Optimizing Diagnostic Strategies for TB Transmission Control in Health-Care Facilities

项目摘要 候选人Ruvandhi Nathavitharana博士是传染病科的医生和讲师 贝丝以色列女执事医疗中心（BIDMC）为期5年的K23职业发展奖将提供 为使她成为执行情况的独立调查员， 科学，重点是评估和优化结核病（TB）诊断的影响。 背景结核病高负担国家卫生保健设施中的结核病传播是一项紧迫的任务， 全球健康问题。据记录，2005年住院患者中未确诊结核病的患病率很高， HBCs，但结核病感染控制的重点是已知或疑似结核病患者。FAST（主动查找案例 使用咳嗽筛查和分子诊断，安全迅速地分开治疗）是一种 国家医院正在评估一种强化的、重新确定重点的方法，以减少结核病传播 Hipolito Unanue（HNHU）在利马，秘鲁（R 01-AI 112748，PI：Nardell）。FAST改进了病例检测， 由于依赖于大量的基于大肠杆菌的分子测试，这是资源密集的。一个具有成本效益， 迫切需要准确的、非基于痰的分诊测试，以使FAST在HBCs中更可行。 RESEARCH. K23的总体目标是优化健康结核病的主动病例发现策略， 负担沉重国家的护理设施。中心假设是，一种简单、廉价、不以痰液为基础的结核病分诊试验 具有高灵敏度的药物可以通过改善药物的性能和可持续性而产生重大的临床影响。 像FAST这样的传输减少策略。使用嵌套在母体内的创新混合研究设计 R 01研究，本研究将追求三个具体目标：1）确定三个非 基于痰液的结核病分诊测试：使用CAD 4 TB软件（dCXR/CAD 4 TB）进行数字化胸部X光检查，手指针刺C- 反应蛋白（CRP）和呼出气测试（EBT），并确定哪些患者因咳嗽而被遗漏 筛查，2）评估在FAST中添加分诊测试的成本效益，3）评估 在HNHU的FAST背景下成功实施这些分类测试，并考虑其潜在作用 在不同的临床环境中。这项研究将回答有关结核病诊断优化的关键问题， 在医疗机构的测试策略，并提供R 01诊断干预试验的基础。 辅导。Nathavitharana博士的主要导师Edward Nardell博士是结核病传播控制专家 他在秘鲁建立了研究伙伴关系。他们组织了一个多学科的指导小组， 整个哈佛网络的团队：Nira Pollock博士（具有诊断专业知识的医生科学家），Dr. Stephen Resch（成本效益专家）和丽莎赫什霍恩博士（医生实施科学家）。 训练研究目标得到了培训计划的支持，该计划包括严格的教学法， 关于诊断评估，决策分析和实施科学的课程，以及强大的 并通过哈佛Catalyst提供赠款支持和发展项目。

PROJECT SUMMARY CANDIDATE. Dr. Ruvandhi Nathavitharana, is a physician and Instructor in the Division of Infectious Diseases at Beth Israel Deaconess Medical Center (BIDMC). A 5-year K23 Career Development Award will provide the necessary training and experience needed for her to become an independent investigator in implementation science, with a focus on evaluating and optimizing the impact of tuberculosis (TB) diagnostics. BACKGROUND. TB transmission in health-care facilities in high TB burden countries (HBCs) is a pressing global health problem. A high prevalence of undiagnosed TB has been documented in hospitalized patients in HBCs but TB infection control focuses on patients with known or suspected TB. FAST (Find cases Actively using cough screening and molecular diagnostics, Separate safely and promptly Treat effectively) is an intensified, refocused approach to decrease TB transmission that is being evaluated at Hospital Nacional Hipolito Unanue (HNHU) in Lima, Peru (R01-AI112748, PI: Nardell). FAST improves case detection but is resource intensive due to reliance on a high volume of sputum-based molecular tests. A cost-effective, accurate, non-sputum based triage test is urgently needed to make FAST more feasible in HBCs. RESEARCH. The overall objective for this K23 is to optimize active case finding strategies for TB in health- care facilities in HBCs. The central hypothesis is that a simple, inexpensive, non-sputum based TB triage test with a high sensitivity could have a major clinical impact by improving the performance and sustainability of a transmission reduction strategy like FAST. Using an innovative hybrid study design nested within the parent R01 study, this research will pursue three specific aims: 1) to determine the diagnostic accuracy of three non- sputum based TB triage tests: digital chest x-ray using CAD4TB software (dCXR/CAD4TB), fingerstick C- reactive protein (CRP) and exhaled breath testing (EBT) and determine which patients are missed by cough screening, 2) to evaluate the cost-effectiveness of adding a triage test to FAST and 3) to evaluate the implementation success of these triage tests in the context of FAST at HNHU and consider their potential role in different clinical settings. This research will answer critical questions about the optimization of TB diagnostic testing strategies in healthcare facilities and provide the foundation for an R01 diagnostic intervention trial. MENTORING. Dr. Nathavitharana's primary mentor, Dr. Edward Nardell, is a TB transmission control expert who has an established research partnership in Peru. They have assembled a multi-disciplinary mentoring team across the Harvard network: Dr. Nira Pollock (a physician scientist with diagnostics expertise), Dr. Stephen Resch (a cost-effectiveness expert) and Dr. Lisa Hirschhorn (a physician implementation scientist). TRAINING. The research objectives are supported by a training plan that includes rigorous didactics and coursework on diagnostic evaluation, decision analysis and implementation science, alongside a strong institutional commitment at BIDMC and grant support and development program through Harvard Catalyst.