Epidemiological Features of Hepatitis C in China From 2015 to 2021: Insights From National Surveillance Data.

The COVID-19 pandemic overwhelmed national health care systems, not least in the context of hepatitis elimination. This study investigates the effects of the pandemic response on the incidence rate, mortality rate, and case fatality rate (CFR) for hepatitis C virus (HCV) cases in China. We extracted the number of hepatitis C cases and HCV-related deaths by month and year for 2015 to 2021 in China and applied two proportional tests to analyze changes in the average yearly incidence rates, mortality rates, and CFRs for 2015 to 2020. We used the autoregressive integrated moving average model to predict these three rates for 2020 based on 2015 to 2019 HCV data. The incidence of hepatitis C decreased by 7.11% and 1.42% (P < .001) in 2020 and 2021, respectively, compared with 2015 to 2019, while it increased by 6.13% (P < .001) in 2021 relative to 2020. The monthly observed incidence in 2020 was significantly lower (-26.07%) than predicted. Meanwhile, no differences in mortality rate or CFR were observed between 2021, 2020, and 2015 to 2019. Our findings suggest that nonpharmaceutical interventions and behavioral changes to mitigate COVID-19 could have reduced hepatitis C incidence and accelerated China's implementation of a plan to eliminate HCV infection.

An outbreak of hepatitis E virus genotype 4d caused by consuming undercooked pig liver in a nursing home in Zhejiang Province, China.

Hepatitis E infection is typically caused by contaminated water or food. In July and August 2022, an outbreak of hepatitis E was reported in a nursing home in Zhejiang Province, China. Local authorities and workers took immediate actions to confirm the outbreak, investigated the sources of infection and routes of transmission, took measures to terminate the outbreak, and summarized the lessons learned. An epidemiological investigation was conducted on all individuals in the nursing home, including demographic information, clinical symptoms, history of dietary, water intake and contact. Stool and blood samples were collected from these populations for laboratory examinations. The hygiene environment of the nursing home was also investigated. A case-control study was conducted to identify the risk factors for this outbreak. Of the 722 subjects in the nursing home, 77 were diagnosed with hepatitis E, for an attack rate of 10.66 %. Among them, 18 (23.38 %, 18/77) individuals had symptoms such as jaundice, fever, and loss of appetite and were defined as the population with hepatitis E. The average age of people infected with hepatitis E virus (HEV) was 59.96 years and the attack rate of hepatitis E among women (12.02 %, 59/491) was greater than that among men (7.79 %, 18/231). The rate was the highest among caregivers (22.22 %, 32/144) and lowest among logistics personnel (6.25 %, 2/32); however, these differences were not statistically significant (P > 0.05). Laboratory sequencing results indicated that the genotype of this hepatitis E outbreak was 4d. A case-control study showed that consuming pig liver (odds ratio (OR) = 7.50; 95 % confidence interval [CI]: 3.84-16.14, P < 0.001) and consuming raw fruits and vegetables (OR = 5.92; 95 % CI: 1.74-37.13, P = 0.017) were risk factors for this outbreak of Hepatitis E. Moreover, a monitoring video showed that the canteen personnel did not separate raw and cooked foods, and pig livers were cooked for only 2 min and 10 s. Approximately 1 month after the outbreak, an emergency vaccination for HEV was administered. No new cases were reported after two long incubation periods (approximately 4 months). The outbreak of HEV genotype 4d was likely caused by consuming undercooked pig liver, resulting in an attack rate of 10.66 %. This was related to the rapid stir-frying cooking method and the hygiene habit of not separating raw and cooked foods.

Prevalence of hepatitis E virus in China from 1997 to 2022: a systematic review and meta-analysis.

Introduction: Several studies have reported on hepatitis E virus (HEV) prevalence in various regions of China, but the results vary widely. Herein, we conducted a systematic review and meta-analysis to assess the seroprevalence, RNA-positive rate, genotype distribution of HEV in China, and its risk factors. Methods: We included 208 related studies involving 1,785,569 participants published between 1997 and 2022. Random-effects models were used to pool prevalence, and subgroup analyses were conducted by population, gender, age, study period, regions, and rural-urban distribution. The meta regression models and pooled odds ratios (OR) were performed to identify risk factors for HEV infections. Results: The pooled anti-HEV IgG, IgM, and Ag seroprevalence, and RNA detection rates in China from 1997 to 2022 were 23.17% [95% confidence interval (CI): 20.23-26.25], 0.73% (95% CI: 0.55-0.93), 0.12% (95% CI: 0.01-0.32), and 6.55% (95% CI: 3.46-12.05), respectively. The anti-HEV IgG seropositivity was higher in the occupational population (48.41%; 95% CI: 40.02-56.85) and older adult aged 50-59 years (40.87%; 95% CI: 31.95-50.11). The dominant genotype (GT) of hepatitis E in China was GT4. Notably, drinking non-tap water (OR = 1.82; 95% CI: 1.50-2.20), consumption of raw or undercooked meat (OR = 1.47; 95% CI: 1.17-1.84), and ethnic minorities (OR = 1.50; 95% CI: 1.29-1.73) were risk factors of anti-HEV IgG seroprevalence. Discussions: Overall, the prevalence of hepatitis E was relatively high in China, especially among older adults, ethnic minorities, and humans with occupational exposure to pigs. Thus, there is a need for preventive measures, including HEV infection screening and surveillance, health education, and hepatitis E vaccine intervention in high-risk areas and populations. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023397036.

The impact of EV71 vaccination program on hand, foot and mouth disease in Zhejiang Province, China: A negative control study.

Objective: To estimate the potential causal impact of Enterovirus A71 (EV71) vaccination program on the reduction of EV71-infected hand, foot, and mouth disease (HFMD) in Zhejiang Province. Methods: We utilized the longitudinal surveillance dataset of HFMD and EV71 vaccination in Zhejiang Province during 2010-2019. We estimated vaccine efficacy using a Bayesian structured time series (BSTS) model, and employed a negative control outcome (NCO) model to detect unmeasured confounding and reveal potential causal association. Results: We estimated that 20,132 EV71 cases (95% CI: 16,733, 23,532) were prevented by vaccination program during 2017-2019, corresponding to a reduction of 29% (95% CI: 24%, 34%). The effectiveness of vaccination increased annually, with reductions of 11% (95% CI: 6%, 16%) in 2017 and 66% (95% CI: 61%, 71%) in 2019. Children under 5 years old obtained greater benefits compared to those over 5 years. Cities with higher vaccination coverage experienced a sharper EV71 reduction compared to those with lower coverage. The NCO model detected no confounding factors in the association between vaccination and EV71 cases reduction. Conclusions: This study suggested a potential causal effect of the EV71 vaccination, highlighting the importance of achieving higher vaccine coverage to control the HFMD.

Changing spatiotemporal patterns for hepatitis of unspecified aetiology in China, 2004-2021: a population-based surveillance study.

Objectives: As global efforts continue toward the target of eliminating viral hepatitis by 2030, the emergence of acute hepatitis of unspecified aetiology (HUA) remains a concern. This study assesses the overall trends and changes in spatiotemporal patterns in HUA in China from 2004 to 2021. Methods: We extracted the incidence and mortality rates of HUA from the Public Health Data Center, the official website of the National Health Commission of the People's Republic of China, and the National Notifiable Infectious Disease Surveillance System from 2004 to 2021. We used R software, ArcGIS, Moran's statistical analysis, and joinpoint regression to examine the spatiotemporal patterns and annual percentage change in incidence and mortality of the HUA across China. Results: From 2004 to 2021, a total of 707,559 cases of HUA have been diagnosed, including 636 deaths. The proportion of HUA in viral hepatitis gradually decreased from 7.55% in 2004 to 0.72% in 2021. The annual incidence of HUA decreased sharply from 6.6957 per 100,000 population in 2004 to 0.6302 per 100,000 population in 2021, with an average annual percentage change (APC) reduction of -13.1% (p < 0.001). The same result was seen in the mortality (APC, -22.14%, from 0.0089/100,000 in 2004 to 0.0002/100,000 in 2021, p < 0.001). All Chinese provinces saw a decline in incidence and mortality. Longitudinal analysis identified the age distribution in the incidence and mortality of HUA did not change and was highest in persons aged 15-59 years, accounting for 70% of all reported cases. During the COVID-19 pandemic, no significant increase was seen in pediatric HUA cases in China. Conclusion: China is experiencing an unprecedented decline in HUA, with the lowest incidence and mortality for 18 years. However, it is still important to sensitively monitor the overall trends of HUA and further improve HUA public health policy and practice in China.

Mosquito swarm counting via attention-based multi-scale convolutional neural network.

Monitoring mosquito density to predict the risk of transmission of the virus and develop a response in advance is an important part of prevention efforts. This paper aims to estimate accurately the mosquito swarm count from a given image. To this end, we proposed an attention-based multi-scale mosquito swarm counting model that consists of the feature extraction network (FEN) and attention based multi-scale regression network (AMRN). The FEN uses VGG-16 network to extract low-level features of mosquitoes. The AMRN adopts a multi-scale convolutional neural network, and with a squeeze and excitation channel attention module in the branch with a 7 × 7 convolution kernel to extract high-level features, map the feature map to the mosquito swarm density map and estimate mosquitoes count. We collected and labelled a data set that includes 391 mosquito swarm images with 15,466 mosquitoes. Experiments show that our method performs well on the data set and achieves mean absolute error (MAE) of 1.810 and root mean square error (RMSE) of 3.467.

A cluster of two psittacosis cases among women farmers exposed to Chlamydia psittaci-infected domestic poultry in Zhejiang Province, China.

A cluster of Chlamydia psittaci (C. psittaci) cases was reported in Zhejiang Province, China, 2019. This study evaluates the extent of the outbreak and determines the source of infection. Real-time PCR and sequencing of the ompA gene of C. psittaci were performed to identify the cases, the domesticated poultry and close contacts. The index patient was a 76-year-old woman with chronic vertigo, and Case 2 was a 64-year-old female farmer with herpes zoster. Both women bought psittaci-infected chickens or ducks from the same mobile street vendor and raised them for 10 days and 23 days before fever onset. There were no direct contact between the two women. C. psittaci test was positive for the two patients, one sick chicken, three healthy ducks and the vendor's chicken cage. Phylogenetic analysis showed that all seven C. psittaci positive samples carried identical ompA genotype A of C. psittaci. Of all of the patients' 148 close contacts, none tested positive for C. psittaci, or developed acute respiratory symptoms. Both patients were discharged after a 4-week hospital stay. In conclusion, the source of this cluster was the poultry infected with C. psittaci, which occasionally cause infections in farmers, but inter-human transmission seems unlikely.

An Intelligent Medical Isolation Observation Management System Based on the Internet of Things.

BACKGROUND: Since COVID-19 (coronavirus disease 2019) was discovered in December 2019, it has spread worldwide. Early isolation and medical observation management of cases and their close contacts are the key to controlling the spread of the epidemic. However, traditional medical observation requires medical staff to measure body temperature and other vital signs face to face and record them manually. There is a general shortage of human and personal protective equipment and a high risk of occupational exposure, which seriously threaten the safety of medical staff. METHODS: We designed an intelligent crowd isolation medical observation management system framework based on the Internet of Things using wireless telemetry and big data cloud platform remote management technology. Through a smart wearable device with built-in sensors, vital sign data and geographical locations of medical observation subjects are collected and automatically uploaded to the big data monitoring platform on demand. According to the comprehensive analysis of the set threshold parameters, abnormal subjects are screened out, and activity tracking and health status monitoring for medical observation and management objectives are performed through monitoring and early warning management and post-event data traceability. In the trial of this system, the subjects wore the wristwatches designed in this study and real-time monitoring was conducted throughout the whole process. Additionally, for comparison, the traditional method was also used for these people. Medical staff came to measure their temperature twice a day. The subjects were 1,128 returned overseas Chinese from Europe. RESULTS: Compared with the traditional vital sign detection method, the system designed in this study has the advantages of a fast response, low error, stability, and good endurance. It can monitor the temperature, pulse, blood pressure, and heart rate of the monitored subject in real time. The system designed in this study and the traditional vital sign detection method were both used to monitor 1,128 close contacts with COVID-19. There were six cases of abnormal body temperature that were missed by traditional manual temperature measurement in the morning and evening, and these six cases (0.53%) were sent to the hospital for further diagnosis. The abnormal body temperature of these six cases was not found in time when the medical staff came to check the temperature on a twice-a-day basis. The system designed in this study, however, can detect the abnormal body temperature of all these six people. The sensitivity and specificity of our system were both 100%. CONCLUSION: The system designed in this study can monitor the body temperature, blood oxygen, blood pressure, heart rate, and geographical location of the monitoring subject in real time. It can be extended to COVID-19 medical observation isolation points, shelter hospitals, infectious disease wards, and nursing homes.

Codon Usage of Hepatitis E Viruses: A Comprehensive Analysis.

Hepatitis E virus (HEV) is an emerging zoonotic pathogen with multiple species and genotypes, which may be classified into human, animal, and zoonotic HEV. Codon usage bias of HEV remained unclear. This study aims to characterize the codon usage of HEV and elucidate the main drivers influencing the codon usage bias. A total of seven HEV genotypes, HEV-1 (human HEV), HEV-3 and HEV-4 (zoonotic HEV), HEV-8, HEV-B, HEV-C1, and HEV-C2 (emerging animal HEV), were included in the study. Complete coding sequences, ORF1, ORF2, and ORF3, were accordingly obtained in the GenBank. Except for HEV-8, the other six genotypes tended to use codons ending in G/C. Based on the analysis of relatively synonymous codon usage (RSCU) and principal component analysis (PCA), codon usage bias was determined for HEV genotypes. Codon usage bias differed widely across human, zoonotic, and animal HEV genotypes; furthermore, it varied within certain genotypes such as HEV-4, HEV-8, and HEV-C1. In addition, dinucleotide abundance revealed that HEV was affected by translation selection to form a unique dinucleotide usage pattern. Moreover, parity rule 2 analysis (PR2), effective codon number (ENC)-plot, and neutrality analysis were jointly performed. Natural selection played a leading role in forming HEV codon usage bias, which was predominant in HEV-1, HEV-3, HEV-B and HEV-C1, while affected HEV-4, HEV-8, and HEV-C2 in combination with mutation pressure. Our findings may provide insights into HEV evolution and codon usage bias.

Codon usage of host-specific P genotypes (VP4) in group A rotavirus.

BACKGROUND: Group A rotavirus (RVA) is a common causative agent of acute gastroenteritis in infants and young children worldwide. RVA P genotypes, determined by VP4 sequences, have been confirmed to infect humans and animals. However, their codon usage patterns that are essential to obtain insights into the viral evolution, host adaptability, and genetic characterization remained unclear, especially across animal hosts. RESULTS: We performed a comprehensive codon usage analysis of eight host-specific RVA P genotypes, including human RVA (P[4] and P[8]), porcine RVA (P[13] and P[23]), and zoonotic RVA (P[1], P[6], P[7] and P[19]), based on 233 VP4 complete coding sequences. Nucleotide composition, relative synonymous codon usage (RSCU), and effective number of codons (ENC) were calculated. Principal component analysis (PCA) based on RSCU values was used to explore the codon usage patterns of different RVA P genotypes. In addition, mutation pressure and natural selection were identified by using ENC-plot, parity rule 2 plot, and neutrality plot analyses. All VP4 sequences preferred using A/U nucleotides (A: 0.354-0.377, U: 0.267-0.314) than G/C nucleotides across genotypes. Similarly, majority of commonly used synonymous codons were likely to end with A/U nucleotides (A: 9/18-12/18, U: 6/18-9/18). In PCA, human, porcine, and zoonotic genotypes clustered separately in terms of RSCU values, indicating the host-specific codon usage patterns; however, porcine and zoonotic genotypes were partly overlapped. Human genotypes, P[4] and P[8], had stronger codon usage bias, as indicated by more over-represented codons and lower ENC, compared to porcine and zoonotic genotypes. Moreover, natural selection was determined to be a predominant driver in shaping the codon usage bias across the eight P genotypes. In addition, mutation pressure contributed to the codon usage bias of human genotypes. CONCLUSIONS: Our study identified a strong codon usage bias of human RVA P genotypes attributable to both natural selection and mutation pressure, whereas similar codon usage bias between porcine and zoonotic genotypes predominantly attributable to natural selection. It further suggests possible cross-species transmission. Therefore, it warrants further surveillance of RVA P genotypes for early identification of zoonotic infection.

Seasonality and Meteorological Factors Associated With Different Hand, Foot, and Mouth Disease: Serotype-Specific Analysis From 2010 to 2018 in Zhejiang Province, China.

Background: Hand-foot-mouth disease (HFMD) is caused by a group of enteroviruses (EVs) and has a high incidence in children; some subtypes had high mortalities in children. The subtypes of HFMD had a different incidence across seasons. Thereby, we suspect that the infection of HFMD is varied by meteorological factors. However, studies examining serotype-specific associations between meteorological factors and HFMD incidence were rare. Methods: We obtained all HFMD cases that occurred from 1 January 2010 to 31 December 2018 in Zhejiang province from the China Information System for Disease Control and Prevention (CISDCP). Daily meteorological data for Zhejiang province were provided by the China Methodological Data Sharing Service System and linked to HFMD cases based on residential addresses and dates of onset. The associations between meteorological factors and HFMDs were examined using distributed lag non-linear models (DLNMs) for each serotype. Results: Overall, the incidences of all HFMD cases were increasing in study years, while the number of severe and fatality cases were decreasing. The dominant serotypes varied by study year. The association between temperature and incidence of both CVA16 and EV71 serotypes showed an inverted U shape. The risk ratio for CVA16 was increasing when temperature is 11-25°C, reaching the maximum RR at 18°C and humidity above 77% can promote the occurrence with CVA16, and temperature between 11 and 32°C with the maximum RR at 21°C and relative humidity above 77% are risk conditions of the occurrence of HFMD associated with EV71. For other enteroviruses causing HFMD, temperature above 11°C and humidity above 76% have a risk effect. CVA16, EV71, and all enteroviruses of HFMD have a maximum effect on lag day 0, and temperature is 35, 34, and 33°C respectively, while the enteroviruses of HFMD other than EV71 and CVA16 has a maximum effect when the temperature is 33°C and the lag time is 7 days. Conclusion: This study shows that meteorological factors have an effect on the occurrence of different HFMD serotypes. Local control strategies for public health should be taken in time to prevent and reduce the risk of HFMD while the weather is getting warmer and wetter.

Improper handling of vomitus as a risk factor in the human norovirus outbreak in a kindergarten in Wuyi County, Zhejiang Province, China.

This study investigated an outbreak in a kindergarten in Wuyi County of acute gastroenteritis concerning a large number of students and teachers. We performed a case-control study, and collected information on the layout of the school, symptoms, onset time of all cases and vomiting sites. A total of 62 individuals fit the definition of probable cases; among these, there were 19 cases of laboratory-confirmed norovirus infection. Nausea and vomiting were the most common symptoms in the outbreak. Seven student norovirus patients vomited in the school. The odds ratio (OR) of norovirus illness was 15.75 times higher among teachers who handled or interacted with student vomitus without respiratory protection than compared to those without this type of exposure (OR 15.75, 95% CI 1.75-141.40). Nine samples were successfully genotyped; eight samples were norovirus GII.2[P16], one sample was norovirus GII.4 Sydney[P16]. This study revealed that improper handling of vomitus is a risk factor of norovirus infection. Therefore, more attention should be given to train school staff in knowledge of disinfection.

Using codon usage analysis to speculate potential animal hosts of hepatitis E virus: An exploratory study.

There has been an increase in the reported number of animals worldwide that carry the hepatitis E virus (HEV). This study aimed to explore potential animal hosts for HEV through codon usage analysis. Full-length HEV sequences of six genotypes as well as codon usage of potential animal hosts were collected. Moreover, nucleotide composition and codon usage bias were compared across HEV genotypes and animal hosts. Based on the analysis for human HEV-1 and humans, the results were basically consistent with epidemiology evidence. Among 17 potential animal hosts, all HEV genotypes exhibited a preference for guanine/cytosine in the third position of synonymous codons. Furthermore, non-human primates and humans have large high-frequency codons identical to HEV in addition to a high correlation of codon fraction with HEV. Some animals in close contact with humans showed high preference for HEV, including cattle, dogs, and rats with HEV-A, cats, dogs, and swine with HEV-C1. Codon usage bias has limited efficiency in determining the hosts for HEV, but it may provide indicative clues for potential animal hosts when combined with experimental and epidemiological evidence.

Impact of a community-based health education intervention on awareness of influenza, pneumonia, and vaccination intention in chronic patients.

The study aimed to examine the impact of a community-based health education intervention on the awareness and attitude of influenza and Streptococcus pneumoniae vaccination in patients with chronic diseases. We selected study participants from two counties in Jiaxing City, Zhejiang Province. We conducted a household baseline survey with quarterly follow-up and health education for all chronic disease patients in the area. A total of 720 patients with chronic diseases were included in two rounds of questionnaire surveys before and after a year-long health education related to the influenza and Streptococcus pneumoniae vaccination. Before the community education, 59.9% and 59.6% of study participants self-report the awareness of the hazards of influenza and pneumonia, respectively; while only 17.7% and 6.0% study participants self-reported awareness of the influenza or pneumonia vaccination, respectively; the self-reported vaccination rates were 1.3% and 0% for influenza and pneumonia, respectively. One year after the intervention, all rates were increased significantly, but the influenza vaccination rate was still far below the WHO minimum target level (75%). The main reason for not getting vaccinated reported by study participants was that participants thought they were in good health and would not become sick easily. There was no statistically significant difference between the impacts of health care practitioners' and general practitioners' recommendations for vaccination. Continued and pertinent health education has a significant impact on influenza and pneumonia vaccination in patients with chronic diseases.

Muscle destruction caused by coxsackievirus A10 in gerbils: Construction of a novel animal model for antiviral evaluation.

The morbidity and mortality of coxsackievirus A10 (CVA10)-associated hand, foot, and mouth disease (HFMD) have been increasing in recent years, while few studies on the vaccine and animal model of CVA10 have been reported. Here, we first established a CVA10-infected gerbil model and employed it to evaluate the immunoprotective effect of an inactivated CVA10 vaccine. The results showed that gerbils up to the age of 14 days were fully susceptible to CVA10, and all died within five days post-infection by intraperitoneal inoculation. Lethargy, wasting, hind-limb paralysis, and even death could be observed in the CVA10-infected gerbils. Pathological examination suggested that CVA10 has a strong tropism toward muscle tissue, and muscle bundle fracture and muscular fibers necrosis were observed in the limb muscles. Additionally, active immunization results showed that gerbils immunized with the inactivated CVA10 vaccine were 100 % protected from lethal CVA10 challenge. The antisera from vaccinated gerbils also showed high neutralizing titers against CVA10. Based on these results, the CVA10-infected gerbil model was a suitable tool for analyzing the pathogenesis of CVA10 and assessing the protective efficacy of CVA10 candidate vaccines.

Epidemiological features and viral shedding in children with SARS-CoV-2 infection.

A pandemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection broke out all over the world; however, epidemiological data and viral shedding in pediatric patients are limited. We conducted a retrospective, multicenter study, and followed-up with all children from the families with SARS-CoV-2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS-CoV-2 RNA with real-time reverse transcription PCR method, and epidemiological data between children and adults in the same families were compared. Effect of antiviral therapy was evaluated observationally and fecal-viral excretion times among groups with different antiviral regiments were compared with Kaplan-Meier plot. By 29 February 2020, 1298 cases from 883 families were confirmed with SARS-CoV-2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty-three children had coronavirus disease 2019 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS-CoV-2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal-viral-excreting children. Children have lower susceptibility of SARS-CoV-2 infection, longer incubation, and fecal-viral excretion time. Positive results of fecal SARS-CoV-2 RNA detection were not used as indication for hospitalization or quarantine.

Development and comparison of forecast models of hand-foot-mouth disease with meteorological factors.

Hand-foot-mouth disease (HFMD) is an acute intestinal virus infectious disease which is one of major public health problems in mainland China. Previous studies indicated that HFMD was significantly influenced by climatic factors, but the associated factors were different in different areas and few study on HFMD forecast models was conducted. Here, we analyzed epidemiological characteristics of HFMD in Yiwu City, Zhejiang Province and constructed three forecast models. Overall, a total of 32554 HFMD cases were reported and 12 cases deceased in Yiwu City, Zhejiang Province. The incidence of HFMD peaked every other year and the curve of HFMD incidence had an approximately W-shape. The majority of HFMD cases were children and 95.76% cases aged ≤5 years old from 2008 to 2016. Furthermore, we constructed and compared three forecast models using autoregressive integrated moving average (ARIMA) model, negative binomial regression model (NBM), and quasi-Poisson generalized additive model (GAM). All the three models had high agreements between predicted values and observed values, while GAM fitted best. The exposure-response curve of monthly mean temperature and HFMD was approximately V-shaped. Our study explored epidemiological characteristics of HFMD in Yiwu City and provided accurate methods for early warning which would be great importance for the control and prevention of HFMD.

An adult gerbil model for evaluating potential coxsackievirus A16 vaccine candidates.

A suitable animal model of CVA16 infection is crucial in order to understand its pathogenesis and to help develop antiviral vaccines or screen therapeutic drugs. The neonatal mouse model has a short sensitivity period to CA16 infection, which is a major limitation. In this study, we demonstrate that adult (60-day-old) gerbils are susceptible to CVA16 infection at high doses (108.0 TCID50). A clinical isolate strain of CVA16 was inoculated intraperitoneally into adult gerbils, which subsequently developed significant clinical symptoms, including hind limb weakness, paralysis of one or both hind limbs, tremors, and eventual death from neurological disorders. Real-time RT-PCR revealed that viral loads in the spinal cord and brainstem were higher than those in other organs/tissues. Histopathological changes, such as neuronal degeneration, neuronal loss, and neuronophagia, were observed in the spinal cord, brainstem, and heart muscle, along with necrotizing myositis. Gerbils receiving both prime and boost immunizations of alum adjuvant inactivated vaccine exhibited no clinical signs of disease or mortality following challenge by CVA16, whereas 80% of control animals showed obvious clinical signs, including slowness, paralysis of one or both hind limbs, and eventual death, suggesting that the CVA16 vaccine can fully protect gerbils against CVA16 challenge. These results demonstrate that an adult gerbil model provides us with a useful tool for studying the pathogenesis and evaluating antiviral reagents of CVA16 infection. The development of this animal model would also be conducive to screening promising CVA16 vaccine candidates as well as further vaccination evaluation.

Acute sporadic hepatitis E in the Zhejiang coastal area of China: a 14-year hospital-based surveillance study.

BACKGROUND: To examine the epidemiological trends and changes of hepatitis E virus (HEV) infection and the potential risk factors for severe infection in the Zhejiang eastern coastal area of China. METHODS: We analyzed statutory hepatitis E cases notifications and inpatient data held by the national surveillance and hospital information systems in Wenzhou, Taizhou, Ningbo, and Zhoushan cities of the Zhejiang eastern coastal area of China. RESULTS: Nine thousand four hundred sixteen hepatitis E cases were reported from 2004 to 2017, with an average incidence of 2.94 per 100,000. The overall death rate was 0.06% (6/9416). A gradual decline of hepatitis E cases was found in the coastal areas since 2007, while a rise was identified in the non-coastal areas. Annual incidence in non-coastal cities was much higher than that in coastal cities (4.345 vs. 2.945 per 100,000, relative risk = 1.5, P value < 0.001). The mean age was 52 years old and 50.55 years with a male-to-female ratio of 2.32:1 and 2.21:1 in coastal and noncoastal areas respectively (all P > 0.05). Hepatitis E cases prevalence increased with age, highest among men in their 70s (9.02 vs. 11.33 per 100,000) and women in their 60s (3.94 vs. 4.66 per 100,000) groups for both coastal and noncoastal areas respectively. A clear seasonal pattern was observed, with a peak in March (0.4429 per 100,000) in coastal areas. 202 inpatients were documented, of which 50.50% (102/202) were severe cases. Male individuals with alcohol consumption, alcohol hepatic diseases, and superinfection were the three independent highest risks for severe infections (all with P value < 0.05). CONCLUSIONS: This is to our knowledge the largest epidemiological study of hepatitis E cases in the eastern coastal area of Zhejiang province of China. The patterns of infection across the coastal areas were similar to those of the non-coastal areas, but the incidence was substantially lower and decreased gradually since 2007.

Sero-molecular epidemiology of enterovirus-associated encephalitis in Zhejiang Province, China, from 2014 to 2017.

BACKGROUND: Recently, both sporadic and outbreak aseptic meningitis caused by enteroviruses have been reported in Zhejiang Province based on a surveillance system. METHODS: This study analysed the epidemiologic features, phylogenetic characteristics and prevalence of enterovirus neutralizing antibodies (nAbs) from 2014 to 2017 in Zhejiang Province. RESULTS: A total of 584 samples were collected. Males accounted for 66.07% while females accounted for 33.93%. The median age was 6 years (range: 1-15 years). Cases peaked in May and August (81.17%) and 162 cases (28.93%) occurred in June. We detected 15 serotypes, some of which (E6, E9, E18 and E30) were the dominant serotypes prevalent in different years and geographical regions. Phylogenetic results revealed that all of the isolates from this study belonged to the human enterovirus B family. A total of 329 subjects sampled from a healthy population were tested for nAbs against B5, E6 and E30 in Rui'an county in 2015. The seropositive rate of E30 in each age group was significantly higher than that of the other serotypes. CONCLUSION: Enterovirus-associated encephalitis pathogens circulating in Zhejiang caused sporadic aseptic meningitis in children. The level of nAbs against human enterovirus reflects the history of previous infections in different age groups. Therefore, additional surveillance sites and more precise seroprevalence studies based on these populations are required to gain better insight into the epidemiology of enterovirus-associated encephalitis in Zhejiang Province.