MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON
CREUTZFELDT JAKOB DISEASE 1978
MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON
CREUTZFELDT JAKOB DISEASE 1978
MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON
CREUTZFELDT-JAKOB DISEASE
Minutes of meeting held on Thursday 9 March 1978 at 20 Park Crescent London
WIN 4AL
Present: Professor J N Walton (Chairman), Dr A M Adelstein, Professor J R
Batchelor, Mr K N Burns (ARC), Professor J A N Corsellis, Dr T J Crow, Dr R
Levy, Professor W B Matthews, Dr J T Stamp, Professor B E Tomlinson, Professor M
P Vessey, Professor P Wildy, Dr A Smithies (Health Department Observer).
Headquarters staff: Dr Katherine levy, Dr Victoria Harrison, Miss Roberta
Withnall.
Amlogies for absence: Professor A N Davison, Dr R H Kimberlin, Dr W A
Lishman, Professor C A Mims-
1. Introduction and background
The Chairman opened the meeting by explaining that its purpose was to
advise the Neurosciences Board on the value and feasibility of carrying out
epidemiological studies on Creutzfeldt—Jakob (C—J) disease; suggestions for work
on other aspects of the disease were not, however, precluded.
***The meeting had been called following the Agricultural Research
Council's (ARC) report of their Advisory Committee on Scrapie, a document which
should be regarded as confidential.
One of the main issues which merited discussion was whether those whose
occupation suggested they might be in contact with scrapie had a higher risk of
developing C—J disease. While fully appreciating that the problem of infectivity
was one of great concern the present meeting was not constituted to discuss this
problem per se. The recently set up ARC Advisory Group on Scrapie would be
taking up this question; it was also of concern to the Health Departments who
wished to be kept informed of developments. Mr Burns reported that the ARC had
already had preliminary discussions on the safety aspects which would be
necessary in the event of C—J work being carried out in their Institute at
Compton. Dr Levy agreed to act as liaison officer between the two Councils and
the Health Departments.
.2 snip...
The meeting considered the mortality data provided by OPCS (CJD 78/2) and
that provided by Professor Matthews (paper tabled). The interpretation of these
data was complicated by possibilities of both under and over reporting.
Under-reporting was likely in that G—J disease might:
(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.
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
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.
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
(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.
(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.
i enclose a list of ICD categories showing the numbers of deaths attributed
to each (as underlying cause) in England and Hales in 1975.
xxxxx...122...1 mentioned C-J with dimentia, 24 mentioned Alzheimer’s
disease, 1 mentioned Pick’s disease.
snip...
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.
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...
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
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).
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
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).
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
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
‘’These results demonstrate that scrapie prions have a zoonotic potential
and raise new questions about the possible link between animal and human
prions.’’
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
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.
Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves
Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle
Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia
Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier Andréoletti1,
Affiliations Contributions Corresponding author Journal name: Nature
Communications Volume: 5, Article number: 5821 DOI: doi:10.1038/ncomms6821
Received 07 August 2014 Accepted 10 November 2014 Published 16 December 2014
Article tools Citation Reprints Rights & permissions Article metrics
Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant
Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie
prions remains unknown. Mice genetically engineered to overexpress the human
prion protein (tgHu) have emerged as highly relevant models for gauging the
capacity of prions to transmit to humans. These models can propagate human
prions without any apparent transmission barrier and have been used used to
confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie
prions transmit to several tgHu mice models with an efficiency comparable to
that of cattle BSE. The serial transmission of different scrapie isolates in
these mice led to the propagation of prions that are phenotypically identical to
those causing sporadic CJD (sCJD) in humans. These results demonstrate that
scrapie prions have a zoonotic potential and raise new questions about the
possible link between animal and human prions.
snip...
Do our transmission results in tgHu imply that sheep scrapie is the cause
of sCJD cases in humans? This question challenges well-established dogma that
sCJD is a spontaneous disorder unrelated to animal prion disease. In our
opinion, our data on their own do not unequivocally establish a causative link
between natural exposure to sheep scrapie and the subsequent appearance of sCJD
in humans. However, our studies clearly point out the need to re-consider this
possibility. Clarification on this topic will be aided by informed and modern
epidemiological studies to up-date previous analysis that was performed at the
end of the last century3, 4. The value of such an approach is highlighted by the
implementation in the year 2000 of large-scale active animal TSE surveillance
programs around the world that provided an informed epidemiological-based view
of the occurrence and geographical spread of prion disease in small ruminant
populations51. The fact that both Australia and New-Zealand, two countries that
had been considered for more than 50 years as TSE-free territories, were finally
identified positive for atypical scrapie in their sheep flocks provides an
example of how prion dogma can be reversed52. However, the incubation period for
prion disease in humans after exposure to prions via the peripheral route, such
as in iatrogenic CJD transmission and Kuru, can exceed several decades53, 54. In
this context, it will be a challenge to combine epidemiological data collected
contemporarily in animal populations and humans to investigate the existence of
a causative link between prion disease occurrence in these different hosts.
Furthermore, it is crucial to bear in mind that sporadic sCJD in humans is a
rare disease (1–2 individuals per million of the population per year) and that
scrapie has been circulating in small ruminants populations used for food
purposes for centuries. Consequently, it is our opinion that even if a causative
link was established between sheep scrapie exposure and the occurrence of
certain sCJD cases, it would be wrong to consider small ruminant TSE agents as a
new major threat for public health. Despite this, it remains clear that our data
provide a new impetus to establish the true zoonotic potential of sheep scrapie
prions.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Transmission of scrapie prions to primate after an extended silent
incubation period
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.
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),
***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.
***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.
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X
Press reports indicate that increased surveillance is catching what
otherwise would have been unreported findings of atypical scrapie in sheep. In
2009, five new cases have been reported in Quebec, Ontario, Alberta, and
Saskatchewan. With the exception of Quebec, all cases have been diagnosed as
being the atypical form found in older animals. Canada encourages producers to
join its voluntary surveillance program in order to gain scrapie-free status.
The World Animal Health will not classify Canada as scrapie-free until no new
cases are reported for seven years. The Canadian Sheep Federation is calling on
the government to fund a wider surveillance program in order to establish the
level of prevalence prior to setting an eradication date. Besides long-term
testing, industry is calling for a compensation program for farmers who report
unusual deaths in their flocks.
Christie M. Loiacono,' Bruce V. Thomsen, S. Mark Hall, Matti Kiupe!, Diane
Sutton, Katherine O'Rourke, Bradd Barr, Lucy Anthenill, Deiwyn Keane
Abstract.
A distinct strain of scrapic identified in sheep of Norway in 1998 has
since been identified in numerous countries throughout Europe. The disease is
known as Nor98 or Not-98-like scrapic. among other names. Distinctions between
classic scrapie and Nor98 scrapie are made based on histopathologv and
immunodiagnostic results. There are also differences in the epidemiology,
typical signalment, and likelihood of clinical signs being observed. In
addition, sheep that have genotypes associated with resistance to classic
scrapie are not spared from Nor98 disease. The various differences between
classic and Nor98 scrapie have been consistently reported in the vast majority
of cases described across Europe. The current study describes in detail the
patholo gic changes and diagnostic results of the first 6 cases of' Nor98
scrapic disease diagnosed in sheep of the United States.
Key words: Hisiopathology: Nor98: PrP imniunolabeling; scrapie: sheep.
snip...
The first case identified as consistent with Nor98 scrapie had nonclassic
PrP distribution in brain tissue, no PrPSC in lymph tissue, and nonclassic
migration of protein bands on a Western blot test. The animal was an aged,
mottled-faced ewe that was traced back to a commercial flock in Wyoming. ...
The second case was a clinically normal 8-year-old Suffolk ewe that had
been in a quarantined flock for 5 years at a USDA facility in Iowa.
A 16-year-old, white-faced, cross-bred wether was born to a black-faced
ewe. He lived his entire life as a pet on a farm in California.
The fourth case of Nor98 scrapie was identified in an approximately
8-year-old Dorset ewe that was born into a flock of approximately 20 ewes in
Indiana.
The fifth case was a clinically normal, approximately 3-year-old,
white-faced, cross-bred ewe from an approximately 400 head commercial flock in
Minnesota.
The sixth case of Nor98 scrapie was identified in a 4-year-old, white-faced
ewe that was purchased and added to a commercial flock in Pennsylvania
snip...
https://journals.sagepub.com/doi/10.1177/104063870902100406
Monday, April 25, 2011 Experimental Oral Transmission of Atypical Scrapie
to Sheep
Volume 17, Number 5-May 2011
Sunday, April 18, 2010
SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010
Thursday, November 18, 2010
Increased susceptibility of human-PrP transgenic mice to bovine spongiform
encephalopathy following passage in sheep
Wednesday, January 19, 2011
EFSA and ECDC review scientific evidence on possible links between TSEs in
animals and humans Webnachricht 19 Januar 2011
Monday, June 27, 2011
Comparison of Sheep Nor98 with Human Variably Protease-Sensitive
Prionopathy and Gerstmann-Sträussler-Scheinker Disease
Thursday, February 23, 2012
Atypical Scrapie NOR-98 confirmed Alberta Canada sheep January 2012
Thursday, March 29, 2012
atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012
NIAA Annual Conference April 11-14, 2011San Antonio, Texas
Atypical NOR98 Scrapie USA UPDATE,2016, to date, atypical NOR98 Scrapie has
been documented in 8 cases.
Positive Cases and Infected/Source Flocks
Positive Scrapie Cases*
Thirteen positive cases have been reported in FY 2016. Eight of the cases
were from a source flock that was designated in October because of an RSSS
positive animal reported in September 2015. Location of the cases is shown in
Table 1and Figure 1, and distribution by face-color (sheep) and type (goats) is
shown in Table 2.
USDA confirmed 41 cases in goats from FY 2002 through FY 2015 (Figure 2).
No goats have tested positive in FY 2016.
Infected and Source Flocks
As of June 30, 2016, there were two flocks with an open infected or source
status
(Figure 3). Two infected and three source flocks have been designated in FY
2016 (Figure 4); four flocks have completed clean-up plans and have been
released (Figure 5). New infected and source statuses from FY 1997 to FY 2016
are depicted in Chart 2.
Introduction –Positive Cases & Infected/Source Flocks
* Samples collected between October 1, 2015 and June 30, 2016 and confirmed
by July 15, 2016.w
Surveillance
Regulatory Scrapie Slaughter Surveillance (RSSS)
RSSS started April 1, 2003. It is a targeted slaughter surveillance program
which is designed to identify infected flocks. Samples have been collected from
511,135 animals since April 1, 2003. There have been 479 NVSL confirmed positive
animals* (471 classical cases and 8 Nor98-like cases) since the beginning of
RSSS. As of June 30, 2016, 28,533 samples have been collected in FY 2016, 22,889
from sheep and 5,644 from goats.
As of June 30, 2016, one black-faced sheep* tested positive for scrapie in
FY 2016. The weighted percentage of samples that have tested positive for each
face color** from FY 2003 through FY 2016 is depicted in Chart 3a. In November
2013, administrative units within APHIS Veterinary Services reorganized from 2
Regions to 6 Districts (Figure 6). The distribution of sheep and goat
populations by District is depicted in Chart 4a. The number of animals collected
for FY 2016 by District where collected is shown in Chart 4b. A monthly
comparison of RSSS collections by fiscal year is displayed in Chart 5. Chart 6is
a retrospective 6-month rolling average of the percent positive, black-faced
sheep sampled at RSSS collection sites.
* RSSS positives are reported based on collection date and may have been
confirmed after June 30, 2016.
** White, black and mottled face color sheep are weighted based on
population. White faced sheep have the highest weight, so when the uncommon
white face positive sheep is found it will cause this statistic to markedly
increase
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.
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.
OR
***The pathology features of Nor98 in the cerebellum of the affected sheep
showed similarities with those of sporadic Creutzfeldt-Jakob disease in
humans.
OR
*** Intriguingly, these conclusions suggest that some pathological features
of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.
*** 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.
Monday, June 27, 2011
Comparison of Sheep Nor98 with Human Variably Protease-Sensitive
Prionopathy and Gerstmann-Sträussler-Scheinker Disease
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 ;
UPDATE American Indian Genocide Continues – Scrapie Prion
American Indian Genocide Continues - Scrapie Prion
July 5, 2009 by admin1
Filed under Featured, Genocide, News
Discuss Now!
FOR IMMEDIATE RELEASE:
The planned genocide against the Navajo People of New Mexico, Arizona and Utah continues with the latest poisoning and cover-up by the United States.
Navajos have faced well documented cases of mining Uranium without required protection, exposing them to facing premature abortions, cancer, degenerative diseases and death.
They have lived in the shadow of Rio Puerco, a Uranium waste spill that exceeds 3 Mile Island in the amount of nuclear material leached into the ground, with hundreds of people effected and which has yet to be cleaned up.
They have been poisoned by the United States at Fort Windgate, where Navajo People were exposed to the Hantavirus for the crime of living downwind from the Fort Windgate Munitions Depot. Though rarely mentioned, all cases of Hantavirus in the United States have occurred downwind of U.S. Military Munitions Storage Depots, in Hanford, in Long Island, New York and in Southern California.
And now:
Below is an urgent report we received from New Mexico. Dr Milo Muller has found evidence of mass poisoning of the sheep supply and gross criminal neglegence in the oversight of the USDA, further poisoning the Navajo People.
Not only are we demanding an investigation to this outbreak of Scrapie Prion (Mad Sheep Disease), but all the horrors that the Navajo people have faced in the last 30 years.
“This is continued planned genocide.” Charges Russell Means. “They cannot explain it otherwise.”
Miloslav Muller, DVM, MPVM 634 Eastlake Drive Rio Rancho, New Mexico 87124 505-892-9288
Dear Friend:
My name is Dr. Milo Muller, I am living in Albuquerque, New Mexico, and my profession is a veterinarian epidemiologist. My specialty is a veterinary public health, and part of my training is to investigate outbreaks of diseases transmissible from animals to humans.
Recently, in dealing with two issues of disparate treatment of American Indians in New Mexico, I found an issue that desperately needs the attention of the American public. In this instance, the Federal Government created this issue, failed to take corrective action when violations
of federal laws became known to the upper management in Washington, DC, and then stonewalled a proper investigation of this malfeasance, comparable only to infamous government Tuskegee Experiment on African-American men in 1940’s.
My first concern is that the U.S. Department of Agriculture (USDA) is unlawfully blocking a proper investigation of reckless exposure of American Indians residing on Navaho Reservation in New Mexico to Scrapie Prion (infection agent similar to Mad Cow Disease). My numerous letters and submissions to the U.S. Office of Special Counsel, U.S. Equal Employment Opportunity Commission (EEOC), and to the USDA Inspector General regarding this malfeasance have been ignored, in direct violations of federal government policies and regulations.
Attached to this email in .PDF file are a few examples of my letters to the U.S. Office of Special Counsel (OSC), a small federal agency responsible for investigation of allegations of prohibited personal practices committed by federal employees.
Regretfully, the OSC management, including the head of the Agency Mr. William Reukauf, do not see any wrongdoing when employees of other federal agencies (USDA) committed fiscal fraud for personal benefits for over $100K, or recklessly causing mutton from Scrapie infected sheep to enter human food chain of American Indians in New Mexico, or destruction of federal documents describing this malfeasance (EEOC, Denver and San Francisco District Office).
Disturbing is also fact that my two submissions to Henry Waxman, Chairman, and Tom Davis, Ranking Member, Committee on Oversight and Government Reform, U.S. House of Representatives, remains unanswered (attached are copies of both submissions). It should come as no surprise that my third letter on this subject dated February 14, 2009, addressed to Edolphus Towns, who replaced Henry Waxman, also remains unanswered.
The second issue is illegal destruction of part of USDA, EEO official complaint file pertinent to discrimination complaint registered by Mr. Carlos Jojola, one-race American Indian from Isleta Pueblo, New Mexico. Destruction of official complaint file documents was committed by the USDA Civil Rights Office employees in close cooperation with the EEOC Phoenix District Office management for sole purpose to falsely claim that in this particular EEO case “no discrimination occurred”.
The case was four and half years inactive (in accordance with federal policy it should be resolved in time limit of 180 calendar days), and then suddenly the Agency (USDA) issued its racist, bizarre decision claiming that “no discrimination occurred”, in contrary to factual evidence of the record.
Mr. Carlos Jojola was my coworker employed by the USDA in Albuquerque, New Mexico. I am still serving as his EEO Representative in this discrimination case that is currently at the administrative EEOC level. The cause of action in this EEO complaint is racial discrimination, failure to provide reasonable accommodation for Mr. Jojola’s disabilities, and harassment by employees of the USDA Personal Operation Branch in Minneapolis, MN.
For your information, attached in .PDF file is an Appeal Form that I submitted to the EEOC in February 2009. Neither USDA nor EEOC contacted me in a good faith for early resolution of this case. Both issues are extreme examples how federal government treats American Indians despite its rhetoric about Equal Employment Opportunity and other baseless claims. I have available 100’s of pages of supporting documents fully confirming my allegations.
In my opinion, after quite frustrating experience with multiple governmental entities, I believe that only solution to this situation would be to contact newspapers and to let American public know this malfeasance.
Please contact any trusted journalist who is willing to report on this issue.
Thank you very much for your time.
Sincerely,
Miloslav Muller, DVM, MPVM 634 Eastlake Drive Rio Rancho, New Mexico 87124 505-892-9288
About the Attached:
In attachments please find four examples of Scrapie positive test results from the Colorado State Diagnostic Laboratory that is part of School of Veterinary Medicine. Hard copies are available upon request.
Also attached is an article describing the Innunohistochemistry test (IHC) that was used at the above mentioned laboratory for regular screening of those samples. As you can see, this test is practically 100 percent accurate. Basically, it is based on molecular markers, and if in particular sample is present infectious agent Prion, part of affected sample will turn purple. Basically, 4th grader can make diagnosis of positive or negative samples based on color change. It is very specific, as you can see from an article.
Do not be confused by statement on test results form that “these results have not been confirmed by National Veterinary Service Laboratory”.
These are standard operating procedures for USDA for any tests performed by a contract laboratories in the USA. In this particular case, this served as a political tool to “decide” what test will be classified as positive or negative, depending on their political agenda, in this case for covering fraud.
Since USDA knew that the collection of samples was fraudulent, and that the collector, USDA technician Mr. Braman, collected samples on monthly basis instead on daily basis as he was paid for, about ten days later, on April 27, 2006, USDA stated that all previously positive samples were “negative”. I will send you hard copies of that “decision” in mail. This was of course whitewash for purpose to cover up for illegal activities of multiple USDA officials.
Also, I am sending you one page of scanned slaughter dates for Hunts Meats in Waterflow, New Mexico. This is a plant that slaughtered those infected animals. Please see that the plant was not operating on January 20, 2006, but USDA technician claimed that on that day he collected samples (Test number 420, attached scanned copy) that had one positive sheep. I have multiple documents proving that this was ongoing issue of fraudulently submitted Scrapie samples. Basically, this plant was not inspected as required by USDA regulations, and it is massive multi-level fraud. The owner of the plant contacted USDA in Washington in writing, but they refused to investigate.
This issue should be presented to the press without any unclear areas, so USDA would not have any legitimate defense.
I also contacted Government Accountability Project in Washington DC, who partially worked on this issue three years ago, together with me and with the plant owners. I will hear from them soon if they would be willing to reopen this case. In th epast, they contacted USDA with request for those samples (for purpose to send them to England for confirmation of Scrapie), but USDA refused to communicate with them.
Milo Muller
-Article about IHC Test
-2nd Letter to OSC Bloch Oct 29 2009
-5th Letter to OSC Reukauf 6 2009
-Carlos Jojola EEOC Appeal Form Feb 2009
-Letter to Rep Henry Waxman Oct 2008
-Letter to RepTom Davis Oct 2008
-Scrapie Pos Test 405
-Scrapie Pos Test 409
-Scrapie Pos Test 419
-Scrapie Pos Test 420
-Slaughter Dates for January 2006
Milo Muller’s Supporting Documents
Friday, February 04, 2011
NMLB and USDA allow scrapie prion infected mutton to enter food chain on
the Navajo Reservation in New Mexico
----- Original Message -----
From: Terry S. Singeltary Sr.
To: President.BenShelly
Cc: sroanhorse ; opvp.nelson ; alaughing; georgehardeen; pressoffice
Sent: Thursday, February 03, 2011 12:15 PM
Subject: NMLB and USDA allow scrapie prion infected mutton to enter food
chain on the Navajo Reservation in New Mexico
Greetings Honorable People of the Great Navajo Nation, and the Honorable
President Ben Shelly,
I send this to you with great concern. ...
With Kindest Regards and Great Respect,
terry
Terry S. Singeltary Sr. P.O. Box Bacliff, Texas USA 77518
flounder9@verizon.net
NMLB and USDA allow scrapie prion infected mutton to enter food chain on
the Navajo Reservation in New Mexico
MULLER v. CULBERTSON
MILOSLAV MULLER, Plaintiff-Appellant,v.MYLES CULBERTSON, DIRECTOR NEW
MEXICO LIVESTOCK BOARD (AGENCY), Defendant-Appellee.
snip...see full text ;
Thursday, October 10, 2013
CJD REPORT 1994 increased risk for consumption of veal and venison and lamb
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH
CODE
Thursday, December 20, 2012
*** OIE GROUP RECOMMENDS THAT SCRAPE PRION DISEASE BE DELISTED, WISHES TO
CONTINUE SPREADING IT AROUND THE GLOBE
Friday, July 01, 2016
*** TEXAS Thirteen new cases of chronic wasting disease (CWD) were
confirmed at a Medina County captive white-tailed deer breeding facility on June
29, 2016***
*** 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...
NEWS RELEASE
April 22, 2016
Scrapie Confirmed in a Hartley County Sheep
AUSTIN - Texas Animal Health Commission (TAHC) officials have confirmed
scrapie in a Hartley County ewe. The ewe was tested by TAHC after the owner
reported signs of weight loss and lack of coordination to their local
veterinarian. The premises was quarantined and a flock plan for monitoring is
being developed by the TAHC and USDA.
"The TAHC is working closely with the flock owner, sharing all of the
options for disease eradication," said Dr. David Finch, TAl-lC Region 1
Director. ‘We are thankful the producer was proactive in identifying a problem
and seeking veterinary help immediately.”
Texas leads the nation in sheep and goat production. Since 2003, there have
been no confirmed cases of scrapie in Texas. The last big spike in Texas scrapie
cases was in 2006 when nine infected herds were identified and the last herd was
released from restrictions in 2013.
According to USDA regulations, Texas must conduct adequate scrapie
surveillance by collecting a minimum of 598 sheep samples annually. Since USDA
slaughter surveillance started in FY 2003, the percent of cull sheep found
positive for scrapie at slaughter (once adjusted for face color) has decreased
90 percent.
Scrapie is the oldest known transmissible spongiform encephalopathies, and
under natural conditions only sheep and goats are known to be affected by
scrapie. It is a fatal disease that affects the central nervous system of sheep
and goats. It is not completely understood how scrapie is passed from one animal
to the next and apparently healthy sheep infected with scrapie can spread the
disease. Sheep and goats are typically infected as young lambs or kids, though
adult sheep and goats can become infected.
The most effective method of scrapie prevention is to maintain a closed
flock. Raising replacement ewes, purchasing genetically resistant rams and ewes,
or buying from a certified-free scrapie flock are other options to reduce the
risk of scrapie. At this time the resistant genetic markers in goats have not
been identified, therefore it is important to maintain your sheep and goat herds
separately.
The incubation period for scrapie is typically two to five years. Producers
should record individual identification numbers and the seller's premise
identification number on purchase and sales records. These records must be
maintained for a minimum of five years.
TEXAS Sheep and Goats
• Most recent scrapie positive animal in Texas was found in April,
2008.
• USDA-APHIS-VS set the national goal for surveillance at 46,000 traceable,
mature sheep or goats. Target for Texas is 1,472.
• The Scrapie Program Review is being scheduled for this summer. No
problems expected.
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.
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
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. ...
also see hand written notes ;
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...
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/20010614054402/http://www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf
RISK OF BSE TO SHEEP VIA FEED
http://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.
Wednesday, January 18, 2012
BSE IN GOATS CAN BE MISTAKEN FOR SCRAPIE
February 1, 2012
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
Wednesday, May 25, 2016
USDA APHIS National Scrapie TSE Prion Eradication Program April 2016
Monthly Report Prion 2016 Tokyo Update
Monday, July 18, 2016
Texas Parks Wildlife Dept TPWD HIDING TSE (CWD) in Deer Herds, Farmers
Sampling Own Herds, Rapid Testing, False Negatives, a Recipe for Disaster
Scrapie-like disorder in a Nyala (Tragelaphus angasi)
IN CONFIDENCE
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...
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.
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
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
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.
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.
Thursday, August 20, 2015 Doctor William J. Hadlow
William J. Hadlow Dr. Hadlow (Ohio State ’48), 94, Hamilton, Montana, died
June 20, 2015.
Spongiform Encephalopathy in Captive Wild ZOO BSE INQUIRY
Tuesday, April 19, 2016
Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards
Singeltary Comment Submission
Tuesday, April 19, 2016
Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards
Singeltary Comment Submission
https://www.regulations.gov/comment/FDA-2003-D-0432-0011
Sunday, July 17, 2016
*** CHRONIC WASTING DISEASE CWD TSE PRION GLOBAL REPORT UPDATE JULY 17 2016
Saturday, May 28, 2016
*** Infection and detection of PrPCWD in soil from CWD infected farm in
Korea Prion 2016 Tokyo ***
Saturday, July 16, 2016
Importation of Sheep, Goats, and Certain Other Ruminants [Docket No.
APHIS-2009-0095]RIN 0579-AD10
WITH great disgust and concern, I report to you that the OIE, USDA, APHIS,
are working to further legalize the trading of Transmissible Spongiform
Encephalopathy TSE Pion disease around the globe.
THIS is absolutely insane. it’s USDA INC.
Friday, January 30, 2015
*** Scrapie: a particularly persistent pathogen ***
Saturday, July 23, 2016
*** BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING,
AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016
Tuesday, July 26, 2016
*** Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY
2016
Sunday, July 17, 2016
*** CHRONIC WASTING DISEASE CWD TSE PRION GLOBAL REPORT UPDATE JULY 17 2016
Monday, June 20, 2016
*** Specified Risk Materials SRMs BSE TSE Prion Program
Saturday, May 28, 2016
*** Infection and detection of PrPCWD in soil from CWD infected farm in
Korea Prion 2016 Tokyo ***
RE: re-Human Prion Diseases in the United States
Singeltary PLoS
part 2 flounder replied to flounder on 02 Jan 2010 at 21:26 GMT
No competing interests declared.
see full text ;
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.***
Monday, May 02, 2016
*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***
*** NIH awards $11 million to UTHealth researchers to study deadly CWD
prion diseases Claudio Soto, Ph.D. ***
Public Release: 29-Jun-2016
I urge everyone to watch this video closely...terry
*** you can see video here and interview with Jeff's Mom, and scientist
telling you to test everything and potential risk factors for humans ***
https://histodb15.usz.ch/pages/Images/videos/video-004/video-004.html
Tuesday, July 12, 2016
Chronic Wasting Disease CWD, Scrapie, Bovine Spongiform Encephalopathy BSE,
TSE, Prion Zoonosis Science History
see history of NIH may destroy human brain collection
FLASHBACK 2001
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep
infected with scrapie?
28 Mar 01 Most doctors believe that sCJD is caused by a prion protein
deforming by chance into a killer. But Singeltary thinks otherwise. He is one of
a number of campaigners who say that some sCJD, like the variant CJD related to
BSE, is caused by eating meat from infected animals. Their suspicions have
focused on sheep carrying scrapie, a BSE-like disease that is widespread in
flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight
to the campaigners' fears. To their complete surprise, the researchers found
that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by
some strains of scrapie," says team member Jean-Philippe Deslys of the French
Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses,
south-west of Paris. Hans Kretschmar of the University of Göttingen, who
coordinates CJD surveillance in Germany, is so concerned by the findings that he
now wants to trawl back through past sCJD cases to see if any might have been
caused by eating infected mutton or lamb...
2001
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep
infected with scrapie?
28 Mar 01
Like lambs to the slaughter
31 March 2001
by Debora MacKenzie Magazine issue 2284.
FOUR years ago, Terry Singeltary watched his mother die horribly from a
degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary
was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded
an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming by
chance into a killer. But Singeltary thinks otherwise. He is one of a number of
campaigners who say that some sCJD, like the variant CJD related to BSE, is
caused by eating meat from infected animals. Their suspicions have focused on
sheep carrying scrapie, a BSE-like disease that is widespread in flocks across
Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight
to the campaigners' fears. To their complete surprise, the researchers found
that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by
some strains of scrapie," says team member Jean-Philippe Deslys of the French
Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses,
south-west of Paris. Hans Kretschmar of the University of Göttingen, who
coordinates CJD surveillance in Germany, is so concerned by the findings that he
now wants to trawl back through past sCJD cases to see if any might have been
caused by eating infected mutton or lamb.
Scrapie has been around for centuries and until now there has been no
evidence that it poses a risk to human health. But if the French finding means
that scrapie can cause sCJD in people, countries around the world may have
overlooked a CJD crisis to rival that caused by BSE.
Deslys and colleagues were originally studying vCJD, not sCJD. They
injected the brains of macaque monkeys with brain from BSE cattle, and from
French and British vCJD patients. The brain damage and clinical symptoms in the
monkeys were the same for all three. Mice injected with the original sets of
brain tissue or with infected monkey brain also developed the same
symptoms.
As a control experiment, the team also injected mice with brain tissue from
people and animals with other prion diseases: a French case of sCJD; a French
patient who caught sCJD from human-derived growth hormone; sheep with a French
strain of scrapie; and mice carrying a prion derived from an American scrapie
strain. As expected, they all affected the brain in a different way from BSE and
vCJD. But while the American strain of scrapie caused different damage from
sCJD, the French strain produced exactly the same pathology.
"The main evidence that scrapie does not affect humans has been
epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute
for Animal Health in Edinburgh, who was a member of the same team as Deslys.
"You see about the same incidence of the disease everywhere, whether or not
there are many sheep, and in countries such as New Zealand with no scrapie." In
the only previous comparisons of sCJD and scrapie in mice, Bruce found they were
dissimilar.
But there are more than 20 strains of scrapie, and six of sCJD. "You would
not necessarily see a relationship between the two with epidemiology if only
some strains affect only some people," says Deslys. Bruce is cautious about the
mouse results, but agrees they require further investigation. Other trials of
scrapie and sCJD in mice, she says, are in progress.
People can have three different genetic variations of the human prion
protein, and each type of protein can fold up two different ways. Kretschmar has
found that these six combinations correspond to six clinical types of sCJD: each
type of normal prion produces a particular pathology when it spontaneously
deforms to produce sCJD.
But if these proteins deform because of infection with a disease-causing
prion, the relationship between pathology and prion type should be different, as
it is in vCJD. "If we look at brain samples from sporadic CJD cases and find
some that do not fit the pattern," says Kretschmar, "that could mean they were
caused by infection."
There are 250 deaths per year from sCJD in the US, and a similar incidence
elsewhere. Singeltary and other US activists think that some of these people
died after eating contaminated meat or "nutritional" pills containing dried
animal brain. Governments will have a hard time facing activists like Singeltary
if it turns out that some sCJD isn't as spontaneous as doctors have
insisted.
Deslys's work on macaques also provides further proof that the human
disease vCJD is caused by BSE. And the experiments showed that vCJD is much more
virulent to primates than BSE, even when injected into the bloodstream rather
than the brain. This, says Deslys, means that there is an even bigger risk than
we thought that vCJD can be passed from one patient to another through
contaminated blood transfusions and surgical instruments.
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14,
2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1
reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD)
has been stable since 1985. These estimates, however, are based only on reported
cases, and do not include misdiagnosed or preclinical cases. It seems to me that
misdiagnosis alone would drastically change these figures. An unknown number of
persons with a diagnosis of Alzheimer disease in fact may have CJD, although
only a small number of these patients receive the postmortem examination
necessary to make this diagnosis. Furthermore, only a few states have made CJD
reportable. Human and animal transmissible spongiform encephalopathies should be
reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob
disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
26 March 2003
Terry S. Singeltary, retired (medically) CJD WATCH
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment
on the CDC's attempts to monitor the occurrence of emerging forms of CJD.
Asante, Collinge et al [1] have reported that BSE transmission to the
129-methionine genotype can lead to an alternate phenotype that is
indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD
and all human TSEs are not reportable nationally. CJD and all human TSEs must be
made reportable in every state and internationally. I hope that the CDC does not
continue to expect us to still believe that the 85%+ of all CJD cases which are
sporadic are all spontaneous, without route/source. We have many TSEs in the USA
in both animal and man. CWD in deer/elk is spreading rapidly and CWD does
transmit to mink, ferret, cattle, and squirrel monkey by intracerebral
inoculation. With the known incubation periods in other TSEs, oral transmission
studies of CWD may take much longer. Every victim/family of CJD/TSEs should be
asked about route and source of this agent. To prolong this will only spread the
agent and needlessly expose others. In light of the findings of Asante and
Collinge et al, there should be drastic measures to safeguard the medical and
surgical arena from sporadic CJDs and all human TSEs. I only ponder how many
sporadic CJDs in the USA are type 2 PrPSc?
http://web.archive.org/web/20140601123343/http://www.neurology.org/content/60/2/176/reply
Freas Monday, January 08,2001 3:03 PM
FDA Singeltary submission 2001
Greetings again Dr. Freas and Committee Members,
I wish to submit the following information to the Scientific Advisors and Consultants Staff 2001 Advisory Committee (short version). I understand the reason of having to shorten my submission, but only hope that you add it to a copy of the long version, for members to take and read at their pleasure, (if cost is problem, bill me, address below). So when they realize some time in the near future of the 'real' risks i speak of from human/animal TSEs and blood/surgical products. I cannot explain the 'real' risk of this in 5 or 10 minutes at some meeting, or on 2 or 3 pages, but will attempt here:
snip...see full text ;
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
From: TSS (216-119-138-163.ipset18.wt.net)
Subject: Louping-ill vaccine documents from November 23rd, 1946
Date: September 10, 2000 at 8:57 am PST
Subject: Louping-ill vaccine documents from November 23rd, 1946
Date: Sat, 9 Sep 2000 17:44:57 –0700
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy To: BSE-L@uni-karlsruhe.de
######### Bovine Spongiform Encephalopathy #########
THE VETERINARY RECORD 516 No 47. Vol. 58 November 23rd, 1946
NATIONAL VETERINARY MEDICAL ASSOCIATION OF GREAT BRITAIN AND IRELAND
ANNUAL CONGRESS, 1946
The annual Congress, 1946, was held at the Royal Veterinary College, Royal
College Street, London, N.W.I. from September 22nd to September 27th.
Opening Meeting
[skip to scrapie vaccine issue...tss]
Papers Presented to Congress
The papers presented to this year's Congress had as their general theme the
progressive work of the profession during the war years. Their appeal was
clearly demonstrated by the large and remarkably uniform attendance in the Grand
Hall of the Royal Veterinary College throughout the series; between 200 and 250
members were present and they showed a keen interest in every paper, which was
reflected in the expression of some disappointment that the time available for
discussion did not permit of the participation of more than a small proportion
of would-be contributors.
In this issue we publish (below) the first to be read and discussed, that
by Dr. W. S. Gordon, M.R.C.V.S., F.R.S.E., "Advances in Veterinary Research."
Next week's issue will contain the paper on "Some Recent Advances in Veterinary
Medicine and Surgery in Large-Animal Practice" by Mr. T. Norman Gold, M.R.C.V.S.
In succeeding numbers of the Record will be reproduced, also with reports of
discussions, that by Mr. W. L. Weipers, M.R.C.V.S., D.V.S.M., on the same
subject as relating to small-animal practice, and the papers by Mr. J. N.
Ritchie, B.SC., M.R.C.V.S., D.V.S.M., and Mr. H.W. Steele-Bodger, M.R.C.V.S., on
"War-time Achievements of the British Home Veterinary Services."
The first scientific paper of Congress was read by Dr. W. S. Gordon,
M.R.C.V.S., F.R.S.E. on Monday, September 23rd, 1946, when Professor J. Basil
Buxton, M.A., F.R.C.V.S, D.V.H., Prinicipal of the Royal Veterinary College,
presided.
Advances in Veterinary Research
by
W.S. GORDON, PH.D., M.R.C.V.S., F.R.S.E.
Agriculteral Research Council, Field Station, Compton, Berks.
Louping-ill, Tick-borne Fever and Scrapie
In 1930 Pool, Browniee & Wilson recorded that louping-ill was a
transmissible disease. Greig et al, (1931) showed that the infective agent was a
filter-passing virus with neurotropic characters and Browniee & Wilson
(1932) that the essential pathology was that of an encephalomyelitis. Gordon,
Browniee, Wilson & MacLeod (1932) and MacLeod & Gordon (1932) confirmed
and extended this work. It was shown that on louping-ill farms the virus was
present in the blood of many sheep which did not show clinical symptoms
indicating involvement of the central nervous system and that for the
perpetuation and spread of the disease these subclinical cases were probably of
greater importance that the frank clinical cases because, in Nature, the disease
was spread by the tick, lxodes ricinus L. More recently Wilson (1945, 1946) has
described the cultivation of the virus in a chick embryo medium, the pathogenic
properties of this culture virus and the preparation of louping-ill antiserum.
Between 1931 and 1934 I carried out experiments which resulted in the
development of an effective vaccine for the prevention of louping-ill.* This
vaccine has been in general use since 1935 and in his annual report to the
Animal Diseases Research Association this year, Dr. Greig stated that about
227,000 doses of vaccine had been issued from Moredun alone.
Dr. Gordon illustrated this portion of his paper by means of graphs and
diagrams projected by the epidiascope.
This investigation, however, did not begin and end with the study of
louping-ill; it had, by good fortune, a more romantic turn and less fortunately
a final dramtic twist which led almost to catastrope. After it had been
established that a solid immunity to louping-ill could be induced in sheep, a
group of immunized and a group of susceptible animals were placed together on
the tick-infected pasture of a louping-ill farm. Each day all the animals were
gathered and their temperatures were recorded. It was anticipated that febrile
reactions with some fatalities would develop in the controls while the
louping-ill immunes would remain normal. Contrary to expectation, however, every
sheep, both immune and control, developed a febrile reaction. This unexpected
result made neccessary further investigation which showed that the febrile
reaction in the louping-ill immunes was due to a hitherto undescribed infective
agent, a Rickettsia-like organism which could be observed in the cytoplasm of
the grannular leucocytes, especially the neutrophil polymorphs (MacLeod (1932),
Gordon, Browniee, Wilson & MacLeod. MacLeod & Gordon (1933). MacLeod
(1936). MacLeod collected ticks over many widely separated parts of Scotland and
all were found to harbour the infective agent of tick-borne fever, and it is
probable that all sheep on tick-infested farms develop this disease, at least on
the first occasion that they become infested with ticks. When the infection is
passed in series through susceptible adult sheep it causes a sever, febrile
reaction, dullness and loss of bodily condition but it rarely, if ever, proves
fatal. It is clear, however, that it aggravates the harmful effects of a
louping-ill infection and it is a serious additional complication to such
infections as pyaemia and the anacrobic infections which beset lambs on the hill
farms of Northern Britain.
Studying the epidemiology of louping-ill on hill farms it became obvious
that the pyaemic condition of lambs described by M'Fadyean (1894) was very
prevalent on tick infested farms Pyaemia is a crippling condition of lambs
associated with tick-bite and is often confused with louping-ill. It is caused
by infection with Staphylococcus aureus and affected animals may show abscess
formation on the skin, in the joints, viscera, meninges and elsewhere in the
body. It was thought that tick-borne fever might have ben a predisposing factor
in this disease and unsuccessful attempts were made by Taylor, Holman &
Gordon (1941) to reproduce the condition by infecting lambs subcutaneously with
the staphylococcus and concurrently produceing infections with tickborne fever
and louping-ill in the same lambs. Work on pyaemia was then continued by
McDiarmid (1946a, 1946b, 1946c), who succeeded in reproducing a pyaemic disease
in mice, guinea-pigs and lambs similar to the naturally occuring condition by
intravenous inoculation of Staphylococcus aureus. He also found a bacteraemic
form of the disease in which no gross pyaemic lesions were observed. The
prevention or treatment of this condition presents a formidable problem. It is
unlikely that staphylococcal ???oid will provide an effective immunity and even
if penicillin proved to be a successful treatment, the difficulty of applying it
in adequate and sustained dosage to young lambs on hill farms would be almost
insurmountable.
>From 1931 to 1934 field trials to test the immunizing value and
harmlessness of the loup-ill vaccine were carried out on a gradually increasing
scale. Many thousands of sheep were vaccinated and similar numbers, living under
identical conditions were left as controls. The end result showed that an
average mortability of about 9 percent in the controls was reduced to less than
1 percent in the vaccinated animals. While the efficiency of the vaccine was
obvious after the second year of work, previous bitter experience had shown the
wisdom of withholding a biological product from widespread use until it had been
successfully produced in bulk, as opposed to small-scale experimental production
and until it had been thoroughly tested for immunizing efficiency and freedom
from harmful effects. It was thought that after four years testing this stage
had been reached in 1935, and in the spring of that year the vaccine was issued
for general use. It comprised a 10 percent saline suspension of brain, spinal
cord and spleen tissues taken from sheep five days after infection with
louping-ill virus by intracerebral inoculation. To this suspension 0-35 percent
of formalin was added to inactivate the virus and its safety for use as a
vaccine was checked by intracerbral inoculation of mice and sheep and by the
inoculation of culture medium. Its protective power was proved by vaccination
sheep and later subjecting them, along with controls, to a test dose of living
virus.
Vaccine for issue had to be free from detectable, living virus and capable
of protecting sheep against a test dose of virus applied subcutaneously. The
1935 vaccine conformed to these standards and was issued for inoculation in
March as three separate batches labelled 1, 2, and 3. The tissues of 140 sheep
were employed to make batch 1 of which 22,270 doses were used; 114 to make batch
2 of which 18,000 doses were used and 44 to make batch 3 of which 4,360 doses
were used. All the sheep tissues incorporated in the vaccine were obtained from
yearling sheep. During 1935 and 1936 the vaccine proved highly efficient in the
prevention of loup-ill and no user observed an ill-effect in the inoculated
animals. In September, 1937, two and a half years after vaccinating the sheep,
two owners complained that scrapie, a disease which had not before been observed
in the Blackface breed, was appearing in their stock of Blackface sheep and
further that it was confined to animals vaccinated with louping-ill vaccine in
1935. At that stage it was difficult to conceive that the occurrence could be
associated with the injection of the vaccine but in view of the implications, I
visited most of the farms on which sheep had been vaccinated in 1935. It was at
this point that the investigation reached its dramatic phase; I shall not forget
the profound effect on my emotions when I visited these farms and was warmly
welcomed because of the great benefits resulting from the application of
louping-ill vaccine, wheras the chief purpose of my visit was to determine if
scrapie was appearing in the inoculated sheep. The enquiry made the position
clear. Scrapie was developing in the sheep vaccinated in 1935 and it was only in
a few instances that the owner was associating the occurrence with louping-ill
vaccination. The disease was affecting all breeds and it was confined to the
animals vaccinated with batch 2. This was clearly demonstrated on a number of
farms on which batch 1 had been used to inoculate the hoggs in 1935 and batch 2
to inoculate the ewes. None of the hoggs, which at this time were three-
year-old ewes. At this time it was difficult to forecast whether all of the
18,000 sheep which had received batch 2 vaccine would develop scrapie. It was
fortunate, however, that the majority of the sheep vaccinated with batch 2 were
ewes and therfore all that were four years old and upwards at the time of
vaccination had already been disposed of and there only remained the ewes which
had been two to three years old at the time of vaccination, consequently no
accurate assessment of the incidence of scrapie could be made. On a few farms,
however, where vaccination was confined to hoggs, the incidence ranged from 1
percent, to 35 percent, with an average of about 5 percent. Since batch 2
vaccine had been incriminated as a probable source of scrapie infection, an
attempt was made to trace the origin of the 112 sheep whose tissues had been
included in the vaccine. It was found that they had been supplied by three
owners and that all were of the Blackface or Greyface breed with the exception
of eight which were Cheviot lambs born in 1935 from ewes which had been in
contact with scrapie infection. Some of these contact ewes developed scrapie in
1936-37 and three surviving fellow lambs to the eight included in the batch 2
vaccine of 1935 developed scrapie, one in September, 1936, one in February,
1937, and one in November, 1937. There was, therefore, strong presumptive
evidence that the eight Cheviot lambs included in the vaccine althought
apparently healthy were, in fact, in the incubative stage of a scrapie infection
and that in their tissues there was an infective agent which had contaminated
the batch 2 vaccine, rendering it liable to set up scrapie. If that assumption
was correct then the evidence indicated that:-
(1) the infective agent of scrapie was present in the brain, spinal cord
and or spleen of infected sheep:
(2) it could withstand a concentration of formalin of 0-35 percent, which
inactivated the virus of louping-ill:
(3) it could be transmitted by subcutaneous inoculation;
(4) it had an incubative period of two years and longer.
Two Frenchmen, Cuille & Chelle (1939) as the result of experiments
commenced in 1932, reported the successful infection of sheep by inoculation of
emulsions of spinal cord or brain material by the intracerebral, epidural,
intraocular and subcutaneous routes The incubation period varied according to
the route employed, being one year intracerebrally, 15 months intraocularly and
20 months subcutaneously. They failed to infect rabbits but succeeded in
infecting goats. Another important part of their work showed that the infective
agent could pass throught a chamberland 1.3 filter, thus demonstrating that the
infective agent was a filtrable virus. It was a curious coincidence that while
they were doing their transmission experiments their work was being confirmed by
the unforeseeable infectivity of a formalinized tissue vaccine.
As a result of this experience a large-scale transmision experiment
involving the ue of 788 sheep was commenced in 1938 on a farm specially taken
for the purpose by the Animal Diseases Research Association with funds provided
by the Agricultural Research Council. The experiment was designed to determine
the nature of the infective agent and the pathogenesis of the disease. It is
only possible here to give a summary of the result which showed that (1) saline
suspensions of brain and spinal cord tissue of sheep affected with scrapie were
infective to normal sheep when inoculatted intracerebrally or subcutaneously;
(2) the incubation period after intracerebral inoculation was seven months and
upwards and only 60 percent of the inoculated sheep developed scrapie during a
period of four and a half years; (3) the incubation period after subcutaneous
inoculation was 15 months and upwards and only about 30 percent of the
inoculated sheep developed the disease during the four and a half years: (4) the
infective agent was of small size and probably a filtrable virus.
The prolonged incubative period of the disease and the remarkable
resistance of the causal agent to formalin are features of distinct interest. It
still remains to determine if a biological test can be devised to detect
infected animals so that they can be killed for food before they develop
clinical symptoms and to explore the possibilities of producing an immunity to
the disease.
==================================================================
Greetings List Members,
pretty disturbing document. now, what would stop this from happening with
the vaccineCJD in children???
kind regards,
Terry S. Singeltary Sr., Bacliff, Texas USA
Sunday, May 18, 2008
MAD COW DISEASE BSE CJD CHILDREN VACCINES
Thursday, April 28, 2016
Persistent residual contamination in endoscope channels; a fluorescence
epimicroscopy study
Saturday, January 16, 2016
Revised Preventive Measures to Reduce the Possible Risk of Transmission of
Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and
Blood Products Guidance for Industry
Saturday, December 12, 2015
CREUTZFELDT JAKOB DISEASE CJD TSE PRION REPORT DECEMBER 14, 2015
2023
0 Comments:
Post a Comment
Subscribe to Post Comments [Atom]
<< Home