Study: Those With Evidence of Exposure to Lyme More Than Four Times As Likely to Have Antibodies Against Other Pathogens Compared to Those Without

Study: Those With Evidence of Exposure to Lyme More Than Four Times As Likely to Have Antibodies Against Other Pathogens Compared to Those Without

September 21, 2026

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2854245

Coseropositivity to Tick-Borne Pathogens Among Patients Suspected to Have Lyme Disease

Yonghong Li, PhD¹; Carmen H. Tong, MS¹; Tara S. Givens, PhD² et al

JAMA Netw Open

Published Online: September 18, 2026

2026;9;(9):e2634800.doi:10.1001/jamanetworkopen.2026.34800

Introduction

Lyme disease (LD), the most frequently reported vector-borne disease in the US,¹ is caused by infection with Borrelia burgdorferi sensu lato and transmitted through the bite of Ixodes ticks. However, Ixodes ticks also harbor other pathogens, including Anaplasma phagocytophilum and the malaria-like parasite Babesia microti.²^,3 Co-infections with other pathogens can complicate diagnosis and treatment.⁴^–6 However, the clinical burden of co-infections is evolving and frequently underappreciated. We sought to investigate patterns and frequencies of codetection of antibodies against B burgdorferi and other tick-borne pathogens in patients undergoing testing for tick-borne disease.

Methods

This cohort study was reviewed by the WCG Institutional Review Board, an independent ethical review board, and deemed to be exempt under federal regulation 45 CFR §46.104(d)(4). Reporting of this study follows the STROBE reporting guideline.

We queried the Quest Diagnostics test database for individuals who had undergone tick-borne disease serological panel testing during the 5 years from January 2021 to December 2025 (eFigure and eMethods in Supplement 1). Data used were deidentified as required by the HIPAA Privacy Rule (45 CFR §164.514). Results without associated information on age, sex, or state of residence were excluded. We restricted the analysis to the first test from unique individuals identified in the period. We performed descriptive analysis of the data in Microsoft 365 (Microsoft Corp), and we used a log-binomial regression model to estimate seropositivity ratio and 95% CIs, with adjustment for age, sex, testing month, and region, using SAS version 9.4 (SAS Institute). Statistical testing was 2-sided, with P < .05 considered statistically significant.

Results

We included 193 260 individuals in the study cohort (108 878 female [56.3%] and 84 382 male [43.7%]; median [IQR] age, 51 [35-64] years). Most were adults (aged ≥18 years; 92.4%) and resided in the Northeast region (70.6%), and 40.7% were tested between June and August. Seropositivity was observed in 9609 individuals (5.0%) for B burgdorferi, 6003 individuals (3.1%) for A phagocytophilum, 6497 individuals (3.4%) for B microti, and 1980 individuals (1.0%) for Ehrlichia spp. Together, 13 014 individuals tested (6.7%) were seropositive for at least 1 non-LD tick-borne pathogen.

Compared with individuals who were seronegative for B burgdorferi, individuals who were seropositive for B burgdorferi were more likely to be seropositive for A phagocytophilum, B microti, and Ehrlichia spp in all 4 US Census regions (Figure 1). While seropositivity for another tick-borne pathogen was observed in 5.5% of tested individuals who were seronegative for B burgdorferi, it was observed in 29.5% of individuals who were seropositive for B burgdorferi. The seropositivity ratio for other tick-borne pathogens in individuals with vs without laboratory evidence of LD was 4.46 (95% CI, 4.30-4.63; P < .001). Compared with individuals in other regions, individuals who were seropositive for B burgdorferi in the Northeast region tested seropositive more frequently for non-LD tick-borne pathogens (31.1% vs 13.6%-16.6%).

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**Comment**

Findings were in spite of the following study limitations:

Unknown clinical indications driving test ordering
Unknown disease stage
Lack of molecular testing
Unknown seropositivity level for non-Lyme disease tick-borne pathogens
Potential false-positive and false-negative serological results

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