Luxembourg Operational Research Unit, Médecins Sans Frontières, Luxembourg City, Luxembourg; Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Luxembourg Operational Research Unit, Médecins Sans Frontières, Luxembourg City, Luxembourg.
Lancet Infect Dis. 2024 Sep;24(9):1037-1044. doi: 10.1016/S1473-3099(24)00184-1. Epub 2024 May 8.
Lassa fever is a viral haemorrhagic fever with few options for diagnosis and treatment; it is also under-researched with knowledge gaps on its epidemiology. A point-of-care bedside test diagnosing Lassa fever, adhering to REASSURED criteria, is not currently available but is urgently needed in west African regions with high Lassa fever burden. We aimed to assess the validity and feasibility of a rapid diagnostic test (RDT) to confirm Lassa fever in people in Nigeria.
We estimated the diagnostic performance of the ReLASV Pan-Lassa RDT (Zalgen Labs, Frederick, MD, USA) as a research-use-only test, compared to RT-PCR as a reference standard, in 217 participants at a federal tertiary hospital in Abakaliki, Nigeria. We recruited participants between Feb 17, 2022, and April 17, 2023. The RDT was performed using capillary blood at the patient bedside and using plasma at the laboratory. The performance of the test, based on REASSURED criteria, was assessed for user friendliness, rapidity and robustness, sensitivity, and specificity.
Participants were aged between 0 and 85 years, with a median age of 33·0 years (IQR 22·0-44·3), and 24 participants were younger than 18 years. 107 (50%) participants were women and 109 (50%) were men; one participant had missing sex data. Although the specificity of the Pan-Lassa RDT was high (>90%), sensitivity at bedside using capillary blood was estimated as 4% (95% CI 1-14) at 15 min and 10% (3-22) at 25 min, far below the target of 90%. The laboratory-based RDT using plasma showed better sensitivity (46% [32-61] at 15 min and 50% [36-64] at 25 min) but did not reach the target sensitivity. Among the 52 PCR-positive participants with Lassa fever, positive RDT results were associated with lower cycle threshold values (glycoprotein precursor [GPC] gene mean 30·3 [SD 4·3], Large [L] gene mean 32·3 [3·7] vs GPC gene mean 24·5 [3·9], L gene mean 28·0 [3·6]). Personnel conducting the bedside test procedure reported being hindered by the inconvenient use of full personal protective equipment and long waiting procedures before a result could be read.
The Pan-Lassa RDT is not currently recommended as a diagnostic or screening tool for suspected Lassa fever cases. Marked improvement in sensitivity and user friendliness is needed for the RDT to be adopted clinically. There remains an urgent need for better Lassa fever diagnostics to promote safety of in-hospital care and better disease outcomes in low-resource settings.
Médecins Sans Frontières.
拉沙热是一种病毒性出血热，其诊断和治疗方法选择有限；对其流行病学的研究也很少，存在知识空白。目前尚无符合 REASSURED 标准的用于床边诊断拉沙热的即时检测（point-of-care bedside test）设备，但西非拉沙热负担高的地区急需这种设备。本研究旨在评估一种快速诊断检测（RDT）在尼日利亚确认拉沙热的有效性和可行性。
我们在尼日利亚阿巴卡利基联邦三级医院的 217 名参与者中，使用 ReLASV Pan-Lassa RDT（Zalgen Labs，弗雷德里克，MD，美国）作为仅限研究使用的检测方法，与 RT-PCR 作为参考标准进行比较，以评估该 RDT 的诊断性能。我们于 2022 年 2 月 17 日至 2023 年 4 月 17 日期间招募参与者。在患者床边使用毛细血管血，在实验室使用血浆进行 RDT。根据 REASSURED 标准评估该检测的用户友好性、快速性和稳健性、灵敏度和特异性。
参与者年龄在 0 至 85 岁之间，中位数为 33.0 岁（IQR 22.0-44.3），24 名参与者年龄小于 18 岁。107 名（50%）参与者为女性，109 名（50%）为男性，1 名参与者的性别数据缺失。虽然 Pan-Lassa RDT 的特异性很高（>90%），但在 15 分钟时使用毛细血管血的床边检测灵敏度估计为 4%（95%CI 1-14），在 25 分钟时为 10%（3-22），远低于 90%的目标灵敏度。基于血浆的实验室 RDT 显示出更好的灵敏度（15 分钟时为 46%[32-61]，25 分钟时为 50%[36-64]），但仍未达到目标灵敏度。在 52 名拉沙热 PCR 阳性的参与者中，阳性 RDT 结果与较低的循环阈值（糖蛋白前体[GPC]基因平均 30.3[SD 4.3]，大[L]基因平均 32.3[3.7] vs GPC 基因平均 24.5[3.9]，L 基因平均 28.0[3.6]）相关。进行床边检测程序的人员报告说，由于使用完整的个人防护设备不方便，以及在得出结果之前等待程序繁琐，他们的工作受到了阻碍。
Pan-Lassa RDT 目前不推荐作为疑似拉沙热病例的诊断或筛查工具。该 RDT 需要在灵敏度和用户友好性方面有显著提高，才能在临床上得到采用。在资源匮乏的环境中，仍迫切需要更好的拉沙热诊断方法，以促进医院内护理的安全性和更好的疾病结局。
无国界医生组织。
