Updates to Serologic Assays for Diagnosis of Lyme Disease

The US Centers for Disease Control and Prevention (CDC) has announced updated recommendations for the serologic diagnosis of Lyme disease. The new recommendations were published in the Morbidity and Mortality Weekly Report.

Laboratory confirmed diagnosis of Lyme disease is principally conducted through serologic testing. Traditional recommendations included the use of a sensitive enzyme immunoassay (EIA) or immunofluorescence assay. For a specimen with a positive or “equivocal result,” follow-up with a western immunoblot assay was also endorsed.

On July 29, 2019, the US Food and Drug Administration (FDA) cleared marketing for 2 previously cleared Lyme disease serologic assays with new indications for use. This introduced a new testing paradigm, allowing 2 EIAs to run concurrently or sequentially, rather than in the previously recommended 2-step process.

The cleared tests include: ZEUS ELISA Borrelia VlsE1/pepC10 IgG/IgM Test System, ZEUS ELISA Borrelia burgdorferi IgG/IgM Test System, ZEUS ELISA Borrelia burgdorferi IgM Test System, and the ZEUS ELISA Borrelia burgdorferi IgG Test System.

“When cleared by the FDA for this purpose, serologic assays that utilize a second EIA in place of western immunoblot assay are acceptable alternatives for the serologic diagnosis of Lyme disease,” the authors of the MMWR report wrote.

The traditional 2-step approach was first recommended in 1994 when the Association of State and Territorial Public Health Laboratory Directors, CDC, FDA, the National Institutes of Health (NIH), the Council of State and Territorial Epidemiologists, and the National Committee for Clinical Laboratory Standards convened the Second National Conference on Serologic Diagnosis of Lyme Disease.

When discussing the development of future tests, the conference proceedings recommended that evaluation of new serologic assays include testing against a challenge panel. Furthermore, new assays should only be recommended if their sensitivity and precision was equal to or surpassed the performance of the traditional 2-test procedure.

Based on the criteria established at the 1994 conference, clinicians and laboratories should consider serologic tests cleared by FDA as CDC-recommended procedures for Lyme disease serodiagnosis.

“Lyme disease can have a devastating impact on patients. [Now] clinicians have a new option to test for Lyme that is easier to interpret by a clinical laboratory due to the streamlined method of conducting the test. These tests may improve confidence in diagnosing a patient for a condition that requires the earliest possible treatment to ensure the best outcome for patients,” Tim Stenzel, MD, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, said in the FDA’s press release.

According to the CDC authors, the FDA marketing clearance of these new assays for Lyme diseases indicates that the assays are “substantially equivalent to or better than a legally marketed predicate test.”