XENODIAGNOSIS FOR EVALUATION OF ANTIMICROBIAL EFFICACY IN LYME DISEASE

用于评估莱姆病抗菌功效的异种诊断

• 批准号: 8358135
• 负责人: MONICA E EMBERS
• 金额: $ 3.72万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358135
• 关键词: Aftercare; Animal Model; Animals; Antibiotic Therapy; Antibiotics; Antibody Formation; Biopsy; Blood; Borrelia; Borrelia Infections; Borrelia burgdorferi; Canis familiaris; Chronic; Detection; Diagnostic; Disease; Effectiveness; Evaluation; Funding; Genetic Transcription; Grant; Infection; Lyme Disease; Macaca; Measures; Methods; Monkeys; Mus; National Center for Research Resources; Needles; Order Spirochaetales; Organism; Patients; Peptides; Primates; Principal Investigator; Recovery; Regimen; Research; Research Infrastructure; Residual state; Resources; Skin; Source; Symptoms; Ticks; Tissues; United States National Institutes of Health; Xenodiagnosis; antimicrobial; cost; experience; feeding; nonhuman primate; research study

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 hostthe nonhuman primate. Importantly, we have not discerned whether these organisms remain infectious and continue to cause objective signs of disease.

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