Finding and Treating Unsuspected and Resistant TB to Reduce Hospital Transmission

描述(申请人提供)：耐多药结核病威胁全球结核病控制，传播是造成所有病例的一半以上的原因。医院和其他聚集地是结核病传播的常见疫源地，包括向患者和卫生保健工作者传播。在多药和广泛耐药的结核病和艾滋病毒的时代，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，并进一步使患者暴露在感染之下。有长期证据表明，传播不是来自接受有效治疗的结核病患者，而是来自非疑似病例和具有非疑似耐药性的已知病例。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地采取一种根本不同的方法来控制结核病。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。这项提案调查了在结核病流行环境中一家繁忙的城市医院实施名为FAST(主动发现病例，暂时分离，并根据分子药敏试验进行有效治疗)的结核病传播控制的重新重点方法的实施情况。除了调查基于Rapd痰的分子诊断测试外，这项研究还将评估一种新的呼气测试是否可以可靠地排除结核病，从而避免对痰检测的需要。同时， 这项研究将调查该医院的卫生保健工作者采用每年一次的结核菌素皮肤测试(TST)，以衡量FAST对传播的影响。分析将纳入RE-AIM框架，以确定计划的关键要素，这些计划将加强这些战略在其他医院的覆盖范围、有效性、采用、实施和维护。提出了三个具体目标。第一个目标是评估FAST在减少治疗延误和医护人员感染方面的作用。第二个目标是评估FAST和卫生保健工作者TST的可接受性和障碍。第三个目标是比较FAST与涂片和培养相比在结核病诊断、耐药性测试和治疗启动方面的成本和成本效益。这项拟议的研究意义重大，因为它寻求在高负担、资源有限的环境中通过减少 结核病向医护人员和病人传播。它具有创新性，因为它将以医院为基础的结核病控制的重点转移到主动发现病例和迅速治疗患有意外肺结核和意外耐药性的患者。

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.