Lung Infection and Immunity Unit, Division of Pulmonology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Department of Immunology, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.
Lancet. 2014 Feb 1;383(9915):424-35. doi: 10.1016/S0140-6736(13)62073-5. Epub 2013 Oct 28.
The Xpert MTB/RIF test for tuberculosis is being rolled out in many countries, but evidence is lacking regarding its implementation outside laboratories, ability to inform same-day treatment decisions at the point of care, and clinical effect on tuberculosis-related morbidity. We aimed to assess the feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing at primary-care health-care facilities in southern Africa.
In this pragmatic, randomised, parallel-group, multicentre trial, we recruited adults with symptoms suggestive of active tuberculosis from five primary-care health-care facilities in South Africa, Zimbabwe, Zambia, and Tanzania. Eligible patients were randomly assigned using pregenerated tables to nurse-performed Xpert MTB/RIF at the clinic or sputum smear microscopy. Participants with a negative test result were empirically managed according to local WHO-compliant guidelines. Our primary outcome was tuberculosis-related morbidity (measured with the TBscore and Karnofsky performance score [KPS]) in culture-positive patients who had begun anti-tuberculosis treatment, measured at 2 months and 6 months after randomisation, analysed by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT01554384.
Between April 12, 2011, and March 30, 2012, we randomly assigned 758 patients to smear microscopy (182 culture positive) and 744 to Xpert MTB/RIF (185 culture positive). Median TBscore in culture-positive patients did not differ between groups at 2 months (2 [IQR 0-3] in the smear microscopy group vs 2 [0·25-3] in the MTB/RIF group; p=0·85) or 6 months (1 [0-3] vs 1 [0-3]; p=0·35), nor did median KPS at 2 months (80 [70-90] vs 90 [80-90]; p=0·23) or 6 months (100 [90-100] vs 100 [90-100]; p=0·85). Point-of-care MTB/RIF had higher sensitivity than microscopy (154 [83%] of 185 vs 91 [50%] of 182; p=0·0001) but similar specificity (517 [95%] 544 vs 540 [96%] of 560; p=0·25), and had similar sensitivity to laboratory-based MTB/RIF (292 [83%] of 351; p=0·99) but higher specificity (952 [92%] of 1037; p=0·0173). 34 (5%) of 744 tests with point-of-care MTB/RIF and 82 (6%) of 1411 with laboratory-based MTB/RIF failed (p=0·22). Compared with the microscopy group, more patients in the MTB/RIF group had a same-day diagnosis (178 [24%] of 744 vs 99 [13%] of 758; p<0·0001) and same-day treatment initiation (168 [23%] of 744 vs 115 [15%] of 758; p=0·0002). Although, by end of the study, more culture-positive patients in the MTB/RIF group were on treatment due to reduced dropout (15 [8%] of 185 in the MTB/RIF group did not receive treatment vs 28 [15%] of 182 in the microscopy group; p=0·0302), the proportions of all patients on treatment in each group by day 56 were similar (320 [43%] of 744 in the MTB/RIF group vs 317 [42%] of 758 in the microscopy group; p=0·6408).
Xpert MTB/RIF can be accurately administered by a nurse in primary-care clinics, resulting in more patients starting same-day treatment, more culture-positive patients starting therapy, and a shorter time to treatment. However, the benefits did not translate into lower tuberculosis-related morbidity, partly because of high levels of empirical-evidence-based treatment in smear-negative patients.
European and Developing Countries Clinical Trials Partnership, National Research Foundation, and Claude Leon Foundation.
结核分枝杆菌/利福平（Xpert MTB/RIF）检测试剂盒用于检测结核病，目前正在许多国家推广使用，但有关该检测试剂盒在实验室以外的环境中的实施情况、能否在护理点为患者提供当日治疗决策所需的信息，以及对结核病相关发病率的临床影响等方面的证据还比较缺乏。我们旨在评估在南非、津巴布韦、赞比亚和坦桑尼亚的五个初级保健医疗机构中，在基层医疗保健环境下使用即时护理点 Xpert MTB/RIF 检测的可行性、准确性和临床效果。
在这项实用性、随机、平行组、多中心试验中，我们从南非、津巴布韦、赞比亚和坦桑尼亚的五家初级保健医疗机构中招募了有活动性结核病疑似症状的成年人。符合条件的患者使用预先生成的表格按比例随机分配至由护士进行的 Xpert MTB/RIF 检测或痰涂片显微镜检查。对检测结果为阴性的患者，根据当地符合世卫组织标准的指南进行经验性管理。我们的主要结局是在开始抗结核治疗的培养阳性患者中，通过 TBscore 和卡诺夫斯基表现评分（KPS）评估结核病相关发病率，在随机分组后 2 个月和 6 个月进行测量，采用意向治疗进行分析。本试验在 ClinicalTrials.gov 上注册，编号为 NCT01554384。
2011 年 4 月 12 日至 2012 年 3 月 30 日，我们随机将 758 名患者分配至显微镜检查组（182 名培养阳性）和 Xpert MTB/RIF 组（185 名培养阳性）。在 2 个月（显微镜检查组 2 [IQR 0-3] vs MTB/RIF 组 2 [0.25-3]；p=0.85）和 6 个月（显微镜检查组 1 [0-3] vs MTB/RIF 组 1 [0-3]；p=0.35）时，培养阳性患者的 TBscore 中位数在两组间无差异，2 个月时 KPS 中位数也无差异（显微镜检查组 80 [70-90] vs MTB/RIF 组 90 [80-90]；p=0.23），6 个月时 KPS 中位数也无差异（显微镜检查组 100 [90-100] vs MTB/RIF 组 100 [90-100]；p=0.85）。即时护理点 MTB/RIF 的敏感性高于显微镜检查（154 [83%] 185 名 vs 91 [50%] 182 名；p=0.0001），但特异性相似（517 [95%] 544 名 vs 540 [96%] 560 名；p=0.25），与实验室基于 MTB/RIF 的敏感性（292 [83%] 351 名 vs 317 [83%] 351 名；p=0.99）相似，但特异性更高（592 [92%] 1037 名 vs 540 [96%] 560 名；p=0.0173）。即时护理点 MTB/RIF 组有 34 次（5%）检测和实验室基于 MTB/RIF 的检测有 82 次（6%）检测失败（p=0.22）。与显微镜检查组相比，MTB/RIF 组有更多患者在当天获得诊断（178 [24%] 744 名 vs 99 [13%] 758 名；p<0.0001）和当天开始治疗（168 [23%] 744 名 vs 115 [15%] 758 名；p=0.0002）。尽管在研究结束时，由于减少了脱落，MTB/RIF 组中更多的培养阳性患者正在接受治疗（15 [8%] 185 名 MTB/RIF 组未接受治疗 vs 28 [15%] 182 名显微镜检查组；p=0.0302），但在每组中，在第 56 天接受治疗的所有患者比例相似（MTB/RIF 组 320 [43%] 744 名 vs 显微镜检查组 317 [42%] 758 名；p=0.6408）。
护士可以在初级保健诊所准确地进行 Xpert MTB/RIF 检测，这可以导致更多的患者开始当天治疗，更多的培养阳性患者开始治疗，并且开始治疗的时间更短。然而，这些益处并没有转化为结核病相关发病率的降低，部分原因是在涂片阴性患者中，经验性基于证据的治疗水平较高。
欧洲和发展中国家临床试验合作组织、南非国家研究基金会和克劳德·莱昂基金会。
