vCJD: A continuing threat

vCJD continues to be a real threat to public health as human to human transmission remains the easiest way to contract the disease – here MedLabNews finds out what can be done to stop the spread of infection

It is tempting to think that variant Creutzfeldt-Jakob Disease (vCJD) was a one-off occurrence – a disease of the last century – something to be consigned to the history books. Sadly, taking such an optimistic view is foolhardy because vCJD remains a very real and continuing threat to public health. Indeed, recent scientific findings indicate that we need to be more vigilant to ensure that people are protected from this devastating and fatal disease.

While the risk of contracting vCJD from BSE infected meat has been greatly diminished by changes in feeding practices in cattle, BSE cases still occur in the UK, Europe, Japan and North America.  Nevertheless, today it is blood donors who are incubating the disease but have not yet developed symptoms who represent the greatest threat. Since this route of transmission is between humans – rather than bovine to human – and the exposure is by transfusion or injection rather than orally, it is expected to be at least 1,000 times more efficient in establishing infection than transmissions from BSE infected food. To date there have been five recognised cases of transfusion transmission of vCJD and one highly probable transmission from a plasma product. The UK collects over 2.1 million blood donations annually (1.8 million in England alone) and it is simply not known how many of these donors are incubating vCJD. The best estimate to date indicated a minimum of 1 in 4,000 and it could be much more.
 
At present, most donated blood is treated to remove white blood cells by a process called leucodepletion, which also removes some vCJD prions. However, animal studies have shown that it removes only 40-70% of the infectivity – the remaining infectivity is more than sufficient to transmit the infection.  

Dr Robert Rohwer, director of the Molecular Neurovirology Laboratory and associate professor of neurology at the University of Maryland believes that recent developments strongly support predictions of second and third waves of long incubation vCJD.

He points to recent research by Professor John Collinge of the National Prion Clinic, published in the Lancet, which describes the first patient to succumb to vCJD from a previously unaffected genetic subgroup of the prion protein. Prior to this point, all 215 people who died of vCJD shared a certain version of the prion gene that is present in only one third of the population. The new finding strengthens an earlier prediction by Collinge of second and third waves of vCJD in people who were infected over the same period as people in the first wave, but whose genetics result in a longer incubation time. Two thirds of the population is in this group. Cases in this longer incubation group may be spreading the infection through blood and tissue donations and other invasive medical procedures. These new routes of exposure are of special concern because person to person transmissions are expected to be much more efficient than cattle to person transmissions.  

The concern generated by the Collinge research is compounded by reports from the Scripps Research Institute, USA which reveals that prions evolve to adapt to new environments. The Scripps experiments showed that prions mutate to more virulent strains and developed resistance to drugs used to suppress their propagation. Rather than being inert as was previously thought, it seems that abnormal prions are more dangerous, elusive adversaries showing adaptive traits similar to bacteria and viruses.

Against this backdrop, it is clear that action to prevent the spread of vCJD is needed. Many groups have sought to develop tests to detect the vCJD prion so that contaminated blood can be excluded. However, this has proved exceptionally difficult. Normal forms of the prion protein exist in every person and in blood they are 100,000 to 1 million times more concentrated than the infectious forms. Other plasma proteins are a million times more concentrated than even the normal prion protein. In spite of an abundance of ingenuity and tremendous development effort there is still no blood-based assay available for vCJD. In December 2009, one of the most advanced tests failed to detect prions in blood samples from clinical-stage patients who have died and been verified to have vCJD at post-mortem. People in the terminal stages of the disease are expected to have the highest concentrations of vCJD infectivity in their blood – significantly higher than symptomless persons incubating the disease.

So – what can be done? The good news is that the UK has been in the vanguard of assessing a novel P-Capt prion reduction filter which removes prion infectivity from red blood cell concentrate with an efficiency of 99.9% or greater.

The P-Capt filter was developed in collaboration between Pathogen Removal and Diagnostic Technologies Inc – a joint venture consortium involving The American Red Cross and ProMetic Life Sciences Inc, and French medical company MacoPharma SA. Today it is manufactured under licence and commercialised by MacoPharma. It is a single use, sterile device which received its CE Mark in 2006. Red blood cells are passed through the filter under gravity and the highly specific affinity adsorbent material within the filter captures and removes any vCJD prion protein.

Over the last three years, P-Capt has been comprehensively evaluated by the UK Blood Services – including the National Blood Service, the Northern Irish Blood Transfusion Service, the Welsh Blood Service, and the Scottish National Blood Transfusion Service – the Irish Blood Transfusion Service and the Health Protection Agency, and has met all targets and milestones. In October last year the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO), which advises the UK Department of Health (DoH), recommended that P-Capt be used to treat red blood cells destined for children born since 1 January 1996. The final decision on implementation rests with the DoH and it is hoped that this will be forthcoming before the General Election.

As part of last year’s recommendation to the DoH, SaBTO indicated that “the requirement for prion filtration should be reviewed in the event that further data on vCJD prevalence or filter efficacy becomes available.” Dr Rohwer warns that the findings of the last six months are more than sufficient to make that review necessary and urgent: “Recent developments warn of a continuing risk from vCJD and the timely and universal adoption of the P-Capt filter would go a long way toward arresting any further spread of the disease between humans by contaminated blood.”