Blood borne diseases

 

While blood transfusions are acclaimed for their life enhancing properties, a darker side that is sometimes overlooked is their capacity to create serious, even fatal, medical complications in the people who receive them. This is because blood, as a complex biological fluid, can serve as the ideal mechanism for transferring a range of viruses, germs and parasites from an unhealthy donor to an uninfected recipient. It is due to these potential hazards that so much emphasis is placed on reviewing the past and present health status of blood donors, along with whether or not they are remunerated for giving blood (due to the contentious view that paid donors are inherently unhealthier than their altruistic counterparts). In this section, we look at the principal diseases which recipients risk being exposed to during transfusion, with an evaluation of their characteristics, indications, and effects. In addition, we look at the preventative measures that can be adopted against each of these threats in an attempt to guarantee the integrity of the blood transfusion system.

 

i) Human Immunodeficiency Virus

In the late 1970s and early 1980s, public health authorities began to notice that groups of homosexuals in various parts of the USA were all falling victim to a series of relatively rare diseases. Soon thereafter, other segments of the more general public started to display similar signs of infection, which alerted the authorities to the possible existence of a new causative virus that was precipitating these undesirable infections. Following an extensive search conducted amidst mounting public anxiety, the common agent that was held responsible for triggering the outbreak of these diseases was finally identified in 1983, where it was subsequently named the Human Immunodeficiency Virus (HIV).

 

HIV has been classified as a retrovirus, which is a type of virus that carries the blueprint to its genetic structure in RNA form, which it then converts into that of human DNA once it has managed to penetrate a CD4 cell (which is a type of white blood cell). In early 2000, there were almost 40 million people with HIV in the world [1], with most being carriers of HIV-I, while a much smaller proportion had the less virulent HIV-II, which is found mainly in West Africa. Regardless of the type, the end result of being infected with HIV is that, after undergoing an incubation period of 7-10 years, the carrier enters a clinical stage where he has what is known as Acquired Immunodeficiency Syndrome (AIDS) [2]. During this period, the body is severely immunocompromised, which means that the white corpuscles are slowly eradicated by the invading virus, allowing for opportunistic infections, such as tuberculosis and pneumonia, to attack the patient. Eventually, after about 2 years of being in this state, the patient’s resistance against such diseases will be irrevocably destroyed, and he will die from the adverse symptoms brought about by the opportunistic infections [3].

 

Although HIV was initially believed to be associated with only certain homosexual acts, research identified further transmission avenues as being intravenous drug abuse, heterosexual sexual activities, mother-to-child (or perinatal) transmission, and, of special interest, blood transfusion. Indeed, many of the earliest cases of HIV to be contracted by non-homosexuals were attributed to the utilization of infected blood products. This is because HIV has been found to be transmitted by most blood products, including whole blood, red cell and platelet concentrates, and a series of FFP derived products, including factor VIII and factor IX concentrates. As a result of this widespread contamination, large numbers of blood users became infected with HIV, with haemophiliacs being especially hard hit early on due to the multiple exposures that they had to products acquired from tainted plasma pools.

 

Fortunately, the incidence of HIV in the blood supply of the developed world has all but disappeared in recent years. This is due to both the implementation of more stringent donor eligibility policies, where high-risk individuals are excluded from donating, and as a result of the treatment of blood products through chemical or heating processes that inactivate the virus (albeit at a loss in the efficiency of the blood product obtained) [4]. However, the most important factor was probably the introduction of routine sample testing on all blood from 1985 onwards. Currently, the standard screening test is an enzyme linked immunosorbent assay (ELISA), which searches for the presence of HIV antibodies within each sample of donated blood. Should the result of the test prove to be positive, then the result can be checked by using the old “Western Blot” test, although as a standard safety precaution, all such donations are immediately destroyed, even if the sample result may have actually been that of a “false positive” (i.e. contained HIV negative blood which appeared to be positive).

 

Despite the benefits provided by these screening tests, a major concern that remains revolves around the issue of donation by a recently infected donor during what is commonly known as the infection “window period”. During this period, a donor may give blood even though he has just been infected with HIV and is undergoing a seroconversion process, where his body has yet to react effectively against the relatively few HIV organisms that are present. An ELISA test conducted at this stage will reveal a “false negative” result as it cannot find sufficient proof of infection, which may result in this unit of blood being passed on as safe for use (to the obvious detriment of any blood recipients). Fortunately, the number of HIV cases attributable to the transfusion of blood collected during this window period is small, since new generation ELISA tests have become so accurate that they have been able to detect increasingly lower quantities of HIV antibodies within about 14 days of infection [5]. Nevertheless, despite all these preventative measures, the HIV infection rate from blood transfusion is not constant across the world, as the extent to which a blood bank is capable of detecting HIV depends largely on how wealthy and well equipped it is. Consequently, there appears to be some link between national wealth and the rate of transmission associated HIV infection, with a poor country such as Namibia having 1 infection for every 1,527 donations against a comparable rate of 1:45,455 in a middle income state such as South Africa [6] and 1:676,000 in a wealthy country such as the USA [7].

 

ii) Hepatitis

Before the arrival of HIV, the most common disease transmitted in blood was hepatitis. Although viral hepatitis has existed for centuries (where it was often mistaken with jaundice), scientists had great difficulty in pinpointing the exact features of this virus. It was only in 1963, when, by accident, a group of researchers identified a previously unknown antigen in the blood of an Australian aborigine who had displayed the symptoms of this disease that the puzzle started to be unravelled [8]. The discovery of this marker, which was referred to as the Australia antigen, was to provide the initial breakthrough for mounting a medical response against this virus, which was, at the time, responsible for infecting a substantial percentage of blood recipients.

 

In general, hepatitis is a disease that affected the liver, although the actual symptoms and affected sites can vary immensely, depending as they do on a range of factors, such as the particular strain of virus, degree of viral exposure, age of patient, and level of patient immunity. In the mildest of cases, only gastrointestinal or influenza-like symptoms are likely to be noticed following an infection, in which case the fact that the patient has the virus may go totally undiagnosed, even by a physician. A more severe hepatitis attack may cause the patient to display, amongst other things, nausea, loss of appetite, weight loss, fatigue and physical discomfort. This attack, which usually lasts for up to one month, is then followed by a recovery period during which most patients become immune to the disease, although occasional relapses may occur. Fortunately for most of those who are infected, they do not suffer from fulminant or acute viral hepatitis, where a patient faces an attack that may result in a coma, liver failure, severe haemorrhaging, or even death [9].

 

There are several varieties of hepatitis virus, each of which has different modes of transmission and levels of potency. Probably the most important variety is hepatitis A (HAV), which is also known as infectious hepatitis, as its ability to spread between people is notorious, especially in the developing world, where standards of hygiene and sanitation are relatively low [10]. While hepatitis A is transmitted mainly via person-to-person contact or following exposure to fecally contaminated food and water, it has been known on rare occasions to be transmitted through blood transfusions, especially in cases where plasma was obtained from donors who were recently infected with the virus. Despite this, tests that screen for the presence of HAV antibody are not performed on a regular basis by blood banks due to the high effort but limited value for money involved [11].

 

The first form of hepatitis to actually have been identified was hepatitis B. This type, which is carried by 250-350 million people worldwide, is thought to be directly responsible for the death of at least one million carriers per annum, making it a greater global killer than HIV/AIDS [12]. In addition to being perinatally and sexually transmitted, this virus can also be passed on via transfusion, where it has been known to survive in most blood products (with the notable exception of pasteurised albumin). As only a minute quantity of viral matter can infect a person, hepatitis B is highly contagious, with even a single infected blood donation being able to contaminate an entire plasma pool. Because of this, it is standard operating procedure to screen all donated blood for the presence of the hepatitis B surface antigen (HbsAg). In addition, other steps that have been taken to reduce the transmission of this virus include the creation of smaller sized plasma pools, the employment of additional tests to search for signs of the virus [13], the use of special processing to destroy or inactivate the virus, and the provision of vaccinations to regular users of potentially infected blood products (although vaccine resistant mutant strains do sometimes appear). As a result of these measures, the estimated hepatitis B infection rate per number of transfusions is in the order of about 1:50,000-100,000 in the UK, and 1:66,000-200,000 in the USA [14].

 

Once hepatitis A and B had been uncovered, researchers found that a considerable number of people with hepatitis symptoms could not be identified as having the biological markers relating to either of these strains. Consequently, they were classified as having non-A, non-B hepatitis, but following a highly innovative virus cloning programme aimed at solving this problem, almost all of these individuals were later be reclassified as having hepatitis C (HCV). This strain, which is estimated to have infected about 200 million people worldwide [15], is nowadays most commonly acquired through intravenous drug abuse and faulty medical safety procedures, although, until the implementation of anti-HCV screening in the early 1990s, it was also widely transmitted through blood. Unlike the previously covered strains, HCV cannot always be found directly through the use of an antigen test. Rather, it is detected through the use of surrogate tests that screen for antibodies to hepatitis C, and for the presence of certain identifying enzymes in the donor liver, although better tests are gradually being developed [16]. Since the introduction of testing, the probability of HCV infection has fallen to about 1 in 121,000 donations in the USA, and 1:200,000 in the UK [17], with new donors being about ten times more likely to donate an infected unit of blood than repeat donors [18].

 

Finally, there are a couple of less important hepatitis types, including hepatitis D (known as the delta agent, which appears in combination with hepatitis B), hepatitis E, and the recently discovered hepatitis G virus. Although the risks that some of these strains pose with respect to blood transfusion are still not fully known, it is certain that their characteristics, along with those of other yet to be discovered hepatitis strains, are likely to be determined in the future as further investigations continue.

 

iii) Syphilis

Until the introduction of penicillin in the 1940s, syphilis was considered to be a serious medical condition, but since then, there has been a widespread perception that the dangers posed by this disease have been largely eliminated. This is, however, unfortunate, since not only does this disease cause serious problems if left untreated, but there is also a misconception that it is only sexually transmitted when, in fact, it can also be acquired via transfusion. Fortunately, the risk of transfusion is extremely low as the parasites (known as spirochetes) which cause this disease cannot survive in blood bank storage temperatures of 1-6° C for longer than 72 hours (although they may survive for longer in platelet concentrates, which are stored at 22°C) [19]. In addition, as many hospitalised patients who receive transfusions often receive antibiotics as part of their course of treatment, so any spirochetes that may have unwittingly been transfused are likely to be eliminated without ever having been detected, reducing the true rate of blood borne infection. Despite the extremely low risk of infection, it is often standard practice to conduct a serological test for syphilis (STS) on blood donations, as this serves as a good proxy for detecting the presence of other STDs in the donor. In particular, it is useful when looking for HIV, as a positive result may indicate that the donor is in a high-risk sexual category, thereby suggesting that he should be excluded from the donor pool.

 

iv) Malaria

In several parts of the inhabited world, mosquitoes serve as the carriers of various types of parasite, some of which, if left untreated, can cause a fatal illness in a human host. These parasites are especially dangerous for not only can they be passed to others via blood donations, but they can also survive in blood bank storage temperatures for up to two weeks, which means that cold storage is no guarantee of safety. While medical treatment can counter malaria, various measures have been implemented by blood banks to ensure that, as a matter of principle, all blood donations are safe against these parasites. In countries where malaria is uncommon, such as the UK and USA, people who have lived in, or travelled to, a malaria prone zone are barred from donating blood indefinitely, or until a period of time has elapsed since they last were in the danger zone. In malaria infested countries however, this approach would be inappropriate as many people would be ineligible to donate, so a range of alternative measures have been introduced to deal with their blood. These include medically examining donors, quarantining their blood for set periods of time, or using only those blood components that do not support the survival of the parasites. Due to the implementation of such measures, the number of cases of malaria transmitted by blood has become insignificant, and so formal testing has, per se, been largely done away with.

 

v) Minor infections

Several other viruses pose a small or theoretical hazard to the safety of blood recipients. Foremost among these is cytomegalovirus (CMV), which is a strain of herpes virus present in most healthy adults. Usually, blood recipients are not harmed when they have this virus, but it can be dangerous when transfused into patients with severely compromised immune systems, such as infants, organ transplant recipients, and HIV sufferers [20]. Despite this risk, blood is not normally tested for the presence of this virus due to both its high frequency amongst donors and its often benign nature amongst recipients [21]. By contrast, one other relatively rare virus whose presence is screened for in some countries is the human T-cell lymphotropic virus (HTLV), which is retrovirus closely related to HIV [22]. While the two known types of HTLV have been held responsible for the deaths of only a few people, there is a fear that if they were to mutate, then an epidemic as destructive as the one wrought by their more famous cousin could arise. One final virus that should be considered is Creutzfeld-Jacob disease (CJD), which has been linked to bovine spongiform encephalopathy (BSE). While it is not yet clear whether this virus can be transmitted via blood to humans, (although it can be transfused via blood among animals) [23], medical authorities in the USA have argued that as a precautionary measure, screening tests for this disease should be introduced until conclusive evidence on the risks of this disease become available [24]. In addition, blood services in several countries, including the USA and Australia [25], have banned donations from all people who have been in the UK between 1980 and 1996 for a period of at least 6 months.

 

Blood can also be contaminated by bacteria, with the risk of infection ranging from 1:1,000,000 for red cell products, to 1:2,400 for platelet concentrates (as bacteria survives more easily in the higher temperatures at which these products are stored) [26]. When exposed to these contaminated products, recipients can suffer from toxic shock, which, if left untreated or misdiagnosed, can rapidly become fatal. While precautionary measures against the spread of bacteria can be taken, contamination still occurs. For example, although donor arms are routinely swabbed clean with a disinfecting agent, and sterile, disposable collection kits are always used, resistant microbes may still survive and be collected during the plugging of a donors skin. In addition, although the plastic storage bags now in use are more sterile and manageable than the bottles they have replaced, they are still not perfect, and must sometimes be destroyed if they have faults in their structure that exposes their contents to the natural environment.

 

Link to: <Contents>  <Previous Section>  <Following Section>