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BACKGROUND: Enteric fever (EF) has become a travel-related disease in industrialized countries. The possible effects of vaccination on typhoid epidemiology in travelers are unknown. We compared the incidence and clinical and microbiologic findings in travelers returning with EF, according to pretravel vaccination status and vaccine type. METHODS: We performed a nationwide descriptive analysis of EF incidence in Israeli travelers; EF is a notified disease in Israel. Data from 1995 through 2003 were evaluated; all cases of EF acquired during recent travel (6 wk) were included. From 1995 to 1999, the Ty21a oral vaccine was used exclusively in Israel. It was replaced with the Vi vaccine from 2000 to 2003. Patients with pretravel typhoid vaccination were compared with unvaccinated patients, and according to vaccine type. RESULTS: Seventy-eight cases met our criteria. The causative agents were Salmonella typhi in 79.5% and Salmonella paratyphi A in 20.5%; 74.4% were acquired by travelers to the Indian Subcontinent. S. paratyphi A accounted for 10.5% of cases among Ty21a vaccinees as compared with 47.4% among Vi vaccinees (p = .02). For the Indian Subcontinent, the general attack rate of S. typhi and S. paratyphi A during the period of vaccination with Ty21a was 2.37 in 10,000 and 0.26 in 10,000 travelers, respectively, whereas during the period of vaccination with Vi, the attack rate was 1.40 in 10,000 and 0.79 in 10,000. There were no deaths; however, more complications and relapses occurred in the S. paratyphi A group. CONCLUSIONS: Among Israeli travelers S. typhi infection is declining whereas S. paratyphi A is increasing, with most cases occurring in vaccinated travelers. Prior typhoid vaccination did not modify the course of the disease. S. paratyphi A infection in travelers is not milder than S. typhi infection. Although this is not a prospective, controlled, randomized trial, it appears that the Ty21a vaccine may be less effective for S. typhi but may offer some protection against S. paratyphi A. Sequential vaccination with the available oral and Vi vaccine may merit consideration. A more effective vaccine for S. typhi and S. paratyphi A is urgently needed.