Effectiveness of EV-A71 vaccination in prevention of paediatric hand, foot, and mouth disease associated with EV-A71 virus infection requiring hospitalisation in Henan, China, 2017-18: a test-negative case-control study.

Abstract

Background: Inactivated monovalent enterovirus A71 (EV-A71) vaccines are now available in China to reduce the substantial public health burden of hand, foot, and mouth disease. However, post-licensure monitoring of vaccine effectiveness is important. We did an observational test-negative study of EV-A71 vaccine effectiveness.

Methods: Children with hand, foot, and mouth disease who were admitted to Henan Children's Hospital (Zhengzhou, China) within 7 days of illness onset were invited to participate in this test-negative case-control study. Participant vaccination history with EV-A71, including the number of doses received and the date of each dose of vaccination, was elicited from parents or legal guardians of participants with a standardised questionnaire. Children must have received two doses before hospitalisation to be counted as fully vaccinated. Patients who had received a single dose before hospitalisation were classified as partly vaccinated. Children who had received no EV-A71 vaccine before hospitalisation were classified as unvaccinated. Throat swabs and stool samples collected from patients were tested by RT-PCR to identify EV-A71 and other enteroviruses. The primary outcome of the study was paediatric hand, foot, and mouth disease associated with EV-A71 requiring hospitalisation. We estimated vaccine effectiveness with conditional logistic regression models adjusted for potential confounders.

Findings: Between Feb 15, 2017, and Feb 15, 2018, we enrolled 1803 children aged 6-71 months with hand, foot, and mouth disease. 234 (13%) children tested positive for EV-A71, 1529 (85%) tested positive for other enteroviruses-528 (29%) were positive for Coxsackievirus (CV)-A6 and 342 (19%) were positive for CV-A16-and 29 (2%) tested negative for all enteroviruses. 11 (1%) children with neither throat swab nor stool testing results were excluded from further analyses. Overall vaccine effectiveness was estimated to be 85·4% (95% CI 53·2 to 95·4) for fully vaccinated children and 63·1% (13·1 to 84·3) for partly vaccinated children. The vaccine effectiveness for full vaccination was estimated to be 91·1% (35·1 to 98·8) among non-severe cases compared with 73·3% (-32·6 to 94·6) in severe cases. The vaccine effectiveness for partial vaccination was 77·9% (4·3 to 94·9) in children aged 24-71 months and 40·8% (-71·1 to 79·5) in children aged 6-23 months. We found no significant association between full or partial vaccination and CV-A6 or CV-A16-related hand, foot, and mouth disease.

Interpretation: EV-A71 vaccination was effective in preventing non-severe hand, foot, and mouth disease associated with EV-A71 virus infection in children aged 6-71 months, and we found evidence that one dose of vaccination provided partial protection for children aged 24-71 months. Introduction of multivalent vaccines could further reduce the burden of hand, foot, and mouth disease.

Funding: The National Science Fund for Distinguished Young Scholars.