Lyme disease can be difficult to diagnose in its early stages because people often arrive at the doctor’s office or hospital with symptoms of the disease but no antibodies detectable through standard serologic lab tests. The current tests miss 60 to 70 percent of early-stage cases of Lyme disease, which leads to over-testing, misdiagnosis, and poor patient management. New diagnostic approaches to Lyme disease are greatly needed.
In a recent study, a team of researchers from the Centers for Disease Control and Prevention, Colorado State University, and New York Medical College, supported by NIAID, explored the feasibility of using metabolic markers to diagnose early-stage Lyme disease. When a disease infects the body, the immune system immediately triggers an inflammatory response. Using a technology called metabolomics, scientists can systematically study the unique footprints left behind by the inflammatory response. Individual metabolites or panels of metabolites observed after infection with a specific disease are designated as markers, or biosignatures, of that disease. The scientists hypothesized that the unique inflammatory response to early Lyme disease could distinguish it from healthy controls and other diseases that cause similar symptoms.
To test their theory, researchers analyzed banked serum samples from people with early-stage Lyme disease, people with other diseases, and healthy people. The analysis revealed small molecule metabolites that were unique to the early Lyme disease samples. The researchers then used statistical modeling to assess whether these metabolic markers could accurately categorize early-stage Lyme disease patients versus healthy controls and other diseases. They found metabolic profiling achieved significantly greater diagnostic sensitivity (88 percent) than the standard lab tests and retained a high specificity of 95 percent in diagnosing early-stage Lyme disease. The markers also correctly identified 77-95 percent of early-stage Lyme disease patients who had been incorrectly identified as disease-free by the standard lab tests.
The study provides proof-of-concept for a novel diagnostic approach for Lyme disease that has improvements over the standard testing process. Lyme disease can be easily confused with other diseases due to similar symptoms, so an enhanced test would reduce misdiagnoses and help patients quickly receive appropriate treatment.
Scientists will need to study the metabolic markers in more depth to optimize specificity and sensitivity to prevent false test results and to promote antibiotic stewardship. Continued development will also require serum samples from patients with other illnesses that have similar symptoms as Lyme disease, such as other tick-borne diseases, cellulitis and fungal infections. Researchers could also analyze sera from patients with other forms of Lyme disease, including neurologic Lyme disease, Lyme carditis, and Lyme arthritis, to discover additional or refined markers for early recognition of these more severe types of disease.
Molins CR et al. Development of a metabolic biosignature for detection of early Lyme disease. Clinical Infectious Diseases. DOI: 10.1093/cid/civ185.