Combination of serological and cytokine release assays for improved diagnosis of childhood tuberculosis in Zambia (PROMISE-TB)

IF 4.8 2区 医学 Q1 INFECTIOUS DISEASES International Journal of Infectious Diseases Pub Date : 2024-09-26 DOI:10.1016/j.ijid.2024.107248
Edouard Tuaillon , Mwiya Mwyia , Karine Bollore , Amandine Pisoni , Pierre-Alain Rubbo , Matthias Richard , Laurent Kremer , Maria M.W. Tonga , Duncan Chanda , Marianne Peries , Roselyne Vallo , Sabrina Eymard-Duvernay , Morgana D'Ottavi , Chipepo Kankasa , Philippe Van de Perre , Jean-Pierre Moles , Nicolas Nagot
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Abstract

Objectives

The diagnostic gaps for childhood tuberculosis (TB) remain considerable in settings with high TB incidence and resource constraints. We established and evaluated the performance of a scoring system based on a combination of serological tests and T-cell cytokine release assays, chosen for their ability to detect immune responses indicative of TB, in a context of high prevalence of pediatric HIV infection.

Methods

We enrolled 628 consecutive children aged ≤15 years, admitted for TB suspicion. Multiple cytokine levels in QuantiFERON Gold In-Tube supernatants and antigen 85B (Ag85B) antibodies were assessed in children who tested positive with either Xpert TB or mycobacterial culture. The results were compared with those of control children.

Results

Among the biomarkers most strongly associated with TB, random forest classification analysis selected Ag85B antibodies, interleukin-2/interferon-γ ratio, and monokine induced by interferon-γ for the scoring system. The receiver operating characteristic curve derived from our scoring system showed an area under the curve of 0.95 (0.91-0.99), yielding 91% sensitivity and 88% specificity. The internal bootstrap validation gave the following 95% confidence intervals for the score performance: sensitivity 71%-97% and specificity 79%-99%.

Conclusions

This study suggests that supplementing the QuantiFERON assay with a combination of serological and T-cell markers could enhance childhood TB screening regardless of HIV status and age. Further validation among the target population is necessary to confirm the performance of this scoring system.

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结合血清学和细胞因子释放测定改进赞比亚儿童结核病诊断(PROMISE-TB)。
背景:在结核病高发和资源紧张的环境中,儿童结核病(TB)的诊断差距仍然很大。我们建立并评估了基于血清学检测和 T 细胞细胞因子释放检测组合的评分系统的性能:我们连续招募了 628 名年龄小于 15 岁、因怀疑患有肺结核而入院的儿童。对经 Xpert TB 或分枝杆菌培养检测呈阳性的儿童,评估了 QuantiFERON Gold 管内上清液中的多种细胞因子水平和抗原 85B 抗体(Ag85B Abs)。结果与对照组儿童进行了比较:结果:在与肺结核关系最密切的生物标志物中,随机森林分类分析选择 Ag85B 抗体、IL2/IFN-γ 比率和 MIG 作为评分系统。根据我们的评分系统得出的 ROC 曲线显示,AUC 为 0.95(0.91-0.99),灵敏度为 91%,特异度为 88%。内部自举验证给出了评分结果的 95% 置信区间:灵敏度 71-97%,特异度 79-99%:这项研究表明,无论 HIV 感染状况和年龄如何,将 QuantiFERON 检测与血清学标记物和 T 细胞标记物相结合可提高儿童结核病筛查的效果。有必要在目标人群中进行进一步验证,以确认该评分系统的性能。
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来源期刊
CiteScore
18.90
自引率
2.40%
发文量
1020
审稿时长
30 days
期刊介绍: International Journal of Infectious Diseases (IJID) Publisher: International Society for Infectious Diseases Publication Frequency: Monthly Type: Peer-reviewed, Open Access Scope: Publishes original clinical and laboratory-based research. Reports clinical trials, reviews, and some case reports. Focuses on epidemiology, clinical diagnosis, treatment, and control of infectious diseases. Emphasizes diseases common in under-resourced countries.
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