Jiayu Hu

Epidemiology of Human Infections with Avian Influenza A(H7N9) Virus in China

BACKGROUND The first identified cases of avian influenza A(H7N9) virus infection in humans occurred in China during February and March 2013. We analyzed data obtained from field investigations to describe the epidemiologic characteristics of H7N9 cases in China identified as of December 1, 2013. METHODS Field investigations were conducted for each confirmed case of H7N9 virus infection. A patient was considered to have a confirmed case if the presence of the H7N9 virus was verified by means of real-time reverse-transcriptase-polymerase-chain-reaction assay (RT-PCR), viral isolation, or serologic testing. Information on demographic characteristics, exposure history, and illness timelines was obtained from patients with confirmed cases. Close contacts were monitored for 7 days for symptoms of illness. Throat swabs were obtained from contacts in whom symptoms developed and were tested for the presence of the H7N9 virus by means of real-time RT-PCR. RESULTS Among 139 persons with confirmed H7N9 virus infection, the median age was 61 years (range, 2 to 91), 71% were male, and 73% were urban residents. Confirmed cases occurred in 12 areas of China. Nine persons were poultry workers, and of 131 persons with available data, 82% had a history of exposure to live animals, including chickens (82%). A total of 137 persons (99%) were hospitalized, 125 (90%) had pneumonia or respiratory failure, and 65 of 103 with available data (63%) were admitted to an intensive care unit. A total of 47 persons (34%) died in the hospital after a median duration of illness of 21 days, 88 were discharged from the hospital, and 2 remain hospitalized in critical condition; 2 patients were not admitted to a hospital. In four family clusters, human-to-human transmission of H7N9 virus could not be ruled out. Excluding secondary cases in clusters, 2675 close contacts of case patients completed the monitoring period; respiratory symptoms developed in 28 of them (1%); all tested negative for H7N9 virus. CONCLUSIONS Most persons with confirmed H7N9 virus infection had severe lower respiratory tract illness, were epidemiologically unrelated, and had a history of recent exposure to poultry. However, limited, nonsustained human-to-human H7N9 virus transmission could not be ruled out in four families.

Human Antibody Responses to Avian Influenza A(H7N9) Virus, 2013

Understanding host antibody response is crucial for predicting disease severity and for vaccine development. We investigated antibody responses against influenza A(H7N9) virus in 48 serum samples from 21 patients, including paired samples from 15 patients. IgG against subtype H7 and neutralizing antibodies (NAbs) were not detected in acute-phase samples, but ELISA geometric mean titers increased in convalescent-phase samples; NAb titers were 20–80 (geometric mean titer 40). Avidity to IgG against subtype H7 was significantly lower than that against H1 and H3. IgG against H3 was boosted after infection with influenza A(H7N9) virus, and its level in acute-phase samples correlated with that against H7 in convalescent-phase samples. A correlation was also found between hemagglutinin inhibition and NAb titers and between hemagglutinin inhibition and IgG titers against H7. Because of the relatively weak protective antibody response to influenza A(H7N9), multiple vaccinations might be needed to achieve protective immunity.

Limited human-to-human transmission of avian influenza A(H7N9) virus, Shanghai, China, March to April 2013

In April 2013, two members of one family were successively confirmed as cases of avian influenza A(H7N9) virus infection in Shanghai, China. Respiratory specimens from the two cases and their close contacts were tested using real-time reverse-transcription (RT)-PCR. Paired serum specimens from contacts were tested by haemagglutination inhibition assay and microneutralisation test. The index patient developed severe pneumonia. Her husband presented with pneumonia shortly thereafter. Both cases had highly similar clinical features and infection with A(H7N9) virus was confirmed in both cases by genetic analysis. Phylogenetic analysis revealed a high level of similarity between the sequences from the two patients and environmental samples collected from wet markets in Minhang and Changning districts. Six samples from the Changning wet market were confirmed as A(H7N9) positive. Of 27 close contacts, one developed mild respiratory symptoms and another tested positive for A(H7N9) antibodies, but both were negative by real-time RT-PCR. The other 25 close contacts of both cases were A(H7N9) negative. Limited human-to-human transmission of the virus most likely occurred in the family cluster. However, other close contacts did not test positive for the virus, suggesting limited potential for extensive human-to-human transmission of the virus.

Epidemiology of norovirus infections among diarrhea outpatients in a diarrhea surveillance system in Shanghai, China: a cross-sectional study

BackgroundNorovirus is an important cause of gastroenteritis both in children and adults. In China, few studies have been conducted on adult populations. This study aimed to determine the contribution of norovirus to gastroenteritis, characterize the features of norovirus infections, compare them with other pathogens, and test the effectiveness of the surveillance system.MethodsA citywide surveillance network on diarrhea patients was established. Samples were collected with intervals from both children and adults among diarrhea outpatients in hospitals and tested for viruses using rRT-PCR and for bacteria in CDCs. Patient information was acquired through interviews and recorded into a dedicated online system. The Pearsonχ2 test, multivariate logistic regression models and discriminant models were fitted into its comparisons with the non-norovirus group and other pathogens.ResultsNorovirus was detected in 22.91% of sampled diarrhea patients. The seasonal distribution of norovirus infections was different from non-norovirus patients (p < 0.001), with a half-year peak. Higher proportions of males (p = 0.001, OR = 1.303, 95% CI = 1.110-1.529), local citizens (p < 0.001) and officials/clerks (p = 0.001, OR = 1.348, 95% CI = 1.124-1.618) were affected with norovirus when compared with non-norovirus patients. Diarrhea patients affected with norovirus featured nausea (p < 0.001, OR = 1.418, 95% CI = 1.176-1.709) and vomiting (p < 0.001, OR = 1.969, 95% CI = 1.618-2.398), while fewer manifested fever (p = 0.046, OR = 0.758, 95% CI = 0.577-0.996) and abdominal pain (p = 0.018, OR = 0.815, 95% CI = 0.689-0.965). Children were more vulnerable to rotavirus (p = 0.008, OR = 1.637, 95% CI = 1.136-2.358) and bacteria (p = 0.027, OR = 1.511, 95% CI = 1.053-2.169) than norovirus. There was a seasonal difference between the GI and GII genotypes (p < 0.001). Officials or clerks were more easily affected with GI than GII (p = 0.006, OR = 1.888, 95% CI = 1.205-2.958).ConclusionsThis study was based on a citywide hospital-sentinel surveillance system with multiple enteric pathogens included. Norovirus was recognized as the most prevalent enteric pathogen in Shanghai. The seasonal peak was from October to April. Males had a higher prevalence than females. Local citizens and officials/clerks were more vulnerable to norovirus than other pathogens. Compared with rotavirus and bacteria, children were less frequently affected by norovirus. Nausea and vomiting were typical of norovirus, whereas fever and abdominal pain were uncommon symptoms of this pathogen. GI and GII infections were centered in different seasons. Officials and clerks were more easily affected by GI than GII.

The development of a combined mathematical model to forecast the incidence of hepatitis E in Shanghai, China

BackgroundSporadic hepatitis E has become an important public health concern in China. Accurate forecasting of the incidence of hepatitis E is needed to better plan future medical needs. Few mathematical models can be used because hepatitis E morbidity data has both linear and nonlinear patterns. We developed a combined mathematical model using an autoregressive integrated moving average model (ARIMA) and a back propagation neural network (BPNN) to forecast the incidence of hepatitis E.MethodsThe morbidity data of hepatitis E in Shanghai from 2000 to 2012 were retrieved from the China Information System for Disease Control and Prevention. The ARIMA-BPNN combined model was trained with 144 months of morbidity data from January 2000 to December 2011, validated with 12 months of data January 2012 to December 2012, and then employed to forecast hepatitis E incidence January 2013 to December 2013 in Shanghai. Residual analysis, Root Mean Square Error (RMSE), normalized Bayesian Information Criterion (BIC), and stationary R square methods were used to compare the goodness-of-fit among ARIMA models. The Bayesian regularization back-propagation algorithm was used to train the network. The mean error rate (MER) was used to assess the validity of the combined model.ResultsA total of 7,489 hepatitis E cases was reported in Shanghai from 2000 to 2012. Goodness-of-fit (stationary R2=0.531, BIC= −4.768, Ljung-Box Q statistics=15.59, P=0.482) and parameter estimates were used to determine the best-fitting model as ARIMA (0,1,1)×(0,1,1)12. Predicted morbidity values in 2012 from best-fitting ARIMA model and actual morbidity data from 2000 to 2011 were used to further construct the combined model. The MER of the ARIMA model and the ARIMA-BPNN combined model were 0.250 and 0.176, respectively. The forecasted incidence of hepatitis E in 2013 was 0.095 to 0.372 per 100,000 population. There was a seasonal variation with a peak during January-March and a nadir during August-October.ConclusionsTime series analysis suggested a seasonal pattern of hepatitis E morbidity in Shanghai, China. An ARIMA-BPNN combined model was used to fit the linear and nonlinear patterns of time series data, and accurately forecast hepatitis E infections.

A reported death case of a novel bunyavirus in Shanghai, China

This paper describes the first case of infection with a recently described novel bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), in Shanghai, China. The case is originally from Chizhou City, Anhui province within an endemic area for SFTSV. We describe the etiology, epidemiological characteristics, clinical diagnosis and treatment of this fatal case. This case is unique because major cause of death was renal failure, whereas other reported cases have been due to hemorrhage. The investigation and response to this case provides meaningful insight for the early and rapid diagnosis, treatment, prevention and control of severe fever with thrombocytopenia syndrome virus in non-endemic regions in China and globally.

Predictors of poor response after primary immunization of hepatitis B vaccines for infants and antibody seroprotection of booster in a metropolis of China.

To evaluate proportion and predictors of poor response in infants and appraise booster seroprotection, we surveyed 2047 infants in Shanghai and detected antibody to hepatitis B (HB) surface antigen (anti-HBs). Poor responders were randomized into 2 groups, given booster with 5 µg and 10 µg hepatitis B vaccine (HepB), respectively. Proportion of infants with titer <10 mIU/mL and 10 to 99 mIU/mL was 1.86% and 15.14%, respectively. Multivariate logistic regression suggested infants of male, aged 13 to 18 months, premature, administered with 5 µg HepB or mother positive for HB surface antigen (HBsAg) and HBe antigen (HBeAg) would more likely develop worse response. Difference of geometric mean concentration between the first and full booster was not statistically significant both for 5 µg and for 10 µg HepB groups. The seroprotective rate were higher for infants with 10 µg HepB than those with 5 µg HepB (P > .05). Therefore, it is concluded that booster for poor vaccinees with 10 µg HepB could achieve satisfactory seroprotection.

Caregiver burden and its determinants among family members of patients with chronic viral hepatitis in Shanghai, China: a community-based survey

BackgroundIn China, caregivers of chronic viral hepatitis patients experience considerable burdens, stress and disruption of their own well-being and social activities. Measurement of the effect on caregivers is an under-researched area. The Family Burden Interview Schedule (FBIS) was primarily devised for the caregivers of schizophrenia patients, and the adverse effect of the disease was similar to the effect of chronic viral hepatitis on family caregivers. In this study, we prospectively evaluated the psychometric properties of FBIS in the field of chronic viral hepatitis and used it to determine the factors affecting the caregiver burden on the family members of chronic viral hepatitis patients in Shanghai, China.MethodsA representative sample of patients (n = 1478) and caregivers (n = 1478) was randomly obtained through a multi-stage cluster sampling in Shanghai, China. Reliability and validity tests were used to verify the psychometric properties of the instrument. The two-level random intercept model was applied to determine the factors of the caregiver burden between the household and the community level.ResultsCronbach’s alpha coefficient was 0.90 for the overall instrument with statistical significance. Factor analysis suggested a three-factor model for the FBIS and confirmed that the adjusted unidimensional model and the second-order multidimensional model had better fit statistics. The average score of the caregiver burden in Shanghai was 12.62 ± 10.74, and financial burden constituted the major effect. The two-level random intercept model demonstrated that the risk factors were hospitalisation (β 1.69, 95%CI 0.48 to 2.90), elevated serum alanine aminotransferase levels (β 1.05, 95%CI 0.15 to 1.95), HCV infection (β 4.49, 95%CI 1.22 to 7.77), and acceptance of the hepatitis B vaccine (β 2.20, 95%CI 0.56 to 3.85), whereas the protective factors were no consumption of alcohol (β -2.69, 95%CI −5.19 to −0.19), average monthly costs for patients less than or equal to 100 US dollars (β -2.96, 95%CI −5.83 to −0.09), and good health status of family caregivers (β -9.91, 95%CI −12.76 to −7.05).ConclusionsFBIS can accurately measure the caregiver burden for chronic hepatitis. Targeting interventions toward the conditions associated with the caregiver burden is of great importance.