During the mid 1990s the issue of Bovine Spongiform Encephalopathy (BSE) hit the headlines. The story, some would argue, became the obsession of the media and a cause for concern among the general public. It was a scandal that threatened the very foundation of the British farming industry.
A short while later it was revealed that the disease could have serious implications. By 2002 there had been 139 reported deaths as a result of variant Creutzfeldt-Jakob Disease (vCJD); 129 of them in Britain, six in France and one each in Canada, Ireland, Italy and the US, according to WHO figures. The British figure had risen to 163 by March 2008 according to statistics released by the CJD Surveillance Unit based in Edinburgh.
Prior to these reports, CJD was only known to exist in three forms. The WHO says that sporadic cases with an unknown cause occur throughout the world at the rate of about one per million people and account for as many as nine in ten reported cases.
Familial cases are associated with a gene mutation and make up 5–10%. Iatrogenic cases result from the accidental transmission of the causative agent. Less than 5% of CJD cases are iatrogenic.
By the end of December 2006 it was revealed that scientists suspected there had been a third death as a result of vCJD acquired through blood transfusions in the UK. After analysis of the third patient they warned that vCJD could be ‘easily transmitted’ through the process of transfusion.
At that time, measures taken to try and avoid transmission through blood included importing blood plasma, and extracting the white blood cells from blood as they are believed to be the most likely carriers of the rogue proteinaceous infectious particles (prions) that can cause the disease. But the biggest challenge was the lack of a test to assess blood prior to it being made available.
While many saw the potential for human-to-human transmission from the reuse of surgical instruments as being the most likely route, the possibility of a transmission through blood was still of major concern.
VCJD: THE STATS
The WHO reports a number of statistics about the deadly virus.
- The first person to develop symptoms of what turned out to be vCJD became ill in January 1994. Most people who have developed vCJD have lived in the UK. Some of the patients had been long-standing residents in Wales, Scotland or Northern Ireland.
- As of early November 2002, the CJD surveillance unit for the UK reported 129 cases of vCJD, including 93 confirmed and 24 probable cases. In addition, there are 12 cases where vCJD is strongly suspected, but the diagnosis has not yet been definitively confirmed by post mortem analysis.
- Some of these patients have donated blood. However, to date vCJD has never been known to have developed in a recipient of this blood; study of possible transmission through blood transfusion continues. The UK no longer sources plasma from its inhabitants, and as a further precautionary measure, has instituted leukocyte reduction (removal of white blood cells) from blood transfusions. Some countries have prohibited donations of blood from persons who have resided in countries with higher risk of BSE. WHO cautions that donor restrictions such as these may not improve safety in some countries, particularly those still unable to institute measures against known hazards such as HIV, HBV and HCV.
By the end of 2006 scientists in the US and UK said they believed they had developed a filter that would remove the prions that carry vCJD from transmitted blood. The P-Capt filter was developed as the result of an extensive research programme.
The Cambridge and Baltimore-based team said they had found a molecule, known as L13, which sticks to prion protein (PrP) in blood infected with scrapie – transmissible spongiform encephalopathy disease similar to vCJD. The compound was coated onto small plastic beads and then placed into a small pouch that formed the filter. As the blood passes through the filter the misfolded and normal prion proteins become attached to the beads.
As part of their study into the device’s effectiveness the team used a batch of blood from hamsters with late-stage vCJD. It was processed in two stages. During the first stage the team followed the usual processes carried out before human blood is allowed to be processed into the blood bank; to remove all white blood cells. During the second stage they passed the same blood through the filter using the L-13 molecule. They also filtered a further part of the batch using L-13A – a variation produced on an industrial scale.
Of the 99 subjects injected with the blood that had the white blood cells removed, 15 went on to develop scrapie. However, of the similar number of hamsters injected with the filtered blood, none went on to develop the disease. Their findings showed that L-13 was able to absorb both the normal human prions and the misfolded prions associated with vCJD.
When the initial development of the filter was announced some in the blood transfusion field expressed concern at the potential problems with using such a technique. They included the possibility that such filtering may alter the make-up of the human blood and hence lead to further complications. However, recent human clinical studies into the effect of filtration of human blood and the alterations to red blood cells revealed that there were no changes. Clinical evaluations of the filter are ongoing in the UK and Ireland but the manufacturer is hoping to receive approval for use within the next year.
Previously, US-based Pall Corporation announced in 2005 that it had received CE marking for what it called the first and only technology that removes infectious prions that may be the causative agent of vCJD from red cells. The Leukotrap Affinity Prion Reduction Filter was found to remove as many as 99.9% of the infectious agent of vCJD that can be harboured in red blood cells.
THE NEED FOR FILTERS
At the end of 2006 two leading US experts in transfusion medicine and hematology called upon the US government and medical organisations to ‘reverse one of the most serious public health policy errors in the history of transfusion therapy in the US.’ Writing in Clinical Infectious Diseases, Neil Blumberg, MD and Joanna M Heal, MD called for the universal adoption of leukocyte reduction – essential to ensuring the lack of adverse reactions to blood transfusions. The pair said removal of all white blood cells by filtration was ‘the greatest advance in preventing short-term complications and death due to blood transfusion in the past half-century.’ It is estimated that just 80% of all donated blood is leukocyte reduced.
It is known that a significant number of Americans harbour latent infection-causing bacteria and viruses. The concern is that without filtration these might be transmitted during transfusion. vCJD was among the diseases cited as being potentially avoidable.
‘All treating physicians should insist on administering leukocyte-reduced blood transfusions to all of their patients and at all times,’ the two concluded. ‘Anything less is suboptimal medical care, will cause needless harm to patients in the short and long term and will cost their hospital and the healthcare system nationally more money than implementation of universal LR.’
The importance of filtering blood ahead of transfusion is undeniable and has for many years been obvious. Filtering can and often takes place in a lab, right through to at the bedside. While it was always an issue for healthcare providers, the events of the mid to late 1990s in the UK highlighted the risk that transfusions can pose to their recipients. We are all now aware of potential infections through diseased blood.
Healthcare providers the world over, but particularly in the West, are continually looking at ways of increasing the safety of blood being used in transfusion procedures. At the same time manufacturers are looking to develop more efficient and effective devices to ensure blood is as safe as possible before being administered. Now scientists are warning that there could be a second wave of such infection in the UK as we come to the end of another incubation period. It remains to be seen what the future holds and where manufacturers will go next to further improve patients’ protection against infection.