Epidemiological shifts in coxsackievirus A-induced hand, foot, and mouth disease in China, 2008–2024

Hand, foot, and mouth disease (HFMD) is primarily caused by enterovirus A71 (EV-A71) and coxsackievirus A (CV-A) serotypes. The introduction of the inactivated EV-A71 vaccine in China in 2016 significantly reduced EV-A71-related severe and fatal HFMD cases but did not confer cross-protection against other enteroviruses. Epidemiological data from China show that while the overall incidence of HFMD has declined since 2018, there has been a significant shift in the pathogen spectrum, with non-EV-A71 enteroviruses particularly CV-A6 and CV-A10 emerging as the predominant serotypes. To investigate the impact of enterovirus infections, we analyzed laboratory-confirmed HFMD case reported by the Chinese Center for Disease Control and Prevention (CDC) and provincial and municipal CDCs across China from 2008 through December 2024. Post-vaccination, EV-A71 incidence declined markedly, while CV-A6, CV-A10, CV-A16, and CV-A4 gradually became predominant, exhibiting distinct geographic and seasonal distributions. These findings underscore the evolving HFMD epidemiology in China and highlight the need for multivalent vaccines and sustained surveillance to effectively control HFMD.