Effectiveness of the Enterovirus A71 Vaccine on Hand, Foot and Mouth Disease: a Real-World Study in China

OBJECTIVES:For the prevention of hand, foot and mouth disease (HFMD), enterovirus A71 (EV-A71) vaccines have been utilized in China since 2016. To better inform vaccination strategies, we assess the real-world effectiveness of EV-A71 vaccination in China. METHODS:The analysis was based on surveillance data of HFMD caused by EV-A71 in children under the age of five in China, along with meteorological and demographic data. The seasonal autoregressive integrated moving average model and the interrupted time-series analysis were used to estimate the effectiveness of the EV-A71 vaccination on the EV-A71 HFMD incidence and to predict the counterfactual cases with no EV-A71 vaccine. RESULTS:Between 2010 and 2018, 6,712,613 cases of HFMD caused by EV-A71 were reported in children under five years old in 260 Chinese cities. During 2017-2018, the EV-A71 vaccination was associated with a reduction in EV-A71 HFMD incidence, with a relative risk of 0.83 (95% confidence interval (CI): 0.81-0.86), and an estimated reduction of 297,946 (95% CI: 250,534-346,658) cases. However, this association varied across cities (I2=85.6%, P<0.001) and the effectiveness of EV-A71 vaccination decreased as population density increased. Higher vaccination coverage was associated with greater effectiveness of the EV-A71 vaccination and an earlier point in EV-A71 cases reduction. Specifically, when the vaccination coverage exceeded approximately 20%, the relative risk was rapidly reduced to below 0.71 (95% CI: 0.69-0.72). CONCLUSIONS:Our study demonstrated that the EV-A71 vaccination was associated with a reduction in the incidence of EV-A71 HFMD, but the association varied with regions and was influenced by vaccination coverage and population density. To optimize EV-A71 HFMD prevention, increasing vaccination coverage (over 20%) is recommended for children under five years old.