在刚果民主共和国东部疫情中，比较四种埃博拉病毒病快速诊断检测与 GeneXpert® 的诊断准确性：一项前瞻性观察研究。

Head-to-head comparison of diagnostic accuracy of four Ebola virus disease rapid diagnostic tests versus GeneXpert® in eastern Democratic Republic of the Congo outbreaks: a prospective observational study.

机构信息

Institut National de Recherche Biomédicale, INRB, Kinshasa, Democratic Republic of the Congo; Rodolphe Mérieux INRB-Goma Laboratory, Goma, North Kivu, Democratic Republic of the Congo; Service de Microbiologie, Departement de Biologie Médicale, Cliniques Universitaires de Kinshasa, Université de Kinshasa, Democratic Republic of the Congo.

Institut National de Recherche Biomédicale, INRB, Kinshasa, Democratic Republic of the Congo; Service de Microbiologie, Departement de Biologie Médicale, Cliniques Universitaires de Kinshasa, Université de Kinshasa, Democratic Republic of the Congo.

出版信息

EBioMedicine. 2023 May;91:104568. doi: 10.1016/j.ebiom.2023.104568. Epub 2023 Apr 19.

DOI:10.1016/j.ebiom.2023.104568

PMID:37084479

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10148093/

Abstract

BACKGROUND

Ebola virus disease (EVD) outbreaks have emerged in Central and West Africa. EVD diagnosis relies principally on RT-PCR testing with GeneXpert®, which has logistical and cost restrictions at the peripheral level of the health system. Rapid diagnostic tests (RDTs) would offer a valuable alternative at the point-of-care to reduce the turn-around time, if they show good performance characteristics. We evaluated the performance of four EVD RDTs against the reference standard GeneXpert® on stored EVD positive and negative blood samples collected between 2018 and 2021 from outbreaks in eastern Democratic Republic of the Congo (DRC).

METHODS

We conducted a prospective and observational study in the laboratory on QuickNavi-Ebola™, OraQuick® Ebola Rapid Antigen, Coris® EBOLA Ag K-SeT, and Standard® Q Ebola Zaïre Ag RDTs using left-over archived frozen EDTA whole blood samples. We randomly selected 450 positive and 450 negative samples from the EVD biorepositories in DRC, across a range of GeneXpert® cycle threshold values (Ct-values). RDT results were read by three persons and we considered an RDT result as "positive", when it was flagged as positive by at least two out of the three readers. We estimated the sensitivity and specificity through two independent generalized (logistic) linear mixed models (GLMM).

FINDINGS

476 (53%) of 900 samples had a positive GeneXpert Ebola result when retested. The QuickNavi-Ebola™ showed a sensitivity of 56.8% (95% CI 53.6-60.0) and a specificity of 97.5% (95% CI 96.2-98.4), the OraQuick® Ebola Rapid Antigen test displayed 61.6% (95% CI 57.0-65.9) sensitivity and 98.1% (95% CI 96.2-99.1) specificity, the Coris® EBOLA Ag K-SeT showed 25.0% (95% CI 22.3-27.9) sensitivity and 95.9% (95% CI 94.2-97.1) specificity, and the Standard® Q Ebola Zaïre Ag displayed 21.6% (95% CI 18.1-25.7) sensitivity and 99.1% (95% CI 97.4-99.7) specificity.

INTERPRETATION

None of the RDTs evaluated approached the "desired or acceptable levels" for sensitivity set out in the WHO target product profile, while all of the tests met the "desired level" for specificity. Nevertheless, the QuickNavi-Ebola™ and OraQuick® Ebola Rapid Antigen Test demonstrated the most favorable profiles, and may be used as frontline tests for triage of suspected-cases while waiting for RT-qPCR confirmatory testing.

FUNDING

Institute of Tropical Medicine Antwerp/EDCTP PEAU-EBOV-RDC project.

摘要

背景

埃博拉病毒病（EVD）疫情在中非和西非爆发。EVD 的诊断主要依赖于 GeneXpert®的 RT-PCR 检测，但这种检测在卫生系统的基层存在后勤和成本限制。如果快速诊断检测（RDT）能够表现出良好的性能特征，那么它们将在即时护理点提供有价值的替代方案，以缩短周转时间。我们评估了四种 EVD RDT 在存储的 EVD 阳性和阴性血液样本上的性能，这些样本是 2018 年至 2021 年期间在刚果民主共和国东部爆发期间采集的，使用的是 GeneXpert®作为参考标准。

方法

我们在实验室中对 QuickNavi-Ebola™、OraQuick® Ebola Rapid Antigen、Coris® EBOLA Ag K-SeT 和 Standard® Q Ebola Zaïre Ag RDT 进行了前瞻性和观察性研究，使用的是来自刚果民主共和国 EVD 生物库的剩余冷冻 EDTA 全血样本。我们从 EVD 生物库中随机选择了 450 份阳性和 450 份阴性样本，涵盖了一系列 GeneXpert®循环阈值（Ct 值）。RDT 结果由三人读取，当至少有两位读者标记为阳性时，我们认为 RDT 结果为“阳性”。我们通过两个独立的广义（逻辑）线性混合模型（GLMM）来估计敏感性和特异性。

结果

当重新测试时，900 份样本中有 476 份（53%）GeneXpert Ebola 结果为阳性。QuickNavi-Ebola™ 的敏感性为 56.8%（95%CI 53.6-60.0），特异性为 97.5%（95%CI 96.2-98.4），OraQuick® Ebola Rapid Antigen 测试的敏感性为 61.6%（95%CI 57.0-65.9），特异性为 98.1%（95%CI 96.2-99.1），Coris® EBOLA Ag K-SeT 的敏感性为 25.0%（95%CI 22.3-27.9），特异性为 95.9%（95%CI 94.2-97.1），Standard® Q Ebola Zaïre Ag 的敏感性为 21.6%（95%CI 18.1-25.7），特异性为 99.1%（95%CI 97.4-99.7）。

结论

评估的 RDT 都没有达到世界卫生组织目标产品概况中规定的敏感性“理想或可接受水平”，而所有测试都达到了特异性的“理想水平”。然而，QuickNavi-Ebola™和 OraQuick® Ebola Rapid Antigen Test 表现出了最有利的特征，因此可以在等待 RT-qPCR 确认性检测时，作为疑似病例的一线筛查试验使用。