The detection of B. burgdorferi in human tissue or body fluids is the most reliable technique to prove the cause of an infectious disease. In Lyme borreliosis, cultivation of the organism has been difficult, probably because of slow growth of B. burgdorferi and its low density in body tissues.

An alternative method to establish proof of infection by B. burgdorferi relies on the detection of its antibody. In early Lyme borreliosis, the immunoglobulin (Ig) M form of the antibody response appears first, peaks 3 to 6 weeks after exposure, and then declines. The IgG then becomes detectable and is present in late-stage disease states. However, antibodies are frequently not detectable in the early stages of the disease by current techniques. In the late stages of the disease, they are almost always positive. Other spirochetal diseases, such as yaws, pinta, or syphilis, may give false-positive results, but can be excluded by clinical evaluation.

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