Zhibin Peng

Human infection with avian influenza A H7N9 virus: an assessment of clinical severity.

Summary Background Characterisation of the severity profile of human infections with influenza viruses of animal origin is a part of pandemic risk assessment, and an important part of the assessment of disease epidemiology. Our objective was to assess the clinical severity of human infections with avian influenza A H7N9 virus, which emerged in China in early 2013. Methods We obtained information about laboratory-confirmed cases of avian influenza A H7N9 virus infection reported as of May 28, 2013, from an integrated database built by the Chinese Center for Disease Control and Prevention. We estimated the risk of fatality, mechanical ventilation, and admission to the intensive care unit for patients who required hospital admission for medical reasons. We also used information about laboratory-confirmed cases detected through sentinel influenza-like illness surveillance to estimate the symptomatic case fatality risk. Findings Of 123 patients with laboratory-confirmed avian influenza A H7N9 virus infection who were admitted to hospital, 37 (30%) had died and 69 (56%) had recovered by May 28, 2013. After we accounted for incomplete data for 17 patients who were still in hospital, we estimated the fatality risk for all ages to be 36% (95% CI 26–45) on admission to hospital. Risks of mechanical ventilation or fatality (69%, 95% CI 60–77) and of admission to an intensive care unit, mechanical ventilation, or fatality (83%, 76–90) were high. With assumptions about coverage of the sentinel surveillance network and health-care-seeking behaviour for patients with influenza-like illness associated with influenza A H7N9 virus infection, and pro-rata extrapolation, we estimated that the symptomatic case fatality risk could be between 160 (63–460) and 2800 (1000–9400) per 100 000 symptomatic cases. Interpretation Human infections with avian influenza A H7N9 virus seem to be less serious than has been previously reported. Many mild cases might already have occurred. Continued vigilance and sustained intensive control efforts are needed to minimise the risk of human infection. Funding Chinese Ministry of Science and Technology; Research Fund for the Control of Infectious Disease; Hong Kong University Grants Committee; China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases; Harvard Center for Communicable Disease Dynamics; US National Institute of Allergy and Infectious Disease; and the US National Institutes of Health.

Effect of closure of live poultry markets on poultry-to-person transmission of avian influenza A H7N9 virus: an ecological study.

BACKGROUND Transmission of the novel avian influenza A H7N9 virus seems to be predominantly between poultry and people. In the major Chinese cities of Shanghai, Hangzhou, Huzhou, and Nanjing--where most human cases of infection have occurred--live poultry markets (LPMs) were closed in April, 2013, soon after the initial outbreak, as a precautionary public health measure. Our objective was to quantify the effect of LPM closure in these cities on poultry-to-person transmission of avian influenza A H7N9 virus. METHODS We obtained information about every laboratory-confirmed human case of avian influenza A H7N9 virus infection reported in the four cities by June 7, 2013, from a database built by the Chinese Center for Disease Control and Prevention. We used data for age, sex, location, residence type (rural or urban area), and dates of illness onset. We obtained information about LPMs from official sources. We constructed a statistical model to explain the patterns in incidence of cases reported in each city on the basis of the assumption of a constant force of infection before LPM closure, and a different constant force of infection after closure. We fitted the model with Markov chain Monte Carlo methods. FINDINGS 85 human cases of avian influenza A H7N9 virus infection were reported in Shanghai, Hangzhou, Huzhou, and Nanjing by June 7, 2013, of which 60 were included in our main analysis. Closure of LPMs reduced the mean daily number of infections by 99% (95% credibility interval 93-100%) in Shanghai, by 99% (92-100%) in Hangzhou, by 97% (68-100%) in Huzhou, and by 97% (81-100%) in Nanjing. Because LPMs were the predominant source of exposure to avian influenza A H7N9 virus for confirmed cases in these cities, we estimated that the mean incubation period was 3·3 days (1·4-5·7). INTERPRETATION LPM closures were effective in the control of human risk of avian influenza A H7N9 virus infection in the spring of 2013. In the short term, LPM closure should be rapidly implemented in areas where the virus is identified in live poultry or people. In the long term, evidence-based discussions and deliberations about the role of market rest days and central slaughtering of all live poultry should be renewed. FUNDING Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease; Hong Kong University Grants Committee; China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases; Harvard Center for Communicable Disease Dynamics; and the US National Institutes of Health.

Risk Factors for Severe Illness with 2009 Pandemic Influenza A (H1N1) Virus Infection in China

BACKGROUND Data on risk factors for severe outcomes from 2009 pandemic influenza A (H1N1) virus infection are limited outside of developed countries. METHODS We reviewed medical charts to collect data from patients hospitalized with laboratory-confirmed 2009 H1N1 infection who were identified across China during the period from September 2009 through February 2010, and we analyzed potential risk factors associated with severe illness (defined as illness requiring intensive care unit admission or resulting in death). RESULTS Among 9966 case patients, the prevalence of chronic medical conditions (33% vs 14%), pregnancy (15% vs 7%), or obesity (19% vs 14%) was significantly higher in those patients with severe illness than it was in those with less severe disease. In multivariable analyses, among nonpregnant case patients aged ≥ 2 years, having a chronic medical condition significantly increased the risk of severe outcome among all age groups, and obesity was a risk factor among those <60 years of age. The risk of severe illness among pregnant case patients was significantly higher for those in the second and third trimesters. The risk of severe illness was increased when oseltamivir treatment was initiated ≥ 5 days after illness onset (odds ratio, 1.42; 95% confidence interval, 1.20-1.67). For persons <60 years of age, the prevalence of obesity among case patients with severe illness was significantly greater than it was among those without severe illness or among the general population. CONCLUSIONS Risk factors for severe 2009 H1N1 illness in China were similar to those observed in developed countries, but there was a lower prevalence of chronic medical conditions and a lower prevalence of obesity. Obesity was a risk factor among case patients < 60 years of age. Early initiation of oseltamivir treatment was most beneficial, and there was an increased risk of severe disease when treatment was started ≥ 5 days after illness onset.

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

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 (64.5×109 cells/L vs 93.0×109 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.

Global epidemiology of avian influenza A H5N1 virus infection in humans, 1997-2015: A systematic review of individual case data

SUMMARY Avian influenza viruses A(H5N1) have caused a large number of typically severe human infections since the first human case was reported in 1997. However, there is a lack of comprehensive epidemiological analysis of global human cases of H5N1 from 1997-2015. Moreover, few studies have examined in detail the changing epidemiology of human H5N1 cases in Egypt, especially given the most recent outbreaks since November 2014 which have the highest number of cases ever reported globally over a similar period. Data on individual cases were collated from different sources using a systematic approach to describe the global epidemiology of 907 human H5N1 cases between May 1997 and April 2015. The number of affected countries rose between 2003 and 2008, with expansion from East and Southeast Asia, then to West Asia and Africa. Most cases (67.2%) occurred from December to March, and the overall case fatality risk was 53.5% (483/903) which varied across geographical regions. Although the incidence in Egypt has increased dramatically since November 2014, compared to the cases beforehand there were no significant differences in the fatality risk , history of exposure to poultry, history of human case contact, and time from onset to hospitalization in the recent cases.

Differences in the epidemiology of human cases of avian influenza A(H7N9) and A(H5N1) viruses infection

BACKGROUND The pandemic potential of avian influenza viruses A(H5N1) and A(H7N9) remains an unresolved but critically important question. METHODS We compared the characteristics of sporadic and clustered cases of human H5N1 and H7N9 infection, estimated the relative risk of infection in blood-related contacts, and the reproduction number (R). RESULTS We assembled and analyzed data on 720 H5N1 cases and 460 H7N9 cases up to 2 November 2014. The severity and average age of sporadic/index cases of H7N9 was greater than secondary cases (71% requiring intensive care unit admission vs 33%, P = .007; median age 59 years vs 31, P < .001). We observed no significant differences in the age and severity between sporadic/index and secondary H5N1 cases. The upper limit of the 95% confidence interval (CI) for R was 0.12 for H5N1 and 0.27 for H7N9. A higher proportion of H5N1 infections occurred in clusters (20%) compared to H7N9 (8%). The relative risk of infection in blood-related contacts of cases compared to unrelated contacts was 8.96 for H5N1 (95% CI, 1.30, 61.86) and 0.80 for H7N9 (95% CI, .32, 1.97). CONCLUSIONS The results are consistent with an ascertainment bias towards severe and older cases for sporadic H7N9 but not for H5N1. The lack of evidence for ascertainment bias in sporadic H5N1 cases, the more pronounced clustering of cases, and the higher risk of infection in blood-related contacts, support the hypothesis that susceptibility to H5N1 may be limited and familial. This analysis suggests the potential pandemic risk may be greater for H7N9 than H5N1.

The substantial hospitalization burden of influenza in central China: surveillance for severe, acute respiratory infection, and influenza viruses, 2010–2012

Published data on influenza in severe acute respiratory infection (SARI) patients are limited. We conducted SARI surveillance in central China and estimated hospitalization rates of SARI attributable to influenza by viral type/subtype.

Knowledge, attitudes and practices (KAP) relating to avian influenza in urban and rural areas of China

BackgroundStudies have revealed that visiting poultry markets and direct contact with sick or dead poultry are significant risk factors for H5N1 infection, the practices of which could possibly be influenced by peoples knowledge, attitudes and practices (KAPs) associated with avian influenza (AI). To determine the KAPs associated with AI among the Chinese general population, a cross-sectional survey was conducted in China.MethodsWe used standardized, structured questionnaires distributed in both an urban area (Shenzhen, Guangdong Province; n = 1,826) and a rural area (Xiuning, Anhui Province; n = 2,572) using the probability proportional to size (PPS) sampling technique.ResultsApproximately three-quarters of participants in both groups requested more information about AI. The preferred source of information for both groups was television. Almost three-quarters of all participants were aware of AI as an infectious disease; the urban group was more aware that it could be transmitted through poultry, that it could be prevented, and was more familiar with the relationship between AI and human infection. The villagers in Xiuning were more concerned than Shenzhen residents about human AI viral infection. Regarding preventative measures, a higher percentage of the urban group used soap for hand washing whereas the rural group preferred water only. Almost half of the participants in both groups had continued to eat poultry after being informed about the disease.ConclusionsOur study shows a high degree of awareness of human AI in both urban and rural populations, and could provide scientific support to assist the Chinese government in developing strategies and health-education campaigns to prevent AI infection among the general population.

Transmission dynamics, border entry screening, and school holidays during the 2009 influenza A (H1N1) pandemic, China.

Screening delayed spread by <4 days; autumn school holidays reduced the effective reproduction number by ≈40%.

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

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.