Americans donate roughly twelve million units of blood per year. These units are then processed into 20 million blood products that are to be transfused to millions of people in the United States1. This is an amazing miracle for patients with injuries that involve extensive blood loss, however donor blood may possess contaminants that are harmful to the human body. Many contaminants have been identified and have cures or solutions. Yet, more and more contaminants that threaten the U.S. blood supply are being discovered every decade, some more vital and deadly than others. Technologies are being developed to save the most lives possible and prevent complications through blood transfusions.
In ranking the emerging threats to the U.S. blood supply, there are four main criteria that need to be considered. First, there is the ability of the contaminant to survive in refrigerated blood for a number of days2. Second is the amount of patients susceptible to infection when administered the given agent through blood transfusion and the impact of the symptoms caused by infection2. Next, the presence and length of an asymptomatic phase in which the infectious agent is resides in the bloodstream2. Lastly, the prevalence of infection in the donor population is vital2. The threat of the agent contaminating the blood supply is statistically much less if the occurrence of infection in the general population is very small.
American trypanosomiasis, more commonly referred to as Chagas Disease, is transmitted in humans by the Trypanosoma cruzi parasite3. It causes illness for 4 to 8 weeks, and in 20-30% of infected patients can potentially lead to fatal cardiac disease and gastrointestinal problems later in life4. Chagas Disease can be transmitted in three ways: through the bite of an infected triatomine insect, by an infected mother giving birth, or via blood transfusion. Although this disease is limited to North and South America, it is prevalent in 21 countries3. Infection rates can range anywhere from 0.1% in Argentina to 24.4% in Bolivia5. Chagas Disease is usually only found in rural areas, yet due to economic and financial rationale, many people living in rural areas are moving into urban areas. This increases the risk of infection by blood transfusion. Studies have shown that about 1 in 25,000 U.S. residents are infected with the protozoan and in areas with high Latin immigrant populations, such as Los Angeles and Miami, the prevalence is estimated to be 1 in 7500 and 1 in 9000 respectively2. Chagas is the top threat to the U.S. blood supply because of its potentially severe symptoms, its transmissibility by transfusion, and its relatively high presence in the U.S. population. Vector control and blood screening are the two main ways to prevent further spread of this disease. Vector control has been quite successful. This is the effort of people trying to restrain carrier animals/insects from infecting humans. Countries involved in this have spent over 400 million dollars on vector control of the Chagas disesase5. Blood screening can also be an effective method. It can identify the specific antigen for Chagas disease in any blood sample. A downside to blood screening is that it’s only mandatory in 10 of the 21 countries Chagas dominates5. Two relatively new drugs (nifurtimox and benznidazole) are known for being able to cure 50% of infections. These drugs are active in the acute phase of Chagas, but have little activity in long-term chronic forms of the disorder. Use of these drugs has been limited because they have serious side-effects, are extremely expensive, and they haven’t been registered in most countries yet5.
Creutzfeldt-Jakob Disease is a rare and incurable brain disorder with a dire prognosis6. CJD is acquired by humans who consume the meat of bovine infected with Transmissable Spongiform Encephalopathy (TSE, also known as Mad Cow Disease)4. It is transmitted through prion, a protein with an abnormal structure, which is found in the brain. Prion refolds native proteins into a diseased state, causing them to lose their function and eventually die6. Prion grows exponentially, so it has the potential to kill its victim in as little as two months! There’s a classical CJD and an emerging variable CJD. vCJD has slight characteristic differences and is often found in younger patients6. It has a very long incubation period, up to 20 years. This poses a great risk because someone could donate blood without knowing they have the disorder. Studies have shown that transfusion of the disease is possible in sheep, and while it has not been confirmed that transfusion is possible in humans, there have been three reported cases7. Worldwide, 157 cases of the disease have been reported, none of which occurred in the United States7. Although the prevalence of the disease is not high (especially in the U.S.), it is ranked the second highest threat to the blood supply because it has recently been reported that some U.S. cows are infected with TSE. The disease can be diagnosed by electroencephalography, cerebrospinal fluid analysis, and MRI6. Cannibalism, hormone products corneal grafts, and implanted electrodes are associated with transmission of CJD6. A way that this deadly disease can be prevented from spreading is to ban blood donations in the United Kingdom from anyone that has received a blood transfusion before 19806. Since there is an asymptomatic period of vCJD, it is wise to control the spread through blood transfusion by simply banning all those who are a potential risk.
Severe Acute Respiratory Syndrome is characterized by fever and severe respiratory symptoms and had a 7-15% fatality rate2. There have been no documented cases of SARS in the U.S., however the high incidence of this disease in Asia and areas of Canada leaves room for a potential U.S. outbreak2. Although SARS is a respiratory disorder, there have been documented cases of viremia. This means there was presence of the agent in the bloodstream, therefore transmission by transfusion exists2. Since SARS could potentially become prevalent in the U.S. in the coming years and has the potential to be transmitted through blood transfusions, it is the third highest risk to the blood supply. There are several screening methods that can be used to reduce the risk of obtaining SARS-infected blood. Although SARS is a respiratory disease, it has a viral phase and possesses viral RNA that can be detected by reverse-transcriptase polymerase chain reaction8. PCR is a specific test, but not very sensitive. A positive test result will accurately indicate an infected sample, but a negative result does not necessarily indicate a clean sample. PCR is also relatively expensive and requires specific equipment and expertise11. Another diagnostic test is an enzyme-linked immunosorbent assay test that can detect antibodies prevalent to SARS. ELISA uses an antibody specific to the SARS-relative antigen and another antibody causes a chromogenic or fluorogenic substrate that produces a signal. This test is much cheaper than PCR, and more sensitive in detecting SARS9. An immunofluorescence assay can also detect antibodies of the disease. Immunofluorescence labels antibodies or antigens that are produced due to the presence of SARS CoV and labels them with fluorescent dyes that can be detected with a special microscope10. Moreover, pre-donor screening to avoid any possible risk of infected blood should include white blood cell or platelet count. Suggestive alerts for SARS, besides visible symptoms, include low white blood cell and platelet count and high levels of lactate dehydrogenase, creatine kinase and C-reactive protein11.
The next category of contaminants to the blood supply pose a medium risk because they are either less transmissible through blood transfusion or have non-severe complications associated with infection. The first disease of this category is Human Herpes Virus 8 (HHV-8). It is linked to Kaposi’s sarcoma, body cavity based lymphoma, and Castleman’s disease. Of all anatomic sites, the presence of HHV-8 is found most frequently in saliva12. It’s transmitted mainly through sexual contact, although it is suspected to have the potential to be transmitted through blood transfusions as well7. Data shows that approximately 3% of donors in the U.S. carry HHV-8 in their bloodstream7. Due to the significance of its resulting diseases and prevalence in the population, HHV-8 is a significant risk to the U.S. blood supply. Nonetheless, it is considered a medium risk because incidence of transfusion is rare. One present examination for HHV-8 transmission involves testing plasma/serum samples. HHV-8 serostatus is measured with an enzyme immunoassay (EIA). The assay detects antibodies to most structural and non-structural antigens present in HHV-8 virions. Transmission risk may also be reduced through routine procedures that remove most circulating B lymphocytes. Acellular blood products have few lymphocytes, thereby conveying a lesser risk13. The next disease is Babesiosis, a parasite infection from a tick bite that is similar to malaria7. It only causes mild flu-like symptoms in most people but could be deadly to immunocompromised patients7. Studies have shown that it can survive in erythrocytes for up to 35 days and there have also been 40 reported cases from blood transfusion since 1980, however there is no current test to screen for babesiosis7. Since the disease can be transmitted through blood transfusion and there is no test for it, babesiosis poses a strong risk, however its mild symptoms place it lower on the threat list.
The final category of threats to the blood supply involves the low risk agents. These include, in order of risk, the bacteria Anaplasma phagocytophilium and Ehrlichia chaffeensis, and the virus Hepatitis G. A. Phagocytophilium is acquired by humans primarily through the bite of a tick and causes mild flu like symptoms but potentially causes severe complications and even death in 5% of the infected. It has been determined that it can survive in blood for 18 days, however there were only 351 cases of it in the US in 20002. It is suspected that the bacteria can be eliminated as a threat in stored blood by the use of leukoreduction filters2. E. Chaffeensis has virtually the same incidence of infection and characteristics as A. Phagocytophilium, however there are not severe complications that occur with its infection making it less of a threat2. These two were low on the list because of their lack of occurrence in the population, low severity of complications, and the potential that exists for their threat to be eliminated by the use of filters. Hepatitis G is a viral strain that has not been found to have any effect on humans, although it is suspected that it could lead to post-transfusion hepatitis7. It can be obtained even though the transfused blood shows negative for Hepatitis A, B, and C. Some believe that the G virus is associated with liver disease, but many researchers are also doubtful that it causes any illness at all14. Currently there is no treatment available for Hepatitis G and the etiology is unknown. It is very similar to Hepatitis C and is seen in 20% of patients with any type of Hepatitis, therefore it is believed to possibly be a co-infectant with other Hepatitis viruses15. Currently the only method of detecting Hepatitis G is through a costly DNA analysis that is not widely available, but there is a strong effort to develop a test for the antibody of this mysterious virus15. Because there are no affects associated with the viral infection it must be considered the lowest risk of potential emerging threats to the U.S. blood supply.
One of the most common obstructions of blood transfusion is bacterial contamination of blood. Bacterial contaminants can result in septic reaction and even death of the blood recipient16. This type of contamination is considered the second most common death from transfusion in the U.S. Fatality rates are raising from one death in every 20,000 donor exposures to one in every 85,00017. Due to the bacteria that have be already been found, new bacteria have been pre-conditioned to proliferate faster than older ones. Bacteria have also formed the most optimal structure of DNA to resist anti-septic protocols. For instance, it is estimated that the level of contamination of bacteria is very low, about 1 to 10 colony units bacteria per mL, but with the appropriate media and temperature, these bacteria can divide and proliferate at a high enough rate to reach 106 units/mL within several hours17! The most common cases for bacterial contaminations are: donor bacteremia (blood donors are either asymtomatic or in recovery phase of a bacterial infection), contamination during within the skin or needles while blood is being withdrawn, and contamination of an improperly prepared blood bag17. Therefore, donated blood with pre-screening still has chances of re-emerging threats for blood transfusion. Based on these common contamination risks, the general solutions for bacterial contamination are: to strictly follow anti-septic procedures for needles and skin regions that are being exposed to blood, take considerations when choosing blood bag and the contamination level, and material being made for blood bag for the optimal storage solution with the least contamination. Pre-detect any bacterial existence by measuring the amount of oxygen being consumed or the amount of CO2 being produced by sensitive micro detection equipment. Finally, the donated blood can be scanned by “pathogen inactivation,†which uses pathogen reduction devices combined the use of psoralen and ultraviolet A light, riboflavin and visible light, ultraviolet B irradiation, and the addition of methylene blue or phthalocyanines with visible light. These combinations will inactivate the bacterial proliferation. Thus, they will be reduced as these lights are scanning through the platelets which they thrive on17. Blood bags should be stored at very low temperatures (about four degrees celcius) 17. All these precautions should be taken to minimize bacterial contamination.
The application of microarray technology to blood testing would be a revolutionary advancement. It would provide an integrated platform for comprehensive testing of donor and donation replacing multiple individual assays18. Researchers are currently trying to achieve a system of implementing microarray technology to screen a blood sample for various impurities and diseases all at once. Such a system would simplify and improve the efficiency of blood screening and has the potential to reduce the cost and time of multiple tests18. The microarray technology would use an antigen microarray consisting of glass slides dotted with thousands of proteins and other molecules that are attacked in autoimmune diseases19For the microarray technology, doctors will draw a blood sample from the patient and incubate it on the array. The antibodies target corresponding molecules on the array and attack them. Then fluorescent molecules are added to create colored spots on the slide that detect which antibodies attacked their molecules. The doctor or lab analyst then counts the spots to observe which antigens the immune system responded to19. In an unaffected, healthy patient, the antibodies will ignore the majority of the antigens on the array. In diabetic patients, the spots on their array will correspond to pancreatic cell proteins. In patients with rheumatoid arthritis, the spots will correspond to molecules found in joints of the body19. Due to large data sets generated by the chips, new statistical and informatics-related challenges have risen. This makes microarray technology is a victim of its own success. Novel statistical methods need to be innovated for analysis of these plenteous and diverse data sets20. There is no standard system for generally managing and providing an expenditure of microarray techniques or their applications20. Although this technology will allow the application of new insights, its potential is limited by the constraints mentioned above. Microarray technology will most likely revolutionize the bio-medicine field in upcoming decades. This tool will help mankind understand more about life on planet earth, but it has also taught us that we have much more to learn in years to come.
With all the tests and solutions to improve blood transfusions, sometimes there’s simply not enough time to get blood to a victim. In these distressing cases, one cannot bleed to death until donor blood arrives to them, so there are temporary solutions. Currently, there are no artificial blood substitutes available on the market, however there is a partial substitute. This blood substitute contains artificially engineered hemoglobin and can carry oxygen throughout the body sufficiently. Although oxygen can be distributed to limbs and various other parts of the body by this innovation, it cannot carry nutrients. Therefore it hasn’t been approved for the market21. Potential uses including trauma, various surgeries, angioplasty, and oxygenation of tumors during chemotherapy or radiation. Also, the product can be made available on the battlefield, at the scene of accidents, and stored in emergency vehicles/departments21.
All in all, there are many modern dangerous contaminants that threaten the U.S. blood supply. Still, there are precautions and tests that can be taken to prevent the further spread of them through blood transfusions. New tests and technologies, such as microarray technology and artificial blood substitutes, are being improved to perfection everyday. Mankind’s potential to overcome these obstacles are endless.
This paper is a collaborative effort by Amy Shah, Bao Dinh, Jonathon Hwee, Andrew Keebaugh, and Brian Rinaldi
