[Hand-Foot-and-Mouth Disease, Aseptic Meningitis, and Encephalitis Caused by Enterovirus]

Enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), and CV-A6 are the major causative agents of Hand-foot-and-mouth disease (HFMD). These viruses belong to the species Enterovirus A of the genus Enterovirus of the family Picornaviridae. These viruses can also cause aseptic meningitis (AM), encephalitis and/or paralysis. EV-A71 is one of the main infectious agents related to severe encephalitis. Between 1997 and 2013, East and Southeast Asia experienced large encephalitis outbreaks caused by EV-A71 infections, which ranged from severe to lethal. In Japan, national surveillance for HFMD has been conducted since 1982 by monitoring both the notifications of HFMD patients and the causative agents. Even though EV-A71 and CV-A16 are the two major causative agents of HFMD, CV-A6 has been reported to cause atypical HFMD in Japan, since 2011. Both CV-A6 and CV-A16 also cause encephalitis: however, the reported numbers of encephalitis caused by CV-A6 and CV-A16 have been far fewer than those caused by EV-A71. Vaccines against EV-A71 have become available in some Asian countries, such as in China, but as of 2017 they remain unavailable in Japan, likely due to the sparsity of fatal cases. This article summarizes the complications of HFMD on the central nervous system, as well as its epidemiology, clinical manifestations, and treatment. Moreover, the article reviews the history of HFMD and discusses the experimental results of research aimed at the prevention, grading, sample collection, diagnosis, and treatment of severe EV-A71 infections.