New Bay Area Lyme Foundation Study Shows Common FDA-Cleared Lyme Tests Miss 64-78% of Early Cases, Underscores Urgent Need for Improved Diagnostics
Research published in the Journal of Clinical Microbiology
Bay Area Lyme Foundation, a national nonprofit and leading sponsor of tick-borne disease research in the US, announced the publication of new research in the Journal of Clinical Microbiology based on data from its Lyme Disease Biobank. The study found that the commonly used FDA-cleared diagnostic testing methods available to providers and major national diagnostic laboratories are highly insensitive and miss 64-78% of early Lyme disease cases, including those who present with the characteristic erythema migrans (EM) Lyme rash.
“This study demonstrates that common two-tiered Lyme tests, utilized for decades, often fail to detect early Lyme disease and are leaving patients behind, highlighting a critical need for improved medical education on the limitations of current diagnostics,” said Liz Horn, PhD, MBI, Principal Investigator of Lyme Disease Biobank and lead author of the study. “Our findings also add to the evidence that improved diagnostics, ideally those that directly detect the bacteria that cause Lyme disease, are urgently needed.”
(Editor’s note: The DualDur® diagnostic method, developed in Hungary, is a diagnostic approach based on the direct detection of the bacterium that causes Lyme disease. Its major advantage is that it does not depend on the body’s immune response, which in many cases may remain below detectable levels—particularly during the early stages of infection.)
This large-scale, head-to-head study comparing 2 standard two-tiered testing (STTT) and 2 modified two-tiered testing (MTTT) diagnostic algorithms (the commonly used Lyme disease diagnostic algorithms) confirms that the sensitivity of two-tiered testing algorithms is low among patients with early infection. For the 107 early Lyme disease cases evaluated, the various testing algorithms missed 64-78% of early Lyme cases. Overall, only 39% (42/107) of participants with early Lyme disease were STTT or MTTT positive by any of the 4 algorithms.
The study found that current Lyme disease diagnostic algorithms (STTT and MTTT), which rely on antibody detection rather than direct detection of the bacteria, have limited accuracy in early infection—particularly within the first one to two weeks, when antibodies may not yet be detectable—potentially contributing to missed or delayed diagnoses. While modified two-tiered testing (MTTT) showed higher sensitivity than standard two-tiered testing (STTT), including in a subset of laboratory-confirmed cases (82% vs. 53–69%), overall performance remained suboptimal, especially in the earliest stage of infection. The authors also observed variability across testing methods, with some samples testing positive by one algorithm and negative by another, and noted that test positivity was more likely in participants with symptoms and increased with longer duration of illness or rash. In participants with EM duration of less than 1 week, neither algorithm was likely to be positive.
“It’s 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, particularly when there has been potential recent tick exposure and compatible signs and symptoms are present, to ensure prompt treatment,” said John A. Branda, MD, Associate Professor, Harvard Medical School and Director, Clinical Microbiology Laboratory, Massachusetts General Hospital and a 2015 Bay Area Lyme Emerging Leader Award winner. “Our study was enabled by a robust collection of samples from Lyme Disease Biobank that included clinical information about patient signs and symptoms. It builds upon previous studies and highlights an urgent need for novel diagnostics for early Lyme disease that do not rely on antibody detection.”
This real-world study uses well-characterized, geographically diverse samples from Lyme Disease Biobank, which enrolled 107 participants with signs and symptoms of early Lyme disease, along with 144 control participants at clinical sites in East Hampton, New York, and several locations in Wisconsin, which are endemic areas for Lyme disease, between 2017 and 2020. Of the 107 cases, 93 (87%) presented with a suspected EM, and 14 (13%) presented with constitutional symptoms compatible with early Lyme disease but without the sign of EM rash.
New Bay Area Lyme Foundation Study Shows Common FDA-Cleared Lyme Tests Miss 64-78% of Early Cases, Underscores Urgent Need for Improved Diagnostics
(C) Lyme Borreliosis Foundation
