Blood Transfusion Safety: Pathogen Inactivation Reduces Transfusion-Transmitted Infections

Historically, blood transfusions were associated with substantial risks of transmitting infectious agents, including hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). The recognition of these risks prompted a series of advancements in blood screening and processing to enhance safety. Early efforts focused on donor selection criteria, excluding individuals at high risk for infectious diseases. This was followed by the development and implementation of serological testing for specific viral markers. For instance, testing for hepatitis B surface antigen (HBsAg) became routine in the 1970s, significantly reducing HBV transmission. The emergence of HIV in the 1980s spurred rapid development of HIV antibody testing, introduced in 1985, which dramatically decreased the risk of HIV transmission via transfusion from an estimated 1 in 2,500 units to less than 1 in 100,000 units by the early 1990s. Nucleic acid testing (NAT) for HIV and HCV, introduced in the late 1990s, further reduced the window period for detection, lowering the risk of HIV transmission to approximately 1 in 2.3 million units and HCV to 1 in 1.5 million units.

Advancements in Blood Processing and Pathogen Inactivation

Beyond donor screening and serological/NAT testing, significant strides have been made in blood product processing. Leukoreduction, the removal of white blood cells from blood components, was implemented to reduce the risk of transfusion-related acute lung injury (TRALI), febrile non-hemolytic transfusion reactions, and cytomegalovirus (CMV) transmission. While not directly targeting bacterial or viral pathogens in plasma, leukoreduction improved overall transfusion safety. The most recent major advancement has been the introduction of pathogen inactivation technologies. These methods aim to inactivate a broad spectrum of viruses, bacteria, parasites, and leukocytes that may be present in blood components, particularly plasma and platelets, without compromising the therapeutic efficacy of the blood product. Technologies such as psoralen-based systems (e.g., INTERCEPT Blood System) involve the addition of a photoactive compound (e.g., amotosalen) to the blood product, followed by ultraviolet A (UVA) light illumination. The photoactive compound intercalates into the nucleic acids (DNA and RNA) of pathogens and leukocytes, and upon UVA activation, forms covalent bonds, irreversibly blocking replication. This process effectively inactivates a wide range of enveloped and non-enveloped viruses, gram-positive and gram-negative bacteria, and protozoa, including those for which routine screening tests are not available or are in early stages of infection (e.g., West Nile virus, dengue virus, Zika virus, chikungunya virus, and emerging pathogens).

Another pathogen inactivation method involves the use of riboflavin and UV light (e.g., Mirasol PRT System). Riboflavin, a naturally occurring vitamin B2, binds to nucleic acids and, when exposed to UV light, generates reactive oxygen species that damage the nucleic acids of pathogens, preventing their replication. This method has demonstrated efficacy against a similar spectrum of pathogens as psoralen-based systems. The implementation of pathogen inactivation for plasma and platelets has provided an additional layer of safety, particularly for regions with endemic emerging infectious diseases or for pathogens with prolonged asymptomatic phases that evade standard donor screening. While these technologies are primarily applied to plasma and platelets, research continues into their application for red blood cell concentrates, which present unique challenges due to the high concentration of hemoglobin and its potential interference with inactivation processes.