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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 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. 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 log10/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. [ABSTRACT FROM AUTHOR]

Background: 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.Study Design and Methods: 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.Results: The P. falciparum viability assay has a limit of detection of a single live parasite per sample. Input parasite titer was >5.7 log10 TCID50 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.Conclusion: A robust level of P. falciparum inactivation was achieved in WB using amustaline/GSH treatment. Parasite log reduction was >5.7 log10 TCID50 per mL. Development of such a pathogen reduction system may provide an opportunity to reduce the risk of TT malaria and improve blood availability. [ABSTRACT FROM AUTHOR]

Radikale Wirkung: Ferroquin ist ein Ferrocen ‐ basiertes Analogon des Antimalariamittels Chloroquin. Wie Fluoreszenzsonden in infizierten roten Blutzellen zeigen, läuft zusätzlich zum primären Mechanismus der Chinolinwirkung noch ein anderer Mechanismus ab. Er beruht auf der Bildung von HO. in der sauren und oxidierenden Umgebung der Verdauungsvakuole des Malariaparasiten und könnte bewirken, dass mit Ferroquin eine Reinvasion verhindert werden kann. [ABSTRACT FROM AUTHOR]

BACKGROUND: Transfusion-transmitted cases of malaria and babesiosis have been well documented. Current efforts to screen out contaminated blood products result in component wastage due to the lack of specific detection methods while donor deferral does not always guarantee safe blood products. This study evaluated the efficacy of a photochemical treatment (PCT) method with amotosalen and long-wavelength ultraviolet light (UVA) to inactivate these agents in red blood cells (RBCs) contaminating platelet (PLT) and plasma components. STUDY DESIGN AND METHODS: Plasmodium falciparum– and Babesia microti–contaminated RBCs seeded into PLT and plasma components were treated with 150 µmol per L amotosalen and 3 J per cm2 UVA. The viability of both pathogens before and after treatment was measured with infectivity assays. Treatment with 150 µmol per L amotosalen and 1 J per cm2 UVA was used to assess the robustness of the PCT system. RESULTS: No viable B. microti was detected in PLTs or plasma after treatment with 150 mol per L amotosalen and 3 J per cm2 UVA, demonstrating a mean inactivation of greater than 5.3 log in PLTs and greater than 5.3 log in plasma. After the same treatment, viable P. falciparum was either absent or below the limit of quantification in three of four replicate experiments both in PLTs and in plasma demonstrating a mean inactivation of at least 6.0 log in PLTs and at least 6.9 log in plasma. Reducing UVA dose to 1 J per cm2 did not significantly affect the level of inactivation. CONCLUSION: P. falciparum and B. microti were highly sensitive to inactivation by PCT. Pathogen inactivation approaches could reduce the risk of transfusion-transmitted parasitic infections and avoid unnecessary donor exclusions. [ABSTRACT FROM AUTHOR]