EV-A71 vaccination and COVID-19 non-pharmaceutical interventions significantly reduced HFMD incidence, accompanied by a near-zero decline in EV-A71 cases and a rise in other enteroviruses.
Observational (n=538,267)
Do EV-A71 vaccination and COVID-19 NPIs impact the incidence and etiology of HFMD?
EV-A71 vaccination and COVID-19 NPIs were associated with a significant decline in overall HFMD incidence and a shift in predominant pathogens.
Effect estimate: β-coefficient -4.37 (95% CI -6.30 to -2.44)
p-value: p=<0.001
Background Hand, foot, and mouth disease (HFMD), a widespread virus-induced infectious disease caused by enteroviruses, imposes a substantial disease burden. This study is to evaluate the impacts of EV-A71 vaccination and COVID-19 non-pharmaceutical interventions (NPI) intensity on HFMD epidemics. Method A retrospective study was performed based on surveillance data from 2009 to 2022 in Jiangxi Province, China. Joinpoint regression analysis was utilized to analyze long-term trends, wavelet analysis was adopted to explore seasonality and periodicity, spatiotemporal scanning was employed to identify clustering, a generalized linear model (GLM) was used to assess effects of EV-A71 vaccination coverage and NPI intensity on HFMD incidence, and the eXtreme Gradient Boosting (XGBoost) algorithm was employed to develop univariate time-series forecasting models for the incidence of HFMD caused by EV-A71, CVA16, and other EVs. Results A marked increase in the annual incidence of HFMD was observed from 2009 to 2016, with a subsequent decrease from 2017 to 2022. Increasing incidence was predominantly detected in the population aged >2 years, especially among those aged 5 to 9 years. The periodicity of HFMD was relatively stable at 12 months and 6 months from 2009 to 2019, but gradually extended to 16 months and 8 months. The proportion of EV-A71 pathogen cases decreased from 28% (Period I) to 0.4% (Period III). The proportion of reported cases aged>2 years demonstrated a chronological upward trend. The model revealed significant independent protection from vaccination and NPI, with the strongest protective effects during autumn and school summer vacation. The forecasts revealed an etiology shift of vaccine-controlled suppression of EV-A71, persistent cyclicality of CVA16, and rising dominance of other EVs. Conclusion The overall incidence of HFMD declined across three periods, while the incidence in the older child populations increased. A shift in predominant HFMD pathogens was observed and predicted following the rollout of vaccination. Vaccination and NPI interventions are effective in reducing HFMD incidence. Clinical trial Not applicable
Hu et al. (2026) conducted an observational in Hand, foot, and mouth disease (HFMD) (n=538,267). EV-A71 vaccination and COVID-19 non-pharmaceutical interventions (NPI) vs. Pre-vaccination and pre-NPI periods was evaluated on HFMD monthly incidence (β-coefficient -4.37, 95% CI -6.30 to -2.44, p=<0.001). EV-A71 vaccination and COVID-19 non-pharmaceutical interventions significantly reduced HFMD incidence, accompanied by a near-zero decline in EV-A71 cases and a rise in other enteroviruses.