Rickettsia ricketti and Rickettsia-like organisms in Maryland

描述（由申请人提供）：在过去十年中，美国报告的蜱传感染数量有所增加。其中最具威胁性的是立克次体感染。人类立克次体感染中最著名的是落基山斑疹热（RMSF），即使采用现代医疗保健，这种疾病的死亡率仍保持在3-10%。RMSF的病原体是立克次体立克次体，立克次体斑疹热组（SFG）的18个公认成员之一，也是NIAID C类优先病原体。马里兰州从1970年至2006年报告了1530例RMSF病例，过去5年平均每年有79例。这些病例大多数报告来自切萨皮克湾沿岸的县，那里的人口密度最高。这一地区还生活着美国东部三种最常见的叮咬人类的蜱虫：变异革蜱、美洲钝目蜱和肩胛硬蜱。虽然变异弓形虫被认为是立克次体的主要媒介，但美洲弓形虫被认为是次要媒介。此外，与家养狗有关的多血鼻头虫也在整个地区发生。虽然不经常叮咬人类，但该物种最近被确定为亚利桑那州群集病例的媒介。尽管初步信息表明这些蜱对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。从这些蜱虫分子中恢复的立克次体是被认为对人类无致病性的物种，或者是身份未知的物种。通常用于确认RMSF等感染的血清学检测不能区分SFG立克次体的成员和引起临床疾病的特定病原体，因此变得相对未知。因此，证明立克次体没有在蜱虫种群中传播，并确定可能导致人类临床疾病的立克次体和立克次体样生物，对公共卫生至关重要。

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.