Co-Infection of Blacklegged Ticks with <i>Babesia microti</i> and <i>Borrelia burgdorferi</i> Is Higher than Expected and Acquired from Small Mammal Hosts

<div><p>Humans in the northeastern and midwestern United States are at increasing risk of acquiring tickborne diseases – not only Lyme disease, but also two emerging diseases, human granulocytic anaplasmosis and human babesiosis. Co-infection with two or more of these pathogens can increase the severity of health impacts. The risk of co-infection is intensified by the ecology of these three diseases because all three pathogens (<i>Borrelia burgdorferi, Anaplasma phagocytophilum</i>, and <i>Babesia microti</i>) are transmitted by the same vector, blacklegged ticks (<i>Ixodes scapularis</i>), and are carried by many of the same reservoir hosts. The risk of exposure to multiple pathogens from a single tick bite and the sources of co-infected ticks are not well understood. In this study, we quantify the risk of co-infection by measuring infection prevalence in 4,368 questing nymphs throughout an endemic region for all three diseases (Dutchess County, NY) to determine if co-infections occur at frequencies other than predicted by independent assortment of pathogens. Further, we identify sources of co-infection by quantifying rates of co-infection on 3,275 larval ticks fed on known hosts. We find significant deviations of levels of co-infection in questing nymphs, most notably 83% more co-infection with <i>Babesia microti</i> and <i>Borrelia burgdorferi</i> than predicted by chance alone. Further, this pattern of increased co-infection was observed in larval ticks that fed on small mammal hosts, but not on meso-mammal, sciurid, or avian hosts. Co-infections involving <i>A. phagocytophilum</i> were less common, and fewer co-infections of <i>A. phagocytophilum</i> and <i>B. microti</i> than predicted by chance were observed in both questing nymphs and larvae fed on small mammals. Medical practitioners should be aware of the elevated risk of <i>B. microti</i>/<i>B. burgdorferi</i> co-infection.</p>