Dose-dependent inactivation of Plasmodium falciparum in red blood cell concentrates by treatment with short wavelength ultraviolet light

Plasmodium species are blood-borne pathogens that are naturally transmitted by female Anopheles mosquitos. The parasite infects red blood cells (RBCs) and can therefore be transfused with blood products. The risk of infection in non-endemic areas is limited to travellers coming back from malaria endemic regions. However, transfusion-transmitted malaria (TTM) constitutes a significant risk of infection in endemic countries. TTM may cause life-threatening complications in patients dependent on blood donations. This study investigates the effectivity of Plasmodium falciparum inactivation in RBC by treatment with short wavelength ultraviolet (UVC) light in the absence of photochemical additives.

RBC suspended in the new developed additive solution PAGGS-C were diluted to a haematocrit of approximately 30% before UVC treatment. RBC (n=3) were spiked with Plasmodium falciparum to a final parasitemia of 0.1-1% and were irradiated with up to 4.5 J/cm2 UVC (254 nm) under agitation (300 rpm). Samples were taken at different time points and the parasitemia was determined by serial dilutions followed by either by GIEMSA staining or flow cytometry over three weeks post irradiation treatment.

The lowest dose of 1.5 J/cm2 UVC led to a ≥ 3 log unit reduction in parasite load compared to the untreated control. The inactivation capacity was shown to be dose-dependent. Strikingly, 4.5 J/cm2 led to ≥ 5 log unit reduction, which was equivalent to a complete inactivation in two out of three experiments.

Additive-free pathogen reduction with UVC light was previously shown to be effective for different bacteria and viruses, but the inactivation of parasites was not addressed until now. The present study provides evidence for significant inactivation of P. falciparum-infected RBCs by UVC light.

SF, MR and BL have no conflict of interest to disclose.UG and AS received grants from the Research Foundation of the German Red Cross Blood Services (Deutsche Forschungsgemeinschaft der Blutspendedienste des Deutschen Roten Kreuzes) and Macopharma for the development of the UVC-based Pathogen inactivation technology for platelets. UG and AS filed a joint patent application for the UVC-based technology for RBC. BL acknowledges support from the Deutsche Forschungsgemeinschaft (LE 2498/9-1 to B.L.). We thank the Hannover Graduate School for Neurosciences, Infection Medicine and Veterinary Sciences (HGNI) for supporting the PhD project of which this manuscript was a part of. Illumination bags used in this study were kindly provided by Macopharma.