Inactivation of Plasmodium falciparum in whole blood using the amustaline and glutathione pathogen reduction technology.

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Tytuł:: Inactivation of Plasmodium falciparum in whole blood using the amustaline and glutathione pathogen reduction technology.
Autorzy:: Sow C; MCAM, UMR 7245, Muséum National d'Histoire Naturelle, CNRS, Paris, France.
Laughhunn A; Cerus Corporation, Concord, California.
Girard YA; Cerus Corporation, Concord, California.
Lanteri MC; Cerus Corporation, Concord, California.
Amar El Dusouqui S; Swiss Transfusion SRC, Bern, Switzerland.
Stassinopoulos A; Cerus Corporation, Concord, California.
Grellier P; MCAM, UMR 7245, Muséum National d'Histoire Naturelle, CNRS, Paris, France.
Źródło:: Transfusion [Transfusion] 2020 Apr; Vol. 60 (4), pp. 799-805. Date of Electronic Publication: 2020 Mar 04.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: Arlington, Va. : American Association Of Blood Banks
MeSH Terms:: Acridines/*pharmacology
Glutathione/*pharmacology
Malaria, Falciparum/*prevention & control
Microbial Viability/*drug effects
Nitrogen Mustard Compounds/*pharmacology
Blood Safety/methods ; Erythrocytes/microbiology ; Erythrocytes/parasitology ; Humans ; Malaria, Falciparum/blood ; Malaria, Falciparum/transmission ; Parasite Load ; Parasitemia/drug therapy ; Plasmodium falciparum/drug effects ; Plasmodium falciparum/growth & development
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Grant Information:: International Cerus Corporation; International Humanitarian Foundation Swiss Red Cross
Substance Nomenclature:: 0 ((N,N-bis(2-chloroethyl))-2-aminoethyl-3-((acridin-9-yl)amino)propionate)
0 (Acridines)
0 (Nitrogen Mustard Compounds)
GAN16C9B8O (Glutathione)
Entry Date(s):: Date Created: 20200305 Date Completed: 20200908 Latest Revision: 20231113
Update Code:: 20240105
PubMed Central ID:: PMC7187285
DOI:: 10.1111/trf.15734
PMID:: 32129497
: Czasopismo naukowe

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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 log 10 TCID 50 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 log 10 TCID 50 per mL. Development of such a pathogen reduction system may provide an opportunity to reduce the risk of TT malaria and improve blood availability.
(© 2020 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.)

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