Protecting the Blood Supply From Emerging Pathogens: The Role of Pathogen Inactivation

Abstract

Although the risk of infection by blood transfusion is relatively low, breakthrough infections still occur, Transfusion-related fatalities caused by infections continue to be reported, and blood is not tested for many potentially dangerous pathogens. The current paradigm for increasing the safety of the blood supply is the development and implementation of laboratory screening methods and restrictive donor criteria. When considering the large number of known pathogens and the fact that pathogens continue to emerge, it is clear that the utility of new tests and donor restrictions will continue to be a challenge when considering the cost of developing and implementing new screening assays, the loss of potential donors, and the risk of testing errors. Despite improving the safety of blood components, testing remains a reactive approach to blood safety. The contaminating organisms must be identified before sensitive tests can be developed. In contrast, pathogen inactivation is a proactive strategy designed to inactivate a pathogen before it enters the blood supply. Almost all pathogen inactivation technologies target nucleic acids, allowing for the inactivation of a variety of nucleic acid-containing pathogens within plasma, platelets, or red blood cells thus providing the potential to reduce transfusion-transmitted diseases. However, widespread use of a pathogen inactivation technology can only be realized when proven safe and efficacious and not cost-prohibitive.

Inactivated human platelet lysate with psoralen: a new perspective for mesenchymal stromal cell production in Good Manufacturing Practice conditions

“…This was done with photochemical treatment by Amotosalem and UVA, a technology that is efficient against the vast majority of known pathogens and which might also prevent the transmission of unknown pathogens (25,(38)(39)(40)(41) INTERCEPT technology is routinely used for PI of PLTs and plasma for clinical use as it is able to inactivate a wide spectrum of bacteria, viruses, and parasites, as well as contaminating leukocytes (42)(43)(44)(45)(46). INTERCEPT process and nucleic acids targeting PI technology is not, however, effective against prion diseases, therefore the risk of prion transmission by treated lysates would remain.…”

Zika Virus

“…In addition to nucleic acid testing of blood donors, prevention of posttransfusion Zika fever can be performed by pathogen inactivation in blood products (314). Pathogen inactivation was of particular interest in the context of the cocirculation of several arboviruses during the ZIKV outbreak in French Polynesia and can be of great interest in the Americas (315).…”

Transfusion-related mortality: the ongoing risks of allogeneic blood transfusion and the available strategies for their prevention

“…Rather than this reactive "agent-by-agent" approach, there can be a more all-encompassing approach to blood safety that would address most transfusion-transmitted pathogens: pathogen reduction (PR) by nucleic-acid intercalating agents such as psoralens or riboflavin that, in the presence of ultraviolet light, bind to the nucleic acids of pathogens and inactivate them, while permitting the nucleic-acidfree constituents of donor blood (plasma proteins, platelets, and RBCs) to continue to function. 85 These technologies can eliminate most of the residual risk of bacteria, as well as the risk associated with a long list of transfusion-transmitted pathogens for which the blood supply is not screened (Table 3). Even more importantly, these technologies offer probable, preemptive protection against the next potentially lethal transfusion-transmitted agent that could emerge in the future, possibly replicating the experience with HIV, HCV, or WNV.…”