Pathogen reduction using riboflavin and UV light is a method by which infectious
pathogen
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
riboflavin
Riboflavin, also known as vitamin B2, is a vitamin found in food and sold as a dietary supplement. It is essential to the formation of two major coenzymes, flavin mononucleotide and flavin adenine dinucleotide. These coenzymes are involved in ...
and irradiating with
UV light
Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30 PHz) to 400 nm (750 THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...
. 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 platelets 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 acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main cl ...
RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
), 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
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Virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
es – both enveloped and non-enveloped including:
Avian Flu
Avian influenza, known informally as avian flu or bird flu, is a variety of influenza caused by viruses adapted to birds.Chikungunya
Chikungunya is an infection caused by the ''Chikungunya virus'' (CHIKV). Symptoms include fever and joint pains. These typically occur two to twelve days after exposure. Other symptoms may include headache, muscle pain, joint swelling, and a ra ...
Hepatitis A
Hepatitis A is an infectious disease of the liver caused by ''Hepatovirus A'' (HAV); it is a type of viral hepatitis. Many cases have few or no symptoms, especially in the young. The time between infection and symptoms, in those who develop them ...
,
Hepatitis B
Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.
Many people have no symptoms during an initial infection. Fo ...
,
Hepatitis C
Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...
,
HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
Influenza
Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms ...
,
Rabies
Rabies is a viral disease that causes encephalitis in humans and other mammals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, vi ...
, and West Nile. 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.
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Bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
E. coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
S. marcescens
''Serratia marcescens'' () is a species of bacillus (shape), rod-shaped, Gram-negative bacteria in the family Yersiniaceae. It is a facultative anaerobe and an opportunistic pathogen in humans. It was discovered in 1819 by Bartolomeo Bizio in Pa ...
S. epidermidis
''Staphylococcus epidermidis'' is a Gram-positive bacterium, and one of over 40 species belonging to the genus ''Staphylococcus''. It is part of the normal human microbiota, typically the skin microbiota, and less commonly the mucosal microbiot ...
S. pyogenes
''Streptococcus pyogenes'' is a species of Gram-positive, aerotolerant bacteria in the genus ''Streptococcus''. These bacteria are extracellular, and made up of non-motile and non-sporing cocci (round cells) that tend to link in chains. They are ...
Parasites
Parasitism is a Symbiosis, close relationship between species, where one organism, the parasite, lives on or inside another organism, the Host (biology), host, causing it some harm, and is Adaptation, adapted structurally to this way of lif ...
– including:
Babesiosis
Babesiosis or piroplasmosis is a malaria-like parasitic disease caused by infection with a eukaryotic parasite in the order Piroplasmida, typically a ''Babesia'' or ''Theileria'', in the phylum Apicomplexa. Human babesiosis transmission via ti ...
,
Chagas disease
Chagas disease, also known as American trypanosomiasis, is a tropical parasitic disease caused by ''Trypanosoma cruzi''. It is spread mostly by insects in the subfamily ''Triatominae'', known as "kissing bugs". The symptoms change over the cou ...
,
Leishmaniasis
Leishmaniasis is a wide array of clinical manifestations caused by parasites of the trypanosome genus ''Leishmania''. It is generally spread through the bite of phlebotomine sandflies, ''Phlebotomus'' and ''Lutzomyia'', and occurs most freq ...
,
Malaria
Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
, and
Scrub typhus
Scrub typhus or bush typhus is a form of typhus caused by the intracellular parasite ''Orientia tsutsugamushi'', a Gram-negative α-proteobacterium of family Rickettsiaceae first isolated and identified in 1930 in Japan.
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White blood cell
White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...
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 (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants.
White blood cells of the donor's immune system which remain wit ...
(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.Healthcare Technology Online. (2008, August 6). CaridianBCT Receives CE Mark for Mirasol Pathogen Reduction Technology System for Plasma. ress Release Retrieved from http://www.healthcaretechnologyonline.com/article.mvc/CaridianBCT-Receives-CE-Mark-For-Mirasol-0001?VNETCOOKIE=NO 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).