According to a new study, the CDC’s standard two-tier testing for Lyme disease failed to accurately diagnose more than 70% of blood samples from individuals with an erythema migrans rash greater than 5 centimeters across.

Additional findings showed that Lyme disease also occurred in individuals with no rash, and those with rashes smaller than 5 cm.

This is significant, because patients with symptoms of Lyme disease are often denied proper diagnosis and treatment based on the CDC’s two-tier testing protocol.

Furthermore, EM rashes less than 5 cm are often disregarded in reporting Lyme disease cases.

The study highlights the unreliability of current diagnostic testing for Lyme disease and underscores the need for more research. Samples for the study came from the Lyme Disease Biobank.

Press release from Bay Area Lyme Foundation:

Bay Area Lyme Foundation, a leading sponsor of Lyme disease research in the U.S., announces results published in the Journal of Clinical Microbiology, a journal of the American Society for Microbiology, that point to limitations of currently available diagnostic tests for early-stage Lyme disease, and highlight the need for more research toward improved diagnostics and treatments.

Among the findings, the Centers for Disease Control’s standard two-tier testing algorithm (STTTA) for Lyme disease failed to accurately diagnose 71% of blood samples from individuals presenting with a Lyme rash, also known as an erythema migrans, greater than 5 cm in endemic areas.

These samples are part of the Lyme Disease Biobank (LDB), which was founded to catalyze new research in the understanding, diagnosis and treatment of Lyme disease and other tick-borne infections. Samples are available for research use through an application process to scientists who already work in tick-borne infections as well as those new to the field.

“For an epidemic like Lyme disease that is growing at such an alarming rate, there needs to be more research, greater understanding, better diagnostics, and improved treatments,” said Charles Chiu, MD, PhD, Professor of Laboratory Medicine and Medicine, Division of Infectious Diseases, University of California, San Francisco, and Bay Area Lyme Foundation scientific advisory board member, who is currently using samples from the Lyme Disease Biobank for his research.

No accurate test

“This study draws attention to the fact that we simply don’t have an accurate test for Lyme disease at present, and this is exactly why clinicians still need to rely on their knowledge of the signs and symptoms of early Lyme disease to diagnose patients and provide prompt treatment.”

These findings also reinforce that Lyme disease does occur in individuals who do not have a erythema migrans, and those with rashes smaller than 5 cm.

Samples that were laboratory confirmed for Lyme disease (N=82) were more likely to be enrolled with a Lyme rash (83%) and more likely to present with a Lyme rash greater than 5 cm (74%). However, 26% of laboratory confirmed Lyme disease did not present with a Lyme rash greater than 5 cm, including 9% enrolled as having a Lyme rash smaller than 5 cm and 17% enrolled without any skin manifestation.

Hard to get diagnosed without a rash

“Patients who do not exhibit a rash likely face the greatest challenges in being diagnosed – not only because many healthcare providers specifically look for this sign to diagnose patients, but because the lack of a rash correlated to less likelihood of an accurate serology test, according to this study,” added Dr. Chiu.

Currently comprised of samples from more than 800 participants, the Lyme Disease Biobank utilized 550 patient and control samples (298 cases and 252 controls) collected from 2014 through 2018 for this study.

Each sample was tested using both a first tier ELISA and second tier immunoblot (i.e., western blot), and the STTTA was applied. Assays were also performed to detect the presence of tick-borne pathogens (polymerase chain reaction (PCR)), and a subset of samples was evaluated by culture.

Of the 298 cases enrolled with signs and symptoms of Lyme disease, only 28% were identified as positive for Lyme disease through these methods, or a modified two-tier testing algorithm, consisting of two positive ELISAs in patients with Lyme rash (erythema migrans) greater than 5 cm. This collection highlights and reinforces the known limitations of STTTA testing in early Lyme disease.

Limitations of available tools

“This study highlights the limitations of available tools for all healthcare providers whose patients may be infected with Borrelia burgdorferi, the bacteria that causes Lyme disease. Our hope is that healthcare providers will consider these findings when evaluating patients with signs and symptoms of early Lyme disease,” said Liz Horn, PhD MBI, the study’s lead author and principal investigator for Lyme Disease Biobank.

“Our original goal was to characterize the samples we were making available to investigators working on new diagnostics for Lyme disease. We didn’t expect to find such large inaccuracies in current laboratory tests that support clinical decision-making.”

According to findings, participants presenting with a Lyme rash greater than 5 cm were more likely to be positive by any serologic test.

For samples taken while patients were experiencing signs and symptoms of early Lyme disease, a positive ELISA was found in 38-43% of patients with Lyme rashes larger than 5 cm, 17-35% of patients with rashes smaller than 5 cm, and 15-27% of patients without a rash, while 5-11% of controls also received a positive ELISA (ranges represent percent positive using different first-tier tests). For the second tier immunoblots, more cases were positive for IgM than IgG (as would be expected for early Lyme disease).

“We are thrilled to see the Lyme Disease Biobank helping to uncover the critical challenges facing patients and physicians as well as the urgent need for more accurate Lyme disease diagnostics,” said Alex Cohen, President and Co-founder of the Steven & Alexandra Cohen Foundation, whose funding has been instrumental in the rapid expansion of the Lyme Disease Biobank over the past four years.

Currently, there are 50 research projects that rely on Lyme Disease Biobank samples.

About Lyme Disease Biobank

The Lyme Disease Biobank (LDB), a program of the Bay Area Lyme Foundation, is a non-profit organization working to accelerate research of Lyme disease and other tick-borne infections. With a collection of biological samples from more than 800 participants, including serum, blood, urine and tissue, LDB provides much-needed samples to researchers working to better understand tick-borne diseases and develop improved tests and therapeutics. Blood and urine samples are collected from the Northeast and Upper Midwest areas of the U.S., as well as the San Francisco area and, now, San Diego, and tissue samples are collected throughout the U.S.

Healthcare providers, and patients interested in donating blood, urine or tissue samples can learn more here.

Researchers interested in obtaining samples should visit www.lymebiobank.org or contact info@lymebiobank.org.