A newly published study in the Journal of Clinical Microbiology puts concrete data behind a long recognized problem in Lyme disease care.

The research, supported by the Bay Area Lyme Foundation and based on data from the Lyme Disease Biobank, found that FDA-cleared testing methods miss between 64 and 78 percent of early Lyme cases.

This includes patients who present with the classic erythema migrans (EM) rash that is widely considered a key indicator of early infection.

This highlights the need for improved diagnostics for Lyme disease.

Comparing four standard testing tools

Researchers compared four diagnostic algorithms that represent the standard tools available to clinicians. These included two standard two tiered tests (STTT) and two modified two tiered tests (MTTT).

Among 107 confirmed early Lyme disease cases, only 39 percent tested positive on any of the four testing approaches.

Liz Horn, PhD, MBI, Principal Investigator of the Lyme Disease Biobank and lead author of the study, noted the implications for patient care.

“Common two tiered Lyme tests, utilized for decades, often fail to detect early Lyme disease and are leaving patients behind. Our findings also add to the evidence that improved diagnostics, ideally those that directly detect the bacteria that cause Lyme disease, are urgently needed.”

The core issue is timing. Current tests rely on detecting antibodies, but during the first one to two weeks of infection, the immune system may not yet have produced enough antibodies to register a positive result. As a result, patients can be symptomatic and still receive a negative test.

Modified tests perform better but still fall short

The study found that MTTT approaches were more sensitive than STTT, particularly in laboratory confirmed cases. Sensitivity reached 82 percent for MTTT compared with 53 to 69 percent for STTT. Even so, performance remained inadequate for the earliest stage of infection. For participants whose EM rash had been present for less than one week, neither testing approach was likely to detect the disease.

John A. Branda, MD, Associate Professor at Harvard Medical School and Director of the Clinical Microbiology Laboratory at Massachusetts General Hospital, emphasized the need for clinical judgment.

“It is important for clinicians to understand the limitations of STTT and MTTT in early disease, and to rely on clinical judgment when evaluating patients with suspected early Lyme disease. This is especially important when there has been potential recent tick exposure and compatible signs and symptoms are present.”

The study drew on samples collected between 2017 and 2020 from endemic regions in East Hampton, New York, and several locations in Wisconsin. Among the 107 Lyme cases enrolled:

• 87 percent presented with a suspected EM rash
• 13 percent had general early Lyme symptoms without a rash
• 144 control participants were included for comparison

The diversity of samples allowed researchers to evaluate how tests perform across different presentations and stages of early infection. The study also found variability across testing methods, with some samples testing positive on one algorithm and negative on another.

SOURCE: Bay Area Lyme Foundation