title: Risk factors of enterovirus 71 infection and associated hand, foot, and mouth disease/herpangina in children during an epidemic in Taiwan.
abstract: OBJECTIVE
  In 1998, an enterovirus 71 (EV71) epidemic in Taiwan was associated with hand, foot, and mouth disease (HFMD)/herpangina and involved 78 fatal cases. We measured EV71 seroprevalence rates before and after the epidemic and investigated risk factors associated with EV71 infection and illness.
  
  
  METHODS
  Neutralizing antibodies to EV71 were assayed for 539 people before the epidemic and 4619 people of similar ages after the epidemic. Questionnaires, which were completed during household interviews after the epidemic, solicited demographic variables, exposure history, and clinical manifestations.
  
  
  RESULTS
  A total of 129 106 cases of HFMD were reported during the epidemic. Age-specific pre-epidemic EV71 seroprevalence rates were inversely related to age-specific periepidemic mortality rates (r = -0.82) or severe case rates (r = -0.93). Higher postepidemic EV71 seropositive rates among children who were younger than 3 years positively correlated with higher mortality rates in different areas (r = 0.88). After the epidemic, 51 (56%) of 91 younger siblings of elder siblings who were EV71-seropositive were EV71-seropositive; otherwise, 2.2% (4 of 186) of younger siblings were EV71-seropositive (matched odds ratio [OR]: 10; 95% confidence interval [CI]: 3.4-29). Stepwise multiple logistic regression revealed other factors associated with EV71 infection to be older age (adjusted OR: 2.5; 95% CI: 1.9-3.4), attendance at kindergartens/child care centers (adjusted OR: 1.8; 95% CI: 1.3-2.5), contact with HFMD/herpangina (adjusted OR: 1.6; 95% CI: 1.2-2.1), greater number of children in a family (adjusted OR: 1.4; 95% CI: 1.1-1.7), and rural residence (adjusted OR: 1.4; 95% CI: 1.2-1.6). Twenty-nine percent of preschool children who were infected with EV71 developed HFMD/herpangina. Younger age and contact with HFMD/herpangina were significant factors for the development of EV71-related HFMD/herpangina in these children.
  
  
  CONCLUSIONS
  An increased incidence of EV71 infection in young children occurred more often in geographic areas with increased mortality rates. Intrafamilial and kindergarten transmissions among preschool children were major modes of disease transmission during the widespread EV71 epidemic in Taiwan in 1998.
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Luan-Yin
authors.initials: LY
authors.lastname: Chang
authors.forename: Chwan-Chuen
authors.initials: CC
authors.lastname: King
authors.forename: Kuang-Hung
authors.initials: KH
authors.lastname: Hsu
authors.forename: Hsiao-Chen
authors.initials: HC
authors.lastname: Ning
authors.forename: Kuo-Chien
authors.initials: KC
authors.lastname: Tsao
authors.forename: Chung-Chen
authors.initials: CC
authors.lastname: Li
authors.forename: Yhu-Chering
authors.initials: YC
authors.lastname: Huang
authors.forename: Shin-Ru
authors.initials: SR
authors.lastname: Shih
authors.forename: Shu-Ti
authors.initials: ST
authors.lastname: Chiou
authors.forename: Po-Yen
authors.initials: PY
authors.lastname: Chen
authors.forename: Hong-Jen
authors.initials: HJ
authors.lastname: Chang
authors.forename: Tzou-Yien
authors.initials: TY
authors.lastname: Lin
mesh_terms: D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004196:Disease Outbreaks; D004769:Enterovirus Infections / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D005260:Female; D006232:Hand, Foot and Mouth Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D006557:Herpangina / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D006801:Humans; D007223:Infant; D008297:Male; D009026:Mortality; D009500:Neutralization Tests; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D013624:Taiwan / Q000453:epidemiology