Predicting temporal propagation of seasonal influenza using improved gaussian process model.

Influenza rapidly spreads in seasonal epidemics and imposes a considerable economic burden on hospitals and other healthcare costs. Thus, predicting the propagation of influenza accurately is crucial in preventing influenza outbreaks and protecting public health. Most current studies focus on the spread simulation of influenza. However, few studies have investigated the dependencies between meteorological variables and influenza activity. This study develops a non-parametric model based on Gaussian process regression for influenza prediction considering meteorological effect to capture temporal dependencies hidden in influenza time series. To identify the most explanatory external variables, L1-regularization is applied to identify meteorology factor subsets, and three types of covariance functions are designed to characterize non-stationary and periodic behavior in influenza activity. The dependencies of diseases and meteorology are modeled through the designed cross-covariance function. A real case in Shenzhen, China was studied to validate our proposed model along with comparisons to recently developed multivariate statistical models for influenza prediction. Results show that our proposed influenza prediction approach achieves superior performance in terms of one-week-ahead prediction of influenza-like illness.

Phenotypic and Genotypic Characterization of Clinical Enterotoxigenic Escherichia coli Isolates from Shenzhen, China.

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is one of the major causes of infectious diarrhea in developing countries. This study aimed to characterize the prevalence and phenotypic and genotypic features of ETEC isolates from Shenzhen, China. METHODS: ETEC isolates were obtained from acute diarrheal patients and evaluated for enterotoxin, classical colonization factors (CFs), serotypes, antimicrobial susceptibility, and multilocus sequencing typing (MLST). RESULTS: A total of 168 (1.3%) ETEC strains were isolated from 13,324 diarrheal outpatients during 2009 and 2014. A vast majority of ETEC-infected patients (82.1%) belonged to the age ranging 20-59 years and only six patients were children aged <5 years. Heat-stable toxin (ST) was most frequently detected (81.5%), followed by heat-labile toxin (LT) (13.1%). One or multiple colonization factors (CFs) were identified in 91 ETEC strains (54.2%). The most frequently detected CF was CS6 (with or without other CFs) (84/91), followed by CS21 (14/91). The most common serotype was O159:H34 (n = 36), followed by O148:H28 (n = 25) and O27:H7 (n = 17). High resistant rate was observed to nalidixic acid (77.4%), cephalothin (41.7%), ampicillin (34.5%), and tetracycline (21.4%). Antimicrobial resistance profiles differed among different serogroups. Sequence type (ST) 10 complex, integrated with connected ST218, ST48, ST4, and ST1312 subgroups, covered 73 (43.5%) isolates. CONCLUSIONS: ETEC isolates in Shenzhen of China appeared highly diverse, yet some isolates belonged to well-defined clonal groups sharing a unique set of virulence factors, serotypes, and MLST sequence types. Facing the challenge of ETEC antigenic diversity and geographic variation, novel molecules and/or classical antigens designed by novel strategies might contribute to ETEC vaccine development.

Genomic characterization of influenza A (H7N9) viruses isolated in Shenzhen, Southern China, during the second epidemic wave.

There were three epidemic waves of human infection with avian influenza A (H7N9) virus in 2013-2014. While many analyses of the genomic origin, evolution, and molecular characteristics of the influenza A (H7N9) virus have been performed using sequences from the first epidemic wave, genomic characterization of the virus from the second epidemic wave has been comparatively less reported. In this study, an in-depth analysis was performed with respect to the genomic characteristics of 11 H7N9 virus strains isolated from confirmed cases and four H7N9 virus strains isolated from environmental samples in Shenzhen during the second epidemic wave. Phylogenetic analysis demonstrated that six internal segments of the influenza A (H7N9) virus isolated from confirmed cases and environmental samples in Shenzhen were clustered into two different clades and that the origin of the influenza A (H7N9) virus isolated from confirmed cases in Shenzhen was different from that of viruses isolated during the first wave. In addition, H9N2 viruses, which were prevalent in southern China, played an important role in the reassortment of the influenza A (H7N9) virus isolated in Shenzhen. HA-R47K and -T122A, PB2-V139I, PB1-I397M, and NS1-T216P were the signature amino acids of the influenza A (H7N9) virus isolated from confirmed cases in Shenzhen. We found that the HA, NA, M, and PA genes of the A(H7N9) viruses underwent positive selection in the human population. Therefore, enhanced surveillance should be carried out to determine the origin and mode of transmission of the novel influenza A (H7N9) virus and to facilitate the formulation of effective policies for prevention and containment of a human infection epidemics.

Risk Factors for Vibrio parahaemolyticus Infection in a Southern Coastal Region of China.

OBJECTIVES: The objectives of the study were to identify dietary and medical risk factors for Vibrio parahaemolyticus (VP) infection in the coastal city Shenzhen in China. METHODS: In April-October 2012, we conducted a case-control study in two hospitals in Shenzhen, China. Laboratory-confirmed VP cases (N = 83) were matched on age, sex, and other social factors to healthy controls (N = 249). Subjects were interviewed using a questionnaire on medical history; contact with seawater; clinical symptoms and outcome; travel history over the past week; and dietary history 3 days prior to onset. Laboratory tests were used to culture, serotype, and genotype VP strains. We used logistic regression to calculate the odds ratios for the association of VP infection with potential risk factors. RESULTS: In multivariate analysis, VP infection was associated with having pre-existing chronic disease (adjusted odds ratio [aOR], 6.0; 95% confidence interval [CI], 1.5-23.7), eating undercooked seafood (aOR, 8.0; 95% CI, 1.3-50.4), eating undercooked meat (aOR, 29.1; 95% CI, 3.0-278.2), eating food from a street food vendor (aOR, 7.6; 95% CI, 3.3-17.6), and eating vegetable salad (aOR, 12.1; 95% CI, 5.2-28.2). CONCLUSIONS: Eating raw (undercooked) seafood and meat is an important source of VP infection among the study population. Cross-contamination of VP in other food (e.g., vegetables and undercooked meat) likely plays a more important role. Intervention should be taken to lower the risks of cross-contamination with undercooked seafood/meat, especially targeted at people with low income, transient workers, and people with medical risk factors.

Seroprevalence to avian influenza A(H7N9) virus among poultry workers and the general population in southern China: a longitudinal study.

BACKGROUND: Confirmed cases of avian influenza A(H7N9) virus infection in humans continue to occur in mainland China. Few confirmed cases have occurred in poultry workers despite potentially higher rates of exposure. METHODS: A serological survey was conducted in May and December 2013 in poultry market workers, and in March and September 2013 in the general population. Blood samples were collected and tested for antibodies to H7N9 and H5N1 viruses by hemagglutination inhibition (HI) assays. Multivariable analysis was employed to identify risk factors related to H7N9 infection indicated by serology among poultry workers. RESULTS: In the poultry workers, 36 of 501 (7.2%) in May and 56 of 375 (14.9%) in December had HI antibody titers ≥1:160 to H7N9. Of 96 individuals who participated in both surveys, 52 (54.2%) workers had a ≥4-fold rise in H7N9 antibody titers from May to December. In a multivariable analysis, female sex (odds ratio [OR], 2.713; 95% confidence interval [CI], 1.098-6.705) and ≥10 years of occupational exposure (OR, 3.592; 95% CI, 1.246-10.354) were identified as risk factors for infection. Seroprevalence against H5N1 at ≥1:160 was low in May (4/501 [0.8%]) and December (3/375 [0.8%]). In the general population, 0 of 417 individuals in March and 0 of 408 individuals in September had antibody titers ≥1:160 to H7N9 or to H5N1. CONCLUSIONS: Although none of the participants in our study had virologically confirmed H7N9 infection, the high proportion of poultry workers with serologic evidence of H7N9 infection between May and December 2013 suggests a substantial risk of mild H7N9 infections in this group, supporting stricter control measures in live poultry markets.

Vibrio parahaemolyticus, Southern Coastal Region of China, 2007-2012.

We analyzed the prevalence and characteristics of Vibrio parahaemolyticus among patients with acute infectious diarrhea in the southern coastal region of China. V. parahaemolyticus was the leading cause of bacterial infectious diarrhea in this region during 2007-2012. Serotype O3:K6 strains were most common, followed by serotypes O4:K8 and O3:K29.

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.

Emergence, circulation, and spatiotemporal phylogenetic analysis of coxsackievirus a6- and coxsackievirus a10-associated hand, foot, and mouth disease infections from 2008 to 2012 in Shenzhen, China.

Sporadic hand, foot, and mouth disease (HFMD) outbreaks and other infectious diseases in recent years have frequently been associated with certain human enterovirus (HEV) serotypes. This study explored the prevalences and genetic characteristics of non-HEV71 and non-coxsackievirus A16 (CV-A16) human enterovirus-associated HFMD infections in Shenzhen, China. A total of 2,411 clinical stool specimens were collected from hospital-based surveillance for HFMD from 2008 to 2012. The detection of HEV was performed by real-time reverse transcription-PCR (RT-PCR) and RT-seminested PCR, and spatiotemporal phylogenetic analysis was performed based on the VP1 genes. A total of 1,803 (74.8%) strains comprising 28 different serotypes were detected. In the past 5 years, the predominant serotypes were HEV71 (60.0%), followed by CV-A16 (21.2%) and two uncommon serotypes, CV-A6 (13.0%) and CV-A10 (3.3%). However, CV-A6 replaced CV-A16 as the second most common serotype between 2010 and 2012. As an emerging pathogen, CV-A6 became as common a causative agent of HFMD as HEV71 in Shenzhen in 2012. Phylogenetic analysis revealed that little variation occurred in the Chinese HEV71 and CV-A16 strains. The genetic characteristics of the Chinese CV-A6 and CV-A10 strains displayed geographic differences. The CV-A6 and CV-A10 strains circulating in Shenzhen likely originated in Europe. It was found that human enteroviruses have a high mutation rate due to evolutionary pressure and frequent recombination (3.2 × 10(-3) to 6.4 ×10(-3) substitutions per site per year for HEV71, CV-A6, CV-A16, and CV-A10). Since certain serotypes are potential threats to the public health, this study provides further insights into the significance of the epidemiological surveillance of HFMD.

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.

An integrated city-driven perinatal HIV prevention program covering 1.8 million pregnant women in Shenzhen, China, 2000 to 2010.

BACKGROUND: Despite the scale-up of prevention of mother-to-child transmission (PMTCT) programs worldwide, the translation from research studies into public health policy has been slow. This report details the experiences of a city-driven PMTCT program in China using existing health resources. METHODS: The PMTCT program was devised to hospital based and city-wide. It achieves full use of available resources: the local Centers for Disease Control and Prevention, the Infectious Disease Hospital, Maternal and Child Health Hospitals, and all qualified comprehensive hospitals. RESULTS: From 2000 to 2010, 1,843,122 pregnant women attended prenatal care or labor and delivery services. Overall, 97.4% received pretest HIV counseling, and 96.2% were tested for HIV. Among the 81.1% (1,495,122) of women who attended prenatal clinics, 97.2% (1,452,753) received pretest counseling and 95.7% (1,430,799) were tested for HIV. Among the 18.9% (348,000) of women with an undocumented HIV status at labor and delivery, 98.6% (343,038) received pretest counseling, and 98.1% (341,371) were tested for HIV. In total, 229 women were determined HIV positive for a prevalence of 1.3 per 10,000 pregnant women. Among the 107 HIV-infected women who carried to delivery, 87.9% received antiretroviral prophylaxis for themselves and their infants. Among the 58 women who were identified HIV positive at labor, 10.3% of mothers and 72.4% of infants received antiretroviral prophylaxis. The estimated mother-to-child transmission rate was 5.3% (95% confidence interval, 2.2%-10.7%). CONCLUSIONS: With appropriate integration, existing health care resources are adequate for a comprehensive city-driven PMTCT program in an area with a low HIV prevalence.

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

BACKGROUND: Studies 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 people's 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. METHODS: We 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. RESULTS: Approximately 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. CONCLUSIONS: Our 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.

The Association between Air Pollution and Outpatient and Inpatient Visits in Shenzhen, China.

Nowadays, air pollution is a severe environmental problem in China. To investigate the effects of ambient air pollution on health, a time series analysis of daily outpatient and inpatient visits in 2015 were conducted in Shenzhen (China). Generalized additive model was employed to analyze associations between six air pollutants (namely SO2, CO, NO2, O3, PM10, and PM2.5) and daily outpatient and inpatient visits after adjusting confounding meteorological factors, time and day of the week effects. Significant associations between air pollutants and two types of hospital visits were observed. The estimated increase in overall outpatient visits associated with each 10 µg/m³ increase in air pollutant concentration ranged from 0.48% (O3 at lag 2) to 11.48% (SO2 with 2-day moving average); for overall inpatient visits ranged from 0.73% (O3 at lag 7) to 17.13% (SO2 with 8-day moving average). Our results also suggested a heterogeneity of the health effects across different outcomes and in different populations. The findings in present study indicate that even in Shenzhen, a less polluted area in China, significant associations exist between air pollution and daily number of overall outpatient and inpatient visits.

Modelling the transmission and control strategies of varicella among school children in Shenzhen, China.

OBJECTIVES: Varicella (chickenpox) is a highly transmissible childhood disease. Between 2010 and 2015, it displayed two epidemic waves annually among school populations in Shenzhen, China. However, their transmission dynamics remain unclear and there is no school-based vaccination programme in Shenzhen to-date. In this study, we developed a mathematical model to compare a school-based vaccination intervention scenario with a baseline (i.e. no intervention) scenario. METHODS: Data on varicella reported cases were downloaded from the Infectious Disease Reporting Information Management System. We obtained the population size, age structure of children aged 15 or under, the class and school distribution from Shenzhen Education Bureau. We developed an Agent-Based Susceptible-Exposed-Infectious-Recovered (ABM-SEIR) Model that considered within-class, class-to-class and out-of-school transmission modes. The intervention scenario was that school-wide vaccination intervention occurred when an outbreak threshold was reached within a school. We varied this threshold level from five to ten cases. We compared the reduction of disease outbreak size and estimated the key epidemiological parameters under the intervention strategy. RESULTS: Our ABM-SEIR model provided a good model fit to the two annual varicella epidemic waves from 2013 to 2015. The transmission dynamics displayed strong seasonality. Our results suggested that a school-based vaccination strategy could effectively prevent large outbreaks at different thresholds. CONCLUSIONS: There was a considerable increase in reported varicella cases from 2013 to 2015 in Shenzhen. Our modelling study provided important theoretical support for disease control decision making during school outbreaks and the development of a school-based vaccination programme.

Highly Sensitive Naked-Eye Assay for Enterovirus 71 Detection Based on Catalytic Nanoparticle Aggregation and Immunomagnetic Amplification.

Development of sensitive, convenient, and cost-effective virus detection product is of great significance to meet the growing demand of clinical diagnosis at the early stage of virus infection. Herein, a naked-eye readout of immunoassay by means of virion bridged catalase-mediated in situ reduction of gold ions and growth of nanoparticles, has been successfully proposed for rapid visual detection of Enterovirus 71 (EV71). Through tailoring the morphologies of the produced gold nanoparticles (GNPs) varying between dispersion and aggregation, a distinguishing color changing was ready for observation. This colorimetric detection assay, by further orchestrating the efficient magnetic enrichment and the high catalytic activity of enzyme, is managed to realize highly sensitive detection of EV71 virions with the limit of detection (LOD) down to 0.65 ng/mL. Our proposed method showed a much lower LOD value than the commercial ELISA for EV71 virion detection. Comparing to the current clinical gold standard polymerase chain reaction (PCR) method, our strategy provided the same diagnostic outcomes after testing real clinical samples. Besides, this strategy has no need of complicated sample pretreatment or expensive instruments. Our presented naked-eye immunoassay method holds a promising prospect for the early detection of virus-infectious disease especially in resource-constrained settings.

Mortality from road traffic accidents in a rapidly urbanizing Chinese city: A 20-year analysis in Shenzhen, 1994-2013.

OBJECTIVE: This study aimed to describe the trends of motorization and mortality rates from road traffic accidents and examine their associations in a rapidly urbanizing city in China, Shenzhen. METHODS: Using data from the Shenzhen Deaths Registry between 1994 and 2013, we calculated the annual mortality rates of road traffic accidents, in addition to the age- and sex-specific mortality rates and their annual percentage changes (APCs) for the period of 2000-2013. We also examined the associations between mortality rate of road traffic accidents and traffic growth with Spearman's rank correlation analysis and a log-linear model derived from Smeed's law. RESULTS: A total of 20,196 deaths due to road traffic accidents, including 14,391 (71.3%) male deaths and 5,805 (28.7%) female deaths, were recorded in Shenzhen from 1994 to 2013. The annual mortality rates in terms of deaths per population and deaths per vehicle changed in similar patterns, demonstrating an increase since 1994 and peaking in 1997, followed by a steady decrease thereafter. The decrease in mortality was faster in individuals aged 20 year or older compared to those younger than 20 years. The mortality rates in term of deaths per population were positively correlated with the total number of vehicles per kilometer of road but negatively correlated with the motorization rate in term of vehicles per population. The estimated model for deaths due to road traffic accidents in relation to the total population and the number of registered vehicles was ln (deaths/10,000 vehicles) = -1.902 × ln (vehicles/population) - 1.961. The coefficient was statistically significant (P < .001) and the coefficient of determination was 0.966, indicating a good model fit. CONCLUSIONS: We described a generally decreasing trend in the mortality rates of road traffic accidents in a rapidly urbanizing Chinese city based observations in the 20-year period from 1994 to 2013. The decreased mortality rate may be explained by the expansion of road network construction, improved road safety regulations and management, as well as more accessible ambulance services in recent years. Nevertheless, road traffic accidents remain a universal problem of great public health concern in the whole population.

Sustained live poultry market surveillance contributes to early warnings for human infection with avian influenza viruses.

Sporadic human infections with the highly pathogenic avian influenza (HPAI) A (H5N6) virus have been reported in different provinces in China since April 2014. From June 2015 to January 2016, routine live poultry market (LPM) surveillance was conducted in Shenzhen, Guangdong Province. H5N6 viruses were not detected until November 2015. The H5N6 virus-positive rate increased markedly beginning in December 2015, and viruses were detected in LPMs in all districts of the city. Coincidently, two human cases with histories of poultry exposure developed symptoms and were diagnosed as H5N6-positive in Shenzhen during late December 2015 and early January 2016. Similar viruses were identified in environmental samples collected in the LPMs and the patients. In contrast to previously reported H5N6 viruses, viruses with six internal genes derived from the H9N2 or H7N9 viruses were detected in the present study. The increased H5N6 virus-positive rate in the LPMs and the subsequent human infections demonstrated that sustained LPM surveillance for avian influenza viruses provides an early warning for human infections. Interventions, such as LPM closures, should be immediately implemented to reduce the risk of human infection with the H5N6 virus when the virus is widely detected during LPM surveillance.

Identification and Whole-Genome Sequencing of Four Enterovirus D68 Strains in Southern China in Late 2015.

Four enterovirus D68 (EV-D68) strains from four children with influenza-like illness were identified in Shenzhen, southern China, in late 2015. Here, we announce the availability of these viral genomes in GenBank. The genomic sequences of these EV-D68 strains showed the closest phylogenetic relationship to strains from northern China.

Preliminary Proteomic Analysis of A549 Cells Infected with Avian Influenza Virus H7N9 and Influenza A Virus H1N1.

A newly emerged H7N9 influenza virus poses high risk to human beings. However, the pathogenic mechanism of the virus remains unclear. The temporal response of primary human alveolar adenocarcinoma epithelial cells (A549) infected with H7N9 influenza virus and H1N1 influenza A virus (H1N1, pdm09) were evaluated using the proteomics approaches (2D-DIGE combined with MALDI-TOF-MS/MS) at 24, 48 and 72 hours post of the infection (hpi). There were 11, 12 and 33 proteins with significant different expressions (P<0.05) at 24, 48 and 72hpi, especially F-actin-capping protein subunit alpha-1 (CAPZA1), Ornithine aminotransferase (OAT), Poly(rC)-binding protein 1 (PCBP1), Eukaryotic translation initiation factor 5A-1 (EIF5A) and Platelet-activating factor acetylhydrolaseⅠb subunit beta (PAFAH1B2) were validated by western-blot analysis. The functional analysis revealed that the differential proteins in A549 cells involved in regulating cytopathic effect. Among them, the down-regulation of CAPZA1, OAT, PCBP1, EIF5A are related to the death of cells infected by H7N9 influenza virus. This is the first time show that the down-regulation of PAFAH1B2 is related to the later clinical symptoms of patients infected by H7N9 influenza virus. These findings may improve our understanding of pathogenic mechanism of H7N9 influenza virus in proteomics.

Genetic evolution of Human Enterovirus A71 subgenotype C4 in Shenzhen, China, 1998-2013.

BACKGROUND: Human Enterovirus A71 (EV-A71) is one of the severest enteroviruses that causes hand, foot, and mouth disease (HFMD) among children. This study identified the mutations of EV-A71 VP1 amino acid residues over a number of years and explored the possible association of identified mutations and HFMD epidemic outbreaks in Shenzhen, China. METHODS: A total of 3760 stool specimens were collected from HFMD patients by Shenzhen Centers for Disease Control and Prevention (CDC) between 1998 and 2013. In total 289 VP1 strains were sequenced in this study, and amino acids mutation frequency was calculated. There were 2040 China nationwide sequences downloaded from Genebank as replication data. RESULTS: In our samples, 1036 subjects (27.6%) were EV-A71 infected. Three amino acid positions on VP1 protein were found to have high mutation prevalence. These are Q22H, S283T, and A289H. Site 22 showed a fast mutation fixation in the year 2008, at the time of the large scale epidemic outbreak in Shenzhen. Analysis of the nationwide data replicated the same trend of mutation prevalence of the three sites. CONCLUSION: The switching from Q to H on site 22 of the EV-A71 VP1 strain might be associated with the HFMD outbreak in Shenzhen in 2008. The identified amino acid sites 22, 283 and 289 provided information for developing anti-viral drugs against EV-A71 in the future.

Epidemiological investigation of a norovirus GII.4 Sydney outbreak in a China elder care facility.

An outbreak of norovirus GII.4/Sydney_2012 affected a China elder care facility in December 2012. A total of 39 elderly people and staff met the outbreak case definition. The attack rates in the elderly and the staff were 15.9% (31/195) and 23.2% (19/82), respectively, including 13 asymptomatic cases in the staff. The result of gene sequencing revealed that the outbreak was caused by norovirus GII.4 Sydney. The mode of transmission of this outbreak was proven to be person-to-person. The first case (a self-cared elder) was affected outside the elder care facility and was not isolated after returning. Norovirus was transmitted via close contact among the self-cared elderly. Then, through service-related close contact, the attendants promoted the cross-transmission between the self-cared elderly and the nursed elderly. The virus was also spread among the staff via daily contact. In the elder care facility, the asymptomatic cases in the attendants played an important role in the transmission of norovirus, which deserves high attention.