# Population-Level Impact of the Enterovirus A71 Vaccination Program on Hand, Foot, and Mouth Disease: Ecological Time-Series Study

## TL;DR

This study shows that the EV71 vaccine significantly reduced hand, foot, and mouth disease cases in Jiangsu Province, especially among young children.

## Contribution

The study provides population-level evidence of the EV71 vaccine's real-world effectiveness in Jiangsu Province, where prior data was limited.

## Key findings

- EV71-associated HFMD cases declined sharply from 22,303 in 2017 to 3900 in 2019.
- The vaccine prevented an estimated 30,117 EV71 cases from 2017 to 2019, with a 45.55% reduction.
- Children under 4 years old experienced the greatest benefit from the vaccination program.

## Abstract

Hand, foot, and mouth disease (HFMD), a common childhood illness caused by various enteroviruses, poses a significant public health threat in the Asia-Pacific region, where severe cases associated with enterovirus A71 (EV71) are a major concern. The EV71 vaccination program was introduced in China in late 2016. Although randomized controlled trials have established the robust efficacy and safety of these vaccines, assessing their real-world performance remains crucial. Subsequent studies have evaluated its real-world effectiveness in several provinces, including Zhejiang and Guangdong. However, evidence on its real-world impact in reducing EV71-associated HFMD in Jiangsu Province remains limited.

This study aimed to describe HFMD epidemiological characteristics and to evaluate the population-level effectiveness of the EV71 vaccination program in Jiangsu Province.

We characterized the temporal distribution of EV71-related HFMD cases based on longitudinal surveillance data collected through the National Notifiable Diseases Surveillance System in Jiangsu Province from 2012 to 2019 and assessed the impact of vaccination using a Bayesian structural time series model under a counterfactual framework. The intervention effect of the EV71 vaccine was estimated by comparing the observed data with predictions from a counterfactual model scenario without vaccination.

A total of 932,274 HFMD cases were reported in Jiangsu from 2012 to 2019, including 5190 (0.56%) severe cases. An estimated 140,876 (15.11%) cases were attributed to EV71. EV71-associated HFMD cases showed a marked decline, with estimated numbers of 22,303, 9796, and 3900 in 2017, 2018, and 2019, respectively. We estimated that 30,117 EV71 cases (95% credible interval −1777 to 93,601) were prevented by the vaccination program from 2017 to 2019, corresponding to a reduction of 45.55% (95% credible interval −5.19% to 72.22%). The effectiveness of vaccination increased annually, with reductions of −1.03% (95% credible interval −94.85% to 48.29%) in 2017, 55.54% (95% credible interval 13.94%-77.56%) in 2018, and 82.28% (95% credible interval 65.77%-90.89%) in 2019. Furthermore, we observed that children younger than 4 years obtained greater benefits compared with those older than 4 years, with the greatest reduction of 57.68% (95% credible interval 13.04%-79.65%) in the 3- to 4-year age group, followed by a 48.09% (95% credible interval 28.00%-62.98%) reduction in the 0- to 2-year age group. In contrast, the reduction was markedly lower, at 16.75 % (95% credible interval −96.53% to 65.47%) in children older than 4 years during the 2017 to 2019 period.

EV71 vaccination is an effective measure to prevent HFMD. The sharp decline in EV71-associated HFMD cases following the implementation of the EV71 vaccination program suggests a potential causal relationship. Therefore, strengthening vaccine coverage remains a public health priority.