EMERGENCE OR RIFAMPIN MONORESISTANT TUBERCULOSIS

出现或利福平单耐药结核病

• 批准号: 2440526
• 负责人: WILLIAMSON Z BRADFORD
• 金额: $ 8.44万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 1998-12-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2440526
• 关键词: African; American; HIV infections; Mycobacterium; antitubercular agents; clinical research; drug resistance; epidemiology; ethambutol; genetic strain; host organism interaction; human subject; isoniazid; laboratory mouse; leukocyte count; malabsorption; pharmacokinetics; pyrazinamide; rifamycins; tuberculosis; virulence

The principal investigator (PI) is an infectious disease clinician and epidemiologist with a career interest in the etiologic determinants of the emergence and dissemination of drug-resistant bacteria. The PI's experience in clinical infectious diseases, epidemiology, molecular epidemiology, and microbiology, provide a solid foundation for the proposed research plan and demonstrate a strong commitment to a career in academic medicine. The career development plan detailed in this proposal integrates these prior training experiences, while allowing the PI to develop new expertise using a murine model to assess parasite virulence. Prior work by the PI has demonstrated that HIV infection plays a pivotal role in the emergence of rifampin mono-resistant (RMR) tuberculosis (TB), an increasingly significant public health problem. The PI now hypothesizes the malabsorption of anti-tuberculous drugs and the ability of relatively avirulent strains to produce disease in HIV-infected patients are important determinants of the emergence of RMR TB. The relationship between HIV and acquired RMR TB will be further elucidated in a case-control and a molecular epidemiologic study in San Francisco. A prospective cohort study in Botswana will define the prevalence and significance of the malabsorption of anti-tuberculous drugs. A series of investigations utilizing molecular epidemiologic techniques and a murine model will determine the relationship between specific mutations conferring rifampin-resistance and strain virulence, and the prevalence of avirulent strain in HIV-infected patients. Ultimately, these investigations will facilitate the formulation of interventions for preventing and controlling RMR TB. The intellectual environment at UCSF and the strong tuberculosis research group which Dr. Hopewell has created in San Francisco afford the PI an ideal opportunity to pursue his career development plan. The close proximity to UC Berkeley, the California Department of Health Services, and Stanford University, allow the PI to maintain important collaborations and to access diverse educational opportunities at these institutions.

首席研究员（PI）是传染病临床医生， 流行病学家对病因的职业生涯对病因学决定因素有兴趣 耐药细菌的出现和传播。 PI的 临床传染病，流行病学，分子经验 流行病学和微生物学为 拟议的研究计划并证明了对职业的坚定承诺 学术医学。 详细介绍的职业发展计划 提案整合了这些先前的培训经验，同时允许 PI使用鼠模型来开发新的专业知识来评估寄生虫 毒力。 PI的先前工作表明，HIV感染起着关键作用 利福平单一耐药（RMR）结核病的作用 （TB），这是一个越来越重大的公共卫生问题。 现在的PI 假设抗通结药物的吸收不良和能力 相对无毒的菌株，在感染HIV的疾病中产生疾病 患者是RMR TB出现的重要决定因素。 这 艾滋病毒与收购RMR结核之间的关系将进一步阐明 在旧金山的病例对照和一项分子流行病学研究中。 博茨瓦纳的一项前瞻性队列研究将定义患病率和 抗通结药物吸收不良的意义。 系列 利用分子流行病学技术和A的研究 鼠模型将确定特定突变之间的关系 赋予利福平的抗性和应变毒力，以及患病率 HIV感染患者的无毒菌株。 最终，这些 调查将有助于制定干预措施 防止和控制RMR TB。 UCSF的智力环境和强大的结核病 Hopewell博士在旧金山成立的研究小组负担 PI是追求其职业发展计划的理想机会。 这 加利福尼亚卫生部靠近加州大学伯克利分校 服务和斯坦福大学允许PI保持重要 合作并在这些方面获得多种教育机会 机构。