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。尽管抗生素治疗在临床上对病程早期莱姆病患者的症状有效，但大量接受延迟治疗的患者报告持续症状。莱姆病患者抗生素治疗后持续症状的原因仍有很大争议。理论包括持续感染，诱导自身免疫反应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有机体的清除，伯氏疏螺旋体。尽管科学界普遍认为细菌在抗生素治疗后被完全清除，但最近对老鼠和狗的研究表明，细菌在治疗后可以持续存在，并且可以通过PCR或异种诊断（将未感染的硬蜱喂食治疗动物）检测到。我们最近在人类身上进行了异种诊断的试点试验。我们发现异种诊断是安全的，在一些接受抗生素治疗的患者中可以检测到伯氏疏螺旋体。在这里，我们建议进行II期研究，以确定通过异种诊断检测细菌是否与感染伯氏疏螺旋体后患者的延长症状相关。在具体目标#1中，我们将招募在完成抗生素治疗后出现特征性迁移性红斑（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表36第2版（SF-36v2）和疲劳严重程度量表（FSS）的连续测试来确定。患者将在治疗后2-4个月和8-10个月再次进行异种诊断。回收的蜱虫将使用多种技术检测细菌的存在，包括培养、PCR、荧光显微镜和质谱。因为在Aim 1中只有少数受试者可能有持续症状，所以在Aim 2中我们将专门针对有持续症状的受试者。我们将招募持久的受试者

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.