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

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.

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    • "Previously, CA10 had been isolated from in sporadic HFMD cases in New Zealand in 1957 and the first clustering outbreak of HFMD caused by CA10 was reported in Japan in 1983 (Seddon et al., 1971; Itagaki et al., 1983). CA10 accounted for 11.8% of all cases in the largest HFMD outbreak in Singapore in 2008 (Wu et al., 2010) and was one of the main pathogens in the Finland outbreak, which occurred around the same time (Blomqvist et al., 2010). A sentinel surveillance study in France in 2010 showed that the predominant serotype was CA10 (39.9%), whereas the infection rate of EV71 and CA16 was low (23.8%) "
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    ABSTRACT: Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) have been the primary causative agents of hand, foot, and mouth disease (HFMD) outbreaks in mainland China in the past. Hence, the surveillance of HFMD has mostly focused on these viruses. However, in recent years, coxsackievirus A10 (CA10) has also been associated with the increasing sporadic HFMD cases and outbreaks. Therefore, a sensitive assay for rapid detection of the CA10 RNA is necessary for disease control. Here, we have developed a specific TaqMan real-time RT-PCR assay by analyzing VP1 gene sequences of CA10 strains from different locations. The assay has been shown to be specific, sensitive, and robust through detection of other related viruses, standard curves, and clinical samples, respectively. This is the first report on development of a VP1 gene-based TaqMan real-time RT-PCR assay for rapid diagnosis of CA10 virus.
    Preview · Article · Dec 2015 · Genetics and molecular research: GMR
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    • "Hand, foot and mouth disease (HFMD) is a common childhood infectious disease that typically presents as vesicular exanthema of the oral mucosa and peripheral extremities [1]. Enteroviruses, such as Coxsackievirus A6, A16 and Enterovirus A71, are the most common etiological agents [2]. HFMD is typically characterized by a brief febrile illness, typical vesicular rashes on the palms, soles, or buttocks, and oropharyngeal ulcers. "
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    ABSTRACT: A statistic analysis based on the available literatures from the year 1972 to 2014 was carried out by cooperating with Elsevier Solution Consultants, in order to learn the radiological research tendency and find out the radiological research direction of Hand, foot and mouth disease. A general summary was analyzed, including the literature quantity, the literature type, the geographic distributions and journal distributions of literatures on radiology of Hand, foot and mouth disease. Such prompting statistic would definitely enable revealing the radiological research on the Hand, foot and mouth disease, enrich the corresponding theoretical connotation and guide the clinical practice.
    Full-text · Article · Nov 2015
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    • "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]. "
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    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.
    Full-text · Article · May 2015 · Journal of Medical Virology
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