Giuseppe
Emeritus
[Source: PLoS ONE, full page: (LINK). Abstract, edited.]
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Research Article
Circulation of Coxsackievirus A10 and A6 in Hand-Foot-Mouth Disease in China, 2009?2011
Qing-Bin Lu 1, Xiao-Ai Zhang 2, Ying Wo 3, Hong-Mei Xu 4, Xiu-Jun Li 5, Xian-Jun Wang 6, Shu-Jun Ding 7, Xiao-Dan Chen 8, Cui He 9, Li-Juan Liu 10, Hao Li 11, Hong Yang 12, Ting-Yu Li 13,
Affiliations: 1 Department of Epidemiology and Health Statistics, Shandong University, Jinan, People?s Republic of China, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People?s Republic of China; 2 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People?s Republic of China; 3 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People?s Republic of China; 4 Children?s Hospital, Chongqing Medical University, Chongqing, People?s Republic of China; 5 Department of Epidemiology and Health Statistics, Shandong University, Jinan, People?s Republic of China; 6 Department of Infectious Disease Control, Shandong Provincial Disease Prevention and Control Center, Jinan, People?s Republic of China; 7 Department of Infectious Disease Control, Shandong Provincial Disease Prevention and Control Center, Jinan, People?s Republic of China; 8 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People?s Republic of China; 9 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People?s Republic of China; 10 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People?s Republic of China; 11 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People?s Republic of China; 12 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People?s Republic of China; 13 Children?s Hospital, Chongqing Medical University, Chongqing, People?s Republic of China
Abstract
Coxsackieviruses A10 (CV-A10) and A6 (CV-A6) have been associated with increasingly occurred sporadic hand-foot-mouth disease (HFMD) cases and outbreak events globally. However, our understanding of epidemiological and genetic characteristics of these new agents remains far from complete. This study was to explore the circulation of CV-A10 and CV-A6 in HFMD and their genetic characteristics in China. A hospital based surveillance was performed in three heavily inflicted regions with HFMD from March 2009 to August 2011. Feces samples were collected from children with clinical diagnosis of HFMD. The detection and genotyping of enteroviruses was performed by real-time PCR and sequencing of 5′UTR/VP1 regions. Phylogenetic analysis and selection pressure were performed based on the VP1 sequences. Logistic regression model was used to identify the effect of predominant enterovirus serotypes in causing severe HFMD. The results showed 92.0% of 1748 feces samples were detected positive for enterovirus, with the most frequently presented serotypes as EV-71 (944, 54.0%) and CV-A16 (451, 25.8%). CV-A10 and CV-A6 were detected as a sole pathogen in 82 (4.7%) and 44 (2.5%) cases, respectively. Infection with CV-A10 and EV-71 were independently associated with high risk of severe HFMD (OR = 2.66, 95% CI: 1.40?5.06; OR = 4.81, 95% CI: 3.07?7.53), when adjusted for age and sex. Phylogenetic analysis revealed that distinct geographic and temporal origins correlated with the gene clusters based on VP1 sequences. An overall ω value of the VP1 was 0.046 for CV-A10 and 0.047 for CV-A6, and no positively selected site was detected in VP1 of both CV-A10 and CV-A6, indicating that purifying selection shaped the evolution of CV-A10 and CV-A6. Our study demonstrates variety of enterovirus genotypes as viral pathogens in causing HFMD in China. CV-A10 and CV-A6 were co-circulating together with EV-71 and CV-A16 in recent years. CV-A10 infection might also be independently associated with severe HFMD.
Citation: Lu Q-B, Zhang X-A, Wo Y, Xu H-M, Li X-J, et al. (2012) Circulation of Coxsackievirus A10 and A6 in Hand-Foot-Mouth Disease in China, 2009?2011. PLoS ONE 7(12): e52073. doi:10.1371/journal.pone.0052073
Editor: Chiyu Zhang, Institut Pasteur of Shanghai, Chinese Academy of Sciences, China
Received: September 14, 2012; Accepted: November 8, 2012; Published: December 18, 2012
Copyright: ? 2012 Lu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was supported by the grants of China Mega-Project on Infectious Disease Prevention (2009ZX10004-204), National Science Fund for Distinguished Young Scholars (30725032) and Shandong Scientific and Technical Supporting Program (2009GG10002055). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: caowc@nic.bmi.ac.cn (WCC); liu_weis@sohu.com (WL)
# These authors contributed equally to this work.
-Circulation of Coxsackievirus A10 and A6 in Hand-Foot-Mouth Disease in China, 2009?2011
Qing-Bin Lu 1, Xiao-Ai Zhang 2, Ying Wo 3, Hong-Mei Xu 4, Xiu-Jun Li 5, Xian-Jun Wang 6, Shu-Jun Ding 7, Xiao-Dan Chen 8, Cui He 9, Li-Juan Liu 10, Hao Li 11, Hong Yang 12, Ting-Yu Li 13,
Affiliations: 1 Department of Epidemiology and Health Statistics, Shandong University, Jinan, People?s Republic of China, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People?s Republic of China; 2 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People?s Republic of China; 3 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People?s Republic of China; 4 Children?s Hospital, Chongqing Medical University, Chongqing, People?s Republic of China; 5 Department of Epidemiology and Health Statistics, Shandong University, Jinan, People?s Republic of China; 6 Department of Infectious Disease Control, Shandong Provincial Disease Prevention and Control Center, Jinan, People?s Republic of China; 7 Department of Infectious Disease Control, Shandong Provincial Disease Prevention and Control Center, Jinan, People?s Republic of China; 8 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People?s Republic of China; 9 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People?s Republic of China; 10 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People?s Republic of China; 11 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People?s Republic of China; 12 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People?s Republic of China; 13 Children?s Hospital, Chongqing Medical University, Chongqing, People?s Republic of China
Abstract
Coxsackieviruses A10 (CV-A10) and A6 (CV-A6) have been associated with increasingly occurred sporadic hand-foot-mouth disease (HFMD) cases and outbreak events globally. However, our understanding of epidemiological and genetic characteristics of these new agents remains far from complete. This study was to explore the circulation of CV-A10 and CV-A6 in HFMD and their genetic characteristics in China. A hospital based surveillance was performed in three heavily inflicted regions with HFMD from March 2009 to August 2011. Feces samples were collected from children with clinical diagnosis of HFMD. The detection and genotyping of enteroviruses was performed by real-time PCR and sequencing of 5′UTR/VP1 regions. Phylogenetic analysis and selection pressure were performed based on the VP1 sequences. Logistic regression model was used to identify the effect of predominant enterovirus serotypes in causing severe HFMD. The results showed 92.0% of 1748 feces samples were detected positive for enterovirus, with the most frequently presented serotypes as EV-71 (944, 54.0%) and CV-A16 (451, 25.8%). CV-A10 and CV-A6 were detected as a sole pathogen in 82 (4.7%) and 44 (2.5%) cases, respectively. Infection with CV-A10 and EV-71 were independently associated with high risk of severe HFMD (OR = 2.66, 95% CI: 1.40?5.06; OR = 4.81, 95% CI: 3.07?7.53), when adjusted for age and sex. Phylogenetic analysis revealed that distinct geographic and temporal origins correlated with the gene clusters based on VP1 sequences. An overall ω value of the VP1 was 0.046 for CV-A10 and 0.047 for CV-A6, and no positively selected site was detected in VP1 of both CV-A10 and CV-A6, indicating that purifying selection shaped the evolution of CV-A10 and CV-A6. Our study demonstrates variety of enterovirus genotypes as viral pathogens in causing HFMD in China. CV-A10 and CV-A6 were co-circulating together with EV-71 and CV-A16 in recent years. CV-A10 infection might also be independently associated with severe HFMD.
Citation: Lu Q-B, Zhang X-A, Wo Y, Xu H-M, Li X-J, et al. (2012) Circulation of Coxsackievirus A10 and A6 in Hand-Foot-Mouth Disease in China, 2009?2011. PLoS ONE 7(12): e52073. doi:10.1371/journal.pone.0052073
Editor: Chiyu Zhang, Institut Pasteur of Shanghai, Chinese Academy of Sciences, China
Received: September 14, 2012; Accepted: November 8, 2012; Published: December 18, 2012
Copyright: ? 2012 Lu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was supported by the grants of China Mega-Project on Infectious Disease Prevention (2009ZX10004-204), National Science Fund for Distinguished Young Scholars (30725032) and Shandong Scientific and Technical Supporting Program (2009GG10002055). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: caowc@nic.bmi.ac.cn (WCC); liu_weis@sohu.com (WL)
# These authors contributed equally to this work.
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