An epidemiological surveillance of hand foot and mouth disease in paediatric patients and in community: A Singapore retrospective cohort study, 2013–2018
Open Access
- 10 February 2021
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Neglected Tropical Diseases
- Vol. 15 (2), e0008885
- https://doi.org/10.1371/journal.pntd.0008885
Abstract
While hand, foot and mouth disease (HFMD) is primarily self-resolving—soaring incidence rate of symptomatic HFMD effectuates economic burden in the Asia-Pacific region. Singapore has seen a conspicuous rise in the number of HFMD cases from 2010s. Here, we aims to identify the serology and genotypes responsible for such outbreaks in hospitals and childcare facilities. We studied symptomatic paediatric HFMD cases from 2013 to 2018 in Singapore. Surveillance for subclinical enterovirus infections was also performed in childcares at the same time period. Genotyping 101 symptomatic HFMD samples revealed CV-A6 as the major etiological agent for recent outbreaks. We detected infections with CV-A6 (41.0%), EV-A71 (7%), CV-A16 (3.0%), coxsackievirus A2, CV-A2 (1.0%) and coxsackievirus A10, CV-A10 (1.0%). Phylogenetic analysis of local CV-A6 strains revealed a high level of heterogeneity compared against others worldwide, dissimilar to other HFMD causative enteroviruses for which the dominant strains and genotypes are highly region specific. We detected sub-clinical enterovirus infections in childcare centres; 17.1% (n = 245) tested positive for enterovirus in saliva, without HFMD indicative symptoms at the point of sample collection. CV-A6 remained as the dominant HFMD causative strain in Singapore. Silent subclinical enteroviral infections were detected and warrant further investigations. In most cases, Hand Foot and Mouth Disease or HFMD typically manifest in mild fever along with sore throat and rashes on the body. From 2010 onwards, Singapore has seen a steady increase in the case number of HFMD reaching tens of thousands in recent years. HFMD is caused by intestinal viruses and in this study, we established with molecular surveillance methods that one of the causative serotypes, CV-A6 is the major etiological agent for HFMD in Singapore for the current decade. We discovered that circulating enterovirus, CV-A6 in Singapore share similarities in genetic make-up to those currently circulating strains found worldwide and found to be especially close to the ones in neighbouring countries. HFMD spreads from person to person, especially in high-risk areas such as childcare centers where children congregate. Therefore, we conducted saliva collections routinely from childcare centers across Singapore and found that subclinical enterovirus infections have also been prevailing in clusters, occurring silently and unnoticed.Keywords
Funding Information
- National Medical Research Council (NMRC/CBRG/0059/2014)
- Ministry of Education - Singapore (MOE2017-T2-1-078)
- Ministry of Education - Singapore (MOE2017-T2-2-014)
This publication has 33 references indexed in Scilit:
- Molecular epidemiology of enterovirus 71, coxsackievirus A16 and A6 associated with hand, foot and mouth disease in SpainClinical Microbiology & Infection, 2014
- RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogeniesBioinformatics, 2014
- Active immunization with a Coxsackievirus A16 experimental inactivated vaccine induces neutralizing antibodies and protects mice against lethal infectionVaccine, 2013
- MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and UsabilityMolecular Biology and Evolution, 2013
- CD-HIT: accelerated for clustering the next-generation sequencing dataBioinformatics, 2012
- The largest outbreak of hand; foot and mouth disease in Singapore in 2008: The role of enterovirus 71 and coxsackievirus A strainsInternational Journal of Infectious Diseases, 2010
- Coxsackievirus A6 and Hand, Foot, and Mouth Disease, FinlandEmerging Infectious Diseases, 2009
- Molecular Epidemiology of Human Enterovirus 71 Strains and Recent Outbreaks in the Asia-Pacific Region: Comparative Analysis of the VP1 and VP4 GenesEmerging Infectious Diseases, 2003
- Direct Detection of Enterovirus 71 (EV71) in Clinical Specimens from a Hand, Foot, and Mouth Disease Outbreak in Singapore by Reverse Transcription-PCR with Universal Enterovirus and EV71-Specific PrimersJournal of Clinical Microbiology, 2002
- Phylogenetic Analysis of Enterovirus 71 Strains Isolated during Linked Epidemics in Malaysia, Singapore, and Western AustraliaJournal of Virology, 2001