Lyme Disease and Related Tick-Borne Infections

Description

Alternative Names

Diagnosis

Proper diagnosis of Lyme disease is important. A diagnosis of Lyme disease is straightforward if the patient meets the following criteria:

• Lives in an area of tick-infestation.
• Has the tell-tale bulls-eye rash.
• Has other symptoms (headache, joint aches, malaise, flu-like symptoms).

If the patient has all of these symptoms, except the rash, then the physician may undertake the enzyme-linked immunosorbent assay (ELISA) or the Western Blot test.

Culture

In some cases, if the patient seeks a diagnosis within the first two or three weeks, the physician may take a sample of the skin or of the blood. If Lyme spirochete is present, it may be identified in the laboratory in a culture medium (a substance in which the organism can thrive and reproduce). This is necessary only if a physician suspects Lyme but the diagnosis is not clear. Basically, it is a research technique.

Immune Testing

If the infection is not obvious from the patient's history and physical symptoms but Lyme disease is suspected, the physician may run tests for evidence of specific factors that suggest infection with B. burgdorferi. Such factors include the following:

• Proteins referred to as Osps. These proteins (referred to as Osp A through F) coat the outer surface of the B. burgdorferi spirochete and then attach to human cells after infection.
• Antibodies that attack these Osps. Antibodies are the weapons of the immune system that are launched when a foreign invaders (called antigens) are detected. In the case of Lyme disease, these antigens are the Osps.

Specific Tests.

Tests have now been developed to detect either the antibodies that attack the Osps or the Osps themselves.

• ELISA and Other Initial Tests. The first tests used are either enzyme-linked immunosorbent assay (ELISA) or an indirect fluorescent antibody (IFA) test. ELISA is the immune test used most often for Lyme disease. (The IFA test is less accurate but may be used when ELISA isn't available.) ELISA measures antibodies that are directed against the B. burgdorferi spirochete. A newer variant is a rapid test (PreVue) that can provide results within an hour. Positive results from any of these tests still require confirmation with a Western blot test.
• Western Blot. If any of these tests is positive or uncertain, then they are followed by the Western immunoblot (WB), which is more accurate and is very helpful in confirming the diagnosis. The Western blot creates a visual graph showing bands of different colors or shading that experts use to interpret the immune response.

Research is underway to create more accurate immune system tests for Lyme disease. One blood test, for example, can directly identify the Osp A protein itself (not just the antibodies to it), which would provide direct evidence of the Lyme spirochete. However, widespread use of this test is probably years away.

Accuracy of the Tests. It should be noted that these tests are very expensive and none are completely accurate in either identifying Lyme or ruling it out. They should never be used to make a primary diagnosis of Lyme disease in patients who do not have obvious symptoms of the disease.

Either false positive and false negative results are common with these tests.

False positive results occur when the test suggests the presence of the disease, but the person does not actually have an active infection. This may occur in different ways:

• The antibodies to the infectious agent triggering the antibodies are not the Lyme spirochetes. Other organisms that can trigger such antibodies include syphilis and relapsing fever. Dental infections may trigger a false positive response. (The recently approved ELISA test, PreVue, is highly specific and may significantly reduce this problem.)
• The patient may have been infected with Lyme disease previously and harbor antibodies to the disease.
• The patient may have received the Lyme disease vaccine, which will trigger a positive response in ELISA.

False negative results are those that miss the actual presence of the disease. These results are also common. (If the results are negative but Lyme disease is highly suspected, the physician will probably prescribe antibiotics anyway.) False negative results occur for a number of reasons:

• The test is taken too early in the course of Lyme disease. In such cases, the antibodies that fight the spirochete might not have reached a level that is high enough to be detected. (Only about 20% to 30% of patients can be identified using immune system tests in the first two to four weeks. By week four, up to 80% of patients will have detectable antibodies.)
• The patient has taken certain medications, such as steroids or certain anti-cancer drugs, which reduce the immune systems ability to produce antibodies, including those in response to Lyme disease.
• There are too many infection-fighting antibodies attached to the bacteria. In this case, there are not enough loose antibodies in the blood sample to trigger a response.
• The laboratory itself has set its sensitivity point too high. Some laboratories establish a standard of very antibody levels before the test results will trigger a finding of Lyme disease. (They do this to avoid too many false-positive responses.) In so doing, however, their tests may miss the disease in patients with lower antibody levels. (A related diagnostic problem in such cases concerns the possibility of missing persistent Lyme disease after antibiotic treatments, when antibody levels would be low.)

In summary, a negative blood test does not rule out a diagnosis of Lyme disease, particularly if symptoms strongly suggest its presence. Conversely, a weakly positive blood test does not prove that Lyme disease is causing the symptoms. A second blood test, taken several weeks later, may help.

Polymerase Chain Reaction (PCR) Test

The polymerase chain reaction (PCR) test is a sophisticated approach that makes multiple copies of a specific region of unknown but suspicious DNA found in urine or blood. Once it produces enough DNA, it can be tested to see if matches the DNA of B. burgdorferi. The test allows detection much more quickly than a culture. This test may be particularly useful in detecting Lyme disease in people who still have persistent symptoms after being treated with antibiotics. It has limitations, however. For one, it requires strict controls to be accurate, and at this time can be performed only in a few laboratories in the country. It can also fail to identify the Lyme spirochete, since organisms do not always show up in bodily fluids at the time the test is being taken. At this point, it is reserved for certain patients with specific diagnostic problems.

Tests for Neurologic Involvement

Analysis of Spinal Fluid. In patients who have neurologic symptoms, a lumbar puncture (a spinal tap) may be used to test for the bacteria in spinal fluid and may be useful for an early diagnosis of Lyme disease. PCR testing is more accurate than attempts to culture the spirochete in the fluid.

Imaging Tests. An advanced imaging test called single photon emission computed tomography (SPECT) is showing promise for revealing patterns in the brain that are indicative of central nervous system involvement in Lyme disease. Other imaging tests, including computed tomography (CT) scans and magnetic resonance imaging (MRI) tests, are not useful.