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Background: Pathogens face strong selection from host immune responses, yet many host populations support pervasive pathogen populations. We investigated this puzzle in a model system of Bartonella and rodents from Israel's northwestern Negev Desert. We chose to study this system because, in this region, 75–100% of rodents are infected with Bartonella at any given time, despite an efficient immunological response. In this region, Bartonella species circulate in three rodent species, and we tested the hypothesis that at least one of these hosts exhibits a waning immune response to Bartonella, which allows reinfections. Methods: We inoculated captive animals of all three rodent species with the same Bartonella strain, and we quantified the bacterial dynamics and Bartonella-specific immunoglobulin G antibody kinetics over a period of 139 days after the primary inoculation, and then for 60 days following reinoculation with the same strain. Results: Contrary to our hypothesis, we found a strong, long-lasting immunoglobulin G antibody response, with protective immunological memory in all three rodent species. That response prevented reinfection upon exposure of the rodents to the same Bartonella strain. Conclusions: This study constitutes an initial step toward understanding how the interplay between traits of Bartonella and their hosts influences the epidemiological dynamics of these pathogens in nature. [ABSTRACT FROM AUTHOR]