The largest outbreak of hand; foot and mouth disease in Singapore in 2008: The role of enterovirus 71 and coxsackievirus A strains

Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge 117597, Singapore.
International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases (Impact Factor: 1.86). 10/2010; 14(12):e1076-81. DOI: 10.1016/j.ijid.2010.07.006
Source: PubMed


During 2008, Singapore experienced its largest ever outbreak of hand, foot and mouth disease (HFMD), resulting in 29686 cases, including four cases of encephalitis and one fatality.
A total of 51 clinical specimens from 43 patients with suspected HFMD at the National University Hospital, Singapore were collected for virus isolation and identification by reverse transcription polymerase chain reaction (RT-PCR) and sequencing.
Enteroviruses were identified in 34 samples (66.7%), with 11 samples (21.6%) being positive for enterovirus 71 (EV71). Other non-EV71 enteroviruses (including coxsackievirus A4, A6, A10, and A16) were identified in 23 samples (45.1%). The most prevalent virus serotypes were CA6, CA10, and EV71. CA6 and CA10 accounted for 35.3% of all HFMD cases, which may explain the high transmissibility and low fatality that characterized this unprecedented epidemic associated with relatively mild disease. Phylogenetic analyses of 10 circulating EV71 strains indicated that they belonged to two subgenogroups, i.e., B5 (80%) and C2 (20%). The VP1 sequences of the 2008 EV71 strains also exhibited continuous mutations during the outbreak, reflecting the relatively high mutation rate of the EV71 capsid protein, which may have implications for future vaccine development.
A safe and effective vaccine against EV71 is certainly warranted in view of its potential neurovirulence and its role in HFMD epidemics of recurring frequency with resultant fatalities in Asia, as well as other parts of the world.

20 Reads
  • Source
    • "Interestingly, there were only four cases of encephalitis and one fatality. The high transmissibility and low fatality of the Singapore HFMD epidemic might due to the dominance of CA6 and CA10 infection [Wu et al., 2010]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hand, foot, and mouth disease (HFMD) is caused by human enteroviruses, especially by enterovirus 71 (EV71) and coxsackievirus A16 (CA16). Patients infected with different enteroviruses show varied clinical symptoms. The aim of this study was to determine whether the etiological spectrum of mild and severe HFMD changed, and the association between pathogens and clinical features. From 2009 to 2013, a total of 2,299 stool or rectal specimens were collected with corresponding patient data. A dynamic view of the etiological spectrum of mild and severe HFMD in Shenzhen city of China was provided. EV71 accounted for the majority proportion of severe HFMD cases and fatalities during 2009-2013. CA16 and EV71 were gradually replaced by coxsackievirus A6 (CA6) as the most common serotype for mild HFMD since 2010. Myoclonic jerk and vomiting were the most frequent severe symptoms. Nervous system complications, including aseptic encephalitis and aseptic meningitis were observed mainly in patients infected by EV71. Among EV71, CA16, CA6, and CA10 infection, fever and pharyngalgia were more likely to develop, vesicles on the hand, foot, elbow, knee and buttock were less likely to develop in patients infected with CA10. Vesicles on the mouth more frequently occurred in the patients with CA6, but less in the patient with EV71. Associations between diverse enterovirus serotypes and various clinical features were discovered in the present study, which may offer further insight into early detection, diagnosis and treatment of HFMD. J. Med. Virol. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Journal of Medical Virology 05/2015; 87(9). DOI:10.1002/jmv.24200 · 2.35 Impact Factor
  • Source
    • "Between February 2011 and July 2012, Vietnam reported a total of 174,677 cases and 200 deaths [12]. In Singapore, recent EV71- associated HFMD epidemics (140,000 cases and 8 deaths) occurred in 2006 and 2008, with the 2008 outbreak being the largest known HFMD outbreak [13] [14]. Thailand first reported a large-scale HFMD outbreak caused by EV71 in 2012 that included 39,000 cases and led to 3 deaths [15]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Enterovirus 71 (EV71) is a common pathogen for hand, foot, and mouth disease (HFMD), which has significant morbidity and mortality, and for which children aged 6-59 months age are at highest risk. Due to lack of effective treatment options, control of EV71 epidemics has mainly focused on development of EV71 vaccines. Clinical trials have been completed on 3 EV71 vaccines, with trial results demonstrating good vaccine efficacy and safety. When EV71 vaccine is approved by China's national regulatory authority, an evidence-based strategy should be developed to optimize impact and safety. An immunization strategy for EV71 vaccine should consider several factors, including the target population age group, the number of doses for primary immunization, the need for a booster dose, concomitant administration of other vaccines, economic value, program capacity and logistics, and public acceptance. Once EV71 vaccines are in use, vaccine effectiveness and safety must be monitored in large populations, and the epidemiology of HFMD must be evaluated to assure a match between vaccination strategy and epidemiology. Evaluation in China is especially important because there are no other EV71 vaccines globally. Copyright © 2014. Published by Elsevier Ltd.
    Vaccine 11/2014; 33(9). DOI:10.1016/j.vaccine.2014.10.081 · 3.62 Impact Factor
  • Source
    • "Studies on clinical complications caused by specific types of enteroviruses have been reported. Among multiple enterovirus types associated with recent HFMD and herpangina outbreaks, CAV6 has been recognized as an emerging causative virus since the epidemics in Finland and Singapore in 2008 [26]–[28] and its global dissemination thereafter in Taiwan in 2010 [29], Japan and Spain in 2011 [30], [31] and the United State in 2012 [32]. In our previous study, we have reported on large scale outbreaks of HFMD and herpangina in Thailand during the rainy season in 2012 with approximately 40,000 suspected cases all over the country, and shown that CAV6 played an important role during the outbreak in 2012 [33]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hand, foot, and mouth disease (HFMD) and herpangina are common infectious diseases caused by several genotypes of human enterovirus species A and frequently occurring in young children. This study was aimed at analyzing enteroviruses from patients with these diseases in Thailand in 2012. Detection and genotype determination of enteroviruses were accomplished by reverse transcription-polymerase chain reaction and sequencing of the VP1 region. Enterovirus-positive samples were differentiated into 17 genotypes (coxsackievirus A4 (CAV4), A5, A6, A8, A9, A10, A12, A16, A21, B1, B2, B4, B5, echovirus 7, 16, 25 and Enterovirus 71). The result showed CAV6 (33.5%), followed by CAV16 (9.4%) and EV71 (8.8%) as the most frequent genotypes in HFMD, CAV8 (19.3%) in herpangina and CAV6 (1.5%) in influenza like illness. Enterovirus infections were most prevalent during July with 34.4% in HFMD, 39.8% in herpangina and 1.6% in ILI. The higher enterovirus infection associated with HFMD and herpangina occurred in infants over one year-old. This represents the first report describing the circulation of multiple enteroviruses in Thailand.
    PLoS ONE 06/2014; 9(6):e98888. DOI:10.1371/journal.pone.0098888 · 3.23 Impact Factor
Show more


20 Reads
Available from