Case-fatality of hand, foot and mouth disease associated with EV71: a systematic review and meta-analysis

Hand, foot and mouth disease (HFMD) associated with enterovirus 71 (EV71) is a growing public health concern. This study aimed to estimate the case-fatality of HFMD associated with EV71 on the basis of a meta-analysis. We searched PubMed, Cochrane, Web of Science, Elsevier, CNKI, Wanfang, and VIP databases. Two authors independently selected relevant studies. The pooled estimate of case-fatality was calculated using a random-effects model. Potential sources of heterogeneity were explored using subgroup analysis, sensitivity analysis and meta-regression. We identified 14 eligible studies with a total population of 112 546. The random-effects pooled case-fatality was 1·7% (95% confidence interval 1·2–2·4). The funnel plot was asymmetrical. The estimate of case-fatality was highest in mainland China (1·8%). Removal of eight local Chinese studies decreased the original estimate. The pooled case-fatality in the period of 1998–2007 (1·5%) was lower than that in the period 2008–2012 (1·8%). Control measures for HFMD associated with EV71 are essential because of the increased case-fatality over time, especially in East Asia.