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.

Fig 1

New test implementation and declining risk of viral infections from transfusion. Reprinted with permission from Lancet 361:161-169,2003 (Ref. [7]).

Fig 2

Approximate timeline (1970-2003) for the introduction of various interventions to improve transfusion safety. This timeline may not apply to all countries. The y-axis indicates the magnitude of the number of tests done annually. *No longer in use.

Fig 3

Sensitivity of bacterial detection methods. Abbreviations: AO, acridine orange stain; AP, antibiotic probe; DNA/RNA, DNA/RNA chemoluminescence; DP, dielectrophoresis; EIA, enzyme-linked immunoassay; EFM, epifluorescence microscopy; ET indicates endotoxin; GS, Gram stain; IFA, immunofluorescence assay; LPA, latex particle agglutination; Po₂, PALL BDS Po₂ method; RNA probe, ribosomal RNA probe; RS, reagent strips; Swirling, platelet swirling patterns. Reprinted with permission from Transfus Med Rev. 2004;18:11-24 (Ref. [52]). Values are based on data from several sources (Refs. 53., 54., 55., 56., 57., 58., 59.).