When Atypical Scrapie cross species barriers

When Atypical Scrapie cross species barriers

Authors

Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.

Content

Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.

The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.

Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.

Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.

(i) the unsuspected potential abilities of atypical scrapie to cross species barriers

(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier

These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.

http://www.neuroprion.org/resources/pdf_docs/conferences/prion2008/abstract-book-prion2008.pdf


SCRAPIE USA


INFECTED AND SOURCE FLOCKS

There were 20 scrapie infected and source flocks with open statuses (Figure 3) as of April, 30, 2008. Twenty eight new infected and source flocks have been designated in FY 2008 (Figure 4); three source flocks were reported in April. ...snip

POSITIVE SCRAPIE CASES

As of April 30, 2008, 122 new scrapie cases have been confirmed and reported by the National Veterinary Services Laboratories (NVSL) in FY 2008 (Figure 6). Of these, 103 were field cases and 19* were Regulatory Scrapie Slaughter Surveillance (RSSS) cases (collected in FY 2008 and reported by May 20, 2008). Positive cases reported for April 2008 are depicted in Figure 7. Eighteen cases of scrapie in goats have been confirmed by NVSL since implementation of the regulatory changes in FY 2002 (Figure 8). The most recent positive goat case was confirmed in February 2008 and originated from the same herd in Michigan as the other FY 2008 goat cases. ...snip

CAPRINE SCRAPIE PREVALENCE STUDY (CSPS)

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However, four positive goats have been identified this fiscal year through field investigations. One was a clinical suspect submitted for testing and the other three originated from the birth herd of the clinical case.

ANIMALS SAMPLED FOR SCRAPIE TESTING

As of April 30, 2008, 26,703 animals have been sampled for scrapie testing: 23,378 RSSS, 1,517 goats for the CSPS study, 1,466 regulatory field cases, 270 regulatory third eyelid biopsies, and 72 regulatory rectal biopsies (chart 8).

TESTING OF LYMPHOID TISSUE OBTAINED BY RECTAL BIOPSY WAS APPROVED BY USDA AS AN OFFICIAL LIVE-ANIMAL TEST ON JANUARY 11, 2008. ...

PLEASE NOTE, (FIGURE 6), Scrapie Confirmed Cases in FY 2008 MAP, PA 3, 1**, Two cases-state of ID UNKNOWN, 1 case Nor98-like**

http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps


http://scrapie-usa.blogspot.com/



P03.141

Aspects of the Cerebellar Neuropathology in Nor98

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute,

Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.



***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf



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.

Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved September 12, 2005 (received for review March 21, 2005)

http://www.pnas.org/cgi/content/abstract/0502296102v1


NOR-98 ATYPICAL SCRAPIE 5 cases documented in USA in 5 different states USA 007

http://nor-98.blogspot.com/2008/04/seac-spongiform-encephalopathy-advisory.html


Tuesday, June 3, 2008 SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA

http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html


http://nor-98.blogspot.com/



TSS

TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption

TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption - Scientific Opinion of the Panel on Biological Hazards Question number: EFSA-Q-2007-202

Adopted date: 05/06/2008 Summary (0.1Mb)

Opinion (0.2Mb)

Summary

Following a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific Opinion on a TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption. Its terms of reference were as follows: to provide an assessment on the existence of a significant additional risk to human health compared with the actual situation, founded on the scientific evidences, from the consumption of carcasses from ovine or caprine animals below 6 months of age from TSE affected flocks (without been subjected to a TSE rapid test and irrespectively of the genotype) provided that the entire head and the viscera of the thoracic and abdominal cavities are removed and excluded from human consumption and provided that BSE is excluded (in the outbreak) according to the procedure laid down in 3.2 (c), Chapter C of Annex X to the Regulation (EC) 999/2001. After clarification from the Commission, the BIOHAZ Panel was able to refine the ToR to focus on the change of human exposure that might result from the proposed change of risk management procedure and that it specifically required an estimate of the relative levels of TSE infectivity in the carcass of a lamb or kid less than 3 months of age from which spleen and ileum have been removed, compared to the carcass of a lamb or kid less than 6 months of age from which the spleen, the ileum, the head and the viscera of the abdominal and thoracic cavity have been removed. In answer to these ToR, the BIOHAZ Panel concluded: A quantitative comparison of infectivity load in both scenarios is not possible, because there are no data available on the amount of infectious tissues that would be still present on the carcasses of 3 months and 6 months of age of lambs and kids, prepared according to the terms of reference (i.e. 3 months with head and viscera from the thoracic and abdominal cavity remaining for human consumption, but excluding the spleen and the ileum which is currently removed as Specified Risk Material; 6 months of age without head and all the viscera from the thoracic and abdominal cavities). There is an increase, between 3 and 6 months of age, of the number of PrPres accumulating lymphoid formations. A part of these newly involved lymphoid formations would remain on dressed carcasses. In the worst case scenario, there would be an increase in infectivity level in lymphoid tissue between ages of 3 and 6 months (approximately 10 fold) on a per unit weight basis. The level of infectivity in secondary lymphoid tissues that may remain on the dressed carcasses, can reach by 6 months of age a level of infectivity per gram equivalent to 1/50 of that found in the same amount of brain tissue from a terminally affected sheep. Removal of the head and the thoracic and abdominal viscera will result in incomplete removal of the infectivity load at both 3 and 6 months of age. In the absence of new quantitative data on the tissue infectivity load in kids and lambs, the risk assessment and procedures for safe sourcing of small ruminant materials proposed in 2002 by the SSC, including the use of the combination of genotype and age as sourcing criteria, remain valid. The BIOHAZ Panel further recommends that to facilitate future attempts at quantitative risk assessments in this field, more experimental work is needed to define the variability and uncertainty of both the estimates of relative infectivity titre at different ages in young lambs and kids and of the weights of lymphoid tissue entering the food chain.

Publication date: 15/07/2008

http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178720552868.htm


TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption Scientific Opinion of the Panel on Biological Hazards (Question No EFSA-Q-2007-202) Adopted on 5 June 2008 SUMMARY Following a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific Opinion on a TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption. Its terms of reference were as follows: to provide an assessment on the existence of a significant additional risk to human health compared with the actual situation, founded on the scientific evidences, from the consumption of carcasses from ovine or caprine animals below 6 months of age from TSE affected flocks (without been subjected to a TSE rapid test and irrespectively of the genotype) provided that the entire head and the viscera of the thoracic and abdominal cavities are removed and excluded from human consumption and provided that BSE is excluded (in the outbreak) according to the procedure laid down in 3.2 (c), Chapter C of Annex X to the Regulation (EC) 999/2001. After clarification from the Commission, the BIOHAZ Panel was able to refine the ToR to focus on the change of human exposure that might result from the proposed change of risk management procedure and that it specifically required an estimate of the relative levels of TSE infectivity in the carcass of a lamb or kid less than 3 months of age from which spleen and ileum have been removed, compared to the carcass of a lamb or kid less than 6 months of age from which the spleen, the ileum, the head and the viscera of the abdominal and thoracic cavity have been removed. In answer to these ToR, the BIOHAZ Panel concluded: • A quantitative comparison of infectivity load in both scenarios is not possible, because there are no data available on the amount of infectious tissues that would be still present on the carcasses of 3 months and 6 months of age of lambs and kids, prepared according to the terms of reference (i.e. 3 months with head and viscera from the thoracic and abdominal cavity remaining for human consumption, but excluding the spleen and the ileum which is currently removed as Specified Risk Material; 6 months of age without head and all the viscera from the thoracic and abdominal cavities). • There is an increase, between 3 and 6 months of age, of the number of PrPres accumulating lymphoid formations. A part of these newly involved lymphoid formations would remain on dressed carcasses. • In the worst case scenario, there would be an increase in infectivity level in lymphoid tissue between ages of 3 and 6 months (approximately 10 fold) on a per unit weight basis. Summary of opinion The EFSA Journal (2008) 719, 2-2 • The level of infectivity in secondary lymphoid tissues that may remain on the dressed carcasses, can reach by 6 months of age a level of infectivity per gram equivalent to 1/50 of that found in the same amount of brain tissue from a terminally affected sheep. • Removal of the head and the thoracic and abdominal viscera will result in incomplete removal of the infectivity load at both 3 and 6 months of age. • In the absence of new quantitative data on the tissue infectivity load in kids and lambs, the risk assessment and procedures for safe sourcing of small ruminant materials proposed in 2002 by the SSC, including the use of the combination of genotype and age as sourcing criteria, remain valid. The BIOHAZ Panel further recommends that to facilitate future attempts at quantitative risk assessments in this field, more experimental work is needed to define the variability and uncertainty of both the estimates of relative infectivity titre at different

http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej719_tse_carcasses_smru_summary_en.pdf


TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption 1 Scientific Opinion of the Panel on Biological Hazards (Question No EFSA-Q-2007-202) Adopted on 5 June 2008

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CONCLUSIONS

1. General conclusions: • Lambs and kids from TSE affected flocks in the form of classical scrapie have a clearly higher probability of infection than those from the general population. In the general EU sheep population TSE prevalence at animal level is estimated to be about 0.1 %. In classical scrapie affected sheep flocks the reported prevalence vary from 3% to 41%. • In susceptible lambs (VRQ/VRQ), infectivity will replicate in lymphoid tissues from birth and involve most secondary lymphoid formations before 4 months old. • In worst cases, infectivity in lymphoid organs reaches its maximal level before 6 months old. This maximal level infectivity in lymphoid organs (per mass unit) can be estimated to be about 1/50 of the infectivity found in obex from a terminally affected ewe. • According to currently available data, carcasses of animals of less than two months of age, providing that the head and the thoracic and abdominal viscera are removed, do not contain detectable PrPres but this does not exclude the possibility of infectivity.

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APPENDIX II. FURTHER DATA RELEVANT TO THE TIMING AND SPREAD OF INFECTION IN VRQ/VRQ LAMBS

a. Colostrum/Milk as a potential source of infectivity. Qualitative TSE risk assessments of the safety of milk from sheep and goats have been made in the past, but little published data have been available. Konold and colleagues have recently published a study of the transmission of scrapie from scrapie-affected dams to lambs by feeding from birth milk (and colostrum) taken during the later stages of scrapie-infection in the dams (Konold et al., 2008). Evidence of infection was detected as early as 44-46 days in the distal ileum of two lambs by immunohistochemistry for abnormal PrP (PrPres) and widespread infection inferred by RAMALT6 testing by 190-210 days of age. Both donor ewes and lambs were of the susceptible VRQ/VRQ genotype and the donor ewes were sourced from a flock with a ~ 10% prevalence of natural infection. This is directly relevant to the consideration of “a worst case scenario” and confirms previous work indicating lambs can become infected very soon after birth and that, within 6-7 months, the infection can be widely disseminated, at least in lymphoid tissue, in the susceptible animal.

b. The role of blood in spreading the agent within the body. One of the critical scientific uncertainties (for any naturally occurring TSE in any species) is that related to the possibility of infectivity in blood. Information on the incubation stage(s) wherein this happens is meagre and it is not yet known if this is an inconsistent chance event or an important way in which the pathogen spreads within the body. The data published by Houston et al. (2000) and Hunter et al. (2002) showed that a high volume blood transfusion from sheep to sheep can transmit BSE as well as scrapie within the same species. With both diseases, infectivity could also be transmitted using blood taken during the asymptomatic incubation period of the disease in the donor sheep. In the specific context of this mandate, Andreoletti and co-workers have reported infectivity in blood of pre-clinical VRQ/VRQ lambs at 3 months of age (Andreoletti et al., Neuroprion Edinburgh 2007).

c. Intestine: the anatomical location where infectivity is first detected. PrPres in the digestive tract has been described in sheep exposed to natural scrapie (van Keulen et al., 1999; Andreoletti et al., 2000). Most of the data available were obtained in natural scrapie and the prion protein genotype of the sheep is a critical factor in the uptake and dissemination of the agents of BSE and scrapie in the gut of the sheep. In VRQ/VRQ sheep exposed to natural scrapie infection, PrPres can be detected in ileal Peyer’s patches (PP) from 21 days post-partum and in other PP’s of the alimentary canal and in the tonsil of the lamb by 60 days of age. In similar conditions, PrPres is detectable in the enteric nervous system (ENS) at 7 months old, almost three months prior to its first detection in the obex (Andreoletti et al., 2000). Hence, during surveillance, screening the obex using rapid testing for PrPres is a poor indicator for the absence of TSE infection in the digestive tract of the lamb. 6 RAMALT stands for recto-anal mucosal associated lymphoid tissue.

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http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej719_tse_carcasses_smru_en.pdf


OPINION ON SAFE SOURCING OF SMALL RUMINANT MATERIALS (SAFE SOURCING OF SMALL RUMINANT MATERIALS SHOULD BSE IN SMALL RUMINANTS BECOME PROBABLE: GENOTYPE, BREEDING, RAPID TSE TESTING, FLOCKS CERTIFICATION AND SPECIFIED RISK MATERIALS) ADOPTED BY THE SCIENTIFIC STEERING COMMITTEE AT ITS MEETING OF 4-5 APRIL 2002

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III.1.2. As for BSE in sheep, research data are available for only a few tens of animals: - Results to date indicate that the relation between sheep genotype and susceptibility to a TSE is similar for scrapie and BSE: the ARR genotypes are apparently resistant to development of clinical disease on challenge with BSE and animals carrying the glutamine (Q) allele at codon 171 are potentially susceptible to BSE and to scrapie. The influence of the genotype at codon 136 and 154 is not yet known for BSE but is being tested by direct challenge studies at IAH, UK. - New research data summarised in EC (2002) are consistent with the previously expressed view that BSE in sheep after oral exposure is pathogenetically closely similar to scrapie, particularly with respect to the tissue distribution of infectivity and/or PrPSc.

page 17 of 69...snip...end

http://ec.europa.eu/food/fs/sc/ssc/out257_en.pdf


ISSUE All Member States are required to produce a contingency plan in the event BSE were found in sheep.

The UK is currently finalising its detailed plan, for submission to the Commission this summer. The European Commission has recently produced guidelines for Member States on the points which should be considered in drawing up their contingency plans. (Annex 1). The guidelines suggest that Member States should consider a worst case scenario where sheep meat is excluded from the food chain. This is based on an opinion, adopted by the Scientific Steering Committee (SSC) in April 2002, entitled “Safe sourcing of small ruminant materials” (Annex 2). The SSC Opinion states that if BSE were found in sheep, then only the following animals should be allowed into the food chain: • ARR homozygous sheep under the age of 18 months • ARR heterozygous sheep under the age of 6 months. • Sheep (and goat) milk, colostrum and milk products from suspect BSE cases should be excluded from the food chain. The EC guidelines (SANCO/19/2003 Rev.2) state a worst case scenario where: • small ruminant meat is excluded from the food chain unless derived from: - homozygous ARR sheep under the age of 18 months - heterozygous sheep under the age of 6 months • sheep and goat milk is excluded from the food and feed chain: - completely, or - unless derived from sheep carrying at least one ARR allele, or - unless derived from holdings certified TSE resistant or TSE free on the basis of solid criteria. They should also make an inventory of their capacity in terms of genotyping, individual identification and registration of animals, TSE testing and in terms of flock certification on the basis of history, monitoring etc.

CONFIDENTIAL PAPER No: SEAC 78/9 Amendment 2 2 In March 2002, a SEAC Sub-Group considered the risks associated with certain genotypes entering the food chain if BSE were ever isolated from sheep. In contrast to the SSC opinion, SEAC concluded that: • In line with previous SEAC advice, only animals carrying the ARR allele should enter the food chain • On a precautionary basis, the 12 month cut off previously advised by SEAC remained appropriate for ARR heterozygotes. However, in view of existing SRM regulations there was no justification for any age cut off in ARR homozygotes • In line with SEAC advice in 2001, only milk from ARR homozygous sheep could be considered as highly unlikely to contain the infectious agent. Further experimental work was required before potential risks from small ruminant milk from goats and semi-resistant or susceptible sheep could be excluded. There is therefore a disparity of opinion between the SSC and SEAC on this issue. Whilst recognising the uncertainties relating to the science in this area, it is important that contingency planning is based on the most up to date scientific developments and assessments of risk that are available. SEAC will be presented with an update on the ongoing BSE in sheep studies, funded by Defra (Annex 31). This covering paper also provides a history of previous SEAC advice on this issue. BACKGROUND...snip...end

http://www.seac.gov.uk/papers/78-9-closed.pdf


12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY

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A The Present Position with respect to Scrapie The Problem

Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it is fatal. It is enzootic in the United Kingdom but not in all countries.

The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep.

It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible.

Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasized by the finding that some strains of scrapie produce lesions identical to the once which characterize the human dementias"

Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the scrapie problem urgent if the sheep industry is not to suffer grievously.

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76/10.12/4.6

http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf


1: J Infect Dis 1980 Aug;142(2):205-8

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

PMID: 6997404

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=6997404&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus


EVIDENCE OF SCRAPIE IN SHEEP AS A RESULT OF FOOD BORNE EXPOSURE

This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies. ........

http://www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf


Like lambs to the slaughter

31 March 2001 Debora MacKenzie Magazine issue 2284

What if you can catch old-fashioned CJD by eating meat from a sheep infectedwith scrapie?FOUR years ago, Terry Singeltary watched his mother die horribly from adegenerative brain disease. Doctors told him it was Alzheimer's, butSingeltary was suspicious. The diagnosis didn't fit her violent symptoms,and he demanded an autopsy. It showed she had died of sporadicCreutzfeldt-Jakob disease.

Most doctors believe that sCJD is caused by a prion protein deforming bychance into a killer. But Singeltary thinks otherwise. He is one of a numberof campaigners who say that some sCJD, like the variant CJD related to BSE,is caused by eating meat from infected animals. Their suspicions havefocused on sheep carrying scrapie, a BSE-like disease that is widespread inflocks across Europe and North America.

Now scientists in France have stumbled across new evidence that adds weightto the campaigners' fears. To their complete surprise, the researchers foundthat one strain of scrapie causes the same brain damage in ...

The complete article is 889 words long.

full text;

http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html


Neurobiology Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt-Jakob disease: Implications for human health

Corinne Ida Lasmézas*,, Jean-Guy Fournier*, Virginie Nouvel*, Hermann Boe*,Domíníque Marcé*, François Lamoury*, Nicolas Kopp, Jean-Jacques Hauw§, JamesIronside¶, Moira Bruce, Dominique Dormont*, and Jean-Philippe Deslys** Commissariat à l'Energie Atomique, Service de Neurovirologie, Directiondes Sciences du Vivant/Département de Recherche Medicale, Centre deRecherches du Service de Santé des Armées 60-68, Avenue du Général Leclerc,BP 6, 92 265 Fontenay-aux-Roses Cedex, France; Hôpital Neurologique PierreWertheimer, 59, Boulevard Pinel, 69003 Lyon, France; § Laboratoire deNeuropathologie, Hôpital de la Salpêtrière, 83, Boulevard de l'Hôpital,75013 Paris, France; ¶ Creutzfeldt-Jakob Disease Surveillance Unit, WesternGeneral Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; andInstitute for Animal Health, Neuropathogenesis Unit, West Mains Road,Edinburgh EH9 3JF, United Kingdom

Edited by D. Carleton Gajdusek, Centre National de la RechercheScientifique, Gif-sur-Yvette, France, and approved December 7, 2000(received for review October 16, 2000)

Abstract

There is substantial scientific evidence to support the notion that bovinespongiform encephalopathy (BSE) has contaminated human beings, causingvariant Creutzfeldt-Jakob disease (vCJD). This disease has raised concernsabout the possibility of an iatrogenic secondary transmission to humans,because the biological properties of the primate-adapted BSE agent areunknown. We show that (i) BSE can be transmitted from primate to primate byintravenous route in 25 months, and (ii) an iatrogenic transmission of vCJDto humans could be readily recognized pathologically, whether it occurs bythe central or peripheral route. Strain typing in mice demonstrates that theBSE agent adapts to macaques in the same way as it does to humans andconfirms that the BSE agent is responsible for vCJD not only in the UnitedKingdom but also in France. The agent responsible for French iatrogenicgrowth hormone-linked CJD taken as a control is very different from vCJD butis similar to that found in one case of sporadic CJD and one sheep scrapieisolate. These data will be key in identifying the origin of human cases ofprion disease, including accidental vCJD transmission, and could providebases for vCJD risk assessment.

http://www.pnas.org/cgi/content/full/041490898v1


full text ;

http://scrapie-usa.blogspot.com/2006/12/scrapie-usa.html


Saturday, December 08, 2007 SCRAPIE HB Parry Seriously’ (YB88/6.8/4.1)

HB Parry Seriously’ (YB88/6.8/4.1)

IF the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease.

http://www.bseinquiry.gov.uk/files/yb/1988/06/08004001.pdf


1: Neuroepidemiology. 1985;4(4):240-9.

Sheep consumption: a possible source of spongiform encephalopathy in humans.

Davanipour Z, Alter M, Sobel E, Callahan M.

A fatal spongiform encephalopathy of sheep and goats (scrapie) shares many characteristics with Creutzfeldt-Jakob disease (CJD), a similar dementing illness of humans. To investigate the possibility that CJD is acquired by ingestion of contaminated sheep products, we collected information on production, slaughtering practices, and marketing of sheep in Pennsylvania. The study revealed that sheep were usually marketed before central nervous system signs of scrapie are expected to appear; breeds known to be susceptible to the disease were the most common breeds raised in the area; sheep were imported from other states including those with a high frequency of scrapie; use of veterinary services on the sheep farms investigated and, hence, opportunities to detect the disease were limited; sheep producers in the area knew little about scrapie despite the fact that the disease has been reported in the area, and animal organs including sheep organs were sometimes included in processed food. Therefore, it was concluded that in Pennsylvania there are some 'weak links' through which scrapie-infected animals could contaminate human food, and that consumption of these foods could perhaps account for spongiform encephalopathy in humans. The weak links observed are probably not unique to Pennsylvania.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3915057&dopt=Abstract


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Scrapie has been transmitted in our laboratory to five species of monkeys (Tables 9 and 10) (23, 31, 32), and such transmission has occurred using infected brain from naturally infected sheep and from experimentally infected goats and mice (Figures 22a, b, c). The disease produced is clinically and pathologically indistinguishable from experimental CJD in these species. .........

SNIP...

22b. Primary transmission of goat-adapted scrapie (Compton, England strain) to the squirrel monkey and to mice and the transmission of mouse-adapted scrapie to two species of Old World and three species of New World monkeys. Numbers in parentheses are the number of months elapsed since inoculation, during which the animal remained asymptomatic.

SNIP...

22c. Transmission of mouse-adapted sheep scrapie (U. S. strain 434-3-897) to a squirrel monkey 38 months following intracerebral inoculation with a suspension of scrapie-infected mouse brain containing 10a7.3 infectious units of virus per ml. This animal showed signs of ataxia, tremors and incoordination, and the disease was confirmed histologically. See (b) for an explanation of symbols.

SNIP...

Figure 23. Transmissible mink encephalopathy (TME), a rare disease of American ranch mink, is possibly a form of scrapie. The clinical picture and histopathological lesions attendant in the brain, resemble that of scrapie, and scrapie sheep carcasses were fed to mink on ranches on which TME appeared. The disease is transmissible to sheep, goats, certain rodents and New and Old World monkeys. Illustrative data on the primary transmissions of transmissible mink encephalopathy to one species of New World monkey and two species of Old World monkeys, and serial passage of the virus in squirrel, rhesus and stumptailed monkeys are presented in this Figure. Incubation periods are shown in months that elapsed between inoculation and onset of clinical disease. (Figure includes information from our laboratory and from R. F. Marsh, R. J. Eckroade, and R. P. Hanson.)

SNIP... end

SOURCE;

UNCONVENTIONAL VIRUSES AND THE ORIGIN

AND DISAPPEARANCE OF KURU

Nobel Lecture, December 13, 1976

by D. CARLETON GAJDUSEK

National Institutes of Health, Bethesda, Maryland, U.S.A.

snip... see ;

http://scrapie-usa.blogspot.com/2007/12/scrapie-hb-parry-seriously-yb886841.html


Monday, December 24, 2007 Pathogenesis of bovine spongiform encephalopathy in sheep

http://scrapie-usa.blogspot.com/2007/12/pathogenesis-of-bovine-spongiform.html


Friday, February 15, 2008 SCRAPIE and TSE to human UPDATE 2008 (ambiguous terms of transition and reality set in)

snip...

2. In relation to conclusion 2 in page 7 the Authority is invited to specify the scientific evidences which do not allow to exclude transmissibility to humans of “other TSE agents” other than BSE. Conclusion 2 in page 7 of the EFSA 2007 opinion states that: “The BSE agent is the only TSE agent identified as zoonotic. However, in view of their diversity it is currently not possible to exclude transmissibility to humans of other animal TSE agents.”

In the EFSA 2007 opinion under 3.2.3. the Panel states that:

• “There are significant uncertainties associated with the question whether TSE agents in their whole spectrum may cross the human transmission barrier under natural conditions”.

This statement is supported both by scientific evidence and considerations, referenced in the EFSA 2007 opinion:

• Scientific evidence from transmission studies to primates: - Transmission of Classical Scrapie from a TSE agent adapted in hamster was demonstrated by oral challenge in squirrel monkey (Saimiri sciureus) (Gibbs et al., 1980);

- Transmission of Classical Scrapie from two distinct sheep sources by intracerebral challenge in cynomologus monkey (Macaca fascicularis) and marmoset monkey (Callithrix jacchus) (Gibbs and Gajdusek, 1972; Baker et al., 1988).

• Scientific considerations on TSE epidemiology: - “The assumed lack of association between TSEs in humans and those in small ruminants […] may be biased by a number of factors: (i) The lack of a data on the historical real prevalence and distribution of small ruminant TSEs, at a time where only passive surveillance was performed; (ii) the lack of understanding of the true biodiversity of TSEs in small ruminants in terms of both Classical and Atypical agents; (iii) the lack of understanding of the diversity of TSEs in humans due to the limited molecular and bioassay characterisation of human TSEs also in relation to the number and spectrum of neurodegenerative diseases of humans; (iv) the predicted phenotype of disease that might arise should an animal derived TSE transmit to humans.” The EFSA Journal (2008) 626, 5-11

Further evidence is provided by:

• In vitro conversion assays: Raymond et al. (1997) studied whether there is a correlation between in vitro conversion efficiencies and known transmissibility of BSE, sheep Scrapie and CJD, and found limited conversion of human PrP-sen to PrP-res driven by PrP-res associated with both Scrapie (PrPSc) and BSE (PrPBSE). They concluded that “the inherent ability of these infectious agents of BSE and Scrapie to affect humans following equivalent exposure may be finite but similarly low”. Nevertheless, uncertainty arises from the fact that this is a simple in vitro model of a complex in vivo situation.

• Laboratory transmission studies with animal models: Since the publication of the Opinion new data have become available with regards to L type of BSE, which has now been identified in various EU members states (Biacabe et al., 2004; Casalone et al., 2004; Baron et al., 2007). This TSE agent, differing from that causing Classical BSE by its biochemical signature and transmission features in mouse models, has been transmitted to a Tg mouse model expressing Human M129 PRP gene (Beringue et al. 2007)2. Here again, uncertainty arises from the limitations of these animal models for the estimation of the human species barrier. These ‘proof of principle’ experiments provide data supporting the ability of TSE agents other than those causing Classical BSE to cross the human species barrier.

Even so, it is important to remember that as mentioned in the EFSA 2007 opinion, transmission to primates:

• “… does not allow to take into account the human gene PRNP polymorphisms (in particular the M/V 129), that have been identified to play a major role on relative susceptibility towards prion disease. In addition, genes other than the PrP gene may also be influential in determining overall susceptibility to TSEs.” Despite the interests in the area, studies of the transmissibility of currently known TSE agents using animal models will remain incomplete for several years.

In conclusion, the reply to the ToR number 2 is:

• Experimental transmissions to primate and to transgenic (Tg) mouse models expressing the human PrP gene, are currently used as to evaluate the potential capacity of a TSE agent to cross the human species barrier.

• TSE agents other than the Classical BSE agent from three field TSE cases (two Classical Scrapie cases and one L type BSE case) have been demonstrated to cross the modelled human species barrier.

• Some limitations to these models have to be considered, which include:

(i) The uncertainty of how well they represent the human species barrier. (ii) The uncertainty of how well the experimental inoculation route employed represents exposure under natural conditions. 2 Transmission of this TSE agent by intracerebral challenge to primates (Macaques) has been reported by Comoy et al. at the 2006 Prion Congress held in Torino. A scientific paper reporting this finding has been submitted for peer review publication. The EFSA Journal (2008) 626, 6-11

snip...

http://ec.europa.eu/dgs/health_consumer/library/pub/pub07_en.pdf


EFSA 2005. Opinion of the Scientific Panel on Biological Hazards on the request from the European Commission on classification of Atypical Transmissible Spongiform Encephalopathy (TSE) cases in small ruminants. The EFSA Journal 276: 1-30.

http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620776235.htm


The EFSA Journal (2008) 626, 11-11

EFSA 2007. Opinion of the Scientific Panel on Biological Hazards on a request from the European Commission on certain aspects related to the risk of Transmissible Spongiform Encephalopathies (TSEs) in ovine and caprine animals. The EFSA Journal 466: 1-10.

http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620775196.htm


Date: September 26, 2007 at 4:06 pm PST

P03.141

Aspects of the Cerebellar Neuropathology in Nor98

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute, Norway

Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. *** The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf


snip... see;

http://scrapie-usa.blogspot.com/2008/02/scrapie-and-tse-to-human-update-2008.html


Saturday, April 12, 2008 Evidence of scrapie transmission via milk

http://scrapie-usa.blogspot.com/2008/04/evidence-of-scrapie-transmission-via.html


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.

Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved September 12, 2005 (received for review March 21, 2005)

http://www.pnas.org/cgi/content/abstract/0502296102v1


Tuesday, June 3, 2008 SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA

http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html


In FY 2007, 331 scrapie cases have been confirmed and reported by the National Veterinary Services Laboratories (NVSL), including 59* Regulatory Scrapie Slaughter Surveillance (RSSS) cases (Figure 5 and Slide 16). In FY 2007, two field cases, one validation case, and two RSSS cases were consistent with Nor-98 scrapie. The Nor98-like cases originated from flocks in California, Minnesota, Colorado, Wyoming and Indiana respectively. Nineteen cases of scrapie in goats have been reported since 1990 (Figure 6). The last goat case was reported in September 2007.

snip...

see full report here ;

http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/yearly_report.pps


http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html


http://nor-98.blogspot.com/


now, confusious is confused again. why do some countries have their TSE reported on the OIE weekly listing of disease on the OIE website, but others like the USA, do not $$$

case in point ;

SCRAPIE PORTUGAL

Information received on 16/07/2008 from Mr Carlos Agrela Pinheiro, Chief Veterinary Officer, Director General, Direcçao-Geral de Veterinária, Ministério da Agricultura, LISBONNE, Portugal


http://www.oie.int/wahid-prod/public.php?page=single_report&pop=1&reportid=7201



Wednesday, June 11, 2008

OIE Recognition of the BSE Status of Members RESOLUTION No. XXI (Adopted by the International Committee of the OIE on 27 May 2008)

snip...

CONSIDERING THAT

1. Adoption of subsequent Resolutions* since the 67th General Session of the OIE International Committee has established a procedure for annually updating a list of Members, categorised by their BSE risk according to the provisions of theTerrestrial Code,

2. During the 70th General Session, the International Committee adopted Resolution No. XVIII asking Members applying for a BSE risk evaluation to meet part of the costs sustained by the OIE Central Bureau in the evaluation process,

3. During the 72nd General Session, the OIE adopted Resolution No. XXI requesting the Director General to inform Delegates of Members whose country or zones are recognised with regard to their BSE risk status should annually confirm during the month of November whether their risk status and the criteria by which their status was recognised have remained unchanged,

4. Information published by the OIE is derived from declarations made by the official Veterinary Services of Members. The OIE is not responsible for inaccurate publication of a Member disease status based on inaccurate information, changes in epidemiological status or other significant events that were not promptly reported to the Central Bureau, subsequent to the time of declaration of the BSE risk status.

THE COMMITTEE

RESOLVES THAT

1. The Director General publish the following list of Members recognised as having a negligible BSE risk in accordance with Chapter 2.3.13. of the Terrestrial Code:

Australia, Argentina, Finland, Iceland, New Zealand, Norway, Paraguay, Singapore, Sweden and Uruguay.

2. The Director General publish the following list of Members recognised as having a controlled BSE risk in accordance with Chapter 2.3.13. of the Terrestrial Code:

Austria Belgium Brazil Canada Chile Chinese Taipei Cyprus Czech Republic Denmark Estonia France Germany Greece Hungary Ireland Italy Latvia Lichtenstein Lithuania Luxembourg Malta Mexico Netherlands Poland Portugal Slovak Republic Slovenia Spain Switzerland United Kingdom United States of America

AND

3. The Delegates of these Members will immediately notify the Central Bureau if BSE occurs in their countries or their territories.

_________

(Adopted by the International Committee of the OIE on 27 May 2008)

* 67th General Session (GS) Resolution No (Res) XVI and Res XI; 69th GS Res XV, and 71st GS Res XXII, 72nd GS Res XXIV and Res XXI..

http://www.oie.int/eng/info/en_statesb.htm?e1d6


IN A NUT SHELL ;

(Adopted by the International Committee of the OIE on 23 May 2006)

11. Information published by the OIE is derived from appropriate declarations made by the official Veterinary Services of Member Countries. The OIE is not responsible for inaccurate publication of country disease status based on inaccurate information or changes in epidemiological status or other significant events that were not promptly reported to the Central Bureau,

http://www.oie.int/eng/Session2007/RF2006.pdf


snip...SEE FULL TEXT with facts and sources @ ;

http://usdavskorea.blogspot.com/2008/06/oie-recognition-of-bse-status-of.html


http://organicconsumers.org/forum/index.php?showtopic=1566


BSE BASE MAD COW TESTING TEXAS, USA, AND CANADA

http://madcowtesting.blogspot.com/


Attachment to Singeltary comment

January 28, 2007

Greetings APHIS,

I would kindly like to submit the following to ;

BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01

[Federal Register: January 9, 2007 (Volume 72, Number 5)] [Proposed Rules] [Page 1101-1129] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr09ja07-21]

http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f8152


BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01 Date: January 9, 2007 at 9:08 am PST

http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f3412


bottom line, you don't look, you dont find, you don't report, you dont have, thus, you have this imaginary classification called the BSE MRR 'CONTROLLED RISK' ;-)

THE REALITY IS ;

EFSA Scientific Report on the Assessment of the Geographical BSE-Risk (GBR) of the United States of America (USA)

Summary of the Scientific Report

The European Food Safety Authority and its Scientific Expert Working Group on the Assessment of the Geographical Bovine Spongiform Encephalopathy (BSE) Risk (GBR) were asked by the European Commission (EC) to provide an up-to-date scientific report on the GBR in the United States of America, i.e. the likelihood of the presence of one or more cattle being infected with BSE, pre-clinically as well as clinically, in USA. This scientific report addresses the GBR of USA as assessed in 2004 based on data covering the period 1980-2003.

The BSE agent was probably imported into USA and could have reached domestic cattle in the middle of the eighties. These cattle imported in the mid eighties could have been rendered in the late eighties and therefore led to an internal challenge in the early nineties. It is possible that imported meat and bone meal (MBM) into the USA reached domestic cattle and leads to an internal challenge in the early nineties.

A processing risk developed in the late 80s/early 90s when cattle imports from BSE risk countries were slaughtered or died and were processed (partly) into feed, together with some imports of MBM. This risk continued to exist, and grew significantly in the mid 90's when domestic cattle, infected by imported MBM, reached processing. Given the low stability of the system, the risk increased over the years with continued imports of cattle and MBM from BSE risk countries.

EFSA concludes that the current GBR level of USA is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent. As long as there are no significant changes in rendering or feeding, the stability remains extremely/very unstable. Thus, the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent persistently increases.

http://www.efsa.europa.eu/en/science/tse_assessments/gbr_assessments/573.html


http://www.efsa.europa.eu/etc/medialib/efsa/science/tse_assessments/gbr_assessments/573.Par.0004.File.dat/sr03_biohaz02_usa_report_v2_en1.pdf


Wednesday, July 16, 2008

Implementation of 2008 Feed Ban Enhancements Questions and Answers July 15, 2008

http://madcowfeed.blogspot.com/2008/07/implementation-of-2008-feed-ban.html


Thursday, July 10, 2008

A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008

http://cjdmadcowbaseoct2007.blogspot.com/2008/07/novel-human-disease-with-abnormal-prion.html


Thursday, July 10, 2008 A New Prionopathy update July 10, 2008

http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.html


SEAC Draft minutes of the 100th meeting held on 25th April 2008

http://seac992007.blogspot.com/2008/07/seac-draft-minutes-of-100th-meeting.html


HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory JUNE 2008

http://cjdmadcowbaseoct2007.blogspot.com/2008/06/human-and-animal-tse-classifications-ie.html


Wednesday, July 16, 2008 Prevalence of the prion protein gene E211K variant in U.S. cattle Research Project:

Haplotype Structure of the Bovine Prion Gene Complex and Association with Bovine Spongiform Encephalopathy (Bse) Location: Animal Health Systems Research

Title: Prevalence of the prion gene E211K variant in U.S. cattle

http://bse-atypical.blogspot.com/2008/07/prevalence-of-prion-protein-gene-e211k.html


PEACE

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

A descriptive study of the prevalence of atypical and classical scrapie in sheep in 20 European countries

Research article

A descriptive study of the prevalence of atypical and classical scrapie in sheep in 20 European countries

Alexandre Fediaevsky , Sue C Tongue , Maria Noremark , Didier Calavas , Giuseppe Ru and Petter Hopp

BMC Veterinary Research 2008, 4:19doi:10.1186/1746-6148-4-19

Published: 10 June 2008

Abstract (provisional) Background The development of active surveillance programmes for transmissible spongiform encephalopathies of small ruminants across Europe has led to the recent identification of a previously undetected form of ovine prion disease, 'atypical' scrapie. Knowledge of the epidemiology of this disease is still limited, as is whether it represents a risk for animal and/or public health. The detection of atypical scrapie has been related to the use of only some of the EU agreed rapid tests. Information about the rapid tests used is not, as yet, available from public reports on the surveillance of transmissible spongiform encephalopathies in small ruminants. We collected detailed results of active surveillance from European countries to estimate and to compare the prevalence of atypical scrapie and classical scrapie in sheep for each country stratified by each surveillance stream; healthy slaughtered and found dead adult sheep.

Results From the 20 participating countries, it appeared that atypical scrapie was detected in Europe wherever the conditions necessary for its diagnosis were present. In most countries, atypical scrapie and classical scrapie occurred at low prevalence level. The classical scrapie prevalence estimates were more variable than those for atypical scrapie, which appeared remarkably homogeneous across countries, surveillance streams and calendar years of surveillance. Differences were observed in the age and genotype of atypical scrapie and classical scrapie cases that are consistent with previous published findings.

Conclusions This work suggests that atypical scrapie is not rare compared to classical scrapie. The homogeneity of its prevalence, whatever the country, stream of surveillance or year of detection, contrasts with the epidemiological pattern of classical scrapie. This suggests that the aetiology of atypical scrapie differs from that of classical scrapie.

http://www.biomedcentral.com/1746-6148/4/19/abstract

full text ;

http://www.biomedcentral.com/content/pdf/1746-6148-4-19.pdf

USA SCRAPIE 2008

INFECTED AND SOURCE FLOCKS

There were 20 scrapie infected and source flocks with open statuses (Figure 3) as of April, 30, 2008. Twenty eight new infected and source flocks have been designated in FY 2008 (Figure 4); three source flocks were reported in April. ...snip

POSITIVE SCRAPIE CASES

As of April 30, 2008, 122 new scrapie cases have been confirmed and reported by the National Veterinary Services Laboratories (NVSL) in FY 2008 (Figure 6). Of these, 103 were field cases and 19* were Regulatory Scrapie Slaughter Surveillance (RSSS) cases (collected in FY 2008 and reported by May 20, 2008). Positive cases reported for April 2008 are depicted in Figure 7. Eighteen cases of scrapie in goats have been confirmed by NVSL since implementation of the regulatory changes in FY 2002 (Figure 8). The most recent positive goat case was confirmed in February 2008 and originated from the same herd in Michigan as the other FY 2008 goat cases. ...snip

CAPRINE SCRAPIE PREVALENCE STUDY (CSPS)

snip...

However, four positive goats have been identified this fiscal year through field investigations. One was a clinical suspect submitted for testing and the other three originated from the birth herd of the clinical case.

ANIMALS SAMPLED FOR SCRAPIE TESTING

As of April 30, 2008, 26,703 animals have been sampled for scrapie testing: 23,378 RSSS, 1,517 goats for the CSPS study, 1,466 regulatory field cases, 270 regulatory third eyelid biopsies, and 72 regulatory rectal biopsies (chart 8).

TESTING OF LYMPHOID TISSUE OBTAINED BY RECTAL BIOPSY WAS APPROVED BY USDA AS AN OFFICIAL LIVE-ANIMAL TEST ON JANUARY 11, 2008. ...

PLEASE NOTE, (FIGURE 6), Scrapie Confirmed Cases in FY 2008 MAP, PA 3, 1**, Two cases-state of ID UNKNOWN, 1 case Nor98-like**

http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps

NOT to forget the 5 cases of the NOR-98 atypical scrapie documented in the USA in 2007, in five different states. WHICH pathologically looks like some sub-types of sporadic CJD, of which Stanely Prusiner warns of a public health risk ;

***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf

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.

Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved September 12, 2005 (received for review March 21, 2005)

http://www.pnas.org/cgi/content/abstract/0502296102v1

Tuesday, June 3, 2008 SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA

http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html

NOR-98 ATYPICAL SCRAPIE 5 cases documented in USA in 5 different states USA 007

http://nor-98.blogspot.com/2008/04/seac-spongiform-encephalopathy-advisory.html

http://nor-98.blogspot.com/

SCRAPIE USA

http://scrapie-usa.blogspot.com/

TSS

SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA

INFECTED AND SOURCE FLOCKS

There were 20 scrapie infected and source flocks with open statuses (Figure 3) as of April, 30, 2008. Twenty eight new infected and source flocks have been designated in FY 2008 (Figure 4); three source flocks were reported in April. ...snip

POSITIVE SCRAPIE CASES

As of April 30, 2008, 122 new scrapie cases have been confirmed and reported by the National Veterinary Services Laboratories (NVSL) in FY 2008 (Figure 6). Of these, 103 were field cases and 19* were Regulatory Scrapie Slaughter Surveillance (RSSS) cases (collected in FY 2008 and reported by May 20, 2008). Positive cases reported for April 2008 are depicted in Figure 7. Eighteen cases of scrapie in goats have been confirmed by NVSL since implementation of the regulatory changes in FY 2002 (Figure 8). The most recent positive goat case was confirmed in February 2008 and originated from the same herd in Michigan as the other FY 2008 goat cases. ...snip

CAPRINE SCRAPIE PREVALENCE STUDY (CSPS)

snip...

However, four positive goats have been identified this fiscal year through field investigations. One was a clinical suspect submitted for testing and the other three originated from the birth herd of the clinical case.

ANIMALS SAMPLED FOR SCRAPIE TESTING

As of April 30, 2008, 26,703 animals have been sampled for scrapie testing: 23,378 RSSS, 1,517 goats for the CSPS study, 1,466 regulatory field cases, 270 regulatory third eyelid biopsies, and 72 regulatory rectal biopsies (chart 8).

TESTING OF LYMPHOID TISSUE OBTAINED BY RECTAL BIOPSY WAS APPROVED BY USDA AS AN OFFICIAL LIVE-ANIMAL TEST ON JANUARY 11, 2008. ...

PLEASE NOTE, (FIGURE 6), Scrapie Confirmed Cases in FY 2008 MAP, PA 3, 1**, Two cases-state of ID UNKNOWN, 1 case Nor98-like**

http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps

Greetings,

Apparently, there is a new strain of the Nor-98 atypical Scrapie here in the USA i.e. new strain called ''Nor98-like'' ;-)

I would like to thank Dr. Sutton et al for adding location of the 'Nor-98like' to map!

----- Original Message -----

From: Diane.L.Sutton
To: Terry S. Singeltary Sr.
Sent: Tuesday, August 21, 2007 7:42 AM
Subject: Re: SCRAPIE MONTHLY REPORT AS OF JUNE 30, 2007

Hi Terry - please see responses below.

snip...

> AND, if these are new cases, and i understand this correctly, how do we know what state they were reported in ?

you can't from the report. The flocks of origin were in WY, CO and CA

> maybe you might can add these atypical cases to the pps presentation on the monthly chart some how,.... just a suggestion ?

We are considering it.

Diane L. Sutton
National Scrapie Program Coordinator
National Center for Animal Health Programs USDA,
APHIS, VS 4700 River Rd.,
Unit 43 Riverdale, MD 20737 301-734-6954

============================

NOT to forget the 5 cases of the NOR-98 atypical scrapie documented in the USA in 2007, in five different states. WHICH pathologically looks like some sub-types of sporadic CJD, of which Stanely Prusiner warns of a public health risk ;

***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf

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.

Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved September 12, 2005 (received for review March 21, 2005)

http://www.pnas.org/cgi/content/abstract/0502296102v1

http://nor-98.blogspot.com/

In FY 2007, 331 scrapie cases have been confirmed and reported by the National Veterinary Services Laboratories (NVSL), including 59* Regulatory Scrapie Slaughter Surveillance (RSSS) cases (Figure 5 and Slide 16). In FY 2007, two field cases, one validation case, and two RSSS cases were consistent with Nor-98 scrapie. The Nor98-like cases originated from flocks in California, Minnesota, Colorado, Wyoming and Indiana respectively. Nineteen cases of scrapie in goats have been reported since 1990 (Figure 6). The last goat case was reported in September 2007.

snip...

see full report here ;

http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/yearly_report.pps

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

The sheep industry's scrapie eradication efforts. American Sheep Nor98-Like Scrapie Found in the United States

SCRAPIE: ERADICATE IT

The sheep industry's scrapie eradication efforts. American Sheep

Industry Association

The goal of the American Sheep Industry Association (ASI) and the U.S. sheep industry is to eradicate scrapie from our borders by 2010. In addition, it is the objective to have the World Organization for Animal Health, OIE, declare the United States scrapie free by 2017. This quarterly publication is created specifically for those of you in the field who are also working to achieve this goal.

This newsletter brings together, into one spot, current information from all 50 states, as well as from the U.S. Department of Agriculture and any other organization providing scrapie news, and reports it back to the field.

If you have first-hand accounts that you believe would be relevant for others to read or have information that you would like included in this newsletter, please let us know at becky@sheepusa.org.

March 2008

Nor98-Like Scrapie Found in the United States

By BECKY TALLEY

Sheep Industry News Associate Editor

In February of last year, the U.S. Department of Agriculture’s (USDA) Animal and Plant Health Inspection Service (APHIS) officially announced the discovery of a Nor98-like scrapie case in a ewe from a flock in Wyoming. This was the first case of scrapie consistent with Nor98 discovered in the United States. Since then, four more cases have been discovered that originated from flocks in Colorado, Indiana, Minnesota and California. These cases are not related to either the first one in Wyoming or to each other. This scrapie type was first found in Norway in 1998 and has since been found in sheep and goats in many countries in Europe.

“It does affect goats,” says Diane Sutton, DVM, national scrapie coordinator for USDA. “So far not here in the United States, but chances are, we might eventually see it in goats here too.” This type of scrapie affects sheep of all commonly occurring genotypes including those that are resistant to classical scrapie.

According to Sutton, those flocks in the United States that are found to be infected with Nor98-like scrapie will not be able to use the current genetic-base approach to flock clean up. Producers whose flocks have risk factors for classical scrapie are still encouraged to test at codon 171 for classical scrapie resistance, as has been done in the past.

The World Organization for Animal Health (OIE) has formed an ad hoc committee to consider how to address Nor98-like scrapie with respect to trade. It will likely be at least two years before a code change could be made should a consensus be reached.

“Until research provides us with other options for eliminating Nor98-like scrapie and the international community reaches a consensus on guidelines for trade we will continue to use flock depopulation and exposure-based clean up plans for Nor98-like scrapie affected flocks,” says Sutton. “As other viable options are identified, we will evaluate them using pilot projects.”

According to Linda Detwiler, DVM, assistant director, Center for Public and Corporate Veterinary Medicine, it is important to note that it isn’t known if the appearance of non-classical scrapie cases in Europe and the United States are more likely due to the increased ability to test for and detect non-classical scrapie than to increasing rates of infection. Scientists in European countries are beginning to look at archived samples in an attempt to identify non-classical cases that may have occurred earlier than 1998. “I would caution everyone that it’s premature to be able to say much of anything about these non- classical cases. At this point in time, there are many unknowns such as: 1) is there more than one strain, 2) what is the origin, 3) are there natural modes of transmission, 4) does the genotype affect incubation time and clinical presentation, 5) do codons other than 136, 141, 154 and 171 influence these cases and 6) how long have these cases been occurring?” she questions.

Because of Europe’s increased awareness of non-classical scrapie, there has been quite a bit of research into understanding how and if the disease is transmitted and how it affects sheep. Research is currently underway in the United States.

“The first U.S. material became available in February, so ARS (Agricultural Research Service) is gearing up to study it. But, because of the nature and long-term aspects of the disease, it will take a while to study, so we will probably be seeing research from Europe published first,” Sutton adds.

In the meantime, it is stressed that officials will continue to handle the disease as it has in the past, and that producers should be aware of Nor98-like scrapie but not alarmed.

“We are going to treat it as scrapie until the international community removes it as a trade barrier or science finds that there is a better way to handle it than the current system,” Sutton says.

Jim Logan’s, DVM, chair of ASI’s Animal Health Committee, best advice to producers to protect their flock from Nor98-like scrapie is to maintain a closed ewe flock. He says that to prevent the introduction of all scrapie types, producers need to be aware of where new purchases are coming from, know the genetics of new purchases and avoid purchasing ewes unless familiar with the scrapie status of the farm of origin or maintain a closed ewe flock.

“Essentially, people need to use common sense and maintain good sanitation and husbandry practices,” he explains.

Nor98 is a relatively common prion disease or transmissible spongiform encephalopathy of sheep. The first descriptions of the disorder were in sheep diagnosed in 1998 in Norway, although a retrospective study has revealed a case in England in 1989. Improved methods for diagnostic testing were published in 2002 and surveillance was initiated in many European countries. Most cases are identified in clinically normal sheep tested in routine slaughter surveillance. The disease is experimentally transmissible to sheep and genetically altered mice by inoculation into their brains but no data are yet available on whether the disease is transmitted between sheep in an affected flock.

Clinical Signs

Most cases have been discovered in clinically normal sheep tested at slaughter. Of the few clinical cases, a common sign is progressive incoordination (ataxia), occurring most likely because the abnormal prions accumulate in the cerebellum, the region of the brain (the cerebellum) that integrates information coming in from the senses with nerve impulses going to the muscles.

Diagnosis

Both classical scrapie and Nor98-like scrapie are characterized by accumulation of abnormal prion proteins. However, the distribution of the prion proteins differ. In classical scrapie, prions are usually found earliest in the lymph nodes and later in the region of the brain associated with innervation of the gut. As discussed above, abnormal prions are found in different areas of the brain in cases of Nor98. Further, prion proteins are not found in the lymph nodes of sheep with Nor98 and the current live animal tests of lymphoid tissues are not suitable. Nor98 is a challenging diagnosis but skilled pathologists, working with a panel of three different diagnostic tests, can accurately diagnose the disease in the brain of affected sheep.

Genetics

Susceptibility to classical scrapie is associated with naturally occurring differences in the gene for the prion protein, particularly differences at position 136 and 171. Each sheep has two copies of this gene and commercially available genotype tests show the differences at those positions. Sheep with the genotypes 136VV 171QQ and 136AV 171QQ are very susceptible to classical scrapie strains. Sheep with the 136AA 171QQ genotype are susceptible to the most common classical scrapie strain in the United States and represent the most common genotype found in U.S. scrapie cases. Sheep with at least one copy of the gene 136A 171R are generally resistant to the more common type of classical scrapie. Although no genotype is considered to be resistant to Nor98-like scrapie, the disorder is found most frequently in sheep with changes in positions 141 and/or 154. The genetic signature AFRQ indicates a sheep with 136A and 171Q with the additional change to “F” at 141. The signature AHQ indicates a sheep with 136A and 171Q with a change to “H” at position 154. A large survey of 4,000 sheep in Europe and numerous reports on smaller study populations has demonstrated that sheep with either the AFRQ or the AHQ gene were eight to 15 times more likely to be diagnosed with Nor98-like scrapie than were sheep with the most common genotype ARQ. Sheep with both changes were more than 20 times more likely to be diagnosed with Nor98-like scrapie. Sheep with the 171R form of the gene are generally resistant to classical scrapie but are susceptible to Nor98-like scrapie, particularly in 171QR sheep that have an AFRQ gene.

Epidemiology

Classical scrapie is usually found in more than one sheep in a flock, with prevalence as high as 30 percent with some scrapie strains. In contrast, more than one sheep with Nor98-like scrapie is usually found

The Science Behind Nor98 in Sheep

only in flocks of more than 500 sheep. In addition to genotype, age appears to represent a significant risk factor for Nor98-like scrapie. In the large European study, 80 percent of the cases of classical scrapie were found in sheep ages 3-5, a finding similar to that reported in the US. In contrast, more than 60 percent of the sheep with Nor98-like scrapie were older than five years and more than 25 percent were more than 10 years old. Nor98 is found in most countries performing large-scale surveillance; the disorder occurs at a rate of approximately one in 1,400 mature sheep at slaughter even if the rate of classical scrapie is very low.

The low prevalence of Nor98 within flocks, the wide geographic distribution of the disorder, the range in age of onset or diagnosis, and the genetic factors increasing the risk of Nor98 are strikingly different than those found in classical scrapie. There may be additional genetic factors influencing development of this disorder, in addition to factors such as route of infection or age at which sheep are infected. Alternatively, Nor98 may be a sporadic disease of sheep, appearing primarily but not exclusively in older sheep. Additional findings from experimental studies and large scale surveillance using improved diagnostic methods will be useful in understanding this wide-spread prion disease of sheep.

Background Information

Luhken and others, 2007, Veterinary Research 38: 65-80. Bruce and others, 2007, Veterinary Record 160: 665-666. Benestad and others, 2003, Veterinary Record 153: 202-208. Animals Sampled for Scrapie Testing

Sheep and Goats

19,667 animals have been sampled for scrapie testing: 16, 710 RSSS; 1,474 goats for the CSPS study; 1,224 regulatory field cases; 227 regulatory third eyelid biopsies; and 32 regulatory rectal biopsies. Testing of lympoid tissue obtained by rectal bopsy was approved by USDA as an official live-animal test on Jan. 11, 2008.

As of February 29, 2008

Infected and Source Flocks New Statuses by Year

FY 1997 – 2008* *Through February 29, 2008 Scrapie Confirmed Cases in 2008 Scrapie Flock Certification Program Participating Flocks SFCP Flocks Enrolled and Certified in February 2008 Through February 29, 2008 Total Enrolled Flocks—2,043 Complete Monitored—1,599 Certified—435 Export Monitored—5 Elective Monitored—4 Slaughter Surveillance Samples Collected by Month, FY 2004 to FY 2008* The Animal and Plant Health Inspection Service's goal is to collect 4,000 slaughter surveillance samples each month from around the United States. Regulatory Scrapie Slaughter Surveillance (RSSS) Statistics through February 29, 2008 *National Veterinary Services Laboratories Web Sites Dedicated to the Eradication of Scrapie Animal and Plant Health Inspection Service www.aphis.usda.gov/vs/nahps/scrapie Maryland Small Ruminant Page www.sheepandgoat.com/scrapie.html National Institute of Animal Agriculture http://www.animalagriculture.org/scrapie/Scrapie.htm Scrapie QuickPlace https://qp01.aphis.usda.gov/QuickPlace/scrapie/Main.nsf?OpenDatabase State and federal employees can access this password-protected site by e-mailing Susan.E.Ledford@APHIS.USDA.gov to receive a password. American Sheep Industry Association www.sheepusa.org Since April 1, 2003: 161,909 samples collected 352 NVSL* confirmed positive In FY2008: 16,710 samples collected 10 NVSL confirmed positive * Through February 29, 2008

http://www.sheepusa.org/index.phtml?page=site/get_file&print=1&file_id=a565d8d1480eca6400d3a2adff9d89bc


Friday, April 11, 2008

SEAC SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE ANNUAL REPORT 2007

It is highly likely that sheep were exposed to BSE during the BSE epidemic in cattle. However, despite extensive Transmissible Spongiform Encephalopathy (TSE) surveillance in sheep there is no evidence that BSE is present in the UK sheep flock now. *{The relatively recent identification of atypical scrapie and paucity of experimental data about its transmissibility either between sheep or to humans have raised concerns about the possible animal and public health implications of this disease}*.

http://www.seac.gov.uk/publicats/annualreport2007.pdf


Tissue distribution. For atypical scrapie, what is PrPres and infectivity distribution within sheep of different genotypes, particularly with respect to SRM removal? For classical scrapie and experimental BSE in sheep, tissue distribution of infectivity is widespread. Thus, even with SRM controls in place, an infected sheep poses around 1000 times the risk to human health than does an infected cow22. Does the distribution depend on whether infection is by the oral or 21 Gubbins S. Prevalence of BSE in sheep: interpreting the results of retrospective and prospective testing of sheep TSE cases. SEAC 84 open meeting 22 paper presented to Food Standards Agency board on 9 December 2004. http://www.foodstandards.gov.uk/multimedia/pdfs/fsa041204.pdf Also see paper SEAC/84/2 Annex 2: McLean, A. Page 13 © SEAC 27 February 2006 intracerebral route? Are some VRQ sheep carriers with no neurological symptoms?

SEAC SHEEP SUBGROUP POSITION STATEMENT

http://www.seac.gov.uk/pdf/positionstatement-sheep-subgroup.pdf


P03.141

Aspects of the Cerebellar Neuropathology in Nor98

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute, Norway

Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. ***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf


Published online before print October 20, 2005

Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0502296102 Medical Sciences

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 * *Virologie Immunologie Moléculaires and Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway

Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved September 12, 2005 (received for review March 21, 2005)

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


http://www.pnas.org/cgi/content/abstract/0502296102v1


Like lambs to the slaughter

31 March 2001

Debora MacKenzie

Magazine issue 2284

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in ...

The complete article is 889 words long.

full text;

http://www.newscientist.com/article.ns?id=mg16922840.300


Neurobiology

Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt- Jakob disease: Implications for human health Corinne Ida Lasmézas*,, Jean-Guy Fournier*, Virginie Nouvel*, Hermann Boe*, Domíníque Marcé*, François Lamoury*, Nicolas Kopp, Jean-Jacques Hauw§, James Ironside¶, Moira Bruce, Dominique Dormont*, and Jean-Philippe Deslys* * Commissariat à l'Energie Atomique, Service de Neurovirologie, Direction des Sciences du Vivant/Département de Recherche Medicale, Centre de Recherches du Service de Santé des Armées 60-68, Avenue du Général Leclerc, BP 6, 92 265 Fontenay-aux-Roses Cedex, France; Hôpital Neurologique Pierre Wertheimer, 59, Boulevard Pinel, 69003 Lyon, France; § Laboratoire de Neuropathologie, Hôpital de la Salpêtrière, 83, Boulevard de l'Hôpital, 75013 Paris, France; ¶ Creutzfeldt-Jakob Disease Surveillance Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Institute for Animal Health, Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, United Kingdom

Edited by D. Carleton Gajdusek, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France, and approved December 7, 2000 (received for review October 16, 2000)

Abstract

There is substantial scientific evidence to support the notion that bovine spongiform encephalopathy (BSE) has contaminated human beings, causing variant Creutzfeldt-Jakob disease (vCJD). This disease has raised concerns about the possibility of an iatrogenic secondary transmission to humans, because the biological properties of the primate-adapted BSE agent are unknown. We show that (i) BSE can be transmitted from primate to primate by intravenous route in 25 months, and (ii) an iatrogenic transmission of vCJD to humans could be readily recognized pathologically, whether it occurs by the central or peripheral route. Strain typing in mice demonstrates that the BSE agent adapts to macaques in the same way as it does to humans and confirms that the BSE agent is responsible for vCJD not only in the United Kingdom but also in France. The agent responsible for French iatrogenic growth hormone-linked CJD taken as a control is very different from vCJD but is similar to that found in one case of sporadic CJD and one sheep scrapie isolate. These data will be key in identifying the origin of human cases of prion disease, including accidental vCJD transmission, and could provide bases for vCJD risk assessment.

http://www.pnas.org/cgi/content/full/041490898v1


typical scrapie transmits to primates by there NON-FORCED ORAL CONSUMPTION ;

76/10.12/4.6

http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf


http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=6997404&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus


snip...full text ;

http://nor-98.blogspot.com/2008/04/seac-spongiform-encephalopathy-advisory.html


Saturday, April 12, 2008

Evidence of scrapie transmission via milk

Research articleS

http://scrapie-usa.blogspot.com/2008/04/evidence-of-scrapie-transmission-via.html


NOR-98

http://nor-98.blogspot.com/


SCRAPIE USA

http://scrapie-usa.blogspot.com/


FOIA MAD SHEEP MAD RIVER VALLEY

http://foiamadsheepmadrivervalley.blogspot.com/


TSS