Hand, foot, and mouth disease reinfection in Quzhou, China: A 16-year retrospective cohort study of epidemiology and risk factors

Previous studies on hand, foot, and mouth disease (HFMD) have primarily addressed initial infections, with limited focus on reinfection trends and multifactorial risk interactions. Conventional methods like logistic regression often fail to capture temporal risk dynamics. This study applied a Cox proportional hazards model to analyze epidemiological traits and risk factors for HFMD reinfection in Quzhou from 2008 to 2024, to guide prevention strategies. Among 79,841 reported cases, 3945 reinfections were identified, yielding a reinfection rate of 4.94%. Most cases experienced 2 episodes (96.53%), with fewer having 3 (3.40%) or 4 (0.08%). Infections showed bimodal seasonal peaks in April-June and November-December. Median intervals between successive infections decreased from 1.38 years (1st to 2nd) to 0.82 years (3rd to 4th). Cox proportional hazards regression modeling identified age under 3 years, scattered children, urban residence, initial infection with coxsackievirus A16, and coxsackievirus A16 being the predominant circulating strain in the year of initial infection as significant risk factors for HFMD reinfection. our study identifies a significant HFMD reinfection burden (4.94%) in Quzhou. These findings highlight the need for targeted health education and sustained vigilance, especially for high-risk groups, to mitigate reinfection risks. However, only 4.16% of reinfection cases in this study were laboratory-confirmed, and the diagnostic reagents did not permit differentiation across all serotypes. Variation in detection rates among reinfection cases may have introduced bias, and the related findings should therefore be interpreted with caution.