MCAM, UMR 7245, Muséum National d'Histoire Naturelle, CNRS, Paris, France.
Cerus Corporation, Concord, California.
Transfusion. 2020 Apr;60(4):799-805. doi: 10.1111/trf.15734. Epub 2020 Mar 4.
Risk of transfusion-transmitted (TT) malaria is mainly associated with whole blood (WB) or red blood cell (RBC) transfusion. Risk mitigation relies mostly on donor deferral while a limited number of countries perform blood testing, both negatively impacting blood availability. This study investigated the efficacy of the pathogen reduction system using amustaline and glutathione (GSH) to inactivate Plasmodium falciparum in WB.
WB units were spiked with ring stage P. falciparum infected RBCs. Parasite loads were measured in samples at time of infection, after 24 hours at room temperature (RT), and after a 24-hour incubation at RT post-treatment with 0.2 mM amustaline and 2 mM GSH. Serial 10-fold dilutions of the samples were inoculated to RBC cultures and maintained up to 4 weeks. Parasitemia was quantified by cytometry.
The P. falciparum viability assay has a limit of detection of a single live parasite per sample. Input parasite titer was >5.7 log TCID per mL. A 24-hour incubation at RT paused parasite development in controls, but they retained viability and infectivity when tested in culture. In contrast, no infectious parasites were detected in the amustaline/GSH-treated sample after 4 weeks of culture.
A robust level of P. falciparum inactivation was achieved in WB using amustaline/GSH treatment. Parasite log reduction was >5.7 log TCID per mL. Development of such a pathogen reduction system may provide an opportunity to reduce the risk of TT malaria and improve blood availability.
输血传播（TT）疟疾的风险主要与全血（WB）或红细胞（RBC）输血有关。风险缓解主要依赖于献血者的延期，而少数国家进行血液检测，这两种方法都对血液供应产生了负面影响。本研究调查了使用 amustaline 和谷胱甘肽（GSH）灭活 WB 中恶性疟原虫的病原体减少系统的疗效。
将环阶段感染的恶性疟原虫 RBC 掺入 WB 单位。在感染时、室温（RT）下 24 小时后以及用 0.2 mM amustaline 和 2 mM GSH 处理后 RT 孵育 24 小时后，测量样品中的寄生虫负荷。对样品进行连续 10 倍稀释，接种到 RBC 培养物中，并保持 4 周。通过细胞计数定量寄生虫血症。
疟原虫活力测定的检测限为每个样品一个活寄生虫。输入寄生虫滴度>5.7 log TCID/mL。RT 孵育 24 小时可使对照中的寄生虫发育暂停，但在培养中检测时，它们仍保持活力和感染力。相比之下，在培养 4 周后，在 amustaline/GSH 处理的样品中未检测到感染性寄生虫。
使用 amustaline/GSH 处理可在 WB 中实现对恶性疟原虫的强大灭活水平。寄生虫对数减少>5.7 log TCID/mL。开发这样的病原体减少系统可能有机会降低 TT 疟疾的风险并提高血液供应。
