholders. meanwhile, as the severe acute respiratory syndrome (sars) epidemic had challenged the traditional rationale of global health protection ( Á ), the international health regulations (ihr) were revised and formally approved by the th world health assembly (wha) in (therefore called international health regulations ; ihr ) ( ). the new regulations require state parties to enhance and monitor eight national core capacities. in addition, it also extends its scope by including the responsibility to respond to zoonotic, food safety, chemical, and radiological hazards ( ) . the intent is to assist countries in focusing their efforts on the improvement of the detection, control, and response to international public health emergencies at their sources. taiwan spared no efforts in conforming to the ihr provisions and announced the willingness to implement them year ahead of schedule. thus, before the ihr was officially enforced on june , , taiwan had coordinated relevant government authorities to adopt the ihr provisions into domestic legislations, specifically in acts such as the 'communicable disease control act' and 'regulations governing quarantine at ports'. the amended legislations, which were regarded as the foundation of fulfilling ihr requirements, combined the goals and measures to be implemented in taiwan, with the emphasis on the improvement of capacities in detecting, assessing, notifying, and responding to public health threats. in the ihr , the provisions for poes have been designed to minimize public health risks caused by the spread of diseases through international traffic ( ) . based on the requirements stated in the regulations, the state party need to designate specific poes, to develop the capacities listed in annex b of the ihr . in , the world health organization (who) published an assessment tool for core capacity requirements at designated airports, ports and ground crossings ( ) . in this tool, the capacity requirements have been transformed into assessing indicators, which enable state parties to identify existing capacities or potential gaps, along with the formulation of plans of action that address the capacities that need to be improved, by assessing the stage of implementation. the assessing indicators can be separated into three parts: ) part a: communication and coordination framework among various stakeholders, ) part bi: capacities necessary at all times (called routine capacities), and ) part bii: responding to public health events of international concern (pheic, also called emergencies). right after the tcdc learned that the who assessment tool was published, the institute found that poe requirements listed in the tool highly echoed its continuous anticipation of improving taiwanese poes' own capacities in routine preparedness and effective response to health emergencies, in a manner that avoids the unnecessary interference with international travel and trade. therefore, the who assessment tool seemed very helpful in this context because it provided a concrete framework for taiwan to identify the capacities to be examined, and the actions to be taken for achieving the goals. subsequently, the tcdc decided to concentrate on adopting this tool in taiwan, as soon as possible. in the absence of the who's guidance on how to adopt this tool to develop pragmatic readiness, the tcdc collected extensive information about the expertise and experiences of other countries by website and article searches ( Á ), email inquiries, and on-site visits (canada and australia). on the other hand, from their experience with previous pandemics, the global societies realized that a consistent policy based on common protocols and the cooperation between authorities at regional, national, and international levels are very critical for effective management of public health risks ( , ) . similarly, as the ihr requirements for core capacities of the poes mainly address the public health events, many additional aspects such as financial support, human resources, poe facilities, poe routine activities, and so on need to be considered while making policies and developing related protocol. it also highlights the importance of close communication and collaboration between international organizations, the central and local governments, and various competent authorities at poes ( ) . it was found that meeting ihr obligations at a poe is a universal challenge involving human resources, multisectoral engagement, and communication ( ) . further, some countries developed a crossdepartmental network/ platform, at either the central or poe level, in order to facilitate the development of these core capacities ( , ) . based on the abovementioned findings, several important conclusions were made, which includes: ) the designation of the poes should be based on consensus; ) the stakeholders with the responsibility of implementing the core capacities should be brought together, not only from the health sector, but also from other public and private sectors; ) the successful implementation of this program requires strong support from the cabinet and its subordinate organizations; ) a coordination mechanism, with clear functions and structure, is necessary; ) an agreed protocol, which clarifies the strategies, timeline, and multidisciplinary/multisectoral duties, is essential, and ) all strategies should be harmonized with the currently available resources, national administrative structure, and consensus made by the participants. in accordance with important conclusions drawn from the preparatory analysis, the tcdc submitted a protocol for a new program (called 'ihr poe program') to the executive yuan. subsequently, through extensive review and discussion, the protocol was formally approved to be implemented in january . after consulting various authorities, four criteria were taken into consideration while identifying designated hsiao-hsuan chiu et al. poes: ) the number of international conveyances, ) the number of international travelers, ) the geographical distribution, and ) the existing facilities and logistic capabilities. thus, one airport (the taoyuan international airport; tia) and one seaport (the port of kaohsiung; pok) were consensually designated at the first stage. every year, over % of the travelers enter taiwan through the tia. the airport has experienced a remarkable annual increase in the number of international travelers and aircraft during recent years, and an additional terminal is being planned. the pok, which is the largest seaport in taiwan, traditionally dealt with freight transportation. however, in the past few years, it is also being used to harbor cruise vessels and has shown a rising trend in the number of arriving travelers. in addition, a new travel center is currently being constructed. it is noted that, to upgrade competencies and promote the development of the tia and pok, during Á , the responsibility of operation and management of both the poes was shifted from the government authority to the state-run corporations. since then, these state-run corporations have been responsible for the coordination and consolidation of various agencies stationed in the designated poes, under the supervision of the ministry of transportation and communications (motc) of the central government. since the beginning of the implementation of the ihr poe program, there has been an interesting discussion on the competent authority at the designated poes. according to the ihr definition, a competent authority means 'an authority responsible for the implementation and application of ''health measures'''. originally, it was perceived that the tcdc shall serve this role. however, when the core capacity requirements were examined in detail, it was realized that some of the health measures mentioned in ihr were being conducted by other government authorities in reality. for example, if an ill traveler with symptoms of a possible communicable disease was reported in the pok, the tcdc will be responsible for the assessment of the traveler. if the tcdc decided to refer the traveler to a hospital for further diagnosis and treatment, the pok fire brigade would be responsible for transporting the traveler to the hospital (with their trained personnel and equipment). thus, in order to cater to the practical situation in taiwan, it was consensually decided that the competent authority shall vary according to the different health measures. at the poe level after the sars outbreak in , the importance of enhancing the cross-sectoral involvement through an integrated coordinative structure at poe level was highlighted. subsequently, while implementing the ihr , each poe in taiwan established a 'port sanitary group' as a network of various stakeholders. the group comprised authorities from departments responsible for customs, immigration, quarantine, security and port management, and conveyance operators, as well as the local health authorities. it has successfully served as a coordinating platform at poe level, targeted to the preparedness and the effective contingency arrangement of port health matters. during the h n pandemic in , the port sanitary group functioned very well on efficient information sharing, policy declaration, and coordination about any public health measures carried out at the poes. based on the positive coordination experiences, a specific taskforce (also called poe taskforce) was established under the port sanitary group at the tia and pok to facilitate the fulfillment of the core capacity requirements. in addition to members of the port sanitary group, this taskforce also involved private sectors such as sky catering, ground handling, and cargo terminal services. the poe taskforce coordinated with members ) to conduct core capacity self-assessment, ) to develop poe action plans that address gaps identified from the assessment, ) to monitor the progress of the action plans, and ) to provide feedback to the central governments on difficulties that have been identified regarding core capacity development. the competent authorities at the poe level in taiwan are mainly under the supervision of central governments that are in charge of national policy making, budget, and legislation. therefore, it is believed that while developing the poe core capacities, it would be more efficient if any important consensus and resource integration can be achieved in advance, at the central level, especially in terms of jurisdiction clarification and financial support. furthermore, problems that universally exist among various poes are often related to issues in general structure, which can never be resolved by the individual poes alone. in this case, problem solving must highly rely on the mobilization of resources/support from the central government to the poes. for example, initially, both tia and pok felt that they lacked the expertise/capability to cope with radiological events, or plan their response to them because the central atomic energy council commissioned no affiliated units at the poes. consequently, the council dispatched experts directly to the tia and pok, to assist them in formulating radiological emergency planning, and provided necessary training for the early detection, operation of equipment, and approach to seek external support from the national radiological response team. an inter-ministerial central government task force (also called central government taskforce) has subsequently been constituted. under the successive leadership of ministers without portfolio, ministries and agencies discussed important issues such as whether to grant poes financial support to purchase protective equipment, when to dispatch radiological/toxic chemical experts to poe to provide technical consultation. the taskforce supervised and regularly reviewed the progress of the designated poes. it can also deliver assignments and provide the poe taskforce policy-related and technical guidance (fig. ) . additionally, authorities stationed in designated poes can seek immediate assistance from their superiors at the central governments, to solve problems or to arbitrate the disagreements. for instance, the tia co. ltd, the government-owned company responsible for the operation and management of the airport, would like to clarify and improve current procedures related to security checks of postal parcels transported through the airport. therefore, apart from police and custom authorities, the company also requested its superior motc to collaborate with the national postal services (also under the supervision of motc) in the discussion. thus, the motc acted as the intermediary as well as the final decision maker (in case of any disagreements), and it was very helpful in facilitating improvement work. the ihr poe program designed three systematic assessments (self-assessment, preliminary external assessment, and follow-up external assessment), together with the implementation of action plans that addressed the identified gaps. each assessment applied the assessment indicators and scoring system provided in the who tool ( ). the self-assessment before investing resources for establishing core capacities, the poes must have an overall idea of its present status. therefore, the tia and pok had respectively completed self-assessments during march , by a poe taskforce. at the first stage, the secretariat of the taskforce led the introduction of the assessment indicators, so that members could thoroughly understand the implication of the ihr core capacity requirements. following this, members were asked to report their field activities concerning the ihr core capacities. in addition, a field visit was arranged for, if necessary. for instance, the tia taskforce visited the airport cargo terminal services to understand the operation of the transportation of dangerous goods according to international air transport association (iata) regulations. finally, members worked together to complete the who assessment tool, by describing any measures, facilities, and approaches available at the poe, and listed documents which can provide evidence on the compliance of the core capacity requirements. based on the information collected, the taskforce jointly decided the perceived stage of implementation (fully implemented, partially implemented, not implemented). the preliminary external assessment through the self-assessment, both the tia and pok obtained the baseline information of their existing core capacities, and then implemented some improvements to address the identified gaps. yet, in order to avoid bias due to subjective judgments, an external expert was invited from japan to conduct an in-depth review of the designated poes, from an international perspective, in august . during the preliminary external assessment, the reviewer carefully verified the documents that evidenced the compliance of assessment indicators. sites were visited to investigate facilities, equipment, and practices implemented in the field. in addition, the reviewer interviewed key personnel, raised inquiries, and obtained feedback during the assessment. to facilitate the assessment, a pre-designed assessment protocol was provided to the reviewer and the poes to prepare them for the same. in addition, background materials such as self-assessment reports and a brief introduction of both the poes, were provided to the reviewer in advance. the reviewer was requested to predesignate the document and the potential sites to be assessed. the follow-up external assessment in order to ensure the poe's efforts for improvement were already consistent with the ihr requirements, two experts were invited from the australia government's department of health and ageing to undertake a follow-up external assessment in mid-march . similar assessment in taiwan, a minister without portfolio refers to a minister who does not head a particular ministry. being the premier's key aides, such ministers are responsible in managing and reviewing the affairs of different government ministries and commissions, to enhance the competencies and governance quality of the cabinet. procedures (document reviews and on-site visits) were applied in the two external assessments to ensure that their results were comparable. improvement intervention on unfulfilled core capacity requirements based on findings discovered from the self and the preliminary external assessment, a series of activities were identified to improve the designated poes in taiwan. firstly, both the poe taskforces respectively prioritized the identified gaps, while taking into account factors such as urgency, resource availability, and achievability. subsequently, action plans that described practicable approaches and resource investments, and which set a defined timeline with checking points, were developed. as improvement is always a dynamic process, regular monitoring and feedback is crucial to ensure progress and that outcomes are in line with expectations. the poe taskforces were allowed to adjust the scope and timeline of the plans according to current need and performance (fig. ) . the who assessment tool also provided an ms excel spreadsheet file model, which enabled reviewers to choose their response (fully implemented, partially implemented, or not implemented) to each indicator. when the performance of each indicator is determined, the model automatically generates numerical results with graphic representations of the same. according to the who, a poe with a final score of above % is defined as fairly consistent with the requirements of the ihr annex . assessment results of the tia the tia taskforce reported a self-assessment score of %. among assessment indicators (six indicators specific to seaports/ground crossing were excluded), . % were assessed as 'fully implemented', while . % were reported to be 'partially implemented' in the airport. it was found that the tia owns a communication network among various stakeholders for communicable diseases or biological events, while the reporting system for radiological and chemical events had not yet been established. the airport exhibited routine capacities of adequate on-site medical services for ill travelers, and an inspection/surveillance program of the terminal environment and aircraft. however, the response plans toward radiological, chemical, and biological emergencies were not in place. the external reviewer of the preliminary external assessment reported that . % of the assessment indicators had been 'fully implemented', while . % had been 'partially implemented'. the total score of the tia was %, which showed a fair progress as compared to the self-assessment. from the reviewer's viewpoint, the tia had already or nearly fulfilled part a (communication & coordination) and part bi (routine) requirements, and suggested that further efforts need to be invested in developing its capabilities to respond to pheic. it was noted that all the competent authorities in the tia answered that if they encountered a problem that was difficult to address, they would consult their headquarters. however, the horizontal communication between agencies at the tia was rarely mentioned. based on the learning from the previous two assessments, the tia applied its action plans on the following areas: ) reconstructing the communication flow to ensure that event information is notified by and disseminated to stakeholders including outsourcing companies and service providers; ) formulating/updating emergency plans with the consideration of the surge response. contents of the plans, along with the communication link with various targets, were validated by table exercises or scenario drills; ) developing regular and irregular inspection mechanisms to ensure the quality of outsourcing services, and specifying all requirements in contracts; ) designating a specific location for the decontamination of pheic; ) replacing personal protective equipments (ppes) that had passed their expiry date, or purchasing required ones; and ( ) updating standard operating procedures (sops) for inspecting and responding to air postal parcels. the reviewers of the follow-up external assessment reported that % of the indicators had been 'fully implemented' (fig. ) . in general, reviewers determined five strengths of the tia: ) communication link with travelers for health-related information; ) the operation control center provides comprehensive infrastructure and management for pheic; ) on-site medical facilities and integration of resources with contracted hospitals; ) capacities for radiological and chemical inspection, and emergency response; and ) providing access to, and training in the use of, ppe for all hazards. in addition, two areas of consideration were proposed in the further implementation of the core capacities. first, as the detection of fever-screening limits for respiratory diseases was an area of concern, broader surveillance parameters may be considered to enable the detection of nonrespiratory diseases. second, it was suggested that a risk assessment may be implemented to determine whether vector control measures are warranted, and whether a response protocol should be established to mitigate the risk of introduction of vectors detected in an aircraft. in response to the reviewers' recommendations, the tcdc, as the competent authority for these matters, are carrying out policy analysis of current entry screening procedures, as well as the vector surveillance/control on aircrafts (table ) . in the self-assessment, the pok taskforce reported that . % of the assessment indicators (seven indicators were not applicable for seaports) had been 'fully implemented', . % had been 'partially implemented', while . % were evaluated as 'not implemented'. the total score of the pok was %. it was found that the communication link with senior health officials and sops for assessing urgent reports and disseminating information from the who were to be established. in addition, inspectors found a lack of knowledge about water management, swimming pool/spa, and air quality management on ships and terminal facilities. emergency planning and ppes toward radiological and chemical events were either absent or out of date, and a place had not been designated for decontamination. concerning the preliminary external assessment, the total score of the pok was %. among the assessing indicators, . % were assessed as 'fully implemented', . % as 'partially implemented', and . % as 'not implemented'. the reviewer observed that, similar to the problems identified at the tia, agencies in the pok sometimes omitted the dissemination of the information to their partners in the poes. on the other hand, since the inspection of conveyances are sometimes closely linked with the management and the inspection of the port facilities (i.e. potable water, ballast water, and waste are transported between ships and seaport), it was appreciated that the pok improved cross-sectional capacities by holding joint training programs for both ship and facility inspectors. in terms of emergencies, the reviewer perceived that the response system in the pok has been improved since the self-assessment. it was also highly valued that the pok planned 'cross-unit human resources support programs', which aimed to seek personnel belonging to other poes to support large-scale events immediately. it might help the surge capacity at the port in total. the previous two assessments provided the pok with clear clues to identify their action plan, which was as follows: ) re-examining the communication flow, taking into account private sectors such as shipping agents; ) completing the emergency response protocols toward pheic. protocols shall not only be approved by both poe stakeholders and central authorities, but also tested by drill exercises; and ) taking the ihr core capacity requirements into consideration while planning the new travel center, especially for terminal facilities such as water supply system, waste management, toilets, food/ beverage services. external reviewers of the follow-up assessment scored the pok . % (fig. ) , which implied that . % of the assessment indicators had been 'fully implemented', and . % were 'partially implemented'. it was mentioned that the sops and arrangements were in place with several hospitals for the diagnosis and treatment of ill travelers, and isolation, if required, including those affected by radiation, toxic chemicals, or explosives. it was noted that the pok disaster mitigation and prevention program had been integrated to handle chemical, microbiological, and radiological emergencies. the reviewers observed the breadth of equipment and supplies used by inspection staff trained in public health risk evaluation. however, the reviewers suggested that training courses shall be developed to address risks from recreational swimming and spa areas on ships, and systems developed for the detection, assessment, and application of the recommended measures. in addition, as a new pok travel center is underway, it was suggested that strategic workforce planning should be undertaken in anticipation of the expansion of the pok to ensure adequate staff to implement and strengthen the ihr core capacities ( table ) . based on reviewers' suggestions, the tcdc implemented inspection and control measures for recreational swimming and spa activities on ships into the annual training program for ship sanitation inspectors. in addition, the clarify the procedure of security inspection of air postal parcels. the preliminary external assessment (august ) ensure vertical consultation within competent authorities, as well as horizontal information sharing among competent authorities at poe when faced by an immediate risk. a communication exercise might be necessary, especially for events with mass casualty or high profile event. as water and food services highly rely on outsourcing companies, it might be required to review documents regularly, and to conduct direct inspection by competent authorities for monitoring the sanitation. event information should be circulated rapidly not only to public health sectors but also to the large number of service providers and outsourcing companies involved at the airport. the competent authority to be responsible for airport facilities will be expected to play a more intensive role as the control center, and it might be necessary to consider the overall appropriate 'surge capacity' of the tia. broader surveillance parameters may be considered to enable detection of non-respiratory diseases. undertake a risk assessment to determine whether expanded measures are warranted, and whether a response protocol should be established to mitigate the risk of introduction of vectors detected in aircrafts. building core capacities at the designated poes in taiwan port management authority is increasing the number of trained inspectors, and arranging for provision of training, to increase staff knowledge. in this section, we have discussed the main issues that originated from the implementation of 'ihr poe program'. results of the self-assessment, preliminary external assessment, and follow-up external assessment revealed continuously progressive trends in the tia and pok (fig. ) . the follow-up external assessment (a final evaluation of this program) found that both of these designated poes were already highly consistent with the ihr requirements. during every assessment, it was ensured that the results were not compared between the poes because the tia is a site for human travelers, while the pok mainly handles cargo. the different situations cause different risks for human health, and need to be responded to differently. furthermore, competition among the poes may lead to the perusal of higher scores, rather than the core capacity itself. such competition should be avoided as far as possible. as the upcoming pok travel center, and a new tia terminal are expected to increase passenger numbers in the next few years, existing core capacities (such as the number of skilled personnel, facilities, or surge capacity) may not be enough to handle the magnitude of travelers. it is therefore necessary to be attentive to the needs of further improvement in the core capacities through an analysis of the potential impact of the rising numbers of passengers. enhancing emergency response capacity: a matter of concern the first two assessments found that capabilities to respond to radiological and chemical events effectively were underdeveloped or nonexistent in both, the tia and the pok; however, the response planning for a large-scale outbreak/pandemic had been established after the sars epidemic. these findings corroborated the evidence generated from the general review of global ihr implementation, specifically indicating that, 'the chemical, nuclear, and radiological threats encompassed in the the self-assessment (march ) develop an inspector training program to fulfill the knowledge/skill gaps. complete emergency response protocol, involving the decontamination planning. replenish equipment for detection and personal protection. the preliminary external assessment (august ) in addition to notifying upper-level authorities, it is necessary to make provisions for sharing information among competent authorities at other poes. all authorities shall be familiarized about the agreed response protocol to handle the information according to the level of confidentiality, reliability, and indicated action determined. as construction of a new travel center is currently being planned, it will be a good opportunity to consider inclusion of capacities that make it an ideal healthy and safe poe. ihr presents a unique challenge to the surveillance and response community in both developed and developing countries' ( ) . since the beginning of the implementation of the ihr poe program, there was a discussion on whether radiological and chemical capacities were needed to be involved in the assessments, as the who ambiguously described in one of the assessment indicators (part bi d. . ) that 'harmful contamination, other than microbial contamination, such as from radionuclear sources, could also be found on ships, but is outside the scope of this guidance'. further, due to the lack of international guidance, it seemed easier and less complicated to restrict the assessments to communicable diseases. however, it was subsequently determined that taiwan should not ignore radiological and chemical hazards because the type of accidents that may occur at the poes cannot be predicted or selected. sometimes, an accidental or deliberate release of chemical, biological, and radiological agents on arriving conveyances would have the potential to cause adverse health and financial consequences ( ) . in this case, imported risks cannot be identified, nor be properly dealt with, without the relevant surveillance and response capacities. the fukushima nuclear disaster in highlighted the need to involve diversified public health risks in taiwan. since then, more than containers imported from japan have been detected as being contaminated in the pok. in this case, once possible potential nuclear hazard was detected, the custom authority, authorized to undertake radiological inspections, will implement a series of sops including risk identification/evaluation, reporting, ppes for staff, etc. through understanding the risk profile of the tia and pok as well as in consultation with technical experts dispatched by the central governments and national disaster response authorities, it was determined that the emergency response at poes level should meet the following six basic criteria: ) poe response protocols are aligned with those at the national and local level to ensure the seamless flow of information from the various response systems; ) clear identification of duties and responsibilities of each stakeholder; ) knowledge and equipment for early detection and personal protection; ) communication mechanisms to disseminate information to relevant stakeholders at the poes; ) access to external assistance from the local or central disaster response system; and ) clear command and control system before the arrival of external assistance, and the process of command transfer. according to the criteria defined above, the tia and pok updated their emergency plans, and integrated them into protocols for various types of pheics ( , ) . the drafts were submitted to stakeholders at the poe and national disaster response authorities for peer-review before finalization. meanwhile, required equipment was provided for the initial detection and personal protection (amount and type of equipment were suggested by experts from central authorities). in addition, as the success of any response is highly linked to the people who perform their roles, the required competencies and skills needed for specific response personnel were identified, and relevant training programs were designed. regular drill exercises were conducted to verify the adequacy and interoperability of the plans, as well as to increase the stakeholders' familiarity with their responsibilities and operational procedures. through the abovementioned efforts, the reviewers of the follow-up assessment noted a significant progress in establishing emergency response sops, as well as ensuring that resources were available to ensure rapid responses. from these experiences, it was learned that despite a lack of international principles and guidance for establishing core capacities, countries should try to take its own decisions on what to do and how to do it, based on its current infrastructure, and resources and demands. in addition, where possible, countries should build on existing systems and infrastructure for strengthening their capacities, rather than immediately investing in large-scale systems or infrastructure changes. the advocacy of the ihr poe program was very challenging initially. due to a lack of understanding of the ihr , key stakeholders at central ministries and poes perceived that the regulations were only under the jurisdiction of the health ministries. therefore, the tcdc invested considerable effort in advocating the aim and concepts of the ihr . despite these efforts, the ihr poe program was not implemented very smoothly, due to the resistance and complaints from the field, until the japan fukushima nuclear disaster occurred in . fearing the impact of nuclear contaminations (as traffic and trade are very frequent between japan and taiwan), people working at the poes were keenly aware of the importance of protecting themselves by enhancing the surveillance and response system. they found a selfmotivated actor ( ) to participate in developing the poe's core capacities, and gradually realized that they were jointly contributing to something beneficial for their own workplace, safety, and health. this change of attitude was helpful for further activities. subsequently, to protect themselves, these stakeholders were willing to think about and invest more efforts in developing capacities to address the emergency response. for instance, people were very concerned if they were to be notified about anything unusual. therefore, they carefully reviewed and updated the contact details of every stakeholder to ensure that event information can be disseminated immediately. it was also observed that the process of preparing for each assessment brought the stakeholders closer. as they shared the same objective of obtaining better results for the next assessment, partners involved in the poe met frequently to discuss matters. this extensive participation of various professionals led to a robust unity and mutual understanding. the reviewers observed that all the relevant units at each poe were united with a well-organized structure, and the contribution of the staff toward the implementation of the ihr was a major strength in the implementation of core capacities at poes in taiwan. it is believed that this solidarity shaped through the ihr poe program will continue even after the core capacity requirements have been fulfilled. it shall be continuously beneficial, not only for the daily operation of the poes, but also in co-confronting future crises. strong national efforts throughout all the governmental agencies, to achieve the core capacity requirements at the poe, were noted by the reviewers of the preliminary and follow-up external assessments. sometimes the application of the program was affected by bureaucracy and sectionalism, especially with reference to jurisdiction and expenditure allocation. the solution was the continuous communication and strong commitment of the higherlevel authorities to carry through the program and to arbitrate contentions. thus, taiwan was inspired by the reviewers' conclusions that the progress achieved is testament to the strong commitment, professionalism, and enthusiasm demonstrated by the staff, in their respective roles. this article introduced a new, but applicable, model that taiwan developed for developing ihr core capacities at designated poes. the ihr poe program focused on ) designating two poes according to the pre-determined criteria, ) identifying the competent authority for each health measure, ) building a close collaborative relationship with stakeholders from the central and poe levels, ) designing and implementing three stages of systematic assessment, and ) undertaking action plans targeting the gaps identified by the assessments. with incessant efforts invested in the 'learning by doing' process, the designated poes of tia and pok were assessed as highly consistent with the capacity requirements of the ihr . as many countries had requested extensions to fulfill the ihr core capacity requirements ( ) , it is expected that experiences generated from taiwan can provide some clues on how to identify and strengthen core capacities at designated poes. nevertheless, the achievements of the ihr poe program do not imply an end, of a process, but are a starting point to address the increase in international traffic, and to respond to future challenges at airports and seaports effectively. as the reviewers suggested, it is necessary to continue to maintain core capacities in the designated poes and flexibly adjust the overall strategy in the face of new diseases (such as middle east respiratory syndrome coronavirus infection or new strains of avian flu), new terms of emergencies, new international guidance, as well as new transporting routes and destinations. for this purpose, the taiwanese government will remain committed toward implementing and reviewing the content of the ihr poe program. so far, the coordination and collaboration at poes functioned well in response to the h n outbreak that began in china at the end of march . the emergency of a new disease reminded taiwan that the collaborative mechanism and the partnership, which were already successfully triggered or shaped, should be continuously maintained to ensure the sustainability of the core capacities. currently, taiwanese government has launched the second stage of the ihr poe program. five more poes (three airports and two seaports) have been identified as designated poes to develop their core capacities. the new task will rely highly on the experiences from the development undertaken at the tia and pok. in addition, it will adapt to the characteristics of the specific poes and the ever-changing environment. these efforts are expected to extend the safety of the lives and property of taiwanese people extensively and to bolster the competitive advantages of poes in taiwan. global health improvement and who: shaping the future learning from sars in hong kong and toronto germs, governance, and global public health in the wake of sars geneva: world health organization ihr core capacity monitoring framework: checklist and indicators for monitoring progress in the development of ihr core capacities in states parties ihr brief no assessment tool for core capacity requirements at designated airports, ports and ground crossings. geneva: world health organization implementation of the international health regulations at points of entry from the german perspective guidance for public health units about the core capacities required at new zealand international airports under the international health regulations meeting on points of entry capacity and preparedness for public health emergency response under the international health regulations international health regulations ports, airports and ground crossings. international health regulations awareness workshop for btwc delegations the decision making process for public health measures related to passenger ships: the example of the influenza pandemic of targeting public health events on ships world health organization department of global capacities, alert and response. world health organization perspective on implementation of international health regulations disease surveillance, capacity building and implementation of the international health regulations (ihr audit report Á quarantine, migration and travel health and international health regulations port of rotterdam. establishment of 'virtual' port health authority rotterdam. press releases and news articles actions for prevention and control of health threats related to maritime transport in european union guide for public health emergency contingency planning at designated points of entry. geneva: world health organization building national public health capacity for managing chemical events: a case study of the development of health protection services in the united kingdom challenges to the implementation of international health regulations ( ) on preventing infectious diseases: experience from julius nyerere international airport report by the director-general in sixty sixth world health assembly a / building core capacities at the designated poes in taiwan citation: glob health action we wish to thank the numerous government agencies and individuals who jointly contributed to the success of fulfillment of ihr core capacities at the designated poes in taiwan through the years. we also thank our partner countries for generously sharing their experiences and providing technical advices. we especially gratefully acknowledge dr. kiyosu taniguchi from japan, ms. teresa morahan and ms. gigi o'sullivan from australia, whose expertise and efforts had been fervently devoted in assisting our works. the authors declare that they have no conflict of interests. key: cord- - rd j authors: chan, khee-siang; liang, fu-wen; tang, hung-jen; toh, han siong; wen-liang, yu title: collateral benefits on other respiratory infections during fighting covid- date: - - journal: med clin (barc) doi: . /j.medcli. . . sha: doc_id: cord_uid: rd j abstract purpose: influenza virus infection is associated with a high disease burden. covid- caused by sars-cov- has become a pandemic outbreak since january . taiwan has effectively contained covid- community transmission. we aimed to validate whether fighting covid- could help to control other respiratory infections in taiwan. method: we collected week-case data of severe influenza, invasive streptococcus pneumoniae disease and death toll from pneumonia among calendar weeks of the influenza season for four years ( - ), which were reported to taiwan cdc. trend and slope differences between years were compared. result: a downturn trend of severe influenza, invasive streptococcus pneumoniae disease and the death toll from pneumonia per week in / season and significant trend difference in comparison to previous seasons were noted, especially after initiation of several disease prevention measures to fight potential covid- outbreak in taiwan. conclusions: fighting covid- achieved collateral benefits on significant reductions of severe influenza burden, invasive streptococcus pneumoniae disease activity, and the death toll from pneumonia reported to cdc in taiwan. resumen propósitos: covid- causado por sars-cov- se ha convertido en un brote de pandemia desde enero de . taiwán ha contenido efectivamente la transmisión comunitaria de covid- . por otra mano, la influenza tambien es una enfermedad se asocia con una alta carga y morbilidades. el objetivo del estudio es para validar si combatir la covid- podría ayudar a controlar otras infecciones respiratorias en taiwán. métodos: recopilamos datos semanales de casos de influenza grave, infecciones invasivas por streptococcus pneumoniae y número de muertes por neumonía, que se informaron a los cdc de taiwán, entre las semanas de la temporada de influenza durante cuatro años ( ) ( ) ( ) ( ) ( ) . comparamos las diferencias de tendencia y pendiente entre los años. resultados: se observó una tendencia a la baja de la influenza grave, la infecciones invasivas por streptococcus pneumoniae, y el número de muertes por neumonía por semana en la temporada de infleunza de / . se observaron diferencias significativas en la tendencia en comparación con las temporadas anteriores, especialmente después del inicio de varias medidas de prevención de enfermedades para combatir el posible brote de covid - en taiwán. conclusiones: por el número de casos reportados a los cdc de taiwán, encontramos que la lucha contra covid- logró beneficios colaterales en reducciones significativas de la carga de la influenza grave, la infecciones invasivas por streptococcus pneumoniae, y el número de muertes por neumonía. palabras clave: covid- , influenza, mascarilla, sars-cov- , streptococcus pneumoniae a recent study in japan reported that influenza activity was significantly lower in the / season versus the to seasons [ ] . the reasons for changing influenza activity might include the closure of schools, suspension of large events, and measures to reduce the risk of severe acute respiratory syndrome coronavirus (sars-cov- ) transmission among the japanese public from early in the year. in january , the taiwan government assembled a taskforce to contain the outbreak we proposed that collateral benefits on changing influenza activity and other respiratory infection activity (invasive streptococcus pneumoniae disease) and outcome (death toll from pneumonia) would have happened in taiwan. we use taiwan cdc national data (https://nidss.cdc.gov.tw/en/ and https://nidss.cdc.gov.tw/ch/misc_query.aspx?dc=death_flu&dt= &position= ) recording the number of pcr-confirmed severe influenza cases requiring admission to an intensive care unit (icu), invasive s. pneumoniae disease and overall patients died in pneumonia per week among calendar weeks of the influenza season each year ( - ). theil-sen trend test was used to calculate the trend of each whole influenza season and slope difference in comparison between years (http://www.singlecaseresearch.org/calculators/theil-sen). the slope between the upward trend (before the peak) or downward trend (after the peak) was compared season by season of each year using linear trend estimation method. sas . for windows (sas institute, inc., cary, nc, usa) was used for statistical analyses. the healthcare systems should report severe influenza cases to cdc in their clinical practice by the law on the prevention and control of infectious diseases in taiwan. the decreasing influenza activity in february was not due to the negligence of physicians while focusing on fighting covid- events, because substantial cases of severe influenzalike illness were still reported to the cdc in the same period, and they were turned out to be negative influenza tests. in addition, the reported death toll from pneumonia during late influenza seasons in was similar to or even higher than those in the same period of previous seasons. finally, as covid- outbreak prevailed in wuhan, the influenza-like illness surveillance was suspended to handle the covid- epidemic from the calendar week (january) in wuhan, china [ ] . meanwhile, the covid- pandemic did not really happen in taiwan, so the cdc did not suspend the usual reporting practice. these facts would not support considering whether fighting against covid- might have an influence on the physicians to report less for other respiratory infections. page of j o u r n a l p r e -p r o o f the theil-sen slope, also known as the nonparametric linear regression slope, is an alternative to the standard linear regression slope and has relatively strong power and precision when data are non-normal and skewed [ ] . therefore, we first use this method to measure the weekly case number of diseases through an influenza season. we found a significant downward trend and slope difference of severe influenza, invasive s. pneumoniae disease and death toll of pneumonia in comparison to previous seasons. then we use the standard linear trend estimation to measure different periods before and after the peak of an influenza season, and we documented significant downward slope difference occurring after initiation of fighting covid- in february . the taiwan government did not lockdown cities nor close schools, restaurants, and nursing institutes. why taiwan could effectively contain the covid- outbreak? sars-cov- was not tested by mass screening but was tested for risk persons who exposed to taiwan government has made several policies to integrate individual information to health care systems and the emask ordering system [ ] [ ] [ ] [ ] . what other measures did taiwanese public do with additional contributions to the significant reduction of severe influenza burden, invasive s. pneumoniae disease activity and the death toll from pneumonia? we herein sum up the preparedness and response to the taiwan essential bundles according to published literatures as follows: traffic flow control in hospitals to separate patients who were infected; alcohol sanitizer dispensers broadly used for hand washing and disinfection; isolation and quarantine persons confirmed or suspected to be infected; wearing mask in public for everyone while entering a hospital or in the crowd; aerosol transmission reduced by social distancing; and no touch the face by hand and keeping safe on mask removal [ ] [ ] [ ] [ ] . the limitation of the study included retrospective data analysis and thus we are unable to discern which measure of the disease prevention bundles, such as universal masking practice or hand hygiene was an independent factor responsible for the successful containment of other respiratory infections. during fighting covid- , patients might avoid visiting a hospital for relatively mild respiratory tract infections. however, this would not influence reported severe influenza cases requiring icu admission. we found collateral benefits of a significant reduction of weekly cases from severe influenza, invasive s. pneumoniae disease and the death toll from pneumonia during fighting in taiwan. people raising public awareness, participating in disease prevention measures, together with hospital preparedness and response, helped taiwan government to contain transmission of respiratory infectious diseases and the outcome of pneumonia during the epidemic of covid- . the collateral benefit of nearly eradicating severe influenza supports to further study on the critical step of the disease prevention bundles, which may offer enormous help to prevent the epidemic influenza burden in the future. estimated influenza illnesses, medical visits, hospitalizations, and deaths and estimated influenza illnesses, medical visits, hospitalizations, and deaths averted by vaccination in the united states seasonal influenza activity during the sars-cov- outbreak in japan response to covid- in taiwan: big data analytics, new technology, and proactive testing initial rapid and proactive response for the covid- outbreak -taiwan's experience policy decisions and use of information technology to fight novel coronavirus disease interrupting covid- transmission by implementing enhanced traffic control bundling: implications for global prevention and control efforts sars-cov- detection in patients with influenza-like illness traditional and proposed tests of slope homogeneity for non-normal and heteroscedastic data author contributions: dr yu had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. concept and design: dr yu invasive streptococcus pneumoniae disease mean (n/week) + sd theil-sen trend (slope, % c.i.) - theil-sen trend (slope, % c.i.) acquisition, analysis, or interpretation of data: all authors.drafting of the manuscript: all authors.critical revision of the manuscript for important intellectual content: all authors. key: cord- - lq r authors: hsu, tien-huan; liu, hao-ping; chin, chieh-yu; wang, chinling; zhu, wan-zhen; wu, bing-lin; chang, yu-chung title: detection, sequence analysis, and antibody prevalence of porcine deltacoronavirus in taiwan date: - - journal: arch virol doi: . /s - - -x sha: doc_id: cord_uid: lq r porcine deltacoronavirus (pdcov) was initially documented in hong kong and later in the united states, south korea, and thailand. to investigate if pdcov is also present in taiwan, three swine coronaviruses—pdcov, porcine epidemic diarrhea virus (pedv), and transmissible gastroenteritis coronavirus (tgev)—were tested using real-time reverse transcription polymerase chain reaction (rrt-pcr) in rectal swab samples from piglets exhibiting diarrhea between january and may on pig farms in taiwan. the rrt-pcr results were positive for pdcov ( / , . %), pedv ( / , . %), tgev ( / , . %), and coinfections ( / , . %). after cloning and sequencing, pdcov nucleocapsid genes were analyzed. phylogeny results indicated that the nucleotide sequences of all isolates were like those reported in other countries. to further trace pdcov in the period of to , an enzyme-linked immunosorbent assay (elisa) was used to detect antibodies against pdcov. the results showed that of , ( . %) sera were positive for the pdcov nucleocapsid protein, implying that pdcov might have existed in taiwan before . porcine deltacoronavirus (pdcov) is an enveloped, positive-sense single-stranded rna virus that belongs to the family coronaviridae. pdcov was first discovered in hong kong, china in [ ] . it was subsequently reported in the united states [ ] [ ] [ ] and south korea [ ] in , followed by thailand and mainland china in [ , ] . currently, there are at least three members of the family coronaviridae that can cause diarrhea in pigs: transmissible gastroenteritis virus (tgev), porcine epidemic diarrhea virus (pedv), and porcine deltacoronavirus (pdcov) [ ] . both tgev and pedv belong to the genus alphacoronavirus, whereas pdcov belongs to the new genus deltacoronavirus. pedv is an important enteric pathogen that causes piglet diarrhea worldwide, and it has caused significant economic losses in the swine industry in taiwan from to [ ] . however, pdcov and pedv share a similar clinical manifestation, and many studies have shown that coinfection with pedv and pdcov is common in piglets [ ] [ ] [ ] . thus, the purpose of this study was to identify the viruses responsible for causing diarrhea in piglets and to specifically investigate the prevalence of pdcov infection in taiwan. in this study, rectal swabs of piglets that suffered from diarrhea from pig farms located in central and southern taiwan were collected between january and may . all rectal swabs were transported in phosphate-buffered saline with % glycerol. the total nucleic acid content was then extracted from the rectal swabs using a labprep™ dna/rna mini kit (taigen biotechnology, taiwan). the isolated nucleic acid samples were tested for the presence of swine enteric coronaviruses-tgev, pedv, and pdcovusing the idexx™ realpcr ® test kits. pdcov-positive samples were further examined by traditional reverse transcription polymerase chain reaction (rt-pcr) with primers pdcov-n ( '-acc atc gct cca agt cat tcttg- ') and pdcov-n ( '-gag tgg agt tgg gtg ggt tta reverse-transcription reaction was performed at °c for minutes, and then a standard polymerase chain reaction was performed: cycles of °c ( seconds), °c ( seconds), and °c ( minute). after electrophoresis and gel elution, amplified products were cloned and sequenced. the nucleotide sequence data were analyzed using chromas lite, and the deduced amino acid sequences of the open reading frames were compared to other pdcov sequences using blast. the sequences of three complete pdcov nucleocapsid (pdcov-n) genes, taiwan , taiwan , and taiwan , were obtained and deposited in genbank (accession numbers ky to ky ). multiple sequence alignment and phylogenetic tree construction were then performed using the mega program [ ] . a pdcov-n clone (taiwan ) was further subcloned into the protein expression vector pet- a(+) using primers pdcov-n-f ( '-acc gga tcc atg gct gca cca gta gtccc- ') and pdcov-n-r ( '-cac aag ctt cta cgc tgc tga ttc ctgct- '). the pdcov-n protein was then expressed by adding isopropyl-β-d-thiogalactoside (iptg) (final concentration . mm) to a bacterial culture and was purified using immobilized metal affinity chromatography for a subsequent enzyme-linked immunosorbent assay (elisa). a total of , serum samples collected from pig farms in taiwan during to were tested, and specific-pathogen-free (spf) pig sera were obtained from the animal technology institute taiwan to be used negative controls. the elisa was conducted following the modified procedures described in a previous study [ ] . in brief, -well microtiter plates were coated with purified his-tagged pdcov-n ( ng/well) in mm carbonate buffer (ph . ) at °c for - hours and blocked with blocking buffer ( % bovine serum albumin in tris-buffered saline (tbs): mm tris-cl, ph . , mm nacl) at room temperature for hour. after washing three times with tbst (tbs containing . % tween- ), μl of the tested sera ( : dilution in blocking buffer) were added to the wells and incubated at room temperature for hour. after incubation, the plate was washed three times with μl of tbst and incubated at room temperature for hour with μl of goat α-porcine ig antibody conjugated with horseradish peroxidase at a concentration of : dilution in blocking buffer. after washing, μl of , ', , '-tetramethylbenzidine (tmb) substrate solution was added, and the plate was incubated at room temperature for minutes. the development reaction was stopped by adding μl of m h so , and the absorbance at nm wavelength was measured. all tests included a blank coated with antigen only, a second antibody control, and six spf sera as negative controls. if the detection value was lower than (mean neg + × sd), the serum was considered negative. on the other hand, a serum detection value larger than [(mean neg + sd) × ] was considered positive. of these tested samples, were positive for pdcov ( . %), were positive for pedv ( . %), and only two were positive for tgev ( . %). regarding coinfection rates, only one of the specimens ( . %) was positive for all three coronaviruses, one was positive for pedv and tgev ( . %), and of them ( . %) were positive for pdcov and pedv. based on the real-time rt-pcr (rrt-pcr) detection results, the percentage of pig farms that were positive for at least of one of the coronaviruses was % for pdcov ( / ), . % for pedv ( / ), and . % for tgev ( / ). we compared the sensitivity of the idexx rrt-pcr kit and the traditional rt-pcr used for cloning the n protein of pdcov in this study. all pdcov-positive samples were re-examined by conventional rt-pcr, which showed that only eight ( / , . %) were positive, accounting for . % ( / ) of total tested samples. the relatively low positive rate determined by conventional rt-pcr was comparable to that determined by a similar method in a recent study, in which pdcov was detected exclusively in nursing piglets, with an overall prevalence of approximate . % ( / ) in southern china [ ] . it is plausible that for the specimens containing pdcov genomic rna of low quantity or quality, most of the commercial rrt-pcr kits, which are designed to amplify short target sequences, can achieve higher sensitivity in detection compared with conventional rt-pcr. in addition, four of the eight positive samples were cloned and sequenced, and the sequence data matched the pdcov-n reference sequences. all of these four sequences covered the complete coding sequences of pdcov-n, but one of them, taiwan , had a nonsense mutation within the pdcov-n gene (data not shown). such a mutation might arise from an occasional change in rna sequence occurring during serial propagation of pdcov [ ] . despite the mutation, the result revealed the presence of the pdcov genome in the specimen in which taiwan was cloned, while it remained to be clarified if mutations occurred in other pdcov-encoded genes as well. phylogeny analysis of pdcov-n genes showed that pdcovs found in taiwan were highly similar in their nucleotide sequences to isolates from the united states, mainland china, and other countries (fig. ) . however, the aminoacid-based phylogeny results of the pdcov-n proteins revealed that taiwan isolates can be clustered into different groups (fig. ) . this might be due to missense mutations in the th (f → y), th (e → k), th (g → r/t), th (f → s), and th (g → e/d) amino acid residues of the pdcov-n protein (fig. ) . the charges of amino acids were changed in three residues ( th , th , and th ), and the remaining residue changes had altered polarity. the phylogeny results imply that pdcovs isolated in taiwan might have existed for a long time. to determine if pdcov had already existed in taiwan before , the pdcov-n protein was cloned, expressed, purified, and coated onto a -well microtiter plates for retrospective testing. swine sera collected between and were tested for their reactivity to a pdcov-n protein. the elisa results showed that of , ( . %) sera were able to react with the pdcov-n protein when [detected value > (mean neg +sd) × ] was used as positive threshold, but only of , ( . %) sera were positive when [detected value > (mean neg +sd) × ] was set as the threshold. the data indicated that pdcov has existed in taiwan since . similar elisa tests were also used to investigate the presence of pdcov in other studies [ , , , ] . based on our findings, we confirm that infection of pdcov and its coinfection with pedv in pigs have existed in taiwan between and . it is known that antibodies against pedv, tgev, or pdcov provide no crossprotection against either of the other two coronaviruses [ , [ ] [ ] [ ] [ ] . coinfection with pedv and pdcov might explain why some efforts have been ineffective in the pedv vaccination program. therefore, a divalent vaccine to control pdcov and pedv is desperately needed. discovery of seven novel mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus rapid detection, complete genome sequencing, and phylogenetic analysis of porcine deltacoronavirus detection and genetic characterization of deltacoronavirus in pigs porcine coronavirus hku detected in us states complete genome characterization of korean porcine deltacoronavirus strain kor/knu - porcine deltacoronavirus in mainland china pathogenecity of porcine deltacoronavirus strains in gnotobiotic pigs us-like strain of porcine epidemic diarrhea virus outbreaks in taiwan mega : molecular evolutionary genetics analysis version . for bigger datasets a recombinant nucleocapsid protein-based indirect enzyme-linked immunosorbent assay to detect antibodies against porcine deltacoronavirus occurrence and sequence analysis of porcine deltacoronaviruses in southern china isolation and characterization of porcine deltacoronavirus from pigs with diarrhea in the united states development and application of an elisa for the detection of porcine deltacoronavirus igg antibodies retrospective testing and case series study of porcine delta coronavirus in us swine herds antigenic relationships among porcine epidemic diarrhea virus and transmissible gastroenteritis virus strains two-way antigenic crossreactivity between porcine epidemic diarrhea virus and porcine deltacoronavirus evaluation of serological cross-reactivity and cross-neutralization between the united states porcine epidemic diarrhea virus prototype and s-indel-variant strains reactivity of porcine epidemic diarrhea virus structural proteins to antibodies against porcine enteric coronaviruses: diagnostic implications funding this study was supported by grants as- . . -bq-b and as- . . -bq-b from the bureau of animal and plant health inspection and quarantine (baphiq), council of agriculture in taiwan. tien-huan hsu has received grants from the bureau of animal and plant health inspection and quarantine. all authors declare no conflict of interest.ethical approval this article does not contain any studies with human participants or animals performed by any of the authors. rectal swabs were collected from clinically diarrheic piglets in pig farms in taiwan, while swine sera were obtained from the animal disease control centers of various counties and the animal technology institute taiwan. key: cord- -qjyooq authors: king, chwan-chuen; chao, day-yu; chien, li-jung; chang, gwong-jen j; lin, ting-hsiang; wu, yin-chang; huang, jyh-hsiung title: comparative analysis of full genomic sequences among different genotypes of dengue virus type date: - - journal: virol j doi: . / - x- - sha: doc_id: cord_uid: qjyooq background: although the previous study demonstrated the envelope protein of dengue viruses is under purifying selection pressure, little is known about the genetic differences of full-length viral genomes of denv- . in our study, complete genomic sequencing of denv- strains collected from different geographical locations and isolation years were determined and the sequence diversity as well as selection pressure sites in the denv genome other than within the e gene were also analyzed. results: using maximum likelihood and bayesian approaches, our phylogenetic analysis revealed that the taiwan's indigenous denv- isolated from and dengue/dhf epidemics and one sporadic case were of the three different genotypes – i, ii, and iii, each associated with denv- circulating in indonesia, thailand and sri lanka, respectively. sequence diversity and selection pressure of different genomic regions among denv- different genotypes was further examined to understand the global denv- evolution. the highest nucleotide sequence diversity among the fully sequenced denv- strains was found in the nonstructural protein a (mean ± sd: . ± . ) and envelope protein gene regions (mean ± sd: . ± . ). further analysis found that positive selection pressure of denv- may occur in the non-structural protein gene region and the positive selection site was detected at position of the ns gene. conclusion: our study confirmed that the envelope protein is under purifying selection pressure although it presented higher sequence diversity. the detection of positive selection pressure in the non-structural protein along genotype ii indicated that denv- originated from southeast asia needs to monitor the emergence of denv strains with epidemic potential for better epidemic prevention and vaccine development. dengue fever (df) and its more severe forms, dengue hemorrhagic fever (dhf) and dengue shock syndrome (dss), have emerged as major public health problems in tropical and subtropical areas [ , ] . infection with dengue viruses (denv), which are maintained in a human-mosquito transmission cycle involving primarily aedes aegypti and aedes albopictus, can result in various clinical manifestations ranging from asymptomatic to df, dhf, dss and death [ ] . the occurrences of dengue epidemics in the past years have been characterized by the rising incidence rates of infection and continuous expansion in geographic distribution of dhf epidemics [ ] . importantly, the epidemics of dhf have become progressively larger in the last years in many dengue endemic countries [ ] . the increasingly widespread distribution and the rising incidence of df and dhf are related to increased distribution of a. aegypti, global urbanization and rapid and frequent international travel. epidemiological analysis reveals that some denv strains are associated with mild epidemics with low occurrences of dhf cases and inefficient virus transmission, whereas others are more likely to cause severe epidemics with high incidence of dhf/dss and rapid virus transmission [ , ] . the large dhf epidemics in indonesia in the s and sri lanka after provided evidence supporting this phenomenon [ , ] . dengue virus serotype (denv- ) re-appeared in latin americain after its absence for seventeen years. the virus was detected initially in panama and soon dispersed throughout central and south america during the following years [ , ] . this introduction coincided with an increased number of dhf cases in this region. although the genotype originating in southeast asia has been postulated as the major cause of the increased virulence, the molecular marker associated with a difference in virulence among genotypes at the fullgenomic level is still largely unknown. dengue is caused by four antigenically related but genetically distinct viruses (denv- , - , - and - ) belonging to the genus flavivirus, family flaviviridae [ ] . denv is a single stranded, positive-sense rna virus, approximately , nucleotides in length. the genome contains a single open reading frame (orf) that encodes a polyprotein, which is co-and post-translationally processed to produce three structural proteins, including capsid (c), pre-membrane (prm) and envelope (e), and seven nonstructural (ns) proteins (ns , ns a, ns b, ns , ns a, ns b and ns ) [ , ] . a considerable number of studies have revealed that each serotype of denv is composed of phylogenetically distinct clusters that have been classified into "genotypes" or "subtypes," and each genotype is also composed of phylogenetically distinct "groups" or "clades." a previous study has classified denv- strains into four genotypes based on limited numbers of nucleic acid sequences from the prm and e protein genes [ ] ; denv- strains have also been re-classified into five genotypes [ ] . growing evidence suggests the existence of denv strains with different epidemic potentials. this evidence is supported by the following observations: ( ) the differences in fitness among various genotypes of denv- reflect their different replication capabilities in human monocytes and dendritic cells [ ] ; ( ) around , clade replacement among denv- genotype ii containing isolates from thailand was associated with changing serotype prevalence and incidence of dhf epidemics [ ] ; and ( ) sudden changes in the genotype of denv at a single locality have been observed that appeared to originate from the genetic bottleneck of a large viral population [ , ] . this sudden genotype replacement has been associated with more severe dhf epidemics in indonesia and sri lanka [ , ] . however, most of these studies involved the e gene alone. this raises an important question: is the introduction of different denv genotypes in disparate geographical locations a result of sequence differences outside of the e gene altering their epidemic potential, or it is simply a stochastic event in viral evolution? dengue epidemics in taiwan are usually initiated by imported index cases (king et al., ) . the re-emergence of dengue outbreaks in taiwan started when denv- was re-introduced into the off-islet of hsiao-liu-chiu in . in - , another large-scale denv- outbreak occurred in kaohsiung and pingtung in southern taiwan [ ] . although denv- was detected sporadically from imported index cases, no denv- -related epidemic occurred until dhf cases were confirmed in kaohsiung in and dhf cases in tainan in [ ] . taiwan neighbors many southeast asian countries and more than , travelers visit these adjacent countries annually. the surveillance system implemented by the center for disease control in taiwan (taiwan-cdc) routinely detects many imported dengue cases each year. thus, taiwan is an ideal place to study the evolution and dispersion of denv that may have different epidemic potential, particularly in the and dhf epidemics in taiwan that coincided with the dhf epidemics in southeast asian countries [ ] . complete genomic sequencing of denv- strains collected from different geographical locations and isolation years offers the opportunity to understand the genetic stasis and possible selection pressure sites in the denv genome other than within the e gene. the blood samples of suspected dengue patients, obtained from the sentinel hospitals/clinics located in tainan, kaohsiung and pingtung in southern taiwan, were sent to the infectious disease epidemiology laboratory at national taiwan university (ntu) and taiwan-cdc for laboratory confirmation. the study protocol was approved by the college of public health research human subject ethics review committee at ntu. a suspected and confirmed dengue case was defined as previously described and confirmed by both laboratories [ , ] . imported and indigenous dengue cases were defined based on the patients' travel history to dengueendemic or -epidemic countries within - days before the onset of the disease. due to few denv- epidemics and limited denv- isolates identified before in taiwan, we focused our study on comparing the sequences of different denv- isolates in and considering various epidemiological characteristics, including temporal, geographical and host factors. six denv- isolates were selected for full-length sequencing: ( ) an isolate from the imported denv- infected case in ; ( ) an isolate from the indigenous df and dhf cases during the epidemic in tainan, taiwan; ( ) the isolate from a geographical location in tainan other than the epidemic area; ( ) an isolate from the same geographical location as the tainan's epidemic but in ; and ( ) an isolate from indoor mosquitoes during the dengue/dhf epidemic in tainan. the epidemiological characteristics of these six denv- isolates are summarized in table , and their genebank accession numbers are dq -dq . in addition to the - denv- strains, four local isolates obtained from taiwan during previous years, kindly provided by taiwan-cdc, were also used for comparison, including four strains isolated from indigenous df patients during the - epidemic in kaohsiung [ twkh (accession no.: dq ), twkh (accession no.: dq ), twkh (accession no.: dq ), tw (accession no.: dq )]. isolate tw with low passage history (two passages in c / cells) was subjected to full-length genomic sequencing together with the above six isolates from - , constituting seven full-length denv- sequences from taiwan. the remaining three denv- isolates were sequenced only from the ' ncr to the cooh-terminus of the e gene region for phylogenetic analysis. acute-phase serum or plasma samples collected from the dengue patients within seven days after the onset of fever were used for both virus isolation and molecular diagnosis [ , ] . molecular diagnosis by reverse transcriptase polymerase chain reaction (rt-pcr) amplification and subsequent nucleic acid sequencing was performed as previously described, and a complete list of the pcr and sequencing primers utilized is available upon request [ ] . the rna genomic ' and ' terminal nucleotide sequences were not confirmed independently and were assumed to be of the same length and sequence as the prototype strain h in this study. a total of complete genomic sequences of denv- strains and one denv- strain a (genbank accession number ab ) were aligned using the multiple sequences alignment clustalx [ ] . these sequences were further combined with all available sequences of the complete e gene or the complete prm and partial e genes (to nucleotide position of the e gene) of denv- deposited in the genbank database at the national center for biotechnology information (ncbi). therefore, the complete e gene ( nt) dataset consisting of a total of sequences and the prm and partial e gene ( nt) dataset of a total of sequences were used for phylogenetic analysis. a complete list of the sequences along with associated epidemiological information is available upon request. the percentage of sequence similarities and differences were calculated using bioedit v . program [ ] . pairwise comparisons of both nucleotide and amino acid sequences of denv- isolates were performed using the program mega v . (molecular evolutionary genetics analysis, pennsylvania state university, pa) to determine the mean and range of the proportional difference (p-distance) [ ] . the model of nucleotide substitution that best described denv- sequence evolution was identified using the program modeltest . [ ] . the resulting most complex gtr+i+Γ substitution model (general time reversible model, gtr, a proportion of sites modeled as invariant, i, variation in rates among sites modeled using the gamma distribution, Ã) was selected to be the best fit to the data using the hierarchical likelihood ratio tests (hlrts) and akaine information criterion (aic). the estimated parameter values from this model were as follows: relative substitution rates among nucleotides were a ↔ c = . , a ↔ g = . , a ↔ t = . , c ↔ g = . , c ↔ t = . , g ↔ t = . ; proportion of invariable sites (i) was . ; gamma distribution of among-site rate variation (Ã) was . ; and estimated base composition of a = . , c = . , g = . , and t = . . a maximum likelihood (ml) tree using these parameter settings was estimated using the dnaml in phylip v . package [ ] . bootstrap analysis with , re-samplings was used to determine confidence values for groupings within the phylogenetic tree. in addition, a posterior probability distribution tree, generated by implementing the recently developed bayesian hierarchical phylogenetic model utilizing a metropolis-coupled monte carlo markov chains (mc) algorithm in the mrbayes program (version . , [ ] ) was compared with the evolutionary tree of denv- generated by the ml method. indeed, the bayesian approaches for constructing phylogenetics have several advantages. first, the primary analysis often provides faster estimates of the tree and measurements than the estimates obtained using ml bootstrapping techniques. secondly, bayesian model selection offers advantages over likelihood methods in that the competing evolutionary hypotheses need not to be nested, and it does not rely on standard likelihood assumptions. in other words, the starting trees in bayesian method are randomly chosen, and multiple runs of the same dataset are generally made with different starting trees to check convergence of the process. the programs' default settings for prior probability were used in our analysis. bayesian markov chain monte carlo (bmcmc) processes, considering the heterogeneity in the evolutionary process and thus incorporating a discrete gamma distribution of four classes of substitution rates across mutation sites, were run for , generations. output trees were sampled every generations but the first , trees were discarded before the process reached the convergence state. the resulting trees were rooted using a denv- strain a isolate as described. to analyze the selection pressure in denv- , the codeml program from the paml package was employed by implementing a maximum-likelihood method. this method presents major advantages over simpler pairwise comparisons in considering the transition/transversion rate bias, non-uniform codon usage, and phylogenetic relationships among the sequences [ ] . positive selection at a small number of codons can be detected by comparing various models of codon evolution which differ in how the rates of synonymous (ds) and nonsynonymous (dn) substitutions (denoted as ω) are treated among codons or within lineages using likelihood ratio tests. to analyze selection pressures at individual codons, we compared the m and m model. in the m model, categories were assigned and estimated from the data, which specified only neutral evolution; however, the m model allowed positive selection by add-ing an th codon category at which dn/ds can exceed . . to examine selection pressures along the lineages, the free ratio model, which allows certain lineages to have ω ratios different from the background, was implemented in the m model. additionally, parameters involving the incorporation of classes of codons where ω > were used by comparing the value of the likelihood from m , in which the specified neutral evolution of ω is constrained to be equal to or less than at all codons among all lineages. the comparison was again assessed using the likelihood ratio test. if positive selection was found, the bayesian method was applied to identify the specific codon that may have been subjected to positive selection pressure. we have determined the complete nucleotide sequences ( , nucleotides in length with an orf of , amino acids) of the seven different denv- strains from taiwan ( table ). the percentages of nucleotide and amino acid identities of the entire orf among these strains, compared with the prototype denv- strain h isolated in the philippines in , are shown in table . the indigenous denv- isolates from the epidemic area in tainan city ( tw and tw ) and from the sporadic case in pingtung ( tw ) displayed the highest similarity, with . % sequence identity in both nucleotide and amino acid sequences. the imported tw strain showed slightly lower nucleotide and amino acid sequence identity ( %) relative to these indigenous taiwanese denv- isolates. the denv- isolates of taiwan from years other than , including the kaoshiung tw and the tainan tw strains, showed higher sequence diversity compared with the denv- taiwan isolates ( % nucleotide and amino acid sequence identity), which suggested that they might have originated from different countries. further phylogenetic analysis revealed that these viruses belong to different genotypes (genotype i and iii; see the section ''phylogenetic analysis of denv- '' for details). compared to the prototype strain h , several unique amino acid substitutions that serve as unique signature sites for each genotype were found within the full genomic sequences of the selected denv- isolates from taiwan or other countries and are listed by the order of the gene in table . among those, several substitutions changed the polarity, charges, or hydrophobicity of these amino acids, which were present only in genotype iii of denv- , including the change from threonine (t) to alanine (a) at position of the c region, leucine (l) to histidine (h) at position of the prm region, l to t at position of the e region, isoleucine (i) to t at position of the ns region, and lysine (k) to t and aspartic acid (d) to asparagine (n) at positions and of the ns region. similar signature sites experiencing amino acid property alterations in genotype ii included a change from t to a at position of the prm region, l to serine (s) at position of the ns region, and a to t at position of the ns a region. thus, our data suggested that different genotypes of denv- experience different amino acid changes at both structural and non-structural genes, and the sites of these substitutions could serve as signature sites for genotype identification. the phylogenetic trees of denv- were constructed from the two different nucleic acid dataset alignments: ( ) partial sequences of the prm and e gene region (prm/e) from isolates obtained from taiwan and sequences available from genbank; ( ) complete e gene sequences including isolates from both taiwan and genbank. the trees derived from the maximum likelihood method the upper-right matrix corresponds to nucleotide sequences and the lower-left matrix to the amino acid sequences. geno v v i i i i ii ii ii ii ii iii iii iii t e v i i i i v i i i i l f f f f ns b v i i i i l and the bayesian method based on both datasets were very similar to each other. thus, only the posterior probability tree derived from the bayesian method based on the complete e gene sequences is shown (fig ) . the denv- strains isolated in taiwan with the lack of full-length sequences of viruses belonging to old american genotype iv, only four denv- genotypes, including representatives of genotype i ( tw ), genotype ii ( tw ), genotype iii ( tw ) and genotype v (h ) were compared. the sequence divergences in nucleotide and amino acid were calculated as the p-distance by adjusting the lengths of different genes [ , ] . the highest nucleotide diversity was found in the ns a gene (mean ± sd: . ± . ), followed by the e gene (mean ± sd: . ± . ). similar results were observed for amino acid diversity, which was also the highest in the capsid gene (mean ± sd: . ± . ), followed by the ns a gene (mean ± sd: . ± . ) ( table ) . to determine whether higher sequence diversity in certain genes could be the result of natural selection pressures, we implemented the m and m selection models to determine whether positive selection pressure among all codons from the full-length denv- sequences could be detected by using the codeml program from paml [ ] . the results suggested that both structural and non-structural genes of denv- were under neutral selection. although the e gene showed positive selection (ω = . ) with statistical significance (p = . ) when using the larger dataset with sequences, no specific site with positive selection could be detected. to further examine the selection pressure along the lineage, genotype i, ii, iii and v, based on the phylogenetic tree of the full-length sequences (fig ) , were examined separately using the m model. the results are summarized in table . although there were positive selection pressures detected in the c and ns b genes of genotype i, and in the e, ns and ns genes of genotype ii, only the ns gene of genotype ii showed statistically significant positive selection pressure. furthermore, positive selection was detected at position of the ns gene (substitution of s for l). changes occurring in the ' ncr and ' ncr were examined among the denv- viruses isolated in taiwan and other countries. in the ' ncr, positions , , and had nucleotide changes that were distinguishable for the specific genotype. among them, a g to a change at position was frequently seen in genotype i, a c to t change at position and a g to a change at position were observed only in genotype ii, and an a to g change at position was present in genotype iii. interestingly, the bayesian hierarchical consensus tree showing the phylogenetic relationships between denv- genotypes is based on the complete e gene sequences ( bp) from the denv- strains sampled globally figure the there was consistently an additional -nucleotide sequence, agtgaaaaaga, inserted in the ' ncr close to the end of the open-reading frame (orf) of the denv- strains isolated in recent years, compared to the prototype strain h . in the ' ncr, nucleotide changes at position , , and (nucleotide numbering beginning at '-terminus of ' ncr after the stop codon) were observed from the strains circulating recently, which differed from the strain h . however, none of these changes had any effect on the predicted secondary structure of the ' ncr rna (data not shown). the putative genome cyclization sequence ucaauaug, located between nucleotides and of the c gene, was conserved in all denv- viruses. viral sequence comparisons among isolates from dengue epidemics of different disease severities may provide valuable information regarding the molecular basis of the epidemic potential of the virus. denv- re-appeared in in taiwan and caused the df/dhf epidemic in tainan city after its first introduction in [ ] . this stimulates a great interest in understanding the molecular relationship of denv- isolates in taiwan during interepidemic periods and in comparing them with the strains circulating globally to understand evolutionary trends and geographical expansions. here, we confirmed that the dengue epidemics in taiwan were strongly associated with the globally circulating denv- due to constant introduction of viruses from southeast asia by taiwanese travelers. our data demonstrates the sequence diversity among the full-genomic sequences of denv- and the positive selection pressures exerted in different lineages (i.e. genotypes) at sites in denv- non-structural genes. since most taiwan dengue epidemics were initiated by the introduction of virus from imported cases [ ] , phylogenetic analysis provides essential information to understand the history and origin of all taiwan denv- isolates originating in other countries (fig. ) . the high nucleotide sequence identity (> . %) among the strains isolated in indicates that they were from a single origin and further spread to different townships, such as pingtung (id# tw ). the only imported denv- isolated from a traveler who had recently visited indonesia was more closely associated with the genotype ii isolates from myanmar and older isolates from thailand. this virus differed from the virus isolated during the tainan outbreak, which might suggest that multiple genotypes of denv- circulated in indonesia. this observation is consistent with a previous study indicating that at least two subtypes of denv- were present in indonesia [ ] . the phylogenetic analysis also suggested that a single isolate (id# tw ) from the same location as the epidemic was grouped together with the genotype iii sri lanka isolates. additional denv- isolates from the first denv- -caused dhf outbreak in taiwan ( ) ( ) were grouped into genotype i. all these results implicated that repeated introductions of different genotypes of denv- into taiwan since were important causes of dengue epidemics, and that denv- was not endemic in taiwan. this situation may be similar in the subtropical region of china. our country initiated airport fever screening during the severe acute respiratory syndrome (sars) outbreak in - , and it successfully identified confirmed, imported dengue cases [ ] . airport fever screening can thus quickly identify imported dengue cases, and may prevent a significant number of dengue outbreaks that would have been initiated by imported index cases. however, its cost-effectiveness in preventing any dengue epidemics in taiwan will need to be evaluated in the future. with different denv- genotypes imported into taiwan from southeast asia and other parts of the world, this virus collection provides an excellent opportunity to examine the sequence diversity of different genes of the full-length denv- viral rna genome for genotypes other than genotype iv. the highest p-distance of nucleotide diversity of the full-length genomes occurred for the ns a gene ( . % ± . %), followed by the e gene ( . % ± . %). in contrast, the highest p-distance of amino acid diversity of the full-length genomes occurred for the cap- the maximum likelihood phylogenetic tree shown here is based on the complete genomic sequences of denv- strains available from genbank figure the maximum likelihood phylogenetic tree shown here is based on the complete genomic sequences of denv- strains available from genbank. the tree was rooted using denv- strain a (genbank accession number: ab ) as the outgroup. the major amino acid changes along lineages within genotype i and ii are also labeled. taiwan denv- isolates are marked with a star. sid gene ( . % ± . %), followed by the ns a gene ( . % ± . %). this observation is consistent with the previous analysis in denv- , denv- and denv- [ , ] , although the precise cause of the increased rate of amino acid change in the ns a gene is unknown. a similar observation could also be made while analyzing the full genomic sequences of west nile virus (wnv) isolated from different animal species [ ] . the flavivirus ns a, a protein important for viral replication and particle formation [ ] , is cleaved by viral serine protease. a mutation at the basic p cleavage site residue in ns a blocks this processing event and is lethal for virus production while still allowing rna replication [ , ] . furthermore, this basic residue in ns a and an acidic residue in ns are important determinants for virus assembly and/or release [ ] . although the relative high sequence diversity of the ns a gene of denv- may be due to the lesser structural constraint required for ns a, it is possible that positive selection pressures may be exerted on this gene. especially in light of recent studies, ns a together with ns b and ns a were identified as dengue virus-encoded proteins that could antagonize the interferon (ifn) response during viral infection [ , ] . our analysis didn't detect any selection pressure exerted on the ns a gene probably due to the small sample size; future studies will be needed to focus the selection pressure analysis on non-structural proteins and denv evolution. several evolutionally conserved amino acid changes are preserved, which are unique in different denv- genotypes (table ) . these substitutions resulted in changes of its polarity, hydrophobicity or charge. especially notable was the change from l to s at position of the ns region, which is an amino acid substitution unique to genotype ii. this might be the result of positive selection within the lineage of genotype ii but not other genotypes. all denv- isolates from thailand belong to genotype ii, and interestingly, based on a previous publication [ ] , strains of denv- isolated prior to in thailand may have been replaced by two new locally evolving strains. this could be a sign of a new genotype evolving in thailand; however, most of the mutations or substitutions occurring were deleterious and a purifying selection of denv- was suggested [ ] . it is very likely that the previous analysis focused on only the e protein gene. determining the possibility of a positive natural selection site in the non-structural genes of the new thailand lineage will require further study. a number of t-and b-cell epitopes are present on the non-structural proteins, especially the ns gene [ ] [ ] [ ] . even though the biological significance of the l to s change at position of the ns region is unclear, growing evidence supported by in vitro and in vivo studies suggest that there are certain evolutionary forces acting on the ns gene shaping the gene flow of the dengue viral population, which might differ during viral replication in mammalian and mosquito cells [ , ] . this is the first time that a positive selection pressure site was detected in a non-structural protein in denv- and its importance together with its functional relevance to epidemic severity will need to be examined with a larger sample size. the global distribution of different genotypes of denv- indicates that they originated in southeast asia; these genotypes demonstrated higher epidemic potential with regards to severe dhf epidemics in sri lanka, central and south america [ , ] . genotype iii, once its transmission cycle was established locally, soon resulted in dhf epidemics regardless of an increase in virus transmission or a change in circulating serotypes [ , ] , supporting the hypothesis that virus strain is an important risk factor for dhf [ , ] . two sub-lineages (isolated before and after ) existed within the denv- genotype iii strains from sri lanka, and the viruses isolated after were associated with the dhf epidemic [ ] . we found that the strain isolated in from a indigenous dengue patient ( tw ) that did not lead to a large-scale epidemic of df or dhf was more closely related to the lineage of the denv- genotype iii sri lankan strain isolated before . similarly, in indonesia two sub-lineages of denv- were present (isolated before and after ), and a greater dhf epidemic, especially in adult cases, was caused by the denv- strains isolated after [ ] . the denv- strain isolated in taiwan during the dhf outbreak in was actually more closely related to the old indonesian strain of genotype i from - . while it is currently unknown how the different sub-lineages within each genotype are associated with different dhf epidemic potential, a recent publication suggested that changing serotype prevalence could lead to differential susceptibility to cross-reactive immune responses [ ] . furthermore, wearing et al suggested that both vector and short-termed host cross-immunity are two factors responsible for dengue epidemics [ ] . it would be necessary to strengthen comprehensive dengue virological surveillance, especially in those endemic and hyper-endemic areas/countries, to monitor the emergence of denv strains with epidemic potential for better epidemic prevention and vaccine development. mulated the idea for this study and also provided critical comments regarding this manuscript. all authors read and approved the final manuscript. dengue and dengue hemorrhagic fever global situation of dengue and dengue haemorrhagic fever and its emergence in the americas dengue viral infections; pathogenesis and epidemiology dengue/dengue hemorrhagic fever: the emergence of a global health problem dengue haemorrhagic fever in sri lanka molecular evolution and epidemiology of dengue- viruses emergence and global spread of a dengue serotype , subtype iii virus epidemic dengue hemorrhagic fever in rural indonesia. i. virological and epidemiological studies epidemiology of dengue in sri lank before and after the emergence of epidemic dengue hemorrhagic fever impact of dengue/dengue hemorrhagic fever on the developing world anonymous: dengue- in central america. dengue surveillance summary, cdc flavivirus genome: organization, expression and replication dengue and dengue hemorrhagic fever. cab international extinction and rapid emergence of strains of dengue virus during an interepidemic period american genotype structures decrease dengue virus output from human monocytes and dendritic cells clade replacement in dengue virus serotypes and are associated with changing serotype prevalence possible occurrence of a genetic bottleneck in dengue serotype viruses between the and epidemic seasons in genetic variations and relationship among dengue virus type strains isolated from patients with mild or severe form of dengue disease in indonesia and thailand dengue fever and dengue hemorrhagic fever dengue hemorrhagic fever epidemic in taiwan major epidemics of dengue in taiwan in - : related to intensive virus activities in asia fever screening at airports and imported dengue mosquito cell cultures and specific monoclonal antibodies in surveillance for dengue viruses flow cytometry compared with indirect immunofluorescence for rapid detection of dengue virus type after amplification in tissue culture strategically examining the full-genome of dengue virus type in clinical isolates reveals its mutation spectra clustal: a package for performing multiple sequence alignment on a microcomputer biological sequence aligment editor for winxp mega : integrated software for molecular evolutionary genetics analysis and sequence alignment modeltest: testing the model of dna substitution phylogeny inference package mrbayes: bayesian inference of phylogenetic trees paml: a program package for phylogenetic analysis by maximum likelihood dengue type virus in plasma is a population of closely related genomes:quasispecies the molecular epidemiology of dengue virus serotype in bangkok complete genome sequences and phylogenetic analysis of west nile virus strains isolated from the united states flaviviridae: the viruses and their replication cleavage of dengue virus ns -ns a requires an octapeptide sequence at the c terminus of ns in vitro processing of dengue virus type nonstructural proteins ns a, ns b, and ns inhibition of interferon signaling by dengue virus inhibition of alpha/beta interferon signaling by the ns b protein of flaviviruses precise location of sequential dengue virus subcomplex and complex b cell epitopes on the nonstructural- glycoprotein recognition of snthetic oligopeptides from nonstructural proteins ns and ns of dengue- virus by sera from dengue virus-infected children development and evaluation of serotype-and group-specific fluorogenic reverse transcriptase pcr (taqman) assays for dengue virus temperature sensitive mutations in the genes encoding the ns , ns a, ns , and ns nonstructural proteins of dengue virus type restrict replication in the brains of mice e/ns modifications of dengue virus after serial passages in mammalian and/or mosquito cells phylogenetic analysis of dengue- viruses prevalent in guatemala during - internaltional notes dengue type infection -nicaragua and panama cities spawn epidemic dengue viruses disease exacerbation caused by sequential dengue infections: myth or reality? evolution of the dengue- virus in indonesia and throughout se asia may contribute to recent changes in outbreak dynamics ecological and immunological determinants of dengue epidemics we sincerely thank shih-ting ho at the sin-lau christian hospital, chien-ming li at the chi-mei foundation medical center and shih-chung lin at the kuo general hospital for cooperation in kindly providing the clinical samples. the study was supported by the grants from the national health research institute (nhri), taipei, taiwan (grant number: nhri#dd - x-cr- p and nhri#cn-cl p) and the national science council (nsc# - -b- - , nsc# - -b- - ) in taiwan. the authors declare that they have no competing interests. dyc and cck designed and performed all the experiments and drafted this manuscript together. dyc participated in the sequence alignment and statistical analysis. jhh and ycw helped with collecting field human isolates and ljc helped with sequencing experiments, together. thl helped for the field mosquito collection and gjc for- key: cord- -cwpz akv authors: hsin, dena hsin-chen; macer, darryl r.j. title: heroes of sars: professional roles and ethics of health care workers date: - - journal: j infect doi: . /j.jinf. . . sha: doc_id: cord_uid: cwpz akv objectives. to examine the professional moral duty of health care workers (hcws) in the outbreak of severe acute respiratory syndrome (sars) in . methods. descriptive discussion of media reports, analysis of ethical principles and political decisions discussed in the outbreak, with particular emphasis on the events in mainland china and taiwan. results. there were differences in the way that taiwan and mainland china responded to the sars epidemic, however, both employed techniques of hospital quarantine. after early policy mistakes in both countries hcws were called heroes. the label ‘hero’ may not be appropriate for the average hcw when faced with the sars epidemic, although a number of self-less acts can be found. the label was also politically convenient. conclusions. a middle ground for reasonable expectations from hcw when treating diseases that have serious risk of infection should be expected. while all should act according to the ethic of beneficence not all persons should be expected to be martyrs for society. it was too heavy to be called as a hero; i just do what i should do. -doctor facing sars in taiwan, may . severe acute respiratory syndrome (sars) will go into the medical records as the first new panic disease that has swept international society in the st century. although the number of persons who died from the disease is currently less than a thousand, it affected the lives of millions of persons in . we want to discuss the important lessons that it raises for medical professionals-the 'heroes' of sars. the focus on sars was so high in the media that news of sars overshadowed the outbreak of another panic disease, ebola virus, that killed more than persons in march in congo. the attention paid on sars meant less attention was given to disease outbreaks like ebola. sars is the latest of more than new or reemerged infectious diseases over the last years. the difference was that most people in the world, especially in safe and secure social settings felt protected from ebola virus of africa, and even the global pandemic of hiv seems distant from most people who donned masks to avoid sars. sars infected and killed young and old, healthy and unhealthy, making everyone seem vulnerable. in taiwan, the sars outbreak started from the time a hospital was detected to have a widespread hospital infection. the hospital was sealed as an emergency and patients and staffs were all locked up inside the hospital building to isolate them from outside, to spread the disease. the quarantine order was announced without any warning and preparation, which caused a massive panic. similar quarantine emergencies were reported in other places also. hcws who were placed in working quarantine experienced fear, depression, anxiety, anger and frustration. there will be long-term psychological consequences for some of these persons. this paper discusses some of the ethical lessons of the first sars outbreak in early , with a hope that lessons will be learnt in time for the next outbreak of sars, or similar new diseases that face those working in the field of infectious diseases control. during the international battle against sars one of the features was the proportion of frontline health care workers (hcw) who were infected and who died. according to the data compiled from the who until the august , % of all persons affected with sars were hcws ( / ). the percentage of hcw was highest in canada ( % with / deaths), and singapore ( %), higher than that reported for mainland china ( %), hong kong ( %) and taiwan ( % with / deaths). in the early stages of the outbreak, they had all unknowingly treated patients with sars. even for the latter stages in the outbreak in the first half of , there were several hcw who became ill with sars in spite of 'full' precautions. when nurses and doctors see their colleagues being critically ill around them, dying or on ventilators, when just few days ago they seemed so robust and well, they realized the dangers of being a professional. despite the rapid advancement of knowledge with the intense research, and papers appearing in all major medical journals, the threat of the disease to hcw will remain for some time. before a vaccine is made, there will always be a threat of being infected and killed on duty as a hcw. we witnessed a number of hcw who started to think about withdrawing from their post. it is ethically unacceptable to abandon patients. however, beyond the duty of a hcw, should we demand (or even expect) that hcw should be ready to sacrifice their lives for our society in severe pandemics, like the outbreak of sars. as one doctor in taiwan said: 'it too heavy to be called as a hero; i just did what i should'. we understand that even a virtuous doctor or nurse might not be willing to die for a patient. does the accepted norm of responsibility mean they must put their own lives at risk? one important point is that the social function of medical professionals can not be replaced by others. even in times of peace, we should always remember the reality that being a helper of sickness will always present a certain risk of being infected. medical professions have been well-rewarded by the society not only because they are competent in operating medicine but they chose the work of being a 'life saver'. in a number of countries in order to encourage hcw, the government and the public started to give the title of 'hero' to nurses and doctors who are working in the frontline of sars outbreak. on the other hand, some suggested to punish those who were afraid of treating sars patients. in taiwan this included threats of retracting their professional license. there are memories of the aids scars in the s when some hospitals in asia refused to admit patients with hiv. in a survey by the japan hospital association it was found that % of hospitals refused hiv positive patients. currently refusals are not permitted. can someone who makes an involuntary sacrifice be called as a hero? most nurses and doctors actually died from taking care of sars patients involuntarily. except for those on international teams who actively sought out sars patients, most did not choose to do so. in large scale hospital quarantines in beijing and taiwan the hospitals were encircled and no one could leave. many hcw in taiwan thus denied the title of hero. some said the more people call them in this way, the more they fear they are in danger. we could even imagine that the spiritual inspiration of being a 'hero' even lessens the implementation of good clinical precautions. in taiwan four nurses and two doctors sacrificed their life in taking care of sars patients. the numbers for other countries are not clear, but one can expect it to be higher for hong kong and mainland china, based on the proportion of infected hcws quoted above. in taiwan, a doctor died from giving airway intubations to a terminal old woman even with the protection of masks and glove; he was so young to graduate from medical school a few months ago and got married only months before. a nurse died with her month old fetus just because of a short contact with an undiagnosed sars patient in the emergency room. as those scary stories are repeated numerous times among hcws, can medical ethics overcome their emotions? in facing the crisis of sars, health professionals may make efforts to combat the enemy like in the war. however, could we regard the hcw as a soldier in an army, as quoted in a china daily report? when the health staffs or soldiers decided to resign from their job just in the moment of crisis/war, some cultures attempt to remind the persons of their sworn duties to contribute to national security by giving the person a feather (sign of shame). while the ethical ideal of self-less sacrifice of life for curing disease is promoted in the public image and media, discussions with hcw in several countries suggests that being a hero is not what modern medical practice is for some hcws. most hcws in taiwan are working in the commercial hospital, where the hirer pushes them to focus their effort of work on business competition rather than the basic role of helpers to human's health. beside academic achievement, the profit they can make for their institute is the element to promote their position in their profession. it is easy to loss the ideas of being heroes that is part of the intrinsic nature of being doctors or nurses. most modern hospitals there are designed under the intention of attracting people to visit frequently. besides for a commercial hospital, the most effective way to limit the budget is to reduce labour costs. to use part time staffs saves much money from less benefit and salary pay. could we expect nurses who were called when they are needed and paid by working hour to devote themselves to the full professional code and make all efforts when their life is threatened? it is obvious that the feeling of belonging and sense of nobility are essential for a professional worker, the problem is do we really respect those health worker as health profession to supply the components to achieve the sense of a professional. many hcw in modern times have only faced remote fears of death, and it is a shock for many to realize that their own lives are in danger. when they considered that even with necessary precaution; they still had to run a certain amount of risk, their duties of being a wife/husband, mother/father or daughter/son will call them home. although sars was reported to have a relatively low mortality rate, it attacks the young and healthy as well as the old and frail. moreover, this is a totally new disease, we know very little about it. the fear and worry of being infected will always be a shadow to their care. will the public accept a health professional to exercise their right to remain off the job in this critical moment? every person of any profession has their personal role in a family to be a father, mother, spouse and child, in addition to their professional roles. the constitution of most countries respect a person's human rights and ego (beyond the superego) i.e. ego is the basic human nature which should be honored too. part of the love of life that makes a bioethics of an ethical person in ethical theories is self-love, not just love of others. those medical practitioners who stick to their post should be respected; however, those who need to take a break to recover themselves would also be acting within their human rights and what is expected of a reasonable citizen. there are cases recorded where doctors spent weeks continuously battling the disease, and there is need for a proper assessment of how fatigue may have led to mistakes in care for patients and mistakes in precautions of carers. there is a human limit for everyone to cope with. those who battled self-lessly are called exceptions, for example, ye xin, , head nurse at the guangdong hospital of traditional chinese medicine, died in march after contracting sars while treating patients infected with the virus. ye, together with nine other nurses, was posthumously awarded the florence nightingale prize by the international committee of the red cross in may for 'courage and dedication in the line of duty'. in carrying out the responsibility of reporting the truth, the media created the sars panic. in most of the infected areas, the government had no control over the media. under the pressure of commercial competition, those narratives reported by media could be exaggerated which cause mass panic and changed the relationships between people. on the contrary there was a lack of information in mainland china especially until april, when the government was attempting to limit panic by controlling the media. however, when the epidemic was revealed, the following month saw panic there also. everywhere society has to pay a price for liberty of the media, and to deal with the result of transparent reporting. there were also rumours spread through the internet that generated fear. there are reports that in china people were charged with spreading 'sars-related rumours', though the exact nature of the types of email they were sending is doubted. however, without media reporting as a way to educate society, the death toll everywhere would have been higher. the media generated fear, stigma and discrimination, but also showed the evil sides of the panics. people who were subjects of discrimination included those working in the hospital or entering and coming back from infected areas, suspected sars patients and their family. even those with very common syndromes of cold (cough, fever, etc.) were psychologically and socially isolated by their friends and relatives. from the narratives reported by media, the mass panic caused by sars has changed the relationships between people. in certain cases by calling health professionals 'heroes' policy makers in government wanted to escape from their guilt of policy mistakes by giving ambiguous honors. governments had to face up to the mass fear that sars created, and any target could be chosen. there were scapegoats in mainland china on the april with the firing of the health minister. in many countries affected by sars, and neighbours like japan, one of the usual targets for blame is foreigners. persons from distant lands have always been blamed in cases of disease. in early april, a hong kong resident came to taiwan to visit his younger brother despite being supposed to be under home isolation in hong kong due to the spread of the disease in his apartment building, amoy garden. his brother was infected by him and it was the first fatal case of sars in taiwan. one woman, who took the same train with him, was highly suspected to be the source of a major hospital outbreak. at first, the doctors were not sensitive about her case since she had no contact history to match the susceptive criteria for sars. thus, she spread sars in the hospital before she was diagnosed. many hospital staff, patients and patients' families were infected at the same time. the hospital was able to detect this spread and sealed its premises entirely without good preparation. four thousand people were locked inside the building to prevent further spread of the disease; and more than people were isolated in their homes. this strong measure resulted in a mass panic. but it was too late. the numbers of infected cases increased exponentially. inside china, the people in guangzhou province are blamed. when one of us was in beijing on april, , some experts said 'the people in guangzhou eat anything that moves. it is their fault.' people in hong kong may have blamed the chinese. people in taiwan or canada blamed those from hong kong. people in japan in may blamed a doctor who traveled from taiwan who later came down with sars. all the people they blamed were just being human, but foreigners are convenient targets. the chinese government was so concerned about the image of china that it is rumoured that persons were threatened by death in case they transmitted the disease to foreign countries. if we view the work of medicine a sacred vocation, an inner calling to dedicate and care for the sick, it is contradictory to imagine some medical doctors may be accused of giving rise to a great loss of our society. taiwanese society decided to punish some of the head doctors who did not detect and report the hospital infection in the early stage. the final decision was to give the very tough punishment of retracting their professional license. ethically a wrong decision should not be punished as a crime of that magnitude unless the health profession had a criminal intention (motivation). although the consequences were a great loss for society it is not a wise move for the future to punish physicians for making mistaken decisions in emergency circumstances over public health if they were not intending any cover-up. there seems to be a threat of political scapegoats in every health crisis. we can expect future hcws to move for greater self-protection and hesitance in making decisions that are necessary for public health crises like emerging diseases. between the hero and the coward, there must have some space where people can be humane. it is normal and proper for people to be scared to die yet fulfill their duty in the frontline. except for special 'danger pay' or another kind of reimbursement, a calling for increased emphasis on workplace safety and a review of precautions is most important for this critical situation. a well trained and equipped health worker also needs to prepare for the frontline of possible bioterrorism, which may be similar to what we saw with sars. we need a well prepared expert more than a hero. there were cases reported where proper diagnosis of other diseases was hindered by the infection prevention measures being applied to treat all patients from sars infected areas as potential sars victims. spiritual motivation should not slacken the implementation of sound precautionary measures. as the who director-general said 'the containment of sars required heroic efforts and extraordinary measures that are difficult to sustain over time'. a taiwanese study of nurses in may-june found that nurses' agreement with the government control measures was a predictor of the extent to which they fulfilled their professional care obligation. this suggests that having the support of the healthcare professions in policy is essential for everyone to work wholeheartedly. before the next outbreak, we need long-term planning and humane intervention to prepare a better response for the expected return of the disease. in the future if some repressive regimes are hit by sars they might employ brutal tactics to quarantine and isolate people, possibly sowing division among outside countries and multilateral organizations over how to respond to apparent human rights violations. calls for development of effective centers for disease control in other regions of the world, including europe, have been made in response to the ways sars was fought. the intention of calling for hcws to above all do good should not be blurred by wrong planning. with sars as with other severe infectious diseases that are readily transmitted, the manner that home and work isolation is handled is a key ethical issue. if people were diagnosed to be suspect or probable cases, all the people around them may as well be suspected of having been contaminated by them. consequently, the persons they have been in close contact with, for example, families, colleagues or schoolmates may be isolated to avoid further possible spread of the disease. such home isolation has serious social and psychological influences. in some cases, those who break home isolation may be punished by imposing a fine. people who were victims of sars in were accused of hindering the prevention or treatment of sudden disease outbreaks if they broke such isolation. it is normal to expect that quarantine will cause fears, and people will lose their patience and self-restraint, but we should assume that all people were originally infected by others with a few recent exceptions infected by laboratory medical research. persons should be taken care of better than being totally restricted to avoid them inflicting possible harm on others. with the policy of respecting human individuals complete needs for physical and mental well being, more people will be motivated not just to protect themselves, but to contribute to the macro wellbeing of the society. there are still lessons for all in society about the ethics of quarantine. modern society has forgotten the past risks of infectious disease outbreaks. we would suggest to respect health worker's autonomy of making their own choice to take a break from intensive physical or emotional loading or to accomplish the historical mission of coping with sars. a well developed society that we live in should have sufficient space to practice humanism to everyone in any kind of situation including a public health crisis. this is one of the lessons, we should learn in preparation for the next crisis of infectious disease. world health organization, summary table of sars cases by country an ebola epidemic simmers in africa sars: an asian catastrophe which has challenged the relationships between people in society-my experience in taiwan what have we experienced and learned from the outbreak of sars in beijing? flying publisher editorial: three lessons of sars too soon to celebrate the foreignness of germs: the persistent association of immigrants and disease in american society nurses' professional care obligation and their attitudes towards sars infection control measures in taiwan during and after the epidemic sars: down but still a threat. scope note (u) united states national intelligence center severe acute respiratory syndrome (sars): loud clang of the leper's bell key: cord- -yzyixucr authors: lin, chih-yen; wang, wen-hung; urbina, aspiro nayim; tseng, sung-pin; lu, po-liang; chen, yen-hsu; yu, ming-lung; wang, seng-fan title: importation of sars-cov- infection leads to major covid- epidemic in taiwan date: - - journal: int j infect dis doi: . /j.ijid. . . sha: doc_id: cord_uid: yzyixucr abstract objective covid- has recently become a pandemic affecting many countries worldwide. this study aims to evaluate current status of covid- in taiwan and analyze the source of infection. methods national data regarding sars-cov- infection were obtained from taiwan cdc at the end of april, . these data were subjected for analysis of the current status and correlation between indigenous and imported covid- cases. phylogenetic tree was performed to analyze the phylogeny of taiwanese sars-cov- isolates. results the initial case of sars-cov- infection in taiwan was detected on january , . epidemiological data indicate that by april , there were a total of covid- confirmed cases with the death rate of . %. most of cases were identified as imported ( . %; / ) with majority transmitted from united states of america ( . %) and united kingdom ( . %). results from phylogenetic tree analyses indicate that the taiwanese sars-cov- isolates were clustered with the sars-cov- isolates from other countries (bootstrap value %) and sub-clustered with bat sars-like coronaviruses (bootstrap value %). conclusion this study suggests that importation of sars-cov- infection was the primary risk-factor resulting in the covid- epidemic in taiwan. other countries (bootstrap value %) and sub-clustered with bat sars-like coronaviruses (bootstrap value %). this study suggests that importation of sars-cov- infection was the primary risk-factor resulting in the covid- epidemic in taiwan. keywords: covdi- , taiwan, imported, indigenous short communication: emerging diseases pose a threat to global health and has the potential to become fatal. in december , an atypical pneumonia prompted by a novel coronavirus, was first reported wuhan, china (huang et al., ) . this novel coronavirus was initially named -novel coronavirus ( -ncov), however, currently the name has been established as the severe acute respiratory syndrome coronavirus- (sars-cov- ); with the disease being named as coronavirus disease (covid- ) (coronaviridae study group of the international committee on taxonomy of, ) since the first reported case, there has been a rapid increase in the number of cases, with outbreaks being reported in countries all over the world. the sars-cov- has gradually disseminated to europe, america and asia via travelers and has caused a covid- pandemic since march (who., b). the world health organization (who) declared the outbreak as a public health emergency of international concern on january , and an official j o u r n a l p r e -p r o o f pandemic on march , . as of april , , more than . million cases of covid- have been reported in countries and territories, resulting in more than , deaths (who., b). coronaviruses are non-segmented enveloped viruses with a single-stranded, positive-sense rna genome. coronaviruses are known to infect a variety of animals with some strains being capable of infecting human. in recent decades, the severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov) has caused regional outbreaks, leading to high mortality in human infections (peeri et al., ) . in , there was an outbreak of sars-cov in taiwan with sars probable cases and laboratory confirmed cases (taiwan taiwan is an island in the pacific ocean, located beside mainland china. international travel has an important role in the transmission of emerging or re-emerging infectious diseases in taiwan . in recent decades, the interactions between taiwan and china have become frequent and close. through this close interaction, sars-cov- infection was initially detected in taiwan on january , (taiwan cdc.) (fig. a& b ). this first case was a -year-old woman who was detected by a fever screen station in taoyuan international airport, as she arrived from wuhan, china. since then, several sporadic covid- cases have been detected in taiwan between january to early march, (fig. a& b ). data indicates that the covid- imported cases have dramatically increased since the middle of march (fig. a) . before the mid of march, the incidence of covid- importation was . average per day. after that, the incidence of covid- importation increased to . average per day (fig. b) . we j o u r n a l p r e -p r o o f further investigated the source of these covid- importation. our results indicated that the imported covid- cases were mainly from united states of america ( . %), united kingdom ( . %) and france ( . %) (fig. c ). in addition to imported cases, there were a few indigenous covid- cases reported. according to taiwan cdc, by the end of april, there were covid- laboratory confirmed cases with the fatality rate of . %. among these cases, ( . %) and ( . %) were identified as imported and indigenous covid- , respectively (fig. d ). the rest of cases ( . %) remain questionable, as their source of infection were not clearly defined. accordingly, we suggest that the constant importation of sars-cov- infection is the major risk factor leading the covid- epidemic in taiwan. further, the source of infection from the indigenous cases were traced. results indicated that most of indigenous cases ( . %; / ) had contact history or exposure to sars-cov- infected patients, sars-cov- contaminated devices or environment through a direct or indirect way (fig. d ). there were ( %) indigenous covid- cases that remained unclear has to their possible source of infection (fig. d) . we further addressed the phylogeny of the sars-cov- isolated in taiwan. results demonstrated that three taiwanese isolates, collected in the early phase of the covid- epidemic, were similar with other sars-cov- isolates from other countries with bootstrap value of % (fig. ) . it was also noted that sars-cov- was sub-clustered with bat sars-like strains isolated from china (bat-sl-covzxc and bat-sl-covzc ) (bootstrap value %) (fig. ) , indicating that sars-cov- might have possibly evolved from bat sars-like viruses. however, the source and origin of sars-cov- still remains controversial, and further studies are demanded. to reduce the effects of covid- importation to taiwan, taiwan cdc has implemented relevant prevention strategies. the international airport reinforced fever screening of arriving passengers, questioning about their travel history, and conducting health assessments. travelers coming from covid- affected countries were required to fill out a "novel coronavirus health declaration and home quarantine notice". furthermore, foreign nationals were prohibited to enter taiwan since march , in response to covid- pandemics. the covid- spectrum of illness severity has been divided into four types: mild, moderate, severe, and critical ( , gao et al., , who., a . the who reported that fever, fatigue and dry coughing are considered the main clinical manifestations of covid- patients. other symptoms may include runny nose, myalgia, pharyngalgia, stuffy nose, and diarrhea, however, these are relatively less common (who., b). in severe cases, the covid- may become fatal due to respiratory failure, shock and organ failure. the clinical features of covid- are shown in table . with this novel coronavirus causing a pandemic, more and more evidences indicate that majority of the covid- cases may not develop to have severe manifestations with some cases even remaining asymptomatic; nevertheless, these individual still have the ability to transmit the virus to others. asymptomatic infections are identified as individuals testing positive for the detection of sars-cov- nucleic acid using rt-pcr (gao et al., ) (table ) , however, these individuals do not display the typical clinical symptoms and there are no apparent abnormalities in their images, including lung x-ray film and computed tomography (ct). taiwan cdc indicates that around - % covid- patients belonged to asymptomatic or mild cases (taiwan cdc.) . similar indicating that most sars-cov- infected patients were asymptomatic. the reasons for majority covid- infections displaying "none-to-mild symptom" remain unclear. it has been proved that sars-cov- invades cells by using angiotensin-converting enzyme (ace ), as its receptor (zhou et al., ) . expression of lower level of ace or weaker binding capacity between sars-cov- and ace should be an essential factor that leads to the absence of any clinical manifestations for asymptomatic infections. in addition, host major histocompatibility complex (mhc) is also proposed to play a certain role to mildly initiate and regulate the sars-cov- induced immunopathogenesis (nguyen et al., ) . it is suggested that more clinical samples should be collected and a comparative examination of ace as well as mhc typing should be carried out. here, we report the current status of covid- epidemic in taiwan. we found that importation of sars-cov- infection was the major risk factor correlating with the outbreak causing a threat to taiwan. the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. the phylogenetic tree was constructed on the basis of nucleotide sequence of full-length genome (~ kb). the filled red circles indicates taiwanese sars-cov- isolates. analysis was performed by using mega software and neighbor-joining method. bootstrap support values > are shown ( , replicates). j o u r n a l p r e -p r o o f ( ) complicated with other organ failure positive j o u r n a l p r e -p r o o f coronaviridae study group of the international committee on taxonomy of v. the species severe acute respiratory syndrome-related coronavirus: classifying -ncov and naming it sars-cov- a systematic review of asymptomatic infections with covid- clinical features of patients infected with novel coronavirus in wuhan, china the sars, mers and novel coronavirus (covid- ) epidemics, the newest and biggest global health threats: what lessons have we learned? imported dengue fever and climatic variation are important determinants facilitating dengue epidemics in southern taiwan clinical management of severe acute respiratory infection (sari) when covid- a pneumonia outbreak associated with a new coronavirus of probable bat origin rr (respiratory rate) spo (blood oxygen saturation levels) these data were referenced with previous publications the authors wish to thank the staff from center for tropical disease control for their assistance in data collection. cyl and whw prepared and revised the manuscript. anu and cyl helped to analyze the data. yhc ,spt and pll revised and edited the manuscript. mly and swf conceived the study and revised the draft. key: cord- -dlpn l j authors: chen, cheng‐ren; huang, hui‐chun; huang, hsiu‐chen; chen, wei title: preparing for covid‐ : the experiences of a long‐term care facility in taiwan date: - - journal: geriatr gerontol int doi: . /ggi. sha: doc_id: cord_uid: dlpn l j nan as of april , there have been > confirmed cases of coronavirus disease (covid- ) worldwide and deaths. one previous study showed that covid- is more likely to affect older men with comorbidities; the highest mortality rate was observed among persons aged ≥ , ranging - %, followed by - % among those aged - years. long-term care facilities (ltcf) are high-risk settings for severe outcomes of the covid- outbreak, owing to both the advanced age and frequent chronic underlying health conditions of the residents. to prevent large-scale community transmission of covid- , taiwan has taken advanced steps in terms of medical care planning (e.g. border control, identifying cases, quarantining suspicious cases, proactively searching for cases, allocating resources etc.). thus far, just covid- patients have been confirmed, six of whom have died. only one nursing home has been in lockdown, because one of its nursing staff became infected. in this article, we share our experiences regarding how we have responded to covid- in our ltfc based on the management of visitors, residents and healthcare professionals (hcp), as well as government support and policies. the first policy we made was to limit the number of visitors when we learned that some infected individuals have no fever or respiratory symptoms. all visitors are required to: wear a mask; have their body temperature checked; voluntarily declare their history of travel, occupation, contacts and cluster; and register before entering the building. visiting hours and the number of persons accompanying patients are gradually being reduced as the number of confirmed cases rises in taiwan. using big data technology, the government later makes the immigration data accessible on health insurance cards. all the visitors are required to present their health insurance card to make known if they have recently visited high-risk countries. regarding management of hcp, we hold regular educational and training seminars to deal with covid- . we actively screen hcp for fever and respiratory symptoms at the beginning of their shifts, and implement sick leave policies that allow ill hcp to stay home. traveling abroad is prohibited, and all employees must report their weekend and vacation activities every week. we now restrict all volunteers and nonessential hcp from entering the building. later on, we decided to cancel all group activities, avoid communal dinners with colleagues, and to re-organize the groupings and schedules of nursing staff and attendants. one member of each group is confined to the same working place and accommodation area. to lower any risk of delayed diagnosis or misdiagnosis, if residents or hcps have a fever or respiratory symptoms, they take a covid- test. in terms of considerations for residents, they are not allowed to leave the facility. to avoid extra contact in the hospital, our staff regularly prescribe medication for them if they are in a stable condition. in addition, we increased the number of rehabilitation clinics in the facility for residents who require rehabilitation at the hospital. to decrease the burden and risks for hcps, our facility has become temporarily unavailable to new residents. to prepare for surge capacity in staffing, equipment and supplies, we asked the residents and their families whether they would like to return home or stay in the facility while there is an outbreak occurring within it. international organizations have recognized the taiwanese government for waging a successful battle against covid- . just like its aggressive efforts toward border control, containment and proactive testing, the attempts to care for patients who require long-term care are not inferior to other aspects of taiwan's overall endeavor. initially, the government coordinated with manufacturers to help our ltfc purchase supplies, such as thermometers and ethyl alcohol. later oneven though there has been no farreaching community transmissionthe government gave the order to keep all visitors from entering nursing homes or ltcf. to plan ahead of time and to mitigate supply shortages if outbreaks in the community were to occur, the government checks the vacancy of ltcf beds, coordinates with neighboring hospitals to satisfy the medical needs of ltfc and has requested a prepared plan from each facility. although we are unable to predict whether there will be extensive community transmission of covid- in taiwan, most ltcf readily cooperate with the government's policies, try to plan ahead and minimize risks as best as they are able. * cheng-ren chen and hui-chun huang contributed equally to this work. geriatric practice during and after the covid- pandemic keywords: covid- , diabetes mellitus, elderly, frailty, geriatrics. dear editor, two aspects warrant consideration regarding the ongoing covid- pandemic: prevention of covid- infection and protection from the related changes among the elderly. for prevention, the tokyo metropolitan government has announced a stay at home campaign that requests residents to stay at home. for the latter, the japan geriatrics society (jgs) established the "covid- , practice caution for older people" in march to raise awareness on "prevention of frailty" (fig. ) . to achieve both goals, we need to avoid close contact and lead a routine, healthy life. covid- influence can trigger age-related diseases other than frailty; therefore, it is necessary to identify the impact of this pandemic on the geriatric population. here, we present two aspects of covid- , i.e., (i) physical effects, including frailty and aggravation of age-related comorbidities, and (ii) psychosocial effects of covid- -induced changes. covid- is known to have poor prognosis in the elderly because it tends to be more severe in that population. there might be an association between angiotensin-converting enzyme (ace) levels and covid- infection, and obese and diabetic patients may have increased ace levels. , therefore, patients with these diseases should be cautious of susceptibility and aggravation of covid- infection. although the long-term effects of covid- infection on humans are unclear, the potential effects of excessive cytokines have been reported; inflammatory cytokines can cause frailty, cognitive deterioration and cardiovascular disease. thus, further research is needed to investigate the effects of covid- on various age-related diseases in addition to frailty. covid- infections have a tremendous effect on the affected individual and the population due to the need for selfrestraint and social distancing. japan has experienced the great east japan earthquake and the kumamoto earthquake, and has developed medical care for disasters. during this pandemic, several situations similar to those observed during natural disasters have emerged for the elderly. decreased physical activity can cause hyperglycemia, increased susceptibility to infection, increased cardiovascular diseases, worsened psychological state, worsened cognitive function and more bone joint diseases. social interaction is particularly important for the elderly. the battle with the covid- pandemic is expected to last a long time, and this situation affects not only our daily life, but also our mental health. mental health issues, including depression, discontent, hopelessness, hostility, anger and life events can cause incidents of stroke or cardiovascular disease and increase mortality. behavioral and psychological symptoms of dementia may worsen. in contrast, protective psychological factors against stressors that include optimism, positive coping style, positive attitude toward aging and sense of coherence are related to a reduced incidence of stroke. psychosocial interventions are crucial for the elderly people during and after the covid- pandemic to prevent stroke and cardiovascular disease. to maintain the physical functions and daily routine of the elderly, the jgs recommends eight points related to the following three aspects: (i) exercise and nutrition, (ii) oral function, and (iii) social support (fig. ) . it has been challenging to achieve these proposed practices and encourage people. moreover, there are several unresolved issues: how do we restore our daily life? is there any other communication option aside from calling our families? is it not important to have an outpatient visit along with telephone consultation? to resolve these points, we need to develop a new medical care system for the elderly in consultation with clinicians, healthcare workers and researchers across the globe. encouraging and educating the elderly in the use of personal computers could enable online group exercise therapy sessions, nutrition guidance and social networking. information technology, including robots, would epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study severe outcomes among patients with coronavirus disease (covid- ) -united states epidemiology of covid- in a long-term care facility in king county, washington response to covid- in taiwan: big data analytics, new technology, and proactive testing preparing for covid- : the experiences of a long-term care facility in taiwan