BSE and its Relationship to Variant CJD in the UK

Abstract

Prion diseases are fatal neurodegenerative disorders that occur in humans and other mammals. In humans, prion diseases occur in sporadic, familial and acquired forms. The commonest of these is the sporadic form of Creutzfeldt-Jakob disease (CJD), which occurs most often in late middle age as a rapidly progressive dementia with other neurological features. The first prion disease to be identified in mammals was scrapie, a disorder of sheep and goats. In 1985-6, a new from of animal prion disease, bovine spongiform encephalopathy (BSE) was identified in the UK. Since then, BSE spread as an epidemic through UK cattle, transmitted by contaminated animal feed and resulting in many thousands of BSE cases. BSE is now in decline in the UK, but it has spread to other countries and is still increasing in numbers, with cases recently identified in Japan, the USA and Canada. In the UK and Europe, the use of active surveillance, with the testing of cattle carcasses for evidence of abnormal prion protein, has resulted in increased numbers of BSE cases identified, many of which appear to represent preclinical infections.

In 1996, the National CJD Surveillance Unit in the UK reported a new form of CJD, now known as variant CJD. Unlike other forms of human prion disease, this disorder usually affects young adults (mean age 28 years) with a lengthy clinical history of average duration 13 months. Presenting features include psychiatric symptoms and sensory abnormalities, which are followed by ataxia, myoclonus, visual problems and terminal akinetic mutism. The neuropathology of variant CJD is unique, with large numbers of florid plaques in the brain. Western blot analysis of the abnormal prion protein in variant CJD has shown a characteristic biochemical profile, which resembles the profile in BSE, but not in sporadic CJD. All cases of variant CJD so far have occurred in one genetic subgroup in the population (homozygotes for methionine at codon 129 in the prion protein gene)

Variant CJD appears to result from human exposure to the bovine spongiform encephalopathy agent, through consumption of contaminated meat products. Strain typing studies in mice have shown that the agent causing variant CJD is very similar to the BSE agent, but distinct from the agent causing sporadic CJD and scrapie. In variant CJD, the abnormal prion protein is also present in lymphoid tissues throughout the body (in addition to the nervous system), raising concerns over iatrogenic transmission by contaminated surgical instruments and there is recent evidence to indicate that variant CJD has been transmitted by blood transfusion. Although the rate of increase of variant CJD in the UK appears to be declining, there is still considerable uncertainty about likely future numbers of cases, since other genetic subgroups may also be susceptible to this infection, but with a different incubation period. Variant CJD has occurred in other countries including France, Italy, USA, Canada and Ireland, indicating that surveillance for CJD is essential in countries where BSE has been identified.