The largest outbreak of hand; foot and mouth disease in Singapore in 2008: The role of enterovirus 71 and coxsackievirus A strains
ABSTRACT 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.
- SourceAvailable from: Long Chen
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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]. "
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; DOI:10.1002/jmv.24200 · 2.22 Impact Factor
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- "In most cases, this illness is mild and self-limiting, but more severe clinical symptoms may occur when there are complications, such as encephalitis, aseptic meningitis, and acute flaccid paralysis (Chen et al. 2007). HFMD is most frequently caused by Coxsackie virus A16 (CA16) and enterovirus 71 (EV71) (Zhang et al. 2009; Wu et al. 2010), among which EV71 is more commonly associated with severe symptoms, including central nervous system disorders and even deaths resulting from pulmonary edema in a small proportion of children, particularly those aged 5 years and younger (Zhang et al. Chun Chen, Hualiang Lin, and Xiaoquan Li contributed to this work equally. "
ABSTRACT: Hand, foot and mouth disease (HFMD) is a contagious viral illness that commonly affects infants and children. The underlying risk factors have not yet been systematically examined. This study analyzed the short-term effects of meteorological factors on children HFMD in Guangzhou, China. Daily count of HFMD among children younger than 15 years and meteorological variables from 2009 to 2011 were collected to construct the time series. A generalized additive model was applied to estimate the effects of meteorological factors on HFMD occurrence, after adjusting for long-term trend, seasonal trend, day of week, and public holidays. A negative association between temperature and children HFMD occurrence was observed at lag days 1-3, with the relative risk (RR) for a 1 °C increase on lag day 2 being 0.983 (95 % confidence intervals (CI) 0.977 to 0.989); positive effect was found for temperature at lag days 5-9, with the highest effect at lag day 6 (RR = 1.014, 95 % CI 1.006 to 1.023). Higher humidity was associated with increased HFMD at lag days 3-10, with the highest effect at lag day 8 (RR = 1.009 for 1 % increase in relative humidity, 95 % CI 1.007 to 1.010). And we also observed significant positive effect for rainfall at lag days 4 and 8 (RR = 1.001, 95 % CI 1.000 to 1.002) for 1-mm increase. Subgroup analyses showed that the positive effects of temperature were more pronounced among younger children. This study suggests that meteorological factors might be important predictors of children HFMD occurrence in Guangzhou.International Journal of Biometeorology 11/2013; 58(7). DOI:10.1007/s00484-013-0764-6 · 2.10 Impact Factor
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- "Over the last decade, HFMD has become endemic in the Asia Pacific region with outbreaks occurring in Singapore, Malaysia, Japan and China every few years (WHO, 2011). After the eradication of poliovirus, EV71 has been regarded as the most important neurotropic enterovirus and a threat to global public health (Bible et al., 2007; Qiu, 2008; Wu et al., 2010). There are no specific antivirals or vaccines for EV71 infection and prevention is mainly achieved by disrupting virus transmission by surveillance, improved hygiene and temporary closure of childcare centers and schools during outbreaks . "
ABSTRACT: Human enterovirus 71 (EV71) has become a major public health threat across Asia Pacific. The virus causes hand, foot, and mouth disease which can lead to neurological complications in young children. There are no specific antivirals or vaccines against EV71 infection. The major neutralizing epitope of EV71 is located in the carboxy-terminal half of the VP1 protein at amino acid positions 215-219 (Lim et al., 2012). To study the immunogenicity of VP1 we have developed a baculovirus vector which displays VP1 as a type II transmembrane protein, providing an accessible C-terminus. Immunization of mice with this recombinant baculovirus elicited neutralizing antibodies against heterologous EV71 in an in vitro microneutralization assay. Passive protection of neonatal mice confirmed the prophylactic efficacy of the antisera. Additionally, EV71 specific T cell responses were stimulated. Taken together, our results demonstrate that the display of VP1 as a type II transmembrane protein efficiently stimulated both humoral and cellular immunities.Virus Research 06/2012; 168(1-2):64-72. DOI:10.1016/j.virusres.2012.06.014 · 2.83 Impact Factor