Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study.
Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study.
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DOI：
10.1016/s0140-6736(11)60438-8
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发表时间：
2011-04-30
期刊：
影响因子：
168.9
通讯作者：
Perkins, Mark D.
中科院分区：
文献类型：
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作者：
Boehme, Catharina C.;Nicol, Mark P.;Nabeta, Pamela;Michael, Joy S.;Gotuzzo, Eduardo;Tahirli, Rasim;Gler, Ma Tarcela;Blakemore, Robert;Worodria, William;Gray, Christen;Huang, Laurence;Caceres, Tatiana;Mehdiyev, Rafail;Raymond, Lawrence;Whitelaw, Andrew;Sagadevan, Kalaiselvan;Alexander, Heather;Albert, Heidi;Cobelens, Frank;Cox, Helen;Alland, David;Perkins, Mark D.
Xpert MTB/RIF检测试剂盒（Cepheid，桑尼维尔，CA，USA）可在对照研究中以极高的灵敏度和特异性检测结核病及其多重耐药形式，但尚无结核病流行国家的地区和分区卫生机构的性能数据。我们的目标是评估在这种情况下实施的操作可行性、准确性和有效性。我们对南非、秘鲁和印度的城市卫生中心、阿塞拜疆和菲律宾的耐药筛查机构以及乌干达的急诊室连续出现咳嗽持续至少2周的疑似结核病或耐多药结核病的成人（≥18岁）进行了评估。如果患者的第二份痰液样本是在第一份样本后超过1周采集的，或者如果没有有效的参考标准或MTB/RIF检测，则将患者从主要分析中排除。我们比较了在研究中心附近的9个显微镜实验室进行的一次性直接MTB/RIF检测（2-3次痰涂片和1-3次培养，取决于研究中心）和药物敏感性检测。我们评估了稳健性指标，包括不确定率和研究中心间性能，并比较了检测、报告和治疗时间以及所用技术的患者脱落率。我们在2009年8月11日至2010年6月26日期间招募了6648名参与者。一次性MTB/RIF检测在1033例培养确诊的结核病病例中检出了933例（90.3%），而显微镜检查检出了1041例中的699例（67.1%）。在涂片阴性、培养阳性患者中，MTB/RIF检测灵敏度为76.9%（385份样本中的296份），特异性为99.0%（2876份非结核病样本中的2846份）。MTB/RIF检测利福平耐药的敏感性为94.4%（236/250），特异性为98.3%（796/810）。与显微镜检查不同，MTB/RIF检测灵敏度在HIV合并感染患者中并不显著降低。MTB/RIF检测的中位结核检出时间为0天（IQR 0-1），而显微镜检查为1天（0-1），固体培养为30天（23-43），液体培养为16天（13-21）。线探针法检测耐药的中位时间为20天（10-26），常规药敏试验为106天（30-124）。使用MTB/RIF检测可将痰涂片阴性结核病的中位治疗时间从56天（39-81天）缩短至5天（2-8天）。MTB/RIF检测的不确定率为2.4%（126/5321份样本），而培养的不确定率为4.6%（441/9690份样本）。MTB/RIF检测可有效地用于低资源环境，以简化患者获得早期和准确诊断的途径，从而可能降低与诊断延迟、脱落和误治相关的发病率。创新诊断基金会、比尔和梅林达·盖茨基金会、欧洲和发展中国家临床试验伙伴关系（TA 2007.40200.009）、惠康信托基金会（085251/B/08/Z）和英国国际发展部。
The Xpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA) can detect tuberculosis and its multidrug-resistant form with very high sensitivity and specificity in controlled studies, but no performance data exist from district and subdistrict health facilities in tuberculosis-endemic countries. We aimed to assess operational feasibility, accuracy, and effectiveness of implementation in such settings. We assessed adults (≥18 years) with suspected tuberculosis or multidrug-resistant tuberculosis consecutively presenting with cough lasting at least 2 weeks to urban health centres in South Africa, Peru, and India, drug-resistance screening facilities in Azerbaijan and the Philippines, and an emergency room in Uganda. Patients were excluded from the main analyses if their second sputum sample was collected more than 1 week after the first sample, or if no valid reference standard or MTB/RIF test was available. We compared one-off direct MTB/RIF testing in nine microscopy laboratories adjacent to study sites with 2–3 sputum smears and 1–3 cultures, dependent on site, and drug-susceptibility testing. We assessed indicators of robustness including indeterminate rate and between-site performance, and compared time to detection, reporting, and treatment, and patient dropouts for the techniques used. We enrolled 6648 participants between Aug 11, 2009, and June 26, 2010. One-off MTB/RIF testing detected 933 (90·3%) of 1033 culture-confirmed cases of tuberculosis, compared with 699 (67·1%) of 1041 for microscopy. MTB/RIF test sensitivity was 76·9% in smear-negative, culture-positive patients (296 of 385 samples), and 99·0% specific (2846 of 2876 non-tuberculosis samples). MTB/RIF test sensitivity for rifampicin resistance was 94·4% (236 of 250) and specificity was 98·3% (796 of 810). Unlike microscopy, MTB/RIF test sensitivity was not significantly lower in patients with HIV co-infection. Median time to detection of tuberculosis for the MTB/RIF test was 0 days (IQR 0–1), compared with 1 day (0–1) for microscopy, 30 days (23–43) for solid culture, and 16 days (13–21) for liquid culture. Median time to detection of resistance was 20 days (10–26) for line-probe assay and 106 days (30–124) for conventional drug-susceptibility testing. Use of the MTB/RIF test reduced median time to treatment for smear-negative tuberculosis from 56 days (39–81) to 5 days (2–8). The indeterminate rate of MTB/RIF testing was 2·4% (126 of 5321 samples) compared with 4·6% (441 of 9690) for cultures. The MTB/RIF test can effectively be used in low-resource settings to simplify patients' access to early and accurate diagnosis, thereby potentially decreasing morbidity associated with diagnostic delay, dropout and mistreatment. Foundation for Innovative New Diagnostics, Bill & Melinda Gates Foundation, European and Developing Countries Clinical Trials Partnership (TA2007.40200.009), Wellcome Trust (085251/B/08/Z), and UK Department for International Development.