Risk Factors of Enterovirus 71 Infection and Associated Hand, Foot, and Mouth Disease/Herpangina in Children During an Epidemic in Taiwan

Objective. In 1998, an enterovirus 71 (EV71) epidemic in Taiwan was associated with hand, foot, and mouth disease (HFMD)/herpangina and in- volved 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 as- sayed 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 his- tory, and clinical manifestations. Results. A total of 129 106 cases of HFMD were re- ported 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 sero- positive 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 re- vealed 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 res- idence (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 infec- tion 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. Pediatrics 2002;109(6). URL: http://www.pediatrics.org/cgi/content/ full/109/6/e88; enterovirus 71; hand, foot, and mouth dis- ease; seroprevalence; transmission; risk factors; symptom- atic ratio; reemerging infectious disease; Taiwan.