Improving the control of multidrug-resistant tuberculosis through targeted screening and use of novel anti-tuberculosis drugs

 描述(由申请人提供)：本提案为耶鲁大学公共卫生学院(YSPH)卫生政策和管理系助理教授Reza Yesoubi博士颁发了为期四年的研究职业发展奖。他的提案旨在解决重要的政策问题，以控制耐多药结核病(MDR-TB)菌株的持续传播，这些菌株对包括在一线结核病治疗方案中的基本抗生素具有耐药性。虽然全球扩大耐多药结核病诊断和治疗以及应对日益严重的耐药性问题的努力进展缓慢，但最近推出的控制耐多药结核病威胁的新工具为加快反应提供了希望。这些新工具包括耐药快速诊断测试和新型抗结核病药物。该提案描述了一项严格的、基于模型的调查，以确定能够最大限度地发挥这些新工具对结核病和耐多药结核病控制的有益影响的战略。为了研究不同控制政策对耐多药结核病传播的总体影响，候选人将开发结核病流行的详细数学和模拟模型，并使用两个耐多药结核病高流行国家--秘鲁和摩尔多瓦共和国的数据进行校准(目标1)。然后，候选人将使用这些模型：1)确定具有成本效益的适应性政策，利用最新的流行病学信息指导结核病和耐多药结核病的定向筛查(目标2)；2)确定药物引进政策，使新的抗T药物和方案的社会效益最大化，同时最大限度地减少出现抗生素耐药性的可能性(目标3)。这项拟议的工作将在YSPH微生物疾病流行病学副教授Ted Cohen博士、医学硕士DrPH博士和YSPH公共卫生和卫生政策与管理教授A.David Paltiel博士的共同指导下进行，并将与艾滋病跨学科研究中心、YSPH传染病建模中心和哈佛公共卫生学院传染病动力学中心合作完成。候选人还将得到HSPH流行病学教授Marc Lipsitch博士和Joshua Salomon博士的建议HSPH的全球健康教授。亚苏比博士的培训目标是(1)对传染病的动态和控制耐药细菌，特别是耐多药结核病出现的生物机制有深入的了解，(2)成为复杂的多因素系统建模方法方面的专家，并通过有效分配可用资源来优化这些系统的整体性能，以及(3)提高他的指导、管理和协作技能，这些技能对于他成功地过渡到独立治疗是至关重要的。候选人的长期目标是成为一名独立的科学家，开发和应用决策科学技术，以改进管理和根除传染病的政策。

 DESCRIPTION (provided by applicant): This proposal presents a four-year research career development award for Dr. Reza Yaesoubi, an Assistant Professor in the Department of Health Policy and Management at the Yale School of Public Health (YSPH). His proposal aims to address important policy questions to control the ongoing spread of multidrug-resistant tuberculosis (MDR-TB) strains, which are resistant to essential antibiotics included in the first-line TB treatment regimen. While global efforts to scale up the diagnosis and treatment of MDR-TB and confront the growing problem of drug resistance have been slow moving, the recent introduction of new tools to control the threat of MDR-TB offer promise to accelerate the response. These new tools include rapid diagnostic tests for drug resistance and the novel anti-TB drugs. This proposal describes a rigorous, model-based investigation to identify strategies that can maximize the beneficial impact of these novel tools for TB and MDR-TB control. To study the overall impact of different control policies on MDR-TB spread, the candidate will develop detailed mathematical and simulation models of TB epidemics and calibrate them using data from two high MDR-TB prevalence countries, Peru and The Republic of Moldova (Aim 1). The candidate will then use these models to i) identify cost-effective, adaptive policies which use updated epidemiological information to guide targeted screening for TB and MDR-TB (Aim 2); and ii) identify drug-introduction policies that maximize the societal benefits of novel anti-T drugs and regimens while minimizing the probability of the emergence of antibiotic resistance (Aim 3). The proposed work will be conducted under the co-mentorship of Dr. Ted Cohen, MD, MPH, DrPH, Associate Professor of Epidemiology of Microbial Diseases at YSPH, and Dr. A. David Paltiel, PhD, MBA, Professor of Public Health, and Health Policy and Management at YSPH, and will be done in collaboration with the Center for Interdisciplinary Research on AIDS, the Center for Infectious Disease Modeling at YSPH, and the Center for Communicable Disease Dynamics at the Harvard School of Public Health (HSPH).The candidate will also be advised by Dr. Marc Lipsitch, DPhill, Professor of Epidemiology at HSPH and Dr. Joshua Salomon, PhD, Professor of Global Health at HSPH. Dr. Yaesoubi's training goals are (1) to develop a solid understanding of the dynamics of infectious diseases and the biological mechanisms governing the emergence of resistant bacteria, in particular MDR-TB, (2) to become an expert in methods for modeling complex multi-agent systems and optimizing the overall performance of these systems through the efficient allocation of available resources, and (3) to improve his mentoring, management, and collaboration skills that are essential for his successful transition to independence. The candidate's long-term goal is to become an independent scientist developing and applying decision science techniques to improve policies for the management and eradication of infectious diseases.