A US laboratory study found that 29.5% of patients with Lyme antibodies were seropositive for at least 1 other tick-borne pathogen.
A large US laboratory analysis found that patients with antibodies to Borrelia burgdorferi were substantially more likely to have antibodies to other tick-borne pathogens, highlighting the need to consider coinfection when symptoms or treatment response are inconsistent with
“The findings demonstrate that tick-borne co-exposure is a frequent clinical reality for many, particularly in Lyme disease-endemic regions like the Northeast,” Emily I. Schindler, MD, PhD, FCAP, medical director of infectious disease and immunology at Quest Diagnostics, said in a press release.2 "This research underlines the importance of comprehensive testing to bring patients the most effective treatments: because the clinical symptoms of Lyme disease, anaplasmosis and babesiosis often overlap, relying solely on single-pathogen testing can result in missed diagnoses, which can be dangerous for patients with babesiosis, which requires entirely different management than Lyme disease."
Published in JAMA Network Open, authors of the retrospective study evaluated deidentified results from 193 260 individuals who underwent testing for tick-borne diseases between January 2021 and December 2025. Researchers from Quest Diagnostics and the University of North Carolina at Chapel Hill examined concurrent seropositivity to B burgdorferi, Babesia microti, Anaplasma phagocytophilum, and Ehrlichia species.¹
Among patients with antibodies to B burgdorferi, 29.5% also had antibodies to at least 1 additional tick-borne pathogen. In comparison, 5.5% of patients without B burgdorferi antibodies were seropositive for another pathogen. These findings indicate an association with co-exposure but do not establish simultaneous active infections.
Across the full cohort, 5.0% of patients were seropositive for B burgdorferi, 3.4% for B microti, 3.1% for A phagocytophilum, and 1.0% for Ehrlichia species. Co-seropositivity was most common for organisms transmitted by the blacklegged tick, particularly B microti and A phagocytophilum.¹
Substantial geographic variation was observed. Among patients with B burgdorferi antibodies, antibodies to non-Lyme pathogens were detected in 31.1% of those in the Northeast, compared with 16.6% in the Midwest, 16.0% in the South, and 13.6% in the West. In the Northeast, Babesia antibodies were detected in 18.5% of patients seropositive for B burgdorferi.
The regional findings should be interpreted in light of the cohort’s composition: 70.6% of tested patients were from the Northeast. Testing was also seasonal, with more than 40% conducted from June through August and nearly 26% from September through November. The study therefore describes a clinician-selected population undergoing laboratory evaluation rather than tick-borne disease prevalence in the general US population.
Lyme disease may cause fever, headache, fatigue, erythema migrans, and, when untreated, articular, cardiac, or neurologic complications. First-line Lyme disease therapies include doxycycline, a tetracycline antibiotic, and the β-lactam agents amoxicillin and cefuroxime axetil. These drugs do not treat Babesia, an intraerythrocytic parasite requiring a different antimicrobial regimen. Consequently, persistent fever, hemolytic anemia, thrombocytopenia, or an atypical clinical course may warrant evaluation for alternative or concurrent tick-borne disease based on exposure history and local epidemiology.
The analysis did not include clinical symptoms, physical findings, molecular testing, treatment, or outcomes. Antibodies can persist after prior infection, so co-seropositivity cannot distinguish remote exposure from active coinfection. Assay ordering and referral patterns may also introduce selection bias. Prospective studies incorporating clinical data and confirmatory testing are needed to determine how multispecies serologic findings should influence treatment decisions.
