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Transmission of Human Pathogens Via Transfusion October 6, 2006

Posted by Hegemony in Health, Science.
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Those with bleeding disorders like hemophilia have long felt the brunt of the unknown in medical transfusions. Despite recent advances in this area of care the risk posed by emerging pathogens is great. The emergence of HIV is an example of what can occur if we are not vigilant in the search for new human pathogens. Coagulation-factor Concentrates (CFC) have been beneficial in that they are treated more thoroughly, but the threat remains.

When a virus enters the human population it goes through three main steps. The first is introduction. This means a new virus come into contact with humans or an existing human virus adapts in some way. An example of this is how SARS was originally introduced by zoonotic transmission from birds, or HIV from chimpanzees.

The next phase is adaptation. At this stage a pathogen establishes itself and spreads in the species. This often occurs after an alteration in the environment; it can be related to expansion of industry, new medical technology, or a change in public health practices. For example the construction of Aswan dam caused 200,000 deaths from Rift Valley fever which was originally spread via an arthropod vector.

In the final stage a pathogen becomes actively dangerous in a population. This is called emergence. This can occur one of two ways: abruptly with a shorter outbreak (like Ebola) or more gradually and thus more wide spread (like HIV).

There are many viruses that blood products are screened for but the question remains if an emerging pathogen will be caught in time. Part of the problem is that some diseases present no clinical symptoms for a time even though the plasma may be highly infective. One such pathogen is West Nile Virus, a flavivirus. At the peak of the epidemic in New York West Nile infection through transfusion was thought to be about 1.5 in 1000. CFC is usually treated in such a way that West Nile is inactivated. West Nile and other lipid envelope viruses are relatively easy to inactivate compared to the non-enveloped viruses.

The non-enveloped, or naked viruses, may cause a greater risk to CFC as some methods will be ineffective at eliminating them. Many different serotypes of enteroviruses have been isolated from human donations. Some of these are potential pathogens. Enterovirus 70 is a known cause of acute hemorrhagic conjunctivitis and Enterovirus 71 seems to cause various encephalitis diseases. Circoviruses are even smaller and resist nanofiltration. There are no known human diseases associated with Circoviruses but it has show the ability to jump species.

Prions are also of particular interest here. The emergence of variant Creutzfeldt – Jakob disease showed that spongiform encephalopathies can be easily transmitted. The normal prion protein (PrPc) is present in the plasma meaning that there is potential for PrPsc to be present as well. The altered prion protein (PrPsc) has been shown to be transmissible 10-20% of the time in sheep. While it is possible to transmit this disease in blood products it is only a theoretical threat at this point.

Those with coagulation disorders like hemophilia have a special risk of contracting these diseases. Receiving transfusions of blood products for their entire life increases the odds dramatically. After the AIDS epidemic got into full swing the life expectancy for a patient with hemophilia went from 57 years to only 35 years by 1995. These patients also tend to be infected with hepatitis B and C, which complicate their care. Recent advancements in clotting factor replacement therapy have shown promise though. While plasma derived clotting factors could carry disease, new recombinant technologies may put an end to this threat.

Clotting factors can be made by immortal cell cultures with less chance of viral contamination. So called first generation cell cultures contain human proteins and thus have the capability to carry prions. In second generation cultures the stabilizing animal proteins are replaced with carbohydrates reducing the risk of prion transmission. Finally, in third generation no human or animal proteins are added. This is believed to be the safest source of human clotting factors.

Hemophilic patients are exposed to the sum of human disease and often pay dearly for it. Recent advances may provide safer sources of the clotting factors they need. But it will never come soon enough for some.

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