Lyme disease tests: Science vs Misconceptions

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Lyme diagnosis and testing can be very confusing, which has contributed to false positive diagnoses and unnecessary treatment.

According to the CDC:

  • Patients who have had Lyme disease for longer than 4-6 weeks, especially those with later stages of illness involving the brain or the joints, will almost always test positive.
  • A patient who has been ill for months or years and has a negative test almost certainly does not have Lyme disease as the cause of their symptoms.
  • Serologic testing is generally not useful or recommended for patients with single EM rashes. For this manifestation, a clinical diagnosis (alone) is recommended.

A 2016 systematic review [8] that included 8 studies of test performance in “Late Lyme” showed Lyme antibody testing to be 99.4% sensitive and 99.3% specific**. 

In other words, out of 100 people with Late Lyme disease, 99-100 of them will test positive. Out of 100 people who may believe they have Late Lyme disease but do not, 99-100 of them will test negative.

Avoid unnecessary and unscientific testing

As part of the admirable “Choosing Wisely” campaign to reduce unnecessary tests and treatments, the American College of Rheumatology (ACR) warns:

Don’t test for Lyme disease as a cause of musculoskeletal symptoms without an exposure history and appropriate exam findings. [1]

The CDC has expressed similar sentiments [4] to the ACR and has also warned against unvalidated testing [5, 9].  Quackwatch [10] and Science-Based Medicine [11] both provide accessible explanations about the differences between validated and unvalidated tests.

The CDC “describes the steps required to properly test for Lyme disease” as follows:

The first required test is the Enzyme Immunoassay (EIA aka ELISA) or Immunofluorescence Assay (IFA). If this test yields negative results, the provider should consider an alternative diagnosis.  Or in cases where the patient has had symptoms for less than or equal to 30 days, the provider may treat the patient and follow up with a convalescent serum.

If the first test yields positive or equivocal results, two options are available:

1) if the patient has had symptoms for less than or equal to 30 days, an IgM Western Blot is performed;

2) if the patient has had symptoms for more than 30 days, the IgG Western Blot is performed.

The IgM should not be used if the patient has been ill for more than 30 days.

LymeScience recommends against:

  • Tests from any of the following labs: IgeneX, DNA Connexions, Galaxy Diagnostics, Medical Diagnostic Laboratories (MDL), Milford Molecular Diagnostics Laboratory, Advanced Lab, Fry Laboratories, Ceres Nanosciences (Nanotrap), Global Lyme Diagnostics, Pharmasan Labs (iSpot Lyme), Coppe Laboratories (myLymeTest), ArminLabs, BCA-Lab (formerly known as Infectolab), Australian Biologics, Melisa Labs, R.E.D. Labs
  • Any lab on Quackwatch’s list of “Laboratories Doing Nonstandard Laboratory Tests“.
  • CD57 testing
  • Diagnosis with microscopy, e.g. Live Blood Cell Analysis.
  • Diagnosis based on magical beliefs, for example applied kinesiology a.k.a Autonomic Response Testing (ART)
  • Urine tests
  • Electrodermal testing
  • Failing to follow testing strategies recommended by the CDC or local infectious diseases organizations
  • Clinical diagnosis without a science-based rationale
  • Diagnosis from an unscientific practitioner, including those who market themselves using the following terminology: Lyme literate (especially those affiliated with ILADS), integrative, functional, alternative, complementary, Traditional Chinese Medicine, holistic, natural, Biological, Ayurvedic, chiropractic, naprapathic, homeopathic, and naturopathic.
  • Any testing not recommended by the CDC.


See also the following LymeScience pages:

Other misconceptions about Lyme disease diagnosis and testing are discussed below.

Common Misconceptions About Lyme Disease

Like tests for other infections like HIV, testing for Lyme disease involves looking for antibodies produced by the immune system in response to infection. This is called serologic testing because the antibodies are found in blood serum.

Testing positive for antibodies is called seropositive and testing negative for antibodies is called seronegative.

Table excerpted and reformatted* from the longer 2013 paper (ref 2 below, which is worth reading):

False negatives

Misconception: “Blood tests are unreliable with many negatives in patients who really have Lyme disease.”

Science: Just as with all antibody-based testing, these are often negative very early before the antibody response develops (<4-6 weeks). They are rarely if ever negative in later disease.

Isolated IgM seropositivity

Misconception: “Patients with many months of symptoms may have only a positive IgM Western blot.”

Science: Because the IgG response develops in 4-6 weeks, patients with symptoms of longer duration than this should be IgG positive; isolated IgM bands in such patients are almost always a false positive.

Seropositivity after treatment

Misconception: “Positive blood tests after treatment mean more treatment is needed.”

Science: After any infection resolves, the immune system continues to produce specific antibodies for an extended period. This is not an indication of persistent infection.

Antibiotics effect on serologic tests

Misconception: “Antibiotics make blood tests negative during treatment”

Science: There is no evidence that this happens and no biologic reason it would.

The clinical diagnosis of Lyme disease

Misconception: “Lyme disease is a clinical diagnosis that should be made based on a list of symptoms.”

Science: No clinical features, except erythema migrans or possibly bilateral facial nerve palsy—in the appropriate context—provide sufficient specificity or positive predictive value. Laboratory confirmation is essential except with erythema migrans.

Persisting fatigue & cognitive symptoms in isolation as evidence of brain infection

Misconception: “Patients with fatigue and memory difficulties have Borrelia burgdorferi infection of the brain.”

Science: These symptoms are not specific for B. burgdorferi infection and only rarely are evidence of a brain disorder.

Severity of Lyme disease

Misconception: “B. burgdorferi infection is potentially lethal.”

Science: Although Lyme disease can cause heart or brain abnormalities, there have been remarkably few—if any—deaths attributable to this infection.

LymeScience note: After this paper was published, the CDC published[3] three case studies of deaths associated with Lyme carditis, though two patients had preexisting heart conditions. While it’s not entirely clear if the infection caused the deaths, the CDC still reiterates, “Prompt recognition and early, appropriate therapy for Lyme disease is essential.”

Prolonged treatment

Misconception: “If, following treatment, symptoms persist, or serologic testing remains positive, additional treatment is required.”

Science: Multiple well-performed studies demonstrate that recommended treatment courses cure this infection. Retreatment is necessary occasionally, but not frequently.

Symptomatic improvement on antibiotics as validation of the diagnosis

Misconception: “Rapid symptomatic improvement on treatment proves the diagnosis despite negative blood tests.”

Science: Non-microbicidal effects of antibiotics may result in symptomatic improvement. In controlled trials, 1 patient in 3 improved in response to placebo.

Bottom Line

There is substantial evidence supporting the accuracy of FDA-cleared tests once antibodies build up in the body (4-6 weeks post-infection).

The CDC concurs:

You may have heard that the blood test for Lyme disease is correctly positive only 65% of the time or less. This is misleading information. As with serologic tests for other infectious diseases, the accuracy of the test depends upon the stage of disease. During the first few weeks of infection, such as when a patient has an erythema migrans rash, the test is expected to be negative.

Several weeks after infection, currently available ELISA, EIA and IFA tests and two-tier testing have very good sensitivity.

It is possible for someone who was infected with Lyme disease to test negative because:

  1. Some people who receive antibiotics (e.g., doxycycline) early in disease (within the first few weeks after tick bite) may not develop antibodies or may only develop them at levels too low to be detected by the test.
  2. Antibodies against Lyme disease bacteria usually take a few weeks to develop, so tests performed before this time may be negative even if the person is infected. In this case, if the person is retested a few weeks later, they should have a positive test if they have Lyme disease. It is not until 4 to 6 weeks have passed that the test is likely to be positive. This does not mean that the test is bad, only that it needs to be used correctly. [7]


* LymeScience reformatted the table and added punctuation, emphasis, a note, and changed the word “evidence” to “science”. Excerpted for educational and commentary purposes.

** 99.4% sensitive (95% confidence interval: 95.7–99.9) and 99.3% (95% confidence interval: 98.5-99.7%) specific.


1. Choosing Wisely: American College of Rheumatology

2. Halperin JJ, Baker P, Wormser GP. Common misconceptions about Lyme disease. Am J Med. 2013 Mar;126(3):264.e1-7.

3. CDC: Three Sudden Cardiac Deaths Associated with Lyme Carditis — United States, November 2012–July 2013

4. CDC: Lyme disease: Diagnosis and Testing

5. CDC: Lyme disease: Laboratory tests that are not recommended

6. CDC scientist Barbara J.B. Johnson, PhD: Book chapter of “Lyme disease: An Evidence-Based Approach”: Laboratory Diagnostic Testing for Borrelia burgdorferi Infection

7. CDC: “I have heard that the diagnostic tests that CDC recommends are not very accurate. Can I be treated based on my symptoms or do I need to use a different test?” Lyme FAQ.

8. Waddell LA, et al. The Accuracy of Diagnostic Tests for Lyme Disease in Humans, A Systematic Review and Meta-Analysis of North American Research. PLoS ONE. 2016;11(12):e0168613.

9. CDC: Notice to Readers: Caution Regarding Testing for Lyme Disease

10. Quackwatch: Some Notes on Nonstandard Lyme Disease Tests

11. Science-Based Medicine: Lemons and Lyme: Bogus tests and dangerous treatments of the Lyme-literati

12. American Lyme Disease Foundation: Limitations of Antibody-Based Diagnostic Tests for Lyme Disease

13. Botman E, et al. Diagnostic behaviour of general practitioners when suspecting Lyme disease: a database study from 2010-2015. BMC Fam Pract. 2018;19(1):43.

14. Article about “ELISpot” Lyme tests: New test has no added value in Lyme disease of the central nervous system

15. Duerden BI. Unorthodox and unvalidated laboratory tests in the diagnosis of Lyme borreliosis and in relation to medically unexplained symptoms. Department of Health, London, UK, 2006.

16. CDC Q and A: Epidemiology and Clinical Features of Lyme Disease

17. Choosing Wisely: Lyme Disease

18. Canadian scientists: Lyme disease: How reliable are serologic results?