AbstractHepatocystis parasites are closely related to mammalian Plasmodium species, the causative agents of malaria. Despite the close phylogenetic relationship, Hepatocystis parasites lack the intermittent erythrocytic replication cycles, the signature and exclusive cause of malaria-related morbidity and mortality. Hepatocystis population expansion in the mammalian host is thought to be restricted to the pre-erythrocytic liver phase. Complete differentiation of first generation blood stages into sexual stages for subsequent vector transmission indicates alternative parasite/host co-evolution. In this study, we identified a region of exceptionally high prevalence of Hepatocystis infections in Old World fruit bats in South Sudan. Investigations over the course of five consecutive surveys revealed an average of 93 percent prevalence in four genera of African epauletted fruit bats. We observed a clear seasonal pattern and tolerance of high parasite loads in these bats. Phylogenetic analyses revealed several cryptic Hepatocystis parasite species and, in contrast to mammalian Plasmodium parasites, neither host specificity nor strong geographical patterns were evident. Together, our study provides evidence for Pan-African distribution and local high endemicity of a Hepatocystis species complex in Pteropodidae.