Title: Phenotypic stability of atypical BSE on passage in ruminants
Funder: Department for Environment, Food and Rural Affairs

Abstract: Description European Union (EU) legislation requires member states to monitor ruminant populations for the presence of TSE (transmissible spongiform encephalopathies) through post mortem testing of brain from slaughtered animals, fallen stock and suspected clinical cases. There is also a specific requirement for small ruminant positive samples to be further tested to determine if the strain of TSE present is bovine spongiform encephalopathy (BSE) rather than scrapie, given that this strain is the only one currently known to be zoonotic. The age groups and total numbers of animals tested are modified based on the disease trends identified by this surveillance process, with the aim of reducing the overall cost of testing as outlined in the TSE roadmap 2, published by the European Commission and endorsed in general by Defra. However, within the last decade, as the numbers of BSE and scrapie cases have dropped dramatically, this active surveillance has identified atypical variants in both sheep (Nor98/atypical scrapie) and cattle (L-type BSE/bovine amyloidotic spongiform encephalopathy), and H-type BSE). While it has been proposed that these rare forms of disease are spontaneous, it has also been shown that transmission can be achieved experimentally into a range of host species (cattle, sheep, transgenic mice, primates) and there is evidence that the disease characteristics do not remain stable in some cases. Given that there is still no robust understanding of what makes a particular TSE isolate zoonotic, it is important that we have as broad an understanding and awareness of how such isolates present in food animal species, and how stable they are on inter- and intra-species transmission. They need to be characterised as fully as possible to assist with accurate detection and classification of these cases should they occur in field situations, and to underpin informed assessment of risk to both human and animal health. This is in keeping with one of Defra’s stated aims (in “Livestock - TSE and animal by products evidence plan 2011/12” ) that one of the highest research priorities is to ensure preparedness to detect and evaluate new or unusual TSEs. Emerging data from an existing Defra project investigating the disease produced by experimental infection of sheep with atypical BSE sources (SE1860) suggests that the clinical disease which results would not be considered as suspect TSE by current criteria, and although a positive diagnosis would be obtained through active surveillance, classification of the strain would be problematic using existing methods. However, experimental challenge of cattle (EU funded) resulted in retention of all diagnostic characteristics of the infecting strain. We propose to use material from these sheep and cattle studies to look at whether our existing bioassay techniques can still classify the agent strain, and whether the strains retain or lose specific identifying characteristics when they are passaged through cattle and sheep more than once. This will complement the data on the intra- and inter-species challenges being undertaken with atypical scrapie (SE1847 and separate study submitted for funding by Defra) Objective 1. Establish the biological stability of H- and L-type BSE, with particular reference to statutory classification, when experimentally subpassaged through cattle. Dec 2016.2. Establish the biological stability of H- and L-type BSE, with particular reference to statutory classification, when experimentally subpassaged through sheep. Jun 2018.3. Define the phenotype (clinical, pathological and biochemical) of L-type BSE on subpassage within sheep. Mar 2016.4. Compare the phenotype of H- and L-type BSE with classical BSE in cattle, sheep and Tg mouse models. Oct 2018.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: NEUROLOGICAL