Department of Haematology, University of Cambridge, Cambridge, UK.
Department of Clinical Microbiology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Lancet. 2016 Apr 23;387(10029):1753-61. doi: 10.1016/S0140-6736(16)00581-X.
Transfusion-transmitted malaria is a frequent but neglected adverse event in Ghana. We did a randomised controlled clinical trial to assess the efficacy and safety of a whole blood pathogen reduction technology at preventing transfusion transmission of Plasmodium spp parasites.
For this randomised, double-blind, parallel-group clinical trial, eligible adult patients (aged ≥ 18 years) with blood group O+, who required up to two whole blood unit transfusions within 3 days of randomisation and were anticipated to remain in hospital for at least 3 consecutive days after initial transfusion, were enrolled from Komfo Anokye Teaching Hospital in Kumasi, Ghana. The main exclusion criteria were symptoms of clinical malaria, antimalaria treatment within 7 days before randomisation, fever, and haemorrhage expected to require transfusion with up to two units of whole blood during the 3 days following study entry. Eligible patients were randomly assigned 1:1 by computer-generated permuted block randomisation (block size four) list to receive transfusion with either pathogen-reduced whole blood (treated) or whole blood prepared and transfused by standard local practice (untreated). Patients, health-care providers, and data collectors were masked to treatment allocation. Patients in both groups received up to two whole blood unit transfusions that were retrospectively tested for parasitaemia. Pre-transfusion and post-transfusion blood samples (taken on days 0, 1, 3, 7, and 28) were tested for presence and amount of parasite genome, and assessed for haematological and biochemical parameters. The primary endpoint was the incidence of transfusion-transmitted malaria in non-parasitaemic recipients exposed to parasitaemic whole blood, defined as two consecutive parasitaemic post-transfusion samples with parasite allelic matching, assessed at 1-7 days after transfusion. Secondary endpoints included haematological parameters and a safety analysis of adverse events in patients. This study is registered with ClinicalTrials.gov, number NCT02118428, and with the Pan African Clinical Trials Registry, number PACTR201406000777310.
Between March 12, 2014, and Nov 7, 2014, 227 patients were enrolled into the study, one of whom was subsequently excluded because she did not meet the inclusion criteria. Of the 226 randomised patients, 113 were allocated to receive treated whole blood and 113 to receive standard untreated whole blood. 223 patients (111 treated and 112 untreated) received study-related transfusions, whereas three patients (two treated and one untreated) did not. 214 patients (107 treated and 107 untreated) completed the protocol as planned and comprised the per-protocol population. Overall, 65 non-parasitaemic patients (28 treated and 37 untreated) were exposed to parasitaemic blood. The incidence of transfusion-transmitted malaria was significantly lower for the pathogen-reduced (treated) patients (1 [4%] of 28 patients) than the untreated group (8 [22%] of 37 patients) in this population (p=0.039). Overall, 92 (41%) of 223 patients reported 145 treatment-related emergent adverse events during the conduct of the study, with a similar incidence of adverse events between groups receiving untreated or treated whole blood. No transfusion-related deaths occurred in the trial.
Treatment of whole blood with the Mirasol pathogen reduction system for whole blood reduced the incidence of transfusion-transmitted malaria. The primary endpoint of the study was achieved in the population of non-parasitaemic patients receiving parasitaemic whole blood. The safety profile and clinical outcomes were similar across the two treatment groups.
Terumo BCT Inc.
在加纳，输血传播疟疾是一种常见但被忽视的不良事件。我们进行了一项随机对照临床试验，以评估全血病原体减少技术在预防疟原虫属寄生虫输血传播方面的疗效和安全性。
这项随机、双盲、平行组临床试验纳入了加纳库马西科福阿南奥耶教学医院符合条件的成年患者（年龄≥18 岁），这些患者在随机分组后 3 天内需要接受多达 2 个全血单位输血，预计在初始输血后至少连续 3 天住院。主要排除标准为有临床疟疾症状、在随机分组前 7 天内接受抗疟治疗、发热以及预计在研究入组后 3 天内需要用多达 2 个全血单位输血来治疗出血。符合条件的患者通过计算机生成的随机化（区组大小为 4）列表按 1:1 随机分组，分别接受病原体减少的全血（处理组）或按照标准当地实践准备和输注的全血（未处理组）输血。患者、医护人员和数据收集人员对治疗分配情况设盲。两组患者均接受多达 2 个全血单位输血，输血后对寄生虫血症进行回顾性检测。在输血前（第 0 天）和输血后（第 1、3、7 和 28 天）采集血样，检测寄生虫载量和寄生虫基因组的存在和数量，并评估血液学和生化参数。主要终点是在非寄生虫血症患者中暴露于寄生虫血症全血后的输血传播疟疾的发生率，定义为在输血后 1-7 天内连续两次寄生虫血症输血后样本中寄生虫等位基因匹配，评估方法为 227 例患者于 2014 年 3 月 12 日至 2014 年 11 月 7 日入组研究，其中 1 例因不符合纳入标准而被排除。226 例随机分组的患者中，113 例被分配接受处理过的全血，113 例接受标准的未处理的全血。223 例患者（处理组 111 例，未处理组 112 例）接受了与研究相关的输血，而 3 例患者（处理组 2 例，未处理组 1 例）未接受输血。214 例患者（处理组 107 例，未处理组 107 例）按计划完成了方案，构成了符合方案人群。共有 65 例非寄生虫血症患者（处理组 28 例，未处理组 37 例）暴露于寄生虫血症血液中。在该人群中，处理组（28 例中的 1 例）输血传播疟疾的发生率明显低于未处理组（37 例中的 8 例）（p=0.039）。在研究过程中，223 例患者中有 92 例（41%）报告了 145 例与治疗相关的紧急不良事件，处理组和未处理组的不良事件发生率相似。试验中没有与输血相关的死亡事件发生。
用 Mirasol 病原体减少系统处理全血可降低输血传播疟疾的发生率。在接受寄生虫血症全血的非寄生虫血症患者人群中达到了研究的主要终点。两组治疗组的安全性和临床结局相似。
泰尔茂 BCT 公司。
