Showing papers by "Timothy M. Uyeki published in 2008"

Update on Avian Influenza A (H5N1) Virus Infection in Humans Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus

Abstract: The members of the writing committee (Abdel-Nasser Abdel-Ghafar, M.D., Tawee Chotpitayasunondh, M.D., Zhancheng Gao, M.D., Ph.D., Frederick G. Hayden, M.D., Nguyen Duc Hien, M.D., Ph.D., Menno D. de Jong, M.D., Ph.D., Azim Naghdaliyev, M.D., J.S. Malik Peiris, M.D., Nahoko Shindo, M.D., Santoso Soeroso, M.D., and Timothy M. Uyeki, M.D.) assume responsibility for the overall content and integrity of the article. Address reprint requests to Dr. Hayden at the Global Influenza Program, Department of Epidemic and Pandemic Alert and Response, World Health Organization, 20 Ave. Appia, Ch-1211, Geneva 27, Switzerland, or at haydenf@who.int.

Influenza-Associated Pediatric Mortality in the United States: Increase of Staphylococcus aureus Coinfection

Abstract: OBJECTIVE. Pediatric influenza-associated death became a nationally notifiable condition in the United States during 2004. We describe influenza-associated pediatric mortality from 2004 to 2007, including an increase of Staphylococcus aureus coinfections. METHODS. Influenza-associated pediatric death is defined as a death of a child who is younger than 18 years and has laboratory-confirmed influenza. State and local health departments report to the Centers for Disease Control and Prevention demographic, clinical, and laboratory data on influenza-associated pediatric deaths. RESULTS. During the 2004–2007 influenza seasons, 166 influenza-associated pediatric deaths were reported (n = 47, 46, and 73, respectively). Median age of the children was 5 years. Children often progressed rapidly to death; 45% died within 72 hours of onset, including 43% who died at home or in an emergency department. Of 90 children who were recommended for influenza vaccination, only 5 (6%) were fully vaccinated. Reports of bacterial coinfection increased substantially from 2004–2005 to 2006–2007 (6%, 15%, and 34%, respectively). S aureus was isolated from a sterile site or endotracheal tube culture in 1 case in 2004–2005, 3 cases in 2005–2006, and 22 cases in 2006–2007; 64% were methicillin-resistant S aureus. Children with S aureus coinfection were significantly older and more likely to have pneumonia and acute respiratory distress syndrome than those who were not coinfected. CONCLUSIONS. Influenza-associated pediatric mortality is rare, but the proportion of S aureus coinfection identified increased fivefold over the past 3 seasons. Research is needed to identify risk factors for influenza coinfection with invasive bacteria and to determine the impact of influenza vaccination and antiviral agents in preventing pediatric mortality.

Preliminary Findings of a Randomized Trial of Non-Pharmaceutical Interventions to Prevent Influenza Transmission in Households

Abstract: Background There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza. We implemented a study of the feasibility and efficacy of face masks and hand hygiene to reduce influenza transmission among Hong Kong household members. Methodology/Principal Findings We conducted a cluster randomized controlled trial of households (composed of at least 3 members) where an index subject presented with influenza-like-illness of <48 hours duration. After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test, the household of the index subject was randomized to 1) control or 2) surgical face masks or 3) hand hygiene. Households were visited within 36 hours, and 3, 6 and 9 days later. Nose and throat swabs were collected from index subjects and all household contacts at each home visit and tested by viral culture. The primary outcome measure was laboratory culture confirmed influenza in a household contact; the secondary outcome was clinically diagnosed influenza (by self-reported symptoms). We randomized 198 households and completed follow up home visits in 128; the index cases in 122 of those households had laboratory-confirmed influenza. There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6%. Clinical secondary attack ratios varied from 5% to 18% depending on case definitions. The laboratory-based or clinical secondary attack ratios did not significantly differ across the intervention arms. Adherence to interventions was variable. Conclusions/Significance The secondary attack ratios were lower than anticipated, and lower than reported in other countries, perhaps due to differing patterns of susceptibility, lack of significant antigenic drift in circulating influenza virus strains recently, and/or issues related to the symptomatic recruitment design. Lessons learnt from this pilot have informed changes for the main study in 2008. Trial Registration ClinicalTrials.gov NCT00425893 HKClinicalTrials.com HKCTR-365

Clinical Characteristics of 26 Human Cases of Highly Pathogenic Avian Influenza A (H5N1) Virus Infection in China

Abstract: Background: While human cases of highly pathogenic avian influenza A (H5N1) virus infection continue to increase globally, available clinical data on H5N1 cases are limited. We conducted a retrospective study of 26 confirmed human H5N1 cases identified through surveillance in China from October 2005 through April 2008. Methodology/Principal Findings: Data were collected from hospital medical records of H5N1 cases and analyzed. The median age was 29 years (range 6–62) and 58% were female. Many H5N1 cases reported fever (92%) and cough (58%) at illness onset, and had lower respiratory findings of tachypnea and dyspnea at admission. All cases progressed rapidly to bilateral pneumonia. Clinical complications included acute respiratory distress syndrome (ARDS, 81%), cardiac failure (50%), elevated aminotransaminases (43%), and renal dysfunction (17%). Fatal cases had a lower median nadir platelet count (64.5610 9 cells/L vs 93.0610 9 cells/L, p=0.02), higher median peak lactic dehydrogenase (LDH) level (1982.5 U/L vs 1230.0 U/L, p=0.001), higher percentage of ARDS (94% [n=16] vs 56% [n=5], p=0.034) and more frequent cardiac failure (71% [n=12] vs 11% [n=1], p=0.011) than nonfatal cases. A higher proportion of patients who received antiviral drugs survived compared to untreated (67% [8/12] vs 7% [1/14], p=0.003). Conclusions/Significance: The clinical course of Chinese H5N1 cases is characterized by fever and cough initially, with rapid progression to lower respiratory disease. Decreased platelet count, elevated LDH level, ARDS and cardiac failure were associated with fatal outcomes. Clinical management of H5N1 cases should be standardized in China to include early antiviral treatment for suspected H5N1 cases.

Human case of swine influenza A (H1N1) triple reassortant virus infection, Wisconsin.

Abstract: Zoonotic infections with swine influenza A viruses are reported sporadically. Triple reassortant swine influenza viruses have been isolated from pigs in the United States since 1998. We report a human case of upper respiratory illness associated with swine influenza A (H1N1) triple reassortant virus infection that occurred during 2005 following exposure to freshly killed pigs.

The burden of influenza in East and South-East Asia: a review of the English language literature

Abstract: While human infections with avian influenza A (H5NI) viruses in Asia have prompted concerns about an influenza pandemic, the burden of human influenza in East and Southeast Asia has received far less attention. We conducted a review of English language articles on influenza in 18 countries in East and Southeast Asia published from 1980 to 2006 that were indexed on PubMed. Articles that described human influenza-associated illnesses among outpatients or hospitalized patients, influenza-associated deaths, or influenza-associated socioeconomic costs were reviewed. We found 35 articles from 9 countries that met criteria for inclusion in the review. The quality of articles varied substantially. Significant heterogeneity was noted in case definitions, sampling schemes and laboratory methods. Early studies relied on cell culture, had difficulties with specimen collection and handling, and reported a low burden of disease. The recent addition of PCR testing has greatly improved the proportion of respiratory illnesses diagnosed with influenza. These more recent studies reported that 11-26% of outpatient febrile illness and 6-14% of hospitalized pneumonia cases had laboratory-confirmed influenza infection. The influenza disease burden literature from East and Southeast Asia is limited but expanding. Recent studies using improved laboratory testing methods and indirect statistical approaches report a substantial burden of disease, similar to that of Europe and North America. Current increased international focus on influenza, coupled with unprecedented funding for surveillance and research, provide a unique opportunity to more comprehensively describe the burden of human influenza in the region.

Global epidemiology of human infections with highly pathogenic avian influenza A (H5N1) viruses

Abstract: From 1997 through 2007, human infections with highly pathogenic avian influenza A (H5N1) viruses resulted in rare, sporadic, severe and fatal cases among persons in 14 countries in Asia, the Middle East, Eastern Europe and Africa. Of 369 reported human H5N1 cases that occurred from 1997 through 2007, overall mortality was 60%. Ten antigenically and genetically distinct clades of H5N1 viruses have been identified to date, and strains from four clades have infected humans. Surveillance has focused upon hospitalized cases of febrile acute lower respiratory tract disease among persons with exposure to sick or dead poultry, or to a human H5N1 case. Detection of H5N1 virus infection is based primarily upon collection of respiratory tract specimens from suspected cases for RT-PCR testing. Most human H5N1 cases were previously healthy children or young adults who developed severe acute pulmonary or multi-organ disease following direct or close contact with sick or dead H5N1 virus-infected poultry. Occasional clusters of H5N1 cases have occurred, predominantly among blood-related family members. Limited human-to-human H5N1 virus transmission has been reported or could not be excluded in some clusters. The frequency of asymptomatic or clinically mild H5N1 virus infection is unknown, but limited investigations suggest that such infections have been rare since 2003. There is no evidence of sustained human-to-human H5N1 virus spread. However, H5N1 viruses continue to circulate and evolve among poultry in many countries, and there are many unanswered questions about human infection with H5N1 viruses. Thus, the pandemic influenza threat presented by H5N1 viruses persists.

Incubation period for human cases of avian influenza A (H5N1) infection, China.

Abstract: To the Editor: Since 1997, more than 400 human cases of highly pathogenic influenza A virus (H5N1) infection have been reported worldwide, including 30 from mainland China. Ascertainment of the incubation period for influenza virus (H5N1) is important to define exposure periods for surveillance of patients with suspected influenza virus (H5N1) infection. Limited data on the incubation period suggest that illness onset occurs <7 days after the last exposure to sick or dead poultry (1–4). For clusters in which limited human-to-human virus transmission likely occurred, the incubation period appeared to be 3–5 days (5–7) but was estimated to be 8–9 days in 1 cluster (5). In China, exposure to sick or dead poultry in rural areas and visiting a live poultry market in urban areas were identified as sources of influenza A virus (H5N1) exposures (8), but the incubation period after such exposures has not been well described. We conducted a retrospective descriptive study of 24 of 30 influenza virus (H5N1) cases in China to estimate and compare incubation periods for different exposure settings, including case-patients exposed only to sick or dead poultry versus those exposed only to a wet poultry market, where small animals and poultry may be purchased live or slaughtered (www.searo.who.int/en/Section23/Section1001/Section1110_11528.htm). Exposures may be direct (e.g., touching poultry) or indirect (e.g., no physical contact, but in close proximity to poultry, poultry products, or poultry feces). We excluded 6 cases, including 2 with unavailable epidemiologic data, 1 without an identified exposure source, 2 in a cluster with limited person-to-person transmission (6), and 1 in which the patient was exposed to both a wet poultry market and to sick or dead poultry. Epidemiologic data were collected through patients and family interviews and a review of case-patients’ medical records. The incubation period was defined as the time from exposure to symptom onset. The maximum time from first exposure to illness onset was limited to 14 days for biological plausibility. For case-patients with exposures on multiple days, we calculated each case-patient’s median incubation period and then calculated the overall median and range of the distribution of these median incubation periods. Similarly, the minimum and maximum incubation periods for case-patients with exposures on multiple days was estimated by using the last or first known exposure day, respectively. The overall incubation period among these case-patients was estimated by determining the median of the distribution of case-patients’ median incubation periods. Incubation periods were compared by using the Wilcoxon rank-sum test. All statistical tests were 2-sided with a significance level of α = 0.05. Of the 24 case-patients, 16 (67%) had exposure to sick or dead poultry only (median age = 25 years [range 6–44]; 25% male; 100% lived in rural areas). Eight (33%) had visited a wet poultry market only (median age = 30 years [range 16–41]; 63% male; 88% [7/8] lived in urban areas) (Table). For case-patients with >2 exposure days (n = 18), and for case-patients with a single exposure day (n = 6), the overall median incubation period was longer for those who had visited a wet poultry market than for those who were exposed to sick or dead poultry, but the difference was not significant. When data for single and multiple exposure days were combined, the overall median incubation period for case-patients exposed to a wet poultry market (n = 8) was significantly longer than for case-patients (n = 16) exposed to sick or dead poultry (7 days [range 3.5–9] vs. 4.3 days [range 2–9]; p = 0.045). Table Estimated incubation period of 24 human cases of infection with avian influenza A virus (H5N1), China* Our findings are subject to limitations. Proxies for deceased case-patients may not have known all of the case-patient’s exposures. Surviving case-patients may not have recalled or identified all exposures that occurred, including environmental exposures. It was impossible to ascertain when infection occurred for case-patients with multiple days of exposures. Our limited data did not permit the use of other methods such as survival analysis to better define incubation periods. We did not quantify exposure duration and could not determine whether repeated exposures (dose-response) or a threshold of exposure to influenza virus (H5N1) exists to initiate infection of the respiratory tract. Laboratory testing was not performed to confirm that the exposure sources contained influenza virus (H5N1) or to quantify exposures. Despite exposures of many persons in China to sick or dead poultry or to wet poultry markets, human influenza A (H5N1) disease remains very rare. Our findings suggest that the incubation period may be longer after exposure to a wet poultry market than after exposure to sick or dead poultry, and, therefore, a longer incubation period than the 7 days that is used widely (4,9) could be considered for surveillance purposes. However, because of the small number of influenza virus (H5N1) case-patients, our study was too underpowered to draw any firm conclusions; results should be interpreted cautiously. In a study of influenza virus (H5N1) cases in Vietnam, 5 case-patients did not have any identified exposure <7 days of illness onset (10). In China, the exposure period for surveillance of suspected influenza virus (H5N1) cases now includes exposure to a wet poultry market <14 days before illness onset. Although data on person-to-person virus transmission are limited, close contacts of patients infected with influenza virus (H5N1) in China are monitored daily for 10 days after the last known exposure. Further studies are needed to quantify the incubation period after exposure to sick or dead infected poultry, a wet poultry market, or to an influenza A virus (H5N1) case-patient and to investigate the basis for any differences.