Department of Field Epidemiology, Epicentre, Paris, France.
Department of Field Epidemiology, Epicentre, Paris, France.
Lancet Glob Health. 2023 Jan;11(1):e126-e135. doi: 10.1016/S2214-109X(22)00463-6.
Development of rapid biomarker-based tests that can diagnose tuberculosis using non-sputum samples is a priority for tuberculosis control. We aimed to compare the diagnostic accuracy of the novel Fujifilm SILVAMP TB LAM (FujiLAM) assay with the WHO-recommended Alere Determine TB-LAM Ag test (AlereLAM) using urine samples from HIV-positive patients.
We did a diagnostic accuracy study at five outpatient public health facilities in Uganda, Kenya, Mozambique, and South Africa. Eligible patients were ambulatory HIV-positive individuals (aged ≥15 years) with symptoms of tuberculosis irrespective of their CD4 T-cell count (group 1), and asymptomatic patients with advanced HIV disease (CD4 count <200 cells per μL, or HIV clinical stage 3 or 4; group 2). All participants underwent clinical examination, chest x-ray, and blood sampling, and were requested to provide a fresh urine sample, and two sputum samples. FujiLAM and AlereLAM urine assays, Xpert MTB/RIF Ultra assay on sputum or urine, sputum culture for Mycobacterium tuberculosis, and CD4 count were systematically carried out for all patients. Sensitivity and specificity of FujiLAM and AlereLAM were evaluated against microbiological and composite reference standards.
Between Aug 24, 2020 and Sept 21, 2021, 1575 patients (823 [52·3%] women) were included in the study: 1031 patients in group 1 and 544 patients in group 2. Tuberculosis was microbiologically confirmed in 96 (9·4%) of 1022 patients in group 1 and 18 (3·3%) of 542 patients in group 2. Using the microbiological reference standard, FujiLAM sensitivity was 60% (95% CI 51-69) and AlereLAM sensitivity was 40% (31-49; p<0·001). Among patients with CD4 counts of less than 200 cells per μL, FujiLAM sensitivity was 69% (57-79) and AlereLAM sensitivity was 52% (40-64; p=0·0218). Among patients with CD4 counts of 200 cells per μL or higher, FujiLAM sensitivity was 47% (34-61) and AlereLAM sensitivity was 24% (14-38; p=0·0116). Using the microbiological reference standard, FujiLAM specificity was 87% (95% CI 85-89) and AlereLAM specificity was 86% (95 CI 84-88; p=0·941). FujiLAM sensitivity varied by lot number from 48% (34-62) to 76% (57-89) and specificity from 77% (72-81) to 98% (93-99).
Next-generation, higher sensitivity urine-lipoarabinomannan assays are potentially promising tests that allow rapid tuberculosis diagnosis at the point of care for HIV-positive patients. However, the variability in accuracy between FujiLAM lot numbers needs to be addressed before clinical use.
ANRS and Médecins Sans Frontières.
开发能够使用非痰液样本诊断结核病的基于快速生物标志物的检测方法是结核病控制的当务之急。我们旨在比较新型富士胶片 SILVAMP TB LAM（FujiLAM）检测与世界卫生组织推荐的 Alere Determine TB-LAM Ag 检测（AlereLAM）在 HIV 阳性患者尿液样本中的诊断准确性。
我们在乌干达、肯尼亚、莫桑比克和南非的五家门诊公共卫生机构进行了一项诊断准确性研究。符合条件的患者是有结核病症状的活动性 HIV 阳性个体（年龄≥15 岁），无论其 CD4 T 细胞计数如何（第 1 组），以及患有晚期 HIV 疾病（CD4 计数<200 个细胞/μL，或 HIV 临床分期 3 或 4；第 2 组）的无症状患者。所有参与者均接受了临床检查、胸部 X 光检查和血液采样，并被要求提供新鲜尿液样本和两份痰液样本。对所有患者进行了富士胶片和 AlereLAM 尿液检测、痰或尿液 Xpert MTB/RIF Ultra 检测、分枝杆菌培养和 CD4 计数。微生物学和综合参考标准评估了 FujiLAM 和 AlereLAM 的敏感性和特异性。
在 2020 年 8 月 24 日至 2021 年 9 月 21 日期间，纳入了 1575 名患者（823 名[52.3%]为女性）：第 1 组 1031 名患者，第 2 组 544 名患者。在第 1 组的 1022 名患者中，96 名（9.4%）和第 2 组的 542 名患者中的 18 名（3.3%）经微生物学确认患有结核病。使用微生物学参考标准，FujiLAM 的敏感性为 60%（95%CI 51-69），AlereLAM 的敏感性为 40%（31-49；p<0·001）。在 CD4 计数<200 个细胞/μL 的患者中，FujiLAM 的敏感性为 69%（57-79），AlereLAM 的敏感性为 52%（40-64；p=0·0218）。在 CD4 计数为 200 个细胞/μL 或更高的患者中，FujiLAM 的敏感性为 47%（34-61），AlereLAM 的敏感性为 24%（14-38；p=0·0116）。使用微生物学参考标准，FujiLAM 的特异性为 87%（95%CI 85-89），AlereLAM 的特异性为 86%（95 CI 84-88；p=0·941）。FujiLAM 的敏感性从 48%（34-62）到 76%（57-89）不等，特异性从 77%（72-81）到 98%（93-99）不等。
新一代、更高敏感性的尿液脂阿拉伯甘露聚糖检测方法具有很大的潜力，可在 HIV 阳性患者的护理点快速诊断结核病。然而，在临床使用之前，需要解决 FujiLAM 批次数量之间准确性的差异。
法国国家艾滋病研究署和无国界医生组织。
