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Background Hand, foot and mouth disease (HFMD) is caused by a variety of enterovirus serotypes and the etiological spectrum worldwide has changed since a large scale of outbreaks occurred in 1997. Methods A large number of clinical specimens of HFMD patients were collected in Xiangyang and genotyping was performed by qRT-PCR, conventional PCR amplification and sequencing. Among the 146 CV-A5 detected cases, the complete genome sequences of representative strains were determined for genotyping and for recombination analysis. Results It was found that CV-A5 was one of the six major serotypes that caused the epidemic from October 2016 to December 2017. Phylogenetic analyses based on the VP1 sequences showed that these CV-A5 belonged to the genotype D which dominantly circulated in China. Recombination occurred between the CV-A5 and CV-A2 strains with a breakpoint in the 2A region at the nucleotide 3791. Conclusions The result may explain the emergence of CV-A5 as one of the major pathogens of HFMD. A multivalent vaccine against HFMD is urgently needed to control the disease and to prevent emerging and spreading of new recombinants.

Background Knowledge of COVID-19 epidemiology remains incomplete and crucial questions persist. We aimed to examine risk factors for COVID-19 death. Methods A total of 80 543 COVID-19 cases reported in China, nationwide, through 8 April 2020 were included. Risk factors for death were investigated by Cox proportional hazards regression and stratified analyses. Results Overall national case-fatality ratio (CFR) was 5.64%. Risk factors for death were older age (≥80: adjusted hazard ratio, 12.58; 95% confidence interval, 6.78–23.33), presence of underlying disease (1.33; 1.19–1.49), worse case severity (severe: 3.86; 3.15–4.73; critical: 11.34; 9.22–13.95), and near-epicenter region (Hubei: 2.64; 2.11–3.30; Wuhan: 6.35; 5.04–8.00). CFR increased from 0.35% (30–39 years) to 18.21% (≥70 years) without underlying disease. Regardless of age, CFR increased from 2.50% for no underlying disease to 7.72% for 1, 13.99% for 2, and 21.99% for ≥3 underlying diseases. CFR increased with worse case severity from 2.80% (mild) to 12.51% (severe) and 48.60% (critical), regardless of region. Compared with other regions, CFR was much higher in Wuhan regardless of case severity (mild: 3.83% vs 0.14% in Hubei and 0.03% elsewhere; moderate: 4.60% vs 0.21% and 0.06%; severe: 15.92% vs 5.84% and 1.86%; and critical: 58.57% vs 49.80% and 18.39%). Conclusions Older patients regardless of underlying disease and patients with underlying disease regardless of age were at elevated risk of death. Higher death rates near the outbreak epicenter and during the surge of cases reflect the deleterious effects of allowing health systems to become overwhelmed.

To mitigate a national shortage of WIBP-CorV COVID-19 vaccine, China's regulator approved administering BBIBP-CorV after WIBP-CorV for completion of a primary series. In a pragmatic observational study, we compared immunogenicity and safety of a primary series of WIBP-CorV followed by BBIBP-CorV with a primary series of two doses of BBIBP-CorV.We invited healthy 18-59-years-old adults who had already received either WIBP-CorV or BBIBP-CorV as their first dose in a primary series to participate in this observational cohort study. Subjects who had received WIBP-CorV as their first dose became the observation group; subjects who had received BBIBP-CorV as their first dose became the control group. All participants received BBIBP-CorV as their second dose. We obtained sera 1, 2, and 6 months after second doses for nAb titer measurement by micro-neutralization cytopathic effect assay with SARS-CoV-2 strain HB01, standardized with WHO International Standard for anti-SARS-CoV-2 immunoglobulin. Safety was assessed for the 7 days after administration of second doses.Between March and December 2021, 275 subjects were included in the observation group and 133 in the control group. Neutralizing seropositivity (≥1:4) rates were 98.91 % and 99.25 % at 1 month and 53.16 % and 70.69 % at 6 months. One-month geometric mean titers (GMTs) were 21.33 and 22.45; one-month geometric mean concentrations (GMCs) were 227.71 IU/mL and 273.27 IU/mL. One to two months after vaccination, observation group seropositivity rates and titers were not significantly different to the control group's. Adverse reaction rates were 11.27 % and 18.80 %, all mild or moderate in severity.Both primary series were immunogenic; immunogenicity of WIBP-CorV followed by BBIBP-CorV was not different than immunogenicity following two doses of BBIBP-CorV for two months after vaccination; safety profiles were acceptable for both regimens. BBIBP-CorV can be used to complete a primary series that started with WIBP-CorV.

Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. Methods We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Results Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). Conclusions On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)

BackgroundIn 2017, an outbreak of onychomadesis occurred in kindergarten H, Hubei province, China. We investigated the field to learn about the magnitude and reason of the outbreak.MethodsThe case definition was that a child with onychomadesis or transverse ridging (Beau’s line) in fingernails and toenails without previous traumatic or systemic disease in kindergarten H from Sep. 1st to Nov. 30th, 2017. A retrospective cohort study was carried out to analyze the epidemiological relationship between onychomadesis and the hand-foot-mouth disease (HFMD) in Primary Class #2, kindergarten H. We also performed a serological survey for neutralizing antibodies against coxsackie virus A6 (CVA6), coxsackie virus A10 (CVA10) among 15 cases and six healthy children in the kindergarten. Meanwhile, some children were carried out with routine blood, fungal microscopic and microelement tests. Indoor environment examinations had been done for all classes.ResultsA total of 20 cases were identified in Kindergarten H. Seventy-five percent (15/20) cases occurred in Primary Class #2. Fifty-five percent of the cases (11/20) had suffered from HFMD within two months. The median time between onychomadesis and HFMD was 45 days (ranging from 31 to 58 days). A retrospective cohort study in Primary Class #2 showed the attack rate was 90.0% among 10 children who suffered from HFMD in the past two months compared to 30.0% among 20 children who didn’t (Rate Ratio [RR] =3.0, 95% Confidence Interval [CI] =1.5–6.0). The positive rates of neutralizing antibodies were 66.7% for CVA6 and 26.7% for CVA10 in tested cases. The result of routine blood, fungal microscopic, microelements tests were normal in cases. The indicators of environment were within the normal range.ConclusionThe results of this study suggested that the outbreak of onychomadesis in Hubei province was probably associated with HFMD epidemic within two months.

Li Cai,1,2 Lixian Wang,3 Xuhua Guan,4 Lei Wang,4 Xinyi Hu,5 Yang Wu,4 Yeqing Tong,4 Peigang Wang1 1School of Health Sciences, Wuhan University, Wuhan, 430071, People’s Republic of China; 2Wuhan Center for Disease Control and Prevention, Wuhan, 430015, People’s Republic of China; 3Xiaonan Center for Disease Control and Prevention, Xiaogan, 432100, People’s Republic of China; 4Hubei Center for Disease Control and Prevention, Wuhan, Hubei, 430079, People’s Republic of China; 5Global Study Institute, University of Geneva, Geneva, SwitzerlandCorrespondence: Peigang Wang Email wpg926@163.comYeqing Tong Tel +8627 87652010Email t_yeqing@163.comObjective: The study aimed to timely grasp the epidemiologic status of rabies in Central China from 2013 to 2018 and provide scientific evidence for the implementation of follow-up prevention and control measures.Methods: We initiated a retrospective observational and descriptive study of bite-related injuries data and rabies disease data in Hubei province from 2013 to 2018, managed by the Center for Disease Control and Prevention.Results: A total of 2,028,691 individuals were exposed to bites from 2013 to 2018, of which 221 were diagnosed with rabies and deceased. Among those cases, the incubation periods of rabies varied from 3 days to 18,406 days, which has been shown to be statistically associated with where the infected person was exposed and whether the wound care has been conducted.Conclusion: Epidemiological studies have shown that from 2013 to 2018, the current situation of rabies in Central China is still severe. The case fatality rate keeps virtually 100%. The rural population is still the most vulnerable group to rabies, characterized by a high exposure ratio and low treatment rate as well as poor vaccination compliance. Hoewever, larger populations are warranted to validate our findings.Keywords: rabies, epidemiology, China

Discharged COVID-19 patients have been found to be retested positive for SARS-CoV-2 (re-positive), which has widely raised concern among the public. We investigated the prevalence and transmission risk of re-positive cases in discharged COVID-19 patients and their SARS-CoV-2-specific antibody levels in Wuhan, China. Of 1065 discharged COVID-19 patients investigated, 518 (48.64%) patients were males; the mean age was 53.29 ± 14.91 years, with a median duration of 40 (IQR: 31–47) days since discharge. 63 patients were tested re-positive for SARS-CoV-2, with the re-positive prevalence to be 5.92% (95%CI: 4.50%-7.33%). The re-positive prevalence was higher in females (7.86%, 95%CI: 5.61%-10.12%) than that in males (3.86%, 95%CI: 2.20%-5.52%, P = 0.006). Re-positive prevalence was similar in patients tested positive and negative for IgG (6.01% vs 5.56%, P = 0.821) or IgM (6.38% vs 5.07%, P = 0.394). Illness severity and duration from illness onset to retest were not associated with the risk of positive results for SARS-CoV-2 after discharge. All 196 environmental samples collected from 49 re-positive patients were tested negative for SAR-CoV-2. Only one close contact to the re-positive patient had been tested positive for SARS-CoV-2; however, he might be a previous COVID-19 case but had not been detected before. Viral culture of 6 nasopharyngeal specimens presented no cytopathic effect of Vero E6 cells. Virus sequencing of 11 nasopharyngeal specimens indicated genomic fragments of SARS-CoV-2. 898 (84.72%) patients and 705 (66.51%) patients were tested positive for SARS-CoV-2-specific IgG and IgM, respectively. Self-report symptoms at the survey were similar, regardless of the level of antibody. All the re-positive patients and their matched non-re-positive patients were tested negative for SARS-CoV-2 four months later. These findings indicate that Testing re-positive of SARS-CoV-2 is common in discharged COVID-19 patients, but no evidence showed the transmission risk of these re-positive cases. Further isolation of recovered COVID-19 patients is unnecessary. However, only 85% recovered COVID-19 patients had SARS-CoV-2-specific antibody, which suggested discharged COVID-19 patients still had potential re-infection risk.

BackgroundShigellosis is one of the main diarrhea diseases in developing countries. However, the transmissibility of shigellosis remains unclear.MethodsWe used the dataset of shigellosis cases reported between January 2005 and December 2017, from Hubei Province, China. A mathematical model was developed based on the natural history and the transmission mechanism of the disease. By fitting the data using the model, transmission relative rate from person to person (b) and from reservoir to person (bw), and the effective reproduction number (Reff) were estimated. To simulate the contribution ofbandbwduring the transmission, we performed a “knock-out” simulation in four scenarios: A)b = 0 andbw = 0; B)b = 0; C)bw = 0; D) control (no intervention).ResultsA total of 130,770 shigellosis cases were reported in Hubei province, among which 13 cases were dead. The median annual incidence was 19.96 per 100,000 persons (range: 5.99 per 100,000 persons – 29.47 per 100,000 persons) with a decreased trend (trendχ2 = 25,470.27,P bandbwwere 0.0898 (95% confidence interval [CI]: 0.0851–0.0946) and 1.1264 × 10− 9(95% CI: 4.1123 × 10− 10–1.8416 × 10− 9), respectively. The “knock-out” simulation showed that the number of cases simulated by scenario A was almost the same as scenario B, and scenario C was almost the same as scenario D. The mean value ofReffof shigellosis was 1.19 (95% CI: 1.13–1.25) and decreased slightly with a Linear model until it decreased to an epidemic threshold of 0.99 (95% CI: 0.65–1.34) in 2029.ConclusionsThe incidence of shigellosis is still in high level. The transmissibility of the disease is low in Hubei Province. The transmission would be interrupted in the year of 2029.

What is already known on this topic? Human brucellosis, a neglected zoonotic disease, causes more than 500,000 new cases each year globally. The disease is of major public health concern in China, and northern provinces are traditionally endemic areas. What is added by this report? This is the first published outbreak of occupational brucellosis involving multiple clusters in Hubei Province. This investigation characterizes the transmission chain of the outbreak and reveals that provinces south of the Yangtze River are faced with a series of challenges and hurdles to overcome including, but not limited to, health education, law enforcement, and occupational protection. What are the implications for public health practice? In addition to measures aimed at this outbreak, the local agricultural department has issued special notices based on this investigation to adjust and strengthen local eradication program of brucellosis.

Background Mumps vaccine immunizations have reduced the incidence of this disease. With the variation of mumps circulating strain, novel vaccine strains are always important. Methods A 2-center parallel, randomized, double-blind noninferiority trial was performed to compare an F-genotype attenuated mumps vaccine (SP strain) to the A-genotype vaccine (S-79, Jeryl-Lynn strain) in 1080 healthy children aged 8-24 months in Hubei, China. Results Participants were randomly assigned to receive a high or low dose of the SP or S79 vaccine and then assessed clinically at 30 minutes and 1-28 days postinoculation. No differences in local or systemic reactivity were observed. A similar incidence of severe adverse events associated with the vaccine was observed in the high-dose group and the positive control group. Based on throat swab collections, no viral shedding was present at the 4th and 10th days in any group. Neutralizing and hemagglutination-inhibiting antibody assays with the F- or A-genotype strains showed similar trends in geometric mean titers in the high-dose SP and S79 groups. Increased cytotoxic T lymphocyte responses were observed in all groups. Conclusions The F-genotype attenuated mumps vaccine is safe, offers immunogenicity against a homologous virus, and is noninferior to the A-genotype vaccine in 8- to 24-month-old children.

Pleiotropic cytokine interleukin-10 (IL-10) has been suggested as modifying risk for atherosclerosis. Promoter region genetic polymorphism of IL-10 gene is known to be associated with the level of IL-10 production. Through these effects, they might be involved with the ischemic stroke (IS). Our aim was to assess the nature of the functional polymorphisms in IL-10 promoter and any links with IS in Chinese Han population.The IL-10 -1082 GA, -819 CT and -592 CA functional polymorphisms were determined by TaqMan SNP Genotyping assays in 1296 subjects (648 IS patients diagnosed by CTs or/and magnetic resonance imaging (MRI) and 648 normal healthy controls from Chinese Han Population). Multivariate logistic regression analysis was used to show the association between the IL-10 genotypes and the IS events.We found that the CC genotype of -819 CT was more common in controls than IS subjects (P0.05, corrected for multiple testing) in the Han population. CC carriage may be associated with the decreased risk of IS in the Han ethnic group (OR 0.65, 95% CI 0.43-0.97). In addition, the CC genotype in -592 CA and GG genotype in -1082 GA are all extremely low in Chinese Han cases and controls.The G allele frequency at the -1082 promoter region of IL-10 was rare in Chinese Han population which are diffierent from American/European populations.. IL-10 -819 CT may be an independent protective factor for IS in the Chinese Han population.

Although evidence has shown that supplementary immunization activity (SIA) campaigns greatly reduce the incidence of measles, their effects on disease transmissibility have seldom been monitored. A great decrease in the number of cases may be a false signal of early success towards measles elimination to policy makers. By interpreting the transmissibility in two different post-SIA periods in Hubei, China, the current study showed sustained measles transmissions despite a reduced number of cases. Two population-based cross-sectional serological surveys of measles antibodies were conducted in Hubei province in mid-2010 and mid-2011 after the implementation of SIAs. Immunoglobulin G (IgG) antibodies against measles were measured by enzyme-linked immunosorbent assay (ELISA). Based on the estimated age-specific susceptibility levels, the effective reproduction number (R), a key indicator of disease transmissibility, was determined by the next generation matrix in transmission model. The results revealed an overall IgG seroprevalence of 88.0% (95% confidence interval [CI]: 85.6-90.4%) and 89.6% (95%CI: 88.0-91.2%), respectively, in the two different periods. Comparatively lower seroprevalence rates were observed among children less than 24months of age and young adults 15 to 19years of age in 2011. The Rs were 0.76 and 1.53 for the two study periods. In conclusion, even though the incidence was reduced to below 1/100,000 in both 2010 and 2011, the reproduction number in 2011 indicates a high risk for sustained measles transmission. This finding was potentially due to a lower seropositivity rate among young adults that had not been covered in the first SIA. Thus, implementation of SIA targeted to appropriate age groups is recommended. Regular monitoring of seroprevalence is also suggested to track disease transmissibility and to align SIA with the appropriate age groups.

Background/Aims. Nucleotide diversity may affect the immune regulation of tuberculosis (TB) patients, leading to the individual susceptibility to TB. In recent years, there are a lot of researches on the association of host genetic factors and TB susceptibility which has attracted increasing attention, and the in-depth study of its mechanism is gradually clear.Materials. We made a minireview on the association of many candidate genes with TB based on recent research studies systematically, such as the human leukocyte antigen (HLA) gene, the solute carrier family 11 member 1 (SLC11A1) gene system, the vitamin D receptor (VDR) gene, the mannan-binding lectin (MBL) gene, the nitric oxide synthase 2A (NOS2A) gene, the speckled 110 (SP110) gene, and the P2X7 receptor (P2X7) gene. The discovery of these candidate genes could reveal the pathogenesis of TB comprehensively and is crucial to provide scientific evidence for formulating the related measures of prevention and cure.Discussion. The host genes play important roles in the development of TB, and the host genes may become new targets for the prevention and treatment of TB. Effective regulation of host genes may help prevent or even treat TB.Conclusion. This minireview focuses on the association of host genes with the development of TB, which may supply some clues for future therapies and novel drug targets for TB.

Background Evaluation of a licensed inactivated enterovirus type 71 (EV71) vaccine is needed in a phase IV study with a large population to identify its effectiveness and safety for further application. Methods An open-label, controlled trial involving a large population of 155 995 children aged 6–71 months was performed; 40 724 were enrolled in the vaccine group and received 2 doses of inactivated EV71 vaccine at an interval of 1 month, and the remaining children were used as the control group. The EV71-infected cases with hand, foot, and mouth disease were monitored in the vaccine and control groups during a follow-up period of 14 months since the 28th day postinoculation through the local database of the Notifiable Infectious Diseases Network. The effectiveness of the vaccine was estimated by comparing the incidence density in the vaccine group versus that in the control group based upon EV71-infected patients identified via laboratory testing. In parallel, the active and passive surveillance for safety of the vaccine was conducted by home or telephone visits and by using the Adverse Event Following Immunization (AEFI) system, respectively. Results An overall level of 89.7% (95% confidence interval, 24.0–98.6%) vaccine effectiveness against EV71 infection and a 4.58% rate of reported adverse events were observed. Passive surveillance demonstrated a 0.31% rate of reported common minor reactions. Conclusions The clinical protection and safety of the EV71 vaccine were demonstrated in the immunization of a large population. Clinical Trials Registration NCT03001986.

PPARγ and PPARα belong to a receptor family of ligand-activated transcription factors involved in the regulation of inflammation, cellular glucose uptake, protection against atherosclerosis and endothelial cell function. Through these effects, they might be involved with the ischemic stroke (IS). We recruited 100 IS patients diagnosed by CTs or/and magnetic resonance imaging (MRI) and 100 normal healthy controls from Chinese Uyghur Population to assess the nature of the functional polymorphisms of PPARs and any links with IS in this unique population which has 60% European ancestry and 40% East Asian ancestry. We found that the Ala allele of the PPARγ Pro12Ala polymorphism was more common in controls than IS subjects (P = 0.008, corrected for multiple testing) in the Uyghur Population. Pro/Ala carriage may be associated with a decreased risk of IS in Uyghurs (OR 0.542, 95% CI 0.346-0.850). Additionally, the 162Val allele frequency at the DNA-binding region of PPARα was extremely rare in Chinese Uguhur IS patients and controls. Our population and ethnic-based study demonstrates that the 162Val allele frequency was extremely low in the Chinese Uyghur Population different from Some European and African populations and the PPARγ 12 Pro/Ala resulting in an amino acid exchange in N-terminal sequence may be an independent protective factor for IS in the Chinese Uyghur Population.

Additional file 1: Table S1. Results of blood and environment tests in Kindergarten H, Hubei province, 2017.

Background: China implemented containment measures to stop SARS-CoV-2 transmission in response to the COVID-19 epidemic After the first epidemic wave, we conducted population-based serological surveys to determine extent of infection, risk factors for infection, and neutralization antibody levels to assess the real infections in the random sampled population Methods: We used a multistage, stratified cluster random sampling strategy to conduct serological surveys in three areas - Wuhan, Hubei Province outside Wuhan, and six provinces selected on COVID-19 incidence and containment strategy Participants were consenting individuals >1 year old who resided in the survey area >14 days during the epidemic Provinces screened sera for SARS-CoV-2-specific IgM, IgG, and total antibody by two lateral flow immunoassays and one magnetic chemiluminescence enzyme immunoassay;positive samples were verified by micro-neutralization assay Findings: We enrolled 34,857 participants (overall response rate, 92%);427 were positive by micro-neutralization assay Wuhan had the highest weighted seroprevalence (4*43%, 95% confidence interval [95%CI]=3*48%-5*62%), followed by Hubei-ex-Wuhan (0*44%, 95%CI=0*26%-0*76%), and the other provinces (

Background Influenza is an important cause of respiratory illness in children, but data are limited on hospitalized children with laboratory‐confirmed influenza in China. Methods We conducted active surveillance for severe acute respiratory infection (SARI; fever and at least one sign or symptom of acute respiratory illness) among hospitalized pediatric patients in Jingzhou, Hubei Province, from April 2010 to April 2012. Data were collected from enrolled SARI patients on demographics, underlying health conditions, clinical course of illness, and outcomes. Nasal swabs were collected and tested for influenza viruses by reverse transcription polymerase chain reaction. We described the clinical and epidemiological characteristics of children with influenza and analyzed the association between potential risk factors and SARI patients with influenza. Results During the study period, 15 354 children aged

Background The prevalence of tuberculosis (TB) in low and middle-income countries is a significant public health and social concern. TB is a common infectious disease caused by the Mycobacterium tuberculosis infection, which has a widespread infection rate. Health care-seeking delay maybe one of the most important neglected risk factors for the spread of TB. Objectives The aim of this study was to understand the situation of health care-seeking delay among rural tuberculosis patients in Hubei Province, and explore its risk factors. Methods A total of 1408 rural tuberculosis patients were surveyed using a standard structured questionnaire in three cities of Hubei Province during the past two years. Results For the 1408cases of pulmonary tuberculosis, 39.70% of them were health care-seeking delayed. Logistic regressions indicate that the Han nationality, farming careers, the over 45 min walk to the township&rsquo, s hospital, and awareness of the national TB free treatment policy, were significantly associated with higher odds of a delay in care seeking. Conclusions The prevalence of health care-seeking delay among tuberculosis patients was high in rural areas. It is essential to take comprehensive targeted interventions to reduce care-seeking delay.

Studies concerning the association between arsenic exposure and hepatitis B virus (HB V) infection have been lacking. The present study aimed to examine the association between total urinary arsenic (TUA) and infection of HBV. A total of 5186 participants from National Health and Nutrition Examination Survey (NHANES) 2003-2014 were included in the analysis. We used logistic regression to evaluate the association. We defined two measures of TUA. TUAI was the sum of arsenous acid, arsenicacid, monomethylarsonic acid and dimethylarsenic acid. TUA2 was defined as TUA minus arsenobetaine and arsenocholine. The results showed that the weighted overall prevalence of HBV infection was 6.08%. For NHANES 2003-2014, the medians (interquartile range) of TUAI and TUA2 were 5.60 μg/L (3.97-8.09 μg/L) and 4.91 μg/L (2.36-9.11 μg/L), respectively. Comparing the highest quartile to the lowest quartile after multivariable adjustment showed that the odds ratios (ORs) and 95% confidence intervals (CIs) for TUAI and TUA2 were 2.44 (1.40-4.27) and 2.84 (1.60-5.05), respectively. In conclusion, elevated urinary arsenic was associated with the risk of HBV infection. Further studies, especially prospective studies, are needed to confirm the causal relationship between arsenic exposure and HBV infection.

Hand, foot and mouth disease (HFMD) is a substantial burden throughout Asia, but the effects of temperature pattern on HFMD risk are inconsistent. To quantify the effect of temperature on HFMD incidence, Wuhan was chosen as the study site because of its high temperature variability and high HFMD incidence. Daily series of HFMD counts and meteorological variables during 2010–2015 were obtained. Distributed lag non-linear models were applied to characterize the temperature-HFMD relationship and to assess its variability across different ages, genders, and types of child care. Totally, 80,219 patients of 0–5 years experienced HFMD in 2010–2015 in Wuhan. The cumulative relative risk of HFMD increased linearly with temperature over 7 days (lag0–7), while it presented as an approximately inverted V-shape over 14 days (lag0–14). The cumulative relative risk at lag0–14 peaked at 26.4 °C with value of 2.78 (95%CI: 2.08–3.72) compared with the 5th percentile temperature (1.7 °C). Subgroup analyses revealed that children attended daycare were more vulnerable to temperature variation than those cared for at home. This study suggests that public health actions should take into consideration local weather conditions and demographic characteristics.

The complete mitogenome sequence of the flea, Ceratophyllus wui (Siphonaptera: Ceratophyllidae), was sequenced. The 18,081 bp long genome has the standard metazoan complement of 37 genes. These genes contain 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and one control region. The nucleotide composition of the C. wui mitogenome was A: 37.72%, T: 38.99%, G: 9.51% and C: 13.78%. The A + T content is 76.71%, showing strong AT skew. Phylogenetic analysis indicated that Siphonapteran has sister relationship with Dipteran.

Endothelial nitric oxide synthase (eNOS) plays an important role in mediating endothelium-dependent vasodilatation and antithrombotic action and is thus involved in the development of ischemic stroke (IS). Controversial results regarding the association of eNOS gene variable number of tandem repeats (VNTR) polymorphism with IS have been reported by conventional PCR-polyacrylamide gel electrophoresis methods. We aimed to identify any common association of eNOS gene VNTR polymorphism with IS in Chinese Han population by capillary electrophoresis (CE). The VNTR polymorphism of 27 bp within the eNOS intron-4 was determined by CE with specially designed tailed primers in Chinese Han patients with IS (n = 457) and matched elderly controls without IS (n = 457). Significant differences in BMI, WHR, hypertension, diabetes, smoking, TG, HDL, LDL, LDL, and FBG were observed between cases and controls. The distributions of eNOS VNTR polymorphism were not significantly associated with IS after adjustment for cardiovascular risk factors (OR = 1.18, 95% CI: 0.82–1.69). This finding was consistent with the further meta-analysis in Asians. The meta-analysis in Americans demonstrated that 4a/4b + 4a/4a genotype was significantly associated with IS risk with an OR of 1.54 (95% CI, 1.09–2.17) compared with the 4b/4b genotype. Our data suggests that BMI, WHR, hypertension, diabetes, smoking, TG, LDL, and FBG may increase the risk of IS. However, eNOS VNTR polymorphism may be not an independent major contributor for IS in Chinese Han population. The VNTR polymorphism might be associated with IS in Americans based on meta-analysis.

Recent genome-wide association studies (GWAS) have identified two key SNPs (rs11833579 and rs12425791) on chromosome 12p13 that were significantly associated with stroke in Caucasians. However, the validity of the association has remained controversial. We performed genetic association analyses in a very unique population which has 60% European ancestry and 40% East Asian ancestry. No significant association between these two SNPs and ischemic stroke was detected in this Chinese Uyghur population.

Background. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral disease in China, caused by SFTS virus (SFTSV). Severe SFTS patients can quickly proceed to multiorgan dysfunction and death; however, underlying pathogenic mechanisms remain unclear. Methods. Serum samples from 15 fatal and 44 nonfatal SFTS cases were subjected to multiplex-microbead immunoassays to detect a broad spectrum of cytokines. The viral load and virus-specific IgG titers were also tested by real-time PCR and ELISA, respectively. Results. Cytokines IL-1RA, IL-6, IL-10, G-CSF, IP-10, and MCP-1 were elevated in SFTS patients and produced at robust levels in fatal cases. In contrast, cytokines PDGF-BB and RANTES decreased in SFTS patients. These cytokines reverted to normal ranges during the convalescent phase of SFTSV infection. Cytokines IL-1β, IL-8, MIP-1α, and MIP-1β showed a unique pattern of elevation in fatal cases but not in nonfatal cases. However, these cytokines increased in the convalescent phase of nonfatal SFTS cases. Our regression analysis revealed that the serum viral load correlated with these cytokines. Moreover, levels of these cytokines correlated with various clinical parameters and virus-specific IgG titers. Conclusion. The study demonstrates that SFTSV infection induces a cytokine storm with abnormally expressed cytokine profiles, which are associated with the disease severity.

Background Streptococcus pneumoniae (Sp) is a leading cause of bacterial pneumonia, meningitis, and sepsis and a major source of morbidity and mortality worldwide. Invasive pneumococcal disease (IPD) is defined as isolation of Sp from a normally sterile site, including blood or cerebrospinal fluid. The aim of this study is to describe outcomes as well as clinical and epidemiological characteristics of hospitalized IPD case patients in central China. Methods We conducted surveillance for IPD among children and adults from April 5, 2010 to September 30, 2012, in four major hospitals in Jingzhou City, Hubei Province. We collected demographic, clinical, and outcome data for all enrolled hospitalized patients with severe acute respiratory infection (SARI) or meningitis, and collected blood, urine, and cerebrospinal fluid (CSF) for laboratory testing for Sp infections. Collected data were entered into Epidata software and imported into SPSS for analysis. Results We enrolled 22,375 patients, including 22,202 (99%) with SARI and 173 (1%) with meningitis. One hundred and eighteen (118, 3%) with either SARI or meningitis were Sp positive, 32 (0.8%) from blood/CSF culture, and 87 (5%) from urine antigen testing. Of those 118 patients, 57% were aged ≥65 years and nearly 100% received antibiotics during hospitalization. None were previously vaccinated with 7-valent pneumococcal conjugate vaccine (PCV 7), 23-valent pneumococcal polysaccharide vaccine, or seasonal influenza vaccine. The main serotypes identified were 14, 12, 3, 1, 19F, 4, 5, 9V, 15 and 18C, corresponding to serotype coverage rates of 42%, 63%, and 77% for PCV7, PCV10, and PCV13, respectively. Conclusions Further work is needed to expand access to pneumococcal vaccination in China, both among children and potentially among the elderly, and inappropriate use of antibiotics is a widespread and serious problem in China.

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.

PPARx03B3; and PPARα belong to a receptor family of ligand-activated transcription factors involved in the regulation of inflammation, cellular glucose uptake, protection against atherosclerosis and endothelial cell function. Through these effects, they might be involved with the ischemic stroke (IS).One thousand two hundred ninety-six subjects from the Chinese Han Population were chosen to assess the nature of the functional polymorphisms of PPARs and any links with IS. Multivariate logistic regression analysis was used to examine the association between PPARx03B3; and PPARα genotypes and a diagnosis of IS.Pro/Ala carriage may be associated with the decreased risk of IS in Hans (OR 0.542, 95% CI 0.346-0.850). The 162Val allele frequency at the DNA-binding region of PPARα was extremely rare in Chinese Han population.PPARx03B3; 12Pro/Ala resulting in an amino acid exchange in N-terminal sequence may be an independent protective factor for IS in the Chinese Han population. However, more populations are warranted to validate our findings.

To estimate the hospitalization rate of severe acute respiratory infection (SARI) cases attributable to influenza in Jingzhou city, Hubei province from 2010 to 2012.SARI surveillance was conducted at four hospitals in Jingzhou city, Hubei province from 2010 to 2012. Inpatients meeting the SARI case definition and with informed consent were enrolled to collect their demographic information, clinical features, treatment, and disease outcomes, with their respiratory tract specimens collected for PCR test of influenza virus.From April, 2010 to September, 2012, 19 679 SARI cases enrolled were residents of Jingzhou, and nasopharyngeal swab was collected from 18 412 (93.6%) cases of them to test influenza virus and 13.3% were positive for influenza. During the three consecutive 2010-2012 flu seasons, laboratory-confirmed influenza was associated with 102 per 100 000, 132 per 100 000 and 244 per 100 000, respectively. As for the hospitalization rate attributable to specific type/subtype of influenza virus, 48 per 100 000, 30 per 100 000 and 24 per 100 000 were attributable to A (H3N2), A (H1N1) pdm2009, and influenza B, respectively in 2010-2011 season; 42 per 100 000 [A (H3N2)] and 90 per 100 000 (influenza B) in 2011-2012 season; 90 per 100 000 [A (H3N2)] and one per 100 000 [influenza B] from April, 2010 to September, 2012. SARI hospitalization caused by influenza A or B occurred both mainly among children younger than five years old, with the peak in children aged 0.5 year old.Influenza could cause a substantial number of hospitalizations and different viral type/subtype result in different hospitalizations over influenza seasons in Jingzhou city, Hubei province. Children less than five years old should be prioritized for influenza vaccination in China.

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease that is caused by a novel bunyavirus, referred to as SFTS virus. During January 2011 to December 2011 we conducted a case-control study in Henan, Hubei and Shandong Provinces of China to determine the risk factors for SFTS. Methods Case-patients were identified in hospitals and reported to provincial Centers for Disease Control and Prevention while being notified electronically to the National Surveillance System. Controls were randomly selected from a pool of patients admitted to the same hospital ward within one week of the inclusion of the cases. They were matched by age (+/−5 years) and gender. Results A total of 422 patients participated in the study including 134 cases and 288 matched controls. The median age of the cases was 58.8 years, ranging from 47.6 to 70.1 years; 54.5% were male. No differences in demographics were observed between cases and controls; however, farmers were frequent and more common among cases (88.8%) than controls (58.7%). In multivariate analysis, the odds for SFTS was 2.4∼4.5 fold higher with patients who reported tick bites or presence of tick in the living area. Other independent risk factors included cat or cattle ownership and reported presence of weeds and shrubs in the working environment. Conclusions Our findings support the hypothesis that ticks are important vectors of SFTS virus. Further investigations are warranted to understand the detailed modes of transmission of SFTS virus while vector management, education on tick bites prevention and personal hygiene management should be implemented for high-risk groups in high incidence areas., Author Summary Since 2009, an emerging infectious disease which was identified as the severe fever with thrombocytopenia syndrome (SFTS) was reported in rural areas of Hubei, Shandong and Henan provinces in China. A novel bunyavirus designated severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) had been identified to be the etiological cause of SFTS. But what risk factors lead to the disease is still not clear. Further investigations for risk factors are needed to effectively prevent and control the disease. Here we have designed case-control study to try to develop the risk factors of the spread of SFTSV. It is hoped that our research could provide epidemiological evidence for further study. Also help to determine the spread of the virus in the environment.

Background Respiratory Syncytial Virus (RSV) is an important human respiratory pathogen, particularly of infants and older adults, and despite several decades of research and development, no licensed vaccine is available. Studies have confirmed that enhancement of RSV disease does not occur after inoculation with RSV live-attenuated vaccine candidates, making such vaccines preferable. In this paper, reverse genetics was used to construct two recombinant viruses, a recombinant Long strain (rLong) and rLong-∆G-EGFP; rLong-∆G-EGFP is a recombinant mutant in which G was replaced with the EGFP gene, based on the Long strain of RSV. Results Both rLong and rLong-∆G-EGFP were constructed successfully and recovered in Hep-2 cells, and autofluorescence was observed in rLong-∆G-EGFP-infected cells during consecutive passages. Titers of rLong and rLong-∆G-EGFP were ~100-fold lower than the parental strain. Although virulence was attenuated, high titers of neutralizing antibodies were induced in BALB/c mice after being inoculated with recombinant viruses in a three-dose schedule. Unexpectedly, the neutralizing antibody titer in rLong-∆G-EGFP-immunized recipients did not decline significantly compared with the rLong strain. Protective efficacy of recombinant viruses in lung tissue was up to 100%, and the serum neutralizing antibody levels could stabilize at 21 days with no significant fall post-challenge. Enzyme-linked immunospot (ELISPOT) assays showed that both recombinant viruses were capable of inducing CD8+ T cell immune responses, which are crucial for virus clearance, and that rLong stimulated a higher level of IFN-γ production by comparison. In terms of inducing a balanced immune response, rLong-∆G-EGFP elicited slightly higher levels of IgG2a antibodies and lower levels of IgG1/IgG2a than the rLong virus. Conclusions This study suggested that immunization with rLong and rLong-∆G-EGFP were immunogenic and protected against RSV infection in the lower respiratory tract of BALB/c mice better than in the nose. Because of a relative low IgG1/IgG2a ratio, rLong-∆G-EGFP was more inclined to make CD4+ T cells, shifting toward a Th1-type response, indicating that the generation of a more balanced Th1/Th2 response was desirable. This explorative study on the recombinant Long viruses also contributed to obtaining more RSV attenuated candidates by a reverse genetics approach.

Background After the 2009 influenza A (H1N1) pandemic, we conducted hospital-based severe acute respiratory infection (SARI) surveillance in one central Chinese city to assess disease burden attributable to influenza among adults and adolescents. Methods We defined an adult SARI case as a hospitalized patient aged ≥ 15 years with temperature ≥38.0°C and at least one of the following: cough, sore throat, tachypnea, difficulty breathing, abnormal breath sounds on auscultation, sputum production, hemoptysis, chest pain, or chest radiograph consistent with pneumonia. For each enrolled SARI case-patient, we completed a standardized case report form, and collected a nasopharyngeal swab within 24 hours of admission. Specimens were tested for influenza viruses by real-time reverse transcription polymerase chain reaction (rRT-PCR). We analyzed data from adult SARI cases in four hospitals in Jingzhou, China from April 2010 to April 2012. Results Of 1,790 adult SARI patients enrolled, 40% were aged ≥ 65 years old. The median duration of hospitalization was 9 days. Nearly all were prescribed antibiotics during their hospitalization, less than 1% were prescribed oseltamivir, and 28% were prescribed corticosteroids. Only 0.1% reported receiving influenza vaccination in the past year. Of 1,704 samples tested, 16% were positive for influenza. Influenza activity in all age groups showed winter-spring and summer peaks. Influenza-positive patients had a longer duration from illness onset to hospitalization and a shorter duration from hospital admission to discharge or death compared to influenza negative SARI patients. Conclusions There is substantial burden of influenza-associated SARI hospitalizations in Jingzhou, China, especially among older adults. More effective promotion of annual seasonal influenza vaccination and timely oseltamivir treatment among high risk groups may improve influenza prevention and control in China.