Searching for Persistence in Lyme Disease

描述(申请人提供)：莱姆病是美国最常见的媒介传播疾病。虽然抗生素治疗在临床上对病程早期的患者有效地治疗莱姆病的症状，但接受延迟治疗的患者中有相当数量的人报告了持续的症状。莱姆病抗生素治疗后患者持续症状的原因仍然存在很大争议。理论包括持续感染、诱导自身免疫反应和不可愈合的组织损伤。目前还没有可用的检测来记录伯氏疏螺旋体的感染解决和清除情况。尽管科学界普遍认为，细菌在抗生素治疗后完全清除，但最近对小鼠和狗的研究表明，细菌在治疗后仍然存在，并可通过聚合酶链式反应或异种诊断(以未感染的硬体动物为食)检测到。我们最近在人类身上进行了一项异种诊断的试点试验。我们发现异种诊断是安全的，可以在抗生素治疗后的一些患者中检测到伯氏杆菌。在这里，我们建议进行第二阶段研究，以确定通过异种诊断检测到细菌是否与患者感染伯氏杆菌后的长期症状相关。在具体目标#1中，我们将招募在抗生素治疗完成后出现特征性移行性红斑(EM)皮疹的受试者。受试者功能能力随时间的变化将通过使用简明36版本2(SF-36v2)和疲劳严重程度量表(FSS)进行系列测试来确定。患者在治疗后2-4个月进行异种诊断，并在治疗后8-10个月再次进行异种诊断。回收的扁虱将使用多种技术进行细菌检测，包括培养、聚合酶链式反应、荧光显微镜和质谱仪。由于目标1中只有一小部分受试者可能有持续性症状，因此在目标2中，我们将专门针对具有持续性症状的受试者。我们将以持之以恒的方式招收科目 与莱姆病相关的症状在最初治疗后超过6个月。功能状态将通过SF-36v2和FSS进行测量，并将按照目标1执行异种诊断。从目标1开始的8-10个月时间点对无症状患者的异种诊断结果将作为目标2中受试者的对照组。这些研究有可能解决有争议的问题，即细菌持久性是否与接受莱姆病治疗的患者的症状延长有关。确定持续性感染和持续性症状之间的联系很重要，因为它可能直接影响用于治疗慢性莱姆病的策略。

DESCRIPTION (provided by applicant): Lyme disease is the most common vector borne disease in the United States. Although antibiotic therapy is clinically effective in treating the symptoms of Lyme disease for patients early in the course of disease, a significant number of patients who receive delayed therapy report persistent symptoms. The cause of persistent symptoms in patients after antibiotic therapy for Lyme disease remains highly controversial. Theories include persistence of infection, induction of autoimmune responses and non-healing tissue damage. There is currently no available test to document resolution of infection and clearance of the organism, Borrelia burgdorferi. Although the prevailing belief in the scientific community has been that bacteria are completely cleared after antibiotic therapy, recent studies in mice and dogs have shown that bacteria can persist after treatment and are detectable by PCR or xenodiagnosis (the feeding of uninfected Ixodes ticks on the treated animals). We have recently performed a pilot trial of xenodiagnosis in humans. We found that xenodiagnosis is safe and can detect B. burgdorferi in some patients after antibiotic therapy. Here we propose the Phase II study to determine whether a detection of bacteria by xenodiagnosis correlates with prolonged symptoms in patients after infection with B. burgdorferi. In specific aim #1, we will enroll subjects who have the characteristic erythema migrans (EM) rash after completion of antibiotic therapy. Changes in the subjects functional capacity over time will be determined by serial testing using the Short Form 36 version 2 (SF-36v2) and the Fatigue Severity Scale (FSS). Patients will have xenodiagnosis performed at 2-4 months after treatment and again at 8-10 months after treatment. Recovered ticks will be tested for the presence of bacteria using multiple technologies including culture, PCR, fluorescent microscopy and mass spectroscopy. Because only a minority of subjects in Aim 1 are likely to have persistent symptoms, in Aim 2 we will specifically target subjects with persistent symptoms. We will enroll subjects with persistent symptoms associated with Lyme greater than 6 months after their original treatment. Functional status will be measured by SF-36v2 and FSS and xenodiagnosis will be performed as in Aim 1. Results of xenodiagnosis in asymptomatic patients at the 8-10 month time point from Aim 1 will serve as the comparison group for the subjects in Aim 2. These studies have the potential to address the controversial issue of whether bacterial persistence is linked to prolonged symptoms in patients who have been treated for Lyme disease. Identifying the link between persistent infections and persistent symptoms is important because it may directly impact strategies that are used to treat chronic Lyme disease.