Shrews and Mice Are Associated with Genetically Distinct Anaplasma phagocytophilum Variants in Northeastern United States

Anaplasma phagocytophilum (Ap) is a tick-borne bacterium that causes human granulocytic anaplasmosis (HGA) in the United States. There are distinct genotypes that seem to differ in capacity to infect humans and may be maintained in separate enzootic cycles. Anaplasma phagocytophilum-var1, which apparently does not infect humans, is found primarily in deer, and Ap-ha isolated from HGA cases is associated with mice. Genetic analyses demonstrate that Ap-ha comprises two lineages; whether these are maintained by the same hosts is not known. We clarified the Ap-ha enzootic cycle by genotyping Ap from host-seeking nymphal deer ticks collected from three sites in northeastern United States. Each genotype was associated with host species using our published tick blood-meal identification assay targeting mammalian retrotransposons. Anaplasma phagocytophilum-var1 was more common than Ap-ha (5.8% versus 3.6% of 2,799 ticks tested), and the two Ap-ha genotypes were unevenly distributed among sites. Although both Ap-ha genotypes were found on Martha's Vineyard, Ap-ha-H1 was the primary type on Nantucket, and Ap-ha-H2 was the only type detected in Rhode Island. Blood-meal analysis confirmed that deer were significantly associated with Ap-var1 infection (odds ratio OR = 11.7, 95% CI = 7.7-18). However, host associations for Ap-ha depended upon the genotype. Anaplasma phagocytophilum-ha-H1 was significantly associated with ticks that had fed on shrews (OR = 3.6, 95% CI = 1.8-7.2), whereas Ap-ha-H2 was associated with ticks that had fed on mice (OR = 8.3, 95% CI = 4-17.3). Spatial heterogeneity of host associations may be a basis for local HGA risk.