Real-world effectiveness of EV-A71 vaccine against encephalitis in children

While the EV-A71 vaccine is available, its real-world effectiveness against severe neurological complications such as encephalitis and its influence on circulating enterovirus serotypes require further clarification. This single-center, retrospective study analyzed 7823 children hospitalized with enterovirus-associated hand, foot, and mouth disease or herpangina between 2016 and 2023. Among them, 414 children had received EV-A71 vaccination (376 fully, 38 partially) and 7409 were unvaccinated. Encephalitis, defined by clinical symptoms, neuroimaging evidence, and CSF pleocytosis (>5 WBC/mm³), occurred in 8.5% of vaccinated children compared to 16.7% in unvaccinated children, representing a 49% relative risk reduction (χ² = 19.768, p < .001). Concurrently, a significant shift in serotype distribution was observed: the proportion of cases caused by EV-A71 decreased from 26.3% to 13.1% (p < .001), while non-EV-A71/CVA16 serotypes became dominant, accounting for 73.2% of cases by 2023. Taken together, these results indicate a dual benefit of EV-A71 vaccination: direct protection against severe neurological disease and an indirect impact on the local epidemiology of enteroviruses. These findings demonstrate that EV-A71 vaccination is highly effective in preventing severe encephalitis and is associated with an evolving enterovirus serotype landscape, underscoring the need to expand immunization programs and develop multivalent vaccines against emerging serotypes.