Hoa Nguyen B, Fajans Mark, Nguyen Van Hung, Vu Ngoc Bao, Nguyen Viet Nhung, Nguyen Thi Hoa, Thi Huong Lien Tran, Tran Minh Dung, Nguyen Kim Cuong, Thi Tuyet Trinh Ha, Huu Tri Nguyen, Bui Ngoc Diep, Nguyen Viet Hai, Khanh An Tran, Lillis Lorraine, Perez Marcos, Thomas Katherine K, Peck Roger B, Cantera Jason L, Murphy Eileen, Halas Olivia R, Storey Helen L, Pinter Abraham, Ruhwald Morten, Drain Paul K, Boyle David S
National Lung Hospital, Hanoi, Vietnam.
Department of Epidemiology, University of Washington, Seattle, Washington, United States of America.
PLOS Glob Public Health. 2024 Nov 6;4(11):e0003891. doi: 10.1371/journal.pgph.0003891. eCollection 2024.
Lipoarabinomannan (LAM) is a promising target biomarker for diagnosing subclinical and clinical tuberculosis (TB). Urine LAM (uLAM) testing using rapid diagnostic tests (RDTs) has been approved for people living with HIV (PLWH), however there is limited data regarding uLAM levels in HIV-negative (HIV-ve) adults with clinical TB. We conducted a clinical study of adults presenting with clinical TB-related symptoms at the National Lung Hospital in Hanoi, Vietnam. The uLAM concentrations were measured using electrochemiluminescent (ECL) immunoassays and compared to a microbiological reference standard (MRS) using GeneXpert Ultra and TB culture testing. Estimated uLAM concentrations above plate specific calculated limit of detection (LOD) were considered uLAM positive. Additional microbiological testing was conducted for possible extrapulmonary TB (EPTB). Among 745 participants enrolled, 335 (44.9%) participants with presumptive pulmonary TB (PTB) and 6 (11.3%) participants with presumptive EPTB had confirmed TB disease. Overall, the S/A antibody pair had a sensitivity of 39% (95% Confidence Interval [CI] 0.33, 0.44) and a specificity of 97% (95% CI 0.96, 0.99) compared to the MRS. The F/A antibody pair had a sensitivity of 41% (95% CI 0.35, 0.47) and a specificity of 79% (95% CI 0.75, 0.84). S/A provided greater discriminatory ability compared to F/A for both individuals with presumptive PTB (AUROC: 0.74 vs 0.63, p<0.0001) and presumptive EPTB (0.76 vs 0.54, p = 0.045) when using the MRS. Among HIV-ve participants in an adult cohort in Vietnam, the concentrations of uLAM remained relatively low for people with clinical TB, which may present challenges for improving RDT sensitivity.
脂阿拉伯甘露聚糖（LAM）是诊断亚临床和临床结核病（TB）的一个有前景的目标生物标志物。使用快速诊断检测（RDT）进行尿液LAM（uLAM）检测已被批准用于艾滋病毒感染者（PLWH），然而，关于临床结核病的艾滋病毒阴性（HIV-ve）成年人的uLAM水平的数据有限。我们在越南河内国家肺病医院对出现临床结核病相关症状的成年人进行了一项临床研究。使用电化学发光（ECL）免疫测定法测量uLAM浓度，并与使用GeneXpert Ultra和结核培养检测的微生物学参考标准（MRS）进行比较。估计的uLAM浓度高于平板特定计算检测限（LOD）被视为uLAM阳性。对可能的肺外结核（EPTB）进行了额外的微生物学检测。在745名登记参与者中，335名（44.9%）疑似肺结核（PTB）参与者和6名（11.3%）疑似EPTB参与者被确诊患有结核病。总体而言，与MRS相比，S/A抗体对的敏感性为39%（95%置信区间[CI]0.33，0.44），特异性为97%（95%CI0.96，0.99）。F/A抗体对的敏感性为41%（95%CI0.35，0.47），特异性为79%（95%CI0.75，0.84）。当使用MRS时，对于疑似PTB个体（受试者工作特征曲线下面积：0.74对0.63，p<0.0001）和疑似EPTB个体（0.76对0.54，p = 0.045），S/A比F/A具有更大的鉴别能力。在越南一个成人队列中的HIV-ve参与者中，临床结核病患者的uLAM浓度仍然相对较低，这可能对提高RDT敏感性构成挑战。
