CDC Provides Updates on Lyme Disease Diagnostics

In a recent webinar, researchers from the Centers for Disease Control and Prevention (CDC), Fort Collins, Colorado, provided updates on Lyme disease diagnostics.

According to Martin Schriefer, PhD, one of the challenges of diagnosing Lyme disease is in the lack of pathognomonic features associated with the disease, which increases the need for effective laboratory testing methods. The small number of spirochetes in a clinical sample also poses a challenge, he said, thus increasing the need for an amplification step (of either the disease marker or causative organism) in the testing method. These amplification steps may involve techniques such as polymerase chain reaction or microbial culture, for example.

More than 3.4 million diagnostic tests are performed for Lyme disease each year in the United States, said Claudia Molins, PhD. The currently recommended testing strategy is serology-based and uses a standardized two-tiered testing (STTT) approach. This involves an enzyme immunoassay (EIA), which, if the result is positive or equivocal, is followed by IgM/IgG western blot to detect the presence of antibodies against Borrelia burgdorferi, the Lyme disease bacterium, in clinical specimens.

However, Dr. Schriefer and Dr. Molins both stressed that the diagnostic sensitivity of STTT is not adequate in the early stages of Lyme disease. Although its sensitivity rises as Lyme disease stage progresses, its current sensitivity range for early Lyme disease ranges between only 29% and 40%. Its specificity for early disease, however, is high and exceeds 95%.

Improved detection of early Lyme disease thus remains a significant area of need in Lyme disease diagnostics. Any new test must achieve similar or higher sensitivity than current STTT offers, said Dr. Molins, while retaining similarly high specificity. It must also be practical for use in a clinical laboratory setting, must be non-subjective, and ideally should differentiate between previous and active Borrelia infection.

Dr. Schriefer discussed using modified two-tier strategies (MTTT) to achieve these objectives. One such MTTT approach uses a 2-EIA (whole cell EIA followed by EIA for C6 antibody). This approach takes advantage of the greater diagnostic sensitivity in early Lyme disease that the C6 EIA provides, minimizes the complexity and subjective interpretation of western blotting, and maintains the specificity of STTT. Overall, MTTT affords similar or improved performance and greatly simplifies testing, said Dr. Schriefer. It can also be performed in most laboratories and allows for more objective testing.

Dr. Molins also discussed using non-antibody-based laboratory tests for early Lyme disease, including metabolomics-based testing, which involves “characterization and identification of small biomolecules (metabolites) that result from cellular processes,” she explained.

Dr. Molins described research performed by CDC in which a metabolomic biosignature was developed that differentiated early Lyme disease from healthy control patients and those with other diseases. The test correctly identified as positive up to 95% of culture/PCR confirmed Lyme disease specimens that were negative by STTT.

Although Dr. Molins highlighted the promise of these results so far, she stressed that the next step is to move this test from a research laboratory to produce a functional assay in the clinical setting.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.