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A Blood Test That Catches Lyme Disease Early

At a Glance

Researchers at Colorado State University have developed a metabolic biosignature—a unique molecular fingerprint found in blood—that detects early Lyme disease with 88% sensitivity and 95% specificity. This new test identifies more than 44 specific metabolites (small molecules) in the blood that are characteristic of early Lyme infection. The biosignature significantly outperforms the current CDC-recommended diagnostic approach, which only catches early Lyme disease 37-44% of the time. By analyzing these metabolites with advanced laboratory techniques, doctors can now identify patients with early Lyme disease more accurately and distinguish it from other similar conditions.

Background

Lyme disease is the most common tick-borne illness in the United States and Europe, with an estimated 300,000 cases occurring annually in the US alone. Early diagnosis is critical for treatment success, yet current diagnostic methods fail to detect early-stage Lyme disease reliably. The CDC-recommended approach uses antibody testing, which is highly accurate for late-stage disease but detects only 29-40% of early infections because antibodies have not developed sufficiently yet. The characteristic skin rash (erythema migrans) used for clinical diagnosis is easily confused with other conditions like tick-bite reactions, STARI (southern tick-associated rash illness), and fungal infections, leading to misdiagnosis and delayed treatment.
This metabolic biosignature approach represents a change in thinking in Lyme disease diagnosis by identifying the actual biochemical signature of infection rather than relying solely on the immune system’s delayed antibody response or clinical appearance alone.

Overview

The metabolic biosignature was developed through advanced analysis of serum samples from patients with early Lyme disease, patients with other diseases, and healthy controls. Using liquid chromatography-mass spectrometry (LC-MS), researchers identified and quantified small molecule metabolites in the blood that distinguish early Lyme disease from non-Lyme conditions. The analysis revealed a signature of more than 44 metabolites that, when analyzed together using a statistical model, correctly identify early Lyme disease patients with 88% sensitivity (84-95% confidence interval) and 95% specificity. This represents a major improvement over the current CDC-recommended 2-tier serologic test, which achieves only 37-44% sensitivity in early-stage disease while maintaining similar specificity (95-100%). The metabolite pattern reflects the biological response to Borrelia burgdorferi infection early in disease progression before sufficient antibodies accumulate for antibody-based detection.

The test workflow involves collecting a blood serum sample, analyzing it with LC-MS instrumentation, and comparing the metabolite profile against the validated biosignature model. This approach is objective, quantitative, and not dependent on clinical interpretation of skin lesions or immune response timing, making it potentially more reliable for early diagnosis when clinical features are ambiguous or absent.

Figure 1. This graph compares three statistical approaches to analyze the metabolic biosignature (colored lines) against the current CDC-recommended Lyme disease test (red dot), showing that the metabolic biosignature is significantly more accurate at detecting early Lyme disease while maintaining accuracy in identifying healthy people.

Benefits

  • Dramatically higher detection rate of early Lyme disease (88% vs. 37-44% with current CDC-recommended testing)
  • Maintains high specificity (95%) to avoid false positives and unnecessary treatment
  • Distinguishes between active Lyme infection and previous or inactive infection through metabolite patterns
  • Objective, laboratory-based test eliminates diagnostic ambiguity from clinical appearance or skin lesion confusion
  • Enables early diagnosis and treatment, improving patient outcomes and preventing progression to late-stage disease
  • Reduces reliance on clinical judgment of skin lesions that can mimic other conditions

Applications

  • Clinical diagnostics for early Lyme disease in acute care and outpatient settings
  • Rapid diagnosis in emergency departments for patients with tick exposure and early symptoms
  • Infectious disease specialist practices for definitive diagnosis of ambiguous cases
  • Occupational health and safety programs in high-risk endemic regions
  • Reference laboratory services for confirmation of suspected early Lyme disease
  • Public health surveillance and epidemiological studies tracking Lyme disease prevalence
  • Research tool for understanding Lyme disease pathogenesis and infection biology

Publications

Molins, Claudia R, et al. “Development of a Metabolic Biosignature for Detection of Early Lyme Disease.” Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, Oxford University Press, 15 June 2015, www.ncbi.nlm.nih.gov/pubmed/25761869.

Last Updated: May 2026
Engorged Ixodes scapularis (deer tick) on a tan sandy surface showing its reddish-brown back and dark legs.
Opportunity

Available for Licensing
TRL: 4

IP Status

US Patent 10669567 B2

Inventors

​John T Belisle
Claudia R Molins
Gary P Wormse

Reference Number
15-049
Licensing Manager

Steve Foster
Steve.Foster@colostate.edu
970-491-7100

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