Searching for Persistence in Lyme Disease

描述（由申请人提供）：莱姆病是美国最常见的媒介传播疾病。虽然抗生素治疗在治疗莱姆病早期患者的症状方面具有临床有效性，但大量接受延迟治疗的患者报告持续症状。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。理论包括感染的持续性、自身免疫反应的诱导和不愈合的组织损伤。目前没有可用的测试来记录感染的解决和生物体伯氏疏螺旋体的清除。尽管科学界普遍认为细菌在抗生素治疗后会被完全清除，但最近对小鼠和狗的研究表明，细菌在治疗后可以持续存在，并且可以通过PCR或异种诊断（在治疗的动物上喂食未感染的硬蜱）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，可以检测到B。部分患者在抗生素治疗后出现伯氏螺旋体感染。 在这里，我们提出了第二阶段的研究，以确定是否检测到细菌的异种诊断与长期症状的患者感染后，与B。burgdorferi。在具体目标1中，我们将入组完成抗生素治疗后出现特征性游走性红斑（EM）皮疹的受试者。将使用简表36第2版（SF-36 v2）和疲劳严重程度量表（FSS）通过系列测试确定受试者功能能力随时间的变化。患者将在治疗后2-4个月和治疗后8-10个月再次进行异种诊断。将使用多种技术（包括培养、PCR、荧光显微镜检查和质谱）检测感染的蜱虫是否存在细菌。由于目标1中只有少数受试者可能有持续症状，因此在目标2中，我们将专门针对有持续症状的受试者。我们将招募持续存在 与莱姆病相关的症状超过6个月后，他们的原始治疗。将通过SF-36 v2和FSS测量功能状态，并将按照目的1进行异种诊断。目标1后8-10个月时间点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长期症状有关。确定持续感染和持续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.