A serologic assay to measure successful Lyme borreliosis antibiotic therapy

描述(申请人提供)：莱姆病(LD)由硬蜱传播的伯氏疏螺旋体(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，但每年确诊病例已上升至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，可能很难治疗。在感染的早期阶段给予抗生素，大多数人都能达到临床治愈。然而，高达25%的患者可能会出现不明原因的症状，这可能是也可能不是由于持续的活动性感染。目前的血清学试验是LD诊断的主要手段，不能用来评估对治疗的反应，也不能区分既往暴露于BB和活动性感染。因此，患者经常接受不必要的和潜在危险的长期抗生素治疗或其他非常规和未经证实的治疗。这项应用旨在通过开发一种新的诊断血清学方法来改善目前的情况，该方法基于一组新的BB抗原，在成功地消除抗生素感染后，抗体水平迅速下降。我们使用莱姆疏螺旋体病的小鼠模型表明，用抗生素治疗成功消除感染与对面板抗原的反应下降有关，而抗生素未能完全消除感染与维持对面板抗原的升高反应有关。我们还在一项对储存的人C6肽阳性莱姆血清的回顾研究中证明，大多数人样本与4个或更多组抗原发生反应。我们将对大量新诊断的接受抗生素治疗的LD患者进行前瞻性研究。我们将监测针对单个抗原的抗体水平的下降，并从我们的小组中选择一组抗原，这种下降与抗生素治疗后症状的缓解最相关。我们还将确定在治疗后3个月出现持续症状的患者是否在一年后保持高水平的群体抗原抗体。作为对目前血清学测试的补充，这项检测将为临床医生提供额外的工具，以客观地根据针对以下症状的额外疗程的抗生素做出决定 可能是由于治疗不彻底或新的BB感染。

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.