Xiaowen Cheng

Knowledge, attitudes and practices (KAP) relating to avian influenza in urban and rural areas of China

BackgroundStudies have revealed that visiting poultry markets and direct contact with sick or dead poultry are significant risk factors for H5N1 infection, the practices of which could possibly be influenced by peoples knowledge, attitudes and practices (KAPs) associated with avian influenza (AI). To determine the KAPs associated with AI among the Chinese general population, a cross-sectional survey was conducted in China.MethodsWe used standardized, structured questionnaires distributed in both an urban area (Shenzhen, Guangdong Province; n = 1,826) and a rural area (Xiuning, Anhui Province; n = 2,572) using the probability proportional to size (PPS) sampling technique.ResultsApproximately three-quarters of participants in both groups requested more information about AI. The preferred source of information for both groups was television. Almost three-quarters of all participants were aware of AI as an infectious disease; the urban group was more aware that it could be transmitted through poultry, that it could be prevented, and was more familiar with the relationship between AI and human infection. The villagers in Xiuning were more concerned than Shenzhen residents about human AI viral infection. Regarding preventative measures, a higher percentage of the urban group used soap for hand washing whereas the rural group preferred water only. Almost half of the participants in both groups had continued to eat poultry after being informed about the disease.ConclusionsOur study shows a high degree of awareness of human AI in both urban and rural populations, and could provide scientific support to assist the Chinese government in developing strategies and health-education campaigns to prevent AI infection among the general population.

Three fatal cases of pandemic 2009 influenza A virus infection in Shenzhen are associated with cytokine storm

China had taken strict measures for pandemic 2009 H1N1 infection with enhanced surveillance and hospital isolation since April 2009. In Shenzhen, over 1200 confirmed cases of H1N1 infection were identified. Three young patients died of severe pneumonia. Among them, two boys developed neurological complications. Cytokine storm seemed an important cause.

Epidemiological Dynamics and Phylogeography of Influenza Virus in Southern China

BACKGROUND Understanding the epidemiological dynamics of influenza virus is central to surveillance and vaccine strain selection. It has been suggested that tropical and subtropical regions represent the global source of influenza epidemics. However, our understanding of the epidemiological dynamics of influenza virus in these regions is limited by a relative lack of long-term data. METHODS We analyzed epidemiological and virological data on influenza recorded over a period of 15 years from the metropolitan city of Shenzhen in subtropical southern China. We used wavelet analysis to determine the periodicity of influenza epidemics and molecular phylogeographic analysis to investigate the role of Shenzhen and southern China in the global evolution of influenza virus. RESULTS We show that southern China is unlikely to represent an epicenter of global influenza activity, because activity in Shenzhen is characterized by significant annual cycles, multiple viral introductions every year, limited persistence across epidemic seasons, and viruses that generally are not positioned on the trunk of the global influenza virus phylogeny. CONCLUSIONS We propose that novel influenza viruses emerge and evolve in multiple geographic localities and that the global evolution of influenza virus is complex and does not simply originate from a southern Chinese epicenter.

Travel Patterns in China

The spread of infectious disease epidemics is mediated by human travel. Yet human mobility patterns vary substantially between countries and regions. Quantifying the frequency of travel and length of journeys in well-defined population is therefore critical for predicting the likely speed and pattern of spread of emerging infectious diseases, such as a new influenza pandemic. Here we present the results of a large population survey undertaken in 2007 in two areas of China: Shenzhen city in Guangdong province, and Huangshan city in Anhui province. In each area, 10,000 randomly selected individuals were interviewed, and data on regular and occasional journeys collected. Travel behaviour was examined as a function of age, sex, economic status and home location. Women and children were generally found to travel shorter distances than men. Travel patterns in the economically developed Shenzhen region are shown to resemble those in developed and economically advanced middle income countries with a significant fraction of the population commuting over distances in excess of 50 km. Conversely, in the less developed rural region of Anhui, travel was much more local, with very few journeys over 30 km. Travel patterns in both populations were well-fitted by a gravity model with a lognormal kernel function. The results provide the first quantitative information on human travel patterns in modern China, and suggest that a pandemic emerging in a less developed area of rural China might spread geographically sufficiently slowly for containment to be feasible, while spatial spread in the more economically developed areas might be expected to be much more rapid, making containment more difficult.

Applicability of a sensitive duplex real-time PCR assay for identifying B/Yamagata and B/Victoria lineages of influenza virus from clinical specimens.

Type B influenza virus is one of the major epidemic strains and responsible for considerable mortality and morbidity. Rapidly and accurately identifying different influenza B virus lineages, i.e., B/Yamagata (B/Y) and B/Victoria (B/V), is desirable during the flu season. However, the available rapid techniques lack sensitivity, and the usual methods for identifying influenza viruses require expansion of virus in tissue culture or embryonated hen’s eggs. Thus, we developed several sets of primer pairs that were able to detect and distinguish B/Y and B/V in a single real-time PCR assay. Used in conjunction with two sets of specific primers that exhibited purine at 3′ end of at least one primer targeting on HA gene of B/Y and B/V lineages allows us to accurately identify approximately 102 copies per microliter for B/Y and B/V with intra- and inter-assay coefficient of variation (CV) <4%. When it was used to test 17,765 throat swab specimens obtained in the 2006–2010 influenza surveillance season, this method was comparable to hemagglutination inhibition assay in detection, typing and subtyping of influenza viruses with 100% true-negative (specificity) and 100% true-positive (sensitivity). Taken together, this method provides sensitive and robust tool for routine diagnosis and on-time epidemiological examination for WHO decisions on vaccine composition.

Clinical symptoms, immune factors, and molecular characteristics of an adult male in Shenzhen, China infected with influenza virus H5N1

On December 29, 2011, a man infected with a subclade of the H5N1 virus was confirmed in Shenzhen, China. The clinical symptoms and immune factors of the patient were investigated and the phylogenetic and molecular characteristics of the virus were analyzed. High fever, rapid development of serious pneumonia and multi‐organ failure were the main clinical symptoms. Arterial blood gas analysis showed that PaCO2 rose sharply and PO2 decreased. Leukocyte and platelet counts decreased rapidly. Peripheral blood lymphocyte counts indicated lymphopenia and inverted ratios of CD4+ to CD8+ cells. Cytokine analysis showed that the levels of serum IL‐6, IL‐10, and IFN‐r continued to increase, whereas the levels of IL‐12 and TNFs decreased during the clinical course. MCP‐1 and IP‐10 remained at a high level after infection. Phylogenetic analysis confirmed that the virus A/Shenzhen/1/2011 belongs to the new subclade 2.3.2.1. An Arg (R) insertion at P6 and an RP8I substitution in the HA cleavage site motif were detected in the virus. Compared to the vaccine strain, 16 specific substitutions occurred in the HA1 protein. Some of them were located on the receptor‐binding site, glycosylation site and the region of the antigenic determinant. In summary, serious complications and immune system disorders were the main features of the infection with H5N1. Gene variation did not weaken the highly pathogenic features of viruses and the pathogenicity and antigenicity of the new subclade virus were changed. J. Med. Virol. 85:760–768, 2013.

Clinical and molecular characteristics of the 2009 pandemic influenza H1N1 infection with severe or fatal disease from 2009 to 2011 in Shenzhen, China

In the past 3 years, the 2009 pandemic influenza virus H1N1 (pH1N1) has led to many severe or fatal cases. The virus‐related factors that cause severe or fatal disease are not clear. The clinical and molecular characteristics of pH1N1 infections with severe or fatal disease were examined to understand the correlation between pH1N1 infection and disease severity. Since 2009, three pH1N1 influenza epidemic outbreaks have occurred in Shenzhen, China. One hundred forty‐six severe cases were confirmed in the first wave in 2009. In severe cases, a high proportion (49.3%) of patents displayed high fever (>39.0°C), and 73.2% of patients had pneumonia and tracheobronchitis. Seven fatal cases were recorded: three with viral encephalitis and four with respiratory failure. The results of sequencing and phylogenetic analysis showed that the viruses from fatal or severe cases were scattered throughout the phylogenetic tree. Four substitutions (D222G, D222N, D222E, and Q223R) were observed on the 220‐loop of the receptor‐binding sites of the HA gene. Both D222G and D222N were associated statistically with severe disease. The 2011 viruses had evolved into two distinct branches. Ten specific point mutations occurred in the 2011 virus. In summary, high fever, lower respiratory tract infections and serious complications were the main features of severe cases. Gene variation seemed not to be the main reason for severe disease. Vaccination is the effective mean to prevent infection and severe disease. J. Med. Virol. 85:405–412, 2013.

Rural Villagers and Urban Residents Exposure to Poultry in China

Patterns of poultry exposure in rural and urban areas in China have not been systematically evaluated and compared. The objective of our study is to investigate patterns in human exposure to poultry in rural and urban China. We conducted a two-stage household-based clustered survey on population exposure to live/sick/dead poultry in Xiuning and Shenzhen. Half of the rural households (51%) in Xiuning raised poultry, mostly (78%) free-range. Around half of those households (40%) allowed poultry to stay in their living areas. One quarter of villagers reported having contact with sick or dead poultry. In Shenzhen, 37% urban residents visited live poultry markets. Among these, 40% purchased live poultry and 16% touched the poultry or cages during purchase. Our findings indicated that human exposure to poultry was different in rural and urban areas in China. This discrepancy could contribute to the observed differences in epidemiologic characteristics between urban and rural cases of influenza A(H7N9) and A(H5N1) virus infection.

Forecasting Influenza Epidemics from Multi-Stream Surveillance Data in a Subtropical City of China

Background Influenza has been associated with heavy burden of mortality and morbidity in subtropical regions. However, timely forecast of influenza epidemic in these regions has been hindered by unclear seasonality of influenza viruses. In this study, we developed a forecasting model by integrating multiple sentinel surveillance data to predict influenza epidemics in a subtropical city Shenzhen, China. Methods Dynamic linear models with the predictors of single or multiple surveillance data for influenza-like illness (ILI) were adopted to forecast influenza epidemics from 2006 to 2012 in Shenzhen. Temporal coherence of these surveillance data with laboratory-confirmed influenza cases was evaluated by wavelet analysis and only the coherent data streams were entered into the model. Timeliness, sensitivity and specificity of these models were also evaluated to compare their performance. Results Both influenza virology data and ILI consultation rates in Shenzhen demonstrated a significant annual seasonal cycle (p<0.05) during the entire study period, with occasional deviations observed in some data streams. The forecasting models that combined multi-stream ILI surveillance data generally outperformed the models with single-stream ILI data, by providing more timely, sensitive and specific alerts. Conclusions Forecasting models that combine multiple sentinel surveillance data can be considered to generate timely alerts for influenza epidemics in subtropical regions like Shenzhen.

Serologic and genetic characterization analyses of a highly pathogenic influenza virus (H5N1) isolated from an infected man in Shenzhen.

Highly pathogenic avian influenza (HPAI) H5N1 virus caused a wave of outbreaks in China during 2005–2006, resulting in a total of 20 cases of human infection in 14 provinces of China. On June16, 2006, a case of H5N1 human infection was confirmed in Shenzhen. The virus isolated from the patient, A/Guangdong/2/06, was characterized genetically and the relationship between the tracheal virus load and the antibody titer of the infected man was analyzed. Serological analysis confirmed that the patients neutralizating antibodies had been generated 2 weeks after the onset of symptoms. The patients serum antibodies could efficiently neutralize A/Guandong/2/06 infectivity in vitro. Phylogenetic analysis showed that the H5N1 virus of Shenzhen belonged to subclade 2.3.4, which contained viruses that were mainly responsible for the outbreaks in domestic poultry and in the cases of human infection in southern China. Homology and molecular characterization analysis revealed that all the segments of Shenzhen H5N1 virus still belonged to avian segments. Several specific amino acid residue mutations were detected. J. Med. Virol. 80:1058–1064, 2008.