In 2022, an estimated 3.1 million people with tuberculosis (TB) remained undiagnosed [1] despite the global roll-out of rapid molecular tests for Mycobacterium tuberculosis, such as Xpert Ultra and Truenat MTB plus [2]. In pulmonary TB, these tests rely on the availability of a respiratory sample. Sputum induction or invasive sampling are required in sputum-scarce individuals, but often unavailable in resource-limited settings. Moreover, even among spontaneous sputum producers, resource constraints may limit the number of rapid molecular tests for M. tuberculosis that can be performed programmatically. Detecting host immune perturbations in response to M. tuberculosis infection, for example with blood RNA biomarkers, has been proposed as a triage approach to guide further confirmatory testing. Such an approach seeks to reduce the number of confirmatory tests performed, and direct these tests to higher risk individuals. Numerous RNA signatures, comprising quantitation of the expression of one or more genes, have been described with excellent diagnostic performance in their discovery populations.

到 2022 年，尽管全球推出了 Xpert Ultra 和 Truenat MTB plus 等结核分枝杆菌快速分子检测方法，但估计仍有 310 万名结核病 (TB) 患者未被确诊 [1]。对于肺结核，这些测试依赖于呼吸道样本的可用性。痰液稀缺的个体需要进行痰液诱​​导或侵入性采样，但在资源有限的环境中通常无法实现。此外，即使在自发痰产生者中，资源限制也可能限制可以以编程方式进行的结核分枝杆菌快速分子检测的数量。检测宿主对结核分枝杆菌感染的免疫扰动（例如使用血液 RNA 生物标志物）已被提议作为一种分类方法来指导进一步的验证性测试。这种方法旨在减少进行的验证性测试的数量，并将这些测试针对较高风险的个体。许多 RNA 特征（包括一种或多种基因表达的定量）已在其发现群体中被描述为具有出色的诊断性能。