vCJD prion infection: improving diagnosis and surveillance

The MRC Prion Unit at UCL has played a key role in addressing the public health issues raised by 'mad cow disease' and its human variant, by developing blood tests to screen donated blood and organs for transplantation.

Bovine spongiform encephalopathy (BSE), popularly known as 'mad cow disease', is related to variant Creutzfeldt-Jakob disease (vCJD) in humans. This degenerative neurological disorder is invariably fatal, and a study by the Health Protection Agency (HPA) estimates that one in 2,000 UK citizens are carriers - clearly alarming when coupled with the known potential for transmission via blood transfusion.

The MRC Prion Unit was established at UCL in 1998 to address this national public health issue. One of its key strategic priorities was to create a validated blood test for vCJD in order to protect public health through the screening of donated blood and organs for transplantation.

Using existing World Health Organization diagnostic criteria for vCJD, disease can only be classified as 'probable' in the presence of significant neurological deficit and confirmed as 'definite' using neuropathological examination. Despite the relentlessly progressive nature and devastating prognosis of these disorders, securing a firm early diagnosis is crucial. This helps to identify potentially reversible conditions, and removes uncertainty, which in itself is distressing. Once a disease is identified, patient care plans can be established, patients and families counselled and appropriate infection control measures implemented. A sensitive and specific blood-based molecular diagnostic test for prion disease facilitates early disease diagnosis and entry into therapeutic trials. In addition, such a test has obvious applications in reducing transmission, screening of blood products for transfusion, food and medicinal products.

Detection of disease-associated, abnormal forms of the prion protein such as PrPSc is the most specific criterion for the diagnosis of prion disease in humans and animals, but there is a counterbalancing limit on the sensitivity of detection. Research led by Professor John Collinge (UCL Institute of Neurology) has identified new methods for the specific detection of abnormal forms of PrP without sacrificing sensitivity. These methods were used in conjunction with monoclonal antibodies developed at UCL to detect the presence of unique conformers of PrP, to develop sensitive methods capable of diagnosing prion infection from biopsies of neural or tonsillar tissue. This is a crucial breakthrough for both individual patients and public health services.

The UCL blood test is now in use at the National Prion Clinic (NPC) - the national referral centre for prion disease based at the National Hospital for Neurology and Neurosurgery - to allow diagnosis of vCJD. Approximately 115 patients have been tested so far through the clinic. The immediate impact of this is that patients can be diagnosed quickly, other conditions can be excluded, and care plans can be put in place quickly. The blood test has been demonstrated to detect infection in over 70% of patients with vCJD with, to date, 100% specificity.

Related links

• MRC Prion Unit at UCL