Molecular epidemiology/drug-resistant tuberculosis /Peru

描述(由申请人提供)： 这份修订后的申请是为了获得导师教师发展奖，为梅赛德斯·贝塞拉博士作为结核病流行病学独立调查员的成功职业生涯做好准备。贝塞拉博士在哈佛大学公共卫生学院完成了流行病学博士项目，目前是哈佛医学院社会医学系助理教授。她现在提出了一个为期五年的培训和研究计划，其中将包括额外的专业培训和密集的研究经验，指导下将由Eric J.Rubin博士担任研究导师，Howard Hiatt博士担任职业发展导师，以及流行病学、生物统计学、社会医学、免疫学和分子遗传学专家咨询委员会。指导项目将与顾问团队正在进行的研究活动联系起来。结核病是导致发病率和死亡率的主要原因，而结核分枝杆菌多药耐药(MDR)菌株的出现威胁到全球结核病控制，因为这些菌株比药物敏感菌株更难治疗，治疗成本也更高。候选人将测试这一假设，即在传播的MDR结核分枝杆菌中发现的突变，与在未传播的MDR菌株中发现的突变相比，很可能与最低的适应成本有关。具体目标是：(1)测量结核分枝杆菌特定耐药突变与家庭接触者继发病例之间的关联。(2)评估结核分枝杆菌的其他突变以及临床和人口学特征对这些关联的影响。候选人将通过在秘鲁1000多名耐多药肺结核患者的临床队列中进行嵌套的病例对照研究来实现这些目标，她在那里开展了富有成效的合作。在资助期结束时，候选人将在纳入和分析在方法上严格研究耐药结核病的自然历史和流行病学的分子遗传数据方面获得丰富的经验。这一奖项的累积效应将使贝塞拉博士能够成功竞争NIH个人研究员的资金，并最大限度地发挥她作为结核病流行病学家的学术生涯的潜力。

DESCRIPTION (provided by applicant): This revised application is for a Mentored Faculty Development Award to prepare Dr. Mercedes Becerra for a successful career as an independent investigator in tuberculosis epidemiology. Dr. Becerra completed a doctoral program in epidemiology at the Harvard School of Public Health and is currently Assistant Professor in the Department of Social Medicine of the Harvard Medical School. She now proposes a five-year training and research program that will consist of additional specialized training and an intensive research experience under the guidance of Dr. Eric J. Rubin as the Research Mentor; Dr. Howard Hiatt as the Career Development Mentor; and an Advisory Committee of experts in epidemiology, biostatistics, social medicine, immunology, and molecular genetics. The mentored project will be linked to ongoing research activities of the team of advisors. Tuberculosis is a leading cause of morbidity and mortality, and the emergence of multidrug-resistant (MDR) strains of M. tuberculosis threatens global tuberculosis control because these strains are much more difficult and expensive to treat than drug-sensitive strains. The candidate will test the hypothesis that mutations found in transmitted MDR M. tuberculosis are likely to be those associated with minimal fitness costs when compared to those found in MDR strains that are not transmitted. Specific aims are: (1) To measure the association between specific resistance-conferring mutations in M. tuberculosis and the occurrence of secondary cases in household contacts. (2) To assess the impact of other mutations in M. tuberculosis, and clinical and demographic characteristics, on these associations. The candidate will achieve these aims by conducting a case-control study nested in a clinical cohort of over 1,000 patients with pulmonary MDR tuberculosis in Peru, where she has developed productive collaborations. At the end of the grant period, the candidate will have gained substantial experience in the inclusion and analysis of molecular-genetic data in the methodologically rigorous study of the natural history and epidemiology of drug-resistant tuberculosis. The cumulative effect of this award will be to enable Dr. Becerra to compete successfully for NIH individual investigator funding and maximize her potential to pursue an academic career as a tuberculosis epidemiologist.