Finding and Treating Unsuspected and Resistant TB to Reduce Hospital Transmission

描述（由申请人提供）：耐多药结核病威胁着全球结核病控制，传播是造成所有病例一半以上的原因。医院和其他聚集场所是结核病传播的常见焦点，包括传播给患者和卫生保健工作者。在结核病和艾滋病毒多重耐药和广泛耐药的时代，结核病在医院传播的后果是致命的。除了发病率、死亡率和医疗费用之外，卫生保健工作者中的活动性结核病还导致劳动力流失，并使患者进一步暴露于感染。长期以来的证据表明，传播不是来自接受有效治疗的结核病患者，而是来自未被怀疑的病例，以及已知的具有未被怀疑的耐药性的病例。全面的国际指南鼓励早期诊断，但往往侧重于已知和疑似病例、环境控制和个人呼吸保护。迫切需要在医院和其他聚集环境中采取根本不同的结核病控制方法。近年来，结核病和耐药性的快速分子检测已经出现并正在实施。本提案调查了在结核病流行环境中的一家忙碌繁忙医院中实施一种称为FAST（主动发现病例，暂时隔离，并根据分子药物敏感性测试进行有效治疗）的结核病传播控制的重新聚焦方法。除了对基于rapd痰液的分子诊断测试进行研究外，该研究还将评估一种新型的结核病呼气测试是否可以通过可靠地排除结核病而避免痰液测试的需要。并行地将第 这项研究将调查医院卫生保健工作者每年结核菌素皮肤试验（TST）的采用情况，以衡量FAST对传播的影响。这些分析将纳入RE-AIM框架，以确定计划的关键要素，这些要素将增强其他医院这些战略的覆盖范围、有效性、采用、实施和维护。提出了三个具体目标。第一个目的是评估FAST减少治疗延迟和医护人员感染的效果。第二个目的是评估FAST和医护人员TST的可接受性和障碍。第三个目的是比较FAST相对于涂片和培养用于结核病诊断、耐药性检测和治疗启动的成本和成本效益。这项拟议中的研究意义重大，因为它旨在通过减少高负担，资源有限的环境中建立更安全的卫生保健设施。 结核病传播给卫生保健工作者和病人。它是创新的，因为它将医院结核病控制的重点转移到主动发现病例和及时治疗未被怀疑的肺结核和未被怀疑的耐药性患者。

DESCRIPTION (provided by applicant): Multidrug resistant tuberculosis threatens global TB control, and transmission is responsible for more than half of all cases. Hospitals and other congregate settings are common foci of TB transmission, including spread to patients and health care workers. In the era of multidrug and extensively drug resistant TB and HIV, the consequences of TB transmission in hospitals are deadly. In addition to the morbidity, mortality and medical costs, active TB in health care workers also leads to workforce attrition and further exposes patients to infection. There is longstanding evidence that transmission is not from TB patients on effective treatment, but from unsuspected cases, and known cases with unsuspected drug resistance. Comprehensive international guidelines encourage early diagnosis, but tend to focus on known and suspected cases, environmental controls, and personal respiratory protection. A fundamentally different approach to TB control in hospitals and other congregate settings is urgently needed. In recent years, rapid molecular tests for TB and drug resistance have emerged and are being implemented. This proposal investigates the implementation of a refocused approach to TB transmission control called FAST (Find cases Actively, Separate temporarily, and Treat effectively based on molecular drug susceptibility testing) in a busy, urban hospital in a TB endemic setting. In addition to the investigation of rapd sputum based molecular diagnostic tests, the study will evaluate whether a novel, exhaled breath test for TB can avoid the need for sputum testing by reliably excluding TB. In parallel, the study will investigate the adoption of annual tuberculin skin testing (TST) of health care workers at the hospital to measure the impact of FAST on transmission. The analyses will incorporate the RE-AIM framework to identify the critical elements of the programs that will enhance the reach, effectiveness, adoption, implementation, and maintenance of these strategies in other hospitals. Three specific aims are proposed. The first aim is to evaluate FAST for reducing treatment delay and health care workers infections. The second aim is to evaluate the acceptability and barriers to FAST and health care worker TST. The third aim is to compare the cost and cost- effectiveness of FAST relative to smear and culture for TB diagnosis, drug resistance testing, and treatment initiation. The proposed research is significant because it seeks to create safer health care facilities in high- burden, resource-limited settings by reducing TB transmission to health care workers and patients. It is innovative because it shifts the focus of hospital based TB control to active case finding and prompt treatment of patients with unsuspected pulmonary TB and unsuspected drug resistance.