Prevalence of human enterovirus infection and complete coding sequence analysis of human enterovirus 71 among patients with hand, foot and mouth disease and herpangina in Thailand, 2008-2014

Abstract

Hand, foot, and mouth disease (HFMD) due to human enterovirus (HEV) infections affects multiple countries worldwide especially in the Asia-Pacific region. Previous studies showed an outbreak of HEV are often fast spread and easily transmitted with some enterovirus infection, for example enterovirus 71(EV71), could potentially develop into neurological complication. The study examined prevalence of enterovirus among patients with HFMD and herpangina in Thailand and evolution of EV71 through conducting a complete genome characterization on circulating strains. To detect and identify all circulating HEV in Thailand a subset of 584 from1221 clinical specimens, from 2008 to 2013, which was negative form specific primers amplification were further detected for other enterovirus detection through amplification of partial VP1 gene with CODEHOP primers. One hundred and fifteen clinical specimens were identified resulted in an increase in detection rate to 61%. All 4 species of HEV, A, B, C, and D, were detected and result show highest prevalence of HEV in HEV-A of 93.5% (n=603) follow by 5.74% (n=37) in HEV-B, 0.930% (n=6) in HEV-C and 0.155% (n=1) in HEV-D. More HEV were detected at the begining of the year, January and Febuary, and during rainy season, June - August. The complete genomic sequences of 14 EV71 strains isolated from children with hand, foot and mouth disease in Thailand from 2012 to 2014 were determined and compared to enterovirus group A prototypes. Phylogenetic analysis revealed that 13 strains resembled B5 subgroup, while one strain from a fatal case designated THA_1219 belonged to C4 subgroup. The phygenetic analysis demonstrates distinct separation of B5 subgenotype between strains detected during and post-HFMD outbreak. Similarity plot and bootscan analyses suggested that THA_1219 underwent recombination in the P2 and P3 regions where such region are closer related to coxsackievirus A4, 14 and 16 than EV71 prototype strain. The study reports first complete enterovirus prevalence in Thailand and demonstrate evolution dynamics of the EV71 strain from fatal patient.