People with laboratory evidence of Lyme disease were more than four times more likely as those without it to have antibodies to other tick-borne pathogens, according to a study published late last week in JAMA Network Open. 

Lyme disease is the most frequently reported tick-borne disease in the United States. It’s caused by the bacterium Borrelia burgdorferi, which is transmitted by infected blacklegged (deer) ticks (Ixodes scapularis). Blacklegged ticks can also carry other pathogens, including Anaplasma phagocytophilum, which causes anaplasmosis, and Babesia microti, which causes babesiosis.

“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,” write researchers from Quest Diagnostics and the University of North Carolina at Chapel Hill. 

The findings also showed a strong correlation between seropositivity for B burgdorferi and Ehrlichia, which the researchers call “notable” because Ehrlichia is thought to be transmitted by the lone star tick (Amblyomma americanum).

For the study, the researchers analyzed data from 193,260 people who underwent testing for tick-borne diseases from January 2021 to December 2025. The average age was 51, and 92% were adults. Roughly 71% lived in the Northeast, where tick-borne diseases are common. 

Of all the people tested, 5.0% were seropositive for B burgdorferi, 3.1% were seropositive for A phagocytophilum, 3.4% for B microti, and 1% for Ehrlichia. Approximately 7% tested positive for at least one non-Lyme tick-borne pathogen. 

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.

Among those without laboratory evidence of Lyme disease, 5.5% had antibodies to another tick-borne pathogen. That proportion rose to 29.5% among those with Lyme disease. After adjusting for confounding factors, people who tested positive for Lyme antibodies were 4.5 times as likely to have antibodies to another tick-borne pathogen (95% confidence interval, 4.3 to 4.6). 

The overlap was greatest in the Northeast, where 31.1% of people with Lyme antibodies also tested positive for at least one other pathogen, compared with 13.6% to 16.6% in other regions. 

The association between Lyme disease and anaplasmosis and babesiosis wasn’t surprising, because all three are transmitted by the blacklegged tick. The researchers hypothesize that the less-expected connection between Lyme and Ehrlichia may be due to cumulative exposure to multiple tick species, cross-reactivity with Anaplasma, or exposure to an Ehrlichia species that’s also transmitted by blacklegged ticks. 

The study has some limitations. The researchers did not know why people opted to get tested (whether they had acute or chronic symptoms, for example) and there was the possibility of false-positive and false-negative tests. The authors also note that being seropositive for more than one tick-borne disease does not prove active co-infection. 

Even so, the researchers write that clinicians should remain alert to the possibility of other tick-borne infections in patients with suspected Lyme disease, adding that this may be especially important for babesiosis, which does not respond to doxycycline. Doxycycline is the first-line antibiotic used to treat Lyme disease.