Luzhao Feng

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.

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.

Influenza-associated mortality in temperate and subtropical chinese cities, 2003-2008

OBJECTIVE To estimate influenza-associated mortality in urban China. METHODS Influenza-associated excess mortality for the period 2003-2008 was estimated in three cities in temperate northern China and five cities in the subtropical south of the country. The estimates were derived from models based on negative binomial regressions, vital statistics and the results of weekly influenza virus surveillance. FINDINGS Annual influenza-associated excess mortality, for all causes, was 18.0 (range: 10.9-32.7) deaths per 100,000 population in the northern cities and 11.3 (range: 7.3-17.8) deaths per 100,000 in the southern cities. Excess mortality for respiratory and circulatory disease was 12.4 (range: 7.4-22.2) and 8.8 (range: 5.5-13.6) deaths per 100,000 people in the northern and southern cities, respectively. Most (86%) deaths occurred among people aged ≥ 65 years. Influenza-associated excess mortality was higher in B-virus-dominant seasons than in seasons when A(H3N2) or A(H1N1) predominated, and more than half of all influenza-associated mortality was associated with influenza B virus. CONCLUSION Between 2003 and 2008, seasonal influenza, particularly that caused by the influenza B virus, was associated with substantial mortality in three cities in the temperate north of China and five cities in the subtropical south of the country.

Epidemiology of avian influenza A H7N9 virus in human beings across five epidemics in mainland China, 2013–17: an epidemiological study of laboratory-confirmed case series

BACKGROUND The avian influenza A H7N9 virus has caused infections in human beings in China since 2013. A large epidemic in 2016-17 prompted concerns that the epidemiology of the virus might have changed, increasing the threat of a pandemic. We aimed to describe the epidemiological characteristics, clinical severity, and time-to-event distributions of patients infected with A H7N9 in the 2016-17 epidemic compared with previous epidemics. METHODS In this epidemiological study, we obtained information about all laboratory-confirmed human cases of A H7N9 virus infection reported in mainland China as of Feb 23, 2017, from an integrated electronic database managed by the China Center for Disease Control and Prevention (CDC) and provincial CDCs. Every identified human case of A H7N9 virus infection was required to be reported to China CDC within 24 h via a national surveillance system for notifiable infectious diseases. We described the epidemiological characteristics across epidemics, and estimated the risk of death, mechanical ventilation, and admission to the intensive care unit for patients admitted to hospital for routine clinical practice rather than for isolation purpose. We estimated the incubation periods, and time delays from illness onset to hospital admission, illness onset to initiation of antiviral treatment, and hospital admission to death or discharge using survival analysis techniques. FINDINGS Between Feb 19, 2013, and Feb 23, 2017, 1220 laboratory-confirmed human infections with A H7N9 virus were reported in mainland China, with 134 cases reported in the spring of 2013, 306 in 2013-14, 219 in 2014-15, 114 in 2015-16, and 447 in 2016-17. The 2016-17 A H7N9 epidemic began earlier, spread to more districts and counties in affected provinces, and had more confirmed cases than previous epidemics. The proportion of cases in middle-aged adults increased steadily from 41% (55 of 134) to 57% (254 of 447) from the first epidemic to the 2016-17 epidemic. Proportions of cases in semi-urban and rural residents in the 2015-16 and 2016-17 epidemics (63% [72 of 114] and 61% [274 of 447], respectively) were higher than those in the first three epidemics (39% [52 of 134], 55% [169 of 306], and 56% [122 of 219], respectively). The clinical severity of individuals admitted to hospital in the 2016-17 epidemic was similar to that in the previous epidemics. INTERPRETATION Age distribution and case sources have changed gradually across epidemics since 2013, while clinical severity has not changed substantially. Continued vigilance and sustained intensive control efforts are needed to minimise the risk of human infection with A H7N9 virus. FUNDING The National Science Fund for Distinguished Young Scholars.

Epidemiological and virological characteristics of influenza B: results of the Global Influenza B Study

Literature on influenza focuses on influenza A, despite influenza B having a large public health impact. The Global Influenza B Study aims to collect information on global epidemiology and burden of disease of influenza B since 2000.

Seasonal influenza vaccine supply and target vaccinated population in China, 2004-2009.

To better understand the gap between limited influenza vaccine supply and the target population for vaccination in China, we conducted a retrospective survey to quantify the production capacity, supply and sale of seasonal trivalent inactive vaccine (TIV) from the 2004-2005 through the 2008-2009 season, and estimated the target population who should receive annual influenza vaccine. The maximum domestic capacity to produce TIV was 126 million doses in 2009. A total of 32.5 million doses of TIV were supplied in 2008-2009, with an average annual increase rate of 18% from 16.9 million in 2004-2005. This represents an amount sufficient to vaccinate 1.9% of Chinese population. The average number of doses of TIV for sale by province ranged from <5 to 108 per 1000 people. The differences are explained in part by level of economic development but also influenced by local reimbursement policies in some provinces. Based on national recommendations, we estimated a target population of 570.6 million or 43% of the total population. Supply and domestic production capacity for influenza vaccine is currently insufficient to vaccinate the estimated target population in China. The Government of China should consider measures to improve domestic production capacity of influenza vaccine, expand successful promotional campaigns, and add cost subsidies in high risk groups to further encourage influenza vaccine usage.

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.