Effectiveness of the inactivated enterovirus 71 vaccine in children aged 6–35 months: protocol for a multicentre, case-control phase IV clinical trial

Pengfei Jin, Jinxing Li, Xuefeng Zhang, Wenqi Shen, Kai Duan, Lianghao Zhang, Fengcai Zhu


Background: Inactivated enterovirus 71 (EV-A71) vaccines have already be introduced for routine childhood immunization in mainland China since 2016. However, it is not well known that the effectiveness of EV-A71 vaccine under ‘real world’ conditions. We aimed to assess the effectiveness and safety of EV-A71 vaccine against EV-A71 associated hand foot and mouth disease (HFMD) in children aged 6–35 months.
Methods: This is a multicentre, phase IV, case-control study of the inactivated EV-A71 vaccine. Through the hospital-based active surveillance of HFMD, a case-control study design with two groups of controls (test-negative control and community control) will be used to estimate vaccine effectiveness of EV-A71 vaccine. We will recruit cases defined as patients aged 6–47 months admitted to presenting hospitals for laboratory-confirmed HFMD induced by EV-A71. For each case, hospital test-negative control and community control are selected. Vaccination status will be determined from electronic immunization records (EIRs) and parent-reported vaccination cards. Logistic regression analysis will be carried out to calculate vaccine effectiveness (one minus the odds ratio of vaccination) by comparing patients with HFMD cases who tested positive for EV-A71 with those who tested negative and with community controls.
Discussion: This is the first evaluation of the performance of EV-A71 vaccines in the context of real-world immunization programs using case-control methodology with community controls and test-negative controls. The findings of this study will provide valid and reliable knowledge on the performance of EV-A71 vaccines in the real-world context.
Trial registration: ClinicalTrial.gov Identifier: NCT03582761.