Etiology of HFMD

Hand, foot, and mouth disease (HFMD) is caused by multiple viruses in the genus Enterovirus, which include the well-known polioviruses (PVs), coxsackieviruses A and B (CV-A and CV-B), and enteric cytopathic human orphan (ECHO) viruses. The genome of EVs is single-stranded, positive-sense RNA. The open reading frame (ORF) region in EVs genome encodes structural proteins that further formed EV capsids. EVs are among the fastest evolving viruses with high genetic variability. Thus, the classification of EVs is initially based on clinical manifestations of their infection, subsequent serological characteristics, and differences in the nucleotide sequences up to the modern era. Currently, the genus Enterovirus consists of 3 human RV species (RV-A, -B and -C), 4 human EV species (HEV-A, -B, -C, and -D), and 6 animal EVs. The major pathogens (EV-A71, CV-A16, CV-A6, CV-A10, etc.) causing HFMD are included in the species of EV-A. The HFMD outbreaks were alternatively caused by infections with CV-A16 and EV-A71 ever since 1990s; however, the pathogenicity of HFMD changed greatly in the past decade, with new pathogens being identified continuously. Rapid diagnosis and genotyping of EV infection are through virus isolation and culture, serological assays, PCR identification or supplementary analysis, such as microarray.