title: Fourteen types of co-circulating recombinant enterovirus were associated with hand, foot, and mouth disease in children from Wenzhou, China.
abstract: BACKGROUND
  Although hand, foot, and mouth disease (HFMD) is a major public concern in China, the prevalence and clinical symptoms associated with the different agents of HFMD in this country remain poorly understood.
  
  
  OBJECTIVE
  We investigated the clinical and molecular characteristics of enteroviruses in patients with HFMD from Wenzhou, China.
  
  
  METHODS
  Patients with laboratory-confirmed HFMD admitted to the Yuying Children's Hospital in Wenzhou, China during 2013 were included in this study. Viral RNA sequences were amplified using RT-PCR, determined by sequencing, and compared by phylogenetic analysis.
  
  
  RESULTS
  A total of 955 clinically diagnosed HFMD cases were determined using PCR, with whole viral genomes obtained for each enterovirus type. 14 types of enterovirus belonging to two viral species were identified. Notably, Coxsackievirus A6 (CV-A6) was the most common species detected (77.8%), followed by EV-A71 (8.2%) and CV-A10 (8.1%). Phylogenetic analysis revealed multiple independent introductions of these viruses into Wenzhou. In addition, the enterovirus observed in Wenzhou had a recombinant history, with two or three recombination breakpoints. Although the illness associated with CV-A6 was milder than that of EV-A71, CV-A6 infection caused more widespread rash, larger blisters, and subsequent skin peeling and/or nail shedding.
  
  
  CONCLUSIONS
  Our study revealed the co-circulation of 14 types of enteroviruses in a single location - Wenzhou, China - with CV-A6 virus the predominant agent of HFMD. This work highlights the need to perform larger-scale surveillance to fully understand the epidemiology of enteroviruses in China and the wider Asia-Pacific region.
authors: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changping Liuzi 5, 102206 Beijing, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors: Wen-Ping
authors: WP
authors: Guo
authors: Wenzhou Center for Disease Control and Prevention, Wenzhou 325001, Zhejiang Province, China.
authors: Xian-Dan
authors: XD
authors: Lin
authors: The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang Province, China.
authors: Yi-Ping
authors: YP
authors: Chen
authors: The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang Province, China.
authors: Qi
authors: Q
authors: Liu
authors: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changping Liuzi 5, 102206 Beijing, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors: Wen
authors: W
authors: Wang
authors: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changping Liuzi 5, 102206 Beijing, China.
authors: Cai-Qiao
authors: CQ
authors: Wang
authors: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changping Liuzi 5, 102206 Beijing, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors: Ming-Hui
authors: MH
authors: Li
authors: Wenzhou Center for Disease Control and Prevention, Wenzhou 325001, Zhejiang Province, China.
authors: Xiao-Yu
authors: XY
authors: Sun
authors: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changping Liuzi 5, 102206 Beijing, China; Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.
authors: Mang
authors: M
authors: Shi
authors: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changping Liuzi 5, 102206 Beijing, China; Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.
authors: Edward C
authors: EC
authors: Holmes
authors: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changping Liuzi 5, 102206 Beijing, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China. Electronic address: zhangyongzhen@icdc.cn.
authors: Yong-Zhen
authors: YZ
authors: Zhang
mesh_terms: D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D015897:Comorbidity; D004770:Enterovirus / Q000145:classification / Q000235:genetics*; D005260:Female; D005838:Genotype; D006232:Hand, Foot and Mouth Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology*; D006801:Humans; D007223:Infant; D008297:Male; D010802:Phylogeny; D011159:Population Surveillance; D012367:RNA, Viral / Q000235:genetics; D016865:Reassortant Viruses; D011995:Recombination, Genetic
chemical_list: D012367:RNA, Viral
keywords: Coxsackievirus A6; Enterovirus 71; Enteroviruses; Hand, foot and mouth disease; Recombination