NRF-DST Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Cape Town, South Africa.
City of Cape Town, Cape Town, South Africa.
Lancet Respir Med. 2020 Apr;8(4):368-382. doi: 10.1016/S2213-2600(19)30370-4. Epub 2020 Feb 14.
Xpert MTB/RIF Ultra (Ultra) is a new test for tuberculosis undergoing global roll-out. We assessed the performance of Ultra compared with Xpert MTB/RIF (Xpert) in an HIV-endemic setting where previous tuberculosis is frequent and current test performance is suboptimal.
In this two-cohort diagnostic accuracy study, we used sputum samples from patients in South Africa to evaluate the accuracy of Ultra and Xpert against a single culture reference standard. For the first cohort (cohort A), we recruited adults (aged ≥18 years) with symptoms of presumptive tuberculosis at Scottsdene clinic in Cape Town, South Africa. We collected three sputum samples from each patient in cohort A, two at the first visit of which one was tested using Xpert and the other was tested using culture, and one sample the next morning which was tested using Ultra. In a separate cohort of patients with presumptive tuberculosis and recent previous tuberculosis (≤2 years) who had submitted sputum samples to the National Health Laboratory Services (cohort B), decontaminated sediments were, after processing, randomly allocated (1:1) for testing with Ultra or Xpert. For both cohorts we calculated the sensitivity and specificity of Ultra and Xpert and evaluated the effects of different methods of interpreting Ultra trace results.
Between Feb 6, 2016, and Feb 2, 2018, we recruited 302 people into cohort A, all of whom provided sputum samples and 239 were included in the head-to-head analyses of Ultra and Xpert. For cohort B, we collected sputum samples from eligible patients who had submitted samples between Dec 6, 2016, and Dec 21, 2017, to give a cohort of 831 samples, of which 352 were eligible for inclusion in analyses and randomly assigned to Ultra (n=173) or Xpert (n=179). In cohort A, Ultra gave more non-actionable results (not positive or negative) than did Xpert (28 [10%] 275 vs 14 [5%] 301; p=0·011). In the head-to-head analysis, in smear-negative patients, sensitivity of Ultra was 80% (95% CI 64-90) and of Xpert was 73% (57-85; p=0·45). Overall, specificity of Ultra was lower than that of Xpert (90% [84-94] vs 99% [95-100]; p=0·001). In cohort B, overall sensitivity was 92% (81-98) for Xpert versus 86% (73-95; p=0·36) for Ultra and overall specificity was 69% (60-77) for Ultra versus 84% (78-91; p=0·005) for Xpert. Ultra specificity estimates improved after reclassification of results with the lowest Ultra-positive semiquantitation category (trace) to negative (15% [8-22]). In cohort A, the positive predictive value (PPV) for Ultra was 78% (67-87) and for Xpert was 96% (87-99; p=0·004); in cohort B, the PPV for Ultra was 50% (43-57) and for Xpert was 70% (61-78; p=0·014). Ultra PPV estimates in previously treated patients were low: at 15% tuberculosis prevalence, half of Ultra-positive patients with presumptive tuberculosis would be culture negative, increasing to approximately 70% in patients with recent previous tuberculosis. In cohort B, 21 (28%) of 76 samples that were Ultra positive were rifampicin indeterminate (all trace) and, like cohort A, most were culture negative (19 [90%] of 21).
In a setting with a high burden of previous tuberculosis, Ultra generated more non-actionable results and had diminished specificity compared with Xpert. In patients with recent previous tuberculosis, a quarter of Ultra-positive samples were indeterminate for rifampicin resistance and culture negative, suggesting that additional drug-resistance testing will probably be unsuccessful. Our data have implications for the handling of Ultra-positive results in patients with previous tuberculosis in high burden settings.
South African Medical Research Council, the EDCTP2 program, and the Faculty of Medicine and Health Sciences, Stellenbosch University.
Xpert MTB/RIF Ultra（Ultra）是一种正在全球推广的新结核病检测方法。我们评估了 Ultra 与 Xpert MTB/RIF（Xpert）在先前结核病频繁且当前检测性能欠佳的艾滋病毒流行地区的表现。
在这项两队列诊断准确性研究中，我们使用来自南非患者的痰液样本，根据单一培养参考标准评估 Ultra 和 Xpert 的准确性。对于第一队列（队列 A），我们招募了南非开普敦斯科茨代恩诊所有疑似结核病症状的成年人（年龄≥18 岁）。我们从队列 A 的每位患者中采集了三份痰液样本，第一次就诊时采集了两份，其中一份用 Xpert 检测，另一份用培养法检测，第二天早上采集了一份用 Ultra 检测。在另一队列中，我们招募了有疑似结核病和最近（≤2 年）先前结核病的患者，他们向国家卫生实验室服务机构提交了痰液样本（队列 B），经过处理后，对去污沉积物进行随机分配（1:1），分别用 Ultra 或 Xpert 进行检测。对于两个队列，我们计算了 Ultra 和 Xpert 的敏感性和特异性，并评估了不同解释 Ultra 痕量结果方法的影响。
在 2016 年 2 月 6 日至 2018 年 2 月 2 日期间，我们招募了 302 人进入队列 A，所有人都提供了痰液样本，其中 239 人被纳入 Ultra 和 Xpert 的头对头分析。对于队列 B，我们收集了符合条件的患者的痰液样本，这些患者在 2016 年 12 月 6 日至 2017 年 12 月 21 日期间向国家卫生实验室服务机构提交了样本，得到了 831 个样本，其中 352 个样本符合纳入分析条件，并随机分配到 Ultra（n=173）或 Xpert（n=179）组。在队列 A 中，Ultra 比 Xpert 产生了更多的非决定性结果（非阳性或阴性）（28 [10%] 275 比 14 [5%] 301；p=0·011）。在头对头分析中，在涂片阴性患者中，Ultra 的敏感性为 80%（95%CI 64-90），Xpert 的敏感性为 73%（57-85；p=0·45）。总体而言，Ultra 的特异性低于 Xpert（90% [84-94] 比 99% [95-100]；p=0·001）。在队列 B 中，Xpert 的总体敏感性为 92%（81-98），Ultra 的总体敏感性为 86%（73-95；p=0·36），Xpert 的总体特异性为 69%（60-77），Ultra 的总体特异性为 84%（78-91；p=0·005）。重新分类 Ultra 阳性半定量类别（痕量）为阴性（15% [8-22]）后，Ultra 的特异性估计值有所提高。在队列 A 中，Ultra 的阳性预测值（PPV）为 78%（67-87），Xpert 的 PPV 为 96%（87-99；p=0·004）；在队列 B 中，Ultra 的 PPV 为 50%（43-57），Xpert 的 PPV 为 70%（61-78；p=0·014）。Ultra 在既往治疗患者中的 PPV 估计值较低：在 15%的结核病患病率下，一半的 Ultra 阳性疑似结核病患者培养结果为阴性，在近期有既往结核病的患者中，这一比例增加到约 70%。在队列 B 中，21 份（28%）Ultra 阳性样本为利福平不确定（均为痕量），与队列 A 一样，这些样本大多为培养阴性（21 份中的 19 份[90%]）。
在先前结核病负担较高的环境中，Ultra 产生了更多的非决定性结果，并且特异性降低。在近期有既往结核病的患者中，四分之一的 Ultra 阳性样本对利福平耐药的检测结果不确定且培养结果为阴性，这表明可能无法进行额外的耐药性检测。我们的数据对高负担地区既往结核病患者处理 Ultra 阳性结果具有重要意义。
南非医学研究理事会、EDCTP2 计划以及斯坦陵布什大学医学校区和健康科学学院。
