The epidemiology of hand, foot and mouth disease in Asia: a systematic review and analysis

Hand, foot and mouth disease (HFMD) is a widespread pediatric disease caused primarily by human enterovirus 71 (EV71) and coxsackievirus A16 (CA16).This study reports a systematic review of the epidemiology of HFMD in Asia.PubMed, Web of Science and Google Scholar were searched up to December 2014.Two reviewers independently assessed studies for epidemiologic and serologic information about prevalence and incidence of HFMD against predetermined inclusion/exclusion criteria.Two reviewers extracted answers for eight specific research questions on HFMD epidemiology. The results are checked by three others.HFMD is found to be seasonal in temperate Asia with a summer peak, and in sub-tropical Asia, with spring and fall peaks, but not in tropical Asia; evidence of a climatic role was identified for temperate Japan. Risk factors for HFMD include hygiene, age, gender and social contacts, but most studies were underpowered to adjust rigorously for confounding variables. Both community-level and school-level transmission have been implicated but their relative importance for HFMD is inconclusive. Epidemiologic indices are poorly understood: No supporting quantitative evidence was found for the incubation period of EV71; the symptomatic rate of EV71/CA16 infection was 10% to 71% in four studies; while the basic reproduction number was between 1.1 to 5.5 in three studies. The uncertainty in these estimates inhibits their use for further analysis.Diversity of study designs complicates attempts to identify features of HFMD epidemiology.Knowledge on HFMD remains insufficient to guide interventions such as the incorporation of an EV71 vaccine in pediatric vaccination schedules. Research is urgently needed to fill these gaps