Defining the ecology of tick-borne relapsing fever Borrelia turicatae in Austin, Texas.

项目摘要/摘要 该项目针对的是一种被忽视的全球疾病，这种疾病经常被误诊，但却导致严重的发病率和死亡率。在美国和墨西哥的干旱地区，斑点疏螺旋体是硬虱传播的复发热(TBRF)的主要物种，由软体硬蜱传播。历史上被认为是穷人的一种疾病，有证据表明，图里卡特氏菌正在德克萨斯州的大都市地区出现。仅在德克萨斯州奥斯汀，2017年人类感染斑疹杆菌的确认率就达到了40多年来的最高水平。这种涌现在奥斯汀市区引发了担忧，超过100万人可能面临风险。此外，公布的证据表明，这种疾病出现在圣安东尼奥、达拉斯和奥斯汀，这是美国最大的11个城市中的三个。不幸的是，对斑疹杆菌生态学的清楚了解是模糊的；主要是维持病原体的脊椎动物宿主。这一建议的假设是，斑疹杆菌在德克萨斯州奥斯汀城市地区的软蜱种群中传播，啮齿类动物的血清学检测将表明这些哺乳动物在维持自然界病原体方面的作用。建议的目标如下： 目的1：了解啮齿动物在TBRF地方性传播循环中的潜在作用。感染斑疹伤寒杆菌的扁虱是从啮齿类动物的巢中收集的；然而，野生啮齿动物作为这种疏螺旋体物种的储蓄者的作用尚不清楚。目标1的假设是，在德克萨斯州奥斯汀的公园里，斑疹杆菌的维持涉及到壁虱-啮齿动物的感染循环。这一目标的目的是使用高度特异的诊断抗原对收集的野生啮齿动物进行血清监测研究，并从病原体可能传播的八个公园收集扁虱。这些发现将提示螺旋体在动物中的繁殖，并为啮齿动物在维持滴虫中的作用提供证据。 目的2：评估奥斯汀地区斑疹伤寒杆菌分离株和居群的遗传变异水平。这个 有限数量的斑疹病毒分离株和稀少的采集斑疹病毒种群阻碍了对该病的生态学和流行病学的了解。因此，目标2的假设是，斑腿假单胞菌变种在自然界中循环，并在不同的斑纹夜蛾种群中保持。目标2的目的是(1)从野外采集的壁虱和野外捕获的啮齿动物中获得新的斑点滴虫分离株，并对病原体进行遗传分型；(2)收集不同的斑点滴虫种群，进行遗传变异分析。 了解这种疾病的自然历史将有助于更好地估计人类健康风险。在一个地区 在证据表明出现了斑疹杆菌的地方，该项目与NIAID更好地了解和预防疾病的使命不谋而合。这一结果将使未来的研究能够更好地评估人类健康风险，这些地区人口稠密，病原体被忽视。

Project Summary/Abstract This project addresses a neglected global disease that is often misdiagnosed yet causes severe morbidity and mortality. In arid regions of the U.S. and Mexico, Borrelia turicatae is the primary species of tick-borne relapsing fever (TBRF) and is transmitted by the soft tick Ornithodoros turicata. Historically considered a disease ofthe impoverished, evidence indicates that B. turicatae is emerging in metropolitan regions of Texas. Just inAustin, TX, the confirmation of B. turicatae in humans in 2017 was the highest in over 40 years. This emergence creates concerns in urban Austin, with more than one million people potentially at risk. Moreover, published evidence indicates the diseases emergence in San Antonio, Dallas, and Austin, three of the top 11 largest cities in the United States. Unfortunately, an clear understanding of the ecology of B. turicatae is vague; primarily the vertebrate hosts that maintain the pathogens. This proposal's hypothesis is that B. turicatae circulates in soft tick populations in urban areas of Austin, TX, and serological detection in rodents will indicate a role of these mammals in maintaining the pathogens in nature. The following Aims are proposed: Aim 1: Understand the potential role of rodents in the enzootic transmission cycle of TBRF. B. turicatae-infected ticks were collected from rodent nests; however, the role of wild rodents as reservoirs for this Borreliaspecies is unknown. The hypothesis of Aim 1 is that the maintenance of B. turicatae in Austin, TX parks involves a tick-rodent infectious cycle. The objective of this aim is to conduct serosurveillance studies with collected wild rodents using highly specific diagnostic antigens, and collect ticks from eight public parks where thepathogens likely circulate. These findings will suggest spirochete propagation in the animals and provide evidence for a role of rodents in maintaining B. turicatae. Aim 2: Assess the level of genetic variation of B. turicatae isolates and O. turicata populations in Austin. The limited number of B. turicatae isolates and a sparsity of collected O. turicata populations has hindered an understanding of the disease's ecology and epidemiology. Thus, the hypothesis of Aim 2 is that B. turicatae variants circulate in nature and are maintained in distinct populations of O. turicata. The objectives of Aim 2 are to (1) obtain novel isolates of B. turicatae from field collected ticks and wild caught rodents, and genetically type the pathogens; and (2) collect distinct populations of O. turicata for an analysis of genetic variance. Understanding the natural history of the disease will lead to better estimates of human health risk. In a region where evidence indicates the emergence of B. turicatae, this project coincides with NIAID's mission to betterunderstand and prevent disease. The results will enable future studies to better assess human health risks indensely populated regions where the pathogens are neglected.