The Detection of Low Levels of BSE-PrPSc in the Presence of an Excess of Scrapie-PrPSc

<p>Prion diseases are fatal brain diseases with no effective treatment. One of the most important events in the history of these disorders was the emergence of the zoonotic strain bovine spongiform encephalopathy (BSE) in cattle. Until the emergence of BSE in the mid 1980’s it was thought that any given prion disease had a very limited natural host range. For example scrapie affecting sheep/goats and Creutzfeldt Jakob disease (CJD) affecting humans. However, the BSE agent not only affected cattle but was also the causal agent of feline spongiform encephalopathy and human variant CJD (vCJD), both arising from the consumption of BSEcontaminated bovine products.</p>

<p>BSE-contaminated bovine-derived meat and bone meal was extensively fed not only to cows, giving rise to the UK cattle BSE epidemic, but also to small ruminants. Yet extensive surveillence has failed to uncover BSE infections in sheep populations throughout Europe, including the UK. This is a surprise given that sheep are susceptible to BSE when fed the agent under experimental conditions. Two cases of BSE infections have been identified in goats. The UK small ruminant population has had endemic scrapie and whilst the incidence of this disease has been significantly reduced it is estimated that approximately 67,000 scrapie infected animals still enter the human food chain each year1. One concern is that low levels of BSE cases may be harboured within the small ruminant population and be masked by concurrent scrapie infections.</p>

<p>The presence of mixed strains of prion agents within an individual host is known to exist for both natural infections and experimental models. Importantly, it is also known that hosts with mixed infections displaying a single pathology can harbour low levels of a distinct strain which can emerge upon further passage. There are limited studies on mixed infections with BSE and scrapie, however within a mouse model this scenario led to the presentation of a scrapie-associated pathology, even when the inoculum had much greater levels of BSE agentcompared to scrapie agent. Together, data suggests that similar mixed infections of sheep or goats may present as scrapie even though the BSE agent is present.</p>

<p>We propose to apply an in vitro prion amplification assay to the detection of very low levels of BSE agent in the presence of an excess of scrapie agent. We have previously demonstrated that this assay is exquisitely sensitive for the BSE agent and does not amplify any scrapie agents. The output from this study would be to establish this novel amplification-assay for the detection of BSE in the presence of scrapie agent and to compare this method with conventional BSE tests applied in routine surveillence. The study would provide a novel, high sensitivity assay to monitor for the presence of very low levels of BSE in small ruminants, even with concurrent scrapie infections. It would also inform policy makers as to the potential risk of BSE agent being present in sheep or goats but not being detected when measured by conventional assays.</p>