A serologic assay to measure successful Lyme borreliosis antibiotic therapy

测量莱姆疏螺旋体病抗生素治疗是否成功的血清学检测

• 批准号: 8715103
• 负责人: Michel Ledizet
• 金额: $ 88.34万
• 依托单位: L2 DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8715103
• 关键词: Aftercare; Animals; Antibiotic Therapy; Antibiotics; Antibodies; Antibody Formation; Antigens; Biological Assay; Borrelia burgdorferi; Case Study; Centers for Disease Control and Prevention (U.S.); Clinical; Complement; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Effectiveness; Enzyme-Linked Immunosorbent Assay; Evaluation; Exposure to; Failure; Goals; Gold; Heart; Human; Immunoblotting; Immunoglobulin G; In Vitro; Incidence; Individual; Infection; Ixodes; Joints; Kinetics; Laboratories; Lyme Disease; Maintenance; Measurable; Measurement; Measures; Medical; Monitor; Mus; Nervous system structure; Newly Diagnosed; Order Spirochaetales; Patients; Pattern; Peptides; Phase; Physicians; Population; Preventive; Prospective Studies; Proteins; Public Health; Resolution; Retrospective Studies; Sampling; Serologic tests; Serological; Serum; Signs and Symptoms; Skin; Small Business Innovation Research Grant; Staging; Symptoms; Syndrome; Testing; Ticks; Time; Tissues; United States; Vector-transmitted infectious disease; base; improved; mouse model; novel; novel diagnostics; prevent; public health relevance; research study; response; tick borne spirochete; tool

DESCRIPTION (provided by applicant): Lyme disease (LD) caused by the Ixodes tick-borne spirochete Borrelia burgdorferi (Bb), is the most common vector-borne disease in the United States. Despite public health preventive measures, the annual confirmed case incidence has risen to over 30,000, the vast majority of which occur in the Northeast. Disseminated infection causes disease in the skin, heart, joints and nervous system and can be difficult to treat. Antibiotics achieve clinical cure in the majority of people when administered in early stages of infection. Unexplained symptoms can linger in up to 25% of patients, however, which may or may not be due to persistence of active infection. Current serologic tests that are the mainstay of LD diagnostics cannot be used to assess response to therapy and cannot distinguish previous exposure to Bb from active infection. Patients thus often receive unnecessary and potentially dangerous long-term antibiotic treatments or other unconventional and unproven treatments. This application seeks to improve the current situation by developing a new diagnostic serologic assay based on a novel panel of Bb antigens to which antibody levels decline rapidly after successful elimination of infection by antibiotics. We have shown using a mouse model of Lyme borreliosis that successful elimination of infection with antibiotic treatment correlates with declining responses to panel antigens, and that failure of antibiotics to completely eliminate infection is associated with maintenance of elevated responses to panel antigens. We also demonstrated in a retrospective study of banked human C6 peptide positive Lyme sera that most human samples react with 4 or more panel antigens. We will conduct a prospective study of a large number of newly diagnosed LD patients undergoing antibiotic therapy. We will monitor the decline of antibody levels to individual antigens and select from our panel a group of antigens for which this decline best correlates with resolution of symptoms after antibiotic treatment. We will also determine if patients with persistent symptoms at 3 months after treatment maintain high levels of antibodies to panel antigens up to one year later. As a strategy that complements current serologic tests, this assay will provide additional tools for clinicians to objectively base decisions on additional courses of antibiotics for symptoms that may be due to incompletely treated or new Bb infections.

描述（由申请人提供）：莱姆病 (LD) 由蜱传螺旋体伯氏疏螺旋体 (Bb) 引起，是美国最常见的媒介传播疾病。尽管采取了公共卫生预防措施，每年确诊病例数仍升至3万多例，其中绝大多数发生在东北地区。播散性感染会导致皮肤、心脏、关节和神经系统疾病，并且很难治疗。在感染的早期阶段使用抗生素可以使大多数人获得临床治愈。然而，高达 25% 的患者可能会出现无法解释的症状，这可能是或可能不是由于活动性感染的持续存在所致。目前血清学检测是 LD 诊断的主要手段，不能用于评估治疗反应，也不能区分既往 Bb 暴露与活动性感染。因此，患者经常接受不必要且有潜在危险的长期抗生素治疗或其他非常规且未经证实的治疗。本申请旨在通过开发一种基于一组新型 Bb 抗原的新诊断血清学测定来改善当前状况，在成功消除抗生素感染后，该抗原的抗体水平会迅速下降。我们使用莱姆疏螺旋体病小鼠模型证明，通过抗生素治疗成功消除感染与对组抗原的反应下降相关，而抗生素未能完全消除感染与维持对组抗原的反应升高有关。我们还在对储存的人类 C6 肽阳性莱姆病血清的回顾性研究中证明，大多数人类样本与 4 种或更多组抗原发生反应。我们将对大量新诊断的LD患者进行抗生素治疗进行前瞻性研究。我们将监测针对个体抗原的抗体水平的下降，并从我们的组中选择一组抗原，其中这种下降与抗生素治疗后症状的缓解最相关。我们还将确定治疗后 3 个月内症状持续存在的患者是否在一年后仍能保持高水平的针对特定抗原的抗体。作为补充当前血清学检测的策略，该测定将为临床医生提供额外的工具，以便客观地根据针对以下症状的额外抗生素疗程做出决定： 可能是由于治疗不彻底或新的 Bb 感染所致。