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Piroplasms of the genus Babesia, along with their relatives to the Theileridae, comprise a genetically and antigenically diverse group of tick-transmitted intraerythrocytic pathogens that together have considerable veterinary, medical, and economic importance. Since the first description of a human case of babesiosis in 1957, this zoonotic infection has now attained a worldwide distribution. In the northeastern and upper midwestern United States, the transmission cycle of Babesia microti overlaps that of another well-known zoonotic agent, Borrelia burgdorferi, the causative agent of
Lyme disease. Phylogenetic analysis of Babesia and Babesia-like piroplasms from human and animal sources has shown that many of the small Babesia spp., including B. microti, B. equi, B. gibsoni, and a recently described piroplasm infectious for humans known as WA1, may be phylogenetically related to Theileria. Implications of this observation may include the possible existence of an exoerythrocytic stage of parasite development and attendant features of chronicity, immune suppression, and perhaps lymphoproliferation. In this review, we provide a brief summary of recent developments in the study of Babesia and related piroplasms and speculate on the ramifications of chronic babesial infection in humans.