Zhongjie Li

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.

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.

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.

Hand, foot and mouth disease: spatiotemporal transmission and climate

BackgroundThe Hand-Foot-Mouth Disease (HFMD) is the most common infectious disease in China, its total incidence being around 500,000 ~1,000,000 cases per year. The composite space-time disease variation is the result of underlining attribute mechanisms that could provide clues about the physiologic and demographic determinants of disease transmission and also guide the appropriate allocation of medical resources to control the disease.Methods and FindingsHFMD cases were aggregated into 1456 counties and during a period of 11 months. Suspected climate attributes to HFMD were recorded monthly at 674 stations throughout the country and subsequently interpolated within 1456 × 11 cells across space-time (same as the number of HFMD cases) using the Bayesian Maximum Entropy (BME) method while taking into consideration the relevant uncertainty sources. The dimensionalities of the two datasets together with the integrated dataset combining the two previous ones are very high when the topologies of the space-time relationships between cells are taken into account. Using a self-organizing map (SOM) algorithm the dataset dimensionality was effectively reduced into 2 dimensions, while the spatiotemporal attribute structure was maintained. 16 types of spatiotemporal HFMD transmission were identified, and 3-4 high spatial incidence clusters of the HFMD types were found throughout China, which are basically within the scope of the monthly climate (precipitation) types.ConclusionsHFMD propagates in a composite space-time domain rather than showing a purely spatial and purely temporal variation. There is a clear relationship between HFMD occurrence and climate. HFMD cases are geographically clustered and closely linked to the monthly precipitation types of the region. The occurrence of the former depends on the later.

Determinants of the incidence of hand, foot and mouth disease in China using geographically weighted regression models

Background Over the past two decades, major epidemics of hand, foot, and mouth disease (HFMD) have occurred throughout most of the West-Pacific Region countries, causing thousands of deaths among children. However, few studies have examined potential determinants of the incidence of HFMD. Methods Reported HFMD cases from 2912 counties in China were obtained for May 2008. The monthly HFMD cumulative incidence was calculated for children aged 9 years and younger. Child population density (CPD) and six climate factors (average-temperature [AT], average-minimum-temperature [ATmin], average-maximum-temperature [ATmax], average-temperature-difference [ATdiff], average-relative-humidity [ARH], and monthly precipitation [MP]) were selected as potential explanatory variables for the study. Geographically weighted regression (GWR) models were used to explore the associations between the selected factors and HFMD incidence at county level. Results There were 176,111 HFMD cases reported in the studied counties. The adjusted monthly cumulative incidence by county ranged from 0.26 cases per 100,000 children to 2549.00 per 100,000 children. For local univariate GWR models, the percentage of counties with statistical significance (p<0.05) between HFMD incidence and each of the seven factors were: CPD 84.3%, ATmax 54.9%, AT 57.8%, ATmin 61.2%, ARH 54.4%, MP 50.3%, and ATdiff 51.6%. The R 2 for the seven factors’ univariate GWR models are CPD 0.56, ATmax 0.53, AT 0.52, MP 0.51, ATmin 0.52, ARH 0.51, and ATdiff 0.51, respectively. CPD, MP, AT, ARH and ATdiff were further included in the multivariate GWR model, with R 2 0.62, and all counties show statistically significant relationship. Conclusion Child population density and climate factors are potential determinants of the HFMD incidence in most areas in China. The strength and direction of association between these factors and the incidence of HFDM is spatially heterogeneous at the local geographic level, and child population density has a greater influence on the incidence of HFMD than the climate factors.

The changing epidemiology of dengue in China, 1990-2014: a descriptive analysis of 25 years of nationwide surveillance data

BackgroundDengue has been a notifiable disease in China since 1 September 1989. Cases have been reported each year during the past 25 years of dramatic socio-economic changes in China, and reached a historical high in 2014. This study describes the changing epidemiology of dengue in China during this period, to identify high-risk areas and seasons and to inform dengue prevention and control activities.MethodsWe describe the incidence and distribution of dengue in mainland China using notifiable surveillance data from 1990-2014, which includes classification of imported and indigenous cases from 2005-2014.ResultsFrom 1990-2014, 69,321 cases of dengue including 11 deaths were reported in mainland China, equating to 2.2 cases per one million residents. The highest number was recorded in 2014 (47,056 cases). The number of provinces affected has increased, from a median of three provinces per year (range: 1 to 5 provinces) during 1990-2000 to a median of 14.5 provinces per year (range: 5 to 26 provinces) during 2001-2014. During 2005-2014, imported cases were reported almost every month and 28 provinces (90.3%) were affected. However, 99.8% of indigenous cases occurred between July and November. The regions reporting indigenous cases have expanded from the coastal provinces of southern China and provinces adjacent to Southeast Asia to the central part of China. Dengue virus serotypes 1, 2, 3, and 4 were all detected from 2009-2014.ConclusionsIn China, the area affected by dengue has expanded since 2000 and the incidence has increased steadily since 2012, for both imported and indigenous dengue. Surveillance and control strategies should be adjusted to account for these changes, and further research should explore the drivers of these trends.Please see related article: http://dx.doi.org/10.1186/s12916-015-0345-0

Human Influenza A (H5N1) Cases, Urban Areas of People’s Republic of China, 2005–2006

We investigated potential sources of infection for 6 confirmed influenza A (H5N1) patients who resided in urban areas of People’s Republic of China. None had known exposure to sick poultry or poultry that died from illness, but all had visited wet poultry markets before illness.

Viral Etiologies of Hospitalized Acute Lower Respiratory Infection Patients in China, 2009-2013

Background Acute lower respiratory infections (ALRIs) are an important cause of acute illnesses and mortality worldwide and in China. However, a large-scale study on the prevalence of viral infections across multiple provinces and seasons has not been previously reported from China. Here, we aimed to identify the viral etiologies associated with ALRIs from 22 Chinese provinces. Methods and Findings Active surveillance for hospitalized ALRI patients in 108 sentinel hospitals in 24 provinces of China was conducted from January 2009-September 2013. We enrolled hospitalized all-age patients with ALRI, and collected respiratory specimens, blood or serum collected for diagnostic testing for respiratory syncytial virus (RSV), human influenza virus, adenoviruses (ADV), human parainfluenza virus (PIV), human metapneumovirus (hMPV), human coronavirus (hCoV) and human bocavirus (hBoV). We included 28,369 ALRI patients from 81 (of the 108) sentinel hospitals in 22 (of the 24) provinces, and 10,387 (36.6%) were positive for at least one etiology. The most frequently detected virus was RSV (9.9%), followed by influenza (6.6%), PIV (4.8%), ADV (3.4%), hBoV (1.9), hMPV (1.5%) and hCoV (1.4%). Co-detections were found in 7.2% of patients. RSV was the most common etiology (17.0%) in young children aged <2 years. Influenza viruses were the main cause of the ALRIs in adults and elderly. PIV, hBoV, hMPV and ADV infections were more frequent in children, while hCoV infection was distributed evenly in all-age. There were clear seasonal peaks for RSV, influenza, PIV, hBoV and hMPV infections. Conclusions Our findings could serve as robust evidence for public health authorities in drawing up further plans to prevent and control ALRIs associated with viral pathogens. RSV is common in young children and prevention measures could have large public health impact. Influenza was most common in adults and influenza vaccination should be implemented on a wider scale in China.

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.

Area Disease Estimation Based on Sentinel Hospital Records

Background Population health attributes (such as disease incidence and prevalence) are often estimated using sentinel hospital records, which are subject to multiple sources of uncertainty. When applied to these health attributes, commonly used biased estimation techniques can lead to false conclusions and ineffective disease intervention and control. Although some estimators can account for measurement error (in the form of white noise, usually after de-trending), most mainstream health statistics techniques cannot generate unbiased and minimum error variance estimates when the available data are biased. Methods and Findings A new technique, called the Biased Sample Hospital-based Area Disease Estimation (B-SHADE), is introduced that generates space-time population disease estimates using biased hospital records. The effectiveness of the technique is empirically evaluated in terms of hospital records of disease incidence (for hand-foot-mouth disease and fever syndrome cases) in Shanghai (China) during a two-year period. The B-SHADE technique uses a weighted summation of sentinel hospital records to derive unbiased and minimum error variance estimates of area incidence. The calculation of these weights is the outcome of a process that combines: the available space-time information; a rigorous assessment of both, the horizontal relationships between hospital records and the vertical links between each hospitals records and the overall disease situation in the region. In this way, the representativeness of the sentinel hospital records was improved, the possible biases of these records were corrected, and the generated area incidence estimates were best linear unbiased estimates (BLUE). Using the same hospital records, the performance of the B-SHADE technique was compared against two mainstream estimators. Conclusions The B-SHADE technique involves a hospital network-based model that blends the optimal estimation features of the Block Kriging method and the sample bias correction efficiency of the ratio estimator method. In this way, B-SHADE can overcome the limitations of both methods: Block Krigings inadequacy concerning the correction of sample bias and spatial clustering; and the ratio estimators limitation as regards error minimization. The generality of the B-SHADE technique is further demonstrated by the fact that it reduces to Block Kriging in the case of unbiased samples; to ratio estimator if there is no correlation between hospitals; and to simple statistic if the hospital records are neither biased nor space-time correlated. In addition to the theoretical advantages of the B-SHADE technique over the two other methods above, two real world case studies (hand-foot-mouth disease and fever syndrome cases) demonstrated its empirical superiority, as well.