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Treatment of Platelet Products with Riboflavin and UV Light: Effectiveness Against High Titer Bacterial Contamination

Contamination of platelet units by bacteria has long been acknowledged as a significant transfusion risk due to their post-donation storage conditions. ...

Scientific Affairs

A medical device is being developed for the reduction of pathogens in PLT concentrates (PCs). The device uses broadband UV light and the compound riboflavin (vitamin B(2)).

Photochemical inactivation of selected viruses and bacteria in platelet concentrates using riboflavin and light.

We are developing a technology based on the combined application of riboflavin (RB) and light for inactivating pathogens in blood products while retaining the biological functions of the treated cells and proteins. Virus and bacteria reduction measured by tissue culture infectivity or colony formation with UV light alone and in combination with RB yield equivalent results. The effects of RB as a sensitizing agent on DNA in white cells, bacteria and viruses in combination with UV light exposure have been evaluated. UV-mediated DNA degradation in Jurkat T cells and leukocytes in plasma as measured by the FlowTACS assay was significantly increased in the presence of RB. Agarose gel electrophoretic analysis of DNA in Escherichia coli and leukocytes in plasma demonstrated enhanced DNA degradation in the presence of RB. UV light in combination with RB prevented the reactivation of lambda phage compared with samples irradiated in the absence of RB. UV-mediated oxidative damage in calf thymus DNA was also enhanced in the presence of RB. These observations clearly demonstrate that the presence of RB and UV light selectively enhances damage to the guanine bases in DNA. These data also suggest that the type and extent of damage to DNA for virus in the presence of RB and light make it less likely to be repaired by normal repair pathways available in host cells.

Riboflavin and UV-light based pathogen reduction: extent and consequence of DNA damage at the molecular level.

Concerns over the risk of bacterial contamination of platelet products have led to implementation of bacteria culture and other screening methods. New approaches for dealing with this issue have also been proposed.

A laboratory comparison of pathogen reduction technology treatment and culture of platelet products for addressing bacterial contamination concerns.

Trypanosoma cruzi, the protozoan parasitic agent of Chagas disease, can be transmitted by blood transfusion. In 2007, most US blood banks started screening blood donations for T. cruzi, but the cost and perceived need of the test have been the subject of ongoing discussion. In this study, we evaluated the ability of the Mirasol System (CaridianBCT), which uses riboflavin (RB) and ultraviolet light to inactivate pathogens, to reduce the levels of infectious T. cruzi in whole blood (WB).

Evaluating pathogen reduction of Trypanosoma cruzi with riboflavin and ultraviolet light for whole blood.

Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that has been responsible for a number of large-scale epidemics as well as imported cases covering a wide geographical range. As a blood-borne virus capable of mounting a high-titer viremia in infected humans, CHIKV was included on a list of risk agents for transfusion and organ transplant by the AABB Transfusion-Transmitted Diseases Committee. Therefore, we evaluated the ability of the Mirasol pathogen reduction technology (PRT) system (CaridianBCT Biotechnologies) to inactivate live virus in contaminated plasma and platelet (PLT) samples.

Photochemical inactivation of chikungunya virus in plasma and platelets using the Mirasol pathogen reduction technology system.

Babesia microti is the parasite most frequently transmitted by blood transfusion in the United States. Previous work demonstrated the efficacy of riboflavin (RB) and ultraviolet (UV) light to inactivate B.microti in apheresis plasma and platelet units. In this study we investigated the effectiveness of RB and UV light to reduce the levels of B.microti in whole blood (WB).

Riboflavin and ultraviolet light reduce the infectivity of Babesia microti in whole blood.

In the United States, blood components are commonly used for patients in need of massive transfusion after blood loss. In combat situations, when severe traumatic injuries occur far from a hospital, fresh whole blood is a valuable transfusion therapy because components may not be available. The risk of infectious or immunological complications from fresh whole blood transfusions could be mitigated by a system that reduces pathogen loads and inactivates white blood cells (WBCs). Such a system is in development and utilizes riboflavin and ultraviolet light to provide pathogen reduction and WBC inactivation.

Development of a riboflavin and ultraviolet light-based device to treat whole blood.

Aux &Eacute;tats-Unis, les produits sanguins labiles sont couramment utilis&eacute;s pour les patients ayant besoin d&#39;une transfusion massive apr&egrave;s la perte de sang. En situation de combat, lorsque des l&eacute;sions traumatiques graves se produisent loin d&#39;un h&ocirc;pital, sang total frais est une th&eacute;rapie transfusionnelle pr&eacute;cieux parce que les composants ne soient pas disponibles. Le risque de complications infectieuses ou immunologiques de la transfusion de sang total frais pourrait &ecirc;tre att&eacute;nu&eacute; par un syst&egrave;me qui r&eacute;duit les charges de l&#39;agent pathog&egrave;ne et inactive les leucocytes (globules blancs). Un tel syst&egrave;me est en d&eacute;veloppement et utilise la riboflavine et la lumi&egrave;re ultraviolette pour fournir la r&eacute;duction des agents pathog&egrave;nes et l&#39;inactivation de la WBC.

D&eacute;veloppement d&#39;un riboflavine et le dispositif de par la lumi&egrave;re ultraviolette pour traiter le sang total.

Negli Stati Uniti, i componenti del sangue sono comunemente usati per i pazienti che necessitano di trasfusione massiccia dopo la perdita di sangue. In situazioni di combattimento, quando si verificano gravi lesioni traumatiche lontano da un ospedale, sangue intero fresco &egrave; una terapia trasfusionale prezioso perch&eacute; componenti potrebbero non essere disponibili. Il rischio di complicanze infettive o immunologiche da trasfusioni di sangue intero fresco potrebbe essere attenuato da un sistema che riduce i carichi agenti patogeni e inattiva le cellule bianche del sangue (globuli bianchi). Tale sistema &egrave; in fase di sviluppo e utilizza la riboflavina e raggi ultravioletti per fornire riduzione del patogeno e inattivazione WBC.

Sviluppo di un dispositivo basato sulla luce ultravioletta per il trattamento di sangue intero riboflavina.

Photochemical treatment of blood products could help prevent transfusion-transmitted malaria and reduce the need for donor deferrals. In this study we evaluated the effectiveness of riboflavin and ultraviolet (UV) light against both Plasmodium falciparum, which causes the most severe form of human malaria, and Plasmodium yoelii, an in vivo murine model for malaria.

Inactivation of Plasmodium spp. in plasma and platelet concentrates using riboflavin and ultraviolet light.

Leishmaniasis is a vector-borne disease caused by the protozoan parasite Leishmania sp. that is transmitted by sandflies. Travelers to endemic areas, and US military personnel stationed in the Middle East, are at risk for contracting the disease.

Reduction of Leishmania donovani infectivity in whole blood using riboflavin and ultraviolet light.

Arboviruses are an emerging threat to transfusion safety and rates of infection are likely to increase with the increased rainfall associated with climate change. Arboviral infections are common in Australia, where Ross River virus (RRV), Barmah Forest virus (BFV), and Murray Valley encephalitis virus (MVEV), among others, have the potential to cause disease in humans. The use of pathogen reduction technology (PRT) may be an alternative approach for blood services to manage the risk of arboviral transfusion transmission. In this study, the effectiveness of the Mirasol PRT (Terumo BCT) system at inactivating RRV, BFV, and MVEV in buffy coat (BC)-derived platelets (PLTs) was investigated.

The effect of riboflavin and ultraviolet light on the infectivity of arboviruses.

Sub-Saharan African countries utilize whole blood (WB) to treat severe anemia secondary to severe blood loss or malaria on an emergency basis. In many areas with high prevalence of transfusion-transmissible agents, blood safety measures are insufficient. Pathogen reduction technology applied to WB might considerably improve blood safety.

Treatment of Whole Blood With Riboflavin and UV Light: Impact on Malaria Parasite Viability and Whole Blood Storage.

Two studies were performed to test the effectiveness of riboflavin and ultraviolet (UV) light treatment (Mirasol PRT, Terumo BCT) against murine cytomegalovirus (MCMV). The first study utilized immune-compromised mice to measure the reduction of cell-free MCMV. A second study used a murine model to evaluate the ability of Mirasol PRT to prevent transfusion-transmitted (TT)-MCMV infection.

Riboflavin and ultraviolet light for pathogen reduction of murine cytomegalovirus in blood products.

Multilayered blood safety programs reduce the risk of transfusion-transmitted diseases; however, there remains a risk of window period transmission of screened viruses and transmission of unscreened and emerging viruses from asymptomatic donors. To reduce this risk, a riboflavin-and-UV-light-based pathogen reduction process was evaluated against eight viral agents.

Shawn D. Keil

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Scientific Affairs

Treatment of Platelet Products with Riboflavin and UV Light: Effectiveness Against High Titer Bacterial Contamination

Terumo BCT