Mulenga Humphrey, Fiore-Gartland Andrew, Mendelsohn Simon C, Penn-Nicholson Adam, Mbandi Stanley Kimbung, Nemes Elisa, Borate Bhavesh, Musvosvi Munyaradzi, Tameris Michèle, Walzl Gerhard, Naidoo Kogieleum, Churchyard Gavin, Scriba Thomas J, Hatherill Mark
South African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Anzio Road, Observatory 7925, South Africa.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Fairview Ave. N., Seattle, WA 98109-1024, USA.
EClinicalMedicine. 2022 Apr 21;47:101396. doi: 10.1016/j.eclinm.2022.101396. eCollection 2022 May.
We evaluated the diagnostic and prognostic performance of a transcriptomic signature of tuberculosis (TB) risk (RISK11) and QuantiFERON-TB Gold-plus (QFTPlus) as combination biomarkers of TB risk.
Healthy South Africans who were HIV-negative aged 18-60 years with baseline RISK11 and QFTPlus results were evaluated in a prospective cohort study conducted between Sept 20, 2016 and Dec 20, 2019. Prevalence and incidence-rate ratios were used to evaluate risk of TB. Positive (LR+) and negative (LR-) likelihood ratios were used to compare individual tests versus Both-Positive (RISK11+/QFTPlus+) and Either-Positive (RISK11+ or QFTPlus+) combinations.
Among 2912 participants, prevalent TB in RISK11+/QFTPlus+ participants was 13·3-fold (95% CI 4·2-42·7) higher than RISK11-/QFTPlus-; 2·4-fold (95% CI 1·2-4·8) higher than RISK11+/QFTPlus-; and 4·5-fold (95% CI 2·5-8·0) higher than RISK11-/QFTPlus+ participants. Risk of incident TB in RISK11+/QFTPlus+ participants was 8·3-fold (95% CI 2·5-27·0) higher than RISK11-/QFTPlus-; 2·5-fold (95% CI 1·0-6·6) higher than RISK11+/QFTPlus-; and 2·1-fold (95% CI 1·2-3·4) higher than RISK11-/QFTPlus+ participants, respectively. Compared to QFTPlus, the Both-Positive test combination increased diagnostic LR+ from 1·3 (95% CI 1·2-1·5) to 4·7 (95% CI 3·2-7·0), and prognostic LR+ from 1·4 (95% CI 1·2-1·5) to 2·8 (95% CI 1·5-5·1), but did not improve upon RISK11 alone. Compared with RISK11, the Either-Positive test combination decreased diagnostic LR- from 0·7 (95% CI 0·6-0·9) to 0·3 (95% CI 0·2-0·6), and prognostic LR- from 0·9 (95% CI 0·8-1·0) to 0·3 (0·1-0·7), but did not improve upon QFTPlus alone.
Combining two tests such as RISK11 and QFTPlus, with discordant individual performance characteristics does not improve overall discriminatory performance, relative to the individual tests.
Bill and Melinda Gates Foundation, South African Medical Research Council.
我们评估了结核病（TB）风险的转录组特征（RISK11）和结核感染T细胞检测升级版（QFTPlus）作为结核病风险联合生物标志物的诊断和预后性能。
在2016年9月20日至2019年12月20日进行的一项前瞻性队列研究中，对18 - 60岁、HIV阴性且有基线RISK11和QFTPlus检测结果的健康南非人进行了评估。患病率和发病率比用于评估结核病风险。阳性（LR +）和阴性（LR -）似然比用于比较单项检测与双阳性（RISK11 + /QFTPlus +）和任一阳性（RISK11 +或QFTPlus +）组合。
在2912名参与者中，RISK11 + /QFTPlus +参与者的结核病患病率比RISK11 - /QFTPlus -参与者高13.3倍（95%CI 4.2 - 42.7）；比RISK11 + /QFTPlus -参与者高2.4倍（95%CI 1.2 - 4.8）；比RISK11 - /QFTPlus +参与者高4.5倍（95%CI 2.5 - 8.0）。RISK11 + /QFTPlus +参与者的结核病发病风险比RISK11 - /QFTPlus -参与者高8.3倍（95%CI 2.5 - 27.0）；比RISK11 + /QFTPlus -参与者高2.5倍（95%CI 1.0 - 6.6）；比RISK11 - /QFTPlus +参与者高2.1倍（95%CI 1.2 - 3.4）。与QFTPlus相比，双阳性检测组合使诊断LR +从1.3（95%CI 1.2 - 1.5）提高到4.7（95%CI 3.2 - 7.0），预后LR +从1.4（95%CI 1.2 - 1.5）提高到2.8（95%CI 1.5 - 5.1），但单独使用RISK11时没有改善。与RISK11相比，任一阳性检测组合使诊断LR -从0.7（95%CI 0.6 - 0.9）降低到0.3（95%CI 0.2 - 0.6），预后LR -从0.9（95%CI ）降低到0.3（0.1 - 0.7），但单独使用QFTPlus时没有改善。
相对于单项检测，将RISK11和QFTPlus等两项具有不一致个体性能特征的检测组合起来并不能提高整体鉴别性能。
比尔及梅琳达·盖茨基金会、南非医学研究理事会。
