Rickettsia ricketti and Rickettsia-like organisms in Maryland

描述（由申请人提供）：在过去十年中，美国报告的蜱媒感染数量有所增加。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（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，立克次体斑点热组（SFG）的18个公认成员之一，也是NIAID C类优先病原体。马里兰州在1970-2006年报告了1,530例RMSF病例，在过去五年中平均每年79例。这些病例中的大多数报告来自切萨皮克湾海岸沿着的县，那里的人口密度最高。该地区还支持美国东部三种最常见的人类叮咬蜱的大量种群，即变异革蜱、美洲钝眼蜱和肩胛硬蜱。虽然D. variabilis被认为是R. rickettsii，A. americanum被认为是第二媒介。此外，血红扇头蜱也发生在整个地区与家犬。虽然不是一个经常咬人的人，这个物种最近被确定为在亚利桑那州的一组病例的载体。尽管初步资料表明，这些蜱有3-4%的感染率SFG立克次体，R。尚未从这些载体中鉴定出立克次氏体。从这些蜱虫中分离出的立克次氏体，要么被认为对人类无致病性，要么身份不明。通常用于确认RMSF等感染的血清学检测无法区分SFG立克次体成员和导致临床疾病的特定病原体，因此变得相对未知。因此，证明R.立克次体不在蜱虫种群中传播，并确定立克次体和立克次体样生物体可能导致人类临床疾病。 这个R21应用程序的探索性意图将使我们能够证明R。立克次氏体不在地方病媒种群中传播，这将使我们能够对可能导致人类疾病的生物体进行初步鉴定。然后，这些数据将用于对病原体暴露、改进诊断、病原体生态和对人类的致病性进行更全面的调查。这是非常重要的，因为许多可能属于NIAID分类的潜在病原体尚未确定。此外，在过去几年中，一些实验室报告了来自硬蜱的立克次体样生物。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.证明立克次氏体在马里兰州东部（被认为是落基山斑疹热的地方性地区）的经典革蜱周期中不流行。 2.识别和表征感染马里兰州咬人蜱的立克次体和立克次体样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.