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: 8173049
• 负责人: MONICA E EMBERS
• 金额: $ 3.94万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173049
• 关键词: Aftercare; Animal Model; Animals; Antibiotic Therapy; Antibiotics; Antibody Formation; Biopsy; Blood; Borrelia; Borrelia Infections; Borrelia burgdorferi; Canis familiaris; Chronic; Computer Retrieval of Information on Scientific Projects Database; Diagnostic; Doxycycline; Effectiveness; Evaluation; Funding; Genetic; Grant; Individual; Infection; Institution; Lyme Disease; Macaca; Measures; Monkeys; Mus; Needles; Oral; Order Spirochaetales; Organism; OspA protein; OspC protein; Patients; Peptides; Phenotype; Primates; Recovery; Regimen; Research; Research Personnel; Resources; Skin; Source; Symptoms; Ticks; Time; United States National Institutes of Health; Xenodiagnosis; antimicrobial; experience; feeding; nonhuman primate; research study; response

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 一部分患者在抗生素治疗后和慢性感染中继续出现莱姆病症状，但很少能从血液或皮肤活检中检测到这种生物体。 抗生素治疗疏螺旋体病的有效性已经在鼠和犬动物模型中进行了探索。治疗后螺旋体的持续存在是明显的，但这些生物体的感染能力仍然不确定。 本研究在非人灵长类动物的对照实验中探讨了抗生素疗效的问题。5只猕猴经针接种B. burgdorferi。 在感染后四个月，五只动物中的三只接受口服强力霉素28天的方案。 在感染后7个月和10个月，将实验室饲养的蜱虫置于所有猴身上，并喂食至饱食，以进行异种诊断。纵向测量对疏螺旋体特异性C6和Ct诊断肽VlsE、OspC和OspA的抗体应答，包括在抗生素治疗之前、期间和之后。 通过异种诊断从3只治疗的猴中的1只中回收完整的螺旋体。VlsE及其衍生肽（C6和Ct）的抗体反应下降，在所有驱虫治疗的动物，但在对照组中仍然升高。 然而，对OspA和OspC的反应在个体之间随时间变化，与抗生素治疗无关。在灵长类动物中，从驱虫治疗的动物中回收完整的螺旋体可以作为治疗可能无法清除生物体的原则的证据。螺旋体的遗传组成、表型和相关的感染性尚未确定，感染性的程度（3只动物中的1只确定）也尚未确定。