Trend of hand, foot, and mouth disease from 2010 to 2021 and estimation of the reduction in enterovirus 71 infection after vaccine use in Zhejiang Province, China
Authors: Wu Haocheng , Xue Ming , Wu Chen , Lu Qinbao , Ding Zheyuan , Wang Xinyi , Fu Tianyin , Yang Ke , Lin Junfen 
Published: September 2022

Background
Zhejiang, ranked in the top three in HFMD (hand, foot, and mouth disease) incidence, is located in the Yangtze River Delta region of southeast China. Since 2016, the EV71 vaccine has been promoted in Zhejiang Province. This study aimed to investigate the trend and seasonal variation characteristics of HFMD from 2010 to 2021 and estimate the reduction in enterovirus 71 infection after vaccine use.

Methods
The data on HFMD cases in Zhejiang Province from January 2010 to December 2021 were obtained from this network system. Individual information on cases and deaths was imported, and surveillance information, including demographic characteristics and temporal distributions, was computed by the system. The Joinpoint regression model was used to describe continuous changes in the incidence trend. The BSTS (Bayesian structural time-series models) model was used to estimate the monthly number of cases from 2017 to 2021 based on the observed monthly incidence during 2010–2016 by accounting for seasonality and long-term trends. The seasonal variation characteristics of HFMD pathogens were detected by wavelet analysis.

Results
From 2010 to 2021, the annual incidence rate fluctuated between 98.81 cases per 100,000 in 2020 and 435.63 cases per 100,000 in 2018, and 1711 severe HFMD cases and 106 fatal cases were reported in Zhejiang Province, China. The annual percent change (APC) in EV71 cases was -30.72% (95% CI: -45.10 to -12.50) from 2016 to 2021. The wavelet transform of total incidence and number of cases of the three pathogens all showed significant periodicity on the 1-year scale. The average 2-year scale periodicity was significant for the total incidence, EV71 cases and Cox A16 cases, but the other enterovirus cases showed significant periodicity on the 30-month scale. The 6-month scale periodicity was significant for the total incidence, EV71 case and Cox A16 case but not for the other enteroviruses case. The relative error percentage of the performance of the BSTS model was 0.3%. The estimated number of cases from 2017 to 2021 after the EV-A71 vaccines were used was 9422, and the reduction in the number of cases infected with the EV71 virus was 73.43% compared to 70.80% when the impact of the COVID-19 epidemic in 2020 was excluded.

Conclusions
Since 2010, the incidence of EV71 infections has shown an obvious downward trend. All types of viruses showed significant periodicity on the 1-year scale. The periodicity of the biennial peak is mainly related to EV71 and Cox A16 before 2017 and other enteroviruses since 2018. The half-year peak cycle of HFMD was mainly caused by EV71 and Cox A6 infection. The expected incidence will be 2.76 times(include the cases of 2020) and 2.43 times(exclude the cases of 2020) higher than the actual value assuming that the measures of vaccination are not taken. EV71 vaccines are very effective and should be administered in the age window between 5 months and 5 years.