Geographic variation in risk of blacklegged tick-borne coinfections in the eastern United States

Blacklegged tick (Ixodes scapularis)-associated diseases are increasing in incidence and geographic range in the United States. Pathogen range expansion may increase the risk of coinfections, which could complicate accurate diagnosis and treatment of tick-borne diseases. To identify regions of coinfection risk across the eastern United States, we used a national database of tick-borne pathogen occurrence to identify areas of co-occurrence between four I. scapularis-borne human pathogens: Anaplasma phagocytophilum human-active variant (Apha; anaplasmosis), Babesia microti (Bam; babesiosis), Borrelia burgdorferi sensu stricto (Bbss; Lyme disease), and Borrelia miyamotoi (Bmiya; hard tick relapsing fever). Using testing data from 13,437 nymphs submitted to the United States Centers for Disease Control and Prevention from 2013 to 2024, we summarized the mean and variation in observed coinfection prevalence from site to regional scales. Bbss-Bam, Bbss-Apha, and Bam-Apha co-occurred primarily in the Northeast and Upper Midwest, whereas Bbss-Bmiya co-occurrence extended from those regions into the Ohio Valley and southern Appalachia. Within zones of co-occurrence, Bbss-Bam was the most prevalent coinfection, followed by Bbss-Apha, Bam-Apha, and Bbss-Bmiya. Except for Bbss-Bmiya, resampling simulations for all coinfections revealed coinfections form more often than expected by chance. This study is a first step in delineating acarological risk for I. scapularis-borne coinfections in the United States.