通过实时聚合酶链反应对肺结核宿主血液转录组生物标志物进行前瞻性多中心直接验证。
Prospective multicentre head-to-head validation of host blood transcriptomic biomarkers for pulmonary tuberculosis by real-time PCR.
作者信息
Mendelsohn Simon C, Mbandi Stanley Kimbung, Fiore-Gartland Andrew, Penn-Nicholson Adam, Musvosvi Munyaradzi, Mulenga Humphrey, Fisher Michelle, Hadley Katie, Erasmus Mzwandile, Nombida Onke, Tameris Michèle, Walzl Gerhard, Naidoo Kogieleum, Churchyard Gavin, Hatherill Mark, Scriba Thomas J
机构信息
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and Division of Immunology, Department of Pathology, University of Cape Town, 7925 Cape Town, South Africa.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
出版信息
Commun Med (Lond). 2022;2(1). doi: 10.1038/s43856-022-00086-8. Epub 2022 Mar 10.
BACKGROUND
Sensitive point-of-care screening tests are urgently needed to identify individuals at highest risk of tuberculosis. We prospectively tested performance of host-blood transcriptomic tuberculosis signatures.
METHODS
Adults without suspicion of tuberculosis were recruited from five endemic South African communities. Eight parsimonious host-blood transcriptomic tuberculosis signatures were measured by microfluidic RT-qPCR at enrolment. Upper respiratory swab specimens were tested with a multiplex bacterial-viral RT-qPCR panel in a subset of participants. Diagnostic and prognostic performance for microbiologically confirmed prevalent and incident pulmonary tuberculosis was tested in all participants at baseline and during active surveillance through 15 months follow-up, respectively.
RESULTS
Among 20,207 HIV-uninfected and 963 HIV-infected adults screened; 2923 and 861 were enroled. There were 61 HIV-uninfected (weighted prevalence 1.1%) and 10 HIV-infected (prevalence 1.2%) tuberculosis cases at baseline. Parsimonious signature diagnostic performance was superior among symptomatic (AUCs 0.85-0.98) as compared to asymptomatic (AUCs 0.61-0.78) HIV-uninfected participants. Thereafter, 24 HIV-uninfected and 9 HIV-infected participants progressed to incident tuberculosis (1.1 and 1.0 per 100 person-years, respectively). Among HIV-uninfected individuals, prognostic performance for incident tuberculosis occurring within 6-12 months was higher relative to 15 months. 1000 HIV-uninfected participants were tested for respiratory microorganisms and 413 HIV-infected for HIV plasma viral load; 7/8 signature scores were higher ( < 0.05) in participants with viral respiratory infections or detectable HIV viraemia than those without.
CONCLUSIONS
Several parsimonious tuberculosis transcriptomic signatures met triage test targets among symptomatic participants, and incipient test targets within 6 months. However, the signatures were upregulated with viral infection and offered poor specificity for diagnosing sub-clinical tuberculosis.
背景
迫切需要敏感的即时护理筛查测试来识别结核病风险最高的个体。我们前瞻性地测试了宿主血液转录组学结核病特征的性能。
方法
从南非五个结核病流行社区招募无结核病嫌疑的成年人。入组时通过微流控逆转录定量聚合酶链反应（RT-qPCR）检测八个简约的宿主血液转录组学结核病特征。在一部分参与者中，用上呼吸道拭子标本通过多重细菌-病毒RT-qPCR检测板进行检测。分别在基线和15个月的主动监测期间，对所有参与者微生物学确诊的现患和新发肺结核的诊断和预后性能进行测试。
结果
在筛查的20207名未感染艾滋病毒和963名感染艾滋病毒的成年人中，2923名和861名被纳入研究。基线时，有61名未感染艾滋病毒者（加权患病率1.1%）和10名感染艾滋病毒者（患病率1.2%）患结核病。与无症状的未感染艾滋病毒参与者（曲线下面积[AUCs]为0.61 - 0.78）相比，简约特征诊断性能在有症状者中更优（AUCs为0.85 - 0.98）。此后，24名未感染艾滋病毒和9名感染艾滋病毒的参与者进展为新发结核病（分别为每100人年1.1例和1.0例）。在未感染艾滋病毒的个体中，6 - 12个月内发生的新发结核病的预后性能相对于15个月更高。对1000名未感染艾滋病毒的参与者进行呼吸道微生物检测，对413名感染艾滋病毒的参与者进行艾滋病毒血浆病毒载量检测；有病毒呼吸道感染或可检测到艾滋病毒病毒血症的参与者中，7/8特征评分高于无上述情况者（P<0.05）。
结论
几个简约的结核病转录组学特征在有症状的参与者中达到了分诊测试目标，以及6个月内的早期测试目标。然而，这些特征在病毒感染时会上调，对诊断亚临床结核病的特异性较差。
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