Emerging Pathogen Threats in Transfusion Medicine: Improving Safety and Confidence with Pathogen Reduction Technologies.

Emerging infectious disease threats are becoming more frequent due to various social, political, and geographical pressures, including increased human-animal contact, global trade, transportation, and changing climate conditions. Since blood products for transfusion are derived from donated blood from the general population, emerging agents spread by blood contact or the transfusion of blood products are also a potential risk. Blood transfusions are essential in treating patients with anemia, blood loss, and other medical conditions.

SARS-CoV-2 seroprevalence among blood donors in Uganda: 2019-2022.

Background: The true burden of COVID-19 in low- and middle-income countries remains poorly characterized, especially in Africa. Even prior to the availability of SARS-CoV-2 vaccines, countries in Africa had lower numbers of reported COVID-19 related hospitalizations and deaths than other regions globally.

Methods: Ugandan blood donors were evaluated between October 2019 and April 2022 for IgG antibodies to SARS-CoV-2 nucleocapsid (N), spike (S), and five variants of the S protein using multiplexed electrochemiluminescence immunoassays (MesoScale Diagnostics, Rockville, MD).

Pathogen reduction of monkeypox virus in plasma and whole blood using riboflavin and UV light.

Background: Monkeypox virus has recently emerged from endemic foci in Africa and, since October 20, 2022, more than 73,000 human infections have been reported by the CDC from over 100 countries that historically have not reported monkeypox cases. The detection of virus in skin lesions, blood, semen, and saliva of infected patients with monkeypox infections raises the potential for disease transmission via routes that have not been previously documented, including by blood and plasma transfusions. Methods for protecting the blood supply against the threats of newly emerging disease agents exist and include Pathogen Reduction Technologies (PRT) which utilize photochemical treatment processes to inactivate pathogens in blood while preserving the integrity of plasma and cellular components.

The Mirasol Evaluation of Reduction in Infections Trial (MERIT): study protocol for a randomized controlled clinical trial.

Background: Transfusion-transmitted infections (TTIs) are a global health challenge. One new approach to reduce TTIs is the use of pathogen reduction technology (PRT). In vitro, Mirasol PRT reduces the infectious load in whole blood (WB) by at least 99%.

A Whole Virion Vaccine for COVID-19 Produced via a Novel Inactivation Method and Preliminary Demonstration of Efficacy in an Animal Challenge Model.

The COVID-19 pandemic has generated intense interest in the rapid development and evaluation of vaccine candidates for this disease and other emerging diseases. Several novel methods for preparing vaccine candidates are currently undergoing clinical evaluation in response to the urgent need to prevent the spread of COVID-19. In many cases, these methods rely on new approaches for vaccine production and immune stimulation.

Preservation of neutralizing antibody function in COVID-19 convalescent plasma treated using a riboflavin and ultraviolet light-based pathogen reduction technology.

Background And Objectives: Convalescent plasma (CP) has been embraced as a safe therapeutic option for coronavirus disease 2019 (COVID-19), while other treatments are developed. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not transmissible by transfusion, but bloodborne pathogens remain a risk in regions with high endemic prevalence of disease. Pathogen reduction can mitigate this risk; thus, the objective of this study was to evaluate the effect of riboflavin and ultraviolet light (R + UV) pathogen reduction technology on the functional properties of COVID-19 CP (CCP).

Releasates of riboflavin/UV-treated platelets: Microvesicles suppress cytokine-mediated endothelial cell migration/proliferation.

Background: Accelerated development of the platelet (PLT) storage lesion upon pathogen inactivation (PI) is associated with the release of proteins from granules and platelet microvesicles (PMVs). Whether PI treatments alter the interaction between PLT factors and the vessel endothelium is of interest in understanding the risk profile of these technologies.

Study Design And Methods: In a pool-and-split study, one platelet concentrate (PC) was treated with riboflavin/UV (RF/UV) light, while the other one was kept as an untreated control.

Pilot Acute Safety Evaluation of Innocell™ Cancer Immunotherapy in Canine Subjects.

Background: We are developing cancer immunotherapy based on the use of autologous tumor tissue that has been rendered replication-incompetent but maintains phenotype and metabolic activity post-preparation.

Aim: The aim of this study was to evaluate safety and tolerance to injection of the inactivated tumor cell and adjuvant preparation (Innocell™) within 24 hours of administration in a pilot study in canine patients with solid organ tumors. .

Pathogen reduction of SARS-CoV-2 virus in plasma and whole blood using riboflavin and UV light.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has recently been identified as the causative agent for Coronavirus Disease 2019 (COVID-19). The ability of this agent to be transmitted by blood transfusion has not been documented, although viral RNA has been detected in serum. Exposure to treatment with riboflavin and ultraviolet light (R + UV) reduces blood-borne pathogens while maintaining blood product quality.

A novel cancer immunotherapy utilizing autologous tumour tissue.

Background: With the recent interest in personalized medicine for cancer patients and immune therapy, the field of cancer vaccines has been resurrected. Previous autologous, whole cell tumour vaccine trials have not produced convincing results due, in part to poor patient selection and inactivation methos that are harsh on the cells. These methods can alter protein structure and antigenic profiles making vaccine candidates ineffective in stimulating immune response to autochthonous tumour cells.

Red Blood Cells Derived from Whole Blood Treated with Riboflavin and UV Light Maintain Adequate Cell Quality through 21 Days of Storage.

Background: The Mirasol system for whole blood (WB) is a non-toxic, non-mutagenic pathogen reduction technology (PRT) that treats WB units with riboflavin (vitamin B) and ultraviolet (UV) light to alter nucleic acids, thereby reducing pathogen infectivity and inactivating white blood cells. This study evaluates the quality of red blood cells (RBCs) derived from WB treated with the Mirasol system.

Study Design And Methods: Paired units of WB were collected from 61 healthy donors.

Improved in vitro quality of stored red blood cells upon oxygen reduction prior to riboflavin/UV light treatment of whole blood.

Background: The application of riboflavin/UV-based pathogen inactivation (PI) to whole blood (WB) is currently limited by its negative impact on red blood cell (RBC) quality. The generation of reactive oxidative species in RBC products contributes to increased hemolysis. This study evaluated the impact of deoxygenation of WB prior to riboflavin/UV light treatment versus deoxygenation of RBC concentrates after PI treatment by monitoring RBC in vitro quality parameters.

Reflections on the dynamics of bacterial and viral contamination of blood components and the levels of efficacy for pathogen inactivation processes.

Blood transfusion safety has been increasingly improving during the past two decades. However, threats from both known and emerging pathogens require continual improvement and re-assessment of blood safety measures. In this respect, we are currently witnessing the broader implementation of Pathogen reduction technology (PRT) for blood complements.

Hemostatic efficacy of pathogen-inactivated vs untreated platelets: a randomized controlled trial.

Pathogen inactivation of platelet concentrates reduces the risk for blood-borne infections. However, its effect on platelet function and hemostatic efficacy of transfusion is unclear. We conducted a randomized noninferiority trial comparing the efficacy of pathogen-inactivated platelets using riboflavin and UV B illumination technology (intervention) compared with standard plasma-stored platelets (control) for the prevention of bleeding in patients with hematologic malignancies and thrombocytopenia.

Special considerations for the use of pathogen reduced blood components in pediatric patients: An overview.

Pediatric patients requiring transfusion constitute one of the most challenging areas of transfusion practice. Due to the limitations posed by their particular physiological conditions they routinely require specialized component support and more personalised transfusion care than what is routinely utilized in the care of adult patients. Pediatric patients, unlike many adult patients requiring transfusion support, also generally have significant lifespans post-transfusion.

Improving the safety of whole blood-derived transfusion products with a riboflavin-based pathogen reduction technology.

Worldwide safety of blood has been positively impacted by technological, economic and social improvements; nevertheless, growing socio-political changes of contemporary society together with environmental changes challenge the practice of blood transfusion with a continuous source of unforeseeable threats with the emergence and re-emergence of blood-borne pathogens. Pathogen reduction (PR) is a proactive strategy to mitigate the risk of transfusion-transmitted infections. PR technologies for the treatment of single plasma units and platelet concentrates are commercially available and have been successfully implemented in more than 2 dozen countries worldwide.

Red blood cells derived from whole blood treated with riboflavin and ultraviolet light maintain adequate survival in vivo after 21 days of storage.

Background: Pathogen reduction (PR) of whole blood (WB) may increase blood safety when applied before component separation. This study evaluates the in vivo performance of red blood cells (RBCs) derived from WB treated with the riboflavin and ultraviolet (UV) light PR (Mirasol) system.

Study Design And Methods: This was a prospective, two-center, single-blind, randomized, two-period, crossover clinical trial designed to evaluate autologous Cr/ Tc-radiolabeled recovery and survival of RBCs derived from Mirasol-treated WB compared to untreated WB.

Reduced MHC alloimmunization and partial tolerance protection with pathogen reduction of whole blood.

Background: Allogeneic blood transfusion can result in an immune response against major histocompatibility complex (MHC) antigens, potentially complicating future transfusions or transplants. We previously demonstrated that pathogen reduction of platelet-rich plasma (PRP) with riboflavin and ultraviolet light (UV+R) can prevent alloimmunization in mice. A similar pathogen-reduction treatment is currently under development for the treatment of whole blood using riboflavin and a higher dose of UV light.

Characterization of posttransfusion Plasmodium falciparum infection in semi-immune nonparasitemic patients.

Background: Transfusion-transmitted malaria (TTM) has not been studied with molecular means in hyperendemic areas where it is assumed to occur frequently. The African Investigation of the Mirasol System (AIMS) trial provided the opportunity to study TTM from standard whole blood (WB) units.

Study Design And Methods: The Plasmodium genome in transfused WB units and patient samples both before transfusion and 1, 3, 7, and 28 days after transfusion was screened and quantified using real-time polymerase chain reaction.

Protein translation occurs in platelet concentrates despite riboflavin/UV light pathogen inactivation treatment.

Purpose: Pathogen inactivation technologies (PITs) were introduced into blood banking to further improve the safety of blood products. However, the UV light used in PITs to terminate pathogen growth might alter the functionality of the cells in the blood product as well as the protein profile of the blood components. This study employed proteomic approaches to assess changes in the platelet proteome and translatome.

Effect of Plasmodium inactivation in whole blood on the incidence of blood transfusion-transmitted malaria in endemic regions: the African Investigation of the Mirasol System (AIMS) randomised controlled trial.

Background: Transfusion-transmitted malaria is a frequent but neglected adverse event in Ghana. We did a randomised controlled clinical trial to assess the efficacy and safety of a whole blood pathogen reduction technology at preventing transfusion transmission of Plasmodium spp parasites.

Methods: For this randomised, double-blind, parallel-group clinical trial, eligible adult patients (aged ≥ 18 years) with blood group O+, who required up to two whole blood unit transfusions within 3 days of randomisation and were anticipated to remain in hospital for at least 3 consecutive days after initial transfusion, were enrolled from Komfo Anokye Teaching Hospital in Kumasi, Ghana.

Reduced alloimmunization in mice following repeated transfusion with pathogen-reduced platelets.

Background: Allogeneic transfusion can result in alloimmunization, leading to platelet (PLT) refractoriness and rejection of solid organ transplants. Previously we demonstrated that pathogen reduction using UV light and riboflavin (UV + R) eliminates the immunogenicity of white blood cells (WBCs) in vitro, blocks alloimmunization from transfusion in mice, and results in reduced ex vivo cytokine responses to subsequent untreated transfusions. We sought to determine if repeated transfusion with pathogen-reduced PLT-rich plasma (PRP) would eventually cause breakthrough alloimmunization or enhanced tolerance.

Treatment of blood with a pathogen reduction technology using ultraviolet light and riboflavin inactivates Ebola virus in vitro.

Background: Transfusion of plasma from recovered patients after Ebolavirus (EBOV) infection, typically called "convalescent plasma," is an effective treatment for active disease available in endemic areas, but carries the risk of introducing other pathogens, including other strains of EBOV. A pathogen reduction technology using ultraviolet light and riboflavin (UV+RB) is effective against multiple enveloped, negative-sense, single-stranded RNA viruses that are similar in structure to EBOV. We hypothesized that UV+RB is effective against EBOV in blood products without activating complement or reducing protective immunoglobulin titers that are important for the treatment of Ebola virus disease (EVD).