http://www.lymeinfo.net/sensiblepursuit.htmlLYME DISEASE:
THE SENSIBLE PURSUIT OF ANSWERS *
Kenneth B. Liegner
Lyme Borreliosis and Related Disorders, Internal and Critical Care Medicine
8 Barnard Road, Armonk, New York 10504
Journal of Clinical Microbiology, Aug. 1993, p. 1961-1963
"Disease is very old and nothing about it has changed.
It is we who change as we learn to recognize what was formerly imperceptible."
-John Martin Charcot, De l'Expectation en Medecine
In 1989, Preac-Mursic et al. published a landmark article (30) documenting recovery by culture of living Borrelia burgdorferi from patients who had been previously treated with regimens believed to cure the disease. Included was one patient who had been treated with 10 days of intravenous ceftriaxone and from whose spinal fluid the organism was grown following treatment (30) This report was greeted ters, with suggestions the cultures must have been contaminated or that the report was otherwise erroneous. Since then there have been a number of corroborating reports confirming survival of B. burgdorferi in humans despite aggressive antibiotic treatment, including the use of the best available intravenous antibiotics (12, 22). These apparently anomalous observations, which reveal the deficiencies of the existing paradigm for Lyme disease, have been very hard for the medical community to reconcile, and they presage a revolution in our conceptualization of this disease (15). Such a shift will be necessary to deal effectively with the biologic realities of B. burgdorferi infection (1).
Emerging scientific research is beginning to clarify how it is possible for a bacterial infection to resist eradication by the powerful antibiotics employed against it. Montgomery et al. reported on the intracellular localization of B. burgdorferi within macrophages and the recovery of spirochetes in culture from these cells (29). Klempner, Georgilis, and coworkers demonstrated very convincingly that B. burgdorferi can adopt an intracellular location within fibroblasts and that the organism can be grown from such cells in vitro after treatment of the tissue cultures with ceftriaxone (9, 14). Ma et al. reported on the intracellular localization of B. burgdorferi within human umbilical vein endothelial cells in vitro (25). In a recent editorial, Mahmoud points out that infections due to intracellular pathogens are notoriously difficult to treat and cure (26). Interestingly, B. burgdorferi was not among the list of pathogens cited. The author suggested that the outcome of infections due to intracellular pathogens may be genetically regulated. Steere et al. have suggested that genetic regulation may be a feature of infections due to B.burgorferi; they found the illness more problematic in individuals bearing HLA-DR 2, 3, or 4 alleles (33). The key to the development of methods to combat such infections, Mahmoud argues, is increased understanding of adhesion to and internalization in host cells by these pathogens. Garcia Monco et al. (8), Coburn et al. (1a), and others are intensively studying this process in B. burgdorferi infection.
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