Department of Virology, Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo; Service of Microbiology, Department of Medical Biology, Kinshasa University Hospital, University of Kinshasa, Kinshasa, Democratic Republic of the Congo; Rodolphe Mérieux Institut National de Recherche Biomédicale-Goma Laboratory, Goma, Democratic Republic of the Congo.
Department of Virology, Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo; Service of Microbiology, Department of Medical Biology, Kinshasa University Hospital, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.
Lancet Microbe. 2024 Oct;5(10):100905. doi: 10.1016/S2666-5247(24)00137-X. Epub 2024 Sep 3.
During the 2018-20 Ebola virus disease outbreak in the Democratic Republic of the Congo, thousands of patients received unprecedented vaccination, monoclonal antibody (mAb) therapy, or both, leading to a large number of survivors. We aimed to report the clinical, virological, viral genomic, and immunological features of two previously vaccinated and mAb-treated survivors of Ebola virus disease in the Democratic Republic of the Congo who developed second episodes of disease months after initial discharge, ultimately complicated by fatal meningoencephalitis associated with viral persistence.
In this case report study, we describe the presentation, management, and subsequent investigations of two patients who developed recrudescent Ebola virus disease and subsequent fatal meningoencephalitis. We obtained data from epidemiological databases, Ebola treatment units, survivor programme databases, laboratory datasets, and hospital records. Following national protocols established during the 2018-20 outbreak in the Democratic Republic of the Congo, blood, plasma, and cerebrospinal fluid (CSF) samples were collected during the first and second episodes of Ebola virus disease from both individuals and were analysed by molecular (quantitative RT-PCR and next-generation sequencing) and serological (IgG and IgM ELISA and Luminex assays) techniques.
The total time between the end of the first Ebola virus episode and the onset of the second episode was 342 days for patient 1 and 137 days for patient 2. In both patients, Ebola virus RNA was detected in blood and CSF samples during the second episode of disease. Complete genomes from CSF samples from this relapse episode showed phylogenetic relatedness to the genome sequenced from blood samples collected from the initial infection, confirming in-host persistence of Ebola virus. Serological analysis showed an antigen-specific humoral response with typical IgM and IgG kinetics in patient 1, but an absence of an endogenous adaptive immune response in patient 2.
We report the first two cases of fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease who had received vaccination and mAb-based treatment in the Democratic Republic of the Congo. Our findings highlight the importance of long-term monitoring of survivors, including continued clinical, virological, and immunological profiling, as well as the urgent need for novel therapeutic strategies to prevent and mitigate the individual and public health consequences of Ebola virus persistence.
Ministry of Health of the Democratic Republic of the Congo, Institut National de Recherche Biomédicale, Infectious Disease Rapid Response Reserve Fund, US Centers for Disease Control and Prevention, US National Cancer Institute (National Institutes of Health), French National Research Institute for Development, and WHO.
在 2018-20 年刚果民主共和国爆发的埃博拉病毒病疫情期间，数千名患者接受了前所未有的疫苗接种、单克隆抗体（mAb）治疗或两者兼施，导致大量幸存者。我们旨在报告在刚果民主共和国，两名先前接受过疫苗接种和 mAb 治疗的埃博拉病毒病幸存者在最初出院数月后出现第二波疾病，最终并发致命性脑膜脑炎，与病毒持续存在有关。
在本病例报告研究中，我们描述了两名患者的表现、治疗和随后的调查，这两名患者在埃博拉病毒病首次发作后数月发生复发性疾病，并随后发生致命性脑膜脑炎。我们从流行病学数据库、埃博拉治疗单位、幸存者计划数据库、实验室数据集和医院记录中获取数据。根据 2018-20 年刚果民主共和国疫情期间制定的国家方案，从这两个人中采集了在埃博拉病毒病的第一和第二波发作期间的血液、血浆和脑脊液（CSF）样本，并通过分子（定量 RT-PCR 和下一代测序）和血清学（IgG 和 IgM ELISA 和 Luminex 检测）技术进行分析。
患者 1 的第一波埃博拉病毒病发作结束与第二波发作开始之间的总时间为 342 天，患者 2 为 137 天。在这两名患者中，在第二波疾病期间均在血液和 CSF 样本中检测到埃博拉病毒 RNA。来自该复发发作 CSF 样本的完整基因组与从最初感染采集的血液样本中测序的基因组显示出系统发育关系，证实了埃博拉病毒在宿主内的持续存在。血清学分析显示患者 1 存在抗原特异性体液免疫反应，具有典型的 IgM 和 IgG 动力学，但患者 2 不存在内源性适应性免疫反应。
我们报告了在刚果民主共和国接受埃博拉病毒疫苗接种和 mAb 治疗的两名埃博拉病毒病幸存者中，首例与埃博拉病毒持续存在相关的致命性脑膜脑炎。我们的研究结果强调了对幸存者进行长期监测的重要性，包括持续的临床、病毒学和免疫学分析，以及迫切需要新的治疗策略，以预防和减轻埃博拉病毒持续存在对个人和公共卫生的影响。
刚果民主共和国卫生部、国家生物医学研究所、传染病快速反应储备基金、美国疾病控制与预防中心、美国国家癌症研究所（美国国立卫生研究院）、法国国家发展研究所以及世界卫生组织。
