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Hand, foot, and mouth disease (HFMD) is a prevalent acute infectious disease caused by enteroviruses, presenting substantial public health challenges in Shanghai, especially among children. The dynamic nature of HFMD's etiology necessitates an ongoing evaluation of its epidemiological and virological trends to inform effective control strategies. This study aims to investigate the epidemiological patterns and viral evolution of HFMD in Fengxian District, Shanghai, China, with a focus on shifts in predominant viral strains over a 14-year period. We conducted a retrospective analysis of HFMD cases reported to the National Notifiable Disease Reporting System in Fengxian District from January 1, 2009 to December 31, 2022. Epidemiological trends, strain prevalence, and demographic impacts were assessed. A total of 27,272 HFMD cases were documented during the study period, with incidence showing pronounced seasonal fluctuations—peaking in spring and summer and a lesser peak in autumn. The disease incidence demonstrated significant positive correlations with several meteorological variables: daily average temperature (r = 0.30, P < 0.05), relative humidity (r = 0.20, P < 0.05), wind speed (r = 0.17, P < 0.05), and precipitation (r = 0.17, P < 0.05). Geographically, Nanqiao Town, Fengcheng Town, and Xidu Subdistrict reported the highest incidence rates. The demographic analysis revealed a male-to-female ratio of 1.60:1, predominantly affecting children aged 1–3 years. Prior to 2017, Enterovirus 71 (EV71) and Coxsackievirus A16 (CoxA16) were the primary detected strains; post-2017, Coxsackievirus A6 (CoxA6) emerged as the dominant strain. Statistical analysis confirmed significant year-to-year variations in virus detection rates, with decreasing trends for EV71 and other enteroviruses and an increasing trend for CoxA6. The findings indicate a distinct seasonal incidence of HFMD in Fengxian District. This study underscores the need for targeted public health education, enhanced surveillance, and proactive measures in childcare facilities to mitigate disease spread during peak seasons. Moreover, the evolving viral landscape warrants accelerated efforts in vaccine development against new strains to reduce HFMD incidence. [ABSTRACT FROM AUTHOR]

Enterovirus A71 (EV-A71) causes hand, foot, and mouth disease in infants and children with potential for fatal complications such as encephalitis and acute flaccid myelitis. This study examined the long-term immunity conferred by EV71vac, an inactivated EV-A71 vaccine adjuvanted with aluminum phosphate, in children from the age of 2 months to <6 years, for up to 5 years after the first immunization. A total of 227 participants between 2 months and <6 years of age who had previously received either EV71vac or placebo in the phase two clinical study were enrolled. Subjects were divided into age groups: 2 years to <6 years (Group 2b), 6 months to <2 years (Group 2c), and 2 months to <6 months (Group 2d). At Year 5, the neutralizing antibody titers against the B4 subgenotype remained high at 621.38 to 978.20, 841.40 to 1159.93, and 477.71 to 745.07 for Groups 2b, 2c, and 2d, respectively. Cross-neutralizing titers at Year 5 remained high against B5 and C4a subgenotypes, respectively. No long-term safety issues were reported. Our study provides novel insights into the long-term immunity conferred by EV71vac in children aged from two months to six years, particularly in those who received EV71vac between two and six months of age. [ABSTRACT FROM AUTHOR]

Abstract Hand, foot, and mouth disease (HFMD) is a prevalent acute infectious disease caused by enteroviruses, presenting substantial public health challenges in Shanghai, especially among children. The dynamic nature of HFMD’s etiology necessitates an ongoing evaluation of its epidemiological and virological trends to inform effective control strategies. This study aims to investigate the epidemiological patterns and viral evolution of HFMD in Fengxian District, Shanghai, China, with a focus on shifts in predominant viral strains over a 14-year period. We conducted a retrospective analysis of HFMD cases reported to the National Notifiable Disease Reporting System in Fengxian District from January 1, 2009 to December 31, 2022. Epidemiological trends, strain prevalence, and demographic impacts were assessed. A total of 27,272 HFMD cases were documented during the study period, with incidence showing pronounced seasonal fluctuations—peaking in spring and summer and a lesser peak in autumn. The disease incidence demonstrated significant positive correlations with several meteorological variables: daily average temperature (r = 0.30, P

ObjectiveTo analyze the epidemiological characteristics and etiology of clustered outbreaks of hand， foot， and mouth disease （HFMD） in Pudong New Area， Shanghai from 2017 to 2022， and to provide a scientific basis for the prevention and control of HFMD in the area.MethodsThe data related to HFMD clustered outbreaks from 2017 to 2022 were obtained from the Pudong New Area HFMD outbreak database. Descriptive analysis was conducted to explore the outbreak scope， seasonal characteristics， distribution of occurrence settings， and etiological composition.ResultsFrom 2017 to 2022， Pudong New Area reported a total of 2 547 HFMD clusters， involving 8 884 cases， with an average of 3.49 cases per event. The majority of events （78.52%） had between 2 and 4 cases. The peak reporting periods for clustered HFMD from 2017 to 2019 and in 2021 were during the summer （May‒July） and autumn （September‒November）. The seasonal pattern was less distinct in 2020 and 2022， likely due to the impact of the COVID-19 pandemic. The majority of clustered outbreaks occurred in childcare facilities （44.64%）， followed by households/neighborhood committees （44.21%）， with schools accounting for a smaller proportion （12.39%）. The etiology revealed the coexistence of multiple enterovirus genotypes， with a positive detection rate of 60.46%， and CoxA6 being the dominant strain.ConclusionHFMD clustered outbreaks in Pudong New Area show fluctuating trends， with significant yearly differences in the number of incidents. The predominant seasons for outbreaks are summer and autumn， with CoxA6 identified as the dominant strain. The implementation of prevention and control measures for COVID-19 significantly reduced the occurrence of HFMD outbreaks. Continuous monitoring and focus on large-scale clustered outbreaks in key institutions are essential for the future.

Hand, foot and mouth disease is a recurring contagious infection in children living under poor sanitary conditions, especially in developing countries, where a substantial increase in the disease has been reported in recent years. The study aimed to describe and analyze the occurrence of such disease in children, focusing on the most outstanding theoretical aspects that characterize it. For this purpose, a systematic review of the literature was conducted in PubMed, Google Scholar and Latin American and Caribbean Literature in Health Sciences (LILACS) using logical operators such as "EMPB" OR "Coxsackie A16" AND "Children" AND "Coxsackievirus Infections" AND "Child". A total of 584 research studies in Spanish and English published between 2010 and 2022 were identified, from which, after a scientific quality assessment process using checklists, quality criteria and relevant strength of recommendation and the PRISMA method, 40 articles were selected, to which three gray literature records were added, and 43 records were selected for quantitative data analysis. Hand, foot and mouth disease has a higher incidence in the Asian continent (India, Singapore, Japan and China), where epidemic outbreaks occur every year, mainly affecting the child population. It is caused by several serotypes such as A5, A7, A10, B1, B2, B3 and B5; however, Coxsackievirus A16 (CA16) and Enterovirus 71 (EV-71) are the most frequent among children. The disease causes fever, papulovesicular rash on the hands, feet and genitalia, as well as ulcerative lesions in the mouth. Its incubation period is four to six days, and it is transmitted by direct contact with secretions, fecal material or contaminated objects; its diagnosis is clinical and based on the patient's epidemiological history. As there is no specific treatment, only general measures are taken to alleviate the symptoms and prevent dehydration. Currently, there are outbreaks and serotypes that cause various complications such as encephalitis, myocarditis, hepatitis, acute hemorrhagic conjunctivitis, enteric diseases and herpangina, among others. For this reason, strict epidemiological surveillance of cases and contacts is required, along with education and communication interventions that reduce the risks of spread and infection. [ABSTRACT FROM AUTHOR]

Hand, foot, and mouth disease (HFMD) poses a significant public health threat primarily caused by four major enteroviruses: enterovirus 71 (EV71), coxsackieviruses A16, A10, and A6. Broadly protective immune responses are essential for complete protection against these major enteroviruses. In this study, we designed a new tetravalent immunogen for HFMD, validated it in silico , in vivo evaluated the immunogenicity of the DNA-based tetravalent vaccine in mice, and identified immunogenic B-cell and T-cell epitopes. A new tetravalent immunogen, VP1me, was designed based on the chimeric protein and epitope-based vaccine principles. It contains a complete EV71 VP1 protein and six reported neutralizing B-cell epitopes derived from the four major enteroviruses causing HFMD. In silico validation using multiple immunoinformatic tools indicated good attributes of the VP1me immunogen suitable for vaccine development. The VP1me-based DNA vaccine efficiently induced both humoral and cellular immune responses in BALB/cAJcl mice. A combination of in silico prediction and immunoassays enabled the identification of immunogenic linear B-cell and CD8 T-cell epitopes within the VP1me immunogen. Immunodominant linear B-cell epitopes were identified in six regions of VP1me, with one epitope located at the N-terminus of the VP1 protein (aa 9–23) regarded as a novel epitope. Interestingly, some B-cell epitopes could also induce the CD8 T-cell response, suggesting their dual functions in immune stimulation. These results lay the groundwork for further development of VP1me as a new vaccine candidate. [ABSTRACT FROM AUTHOR]

Background: The evidence on the effects of extreme meteorological conditions and high air pollution levels on incidence of hand, foot and mouth disease (HFMD) is limited. Moreover, results of the available studies are inconsistent. Further investigations are imperative to elucidate the specific issue. Methods: Data on the daily cases of HFMD, meteorological factors and air pollution were obtained from 2017 to 2022 in Jining City. We employed distributed lag nonlinear model (DLNM) incorporated with Poisson regression to explore the impacts of extreme meteorological conditions and air pollution on HFMD incidence. Results: We found that there were nonlinear relationships between temperature, wind speed, PM2.5, SO2, O3 and HFMD. The cumulative risk of extreme high temperature was higher at the 95th percentile (P95th) than at the 90th percentile(P90th), and the RR values for both reached their maximum at 10-day lag (P95th RR = 1.880 (1.261–2.804), P90th RR = 1.787 (1.244–2.569)), the hazardous effect of extreme low temperatures on HFMD is faster than that of extreme high temperatures. The cumulative effect of extreme low wind speeds reached its maximum at 14-day lag (P95th RR = 1.702 (1.389-2.085), P90th RR = 1.498(1.283–1.750)). The cumulative effect of PM2.5 concentration at the P90th was largest at 14-day lag (RR = 1.637 (1.069–2.506)), and the cumulative effect at the P95th was largest at 10-day lag (RR = 1.569 (1.021–2.411)). High SO2 concentration at the P95th at 14-day lag was associated with higher risk for HFMD (RR: 1.425 (1.001–2.030)). Conclusion: Our findings suggest that high temperature, low wind speed, and high concentrations of PM2.5 and SO2 are associated with an increased risk of HFMD. This study not only adds insights to the understanding of the impact of extreme meteorological conditions and high levels of air pollutants on HFMD incidence but also holds practical significance for the development and enhancement of an early warning system for HFMD. [ABSTRACT FROM AUTHOR]

Abstract Background Since December 2019, COVID-19 has spread rapidly around the world, and studies have shown that measures to prevent COVID-19 can largely reduce the spread of other infectious diseases. This study explored the impact of the COVID-19 outbreak and interventions on the incidence of HFMD. Methods We gathered data on the prevalence of HFMD from the Children’s Hospital Affiliated to Zhengzhou University. An autoregressive integrated moving average model was constructed using HFMD incidence data from 2014 to 2019, the number of cases predicted from 2020 to 2022 was predicted, and the predicted values were compared with the actual measurements. Results From January 2014 to October 2022, the Children’s Hospital of Zhengzhou University admitted 103,995 children with HFMD. The average number of cases of HFMD from 2020 to 2022 was 4,946, a significant decrease from 14,859 cases from 2014 to 2019. We confirmed the best ARIMA (2,0,0) (1,1,0)12 model. From 2020 to 2022, the yearly number of cases decreased by 46.58%, 75.54%, and 66.16%, respectively, compared with the forecasted incidence. Trends in incidence across sexes and ages displayed patterns similar to those overall. Conclusions The COVID-19 outbreak and interventions reduced the incidence of HFMD compared to that before the outbreak. Strengthening public health interventions remains a priority in the prevention of HFMD.

Objective To explore changes in prevalence characteristics and pathogen spectrum of severe hand, foot and mouth disease (HFMD) in Henan province before and after launching vaccination of enterovirus 71 (EV71) vaccine for developing strategies on HFMD prevention and control. MethodsThe data on all HFMD cases registered in Henan province from 2014 through 2020 were extracted from the Infectious Disease Report Information Management System of the Chinese Center for Disease Control and Prevention. Descriptive statistics was performed on the data to assess changes in constituent ratio of and distribution of pathogens detected in the severe HFMD cases before and after of the launch of EV71 vaccination from 2017 in the province. ResultsDuring 2014 to 2020, totally 13 535 severe HFMD cases were reported in the province, with a male-to-female ratio of 1.58:1 and the most (97.34%, 13 175) of the cases were children under the age of 5 years. A unimodal pattern throughout the year was observed in the incidence of severe HFMD, with the peak season mainly occurring from April to July and 75.53% (10 223) of the registered severe cases occurred during the season. The ratio of severe cases decreased significantly from 3.19% (10 948/343 585) for the period of 2014 – 2016 to 0.93% (2 587/278 075) for the period of 2017 – 2020 with the launch of EV71 vaccination (χ2 = 3672.874, P < 0.001). For the severe HFMD cases reported during 2017 – 2020, the proportion of the cases of one- and two-year-old decreased significantly from 47.23% to 42.83% (χ2 = 16.311, P1 < 0.001) and from 25.57% to 22.84% (χ2 = 8.255, P2 = 0.004); but the proportion of the cases occurred in preschool care facilities increased significantly from 9.13% to 16.24% (χ2 = 112.359, P < 0.001). Following the promotion of EV71 vaccination among the public, the detection rate of EV71 among the severe HFMD cases decreased from 65.14% to 29.63%, while that of other enteroviruses increased from 27.49% to 56.13%, indicating that other enteroviruses became dominant serotypes for pathogens of HFMD epidemic. ConclusionThe ratio of severe cases among registered HFMD cases had significantly decreased after the launch of the EV71 vaccination in Henan province and the dominant pathogen of HFMD changed from EV71 to other enteroviruses. The results suggest that EV71 vaccination ought to be promoted among key populations and in peak season to prevent severe HFMD epidemic.

ObjectiveTo analyze epidemiological characteristics and determinants of hand, foot, and mouth disease (HFMD) outbreaks in Jiangsu province over the period of 2010 to 2022 for developing local HFMD prevention and control measures. MethodsThe data on 238 HFMD outbreaks reported in Jiangsu province from 2010 through 2022 were collected from the Public Health Emergency Information Management System of the Chinese Center for Disease Control and Prevention. The epidemiological characteristics of the HFMD outbreaks were described using statistical analysis. The spatial distribution characteristics of the outbreaks were analyzed using ArcGIS10.7 and GeoDa1.18 software. The main influencing factors of the incidence and duration of the HFMD outbreaks were analyzed using a unconditional multivariate logistic regression model. ResultsA total of 238 outbreaks of HFMD were reported in the province during the study period, involving a total of 167 934 individuals exposed to the epidemic and resulting in 5 296 confirmed cases. The median attack rate for these outbreaks was 3.43%. The HFMD outbreaks were more frequently observed during the spring season (March to May) and autumn season (September to November), accounting for 36.97% and 29.83% of all outbreaks respectively. Furthermore, 68.07% of the outbreaks occurred in the southern region of the province. Almost all (99.16%) of these outbreaks took place in childcare institutions and schools. The time interval between incidence and identification ranged from 0 to 44 days (median = 8 days), while the outbreak duration varied from 3 to 78 days, with a median duration of 15.5 days. The predominant strains responsible for the HFMD outbreaks differed by year: Coxsackievirus A16 (Cox A16) was prevalent in 2010, 2012, 2014, 2015, 2018, 2019, and 2021; enterovirus 71 (EV71) dominated in 2011, 2013, and 2017; Coxsackievirus (Cox A6) was prominent in 2020; and both Cox A16 and EV71 were significant contributors in 2016; finally, Cox A16 and Cox A6 were identified as major strains in 2022. Geographically speaking, the HFMD outbreaks exhibited an aggregated distribution pattern with high-high clustering areas primarily located within three districts in Wuxi city, a district and a prefecture in Changzhou city, and three districts in Lianyungang city. Results obtained from multivariate logistic regression analysis indicated that certain characteristics were associated with higher attack rates among these outbreaks. These included being caused by Cox A16 or multiple viruses, having an epidemic duration lasting 21 days or longer, and being reported by schools, health centers, and education department. On the other hand, outbreaks occurring outside childcare institutions tended to have lower attack rates. Additionally, outbreaks classified as general epidemics, taking place in towns, and having a lag identification time of 15 days or more were more likely to have a longer epidemic duration. ConclusionThe HFMD outbreaks in Jiangsu province from 2010 to 2022 predominantly occurred during the spring and autumn seasons, with Cox A16 as the predominant strain. The southern region of Jiangsu province was the clustering area for the HFMD outbreaks. The main factors influencing the incidence and duration of these outbreaks include the outbreak setting, type of predominant virus, epidemic duration, reporting institution and epidemic level, location of the site, and lag time of epidemic identification.

Background: Enterovirus A71 (EV-A71) is capable of causing hand, foot and mouth disease (HFMD), which may lead to neurological sequelae and even death. As EV-A71 is resistant to environmental changes and mutates easily, there is still a lack of effective treatments or globally available vaccines. Aim of Review: For more than 50 years since the HFMD epidemic, related drug research has been conducted. Progress in this area can promote the further application of existing potential drugs and develop more efficient and safe antiviral drugs, and provide useful reference for protecting the younger generation and maintaining public health security. Key Scientific Concepts of Review: At present, researchers have identified hundreds of EV-A71 inhibitors based on screening repurposed drugs, targeted structural design, and rational modification of previously effective drugs as the main development strategies. This review systematically introduces the current potential drugs to inhibit EV-A71 infection, including viral inhibitors targeting key sites such as the viral capsid, RNA-dependent RNA polymerase (RdRp), 2C protein, internal ribosome entry site (IRES), 3C proteinase (3Cpro), and 2A proteinase (2Apro), starting from each stage of the viral life cycle. Meanwhile, the progress of host-targeting antiviral drugs and their development are summarized in terms of regulating host immunity, inhibiting autophagy or apoptosis, and regulating the cellular redox environment. In addition, the current clinical methods for the prevention and treatment of HFMD are summarized and discussed with the aim of providing support and recommendations for the treatment of enterovirus infections including EV-A71.

Background: Since December 2019, COVID-19 has spread rapidly around the world, and studies have shown that measures to prevent COVID-19 can largely reduce the spread of other infectious diseases. This study explored the impact of the COVID-19 outbreak and interventions on the incidence of HFMD. Methods: We gathered data on the prevalence of HFMD from the Children's Hospital Affiliated to Zhengzhou University. An autoregressive integrated moving average model was constructed using HFMD incidence data from 2014 to 2019, the number of cases predicted from 2020 to 2022 was predicted, and the predicted values were compared with the actual measurements. Results: From January 2014 to October 2022, the Children's Hospital of Zhengzhou University admitted 103,995 children with HFMD. The average number of cases of HFMD from 2020 to 2022 was 4,946, a significant decrease from 14,859 cases from 2014 to 2019. We confirmed the best ARIMA (2,0,0) (1,1,0)12 model. From 2020 to 2022, the yearly number of cases decreased by 46.58%, 75.54%, and 66.16%, respectively, compared with the forecasted incidence. Trends in incidence across sexes and ages displayed patterns similar to those overall. Conclusions: The COVID-19 outbreak and interventions reduced the incidence of HFMD compared to that before the outbreak. Strengthening public health interventions remains a priority in the prevention of HFMD. [ABSTRACT FROM AUTHOR]

Vaccination has been proven effective against infection with enterovirus A71 (EV-A71) in clinical trials, but vaccine effectiveness in real-world situations remains incompletely understood. Furthermore, it is not clear whether previous vaccination will result in symptom attenuation among post-vaccinated cases. Based on long-term data extracted from the only designed referral hospital for infectious diseases, we used a test-negative case-control design and multivariate logistic regression models to analyze the effectiveness of EV-A71 vaccine against hand, foot and mouth disease (HFMD). And then, generalized linear regression models were used to evaluate the associations between prior vaccination and disease profiles. We selected 4883 inpatients for vaccine efficacy estimations and 2188 inpatients for disease profile comparisons. Vaccine effectiveness against EV-A71-induced HFMD for complete vaccination was 63.4 % and 51.7 % for partial vaccination. The vaccine effectiveness was higher among cases received the first dose within 12 months. No protection was observed against coxsackievirus (CV) A6-, CV-A10- or CV-A16-associated HFMD among children regardless of vaccination status. Completely vaccinated cases had shorter hospital stay and disease course compared to unvaccinated cases (P < 0.05). These findings reiterate the need to continue the development of a multivalent vaccine or combined vaccines, and have implications for introducing optimized vaccination strategies. [ABSTRACT FROM AUTHOR]

[Display omitted] • The structural characteristics of EV71 and the mechanism of infection were reviewed. • Anti-EV71 drug candidates for different targets based on in vitro , animal, and clinical data were summarized. • The main therapeutic approaches for EV71 infection were discussed, and suggestions were made for further drug development. Enterovirus A71 (EV-A71) is capable of causing hand, foot and mouth disease (HFMD), which may lead to neurological sequelae and even death. As EV-A71 is resistant to environmental changes and mutates easily, there is still a lack of effective treatments or globally available vaccines. For more than 50 years since the HFMD epidemic, related drug research has been conducted. Progress in this area can promote the further application of existing potential drugs and develop more efficient and safe antiviral drugs, and provide useful reference for protecting the younger generation and maintaining public health security. At present, researchers have identified hundreds of EV-A71 inhibitors based on screening repurposed drugs, targeted structural design, and rational modification of previously effective drugs as the main development strategies. This review systematically introduces the current potential drugs to inhibit EV-A71 infection, including viral inhibitors targeting key sites such as the viral capsid, RNA-dependent RNA polymerase (RdRp), 2C protein, internal ribosome entry site (IRES), 3C proteinase (3Cpro), and 2A proteinase (2Apro), starting from each stage of the viral life cycle. Meanwhile, the progress of host-targeting antiviral drugs and their development are summarized in terms of regulating host immunity, inhibiting autophagy or apoptosis, and regulating the cellular redox environment. In addition, the current clinical methods for the prevention and treatment of HFMD are summarized and discussed with the aim of providing support and recommendations for the treatment of enterovirus infections including EV-A71. [ABSTRACT FROM AUTHOR]

Aim: This study focuses on the nonlinear characteristics of two linearly stable equilibrium states within a theoretical hand, foot and mouth disease (HFMD) dynamics model. Methods: The conditional nonlinear optimal perturbation method, the Lyapunov method and the linear singular vector method are employed. Results: By utilizing the conditional nonlinear optimal perturbation method, it is determined that the two linearly stable equilibrium states (namely the free disease and disease HFMD states) also exhibit nonlinear stability. It is found that the stabilities of the free disease and disease HFMD equilibrium states differ in terms of returning to their original states. Conclusion: It is discovered that nonlinearity plays a crucial role in reinstating the original equilibrium states. In this paper, from the perspective of stability analysis of equilibrium states, it is revealed that the stabilities of the free-disease and disease hand, foot and mouth disease equilibrium states differ in terms of returning to their original states. Through an examination of the nonlinearity factor in transmission, it is discovered that nonlinearity plays a crucial role in reinstating the original equilibrium states when using conditional nonlinear optimal perturbation-type and linear singular vector-type initial perturbations. Our results imply that it is important to consider nonlinear physical processes if one wants to be more prepared to forecast disease outbreaks, persistence and even seasonal characteristics. [ABSTRACT FROM AUTHOR]

Background The evidence on the effects of extreme meteorological conditions and high air pollution levels on incidence of hand, foot and mouth disease (HFMD) is limited. Moreover, results of the available studies are inconsistent. Further investigations are imperative to elucidate the specific issue. Methods Data on the daily cases of HFMD, meteorological factors and air pollution were obtained from 2017 to 2022 in Jining City. We employed distributed lag nonlinear model (DLNM) incorporated with Poisson regression to explore the impacts of extreme meteorological conditions and air pollution on HFMD incidence. Results We found that there were nonlinear relationships between temperature, wind speed, PM2.5, SO2, O3 and HFMD. The cumulative risk of extreme high temperature was higher at the 95th percentile (P95th) than at the 90th percentile(P90th), and the RR values for both reached their maximum at 10-day lag (P95th RR = 1.880 (1.261–2.804), P90th RR = 1.787 (1.244–2.569)), the hazardous effect of extreme low temperatures on HFMD is faster than that of extreme high temperatures. The cumulative effect of extreme low wind speeds reached its maximum at 14-day lag (P95th RR = 1.702 (1.389-2.085), P90th RR = 1.498(1.283–1.750)). The cumulative effect of PM2.5 concentration at the P90th was largest at 14-day lag (RR = 1.637 (1.069–2.506)), and the cumulative effect at the P95th was largest at 10-day lag (RR = 1.569 (1.021–2.411)). High SO2 concentration at the P95th at 14-day lag was associated with higher risk for HFMD (RR: 1.425 (1.001–2.030)). Conclusion Our findings suggest that high temperature, low wind speed, and high concentrations of PM2.5 and SO2 are associated with an increased risk of HFMD. This study not only adds insights to the understanding of the impact of extreme meteorological conditions and high levels of air pollutants on HFMD incidence but also holds practical significance for the development and enhancement of an early warning system for HFMD.

Enterovirus A71 (EV-A71) causes hand, foot, and mouth disease in infants and children with potential for fatal complications such as encephalitis and acute flaccid myelitis. This study examined the long-term immunity conferred by EV71vac, an inactivated EV-A71 vaccine adjuvanted with aluminum phosphate, in children from the age of 2 months to

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Hand, foot and mouth disease (HFMD) is highly prevalent in the Asia Pacific region, particularly in Vietnam. To develop effective interventions and efficient vaccination programs, we inferred the age-time-specific transmission patterns of HFMD serotypes enterovirus A71 (EV-A71), coxsackievirus A6 (CV-A6), coxsackievirus A10 (CV-A10), coxsackievirus A16 (CV-A16) in Ho Chi Minh City, Vietnam from a case data collected during 2013–2018 and a serological survey data collected in 2015 and 2017. We proposed a catalytic model framework with good adaptability to incorporate maternal immunity using various mathematical functions. Our results indicate the high-level transmission of CV-A6 and CV-A10 which is not obvious in the case data, due to the variation of disease severity across serotypes. Our results provide statistical evidence supporting the strong association between severe illness and CV-A6 and EV-A71 infections. The HFMD dynamic pattern presents a cyclical pattern with large outbreaks followed by a decline in subsequent years. Additionally, we identify the age group with highest risk of infection as 1-2 years and emphasise the risk of future outbreaks as over 50% of children aged 6-7 years were estimated to be susceptible to CV-A16 and EV-A71. Our study highlights the importance of multivalent vaccines and active surveillance for different serotypes, supports early vaccination prior to 1 year old, and points out the potential utility for vaccinating children older than 5 years old in Vietnam.

Prior studies of hand, foot, and mouth disease (HFMD) have often observed inconsistent results regarding meteorological factors. We propose the hypothesis that these meteorological associations vary in regions because of the heterogeneity of their geographical characteristics. We have tested this hypothesis by applying a geographical detector and Bayesian space–time hierarchy model to measure stratified spatiotemporal heterogeneity and local associations between meteorological factors and HFMD risk in five climate zones in China from January 2016 to December 2017. We found a significant spatial stratified heterogeneity in HFMD risk and climate zone explained 15% of the spatial stratified heterogeneity. Meanwhile, there was a significant temporal stratified heterogeneity of 14% as determined by meteorological factors. Average temperatures and relative humidity had a significant positive effect on HFMD in all climate zones, they were the most obvious in the southern temperate zone. In northern temperate, southern temperate, northern subtropics, middle subtropics and southern subtropics climate zone, a 1 °C rise in temperature was related to an increase of 3.99%, 13.76%, 4.38%, 3.99%, and 7.74% in HFMD, and a 1% increment in relative humidity was associated with a 1.51%, 5.40%, 2.21%, 3.44%, and 4.78% increase, respectively. These findings provide strong support for our hypotheses that HFMD incidence has a significant spatiotemporal stratified heterogeneity and different climate zones have distinct influences on the disease. These findings provide strong support for our hypotheses: HFMD incidence had significant spatiotemporal stratified heterogeneity and different climate zones had distinct influences on it. The study suggested that HFMD prevention and policy should be made according to meteorological variation in each climate zone. [ABSTRACT FROM AUTHOR]

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Abstract Background To understand the factors influencing clinical outcomes of severe hand, foot, and mouth diseases (HFMD), and to provide scientific evidence for reducing the mortality risk of severe HFMD. Methods From 2014 to 2018, children diagnosed with severe HFMD cases in Guangxi, China, were enrolled in this hospital-based study. The epidemiological data obtained through face-to-face interviews with the parents and guardians. Univariate and multivariate logistics regression models were used to analyze the factors influencing the clinical outcomes of severe HFMD. The impact of the EV-A71 vaccination on inpatient mortality was analyzed by a comparison approach. Results A total of 1565 severe HFMD cases were enrolled in this survey, including 1474 (94.19%) survival cases and 91 (5.81%) death cases. The multivariate logistic analysis demonstrated that HFMD history of playmates in the last three months, first visit to the village hospital, time from the first visit to admission less than two days, no correct diagnosis for HFMD at the first visit, and having no rash symptoms were the independent risk factors for severe HFMD cases (all p

ObjectiveTo analyze prevalence characteristics of hand, foot and mouth disease (HFMD) in Shenzhen city from 2008 to 2020 and to evaluate the impact of inactivated enterovirus 71 (EV71) vaccination on HFMD incidence for providing evidence to promoting inactivated EV71 vaccination and formulating strategies on HFMD prevention and control. MethodsThe data on HFMD incidence for Shenzhen municipality during 2008 – 2020 were retrieved from China′s Infectious Disease Information System and that on inactivated EV71 vaccination were extracted from Childhood Immunization Planning Information System of Shenzhen Municipality; the information on prevalent strains related to HFMD epidemics in the city was collected simultaneously from pathogenic surveillance dataset. Descriptive epidemiological statistics was conducted to analyze prevalence characteristics of HFMD and the effect of inactivated EV71 vaccination on HFMD incidence and prevalent pathogenic strains. ResultsTotally 469 686 HFMD cases were reported during the 13-year period in the city, with an average annual incidence rate of 312.25/100 000. During a year, HFMD incidence was obviously higher in summer season than in winter season, with two incidence peaks in April – July and September – October. Higher incidence rate were observed in the regions with a large number of migrant workers or high population density. The majority of the reported cases were males, children aged 4 years and younger, and homebound children, accounting for 60.54%, 89.69%, and 76.58% of total cases, respectively. The HFMD incidence declined evidently from 516.13/100 000 in 2016 to 84.42/100 000 in 2020 with the yearly increasing of EV71 vaccination rate; the proportion of HFMD cases due to the infection of EV71 also decreased from 16.19% in 2016 to zero in 2020. ConclusionInactivated EV71 vaccination can effectively prevent and control HFMD epidemic, especially for the HFMD epidemic caused by EV71 infection.

BackgroundHand, foot, and mouth disease (HFMD) is a significant public health issue in China, and numerous studies have indicated a close association between HFMD incidence and meteorological factors. This study aims to investigate the relationship between meteorological factors and HFMD in Yangzhou City, Jiangsu Province, China.MethodsHFMD case reports and meteorological data from Yangzhou City between 2017 and 2022 were extracted from the National Notifiable Infectious Disease Surveillance System and the Meteorological Data Sharing Service System, respectively. A generalized additive model (GAM) was employed to assess the exposure-response relationship between meteorological factors and HFMD. Subsequently, a distributed lag nonlinear model (DLNM) was used to explore the exposure-lag-effect of meteorological factors on HFMD.ResultsHFMD in Yangzhou City exhibits obvious seasonality and periodicity. There is an inverted “U” shaped relationship between average temperature and the risk of HFMD, with the maximum lag effect observed at a temperature of 25°C with lag 0 day (RR = 2.07, 95% CI: 1.74–2.47). As the duration of sunshine and relative humidity increase, the risk of HFMD continuously rises, with the maximum lag effect observed at a sunshine duration of 12.4 h with a lag of 14 days (RR = 2.10, 95% CI: 1.17–3.77), and a relative humidity of 28% with a lag of 14 days (RR = 1.21, 95% CI: 1.01–1.64). There is a “U” shaped relationship between average atmospheric pressure and the risk of HFMD, with the maximum effect observed at an atmospheric pressure of 989 hPa with no lag (RR = 1.45, 95% CI: 1.25–1.69). As precipitation increases, the risk of HFMD decreases, with the maximum effect observed at a precipitation of 151 mm with a lag of 14 days (RR = 1.45, 95% CI: 1.19–2.53).ConclusionMeteorological factors including average temperature, average atmospheric pressure, relative humidity, precipitation, and sunshine duration significantly influenced the risk of HFMD in Yangzhou City. Effective prevention measures for HFMD should be implemented, taking into account the local climate conditions.

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EV71 vaccine immunization mainly protects the human population against severe and fatal HFMD and has a positive effect on reducing the overall incidence rates of HFMD and of hospitalized cases. In the analysis of data collected over 4 years, we compared HFMD's incidence rate, severity, and etiological changes in a target population before and after vaccine intervention. The incidence rate of HFMD decreased from 39.02‰ in 2014 to 11.02‰ in 2021, with a decrease rate of 71.7%, and the decrease was statistically significant (p < 0.001). The number of hospitalized cases decreased by 68.88%, the number of severe cases dropped by 95.60% and the number of deaths dropped to 0. The proportion of cases caused by the EV71 virus in different populations decreased significantly after the intervention, specifically, by 68.41% among individuals 0–4 years of age, by 74.32% among kindergarten children, by 86.07% in severe cases and by 100% with respect to the number of deaths. [ABSTRACT FROM AUTHOR]