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BACKGROUND: Influenza outbreaks have been reported among travelers, but attack rates and incidence are unknown. METHODS: A cohort study was conducted. Travelers to subtropical and tropical countries recruited at the University of Zurich Travel Clinic (Switzerland), January 1998 to March 2000, were investigated with pre- and posttravel assessment of hemagglutination inhibition and by questionnaire. RESULTS: Among 1450 travelers recruited who completed questionnaires and provided serum samples before departure, 289 (19.9%) reported febrile illness during or after traveling abroad; of these, 211 (73.0%) provided paired serum samples. Additionally, paired serum samples were collected from 321 frequency-matched afebrile control subjects among the remaining 1161 subjects of the study population. Seroconversion for influenza virus infection was demonstrated in 40 (2.8%) of all travelers; 18 participants (1.2%) had a > or = 4-fold increase in antibody titers. This corresponds to an incidence of 1.0 influenza-associated events per 100 person-months abroad. Among the 211 febrile participants, 27 (12.8%) had seroconversion, 13 (6.2%) with a > or = 4-fold increase; among the 321 afebrile control subjects, 13 (4.0%) had seroconversion, 5 (1.6%) with a > or = 4-fold increase. Twenty-five seroconverters (62.5%; P = .747) acquired influenza outside of the European epidemic season. Sixteen patients (40.0%) sought medical attention either abroad or at home, and 32 (80.0%) were asymptomatic at the time of completion of the survey. CONCLUSIONS: This survey indicates that influenza is the most frequent vaccine-preventable infection among travelers to subtropical and tropical countries. Infections occur mainly outside the domestic epidemic season, and they have a considerable impact. Pretravel vaccination should be considered for travelers to subtropical and tropical countries.