Gina Phindile, Randall Philippa J, Muchinga Tapuwa E, Pooran Anil, Meldau Richard, Peter Jonny G, Dheda Keertan
Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
BMC Infect Dis. 2017 May 12;17(1):339. doi: 10.1186/s12879-017-2313-0.
Urine LAM testing has been approved by the WHO for use in hospitalised patients with advanced immunosuppression. However, sensitivity remains suboptimal. We therefore examined the incremental diagnostic sensitivity of early morning urine (EMU) versus random urine sampling using the Determine® lateral flow lipoarabinomannan assay (LF-LAM) in HIV-TB co-infected patients.
Consenting HIV-infected inpatients, screened as part of a larger prospective randomized controlled trial, that were treated for TB, and could donate matched random and EMU samples were included. Thus paired sample were collected from the same patient, LF-LAM was graded using the pre-January 2014, with grade 1 and 2 manufacturer-designated cut-points (the latter designated grade 1 after January 2014). Single sputum Xpert-MTB/RIF and/or TB culture positivity served as the reference standard (definite TB). Those treated for TB but not meeting this standard were designated probable TB.
123 HIV-infected patients commenced anti-TB treatment and provided matched random and EMU samples. 33% (41/123) and 67% (82/123) had definite and probable TB, respectively. Amongst those with definite TB LF-LAM sensitivity (95%CI), using the grade 2 cut-point, increased from 12% (5-24; 5/43) to 39% (26-54; 16/41) with random versus EMU, respectively (p = 0.005). Similarly, amongst probable TB, LF-LAM sensitivity increased from 10% (5-17; 8/83) to 24% (16-34; 20/82) (p = 0.001). LF-LAM specificity was not determined.
This proof of concept study indicates that EMU could improve the sensitivity of LF-LAM in hospitalised TB-HIV co-infected patients. These data have implications for clinical practice.
尿液脂阿拉伯甘露聚糖(LAM)检测已获世界卫生组织批准,用于住院的晚期免疫抑制患者。然而,其敏感性仍不理想。因此,我们使用Determine® 侧向流动脂阿拉伯甘露聚糖检测法(LF-LAM),研究了HIV-TB合并感染患者晨尿(EMU)与随机尿样相比在诊断上的增量敏感性。
纳入同意参与一项更大规模前瞻性随机对照试验筛查的HIV感染住院患者,这些患者正在接受结核病治疗,且能够提供匹配的随机尿样和晨尿样本。因此,从同一患者收集配对样本,LF-LAM按照2014年1月前的标准分级,采用制造商指定的1级和2级截断点(2014年1月后后者指定为1级)。单次痰Xpert-MTB/RIF检测和/或结核培养阳性作为参考标准(确诊结核病)。那些接受结核病治疗但未达到该标准的患者被指定为疑似结核病。
123例HIV感染患者开始抗结核治疗,并提供了匹配的随机尿样和晨尿样本。分别有33%(41/123)和67%(82/123)的患者确诊和疑似患有结核病。在确诊结核病的患者中,使用2级截断点时,LF-LAM的敏感性(95%CI),随机尿样为12%(5-24;5/43),晨尿为39%(26-54;16/41),分别提高(p = 0.005)。同样,在疑似结核病患者中,LF-LAM的敏感性从10%(5-17;8/83)提高到24%(16-34;20/82)(p = 0.001)。未测定LF-LAM的特异性。
这项概念验证研究表明,晨尿可提高LF-LAM在住院的TB-HIV合并感染患者中的敏感性。这些数据对临床实践具有重要意义。