key: cord-0006575-sjmu0u3t authors: Pečavar, B.; Nadrah, K.; Papst, L.; Čeč, V.; Kotar, T.; Matičič, M.; Meglič-Volkar, J.; Vidmar, L.; Beović, B. title: Clinical characteristics of adult patients with influenza-like illness hospitalized in general ward during Influenza A H1N1 pandemic 2009/2010 date: 2011-09-22 journal: Wien Klin Wochenschr DOI: 10.1007/s00508-011-0054-4 sha: 030c7a16194aaa01e25bd6a816fa67348dcccc06 doc_id: 6575 cord_uid: sjmu0u3t OBJECTIVE: To investigate clinical and laboratory features of patients with Influenza A H1N1 virus infection hospitalized during 2009/2010 pandemic. METHODS: Prospective observational study comparing clinical and laboratory characteristics of Influenza A H1N1 positive and negative patients with influenza-like illness (ILI). RESULTS: From October 21, 2009 to February 14, 2010 196 ILI patients were admitted, of which 66 tested positive for Influenza A H1N1. The patients with H1N1 infection were younger (43 years vs. 65 years; P < 0.01), more patients were pregnant (P < 0.01), had allergies (P < 0.05) or, asthma (P < 0.01). H1N1 positive patients were more often febrile (91% vs. 72.9%; P < 0.01) and had a higher prevalence of headache (31.8% vs. 18.5%; P < 0.05). Lower values of C-reactive protein (88 pg/dl vs. 126 pg/dl; P < 0.01), procalcitonine (0.42 µg/l vs. 3.98 µg/l; P < 0.05), leukocyte count (7.4*10(9)/l vs. 11.7*10(9)/l; P < 0.01) and higher values of troponin (0.162 µ/l vs. 0.146 µg/l; P < 0.01) were found in H1N1 positive patients. More bacterial infections were found in H1N1 negative group (68.8% vs. 89.2%; P < 0.05). CONCLUSIONS: In this study patients infected with Influenza A H1N1 differed from H1N1 negative ILI patients in several clinical and laboratory characteristics. The same was observed also by other investigators. The results of the study suggest some other specific features, such as a higher incidence of headache and higher values of troponin in Influenza A H1N1 infected patients. Th e 2009/2010 infl uenza pandemic put a heavy burden on society and the healthcare system. In Slovenia the fi rst case of infection with triple-reassortant swine Infl uenza A H1N1 virus was confi rmed on June 19, 2009 in a patient arriving from New York who had infl uenza-like illness (ILI) [1] . After that the virus spread throughout the country, with the total number of confi rmed cases 1,152 by week 23, 2010 . Th e last case was confi rmed in week 6, 2010. Nineteen patients died by week 23, 2010 [2, 3] . Th e novel pandemic infl uenza is reported to be a mild self-limiting disease similar to seasonal infl uenza, with the highest incidence rate in younger population and overall fatality less than 0.5% (WHO). However, the disease can have a more destructive course with the possible development of diff use viral pneumonitis, associated with hypoxemia, ARDS, shock and renal failure. Next to the diff erence in aff ected age group some researchers have encountered clinical features that may defi ne the novel infl uenza as a new clinical entity, e.g. higher risk for pregnant women, more obstetric problems, strong association with obesity, more gastrointestinal symptoms [4] [5] [6] [7] . Patients with ILI admitted to adult general ward of the hospital were prospectively studied and their clinical characteristics and the course of illness were evaluated. Patients with ILI admitted to adult general ward of the Department of Infectious Diseases, University Medical Centre Ljubljana, Slovenia between October 21, 2009 and February 14, 2010 were prospectively included in the study. Th ose admitted directly to the intensive care unit (ICU) or pediatric ward were excluded from the study. Data were collected using a standardized form. A case of ILI was defi ned as body temperature ≥37.5°C with symptoms of upper or lower respiratory tract disease (e.g. sore throat, cough, rhinorrhea, nasal congestion). Patients with suspected bacterial infection of the lower respiratory tract during epidemics were considered, until proven otherwise to have co-infection with Infl uenza A H1N1 virus and they were also included in the study. Confi rmed Infl uenza A H1N1 infection was defi ned as ILI and positive real-time reverse transcriptase polymerase chain reaction (rRT-PCR) specifi c for Infl uenza A H1N1 virus. In few cases, positive with rRT-PCR for Infl uenza A, subtype could not be determined. As no other Infl uenza A virus was present at that time in the region [8], these cases were considered confi rmed for further analysis. If rRT-PCR was negative, the diagnosis of Infl uenza A H1N1 infection was excluded and the case was classifi ed as negative. A case of bacterial infection was defi ned either as confi rmed or probable. Probable case was defi ned by the following criteria: C-reactive protein (CRP) ≥ 100 pg/dl or leukocyte count >10.0*10 9 /l or procalcitonine (PCT) > 0.5 μg/l or antibiotic therapy on admission. Confi rmed bacterial infection was defi ned by detection of bacteria using standard microbiological tests, in the absence of an alternative explanation and in addition to the above mentioned laboratory parameters for bacterial infection. Th e study was approved by the National Medical Ethics Committee. Upon admission laboratory tests including whole blood count, CRP, PCT, hepatic enzymes, lactate dehydrogenase (LDH), creatine kinase, and troponin were performed. All cases of ILI had nasopharyngeal swab taken and were tested for Infl uenza A H1N1 by rRT-PCR. Samples for detection of bacterial infection were taken when appropriate. Continuous variables were summarized as means ± standard deviation (SD) or medians with interquartile ranges (IQR). For categorical variables, the percentage of patients in each category was calculated. Clinical characteristics were compared between groups of patients using the Mann-Whitney U test and independent-samples T test. P values were considered signifi cant if <0.05 (IBM SPSS statistics, version 18; SPSS). Nine ILI patients died, 2 were Infl uenza A H1N1 positive: a 54-year-old woman with hypothyroidism and no other preexisting condition and 57-year-old man with decompensated alcoholic liver disease. Th e mortality rate of H1N1 positive and negative group did not show a significant diff erence (0.03% vs. 0.046%; P ≥ 0.05). Th irteen patients (7 H1N1 positive, 6 negative) were transferred to ICU; of them, 1 H1N1 positive and 2 negative patients died (P ≥ 0.05). Need for mechanical ventilation due to inability to maintain optimal blood oxygenation with addition of supplementary oxygen alone and secondary bacterial infection with sepsis and hemodinamic instability were the two dominant reasons for the transfer to ICU. Th e following conditions were documented in H1N1 positive patients transferred to ICU: pregnancy (1), decompensated alcoholic liver disease (1), COPD (1), cardiovascular diseases (2), hypothyroidism (1), diabetes (1) and kidney disease (1). Mean age of patients admitted to ICU was 56.1 vs. 48.6 years for those not admitted to ICU (P ≥ 0.05). Six pregnant women with ILI were admitted, infection with Infl uenza A H1N1 virus was confi rmed in 5. One of them had a miscarriage; the other four did not have any obstetric problems during their hospital stay. Demographic characteristics of patients are presented in Table 1 , medical history and clinical presentation in Table 2 , and signs and symptoms together with laboratory tests' in Table 3 . Th e criteria for probable bacterial infection were met by 44/64 (68.8%) Infl uenza A H1N1 positive and 116/130 (89.2%) negative patients; P < 0.05. Bacteria associated with pneumonia were isolated in 5/63 (7.9%) Infl uenza A H1N1 positive and 19/128 (14.8 %) negative patients (P ≥ 0.05). Streptococcus pneumoniae was the most often detected bacteria (40% vs. 47.3%) in both groups, followed by Haemophilus infl uenzae (40% vs. 5.3%), Escherichia coli (20% vs. 0%), Staphylococcus aureus (0% vs. 15.8%), Klebsiella pneumoniae (0% vs. 10.5%), Mycoplasma pneumoniae (0% vs. 10.5%), Legionella pneumophila (0% vs. 5.3%) and Streptococcus pyogenes (0% vs. 5.3%). All ILI patients received oseltamivir (75 mg bid) at admission; if rRT-PCR was negative, treatment was stopped. Th e average duration of treatment was 4.6 ± 1.1 days (median 5; range from 0 to 7 days) for H1N1 positive patients and 1.2 ± 1.6 days (median 1; range from 0 to 16) for negative patients. Five patients received the fi rst dose on the second day and 4 on the third day after admission. Th e treatment of patients in the study is presented in Table 4 . During Infl uenza A H1N1 pandemics in 2009/2010 196, adult ILI patients were admitted to our ward; 66 suff ered from Infl uenza A H1N1 infection. Admission rate for the whole country cannot be calculated because the cumulative number of all admitted patients in Slovenia is not available. Mortality rate (0.03%) for hospitalized patients, with confi rmed Infl uenza A H1N1 infection is comparable to data available from WHO and does not change with H1N1 negative patients [4] . Since patients admitted directly to ICU are not included in the study, the overall mortality rate is probably underestimated, as other sources state that mortality rate of patients in ICU is signifi cantly higher (14-36%) [4] . Th is mortality rate is in accordance with mortality rate of H1N1 patients transferred from normal ward to ICU. NS-non-significant. Most (66.7%) H1N1 positive patients were admitted between week 47 and 51; this is slightly later than the peak of confi rmed cases in Slovenia and other countries of EURO region of WHO [9] . On average, H1N1 positive patients had shorter hospital stay, which indicates a relatively mild disease and quick recuperation. Longer hospital stay of H1N1 positive patients with probable bacterial infection is ex-pected, since bacterial infection is a known complication of infl uenza. Sexes were equally distributed among H1N1 positive and negative patients (50% vs. 51.5%). Mean age was lower in H1N1 positive patients (43 years vs. 65 years); this feature was also noticed by other researchers [4, 6, 10, 11] . Younger age is presumed to be a risk factor, as young Abnormalities on chest radiograph -no./no. of all patients with available data (%) 7 29/57 (50.9) 70/116 (60.3) NS 1 blood oxygen saturation of less than 91% measured by pulse oxymeter; 2 most frequent abnormal breath sounds were inspiratory crackles (49.2%; 37.7% vs. 54.8%) and expiratory wheezing (5.9%; 9.8% vs. 4%), combination of both was present in 11.4% (11.5% vs. 11.3%); 3 alkaline phospathasis; 4 aspartat aminotransferase; 5 alanine aminotransferase; 6 γ-glutamyltransferase; 7 the abnormalities were most often located in two or less lobes (91.3%) and pleural effusion was found in 7.1%; NS -non-significant. people do not have cross-protective antibodies derived from lifelong exposure to antigenically related infl uenza viruses [4, 12] . Contributing factors are also a higher degree of close social contacts with a wider variety of people in younger population, higher likeliness for travel to foreign countries and visiting areas with high concentration of people (e.g. hotels, airports, bars, nightclubs, malls). Our H1N1 positive patients were older in comparison to other studies; however, mean age was in agreement with fi ndings of WHO [4, 11, [13] [14] [15] [16] . Th e reason for this may be the exclusion of pediatric patients. Fever and cough were the most frequent symptoms in ILI patients. Fever was reported more often by H1N1 positive patients (91% vs. 72.9%; P < 0.01), with similar numbers found in literature, 87.3-95.9% [13, 14, 18, 19] . Incidence of headache was also higher in H1N1 positive group (31.8% vs. 18.5%; P < 0.05). Other symptoms (cough, myalgia, arthragia, chills, dispnoa, pleuritic pain, gastrointestinal symptoms) did not diff er between the two observed groups of ILI patients. Body temperature measured upon admission was higher in H1N1 positive patients (37.5°C vs. 37.2°C; P < 0.05), and was the only sign that showed diff erences between the two groups. Th e number of pregnant women among ILI patients in the study (6.3% of all women) was low, however, most of them (5/6) belonged to H1N1 positive group. Association between H1N1 infection and pregnancy was also noticed by WHO [4] . One H1N1 positive pregnant woman in the study had a medically unexplained miscarriage on the second day after admission. Complications of pregnancy related to H1N1 infection were described by other authors as well [17, 18] . History of drug allergies or asthma was more common in H1N1 positive patients; the same is reported by other researchers [4, 19] . Other chronic pulmonary diseases (e.g. COPD) were equally distributed between the two groups. Cardiovascular disorders were found mainly in H1N1 negative patients. As the incidence of cardiovascular diseases increases with age, the fi nding of this study may be related to the higher age of H1N1 negative patients. Both groups had elevated levels of CRP and PCT; however, the levels were higher in H1N1 negative group. Th is is probably related to bacterial infection which was, according to the criteria in the study, more frequent in H1N1 negative patients. Mean white blood cell count was lower in H1N1 positive patients and signifi cantly more H1N1 positive patients had leucopenia, a feature also observed in the Chinese study (23.4% in Slovenian and 21.4% in Chinese patients) [15] . Troponin level was higher in H1N1 positive patients; the values were in the so-called grey-zone and cannot be interpreted as a reliable marker of higher viral tropism for myocardial cells. In literature two studies preformed prior to Infl uenza A H1N1 pandemic on 30 and 152 patients with Infl uenza infection did not fi nd any patients with an increased troponin level [19, 20] . Th e study is limited by the relatively small group of patients and missing data in spite of the prospective design of the study. Nevertheless the data collected allow some statistically signifi cant conclusions and some of the fi ndings add to the knowledge on clinical presentation of Infl uenza A H1N1 infection. Infl uenza A H1N1 is a disease with some characteristics diff erent for Infl uenza A from seasons before and these were also observed in the study (younger age of aff ected patients, pregnancy as a risk factor). Most often reported symptoms and signs are those found also in patients with Infl uenza A. Laboratory tests routinely done did not disclose any new insights; however, higher troponin levels were observed in our patients, a feature not reported before by other researchers. Further investigation of this feature could provide new data on the Infl uenza A H1N1. None. 2 patients did not receive therapy because of a less than 24 hour stay and 1 patient was already receiving oseltamivir prior to admission; NS -nonsignificant. Prvi primer okužbe z virusom nove gripe v Sloveniji. 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