title: An outbreak of hand, foot, and mouth disease associated with subgenotype C4 of human enterovirus 71 in Shandong, China.
abstract: BACKGROUND
  An outbreak of hand, foot, and mouth disease (HFMD) included 1149 people in Linyi City, Shandong Province, China, in 2007: three children died.
  
  
  OBJECTIVE
  To characterize the pathogens responsible for this outbreak and to analyze their genetic features.
  
  
  METHODS
  A total of 233 clinical specimens were collected from 105 hospitalized patients, including 11 patients with severe HFMD. Virological investigations (direct RT-PCR, viral isolation and molecular identification) and phylogenetic analysis were performed.
  
  
  RESULTS
  Human enterovirus 71 (HEV71) was the main pathogen that caused this outbreak, based on clinical manifestations, epidemiological data, and laboratory results. Phylogenetic analysis indicated that the Shandong HEV71 isolates belonged to 3 lineages in subgenotype C4. Subgenotype C4 could be further divided into two clusters (C4a and C4b), which corresponded to two time periods. Cluster C4a HEV71 has been the predominant virus circulating in mainland China in the past 5 years.
  
  
  CONCLUSIONS
  The 2007 HFMD outbreak was mainly caused by HEV71 subgenotype C4 with 3 transmission chains. This virus has been continuously circulating in China since 1998. The Shandong strains co-evolved with isolates from other provinces in mainland China and neighboring countries.
authors.affiliation: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Xuanwu District, Beijing, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Tan
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Wang
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Yan
authors.forename: Shuang-Li
authors.initials: SL
authors.lastname: Zhu
authors.forename: Dong-Yan
authors.initials: DY
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Ji
authors.forename: Xian-Jun
authors.initials: XJ
authors.lastname: Wang
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Gao
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Hong-Qiu
authors.initials: HQ
authors.lastname: An
authors.forename: De-Xin
authors.initials: DX
authors.lastname: Li
authors.forename: Shi-Wen
authors.initials: SW
authors.lastname: Wang
authors.forename: Ai-Qiang
authors.initials: AQ
authors.lastname: Xu
authors.forename: Zi-Jun
authors.initials: ZJ
authors.lastname: Wang
authors.forename: Wen-Bo
authors.initials: WB
authors.lastname: Xu
mesh_terms: D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D016000:Cluster Analysis; D004196:Disease Outbreaks; D029821:Enterovirus A, Human / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D006232:Hand, Foot and Mouth Disease / Q000453:epidemiology* / Q000821:virology*; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017385:Sequence Homology
chemical_list: D012367:RNA, Viral