How Effective Are Lyme Disease Tests? Everything You Need To Know


lymes disease test false negative

The lack of a conclusive Lyme Disease test is one of the most frustrating aspects of the disease for sufferers and their loved ones.

Numerous tests are available, but many patients receive false negative results because the most commonly used tests are not sensitive enough.

The consequence of a delay in diagnosis can be devastating for the patient, as it often delays the start of an effective treatment plan.

The longer Lyme Disease is left untreated, the more likely it is that the patient’s immune system will be weakened and other body systems become compromised.

The aim of this article is to provide information about the problems associated with Lyme tests, an outline of the tests available and information about how a diagnosis can be achieved effectively in the light of all these problems.

You can jump straight through to specific sections of this article from here:

The problem with CDC surveillance criteria in Lyme Disease testing

The problem of testing for Lyme Disease starts with the fact that CDC surveillance criteria, that are commonly used in diagnosis, were never meant to be used as a diagnostic test.

In-stead, they were created by epidemiologists to track the disease.

In order to receive a diagnosis of Lyme Disease, the patient must receive a positive ELISA or IFA test result followed by a positive Western Blot test result.

As the ELISA and IFA are often not sensitive enough to detect the disease and therefore produce a false negative result, this system is flawed from the start.

What is the meaning of “sensitivity”?

The effectiveness of diagnostic tests is often assessed by how sensitive or specific they are considered to be.

Lyme tests are often criticized for not being “sensitive” enough, but what does this mean?

If a test is highly sensitive, it will lead to a positive result in a high percentage of cases for the disease it is being used to test. It is considered effective if it is sensitive in 95% of cases.

If a test is not very sensitive, as is the case for Lyme Disease tests, it is likely to result in false negatives, which means a high proportion of people with the disease will not be diagnosed using the test.

In contrast, a test is considered highly specific if a high proportion of the people who test positive have the disease. A highly specific test produces fewer false positives.

Direct and Indirect Lyme Disease Tests

Lyme Disease tests can be categorized into two groups: Direct and Indirect.

  • Direct tests – seek to find the Borrelia bacteria or co-infections in body tissues and fluids. Examples of direct Lyme tests include PCR, FISH, cultures and biopsies and antigen-capture tests.
  • Indirect tests – measure the response of the immune system to Borrelia bacteria or co-infections. Examples of indirect Lyme tests include ELISA, IFA, Western Blots for Borrelia, IgG and IgM antibody tests for co-infections.

Direct Tests

PCR (Polymerase Chain Reaction)

In a PCR test, bodily fluids such as blood are tested to see if the DNA of the bacteria can be detected. This is a specific test, but it is not very sensitive. It is most useful in the early stages of infection.

what is the most accurate test for lyme disease

PCR is not dependent on the reaction of the immune system, which is a good thing as the immune system is often weakened in Lyme Disease sufferers.

However, it is limited by the number of strains it can identify and does not account for the fact that bacteria are often found in tissues rather than in fluids.


In culture tests, blood samples are removed from the patient and tested over a period of time to see if the Borrelia grow. They are then tested using PCR to identify the strain.

This test is more reliable than Western Blot and more sensitive than PCR.


During a biopsy tissue samples are taken from the patient and examined for infections.

A biopsy is most useful where there is a specific area of the body that is infected, such as a rash.

This test is not common practice as it is more invasive than other tests.

Lyme Direct Antigen Test

In a Lyme Direct Antigen Test urine is examined to identify Borrelia. The patient is given antibiotics in advance to provoke bacteria.

As the antibiotics work on destroying bacteria, what is left over will show up in urine.

This is a useful test as, like PCR it is not dependent on the reaction of the immune system.

Indirect Tests

Indirect tests measure the response of the immune system to bugs.

There are two antibodies used to test for an infection: IgM and IgG.

  • IgM antibodies appear 2-4 weeks after exposure.
  • IgG antibodies appear much later, months or even years after the initial infection.

One of the problems with indirect tests is by the time the antibodies can be detected, the patient has already been infected for weeks. The most effective treatment time is early after infection, so by the time it has been detected this window may have been missed.

IgG also confuse the issue as they can indicate exposure to a disease rather than infection. For example, antibodies will be detected after a vaccine. They can, therefore, show the presence of the bacteria, even if the patient is not sick.

Relying on tests for Lyme Disease that depend on a response from the immune system is a problem, as a weakened immunological response is a characteristic of the disease. Indirect tests can therefore lead to false negatives.

In addition, patients are commonly treated with antibiotics early in the disease which can affect their antibody response. This can lead to a negative result even if they have the infection.

ELISA test

The ELISA test is the most widely used of the Lyme Disease tests even though it is possibly the least useful.

This test is the one that is most often covered by insurance, indeed many insurance companies require this test first before other tests will be funded.

The ELISA test often leads to a false negative result with the result that no further testing is done.

The test looks for the presence of antibodies produced by the immune system in response to infection.

The main problem with this test is it is not sensitive enough. A screening test must have 95% sensitivity to be effective, only 65-70% of people with confirmed Lyme Disease show a positive response to this test.

It is also not specific enough to cope with many of the strains of the bacteria and it is dependent on an immunological response which might have been dampened because of the weakened immune system which is a common characteristic of Lyme Disease.

As the IgM and IgG antibodies are produced at specific times, this test can also be ineffective as it is time-sensitive.

IFA test

The IFA test works in the same way as ELISA looking for antibodies, but in this test the anti-bodies are pooled, it is looking for IgM, IgG and IgA so is not time sensitive.

The IFA test can have a good level of specificity and sensitivity if carried out correctly.

It should be used in conjunction with other tests to give information about the progress of the disease.

Western Blot

The Western Blot test can be sensitive if the lab looks for all the bands for Borrelia.  The CDC has identified certain numbers or bands that they consider indicate a positive result.

According to a Naturopathic Physician who specialises in Lyme disease, Nicola McFadzean says there is a difference between the bands that are clinically significant and the number that need to be positive in order to achieve a positive result.[1]

The FDA commercially available kits only report the bands required by the CDC. The consequence is only private labs that don’t have to follow these rules can carry out tests that give an accurate result.

The CDC also states that Western Blot testing should only be used in the first month after infection, whereas studies have shown that Western Blot can still be positive even in persistent or recurrent Lyme Disease.

The Western Blot is the most clinically useful of indirect Lyme tests, but its effectiveness is restricted by how it is currently used and it still only shows exposure to Lyme Disease not necessarily infection.

Lyme IGX Spot

This test is a relatively new and advanced enzyme-Linked ImmunoSpot (ELISPOT) assay that specifically tests for the Borrelia burgdorferi strain, by detecting T-cell responses to B.burgdorferi antigens.

This test is showing earlier detection than the Western blot.

It does not, however detect the other species of Borrelia.

Testing for Co-infections

Many Doctors believe that the failure to treat co-infections is a big factor in the failure to effectively treat Lyme Disease.

Information about co-infections can make a big difference in deciding on which treatment path to follow. For example, Babesia is a parasite so it will require a different treatment than Borrelia bacteria.

Common tests for co-infections include Antibody tests, FISH tests, and PCR tests.

Antibody tests – can identify six specific co-infections.

Like all indirect tests, they rely on the immune system response which can be weak for Lyme sufferers.

FISH tests (Fluorescent In-Situ Hybridization) detect Babesia and Bartonella co-infections.

Although FISH has a high level of specificity with few false positives, negative results only mean the infection was not present in the sample tested.

how do doctors test for lymes disease

PCR tests look for the DNA of the bacteria in a blood sample. PCR tests are not as sensitive as FISH tests in co-infections

There are other tests available that can help make an assessment for Lyme Disease.

CD-57 natural killer cells test

CD-57 is an immune system marker that is often low in a patient with Lyme Disease and is useful because although diseases such as Chronic Fatigue, MS, and Rheumatoid Arthritis may look like Lyme Disease, they will not cause a drop in CD-57.

CD-57 can also be used to track treatment as levels will return to normal as the patient gets better. If it rises as treatment progresses but the symptoms of Lyme Disease are not going away, it can indicate the co-infections are causing the symptoms rather than Borrelia.

There are also problems with this test. Counts can fluctuate between readings in a way that seems to bear no relation to the progression of the illness or the treatment, and for some people, the count stays low despite treatment and the fact the symptoms are lessening.

Fry Labs Advanced Stain for Biofilm

This test is useful for patients who are on antibiotics and not making the expected level of progress.

The test gives a visual picture of the biofilm, which is produced by the bacteria to create a defense system to hide in.

This defense system can stop antibiotics working and evade attacks by the immune system.

Elispot-LTT (Lymphocyte Transformation Test)

Measuring T-cell reactivity to Borrelia is another diagnostic tool.

Borrelia infection activates T-cells as well as antibodies immediately after infection until 6-8 weeks after completion of effective therapy.

If the results of the tests are so flawed, why do we bother testing at all?

Even though the tests are not conclusive, they are still useful because the more information we can gather the better able we are to confirm an illness, identify co-infections, and assess the progress of the disease.

McFadzean likens test results to the pieces of a puzzle. While they can’t rule out or rule in an infection, they can be combined with the patient’s history and symptoms to form a bigger picture.

How can a diagnosis of Lyme disease be made?

Currently, many cases of Lyme are being missed by diagnostic tests.

Many patients are not diagnosed with Lyme Disease even though they have symptoms and are known to have been in an area where they are at risk.

An effective Lyme Disease diagnosis can only be made by taking all the information into account.

The Doctor needs to know the patient’s history, particularly if they have been in a high-risk area, and they need to take into account the patient’s symptoms based on a physical examination.

This information can then be backed up with evidence from diagnostic tests.

It is hoped that further research leads to more conclusive tests becoming available, but in the meantime, more information about the pros and cons of the current tests can help in-form patients about their options.

Most importantly patients should be aware that while a Lyme Disease test is not a conclusive diagnostic tool on its own, it can be useful when combined with other tests and information about their history and symptoms.

If you are interested in starting on a treatment plan then take a look at our Lyme disease treatment options HERE:


So what has your experience been with Lyme disease testing?

Let us know in the comments below, we would love to hear from you…



[1] McFadzean, N., 2012. Lyme Disease in Australia: Fundamentals of an Emerging Epidem-ic. South Lake Tahoe, BioMed Publishing Group, 2012.

[2] Rawls, w., 2017. Unlocking Lyme. First Do No Harm Publishing, Cary, NC, 2017.


Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Lyme Disease Advice or its staff.

Share the Knowledge:

Leave a Reply

Your email address will not be published. Required fields are marked *