Epidemiological characteristics and influencing factors of hand, foot and mouth disease reinfection cases in a large district of southern China

Objective: To analyze the epidemiological characteristics of hand, foot and mouth disease (HFMD) reinfection cases in southern China and systematically evaluate key influencing factors from individual characteristics, epidemic cycles, and regional features, aiming to provide evidence for targeted prevention and control strategies. Methods: We extracted HFMD cases in a district of southern China from the China Information System for Disease Control and Prevention (2008-2024). Descriptive analysis was used to analyze the epidemiological characteristics of HFMD reinfection, and spatial autocorrelation analysis to identify geographic clusters of cases. Cox proportional hazards regression was used to evaluate reinfection risk factors. Results: During the study period, 16,766 HFMD reinfection cases involving 8,210 individuals were reported in the district, with a reinfection rate of 6.41%. The interval between the two infections ranged from 0.06 to 9.92 years, and 77.42% of patients were reinfected within 2.5 years. There was a bimodal distribution in time (May-July and September-October). The spatial distribution of HFMD reinfections predominantly followed a random pattern, with cold spots clustered in a non-urban sub-district. Cox proportional hazards regression revealed significantly lower risks of HFMD reinfection among children aged >3 years, in early childhood education and care, students, and females. Individuals initially infected with prevalent strains of CV-A16, CV-A6, or other enteroviruses exhibited significantly higher risks of HFMD reinfection. Temporally, reinfection risks were significantly higher during epidemic years and peak transmission periods. Spatially, elevated HFMD reinfection risks were observed in urban areas, high population density regions, and areas with greater medical resource availability. Conclusion: HFMD reinfections in a district of southern China demonstrated distinct population heterogeneity, clustering temporally during epidemic peaks and spatially in urban centers with high population density and advanced medical resources. These findings underscore the need for a targeted early-warning system and enhanced control measures in high-risk transmission hotspots.