User:Ryan Alfonso/Pathogen inactivation

Transfusion-transmitted infections are a very rare event thanks to detailed screening of volunteer blood donors. Donated blood is then tested for a variety of pathogens including HIV, HBV, HCV, HTLV-1&2, and Syphilis. Recently, testing for West Nile Virus (WNV) has been undertaken by some blood centers as an additional means of ensuring the safety of blood products for transfusion.

Risk: Yet still there is a measurable risk of a pathogen slipping through the system and infecting a patient, presumably when they're already battling injury or illness. What could these pathogens be? As we've seen, it took more than a year to implement processes to eliminate WNV positive blood from blood banks. Several documented cases of WNV transmission are in the literature. In the 80s, hundreds of people around the globe were infected with HIV before the illness was even recognized. We could be in the midst of something similar right now and not be aware of it.

- France HIV - Hemophiliacs:  F VIII deficiency - Italy HAV In today's world, H5N1 and H1N1 are at the top of everyone's watch list. Other than inspecting the general health of the donor by asking "do you feel well today?", there are no measures in place to assure the donation is free of influenza virus. It has been estimated that the latency period for flu viruses can be as many as seven days, giving an infected person ample time to donate blood before falling ill. One could argue that the benefits of protecting patients from a community acquired infection like a cold or a flu is a waste of time, but again, the recipients of these blood products are typically profoundly weakened by injury or cancer -- no time to be contracting illnesses from blood products.
 * Notable wide-scale transfusion associated infections

Risks from each blood component - distinguish bacteria as major threat to platelet concentrates (address how it gets there).

Another infrequent and life-threatening complication of transfusion is graft-versus-host disease (GvHD). GvHD results from donor Leukocytes mounting an immune reaction against the host. In essence, one can add donor white cells to the list of pathogens jeopardizing a transfusion recipient. Leukofiltration, removal of contaminating donor white cells, has been very successful at minimizing occurrences of GvHD and is a common practice. But in cases of immunodeficiency induced by chemotherapy, the risk is higher since the patient is unable to combat the invading donor immune cells. Tranfusion medicine specialists, hematologists, oncologists, know that by irradiating a blood product with gamma radiation, GvHD is mitigated. The downside to this is that the blood center has to maintain a nuclear medicine area

Solution: What is the solution to these problems? For decades scientists have been investigating proactive solutions to the problem. In essense, the goal is to kill anything "alive" in a blood product, whether it's an identified pathogen, or one you don't know exists yet. A transfusion blood product does not require that the cells have viable DNA, so DNA targeting the therapy is ideal. Red cells = no DNA, platelets, not an issue.

Autoclaves are used to sterilize surgical instruments, but no similar process exists for complicated biological products like blood components. During the last ten years, several companies have sought to commercialize photochemical means of decontaminating blood products. In this type of system, illuminating a blood bag with a bright light source activates a drug added to the blood. The resulting active compounds kill any contaminating virus, bacteria, or protozoa, that may have come from the donor. This type of system is of most use in plasma and platelet concentrates where light can readily pass through. Pathogen inactivation of packed red cell units is particularly challenging by photochemical means because of the absorption spectrum of hemoglobin and the sheer density of the material. UVA and white light penetrates only 7mm (ref) meaning that the triggering the photo-active compound would be inefficient at best.

The light sources range from broad spectrum white light, ultraviolet (UV-A), UV-C, or red light [ref wavelengths]. The drugs range from psoralen analogs (amotosalen), dyes (methylene blue), or photo-active vitamins (riboflavin).

Mechanism of action: DNA cross-linking, specific Oxygen radicals, non-specific protein damage

Impact of PI on quality of blood product

Benefits: No infection No GvHD Platelet - extend shelf-life Cost avoidance - plasma quarantine

Pathogen Inactivation in Global Use: Chikungunya in La Reunion EU: Amotosalen, Methylene blue, Riboflavin Potential benefit in areas of endemic HIV in RSA, Malaria, Chagas, in development for battle-field, disaster use

Clinical studies with PI blood products:

Cost-Benefit, ethics