Implementation Science Approaches for Novel TB Diagnostics in HIV Prevalent Areas

描述(由申请人提供)：我的长期目标是成为一名独立的调查员，专注于检测和控制艾滋病毒和结核病(TB)的新的、成本效益高的战略。在获奖期间，我将在临床调查、传染病建模和经济评估的方法和实施方面积累专业知识。我的职业发展计划将正式的教学与相关的研究经验结合起来，解决全球艾滋病毒/结核病的优先事项。一个由艾滋病毒/结核病研究领域公认的领导者组成的跨学科团队将在职业发展的这一阶段提供专业和科学指导。研究：低病例发现率阻碍了艾滋病患者结核病和耐多药结核病的有效控制加强结核病病例发现(ICF)是世卫组织倡导的一项艾滋病毒/结核病控制战略，但存在关键的知识缺口。首先，目前尚不清楚艾滋病毒患者的结核病ICF是否会增加病例发现率和降低艾滋病毒/结核病死亡率。其次，作为未来ICF算法的一部分，新兴的快速结核病诊断工具的最佳使用尚不清楚。最后，新的ICF干预措施的成本效益尚未阐明。这项建议的目的是：1)确定标准化结核病ICF对HIV患者结局的影响。使用世界卫生组织最近推荐的标准化结核病筛查/诊断战略的ICF将在乌干达的艾滋病毒患者纵向队列中实施。将使用研究前/研究后设计评估结核病病例发现率和艾滋病毒/结核病死亡率。2)确定利用新的快速结核病诊断工具的ICF算法的比较有效性。我们将评估尿液LAM-ELISA、侧向流动LAM和Cepheid Xpert快速诊断测试在乌干达疑似结核病患者中的相对准确性。决策分析将被用来评估ICF算法的准确性、效率和产量，这些算法以串联和/或并行的方式结合了这些工具[具有/不具有传统诊断]的组合。2)模拟将新的、快速的结核病诊断方法结合到ICF算法中的影响、成本和成本效益。我们将模拟新的ICF干预措施对艾滋病毒流行地区人口结核病发病率、流行率和死亡率的影响，并进行经济评估，以指导在卫生系统中以经济高效的方式放置新的、快速的结核病诊断方法。环境：约翰霍普金斯大学提供丰富的智力和物质资源。传染病系有50多名全职教员，其中包括国际艾滋病毒和结核病研究的带头人。JH结核病研究中心进一步提供了独特的研究基础设施，拥有多学科的教员、广泛的国际合作伙伴关系以及超过5500平方英尺的新实验室和办公空间。约翰霍普金斯公共卫生学院是世界上最大的此类机构，在临床研究设计、管理和分析的各个方面提供密集的课程，包括卫生干预的经济评估。这一全面的投资组合将促进作为独立临床研究人员的发展。

DESCRIPTION (provided by applicant): My long-term goal is to become an independent investigator focusing on novel, cost- effective strategies for the detection and control of HIV and tuberculosis (TB). During the award period, I will build expertise in the methodology and conduct of clinical investigation, infectious disease modeling and economic evaluation. My career development plan combines formal didactics with relevant research experiences that address global HIV/TB priorities. A cross-disciplinary team of recognized leaders in HIV /TB research will provide professional and scientific mentorship during this phase of career development. Research: Effective control of TB and MDR-TB in HIV patients is hindered by low case-detection rates. Intensified Case Finding (ICF) of TB is advocated by the WHO as a strategy for HIV/TB control, but critical knowledge gaps exist. First, it is unknown if ICF of TB in HIV patients will increase case-detection and reduce HIV/TB mortality. Second, the optimal usage of emerging, rapid TB diagnostic tools as part of future ICF algorithms is not clear. Finally, the cost-effectiveness of novel ICF interventions has yet to be elucidated. The Aims of this proposal are: 1) To determine the impact of standardized TB ICF on HIV patient outcomes. ICF using a standardized TB screening/diagnostic strategy recently recommended by the WHO will be implemented for a longitudinal cohort of HIV patients in Uganda. TB case-detection and HIV/TB mortality rates will be assessed using a pre/post study design. 2) To determine the comparative- effectiveness of ICF algorithms that utilize new rapid TB diagnostic tools. We will evaluate the comparative accuracy of the urine LAM-ELISA, Lateral-Flow LAM, and Cepheid Xpert rapid diagnostic tests among TB suspects in Uganda. Decision-analysis will be used to estimate the accuracy, efficiency, and yield of ICF algorithms that incorporate combinations of these tools [with/without conventional diagnostics] either serially and/or in parallel. 2) To model the impact, costs, and cost-effectiveness of incorporating novel, rapid TB diagnostics into ICF algorithms. We will model the impact of novel ICF interventions on population TB incidence, prevalence, and mortality in HIV-prevalent regions, and perform an economic evaluation to guide cost-effective placement of novel, rapid TB diagnostics in the health system. Environment: Johns Hopkins University offers substantial intellectual and physical resources. The Division of Infectious Diseases has over 50 full-time faculty including leaders in international HIV and TB research. The JH Center for TB Research further provides a unique research infrastructure with multi-disciplinary faculty, extensive international partnerships, and over 5,500 square feet of new lab and office space. Johns Hopkins Public Health School is the largest such institution in the world and offers intensive coursework in all aspects of clinical research design, management, and analysis, including economic evaluation of health interventions. This comprehensive portfolio will facilitate development as an independent clinical investigator.