Inactivation of a broad spectrum of pathogens by photochemical treatment of plasma and platelets using Amotosalen and ultraviolet a light

Background: The INTERCEPT Blood System pathogen reduction (PR) technology using amotosalen and ultraviolet A light (UVA) was developed for the inactivation of pathogens and leukocytes in plasma and platelet components The technology has been used worldwide with kits sold to produce more than 6 9 million transfusable blood products Aims: To summarize the published data describing inactivation efficacy for viruses, bacteria, and parasites Methods: Twenty-five enveloped and 6 non-enveloped viruses, 22 bacterial strains and 4 parasites species, were evaluated for sensitivity to amotosalen/UVA treatment The data were obtained in studies in which high titers of pathogens were spiked into plasma or platelet concentrates (PC) resuspended in 35% plasma/ 65% platelet additive solution (PAS) or in 100% plasma Samples harvested pre- and post-PR treatment were assessed for infectivity using culture systems and, where appropriate, animal models Log10 reduction factors (LRF) were defined as the difference in infectious titers pre- and post-PR treatment Results: Inactivation data have been obtained for 25 enveloped viruses, 6 nonenveloped viruses, 22 bacterial strains, and 4 parasites including vector-borne disease agents that have emerged over the past two decades LRF of ≥ 4 0 have been claimed for 13 viruses, 19 bacterial strains, and 4 parasites in platelets in plasma/ PAS [\u003e4 3-\u003e7], 14 viruses, 8 bacterial strains, 3 parasites in platelets in 100% plasma [\u003e4 2 to \u003e 7 6], and 15 viruses, 6 bacterial strains, and 3 parasites [\u003e4 2- \u003e10 6] in plasma Inactivation of flaviviruses by amotosalen/UVA was demonstrated for West Nile, dengue virus, Zika (ZIKV) and yellow fever virus with LRFs \u003e 4 0 in PCs and plasma Inactivation of alphaviruses was demonstrated for chikungunya virus (CHIKV), with LRFs \u003e 6 4 in PC and ≥ 7 6 in plasma, and with LRF \u003e 5 1 for Ross River virus and \u003e 6 9 for Mayaro virus in PC With the recent emergence of the new coronavirus 2019-nCoV, it is important to note that LRFs ≥ 5 5 in plasma and \u003e 6 2 in PC were documented for the closely related SARS-CoV, and recent investigator-initiated studies have demonstrated LRFs ≥ 4 5 for MERS-CoV in PC and \u003e 4 7 in plasma Parasites with large global impact on immunocompromised transfusion recipients demonstrated high sensitivity to PR treatment with LRFs \u003e 6 0 in PC and ≥ 6 9 in plasma for P falciparum, \u003e5 0 in PC and plasma for T cruzi, and \u003e 5 3 in PC and plasma for B microti Beyond emerging viruses and parasites, bacteria were evaluated including 9 Gram-negative, 11 Gram-positive, and 2 spirochetes Out of 22 evaluated bacterial strains, 21 exhibited LRF \u003e 4 5, with LRFs \u003e 6 0 for 18 of them Routine-use hemovigilance data have shown that the system is efficacious to reduce septic transfusion reactions Summary/Conclusions: The amotosalen/UVA PRT is effective at reducing infectivity levels of a broad spectrum of pathogens in plasma and PC Industry guidelines consider INTERCEPT Blood System for platelets as an alternative to screening strategies for bacteria, ZIKV, cytomegalovirus, and parasites that cause malaria and babesia, or as an alternative to procedures such as gamma irradiation The data here presented are of interest to inform worldwide blood safety and emerging infectious diseases (EID) preparedness programs