Chronic Lyme disease (CLD) remains a controversial illness. The controversy is based on a profound disagreement over the existence of persistent infection with the Lyme spirochete, Borrelia burgdorferi, and the ability of this persistent infection to cause chronic symptoms in patients who are untreated or undertreated for the spirochetal disease. Based on a review of the medical literature, we identified 56 studies confirming B. burgdorferi persistence. In this article, we summarize evidence from animal models and human studies that support persistent spirochetal infection as the cause of CLD. Specifically, direct and functional testing using culture, histology and xenodiagnosis has shown viable organisms following antibiotic therapy, and the potential role of cysts (L-forms) and biofilms in this process is examined. Future studies are required to investigate the mechanism of persistent infection in CLD.
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