Pathogen reduction using riboflavin and UV light
Encyclopedia
Pathogen reduction using riboflavin and UV light is a method by which infectious pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...

s in blood for transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...

 are inactivated by adding riboflavin
Riboflavin
Riboflavin, also known as vitamin B2 or additive E101, is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors FAD and FMN, and is therefore required by all flavoproteins. As such, vitamin B2 is required for a...

 and irradiating with UV light
Ultraviolet
Ultraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...

. This method reduces the infectious levels of disease-causing agents that may be found in donated blood components, while still maintaining good quality blood components for transfusion. This type of approach to increase blood safety is also known as “pathogen inactivation” in the industry.

Despite measures that are in place in the developed world to ensure the safety of blood products for transfusion, a risk of disease transmission still exists. Consequently, the development of pathogen inactivation/reduction technologies for blood products has been an ongoing effort in the field of transfusion medicine. A new procedure for the treatment of individual units of single-donor (apheresis) or whole blood–derived, pooled, platelets has recently been introduced. This technology uses riboflavin and light for the treatment of PLTs and plasma.

Method

This pathogen reduction process involves adding riboflavin (vitamin B2) to the blood component, which is then placed into an illuminator where it is exposed to UV light for about five to ten minutes. Exposure to UV light activates riboflavin and when it is associated with nucleic acid
Nucleic acid
Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...

s (DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 and RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

), riboflavin causes a chemical alteration to functional groups of the nucleic acids thereby making pathogens unable to replicate. In this way the process prevents viruses, bacteria, parasites and white blood cells, from replicating and causing disease.
UV Light + Riboflavin → Irreversible Inactivation


This method using riboflavin and UV light renders pathogens harmless by using a non-mutagenic, non-toxic method. Riboflavin and its photoproducts are already present in the human body and do not need to be removed from blood products prior to transfusion.

Examples of pathogens inactivated by this method

  • Virus
    Virus
    A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...

    es – both enveloped and non-enveloped including: Avian Flu, Chikungunya
    Chikungunya
    Chikungunya virus is an insect-borne virus, of the genus Alphavirus, that is transmitted to humans by virus-carrying Aedes mosquitoes. There have been recent breakouts of CHIKV associated with severe illness...

    , CMV
    Cytomegalovirus
    Cytomegalovirus is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV or human herpesvirus-5 , and is the most studied of all cytomegaloviruses...

    , Hepatitis A
    Hepatitis A
    Hepatitis A is an acute infectious disease of the liver caused by the hepatitis A virus , an RNA virus, usually spread the fecal-oral route; transmitted person-to-person by ingestion of contaminated food or water or through direct contact with an infectious person...

    , Hepatitis B, Hepatitis C
    Hepatitis C
    Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...

    , HIV
    HIV
    Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

    , Human B-19, Influenza
    Influenza
    Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...

    , Rabies
    Rabies
    Rabies is a viral disease that causes acute encephalitis in warm-blooded animals. It is zoonotic , most commonly by a bite from an infected animal. For a human, rabies is almost invariably fatal if post-exposure prophylaxis is not administered prior to the onset of severe symptoms...

    , and West Nile
    West Nile virus
    West Nile virus is a virus of the family Flaviviridae. Part of the Japanese encephalitis antigenic complex of viruses, it is found in both tropical and temperate regions. It mainly infects birds, but is known to infect humans, horses, dogs, cats, bats, chipmunks, skunks, squirrels, domestic...

    . This adds a level of protection for those receiving the transfusion product against viruses that donors are screened for (and may be at a level too low to be detected- window period) as well as those that they are not screened for at the time of their donation.
  • Bacteria
    Bacteria
    Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

     – such as: B. cereus
    Bacillus cereus
    Bacillus cereus is an endemic, soil-dwelling, Gram-positive, rod-shaped, beta hemolytic bacterium. Some strains are harmful to humans and cause foodborne illness, while other strains can be beneficial as probiotics for animals...

    , E. cloacae
    Enterobacter cloacae
    Enterobacter cloacae is a clinically significant Gram-negative, facultatively-anaerobic, rod-shaped bacterium.-Microbiology:*BioHazard Level: 1 *Growth Temperature: 30°CAppropriate growth media:nutrient agar, nutrient broth...

    , E. coli
    Escherichia coli
    Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...

    , K. pneumonia
    Klebsiella pneumoniae
    Klebsiella pneumoniae is a Gram-negative, non-motile, encapsulated, lactose fermenting, facultative anaerobic, rod shaped bacterium found in the normal flora of the mouth, skin, and intestines....

    , P. acnes
    Propionibacterium acnes
    Propionibacterium acnes is a relatively slow growing, typically aerotolerant anaerobic gram positive bacterium that is linked to the skin condition acne; it can also cause chronic blepharitis and endophthalmitis, the latter particularly following intraocular surgery...

    , S. marcescens
    Serratia marcescens
    Serratia marcescens is a species of Gram-negative, rod-shaped bacterium in the family Enterobacteriaceae. A human pathogen, S. marcescens is involved in nosocomial infections, particularly catheter-associated bacteremia, urinary tract infections and wound infections, and is responsible for 1.4% of...

    , S. aureus
    Staphylococcus aureus
    Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...

    , S. epidermidis
    Staphylococcus epidermidis
    Staphylococcus epidermidis is one of thirty-three known species belonging to the genus Staphylococcus. It is part of human skin flora, and consequently part of human flora. It can also be found in the mucous membranes and in animals. Due to contamination, it is probably the most common species...

    , S. agalactiae
    Streptococcus agalactiae
    Streptococcus agalactiae is a beta-hemolytic Gram-positive streptococcus.- Identification :The CAMP test is an important test for identification...

    , S. mitis
    Streptococcus mitis
    Streptococcus mitis is a mesophilic alpha-hemolytic species of Streptococcus that inhabits the human mouth. It is a Gram positive, coccus, facultative anaerobe and catalase negative. It can cause endocarditis...

    , S. pyogenes
    Streptococcus pyogenes
    Streptococcus pyogenes is a spherical, Gram-positive bacterium that is the cause of group A streptococcal infections. S. pyogenes displays streptococcal group A antigen on its cell wall. S...

    , and Y. enterocolitica
    Yersinia enterocolitica
    Yersinia enterocolitica is a species of gram-negative coccobacillus-shaped bacterium, belonging to the family Enterobacteriaceae. Yersinia enterocolitica infection causes the disease yersiniosis, which is a zoonotic disease occurring in humans as well as a wide array of animals such as cattle,...

    .
  • Parasites
    Parasitism
    Parasitism is a type of symbiotic relationship between organisms of different species where one organism, the parasite, benefits at the expense of the other, the host. Traditionally parasite referred to organisms with lifestages that needed more than one host . These are now called macroparasites...

     – including: Babesiosis
    Babesiosis
    Babesiosis is a malaria-like parasitic disease caused by infection with Babesia, a genus of protozoal piroplasms. After trypanosomes, Babesia are thought to be the second most common blood parasites of mammals and they can have a major impact on health of domestic animals in areas without severe...

    , Chagas disease
    Chagas disease
    Chagas disease is a tropical parasitic disease caused by the flagellate protozoan Trypanosoma cruzi. T. cruzi is commonly transmitted to humans and other mammals by an insect vector, the blood-sucking insects of the subfamily Triatominae most commonly species belonging to the Triatoma, Rhodnius,...

    , Leishmaniasis
    Leishmaniasis
    Leishmaniasis is a disease caused by protozoan parasites that belong to the genus Leishmania and is transmitted by the bite of certain species of sand fly...

    , Malaria
    Malaria
    Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...

    , and Scrub typhus
    Scrub typhus
    Scrub typhus or Bush typhus is a form of typhus caused by Orientia tsutsugamushi first isolated and identified in 1930 in Japan., accessdate: 16 October 2011...

    .
  • White blood cell
    White blood cell
    White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...

    s – due to the effective inactivation of white blood cells in donated blood products, riboflavin and UV light treatment may be used as an alternative to gamma-irradiation for the prevention of transfusion-associated graft-versus-host disease
    Graft-versus-host disease
    Graft-versus-host disease is a common complication after a stem cell transplant or bone marrow transplant from another person . Immune cells in the donated marrow or stem cells recognize the recipient as "foreign". The transplanted immune cells then attack the host's body cells...

    (TA-GVHD), a serious blood transfusion related complication.

Application

The riboflavin and UV light method for pathogen reduction of platelets and plasma is in routine use in multiple countries throughout Europe. This same process is currently in development for the treatment of whole blood, resulting in pathogen reduction of the three components (RBCs, platelets and plasma).
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