title: Genetic diversity of enterovirus 71 associated with hand, foot and mouth disease epidemics in Japan from 1983 to 2003.
abstract: BACKGROUND
  Enterovirus 71 (EV71) is one of the major etiologic agents of hand, foot and mouth disease (HFMD). The surveillance data indicate that EV71 infection follows an epidemic mode of transmission, causing large outbreaks and then becoming quiescent for a few years.
  
  
  METHODS
  We investigated the genetic diversity of a total of 121 EV71 strains isolated from patients with HFMD in Fukushima, Japan, from 1983 to 2003 and compared their genetic relation with the 164 EV71 strains isolated in the world using phylogenetic analysis based on the VP4 sequence.
  
  
  RESULTS
  We observed EV71-related HFMD outbreaks in Fukushima in 1984, 1987, 1990, 1993, 1997, 2000 and 2003. Phylogenetic reconstruction of EV71 strains isolated in Fukushima demonstrated 8 genetically distinct clusters, including 6 subgroups previously designated as B-1, B-2 and 3, B-4, C-1, C-2, and C-3 and 2 subgroups newly designated as B-5 and C-4. Additional 2 indistinct clusters belonged to genogroup C and were named C-U1 and C-U2. Of those subgroups, B-1, C-U1, C-U2, C-2, B4, and C-4 and B-5 dominantly related to epidemics that occurred in the years 1984, 1987 and 1990, 1993, 1997, 2000 and 2003, respectively. EV71 strains derived from each outbreak in Fukushima formed a single cluster with those isolated during almost the same time period in other area of Japan and in other countries.
  
  
  CONCLUSIONS
  Our results suggested that the repeated EV71 outbreaks might be the result of the worldwide transmission of the newly introduced genetically divergent EV71 strains.
authors.affiliation: Department of Pediatrics, Fukushima Medical University School of Medicine, Fukushima, Japan. mhosoya@fmu.ac.jp
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Hosoya
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Masatoki
authors.initials: M
authors.lastname: Sato
authors.forename: Ken
authors.initials: K
authors.lastname: Honzumi
authors.forename: Asako
authors.initials: A
authors.lastname: Kato
authors.forename: Toyomasa
authors.initials: T
authors.lastname: Hiroshima
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ishiko
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D016000:Cluster Analysis; D004196:Disease Outbreaks; D004770:Enterovirus / Q000235:genetics* / Q000302:isolation & purification; D005260:Female; D014644:Genetic Variation; D006232:Hand, Foot and Mouth Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D011159:Population Surveillance; D020133:Reverse Transcriptase Polymerase Chain Reaction