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Lyme Disease in Humans

Justin D. Radolf
Klemen Strle
Jacob E. Lemieux
7 and
Franc Strle
Departments of Medicine, UConn Health, Farmington, CT 06030, USA
Departments of Pediatrics, UConn Health, Farmington, CT 06030, USA
Departments of Genetics and Genome Sciences, UConn Health, Farmington, CT 06030, USA
Departments of Molecular Biology and Biophysics, UConn Health, Farmington, CT 06030, USA
Departments of Immunology, UConn Health, Farmington, CT 06030, USA
Division of Infectious Diseases, Wadsworth Center, NY Department of Health, Albany, NY 12208, USA
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia
Author to whom correspondence should be addressed.
Curr. Issues Mol. Biol. 2021, 42(1), 333-384;
Submission received: 19 September 2020 / Revised: 15 October 2020 / Accepted: 12 November 2020 / Published: 11 December 2020


Lyme disease (Lyme borreliosis) is a tick-borne, zoonosis of adults and children caused by genospecies of the Borrelia burgdorferi sensu lato complex. The ailment, widespread throughout the Northern Hemisphere, continues to increase globally due to multiple environmental factors, coupled with increased incursion of humans into habitats that harbor the spirochete. B. burgdorferi sensu lato is transmitted by ticks from the Ixodes ricinus complex. In North America, B. burgdorferi causes nearly all infections; in Europe, B. afzelii and B. garinii are most associated with human disease. The spirochete's unusual fragmented genome encodes a plethora of differentially expressed outer surface lipoproteins that play a seminal role in the bacterium's ability to sustain itself within its enzootic cycle and cause disease when transmitted to its incidental human host. Tissue damage and symptomatology (i.e., clinical manifestations) result from the inflammatory response elicited by the bacterium and its constituents. The deposition of spirochetes into human dermal tissue generates a local inflammatory response that manifests as erythema migrans (EM), the hallmark skin lesion. If treated appropriately and early, the prognosis is excellent. However, in untreated patients, the disease may present with a wide range of clinical manifestations, most commonly involving the central nervous system, joints, or heart. A small percentage (~10%) of patients may go on to develop a poorly defined fibromyalgia-like illness, post-treatment Lyme disease (PTLD) unresponsive to prolonged antimicrobial therapy. Below we integrate current knowledge regarding the ecologic, epidemiologic, microbiologic, and immunologic facets of Lyme disease into a conceptual framework that sheds light on the disorder that healthcare providers encounter.

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MDPI and ACS Style

Radolf, J.D.; Strle, K.; Lemieux, J.E.; Strle, F. Lyme Disease in Humans. Curr. Issues Mol. Biol. 2021, 42, 333-384.

AMA Style

Radolf JD, Strle K, Lemieux JE, Strle F. Lyme Disease in Humans. Current Issues in Molecular Biology. 2021; 42(1):333-384.

Chicago/Turabian Style

Radolf, Justin D., Klemen Strle, Jacob E. Lemieux, and Franc Strle. 2021. "Lyme Disease in Humans" Current Issues in Molecular Biology 42, no. 1: 333-384.

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