XENODIAGNOSIS FOR EVALUATION OF ANTIMICROBIAL EFFICACY IN LYME DISEASE

Tulane University Of Louisiana, New Orleans LA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A proportion of patients continue to experience symptoms of Lyme disease after antibiotic treatment and in chronic infection, yet the organism can rarely be detected from blood or skin biopsy. The effectiveness of antibiotic treatment for borreliosis has been explored in murine and canine animal models. Persistence of spirochetes post-treatment is evident, but the infectious capacity of these organisms remains indeterminate. This study examines the question of antibiotic efficacy in a controlled experiment with nonhuman primates. Five macaques were infected by needle inoculation of B. burgdorferi. At four months post-infection, three of five animals received a regimen of oral doxycycline for 28 days. At 7 and 10 months post-infection, lab-reared ticks were placed on all monkeys and fed to repletion for xenodiagnosis. The antibody responses to the Borrelia-specific C6 and Ct diagnostic peptides, VlsE, OspC and OspA were measured longitudinally to include before, during, and after antibiotic treatment. Intact spirochetes were recovered by xenodiagnosis from 1 of 3 treated monkeys. Antibody responses to VlsE and its derivative peptides (C6 and Ct) declined in all antibiotic-treated animals but remained elevated in controls. Responses to OspA and OspC, however, were variable over time among individuals, irrespective of antibiotic treatment. Recovery of intact spirochetes from an antibiotic-treated animal serves as proof of principle, in primates, that therapy may not clear organisms. The genetic composition, phenotype, and associated infectivity of the spirochetes are yet to be determined, as is the extent (1 of 3 animals definitive) of infectivity.