Background People with human immunodeficiency virus (PHIV) admitted to the hospital have high mortality, with tuberculosis (TB) being the major cause of death. Systematic use of new TB diagnostics could improve TB diagnosis and might improve outcomes. Methods We conducted a cluster randomized trial among adult PHIV admitted to Zomba Central Hospital, Malawi. Admission days were randomly assigned to: enhanced TB diagnostics using urine lipoarabinomannan (LAM) antigen tests (SILVAMP-LAM, Fujifilm, Japan and Determine-LAM, Alere/Abbot, USA), digital chest X-ray with computer-aided diagnosis (dCXR-CAD, CAD4TBv6, Delft, Netherlands), plus usual care (“enhanced TB diagnostics”); or usual care alone (“usual care”). The primary outcome was TB treatment initiation during admission. Secondary outcomes were 56-day mortality, TB diagnosis within 24 hours, and undiagnosed TB at discharge, ascertained by culture of one admission sputum sample. Findings Between 2 September 2020 and 15 February 2022, we recruited 419 people. Four were excluded postrecruitment, leaving 415 adults recruited during 207 randomly assigned admission days in modified intention-to-treat analysis. At admission, 90.8% (377/415) were taking antiretroviral therapy with a median CD4 cell count of 240 cells/mm3. In the enhanced diagnostic arm, median CAD4TBv6 score was 60 (interquartile range: 51–71), 4.4% (9/207) had SILVAMP-LAM–positive and 14.4% (29/201) had Determine-LAM–positive urine with 3 samples positive by both urine tests. TB treatment was initiated in 46/207 (22.2%) in the enhanced TB diagnostics arm and 24/208 (11.5%) in the usual care arm (risk ratio, 1.92; 95% confidence interval [CI]: 1.20–3.08). There was no difference in mortality by 56 days (enhanced TB diagnosis: 54/207, 26.1%; usual care: 52/208, 25.0%; hazard ratio. 1.05; 95% CI: .72–1.53); TB treatment initiation within 24 hours (enhanced TB diagnosis: 8/207, 3.9%; usual care: 5/208, 2.4%; risk ratio, 1.61; 95% CI: .53–4.71); or undiagnosed microbiological-confirmed TB at discharge (enhanced TB diagnosis, 0/207 [0.0%], usual care arm 2/208 [1.0%]; P = .50. Interpretation Urine SILVAMP-LAM/Determine-LAM plus dCXR-CAD diagnostics identified more hospitalized PHIV with TB than usual care. The increase in TB treatment appeared mainly because of greater use of Determine-LAM, rather than SILVAMP-LAM or dCXR-CAD. Poor concordance between Determine-LAM and SILVAMP-LAM urine tests requires further investigation. Inpatient mortality for adults with human immunodeficiency virus remains unacceptability high.

中文翻译：

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在入院的人类免疫缺陷病毒成人患者中使用计算机辅助胸部 X 光和尿液脂阿拉伯甘露聚糖增强结核病诊断（CASTLE 研究）：一项整群随机试验


背景 住院的人类免疫缺陷病毒 （PHIV） 患者死亡率高，结核病 （TB） 是主要死因。系统使用新的结核病诊断方法可以改善结核病诊断，并可能改善结局。方法 我们在马拉维 Zomba 中心医院收治的成人 PHIV 中进行了一项整群随机试验。入院天数被随机分配为：使用尿液脂阿拉伯甘露聚糖 （LAM） 抗原检测的增强结核病诊断（SILVAMP-LAM，Fujifilm，日本和 Determine-LAM，Alere/Abbot，美国）、数字胸部 X 光检查和计算机辅助诊断（dCXR-CAD，CAD4TBv6，荷兰代尔夫特），加上常规护理（“增强结核病诊断”）;或仅常规护理（“常规护理”）。主要结局是入院期间 TB 治疗的开始。次要结局是 56 天死亡率、24 小时内诊断为 TB 和出院时未确诊的 TB，通过对 1 个入院痰标本的培养确定。调查结果 在 2020 年 9 月 2 日至 2022 年 2 月 15 日期间，我们招募了 419 人。4 例在招募后被排除在外，在改良的意向治疗分析中，在 207 个随机分配的入院日内招募了 415 名成年人。入院时，90.8% （377/415） 正在接受抗逆转录病毒治疗，CD4 细胞计数中位数为 240 个细胞/mm3。在增强诊断组中，CAD4TBv6 评分中位为 60 （四分位距： 51-71），4.4% （9/207） 为 SILVAMP-LAM 阳性，14.4% （29/201） 为 Determine-LAM 阳性尿液，3 个样本两次尿检均呈阳性。加强结核病诊断组有 46/207 （22.2%） 开始结核病治疗，常规护理组有 24/208 （11.5%） 开始结核病治疗 （风险比，1.92;95% 置信区间 [CI]： 1.20-3.08）。到 56 天死亡率没有差异（增强 TB 诊断：54/207,26。1%;常规护理：52/208,25.0%;风险比。1.05;95% CI：.72–1.53）;24 小时内开始结核病治疗（增强结核病诊断：8/207,3.9%;常规护理：5/208,2.4%;风险比，1.61;95% CI：.53-4.71）;或出院时经微生物学证实的结核病（增强结核病诊断，0/207 [0.0%]，常规护理组 2/208 [1.0%];P = .50。解释 尿液 SILVAMP-LAM/Determine-LAM 加 dCXR-CAD 诊断发现比常规护理更多的住院 PHIV 患有结核病。结核病治疗的增加主要是因为更多地使用 Determine-LAM，而不是 SILVAMP-LAM 或 dCXR-CAD。Determine-LAM 和 SILVAMP-LAM 尿液检测之间的一致性不佳需要进一步调查。人类免疫缺陷病毒成人患者的住院死亡率仍然很高，令人无法接受。