Xenodiagnosis to detect Borrelia burgdorferi infection: a first-in-human study.

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Abstract

Animal studies suggest that Borrelia burgdorferi, the agent of Lyme disease, may persist after antibiotic therapy and can be detected by various means including xenodiagnosis using the natural tick vector (Ixodes scapularis). No convincing evidence exists for the persistence of viable spirochetes after recommended courses of antibiotic therapy in humans. We determined the safety of using I. scapularis larvae for the xenodiagnosis of B. burgdorferi infection in humans.

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Most cited references 20

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A critical appraisal of "chronic Lyme disease".

Henry Feder, Barbara Johnson, Susan O’Connell … (2007)

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Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection

Monica E. Embers, Stephen W. Barthold, Juan T. Borda … (2012)

The persistence of symptoms in Lyme disease patients following antibiotic therapy, and their causes, continue to be a matter of intense controversy. The studies presented here explore antibiotic efficacy using nonhuman primates. Rhesus macaques were infected with B. burgdorferi and a portion received aggressive antibiotic therapy 4–6 months later. Multiple methods were utilized for detection of residual organisms, including the feeding of lab-reared ticks on monkeys (xenodiagnosis), culture, immunofluorescence and PCR. Antibody responses to the B. burgdorferi-specific C6 diagnostic peptide were measured longitudinally and declined in all treated animals. B. burgdorferi antigen, DNA and RNA were detected in the tissues of treated animals. Finally, small numbers of intact spirochetes were recovered by xenodiagnosis from treated monkeys. These results demonstrate that B. burgdorferi can withstand antibiotic treatment, administered post-dissemination, in a primate host. Though B. burgdorferi is not known to possess resistance mechanisms and is susceptible to the standard antibiotics (doxycycline, ceftriaxone) in vitro, it appears to become tolerant post-dissemination in the primate host. This finding raises important questions about the pathogenicity of antibiotic-tolerant persisters and whether or not they can contribute to symptoms post-treatment.

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Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy.

Linda Bockenstedt, David G. González, Ann Haberman … (2012)

An enigmatic feature of Lyme disease is the slow resolution of musculoskeletal symptoms that can continue after treatment, with some patients developing an inflammatory arthritis that becomes refractory to antibiotic therapy. Using intravital microscopy and the mouse model of Lyme borreliosis, we observed that Borrelia burgdorferi antigens, but not infectious spirochetes, can remain adjacent to cartilage for extended periods after antibiotic treatment. B. burgdorferi was not recovered by culture or xenodiagnosis with ticks after antibiotic treatment of WT mice and all but one of the immunodeficient mice with heightened pathogen burden due to impaired TLR responsiveness. Amorphous GFP+ deposits were visualized by intravital microscopy in the entheses of antibiotic-treated mice infected with GFP-expressing spirochetes and on the ear cartilage surface in sites where immunofluorescence staining detected spirochete antigens. Naive mice were not infected by tissue transplants from antibiotic-treated mice even though transplants contained spirochete DNA. Tissue homogenates from antibiotic-treated mice induced IgG reactive with B. burgdorferi antigens after immunization of naive mice and stimulated TNF-α production from macrophages in vitro. This is the first direct demonstration that inflammatory B. burgdorferi components can persist near cartilaginous tissue after treatment for Lyme disease. We propose that these deposits could contribute to the development of antibiotic-refractory Lyme arthritis.

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Author and article information

Journal

Journal ID (iso-abbrev): Clin. Infect. Dis.

Title: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

ISSN (Electronic): 1537-6591

ISSN (Print): 1058-4838

Publication date (Electronic): Apr 2014

Volume: 58

Issue: 7

Affiliations

[1 ] Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.

Article

Publisher Item ID: cit939

DOI: 10.1093/cid/cit939

PubMed ID: 24523212

SO-VID: 65b41aed-c66b-4b7a-859e-17683b7f0efa

History

Keywords: Borrelia burgdorferi,Ixodes scapularis,Lyme disease,human,xenodiagnosis

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Keywords: Borrelia burgdorferi, Ixodes scapularis, Lyme disease, human, xenodiagnosis

Xenodiagnosis to detect Borrelia burgdorferi infection: a first-in-human study.

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Abstract

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Ticks and tick-borne pathogens

Most cited references 20

A critical appraisal of "chronic Lyme disease".

Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection

Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy.

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