title: Enterovirus 71 infection in children with hand, foot, and mouth disease in Shanghai, China: epidemiology, clinical feature and diagnosis.
abstract: BACKGROUND
  In 2012 a large outbreak of hand, foot, and mouth disease (HFMD) widely spread over China, causing more than 2 million cases and 567 deaths. Our purpose was to characterize the major pathogens responsible for the 2012 HFMD outbreak and analyze the genetic characterization of the enterovirus 71 (EV71) strains in Shanghai; also, to analyze the dynamic patterns of neutralizing antibody (NAb) against EV71 and evaluate the diagnostic value of several methods for clinical detection of EV71.
  
  
  METHODS
  Clinical samples including stool, serum and CSF were collected from 396 enrolled HFMD inpatients during the peak seasons in 2012. We analyzed the molecular epidemiology, clinical feature, and diagnostic tests of EV71 infection.
  
  
  RESULTS
  EV71 was responsible for 60.35 % of HFMD inpatients and 88.46 % of severe cases. The circulating EV71 strains belonged to subgenogroup C4a. The nucleotide sequences of VP1 between severe cases and uncomplicated cases shared 99.2 ~ 100 % of homology. Among 218 cases with EV71 infection, 211 (96.79 %) serum samples showed NAb positive against EV71 and NAb titer reached higher level 3 days after disease onset. Of 92 cases with EV71-associated meningitis or encephalitis, 5 (5.43 %) of 92 had EV71 RNA detected in CSF samples. The blood anti-EV71 IgM assay showed a sensitivity of 93.30 % and a specificity of 50 %.
  
  
  CONCLUSIONS
  EV71 C4a remained the predominant subgenotype circulating in Shanghai. The severity of the EV71 infection is not associated with the virulence determinants in VP1. RT-PCR together with IgM detection can enhance the early diagnosis of severe EV71-associated HFMD.
authors.affiliation: Institute of Molecular Ecology and Evolution, SKLEC & IECR, East China Normal University, Shanghai, 200062, China. ywang@ips.ac.cn.|Unit of Anti-infective Research, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China. ywang@ips.ac.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Unit of Anti-infective Research, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China. gangzou@ips.ac.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Zou
authors.affiliation: Department of Infectious Diseases, Children's Hospital of Fudan University, Shanghai, 201102, China. 46562647@qq.com.
authors.forename: Aimei
authors.initials: A
authors.lastname: Xia
authors.affiliation: Department of Infectious Diseases, Children's Hospital of Fudan University, Shanghai, 201102, China. shi_16811@163.com.
authors.forename: Xiangshi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Children's Hospital of Fudan University, Shanghai, 201102, China. caijiehao@aliyun.com.
authors.forename: Jiehao
authors.initials: J
authors.lastname: Cai
authors.affiliation: Institute of Molecular Ecology and Evolution, SKLEC & IECR, East China Normal University, Shanghai, 200062, China. qqgao@ips.ac.cn.|Unit of Anti-infective Research, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China. qqgao@ips.ac.cn.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Unit of Anti-infective Research, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China. slyuan@ips.ac.cn.
authors.forename: Shilin
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Institute of Molecular Ecology and Evolution, SKLEC & IECR, East China Normal University, Shanghai, 200062, China. gmhe@bio.ecnu.edu.cn.
authors.forename: Guimei
authors.initials: G
authors.lastname: He
authors.affiliation: Institute of Molecular Ecology and Evolution, SKLEC & IECR, East China Normal University, Shanghai, 200062, China. syzhang@bio.ecnu.edu.cn.
authors.forename: Shuyi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Children's Hospital of Fudan University, Shanghai, 201102, China. zengmeigao@aliyun.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Unit of Anti-infective Research, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China. raltmeyer@ips.ac.cn.
authors.forename: Ralf
authors.initials: R
authors.lastname: Altmeyer
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002555:Cerebrospinal Fluid / Q000821:virology; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D016000:Cluster Analysis; D004196:Disease Outbreaks; D042241:Early Diagnosis; D029821:Enterovirus A, Human / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D005243:Feces / Q000821:virology; D005260:Female; D006232:Hand, Foot and Mouth Disease / Q000175:diagnosis* / Q000453:epidemiology* / Q000473:pathology; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D007223:Infant; D008297:Male; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D044967:Serum / Q000821:virology; D015678:Viral Structural Proteins / Q000235:genetics
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007075:Immunoglobulin M; D012367:RNA, Viral; D015678:Viral Structural Proteins