ROCHALIMAEA--AN EMERGING PATHOGEN OF AIDS

Rochalimaea——一种新出现的艾滋病病原体

• 批准号: 2672336
• 负责人: JANE E KOEHLER
• 金额: $ 10.5万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2672336
• 关键词: AIDS; Rickettsia; Rickettsiales disease; Siphonaptera; blood vessel disorder; cats; communicable disease transmission; disease /disorder proneness /risk; human subject; humoral immunity; immunofluorescence technique; microorganism classification; molecular cloning; opportunistic infections; serology /serodiagnosis

The long range objective of the proposed study is to understand the microbiologic, serologic and molecular epidemiologic basis of infection with opportunistic Rochalimaea species in individuals with HIV infection. The four Rochalimaea species are among the newest emerging pathogens, having been identified in the US only in the 1990s, and producing syndromes including bacillary angiomatosis and peliosis hepatis. HIV antibody-positive individuals are at markedly increased risk of developing severe, even lethal, infection with the Rochalimaea species, yet these infections are curable if diagnosed in a timely manner, and may be preventable if sources of infection can be identified. The immediate objective of these studies will be: 1. Identification of epidemiologic risk factors associated with infection by the different Rochalimaea species: A case-control epidemiologic study to determine various exposures associated with developing infection with the different Rochalimaea species, including mammalian reservoirs and arthropod vectors implicated in transmission of each species, will be performed. Prevention of infection is dependent on identifying the risk factors for these infections. 2. Characterization of the Rochalimaea species isolated from humans, reservoirs and vectors: Preliminary data suggest that the reservoir and vector exposures differ for infection with the different species. Because so few data exist regarding these infections, a) cultures will be performed from all patients, reservoirs and vectors with suspected Rochalimaea infection, b) molecular techniques will be utilized to speciate isolates, and to determine genetic relationships between isolates and c) the new species or subspecies of Rochalimaea which we have isolated will be characterized. 3. Characterization of the serologic response of the HIV-infected individual to Rochalimaea infection: We will utilize an IFA test to investigate a) duration of antibody response, b) species-specificity of the IFA test and c) if this test can be used to predict relapse. A sensitive and specific serologic test will substantially facilitate diagnosis and management of this infection in HIV-infected people. 4. Preliminary characterization of the angiogenic response to Rochalimaea infection: Rochalimaea infection in HIV-infected patients causes a unique vascular proliferative response. Using isolates derived from the above studies, we will evaluate several different assay systems to determine the angiogenic potential of these species. The elucidation/characterization of these parameters of human infection with Rochalimaea species will provide a basis for diagnostic, therapeutic and preventive strategies which will decrease morbidity and mortality among individuals with HIV infection. R01AI36086 The overall aim of the studies described in this proposal is to relate alterations in patterns of cytokine expression to the course of HIV infection and disease, by quantifying cytokine production in specific subpopulations of men in the Multicenter AIDS Cohort (MACS). In preliminary studies, cytokines that determine immune function were found to be substantially altered in HIV infection. the proposed studies are designed to determine: 1) whether high levels of those cytokines fostering cell-mediated immunity (the TH1 cytokines IFN(gamma) and IL-2, as well as IL-12, a cytokine that induces TH1 cells) are associated with relatively stable CD4 T cell levels and with the absence of opportunistic infections (OI), in HIV infection; 2) if the predominance of TH2 cytokines (IL-4 and IL-10) is associated with falling CD4 T cell levels and with the occurrence of OI, in HIV infection; 3) if increases in TNF(alpha) and IL-6 gene expression/levels are associated with an adverse disease course in HIV infected people, and to determine whether these cytokines are a better predictor of disease progression than the over- expression of TH2 cytokines (IL-4 and IL-10); 4) the relevance to prognosis (relative hazard) of individual and complex changes in cytokine expression and to find if these changes provide prognostic information not available from the measurement of CD4 T cell number of serum activation markers (such as neopterin or beta-2-M). Populations for investigation include cohorts from the MACS studies: a) HIV seroconverters, b) HIV-seropositive (HIV+) men with different rates of decline of CD4T cell number, c) HIV+ men progressing to AIDs within 3 years, d) long term HIV+ survivors with little or no measurable loss of CD4 T cells, e) HIV+ men who have had low CD4 numbers for an extended time without the occurrence of opportunistic infection, and f) a population in which selected cytokines can be evaluated for relative hazard of AIDS occurrence. We will measure: 1) serum levels of these cytokines, 2) levels of cytokine gene expression (mRNA) in peripheral blood mononuclear cells (PBMC) by RNA PCR, 3) cytokine production, and levels of cytokine mRNA, in response to in vitro stimulation of PBMC, in HIV+ subjects and in HIV seronegative people. These studies will provide valuable new information on the role of cytokines in the progression of HIV disease, as well as determining the patterns of cytokine expression that are associated with HIV disease progression and the pathogenesis of AIDS.

拟议的研究的远距离目标是了解 感染的微生物，血清学和分子流行病学基础 在艾滋病毒感染的个体中，有机会性的rochalimaea物种。 四种rochalimaea物种是最新的新兴病原体之一， 仅在1990年代才在美国确定，并生产 综合征包括细菌血管瘤病和脊髓病。 艾滋病病毒 抗体阳性个体的风险显着增加 rochalimaea物种产生严重甚至致命的感染， 然而，如果及时诊断出这些感染，则可以治愈 如果可以识别感染来源，请预防。 这些研究的直接目标将是： 1。鉴定与感染相关的流行病学风险因素 由不同的rochalimaea物种：病例对照流行病学研究 确定与发展感染有关的各种暴露 不同的rochalimaea物种，包括哺乳动物的水库和 与每个物种传播有关的节肢动物向量将是 执行。 预防感染取决于确定风险 这些感染的因素。 2。从人类分离的rochalimaea物种的表征， 水库和向量：初步数据表明水库和 载体暴露因不同物种的感染而有所不同。 因为关于这些感染的数据很少，所以a）文化将 由所有患者，储层和矢量进行的 rochalimaea感染，b）分子技术将用于 分类分离物，并确定 分离株和c）我们的新物种或rochalimaea的亚种我们 孤立将被描述。 3。艾滋病毒感染的血清学反应的表征 个人到rochalimaea感染：我们将利用IFA测试 研究a）抗体反应的持续时间，b） IFA测试和c）是否可以使用此测试来预测复发。 一个 敏感和特定的血清学测试将基本上有助于 艾滋病毒感染者对这种感染的诊断和管理。 4。对rochalimaea的血管生成反应的初步表征 感染：HIV感染患者的rochalimaea感染引起了独特的 血管增殖反应。 使用从上面得出的分离株 研究，我们将评估几种不同的测定系统以确定 这些物种的血管生成潜力。 这些参数的阐明/表征人类感染 与rochalimaea物种一起将为诊断，治疗性提供基础 以及将降低发病率和死亡率的预防策略 在艾滋病毒感染的个体中。 R01AI36086 本提案中描述的研究的总体目的是联系 细胞因子表达模式对HIV的过程的改变 通过量化特异性细胞因子的产生，感染和疾病 多中心艾滋病队列中男性的亚群（MAC）。 在 初步研究，确定免疫功能的细胞因子 在艾滋病毒感染中会大大改变。 拟议的研究是 设计用于确定：1）这些细胞因子是否高水平 促进细胞介导的免疫（Th1细胞因子IFN（伽马）和IL-2， 以及IL-12，诱导Th1细胞的细胞因子与 相对稳定的CD4 T细胞水平，没有机会 感染（OI），在HIV感染中； 2）如果TH2的优势 细胞因子（IL-4和IL-10）与CD4 T细胞水平下降有关 随着OI的发生，在HIV感染中； 3）如果增加 TNF（alpha）和IL-6基因表达/水平与不利有关 艾滋病毒感染的人的疾病课程，并确定这些是否是否 细胞因子是疾病进展的更好的预测指标，而不是过度 Th2细胞因子的表达（IL-4和IL-10）； 4）与 细胞因子个体和复杂变化的预后（相对危害） 表达并查找这些变化是否提供了预后信息 无法从CD4 T细胞数量的血清数量中获得 激活标记（例如Neopterin或beta-2-M）。 调查的人群包括来自MACS研究的队列：A） 艾滋病毒血清逆变器，b）率不同 CD4T细胞数量下降，c）艾滋病毒+男性发展为艾滋病 3年，D）长期艾滋病毒+幸存者，几乎没有可测量的损失 CD4 T细胞的e）HIV+男性的CD4数量较低。 没有机会感染的时间，f）a 可以评估选择细胞因子的种群 艾滋病发生的危害。 我们将测量：1）这些细胞因子的血清水平，2） 外周血单核细胞中的细胞因子基因表达（mRNA） （PBMC）通过RNA PCR，3）细胞因子的产生和细胞因子mRNA的水平， 响应于PBMC的体外刺激，HIV+受试者和HIV中 血浆式的人。 这些研究将提供有关其作用的宝贵新信息 艾滋病毒疾病进展中的细胞因子，并确定 与HIV疾病相关的细胞因子表达模式 进展和艾滋病的发病机理。

项目成果

Use of retinal biopsy to diagnose Bartonella (formerly Rochalimaea) henselae retinitis in an HIV-infected patient.

使用视网膜活检来诊断 HIV 感染患者的巴尔通体（以前称为 Rochalimaea）汉赛视网膜炎。

• DOI: 10.1001/archopht.116.7.937
• 发表时间: 1998
• 期刊: Archives of ophthalmology (Chicago, Ill. : 1960)
• 作者: Warren,K;Goldstein,E;Hung,VS;Koehler,JE;Richardson,W
• 通讯作者: Richardson,W

Absence of Kaposi's sarcoma-associated herpesvirus DNA in bacillary angiomatosis-peliosis lesions.

杆菌性血管瘤病-紫癜病病变中不存在卡波西肉瘤相关疱疹病毒 DNA。

• DOI: 10.1086/314975
• 发表时间: 1999
• 期刊: The Journal of infectious diseases.
• 作者: Relman,DA;Fredricks,DN;Yoder,KE;Mirowski,G;Berger,T;Koehler,JE
• 通讯作者: Koehler,JE

Granulomatous hepatitis and necrotizing splenitis due to Bartonella henselae in a patient with cancer: case report and review of hepatosplenic manifestations of bartonella infection.

癌症患者汉塞巴尔通体引起的肉芽肿性肝炎和坏死性脾炎：病例报告和巴尔通体感染肝脾表现的回顾。

• DOI: 10.1093/clinids/22.6.951
• 发表时间: 1996
• 期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
• 作者: Liston,TE;Koehler,JE
• 通讯作者: Koehler,JE

Bacillary angiomatosis associated with myositis in a patient infected with human immunodeficiency virus.

感染人类免疫缺陷病毒的患者出现与肌炎相关的杆菌性血管瘤病。

• DOI: 10.1093/clind/24.4.562
• 发表时间: 1997
• 期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
• 作者: Whitfeld,MJ;Kaveh,S;Koehler,JE;Mead,P;Berger,TG
• 通讯作者: Berger,TG

Bacillary angiomatosis and bacillary peliosis in patients infected with human immunodeficiency virus: clinical characteristics in a case-control study.

人类免疫缺陷病毒感染患者的杆菌性血管瘤病和杆菌性紫癜病：病例对照研究的临床特征。

• DOI: 10.1093/clinids/22.5.794
• 发表时间: 1996
• 期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
• 作者: Mohle-Boetani,JC;Koehler,JE;Berger,TG;LeBoit,PE;Kemper,CA;Reingold,AL;Plikaytis,BD;Wenger,JD;Tappero,JW
• 通讯作者: Tappero,JW