Fenyang Tang

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.

Probable person to person transmission of novel avian influenza A (H7N9) virus in Eastern China, 2013: epidemiological investigation

Objective To determine whether the novel avian influenza H7N9 virus can transmit from person to person and its efficiency. Design Epidemiological investigations conducted after a family cluster of two patients with avian H7N9 in March 2013. Setting Wuxi, Eastern China. Participants Two patients, their close contacts, and relevant environments. Samples from the patients and environments were collected and tested by real time reverse transcriptase-polymerase chain reaction (rRT-PCR), viral culture, and haemagglutination inhibition assay. Any contacts who became ill had samples tested for avian H7N9 by rRT-PCR. Paired serum samples were obtained from contacts for serological testing by haemagglutination inhibition assays. Main outcomes measures Clinical data, history of exposure before the onset of illnesses, and results of laboratory testing of pathogens and further analysis of sequences and phylogenetic tree to isolated strains. Results The index patient became ill five to six days after his last exposure to poultry. The second patient, his daughter aged 32, who provided unprotected bedside care in the hospital, had no known exposure to poultry. She developed symptoms six days after her last contact with her father. Two strains were isolated successfully from the two patients. Genome sequence and analyses of phylogenetic trees showed that both viruses were almost genetically identical. Forty three close contacts of both patients were identified. One had mild illness but had negative results for avian H7N9 by rRT-PCR. All 43 close contacts tested negative for haemagglutination inhibition antibodies specific for avian H7N9. Conclusions The infection of the daughter probably resulted from contact with her father (the index patient) during unprotected exposure, suggesting that in this cluster the virus was able to transmit from person to person. The transmissibility was limited and non-sustainable.

Dynamic reassortments and genetic heterogeneity of the human-infecting influenza A (H7N9) virus

Influenza A (H7N9) virus has been causing human infections in China since February 2013, raising serious concerns of potential pandemics. Previous studies demonstrate that human infection is directly linked to live animal markets, and that the internal genes of the virus are derived from H9N2 viruses circulating in the Yangtze River Delta area in Eastern China. Here following analysis of 109 viruses, we show a much higher genetic heterogeneity of the H7N9 viruses than previously reported, with a total of 27 newly designated genotypes. Phylogenetic and genealogical inferences reveal that genotypes G0 and G2.6 dominantly co-circulate within poultry, with most human isolates belonging to the genotype G0. G0 viruses are also responsible for the inter- and intra-province transmissions, leading to the genesis of novel genotypes. These observations suggest the province-specific H9N2 virus gene pools increase the genetic diversity of H7N9 via dynamic reassortments and also imply that G0 has not gained overwhelming fitness and the virus continues to undergo reassortment.

Emergence of a new GII.17 norovirus variant in patients with acute gastroenteritis in Jiangsu, China, September 2014 to March 2015.

From September 2014 to March 2015, 23 outbreaks of norovirus (NoV) acute gastroenteritis occurred in Jiangsu, China. Partial sequencing of the NoV capsid gene suggested that 16 of the 23 outbreaks were related to a new GII.17 variant. This variant was first detected in sporadic specimens in October 2014, and became predominant in February 2015. Analysis of the RNA-dependent RNA polymerase (RdRp), and complete capsid including the protruding domain P2 sequences confirmed this GII.17 variant as distinct from previously identified GII variants.

Cytokine and Chemokine Levels in Patients Infected with the Novel Avian Influenza A (H7N9) Virus in China

H7N9 avian influenza is an emerging viral disease in China caused by avian influenza A (H7N9) virus. We investigated host cytokine and chemokine profiles in serum samples of H7N9 patients by multiplex-microbead immunoassays. Statistical analysis showed that IP-10, IL-6, IL-17, and IL-2 were increased in H7N9 infected patients. Furthermore, IL-6 and the chemokine IP-10 were significantly higher in severe H7N9 patients compared to nonsevere H7N9 cases. We suggest that proinflammatory cytokine responses, characterized by a combined Th1/Th17 cytokine induction, are partially responsible for the disease progression of patients with H7N9 infection.

Suppression of the Interferon and NF-κB Responses by Severe Fever with Thrombocytopenia Syndrome Virus

ABSTRACT Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease characterized by high fever, thrombocytopenia, multiorgan dysfunction, and a high fatality rate between 12 and 30%. It is caused by SFTS virus (SFTSV), a novel Phlebovirus in family Bunyaviridae. Although the viral pathogenesis remains largely unknown, hemopoietic cells appear to be targeted by the virus. In this study we report that human monocytes were susceptible to SFTSV, which replicated efficiently, as shown by an immunofluorescence assay and real-time reverse transcription-PCR. We examined host responses in the infected cells and found that antiviral interferon (IFN) and IFN-inducible proteins were induced upon infection. However, our data also indicated that downregulation of key molecules such as mitochondrial antiviral signaling protein (MAVS) or weakened activation of interferon regulatory factor (IRF) and NF-κB responses may contribute to a restricted innate immunity against the infection. NSs, the nonstructural protein encoded by the S segment, suppressed the beta interferon (IFN-β) and NF-κB promoter activities, although NF-κB activation appears to facilitate SFTSV replication in human monocytes. NSs was found to be associated with TBK1 and may inhibit the activation of downstream IRF and NF-κB signaling through this interaction. Interestingly, we demonstrated that the nucleoprotein (N), also encoded by the S segment, exhibited a suppressive effect on the activation of IFN-β and NF-κB signaling as well. Infected monocytes, mainly intact and free of apoptosis, may likely be implicated in persistent viral infection, spreading the virus to the circulation and causing primary viremia. Our findings provide the first evidence in dissecting the host responses in monocytes and understanding viral pathogenesis in humans infected with a novel deadly Bunyavirus.

Case-control study of risk factors for human infection with influenza A(H7N9) virus in Jiangsu Province, China, 2013

We describe a case-control study performed in Jiangsu, China, to evaluate risk factors for human infection with novel avian influenza A(H7N9) virus. Twenty-five cases and 93 controls matched by age, sex, and location were included in the study. Direct contact with poultry or birds in the two weeks before illness onset, chronic medical conditions (hypertension excluded), and environment-related exposures were significantly associated with A(H7N9) infection.

Seroprevalence of antibodies against SFTS virus infection in farmers and animals, Jiangsu, China

BACKGROUND Severe fever with thrombocytopenia syndrome (SFTS) is a newly identified viral zoonosis caused by a phlebovirus. Most reported SFTS cases are farmers living in rural areas. The seroprevalence of SFTS virus in farmers has not been investigated. The current knowledge of SFTS virus seroprevalence in animals, especially in wild animals, is still poor. OBJECTIVES To investigate SFTS virus seroprevalence among farmers and a variety of animal species. STUDY DESIGN SFTS virus antibodies in sera were determined using a double-antigen sandwich ELISA. Serum samples were collected from 2547 farmers and 2741 animals in 6 SFTS-endemic counties from March 2012 to February 2013 in Jiangsu province. The farmer participants aged from 15 to 90 years. All of them were interviewed using a structured questionnaire. The animals sampled included 6 domesticated animal species and 2 wild animal species. RESULTS SFTSV antibodies were found in a total of 33 farmers (1.30%) and was more prevalent in males than in females (respectively 1.87% and 0.71%, P<0.01). The mean age of seropositive farmers was 56.5 years and seroprevalence increased gradually with age. Seroprevalence in animal species were: goats (66.8%), cattle (28.2%), dogs (7.4%), pigs (4.7%), chickens (1.2%), geese (1.7%), rodents (4.4%) and hedgehogs (2.7%). Multiple variable logistic regression analysis showed that grazing, grass mowing, raising cattle, age, farm work time and tick bites were risk factors for SFTS virus infection among farmers. CONCLUSIONS SFTSV readily infects humans with farming-related exposures as well as numerous domestic and wild animals. Serological results further suggest that the virus circulates widely in Jiangsu province.

Seroepidemiology of human enterovirus71 and coxsackievirusA16 in Jiangsu province, China

BackgroundThe major etiology of hand, foot and mouth disease (HFMD) is infection with human enterovirus A (HEV-A). Among subtypes of HEV-A, coxsackievirusA16 (CoxA16) and enterovirus 71 (EV71) are major causes for recurrent HFMD among infants and children in Jiangsu Province, mainland China. Here, we analyzed maternal antibodies between prenatal women and their neonates, to determine age-specific seroprevalence of human EV71 and CoxA16 infections in infants and children aged 0 to 15 years. The results may facilitate the development of immunization against HFMD.MethodsThis study used cross-section of 40 pairs of pregnant women and neonates and 800 subjects aged 1 month to 15 years old. Micro-dose cytopathogenic effects measured neutralizing antibodies against EV71 and CoxA16. Chi-square test compared seroprevalence rates between age groups and McNemar test, paired-Samples t-test and independent-samples t-test analyzed differences of geometric mean titers.ResultsA strong correlation between titers of neutralizing antibody against EV71 and CoxA16 in prenatal women and neonates was observed (rEV71 = 0.67, rCoxA16 = 0.56, respectively, p < 0.05). Seroprevalence rates of anti-EV71 antibody gradually decreased with age between 0 to 6 months old, remained low between 7 to 11 months (5.0–10.0%), and increased between 1 and 4 years (22.5–87.5%). Age-specific seroprevalence rates of anti-EV71 antibody stabilized in >80% of children between 5 to 15 years of age. However, seroprevalence rates of anti-CoxA16 antibody were very low (0.0–13.0%) between 0 to 6 months of age, gradually increased between 7 months to 4 years (15.0–70.0%), and stabilized at 54.0% (108/200) between 5 to 15 years. Seroprevalence rates against EV71 and CoxA16 were low under 1 year (0.0–10.0%), and showed an age dependent increase with high seroprevalence (52.5–62.5%) between 4 and10 years of age.ConclusionsConcomitant infection of EV71 and CoxA16 was common in Jiangsu Province. Therefore, development of bivalent vaccine against both EV71 and CoxA16 is critical. The optimal schedule for vaccination may be 4 to11 months of age.

Seroprevalence of avian influenza A (H5N1) virus among poultry workers in Jiangsu Province, China: an observational study

BackgroundSince 2003 to 06 Jan 2012, the number of laboratory confirmed human cases of infection with avian influenza in China was 41 and 27 were fatal. However, the official estimate of the H5N1 case-fatality rate has been described by some as an over estimation since there may be numerous undetected asymptomatic/mild cases of H5N1 infection. This study was conducted to better understand the real infection rate and evaluate the potential risk factors for the zoonotic spread of H5N1 viruses to humans.MethodsA seroepidemiological survey was conducted in poultry workers, a group expected to have the highest level of exposure to H5N1-infected birds, from 3 counties with habitat lakes of wildfowl in Jiangsu province, China. Serum specimens were collected from 306 participants for H5N1 serological test. All participants were interviewed to collect information about poultry exposures.ResultsThe overall seropositive rate was 2.61% for H5N1 antibodies. The poultry number was found associated with a 2.39-fold significantly increased subclinical infection risk after adjusted with age and gender.ConclusionsAvian-to -human transmission of avian H5N1 virus remained low. Workers associated with raising larger poultry flocks have a higher risk on seroconversion.