Diagnostic yield of induced sputum for rapid diagnosis of pulmonary tuberculosis

描述（由申请人提供）：这项以社区为基础的横断面研究将测试一种简单、低成本的快速诊断肺结核（TB）的诊断方法。我们将测试盐水诱导痰是否能提高HIV感染和未感染HIV的青少年和成人的涂阳结核的诊断率。它将在我们在南非开普敦附近建立的研究基地进行测试，那里正在进行临床和流行病学研究，为新型结核病疫苗的试验做准备。我们已经成功地使用这种技术在第四阶段BCG疫苗试验中调查了1，800多名儿童。具体目标：确定诱导痰是否能提高以下人群中肺结核的快速微生物诊断：（a）HIV感染者，和（B）所有疑似肺结核患者，无论HIV状态如何。我们将招募600名到社区卫生服务机构就诊的疑似结核病患者。将进行两次常规痰液采集、一次盐水雾化诱导痰液采集和一次HIV检测。直接涂片痰液显微镜检查和分枝杆菌培养将在经认证的实验室进行。将使用HIV检测结果对受试者进行分层，以评价主要结局（直接涂片镜检阳性）和次要结局（结核分枝杆菌培养阳性）。这些结果将被分析为通过一次或两次常规痰采集的直接涂片显微镜检查检测到的诊断率（培养证实的TB病例的比例）与单次诱导痰相比的差异。2004年，结核病占该地区所有死亡人数的10%。肺结核的快速诊断对艾滋病毒感染者尤其重要，因为延误治疗可能是致命的。奇怪的是，诊断是更困难的艾滋病毒感染者的少菌性疾病。先前的研究已经证明了诱导痰在常规痰涂片镜检阴性的个体中的诊断益处。这项研究将允许客观评估诱导痰对HIV感染者和HIV未感染者中结核病病例检测的影响，通过计算在高流行率发展中国家的区域结核病控制计划可能实现的诊断率的增益。

DESCRIPTION (provided by applicant): This community-based, cross-sectional study will test a simple low-cost diagnostic modality for rapid diagnosis of pulmonary tuberculosis (TB). We shall test whether saline-induced sputum improves the diagnostic yield of smear positive TB in HIV-infected and HIV-uninfected adolescents and adults. It will be tested at our established research site near Cape Town, South Africa, where clinical and epidemiological studies are being conducted in preparation for trials of novel TB vaccines. We have successfully used this technique to investigate over 1,800 children in a Phase IV BCG vaccine trial. Specific aims: To determine whether induced sputum improves rapid microbiological diagnosis of pulmonary TB in: (a) HIV-infected people, and (b), in all people with suspected tuberculosis, regardless of HIV status. We shall enroll 600 patients presenting to community health services with suspected TB. Two routine sputum collections, one induced sputum collection with saline nebulization, and an HIV test will be performed. Direct smear sputum microscopy and mycobacterial culture will be performed in an accredited laboratory. HIV test results will be used to stratify participants for evaluation of the primary outcome, positive direct smear microscopy, and the secondary outcome, positive culture of Mycobacterium tuberculosis. These outcomes will be analyzed as the difference in diagnostic yield (proportion of culture-proven TB cases) detected by direct smear microscopy of one, or two, routine sputum collections, compared to a single induced sputum. TB accounted for 10% of all deaths in this region in 2004. Rapid diagnosis of pulmonary TB is especially critical in HIV-infected individuals, since delay in therapy may be fatal. Paradoxically, diagnosis is more difficult in HIV-infected people with pauci-bacillary disease. Previous studies have demonstrated diagnostic benefit of induced sputum among individuals with negative routine sputum smear microscopy. This study will allow objective assessment of the impact of induced sputum on TB case detection among HIV-infected and HIV-uninfected persons, by calculating the gain in diagnostic yield that might be achieved by a regional TB control program in a high-prevalence developing country.