van Griensven Johan, Edwards Tansy, de Lamballerie Xavier, Semple Malcolm G, Gallian Pierre, Baize Sylvain, Horby Peter W, Raoul Hervé, Magassouba N'Faly, Antierens Annick, Lomas Carolyn, Faye Ousmane, Sall Amadou A, Fransen Katrien, Buyze Jozefien, Ravinetto Raffaella, Tiberghien Pierre, Claeys Yves, De Crop Maaike, Lynen Lutgarde, Bah Elhadj Ibrahima, Smith Peter G, Delamou Alexandre, De Weggheleire Anja, Haba Nyankoye
From the Institute of Tropical Medicine, Antwerp (J.G., K.F., J.B., R.R., Y.C., M.D.C., L.L., A.D.W.), Médecins sans Frontières, Brussels (A.A., C.L.), and the Clinical Pharmacology and Pharmacotherapy Department, Katholieke Universiteit Leuven, Leuven (R.R.) - all in Belgium; Medical Research Council Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London (T.E., P.G.S.), Institute of Translational Medicine and National Institute for Health Research (NIHR) Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool (M.G.S.), and Centre for Tropical Medicine and Global Health, University of Oxford, Oxford (P.W.H.) - all in the United Kingdom; Aix Marseille University (X.L., P.G.), French Institute of Research for Development (X.L.), École des Hautes Études en Santé Publique (X.L.), and Institut Hospitalo-Universitaire Méditerranée Infection (X.L., P.G.), Marseille, Etablissement Français du Sang, La Plaine Saint Denis (P.G., P.T.), Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, Centre International de Recherche en Infectiologie (S.B.), Laboratoire P4 INSERM-Jean Mérieux (H.R.), Lyon, and Université de Franche Comté, Etablissement Français du Sang, INSERM UMR 1098, Besançon (P.T.) - all in France; Laboratory of Viral Hemorrhagic Fever, Gamal Abdel Nasser University of Conakry (N.M.), Service des Maladies Infectieuses et Tropicales de l'Hôpital National Donka, Conakry (E.I.B.), National Blood Transfusion Center (N.H.), Conakry, and National Center for Training and Research in Rural Health of Maferinyah, Forecariah (A.D.) - all in Guinea; and Institut Pasteur de Dakar, Dakar, Senegal (O.F., A.A.S.).
N Engl J Med. 2016 Jan 7;374(1):33-42. doi: 10.1056/NEJMoa1511812.
In the wake of the recent outbreak of Ebola virus disease (EVD) in several African countries, the World Health Organization prioritized the evaluation of treatment with convalescent plasma derived from patients who have recovered from the disease. We evaluated the safety and efficacy of convalescent plasma for the treatment of EVD in Guinea.
In this nonrandomized, comparative study, 99 patients of various ages (including pregnant women) with confirmed EVD received two consecutive transfusions of 200 to 250 ml of ABO-compatible convalescent plasma, with each unit of plasma obtained from a separate convalescent donor. The transfusions were initiated on the day of diagnosis or up to 2 days later. The level of neutralizing antibodies against Ebola virus in the plasma was unknown at the time of administration. The control group was 418 patients who had been treated at the same center during the previous 5 months. The primary outcome was the risk of death during the period from 3 to 16 days after diagnosis with adjustments for age and the baseline cycle-threshold value on polymerase-chain-reaction assay; patients who had died before day 3 were excluded. The clinically important difference was defined as an absolute reduction in mortality of 20 percentage points in the convalescent-plasma group as compared with the control group.
A total of 84 patients who were treated with plasma were included in the primary analysis. At baseline, the convalescent-plasma group had slightly higher cycle-threshold values and a shorter duration of symptoms than did the control group, along with a higher frequency of eye redness and difficulty in swallowing. From day 3 to day 16 after diagnosis, the risk of death was 31% in the convalescent-plasma group and 38% in the control group (risk difference, -7 percentage points; 95% confidence interval [CI], -18 to 4). The difference was reduced after adjustment for age and cycle-threshold value (adjusted risk difference, -3 percentage points; 95% CI, -13 to 8). No serious adverse reactions associated with the use of convalescent plasma were observed.
The transfusion of up to 500 ml of convalescent plasma with unknown levels of neutralizing antibodies in 84 patients with confirmed EVD was not associated with a significant improvement in survival. (Funded by the European Union's Horizon 2020 Research and Innovation Program and others; ClinicalTrials.gov number, NCT02342171.).
在近期几个非洲国家爆发埃博拉病毒病（EVD）之后，世界卫生组织将评估使用从该病康复患者身上获取的恢复期血浆进行治疗列为优先事项。我们评估了恢复期血浆治疗几内亚埃博拉病毒病的安全性和有效性。
在这项非随机对照研究中，99例确诊为埃博拉病毒病的不同年龄段患者（包括孕妇）连续接受两次200至250毫升ABO血型相容的恢复期血浆输注，每单位血浆均来自不同的恢复期供者。输血在诊断当天或诊断后2天内开始。输血时血浆中抗埃博拉病毒中和抗体水平未知。对照组为前5个月在同一中心接受治疗的418例患者。主要结局是诊断后3至16天内的死亡风险，并根据年龄和聚合酶链反应检测的基线循环阈值进行调整；在第3天之前死亡的患者被排除。临床重要差异定义为恢复期血浆组与对照组相比死亡率绝对降低20个百分点。
共有84例接受血浆治疗的患者纳入主要分析。基线时，恢复期血浆组的循环阈值略高于对照组，症状持续时间短于对照组，眼红和吞咽困难的发生率也更高。诊断后第3天至第16天，恢复期血浆组的死亡风险为31%，对照组为38%（风险差异为-7个百分点；95%置信区间[CI]，-18至4）。在根据年龄和循环阈值进行调整后，差异减小（调整后的风险差异为-3个百分点；95%CI，-13至8）。未观察到与使用恢复期血浆相关的严重不良反应。
对84例确诊为埃博拉病毒病的患者输注高达500毫升中和抗体水平未知的恢复期血浆，并未使生存率得到显著改善。（由欧盟“地平线2020”研究与创新计划及其他机构资助；ClinicalTrials.gov编号，NCT02342171。）
