A serologic assay to measure successful Lyme borreliosis antibiotic therapy

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，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部。播散性感染会引起皮肤、心脏、关节和神经系统的疾病，并且很难治疗。如果在感染的早期阶段使用抗生素，大多数人都能获得临床治愈。然而，多达25%的患者可能会出现无法解释的症状，这可能是由于持续的活动性感染，也可能不是。目前的血清学检测是LD诊断的主要手段，不能用于评估对治疗的反应，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和有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。本申请旨在通过开发一种新的诊断血清学检测来改善现状，该检测基于一组新的Bb抗原，在抗生素成功消除感染后，抗体水平迅速下降。我们已经使用莱姆病小鼠模型表明，抗生素治疗成功消除感染与对小组抗原的反应下降有关，抗生素不能完全消除感染与维持对小组抗原的反应升高有关。我们还在对储存的人C6肽阳性莱姆病血清的回顾性研究中证明，大多数人样本与4种或更多的面板抗原反应。我们将对大量接受抗生素治疗的新诊断的LD患者进行前瞻性研究。我们将监测单个抗原抗体水平的下降，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仍保持高水平的抗体。作为现有血清学试验的补充，该试验将为临床医生提供额外的工具，以客观地决定针对以下症状的额外抗生素疗程

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.