Background Tuberculosis (TB) remains a significant global health concern. Accurate detection of latent TB infection is crucial for effective control and prevention. We aimed to assess the performance of an interferon-gamma release assay blood test (QuantiFERON-TB Gold Plus [QFT-Plus]) in various clinical contexts and identify conditions that affect its results. Methods We conducted a retrospective analysis of 31 000 QFT-Plus samples collected from 26 000 subjects at a tertiary hospital in South Korea over a 4-year period and compared the rates of positivity and indeterminate results across diverse clinical situations. We also analysed the contribution of the QuantiFERON TB2 tube to the test’s sensitivity and determined optimal cutoff values for 3 hematologic parameters to distinguish false-negative results. These cutoff values were validated in a separate cohort of subjects with microbiologically confirmed subclinical TB. Results Rates of QFT-Plus positivity and indeterminate results were disparate across diagnoses. The TB2 tube increased QFT-Plus sensitivity by 4.1% (95% CI, 1.1%–7.0%) in patients with subclinical TB. Absolute lymphocyte count ≤1.19 × 109/L, absolute neutrophil count ≥5.88 × 109/L, and neutrophil-to-lymphocyte ratio ≥4.33 were effective criteria to discriminate false-negative QFT-Plus results. Application of the hematologic criteria, individually or combined with mitogen response <10 IU/mL, substantially improved performance in the main study cohort and the validation cohort. Conclusions These findings highlight the influence of clinical context and patient hematologic profiles on QFT-Plus results. To minimise neglected latent TB infections due to false-negative QFT-Plus results, serial retesting is advisable in patients with severe lymphopenia or neutrophilia, particularly when the mitogen response is <10 IU/mL.

中文翻译：

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影响结核感染干扰素-γ释放测定血液检测性能的因素的回顾性研究

背景 结核病 (TB) 仍然是一个重大的全球健康问题。准确检测潜伏结核感染对于有效控制和预防至关重要。我们的目的是评估干扰素γ释放测定血液测试（QuantiFERON-TB Gold Plus [QFT-Plus]）在各种临床环境中的性能，并确定影响其结果的条件。方法 我们对 4 年来从韩国一家三级医院的 26 000 名受试者收集的 31 000 个 QFT-Plus 样本进行了回顾性分析，并比较了不同临床情况下的阳性率和不确定结果率。我们还分析了 QuantiFERON TB2 管对测试灵敏度的贡献，并确定了 3 个血液学参数的最佳截止值，以区分假阴性结果。这些临界值在微生物学确诊的亚临床结核病受试者的单独队列中得到验证。结果 QFT-Plus 阳性率和不确定结果的发生率在不同诊断中存在差异。 TB2 管使亚临床结核病患者的 QFT-Plus 敏感性提高了 4.1%（95% CI，1.1%–7.0%）。淋巴细胞绝对计数≤1.19×109/L、中性粒细胞绝对计数≥5.88×109/L、中性粒细胞与淋巴细胞比值≥4.33是区分假阴性QFT-Plus结果的有效标准。单独或与＜10IU/mL的有丝分裂原反应组合应用血液学标准，显着改善了主要研究队列和验证队列中的表现。结论 这些发现强调了临床背景和患者血液学特征对 QFT-Plus 结果的影响。为了尽量减少由于假阴性 QFT-Plus 结果而被忽视的潜伏性结核感染，建议对患有严重淋巴细胞减少或中性粒细胞增多的患者进行系列重新测试，特别是当丝裂原反应＜10 IU/mL 时。