UMR7245 MCAM, Muséum National d'Histoire Naturelle, Team PPL, CNRS, Paris, France.
Cerus Corporation, Concord, California, USA.
Transfusion. 2022 May;62(5):1073-1083. doi: 10.1111/trf.16867. Epub 2022 Apr 6.
Plasmodium falciparum is the parasite responsible for most malaria cases globally. The risk of transfusion-transmitted malaria (TTM) is mitigated by donor deferrals and blood screening strategies, which adversely impact blood availability. Previous studies showed robust inactivation of P. falciparum using nucleic acid-targeting pathogen reduction technologies (PRT) for the treatment of plasma and platelet components or whole blood (WB). The efficacy of the amustaline-glutathione (GSH) PRT to inactivate P. falciparum is here evaluated in red blood cells (RBC), as well the impact of PRT on parasite loads, stages, and strains.
RBC units resuspended in AS-1 or AS-5 additive solutions were spiked with ring stage-infected RBC and treated with the amustaline-GSH PRT. Parasite loads and viability were measured in samples at the time of contamination, and after treatment, using serial 10-fold dilutions of the samples in RBC cultures maintained for up to 4 weeks.
P. falciparum viability assays allow for the detection of very low levels of parasite. Initial parasite titer was >5.2 log /ml in AS-1/5 RBC. No infectious parasites were detected in amustaline-GSH-treated samples after 4 weeks of culture. Amustaline-GSH inactivated high parasite loads regardless of parasite stages and strains. Amustaline readily penetrates the parasite, irreversibly blocks development, and leads to parasite death and expulsion from RBC.
Amustaline-GSH PRT demonstrated robust efficacy to inactivate malaria parasites in RBC concentrates. This study completes the portfolio of studies demonstrating the efficacy of nucleic acid-targeting PRTs to mitigate TTM risks as previously reported for platelet concentrates, plasma, and WB.
恶性疟原虫是全球大多数疟疾病例的寄生虫。通过献血者延期和血液筛查策略，可以降低输血传播疟疾（TTM）的风险，但这会对血液供应产生不利影响。以前的研究表明，核酸靶向病原体减少技术（PRT）可有效灭活恶性疟原虫，用于治疗血浆和血小板成分或全血（WB）。本研究评估了氨丁三醇-谷胱甘肽（GSH）PRT 在红细胞（RBC）中对恶性疟原虫的灭活效果，以及 PRT 对寄生虫负荷、阶段和株的影响。
将悬浮在 AS-1 或 AS-5 添加剂溶液中的 RBC 单位与环状期感染的 RBC 混合，并使用氨丁三醇-GSH PRT 处理。在污染时和处理后，通过对样本进行连续 10 倍稀释，在 RBC 培养物中测量寄生虫负荷和活力，培养时间长达 4 周。
恶性疟原虫活力测定可检测到非常低水平的寄生虫。AS-1/5 RBC 中初始寄生虫滴度>5.2 log/ml。在 4 周的培养后，在氨丁三醇-GSH 处理的样本中未检测到感染性寄生虫。无论寄生虫阶段和株如何，氨丁三醇-GSH 均可灭活高寄生虫负荷。氨丁三醇容易穿透寄生虫，不可逆地阻止其发育，导致寄生虫死亡并从 RBC 中排出。
氨丁三醇-GSH PRT 证明了在 RBC 浓缩物中有效灭活疟原虫的能力。这项研究完成了以前报道的血小板浓缩物、血浆和 WB 中核酸靶向 PRT 降低 TTM 风险的功效研究组合。
