Amofa-Sekyi Modupe, Schaap Ab, Mureithi Linda, Kosloff Barry, Cheeba Maina, Kangololo Bxyn, Vermaak Redwaan, Paulsen Robynn, Ruperez Maria, Floyd Sian, de Haas Petra, Fidler Sarah, Hayes Richard, Ayles Helen, Shanaube Kwame
Zambart, Lusaka, Zambia.
London School of Hygiene & Tropical Medicine, London, United Kingdom.
PLOS Glob Public Health. 2024 May 20;4(5):e0003182. doi: 10.1371/journal.pgph.0003182. eCollection 2024.
One quarter of the world's population is estimated to be infected with Mycobacterium tuberculosis. Identifying recent TB infection (TBI) offers an avenue to targeted TB preventative therapy provision, and prevention to disease progression. However, detecting recent TBI remains challenging. The QuantiFERON-TB Gold Plus assay (QFT-Plus) claims to have improved sensitivity in detecting recent TBI, by the addition of the TB2 antigen tube to the TB1 tube used in previous tests. TB2 detects CD8-mediated interferon gamma response, a potential marker of recent infection. We compared QFT-Plus TB1 and TB2 responses in individuals with recent and remote infection in high-burden settings. The Tuberculosis Reduction through Expanded Antiretroviral Treatment and TB Screening (TREATS) Project followed a cohort of adolescents and young people (AYP) aged 15-24 years in Zambia and South Africa to determine TBI incidence measured by QFT-Plus over 24 months. We categorised individuals with QTF-Plus positive result into recent and remote infection. We compared their TB1 and TB2 responses and the antigen tube differential [TB2-TB1], an indicator of CD8-activity, using logistic regression. At baseline, 3876 AYP, 1852/3876 (47.8%) were QFT-Plus positive whilst 2024/3876 (52.2%) QFT-Plus negative. Of the QFT-Plus baseline positives, 1069/1852 (57.7%) tested positive at both 12 and 24 months-remote infection. Of the QFT-Plus baseline negatives, 274/2024(13.3%) converted within a 12-month period- recent infection. TB1 and TB2 responses were higher in remote than recent infection. In recent infection, TB2 responses were greater than TB1 responses. The mean differential was 0.01 IU/ml in recent and -0.22 IU/ml in remote infection, (p = 0.145). The quantitative QFT-Plus results did not appear to reflect a marked distinction between recent and remote infection. Further analysis of the responses of infected individuals who developed disease is required to determine whether any signal in QFT-Plus results may predict progression to disease.
据估计，世界四分之一的人口感染了结核分枝杆菌。识别近期结核感染（TBI）为提供有针对性的结核预防性治疗以及预防疾病进展提供了一条途径。然而，检测近期TBI仍然具有挑战性。结核感染T细胞检测金标加强版检测（QFT-Plus）声称，通过在先前测试中使用的TB1管中添加TB2抗原管，在检测近期TBI方面提高了灵敏度。TB2检测CD8介导的干扰素γ反应，这是近期感染的一个潜在标志物。我们比较了高负担地区近期和既往感染个体的QFT-Plus TB1和TB2反应。通过扩大抗逆转录病毒治疗和结核筛查减少结核病（TREATS）项目对赞比亚和南非15至24岁的青少年和年轻人（AYP）队列进行了为期24个月的随访，以确定通过QFT-Plus测量的TBI发病率。我们将QTF-Plus检测结果呈阳性的个体分为近期感染和既往感染。我们使用逻辑回归比较了他们的TB1和TB2反应以及抗原管差异[TB2 - TB1]，这是CD8活性的一个指标。在基线时，3876名AYP中，1852/3876（47.8%）的QFT-Plus检测结果为阳性，而2024/3876（52.2%）的QFT-Plus检测结果为阴性。在QFT-Plus基线检测呈阳性的个体中，1069/1852（57.7%）在12个月和24个月时检测均为阳性——既往感染。在QFT-Plus基线检测呈阴性的个体中，274/2024（13.3%）在12个月内发生了转变——近期感染。既往感染的TB1和TB反应高于近期感染。在近期感染中，TB2反应大于TB1反应。近期感染的平均差异为0.01 IU/ml，既往感染为 -0.22 IU/ml，（p = 0.145）。QFT-Plus的定量结果似乎并未反映出近期感染和既往感染之间的明显差异。需要对发病的感染个体的反应进行进一步分析，以确定QFT-Plus结果中的任何信号是否可以预测疾病进展。
