OBJECTIVE:Our goal was to estimate the impact of a Shigella vaccine in an area where shigellosis is endemic by characterizing the disease burden and antibiotic-resistance profiles of isolates and by determining the prevalence of Shigella flexneri serotypes. PATIENTS AND METHODS:We conducted a 43-month-long prospective, community-based diarrheal disease surveillance in 442 children <72 months of age in the Peruvian Amazon between October 1, 2002, and April 15, 2006. RESULTS:The incidence of diarrheal disease was 4.38 episodes per child-year. The incidence rate for shigellosis was 0.34 episodes per child-year in children <72 months of age and peaked in children between 12 and 23 months at 0.43 episodes per child-year. Maternal education at or beyond the primary grade level, piped water supply, weight-for-age z score, and improved water-storage practices were the most significant determinants of disease in this community with living conditions comparable to many rural areas in the developing world. CONCLUSIONS:Children living in this region had a 20-fold higher rate of disease incidence detected by active surveillance as those recently estimated by passive detection. Most symptomatic disease was caused by S flexneri, although the diversity of serotypes will require a multivalent vaccine to have a significant impact on the burden of disease caused by shigellosis. Several other public health disease-control interventions targeted at water source and improved storage, nutritional interventions, and improved maternal education seem to have a greater impact than a univalent S flexneri 2a vaccine.