This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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. Spirochetal persistence post-treatment is evident, but the recovery of intact organisms has been infrequent. Further, the infectious capacity of persistent organisms remains indeterminate. This study examines the question of antibiotic efficacy in two controlled experiments with nonhuman primates. Macaques were infected by needle inoculation of B. burgdorferi. At four to 6 months post-inoculation, a portion of the animals received aggressive antibiotic therapy regimens. Multiple methods were employed for the detection of residual organisms, including the placement and feeding of lab-reared ticks on monkeys for xenodiagnosis. The antibody responses to the Borrelia-specific C6 diagnostic peptides were measured longitudinally to include before, during, and after antibiotic treatment. Antibody responses to C6 declined in all antibiotic-treated animals but remained elevated in controls. Intact spirochetes were recovered by xenodiagnosis from 2 of 3 treated monkeys. Active spirochetal transcription was also frequently detected in the tissues of treated animals. These results demonstrate an ability of B. burgdorferi spirochetes to withstand antibiotic treatment, administered post-dissemination, in an incidental host?the nonhuman primate. Importantly, we have not discerned whether these organisms remain infectious and continue to cause objective signs of disease.
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