Causative agents of hand, foot and mouth disease in University Malaya Medical Centre, Kuala Lumpur, Malaysia in 2012-2013.

Hand, foot and mouth disease (HFMD) is a childhood illness, commonly caused by enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16). In recent years, unusual HFMD outbreaks caused by coxsackievirus A6 (CV-A6) have been reported. From May 2012 to September 2013, enteroviruses were detected in 25 HFMD patients in University Malaya Medical Centre, Kuala Lumpur, Malaysia. The predominant serotypes were EV-A71 (48%) and CV-A6 (48%), followed by CV-A16 (4%). CV-A6 patients (mean age, 2.1) were significantly younger than EV-A71 patients (mean age, 3.3). There were no significant differences observed in clinical features between EV-A71 and CV-A6 patients. Since enteroviruses are difficult to differentiate clinically, the conserved 5' untranslated region (5' UTR) was used to identify enterovirus serotypes. Phylogenetic analysis of 5' UTR showed distinct clustering of viruses as EV-A71, CV-A16 and CV-A6. Further genotyping with capsid genes showed that all the EVA71 sequences belonged to subgenotype B5, while the CV-A16 sequence belonged to subgenotype B2b. CV-A6 sequences were clustered into genotypes D1 and D2, with recent isolates from Seri Kembangan, Malaysia and China. In summary, 59.5% of HFMD cases in our centre in 2012-2013 were caused by EV-A71, CV-A16 and the newly emerging CV-A6. This study also demonstrated that 5' UTR is suitable for preliminary identification of enteroviruses during HFMD outbreaks, but specific capsid genes such as VP1 and VP4/VP2 are required for further genotyping. Apart from measures to control the spread of the virus during an outbreak of HFMD, identification of EV-A71 as the etiological agent is important as EV-A71 is a major cause of severe neurological complications and potentially fatal.