New test promises faster, more accurate Lyme disease diagnosis, researchers say

James Gathany / CDC

Researchers at Dartmouth Hitchcock Medical Center have developed a way to detect Lyme disease more rapidly and reliably than current testing methods. The team presented the new molecular test late last week at the Association for Molecular Pathology 2025 Annual Meeting & Expo.

The project originated with a patient whose antibody tests showed evidence of previous, but not current, Lyme infection (existing serologic tests cannot distinguish between active and past infection).

When the patient's symptoms (skin hardening, inflammation, and joint immobility) improved with doxycycline, an antibiotic often used to treat Lyme disease, her care team asked researchers to develop a molecular test to confirm the presence of Borrelia burgdorferi, the bacterium that causes most Lyme disease cases in the United States.

Ability to detect as few as 5 bacterial cells

The team developed three droplet digital polymerase chain reaction (ddPCR) tests to detect different types of Borrelia bacteria: one identifies all Borrelia species; one finds all Borrelia species responsible for Lyme disease; and one targets B burgdorferi. The new assays detected as few as five to 10 bacterial cells, which the researchers describe as "excellent accuracy."

The B burgdorferi test had 91% sensitivity in detecting the bacteria. "Using the ddPCR assay, we successfully detected B. burgdorferi DNA in this patient's skin biopsy," explains lead researcher Guohong (Grace) Huang, PhD, in the press release. "This finding was further confirmed by DNA sequencing, supporting the diagnosis of chronic Lyme disease."

"Antibody levels may remain elevated even after successful treatment. This is another clinical scenario where the ddPCR assay offers a clear advantage by detecting active bacterial presence rather than relying on indirect immune markers," adds Huang.

This is another clinical scenario where the ddPCR assay offers a clear advantage by detecting active bacterial presence rather than relying on indirect immune markers.

Guohong (Grace) Huang, PhD

Diagnosing Lyme disease can be challenging. Antibody tests frequently produce false-negative results, and the characteristic bullseye rash occurs in only about 25% of patients. Plus, many patients develop skin lesions that resemble those of other illnesses. These factors can complicate and delay accurate diagnosis (the patient whose case was the inspiration for developing the new test waited four years.)

Lyme disease has been on the rise in the United States over the past 30 years, which underscores the need for faster, more accurate testing. Left untreated, infection can lead to heart, joint, and nervous system problems and produce symptoms that can impair quality of life.

Pain, cognitive difficulties

In a separate matched cohort study published in Emerging Infectious Diseases, a team of researchers at the Centers for Disease Control and Prevention found that symptoms such as pain, fatigue, and cognitive difficulties occurred 5% more frequently among people with Lyme disease than those with other conditions such as COVID-19.

For the study, the researchers looked at insurance claims data from 2017 to 2021 in regions where Lyme disease is common. They identified 24,503 patients with Lyme disease and 122,095 patients with other diagnoses (control group). They also compared the relative frequencies of diagnosis codes for pain, fatigue, and cognitive problems in the two groups in the year after diagnosis.

Those symptom codes occurred 5.0% more often among case-patients than among controls and made up 11.0% of all symptom codes among Lyme patients. Except for fatigue, symptom-code frequency among patients with Lyme disease decreased significantly in the six to 12 months after diagnosis and reached levels similar to those of controls by year's end.

The team's findings are consistent with those of previous clinical studies that show "similar persisting symptoms of unclear pathogenesis among a subset of persons who received diagnosis and treatment," write the researchers.