The Clinical Relevance of Studies on Borrelia burgdorferi Persisters.

In North America, Lyme disease is principally caused by Borrelia burgdorferi sensu stricto, hereafter referred to as “B. burgdorferi.” It is acquired by the bite of an infected Ixodes tick. The most common clinical manifestation is a skin lesion, referred to as “erythema migrans,” which is due to cutaneous infection with B. burgdorferi. Other objective manifestations may involve the nervous system, heart, or joints. Treatment with antibiotics typically resolves the objective clinical manifestation. Accompanying subjective symptoms, such as fatigue and joint or muscle pain, often persist for many weeks. Patients with such subjective symptoms lasting 6 months or more are often referred to as having “post-treatment Lyme disease symptoms.” Such prolonged symptoms occur in approximately 10% of US patients treated for erythema migrans. One theory advanced to explain the long-term persistence of symptoms is failure of the initial course of antibiotic therapy to eradicate fully B. burgdorferi cells. Why or how residual bacterial cells might result in persistence of nonspecific symptoms, in the absence of a localized inflammatory lesion at the site of the residual infection, is not known. However, the possibility that post-treatment symptoms are due to persistent B. burgdorferi infection has been explored in several placebo-controlled, antibiotic retreatment studies. The results of 5 such clinical trials failed to provide evidence of convincing clinical benefit or that the risk/benefit ratio favored this therapeutic approach. Because considerable improvement (up to 38%) was observed among placebo controls, this suggests that persistent symptoms are often reversible. Some of these studies also attempted to establish evidence of persistence of