Rickettsia ricketti and Rickettsia-like organisms in Maryland

描述(由申请人提供)：在过去的十年中，美国报告的扁虱传播感染人数有所增加。其中最具威胁性的是立克次体感染。最著名的人类立克次体感染是落基山斑点热病(RMSF)，即使有现代医疗护理，这种疾病的死亡率也保持在3%-10%。RMSF的病原体是立克次体立克次体，它是立克次体斑点热群(SFG)的18个公认成员之一，是NIAID C类优先病原体。1970年至2006年，马里兰州报告了1530例RMSF病例，在过去五年中，平均每年有79例。其中大多数病例报告来自切萨皮克湾沿岸的县，那里的人口密度最高。这一地区还支持美国东部三种最常见的叮咬人的扁虱的大量种群，这三种扁虱是变种革螨、美洲Amblyomma americanum和肩部硬蜱。虽然变盘丝虫被认为是立克次体的主要媒介，美洲锥体却被认为是次要媒介。此外，血缘裂头吸虫在该地区也与家犬有关。尽管不是经常咬人，但这种物种最近被确认为亚利桑那州一系列病例的媒介。尽管初步信息显示这些硬蜱对SFG立克次体的感染率为3-4%，但尚未从这些媒介中鉴定出立克次体。从这些硬体中从分子中提取的立克次体是被认为对人类无致病性或身份不明的物种。通常用于确认感染的血清学测试，如RMSF，没有区分SFG立克次体成员和导致临床疾病的特定病原体，因此成为相对未知的。因此，证明立克次体没有在壁虱种群中传播，并确定哪些立克次体和类似立克次体的生物体可能导致人类临床疾病，这对公共卫生是不可或缺的。 这一R21应用的探索意图将使我们能够证明立克次杆菌不在地方性媒介种群中传播的假设，并将另外使我们能够获得可能导致人类疾病的生物体的初步鉴定。然后，这些数据将被用于构建更全面的病原体暴露、改进的诊断、病原体生态和对人类群体致病性的调查。这一点极其重要，因为许多可能属于NIAID分类的潜在病原体尚未确定。此外，在过去的几年里，几个实验室报告了硬蜱的类似立克次体的生物。这些潜在的新病原体对人类健康的影响目前尚不清楚。 具体目标是： 1.证明里氏立克次体没有在马里兰州东部的经典德马森特循环中传播，该地区被认为是落基山斑点热病的地方病。 2.鉴定和鉴定感染马里兰州叮咬人蚤的立克次体和类似立克次体的NIAID优先病原体。

DESCRIPTION (provided by applicant): There has been an increase in the number of tick-borne infections reported in the United States over the last decade. Among the most threatening of these are the rickettsial infections. The best known of the human rickettsial infections is Rocky Mountain Spotted Fever (RMSF), a disease that maintains a fatality rate of 3-10%, even with modern medical care. The etiologic agent of RMSF is Rickettsia rickettsii, one of 18 recognized members of the Rickettsia Spotted Fever Group (SFG) and a NIAID Category C Priority Pathogen. Maryland reported 1,530 cases of RMSF from 1970-2006 with an average of 79 cases during each of the last five years. The majority of these cases were reported from the counties along the shore of the Chesapeake Bay, where human densities are highest. This region also supports large populations of the three most common human-biting ticks in the eastern United States, Dermacentor variabilis, Amblyomma americanum and Ixodes scapularis. Although D. variabilis is considered the primary vector of R. rickettsii, A. americanum has been incriminated as a secondary vector. Additionally, Rhipicephalus sanguineus also occurs throughout the region in association with domestic dogs. Although not a frequent human-biter, this species was recently identified as the vector for a cluster of cases in Arizona. Despite preliminary information illustrating that these ticks have a 3-4% infection rate for SFG Rickettsia, R. rickettsii has NOT been identified from these vectors. The Rickettsia that have been molecularly recovered from these ticks are species that are either considered to be non-pathogenic in humans, or of unknown identity. The serologic tests commonly used to confirm infections such as RMSF do not differentiate between members of the SFG rickettsiae and the specific pathogens causing clinical disease then become relative unknowns. It is therefore integral to public health to prove that R. rickettsii is not circulating in tick populations, and to identify what Rickettsia and Rickettsia-like organisms may be responsible for human clinical disease. The exploratory intent of this R21 application will allow us to prove the hypothesis that R. rickettsii is NOT circulating in endemic vector populations and will additionally allow us to acquire the preliminary identifications of organisms that may be responsible for human disease. This data will then be used to construct more comprehensive investigations of pathogen exposure, improved diagnostics, pathogen ecology and pathogenicity to human populations. This is extremely important as many potential pathogens that may fall under NIAID categorization have yet to be identified. Additionally, in the last few years, several laboratories have reported Rickettsia-like organisms from Ixodes ticks. The impact of these potential new pathogens to human health is currently unknown. Specific aims are to: 1. Demonstrate that Rickettsia rickettsii is not circulating in the classic Dermacentor cycle in eastern Maryland, a region considered endemic for Rocky Mountain Spotted Fever. 2. Identify and characterize Rickettsia and Rickettsia-like NIAID Priority Pathogens infecting man-biting ticks of Maryland.