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

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The largest outbreak of hand; foot and mouth disease in Singapore in 2008: The role of enterovirus 71 and coxsackievirus A strains  Yan Wu, Andrea Yeo, M.C. Phoon, E.L. Tan, C.L. Poh, S.H. Quak, Vincent T.K. Chow  International Journal of Infectious Diseases  Volume 14, Issue 12, Pages e1076-e1081 (December 2010) DOI: 10.1016/j.ijid.2010.07.006 Copyright © 2010 International Society for Infectious Diseases Terms and Conditions

Figure 1 Distribution of clinical features in EV71 and non-EV71 patients. International Journal of Infectious Diseases 2010 14, e1076-e1081DOI: (10.1016/j.ijid.2010.07.006) Copyright © 2010 International Society for Infectious Diseases Terms and Conditions

Figure 2 Sequence alignment of 10 outbreak EV71 strains against the hybridization acceptor probe for real-time RT-PCR. The highlighted mismatches may explain the failure of detection of the EV71 strains using this assay. The subgenogroups of the strains, and nucleotide positions at the 5′ (2496) and 3′ (2519) ends of the probe are shown. International Journal of Infectious Diseases 2010 14, e1076-e1081DOI: (10.1016/j.ijid.2010.07.006) Copyright © 2010 International Society for Infectious Diseases Terms and Conditions

Figure 3 Dendrogram constructed based on the complete VP1 gene sequences of 10 outbreak EV71 strains and selected known strains, elucidating B5 and C2 as the respective major and minor EV71 subgenogroups circulating during the 2008 Singapore epidemic. The percentages of replicate trees in which the associated taxa are clustered together are shown next to the branches. Branch lengths are proportional to the number of nucleotide differences. International Journal of Infectious Diseases 2010 14, e1076-e1081DOI: (10.1016/j.ijid.2010.07.006) Copyright © 2010 International Society for Infectious Diseases Terms and Conditions

Figure 4 Alignment of VP1 nucleotides of eight EV71 strains belonging to subgenogroup B5 according to the time of specimen receipt. The disparities at 12 different positions highlight the evolution of the VP1 regions of B5 strains during the course of the large epidemic. For example, five disparities at positions 644, 658, 820, 832, and 866 emerged in strains that were obtained later in the outbreak. Common disparities at nucleotides 19, 373, and 756 were also identified only in strains detected later. International Journal of Infectious Diseases 2010 14, e1076-e1081DOI: (10.1016/j.ijid.2010.07.006) Copyright © 2010 International Society for Infectious Diseases Terms and Conditions

Figure 5 Amino acid sequence variations within the VP1 neutralizing antibody epitopes SP12, SP55, and SP70 of the 2008 outbreak EV71 strains. International Journal of Infectious Diseases 2010 14, e1076-e1081DOI: (10.1016/j.ijid.2010.07.006) Copyright © 2010 International Society for Infectious Diseases Terms and Conditions

Figure 6 Weekly incidence of hand, foot and mouth disease in Singapore during 2008 and 2009. The dotted line depicts the epidemic threshold of 665 cases (www.moh.gov.sg/mohcorp/statisticsweeklybulletins.aspx). International Journal of Infectious Diseases 2010 14, e1076-e1081DOI: (10.1016/j.ijid.2010.07.006) Copyright © 2010 International Society for Infectious Diseases Terms and Conditions