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An outbreak of enterovirus 71 infection in Taiwan in 1998 killed 78 people and made over 120,000 people sick. Normally, this virus can cause blisters on the hands, feet and mouth, but is usually not life-threatening. In the Taiwan outbreak, 405 people had severe disease, and most were five years old or younger. Ninety-one percent of the deaths were children five years old or younger. Eighty-three percent of the patients who died had fluid in their lungs or blood in their lungs. Ninety-two percent had been infected with enterovirus 71.

Doctors need to be aware of the potential for an outbreak of enterovirus 71. In 1999, several doctors reported 129,106 cases of enterovirus 71 infection in Taiwan in 1998. This means that as many as 1.4 million cases may have occurred in Taiwan that year. About 400 patients had severe disease and the mortality rate in that group was 19%. Most of these severely ill patients were children five years old or younger. In addition to the Taiwan outbreak, large outbreaks have occurred in Bulgaria, Hungary and Malaysia. The cause of these outbreaks is not known.

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. Pediatrics 2002;109(6). URL: http://www.pediatrics.org/cgi/content/ full/109/6/e88; enterovirus 71; hand, foot, and mouth disease; seroprevalence; transmission; risk factors; symptomatic ratio; reemerging infectious disease; Taiwan.