BACKGROUND: Hand, foot, and mouth disease (HFMD) is a major public health issue in China while temperature and humidity are well-documented predictors. However, evidence on the combined effect of temperature and humidity is still limited. It also remains unclear whether such an effect could be modified by the enterovirus 71 (EV71) vaccination.
METHODS: Based on 320,042 reported HFMD cases during the summer months between 2012 and 2019, we conducted a study utilizing Distributed Lag Non-Linear Models (DLNM) and time-varying DLNM to examine how China\'s HFMD EV71 vaccine strategy would affect the correlation between meteorological conditions and HFMD risk.
RESULTS: The incidence of HFMD changed with the Discomfort Index in an arm-shaped form. The 14-day cumulative risk of HFMD exhibited a statistically significant increase during the period of 2017-2019 (following the implementation of the EV71 vaccine policy) compared to 2012-2016 (prior to the vaccine implementation). For the total population, the range of relative risk (RR) values for HFMD at the 75th, 90th, and 99th percentiles increased from 1.082-1.303 in 2012-2016 to 1.836-2.022 in 2017-2019. In the stratified analyses, Han Chinese areas show stronger relative growth, with RR values at the 75th, 90th, and 99th percentiles increased by 14.3%, 39.1%, and 134.4% post-vaccination, compared to increases of 22.7%, 41.6%, and 38.8% in minority areas. Similarly, boys showed greater increases (24.4%, 47.7%, 121.5%) compared to girls (8.1%, 28.1%, 58.3%). Additionally, the central Guizhou urban agglomeration displayed a tendency for stronger relative growth compared to other counties.
CONCLUSIONS: Although the EV71 vaccine policy has been implemented, it hasn\'t effectively controlled the overall risk of HFMD. There\'s been a shift in the main viral subtypes, potentially altering population susceptibility and influencing HFMD occurrences. The modulating effects of vaccine intervention may also be influenced by factors such as race, sex, and economic level.

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.

The Enterovirus A71 (EV-A71) vaccine was introduced in China in December 2015 as a preventive measure against hand, foot, and mouth disease (HFMD) caused by EV-A71. However, the effectiveness of the vaccine (VE) in real-world settings needs to be evaluated. We conducted a test-negative case-control study to assess the effectiveness of EV-A71 vaccines in preventing EV-A71-associated HFMD. Children aged 6-71 months with HFMD were enrolled as participants. The case group comprised those who tested positive for EV-A71, while the control group comprised those who tested negative for EV-A71. To estimate VE, a logistic regression model was employed, adjusting for potential confounders including age, gender, and clinical severity. In total, 3223 children aged 6 to 71 months were included in the study, with 162 in the case group and 3061 in the control group. The proportion of children who received EV-A71 vaccination was significantly lower in the case group compared to the control group (p < .001). The overall VEadj was estimated to be 90.8%. The VEadj estimates for partially and fully vaccinated children were 90.1% and 90.9%, respectively. Stratified by age group, the VEadj estimates were 88.7% for 6 to 35-month-olds and 95.5% for 36 to 71-month-olds. Regarding disease severity, the VEadj estimates were 86.3% for mild cases and 100% for severe cases. Sensitivity analysis showed minimal changes in the VE point estimates, with most changing by no more than 1% point. Our study demonstrates a high level of vaccine effectiveness against EV-A71-HFMD, especially in severe cases. Active promotion of EV-A71 vaccination is an effective strategy in preventing EV-A71 infections.

The non-pharmaceutical interventions (NPIs) against COVID-19 may have affected the transmission of hand, foot and mouth disease (HFMD). We aimed to assess the impact of the NPIs on HFMD in the high epidemic area of HFMD, Guangdong Province.
The data of HFMD cases, etiological information, and meteorological factors in Guangdong from January 1, 2012, to December 31, 2021, were collected. Using a Bayesian structural time series (BSTS) model integrated counterfactual framework, we assessed the effect of NPIs on HFMD by different intervention periods, populations (gender, age, occupation), and cities. We further explored the correlation between the reduction of HFMD and socioeconomic factors in 21 cities.
A total of 351,217 HFMD cases were reported and 455,327 cases were averted in Guangdong Province during 2020-2021 with a reduction of 84.94% (95%CI: 81.63-87.22%) in 2020 and 29.49% (95%CI: 15.26-39.54%) in 2021. The impact of NPIs on HFMD differed by age and gender. The effects of NPIs were more remarkable for children aged 0-2 years and scattered children. We found that the relative reductions in 21 cities were related to the composition ratio of children and COVID-19 incidence.
The reduction of HFMD incidence was significantly associated with COVID-19 NPIs, and school closure was an effective intervention to prevent HFMD outbreaks. Our findings will contribute to the development of HFMD prevention and control measures.

The occurrence of hand, foot, and mouth disease (HFMD) is closely related to meteorological factors. However, location-specific characteristics, such as persistent air pollution, may increase the complexity of the impact of meteorological factors on HFMD, and studies across different areas and populations are largely lacking. In this study, a two-stage multisite time-series analysis was conducted using data from 16 cities in Shandong Province from 2015 to 2019. In the first stage, we obtained the cumulative exposure-response curves of meteorological factors and the number of HFMD cases for each city. In the second stage, we merged the estimations from the first stage and included city-specific air pollution variables to identify significant effect modifiers and how they modified the short-term relationship between HFMD and meteorological factors. High concentrations of air pollutants may reduce the risk effects of high average temperature on HFMD and lead to a distinct peak in the cumulative exposure-response curve, while lower concentrations may increase the risk effects of high relative humidity. Furthermore, the effects of average wind speed on HFMD were different at different levels of air pollution. The differences in modification effects between subgroups were mainly manifested in the diversity and quantity of significant modifiers. The modification effects of long-term air pollution levels on the relationship between sunshine hours and HFMD may vary significantly depending on geographical location. The people in age＜3 and male groups were more susceptible to long-term air pollution. These findings contribute to a deepening understanding of the relationship between meteorological factors and HFMD and provide evidence for relevant public health decision-making.

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Hand, 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.
HFMD 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.
HFMD 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).
Meteorological 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.

Hand, foot and mouth disease (HFMD) is a public health concern that threatens the health of children. Accurately forecasting of HFMD cases multiple days ahead and early detection of peaks in the number of cases followed by timely response are essential for HFMD prevention and control. However, many studies mainly predict future one-day incidence, which reduces the flexibility of prevention and control.
We collected the daily number of HFMD cases among children aged 0-14 years in Chengdu from 2011 to 2017, as well as meteorological and air pollutant data for the same period. The LSTM, Seq2Seq, Seq2Seq-Luong and Seq2Seq-Shih models were used to perform multi-step prediction of HFMD through multi-input multi-output. We evaluated the models in terms of overall prediction performance, the time delay and intensity of detection peaks.
From 2011 to 2017, HFMD in Chengdu showed seasonal trends that were consistent with temperature, air pressure, rainfall, relative humidity, and PM10. The Seq2Seq-Shih model achieved the best performance, with RMSE, sMAPE and PCC values of 13.943~22.192, 17.880~27.937, and 0.887~0.705 for the 2-day to 15-day predictions, respectively. Meanwhile, the Seq2Seq-Shih model is able to detect peaks in the next 15 days with a smaller time delay.
The deep learning Seq2Seq-Shih model achieves the best performance in overall and peak prediction, and is applicable to HFMD multi-step prediction based on environmental factors.

BACKGROUND: This study adopted complete meteorological indicators, including eight items, to explore their impact on hand, foot, and mouth disease (HFMD) in Fuzhou, and predict the incidence of HFMD through the long short-term memory (LSTM) neural network algorithm of artificial intelligence.
METHODS: A distributed lag nonlinear model (DLNM) was used to analyse the influence of meteorological factors on HFMD in Fuzhou from 2010 to 2021. Then, the numbers of HFMD cases in 2019, 2020 and 2021 were predicted using the LSTM model through multifactor single-step and multistep rolling methods. The root mean square error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE) and symmetric mean absolute percentage error (SMAPE) were used to evaluate the accuracy of the model predictions.
RESULTS: Overall, the effect of daily precipitation on HFMD was not significant. Low (4 hPa) and high (≥ 21 hPa) daily air pressure difference (PRSD) and low (< 7 °C) and high (> 12 °C) daily air temperature difference (TEMD) were risk factors for HFMD. The RMSE, MAE, MAPE and SMAPE of using the weekly multifactor data to predict the cases of HFMD on the following day, from 2019 to 2021, were lower than those of using the daily multifactor data to predict the cases of HFMD on the following day. In particular, the RMSE, MAE, MAPE and SMAPE of using weekly multifactor data to predict the following week\'s daily average cases of HFMD were much lower, and similar results were also found in urban and rural areas, which indicating that this approach was more accurate.
CONCLUSIONS: This study\'s LSTM models combined with meteorological factors (excluding PRE) can be used to accurately predict HFMD in Fuzhou, especially the method of predicting the daily average cases of HFMD in the following week using weekly multifactor data.

Hand, foot, and mouth disease (HFMD) is a major public health concern in the Asia-Pacific region. Previous studies have implied that ambient air pollution may affect the incidence of HFMD, but the results among different regions are inconsistent. We aimed to deepen the understanding of the associations between air pollutants and HFMD by conducting a multicity study. Daily data on childhood HFMD counts and meteorological and ambient air pollution (PM2.5, PM10, NO2, CO, O3, and SO2) concentrations in 21 cities in Sichuan Province from 2015 to 2017 were collected. A spatiotemporal Bayesian hierarchical model framework was established, and then a distributed lag nonlinear models (DLNMs) was constructed to reveal exposure-lag-response relationships between air pollutants and HFMD while controlling for spatiotemporal effects. Furthermore, given the differences in the levels and seasonal trends of air pollutants between the basin region and plateau region, we explored whether these associations varied between different areas (basin and plateau). The associations between air pollutants and HFMD were nonlinear, with different lag responses. Low NO2 concentrations and both low and high PM2.5 and PM10 concentrations were associated with a decreased risk of HFMD. No significant associations between CO, O3, and SO2 and HFMD were found. The associations between air pollutant concentrations and HFMD were different between the basin and plateau regions. Our study revealed associations between PM2.5, PM10, and NO2 concentrations and HFMD, deepening the understanding of the relationships between air pollutants and HFMD. These findings provide evidence to support the formulation of relevant prevention measures and the establishment of an early warning system.