Co-infection of blacklegged ticks with Babesia microti and Borrelia burgdorferi is higher than expected and acquired from small mammal hosts

Abstract

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 (Borrelia burgdorferi, Anaplasma phagocytophilum, and Babesia microti) are transmitted by the same vector, blacklegged ticks (Ixodes scapularis), 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 Babesia microti and Borrelia burgdorferi 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 A. phagocytophilum were less common, and fewer co-infections of A. phagocytophilum and B. microti 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 B. microti/B. burgdorferi co-infection.

Figure 1. Mean levels of co-infection prevalence of Anaplasma phagocytophilum, Babesia microti, and Borrelia burgdorferi in questing Ixodes scapularis nymphs, by site.

Mean levels of co-infection with Anaplasma phagocytophilum (Ap), Babesia microti (Bm), and Borrelia burgdorferi (Bb) in questing nymphal Ixodes scapularis ticks by site, 2011–2012. Each category represents mean overall prevalence as opposed to the prevalence of each specific infection type – for example, the “Ap” bar represents not just single infections but also ticks co-infected with Ap and either or both of the other two pathogens. Error bars represent standard error. For individual years see Figure S2.

Figure 2. Log (base 2) of the observed: expected ratio of questing Ixodes scapularis nymphs.

Log (base 2) of observed: expected ratio of each infection status of questing Ixodes scapularis ticks sampled at 161 sites across Dutchess County, NY, USA. The magnitude and direction of the log ratios illustrates the extent to which the observed levels of co-infection differed from expected levels of co-infection due to random assortment of pathogens. Pathogens sampled include Anaplasma phagocytophilum (Ap), Babesia microti (Bm), and Borrelia burgdorferi (Bb). Expected infection frequencies are based on 100,000 random permutations of infection frequencies for each pathogen.

Figure 3. Co-infection prevalence of Anaplasma phagocytophilum, Babesia microti, and Borrelia burgdorferi in wildlife host species groups.

Mean co-infection prevalence for Anaplasma phagocytophilum (Ap), Babesia microti (Bm), and Borrelia burgdorferi (Bb) of host-collected Ixodes scapularis ticks fed on (A) small mammal, (B) meso-mammal, (C) sciurid, and (D) bird host species. Each category represents the mean prevalence of each specific co-infection type as opposed to overall prevalence. Error bars show standard error. Note that no co-infections were observed in D. carolinensis.