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From: TSS ()
SEAC SHEEP SUBGROUP POSITION STATEMENT In view of SEAC’s commitment to keep the scientific evidence underpinning the strategy of the National Scrapie Plan (NSP) under review1, and in light of rapidly emerging scientific findings relating to atypical scrapie, the opinion of the sheep subgroup was sought by SEAC in consultation with Defra. A meeting of the SEAC sheep subgroup was held on January 24th 2006, with the following aims: • To give the best interpretation of the current data on atypical scrapie and of the potential risks for a) animal health and b) human health. To consider whether new data change the risk basis underpinning the NSP, flock control, or relevant sections of the TSE roadmap. • To consider what additional information is necessary in order to improve assessment of the risk for animal and human health. • To produce a statement for consideration at SEAC 91 The meeting brought together European experts on atypical scrapie, as well as UK experts and officials from the relevant Government Departments. The subgroup considered a body of unpublished data as well as published information and ongoing studies. Background snip... Data from active surveillance show that the frequency of atypical scrapie infections in the British sheep flock is similar to that of classical scrapie, and may be slightly higher. Modelling of the abattoir survey results for the Great British sheep population over 18 months old (14 million sheep) shows that around 56 000 sheep could be infected with classical scrapie and around 82 000 infected with atypical scrapie15. These numbers are considerably greater than the number of known clinical cases, in part because many infected animals may be sent to the abattoir at an age before clinical signs appear, but it may also reflect a degree of underreporting16. • Atypical scrapie has been identified in many European countries and in at least some may also be of similar or higher prevalence than classical scrapie. For instance, Portugal has only notified atypical scrapie cases so far from active surveillance17, with no classical scrapie cases. • That there are generally smaller numbers of atypicals per infected flock compared with classical scrapie. One interpretation is that atypical scrapie may be less readily 14 paper SS/Jan 06/5 tables 1 and 2 for the sheep subgroup meeting 24 January 2006 15 modelled data from active surveillance (abattoir survey) provided by Professor John Wilesmith post meeting. 16 Sivam S.K., Baylis M., Gravenor M.B., Gubbins S. and Wilesmith J.W. (2003) Results of a postal survey in 2002 into the occurrence of scrapie in Great Britain. Vet. Rec. 153, 782-783 17http://www.efsa.eu.int/science/biohaz/biohaz_opinions/1216/biohaz_op_ej_276_atypicalscrapiedefinition_en_vf1.pdf Page 7 © SEAC 27 February 2006 transmitted naturally between sheep within a flock than is classical scrapie. • Atypical and classical scrapie can occur together in the same flock but do not always do so. There is no evidence for a direct link between the occurrence of classical scrapie and atypical scrapie, consistent with the view that classical scrapie and atypical scrapie should be considered as independent TSEs. The subgroup agreed that it was critical to know whether or not the prevalence of atypical scrapie in the UK (and other European) flocks is increasing. This knowledge will inform the question of whether atypical scrapie is likely to pose a human health risk. The subgroup agreed that: • Biochemical tests able to discriminate atypical and classical scrapie have only been available for a few years. The limited data available from the last 4 years only, do not suggest a significant change in prevalence over that period. Nevertheless, on the basis of current data it is not possible to ascertain whether atypical scrapie is an old or new disease of sheep, or whether the prevalence of atypical scrapie is changing over time. • A retrospective analysis of historical samples might help ascertain whether atypical scrapie is a new disease and whether or not its prevalence is changing. It was acknowledged that only limited samples may be available from the last 40 years, and some may not be suitable for analysis. • Continued surveillance using an appropriate combination of tests is essential to ensure that atypical cases continue to be identified. • Proactive approaches should be taken to monitor any change in the prevalence of atypical scrapie in UK flocks with some urgency. It should be noted that the changing sheep PrP genotype ratios resulting from the NSP implementation may be a confounding factor which should be taken into account in analysing any possible changes in prevalence of atypical scrapie. snip... The subgroup agreed that: • The species barrier from atypical scrapie in sheep to VRQ ovinised mice appeared low since atypical scrapie could be transmitted relatively easily to VRQ ovinised mice. However general information on the species barriers is currently limited. As atypical scrapie is experimentally transmissible the possibility that it may be transmissible to humans must be considered. It was noted that BSE may be transmitted to humans while there is no evidence that scrapie can cross this species barrier. Further studies on the effect of route of transmission (oral or intracerebral) on the pathogenesis of atypical scrapie will inform on the potential risk to human and animal health. • The available evidence suggests that, unlike experimental BSE in sheep, atypical scrapie may be absent from the lymphoreticular system. Thus, assuming Specified Risk Material (SRM) regulations remain in place, if atypical scrapie can be transmitted to humans, it may pose a relatively lower health risk than BSE if it ever enters the sheep flock. However, one study using oral delivery to a VRQ sheep suggests that PrPres may be present in the LRS. It is urgent to clarify this issue. • Transmission experiments between sheep of the same and different genotypes will be very informative. The results of experimental transmission of atypical scrapie to transgenic mice expressing the human forms of PrP might indicate its relative transmissibility to humans and thus inform on the potential risk to human health of exposure to atypical scrapie. 5. Environmental persistence of TSEs and maternal transmission The subgroup noted that transmission of classical scrapie can occur in the absence of lambing and in the absence of direct contact with infected sheep. Infectivity survives on pasture left fallow for at least 2 months (from ongoing VLA studies) after removal of an infected flock. It has been speculated that this is a consequence of the widespread distribution of classical scrapie in the body. This is in contrast to BSE in cattle which is restricted primarily to neural tissues and does not appear to be shed into the environment. However, BSE experimentally introduced into genetically susceptible sheep, like classical scrapie, appears to have a wide distribution in the body19, and it was recently 19 Bellworthy S.J., Hawkins S.A.C., Green R.B., Blamire I., Dexter G., Dexter I., Lockey R., Jeffrey, M., Ryder S., Berthelin-Baker C. and Simmons M.M. (2005) Tissue distribution of bovine spongiform encephalopathy infectivity in Romney sheep up to the onset of clinical disease after oral challenge. Vet. Rec. 156, 197-202 Page 10 © SEAC 27 February 2006 demonstrated that a BSE infection can be maintained within a sheep flock by spreading the disease from infected ewes to their lambs20. The detailed pathway of the infectious agent from ewe to lamb still needs to be elucidated. It is not known how atypical scrapie is transmitted between animals. The possibility that it has spread through feed cannot be excluded. The environmental persistence of atypical scrapie is unknown. The fact that more than one case may be found in a flock may reflect a level of environmental transmission, or a common alternative route of exposure. It is clearly important to assess its possible route of transmission if control measures are to be effective. snip... full text 13 pages; http://www.seac.gov.uk/pdf/positionstatement-sheep-subgroup.pdf REPORT OF THE COMMITTEE ON SCRAPIE Chair: Dr. Jim Logan, Cheyenne, WY Vice Chair: Dr. Joe D. Ross, Sonora, TX Dr. Deborah L. Brennan, MS; Dr. Beth Carlson, ND; Dr. John R. Clifford, DC; Dr. Thomas F. Conner, OH; Dr. Walter E. Cook, WY; Dr. Wayne E. Cunningham, CO; Dr. Jerry W. Diemer, TX; Dr. Anita J. Edmondson, CA; Dr. Dee Ellis, TX; Dr. Lisa A. Ferguson, MD; Dr. Keith R. Forbes, NY; Dr. R. David Glauer, OH; Dr. James R. Grady, CO; Dr. William L. Hartmann, MN; Dr. Carolyn Inch, CAN; Dr. Susan J. Keller, ND; Dr. Allen M. Knowles, TN; Dr. Thomas F. Linfield, MT; Dr. Michael R. Marshall, UT; Dr. Cheryl A. Miller, In; Dr. Brian V. Noland, CO; Dr. Charles Palmer, CA; Dr. Kristine R. Petrini, MN; Mr. Stan Potratz, IA; Mr. Paul E. Rodgers, CO; Dr. Joan D. Rowe, CA; Dr. Pamela L. Smith, IA; Dr. Diane L. Sutton, MD; Dr. Lynn Anne Tesar, SD; Dr. Delwin D. Wilmot, NE; Dr. Nora E. Wineland, CO; Dr. Cindy B. Wolf, MN. The Committee met on November 9, 2005, from 8:00am until 11:55am, Hershey Lodge and Convention Center, Hershey, Pennsylvania. The meeting was called to order by Dr. Jim Logan, chair, with vice chairman Dr. Joe D. Ross attending. There were 74 people in attendance. The Scrapie Program Update was provided by Dr. Diane Sutton, National Scrapie Program Coordinator, United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS), Veterinary Services (VS). The complete text of the Status Report is included in these Proceedings. Dr. Patricia Meinhardt, USDA-APHIS-VS-National Veterinary Services Laboratory (NVSL) gave the Update on Genotyping Labs and Discrepancies in Results. NVSL conducts investigations into discrepancies on genotype testing results associated with the Scrapie Eradication Program. It is the policy of the Program to conduct a second genotype test at a second laboratory on certain individual animals. Occasionally, there are discrepancies in those results. The NVSL conducts follow-up on these situations through additional testing on additional samples from the field and archive samples from the testing laboratories. For the period of time from January 1, 2005, until October 15, 2005, there were 23 instances of discrepancies in results from 35 flocks. Of those 23 instances, 14 were caused by laboratory error (paperwork or sample mix-up), 3 results from field error, 5 were not completely resolved, and 1 originated from the use of a non-approved laboratory for the first test. As a result of inconsistencies, one laboratory’s certification was revoked by APHIS-VS. As of September 30, 2005, there were 105 scrapie infected and source flocks. There were a total of 165** new infected and source flocks reported for FY 2005. The total infected and source flocks that have been released in FY 2005 was 128. The ratio of infected and source flocks cleaned up or placed on clean up plans vs. new infected and source flocks discovered in FY 2005 was 1.03 : 1*. In addition 622 scrapie cases were confirmed and reported by the National Veterinary Services Laboratories (NVSL) in FY 2005, of which 130 were RSSS cases. Fifteen cases of scrapie in goats have been reported since 1990. The last goat case was reported in May 2005. Approximately 5,626 animals were indemnified comprised of 49% non-registered sheep, 45% registered sheep, 1.4% non-registered goats and 4.6% registered goats. Regulatory Scrapie Slaughter Surveillance (RSSS) RSSS was designed to utilize the findings of the Center for Epidemiology and Animal Health (CEAH) Scrapie: Ovine Slaughter Surveillance (SOSS) study. The results of SOSS can be found at http://www.aphis.usda.gov/vs/ceah/cahm/Sheep/sheep.htm . RSSS started April 1, 2003. It is a targeted slaughter surveillance program which is designed to identify infected flocks for clean-up. During FY 2005 collections increased by 32% overall and by 90% for black and mottled faced sheep improving overall program effectiveness and efficiency as demonstrated by the 26% decrease in percent positive black faced sheep compared to FY 2004. Samples have been collected from 62,864 sheep since April 1, 2003, of which results have been reported for 59,105 of which 209 were confirmed positive. During FY 2005, 33,137 samples were collected from 81 plants. There have been 130 NVSL confirmed positive cases (30 collected in FY 2004 and confirmed in FY 2005 and 100 collected and confirmed in FY 2005) in FY 2005. Face colors of these positives were 114 black, 14 mottled, 1 white and 1 unknown. The percent positive by face color is shown in the chart below. Scrapie Testing In FY 2005, 35,845 animals have been tested for scrapie: 30,192 RSSS; 4,742 regulatory field cases; 772 regulatory third eyelid biopsies; 10 third eyelid validations; and 129 necropsy validations (chart 9). Animal ID As of October 04, 2005, 103,580 sheep and goat premises have been assigned identification numbers in the Scrapie National Generic Database. Official eartags have been issued to 73,807 of these premises. *This number based on an adjusted 12 month interval to accommodate the 60 day period for setting up flock plans. http://www.usaha.org/committees/reports/2005/report-scr-2005.pdf Published online before print October 20, 2005 Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0502296102 A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes ( sheep prion | transgenic mice ) Annick Le Dur *, Vincent Béringue *, Olivier Andréoletti , Fabienne Reine *, Thanh Lan Laï *, Thierry Baron , Bjørn Bratberg ¶, Jean-Luc Vilotte ||, Pierre Sarradin **, Sylvie L. Benestad ¶, and Hubert Laude * Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health. Author contributions: H.L. designed research; A.L.D., V.B., O.A., F.R., T.L.L., J.-L.V., and H.L. performed research; T.B., B.B., P.S., and S.L.B. contributed new reagents/analytic tools; V.B., O.A., and H.L. analyzed data; and H.L. wrote the paper. A.L.D. and V.B. contributed equally to this work. To whom correspondence should be addressed. Hubert Laude, E-mail: laude@jouy.inra.fr www.pnas.org/cgi/doi/10.1073/pnas.0502296102 snip... A The Present Position with respect to Scrapie Scrapie is a natural disease of sheep and goats. It is a slow The field problem has been reviewed by a MAFF working group It is clear that scrapie in sheep is important commercially and Recently the question has again been brought up as to whether Whether true or not. the hypothesis that these agents might be snip... 76/10.12/4.6 http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf Most doctors believe that sCJD is caused by a prion protein deforming by Now scientists in France have stumbled across new evidence that adds weight The complete article is 889 words long. full text; http://www.newscientist.com/article.ns?id=mg16922840.300 Edited by D. Carleton Gajdusek, Centre National de la Recherche There is substantial scientific evidence to support the notion that bovine Evidence of a molecular barrier limiting G.J. Raymond1, A. Bossers2, L.D. Raymond1, K.I. O?Rourke3, 1NIAID/NIH Rocky Mountain Laboratories, Hamilton, MT 59840, Abstract Chronic wasting disease (CWD) is a transmissible snip... Clearly, it is premature to draw firm conclusions about CWD snip... http://www.emboj.org/current.shtml Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC. Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of This patient had worked with sheep and human dura mater from 1968 to 1972. It is tempting to speculate that prions were transmitted to this patient 2. Schoene WC, Masters CL, Gibbs CJ Jr, et al. Transmissible spongiform 3. Gorman DG, Benson DF, Vogel DG, Vinters HV. Creutzfeldt-Jakob disease in 4. Miller DC. Creutzfeldt-Jakob disease in histopathology technicians. N 5. Sitwell L, Lach B, Atack E, Atack D, Izukawa D. Creutzfeldt-Jakob disease 6. Wakayama Y, Shibuya S, Kawase J, Sagawa F, Hashizume Y. High 7. Bruhn H, Weber T, Thorwirth V, Frahm J. In-vivo monitoring of neuronal 8. Collinge J, Palmer MS, Dryden AJ. Genetic predisposition to iatrogenic TSS
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