CONFIDENTIAL IN CONFIDENCE THE SCRAPIE sCJD FILES

[Terry S. Singeltary Sr.]

THE SCRAPIE, SPORADIC CJD FILES, CONFIDENTIAL

MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON CREUTZFELDT JAKOB DISEASE 1978

THE SCRAPIE FILES IN CONFIDENCE CONFIDENTIAL SCJD

MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON CREUTZFELDT JAKOB DISEASE 1978

THE SCRAPIE FILES

CONFIDENTIAL

IN CONFIDENCE SCJD

Subject: 1978 SCRAPIE IN CONFIDENCE SCJD

1978 SCRAPIE IN CONFIDENCE SCJD

Annex:

MEDICAL RESEARCH COUNCIL

IN CONFIDENCE

Circulation Participants

MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON CREUTZFELDT-JAKOB DISEASE

Minutes of meeting held on Thursday 9 March 1978 at 20 Park Crescent London WIN 4AL

Present: Professor J N Walton (Chairman), Dr A M Adelstein, Professor J R Batchelor, Mr K N Burns (ARC), Professor J A N Corsellis, Dr T J Crow, Dr R Levy, Professor W B Matthews, Dr J T Stamp, Professor B E Tomlinson, Professor M P Vessey, Professor P Wildy, Dr A Smithies (Health Department Observer).

Headquarters staff: Dr Katherine levy, Dr Victoria Harrison, Miss Roberta Withnall.

Amlogies for absence: Professor A N Davison, Dr R H Kimberlin, Dr W A Lishman, Professor C A Mims-

1. Introduction and background

The Chairman opened the meeting by explaining that its purpose was to advise the Neurosciences Board on the value and feasibility of carrying out epidemiological studies on Creutzfeldt—Jakob (C—J) disease; suggestions for work on other aspects of the disease were not, however, precluded.

***The meeting had been called following the Agricultural Research Council's (ARC) report of their Advisory Committee on Scrapie, a document which should be regarded as confidential.

One of the main issues which merited discussion was whether those whose occupation suggested they might be in contact with scrapie had a higher risk of developing C—J disease. While fully appreciating that the problem of infectivity was one of great concern the present meeting was not constituted to discuss this problem per se. The recently set up ARC Advisory Group on Scrapie would be taking up this question; it was also of concern to the Health Departments who wished to be kept informed of developments. Mr Burns reported that the ARC had already had preliminary discussions on the safety aspects which would be necessary in the event of C—J work being carried out in their Institute at Compton. Dr Levy agreed to act as liaison officer between the two Councils and the Health Departments.

.2 snip...

The meeting considered the mortality data provided by OPCS (CJD 78/2) and that provided by Professor Matthews (paper tabled). The interpretation of these data was complicated by possibilities of both under and over reporting. Under-reporting was likely in that G—J disease might:

(a) be undiagnosed, particularly in large mental hospitals; and

(b) not appear on death certificates either because the actual cause of death was eg. bronchial pneumonia, or because reference to dementia (in any form) was excluded to spare the feelings of the family. Over-reporting might occur because, although the rapidly progressive form of the disease was readily diagnosed in life, the less dramatic forms were more difficult. to recognise clinically and could be diagnosed in error (see below). It was notes: that the OPCS data showed an apparently higher incidence of the disease in social class I: a possible explanation was that this group was investigated more carefully. An added difficulty, common to all occupational data obtained from death certificates alone, was that it was based solely on information provided by the person registering the death. Professor Vessey drew attention to the temporal differences between the OPCS data and those provided by Professor Matthews.

S 803/10 78/3.9/1.1

The meeting then considered the implication of:

a) incompleteness; and

b) inaccuracy of the data. Incompleteness would matter if it was associated with the factor under study, eg. if only those cases occurring in certain occupational groups were missing: if accurate incidence, prevalence or mortality rates were required; and in examining space/time clustering (see below). Inaccuracy would matter less since the dilution of the mortality data with diseases other than C—J would merely tend to weaken any association present.

3. Accuracy of clinical diagnosis: neuropathology

The neuropathologists present explained that it was now generally considered that there were 3 categories of the disease:

(i) a rapidly progressive form of subacute spongiform encephalopathy (the Nevin—Jones Syndrome) usually leading to death within 6—9 months; this is the only form which has been transmitted to animals;

(ii) a variant in which the cerebellum appears to bear the brunt of the pathology and

(iii) "classical" C—J disease which follows a more protracted course. Diagnosis is based on the typical EEG picture - which in the slower forms of the disease may not arise until late in the course of the illness — and on the characteristic spongiform features seen on neuropathological examination. The less rapidly progressive forms could be confused with other forms of dementia or arteriosclerotic disease, Alzheimer's disease with myoclonus, myoclonic epilepsy, corticostrionigral degeneration, Pick's disease or motor neurone disease.

While there could be doubt about a diagnosis made on a biopsy specimen it would be very rare for a neuropathologist to make a mistake at autopsy. However, in less specialised hands there was a very significant chance that cases could be missed.

Dr Stamp pointed out that in scrapie no spongiform encephalopathy was detected and that in many cases confirmed by transmission experiments no neuropathological abnormality could be found.

4. Specialist care of C—J patients

The question of whether C—J patients Were in the main looked after by neurologists or by psychiatrists was discussed. The View of the meeting was that most patients were seen by neurologists, but that there might be an unknown, even considerable number of cases (presumably of the more chronic form) in major mental hospitals.

5. Frequency of biopsies and post mortems

Until a few years ago a biopsy was carried out in the majority of suspected case. referred to major centres: the situation had now changed and biopsies were performed less often, partly because diagnosis could be based on the clinical and EEG picture .

Dr Adelstein pointed out that 50% of C-J deaths recorded in the OPCS figures had come to post mortem, during the six year period up to 1976. The figures may be dropping for both biopsies and post mortems not only because they are thought unnecessary in view of the improvement in other methods of diagnosis but also because of both the shortage of neuropathologists and their awareness of the possible infectivity of the agent.*

*‘There is no evidence to suggest that there is only one agent; there may well be several. But for the purposes of this record the term 'agent‘ is used throughout

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78/3.9/1.2

6. Gajdusek's evidence

The Chairman invited Professor Wildy to speak to his paper (CJD 78/3) on the hazards of the C—J agent and other possible agents to hospital staff and pathologists. Professor Wildy emphasised that in general Gajdusek's evidence should be treated with great caution since his hypothesis was based on the presumed analogy with the scrapie agent (or agents). Hard data were not available about the C—J agent itself. It was resistant to many physical and chemical treatments: there was a need to establish a reliable means of sterilisation, as Gajdusek's published data on autoclaving was open to criticism. It is likely that, as with scrapie, some C—J strains would prove to be much more resistant than others.

7. Risk of infection

The two reports of iatrogenic man—to—man transmission of C—J disease have involved corneal grafting and neurosurgery respectively. While the implications for sterilisation of instruments etc. had been widely discussed in the literature the additional point was made that corneae for grafts were often obtained from old peoples' homes: caution should therefore be exercised in using tissue from this source.

Overall there was no indication either from OPCS data or from anecdotal evidence that pathologists, mortuary attendants or research workers had ever developed C—J disease. On available evidence it was, however, clear that contact between C—J infected material and lacerated skin must be avoided. Nor was there evidence that anyone working with scrapie diseased animals (veterinary surgeons, slaughter house workers, butchers, shepherds and shepherdesses or research workers) have developed the disease. It was nonetheless worth undertaking retrospective epidemiological studies if only to provide reassurance that there was no excess mortality from C—J disease in these and other professional groups — including neurosurgeons, neurologists, undertakers and embalmers. It should however be borne in mind that some of the latter categories may be under—represented, occupation euphemisms having been used on the death certificates.

8. Prevalence and mode of infectivity of C—J agent

While the prevalence and mode of infectivity of the C—J agent are unknown it would be difficult to account for the world wide distribution of the disease unless the agent were common. If prevalence were low it would be difficult to postulate how the agent would replicate. This suggested that one might be dealing with a transferred ubiquitous and relatively banal agent — the analogy being measles and SSPE. It was agreed that while this was pure speculation, the possibility could not be ruled out. Dr Crow pointed out that the age incidence of C—J disease would not suggest that it was due to an infective agent. In this connection Dr Stamp reported that both lateral and vertical transmission occur in scrapie: genetic factors determine the incubation period and so—called "resistant" sheep may die before there was time for them to show clinical signs of the disease. It was not known how scrapie was transmitted, though it can exist outside its host for an indefinite period. However the usefulness of the scrapie analogy is uncertain. Dr Stamp emphasised that in scrapie the innoculated and natural disease are two very different conditions.

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78/3.9/1.3

9. Clusters, familial incidence and conjugal C—J disease

Geographical and temporal clustering have been reported; these however had been small and difficult to evaluate statistically. In Professor Tomlinson's experience all cases of C—J were referrals from the better known neurological or psychiatric centres, implying that clustering could be an artefact. Professor Vessey offered with colleagues to examine the data provided by OPCS and Professor Matthews to see if these revealed any evidence of clustering. Different incubation periods could be built in and contact between cases could be looked for - the complex statistics had been worked out for Hodgkin's disease. The technique involved was nevertheless a crude one. Familial cases had been reported but the numbers involved were too low to be significant. Occurrence of the disease in cousins (2 in the UK, and 2 in the USA) and two cases of conjugal C—J disease were briefly mentioned.

10. Genetic screening, including HLA status

Professor Batchelor confirmed that the HLA status of C—J patients had not been investigated. Dr Stamp reported that there was no association with mouse histocompatibility antigens in scrapie; this had not been investigated in sheep. Professor Batchelor said that typing would not be difficult: 30—60 patients would be required depending on the rarity of the antigen. General genetic screening might also be worthwhile; he suggested that the Galton laboratories might be approached with a view to studying various isoenzymes in such cases. Samples of serum should be stored for future study of antibody profiles.

11 . General conclusions

(i) The meeting could only confirm that the epidemiology of C—J disease is poorly understood.

(ii) The existing mortality data were likely to be inaccurate; so far as they went no occupational association with the disease could be demonstrated. The prevalence and mode of infectivity of the agent were unknown and clusters reported had been small and difficult to evaluate statistically.

(iii) Gajdusek‘s evidence was open to criticism: however, while his assertions are unsupported by hard data, his claims might nonetheless have substance.

(iv) While the-analogy with scrapie was interesting and the scrapie and C—J agents displayed similarities in behaviour and character, there was no proof that the scrapie agent was in any way associated with C-J disease.

12. Possible action

The following suggestions were made about action which might be taken:

(1) OPCS might be asked to provide data on the occupations listed for all deaths due to dementia and the other diseases with which C—J might be confused recorded within, say, the last 3 years.

(ii) OPCS might be asked to collect prospectively notifications of all deaths from C—J disease, the dementias and other diseases with which it might be confused.

(iii) The data provided by OPCS might be correlated with that obtained by Professor Matthews (confirming diagnoses from case notes etc. in at least a sample of these cases) to see how many of the same C—J patients were involved. These data should be analysed for evidence of clustering.

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(iv) Data provided by the Doll/Hill study of 34,000 doctors on the medical register in 1953 might (with the authors' agreement) be utilised to see if any excess death rates from C—J-disease, the dementias or other diseases with which it may be confused, could be identified among certain specialist groups.

(v) HLA status of C—J patients should be determined.

(vi) General genetic screening might be undertaken of patients with C—J disease.

(vii) Samples of serum from C—J patients should be stored for future study of antibody profiles.

(viii) Although technically outside their remit the meeting recommended that good work should be encouraged on the isolation, characterisation, distribution in the body, routes of infection and methods of destruction of the C—J agent.

The Chairman closed the meeting by thanking the participants for attending and for their help in reaching these conclusions.

78/3.9/1.5

web.archive.org/web/20090505233518/http://www.bseinquiry.gov.uk/files/yb/1978/03/09001001.pdf

web.archive.org/web/20090506012627/http://www.bseinquiry.gov.uk/files/yb/1978/06/01001001.pdf

web.archive.org/web/20090506012518/http://www.bseinquiry.gov.uk/files/yb/1978/06/27001001.pdf

BE SURE TO SEE THIS NEXT ONE WITH FIGURES...TSS

STUDIES ON CREUTZFELDT-JAKOB DISEASE

i enclose a list of ICD categories showing the numbers of deaths attributed to each (as underlying cause) in England and Hales in 1975.

ICD NO...Number of Certificates examined

xxxxx...18...15 mentioned C-J

xxxxx...122...1 mentioned C-J with dimentia, 24 mentioned Alzheimer’s disease, 1 mentioned Pick’s disease.

xxxxx...22...4 mentioned Myoclonic epilepsy

xxxxx...384...none mentioned Corticostrionigral degeneration

xxxxx...2...none mentioned Corticostrionigral degeneration

snip...

web.archive.org/web/20090506012512/http://www.bseinquiry.gov.uk/files/yb/1978/06/27002001.pdf

web.archive.org/web/20090506012538/http://www.bseinquiry.gov.uk/files/yb/1978/06/27003001.pdf

web.archive.org/web/20090506012525/http://www.bseinquiry.gov.uk/files/yb/1978/06/27004001.pdf

web.archive.org/web/20090506012546/http://www.bseinquiry.gov.uk/files/yb/1978/08/18001001.pdf

web.archive.org/web/20090506012532/http://www.bseinquiry.gov.uk/files/yb/1978/10/06001001.pdf

web.archive.org/web/20090505233520/http://www.bseinquiry.gov.uk/files/yb/1978/10/06002001.pdf

1979

SILENCE ON CJD AND SCRAPIE

1980

SILENCE ON CJD AND SCRAPIE

*** 1981 NOVEMBER

web.archive.org/web/20090505235701/http://www.bseinquiry.gov.uk/files/yb/1981/11/26001001.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.

snip...

The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.

PMID: 6997404

www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract

12/10/76

AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE

Office Note CHAIRMAN: PROFESSOR PETER WILDY

snip...

A The Present Position with respect to Scrapie A] 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 ia 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 emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise 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 acrapie problem urgent if the sheep industry is not to suffer grievously.

snip...

76/10.12/4.6

web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf

*** 1976 Scrapie Research USDA worried about Scrapie and sCJD in man...tss

web.archive.org/web/20090506012956/http://www.bseinquiry.gov.uk/files/yb/1976/10/12002001.pdf

Nature. 1972 Mar 10;236(5341):73-4.

Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).

Gibbs CJ Jr, Gajdusek DC. Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

C. J. GIBBS jun. & D. C. GAJDUSEK National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland

SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).

www.nature.com/nature/journal/v236/n5341/abs/236073a0.html

Nature. 1972 Mar 10;236(5341):73-4.

Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).

Gibbs CJ Jr, Gajdusek DC. Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

C. J. GIBBS jun. & D. C. GAJDUSEK National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland

SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).

www.nature.com/nature/journal/v236/n5341/abs/236073a0.html

why do we not want to do TSE transmission studies on chimpanzees $

IN CONFIDENCE

TRANSMISSION TO CHIMPANZEES

snip...

5. A positive result from a chimpanzee challenged severely would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

snip...

R. BRADLEY

web.archive.org/web/20090506041740/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf

full text ;

RB3.20

IN CONFIDENCE

TRANSMISSION TO CHIMPANZEE

1. Kuru and CJD have been successfully transmitted to chimpanzees but scrapie and TME have not.

2. We cannot say that scrapie will not transmit to chimpanzees. There are several scrapie strains and I am not aware that all have been tried (that would have to be from mouse passaged material). Nor has a wide enough range of field isolates subsequently strain typed in mice been inoculated by the appropriate routes (i/c, i/p and i v);

3. I believe the proposed experiment to determine transmissibility, if conducted, would only show the susceptibility or resistance of the chimpanzee to infection/disease by the routes used and the result could not be interpreted for the predictability of the susceptibility for man. Proposals for prolonged oral exposure of chimpanzees to milk from cattle were suggested a long while ago and rejected.

4. In view of Dr Gibbs‘ probable use of Chimpazees Mr Wells‘ comments (enclosed) are pertinent. I have yet to receive a direct communication from Dr Schellekers but before any collaboration or provision of material we should identify the Gibbs' proposals and objectives.

5. A positive result from a chimpanzee challenged severely would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

A negative result would take a lifetime to determine but that would be a shorter period than might be available for human exposure and it would still not answer the question regarding mans' susceptibility. In the meantime no doubt the negativity would be used defensively. It would however be counterproductive if the experiment finally became positive- We may learn more about public reactions following next Monday‘s meeting. CVO (+ Mr. Wells’ comments)

Dr. T W A Little

Dr. B J Shreeve

R Bradley September 1990

90/9.23/1/1

web.archive.org/web/20090506041740/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf

Wednesday, February 16, 2011

IN CONFIDENCE

SCRAPIE TRANSMISSION TO CHIMPANZEES

IN CONFIDENCE

scrapie-usa.blogspot.com/2011/02/in-confidence-scrapie-transmission-to.html

2016 PRION CONFERENCE TOKYO

‘’These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.’’

Saturday, April 23, 2016

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,

Natalia Fernandez-Borges a. and Alba Marin-Moreno a

"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France

Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.

To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.

These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.

Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

Tuesday, December 16, 2014

Evidence for zoonotic potential of ovine scrapie prions

Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier Andréoletti1, Affiliations Contributions Corresponding author Journal name: Nature Communications Volume: 5, Article number: 5821 DOI: doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014 Published 16 December 2014 Article tools Citation Reprints Rights & permissions Article metrics

Abstract

Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human​prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE. The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

snip...

Do our transmission results in tgHu imply that sheep scrapie is the cause of sCJD cases in humans? This question challenges well-established dogma that sCJD is a spontaneous disorder unrelated to animal prion disease. In our opinion, our data on their own do not unequivocally establish a causative link between natural exposure to sheep scrapie and the subsequent appearance of sCJD in humans. However, our studies clearly point out the need to re-consider this possibility. Clarification on this topic will be aided by informed and modern epidemiological studies to up-date previous analysis that was performed at the end of the last century3, 4. The value of such an approach is highlighted by the implementation in the year 2000 of large-scale active animal TSE surveillance programs around the world that provided an informed epidemiological-based view of the occurrence and geographical spread of prion disease in small ruminant populations51. The fact that both Australia and New-Zealand, two countries that had been considered for more than 50 years as TSE-free territories, were finally identified positive for atypical scrapie in their sheep flocks provides an example of how prion dogma can be reversed52. However, the incubation period for prion disease in humans after exposure to prions via the peripheral route, such as in iatrogenic CJD transmission and Kuru, can exceed several decades53, 54. In this context, it will be a challenge to combine epidemiological data collected contemporarily in animal populations and humans to investigate the existence of a causative link between prion disease occurrence in these different hosts. Furthermore, it is crucial to bear in mind that sporadic sCJD in humans is a rare disease (1–2 individuals per million of the population per year) and that scrapie has been circulating in small ruminants populations used for food purposes for centuries. Consequently, it is our opinion that even if a causative link was established between sheep scrapie exposure and the occurrence of certain sCJD cases, it would be wrong to consider small ruminant TSE agents as a new major threat for public health. Despite this, it remains clear that our data provide a new impetus to establish the true zoonotic potential of sheep scrapie prions.

Subject terms: Biological sciences• Medical research At a glance

www.nature.com/ncomms/2014/141216/ncomms6821/full/ncomms6821.html

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

Title: Transmission of scrapie prions to primate after an extended silent incubation period

Authors

item Comoy, Emmanuel - item Mikol, Jacqueline - item Luccantoni-Freire, Sophie - item Correia, Evelyne - item Lescoutra-Etchegaray, Nathalie - item Durand, Valérie - item Dehen, Capucine - item Andreoletti, Olivier - item Casalone, Cristina - item Richt, Juergen item Greenlee, Justin item Baron, Thierry - item Benestad, Sylvie - item Hills, Bob - item Brown, Paul - item Deslys, Jean-Philippe -

Submitted to: Scientific Reports Publication Type: Peer Reviewed Journal Publication Acceptance Date: May 28, 2015 Publication Date: June 30, 2015 Citation: Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E., Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C., Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J. 2015. Transmission of scrapie prions to primate after an extended silent incubation period. Scientific Reports. 5:11573.

Interpretive Summary: The transmissible spongiform encephalopathies (also called prion diseases) are fatal neurodegenerative diseases that affect animals and humans. The agent of prion diseases is a misfolded form of the prion protein that is resistant to breakdown by the host cells. Since all mammals express prion protein on the surface of various cells such as neurons, all mammals are, in theory, capable of replicating prion diseases. One example of a prion disease, bovine spongiform encephalopathy (BSE; also called mad cow disease), has been shown to infect cattle, sheep, exotic undulates, cats, non-human primates, and humans when the new host is exposed to feeds or foods contaminated with the disease agent. The purpose of this study was to test whether non-human primates (cynomologous macaque) are susceptible to the agent of sheep scrapie. After an incubation period of approximately 10 years a macaque developed progressive clinical signs suggestive of neurologic disease. Upon postmortem examination and microscopic examination of tissues, there was a widespread distribution of lesions consistent with a transmissible spongiform encephalopathy. This information will have a scientific impact since it is the first study that demonstrates the transmission of scrapie to a non-human primate with a close genetic relationship to humans. This information is especially useful to regulatory officials and those involved with risk assessment of the potential transmission of animal prion diseases to humans. Technical Abstract: Classical bovine spongiform encephalopathy (c-BSE) is an animal prion disease that also causes variant Creutzfeldt-Jakob disease in humans. Over the past decades, c-BSE's zoonotic potential has been the driving force in establishing extensive protective measures for animal and human health.

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.

www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160

2015

O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations

Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.

*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,

***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),

***is the third potentially zoonotic PD (with BSE and L-type BSE),

***thus questioning the origin of human sporadic cases. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.

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

***thus questioning the origin of human sporadic cases***

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

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.

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

web.archive.org/web/20151231064020/https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf

SCRAPIE AND CWD ZOONOSIS

PRION 2016 CONFERENCE TOKYO

Saturday, April 23, 2016

*** SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016 ***

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X

scrapie-usa.blogspot.com/2016/04/scrapie-ws-01-prion-diseases-in-animals.html

Increased Atypical Scrapie Detections

Press reports indicate that increased surveillance is catching what otherwise would have been unreported findings of atypical scrapie in sheep. In 2009, five new cases have been reported in Quebec, Ontario, Alberta, and Saskatchewan. With the exception of Quebec, all cases have been diagnosed as being the atypical form found in older animals. Canada encourages producers to join its voluntary surveillance program in order to gain scrapie-free status. The World Animal Health will not classify Canada as scrapie-free until no new cases are reported for seven years. The Canadian Sheep Federation is calling on the government to fund a wider surveillance program in order to establish the level of prevalence prior to setting an eradication date. Besides long-term testing, industry is calling for a compensation program for farmers who report unusual deaths in their flocks.

web.archive.org/web/20111017012241/http://gain.fas.usda.gov/Recent%20GAIN%20Publications/This%20Week%20in%20Canadian%20Agriculture%20%20%20%20%20Issue%2028_Ottawa_Canada_11-6-2009.pdf

J Vet Diagn Invest 21:454-463 (2009)

Nor98 scrapie identified in the United States

Christie M. Loiacono,' Bruce V. Thomsen, S. Mark Hall, Matti Kiupe!, Diane Sutton, Katherine O'Rourke, Bradd Barr, Lucy Anthenill, Deiwyn Keane

Abstract.

A distinct strain of scrapic identified in sheep of Norway in 1998 has since been identified in numerous countries throughout Europe. The disease is known as Nor98 or Not-98-like scrapic. among other names. Distinctions between classic scrapie and Nor98 scrapie are made based on histopathologv and immunodiagnostic results. There are also differences in the epidemiology, typical signalment, and likelihood of clinical signs being observed. In addition, sheep that have genotypes associated with resistance to classic scrapie are not spared from Nor98 disease. The various differences between classic and Nor98 scrapie have been consistently reported in the vast majority of cases described across Europe. The current study describes in detail the patholo gic changes and diagnostic results of the first 6 cases of' Nor98 scrapic disease diagnosed in sheep of the United States.

Key words: Hisiopathology: Nor98: PrP imniunolabeling; scrapie: sheep.

snip...

Results

Case I

The first case identified as consistent with Nor98 scrapie had nonclassic PrP distribution in brain tissue, no PrPSC in lymph tissue, and nonclassic migration of protein bands on a Western blot test. The animal was an aged, mottled-faced ewe that was traced back to a commercial flock in Wyoming. ...

Case 2

The second case was a clinically normal 8-year-old Suffolk ewe that had been in a quarantined flock for 5 years at a USDA facility in Iowa.

Case 3

A 16-year-old, white-faced, cross-bred wether was born to a black-faced ewe. He lived his entire life as a pet on a farm in California.

Case 4

The fourth case of Nor98 scrapie was identified in an approximately 8-year-old Dorset ewe that was born into a flock of approximately 20 ewes in Indiana.

Case 5

The fifth case was a clinically normal, approximately 3-year-old, white-faced, cross-bred ewe from an approximately 400 head commercial flock in Minnesota.

Case 6

The sixth case of Nor98 scrapie was identified in a 4-year-old, white-faced ewe that was purchased and added to a commercial flock in Pennsylvania

snip...

see full text ;

ddr.nal.usda.gov/bitstream/10113/33943/1/IND44241920.pdf

see updated link;

journals.sagepub.com/doi/10.1177/104063870902100406

Monday, April 25, 2011 Experimental Oral Transmission of Atypical Scrapie to Sheep

Volume 17, Number 5-May 2011

nor-98.blogspot.com/2011/04/experimental-oral-transmission-of.html

Sunday, April 18, 2010

SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010

scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html

Thursday, November 18, 2010

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html

Wednesday, January 19, 2011

EFSA and ECDC review scientific evidence on possible links between TSEs in animals and humans Webnachricht 19 Januar 2011

transmissiblespongiformencephalopathy.blogspot.com/2011/01/efsa-and-ecdc-review-scientific.html

Monday, June 27, 2011

Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease

prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html

Thursday, February 23, 2012

Atypical Scrapie NOR-98 confirmed Alberta Canada sheep January 2012

transmissiblespongiformencephalopathy.blogspot.com/2012/02/atypical-scrapie-nor-98-confirmed.html

Thursday, March 29, 2012

atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012

NIAA Annual Conference April 11-14, 2011San Antonio, Texas

nor-98.blogspot.com/2012/03/atypical-nor-98-scrapie-has-spread-from.html

Atypical NOR98 Scrapie USA UPDATE,2016, to date, atypical NOR98 Scrapie has been documented in 8 cases.

Positive Cases and Infected/Source Flocks

Positive Scrapie Cases*

Thirteen positive cases have been reported in FY 2016. Eight of the cases were from a source flock that was designated in October because of an RSSS positive animal reported in September 2015. Location of the cases is shown in Table 1and Figure 1, and distribution by face-color (sheep) and type (goats) is shown in Table 2.

USDA confirmed 41 cases in goats from FY 2002 through FY 2015 (Figure 2). No goats have tested positive in FY 2016.

Infected and Source Flocks

As of June 30, 2016, there were two flocks with an open infected or source status

(Figure 3). Two infected and three source flocks have been designated in FY 2016 (Figure 4); four flocks have completed clean-up plans and have been released (Figure 5). New infected and source statuses from FY 1997 to FY 2016 are depicted in Chart 2.

Introduction –Positive Cases & Infected/Source Flocks

* Samples collected between October 1, 2015 and June 30, 2016 and confirmed by July 15, 2016.w

Surveillance

Regulatory Scrapie Slaughter Surveillance (RSSS)

RSSS started April 1, 2003. It is a targeted slaughter surveillance program which is designed to identify infected flocks. Samples have been collected from 511,135 animals since April 1, 2003. There have been 479 NVSL confirmed positive animals* (471 classical cases and 8 Nor98-like cases) since the beginning of RSSS. As of June 30, 2016, 28,533 samples have been collected in FY 2016, 22,889 from sheep and 5,644 from goats.

As of June 30, 2016, one black-faced sheep* tested positive for scrapie in FY 2016. The weighted percentage of samples that have tested positive for each face color** from FY 2003 through FY 2016 is depicted in Chart 3a. In November 2013, administrative units within APHIS Veterinary Services reorganized from 2 Regions to 6 Districts (Figure 6). The distribution of sheep and goat populations by District is depicted in Chart 4a. The number of animals collected for FY 2016 by District where collected is shown in Chart 4b. A monthly comparison of RSSS collections by fiscal year is displayed in Chart 5. Chart 6is a retrospective 6-month rolling average of the percent positive, black-faced sheep sampled at RSSS collection sites.

* RSSS positives are reported based on collection date and may have been confirmed after June 30, 2016.

** White, black and mottled face color sheep are weighted based on population. White faced sheep have the highest weight, so when the uncommon white face positive sheep is found it will cause this statistic to markedly increase

www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_report.pdf

Atypical NOR98 Scrapie to humans as sporadic CJD

Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits, see also ; All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.

cjdusa.blogspot.com/2009/09/co-existence-of-scrapie-prion-protein.html

AND WHAT HAVE THE PRION GODS SAID OF THE ATYPICAL NOR-98, AND IT'S POTENTIAL FOR TRANSMISSION TO HUMANS ;

A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes

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*,?? +Author Affiliations

*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 (received for review March 21, 2005)

Abstract 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.

www.pnas.org/content/102/44/16031.abstract

OR

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

web.archive.org/web/20140722084143/http://www.neuroprion.org/resources/pdf_docs/conferences/prion2007/abstract_book.pdf

OR

*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.

web.archive.org/web/20070217062130/http://www.neuroprion.com/pdf_docs/conferences/prion2006/abstract_book.pdf

*** The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.

VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion poker goes up again $

OR-10: Variably protease-sensitive prionopathy is transmissible in bank voles

Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1 Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome, Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna, Italy; 3Case Western Reserve University; Cleveland, OH USA

Background. Variably protease-sensitive prionopathy (VPSPr) is a recently described “sporadic”neurodegenerative disease involving prion protein aggregation, which has clinical similarities with non-Alzheimer dementias, such as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is the electrophoretic pattern of PrPSc after digestion with proteinase K (PK). After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern similar to that described in GSS cases. The clinical and pathological features of VPSPr raised the question of the correct classification of VPSPr among prion diseases or other forms of neurodegenerative disorders. Here we report preliminary data on the transmissibility and pathological features of VPSPr cases in bank voles.

Materials and Methods. Seven VPSPr cases were inoculated in two genetic lines of bank voles, carrying either methionine or isoleucine at codon 109 of the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical diagnosis in voles was confirmed by brain pathological assessment and western blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.

Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission in BvM109. Overall, 3 voles were positive with survival time between 290 and 588 d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form of the typical PrP27–30, which was indistinguishable to that previously observed in BvM109 inoculated with sCJDMM1 cases.

In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until now. Overall, 5 voles were positive with survival time between 281 and 596 d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like PrPSc electrophoretic pattern, characterized by low molecular weight PrPres. These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus and the N-terminus. Second passages are in progress from these first successful transmissions.

Conclusions. Preliminary results from transmission studies in bank voles strongly support the notion that VPSPr is a transmissible prion disease. Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109.

The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.

web.archive.org/web/20140414032515/http://www.landesbioscience.com/journals/prion/01-Prion6-2-OralPresentations.pdf?nocache=1216084967

Monday, June 27, 2011

Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease

prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html

CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL REPORT AUGUST 1994

Consumption of venison and veal was much less widespread among both cases and controls. For both of these meats there was evidence of a trend with increasing frequency of consumption being associated with increasing risk of CJD. (not nvCJD, but sporadic CJD...tss) These associations were largely unchanged when attention was restricted to pairs with data obtained from relatives. ...

Table 9 presents the results of an analysis of these data.

There is STRONG evidence of an association between ‘’regular’’ veal eating and risk of CJD (p = .0.01).

Individuals reported to eat veal on average at least once a year appear to be at 13 TIMES THE RISK of individuals who have never eaten veal.

There is, however, a very wide confidence interval around this estimate. There is no strong evidence that eating veal less than once per year is associated with increased risk of CJD (p = 0.51).

The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).

There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02).

The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).

snip...

It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).

snip...

In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...

snip...

In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (...TSS)

snip...see full report ;

web.archive.org/web/20090506050043/http://www.bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf

UPDATE American Indian Genocide Continues – Scrapie Prion

American Indian Genocide Continues - Scrapie Prion

July 5, 2009 by admin1

Filed under Featured, Genocide, News

Discuss Now!

FOR IMMEDIATE RELEASE:

The planned genocide against the Navajo People of New Mexico, Arizona and Utah continues with the latest poisoning and cover-up by the United States.

Navajos have faced well documented cases of mining Uranium without required protection, exposing them to facing premature abortions, cancer, degenerative diseases and death.

They have lived in the shadow of Rio Puerco, a Uranium waste spill that exceeds 3 Mile Island in the amount of nuclear material leached into the ground, with hundreds of people effected and which has yet to be cleaned up.

They have been poisoned by the United States at Fort Windgate, where Navajo People were exposed to the Hantavirus for the crime of living downwind from the Fort Windgate Munitions Depot. Though rarely mentioned, all cases of Hantavirus in the United States have occurred downwind of U.S. Military Munitions Storage Depots, in Hanford, in Long Island, New York and in Southern California.

And now:

Below is an urgent report we received from New Mexico. Dr Milo Muller has found evidence of mass poisoning of the sheep supply and gross criminal neglegence in the oversight of the USDA, further poisoning the Navajo People.

Not only are we demanding an investigation to this outbreak of Scrapie Prion (Mad Sheep Disease), but all the horrors that the Navajo people have faced in the last 30 years.

“This is continued planned genocide.” Charges Russell Means. “They cannot explain it otherwise.”

Miloslav Muller, DVM, MPVM 634 Eastlake Drive Rio Rancho, New Mexico 87124 505-892-9288

Dear Friend:

My name is Dr. Milo Muller, I am living in Albuquerque, New Mexico, and my profession is a veterinarian epidemiologist. My specialty is a veterinary public health, and part of my training is to investigate outbreaks of diseases transmissible from animals to humans.

Recently, in dealing with two issues of disparate treatment of American Indians in New Mexico, I found an issue that desperately needs the attention of the American public. In this instance, the Federal Government created this issue, failed to take corrective action when violations

of federal laws became known to the upper management in Washington, DC, and then stonewalled a proper investigation of this malfeasance, comparable only to infamous government Tuskegee Experiment on African-American men in 1940’s.

My first concern is that the U.S. Department of Agriculture (USDA) is unlawfully blocking a proper investigation of reckless exposure of American Indians residing on Navaho Reservation in New Mexico to Scrapie Prion (infection agent similar to Mad Cow Disease). My numerous letters and submissions to the U.S. Office of Special Counsel, U.S. Equal Employment Opportunity Commission (EEOC), and to the USDA Inspector General regarding this malfeasance have been ignored, in direct violations of federal government policies and regulations.

Attached to this email in .PDF file are a few examples of my letters to the U.S. Office of Special Counsel (OSC), a small federal agency responsible for investigation of allegations of prohibited personal practices committed by federal employees.

Regretfully, the OSC management, including the head of the Agency Mr. William Reukauf, do not see any wrongdoing when employees of other federal agencies (USDA) committed fiscal fraud for personal benefits for over $100K, or recklessly causing mutton from Scrapie infected sheep to enter human food chain of American Indians in New Mexico, or destruction of federal documents describing this malfeasance (EEOC, Denver and San Francisco District Office).

Disturbing is also fact that my two submissions to Henry Waxman, Chairman, and Tom Davis, Ranking Member, Committee on Oversight and Government Reform, U.S. House of Representatives, remains unanswered (attached are copies of both submissions). It should come as no surprise that my third letter on this subject dated February 14, 2009, addressed to Edolphus Towns, who replaced Henry Waxman, also remains unanswered.

The second issue is illegal destruction of part of USDA, EEO official complaint file pertinent to discrimination complaint registered by Mr. Carlos Jojola, one-race American Indian from Isleta Pueblo, New Mexico. Destruction of official complaint file documents was committed by the USDA Civil Rights Office employees in close cooperation with the EEOC Phoenix District Office management for sole purpose to falsely claim that in this particular EEO case “no discrimination occurred”.

The case was four and half years inactive (in accordance with federal policy it should be resolved in time limit of 180 calendar days), and then suddenly the Agency (USDA) issued its racist, bizarre decision claiming that “no discrimination occurred”, in contrary to factual evidence of the record.

Mr. Carlos Jojola was my coworker employed by the USDA in Albuquerque, New Mexico. I am still serving as his EEO Representative in this discrimination case that is currently at the administrative EEOC level. The cause of action in this EEO complaint is racial discrimination, failure to provide reasonable accommodation for Mr. Jojola’s disabilities, and harassment by employees of the USDA Personal Operation Branch in Minneapolis, MN.

For your information, attached in .PDF file is an Appeal Form that I submitted to the EEOC in February 2009. Neither USDA nor EEOC contacted me in a good faith for early resolution of this case. Both issues are extreme examples how federal government treats American Indians despite its rhetoric about Equal Employment Opportunity and other baseless claims. I have available 100’s of pages of supporting documents fully confirming my allegations.

In my opinion, after quite frustrating experience with multiple governmental entities, I believe that only solution to this situation would be to contact newspapers and to let American public know this malfeasance.

Please contact any trusted journalist who is willing to report on this issue.

Thank you very much for your time.

Sincerely,

Miloslav Muller, DVM, MPVM 634 Eastlake Drive Rio Rancho, New Mexico 87124 505-892-9288

About the Attached:

In attachments please find four examples of Scrapie positive test results from the Colorado State Diagnostic Laboratory that is part of School of Veterinary Medicine. Hard copies are available upon request.

Also attached is an article describing the Innunohistochemistry test (IHC) that was used at the above mentioned laboratory for regular screening of those samples. As you can see, this test is practically 100 percent accurate. Basically, it is based on molecular markers, and if in particular sample is present infectious agent Prion, part of affected sample will turn purple. Basically, 4th grader can make diagnosis of positive or negative samples based on color change. It is very specific, as you can see from an article.

Do not be confused by statement on test results form that “these results have not been confirmed by National Veterinary Service Laboratory”.

These are standard operating procedures for USDA for any tests performed by a contract laboratories in the USA. In this particular case, this served as a political tool to “decide” what test will be classified as positive or negative, depending on their political agenda, in this case for covering fraud.

Since USDA knew that the collection of samples was fraudulent, and that the collector, USDA technician Mr. Braman, collected samples on monthly basis instead on daily basis as he was paid for, about ten days later, on April 27, 2006, USDA stated that all previously positive samples were “negative”. I will send you hard copies of that “decision” in mail. This was of course whitewash for purpose to cover up for illegal activities of multiple USDA officials.

Also, I am sending you one page of scanned slaughter dates for Hunts Meats in Waterflow, New Mexico. This is a plant that slaughtered those infected animals. Please see that the plant was not operating on January 20, 2006, but USDA technician claimed that on that day he collected samples (Test number 420, attached scanned copy) that had one positive sheep. I have multiple documents proving that this was ongoing issue of fraudulently submitted Scrapie samples. Basically, this plant was not inspected as required by USDA regulations, and it is massive multi-level fraud. The owner of the plant contacted USDA in Washington in writing, but they refused to investigate.

This issue should be presented to the press without any unclear areas, so USDA would not have any legitimate defense.

I also contacted Government Accountability Project in Washington DC, who partially worked on this issue three years ago, together with me and with the plant owners. I will hear from them soon if they would be willing to reopen this case. In th epast, they contacted USDA with request for those samples (for purpose to send them to England for confirmation of Scrapie), but USDA refused to communicate with them.

Milo Muller

-Article about IHC Test

-2nd Letter to OSC Bloch Oct 29 2009

-5th Letter to OSC Reukauf 6 2009

-Carlos Jojola EEOC Appeal Form Feb 2009

-Letter to Rep Henry Waxman Oct 2008

-Letter to RepTom Davis Oct 2008

-Scrapie Pos Test 405

-Scrapie Pos Test 409

-Scrapie Pos Test 419

-Scrapie Pos Test 420

-Slaughter Dates for January 2006

Milo Muller’s Supporting Documents

web.archive.org/web/20090710042704/http://www.russellmeansfreedom.com/wp-content/uploads/2009/07/american-indian-genocide-continues-scrapie-prion.zip

web.archive.org/web/20090710042704/http://www.russellmeansfreedom.com/2009/scrapie-prion/

Friday, February 04, 2011

NMLB and USDA allow scrapie prion infected mutton to enter food chain on the Navajo Reservation in New Mexico

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

From: Terry S. Singeltary Sr.

To: President.BenShelly

Cc: sroanhorse ; opvp.nelson ; alaughing; georgehardeen; pressoffice

Sent: Thursday, February 03, 2011 12:15 PM

Subject: NMLB and USDA allow scrapie prion infected mutton to enter food chain on the Navajo Reservation in New Mexico

Greetings Honorable People of the Great Navajo Nation, and the Honorable President Ben Shelly,

I send this to you with great concern. ...

With Kindest Regards and Great Respect,

terry

Terry S. Singeltary Sr. P.O. Box Bacliff, Texas USA 77518 [e-mail]

NMLB and USDA allow scrapie prion infected mutton to enter food chain on the Navajo Reservation in New Mexico

MULLER v. CULBERTSON

MILOSLAV MULLER, Plaintiff-Appellant,v.MYLES CULBERTSON, DIRECTOR NEW MEXICO LIVESTOCK BOARD (AGENCY), Defendant-Appellee.

snip...see full text ;

scrapie-usa.blogspot.com/2011/02/nmlb-and-usda-allow-scrapie-prion.html

Thursday, October 10, 2013

CJD REPORT 1994 increased risk for consumption of veal and venison and lamb

creutzfeldt-jakob-disease.blogspot.com/2013/10/cjd-report-1994-increased-risk-for.html

Monday, November 30, 2009

USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE

nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html

Thursday, December 20, 2012

*** OIE GROUP RECOMMENDS THAT SCRAPE PRION DISEASE BE DELISTED, WISHES TO CONTINUE SPREADING IT AROUND THE GLOBE

transmissiblespongiformencephalopathy.blogspot.com/2012/12/oie-group-recommends-that-scrape-prion.html

Friday, July 01, 2016

*** TEXAS Thirteen new cases of chronic wasting disease (CWD) were confirmed at a Medina County captive white-tailed deer breeding facility on June 29, 2016***

chronic-wasting-disease.blogspot.com/2016/07/texas-thirteen-new-cases-of-chronic.html

*** How Did CWD Get Way Down In Medina County, Texas?

DISCUSSION Observations of natural outbreaks of scrapie indicated that the disease spread from flock to flock by the movement of infected, but apparently normal, sheep which were incubating the disease.

There was no evidence that the disease spread to adjacent flocks in the absent of such movements or that vectors or other host species were involved in the spread of scrapie to sheep or goats; however, these possibilities should be kept open...

web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf

scrapie-usa.blogspot.com/2016/06/scrapie-field-trial-experiments-mission.html

chronic-wasting-disease.blogspot.com/2016/06/how-did-cwd-get-way-down-in-medina.html

NEWS RELEASE

April 22, 2016

Scrapie Confirmed in a Hartley County Sheep

AUSTIN - Texas Animal Health Commission (TAHC) officials have confirmed scrapie in a Hartley County ewe. The ewe was tested by TAHC after the owner reported signs of weight loss and lack of coordination to their local veterinarian. The premises was quarantined and a flock plan for monitoring is being developed by the TAHC and USDA.

"The TAHC is working closely with the flock owner, sharing all of the options for disease eradication," said Dr. David Finch, TAl-lC Region 1 Director. ‘We are thankful the producer was proactive in identifying a problem and seeking veterinary help immediately.”

Texas leads the nation in sheep and goat production. Since 2003, there have been no confirmed cases of scrapie in Texas. The last big spike in Texas scrapie cases was in 2006 when nine infected herds were identified and the last herd was released from restrictions in 2013.

According to USDA regulations, Texas must conduct adequate scrapie surveillance by collecting a minimum of 598 sheep samples annually. Since USDA slaughter surveillance started in FY 2003, the percent of cull sheep found positive for scrapie at slaughter (once adjusted for face color) has decreased 90 percent.

Scrapie is the oldest known transmissible spongiform encephalopathies, and under natural conditions only sheep and goats are known to be affected by scrapie. It is a fatal disease that affects the central nervous system of sheep and goats. It is not completely understood how scrapie is passed from one animal to the next and apparently healthy sheep infected with scrapie can spread the disease. Sheep and goats are typically infected as young lambs or kids, though adult sheep and goats can become infected.

The most effective method of scrapie prevention is to maintain a closed flock. Raising replacement ewes, purchasing genetically resistant rams and ewes, or buying from a certified-free scrapie flock are other options to reduce the risk of scrapie. At this time the resistant genetic markers in goats have not been identified, therefore it is important to maintain your sheep and goat herds separately.

The incubation period for scrapie is typically two to five years. Producers should record individual identification numbers and the seller's premise identification number on purchase and sales records. These records must be maintained for a minimum of five years.

tvmdl.tamu.edu/wp-content/uploads/2016/04/2016-04-22_TAHCScrapie-1.jpg

web.archive.org/web/20160610000545/http://tvmdl.tamu.edu/2016/04/26/tahc-confirms-scrapie-hartley/

TEXAS Sheep and Goats

• Most recent scrapie positive animal in Texas was found in April, 2008.

• USDA-APHIS-VS set the national goal for surveillance at 46,000 traceable, mature sheep or goats. Target for Texas is 1,472.

• The Scrapie Program Review is being scheduled for this summer. No problems expected.

web.archive.org/web/20100725200249/http://www.tahc.state.tx.us/agency/meetings/minutes/Minutes_CommMtg_3-23-2010.pdf

PRION 2016 CONFERENCE TOKYO

IL-13 Transmission of prions to non human-primates: Implications for human populations

Jean-Philippe Deslys, Emmanuel E. Comoy

CEW, Institute of Emerging Diseases and Innovative Therapies (iMETI), Division of Prions and Related Diseases (SEPIA), Fontenay-aux-Roses, France

Prion diseases are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal prion disease might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, prion diseases, like the other proteinopathies, are reputed to occur spontaneously (atypical animal prion strains, sporadic CJD summing 80 % of human prion cases).

Non-human primate models provided the first evidences supporting the transmissibility of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health1, according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the risk of primary (oral) and secondary (transfusional) risk of BSE, and also the zoonotic potential of other animal prion diseases from bovine, ovine and cervid origins even after very long silent incubation periods.

We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period, with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold' . longer incubation than BSE2. Scrapie, as recently evoked in humanized mice3, is the third potentially zoonotic prion disease (with BSE and L-type BSE4), thus questioning the origin of human sporadic cases. We also observed hidden prions transmitted by blood transfusion in primate which escape to the classical diagnostic methods and extend the field of healthy carriers. We will present an updated panorama of our different long-term transmission studies and discuss the implications on risk assessment of animal prion diseases for human health and of the status of healthy carrier5.

1. Chen, C. C. & Wang, Y. H. Estimation of the Exposure of the UK Population to the Bovine Spongiform Encephalopathy Agent through Dietary Intake During the Period 1980 to 1996. PLoS One 9, e94020 (2014).

2. Comoy, E. E. et al. Transmission of scrapie prions to primate after an extended silent incubation period. Sci Rep 5, 11573 (2015).

3. Cassard, H. et al. Evidence for zoonotic potential of ovine scrapie prions. Nat Commun 5, 5821-5830 (2014).

4. Comoy, E. E. et al. Atypical BSE (BASE) transmitted from asymptomatic aging cattle to a primate. PLoS One 3, e3017 (2008).

5. Gill O. N. et al. Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey. BMJ. 347, f5675 (2013).

Curriculum Vitae

Dr. Deslys co-authored more than one hundred publications in international scientific journals on main aspects of applied prion research (diagnostic, decontamination techniques, risk assessment, and therapeutic approaches in different experimental models) and on underlying pathological mechanisms. He studied the genetic of the first cases of iatrogenic CJD in France. His work has led to several patents including the BSE (Bovine Spongiform Encephalopathy) diagnostic test most widely used worldwide. He also wrote a book on mad cow disease which can be downloaded here for free (http://www.neuroprion.org/pdf_docs/documentation/madcow_deslys.pdf). His research group is Associate Laboratory to National Reference Laboratory for CJD in France and has high security level microbiological installations (NeuroPrion research platform) with different experimental models (mouse, hamster, macaque). The primate model of BSE developed by his group with cynomolgus macaques turned out to mimick remarkably well the human situation and allows to assess the primary (oral) and secondary (transfusional) risks linked to animal and human prions even after very long silent incubation periods. For several years, his interest has extended to the connections between PrP and Alzheimer and the prion mechanisms underlying neurodegenerative diseases. He is coordinating the NeuroPrion international association (initially european network of excellence now open to all prion researchers).

- 59-

P-088 Transmission of experimental CH1641-like scrapie to bovine PrP overexpression mice

Kohtaro Miyazawa1, Kentaro Masujin1, Hiroyuki Okada1, Yuichi Matsuura1, Takashi Yokoyama2

1Influenza and Prion Disease Research Center, National Institute of Animal Health, NARO, Japan; 2Department of Planning and General Administration, National Institute of Animal Health, NARO

Introduction: Scrapie is a prion disease in sheep and goats. CH1641-lke scrapie is characterized by a lower molecular mass of the unglycosylated form of abnormal prion protein (PrpSc) compared to that of classical scrapie. It is worthy of attention because of the biochemical similarities of the Prpsc from CH1641-like and BSE affected sheep. We have reported that experimental CH1641-like scrapie is transmissible to bovine PrP overexpression (TgBoPrP) mice (Yokoyama et al. 2010). We report here the further details of this transmission study and compare the biological and biochemical properties to those of classical scrapie affected TgBoPrP mice.

Methods: The details of sheep brain homogenates used in this study are described in our previous report (Yokoyama et al. 2010). TgBoPrP mice were intracerebrally inoculated with a 10% brain homogenate of each scrapie strain. The brains of mice were subjected to histopathological and biochemical analyses.

Results: Prpsc banding pattern of CH1641-like scrapie affected TgBoPrP mice was similar to that of classical scrapie affected mice. Mean survival period of CH1641-like scrapie affected TgBoPrP mice was 170 days at the 3rd passage and it was significantly shorter than that of classical scrapie affected mice (439 days). Lesion profiles and Prpsc distributions in the brains also differed between CH1641-like and classical scrapie affected mice.

Conclusion: We succeeded in stable transmission of CH1641-like scrapie to TgBoPrP mice. Our transmission study demonstrates that CH 1641-like scrapie is likely to be more virulent than classical scrapie in cattle.

WS-02

Scrapie in swine: A diagnostic challenge

Justin J Greenlee1, Robert A Kunkle1, Jodi D Smith1, Heather W. Greenlee2

1National Animal Disease Center, US Dept. of Agriculture, Agricultural Research Service, United States; 2Iowa State University College of Veterinary Medicine

A naturally occurring prion disease has not been recognized in swine, but the agent of bovine spongiform encephalopathy does transmit to swine by experimental routes. Swine are thought to have a robust species barrier when exposed to the naturally occurring prion diseases of other species, but the susceptibility of swine to the agent of sheep scrapie has not been thoroughly tested.

Since swine can be fed rations containing ruminant derived components in the United States and many other countries, we conducted this experiment to test the susceptibility of swine to U.S. scrapie isolates by intracranial and oral inoculation. Scrapie inoculum was a pooled 10% (w/v) homogenate derived from the brains of clinically ill sheep from the 4th passage of a serial passage study of the U.S scrapie agent (No. 13-7) through susceptible sheep that were homozygous ARQ at prion protein residues 136, 154, and 171, respectively. Pigs were inoculated intracranially (n=19) with a single 0.75 ml dose or orally (n=24) with 15 ml repeated on 4 consecutive days. Necropsies were done on a subset of animals at approximately six months post inoculation (PI), at the time the pigs were expected to reach market weight. Remaining pigs were maintained and monitored for clinical signs of TSE until study termination at 80 months PI or when removed due to intercurrent disease (primarily lameness). Brain samples were examined by immunohistochemistry (IHC), western blot (WB), and enzyme-linked immunosorbent assay (ELISA). Brain tissue from a subset of pigs in each inoculation group was used for bioassay in mice expressing porcine PRNP.

At six-months PI, no evidence of scrapie infection was noted by any diagnostic method. However, at 51 months of incubation or greater, 5 animals were positive by one or more methods: IHC (n=4), WB (n=3), or ELISA (n=5). Interestingly, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study).

Swine inoculated with the agent of scrapie by the intracranial and oral routes do not accumulate abnormal prion protein (PrPSc) to a level detectable by IHC or WB by the time they reach typical market age and weight. However, strong support for the fact that swine are potential hosts for the agent of scrapie comes from positive bioassay from both intracranially and orally inoculated pigs and multiple diagnostic methods demonstrating abnormal prion protein in intracranially inoculated pigs with long incubation times.

Curriculum Vitae

Dr. Greenlee is Research Veterinary Medical Officer in the Virus and Prion Research Unit at the National Animal Disease Center, US Department of Agriculture, Agricultural Research Service. He applies his specialty in veterinary anatomic pathology to focused research on the intra- and interspecies transmission of prion diseases in livestock and the development of antemortem diagnostic assays for prion diseases. In addition, knockout and transgenic mouse models are used to complement ongoing experiments in livestock species. Dr. Greenlee has publications in a number of topic areas including prion agent decontamination, effects of PRNP genotype on susceptibility to the agent of sheep scrapie, characterization of US scrapie strains, transmission of chronic wasting disease to cervids and cattle, features of H-BSE associated with the E211 K polymorphism, and the development of retinal assessment for antemortem screening for prion diseases in sheep and cattle. Dr. Greenlee obtained his DVM degree and completed the PhD/residency program in Veterinary Pathology at Iowa State University. He is a Diplomate of the American College of Veterinary Pathologists.

www.tandfonline.com/doi/full/10.1080/19336896.2016.1163048?journalCode=kprn20

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

Title: Comparison of two US sheep scrapie isolates supports identification as separate strains

Authors

item Moore, Sarah - item Smith, Jodi item West Greenlee, Mary - item Nicholson, Eric item Richt, Juergen item Greenlee, Justin

Submitted to: Veterinary Pathology Publication Type: Peer Reviewed Journal Publication Acceptance Date: December 22, 2015 Publication Date: N/A

Interpretive Summary: Scrapie is a fatal disease of sheep and goats that causes damaging changes in the brain. The infectious agent is an abnormal protein called a prion that has misfolded from its normal state. Whether or not a sheep will get scrapie is determined primarily by their genetics. Furthermore, different scrapie strains exist that may result in a different expression of disease such as shorter incubation periods, unusual clinical signs, or unique patterns of lesions within the brain. This study evaluated two U.S. scrapie isolates in groups of sheep with varying susceptibilities to scrapie. Our data indicates that there are differences in incubation periods, sheep genotype susceptibilities, and lesion profiles that support designating these scrapie isolates as unique strains. The identification of a new scrapie strain in the United States means that control measures, methods of decontamination, and the potential for transmission to other species may need to be reevaluated. This information is useful to sheep farmers and breeders that are selectively breeding animals with genotypes resistant to the most prevalent strain of scrapie and could impact future regulations for the control of scrapie in the United States. Technical Abstract: Scrapie is a naturally occurring transmissible spongiform encephalopathy (TSE) of sheep and goats. There are different strains of sheep scrapie that are associated with unique molecular, transmission, and phenotype characteristics, but very little is known about the potential presence of scrapie strains within sheep in the US. Scrapie strain and PRNP genotype could both affect susceptibility, potential for transmission, incubation period, and control measures required for eliminating scrapie from a flock. Here we evaluate two US scrapie isolates, No. 13-7 and x124, after intranasal inoculation to compare clinical signs, incubation periods (IP), spongiform lesions, and patterns of PrPSc deposition in sheep with scrapie-susceptible PRNP genotypes (QQ171). After inoculation with x124, susceptibility and IP were associated with valine at codon 136 (V136) of the prion protein: VV136 had short IPs (6.9 months), AV136 sheep were 11.9 months, and AA136 sheep did not develop scrapie. All No.13-7 inoculated sheep developed scrapie with IP’s of 20.1 months for AA136 sheep, 22.8 months for AV136 sheep, and 26.7 months for VV136 sheep. Patterns of immunoreactivity in the brain were influenced by challenge isolate and host genotype. Differences in PrPSc profiles versus isolate were most striking when examining brains from sheep with the VV136 genotype. In summary, intranasal inoculation with isolates x124 and No. 13-7 resulted in differences in IP, sheep genotype susceptibility, and PrPSc profile that support designation as separate strains.

Last Modified: 6/6/2016

www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=315505

31

Appendix I VISIT TO USA - OR A E WRATHALL — INFO ON BSE AND SCRAPIE

Dr Clark lately of the scrapie Research Unit, Mission Texas has

successfully transmitted ovine and caprine scrapie to cattle. The

experimental results have not been published but there are plans to do

this. This work was initiated in 1978. A summary of it is:-

Expt A 6 Her x Jer calves born in 1978 were inoculated as follows with

a 2nd Suffolk scrapie passage:-

i/c 1ml; i/m, 5ml; s/c 5ml; oral 30ml.

1/6 went down after 48 months with a scrapie/BSE-like disease.

Expt B 6 Her or Jer or HxJ calves were inoculated with angora Goat

virus 2/6 went down similarly after 36 months.

Expt C Mice inoculated from brains of calves/cattle in expts A & B were resistant, only 1/20 going down with scrapie and this was the reason given for not publishing.

Diagnosis in A, B, C was by histopath. No reports on SAF were given.

Dr Warren Foote indicated success so far in eliminating scrapie in offspring from experimentally— (and naturally) infected sheep by ET. He had found difficulty in obtaining embryos from naturally infected sheep (cf SPA).

Prof. A Robertson gave a brief accout of BSE. The us approach was to

32

accord it a very low profile indeed. Dr A Thiermann showed the picture in the "Independent" with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs.

BSE was not reported in USA.

4. Scrapie incidents (ie affected flocks) have shown a dramatic increase since 1978. In 1953 when the National Control scheme was started there were 10-14 incidents, in 1978 - 1 and in 1988 so far 60.

5. Scrapie agent was reported to have been isolated from a solitary fetus.

6. A western blotting diagnostic technique (? on PrP) shows some promise.

7. Results of a questionnaire sent to 33 states on the subject of the national sheep scrapie programme survey indicated

17/33 wished to drop it

6/33 wished to develop it

8/33 had few sheep and were neutral

Information obtained from Dr Wrathall‘s notes of a meeting of the u.s.

Animal Health Association at Little Rock, Arkansas Nov. 1988.

33

In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells

3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ...

web.archive.org/web/20090506002237/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf

also see hand written notes ;

web.archive.org/web/20090505234344/http://www.bseinquiry.gov.uk/files/yb/1988/10/00001001.pdf

Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle

Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.

snip...

The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...

web.archive.org/web/20030516051623/http://bseinquiry.gov.uk/files/mb/m09/tab05.pdf

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. ........

web.archive.org/web/20010614054402/http://www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf

RISK OF BSE TO SHEEP VIA FEED

web.archive.org/web/20090506010340/http://www.bseinquiry.gov.uk/files/sc/seac31/tab01.pdf

OPII-1

Disease incidence and incubation period of BSE and CH1641 in sheep is associated with PrP gene polymorphisms.

Goldman WI, Hunter N., Benson G., Foster J. and Hope J. AFRC&MRC Neuropathogenesis Unit, Institute for Animal Health, West Mains Rd. Edinburgh EH9 3JF. U.K.

The relative survival periods of mice with different Sine genotype have long been used for scrapie strain typing. The PrP protein. a key molecule in the pathogenesis of scrapie and related diseases, is a product of the Sine locus and homologous proteins are also linked to disease-incidence loci in sheep and man. In sheep alleles of this locus (Sip) encode several PrP protein variants, of which one has been associated with short incubation periods of Cheviot sheep infected with SSBP/1 scrapie. Other isolates, i.e. BSE or CH1641. cause a different pattern of incubation periods and a lower disease incidence in the same flock of Cheviot sheep. Using transmission to sheep of known PrP genotype as our criterion for agent strain typing. we have found a link between BSE and CH1641. a C-group strain of scrapie. Disease susceptibility of sheep to these isolates is associated with different PrP genotypes compared to SSBP/1 scrapie.

OPII –2

Transmission of Bovine Spongiform Encephalopathy in sheep, goats and mice.

Foster J., Hope J., McConnell I. and Fraser H. Institute for Animal Health, AFRC and MRC Neuropathogenesis Unit, Kings Buildings, West Mains Road, Edinburgh EH9 3JF

Bovine Spongiform Encephalopathy (BSE) has been transmitted in two lines of genetically selected sheep [differing in their susceptibilities to the SSBP/1 source of scrapie), and to goats by intracerebral injection and by oral dosing. Incubation periods in sheep for both routes of challenge ranged from 440-994 days. In goats this range was 506-1508 days. Both routes of infection in sheep and goats were almost equally efficient. In mice, primary transmission of BSE identified a sinc-independant genetic control of incubation period. Also, intermediate passage of BSE in sheep or goats did not alter these primary transmission properties. Hamsters were susceptible to BSE only after intervening passage through mice.

web.archive.org/web/20060517075714/http://www.bseinquiry.gov.uk/files/mb/m09/tab11.pdf

Wednesday, January 18, 2012

BSE IN GOATS CAN BE MISTAKEN FOR SCRAPIE

February 1, 2012

transmissiblespongiformencephalopathy.blogspot.com/2012/01/bse-in-goats-can-be-mistaken-for.html

Wednesday, January 18, 2012

Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural Scrapie Isolates Similar to CH1641 Experimental Scrapie

Journal of Neuropathology & Experimental Neurology:

February 2012 - Volume 71 - Issue 2 - p 140–147

transmissiblespongiformencephalopathy.blogspot.com/2012/01/selection-of-distinct-strain-phenotypes.html

Wednesday, May 25, 2016

USDA APHIS National Scrapie TSE Prion Eradication Program April 2016 Monthly Report Prion 2016 Tokyo Update

scrapie-usa.blogspot.com/2016/05/usda-aphis-national-scrapie-tse-prion.html

Monday, July 18, 2016

Texas Parks Wildlife Dept TPWD HIDING TSE (CWD) in Deer Herds, Farmers Sampling Own Herds, Rapid Testing, False Negatives, a Recipe for Disaster

chronic-wasting-disease.blogspot.com/2016/07/texas-parks-wildlife-dept-tpwd-hiding.html

Scrapie-like disorder in a Nyala (Tragelaphus angasi)

IN CONFIDENCE

web.archive.org/web/20090506014205/http://www.bseinquiry.gov.uk/files/yb/1986/11/00001001.pdf

web.archive.org/web/20090505225907/http://www.bseinquiry.gov.uk/files/yb/1986/06/23001001.pdf

web.archive.org/web/20090505225848/http://www.bseinquiry.gov.uk/files/yb/1986/07/08001001.pdf

Spongiform encephalopathy has so far only been recorded in the sheep and goat, man, mink, and several deer including the mule deer, black tailed deer and the elk (most, if not all, of the deer incidents occurred in wild life parts in Wyoming and Colorado). Clinical cases in deer all occurred from 3 1/2 to 5 years old and usually 60-80% losses occurred over a 4 year period...

web.archive.org/web/20090506014223/http://www.bseinquiry.gov.uk/files/yb/1986/07/24001001.pdf

The clinical and neuropathological findings in F22 are consistent with the spongiform encephalopathies of animals and man. The agents causing spongiform encephalopathy in various species cannot be unequivocally distinguished and some isolates of human agent cause neurologic disease in goats indistinguishable from scrapie. The spongiform encephalopathies are invariably fatal once clinical signs of disease are evident and as very high fatality rates (79% of 67 animals) are recorded in Mule deer it is important that an awareness of the disease is maintained at Marwell.

web.archive.org/web/20090506014255/http://www.bseinquiry.gov.uk/files/yb/1986/07/21001001.pdf

STRICTLY IN CONFIDENCE

EXTRACT FROM MINUTES OF SCIENTIFIC COMMITTEE MEETING HELD ON 29 SEPTEMBER 1994

BSE: S33/94

a) Sampling of Ruminant Feeding stuffs for Ruminant Protein:

The voluntary sampling‘ on farms with suspected cases of BSE had commenced on 1 July 1994. The ELISA technique detected the presence of ruminant meat and bone meal to a level of 0.25% in finished feeding stuffs. MAFF had released a pre-publication copy of a paper discussing this technique which had been developed at the VI Centre Luddington. It provided detail of the use of the technique in meat and bone meal. It did not, however, discuss the extension of the assay for use in compound feeding stuffs. At the request of UKASTA, MAFF was looking at making the service commercially available in order for individual compounders to do their own testing. MAFF estimated that the charge for such testing would be £35 per sample (plus VAT).

It was reported that Luddington was carrying out further work in identifying potential sources of interference, from individual raw materials, which might produce a false positive result It was understood that glutens were considered to present a particular problem. During a discussion the Committee suggested that the conditioning temperatures, in different mills, might have varying effects on the breakdown of proteins in animal feeding stuffs.

A number of sites where cross contamination between animal proteins and other types of raw materials might occur were identified. These included not only on-farm but in-store, in the country of origin, in boats, in transport as well as different points within the feed mill. It was noted, however, that it might be counter productive to stress these varying numbers and sites.

Concern was expressed that the MAFF had commenced on-farm testing without necessarily thinking through the consequences for the whole of the agricultural industry. Officials were aware that one course of action open to feed compounders was to stop using meat and bone meal in the manufacture of any feeding stuff. An alternative for the industry was the establishment of ruminant feed only Such a step would only be open to those companies with more than one manufacturing site.

Cont'd/...2

94/9.29/3.1

b)

-2-

A decision by the industry as a whole to stop using meat and bone meal would have cost implications for the whole livestock industry. Not only would there be poorer returns to beef producers but also higher raw material costs for compounders when producing pig and poultry feeding stuffs. There would also be the problem of disposing of the unwanted animal by-products. Thus, it was agreed that whatever the actual consequences the effect o:n the livestock industry as a whole would be very damaging.

Proposed Survey of Past a.nd Present Practices in Members Feed Mills:

A copy of the draft questionnaire was circulated to Committee members “Strictly in Confidence". This was designed to investigate the likelihood that feed produced after the introduction of the ruminant feed ban could have become contaminated with ruminant derived protein and whether the likelihood of contamination had changed over time. In discussing the contents, UKASTA had not given any indication, on behalf of members, that they wanted them to complete the questionnaire when finalised. MAFF had also been made fully aware of UKASTA's concern that information submitted in response to the questionnaire by individual companies might, at some future time, be subpoenaed by a Court. This would be in any case taken against the company by a farmer seeking compensation for BSE in his herd.

The Committee was advised that a member company was still in debate over a case concerning the Fowl Pest outbreak in 1984. Lawyers acting for poultry producers had. submitted subpoenas for relevant Ministry documents. MAFF Legal Department was looking at the papers and aimed to resist the subpoena. However, the outcome of this action would not be known until March 1995. At the very least, it was considered that compounders should not: complete the questionnaire until the outcome of the Fowl Pest discussions were known. It was also reported that another company had been recommended, by its legal advisors, not to complete the questionnaire.

At a scientific level, it was noted that the aim of the CVL was to explain why BABs had occurred. Unfortunately, in the investigations it was necessary to identify the name and address of individual mills on the questionnaire in order to reconcile information on BABs regarding feeding practices on farm. It would not be possible for questionnaires to be sent to the CVL via UKASTA on an anonymous basis. UKASTA was seeking guidance from the Association's solicitors on what powers MAFF might have to require completion of the questionnaire.

It was suggested that whilst the CVL was finalising details of the questionnaire UKASTA should co-operate. Thus members were asked to send to the Secretariat their comments on the contents of the questionnaire by mid-November. Views were particularly required on which questions were difficult and/ or impossible to answer both because they were

Cont'd/...3 94/9.29/3.2

-3-

impractical as well as being able to put individual companies in a vulnerable position. These were to be passed on to the CVL with a request for amendments and/ or detailed responses in time for the Committee to discuss at the December meeting. Members were asked to discuss the questionnaire with as few people as possible because of the sensitive nature of this subject.

Members were also asked to keep the Secretariat informed of the nature of any enquiries which MAFF officials might address to them. It was also noted, by one member company who no longer used meat and bone meal, that since taking such action they had not received any queries from MAFF.

C) Recent Legislation:

The MAFF was implementing the two EU Decisions agreed in May. The ban on the use of mammalian meat and bone meal in ruminant feedingstuffs was to be incorporated into the BSE Order. At the same time the SBO ban was to be extended to cover the thymus and intestines of calves less than six months of age.

The European legislation on the rendering industry introduced a processing time/ temperature combination based on the results of rendering trials which had achieved an 80-fold diminution of the BSE agent. The legislation was not due to be brought into operation until the end of 1994. It was, however, hoped that UK rendering plants could have their processes validated and thus be in compliance with the new legislation by the end of October. Although it was not possible to prove zero infectivity, MAFF considered that adherence to the new standards would be a huge step forward in the control of BSE.

The Ministry was also reviewing the SBO legislation in order to make it more straightforward an.d simple to operate. The Committee also noted that, because of the nature of the material concerned, it would be extremely difficult to enforce the legislation. Concern was expressed, therefore, that the Ministry might just be introducing controls on paper. Effective auditing of the legislation should be introduced; for example by weighing the amount of SBO's collected and comparing this against the number of animals slaughtered.

In the light of all these concerns, the Committee considered that an easy reaction would be for the feed industry to stop using meat and bone meal in the manufacture of any animal feeding stuff. However, whereas this would be relatively painless, if somewhat expensive, for the feed industry, it would have serious repercussions throughout the whole of the livestock industry. It would also beg the question as to why it was safe for humans to eat meat whilst the by-products of the butchery trade that we use to produce meat and bone meal were unsatisfactory for animals.

Cont'd/...4

94/9.29/3.3

-4-

d) Origins of BSE:

A transcript of the Radio 4 interview with Mr. Keith Meldrum, Chief Veterinary Officer, held on 22 September was circulated. This raised the possibility of BSE being of bovine as opposed to ovine origin. Clarification had, therefore, been sought from the CVL. The response was that it was not possible to dismiss the possibility that BSE was bovine in origin. However, it was more difficult to support such a theory given current knowledge whereby the BSE epidemic had seen a sudden increase in numbers in the mid 1980's. It was thus still considered that the epidemic was explained by :-

- High level of sheep numbers in the UK;

- A change in the rendering practices in the late 1970's which permitted infected ovine material to survive the production process;

- The recycling of bovine material in the cattle population.

For BSE to be solely of bovine origin there would have had to have been a high prevalence of infected animals prior to the mid—1980‘s and this was not seen. It was thus possible that there was an element of politics in the comments made by Mr. Meldrum and it was probably no coincidence that a report of possible BSE cases in northern Germany had emerged at about the same time.

Meeting with Minister:

The Committee was advised that if necessary the Association would request

a meeting with the Minister to outline members‘ concerns regarding BSE and associated matters.

94/9.29/3.4

web.archive.org/web/20090506020855/http://www.bseinquiry.gov.uk/files/yb/1994/09/29003001.pdf

1988: Letter entitled ‘Scrapie, Time to take HB Parry Seriously’ (YB88/6.8/4.1)

24. In this letter I stated that BSE had been officially confirmed as a TSE (when much of the veterinary profession still favoured a variety of alternate hypotheses). I also suggested that scrapie should be made a notifiable disease, and drew attention to the work of HB 'James' Parry and the possibility that natural scrapie in sheep might be of genetic origin.

25. I withdrew the letter following advice from Professor Barlow (who as far as I can recall had been contacted by MAFF and the Veterinary Record) that it might not be in my interests to pursue publication at that moment in time.

26. I received a letter from the then editor, Edward Boden, questioning my permission to release the information that BSE was indeed a proven TSE. I had no permission, though was unaware that any was needed, to inform my profession of this urgent and important fact.

snip...

Surveillance for emerging scrapie-like diseases in animals in the UK

36. Working with Gerald Wells and other pathologists from the State Veterinary Service, I was involved with surveillance for neurological disease of animals in the UK. This was with particular reference to surveillance for, and subsequent confirmation of TSEs. During my time of employment, novel TSEs arose in domestic cats and in exotic ungulates in zoological collections. I also became involved in the investigation of a putative TSE in hound packs detected by Robert Higgins.

FSE, and BSE in exotic ungulates published in reviews:

1991 (Wells and McGill) ref 5

7

1992 (Wells and McGill) ref 7

FSE discussed in para 15.

37. Putative TSE in hounds - work started 1990 –(see para 41)

Robert Higgins, a Veterinary Investigation Officer at Thirsk, had been working on a hound survey in 1990. Gerald Wells and I myself received histological sections from this survey along with the accompanying letter (YB90/11.28/1.1) dated November 1990. This letter details spongiform changes found in brains from hunt hounds failing to keep up with the rest of the pack, along with the results of SAF extractions from fresh brain material from these same animals. SAFs were not found in brains unless spongiform changes were also present. The spongiform changes were not pathognomonic (ie. conclusive proof) for prion disease, as they were atypical, being largely present in white matter rather than grey matter in the brain and spinal cord. However, Tony Scott, then head of electron microscopy work on TSEs, had no doubt that these SAFs were genuine and that these hounds therefore must have had a scrapie-like disease. I reviewed all the sections myself (original notes appended) and although the pathology was not typical, I could not exclude the possibility that this was a scrapie-like disorder, as white matter vacuolation is seen in TSEs and Wallerian degeneration was also present in the white matter of the hounds, another feature of scrapie.

38. I reviewed the literature on hound neuropathology, and discovered that micrographs and descriptive neuropathology from papers on ‘hound ataxia’ mirrored those in material from Robert Higgins’ hound survey. Dr Tony Palmer (Cambridge) had done much of this work, and I obtained original sections from hound ataxia cases from him. This enabled me provisionally to conclude that Robert Higgins had in all probability detected hound ataxia, but also that hound ataxia itself was possibly a TSE. Gerald Wells confirmed in ‘blind’ examination of single restricted microscopic fields that there was no distinction between the white matter vacuolation present in BSE and scrapie cases, and that occurring in hound ataxia and the hound survey cases.

39. Hound ataxia had reportedly been occurring since the 1930’s, and a known risk factor for its development was the feeding to hounds of downer cows, and particularly bovine offal. Circumstantial evidence suggests that bovine offal may also be causal in FSE, and TME in mink. Despite the inconclusive nature of the neuropathology, it was clearly evident that this putative canine spongiform encephalopathy merited further investigation.

40. The inconclusive results in hounds were never confirmed, nor was the link with hound ataxia pursued. I telephoned Robert Higgins six years after he first sent the slides to CVL. I was informed that despite his submitting a yearly report to the CVO including the suggestion that the hound work be continued, no further work had been done since 1991. This was surprising, to say the very least.

41. The hound work could have provided valuable evidence that a scrapie-like agent may have been present in cattle offal long before the BSE epidemic was recognised. The MAFF hound survey remains unpublished.

Histopathological support to various other published MAFF experiments

web.archive.org/web/20071027050415/http://www.bseinquiry.gov.uk/files/ws/s067.pdf

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.

web.archive.org/web/20030714133556/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.

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

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

Thursday, August 20, 2015 Doctor William J. Hadlow

William J. Hadlow Dr. Hadlow (Ohio State ’48), 94, Hamilton, Montana, died June 20, 2015.

scrapie-usa.blogspot.com/2015/08/doctor-william-j-hadlow.html

Spongiform Encephalopathy in Captive Wild ZOO BSE INQUIRY

web.archive.org/web/20090506001201/http://www.bseinquiry.gov.uk/files/mb/m09a/tab03.pdf

Tuesday, April 19, 2016

Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards Singeltary Comment Submission

www.regulations.gov/comment/FDA-2013-N-0764-0008

web.archive.org/web/20150609094908/http://www.plosone.org/annotation/listThread.action?root=85351

web.archive.org/web/20160415043607/http://journals.plos.org/plosone/article/comment?id=info:doi/10.1371/annotation/09676b86-bbc2-4c69-9032-c319f13a7ad0

Tuesday, April 19, 2016

Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards Singeltary Comment Submission

www.regulations.gov/comment/FDA-2003-D-0432-0011

Sunday, July 17, 2016

*** CHRONIC WASTING DISEASE CWD TSE PRION GLOBAL REPORT UPDATE JULY 17 2016

chronic-wasting-disease.blogspot.com/2016/07/chronic-wasting-disease-cwd-tse-prion.html

Saturday, May 28, 2016

*** Infection and detection of PrPCWD in soil from CWD infected farm in Korea Prion 2016 Tokyo ***

chronic-wasting-disease.blogspot.com/2016/05/infection-and-detection-of-prpcwd-in.html

Saturday, July 16, 2016

Importation of Sheep, Goats, and Certain Other Ruminants [Docket No. APHIS-2009-0095]RIN 0579-AD10

WITH great disgust and concern, I report to you that the OIE, USDA, APHIS, are working to further legalize the trading of Transmissible Spongiform Encephalopathy TSE Pion disease around the globe.

THIS is absolutely insane. it’s USDA INC.

scrapie-usa.blogspot.com/2016/07/importation-of-sheep-goats-and-certain.html

Friday, January 30, 2015

*** Scrapie: a particularly persistent pathogen ***

transmissiblespongiformencephalopathy.blogspot.com/2015/01/scrapie-particularly-persistent-pathogen.html

Saturday, July 23, 2016

*** BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016

bovineprp.blogspot.com/2016/07/bovine-spongiform-encephalopathy-bse.html

Tuesday, July 26, 2016

*** Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016

bse-atypical.blogspot.com/2016/07/atypical-bovine-spongiform.html

Sunday, July 17, 2016

*** CHRONIC WASTING DISEASE CWD TSE PRION GLOBAL REPORT UPDATE JULY 17 2016

chronic-wasting-disease.blogspot.com/2016/07/chronic-wasting-disease-cwd-tse-prion.html

Monday, June 20, 2016

*** Specified Risk Materials SRMs BSE TSE Prion Program

specifiedriskmaterial.blogspot.com/2016/06/specified-risk-materials-srms-bse-tse.html

Saturday, May 28, 2016

*** Infection and detection of PrPCWD in soil from CWD infected farm in Korea Prion 2016 Tokyo ***

chronic-wasting-disease.blogspot.com/2016/05/infection-and-detection-of-prpcwd-in.html

RE: re-Human Prion Diseases in the United States

Singeltary PLoS

part 2 flounder replied to flounder on 02 Jan 2010 at 21:26 GMT

No competing interests declared.

see full text ;

www.plosone.org/annotation/listThread.action?root=363

spontaneous TSE Prion disease

Transmission of scrapie prions to primate after an extended silent incubation period

***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***

www.nature.com/articles/srep11573

Monday, May 02, 2016

*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***

chronic-wasting-disease.blogspot.com/2016/05/zoonotic-potential-of-cwd-prions-update.html

*** NIH awards $11 million to UTHealth researchers to study deadly CWD prion diseases Claudio Soto, Ph.D. ***

Public Release: 29-Jun-2016

transmissiblespongiformencephalopathy.blogspot.com/2016/06/nih-awards-11-million-to-uthealth.html

I urge everyone to watch this video closely...terry

*** you can see video here and interview with Jeff's Mom, and scientist telling you to test everything and potential risk factors for humans ***

histodb15.usz.ch/pages/Images/videos/video-004/video-004.html

Tuesday, July 12, 2016

Chronic Wasting Disease CWD, Scrapie, Bovine Spongiform Encephalopathy BSE, TSE, Prion Zoonosis Science History

see history of NIH may destroy human brain collection

transmissiblespongiformencephalopathy.blogspot.com/2016/07/chronic-wasting-disease-cwd-scrapie.html

FLASHBACK 2001

Suspect symptoms

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

28 Mar 01 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 mice as sCJD.

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb...

2001

Suspect symptoms

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

28 Mar 01

Like lambs to the slaughter

31 March 2001

by Debora MacKenzie Magazine issue 2284.

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 mice as sCJD.

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.

Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.

Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.

As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.

"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.

But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.

People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.

But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."

There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.

Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.

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

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.

Terry S. Singeltary, Sr Bacliff, Tex

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.

jama.jamanetwork.com/article.aspx?articleid=1031186

26 March 2003

Terry S. Singeltary, retired (medically) CJD WATCH

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?

web.archive.org/web/20140601123343/http://www.neurology.org/content/60/2/176/reply

Freas Monday, January 08,2001 3:03 PM

FDA Singeltary submission 2001

Greetings again Dr. Freas and Committee Members,

I wish to submit the following information to the Scientific Advisors and Consultants Staff 2001 Advisory Committee (short version). I understand the reason of having to shorten my submission, but only hope that you add it to a copy of the long version, for members to take and read at their pleasure, (if cost is problem, bill me, address below). So when they realize some time in the near future of the 'real' risks i speak of from human/animal TSEs and blood/surgical products. I cannot explain the 'real' risk of this in 5 or 10 minutes at some meeting, or on 2 or 3 pages, but will attempt here:

snip...see full text ;

web.archive.org/web/20030830045651/http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf

2 January 2000

British Medical Journal

U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well

www.bmj.com/rapid-response/2011/10/28/us-scientist-should-be-concerned-cjd-epidemic-us-well

15 November 1999

British Medical Journal

vCJD in the USA * BSE in U.S.

www.bmj.com/rapid-response/2011/10/28/re-vcjd-usa-bse-us

From: TSS (216-119-138-163.ipset18.wt.net)

Subject: Louping-ill vaccine documents from November 23rd, 1946

Date: September 10, 2000 at 8:57 am PST

Subject: Louping-ill vaccine documents from November 23rd, 1946

Date: Sat, 9 Sep 2000 17:44:57 –0700

From: "Terry S. Singeltary Sr."

Reply-To: Bovine Spongiform Encephalopathy To: [e-mail]

######### Bovine Spongiform Encephalopathy #########

THE VETERINARY RECORD 516 No 47. Vol. 58 November 23rd, 1946

NATIONAL VETERINARY MEDICAL ASSOCIATION OF GREAT BRITAIN AND IRELAND

ANNUAL CONGRESS, 1946

The annual Congress, 1946, was held at the Royal Veterinary College, Royal College Street, London, N.W.I. from September 22nd to September 27th.

Opening Meeting

[skip to scrapie vaccine issue...tss]

Papers Presented to Congress

The papers presented to this year's Congress had as their general theme the progressive work of the profession during the war years. Their appeal was clearly demonstrated by the large and remarkably uniform attendance in the Grand Hall of the Royal Veterinary College throughout the series; between 200 and 250 members were present and they showed a keen interest in every paper, which was reflected in the expression of some disappointment that the time available for discussion did not permit of the participation of more than a small proportion of would-be contributors.

In this issue we publish (below) the first to be read and discussed, that by Dr. W. S. Gordon, M.R.C.V.S., F.R.S.E., "Advances in Veterinary Research." Next week's issue will contain the paper on "Some Recent Advances in Veterinary Medicine and Surgery in Large-Animal Practice" by Mr. T. Norman Gold, M.R.C.V.S. In succeeding numbers of the Record will be reproduced, also with reports of discussions, that by Mr. W. L. Weipers, M.R.C.V.S., D.V.S.M., on the same subject as relating to small-animal practice, and the papers by Mr. J. N. Ritchie, B.SC., M.R.C.V.S., D.V.S.M., and Mr. H.W. Steele-Bodger, M.R.C.V.S., on "War-time Achievements of the British Home Veterinary Services."

The first scientific paper of Congress was read by Dr. W. S. Gordon, M.R.C.V.S., F.R.S.E. on Monday, September 23rd, 1946, when Professor J. Basil Buxton, M.A., F.R.C.V.S, D.V.H., Prinicipal of the Royal Veterinary College, presided.

Advances in Veterinary Research

by

W.S. GORDON, PH.D., M.R.C.V.S., F.R.S.E.

Agriculteral Research Council, Field Station, Compton, Berks.

Louping-ill, Tick-borne Fever and Scrapie

In 1930 Pool, Browniee & Wilson recorded that louping-ill was a transmissible disease. Greig et al, (1931) showed that the infective agent was a filter-passing virus with neurotropic characters and Browniee & Wilson (1932) that the essential pathology was that of an encephalomyelitis. Gordon, Browniee, Wilson & MacLeod (1932) and MacLeod & Gordon (1932) confirmed and extended this work. It was shown that on louping-ill farms the virus was present in the blood of many sheep which did not show clinical symptoms indicating involvement of the central nervous system and that for the perpetuation and spread of the disease these subclinical cases were probably of greater importance that the frank clinical cases because, in Nature, the disease was spread by the tick, lxodes ricinus L. More recently Wilson (1945, 1946) has described the cultivation of the virus in a chick embryo medium, the pathogenic properties of this culture virus and the preparation of louping-ill antiserum.

Between 1931 and 1934 I carried out experiments which resulted in the development of an effective vaccine for the prevention of louping-ill.* This vaccine has been in general use since 1935 and in his annual report to the Animal Diseases Research Association this year, Dr. Greig stated that about 227,000 doses of vaccine had been issued from Moredun alone.

Dr. Gordon illustrated this portion of his paper by means of graphs and diagrams projected by the epidiascope.

This investigation, however, did not begin and end with the study of louping-ill; it had, by good fortune, a more romantic turn and less fortunately a final dramtic twist which led almost to catastrope. After it had been established that a solid immunity to louping-ill could be induced in sheep, a group of immunized and a group of susceptible animals were placed together on the tick-infected pasture of a louping-ill farm. Each day all the animals were gathered and their temperatures were recorded. It was anticipated that febrile reactions with some fatalities would develop in the controls while the louping-ill immunes would remain normal. Contrary to expectation, however, every sheep, both immune and control, developed a febrile reaction. This unexpected result made neccessary further investigation which showed that the febrile reaction in the louping-ill immunes was due to a hitherto undescribed infective agent, a Rickettsia-like organism which could be observed in the cytoplasm of the grannular leucocytes, especially the neutrophil polymorphs (MacLeod (1932), Gordon, Browniee, Wilson & MacLeod. MacLeod & Gordon (1933). MacLeod (1936). MacLeod collected ticks over many widely separated parts of Scotland and all were found to harbour the infective agent of tick-borne fever, and it is probable that all sheep on tick-infested farms develop this disease, at least on the first occasion that they become infested with ticks. When the infection is passed in series through susceptible adult sheep it causes a sever, febrile reaction, dullness and loss of bodily condition but it rarely, if ever, proves fatal. It is clear, however, that it aggravates the harmful effects of a louping-ill infection and it is a serious additional complication to such infections as pyaemia and the anacrobic infections which beset lambs on the hill farms of Northern Britain.

Studying the epidemiology of louping-ill on hill farms it became obvious that the pyaemic condition of lambs described by M'Fadyean (1894) was very prevalent on tick infested farms Pyaemia is a crippling condition of lambs associated with tick-bite and is often confused with louping-ill. It is caused by infection with Staphylococcus aureus and affected animals may show abscess formation on the skin, in the joints, viscera, meninges and elsewhere in the body. It was thought that tick-borne fever might have ben a predisposing factor in this disease and unsuccessful attempts were made by Taylor, Holman & Gordon (1941) to reproduce the condition by infecting lambs subcutaneously with the staphylococcus and concurrently produceing infections with tickborne fever and louping-ill in the same lambs. Work on pyaemia was then continued by McDiarmid (1946a, 1946b, 1946c), who succeeded in reproducing a pyaemic disease in mice, guinea-pigs and lambs similar to the naturally occuring condition by intravenous inoculation of Staphylococcus aureus. He also found a bacteraemic form of the disease in which no gross pyaemic lesions were observed. The prevention or treatment of this condition presents a formidable problem. It is unlikely that staphylococcal ???oid will provide an effective immunity and even if penicillin proved to be a successful treatment, the difficulty of applying it in adequate and sustained dosage to young lambs on hill farms would be almost insurmountable.

>From 1931 to 1934 field trials to test the immunizing value and harmlessness of the loup-ill vaccine were carried out on a gradually increasing scale. Many thousands of sheep were vaccinated and similar numbers, living under identical conditions were left as controls. The end result showed that an average mortability of about 9 percent in the controls was reduced to less than 1 percent in the vaccinated animals. While the efficiency of the vaccine was obvious after the second year of work, previous bitter experience had shown the wisdom of withholding a biological product from widespread use until it had been successfully produced in bulk, as opposed to small-scale experimental production and until it had been thoroughly tested for immunizing efficiency and freedom from harmful effects. It was thought that after four years testing this stage had been reached in 1935, and in the spring of that year the vaccine was issued for general use. It comprised a 10 percent saline suspension of brain, spinal cord and spleen tissues taken from sheep five days after infection with louping-ill virus by intracerebral inoculation. To this suspension 0-35 percent of formalin was added to inactivate the virus and its safety for use as a vaccine was checked by intracerbral inoculation of mice and sheep and by the inoculation of culture medium. Its protective power was proved by vaccination sheep and later subjecting them, along with controls, to a test dose of living virus.

Vaccine for issue had to be free from detectable, living virus and capable of protecting sheep against a test dose of virus applied subcutaneously. The 1935 vaccine conformed to these standards and was issued for inoculation in March as three separate batches labelled 1, 2, and 3. The tissues of 140 sheep were employed to make batch 1 of which 22,270 doses were used; 114 to make batch 2 of which 18,000 doses were used and 44 to make batch 3 of which 4,360 doses were used. All the sheep tissues incorporated in the vaccine were obtained from yearling sheep. During 1935 and 1936 the vaccine proved highly efficient in the prevention of loup-ill and no user observed an ill-effect in the inoculated animals. In September, 1937, two and a half years after vaccinating the sheep, two owners complained that scrapie, a disease which had not before been observed in the Blackface breed, was appearing in their stock of Blackface sheep and further that it was confined to animals vaccinated with louping-ill vaccine in 1935. At that stage it was difficult to conceive that the occurrence could be associated with the injection of the vaccine but in view of the implications, I visited most of the farms on which sheep had been vaccinated in 1935. It was at this point that the investigation reached its dramatic phase; I shall not forget the profound effect on my emotions when I visited these farms and was warmly welcomed because of the great benefits resulting from the application of louping-ill vaccine, wheras the chief purpose of my visit was to determine if scrapie was appearing in the inoculated sheep. The enquiry made the position clear. Scrapie was developing in the sheep vaccinated in 1935 and it was only in a few instances that the owner was associating the occurrence with louping-ill vaccination. The disease was affecting all breeds and it was confined to the animals vaccinated with batch 2. This was clearly demonstrated on a number of farms on which batch 1 had been used to inoculate the hoggs in 1935 and batch 2 to inoculate the ewes. None of the hoggs, which at this time were three- year-old ewes. At this time it was difficult to forecast whether all of the 18,000 sheep which had received batch 2 vaccine would develop scrapie. It was fortunate, however, that the majority of the sheep vaccinated with batch 2 were ewes and therfore all that were four years old and upwards at the time of vaccination had already been disposed of and there only remained the ewes which had been two to three years old at the time of vaccination, consequently no accurate assessment of the incidence of scrapie could be made. On a few farms, however, where vaccination was confined to hoggs, the incidence ranged from 1 percent, to 35 percent, with an average of about 5 percent. Since batch 2 vaccine had been incriminated as a probable source of scrapie infection, an attempt was made to trace the origin of the 112 sheep whose tissues had been included in the vaccine. It was found that they had been supplied by three owners and that all were of the Blackface or Greyface breed with the exception of eight which were Cheviot lambs born in 1935 from ewes which had been in contact with scrapie infection. Some of these contact ewes developed scrapie in 1936-37 and three surviving fellow lambs to the eight included in the batch 2 vaccine of 1935 developed scrapie, one in September, 1936, one in February, 1937, and one in November, 1937. There was, therefore, strong presumptive evidence that the eight Cheviot lambs included in the vaccine althought apparently healthy were, in fact, in the incubative stage of a scrapie infection and that in their tissues there was an infective agent which had contaminated the batch 2 vaccine, rendering it liable to set up scrapie. If that assumption was correct then the evidence indicated that:-

(1) the infective agent of scrapie was present in the brain, spinal cord and or spleen of infected sheep:

(2) it could withstand a concentration of formalin of 0-35 percent, which inactivated the virus of louping-ill:

(3) it could be transmitted by subcutaneous inoculation;

(4) it had an incubative period of two years and longer.

Two Frenchmen, Cuille & Chelle (1939) as the result of experiments commenced in 1932, reported the successful infection of sheep by inoculation of emulsions of spinal cord or brain material by the intracerebral, epidural, intraocular and subcutaneous routes The incubation period varied according to the route employed, being one year intracerebrally, 15 months intraocularly and 20 months subcutaneously. They failed to infect rabbits but succeeded in infecting goats. Another important part of their work showed that the infective agent could pass throught a chamberland 1.3 filter, thus demonstrating that the infective agent was a filtrable virus. It was a curious coincidence that while they were doing their transmission experiments their work was being confirmed by the unforeseeable infectivity of a formalinized tissue vaccine.

As a result of this experience a large-scale transmision experiment involving the ue of 788 sheep was commenced in 1938 on a farm specially taken for the purpose by the Animal Diseases Research Association with funds provided by the Agricultural Research Council. The experiment was designed to determine the nature of the infective agent and the pathogenesis of the disease. It is only possible here to give a summary of the result which showed that (1) saline suspensions of brain and spinal cord tissue of sheep affected with scrapie were infective to normal sheep when inoculatted intracerebrally or subcutaneously; (2) the incubation period after intracerebral inoculation was seven months and upwards and only 60 percent of the inoculated sheep developed scrapie during a period of four and a half years; (3) the incubation period after subcutaneous inoculation was 15 months and upwards and only about 30 percent of the inoculated sheep developed the disease during the four and a half years: (4) the infective agent was of small size and probably a filtrable virus.

The prolonged incubative period of the disease and the remarkable resistance of the causal agent to formalin are features of distinct interest. It still remains to determine if a biological test can be devised to detect infected animals so that they can be killed for food before they develop clinical symptoms and to explore the possibilities of producing an immunity to the disease.

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

Greetings List Members,

pretty disturbing document. now, what would stop this from happening with the vaccineCJD in children???

kind regards,

Terry S. Singeltary Sr., Bacliff, Texas USA

Sunday, May 18, 2008

MAD COW DISEASE BSE CJD CHILDREN VACCINES

bseinquiry.blogspot.com/2008/05/mad-cow-disease-bse-cjd-children.html

bseinquiry.blogspot.com/

www.mad-cow.org/00/jul00_dont_eat_sheep.html#hhh

www.mad-cow.org/00/aug00_late_news.html#ggg

www.mad-cow.org/~tom/dec99_news.html#bbb

Thursday, April 28, 2016

Persistent residual contamination in endoscope channels; a fluorescence epimicroscopy study

creutzfeldt-jakob-disease.blogspot.com/2016/04/persistent-residual-contamination-in.html

Saturday, January 16, 2016

Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Products Guidance for Industry

creutzfeldt-jakob-disease.blogspot.com/2016/01/revised-preventive-measures-to-reduce.html

creutzfeldt-jakob-disease.blogspot.com/2016/01/of-grave-concern-heidenhain-variant.html

Saturday, December 12, 2015

CREUTZFELDT JAKOB DISEASE CJD TSE PRION REPORT DECEMBER 14, 2015

creutzfeldt-jakob-disease.blogspot.com/2015/12/creutzfeldt-jakob-disease-cjd-tse-prion.html

2023

Bovine Spongiform Encephalopathy BSE TSE Prion Origin USA?, what if?

Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research

Title: Sheep are susceptible to the agent of TME by intracranial inoculation and have evidence of infectivity in lymphoid tissues

Author item CASSMANN, ERIC - Oak Ridge Institute For Science And Education (ORISE) item MOORE, SARA - Oak Ridge Institute For Science And Education (ORISE) item SMITH, JODI - Iowa State University item Greenlee, Justin

Submitted to: Frontiers in Veterinary Science Publication Type: Peer Reviewed Journal Publication Acceptance Date: 11/14/2019 Publication Date: 11/29/2019 Citation: Cassmann, E.D., Moore, S.J., Smith, J.D., Greenlee, J.J. 2019.

Sheep are susceptible to the agent of TME by intracranial inoculation and have evidence of infectivity in lymphoid tissues.

Frontiers in Veterinary Science. 6:430. doi.org/10.3389/fvets.2019.00430
DOI: doi.org/10.3389/fvets.2019.00430

Interpretive Summary: Prion diseases are protein misfolding diseases that are transmissible between animals. The outcome of prion infection is irreversible brain damage and death. Transmission can occur between animals of the same or different species, however, transmission between different species is usually less efficient due to the species barrier, which results from differences in the amino acid sequence of the prion protein between the donor and recipient species. The present work evaluated whether transmissible mink encephalopathy (TME) can infect sheep. Our results demonstrate that sheep are susceptible to the TME agent and that the TME agent has similar properties to the agent of L-type atypical bovine spongiform encephalopathy (L-BSE). This work supports the ideas that L-BSE is a possible source for TME in mink and that the practice of feeding cattle with neurologic disease to mink should be avoided. This information is important to farmers who raise cattle, sheep, or mink.

Technical Abstract: Transmissible mink encephalopathy (TME) is a food borne prion disease. Epidemiological and experimental evidence suggests similarities between the agent of TME and L-BSE. This experiment demonstrates the susceptibility of four different genotypes of sheep to the agent of TME by intracranial inoculation. The four genotypes of sheep used in this experiment had polymorphisms corresponding to codons 136 and 171 of the prion gene: VV136QQ171, AV136QQ171, AA136QQ171, and AA136QR171. All intracranially inoculated sheep without comorbidities (15/15) developed clinical scrapie and had detectable PrPSc by immunohistochemistry, western blot, and enzyme immunoassay (EIA). The mean incubation periods in TME infected sheep correlated with their relative genotypic susceptibility. There was peripheral distribution of PrPSc in the trigeminal ganglion and neuromuscular spindles; however, unlike classical scrapie and C-BSE in sheep, ovine TME did not accumulate in the lymphoid tissue. To rule out the presence of infectious, but proteinase K susceptible PrPSc, the lymph nodes of two sheep genotypes, VV136QQ171 and AA136QQ171, were bioassayed in transgenic ovinized mice. None of the mice (0/32) inoculated by the intraperitoneal route had detectable PrPSc by EIA. Interestingly, mice intracranially inoculated with RPLN tissue from a VV136QQ171 sheep were EIA positive (3/17) indicating that sheep inoculated with TME harbor infectivity in their lymph nodes. Western blot analysis demonstrated similarities in the migration patterns between ovine TME and the bovine TME inoculum. Overall, these results demonstrate that sheep are susceptible to the agent of TME, and that the tissue distribution of PrPSc in TME infected sheep is distinct from classical scrapie.

www.ars.usda.gov/research/publications/publication/?seqNo115=363305

www.ars.usda.gov/research/publications/publication/?seqNo115=360665

www.ars.usda.gov/research/publications/publication/?seqNo115=373668

Previous work has shown that the Stetsonville, WI outbreak of TME could have been precipitated by feeding mink a downer cow with atypical BSE; therefore, it very well may have originated from a cow with L-BSE. The agent of TME appears to remain stable, and it has a high transmission efficiency after a sequence of interspecies transmission events. Although C-BSE is the archetypal foodborne TSE, our findings indicate that L-BSE and bTME have greater transmission efficiencies in bovinized mice. Previous work has demonstrated that L-BSE also is more virulent than C-BSE in mice expressing the human prion protein [46, 55]. Although the documented incidence of L-BSE is low, the propensity of L-BSE and the TME agent to cross species barriers support the continued monitoring for atypical BSE.

bmcvetres.biomedcentral.com/articles/10.1186/s12917-020-02611-0

***>This work supports the ideas that L-BSE is a possible source for TME in mink and that the practice of feeding cattle with neurologic disease to mink should be avoided. This information is important to farmers who raise cattle, sheep, or mink.<***

1985

Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.

snip...

The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...

web.archive.org/web/20090506002258/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf

web.archive.org/web/20090506001031/http://www.bseinquiry.gov.uk/files/mb/m09a/tab01.pdf

web.archive.org/web/20090506024922/http://www.bseinquiry.gov.uk/files/yb/1987/06/10004001.pdf

FRIDAY, MAY 19, 2023

USDA Announces Atypical L-Type Bovine Spongiform Encephalopathy BSE Detection

bovineprp.blogspot.com/2023/05/usda-announces-atypical-l-type-bovine.html

prpsc.proboards.com/thread/122/announces-atypical-bovine-spongiform-encephalopathy

SATURDAY, MAY 20, 2023

Tennessee State Veterinarian Alerts Cattle Owners to Disease Detection Mad Cow atypical L-Type BSE

bse-atypical.blogspot.com/2023/05/tennessee-state-veterinarian-alerts.html

prpsc.proboards.com/thread/123/tennessee-veterinarian-alerts-cattle-confirmed

Monday, May 22, 2023

BSE TSE Prion MAD COW TESTING IN THE USA COMPARED TO OTHER COUNTRIES?

specifiedriskmaterial.blogspot.com/2023/05/bse-tse-prion-mad-cow-testing-in-usa.html

FRIDAY, JULY 07, 2023

TME, 589.2000 (21 C.F.R. 589.2000), atypical L-BSE, who’s testing MINK for TSE?

bse-atypical.blogspot.com/2023/07/tme-5892000-21-cfr-5892000-atypical-l.html

Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health.

2. Determined that pigs naturally exposed to chronic wasting disease (CWD) may act as a reservoir of CWD infectivity. Chronic wasting disease is a naturally occurring, fatal, neurodegenerative disease of cervids. The potential for swine to serve as a host for the agent of CWD disease is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation. Pigs were assigned to 1 of 3 groups: intracranially inoculated; orally inoculated; or non-inoculated. At market weight age, half of the pigs in each group were tested ('market weight' groups). The remaining pigs ('aged' groups) were allowed to incubate for up to 73 months post inoculation (MPI). Tissues collected at necropsy were examined for disease-associated prion protein (PrPSc) by multiple diagnostic methods. Brain samples from selected pigs were bioassayed in mice expressing porcine prion protein. Some pigs from each inoculated group were positive by one or more tests. Bioassay was positive in 4 out of 5 pigs assayed. Although only small amounts of PrPSc were detected using sensitive methods, this study demonstrates that pigs can serve as hosts for CWD. Detection of infectivity in orally inoculated pigs using mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity. Currently, swine rations in the U.S. could contain animal derived components including materials from deer or elk. In addition, feral swine could be exposed to infected carcasses in areas where CWD is present in wildlife populations. The current feed ban in the U.S. is based exclusively on keeping tissues from TSE infected cattle from entering animal feeds. These results indicating the susceptibility of pigs to CWD, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health.

www.ars.usda.gov/research/publications/publication/?seqNo115=353091

www.ars.usda.gov/research/project/?accnNo=432011&fy=2017

www.ars.usda.gov/research/publications/publication/?seqNo115=337105

www.ars.usda.gov/research/publications/publication/?seqNo115=326166

CONFIDENTIAL

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

LINE TO TAKE

3. If questions on pharmaceuticals are raised at the Press conference, the suggested line to take is as follows:-

"There are no medicinal products licensed for use on the market which make use of UK-derived porcine tissues with which any hypothetical “high risk" ‘might be associated. The results of the recent experimental work at the CSM will be carefully examined by the CSM‘s Working Group on spongiform encephalopathy at its next meeting.

DO Hagger RM 1533 MT Ext 3201

web.archive.org/web/20030822054419/www.bseinquiry.gov.uk/files/yb/1990/09/21009001.pdf

While this clearly is a cause for concern we should not jump to the conclusion that this means that pigs will necessarily be infected by bone and meat meal fed by the oral route as is the case with cattle. ...

web.archive.org/web/20031026000118/www.bseinquiry.gov.uk/files/yb/1990/08/23004001.pdf

we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.

web.archive.org/web/20030822031154/www.bseinquiry.gov.uk/files/yb/1990/09/10007001.pdf

May I, at the outset, reiterate that we should avoid dissemination of papers relating to this experimental finding to prevent premature release of the information. ...

web.archive.org/web/20030822052332/www.bseinquiry.gov.uk/files/yb/1990/09/11005001.pdf

3. It is particularly important that this information is not passed outside the Department, until Ministers have decided how they wish it to be handled. ...

web.archive.org/web/20030822052438/www.bseinquiry.gov.uk/files/yb/1990/09/12002001.pdf

But it would be easier for us if pharmaceuticals/devices are not directly mentioned at all. ...

web.archive.org/web/20030518170213/www.bseinquiry.gov.uk/files/yb/1990/09/13004001.pdf

Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....

web.archive.org/web/20030822054419/www.bseinquiry.gov.uk/files/yb/1990/09/21009001.pdf

Title: Transmission of scrapie prions to primate after an extended silent incubation period)

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.

www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160

***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.

***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***

Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.

www.nature.com/articles/srep11573

www.ars.usda.gov/research/publications/publication/?seqNo115=361032

Tuesday, May 30, 2023

World Organisation for Animal Health 90th General Session of the World Assembly of Delegates BSE TSE Prion 2023

woahoie.blogspot.com/2023/05/world-organisation-for-animal-health.html


Terry S. Singeltary Sr.