Changing epidemiology of hand, foot, and mouth disease in China, 2013−2019:a population-based study

Background: Hand, foot, and mouth disease (HFMD) is an important public health problem. A monovalent EV-A71 vaccine was launched in China in 2016. Previous studies showed that inactivated monovalent EV-A71 vaccines were highly efficient against HFMD associated with EV-A71 but not against HFMD with other etiologies, leading to a hypothesis that the introduction of EV-A71 vaccines might change the pathogen spectrum and epidemiological trend of HFMD. In this study, we described for the first time the changing epidemiological characteristics of HFMD after the launch of the EV-A71 vaccine. Methods: We extracted individual-based epidemiological data on HFMD cases reported to the Chinese Center for Disease Control and Prevention between January 2013 and December 2019. We described the changing epidemiological characteristics of HFMD before and after vaccine launch according to the distribution of diseases characteristics (demographic, temporal, and geographical) and evaluated the potential changes in risk factors of severe patients. All analyses were stratified by the phase before and after vaccine launch, and by enterovirus serotype. Findings: During 2013−2019, 15,316,710 probable cases of HFMD were reported. Of these, 787,197 (5·1%) were laboratory confirmed and 76,982 (0·5%) were severe. After the launch of the EV-A71 vaccine, the median age of HFMD patients infected with EV-A71 increased from 2·24 years (IQR:1·43, 3·56) to 2·81 years (IQR:1·58, 4·01). The proportion of patients less than 3 years of age decreased while the proportion of patients 3−5 years of age increased. There was a large decrease (60·7%) in the proportion of severe cases as well as a decline (28·3%) in HFMD patients infected with EV-A71. After the launch of the EV-A71 vaccine, the severe illness rate and mortality rate of HFMD patients in all age groups has decreased sharply, 62·20% and 83·78% respectively. The timing of the HFMD epidemic peak was delayed (1-2 months). After the launch of EV-A71 v