Lyme disease is recognized as a clinical diagnosis that is supported by diagnostic tests. However, a patient may have Lyme disease but not test positive on a particular test. Many different tests may be ordered for an individual patient for two reasons. First, the internist will want to rule out other possible causes of the persistent symptoms that may not yet have been considered. Second, the physician will want to determine whether the constellation of findings in this particular patient is similar to that which one finds with other patients who have Lyme disease.
The two tests most commonly used when checking for Lyme disease are the ELISA and the Western blot. These tests detect antibodies present in the patient’s blood that have been triggered by infection with the spirochete, B.burgdorferi. These antibodies however do not necessarily tell us whether or not the infection is still present, as the human immune response continues to “recall” the previous infection for many months to years and thus continues to produce the Bb-specific antibodies. The indirect nature of these tests is thus problematic as it does not reveal whether or not infection continues to persist in the patient.
Culture of the organism is the gold standard for the evaluation of all infections. Borrelia burgdorferi is a slow growing organism, so culture may take weeks. More problematic is that culture is rarely positive once the infection has disseminated beyond the stage of erythema migrans. Studies indicate that certain high volume blood collection methods may yield positive culture results at the time of the erythema migrans, but this is not necessary in most cases as the Erythema migrans rash itself is sufficient to make the diagnosis of Lyme disease and initiate treament. Because of the low yield of this test in cases of late stage or disseminated Lyme disease, culture is rarely used.
The Enzyme Linked Immunosorbent Assay (ELISA) is inexpensive, automated, and widely used as a screening test for Lyme disease. A single number is reported that reveals the relative quantity of antibodies in the patient’s serum against the agent of Lyme disease. Most commonly, the whole cell sonicate of Bb is used for the ELISA assay, but this assay can result in both false negatives and false positive. More recently, the C6 Peptide ELISA has been used as a screening assay as it has specificity rates of 90-100%. Unfortunately, the sensitivity of the ELISA and the IFA (immunoflourescence assay) vary considerably, with estimates ranging from 55% to 90% depending upon the clinical manifestations and duration of infection.
While the ELISA/IFA are quantitative tests, the Western blot provides qualitative data. Interpretation of the Western blot requires considerable skill on the part of the laboratory expert as a visual assessment of the intensity of each “band” determines whether or not that band would be considered present or absent. More recently, automated methods have been developed to make such decisions (removing subjective error), with reports that provide both categorical information (present/absent based on an intensity cutoff) and continuous information (%intensity) for each band. Criteria vary for the Western blot in the United States and in Europe. Within the United States, the Centers for Disease Control advocate a standard method for evaluating the Western blot as positive: 2 out of 3 bands (23, 39 or 41 kD) on the IgM or 5 out of 10 bands on the IgG (18, 23, 28, 30, 39, 41, 45, 58, 66, 93). While this method has the advantage of providing uniformity, the list of “specific” bands excludes several other bands known to be specific for Bb, such as the 31 kD and 34 kD bands.
PCR assays are among the most specific of the diagnostic assays in that the PCR detects the genetic material of the organism. Rather than providing indirect evidence of infection by looking at the immune response (as is done when the ELISA or Western blot is used to detect antibodies specifically generated against Bb), the PCR detects the genetic material itself. While a positive PCR result does not demonstrate definitively that current infection is present, it is strongly suggestive of current or very recent infection. Unfortunately the PCR assay is often negative when used conducted to assist in the diagnosis of Lyme disease. This may be because the genetic load in the specimen is below the detection level or because the Bb is well known to reside in the blood for only short periods of time. Because Bb is tissue tropic and may reside in areas of reduced vascular circulation, the PCR assay of the blood or CSF may be negative.
e. Other Lab tests. Over the last 2 decades, various investigators have studied other laboratory methods for detecting Lyme disease, such as the immune complex dissociation assay, the Lymphocyte Stimulation Assay, the Borreliacidal assay. These assays have never come to commercial production and hence will not be discussed in detail here. The reliability of other assays, such as the Lyme urine antigen test, have been questioned in recent reports.
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