Passage of scrapie to deer results in a new phenotype upon return passage to sheep
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
Title: Passage of scrapie to deer results in a new phenotype upon return passage to sheep
Author item Greenlee, Justin item Kokemuller, Robyn item Moore, Sarah item West Greenlee, N Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 3/15/2017 Publication Date: N/A Citation: N/A
Interpretive Summary:
Technical Abstract:
Aims: We previously demonstrated that scrapie has a 100% attack rate in white-tailed deer after either intracranial or oral inoculation.
Samples from deer that developed scrapie had two different western blot patterns: samples derived from cerebrum had a banding pattern similar to the scrapie inoculum, but samples from brainstem had a banding pattern similar to CWD.
In contrast, transmission of CWD from white-tailed deer to sheep by the intracranial route has a low attack rate and to-date oronasal exposure has been unsuccessful. The purpose of this study was to determine if sheep are susceptible to oronasal exposure of the scrapie agent derived from white-tailed deer.
Methods: At approximately 5 months of age, Suffolk sheep of various PRNP genotypes were challenged by the oronasal route with 10% brain homogenate derived from either the cerebrum or the brainstem of scrapie-affected deer. Genotypes represented in each inoculation group were VV136RR154QQ171 (n=2), AA136RR154QQ171 (n=2), and AV136RR154QR171 (n=1). After inoculation, sheep were observed daily for clinical signs. Upon development of clinical signs, sheep were killed with an overdose of pentobarbital sodium and necropsied. Tissue samples were tested for the presence of PrPSc by EIA, western blot, and immunohistochemistry (IHC). The No. 13-7 scrapie inoculum used for the deer has a mean incubation period of 20.1 months in sheep with the AA136RR154QQ171 genotype and 26.7 months in sheep with the VV136RR154QQ171 genotype.
Results: Sheep inoculated oronasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum from the cerebrum that had a scrapie-like profile. The first sheep to develop clinical signs at approximately 29 months post inoculation had the VV136RR154QQ171 genotype. Eventually sheep of the AA136RR154QQ171 genotype developed clinical signs, but at a mean incubation of 52 months. At 62 months post-inoculation, none of the sheep inoculated with material from the deer brainstem have developed clinical disease.
Conclusions: The No. 13-7 inoculum used in the original deer experiment readily infects white-tailed deer and sheep of various genotypes by the oronasal route. When inoculum is made from different brain regions of No 13-7 scrapie-infected deer from either cerebrum with a scrapie-like western blot pattern or brainstem with a CWD-like western blot pattern, sheep with the VV136RR154QQ171 genotype are the first to develop clinical signs. This is in contrast to the original No. 13-7 inoculum that has a faster incubation period in sheep with the AA136RR154QQ171 genotype. Similar to experiments conducted with CWD, sheep oronasally inoculated with brainstem material from deer with a CWD-like molecular profile have no evidence of disease after 62 months of incubation.
While scrapie is not known to occur in free-ranging populations of white-tailed deer, experimental cases are difficult to differentiate from CWD.
This work raises the potential concern that scrapie infected deer could serve as a confounding factor to scrapie eradication programs as scrapie from deer seems to be transmissible to sheep by the oronasal route.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=337278
-----Original Message-----
From: Terry Singeltary
To: bse-l
Cc: cjdvoice; bloodcjd
Sent: Wed, Jun 13, 2018 5:01 pm
Subject: National Scrapie Eradication Program April 2018 Monthly Report Fiscal Year 2018
National Scrapie Eradication Program April 2018 Monthly Report Fiscal Year 2018
U.S. Department of Agriculture Animal and Plant Health Inspection Service Veterinary Services
Surveillance, Response and Preparedness Services Sheep and Goat Health Program May 15, 2018
Program Summary
Performance Measures - At the end of FY 2017 and continuing into FY 2018, the percent of cull black face sheep found positive at slaughter was 0 percent (Chart 1) and the percent of cull sheep found positive at slaughter and adjusted for face color* was 0 percent (Chart 2).
Positive Animals – In April, APHIS identified scrapie in a 171 RR sheep from a flock in NC. There was insufficient positive tissue available to rule out non-classical scrapie. As a result, APHIS is conducting additional testing of the flock before determining whether to classify the case as classical scrapie. One Nor98-like case was reported in October 2017. Other than one goat in a herd quarantined since 2005 and depopulated in 2017, no goats have tested positive for scrapie since February 2015. The retrospective 6-month rolling average of the percent positive, black-faced sheep sampled at RSSS collection sites has been 0 since June 2016.
*White, black and mottled-faced color sheep are weighted based on population; white-faced sheep have the greatest weight. If a white-faced positive sheep is found, this statistic will markedly increase. See notes below for details.
**Samples collected between October 1, 2017 and April 30, 2018 and confirmed by May 15, 2018.
Program Summary
Infected and Source Flocks - No classical scrapie infected or source flocks have been designated since June 2016 (Chart 3). Two flocks, one in Colorado and one in Texas, have open statuses, but there are no exposed animals on the premises of these flocks. Cleaning and disinfection of these premises has to be completed before the infect or source status can be closed.
Scrapie in Goats - Only one positive goat (FY 2015) has been found through RSSS since the start of RSSS in 2003. Since 2002, the total number of positive field cases in goats is 41. Figure 1 shows the number of positive cases by State and by fiscal year of last reported case.
Program Summary
Scrapie Flock Certification Program (SFCP) – As of April 30, 2018, there were 276 flocks participating in the Scrapie Flock Certification Program (SFCP). Statuses of these flocks were 59 export monitored, 45 export certified, and 172 select monitored flocks (Figure 2). SFCP open statuses by fiscal year of Status date* from FY 2007 to FY 2018 are depicted in Chart 4.
* Previous charts of SFCP participation by year were manually updated and used the enrollment date to determine the year of participation in SFCP. With the change to Tableau charts, the start/status date is used. Many participating flocks were grandfathered into the Export category in 2013 with an earlier status date.
Surveillance
Surveillance activities are State-based and are administered as districts by APHIS (Figure
3). For this reason, reporting of surveillance activities is also by District. Surveillance minimums are based on estimated sheep and goat populations in each State. The distribution of sheep and goat populations by District is depicted in Chart 5. Components of Scrapie Surveillance
• Regulatory Scrapie Slaughter Surveillance (RSSS) started April 1, 2003. It is a targeted slaughter surveillance program which is designed to identify infected flocks. Samples have been collected from 583,678 animals since April 1, 2003. There have been 484 NVSL confirmed positive animals (471 classical cases, 12 Nor98-like cases, and 1 pending designation) since the beginning of RSSS. As of April 30, 2018, 23,370 samples have been collected in FY2018, 18,530 from sheep and 4,840 from goats. A positive was confirmed in April and is pending designation as classical or non-classical scrapie. The number of sheep and goats collected in each District is shown in Chart 6. Figure 4 is a hex map, representing the number of animals collected in each State. Chart 7 compares RSSS sampling by month for the current year with the monthly average of the previous 4 years.
Surveillance
Components of Scrapie Surveillance (continued)
• On-farm Surveillance includes both regulatory testing of scrapie exposed and potentially exposed sheep and goats and testing sheep and goats on farm for routine surveillance. As of April 30, 2018, 684 sheep and 307 goats have been tested on-farm for FY 2018.
Surveillance Minimums
The annual target is to test at least 40,000 animals each year for scrapie. As of April 30, 2018, 24,498 animals have been sampled for scrapie testing in FY 2018:
• 23,370 RSSS samples and 1,128 on-farm samples
• Of which 19,316 were sheep and 5,182 were goats.
Progress towards meeting the national surveillance target is depicted in Chart 8. Distribution of sampling by type (RSSS or on-farm) and by species is shown in Chart 9. Chart 10 and Table 1 is a breakdown by face-color (sheep) and type (goats) by age.
snip...SEE FULL TEXT;
https://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_report.pdf
WHAT'S up with the scrapie(?) TSE Prion outbreak, in goats in Michigan and California???
SUNDAY, JUNE 3, 2018
Clinical, pathological, and molecular features of classical and L-type atypical-BSE in goats
http://bovineprp.blogspot.com/2018/06/clinical-pathological-and-molecular.html
FRIDAY, APRIL 22, 2016
Texas Scrapie Confirmed in a Hartley County Sheep where CWD was detected in a Mule Deer April 22, 2016
http://scrapie-usa.blogspot.com/2016/04/texas-scrapie-confirmed-in-hartley.html
Thursday, June 09, 2016
Scrapie Field Trial Experiments Mission, Texas, The Moore Air Force Base Scrapie TSE Prion Experiment 1964 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...
http://web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf
http://scrapie-usa.blogspot.com/2016/06/scrapie-field-trial-experiments-mission.html
http://chronic-wasting-disease.blogspot.com/2016/06/how-did-cwd-get-way-down-in-medina.html
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.
==============
https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf
***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.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
PRION 2016 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 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.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly 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
https://web.archive.org/web/20170126051158/http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf
IN CONFIDENCE
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.
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
-2-
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.
-3-
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.
-4- 78/3.9/1.4
(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
https://web.archive.org/web/20090505233518/http://www.bseinquiry.gov.uk/files/yb/1978/03/09001001.pdf
IN CONFIDENCE
https://web.archive.org/web/20090506012627/http://www.bseinquiry.gov.uk/files/yb/1978/06/01001001.pdf
https://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...
https://web.archive.org/web/20090506012512/http://www.bseinquiry.gov.uk/files/yb/1978/06/27002001.pdf
see board meeting on questions raised on whether risk factors, occupation, for those that worked with scrapie, had a higher risk of developing creutzfeldt jakob disease...see;
https://web.archive.org/web/20170126051837/http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/06/27003001.pdf
https://web.archive.org/web/20090506012538/http://www.bseinquiry.gov.uk/files/yb/1978/06/27003001.pdf
https://web.archive.org/web/20090506012525/http://www.bseinquiry.gov.uk/files/yb/1978/06/27004001.pdf
https://web.archive.org/web/20090506012532/http://www.bseinquiry.gov.uk/files/yb/1978/10/06001001.pdf
IN CONFIDENCE
https://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
https://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
http://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
http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.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).
http://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).
http://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
https://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
https://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
http://scrapie-usa.blogspot.com/2011/02/in-confidence-scrapie-transmission-to.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.
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160
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.
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160
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.
http://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.
http://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.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
OR
*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.
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.
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
http://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 ;
https://web.archive.org/web/20090506050043/http://www.bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf
Thursday, October 10, 2013
CJD REPORT 1994 increased risk for consumption of veal and venison and lamb
http://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
http://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
http://transmissiblespongiformencephalopathy.blogspot.com/2012/12/oie-group-recommends-that-scrape-prion.html
P.97: Scrapie transmits to white-tailed deer by the oral route and has a molecular profile similar to chronic wasting disease and distinct from the scrapie inoculum
Justin Greenlee1, S JO Moore1, Jodi Smith1, M Heather WestGreenlee2 and Robert Kunkle1
1National Animal Disease Center; Ames, IA USA
2Iowa State University; Ames, IA USA
The purpose of this work was to determine susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to that of the original inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (IN); n = 5) with a US scrapie isolate. All scrapie-inoculated deer had evidence of PrPSc accumulation. PrPSc was detected in lymphoid tissues at preclinical time points, and deer necropsied after 28 months post-inoculation had clinical signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural and lymphoid tissues. Western blotting (WB) revealed PrPSc with 2 distinct molecular profiles. WB on cerebral cortex had a profile similar to the original scrapie inoculum, whereas WB of brainstem, cerebellum, or lymph nodes revealed PrPSc with a higher profile resembling CWD. Homogenates with the 2 distinct profiles from WTD with clinical scrapie were further passaged to mice expressing cervid prion protein and intranasally to sheep and WTD. In cervidized mice, the 2 inocula have distinct incubation times. Sheep inoculated intranasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum that had a scrapie-like profile. The WTD study is ongoing, but deer in both inoculation groups are positive for PrPSc by rectal mucosal biopsy.
***In summary, this work demonstrates that WTD are susceptible to the agent of scrapie, 2 distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile readily passes to deer.
https://www.tandfonline.com/doi/full/10.1080/19336896.2015.1033248
*** After a natural route of exposure, 100% of WTD were susceptible to scrapie.
PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA
http://www.landesbioscience.com/journals/prion/03-Prion6-2-Transmission-and-strains.pdf
White-tailed deer are susceptible to the agent of sheep scrapie by intracerebral inoculation
snip...
It is unlikely that CWD will be eradicated from free-ranging cervids, and the disease is likely to continue to spread geographically [10]. However, the potential that white-tailed deer may be susceptible to sheep scrapie by a natural route presents an additional confounding factor to halting the spread of CWD. This leads to the additional speculations that
1) infected deer could serve as a reservoir to infect sheep with scrapie offering challenges to scrapie eradication efforts and
2) CWD spread need not remain geographically confined to current endemic areas, but could occur anywhere that sheep with scrapie and susceptible cervids cohabitate.
This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by intracerebral inoculation with a high attack rate and that the disease that results has similarities to CWD. These experiments will be repeated with a more natural route of inoculation to determine the likelihood of the potential transmission of sheep scrapie to white-tailed deer. If scrapie were to occur in white-tailed deer, results of this study indicate that it would be detected as a TSE, but may be difficult to differentiate from CWD without in-depth biochemical analysis.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199251/?tool=pubmed
http://chronic-wasting-disease.blogspot.com/2011/10/white-tailed-deer-are-susceptible-to.html
2012
PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer
Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA
snip...
The results of this study suggest that there are many similarities in the manifestation of CWD and scrapie in WTD after IC inoculation including early and widespread presence of PrPSc in lymphoid tissues, clinical signs of depression and weight loss progressing to wasting, and an incubation time of 21-23 months. Moreover, western blots (WB) done on brain material from the obex region have a molecular profile similar to CWD and distinct from tissues of the cerebrum or the scrapie inoculum. However, results of microscopic and IHC examination indicate that there are differences between the lesions expected in CWD and those that occur in deer with scrapie: amyloid plaques were not noted in any sections of brain examined from these deer and the pattern of immunoreactivity by IHC was diffuse rather than plaque-like.
*** After a natural route of exposure, 100% of WTD were susceptible to scrapie.
Deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 months PI. Tissues from these deer were positive for PrPSc by IHC and WB. Similar to IC inoculated deer, samples from these deer exhibited two different molecular profiles: samples from obex resembled CWD whereas those from cerebrum were similar to the original scrapie inoculum. On further examination by WB using a panel of antibodies, the tissues from deer with scrapie exhibit properties differing from tissues either from sheep with scrapie or WTD with CWD. Samples from WTD with CWD or sheep with scrapie are strongly immunoreactive when probed with mAb P4, however, samples from WTD with scrapie are only weakly immunoreactive. In contrast, when probed with mAb’s 6H4 or SAF 84, samples from sheep with scrapie and WTD with CWD are weakly immunoreactive and samples from WTD with scrapie are strongly positive. This work demonstrates that WTD are highly susceptible to sheep scrapie, but on first passage, scrapie in WTD is differentiable from CWD.
http://www.landesbioscience.com/journals/prion/03-Prion6-2-Transmission-and-strains.pdf
2011
*** After a natural route of exposure, 100% of white-tailed deer were susceptible to scrapie.
http://www.usaha.org/Portals/6/Reports/2011/report-cwal-2011.pdf
FRIDAY, APRIL 20, 2018
*** Scrapie Transmits To Pigs By Oral Route, what about the terribly flawed USA tse prion feed ban?
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies
http://scrapie-usa.blogspot.com/2018/04/scrapie-transmits-to-pigs-by-oral-route.html
***> CWD TO PIGS <***
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Location: Virus and Prion Research
Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease
Author item Moore, Sarah item Kunkle, Robert item Kondru, Naveen item Manne, Sireesha item Smith, Jodi item Kanthasamy, Anumantha item West Greenlee, M item Greenlee, Justin
Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 3/15/2017 Publication Date: N/A Citation: N/A Interpretive Summary:
Technical Abstract: Aims: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study, neurological signs consistent with prion disease were observed only in one pig: an intracranially challenged pig that was euthanized at 64 months post-challenge. The purpose of this study was to use an antigen-capture immunoassay (EIA) and real-time quaking-induced conversion (QuIC) to determine whether PrPSc is present in lymphoid tissues from pigs challenged with the CWD agent.
Methods: At two months of age, crossbred pigs were challenged by the intracranial route (n=20), oral route (n=19), or were left unchallenged (n=9). At approximately 6 months of age, the time at which commercial pigs reach market weight, half of the pigs in each group were culled (<6 challenge="" groups="" month="" pigs="" remaining="" the="">6 month challenge groups) were allowed to incubate for up to 73 months post challenge (mpc). The retropharyngeal lymph node (RPLN) was screened for the presence of PrPSc by EIA and immunohistochemistry (IHC). The RPLN, palatine tonsil, and mesenteric lymph node (MLN) from 6-7 pigs per challenge group were also tested using EIA and QuIC.
Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 5="" 6="" at="" by="" detected="" eia.="" examined="" group="" in="" intracranial="" least="" lymphoid="" month="" months="" of="" one="" pigs="" positive="" prpsc="" quic="" the="" tissues="" was="">6 months group, 5/6 pigs in the oral <6 4="" and="" group="" months="" oral="">6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%). Conclusions:
This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge.
CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease.
Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=337105
CONFIDENTIAL
EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY
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. ...
http://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.
http://web.archive.org/web/20030822031154/www.bseinquiry.gov.uk/files/yb/1990/09/10007001.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.....
http://web.archive.org/web/20030822054419/www.bseinquiry.gov.uk/files/yb/1990/09/21009001.pdf
snip...see much more here ;
WEDNESDAY, APRIL 05, 2017
Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease
http://chronic-wasting-disease.blogspot.com/2017/04/disease-associated-prion-protein.html
WEDNESDAY, APRIL 05, 2017
*** Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease ***
http://chronic-wasting-disease.blogspot.com/2017/04/disease-associated-prion-protein.html
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.
http://prion2016.org/
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
http://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. ...
http://web.archive.org/web/20060307063531/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
also see hand written notes ;
https://web.archive.org/web/20071019203707/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...
https://web.archive.org/web/20090506002258/http://www.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. ........
http://web.archive.org/web/20010305222246/www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf
RISK OF BSE TO SHEEP VIA FEED
https://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.
https://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
http://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
http://transmissiblespongiformencephalopathy.blogspot.com/2012/01/selection-of-distinct-strain-phenotypes.html
Scrapie-like disorder in a Nyala (Tragelaphus angasi)
IN CONFIDENCE
https://web.archive.org/web/20090506014205/http://www.bseinquiry.gov.uk/files/yb/1986/11/00001001.pdf
https://web.archive.org/web/20090505225907/http://www.bseinquiry.gov.uk/files/yb/1986/06/23001001.pdf
https://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...
https://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.
https://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
STRICTLY IN CONFIDENCE
https://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
https://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.
https://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.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3915057&dopt=Abstract
http://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.
http://scrapie-usa.blogspot.com/2015/08/doctor-william-j-hadlow.html
Spongiform Encephalopathy in Captive Wild ZOO BSE INQUIRY
https://web.archive.org/web/20090506001201/http://www.bseinquiry.gov.uk/files/mb/m09a/tab03.pdf
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.***
http://www.nature.com/articles/srep11573
FEED TSE PRION
2017 Section 21 C.F.R. 589.2000, Animal Proteins Prohibited in Ruminant Feed
Subject: MICHIGAN FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE BREACH APRIL 4, 2017
MICHIGAN FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE BREACH APRIL 4, 2017
FDA BSE/Ruminant Feed Inspections Firms Inventory
11998 DET-DO MI 48846-847 OPR 4/4/2017 OAI
http://www.accessdata.fda.gov/scripts/BSEInspect/bseinspections.csv
NAI = NO ACTION INDICATED
OAI = OFFICIAL ACTION INDICATED
VAI = VOLUNTARY ACTION INDICATED
RTS = REFERRED TO STATE
OAI (Official Action Indicated) when inspectors find significant objectionable conditions or practices and believe that regulatory sanctions are warranted to address the establishment’s lack of compliance with the regulation. An example of an OAI classification would be findings of manufacturing procedures insufficient to ensure that ruminant feed is not contaminated with prohibited material. Inspectors will promptly re-inspect facilities classified OAI after regulatory sanctions have been applied to determine whether the corrective actions are adequate to address the objectionable conditions...end...TSS
V. Use in animal feed of material from deer and elk NOT considered at high risk for CWD
FDA continues to consider materials from deer and elk NOT considered at high risk for CWD to be acceptable for use in NON-RUMINANT animal feeds in accordance with current agency regulations, 21 CFR 589.2000.
Deer and elk not considered at high risk include:
(1) deer and elk from areas not declared by State officials to be endemic for CWD and/or to be CWD eradication zones; and
(2) deer and elk that were not at some time during the 60-month period immediately before the time of slaughter in a captive herd that contained a CWD-positive animal.
https://www.fda.gov/downloads/animalveterinary/guidancecomplianceenforcement/guidanceforindustry/ucm052506.pdf
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012
snip...
In the USA, under the Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law.
Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and
2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES. It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.
snip...
36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011).
The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE).
Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison.
snip...
The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008).
snip...
In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion.
snip...
In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible. For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates.
snip...
Therefore, it is considered that farmed and park deer may have a higher probability of exposure to CWD transferred to the environment than wild deer given the restricted habitat range and higher frequency of contact with tourists and returning GB residents.
snip...
http://webarchive.nationalarchives.gov.uk/20130908115835/http://www.defra.gov.uk/animal-diseases/files/qra_chronic-wasting-disease-121029.pdf
TUESDAY, APRIL 18, 2017
*** EXTREME USA FDA PART 589 TSE PRION FEED LOOP HOLE STILL EXIST, AND PRICE OF POKER GOES UP ***
http://usdameatexport.blogspot.com/2017/04/extreme-usa-fda-part-589-tse-prion-feed.html
TUESDAY, JANUARY 17, 2017
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION
http://bovineprp.blogspot.com/2017/01/fda-part-589-substances-prohibited-from.html
THIS April, 4, 2017 violation of the mad cow 21 CFR 589.2000 OAI is very serious for the great state of Michigan, some 20 years post FDA mad cow feed of August 1997. if would most likely take a FOIA request and a decade of wrangling to find out more.
TUESDAY, JANUARY 17, 2017
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION
I would kindly like to comment on this FDA BSE/Ruminant Feed Inspections Firms Inventory (excel format)4 format, for reporting these breaches of BSE TSE prion protocols, from the extensive mad cow feed ban warning letters the fda use to put out for each violations. simply put, this excel format sucks, and the FDA et al intentionally made it this difficult to follow the usda fda mad cow follies. this is an intentional format to make it as difficult as possible to follow these breaches of the mad cow TSE prion safety feed protocols. to have absolutely no chronological or numerical order, and to format such violations in a way that they are almost impossible to find, says a lot about just how far the FDA and our fine federal friends will go through to hide these continued violations of the BSE TSE prion mad cow feed ban, and any breaches of protocols there from. once again, the wolf guarding the henhouse $$$
NAI = NO ACTION INDICATED
OAI = OFFICIAL ACTION INDICATED
VAI = VOLUNTARY ACTION INDICATED
RTS = REFERRED TO STATE
OAI (Official Action Indicated) when inspectors find significant objectionable conditions or practices and believe that regulatory sanctions are warranted to address the establishment’s lack of compliance with the regulation. An example of an OAI classification would be findings of manufacturing procedures insufficient to ensure that ruminant feed is not contaminated with prohibited material. Inspectors will promptly re-inspect facilities classified OAI after regulatory sanctions have been applied to determine whether the corrective actions are adequate to address the objectionable conditions.
2016
http://bovineprp.blogspot.com/2017/01/fda-part-589-substances-prohibited-from.html
ONE more thing, please remember, the label does not have to say ''deer ration'' for cervid to be pumped up with. you can get the same ''high protein'' from many sources of high protein feed for animals other than cattle, and feed them to cervid...
Saturday, August 29, 2009
FOIA REQUEST FEED RECALL 2009 Product may have contained prohibited materials Bulk Whole Barley, Recall # V-256-2009
http://madcowfeed.blogspot.com/2009/08/foia-request-feed-recall-2009-product.html
Friday, September 4, 2009
FOIA REQUEST ON FEED RECALL PRODUCT 429,128 lbs. feed for ruminant animals may have been contaminated with prohibited material Recall # V-258-2009
http://madcowfeed.blogspot.com/2009/09/foia-request-on-feed-recall-product.html
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II
___________________________________
PRODUCT
Bulk cattle feed made with recalled Darling’s 85% Blood Meal, Flash Dried, Recall # V-024-2007
CODE
Cattle feed delivered between 01/12/2007 and 01/26/2007
RECALLING FIRM/MANUFACTURER
Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007. Firm initiated recall is ongoing.
REASON
Blood meal used to make cattle feed was recalled because it was cross-contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE
42,090 lbs.
DISTRIBUTION
WI ___________________________________
PRODUCT
Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot-Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI – 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J – PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A-BYPASS ML W/SMARTA, Recall # V-025-2007
CODE
The firm does not utilize a code - only shipping documentation with commodity and weights identified.
RECALLING FIRM/MANUFACTURER
Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.
REASON
Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE
9,997,976 lbs.
DISTRIBUTION
ID and NV
END OF ENFORCEMENT REPORT FOR MARCH 21, 2007
###
https://webcache.googleusercontent.com/search?q=cache:Tfx9dduMyQEJ:https://www.fda.gov/Safety/Recalls/EnforcementReports/ucm120446.htm+&cd=1&hl=en&ct=clnk&gl=us
Tuesday, April 19, 2016
Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards Singeltary Comment Submission
https://www.regulations.gov/#!documentDetail;D=FDA-2003-D-0432-0011
http://chronic-wasting-disease.blogspot.com/2018/03/docket-no-aphis-2018-0011-chronic.html
http://usdameatexport.blogspot.com/2017/04/extreme-usa-fda-part-589-tse-prion-feed.html
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission
Greetings again FDA and Mr. Pritchett et al,
MY comments and source reference of sound science on this very important issue are as follows ;
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission
I kindly wish to once again submit to Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed.
Thank you kindly for allowing me to comment again, ...and again...and again, on a topic so important, why it is 'NON-BINDING' is beyond me.
this should have been finalized and made 'BINDING' or MANDATORY OVER A DECADE AGO.
but here lay the problem, once made 'BINDING' or 'MANDATORY', it is still nothing but ink on paper.
we have had a mad cow feed ban in place since August 1997, and since then, literally 100s of millions of pounds BANNED MAD COW FEED has been sent out to commerce and fed out (see reference materials).
ENFORCEMENT OF SAID BINDING REGULATIONS HAS FAILED US TOO MANY TIMES.
so, in my opinion, any non-binding or voluntary regulations will not work, and to state further, 'BINDING' or MANDATORY regulations will not work unless enforced.
with that said, we know that Chronic Wasting Disease CWD TSE Prion easily transmits to other cervid through the oral route.
the old transmission studies of BSE TSE floored scientist once they figured out what they had, and please don't forget about those mink that were fed 95%+ dead stock downer cow, that all came down with TME. please see ;
It is clear that the designing scientists must also have shared Mr Bradleys surprise at the results because all the dose levels right down to 1 gram triggered infection...snip...see full text Singeltary submission;
https://www.regulations.gov/document?D=FDA-2013-N-0764-0008
https://www.regulations.gov/document?D=FDA-2003-D-0432-0011
CWD TSE PRION MAD COW DEER DISEASE TEXAS UPDATE
ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE ???
here is the latest;
PRION 2018 CONFERENCE
Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Hermann M. Schatzl, Samia Hannaoui, Yo-Ching Cheng, Sabine Gilch (Calgary Prion Research Unit, University of Calgary, Calgary, Canada) Michael Beekes (RKI Berlin), Walter Schulz-Schaeffer (University of Homburg/Saar, Germany), Christiane Stahl-Hennig (German Primate Center) & Stefanie Czub (CFIA Lethbridge).
To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys.
Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years. After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were detected in spinal cord and brain of some euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and pre-clinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles.
Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate. The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology. Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP. The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
https://prion2018.org/
READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT from this study ;
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1) (1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.
SEEMS THAT THEY FOUND Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states.
AND ANOTHER STUDY;
P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2) (1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio.
IN THIS STUDY, THERE WERE autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017, AND included 104 patients.
SEEMS THEY FOUND THAT The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%), AND THAT The Majority of cases were male (60%), AND half of them had exposure to wild game.
https://prion2018.org/wp-content/uploads/2018/05/program.pdf
Prion 2017
Conference Abstracts CWD 2017 PRION CONFERENCE
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1
University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen
This is a progress report of a project which started in 2009. 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation.
PRION 2017
DECIPHERING NEURODEGENERATIVE DISORDERS
Subject: PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS VIDEO
PRION 2017
CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS
*** PRION 2017 CONFERENCE VIDEO
https://www.youtube.com/embed/Vtt1kAVDhDQ http://prion2017.org/programme/
https://www.cste2.org/Webinars/files/CWD_Slides_FINAL.pdf
TUESDAY, JUNE 13, 2017
PRION 2017 CONFERENCE ABSTRACT
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
http://chronic-wasting-disease.blogspot.com/2017/06/prion-2017-conference-abstract-first.html
https://www.cste2.org/Webinars/files/CWD_Slides_FINAL.pdf
SATURDAY, JULY 29, 2017
Risk Advisory Opinion: Potential Human Health Risks from Chronic Wasting Disease CFIA, PHAC, HC (HPFB and FNIHB), INAC, Parks Canada, ECCC and AAFC
http://chronic-wasting-disease.blogspot.com/2017/07/risk-advisory-opinion-potential-human.html
just out CDC...see;
Research
Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions
Marcelo A. BarriaComments to Author , Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell)
M. A. Barria et al.
ABSTRACT
Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form. We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted.
https://wwwnc.cdc.gov/eid/article/24/8/16-1888_article
Molecular Barriers to Zoonotic Transmission of Prions
Marcelo A. Barria, Aru Balachandran, Masanori Morita, Tetsuyuki Kitamoto, Rona Barron, Jean Manson, Richard Knight, James W. Ironside, and Mark W. Headcorresponding author
snip...
The conversion of human PrPC by CWD brain homogenate in PMCA reactions was less efficient when the amino acid at position 129 was valine rather than methionine.
***Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.
snip...
However, we can say with confidence that under the conditions used here, none of the animal isolates tested were as efficient as C-type BSE in converting human PrPC, which is reassuring.
***Less reassuring is the finding that there is no absolute barrier to the conversion of human PrPC by CWD prions in a protocol using a single round of PMCA and an entirely human substrate prepared from the target organ of prion diseases, the brain.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884726/
***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. CWD is unique among prion diseases in its rapid spread in natural populations. BSE prions are essentially unaltered upon passage to a new species, while CWD adapts to the new species. This adaptation has consequences for surveillance of humans exposed to CWD. Wildlife Disease Risk Communication Research Contributes to Wildlife Trust Administration Exploring perceptions about chronic wasting disease risks among wildlife and agriculture professionals and stakeholders
http://www.wda2016.org/uploads/5/8/6/1/58613359/wda_2016_conference_proceedings_low_res.pdf
CDC CWD 2018 TRANSMISSION
https://www.cdc.gov/prions/cwd/transmission.html
*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.
http://cdmrp.army.mil/prevfunded/nprp/NPRP_Summit_Final_Report.pdf
SATURDAY, JULY 21, 2018
Chronic Wasting Disease: new experience in Europe
http://chronic-wasting-disease.blogspot.com/2018/07/chronic-wasting-disease-new-experience.html
SUNDAY, JUNE 10, 2018
TEXAS SUMMARY MINUTES OF THE 400th COMMISSION MEETING CWD TSE PRION TAHC April 17, 2018
http://chronic-wasting-disease.blogspot.com/2018/06/texas-summary-minutes-of-400th.html
THURSDAY, MAY 17, 2018
Texas TAHC CWD TSE Prion Pay to Play Federal Indemnity Program, or what i call, ENTITLEMENT PROGRAM for Game Farm Industry
http://chronic-wasting-disease.blogspot.com/2018/05/texas-tahc-cwd-tse-prion-pay-to-play.html
SATURDAY, MARCH 31, 2018
TEXAS DETECTS IT'S 101 CASE of CWD TSE PRION Breeder White-tailed Deer with no end in sight
2018 03/27/18 Breeder Deer Uvalde Facility #3 White-tailed Deer M 2.5
http://chronic-wasting-disease.blogspot.com/2018/03/texas-detects-its-101-case-of-cwd-tse.html
THURSDAY, MARCH 22, 2018
TEXAS CWD TSE PRION JUMP TO 100 POSITIVE, NEW CASES 17 BREEDER, 1 BREEDER RELEASE, AND 1 WILD SINCE JAN 31, 2018
http://chronic-wasting-disease.blogspot.com/2018/03/texas-cwd-tse-prion-jump-to-100.html
WEDNESDAY, JUNE 13, 2018
Wisconsin DATCP NVSL confirmed 21 WTD from a deer farm Iowa County tested positive for chronic wasting disease (CWD)
http://chronic-wasting-disease.blogspot.com/2018/06/wisconsin-datcp-nvsl-confirmed-21-wtd.html
SUNDAY, JUNE 10, 2018
TEXAS SUMMARY MINUTES OF THE 400th COMMISSION MEETING CWD TSE PRION TAHC April 17, 2018
http://chronic-wasting-disease.blogspot.com/2018/06/texas-summary-minutes-of-400th.html
FRIDAY, JUNE 08, 2018
Pennsylvania Two Deer on Blair County Hobby Farm, One on Lancaster County Breeding Farm Test Positive for Chronic Wasting Disease cwd tse prion
http://chronic-wasting-disease.blogspot.com/2018/06/pennsylvania-two-deer-on-blair-county.html
THURSDAY, JUNE 07, 2018
Michigan DNR to present chronic wasting disease recommendations to Natural Resources Commission Singeltary submission
http://chronic-wasting-disease.blogspot.com/2018/06/michigan-dnr-to-present-chronic-wasting.html
WEDNESDAY, JUNE 13, 2018
National Scrapie Eradication Program April 2018 Monthly Report Fiscal Year 2018
http://scrapie-usa.blogspot.com/2018/06/national-scrapie-eradication-program.html
SATURDAY, JULY 21, 2018
Chronic Wasting Disease: new experience in Europe
http://chronic-wasting-disease.blogspot.com/2018/07/chronic-wasting-disease-new-experience.html
WEDNESDAY, JULY 11, 2018
CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS FDA EMERGENCY REQUEST FOR RULE CHANGE USA Section 21 C.F.R. 589.2000
http://transmissiblespongiformencephalopathy.blogspot.com/2018/07/confidential-in-confidence-spongiform.html
TUESDAY, JULY 10, 2018
CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS
*** ''but feeding of other ruminant protein, including scrapie-infected sheep, can continue to pigs.''
CONFIDENTIAL SPONGIFORM ENCEPHALOPATHY OF PIGS
http://madporcinedisease.blogspot.com/2018/07/confidential-in-confidence-spongiform.html
TUESDAY, JULY 03, 2018
Chronic Wasting Disease CWD TSE Prion Global Report Update, USA, CANADA, KOREA, NORWAY, FINLAND, Game Farms and Fake news
http://chronic-wasting-disease.blogspot.com/2018/07/chronic-wasting-disease-cwd-tse-prion.html
SUNDAY, APRIL 8, 2018
Transmissible Spongiform Encephalopathy TSE Prion Disease Global Pandemic Urgent Update April 9, 2018
http://transmissiblespongiformencephalopathy.blogspot.com/2018/04/transmissible-spongiform-encephalopathy.html
***> NEW TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE (MAD CAMEL DISEASE) IN A NEW SPECIES <***
NEW OUTBREAK OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE IN A NEW SPECIES
Subject: Prion Disease in Dromedary Camels, Algeria
Our identification of this prion disease in a geographically widespread livestock species requires urgent enforcement of surveillance and assessment of the potential risks to human and animal health.
https://wwwnc.cdc.gov/eid/article/24/6/17-2007_article
http://camelusprp.blogspot.com/2018/04/tse-prion-disease-in-dromedary-camels.html
Wednesday, May 30, 2018
Dromedary camels in northern Africa have a neurodegenerative prion disease that may have originated decades ago
http://camelusprp.blogspot.com/2018/05/dromedary-camels-in-northern-africa.html
http://camelusprp.blogspot.com/
TUESDAY, AUGUST 7, 2018
Unexpected prion phenotypes in experimentally transfused animals: predictive models for humans?
http://transmissiblespongiformencephalopathy.blogspot.com/2018/08/unexpected-prion-phenotypes-in.html
TUESDAY, JULY 31, 2018
USA CJD TSE Tables of Cases Examined National Prion Disease Pathology Surveillance Center Cases Examined May 1, 2018
http://prionunitusaupdate.blogspot.com/2018/07/usa-cjd-tse-tables-of-cases-examined.html
Volume 2: Science
4. The link between BSE and vCJD
Summary
4.29 The evidence discussed above that vCJD is caused by BSE seems overwhelming. Uncertainties exist about the cause of CJD in farmers, their wives and in several abattoir workers. It seems that farmers at least might be at higher risk than others in the general population. 1 Increased ascertainment (ie, increased identification of cases as a result of greater awareness of the condition) seems unlikely, as other groups exposed to risk, such as butchers and veterinarians, do not appear to have been affected. The CJD in farmers seems to be similar to other sporadic CJD in age of onset, in respect to glycosylation patterns, and in strain-typing in experimental mice. Some farmers are heterozygous for the methionine/valine variant at codon 129, and their lymphoreticular system (LRS) does not contain the high levels of PrPSc found in vCJD. It remains a remote possibility that when older people contract CJD from BSE the resulting phenotype is like sporadic CJD and is distinct from the vCJD phenotype in younger people...
BSE INQUIRY
TUESDAY, JULY 31, 2018
USA CJD TSE Tables of Cases Examined National Prion Disease Pathology Surveillance Center Cases Examined May 1, 2018
http://prionunitusaupdate.blogspot.com/2018/07/usa-cjd-tse-tables-of-cases-examined.html
Terry S. Singeltary Sr.
Bacliff, Texas USA 77518
Galveston Bay, on the bottom...
Title: Passage of scrapie to deer results in a new phenotype upon return passage to sheep
Author item Greenlee, Justin item Kokemuller, Robyn item Moore, Sarah item West Greenlee, N Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 3/15/2017 Publication Date: N/A Citation: N/A
Interpretive Summary:
Technical Abstract:
Aims: We previously demonstrated that scrapie has a 100% attack rate in white-tailed deer after either intracranial or oral inoculation.
Samples from deer that developed scrapie had two different western blot patterns: samples derived from cerebrum had a banding pattern similar to the scrapie inoculum, but samples from brainstem had a banding pattern similar to CWD.
In contrast, transmission of CWD from white-tailed deer to sheep by the intracranial route has a low attack rate and to-date oronasal exposure has been unsuccessful. The purpose of this study was to determine if sheep are susceptible to oronasal exposure of the scrapie agent derived from white-tailed deer.
Methods: At approximately 5 months of age, Suffolk sheep of various PRNP genotypes were challenged by the oronasal route with 10% brain homogenate derived from either the cerebrum or the brainstem of scrapie-affected deer. Genotypes represented in each inoculation group were VV136RR154QQ171 (n=2), AA136RR154QQ171 (n=2), and AV136RR154QR171 (n=1). After inoculation, sheep were observed daily for clinical signs. Upon development of clinical signs, sheep were killed with an overdose of pentobarbital sodium and necropsied. Tissue samples were tested for the presence of PrPSc by EIA, western blot, and immunohistochemistry (IHC). The No. 13-7 scrapie inoculum used for the deer has a mean incubation period of 20.1 months in sheep with the AA136RR154QQ171 genotype and 26.7 months in sheep with the VV136RR154QQ171 genotype.
Results: Sheep inoculated oronasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum from the cerebrum that had a scrapie-like profile. The first sheep to develop clinical signs at approximately 29 months post inoculation had the VV136RR154QQ171 genotype. Eventually sheep of the AA136RR154QQ171 genotype developed clinical signs, but at a mean incubation of 52 months. At 62 months post-inoculation, none of the sheep inoculated with material from the deer brainstem have developed clinical disease.
Conclusions: The No. 13-7 inoculum used in the original deer experiment readily infects white-tailed deer and sheep of various genotypes by the oronasal route. When inoculum is made from different brain regions of No 13-7 scrapie-infected deer from either cerebrum with a scrapie-like western blot pattern or brainstem with a CWD-like western blot pattern, sheep with the VV136RR154QQ171 genotype are the first to develop clinical signs. This is in contrast to the original No. 13-7 inoculum that has a faster incubation period in sheep with the AA136RR154QQ171 genotype. Similar to experiments conducted with CWD, sheep oronasally inoculated with brainstem material from deer with a CWD-like molecular profile have no evidence of disease after 62 months of incubation.
While scrapie is not known to occur in free-ranging populations of white-tailed deer, experimental cases are difficult to differentiate from CWD.
This work raises the potential concern that scrapie infected deer could serve as a confounding factor to scrapie eradication programs as scrapie from deer seems to be transmissible to sheep by the oronasal route.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=337278
-----Original Message-----
From: Terry Singeltary
To: bse-l
Cc: cjdvoice
Sent: Wed, Jun 13, 2018 5:01 pm
Subject: National Scrapie Eradication Program April 2018 Monthly Report Fiscal Year 2018
National Scrapie Eradication Program April 2018 Monthly Report Fiscal Year 2018
U.S. Department of Agriculture Animal and Plant Health Inspection Service Veterinary Services
Surveillance, Response and Preparedness Services Sheep and Goat Health Program May 15, 2018
Program Summary
Performance Measures - At the end of FY 2017 and continuing into FY 2018, the percent of cull black face sheep found positive at slaughter was 0 percent (Chart 1) and the percent of cull sheep found positive at slaughter and adjusted for face color* was 0 percent (Chart 2).
Positive Animals – In April, APHIS identified scrapie in a 171 RR sheep from a flock in NC. There was insufficient positive tissue available to rule out non-classical scrapie. As a result, APHIS is conducting additional testing of the flock before determining whether to classify the case as classical scrapie. One Nor98-like case was reported in October 2017. Other than one goat in a herd quarantined since 2005 and depopulated in 2017, no goats have tested positive for scrapie since February 2015. The retrospective 6-month rolling average of the percent positive, black-faced sheep sampled at RSSS collection sites has been 0 since June 2016.
*White, black and mottled-faced color sheep are weighted based on population; white-faced sheep have the greatest weight. If a white-faced positive sheep is found, this statistic will markedly increase. See notes below for details.
**Samples collected between October 1, 2017 and April 30, 2018 and confirmed by May 15, 2018.
Program Summary
Infected and Source Flocks - No classical scrapie infected or source flocks have been designated since June 2016 (Chart 3). Two flocks, one in Colorado and one in Texas, have open statuses, but there are no exposed animals on the premises of these flocks. Cleaning and disinfection of these premises has to be completed before the infect or source status can be closed.
Scrapie in Goats - Only one positive goat (FY 2015) has been found through RSSS since the start of RSSS in 2003. Since 2002, the total number of positive field cases in goats is 41. Figure 1 shows the number of positive cases by State and by fiscal year of last reported case.
Program Summary
Scrapie Flock Certification Program (SFCP) – As of April 30, 2018, there were 276 flocks participating in the Scrapie Flock Certification Program (SFCP). Statuses of these flocks were 59 export monitored, 45 export certified, and 172 select monitored flocks (Figure 2). SFCP open statuses by fiscal year of Status date* from FY 2007 to FY 2018 are depicted in Chart 4.
* Previous charts of SFCP participation by year were manually updated and used the enrollment date to determine the year of participation in SFCP. With the change to Tableau charts, the start/status date is used. Many participating flocks were grandfathered into the Export category in 2013 with an earlier status date.
Surveillance
Surveillance activities are State-based and are administered as districts by APHIS (Figure
3). For this reason, reporting of surveillance activities is also by District. Surveillance minimums are based on estimated sheep and goat populations in each State. The distribution of sheep and goat populations by District is depicted in Chart 5. Components of Scrapie Surveillance
• Regulatory Scrapie Slaughter Surveillance (RSSS) started April 1, 2003. It is a targeted slaughter surveillance program which is designed to identify infected flocks. Samples have been collected from 583,678 animals since April 1, 2003. There have been 484 NVSL confirmed positive animals (471 classical cases, 12 Nor98-like cases, and 1 pending designation) since the beginning of RSSS. As of April 30, 2018, 23,370 samples have been collected in FY2018, 18,530 from sheep and 4,840 from goats. A positive was confirmed in April and is pending designation as classical or non-classical scrapie. The number of sheep and goats collected in each District is shown in Chart 6. Figure 4 is a hex map, representing the number of animals collected in each State. Chart 7 compares RSSS sampling by month for the current year with the monthly average of the previous 4 years.
Surveillance
Components of Scrapie Surveillance (continued)
• On-farm Surveillance includes both regulatory testing of scrapie exposed and potentially exposed sheep and goats and testing sheep and goats on farm for routine surveillance. As of April 30, 2018, 684 sheep and 307 goats have been tested on-farm for FY 2018.
Surveillance Minimums
The annual target is to test at least 40,000 animals each year for scrapie. As of April 30, 2018, 24,498 animals have been sampled for scrapie testing in FY 2018:
• 23,370 RSSS samples and 1,128 on-farm samples
• Of which 19,316 were sheep and 5,182 were goats.
Progress towards meeting the national surveillance target is depicted in Chart 8. Distribution of sampling by type (RSSS or on-farm) and by species is shown in Chart 9. Chart 10 and Table 1 is a breakdown by face-color (sheep) and type (goats) by age.
snip...SEE FULL TEXT;
https://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_report.pdf
WHAT'S up with the scrapie(?) TSE Prion outbreak, in goats in Michigan and California???
SUNDAY, JUNE 3, 2018
Clinical, pathological, and molecular features of classical and L-type atypical-BSE in goats
http://bovineprp.blogspot.com/2018/06/clinical-pathological-and-molecular.html
FRIDAY, APRIL 22, 2016
Texas Scrapie Confirmed in a Hartley County Sheep where CWD was detected in a Mule Deer April 22, 2016
http://scrapie-usa.blogspot.com/2016/04/texas-scrapie-confirmed-in-hartley.html
Thursday, June 09, 2016
Scrapie Field Trial Experiments Mission, Texas, The Moore Air Force Base Scrapie TSE Prion Experiment 1964 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...
http://web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf
http://scrapie-usa.blogspot.com/2016/06/scrapie-field-trial-experiments-mission.html
http://chronic-wasting-disease.blogspot.com/2016/06/how-did-cwd-get-way-down-in-medina.html
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.
==============
https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf
***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.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
PRION 2016 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 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.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly 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
https://web.archive.org/web/20170126051158/http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf
IN CONFIDENCE
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.
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
-2-
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.
-3-
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.
-4- 78/3.9/1.4
(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
https://web.archive.org/web/20090505233518/http://www.bseinquiry.gov.uk/files/yb/1978/03/09001001.pdf
IN CONFIDENCE
https://web.archive.org/web/20090506012627/http://www.bseinquiry.gov.uk/files/yb/1978/06/01001001.pdf
https://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...
https://web.archive.org/web/20090506012512/http://www.bseinquiry.gov.uk/files/yb/1978/06/27002001.pdf
see board meeting on questions raised on whether risk factors, occupation, for those that worked with scrapie, had a higher risk of developing creutzfeldt jakob disease...see;
https://web.archive.org/web/20170126051837/http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/06/27003001.pdf
https://web.archive.org/web/20090506012538/http://www.bseinquiry.gov.uk/files/yb/1978/06/27003001.pdf
https://web.archive.org/web/20090506012525/http://www.bseinquiry.gov.uk/files/yb/1978/06/27004001.pdf
https://web.archive.org/web/20090506012532/http://www.bseinquiry.gov.uk/files/yb/1978/10/06001001.pdf
IN CONFIDENCE
https://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
https://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
http://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
http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.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).
http://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).
http://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
https://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
https://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
http://scrapie-usa.blogspot.com/2011/02/in-confidence-scrapie-transmission-to.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.
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160
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.
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160
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.
http://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.
http://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.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
OR
*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.
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.
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
http://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 ;
https://web.archive.org/web/20090506050043/http://www.bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf
Thursday, October 10, 2013
CJD REPORT 1994 increased risk for consumption of veal and venison and lamb
http://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
http://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
http://transmissiblespongiformencephalopathy.blogspot.com/2012/12/oie-group-recommends-that-scrape-prion.html
P.97: Scrapie transmits to white-tailed deer by the oral route and has a molecular profile similar to chronic wasting disease and distinct from the scrapie inoculum
Justin Greenlee1, S JO Moore1, Jodi Smith1, M Heather WestGreenlee2 and Robert Kunkle1
1National Animal Disease Center; Ames, IA USA
2Iowa State University; Ames, IA USA
The purpose of this work was to determine susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to that of the original inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (IN); n = 5) with a US scrapie isolate. All scrapie-inoculated deer had evidence of PrPSc accumulation. PrPSc was detected in lymphoid tissues at preclinical time points, and deer necropsied after 28 months post-inoculation had clinical signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural and lymphoid tissues. Western blotting (WB) revealed PrPSc with 2 distinct molecular profiles. WB on cerebral cortex had a profile similar to the original scrapie inoculum, whereas WB of brainstem, cerebellum, or lymph nodes revealed PrPSc with a higher profile resembling CWD. Homogenates with the 2 distinct profiles from WTD with clinical scrapie were further passaged to mice expressing cervid prion protein and intranasally to sheep and WTD. In cervidized mice, the 2 inocula have distinct incubation times. Sheep inoculated intranasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum that had a scrapie-like profile. The WTD study is ongoing, but deer in both inoculation groups are positive for PrPSc by rectal mucosal biopsy.
***In summary, this work demonstrates that WTD are susceptible to the agent of scrapie, 2 distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile readily passes to deer.
https://www.tandfonline.com/doi/full/10.1080/19336896.2015.1033248
*** After a natural route of exposure, 100% of WTD were susceptible to scrapie.
PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA
http://www.landesbioscience.com/journals/prion/03-Prion6-2-Transmission-and-strains.pdf
White-tailed deer are susceptible to the agent of sheep scrapie by intracerebral inoculation
snip...
It is unlikely that CWD will be eradicated from free-ranging cervids, and the disease is likely to continue to spread geographically [10]. However, the potential that white-tailed deer may be susceptible to sheep scrapie by a natural route presents an additional confounding factor to halting the spread of CWD. This leads to the additional speculations that
1) infected deer could serve as a reservoir to infect sheep with scrapie offering challenges to scrapie eradication efforts and
2) CWD spread need not remain geographically confined to current endemic areas, but could occur anywhere that sheep with scrapie and susceptible cervids cohabitate.
This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by intracerebral inoculation with a high attack rate and that the disease that results has similarities to CWD. These experiments will be repeated with a more natural route of inoculation to determine the likelihood of the potential transmission of sheep scrapie to white-tailed deer. If scrapie were to occur in white-tailed deer, results of this study indicate that it would be detected as a TSE, but may be difficult to differentiate from CWD without in-depth biochemical analysis.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199251/?tool=pubmed
http://chronic-wasting-disease.blogspot.com/2011/10/white-tailed-deer-are-susceptible-to.html
2012
PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer
Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA
snip...
The results of this study suggest that there are many similarities in the manifestation of CWD and scrapie in WTD after IC inoculation including early and widespread presence of PrPSc in lymphoid tissues, clinical signs of depression and weight loss progressing to wasting, and an incubation time of 21-23 months. Moreover, western blots (WB) done on brain material from the obex region have a molecular profile similar to CWD and distinct from tissues of the cerebrum or the scrapie inoculum. However, results of microscopic and IHC examination indicate that there are differences between the lesions expected in CWD and those that occur in deer with scrapie: amyloid plaques were not noted in any sections of brain examined from these deer and the pattern of immunoreactivity by IHC was diffuse rather than plaque-like.
*** After a natural route of exposure, 100% of WTD were susceptible to scrapie.
Deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 months PI. Tissues from these deer were positive for PrPSc by IHC and WB. Similar to IC inoculated deer, samples from these deer exhibited two different molecular profiles: samples from obex resembled CWD whereas those from cerebrum were similar to the original scrapie inoculum. On further examination by WB using a panel of antibodies, the tissues from deer with scrapie exhibit properties differing from tissues either from sheep with scrapie or WTD with CWD. Samples from WTD with CWD or sheep with scrapie are strongly immunoreactive when probed with mAb P4, however, samples from WTD with scrapie are only weakly immunoreactive. In contrast, when probed with mAb’s 6H4 or SAF 84, samples from sheep with scrapie and WTD with CWD are weakly immunoreactive and samples from WTD with scrapie are strongly positive. This work demonstrates that WTD are highly susceptible to sheep scrapie, but on first passage, scrapie in WTD is differentiable from CWD.
http://www.landesbioscience.com/journals/prion/03-Prion6-2-Transmission-and-strains.pdf
2011
*** After a natural route of exposure, 100% of white-tailed deer were susceptible to scrapie.
http://www.usaha.org/Portals/6/Reports/2011/report-cwal-2011.pdf
FRIDAY, APRIL 20, 2018
*** Scrapie Transmits To Pigs By Oral Route, what about the terribly flawed USA tse prion feed ban?
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies
http://scrapie-usa.blogspot.com/2018/04/scrapie-transmits-to-pigs-by-oral-route.html
***> CWD TO PIGS <***
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Location: Virus and Prion Research
Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease
Author item Moore, Sarah item Kunkle, Robert item Kondru, Naveen item Manne, Sireesha item Smith, Jodi item Kanthasamy, Anumantha item West Greenlee, M item Greenlee, Justin
Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 3/15/2017 Publication Date: N/A Citation: N/A Interpretive Summary:
Technical Abstract: Aims: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study, neurological signs consistent with prion disease were observed only in one pig: an intracranially challenged pig that was euthanized at 64 months post-challenge. The purpose of this study was to use an antigen-capture immunoassay (EIA) and real-time quaking-induced conversion (QuIC) to determine whether PrPSc is present in lymphoid tissues from pigs challenged with the CWD agent.
Methods: At two months of age, crossbred pigs were challenged by the intracranial route (n=20), oral route (n=19), or were left unchallenged (n=9). At approximately 6 months of age, the time at which commercial pigs reach market weight, half of the pigs in each group were culled (<6 challenge="" groups="" month="" pigs="" remaining="" the="">6 month challenge groups) were allowed to incubate for up to 73 months post challenge (mpc). The retropharyngeal lymph node (RPLN) was screened for the presence of PrPSc by EIA and immunohistochemistry (IHC). The RPLN, palatine tonsil, and mesenteric lymph node (MLN) from 6-7 pigs per challenge group were also tested using EIA and QuIC.
Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 5="" 6="" at="" by="" detected="" eia.="" examined="" group="" in="" intracranial="" least="" lymphoid="" month="" months="" of="" one="" pigs="" positive="" prpsc="" quic="" the="" tissues="" was="">6 months group, 5/6 pigs in the oral <6 4="" and="" group="" months="" oral="">6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%). Conclusions:
This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge.
CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease.
Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=337105
CONFIDENTIAL
EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY
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. ...
http://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.
http://web.archive.org/web/20030822031154/www.bseinquiry.gov.uk/files/yb/1990/09/10007001.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.....
http://web.archive.org/web/20030822054419/www.bseinquiry.gov.uk/files/yb/1990/09/21009001.pdf
snip...see much more here ;
WEDNESDAY, APRIL 05, 2017
Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease
http://chronic-wasting-disease.blogspot.com/2017/04/disease-associated-prion-protein.html
WEDNESDAY, APRIL 05, 2017
*** Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease ***
http://chronic-wasting-disease.blogspot.com/2017/04/disease-associated-prion-protein.html
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.
http://prion2016.org/
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
http://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. ...
http://web.archive.org/web/20060307063531/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
also see hand written notes ;
https://web.archive.org/web/20071019203707/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...
https://web.archive.org/web/20090506002258/http://www.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. ........
http://web.archive.org/web/20010305222246/www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf
RISK OF BSE TO SHEEP VIA FEED
https://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.
https://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
http://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
http://transmissiblespongiformencephalopathy.blogspot.com/2012/01/selection-of-distinct-strain-phenotypes.html
Scrapie-like disorder in a Nyala (Tragelaphus angasi)
IN CONFIDENCE
https://web.archive.org/web/20090506014205/http://www.bseinquiry.gov.uk/files/yb/1986/11/00001001.pdf
https://web.archive.org/web/20090505225907/http://www.bseinquiry.gov.uk/files/yb/1986/06/23001001.pdf
https://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...
https://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.
https://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
STRICTLY IN CONFIDENCE
https://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
https://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.
https://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.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3915057&dopt=Abstract
http://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.
http://scrapie-usa.blogspot.com/2015/08/doctor-william-j-hadlow.html
Spongiform Encephalopathy in Captive Wild ZOO BSE INQUIRY
https://web.archive.org/web/20090506001201/http://www.bseinquiry.gov.uk/files/mb/m09a/tab03.pdf
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.***
http://www.nature.com/articles/srep11573
FEED TSE PRION
2017 Section 21 C.F.R. 589.2000, Animal Proteins Prohibited in Ruminant Feed
Subject: MICHIGAN FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE BREACH APRIL 4, 2017
MICHIGAN FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE BREACH APRIL 4, 2017
FDA BSE/Ruminant Feed Inspections Firms Inventory
11998 DET-DO MI 48846-847 OPR 4/4/2017 OAI
http://www.accessdata.fda.gov/scripts/BSEInspect/bseinspections.csv
NAI = NO ACTION INDICATED
OAI = OFFICIAL ACTION INDICATED
VAI = VOLUNTARY ACTION INDICATED
RTS = REFERRED TO STATE
OAI (Official Action Indicated) when inspectors find significant objectionable conditions or practices and believe that regulatory sanctions are warranted to address the establishment’s lack of compliance with the regulation. An example of an OAI classification would be findings of manufacturing procedures insufficient to ensure that ruminant feed is not contaminated with prohibited material. Inspectors will promptly re-inspect facilities classified OAI after regulatory sanctions have been applied to determine whether the corrective actions are adequate to address the objectionable conditions...end...TSS
V. Use in animal feed of material from deer and elk NOT considered at high risk for CWD
FDA continues to consider materials from deer and elk NOT considered at high risk for CWD to be acceptable for use in NON-RUMINANT animal feeds in accordance with current agency regulations, 21 CFR 589.2000.
Deer and elk not considered at high risk include:
(1) deer and elk from areas not declared by State officials to be endemic for CWD and/or to be CWD eradication zones; and
(2) deer and elk that were not at some time during the 60-month period immediately before the time of slaughter in a captive herd that contained a CWD-positive animal.
https://www.fda.gov/downloads/animalveterinary/guidancecomplianceenforcement/guidanceforindustry/ucm052506.pdf
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012
snip...
In the USA, under the Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law.
Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and
2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES. It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.
snip...
36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011).
The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE).
Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison.
snip...
The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008).
snip...
In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion.
snip...
In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible. For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates.
snip...
Therefore, it is considered that farmed and park deer may have a higher probability of exposure to CWD transferred to the environment than wild deer given the restricted habitat range and higher frequency of contact with tourists and returning GB residents.
snip...
http://webarchive.nationalarchives.gov.uk/20130908115835/http://www.defra.gov.uk/animal-diseases/files/qra_chronic-wasting-disease-121029.pdf
TUESDAY, APRIL 18, 2017
*** EXTREME USA FDA PART 589 TSE PRION FEED LOOP HOLE STILL EXIST, AND PRICE OF POKER GOES UP ***
http://usdameatexport.blogspot.com/2017/04/extreme-usa-fda-part-589-tse-prion-feed.html
TUESDAY, JANUARY 17, 2017
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION
http://bovineprp.blogspot.com/2017/01/fda-part-589-substances-prohibited-from.html
THIS April, 4, 2017 violation of the mad cow 21 CFR 589.2000 OAI is very serious for the great state of Michigan, some 20 years post FDA mad cow feed of August 1997. if would most likely take a FOIA request and a decade of wrangling to find out more.
TUESDAY, JANUARY 17, 2017
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION
I would kindly like to comment on this FDA BSE/Ruminant Feed Inspections Firms Inventory (excel format)4 format, for reporting these breaches of BSE TSE prion protocols, from the extensive mad cow feed ban warning letters the fda use to put out for each violations. simply put, this excel format sucks, and the FDA et al intentionally made it this difficult to follow the usda fda mad cow follies. this is an intentional format to make it as difficult as possible to follow these breaches of the mad cow TSE prion safety feed protocols. to have absolutely no chronological or numerical order, and to format such violations in a way that they are almost impossible to find, says a lot about just how far the FDA and our fine federal friends will go through to hide these continued violations of the BSE TSE prion mad cow feed ban, and any breaches of protocols there from. once again, the wolf guarding the henhouse $$$
NAI = NO ACTION INDICATED
OAI = OFFICIAL ACTION INDICATED
VAI = VOLUNTARY ACTION INDICATED
RTS = REFERRED TO STATE
OAI (Official Action Indicated) when inspectors find significant objectionable conditions or practices and believe that regulatory sanctions are warranted to address the establishment’s lack of compliance with the regulation. An example of an OAI classification would be findings of manufacturing procedures insufficient to ensure that ruminant feed is not contaminated with prohibited material. Inspectors will promptly re-inspect facilities classified OAI after regulatory sanctions have been applied to determine whether the corrective actions are adequate to address the objectionable conditions.
2016
http://bovineprp.blogspot.com/2017/01/fda-part-589-substances-prohibited-from.html
ONE more thing, please remember, the label does not have to say ''deer ration'' for cervid to be pumped up with. you can get the same ''high protein'' from many sources of high protein feed for animals other than cattle, and feed them to cervid...
Saturday, August 29, 2009
FOIA REQUEST FEED RECALL 2009 Product may have contained prohibited materials Bulk Whole Barley, Recall # V-256-2009
http://madcowfeed.blogspot.com/2009/08/foia-request-feed-recall-2009-product.html
Friday, September 4, 2009
FOIA REQUEST ON FEED RECALL PRODUCT 429,128 lbs. feed for ruminant animals may have been contaminated with prohibited material Recall # V-258-2009
http://madcowfeed.blogspot.com/2009/09/foia-request-on-feed-recall-product.html
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II
___________________________________
PRODUCT
Bulk cattle feed made with recalled Darling’s 85% Blood Meal, Flash Dried, Recall # V-024-2007
CODE
Cattle feed delivered between 01/12/2007 and 01/26/2007
RECALLING FIRM/MANUFACTURER
Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007. Firm initiated recall is ongoing.
REASON
Blood meal used to make cattle feed was recalled because it was cross-contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE
42,090 lbs.
DISTRIBUTION
WI ___________________________________
PRODUCT
Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot-Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI – 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J – PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A-BYPASS ML W/SMARTA, Recall # V-025-2007
CODE
The firm does not utilize a code - only shipping documentation with commodity and weights identified.
RECALLING FIRM/MANUFACTURER
Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.
REASON
Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE
9,997,976 lbs.
DISTRIBUTION
ID and NV
END OF ENFORCEMENT REPORT FOR MARCH 21, 2007
###
https://webcache.googleusercontent.com/search?q=cache:Tfx9dduMyQEJ:https://www.fda.gov/Safety/Recalls/EnforcementReports/ucm120446.htm+&cd=1&hl=en&ct=clnk&gl=us
Tuesday, April 19, 2016
Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards Singeltary Comment Submission
https://www.regulations.gov/#!documentDetail;D=FDA-2003-D-0432-0011
http://chronic-wasting-disease.blogspot.com/2018/03/docket-no-aphis-2018-0011-chronic.html
http://usdameatexport.blogspot.com/2017/04/extreme-usa-fda-part-589-tse-prion-feed.html
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission
Greetings again FDA and Mr. Pritchett et al,
MY comments and source reference of sound science on this very important issue are as follows ;
Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed Singeltary Submission
I kindly wish to once again submit to Docket No. FDA-2003-D-0432 (formerly 03D-0186) Use of Material from Deer and Elk in Animal Feed.
Thank you kindly for allowing me to comment again, ...and again...and again, on a topic so important, why it is 'NON-BINDING' is beyond me.
this should have been finalized and made 'BINDING' or MANDATORY OVER A DECADE AGO.
but here lay the problem, once made 'BINDING' or 'MANDATORY', it is still nothing but ink on paper.
we have had a mad cow feed ban in place since August 1997, and since then, literally 100s of millions of pounds BANNED MAD COW FEED has been sent out to commerce and fed out (see reference materials).
ENFORCEMENT OF SAID BINDING REGULATIONS HAS FAILED US TOO MANY TIMES.
so, in my opinion, any non-binding or voluntary regulations will not work, and to state further, 'BINDING' or MANDATORY regulations will not work unless enforced.
with that said, we know that Chronic Wasting Disease CWD TSE Prion easily transmits to other cervid through the oral route.
the old transmission studies of BSE TSE floored scientist once they figured out what they had, and please don't forget about those mink that were fed 95%+ dead stock downer cow, that all came down with TME. please see ;
It is clear that the designing scientists must also have shared Mr Bradleys surprise at the results because all the dose levels right down to 1 gram triggered infection...snip...see full text Singeltary submission;
https://www.regulations.gov/document?D=FDA-2013-N-0764-0008
https://www.regulations.gov/document?D=FDA-2003-D-0432-0011
CWD TSE PRION MAD COW DEER DISEASE TEXAS UPDATE
ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE ???
here is the latest;
PRION 2018 CONFERENCE
Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Hermann M. Schatzl, Samia Hannaoui, Yo-Ching Cheng, Sabine Gilch (Calgary Prion Research Unit, University of Calgary, Calgary, Canada) Michael Beekes (RKI Berlin), Walter Schulz-Schaeffer (University of Homburg/Saar, Germany), Christiane Stahl-Hennig (German Primate Center) & Stefanie Czub (CFIA Lethbridge).
To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys.
Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years. After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were detected in spinal cord and brain of some euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and pre-clinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles.
Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate. The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology. Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP. The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
https://prion2018.org/
READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT from this study ;
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1) (1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.
SEEMS THAT THEY FOUND Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states.
AND ANOTHER STUDY;
P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2) (1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio.
IN THIS STUDY, THERE WERE autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017, AND included 104 patients.
SEEMS THEY FOUND THAT The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%), AND THAT The Majority of cases were male (60%), AND half of them had exposure to wild game.
https://prion2018.org/wp-content/uploads/2018/05/program.pdf
Prion 2017
Conference Abstracts CWD 2017 PRION CONFERENCE
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1
University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen
This is a progress report of a project which started in 2009. 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation.
PRION 2017
DECIPHERING NEURODEGENERATIVE DISORDERS
Subject: PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS VIDEO
PRION 2017
CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS
*** PRION 2017 CONFERENCE VIDEO
https://www.youtube.com/embed/Vtt1kAVDhDQ http://prion2017.org/programme/
https://www.cste2.org/Webinars/files/CWD_Slides_FINAL.pdf
TUESDAY, JUNE 13, 2017
PRION 2017 CONFERENCE ABSTRACT
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
http://chronic-wasting-disease.blogspot.com/2017/06/prion-2017-conference-abstract-first.html
https://www.cste2.org/Webinars/files/CWD_Slides_FINAL.pdf
SATURDAY, JULY 29, 2017
Risk Advisory Opinion: Potential Human Health Risks from Chronic Wasting Disease CFIA, PHAC, HC (HPFB and FNIHB), INAC, Parks Canada, ECCC and AAFC
http://chronic-wasting-disease.blogspot.com/2017/07/risk-advisory-opinion-potential-human.html
just out CDC...see;
Research
Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions
Marcelo A. BarriaComments to Author , Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell)
M. A. Barria et al.
ABSTRACT
Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form. We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted.
https://wwwnc.cdc.gov/eid/article/24/8/16-1888_article
Molecular Barriers to Zoonotic Transmission of Prions
Marcelo A. Barria, Aru Balachandran, Masanori Morita, Tetsuyuki Kitamoto, Rona Barron, Jean Manson, Richard Knight, James W. Ironside, and Mark W. Headcorresponding author
snip...
The conversion of human PrPC by CWD brain homogenate in PMCA reactions was less efficient when the amino acid at position 129 was valine rather than methionine.
***Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.
snip...
However, we can say with confidence that under the conditions used here, none of the animal isolates tested were as efficient as C-type BSE in converting human PrPC, which is reassuring.
***Less reassuring is the finding that there is no absolute barrier to the conversion of human PrPC by CWD prions in a protocol using a single round of PMCA and an entirely human substrate prepared from the target organ of prion diseases, the brain.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884726/
***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. CWD is unique among prion diseases in its rapid spread in natural populations. BSE prions are essentially unaltered upon passage to a new species, while CWD adapts to the new species. This adaptation has consequences for surveillance of humans exposed to CWD. Wildlife Disease Risk Communication Research Contributes to Wildlife Trust Administration Exploring perceptions about chronic wasting disease risks among wildlife and agriculture professionals and stakeholders
http://www.wda2016.org/uploads/5/8/6/1/58613359/wda_2016_conference_proceedings_low_res.pdf
CDC CWD 2018 TRANSMISSION
https://www.cdc.gov/prions/cwd/transmission.html
*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.
http://cdmrp.army.mil/prevfunded/nprp/NPRP_Summit_Final_Report.pdf
SATURDAY, JULY 21, 2018
Chronic Wasting Disease: new experience in Europe
http://chronic-wasting-disease.blogspot.com/2018/07/chronic-wasting-disease-new-experience.html
SUNDAY, JUNE 10, 2018
TEXAS SUMMARY MINUTES OF THE 400th COMMISSION MEETING CWD TSE PRION TAHC April 17, 2018
http://chronic-wasting-disease.blogspot.com/2018/06/texas-summary-minutes-of-400th.html
THURSDAY, MAY 17, 2018
Texas TAHC CWD TSE Prion Pay to Play Federal Indemnity Program, or what i call, ENTITLEMENT PROGRAM for Game Farm Industry
http://chronic-wasting-disease.blogspot.com/2018/05/texas-tahc-cwd-tse-prion-pay-to-play.html
SATURDAY, MARCH 31, 2018
TEXAS DETECTS IT'S 101 CASE of CWD TSE PRION Breeder White-tailed Deer with no end in sight
2018 03/27/18 Breeder Deer Uvalde Facility #3 White-tailed Deer M 2.5
http://chronic-wasting-disease.blogspot.com/2018/03/texas-detects-its-101-case-of-cwd-tse.html
THURSDAY, MARCH 22, 2018
TEXAS CWD TSE PRION JUMP TO 100 POSITIVE, NEW CASES 17 BREEDER, 1 BREEDER RELEASE, AND 1 WILD SINCE JAN 31, 2018
http://chronic-wasting-disease.blogspot.com/2018/03/texas-cwd-tse-prion-jump-to-100.html
WEDNESDAY, JUNE 13, 2018
Wisconsin DATCP NVSL confirmed 21 WTD from a deer farm Iowa County tested positive for chronic wasting disease (CWD)
http://chronic-wasting-disease.blogspot.com/2018/06/wisconsin-datcp-nvsl-confirmed-21-wtd.html
SUNDAY, JUNE 10, 2018
TEXAS SUMMARY MINUTES OF THE 400th COMMISSION MEETING CWD TSE PRION TAHC April 17, 2018
http://chronic-wasting-disease.blogspot.com/2018/06/texas-summary-minutes-of-400th.html
FRIDAY, JUNE 08, 2018
Pennsylvania Two Deer on Blair County Hobby Farm, One on Lancaster County Breeding Farm Test Positive for Chronic Wasting Disease cwd tse prion
http://chronic-wasting-disease.blogspot.com/2018/06/pennsylvania-two-deer-on-blair-county.html
THURSDAY, JUNE 07, 2018
Michigan DNR to present chronic wasting disease recommendations to Natural Resources Commission Singeltary submission
http://chronic-wasting-disease.blogspot.com/2018/06/michigan-dnr-to-present-chronic-wasting.html
WEDNESDAY, JUNE 13, 2018
National Scrapie Eradication Program April 2018 Monthly Report Fiscal Year 2018
http://scrapie-usa.blogspot.com/2018/06/national-scrapie-eradication-program.html
SATURDAY, JULY 21, 2018
Chronic Wasting Disease: new experience in Europe
http://chronic-wasting-disease.blogspot.com/2018/07/chronic-wasting-disease-new-experience.html
WEDNESDAY, JULY 11, 2018
CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS FDA EMERGENCY REQUEST FOR RULE CHANGE USA Section 21 C.F.R. 589.2000
http://transmissiblespongiformencephalopathy.blogspot.com/2018/07/confidential-in-confidence-spongiform.html
TUESDAY, JULY 10, 2018
CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS
*** ''but feeding of other ruminant protein, including scrapie-infected sheep, can continue to pigs.''
CONFIDENTIAL SPONGIFORM ENCEPHALOPATHY OF PIGS
http://madporcinedisease.blogspot.com/2018/07/confidential-in-confidence-spongiform.html
TUESDAY, JULY 03, 2018
Chronic Wasting Disease CWD TSE Prion Global Report Update, USA, CANADA, KOREA, NORWAY, FINLAND, Game Farms and Fake news
http://chronic-wasting-disease.blogspot.com/2018/07/chronic-wasting-disease-cwd-tse-prion.html
SUNDAY, APRIL 8, 2018
Transmissible Spongiform Encephalopathy TSE Prion Disease Global Pandemic Urgent Update April 9, 2018
http://transmissiblespongiformencephalopathy.blogspot.com/2018/04/transmissible-spongiform-encephalopathy.html
***> NEW TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE (MAD CAMEL DISEASE) IN A NEW SPECIES <***
NEW OUTBREAK OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE IN A NEW SPECIES
Subject: Prion Disease in Dromedary Camels, Algeria
Our identification of this prion disease in a geographically widespread livestock species requires urgent enforcement of surveillance and assessment of the potential risks to human and animal health.
https://wwwnc.cdc.gov/eid/article/24/6/17-2007_article
http://camelusprp.blogspot.com/2018/04/tse-prion-disease-in-dromedary-camels.html
Wednesday, May 30, 2018
Dromedary camels in northern Africa have a neurodegenerative prion disease that may have originated decades ago
http://camelusprp.blogspot.com/2018/05/dromedary-camels-in-northern-africa.html
http://camelusprp.blogspot.com/
TUESDAY, AUGUST 7, 2018
Unexpected prion phenotypes in experimentally transfused animals: predictive models for humans?
http://transmissiblespongiformencephalopathy.blogspot.com/2018/08/unexpected-prion-phenotypes-in.html
TUESDAY, JULY 31, 2018
USA CJD TSE Tables of Cases Examined National Prion Disease Pathology Surveillance Center Cases Examined May 1, 2018
http://prionunitusaupdate.blogspot.com/2018/07/usa-cjd-tse-tables-of-cases-examined.html
Volume 2: Science
4. The link between BSE and vCJD
Summary
4.29 The evidence discussed above that vCJD is caused by BSE seems overwhelming. Uncertainties exist about the cause of CJD in farmers, their wives and in several abattoir workers. It seems that farmers at least might be at higher risk than others in the general population. 1 Increased ascertainment (ie, increased identification of cases as a result of greater awareness of the condition) seems unlikely, as other groups exposed to risk, such as butchers and veterinarians, do not appear to have been affected. The CJD in farmers seems to be similar to other sporadic CJD in age of onset, in respect to glycosylation patterns, and in strain-typing in experimental mice. Some farmers are heterozygous for the methionine/valine variant at codon 129, and their lymphoreticular system (LRS) does not contain the high levels of PrPSc found in vCJD. It remains a remote possibility that when older people contract CJD from BSE the resulting phenotype is like sporadic CJD and is distinct from the vCJD phenotype in younger people...
BSE INQUIRY
TUESDAY, JULY 31, 2018
USA CJD TSE Tables of Cases Examined National Prion Disease Pathology Surveillance Center Cases Examined May 1, 2018
http://prionunitusaupdate.blogspot.com/2018/07/usa-cjd-tse-tables-of-cases-examined.html
Terry S. Singeltary Sr.
Bacliff, Texas USA 77518
Galveston Bay, on the bottom...
posted by Terry S. Singeltary Sr. | 3:03 PM
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