Vol. 22 • Issue 7 • Page 42
Blood transfusion in the U.S. today is dramatically safer than in the early 1980s, prior to the availability of tests to detect units contaminated with hepatitis C and HIV. The risk for infection with hepatitis C virus or HIV has dropped to below one in a million in the United States.1 This is good news for patients and a triumph of modern laboratory medicine.
The leading risks of transfusion are due to non-infectious causes, such as blood type mismatch (human error) or transfusion-associated acute lung injury (TRALI), a potentially fatal immune reaction that causes damage to the transfusion recipient’s lungs. While infectious disease risks of the blood supply are undeniably improved compared to decades ago, dangers still lurk from emerging pathogens, some known and others not yet identified.
Case Study: West Nile Virus
In the summer of 1999, a cluster of patients with encephalitis (brain inflammation) was identified in New York City by an astute infectious disease physician in Queens. It soon became apparent that a new pathogen had emerged in the U.S., with West Nile virus (WNV) spreading rapidly across the U.S. in the coming years. The primary transmission cycle of WNV is between mosquitoes and birds, which develop high levels of the virus in their blood. Humans and horses can get infected but have such low levels of virus in the blood that they are called “dead end” hosts, meaning they don’t transmit the disease to mosquitoes that bite them.
However, in 2002 a fatal transfusion transmission of WNV was documented. In a model for collaboration, private industry, the not-for-profit blood banks, and multiple government agencies responded to develop new tests to screen the blood supply, implemented in June 2003, much more rapidly than for a typical new diagnostic test. Since implementation, thousands of blood products contaminated with WNV have been detected and removed from the blood supply, and transfusion transmission of WNV is now exceedingly rare.
Emerging or Rare Pathogens
Although screening tests exist for many pathogens potentially found in blood products, licensed blood screening tests are not available for some known pathogens. Examples include malaria or babesia, parasites that infect red blood cells. Transfusion of these pathogens can cause ðserious disease or death. In the case of malaria, blood donors who have visited an area of the world where malaria is endemic (where transmission from mosquitos is common) are deferred from blood donation for a year. This is a fairly effective strategy for preventing malaria transmission, but comes at the cost of deferring many donors who do not have malaria. In contrast, since babesia is found in the U.S., primarily the Northeast, deferral based on travel history is not feasible. Efforts are under way to develop screening assays for this pathogen, and occasional transfusion transmission of babesia still occurs.
Another pathogen that is a potential threat to the U.S. blood supply is dengue virus. This virus infects humans and is transmitted by mosquitos that have bitten infected animals or humans. This virus has enjoyed a resurgence in activity worldwide as mosquito populations have rebounded in the post-DDT era, and is prevalent in the Caribbean and many Latin American countries. Mosquitos able to transmit dengue virus exist in the U.S., though the virus has not gained a sustained foothold in the continental U.S. There is ongoing transmission in Puerto Rico, and studies of dengue virus infection rates in blood donors are ongoing in that region. The high cost of developing blood screening assays makes targeting pathogens that are rare in the U.S., such as dengue virus or malaria, less attractive to companies that manufacture the assays. Potential solutions to these “orphan” pathogen tests would be alternative approval pathways at the FDA or public-private partnerships for test development.
The nightmare scenario for blood banks is the appearance of a deadly, unknown pathogen that can be transmitted through blood transfusion. While surveillance and testing paradigms are much more sophisticated than they were at the time of the introduction of HIV into the U.S. blood supply, there is still vulnerability from a new, as yet unrecognized pathogen. With modern high-throughput DNA sequencing, new viruses are identified much more rapidly than even a decade ago, but developing an effective test still takes time once a novel pathogen is identified.
Pathogen Reduction Technology
The ideal scenario to prevent new and rare threats to the blood supply would be to develop a treatment that could inactivate pathogens that had escaped detection. These treatments exist for plasma, the liquid part of blood, but are too harsh to be applied to platelets or red blood cells as they would damage the product. Several companies have developed technologies to eliminate pathogens from blood products, and two are licensed for treatment of platelets in Europe, Intercept® produced by Cerus Corporation and Mirasol® produced by Terumo BCT. Both systems rely on ultraviolet (UV) light to activate amotosalen or riboflavin to damage nucleic acids in pathogens and kill them. These systems can reduce the level of viruses, bacteria and parasites (such as malaria) by one thousand- to one million-fold.
Although these systems are effective in treating platelets, they have not yet been approved to treat blood products containing red blood cells. The hemoglobin in red blood cells absorbs UV light, decreasing the ability of the light to reach pathogens to kill them. Cerus Corporation has developed a product to chemically target nucleic acids for inactivation. Initial trials revealed problems with immune responses developing against the treated products, and the original process has been modified to eliminate those problems. Terumo BCT is modifying the dose and delivery of UV light to inactivate pathogens in red cell-containing products, but both companies have yet to field an approved treatment for red blood cells. The full promise of pathogen reduction technologies will not be realized until all blood products can be treated effectively, since patients often receive more than one type of blood component. Also of note, no pathogen reduction technologies are currently approved in the U.S.
Although blood is safer now than any time in recent history, our blood supply still remains vulnerable to introduction of a novel infectious agent that is bloodborne. Continued vigilance in terms of monitoring and testing the blood supply will mitigate these risks, and ultimately the ability to inactivate broad classes of pathogens would provide an added layer of security for blood recipients.
Dr. Norris is associate director and senior investigator, Blood Systems Research Institute, and associate adjunct professor, UCSF Department of Laboratory Medicine.
Zou S, Dorsey KA, Notari EP, et al. Prevalence, incidence, and residual risk of human immunodeficiency virus and hepatitis C virus infections among United States blood donors since the introduction of nucleic acid testing. Transfusion 2010;50(7):1495-1504.