Comparison of two methods for acquisition of sputum samples for diagnosis of suspected tuberculosis in smear-negative or sputum-scarce people: a randomised controlled trial.
Comparison of two methods for acquisition of sputum samples for diagnosis of suspected tuberculosis in smear-negative or sputum-scarce people: a randomised controlled trial.
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DOI：
10.1016/s2213-2600(13)70120-6
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发表时间：
2013-08
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影响因子：
--
通讯作者：
Dheda K
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文献类型：
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作者：
Peter JG;Theron G;Pooran A;Thomas J;Pascoe M;Dheda K
在卫生保健工作者的指导下或通过诱导获得的痰液可以提高活动性结核病病例的检出率。然而，对于初级保健中疑似涂片阴性或痰稀结核病的成人，最佳的初始痰液取样策略尚不清楚。我们比较了此类患者的这两种样本采集方法。在这项随机对照试验中，我们招募了来自南非开普敦三个初级保健诊所的痰液稀少或涂片阴性疑似结核病的成年人（年龄≥18岁）。患者被随机分配（1:1）接受医护人员指导或诱导以获取痰样本。患者和研究人员都没有被告知分配情况。主要结局是在改良的意向治疗人群中 8 周后开始治疗的患者比例。次要结局是不同时间段内开始治疗的比例、产生痰用于诊断的患者比例、不良反应、痰样本的质量以及诊断方法的病例检出。本研究已在 ClinicalTrials.gov 注册，编号 NCT01545661。我们招募了 481 名患者，其中 213 名患者被分配接受医护人员指导，268 名患者被分配接受诱导治疗。入组后 8 周内开始治疗的患者比例在各组之间没有显着差异（53/213 [25%] vs 73/268 [27%]；OR 0.88，95% CI 0.57–1.36；p=0.56）。与诱导患者相比，根据临床和放射学检查结果开始经验性治疗的患者比例更高（32/53 [60%] vs 28/73 [38%]；p=0.015）。与诱导患者相比，获得足够痰样本≥1 mL的比例较低（164/213 [77%] vs 238/268 [89%]；p<0.0001），并且基于培养的诊断率在指导患者与诱导患者中较低（24/213 [11%] vs 51/268 [19%]；p=0.020）。然而，使用涂片显微镜检查（13/213 [6%] vs 22/268 [8%]；p=0.38）或 Xpert-MTB/RIF 检测（13/89 [15%] vs 20/138 [14%]；p=0.98），两组的当天结核病例检测相似。两组均未发生严重不良事件；在 268 名进行痰诱导的患者中，有 32 名 (12%) 报告了与样本采集相关的副作用，而没有接受指导的患者报告了与样本采集相关的副作用。指导患者的每次手术费用低于诱导患者的每次手术费用（2.14 美元 vs 7.88 美元）。尽管诱导提供了足够的样本，并且比卫生保健工作者的指导更频繁地进行细菌学诊断，但它的成本更高，不会导致当天诊断的比例更高，并且由于广泛的经验性治疗，可能不会导致更多的患者开始治疗。因此，在高负担初级保健环境中，医护人员的指导可能是疑似痰稀少或涂片阴性结核病成人初次采集痰样本的首选策略。南非国家研究基金会、欧盟委员会、美国国立卫生研究院、欧洲和发展中国家临床试验合作伙伴、发现基金会。
Sputum obtained either under instruction from a health-care worker or through induction can improve case detection of active tuberculosis. However, the best initial sputum sampling strategy for adults with suspected smear-negative or sputum-scarce tuberculosis in primary care is unclear. We compared these two methods of sample acquisition in such patients. In this randomised controlled trial, we enrolled adults (age ≥18 years) with sputum-scarce or smear-negative suspected tuberculosis from three primary care clinics in Cape Town, South Africa. Patients were randomly assigned (1:1) to receive either health-care worker instruction or induction to obtain sputum samples. Neither patients nor investigators were masked to allocation. The primary outcome was the proportion of patients who had started treatment after 8 weeks in a modified intention-to-treat population. Secondary outcomes were proportions starting treatment within different time periods, proportion of patients producing sputum for diagnosis, adverse effects, sputum samples’ quality, and case detection by diagnostic method. This study is registered with ClinicalTrials.gov, number NCT01545661. We enrolled 481 patients, of whom 213 were assigned to health-care worker instruction versus 268 assigned to induction. The proportion of patients who started treatment in the 8 weeks after enrolment did not differ significantly between groups (53/213 [25%] vs 73/268 [27%]; OR 0.88, 95% CI 0.57–1.36; p=0.56). A higher proportion of instructed versus induced patients initiated empiric treatment based on clinical and radiography findings (32/53 [60%] vs 28/73 [38%]; p=0.015). An adequate sputum sample ≥1 mL was acquired in a lower proportion of instructed versus induced patients (164/213 [77%] vs 238/268 [89%]; p<0.0001), and culture-based diagnostic yield was lower in instructed versus induced patients (24/213 [11%] vs 51/268 [19%]; p=0.020). However, same-day tuberculosis case detection was similar in both groups using either smear microscopy (13/213 [6%] vs 22/268 [8%]; p=0.38) or Xpert-MTB/RIF assay (13/89 [15%] vs 20/138 [14%]; p=0.98). No serious adverse events occurred in either group; side-effects related to sample acquisition were reported in 32 of 268 (12%) patients who had sputum induction and none who had instruction. Cost per procedure was lower for instructed than for induced patients (US$2.14 vs US$7.88). Although induction provides an adequate sample and a bacteriological diagnosis more frequently than instruction by a health-care worker, it is more costly, does not result in a higher proportion of same-day diagnoses, and—because of widespread empiric treatment—may not result in more patients starting treatment. Thus, healthcare worker instruction might be the preferred strategy for initial collection of sputum samples in adults with suspected sputum-scarce or smear-negative tuberculosis in a high burden primary care setting. South African National Research Foundation, European Commission, National Institutes of Health, European and Developing Countries Clinical Trials Partnership, Discovery Foundation.