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.
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ABSTRACT: Increased incidence of hand, foot and mouth disease (HFMD) has been recognized as a critical challenge to communicable disease control and public health response. This study aimed to quantify the association between climate variation and notified cases of HFMD in selected cities of Shanxi Province, and to provide evidence for disease control and prevention. Meteorological variables and HFMD cases data in 4 major cities (Datong, Taiyuan, Changzhi and Yuncheng) of Shanxi province, China, were obtained from the China Meteorology Administration and China CDC respectively over the period 1 January 2009 to 31 December 2013. Correlations analyses and Seasonal Autoregressive Integrated Moving Average (SARIMA) models were used to identify and quantify the relationship between the meteorological variables and HFMD. HFMD incidence varied seasonally with the majority of cases in the 4 cities occurring from May to July. Temperatures could play important roles in the incidence of HFMD in these regions. The SARIMA models indicate that a 1° C rise in average, maximum and minimum temperatures may lead to a similar relative increase in the number of cases in the 4 cities. The lag times for the effects of temperatures were identified in Taiyuan, Changzhi and Yuncheng. The numbers of cases were positively associated with average and minimum temperatures at a lag of 1 week in Taiyuan, Changzhi and Yuncheng, and with maximum temperature at a lag of 2 weeks in Yuncheng. Positive association between the temperature and HFMD has been identified from the 4 cities in Shanxi Province, although the role of weather variables on the transmission of HFMD varied in the 4 cities. Relevant prevention measures and public health action are required to reduce future risks of climate change with consideration of local climatic conditions.PLoS neglected tropical diseases 03/2015; 9(3):e0003572. DOI:10.1371/journal.pntd.0003572 · 4.72 Impact Factor
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ABSTRACT: Since 2008, Mainland China has undergone widespread outbreaks of hand, foot, and mouth disease (HFMD). In order to determine the characteristics of epidemics and enteroviruses (EV) associated with HFMD in Tianjin, in northern China, epidemiological and virological data from routine surveillance were collected and analyzed. In Tianjin, a persistent epidemic of HFMD was demonstrated during 2008-2013, involving 102,705 mild, 179 severe, and 16 fatal cases. Overall, 8234 specimens were collected from 7829 HFMD patients for EV detection during 2008-2013. Enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) were the dominant serotypes during 2008-2012, and they were replaced by CV-A6 as the major causative agent in 2013. Phylogenetic analysis based on complete VP1 nucleotide sequences revealed that multiple CV-A6 lineages co-circulated in Tianjin, which grouped together with strains from China and other countries and split into two distinct clusters (clusters 1 and 2). Most Tianjin strains grouped in cluster 1 and were closely related to strains from several eastern and southern provinces of China during 2012 and 2013. Estimates from Bayesian MCMC analysis suggested that multiple lineages had been transmitted silently before the outbreaks at an estimated evolutionary rate of 4.10 × 10(-3) substitutions per site per year without a specific distribution of rate variances among lineages. The sudden outbreak of CV-A6 in Tianjin during 2013 is attributed to indigenous CV-A6 lineages, which were linked to the wide spread of endemic strains around eastern and southern China.Archives of Virology 02/2015; DOI:10.1007/s00705-015-2340-3 · 2.28 Impact Factor
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ABSTRACT: The inability of molecular detection methods to distinguish disinfected virions from infectious ones has hampered the assessment of infectivity for enteric viruses caused by disinfection practices. In the present study, the reduction of infectivity of murine norovirus S7-PP3 and mengovirus vMC0, surrogates of human noroviruses and enteroviruses, respectively, caused by free chlorine treatment was characterized culture-independently by detecting carbonyl groups on viral capsid protein. The amount of carbonyls on viral capsid protein was evaluated by the proportion of biotinylated virions trapped by avidin-immobilized gel (%adsorbed). This culture-independent approach demonstrated that the %adsorbed was significantly correlated with the logarithm of the infectious titer of tested viruses. Taken together with the results of previous reports, the result obtained in this study indicates that the amount of carbonyls on viral capsid protein of four important families of waterborne pathogenic viruses: Mastroviridae, Reoviridae, Caliciviridae, and Picornaviridae, is increased in proportion to the received oxidative stress of free chlorine. There was also a significant correlation between the %adsorbed and the logarithm of the ratio of genome copy number to PFU, which enables estimation of the infectious titer of a subject virus by measuring values of the total genome copy number and the %adsorbed. The proposed method is applicable when the validation of 4-log reduction of viruses, a requirement in USEPA guidelines for virus removal from water, is needed along with clear evidence of the oxidation of virus particles with chlorine-based disinfectants. Copyright © 2015, American Society for Microbiology. All Rights Reserved.Applied and Environmental Microbiology 02/2015; DOI:10.1128/AEM.03802-14 · 3.95 Impact Factor