What is the diagnostic test for Lyme disease and what factors increase the risk of infection?

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Last updated: June 18, 2025View editorial policy

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From the Guidelines

The primary diagnostic test for Lyme disease is a two-step blood test consisting of an enzyme-linked immunosorbent assay (ELISA) followed by a Western blot if the ELISA is positive or equivocal, as recommended by current guidelines 1. This testing approach detects antibodies against Borrelia burgdorferi, the bacterium that causes Lyme disease. Several factors increase the risk of Lyme disease infection, including:

  • Living in or visiting wooded or grassy areas, particularly in the northeastern and north-central United States and parts of Europe, which significantly raises risk due to higher tick populations 1
  • Outdoor activities such as hiking, camping, gardening, and hunting in these regions, which increase exposure to ticks 1
  • Exposed skin and failure to use tick repellents or perform regular tick checks after outdoor activities, which also elevate risk
  • The time of year, with late spring through early fall being peak seasons when ticks are most active
  • Having pets that go outdoors, which can bring ticks into the home The risk of infection increases with longer tick attachment time, with transmission typically requiring at least 36-48 hours of attachment, which is why prompt tick removal is essential for prevention. It's worth noting that the sensitivity of the 2-tiered testing is low (30%–40%) during early infection, while the antibody response is developing, but specificity is high (>95%) during all stages of disease 1.

From the Research

Diagnostic Test for Lyme Disease

  • The diagnostic test for Lyme disease primarily relies on serologic responses to infection, with a two-tiered approach recommended by the Centers for Disease Control and Prevention (CDC) 2.
  • The two-tiered approach consists of initial IgM and IgG quantitative enzyme-linked immunosorbent assay (ELISA), followed by confirmation of all indeterminate or positive ELISA tests with separate IgG and IgM Western blots 2, 3.
  • Other testing modalities, such as IgG vlsE C6 peptide ELISA, are also available and have been evaluated for their sensitivity and specificity in diagnosing Lyme disease 3, 4.

Factors that Increase the Risk of Infection

  • Individuals who spend time outdoors in areas where ticks are common, such as wooded or grassy areas, are at increased risk of infection 4.
  • People who engage in activities such as hiking, camping, or gardening are also at higher risk of exposure to ticks and subsequent infection 4.
  • The risk of infection can be reduced by taking preventive measures, such as using insect repellents, wearing protective clothing, and conducting regular tick checks 4.
  • It is essential to note that the risk of infection is not limited to specific geographic areas, and Lyme disease can be found in various parts of the world 5, 6.

Sensitivity and Specificity of Diagnostic Tests

  • The sensitivity and specificity of serologic tests for Lyme disease can vary depending on the stage of the disease and the testing modality used 2, 3, 6.
  • Western blotting can be used to increase the specificity of serologic testing in Lyme disease, particularly in cases with indeterminate IgG responses by ELISA 6.
  • The use of US Food and Drug Administration-approved serologic tests, such as an enzyme immunoassay (EIA), followed by Western blot testing, is supported by evidence for diagnosing extracutaneous manifestations of Lyme disease 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Prospective study of serologic tests for lyme disease.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2008

Research

Laboratory diagnosis of Lyme disease.

Rheumatic diseases clinics of North America, 1989

Research

Western blotting in the serodiagnosis of Lyme disease.

The Journal of infectious diseases, 1993

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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