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Urine lipoarabinomannan glycan in HIV-negative patients with pulmonary tuberculosis correlates with disease severity
Science Translational Medicine ( IF 15.8 ) Pub Date : 2017-12-13 , DOI: 10.1126/scitranslmed.aal2807
Luisa Paris 1 , Ruben Magni 1 , Fatima Zaidi 1 , Robyn Araujo 2 , Neal Saini 1 , Michael Harpole 1 , Jorge Coronel 3 , Daniela E. Kirwan 4 , Hannah Steinberg 5 , Robert H. Gilman 5 , Emanuel F. Petricoin 1 , Roberto Nisini 6 , Alessandra Luchini 1 , Lance Liotta 1
Affiliation  

An accurate urine test for pulmonary tuberculosis (TB), affecting 9.6 million patients worldwide, is critically needed for surveillance and treatment management. Past attempts failed to reliably detect the mycobacterial glycan antigen lipoarabinomannan (LAM), a marker of active TB, in HIV-negative, pulmonary TB–infected patients’ urine (85% of 9.6 million patients). We apply a copper complex dye within a hydrogel nanocage that captures LAM with very high affinity, displacing interfering urine proteins. The technology was applied to study pretreatment urine from 48 Peruvian patients, all negative for HIV, with microbiologically confirmed active pulmonary TB. LAM was quantitatively measured in the urine with a sensitivity of >95% and a specificity of >80% (n = 101) in a concentration range of 14 to 2000 picograms per milliliter, as compared to non-TB, healthy and diseased, age-matched controls (evaluated by receiver operating characteristic analysis; area under the curve, 0.95; 95% confidence interval, 0.9005 to 0.9957). Urinary LAM was elevated in patients with a higher mycobacterial burden (n = 42), a higher proportion of weight loss (n = 37), or cough (n = 50). The technology can be configured in a variety of formats to detect a panel of previously undetectable very-low-abundance TB urinary analytes. Eight of nine patients who were smear-negative and culture-positive for TB tested positive for urinary LAM. This technology has broad implications for pulmonary TB screening, transmission control, and treatment management for HIV-negative patients.



中文翻译:

HIV阴性肺结核患者的尿脂阿拉伯糖甘露聚糖聚糖与疾病严重程度相关

监测和治疗管理迫切需要准确的尿液肺结核(TB)检测,全世界的960万患者受到影响。过去的尝试未能在HIV阴性,肺结核感染的患者尿液(960万患者中的85%)中可靠地检测到分枝杆菌聚糖抗原lipoarabinomannan(LAM),它是活性TB的标志物。我们在水凝胶纳米笼中应用一种铜络合物染料,该染料以非常高的亲和力捕获LAM,取代了干扰尿液的蛋白质。该技术被用于研究48名秘鲁患者的预处理尿液,这些患者全部都是HIV阴性,并经微生物学证实为活动性肺结核。对尿液中的LAM进行定量测定,灵敏度> 95%,特异性> 80%(n= 101),浓度范围为每毫升14至2000皮克,与非结核病,健康和患病年龄匹配的对照组相比(通过接受者的操作特征分析进行评估;曲线下面积为0.95;置信区间为95%, 0.9005至0.9957)。分枝杆菌负担较高(n = 42),体重减轻比例(n = 37)或咳嗽(n= 50)。可以采用多种格式配置该技术,以检测一组先前无法检测到的极低丰度TB尿液分析物。结核涂片阴性和培养阳性的9名患者中有8名尿LAM呈阳性。该技术对HIV阴性患者的肺结核筛查,传播控制和治疗管理具有广泛的意义。

更新日期:2017-12-15
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