Study Finds Frequent Overlap in Antibodies to Lyme and Other Tick-Borne Pathogens

Lyme disease and other tick-borne illnesses cause overlapping symptoms, making them difficult to distinguish clinically. The Centers for Disease Control and Prevention estimates that more than 476,000 people are diagnosed and treated for Lyme disease annually in the United States. Antibodies to multiple tick-borne pathogens can further complicate interpretation because they do not necessarily indicate active infection. A new study explores this overlap by examining how often these antibodies occur together in patients tested for suspected Lyme disease.

Quest Diagnostics and the University of North Carolina at Chapel Hill examined simultaneous serologic testing for multiple tick-borne pathogens. This approach detects antibodies to Borrelia burgdorferi, the bacterium that causes Lyme disease, alongside antibodies to pathogens including Babesia microti, Anaplasma phagocytophilum, and Ehrlichia species. The researchers analyzed de-identified results from 193,260 people tested for tick-borne diseases across the United States between January 2021 and December 2025.

Image: The findings reveal that individuals exposed to Borrelia burgdorferi, the bacterium that causes Lyme disease, are more than four times as likely to have antibodies against other tick-borne pathogens (Image Credit: Shutterstock)

Among people with antibodies to B. burgdorferi, 29.5% also had antibodies to at least one other tick-borne pathogen, compared with 5.5% of those without B. burgdorferi antibodies. Across the full cohort, 5% were seropositive for B. burgdorferi, 3.4% for B. microti, 3.1% for A. phagocytophilum, and 1.0% for Ehrlichia species. The most frequent co-seropositivity involved pathogens transmitted by blacklegged ticks, including B. microti and A. phagocytophilum. 

Co-detection of antibodies to non-Lyme pathogens among B. burgdorferi-seropositive patients was highest in the Northeast at 31.1%, compared with 16.6% in the Midwest, 16.0% in the South, and 13.6% in the West. In the Northeast, 18.5% of B. burgdorferi-seropositive patients also had Babesia antibodies. The Northeast accounted for 70.6% of the cohort, while more than 40% of diagnostic panel testing occurred from June through August.

The study was published in JAMA Network Open. The findings describe patterns of antibody co-detection in a large national dataset, but the researchers noted that the results lacked clinical context. Some positive antibody results may therefore reflect past exposure rather than confirmed, active infection. 

"The findings demonstrate that tick-borne co-exposure is a frequent clinical reality for many, particularly in Lyme disease-endemic regions like the Northeast," said Emily I. Schindler, M.D., Ph.D., FCAP, Medical Director, Infectious Disease & Immunology, Quest Diagnostics.

"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," added Dr. Schindler.