Estimating the nationwide incidence of coxsackievirus A6-associated hand, foot and mouth disease in China, 2008–2022

BACKGROUND: Due to insufficient routine surveillance, the nationwide disease burden of hand, foot and mouth disease (HFMD) caused by coxsackievirus A6 (CVA6), an emerging serotype, in China remains unclear. This study aimed to estimate the incidence of CVA6-associated HFMD across the Chinese mainland. METHODS: CVA6 positive data from 511 locations across the Chinese mainland during 2008-2022 were integrated from the national pathogen surveillance system and literature, and reported HFMD cases during the same period were obtained from the national infectious disease surveillance system. The predicted positivity rate and incidence of CVA6-associated HFMD in children under five years of age across the Chinese mainland were estimated using a Bayesian geostatistical Gaussian model based on positivity data, reported cases, and environmental, socioeconomic, demographic, and vaccination factors. RESULTS: The model estimated that the average positivity rate of CVA6 in the Chinese mainland from 2008 to 2022 was 24.1%, with a 95% Bayesian credible interval (BCI) of 11.9-43.3%. The corresponding average annual incidence of CVA6-associated HFMD in children under five years of age was 506 (95% BCI: 272-805) per 100,000. The yearly incidence of CVA6-associated HFMD in children under five years of age peaked in 2018 (873 per 100,000; 95% BCI: 513-1309) before a subsequent decline after 2020. The incidence was highest in South China (1571 per 100,000; 95% BCI: 890-2420) and lowest in Northeast China (208 per 100,000; 95% BCI: 106-340). The estimated CVA6-associated HFMD incidence showed a consistent upward trend across different economic level groups before 2020, and tended to be higher in high-gross domestic product (GDP) per capita regions than in medium- and low-GDP regions. CONCLUSIONS: Model-based estimates indicate a potentially high incidence of CVA6-associated HFMD on the Chinese mainland, particularly in South China, highlighting the need for enhanced surveillance of CVA6 and targeted control efforts in high-incidence regions.