September 5, 2023Infectious Disease ModellingOpen Access

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

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Why the study?

The study was conducted to estimate the potential causal impact of the EV71 vaccination program on reducing EV71-infected hand, foot, and mouth disease in Zhejiang Province.

Does the EV71 vaccination program reduce EV71-infected hand, foot, and mouth disease in the population of Zhejiang Province?

Structured PICO

Does the EV71 vaccination program reduce EV71-infected hand, foot, and mouth disease in the population of Zhejiang Province?

Population

Population of Zhejiang Province, China, monitored for hand, foot, and mouth disease (HFMD) and EV71 vaccination during 2010-2019, including children under and over 5 years old.

Intervention

Enterovirus A71 (EV71) vaccination program

Comparator

Pre-vaccination period / negative control outcome model

Outcome

Reduction of EV71-infected hand, foot, and mouth disease (HFMD)hard clinical

The EV71 vaccination program significantly reduced EV71-infected hand, foot, and mouth disease cases, with greater benefits seen in children under 5 years old and in areas with higher vaccination coverage.

Implication

May support EV71 vaccination programs in modeled regions; leaves open causal confirmation in randomized trials.

Abstract

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.