Types of Lyme Disease Tests: Why Results Can Be Misleading

Testing does not always confirm Lyme
Results depend on timing and immune response
Clinical diagnosis remains essential

Types of Lyme disease tests vary widely in what they measure and how reliable they are in different stages of infection.

While laboratory testing can support diagnosis, Lyme disease is often best identified clinically based on symptoms, exposure history, and physical findings.

This becomes clearer when reviewing Lyme disease test accuracy, where timing and immune response significantly affect results.

Here’s how these tests actually work in real-world settings.

Clinical Diagnosis Remains Essential

Lyme disease cannot always be confirmed with a single test.

Diagnosis often depends on a physician’s ability to recognize patterns, including tick exposure and evolving symptoms.

This pattern is often missed because testing is expected to provide clear answers—even when it cannot.

This issue is frequently seen in delayed Lyme disease diagnosis, where patients may test negative early in illness.

Why Lyme Disease Tests Can Be Inaccurate

Test accuracy depends on several factors:

• Stage of infection
• Timing of immune response
• Prior antibiotic treatment
• Variability in Borrelia strains

Antibodies may not appear until weeks after infection.

Early testing may therefore be negative—even in infected patients.

This limitation is explained further in why early Lyme tests may be negative.

Additionally, the bacteria are not always present in the bloodstream, making direct detection difficult.

Most Common Types of Lyme Disease Tests

Several laboratory tests are used in clinical practice:

• ELISA (enzyme-linked immunosorbent assay)
• Western blot
• Two-tier antibody testing
• C6 peptide ELISA
• PCR testing
• Culture testing

Each test evaluates a different aspect of infection—and each has limitations.

ELISA Lyme Disease Test

The ELISA test is typically used as the first screening tool.

It detects antibodies to Borrelia burgdorferi.

However, early in infection, sensitivity may be low.

Studies have reported sensitivities as low as 33% to 49% in patients with an erythema migrans rash.

This means many infected patients may test negative.

Western Blot Lyme Test

The Western blot identifies specific antibody bands reacting to Borrelia proteins.

CDC criteria include:

• IgM: 2 of 3 bands (23, 39, 41 kDa)
• IgG: 5 of 10 bands

While more specific than ELISA, it can still miss cases and may be difficult to interpret.

For a deeper explanation, see Lyme disease test accuracy.

Two-Tier Lyme Testing

The standard CDC approach uses two-tier testing:

• ELISA first
• Western blot if ELISA is positive or indeterminate

This system may miss cases because both tests must be positive.

Sensitivity has been reported as low as 35% to 38% in confirmed cases.

PCR Lyme Test

PCR testing detects bacterial DNA rather than antibodies.

However, sensitivity is often low in routine practice.

Reported detection rates may range from 5% to 25%.

Culture Testing

Culturing Borrelia burgdorferi is difficult due to slow growth and low bacterial presence in blood.

Newer culture methods are under investigation but are not widely used.

Testing for Lyme Disease Co-Infections

Testing for co-infections such as Babesia, Bartonella, Ehrlichia, and Anaplasmosis can also be challenging.

Laboratory findings may be subtle and easily missed.

Because of this, clinicians often rely on pattern recognition and clinical judgment.

For more, see the Lyme coinfections guide.

Why This Matters

Testing can support diagnosis—but it cannot replace clinical judgment.

Relying solely on laboratory results may lead to missed diagnoses and delayed care.

This reflects a broader issue explored in why Lyme disease tests the limits of medicine.

Clinical Perspective

Lyme disease diagnosis requires integrating test results with clinical findings.

Negative tests do not exclude infection—especially early in disease.

Understanding test limitations helps guide better decision-making.

Clinical Takeaway

Types of Lyme disease tests provide useful information—but they are not definitive.

Clinical judgment remains essential, particularly when symptoms and exposure history suggest infection.

Frequently Asked Questions

Can Lyme disease tests be negative even if someone is infected?
Yes. Antibodies may take weeks to develop, leading to false-negative results early in infection.

What are the most common Lyme disease tests?
ELISA and Western blot are the most commonly used tests.

Can Lyme disease be diagnosed without a positive test?
Yes. Diagnosis is often clinical, based on symptoms and exposure risk.

Related Reading

• Lyme Disease Test Accuracy
• Why Early Lyme Tests May Be Negative
• Delayed Lyme Diagnosis
• Lyme Disease Symptoms Guide

References

1. Branda JA, Steere AC. Laboratory diagnosis of Lyme disease. Clin Microbiol Rev. 2021.

Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.

Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention