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From: TSS ()
SEAC -------------------------------------------------------------------------------- Sequencing PRNP of BARB cases 88/4 (52 KB) 88/5* (52 KB) Update on the National Scrapie Plan On the afternoon of Thursday 30th June, SEAC will consider research into ‘atypical’ cases of scrapie. These discussions will be held in a closed session to allow discussion of unpublished scientific information. This is in accordance with SEAC's code of practice. SUMMARY OF FSA RESEARCH 9. In November 2002, SEAC was informed about a study the FSA was commissioning due to the continuing uncertainty about potential low levels of BSE infectivity in milk. The purpose of this study was to develop methods to detect the BSE infection associated form of the prion protein (PrPBSE) in bovine milk and to determine whether PrPBSE could be detected in milk samples from cattle that had been experimentally infected with the BSE agent. The committee agreed that research relating to milk should be a key priority, as it was a product that could be derived from animals over thirty months of age, whose meat would not be allowed into the food chain under the Over Thirty Month rule. The committee recommended that a joint FSA/SEAC Working Group should be convened to monitor the progress of the research, advise on research approaches, evaluate the diagnostic methods developed and assess the robustness of the analytical results. The membership and terms of reference of the Group are given in Annex 3. 10. The research has recently been completed and the raw data evaluated by the joint FSA/SEAC Working Group. A prepublication paper reporting the methods used and the findings in full is at Annex 4. Please note Annex 4 has not been circulated outside of the committee. This is at the authors’ request as the report contains new scientific data that have not yet been published in a scientific journal. As premature release of unpublished data may prejudice publication, the report has not been released more widely in hard copy prior to publication (this is in accordance with SEAC's code of practice). However, the authors are content for the committee to discuss the report in the public meeting. 11. A summary of the research is provided below. snip... 4 16. Twenty-eight milk samples (out of a total of 541 individual samples tested) were determined as "final test reactive" using the adapted BioRad Platelia ELISA test. Confirmatory analysis of these samples using the SEPRION-PAGE/ Western blot test resulted in 12 samples, all of which were colostrum samples collected within one week of calving and represented in all of the challenge groups, which contained positive staining bands in the Western blot. Importantly, however, these bands were also present when the analyses were repeated omitting the prionspecific monoclonal antibody (6H4), indicating that they represented non-PrP specific staining material. 17. The data generated in this study do not provide any evidence for the presence of the abnormal BSE-infection associated prion in the milk from cattle incubating BSE at levels defined by the limits of sensitivity of the two analytical methods used. ADVICE SOUGHT FROM THE COMMITTEE health. snip... 13 In view of the findings of the analyses that are summarised above, the Subcommittee concludes that there is some evidence for direct maternal transmission of BSE at a low level, but some variation in genetic susceptibility to BSE following feed-borne exposure may occur. The risk of transmission of BSE from dam to calf is likely to be less than 10%, and appears to be confined to animals born after the onset of BSE in the dam or up to two years beforehand. This level of transmission is not sufficient, by itself, to perpetuate BSE in the cattle population and is likely to have only a minor effect on the rate at which the incidence of BSE declines. It is inevitable that cases infected via animal feed will continue to appear in diminishing numbers for several years. Therefore, although the number of cases infected maternally will be small, they may represent an increasing proportion of the remaining cases detected. Given the evidence that variation in genetic susceptibility may have contributed to the results of the cohort study, and of the importance of genetic factors in TSEs in other species, the Subcommittee considers that further research is necessary to clarify whether or not variations in the PrP gene or other genes may be influencing the transmission of, or susceptibility to, BSE in cattle. Research should seek to identify polymorphisms of the PrP gene which may be associated with BSE susceptibility, including stored samples from the cohort study. There should also be a search [AVMC1] for other genetic markers, outside the PrP gene, which may be associated with an increased BSE risk in cattle. snip... 1 FOR INFORMATION SEAC 88/6 SUMMARY OF SEAC EPIDEMIOLOGY SUBGROUP MEETING Issue 1. The SEAC Epidemiology Subgroup held its first meeting in London on 11th May 2005 to discuss the nature and future profile of the vCJD epidemic. A summary of the meeting is given below. Background 2. Projections of the profile of the vCJD epidemic, based on data from clinical vCJD cases, suggest the number of additional cases may be relatively small. However, recent experimental and epidemiological findings suggest that the nature of the epidemic might be more complex. There may be a substantial number of people who are carriers of infectivity and who will not develop clinical disease or will do so on a prolonged timescale. Furthermore, potential human to human infection via medical procedures (e.g. use of contaminated surgical instruments or blood) might influence the profile of the epidemic such that, if appropriate intervention is not taken, a self-sustaining epidemic could be arising. 3. SEAC agreed (03/03/05) that further epidemiological analysis and modelling work is required to comprehensively reassess the nature and future profile of the vCJD epidemic. The Committee tasked the SEAC Epidemiology Subgroup to conduct this assessment, taking into account new research, and the possibility of human to human transmission. The Subgroup was also asked to identify critical factors that could influence the nature of the epidemic and to consider the likelihood of a self-sustaining epidemic and possible preventative interventions. Consideration would also be given to potential information barriers to assessment of the public health risks. Meeting summary 4. The Subgroup considered the available sources of data for direct ascertainment of the prevalence of vCJD infection. An update on 2 the progress of the National Anonymous Tonsil Archive that is prospectively collecting tonsils for PrPSc screening was presented. Potential additional sources of data to allow direct ascertainment of infection prevalence and assessment of transmission risks were discussed. A summary table of additional surveillance options and the data they could provide together with associated practical/ethical considerations will be developed for further consideration. This will be a key output from the Subgroup. 5. Preliminary results were presented from new modelling work to examine the influence of age and PrP genotype on infection prevalence (clinical cases and pre- or sub-clinical infection carriers) using the published and some unpublished data. The scope of the modelling was discussed. The Subgroup will review the results from this continuing work at its next meeting in the autumn. 6. Routes of secondary transmission and potential data sources to define the extent of their possible interactions were considered. A summary table of routes in terms of their importance (i.e. likelihood to contribute to a secondary epidemic) and possible major interactions will be developed for further discussion. This will be a key output from the Subgroup. 7. It was agreed that a second Subgroup meeting will be held in September 2005 to consider the issues further. A draft position statement that addresses the issues identified by SEAC will be prepared for the Subgroup’s consideration. snip... http://www.seac.gov.uk/papers/88-6.pdf http://www.seac.gov.uk/papers/88-2.pdf TSS
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