Jiandong Zheng

Comparative epidemiology of human infections with avian influenza A H7N9 and H5N1 viruses in China: a population-based study of laboratory-confirmed cases

BACKGROUND The novel influenza A H7N9 virus emerged recently in mainland China, whereas the influenza A H5N1 virus has infected people in China since 2003. Both infections are thought to be mainly zoonotic. We aimed to compare the epidemiological characteristics of the complete series of laboratory-confirmed cases of both viruses in mainland China so far. METHODS An integrated database was constructed with information about demographic, epidemiological, and clinical variables of laboratory-confirmed cases of H7N9 (130 patients) and H5N1 (43 patients) that were reported to the Chinese Centre for Disease Control and Prevention until May 24, 2013. We described disease occurrence by age, sex, and geography, and estimated key epidemiological variables. We used survival analysis techniques to estimate the following distributions: infection to onset, onset to admission, onset to laboratory confirmation, admission to death, and admission to discharge. FINDINGS The median age of the 130 individuals with confirmed infection with H7N9 was 62 years and of the 43 with H5N1 was 26 years. In urban areas, 74% of cases of both viruses were in men, whereas in rural areas the proportions of the viruses in men were 62% for H7N9 and 33% for H5N1. 75% of patients infected with H7N9 and 71% of those with H5N1 reported recent exposure to poultry. The mean incubation period of H7N9 was 3·1 days and of H5N1 was 3·3 days. On average, 21 contacts were traced for each case of H7N9 in urban areas and 18 in rural areas, compared with 90 and 63 for H5N1. The fatality risk on admission to hospital was 36% (95% CI 26-45) for H7N9 and 70% (56-83%) for H5N1. INTERPRETATION The sex ratios in urban compared with rural cases are consistent with exposure to poultry driving the risk of infection--a higher risk in men was only recorded in urban areas but not in rural areas, and the increased risk for men was of a similar magnitude for H7N9 and H5N1. However, the difference in susceptibility to serious illness with the two different viruses remains unexplained, since most cases of H7N9 were in older adults whereas most cases of H5N1 were in younger people. A limitation of our study is that we compared laboratory-confirmed cases of H7N9 and H5N1 infection, and some infections might not have been ascertained. FUNDING Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special Administrative Region, China; 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.

Detection of mild to moderate influenza A/H7N9 infection by China’s national sentinel surveillance system for influenza-like illness: case series

Objective To characterise the complete case series of influenza A/H7N9 infections as of 27 May 2013, detected by China’s national sentinel surveillance system for influenza-like illness. Design Case series. Setting Outpatient clinics and emergency departments of 554 sentinel hospitals across 31 provinces in mainland China. Cases Infected individuals were identified through cross-referencing people who had laboratory confirmed A/H7N9 infection with people detected by the sentinel surveillance system for influenza-like illness, where patients meeting the World Health Organization’s definition of influenza-like illness undergo weekly surveillance, and 10-15 nasopharyngeal swabs are collected each week from a subset of patients with influenza-like illness in each hospital for virological testing. We extracted relevant epidemiological data from public health investigations by the Centers for Disease Control and Prevention at the local, provincial, and national level; and clinical and laboratory data from chart review. Main outcome measure Epidemiological, clinical, and laboratory profiles of the case series. Results Of 130 people with laboratory confirmed A/H7N9 infection as of 27 May 2013, five (4%) were detected through the sentinel surveillance system for influenza-like illness. Mean age was 13 years (range 2-26), and none had any underlying medical conditions. Exposure history, geographical location, and timing of symptom onset of these five patients were otherwise similar to the general cohort of laboratory confirmed cases so far. Only two of the five patients needed hospitalisation, and all five had mild or moderate disease with an uneventful course of recovery. Conclusion Our findings support the existence of a “clinical iceberg” phenomenon in influenza A/H7N9 infections, and reinforce the need for vigilance to the diverse presentation that can be associated with A/H7N9 infection. At the public health level, indirect evidence suggests a substantial proportion of mild disease in A/H7N9 infections.

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.

Poultry Market Closures and Human Infection with Influenza A(H7N9) Virus, China, 2013–14

Closure of live poultry markets was implemented in areas affected by the influenza virus A(H7N9) outbreak in China during winter, 2013–14. Our analysis showed that closing live poultry markets in the most affected cities of Guangdong and Zhejiang provinces was highly effective in reducing the risk for H7N9 infection in humans.

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%.

Human Infection with Influenza A(H7N9) Virus during 3 Major Epidemic Waves, China, 2013–2015

Variation in risk for death might be associated with differences in case ascertainment, changes in clinical management, or virus genetic diversity.

Preliminary Epidemiologic Assessment of Human Infections With Highly Pathogenic Avian Influenza A(H5N6) Virus, China

Background Since 2014, 17 human cases of infection with the newly emerged highly pathogenic avian influenza A(H5N6) virus have been identified in China to date. The epidemiologic characteristics of laboratory-confirmed A(H5N6) cases were compared to A(H5N1) and A(H7N9) cases in mainland China. Methods Data on laboratory-confirmed H5N6, H5N1, and H7N9 cases identified in mainland China were analyzed to compare epidemiologic characteristics and clinical severity. Severity of confirmed H5N6, H5N1 and H7N9 cases was estimated based on the risk of severe outcomes in hospitalized cases. Results H5N6 cases were older than H5N1 cases with a higher prevalence of underlying medical conditions but younger than H7N9 cases. Epidemiological time-to-event distributions were similar among cases infected with the 3 viruses. In comparison to a fatality risk of 70% (30/43) for hospitalized H5N1 cases and 41% (319/782) for hospitalized H7N9 cases, 12 (75%) out of the 16 hospitalized H5N6 cases were fatal, and 15 (94%) required mechanical ventilation. Conclusion Similar epidemiologic characteristics and high severity were observed in cases of H5N6 and H5N1 virus infection, whereas severity of H7N9 virus infections appeared lower. Continued surveillance of human infections with avian influenza A viruses remains an essential component of pandemic influenza preparedness.