The impact of EV71 vaccination program on hand, foot and mouth disease in Zhejiang Province, China: A negative control study

Objective

To estimate the potential causal impact of Enterovirus A71 (EV71) vaccination program on the reduction of EV71-infected hand, foot, and mouth disease (HFMD) in Zhejiang Province.

Methods

We utilized the longitudinal surveillance dataset of HFMD and EV71 vaccination in Zhejiang Province during 2010–2019. We estimated vaccine efficacy using a Bayesian structured time series (BSTS) model, and employed a negative control outcome (NCO) model to detect unmeasured confounding and reveal potential causal association.

Results

We estimated that 20,132 EV71 cases (95% CI: 16,733, 23,532) were prevented by vaccination program during 2017–2019, corresponding to a reduction of 29% (95% CI: 24%, 34%). The effectiveness of vaccination increased annually, with reductions of 11% (95% CI: 6%, 16%) in 2017 and 66% (95% CI: 61%, 71%) in 2019. Children under 5 years old obtained greater benefits compared to those over 5 years. Cities with higher vaccination coverage experienced a sharper EV71 reduction compared to those with lower coverage. The NCO model detected no confounding factors in the association between vaccination and EV71 cases reduction.

Conclusions

This study suggested a potential causal effect of the EV71 vaccination, highlighting the importance of achieving higher vaccine coverage to control the HFMD.