Evidence shows there is a risk of transmitting the neurodegenerative condition variant Creutzfeldt-Jakob disease (vCJD) through transfusion of blood and blood products, and thus also via surgery and dental procedures. Current strategies to reduce this risk in the UK are expensive and their benefit is uncertain. Furthermore, the disease-causing proteins (or prions) responsible for vCJD can lay dormant in humans for decades, meaning there are concerns there could be a time-bomb of vCJD hidden in the general population arising from the time of the mad-cow disease scare in the late1980s (mad cow disease, or bovine spongiform encephalopathy [BSE] is caused by the same prions). Estimates from a previous study, and used currently by the Department of Health, England, suggest that as many as 1 in 4000 people could be infected.

In an Article published Online First and an upcoming Lancet, researchers announce the creation of a new assay test that can detect minute amounts of the tiny CJD-causing particles, known as prions, in human blood. The Article is by Professor John Collinge, of The UK Medical Research Council Prion Unit and University College London, UK, and colleagues. The study was funded by the UK Medical Research Council. The authors hope this test, once fully developed, could ultimately be used to reveal the true prevalence of vCJD in the population.

To establish the sensitivity and specificity of the assay for detection of vCJD, the authors analysed a masked panel of 190 whole blood samples from 21 patients with vCJD, 27 with sporadic* CJD, 42 with other neurological diseases, and 100 normal controls. The researchers found the new method to be more sensitive by many orders of magnitude than the best current standard tests, since they were able to detect levels of CJD-causing prions at a dilution of 100,000-fold greater. 15 samples tested positive in the assay, and all 15 samples were from patients with vCJD, showing an assay sensitivity for vCJD of 71•4% (15 out of 21 cases) and a specificity of 100% (no false positives). Regarding the six vCJD cases that did not test positive, the authors suggest this could be because either their prion levels were too low, or possibly that not everyone infected with vCJD has prions in their blood.

The findings lead the authors to suggest that an assay-style test such as this could be used in the future to screen donated blood before it is accepted. As mentioned above, current methods to protect the population are expensive. These include leucocyte depletion - "this is removal of white blood cells. It was thought when this was recommended that this would remove most of the prions but this may not be the case. Other protection methods include sourcing blood plasma from the USA (where there was minimal exposure of the population to BSE) and importing blood for transfusion to young children from countries with no history of BSE (as discussed above, all countries have sporadic CJD). The UK Department of Health is also considering using prion blood filters through which the transfused blood is passed to try to remove most of the prions. Both the existing and proposed methods are extremely expensive, in the order of hundreds of millions of pounds annually. Thus a cheap, easy to use screening test could mitigate these costs.

However, the authors caution that, prior to large scale roll-out, large numbers (>10 000) of negative controls with low exposure to these prions would be needed to accurately determine the specificity of the test. They add that extended longitudinal study of individuals testing positive will be needed to establish the proportion of patients with positive tests that go on to develop clinical vCJD and how many are chronic carriers that pose a risk to others via blood transfusion or contamination of surgical instruments, but who do not themselves develop the disease.

They conclude: "Our findings demonstrate the ability to detect prion infection in blood and show that a donor blood screening test is technically feasible. The use of this test in differential diagnosis of suspected vCJD will be further investigated in large case series."

Prof Collinge adds*: "Long term co-ordinated research at the Medical Research Council (MRC) Prion Unit and NHS National Prion Clinic has been necessary to achieve this key breakthough. We expect this research will lead to improved and earlier diagnosis for our patients and, with further development and testing, provide the means to screen donated blood for prion infection. Such a screening test would allow estimation of the number of silently infected healthy individuals in the UK and other BSE-exposed populations to more effectively guide public health risk management in future."

In a linked Comment, Dr Luisa Gregori, US Food and Drug Administration, Rockville, MD, USA., asks whether the assay has sufficient sensitivity to detect the presumably lower concentrations of abnormal prion proteins that are expected to be present in blood of asymptomatic donors.

She agrees that large numbers of negative donors will have to be screened to determine the specificity of the test, and concludes: "Communication to the public of the uncertainty around a positive test result will be challenging and could result in fewer donors as well as causing unnecessary anxiety to deferred uninfected donors. These practical issues need to be addressed before this assay or others like it can be considered for clinical use as a donor screening test."


Sporadic (or classical) CJD is present all over the world and has been recognised since the 1920's. It arises seemingly at random in the population without evidence for patients being exposed to prions. It is thought to result from prions forming spontaneously in the brain as an unlucky event although it is possible that some cases will be due to unrecognised environmental exposure to prions either via diet or medical procedures. Variant CJD was first recognised in 1996 in the UK and was a new form of prion disease different from other types described. It predominantly affected young people (in sharp contrast to sporadic CJD which is a disease of late adult life) and had a very different appearance of the brain when examined microscopically. It was suspected this was due to BSE and this was confirmed by strain typing which showed vCJD patients had the same prion strain as that causing BSE. In vCJD prions are present in many tissues of the body (including blood) whereas in sporadic CJD prions are very largely confined to nervous tissue.

**Quote direct from Prof Collinge that does not appear in text of Article

***Dr. Gregori's views are her own and should not be taken to represent any FDA determination or policy.

Link to article

The Lancet