New research indicates that standard and modified two-tiered testing algorithms fail to detect infection in up to 78% of patients during the early stages of the disease.
The Bay Area Lyme Foundation announced new research showing that commonly used Food and Drug Administration (FDA)-cleared diagnostic testing methods miss 64-78% of early Lyme disease cases. The study, published in the Journal of Clinical Microbiology, highlights the limitations of current diagnostic algorithms for patients presenting with early symptoms, including the characteristic erythema migrans (EM) rash.
This head-to-head study compared two standard two-tiered testing (STTT) and two modified two-tiered testing (MTTT) diagnostic algorithms. For the 107 early Lyme disease cases evaluated, only 39% of participants tested positive by any of the four algorithms.
“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,” says Liz Horn, PhD, MBI, principal investigator of Lyme Disease Biobank and lead author of the study, in a release. “Our findings also add to the evidence that improved diagnostics, ideally those that directly detect the bacteria that cause Lyme disease, are urgently needed.”
Limitations of Antibody-Based Detection
The study found that current diagnostic algorithms, which rely on antibody detection rather than direct detection of the bacteria, have limited accuracy in early infection. This is particularly evident within the first one to two weeks, when antibodies may not yet be detectable, potentially contributing to missed or delayed diagnoses.
While MTTT showed higher sensitivity than STTT in a subset of laboratory-confirmed cases (82% vs 53–69%), overall performance remained suboptimal in the earliest stage of infection. In participants with an EM duration of less than one week, neither algorithm was likely to return a positive result. Researchers also observed variability across testing methods, noting that some samples tested positive by one algorithm and negative by another.
“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,” says John A Branda, MD, associate professor at Harvard Medical School and director, clinical microbiology laboratory, Massachusetts General Hospital, in a release.
Study Methodology and Data
The research utilized geographically diverse samples from the Lyme Disease Biobank, which enrolled 107 participants with signs and symptoms of early Lyme disease and 144 control participants. The samples were collected between 2017 and 2020 at clinical sites in East Hampton, New York, and several locations in Wisconsin, which are endemic areas for the disease.
Of the 107 cases evaluated, 93 participants presented with a suspected EM rash, and 14 presented with constitutional symptoms compatible with early Lyme disease without a rash. The findings build upon previous studies emphasizing the need for novel diagnostics that do not rely on antibody detection to improve patient outcomes in the US.
Lyme disease is the most common vector-borne infection in the US, with approximately 500,000 Americans diagnosed each year. According to the Bay Area Lyme Foundation, the disease is often misdiagnosed, and up to two million Americans may be living with long-term complications due to delayed or missed treatment.
