Robust inactivation of Plasmodium falciparum in red blood cell concentrates using amustaline and glutathione pathogen reduction

Abstract

Background: 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 amustalineglutathione (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.Study Design and Methods: 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.Results: P. falciparum viability assays allow for the detection of very low levels of parasite. Initial parasite titer was >5.2 log 10 /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.Discussion: 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.Cissé Sow and Amélie Bouissou are co-first authors.

Canadian Blood Services traceback investigation of a suspected case of transfusion‐transmitted malaria

“…Pathogen reduction technology for RBCs or whole blood may potentially reduce the risk of TTM in the future. 26,27…”

“…The main source of TTM risk in Canada and other malaria‐non‐endemic countries is asymptomatic, semi‐immune donors from unrecognized, prior malaria infection. Pathogen reduction technology for RBCs or whole blood may potentially reduce the risk of TTM in the future 26,27 …”

“…In future, pathogen reduction technology may offer further protection against the small, residual risk of TTM; however this technology is not yet commercially available for RBCs, the blood product most likely to be associated with TTM. 26,27 Questionnaire-based donor malaria risk assessment criteria that are used by many non-malaria-endemic countries may not assure interdiction of asymptomatic, semi-immune, malaria-infectious donors, who will continue to pose an ongoing risk of TTM. 25,28 Blood donor lack of recall of prior malaria infection does not negate the risk of TTM from those who have lived in malaria-endemic countries.…”

“…This case serves as a reminder to clinicians in malaria non‐endemic countries that TTM remains a potential risk associated with transfused cellular blood products. In future, pathogen reduction technology may offer further protection against the small, residual risk of TTM; however this technology is not yet commercially available for RBCs, the blood product most likely to be associated with TTM 26,27 . Questionnaire‐based donor malaria risk assessment criteria that are used by many non‐malaria‐endemic countries may not assure interdiction of asymptomatic, semi‐immune, malaria‐infectious donors, who will continue to pose an ongoing risk of TTM 25,28 .…”