European Respiratory Journal ( IF 16.6 ) Pub Date : 2024-08-15 , DOI: 10.1183/13993003.00153-2024 Vanessa Mwebaza Muwanga 1 , Simon C Mendelsohn 1 , Vinzeigh Leukes 2 , Kim Stanley 2 , Stanley Kimbung Mbandi 1 , Mzwandile Erasmus 1 , Marika Flinn 2 , Tarryn-Lee Fisher 2 , Rodney Raphela 1 , Nicole Bilek 1 , Stephanus T Malherbe 2 , Gerard Tromp 2 , Gian Van Der Spuy 3 , Gerhard Walzl 2 , Novel N Chegou 2 , Thomas J Scriba 4 ,
Multiple host blood transcriptional signatures have been developed as non-sputum triage tests for tuberculosis (TB). We aimed to compare the diagnostic performance of 20 blood transcriptomic TB signatures for differentiating between symptomatic patients who have TB versus other respiratory diseases (ORD).
As part of a nested case–control study, individuals presenting with respiratory symptoms at primary healthcare clinics in Ethiopia, Malawi, Namibia, Uganda, South Africa and The Gambia were enrolled. TB was diagnosed based on clinical, microbiological and radiological findings. Transcriptomic signatures were measured in whole blood using microfluidic real-time quantitative PCR. Diagnostic performance was benchmarked against the World Health Organization Target Product Profile (TPP) for a non-sputum TB triage test.
Among 579 participants, 158 had definite, microbiologically confirmed TB, 32 had probable TB, while 389 participants had ORD. Nine signatures differentiated between ORD and TB with equivalent performance (Satproedprai7: area under the curve 0.83 (95% CI 0.79–0.87); Jacobsen3: 0.83 (95% CI 0.79–0.86); Suliman2: 0.82 (95% CI 0.78–0.86); Roe1: 0.82 (95% CI 0.78–0.86); Kaforou22: 0.82 (95% CI 0.78–0.86); Sambarey10: 0.81 (95% CI 0.77–0.85); Duffy9: 0.81 (95% CI 0.76–0.86); Gliddon3: 0.8 (95% CI 0.75–0.85); Suliman4 0.79 (95% CI 0.75–0.84)). Benchmarked against a 90% sensitivity, these signatures achieved specificities between 44% (95% CI 38–49%) and 54% (95% CI 49–59%), not meeting the TPP criteria. Signature scores significantly varied by HIV status and country. In country-specific analyses, several signatures, such as Satproedprai7 and Penn-Nicholson6, met the minimal TPP criteria for a triage test in Ethiopia, Malawi and South Africa.
No signatures met the TPP criteria in a pooled analysis of all countries, but several signatures met the minimum criteria for a non-sputum TB triage test in some countries.
中文翻译:
非洲多队列研究中症状性结核病的血液转录组学特征
多种宿主血液转录特征已被开发为结核病 (TB) 的非痰液分诊试验。我们旨在比较 20 种血液转录组 TB 特征的诊断性能,以区分有症状的 TB 患者与其他呼吸系统疾病 (ORD) 患者。
作为嵌套病例对照研究的一部分,在埃塞俄比亚、马拉维、纳米比亚、乌干达、南非和冈比亚的初级卫生保健诊所出现呼吸道症状的个体被纳入。结核病的诊断基于临床、微生物学和放射学检查结果。使用微流控实时定量 PCR 测量全血中的转录组特征。诊断性能以世界卫生组织非痰结核分诊检测的目标产品概况 (TPP) 为基准。
在 579 名参与者中,158 名患有明确的、经微生物学证实的结核病,32 名患有疑似结核病,而 389 名参与者患有 ORD。在 ORD 和 TB 之间区分的 9 个特征具有同等性能(Satproedprai7:曲线下面积 0.83 (95% CI 0.79-0.87);Jacobsen3:0.83 (95% CI 0.79–0.86);苏利曼 2:0.82 (95% CI 0.78–0.86);Roe1:0.82 (95% CI 0.78–0.86);Kaforou22:0.82 (95% CI 0.78–0.86);Sambarey10:0.81 (95% CI 0.77–0.85);Duffy9:0.81 (95% CI 0.76–0.86);Gliddon3:0.8 (95% CI 0.75–0.85);苏利曼4 0.79 (95% CI 0.75–0.84))。以 90% 的敏感性为基准,这些特征的特异性在 44% (95% CI 38-49%) 和 54% (95% CI 49-59%) 之间,不符合 TPP 标准。签名评分因 HIV 状况和国家/地区而异。在针对特定国家/地区的分析中,Satproedprai7 和 Penn-Nicholson6 等几个特征符合埃塞俄比亚、马拉维和南非分诊测试的最低 TPP 标准。
在对所有国家的汇总分析中,没有签名符合 TPP 标准,但在一些国家/地区,一些签名符合非痰结核分诊检测的最低标准。