A study of 193,260 individuals found overlapping tick-borne antibody levels more frequently among those with Lyme antibodies, highlighting diagnostic challenges when active coinfections are not confirmed.
A positive Lyme disease antibody result may signal a need to consider other tick-borne pathogens, according to a study of 193,260 individuals tested at Quest Diagnostics. Researchers found antibodies to at least 1 additional tick-borne pathogen in 29.5% of individuals who were seropositive for Borrelia burgdorferi, compared with 5.5% of those who were seronegative. However, the findings identify overlapping antibody responses, which do not establish that patients had multiple active infections simultaneously.
Published September 18, 2026, in
Lyme disease is transmitted through the bite of infected Ixodes ticks, which can also carry Anaplasma phagocytophilum and Babesia microti. These organisms cause anaplasmosis and babesiosis, respectively. Because multiple pathogens share a tick vector, focusing exclusively on Lyme disease may leave other possible causes of illness unexamined. As the investigators noted, “The strong association between seropositivity for B burgdorferi, A phagocytophilum, and B microti is consistent with underlying biology given that all 3 are transmitted by Ixodes scapularis ticks.”
Researchers analyzed each individual’s first eligible tick-borne disease serological panel during the study period, excluding results without age, sex, or state-of-residence information. The cohort included 108,878 female and 84,382 male individuals, with a median age of 51 years. Adults represented 92.4% of participants, 70.6% lived in the Northeast, and 40.7% underwent testing between June and August. These characteristics are important when considering how broadly the findings apply beyond this tested population.
Overall, 9609 individuals (5.0%) were seropositive for B burgdorferi. Antibodies to A phagocytophilum were detected in 6003 individuals, or 3.1%; antibodies to B microti in 6497, or 3.4%; and antibodies to Ehrlichia species in 1980, or 1.0%. Altogether, 13,014 individuals, representing 6.7% of the cohort, had antibodies to at least 1 tick-borne pathogen other than the organism associated with Lyme disease.
The association persisted after researchers accounted for age, sex, testing month, and region. Individuals with B burgdorferi antibodies had an adjusted seropositivity ratio of 4.46 for other tick-borne pathogens compared with those without those antibodies (95% CI, 4.30–4.63; P < .001). Among individuals seropositive for B burgdorferi, 31.1% in the Northeast also had antibodies to another tick-borne pathogen, compared with 13.6% to 16.6% in other regions.
The investigators considered the associations between Anaplasma and Babesia to be biologically consistent with their shared transmission via Ixodes scapularis. The association with Ehrlichia was more complicated. Possible explanations included exposure to multiple tick species through work or outdoor recreation, cross-reactivity with Anaplasma, or regional exposure to Ehrlichia muris eauclairensis, which is also transmitted by I scapularis. The study could not determine which explanation accounted for individual results.
Babesia findings are of particular clinical significance because doxycycline, a first-line treatment for Lyme disease, is ineffective against the parasite. The authors therefore emphasized maintaining a high index of suspicion for other tick-borne pathogens, particularly in the Northeast. That message requires careful interpretation: an antibody result alone does not establish an active infection or determine whether additional treatment is necessary.
Several limitations prevent translating these findings into a coinfection rate.
“This study has limitations, including unknown clinical indications driving test ordering and unknown disease stage (eg, acute or chronic symptoms), a lack of molecular testing, and an unknown seropositivity level for non-LD tick-borne pathogens, as well as potential false-positive and false-negative serological results,” the authors wrote.
Serological assays can produce false-positive and false-negative results, and the less specific IgM component may “which may partly explain the higher rates of coseropositivity observed across pathogens.” Early Lyme disease can also be missed by standard 2-tier antibody testing. The investigators explicitly cautioned that “coseropositivity does not prove active coinfection.”
The investigators admit that “[w]hile somewhat expected, the increased seropositivity for A phagocytophilum and B microti among individuals with laboratory evidence of LD reinforces the need for clinicians to maintain a high index of suspicion for non-LD tick-borne pathogens, particularly in the Northeast region.”
For health care teams, the study supports broader awareness without overstating what laboratory evidence can establish. Education should address shared tick exposures, the possibility of additional pathogens, and differences in treatment coverage. Equally essential is distinguishing antibody detection from confirmed illness. The practical implication is to keep the diagnostic assessment open while interpreting test results in the context of each patient’s presentation and exposure history.
