Hand, foot, and mouth disease in mainland China

Abstract

Weijia Xing and colleagues reported the epidemiological profile of hand, foot, and mouth disease in mainland China between 2008 and 2012, according to variations in climate, population, and geographical region, 1Xing W Liao Q Viboud C et al.Hand, foot, and mouth disease in China, 2008–12: an epidemiological study.Lancet Infect Dis. 2014; 14: 308-318Summary Full Text Full Text PDF PubMed Scopus (681) Google Scholar and their findings support the introduction of enterovirus 71 (EV71) vaccines in China and other countries. Their Article is interesting and important, but the incidences and aetiological profiles of hand, foot, and mouth disease were underestimated because of the limitations of passive surveillance in the national infectious disease information management system. Usually, patients who are not admitted to hospital are not included in the national disease information management reporting system. In a retrospective study, Feng-Cai Zhu and colleagues2Zhu F Liang Z Meng F et al.Retrospective study of the incidence of HFMD and seroepidemiology of antibodies against EV71 and CoxA16 in prenatal women and their infants.PLoS One. 2012; 7: e37206Crossref PubMed Scopus (58) Google Scholar reported that cases of hand, foot, and mouth disease reported to this system were far fewer than the actual number of cases (only 16 [11%] of 143 cases). Additionally, the incidence of hand, foot, and mouth disease obtained by active surveillance in three phase 3 clinical trials of EV71 inactivated vaccine was between two-times and six-times greater than that reported by Xing and colleagues.3Zhu F Xu W Xia J et al.Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China.N Engl J Med. 2014; 370: 818-828Crossref PubMed Scopus (341) Google Scholar, 4Li R Liu L Mo Z et al.An inactivated enterovirus 71 vaccine in healthy children.N Engl J Med. 2014; 370: 829-837Crossref PubMed Scopus (300) Google Scholar, 5Zhu F Meng F Li J et al.Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.Lancet. 2013; 381: 2024-2032Summary Full Text Full Text PDF PubMed Scopus (320) Google Scholar Xing and colleagues also pointed out that most cases went undetected. Therefore, we want to emphasise that the actual prevalence of hand, foot, and mouth disease is far more serious in mainland China than has been reported, and we speculate that a similar situation might exist in other countries. Furthermore, in addition to EV71 and Coxsackievirus A16, other enteroviruses that can cause severe hand, foot, and mouth disease also deserve our attention. Recently published studies propose that Coxsackievirus A6, A10, B3, B5, and E30 (CA6, CA10, CB3, CB5, and E30) account for a large proportion of the disease's pathogenic range. CB3 can cause viral myocarditis, whereas E30 and CB5 are associated with encephalitis and aseptic encephalitis. The alternation or co-circulation of different enteroviruses in infants and young children can cause serious complications in the CNS and increase the chances of genetic recombination. Therefore, although the results of phase 3 clinical trials of inactivated enterovirus 71 vaccine are promising, when these vaccines become available in the market, the epidemiological characteristics and pathogenic range of hand, foot, and mouth disease should be actively monitored in highly epidemic areas. Future research should focus on the development of bivalent and multivalent vaccines of enteroviruses to reduce the harm caused by hand, foot, and mouth disease and other related nervous system disorders in infants and children. We declare no competing interests. Hand, foot, and mouth disease in mainland China–Authors' replyWe thank Qunying Mao and colleagues, Bin Lu and colleagues, and Peiqing Li and colleagues for their comments on our recent Article.1 Full-Text PDF