Characterization of enteroviruses from hand, foot and mouth disease cases in the Philippines, 2012–2017

Abstract

Background: Hand, foot and mouth disease (HFMD) surveillance began in the Philippines in 2012 following an outbreak in Cambodia. Since then, the National Reference Laboratory for Polio and other Enteroviruses has been providing laboratory support for the surveillance. HFMD is one of the notifiable diseases with a case definition any individual who developed acute febrile illness with papulovesicular or maculopapular rash on palms and soles, with or without vesicular lesion/ulcers in the mouth. Much has been known about the epidemiology of HFMD in the Asia Pacific region, however, data in the Philippines is yet to be established. Previous enterovirus study in the country only focused among acute flaccid paralysis and environmental samples. In this study, enterovirus epidemiology implicated in HFMD was elucidated. Methods and materials: From 2012 to 2017, 3021 samples from all regions of the Philippines were reported and tested using a hemi-nested PCR targeting the 5′ UTR to screen for enterovirus and a multiplex assay targeting the VP1 region to identify the common causative agents, namely, Enterovirus A71 (EV-A71), Coxsackievirus A6 (CVA6) and CVA16. Phylogenetic analysis of the complete VP1 genes was done to describe the genetic characteristics of these enteroviruses in the Philippines. Results: Majority of the tested samples are positive for enterovirus, 74% (2232/3021). Of these, 76.7% were identified as CVA6 (1101/1436), 8.9% are CVA16 (128/1436) and 3% are EV-A71 (62/2232). A steady increase in the detection of CVA6 has been observed, with its detection rate increasing from 62% in 2012 to 88% in 2017, while a decreasing trend in CVA16 was noted. Phylogenetic analysis showed that EV-A71 implicated in HFMD clustered with genogroup C2. Conclusion: CVA6 is the most common cause of HFMD in reported cases in the Philippines from 2012 to 2017. EV-A71 used to be the cause of HFMD worldwide, however, our study supports a new trend and that there is a shift in the etiologic agent for HFMD as seen in the Asia Pacific region like Thailand, China and Japan since 2010. Moreover, the EV-A71 C2 cluster is indigenously circulating in the Philippines as only the C2 cluster was seen from AFP cases since 2000 and also from environmental studies.