key: cord-0004750-j9mli4h0
authors: Brown, C.S.
title: The role of the WHO Regional Office for Europe in response to seasonal, avian, and pandemic influenza
date: 2012-12-19
journal: Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz
DOI: 10.1007/s00103-012-1587-z
sha: 87d4da84361899f3c98e76b226a70c056899d5db
doc_id: 4750
cord_uid: j9mli4h0

Between 2005 and 2011, the WHO Regional Office for Europe assisted the member states of the WHO European Region to prepare and respond to outbreaks of avian influenza H5N1, the 2009 pandemic, and to enhance their capacities for the prevention and control of seasonal influenza. It did this through conducting a combination of regional and subregional meetings and trainings, establishing a regional network for influenza surveillance, providing operational guidance for implementing influenza surveillance and strengthening the capacities of National Influenza Centers, and through assistance at the country-level where needed. In all, close to 60 country-missions or country-level activities were conducted. These activities were conducted in close coordination with WHO headquarters, WHO European Region Country Offices, the European Commission, the European Centre for Disease Prevention and Control, and with other partner organizations, and were in line with the implementation of the International Health Regulations (2005). The results of activities as well as guidance documents were disseminated to a wide audience through publication on the WHO Regional Office for Europe Influenza website, on the EuroFlu website, and through peer-reviewed publications.

The World Health Organization (WHO) Regional Office for Europe (WHO/Europe) is one of the six regional offices of the WHO. It serves the WHO European Region that comprises 53 member states (MS), covering a vast and varied geographical region from the Atlantic to Pacific oceans. Approximately 900 million people live in diverse economic, political, and social and conditions, in countries that have built different health systems and approaches to health. WHO/Europe has country offices in 30 countries, in 12 countries of the European Union (EU), and in countries of the Southeastern Europe Health Network (SEEHN [1]) and the newly independent states (NIS).

The objective of the WHO as described in its constitution [2] is the attainment by all peoples of the highest possible level of health. The WHO is the directing and coordinating authority on international health work: in emergencies, including outbreaks of infectious disease, the WHO provides appropriate technical assistance if requested to do so by governments. The WHO's responsibilities in these situations are mandated primarily by the International Health Regulations (IHR, 2005) [3] , and this was tested to the utmost during the 2009 pandemic. The response by the WHO to the 2009 pandemic, as well as the preceding preparedness activities, has been scrutinized extensively during the external review of the IHR [4] . The committee concluded that the IHR helped make the world better prepared to cope with public health emergencies, but that the world is ill prepared to respond to a severe influenza pandemic or to any similarly global, sustained and threatening public health emergency. The WHO was considered to have performed well in many ways, but demonstrated shortcomings in responding to a global public health emergency of protracted duration. The committee found no evidence of malfeasance on the part of the WHO, refuting allegations that WHO recommendations regarding the use of pandemic vaccines were influenced by the pharmaceutical industry.

Although the review was comprehensive, the full extent of the activities conducted in the area of pandemic preparedness and response by the WHO regional and country offices, and how these were coordinated with other (UN) organizations, stakeholders, and WHO collaborating centers, is not captured by the report. Against this backdrop, this article reviews the activities of WHO/Europe in this area from 2005 throughout the 2009 pandemic until the present time. It concludes with a forward look based on the lessons learned.

Influenza is a priority disease in the WHO European region. Activities in the area of influenza are led by the Influenza & Other Respiratory Pathogens program (IRP), supported by programs dealing with vaccine-preventable diseases and immunization, alert and response operations, IHR area coordinators, country emergency preparedness, and the division of health systems and public health. The aims of the IRP are to: F Strengthen surveillance for mild and severe disease caused by influenza across the region and share data to in-form global influenza vaccine strain selection F Use surveillance data to estimate the burden of influenza to prioritize national influenza vaccination and treatment programs F Support pandemic preparedness activities at the national level and the implementation of core capacities required under the IHR F Support the response of MS to outbreaks caused by influenza or other respiratory pathogens Implementation through coordination and collaboration WHO/Europe conducts its work jointly with its country offices and with WHO headquarters. Activities are conducted at the regional level involving all 53 MS, at the subregional level involving countries of the SEEHN or NIS, or with individual countries. These activities include meetings to present new WHO guidance and discuss their implementation, discuss new developments, and exchange good practice and training. MS participants are either formally nominated by the Ministries of Health (MoH) to represent their country or invited in their own right as experts, depending on the activity. In addition, WHO/Europe develops operational guidance (e.g., for the implementation of influenza surveillance and standards for laboratories), and through weekly bulletins and reports it collects, analyzes, and disseminates influenza surveillance data and data related to influenza vaccine policies and uptake that are reported by all 53 the MS. All key documents related to influenza are published in English and Rus- Work with countries is conducted in collaboration with the MoH based on a biennial cooperative agreement (BCA) that covers policy and technical support, including knowledge transfer, assessments, and evaluations. Country offices play a crucial role in the implementation of the BCA through liaison with the MoH as well as other organizations that are supporting programs in the area of health. Depending on the country needs, country offices have national and sometimes international staff. Country work in the area of influenza focuses on countries of the NIS and SEEHN.

As part of the WHO secretariat, WHO/ Europe participated in the intergovernmental meeting that led to the establishment of the Pandemic Influenza Preparedness Framework for the sharing of influenza viruses and access to vaccines and other benefits ("PIP Framework"), bringing together MS, industry, other key stakeholders, and WHO [9] .

Acute public health events in the WHO European region and the response of WHO/Europe 

Between 2005 and 2011, the WHO Regional Office for Europe assisted the member states of the WHO European Region to prepare and respond to outbreaks of avian influenza H5N1, the 2009 pandemic, and to enhance their capacities for the prevention and control of seasonal influenza. It did this through conducting a combination of regional and subregional meetings and trainings, establishing a regional network for influenza surveillance, providing operational guidance for implementing influenza surveillance and strengthening the capacities of National Influenza Centers, and through assistance at the country-level where needed. In all, close to 60 country-missions or country-level activities were conducted. These activities were conducted in close coordination with WHO headquarters, WHO European Region Country Offices, the European Commission, the European Centre for Disease Prevention and Control, and with other partner organizations, and were in line with the implementation of the International Health Regulations (2005) . The results of activities as well as guidance documents were disseminated to a wide audience through publication on the WHO Regional Office for Europe Influenza website, on the EuroFlu website, and through peer-reviewed publications. 

As IHR Regional Contact Point for the European Region, WHO/Europe receives and exchanges information on outbreaks in countries with the IHR National Focal Points, who under IHR 2005 are obliged to notify public health events of potential international concern and to verify in a timely manner events detected by WHO through its surveillance programs. WHO conducts missions to countries to perform a joint risk assess-ment and assist with the investigation and response to an outbreak if formally requested to do so by the MoH. Such requests are channeled through the country offices, who lead the mission supported by WHO/Europe staff. WHO/Europe, with the assistance of headquarters and the Global Outbreak Alert and Response Network (GOARN), mobilizes the necessary experts and other required resources, such as supplies of personal protective equipment, mobile laboratory, or antiviral drugs. Mission teams are multidisciplinary, comprising experts chosen according to the type of outbreak, in infection control and clinical management, epidemiology, laboratory, human and animal public health, communications, social mobilization, and logistics. Their mode of operation is reflected in the mis-sions to Turkey and Azerbaijan in 2006, described below. WHO/Europe, with international partners, supported the governments of Azerbaijan and Turkey in responding to the outbreaks of avian influenza H5N1 in 2006. These followed the first outbreaks of H5N1 in the WHO European region that occurred in poultry in the summer of 2005 in the Russian Federation and Kazakhstan. They were to be followed by multiple outbreaks in poultry and wild birds in a total of 28 WHO European region MS that occurred mainly between 2005 and 2008, after which outbreaks became sporadic as countries controlled the outbreaks among the animal population. The last outbreak in poultry in a WHO/Europe MS was reported to the World Organization for Animal Health (OIE) in March 2012 [11] .

Late 2005/early 2006, amidst widespread outbreaks in poultry, the only human cases to have been reported in Europe to date occurred in Turkey (12 confirmed human cases 4 of which were fatal) [12] . WHO/Europe deployed multidisciplinary teams of experts for several weeks in both countries, who worked with national and local authorities at the epicenter of the outbreaks to investigate the outbreak and detect possible new cases, to provide advice on the clinical management of patients and on infection control measures in health care facilities, surveillance, and laboratory settings, and to support the provision of regular government communications on the outbreak. The mission team leader has an important role, exercising health diplomacy when liaising with the MoH to explain the work being done and when requesting certain actions from the ministry. One potentially sensitive area is the sharing of viruses with the WHOCC: obtaining agreement for their shipment requires knowledge of national regulations and procedures. Clinical specimens and viruses from the outbreaks of avian influenza H5N1 in humans in Turkey and Azerbaijan were shared with the WHOCCRRI, facilitating in-depth analyses that informed further risk assessment of the outbreak and its implications for public health.

A description of the outbreak in Turkey as well as practical lessons that national and international public health agencies The map presents the intensity of influenza activity. Low: no influenza activity or influenza at baseline* level. Medium: level of influenza activity usually seen when influenza virus is circulating in the country based on historical data. High: higher than usual levels of influenza activity compared to historical data. Very high: influenza activity is particularly severe compared to historical data. *Baseline influenza activity is the level in which clinical influenza activity remains throughout the summer and most of the winter and policy makers can use to respond effectively to future outbreaks and an influenza pandemic have been published by the WHO [13] and in peer-reviewed journals [14] .

The mission team deployed to Azerbaijan in March 2006 was assisted by two epidemiologists who had been deployed previously to assist the MoH establish surveillance for human cases of H5N1. Of note is that the H5N1 cases in Azerbaijan are the only human cases of H5N1 reported so far to have become infected after contact with sick or dead wild birds (swans). The details of this outbreak have been published in full cooperation with the MoH [15, 16] . The surveillance system that was established is still functioning today and is being modified with WHO/ Europe support to detect severe cases of respiratory illness caused by influenza, whether seasonal, H5N1, or pandemic. [20] . Through the national focal points, MS provide weekly data to the Eu-roFlu platform from which the bulletin is published in English and Russian. As described above, EU/EEA MS provide data through the ECDC platform, Tessy, to avoid duplication of data provision.

The first EuroFlu bulletin was published in February 2009, which was extremely timely occurring as it did only weeks before the start of the 2009 pandemic. It resulted in almost a doubling of the number of countries reporting data to the WHO throughout the pandemic and increased the geographic coverage dramatically (shown in . Fig. 1 and  . Tab. 2) . The number of visits to the Eu-roFlu website was greater than 1 million in April 2009, and over 2 million at the peak of the winter pandemic influenza activity in Europe in November 2009. A survey performed among EuroFlu bulletin users indicated a high level of satisfaction [21] . Taken together, the above confirms the importance of the regional influenza surveillance network and positions the EuroFlu bulletin as a key WHO/Europe publication that reaches a wide audience. EuroFlu data are also used to develop season overviews and situation analyses [5] .

WHO/Europe, in coordination with ECDC, supports the surveillance network through the organization of joint annual influenza surveillance meetings [22], the development of the "WHO Regional Office for Europe guidance for sentinel influenza surveillance in humans" [23] , and the provision of methodologies for calculating thresholds for influenza activity (currently implemented for 18 MS on EuroFlu [24] ), for analyzing risk factors for severe disease associated with influenza, and for estimating the burden of disease. For estimates of mortality associated with influenza, WHO/Europe works with the European Mortality Monitoring Project (Eu-roMOMO [25] ). WHO/Europe also conducts missions to assist countries with the development of national guidelines for the implementation of sentinel influenza surveillance.

The influenza laboratory network currently includes WHO-recognized NIC in 40 WHO/Europe MS and another ten countries have designated national influenza laboratories. In close collaboration with the WHOCCRRI and the CNRL, WHO/Europe supports these laboratories, especially those that seek to attain WHO recognition, through the provision of guidance and assessment tools [26], training in biosafety and influenza laboratory techniques, and the shipment of infectious substances, logistics support with the shipment of viruses, and provision of proficiency testing programs. This has resulted in improved capacities to perform virus isolation, share viruses with the WHO, and detect novel influenza viruses as part of pandemic early warning.

Taken together, these activities have resulted in tangible improvements to surveillance in the region since 2008. The number of countries with sentinel surveillance systems in the region, including sentinel hospital surveillance for severe acute respiratory infections (SARI), has increased considerably, as has reporting the data to EuroFlu (. Tab. 2) . This, together with the improved capacities of the laboratories, has significantly increased the region's capacity for: (a) monitoring influenza types/subtypes and antigenic/ genetic characteristics of locally circulating influenza viruses, thereby increasing the representativeness of viruses provided for the annual vaccine strain selection process, (b) understanding and determining the timing and spread of influenza viruses, (c) identifying changes in circulating viruses, and (d) responding to potential pandemic viruses. [28] and are currently being revised with input from MS to incorporate lessons learned. All in all, by the time the pandemic was declared by the WHO in June 2009, all 53 MS in the WHO European region had developed a national pandemic plan and were relatively well prepared compared with other regions. However, country assessments and other activities identified a number of gaps, chiefly that national plans were not operational-they described what had to be done but few activities had been (fully) implemented, at national or local level. Examples include strategies for vaccine and antiviral delivery, surge capacity in the healthcare services, routine surveillance for severe disease associated with influenza, and business continuity in essential services.

The world has recently experienced the first influenza pandemic of the twentyfirst century lasting 14 months between June 2009 and August 2010. Although the 2009 pandemic was less severe than the three pandemics of the twentieth century, it caused a wide spectrum of illness [30] and in the USA caused severe disease and death more frequently in the under-60s, compared with seasonal influenza, in persons with underlying conditions, pregnant women, but also healthy individuals [29] . Regarding the community effect of the 2009 influenza pandemic, analysis of EuroFlu data showed it arrived earlier than previous seasons and caused a significantly higher number of outpatient consultations in children [31] .

On 17 April 2009, the United States government alerted the WHO about two children living in adjacent counties in southern California infected with a new influenza H1N1 virus of swine origin that had not been previously detected in pigs or humans. In Mexico, unusual levels of influenza-like illness had been detected in mid-March 2009, and by mid-April atypical cases and clusters of severe pneumonia occurring mainly among previously healthy young adults in different areas of Mexico were observed. On 23 April, samples from Mexico were found to contain genetically identical viruses to the influenza H1N1 viruses from California and this information was immediately reported by the MoH to the WHO [32] . On 25 April, nearly 2 years after the IHR came into force, the 2009 (H1N1) pandemic was the first event to be declared a public health emergency of international concern (PHEIC) by the Director-Gen- eral of WHO, after consultation with an Emergency Committee and in accordance with IHR provisions. These events signaled the emergence of the 2009 pandemic. WHO continued to alert countries to the situation by the declaration of phases describing the global spread of the virus [33] . Phase 6 is the pandemic phase, declared when it is considered inevitable that the new virus has the potential to cause epidemics in every country. Summarized in . Tab. 3 is a timeline showing the declaration by the WHO of the phases and the main recommendations provided by the WHO (a full timeline of events has been published by the WHO [34]). Recommendations were based on the spread of the virus but also on severity and impact from information received from early-affected countries.

The WHO mounted a full-blown response to the pandemic, which has been described in detail in the external review of the IHR [4] . WHO/Europe, along with the other five regional offices and country offices, played a crucial role in this response. The response mounted by WHO/ Europe was essentially a continuation of the activities being conducted since 2005, but with additional manpower and increased working hours. By 25 April 2009, WHO/Europe had activated its emergency steering committee and established a Pandemic Response Team (PRT). Up until July 2009, the PRT consisted of about 25 technical staff available 24/7 on a rotational basis and held daily meetings. During the remainder of the pandemic, the PRT core team consisted of about 15 technical staff, with additional staff as needed. The responsibilities of the PRT were as follows: F Coordinate activities with WHO headquarters, country offices, and key partners such as the EC and ECDC (mainly through the early warning and response system for EU MS, EWRS) F Collect, analyze, and present information obtained through IHR channels, EuroFlu, public national bulletins, and other sources, and assess the situation together with WHO headquarters; disseminate information on the severity and impact of the pandemic in the region through the WHO/Eu-rope website and the influenza surveillance network F Publish the weekly EuroFlu bulletin throughout the pandemic, also in the summer months of 2009 and 2010, in English and Russian F Provide information and guidance to MS and to country offices F Provide input to global efforts to mobilize resources for low-resource countries in the region

The PRT also provided operational support to MS in the following areas: 

The ability to respond to a complex health emergency such as an influenza pandemic requires a continuous process of pandemic preparedness planning, exercising plans, and incorporating lessons learned into plans. For the first time in history, countries implemented a pandemic response that drew on pandemic plans and activities undertaken in the few preceding years, and for the first time in history a pandemic vaccine was available during the first wave of the pandemic. By January 2010, most countries in the WHO European region had experienced an epidemic caused by the new virus and countries and international organizations alike started to evaluate their response to the pandemic and to take the necessary steps in the transition to seasonal influenza. In light of a main conclusion of the IHR review, that"the world is ill-prepared to respond to a severe influenza pandemic or to any similarly global, sustained and threatening public-health emergency, " these are critical steps.

In the WHO European region, from evaluations performed by individual countries at the EU and regional level, the following key lessons learned were identified: F The process of pandemic planning with broad stakeholder involvement and the pandemic plans themselves were useful. However, national pandemic plans had been insufficiently implemented at the subnational and local level. F Global phases describing the spread of the pandemic virus were not useful as triggers for response measures at the national level and local level. F A rapid assessment of severity and impact was hampered by a lack of standardized protocols and indicators, by a lack of routine surveillance for severe disease associated with influenza, and by tenuous links between public health authorities and health service providers. F The deployment of, and risk communication activities related to, pandemic vaccine were considered extremely difficult, with generally low uptake in risk groups, some countries having a surplus of vaccine and others receiving vaccine only after the epidemic, particularly those countries that received donations through the WHO. F Front-line responders-family physicians and hospital healthcare workers-had been insufficiently included in the pandemic planning process and were hard to reach during the pandemic.

The evaluation performed by WHO/Europe together with the WHOCCPIR in seven countries focused on the degree to which pandemic preparedness plans and associated activities proved useful during the 2009 pandemic. The goal was to provide recommendations for pandemic plan revisions and to identify areas of planning that require further strengthening. Using a systematic approach, more than 200 individuals representing national, regional, and local responders in seven MS were interviewed. In addition to the lessons learned summarized above, the evaluation revealed six major themes essential for effective pandemic preparedness: communication; coordination; capacity; adaptability/flexibility; leadership; and mutual support. With respect to the theme of sup-port, the WHO pandemic planning guidance and the guidelines produced during the pandemic were considered extremely important. With respect to capacity, preparedness activities including training, inter-country exchange of expertise and experience, assessments and strengthening in specific fields such as surveillance and risk communication had a positive impact on the ability of MS to respond to the pandemic [10, 37].

Based on the experience of the past 7 years and feedback from MS, it can be concluded that the activities conducted by WHO/Europe in the area of influenza and pandemic preparedness have been useful and have filled a number of gaps. The level of pandemic preparedness and the capacity for influenza surveillance in the region, both epidemiological and virological along with early warning, has increased. These capacities will benefit public health in a broader context, as influenza surveillance can detect other respiratory infections; the capacities built as part of pandemic preparedness will support preparedness for other infectious diseases as well as the implementation of IHR core capacities. WHO/Europe was well positioned to guide and assist its country offices in the implementation of activities, and has coordinated activities with WHO headquarters as well as regional and global partners. This is commensurate with the goals of the WHO Reform [38] regarding health security, whereby the WHO will provide surveillance, alert-verificationassessment support, and event management mechanisms, along with direct operational support on the ground when needed, as well as assist countries to build their institutional capacities. However, a number of gaps were also identified, and to address these in times of shrinking resources, in 2011 the IRP program performed a situation analysis and developed a 5-year strategy. Based on this strategy, WHO/Europe will continue to assist MS efforts to strengthen surveillance for severe disease due to influenza and it will focus more on assist-ing countries to determine the burden of disease and risk factors for severe disease so as to inform seasonal influenza vaccination programs. Therefore, in collaboration with the VENICE project and ECDC [39] , in 2011 the first regional survey of seasonal influenza vaccine policies and uptake in the 53 MS was conducted. Currently, only one country in the region meets the 2005 WHO target of 75% vaccine uptake in the elderly, and few countries have programs to vaccinate other risk groups, such as persons with underlying conditions and pregnant women, or systems in place to monitor uptake (unpublished data). WHO/Europe will continue to conduct regular surveys to target assistance to countries in this area. WHO/Europe will continue to assist national influenza laboratories in the ten countries that currently are not recognized by WHO to obtain WHO recognition, to measure the impact of seasonal influenza in the region, as was done for the pandemic [31] , and to respond to requests for assistance in periods of unusual influenza activity. In 2011, during the first post-pandemic season that was dominated by the pandemic (H1N1) virus and which caused strains on critical care services in a number of countries, WHO/Europe together with the EC and ECDC organized regional teleconferences for clinicians from the first affected countries to share their experience in the management of severe cases with clinicians from countries that had not yet been affected [40]. WHO/Europe will continue to support MS efforts to revise their pandemic plans, through inter-country workshops jointly with ECDC similar to those organized in 2011 [41], through sharing of good practice, and through assistance to individual countries. This work will be integrated with efforts to enhance general preparedness for public health emergencies as well as the implementation of IHR core capacities. WHO/Europe together with MS experts and ECDC is currently revising the European pandemic indicators [27] that will form a new European guidance for pandemic preparedness. WHO/ Europe, as WHO secretariat, will support the implementation of the PIP Framework [9] .

Influenza, whether seasonal, avian, or pandemic, will continue to feature on the public health agenda, and to take us by surprise: the 2009 pandemic was first detected not in Southeast Asia, the epicenter of the H5N1 outbreak, but in the Americas. It was milder than previous pandemics but yet was difficult to manage for many countries. WHO/Europe will therefore continue to work in this area, based on the needs of countries as well as the requirements for global surveillance and response.

Corresponding address C.S. Brown WHO Regional Office for Europe Scherfigsvej 8, 2100 Copenhagen Denmark cbr@euro.who.int

Report of the Review Committee on the Functioning of the International Health Regulations (2005) in relation to Pandemic (H1N1)

WHO global influenza surveillance platforms FluNet

Recommendations for good practice in pandemic preparedness: identified through evaluation of the response to pandemic (H1N1)

Cumulative number of confirmed human cases of avian influenza A(H5N1) reported to WHO

Avian Influenza A (H5N1) Infection in Eastern

Two clusters of human infection with influenza A/H5N1 virus in the Republic of Azerbaijan

Expansion of the global measles and rubella laboratory network 2005-09

Joint WHO Regional Office for Europe/ECDC Influenza Surveillance Meeting

WHO Regional Office for Europe guidance for sentinel influenza surveillance in humans

Influenza surveillance in Europe: Establishing epidemic thresholds by the Moving Epidemic Method (accepted for publication)

How to become a WHO-recognized National Influenza Centre: Guidance on the process for influenza laboratories in the WHO European Region

Developing pandemic preparedness in Europe in the 21st century: experience, evolution and next steps

Joint European Pandemic Preparedness Self-Assessment Indicators

Estimating the Burden of 2009 Pandemic Influenza A (H1N1) in the United States

Risk factors for hospitalisation and poor outcome with pandemic A/H1N1 influenza: United Kingdom first wave

The community impact of the 2009 influenza pandemic in the WHO European Region: a comparison with historical seasonal data from 28 countries

Current WHO phase of pandemic alert for Pandemic (H1N1)

Monitoring and Information Centre for Humanitarian Aid and Civil Response of the European Commission

Did pandemic preparedness aid the response to pandemic (H1N1) 2009? A qualitative analysis in seven countries within the WHO European Region. In press for Journal of Infection and Public Health 38

Vaccine European New Collaborative Integrated Effort (VENICE)

Acknowledgments. The author gratefully acknowledges Ana Paula Coutinho, of the Alert and Response Operations Programme, WHO/Europe, for reviewing this manuscript. The author further gratefully acknowledges all of the following without whose contribution the work described in this paper would not have been possible: the 53 MS of the WHO European Region and the members of the WHO European Influenza Surveillance Network, ECDC (particularly Angus Nicoll) and the US CDC, the WHOCCRRI and WHOCCPIR, the members of the SEEHN for communicable diseases, GOARN partners and MS experts who participated in missions, assessments and training. Last but not least, I acknowledge colleagues at WHO/Europe, the Country Offices, and WHO headquarters. This work was supported by funding from CDC, Atlanta, US, Asian Development Bank, USAID, DG-SANCO of the European Commission, and the governments of Belgium, Canada, Czech Republic, France, The Netherlands, and United Kingdom.

The corresponding author states that there are no conflicts of interest.