Hand, foot, and mouth disease: A systematic review of global evidence, climatic drivers, and research gaps (2000–2023)

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a major public health concern in Asia, particularly among children under five years of age. Although substantial research has been conducted, evidence remains geographically concentrated and methodologically narrow, limiting its generalizability and policy relevance. OBJECTIVE: The systematic review synthesizes the global peer-reviewed evidence base on HFMD to identify study characteristics, methodological approaches, environmental determinants, communication strategies, surveillance systems, and outcomes. METHODS: A comprehensive search of Web of Science, PubMed, Scopus, and IEEE Xplore (2000-2023) identified 125 eligible studies. Data extraction followed a standardized template, and study quality was appraised using an adapted Mixed Methods Appraisal Tool (MMAT). Narrative synthesis was supported by descriptive and visualization techniques. RESULTS: A total of 125 studies were included. Most originated from China, Malaysia, and Singapore, with limited contributions from other endemic regions. Research predominantly targeted children under five and relied on observational designs. Climatic factors, especially temperature and humidity, were frequently studied, while sanitation, land use, and air quality were underexplored. Communication strategies emphasized health advisories and school-based interventions, whereas digital and community-based approaches were rarely evaluated. Surveillance systems largely depended on traditional reporting, and outcomes were restricted to incidence and outbreak counts, with minimal attention to severity, hospitalization, or policy impacts. CONCLUSIONS: HFMD research has advanced climate-epidemiological understanding but remains regionally and thematically constrained. Addressing gaps in interventions, adult and community dynamics, novel surveillance technologies, and long-term outcome evaluation is critical for developing evidence-based, sustainable strategies for HFMD prevention and control.