Diagnostic performance of host protein signatures as a triage test for active pulmonary TB.

Diagnostic performance of host protein signatures as a triage test for active pulmonary TB.
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DOI:
10.1128/jcm.00264-23
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发表时间:
2023-10-24
影响因子:
9.4
通讯作者:
Fernandez Suarez, Marta
Fernandez Suarez, Marta
中科院分区:
医学2区
文献类型:
--
作者:
Koeppel, Lisa;Denkinger, Claudia M.;Wyss, Romain;Broger, Tobias;Chegou, Novel N.;Dunty, Jill M.;Scott, Kerry;Caceres, Tatiana;Dutoit, Elloise;Ugarte-Gil, Cesar;Nicol, Mark;Gotuzzo, Eduardo;Corstjens, Paul L. A. M.;Geluk, Annemieke;Sutherland, Jayne;Sigal, George B.;Moreau, Emmanuel;Albertini, Audrey;Mantsoki, Anna;Ongarello, Stefano;Walzl, Gerhard;Fernandez Suarez, Marta

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目前世界卫生组织(WHO)推荐的四症状筛查被广泛用作启动活动性肺结核(TB)诊断测试的筛查,但性能较差,特别是当TB患病率较低时。相比之下,更敏感的分子检测不太适合在低资源环境下的初级保健水平。为了实现世卫组织终止结核病的目标,迫切需要新的诊断方法来发现缺失的未确诊病例。蛋白质组学衍生的血液宿主生物标志物已被探索,因为蛋白质检测技术适用于护理点环境,并且可以满足成本目标。本研究旨在寻找符合WHO结核病筛查目标产物谱(TPP)的生物标志物特征。通过先进的统计方法和机器学习算法,对来自三个样本人群(越南、秘鲁和南非)的12种基于血液的蛋白质生物标志物进行了单独和组合分析。I-309、SYWC和制激肽的组合显示出在两个国家(秘鲁和南非)的成人中识别活动性结核病的最有希望的结果,该结果符合TPP的分类测试。在全球范围内发现的表现最好的个体标记(I-309和SYWC)也是南非和越南国家一级表现最好的标记之一。该分析清楚地表明,基于一种或两种生物标志物,宿主蛋白生物标志物测定法在某些地理区域的成人中是可行的,其性能符合最低WHO TPP标准。
The current four-symptom screen recommended by the World Health Organization (WHO) is widely used as screen to initiate diagnostic testing for active pulmonary tuberculosis (TB), yet the performance is poor especially when TB prevalence is low. In contrast, more sensitive molecular tests are less suitable for placement at primary care level in low-resource settings. In order to meet the WHO End TB targets, new diagnostic approaches are urgently needed to find the missing undiagnosed cases. Proteomics-derived blood host biomarkers have been explored because protein detection technologies are suitable for the point-of-care setting and could meet cost targets. This study aimed to find a biomarker signature that fulfills WHO’s target product profile (TPP) for a TB screening. Twelve blood-based protein biomarkers from three sample populations (Vietnam, Peru, and South Africa) were analyzed individually and in combinations via advanced statistical methods and machine learning algorithms. The combination of I-309, SYWC and kallistatin showed the most promising results to discern active TB throughout the data sets meeting the TPP for a triage test in adults from two countries (Peru and South Africa). The top-performing individual markers identified at the global level (I-309 and SYWC) were also among the best-performing markers at country level in South Africa and Vietnam. This analysis clearly shows that a host protein biomarker assay is feasible in adults for certain geographical regions based on one or two biomarkers with a performance that meets minimal WHO TPP criteria.
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