Background An accurate, rapid, non-sputum-based triage test for diagnosing tuberculosis (TB) is needed. Methods A prospective evaluation of the Cepheid GeneXpert Mycobacterium tuberculosis Host Response cartridge (Xpert-MTB-HR), a prototype blood-based host response mRNA signature assay, among individuals presenting with TB-like symptoms was performed in Pakistan and results were compared to 3 reference standards: Xpert MTB/RIF Ultra, bacteriological confirmation (Xpert MTB/RIF Ultra and/or culture positivity), and composite clinical diagnosis (clinician diagnosis, treatment initiation, Xpert MTB/RIF Ultra, and/or culture positivity). Analyses were conducted both for the entire study cohort and separately in the adolescent and young adult cohort (aged 10–24 years). Results A total of 497 participants, aged 6–83 years, returned valid Xpert-MTB-HR results. When a diagnostic threshold was set for a sensitivity of >90%, specificity was 32% (95% confidence interval [CI], 28%–37%) compared to Xpert MTB/RIF Ultra, 29% (95% CI, 25%–34%) compared to a bacteriological confirmation, and 22% (95% CI, 18%–26%) compared to a composite clinical diagnosis. However, when evaluating only the adolescent and young adult cohort with a diagnostic threshold set for sensitivity of >90%, specificity was 82% (95% CI, 74%–89%) compared to Xpert MTB/RIF Ultra, 84% (95% CI, 75%–90%) compared to a bacteriological confirmation, and 54% (95% CI, 44%–64%) compared to a composite clinical diagnosis. Conclusions While the Xpert-MTB-HR does not meet World Health Organization minimum criteria in the general population, in our study it does meet the minimum sensitivity and specificity requirements for a non-sputum-based triage test among adolescents and young adults when compared to Xpert MTB/RIF Ultra or bacteriological confirmation.

中文翻译：

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Cepheid Xpert 结核分枝杆菌宿主反应盒的前瞻性探索性评估：以青少年和年轻人为重点


背景 需要一种准确、快速、非基于痰液的分诊测试来诊断结核病 （TB）。方法 在巴基斯坦对 Cepheid GeneXpert 结核分枝杆菌宿主反应盒 （Xpert-MTB-HR） 进行了前瞻性评估，这是一种原型基于血液的宿主反应 mRNA 特征测定，在出现 TB 样症状的个体中，并将结果与 3 个参考标准进行比较：Xpert MTB/RIF Ultra、细菌学确认（Xpert MTB/RIF Ultra 和/或培养阳性）和复合临床诊断（临床医生诊断、 治疗开始、Xpert MTB/RIF Ultra 和/或培养阳性）。对整个研究队列以及青少年和年轻成人队列 （10-24 岁） 分别进行了分析。结果 共有 497 名年龄在 6-83 岁之间的参与者返回了有效的 Xpert-MTB-HR 结果。当诊断阈值设置为 >90% 的敏感性时，与 Xpert MTB/RIF Ultra 相比，特异性为 32%（95% 置信区间 [CI]，28%-37%），与细菌学确认相比为 29%（95% CI，25%-34%），与复合临床诊断相比为 22%（95% CI，18%-26%）。然而，当仅评估诊断阈值设置为 >90% 的青少年和年轻成人队列时，与 Xpert MTB/RIF Ultra 相比，特异性为 82%（95% CI，74%-89%），与细菌学确认相比为 84%（95% CI，75%-90%），与复合临床诊断相比为 54%（95% CI，44%-64%）。 结论虽然 Xpert-MTB-HR 在普通人群中不符合世界卫生组织的最低标准，但在我们的研究中，与 Xpert MTB/RIF Ultra 或细菌学确认相比，它确实满足了青少年和年轻人非基于痰液的分诊测试的最低灵敏度和特异性要求。