Lyme Disease Serology: Testing, Sensitivity & Interpretation

Instructor: Lori Haag

Lori has teaching experience in the health care setting. She has an associate's degree in Nursing and a bachelor's degree in Psychology.

In this lesson, you will learn about Lyme disease, indications and contraindications for serological testing, and the most common tests used to make a positive diagnosis.


Amanda was concentrating on the wall in front of her as she held the dart steadily in her hand. She pulled her elbow back, then gently thrust her hand forward. She watched closely as the sharp tip sailed through the air and landed smack dab in the middle of the board. ''Bulls-eye,'' she thought to herself. That was enough to win the game!

After the dart game, as Amanda pulled the darts from the board, she thought back to the rash she had a few weeks ago that looked strikingly similar to the board in front of her. It was almost a perfect circle on the side of her neck with a dark center in the middle. She wasn't sure where she had gotten it, but it had gone away on it's own. Apparently it wasn't anything to worry about-- or was it?

Lyme Disease

Lyme disease is a tick-borne infection indigenous to the United States, Canada, and Europe. It is caused by six different species of Borreliaceae bacteria, but only two of these species are found in ticks in North America. The blacklegged tick, also known as the deer tick, can spread the disease in the north-eastern, mid-atlantic, and north-central parts of the United States. Borreliaceae burgdorferi is a spirochete (spiral shaped bacteria), and is the most common species of Borreliaceae to cause illness in North America.

Deer ticks carry B. burgdorferi

Stages, Symptoms, and Serological Response

There are three stages of Lyme disease, and symptoms of each may overlap with symptoms of another. The first stage is early localized disease. This stage generally occurs within one month following a tick bite, and has the characteristic bullseye skin rash, erythema migrans, or EM. The EM rash precedes serologic immune response, and serological tests at this time will likely produce a false-negative result. For this reason, no serological testing is indicated when the rash is present. In people who have traveled to or live in areas where Lyme Disease is endemic, the presence of the rash is sufficient evidence to make a positive diagnosis.

Early Disseminated Disease is characterized by multiple EM lesions accompanied by neurological and/or cardiac involvement. Neurological symptoms that may be present include lymphocytic meningitis, facial palsy, or radiculoneuropathy. This stage occurs weeks to months after infection, and serological tests are usually positive for antibodies to B. burgdorferi.

Late Lyme Disease may occur months to a few years after an initial infection. This stage often presents with arthritis in the larger joints, especially the knees. Neurologic problems such as encephalopathy or polyneuropathy may also manifest during Late Lyme Disease. Serological testing is indicated in this stage of the disease because antibodies are usually present in the blood at this time. In people with early disseminated and late diseases, diagnosis is based on the presence of positive serological tests and clinical manifestation of symptoms.

Lyme disease can cause joint pain
Arthritis in Knee

A Two-Tiered Approach

A two-tiered algorithm is recommended when testing for Lyme Disease, beginning with the ELISA followed by the Western blot test. The ELISA, or enzyme-linked immunosorbent assay, detects antibodies to B. burgdorferi. The ELISA can sometimes produce false-positive results and therefore a positive diagnosis of Lyme Disease should not be based on ELISA results alone. However, if the ELISA produces negative results, no further serological testing is indicated.

False positive ELISA test results can occur with the following:

  • Other Borrelial diseases
  • Other spirochetal diseases such as: syphilis, leptospirosis, pinta, yaws, and gingivitis
  • People who have been vaccinated against Lyme disease

If the results of the ELISA are positive, then the Western blot should be done. The Western blot is also known as the immunoblot. It is more specific than the ELISA in that it detects antibodies to specific components of an organism rather than the whole organism itself.

The American College of Physicians and the Infectious Diseases Society have set guidelines for laboratory testing in patients suspected of having Lyme disease. These guidelines are as follows:

Testing is indicated when:

  • A person has a recent history of traveling to or residing where Lyme disease is endemic
  • AND exposure to ticks
  • AND having symptoms of early disseminated or late Lyme disease

Situations where testing is NOT INDICATED:

  • People with the early stage EM rash
  • Screening of asymptomatic patients living in endemic areas
  • For patients with non-specific symptoms, such as fatigue or arthritis

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