Tuberculosis, a major cause of death in people living with HIV, remains challenging to diagnose. Diagnostic accuracy data are scarce for promising triage and confirmatory tests such as C-reactive protein (CRP), sputum and urine Xpert MTB/RIF Ultra (Xpert Ultra), and urine Determine TB LAM Ag (a lateral flow lipoarabinomannan [LF-LAM] test), without symptom selection. We evaluated novel triage and confirmatory tests in ambulatory people with HIV initiating antiretroviral therapy (ART). 897 ART-initiators were recruited irrespective of symptoms and sputum induction offered. For triage (n=800), we evaluated point-of-care blood-based CRP testing, compared with the WHO-recommended four-symptom screen (W4SS). For sputum-based confirmatory testing (n=787), we evaluated Xpert Ultra versus Xpert MTB/RIF (Xpert). For urine-based confirmatory testing (n=732), we evaluated Xpert Ultra and LF-LAM. We used a sputum culture reference standard. 463 (52%) of 897 participants were female. The areas under the receiver operator characteristic curves for CRP was 0·78 (95% CI 0·73–0·83) and for number of W4SS symptoms was 0·70 (0·64–0·75). CRP (≥10 mg/L) had similar sensitivity to W4SS (77% [95% CI 68–85; 80/104] 77% [68–85; 80/104]; p>0·99] but higher specificity (64% [61–68; 445/696] 48% [45–52; 334/696]; p<0·0001]; reducing unnecessary confirmatory testing by 138 (95% CI 117–160) per 1000 people and number-needed-to-test from 6·91 (95% CI 6·25–7·81) to 4·87 (4·41–5·51). Sputum samples with Xpert Ultra, which required induction in 49 (31%) of 158 of people (95% CI 24–39), had higher sensitivity than Xpert (71% [95% CI 61–80; 74/104] 56% [46–66; 58/104]; p<0·0001). Of the people with one or more confirmatory sputum or urine test results that were positive, the proportion detected by Xpert Ultra increased from 45% (26–64) to 66% (46–82) with induction. Programmatically done haemoglobin, triage test combinations, and urine tests showed comparatively worse results. CRP is a more specific triage test than W4SS in those initiating ART. Sputum induction improves diagnostic yield. Sputum samples with Xpert Ultra is a more accurate confirmatory test than with Xpert. South African Medical Research Council, EDCTP2, US National Institutes of Health–National Institute of Allergy and Infectious Diseases.

中文翻译：

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护理点 C 反应蛋白和 Xpert MTB/RIF Ultra 用于未选择的抗逆转录病毒治疗起始者中的结核病筛查和诊断：一项前瞻性、横断面、诊断准确性研究


结核病是艾滋病毒感染者死亡的一个主要原因，但诊断仍然具有挑战性。对于有前途的分类和确认测试，例如 C 反应蛋白 (CRP)、痰液和尿液 Xpert MTB/RIF Ultra (Xpert Ultra) 以及尿液确定 TB LAM Ag（一种侧流阿拉伯脂甘露聚糖 [LF-LAM]），诊断准确性数据匮乏测试），没有症状选择。我们对开始抗逆转录病毒治疗 (ART) 的 HIV 流动患者进行了新型分诊和确认测试。无论症状和是否提供痰液诱导，均招募了 897 名 ART 发起者。对于分诊 (n=800)，我们评估了基于血液的 CRP 检测，并与 WHO 推荐的四症状筛查 (W4SS) 进行比较。对于基于痰的确认性检测 (n=787)，我们评估了 Xpert Ultra 与 Xpert MTB/RIF (Xpert)。对于基于尿液的确认性检测 (n=732)，我们评估了 Xpert Ultra 和 LF-LAM。我们使用痰培养参考标准。 897 名参与者中有 463 名（52%）是女性。 CRP 的受试者工作特征曲线下面积为 0·78 (95% CI 0·73–0·83)，W4SS 症状数量为 0·70 (0·64–0·75)。 CRP (≥10 mg/L) 与 W4SS 具有相似的敏感性 (77% [95% CI 68–85; 80/104] 77% [68–85; 80/104]; p>0·99]，但特异性更高 ( 64% [61–68; 445/696] 48% [45–52; 334/696]；p<0·0001]；每 1000 人减少 138 例（95% CI 117–160）需要用 Xpert Ultra 检测痰液样本，从 6·91 (95% CI 6·25–7·81) 到 4·87 (4·41–5·51)，其中 49 例 (31%) 需要进行诱导。 158 人 (95% CI 24–39) 的敏感性高于 Xpert (71% [95% CI 61–80; 74/104] 56% [46–66; 58/104]; p<0·0001 ）。 在一项或多项痰液或尿液检测结果呈阳性的患者中，通过诱导，Xpert Ultra 检测到的比例从 45% (26–64) 增加到 66% (46–82)。程序化完成的血红蛋白、分类测试组合和尿液测试显示出相对较差的结果。对于开始 ART 的患者来说，CRP 是比 W4SS 更具体的分类测试。痰液诱导可提高诊断率。使用 Xpert Ultra 进行痰样本验证测试比使用 Xpert 更准确。南非医学研究委员会、EDCTP2、美国国立卫生研究院 - 国家过敏和传染病研究所。