Experimental interspecies transmission studies of the transmissible
spongiform encephalopathies to cattle: comparison to bovine spongiform
encephalopathy in cattle
Amir N. Hamir, Marcus E. Kehrli, Jr,1 Robert A. Kunkle, Justin J. Greenlee, Eric M. Nicholson, Jürgen A. Richt, Janice M. Miller, Randall C. Cutlip
Abstract.
Prion diseases or transmissible spongiform encephalopathies (TSEs) of animals include scrapie of sheep and goats; transmissible mink encephalopathy (TME); chronic wasting disease (CWD) of deer, elk and moose; and bovine spongiform encephalopathy (BSE) of cattle. The emergence of BSE and its spread to human beings in the form of variant Creutzfeldt-Jakob disease (vCJD) resulted in interest in susceptibility of cattle to CWD, TME and scrapie. Experimental cross-species transmission of TSE agents provides valuable information for potential host ranges of known TSEs. Some interspecies transmission studies have been conducted by inoculating disease-causing prions intracerebrally (IC) rather than orally; the latter is generally effective in intraspecies transmission studies and is considered a natural route by which animals acquire TSEs. The “species barrier” concept for TSEs resulted from unsuccessful interspecies oral transmission attempts. Oral inoculation of prions mimics the natural disease pathogenesis route whereas IC inoculation is rather artificial; however, it is very efficient since it requires smaller dosage of inoculum, and typically results in higher attack rates and reduces incubation time compared to oral transmission. A species resistant to a TSE by IC inoculation would have negligible potential for successful oral transmission. To date, results indicate that cattle are susceptible to IC inoculation of scrapie, TME, and CWD but it is only when inoculated with TME do they develop spongiform lesions or clinical disease similar to BSE. Importantly, cattle are resistant to oral transmission of scrapie or CWD; susceptibility of cattle to oral transmission of TME is not yet determined.
SNIP...
Chronic wasting disease of cervids
Naturally occurring CWD has been documented in mule deer (Odocoileus hemionus hemionus), black-tailed deer (Odocoileus hemionus columbianus), white-tailed deer (Odocoileus virginianus), Rocky Mountain elk (Cervus elaphus nelsoni) and moose (Alces alces shirasi).3,115 The disease was first recognized in a captive population of mule deer at the Colorado Division of Wildlife Foothills Wildlife Research Facility in Fort Collins during 1967, although identification of the disease as a TSE did not occur until 1978.84,115 Chronic wasting disease can be spread horizontally with an efficiency sufficient to sustain local persistence of CWD in natural populations74 and no defined route of transmission has been determined to date,75 although urine, feces, saliva, velvet, lymphoid tissues and blood of CWDaffected animals have been found to carry PrPd. Recent studies report experimental transmission via saliva and blood is possible.73 Testing of hunter-harvested animals indicates that between approximately 1% and 20% of animals in free ranging deer populations in endemic areas may be affected. Natural transmission may be associated with prions shed in saliva followed by oral uptake during deer-to-deer social interactions or contamination of grazing areas.76 The most prominent clinical sign of CWD is the basis for its name, namely progressive debilitation and eventual emaciation. Some animals may show hypersalivation and difficulty swallowing; elk, in particular, exhibit ataxia and tremors.115 However, reports of carnivorous behavior of deer consuming cervid entrails left behind by hunter harvest of deer or natural causes merits further investigation as a potentially significant factor in horizontal transmission between cervids (Pete Squibb, Consultant Wildlife Solutions LLC, Potterville, Michigan, personal communication).
The most widely accepted hypothesis at this time is that CWD may have originated from an interspecies transmission of scrapie. It is worth noting that experimental transmission of scrapie into elk via IC inoculation is clinically and neuropathologically indistinguishable from CWD with currently available experimental methods.44
Greetings,
I disagree with any statement of certainty when scientist use the word ‘resistant’, with any TSE prion disease. time and time again, once touted as a resistant species, that species go down with a TSE prion disease eventually, as proven recently with the rabbit and the TSE prion, and the finding that ARR/ARR sheep are not as resistant to the TSE prion as first thought. with the many TSE prion strains mounting, and the many atypical TSE prion strains emerging, I again stress the need to refrain from saying ‘never’ or ‘resistant’, when addressing these many TSE prion strains. I feel strongly that under different environmental circumstances, load of the TSE prion agent, infectivity, genetics, all these factors (and more), all these different TSE prion strains can become transmissible, under the right conditions, with any species, and until proven otherwise, regulation on human and animal health _should_ be based on the fact that all TSE prions are transmissible. two decades have been wasted on wishing something would happen, rather than going by science showing that it already has happened. ...
please see ;
Classic Scrapie in Sheep with the ARR/ARR Prion Genotype in Germany and France
Martin H. Groschup,*1 Caroline Lacroux,†1 Anne Buschmann,* Gesine Lühken,‡ Jacinthe Mathey,† Martin Eiden,* Séverine Lugan,† Christine Hoffmann,* Juan Carlos Espinosa,§ Thierry Baron,¶ Juan Maria Torres,§ Georg Erhardt,‡ and Olivier Andreoletti†
In the past, natural scrapie and bovine spongiform encephalopathy (BSE) infections have essentially not been diagnosed in sheep homozygous for the A136R154R171 haplotype of the prion protein. This genotype was therefore assumed to confer resistance to BSE and classic scrapie under natural exposure conditions. Hence, to exclude prions from the human food chain, massive breeding efforts have been undertaken in the European Union to amplify this gene. We report the identifi cation of 2 natural scrapie cases in ARR/ARR sheep that have biochemical and transmission characteristics similar to cases of classic scrapie, although the abnormally folded prion protein (PrPSc) was associated with a lower proteinase-K resistance. PrPSc was clearly distinct from BSE prions passaged in sheep and from atypical scrapie prions. These fi ndings strongly support the idea that scrapie prions are a mosaic of agents, which harbor different biologic properties, rather than a unique entity.
snip...
However, the successful transmission of BSE prions to ARR/ARR sheep showed that the resistance of this genotype toward the TSE agent was not absolute (11). Recently, the identifi cation of previously unrecognized so-called atypical scrapie in sheep of various genotypes, including ARR/ARR, has reinforced this statement (4). We report here the identifi cation and characterization of 2 natural classic scrapie cases in sheep of the ARR/ARR genotype, which are clearly different from BSE and atypical scrapie.
Transgenic Mice Expressing Porcine Prion Protein Resistant to Classical Scrapie but Susceptible to Sheep Bovine Spongiform Encephalopathy and Atypical Scrapie
Juan-Carlos Espinosa,1 María-Eugenia Herva,1 Olivier Andréoletti, Danielle Padilla, Caroline Lacroux, Hervé Cassard, Isabelle Lantier, Joaquin Castilla, and Juan-María Torres
How susceptible pigs are to infection with sheep prions is unknown. We
show, through transmission experiments in transgenic mice expressing porcine
prion protein (PrP), that the susceptibility of this mouse model to bovine
spongiform encephalopathy (BSE) can be enhanced after its passage in ARQ sheep,
indicating that the pathogenicity of the BSE agent is modified after passage in
sheep. Transgenic mice expressing porcine PrP were, nevertheless, completely
resistant to infection with a broad panel of classical scrapie isolates from
different sheep PrP genotypes and with different biochemical characteristics.
The atypical (Nor98 like) isolate (SC-PS152) was the only scrapie isolate
capable of transmission in these mice, although with a marked transmission
barrier. Unexpectedly, the atypical scrapie agent appeared to undergo a strain
phenotype shift upon transmission to porcine-PrP transgenic mice and acquired
new strain properties, suggesting that atypical scrapie agent may exhibit
different phenotypes depending on the host cellular PrP or other genetic
factors.
snip...
Our results could also suggest a common origin for sheep BSE and atypical scrapie agents, which may exhibit different phenotypes depending on the host PrPC or other host factors. Although this last explanation seems to be less likely, so far we cannot draw any definitive conclusion on this issue. Whichever the case, the ability of an atypical scrapie to infect other species and its potential capacity to undergo a strain phenotype shift in the new host prompts new concerns about the possible spread of this uncommon TSE in other species as a masked prion undistinguishable from other strains.
snip...see much more here ;
Increased Atypical Scrapie Detections
Press reports indicate that increased surveillance is catching what otherwise would have been unreported findings of atypical scrapie in sheep. In 2009, five new cases have been reported in Quebec, Ontario, Alberta, and Saskatchewan. With the exception of Quebec, all cases have been diagnosed as being the atypical form found in older animals. Canada encourages producers to join its voluntary surveillance program in order to gain scrapie-free status. The World Animal Health will not classify Canada as scrapie-free until no new cases are reported for seven years. The Canadian Sheep Federation is calling on the government to fund a wider surveillance program in order to establish the level of prevalence prior to setting an eradication date. Besides long-term testing, industry is calling for a compensation program for farmers who report unusual deaths in their flocks.
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
Monday, April 25, 2011
Experimental Oral Transmission of Atypical Scrapie to Sheep
Volume 17, Number 5-May 2011
However, work with transgenic mice has demonstrated the potential
susceptibility of pigs, with the disturbing finding that the biochemical
properties of the resulting PrPSc have changed on transmission (40).
***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.
*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.
119
*** 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.
Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.
Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.
(i) the unsuspected potential abilities of atypical scrapie to cross species barriers
(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier
These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.
Friday, February 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to
nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep
and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were
exposed to the infectious agents only by their nonforced consumption of known
infectious tissues. The asymptomatic incubation period in the one monkey exposed
to the virus of kuru was 36 months; that in the two monkeys exposed to the virus
of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the
two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively.
Careful physical examination of the buccal cavities of all of the monkeys failed
to reveal signs or oral lesions. One additional monkey similarly exposed to kuru
has remained asymptomatic during the 39 months that it has been under
observation.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY
snip...
A The Present Position with respect to Scrapie
A1 The Problem
Scrapie is a natural disease of sheep and goats. It is a slow and
inexorably progressive degenerative disorder of the nervous system and it ia
fatal. It is enzootic in the United Kingdom but not in all countries.
The field problem has been reviewed by a MAFF working group (ARC 35/77). It
is difficult to assess the incidence in Britain for a variety of reasons but the
disease causes serious financial loss; it is estimated that it cost Swaledale
breeders alone $l.7 M during the five years 1971-1975. A further inestimable
loss arises from the closure of certain export markets, in particular those of
the United States, to British sheep.
It is clear that scrapie in sheep is important commercially and for that
reason alone effective measures to control it should be devised as quickly as
possible.
Recently the question has again been brought up as to whether scrapie is
transmissible to man. This has followed reports that the disease has been
transmitted to primates. One particularly lurid speculation (Gajdusek 1977)
conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and
transmissible encephalopathy of mink are varieties of a single "virus". The U.S.
Department of Agriculture concluded that it could "no longer justify or permit
scrapie-blood line and scrapie-exposed sheep and goats to be processed for human
or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is
emphasised by the finding that some strains of scrapie produce lesions identical
to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be
transmissible to man raises two considerations. First, the safety of laboratory
personnel requires prompt attention. Second, action such as the "scorched meat"
policy of USDA makes the solution of the acrapie problem urgent if the sheep
industry is not to suffer grievously.
snip...
76/10.12/4.6
Epidemiology of Scrapie in the United States 1977
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 ...
Wednesday, February 16, 2011
IN CONFIDENCE
SCRAPIE TRANSMISSION TO CHIMPANZEES
IN CONFIDENCE
Sunday, April 18, 2010
SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010
Monday, April 25, 2011
Experimental Oral Transmission of Atypical Scrapie to Sheep
Volume 17, Number 5-May 2011
Saturday, May 2, 2009
APHIS AND WHO PLAN TO EXEMPT THE ATYPICAL SCRAPIE NOR-98 FROM REGULATIONS
AT MEETING THIS MONTH
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 AND SAME OLD BSe
WITH BOVINE MAD COW DISEASE
*** I strenuously urge the USDA and the OIE et al to revoke the exemption of the legal global trading of atypical Nor-98 scrapie TSE. ...TSS
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.
Wednesday, February 16, 2011
IN CONFIDENCE SCRAPIE TRANSMISSION TO CHIMPANZEES IN CONFIDENCE
reference...
RB3.20 TRANSMISSION TO CHIMPANZEES
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, ilp 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.
6. 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.
R. Bradley 23 September 1990 CVO (+Mr Wells' comments) Dr T W A Little Dr B
J Shreeve 90/9.23/1.1.
see more here ;
Rabbits are not resistant to prion infection
Francesca Chianinia,1, Natalia Fernández-Borgesb,c,1, Enric Vidald, Louise
Gibbarda, Belén Pintadoe, Jorge de Castroc, Suzette A. Priolaf, Scott Hamiltona,
Samantha L. Eatona, Jeanie Finlaysona, Yvonne Panga, Philip Steelea, Hugh W.
Reida, Mark P. Dagleisha, and Joaquín Castillab,c,g,2
snip...
Discussion
Slightly more than 25 y ago, cattle were considered free of prion diseases. No one would have predicted the BSE epidemic with the considerable human and animal health repercussions, and the political and economic impacts that it had in Europe during the 1990s. At that time, the scientific knowledge of prions was too limited to determine its role in the development of spontaneous cases of BSE and their subsequent impact on human health. By 2011, however, several new prion strains, naturally occurring (19, 20) or artificially generated (10), have been described, indicating that their number has increased and that a species should be considered resistant to disease only after careful consideration. The degree of resistance and susceptibility to prion disease(s) differs within species. Animals can be both extremely susceptible to the majority of prion diseases or strains yet remain resistant to others on first passage (21). Therefore, it would be unwise to assume that a species generally resistant to TSEs would represent a minor risk to human health, as new TSEs and strains are continually being detected.
It is notoriously difficult to predict how a new TSE or strain will behave
in different species, so great caution must be exercised when determining the
transmissibility of prions between species. To evaluate the potential risk of
transmission, every tool in the prion toolkit is essential, including artificial
methods, such as the use of transgenic animals, or secondary in vivo
transmission, which can exaggerate the possibility of infection (2, 22).
Even these extreme measures, which probably do not reflect the normal
mechanisms of infection, have to be considered to avoid future epidemics similar
to that observed with the new variant Creutzfeldt-Jakob disease (vCJD). For this
reason, we selected PMCA with its associated advantages, including the ability
to overcome the transmission barrier (8), as the preferred tool to evaluate the
absolute susceptibility of rabbits to TSEs.
Using only normal rabbit brain homogenate as a substrate for PMCA, PrPC was
efficiently converted to rabbit PrPres when seeded with strains originating from
four different species (Table 1), and at least three biochemically
distinguishable rabbit PrPres strains were obtained (Fig. 1). This suggests that
rabbit PrPC is more readily misfolded than originally thought. However, a prion
disease is more than a simple misfolding process, and other factors are probably
required for successful disease progression in vivo.
To address this point, we inoculated three groups of rabbits, two groups
with ME7 based inocula (murine and leporine) and a further group with the de
novo rabbit PMCA derived PrPres. Selection of these particular strains was
carried out on the basis that ME7 was stable and well characterized and the de
novo strain was an unknown entity. The number of strains tested and rabbits
challenged were limited because of the necessity of housing these animals in
containment level 3 facilities for protracted periods of time that maximized the
possibility of transmission and development of disease.
Although rabbits were inoculated with prions derived from the same species,
a 25-mo period was necessary to observe the standard prion disease. The three
animals that died without clinical signs of TSE were all negative by IHC and WB,
although the first of these deaths was in a rabbit challenged with ME7 RaPrPSc,
which had PrPSc levels in the brain detectable only by PMCA. This result
indicates that even though the animal died of a non– TSE-related disease, it
might have been at an early preclinical stage of prion disease. However, we
cannot rule out the possibility that the limited PrPSc level in the brain sample
was due to residual inoculum, as shown previously in PrP knock-out mice (23). To
date, the rabbits inoculated with mouse ME7 remain healthy after more than 43
mo, which is in agreement with the experiments performed approximately 35 y ago
by Barlow and Rennie (17).
In summary, after 3 y postchallenge with three different rabbitderived
inocula, we have obtained one positive clinical case, one possible preclinical
case, two intercurrent deaths, and six animals that have remained healthy.
Although the incubation periods do not directly correlate with the degree of
susceptibility, these data might indicate that rabbits are poorly susceptible to
prion infection. Although the rabbits used in this study were not inbred, they
all had identical full-length PrP sequences and, to date, no difference has been
detected in the ORF PrP sequence in any other published rabbit PrP sequence
placed in GenBank. To further investigate this, two types of second passage
experiment were performed; three raPrPTg mice and 10 rabbits were all
intracerebrally inoculated using brain homogenate from the clinically affected
rabbit. In contrast to 100% of the de novo RaPrPSc-inoculated transgenic mice
having succumbed to a standard clinical prion disease and thereby demonstrating
a high rate of transmissibility in vivo, two of 10 rabbits developed a TSE (477
and 540 dpi, respectively) to date. A plausible explanation for the evident
differences between these two transmission studies would be the high level of
rabbit PrPC expression (4- to 6-fold) in the murine model. In addition, it is
well known that even if overexpression does not increase susceptibility, it can
significantly reduce the incubation time of disease (2). However, the two
positive TSE cases in the second rabbit passage, even though 8 rabbits remained
clinically normal at 560 dpi, have led us to conclude that rabbits can no longer
be considered a prionresistant species. The long incubation times, even after a
second passage, might be due to the presence of some unknown, and probably rare,
susceptibility factor in rabbits, which may also be present, for example, in
equids and canids.
To critically evaluate this risk, several experiments are currently
underway to characterize this new prion disease in rabbits and other species to
examine its ability to cross the species barrier. In addition, supplementary
experiments have been initiated in rabbits and also in transgenic mice that
overexpress rabbit PrPC, to evaluate their susceptibilities to other important
prion diseases including CWD and BSE. There are several factors that any
potential new TSE epidemic would require: (i) the new prion should be
efficiently transmitted through the homologous species; (ii) animals should be
edible by humans and should be slaughtered at an age at which the disease has
developed, thereby increasing the chance that prions have replicated (especially
for those prions that require long incubation times); and (iii) the meat and
bone meal should be recycled and fed to new members of the same species. In the
light of these data and taking into account the previous three factors, it is
unlikely there will be an outbreak of “mad rabbit disease,” and consumers of
rabbit meat face much less of a risk than consumers of cattle or sheep products.
> The long incubation times, even after a second passage, might be due
to the presence of some unknown, and probably rare, susceptibility factor in
rabbits, which may also be present, for example, in equids and canids.
> equids and canids
TSE in dogs have not been documented simply because OF THE ONLY STUDY,
those brain tissue samples were screwed up too. see my investigation of this
here, and to follow, later follow up, a letter from defra, AND SEE SUSPICIOUS
BRAIN TISSUE SAF's. ...TSS
TSE & HOUNDS
GAH WELLS (very important statement here...TSS)
HOUND STUDY
AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to
other species will invariably present pathology typical of a scrapie-like
disease.
snip...
76 pages on hound study;
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
42.These included neuropathological examination of material from
experiments studying the attempted transmission of BSE to chickens and pigs (CVL
1991) and to mice (RVC 1994).
It was thought likely that at least some, and probably all, of the cases in zoo animals were caused by the BSE agent. Strong support for this hypothesis came from the findings of Bruce and others (1994) ( Bruce, M.E., Chree, A., McConnell, I., Foster, J., Pearson, G. & Fraser, H. (1994) Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and species barrier. Philosophical Transactions of the Royal Society B 343, 405-411: J/PTRSL/343/405 ), who demonstrated that the pattern of variation in incubation period and lesion profile in six strains of mice inoculated with brain homogenates from an affected kudu and the nyala, was similar to that seen when this panel of mouse strains was inoculated with brain from cattle with BSE. The affected zoo bovids were all from herds that were exposed to feeds that were likely to have contained contaminated ruminant-derived protein and the zoo felids had been exposed, if only occasionally in some cases, to tissues from cattle unfit for human consumption.
snip...
2005
DEFRA Department for Environment, Food & Rural Affairs
Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail: h.mcdonagh.defra.gsi.gov.uk
GTN: FAX:
Mr T S Singeltary P.O. Box 42 Bacliff Texas USA 77518
21 November 2001
Dear Mr Singeltary
TSE IN HOUNDS
Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding.
As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government's independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.
Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.
Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to r~eer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less critical. For more details see-
http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
As this study remains unpublished, my understanding is that the ownership
of the data essentially remains with the original researchers. Thus
unfortunately, I am unable to help with your request to supply information on
the hound survey directly. My only suggestion is that you contact one of the
researchers originally involved in the project, such as Gerald Wells. He can be
contacted at the following address.
Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone,
Surrey, KT 15 3NB, UK
You may also wish to be aware that since November 1994 all suspected cases
of spongiform encephalopathy in animals and poultry were made notifiable. Hence
since that date there has been a requirement for vets to report any suspect SE
in dogs for further investigation. To date there has never been positive
identification of a TSE in a dog.
I hope this is helpful
Yours sincerely 4
HUGH MCDONAGH BSE CORRESPONDENCE SECTION
======================================
IN CONFIDENCE
SUSPECT BSE IN A HORSE
CYO BSE 1 9
IN CONFIDENCE
SUSPECT BSE IN A HORSE
The Parliamentary Secretary (Mr Maclean) will wish to be aware that, in
making his differential diagnosis, a veterinary surgeon in the Reading area has
included the possibility of BSE in a horse under his care. Although it is
unlikely to be BSE, because of the symptoms exhibited the veterinarian believes
that he cannot exclude the possibility. The case was brought to the notice of
one of the veterinary staff at the CVL by the owner's veterinary surgeon and
liaison is being maintained.
The horse in question is a five-year old eventing gelding which was
purchased by the present owner about four months ago. Approximately two months
after purchase the animal became a little apprehensive, developed mild nervous
symptoms and became over-sensitive to noise. The nervous symptoms have increased
and the horse is now practically impossible to ride. Investigations by the
owner's private veterinary surgeon are continuing but it is likely that the
animal will have to be destroyed.
If the horse should die or be destroyed, a full post-mortem examination
will be required for insurance purposes and will probably be carried out at a
non-Ministry laboratory. However, Mr Bradley of the Pathology Department, CVL,
has informed the private veterinary surgeon that he is willing to provide a
second opinion on the brain histology if requested.
I will keep the Parliamentary Secretary informed of any further
developments in the case.
I CRAWFORD
14 May 1990
Mr M P H Hill, PS/Parliamentary secretary (Mr Maclean) - by FAX
cc:
Private Offices
Mr K C Meldrum
Mrs E A J Attridge D J Evans Mr K C Taylor Mr R Lawson Mr R Bradley. CVL
(hand written notes i cannot read all (cut short) as follows...tss)
The Parliamentary Secretary (Mr Maclean was grateful for this. He said
that we must keep very close to ...on it, and when the horse dies, or is put
down we must be told immediately. He also feels it is very important that our
veterinary staff be involved in the brain examination. .........(cannot read the
rest .............TSS)
90/05.14/10.1
Mr A Huws Principal WOAD2A CP2
SUSPECT BSE IN A HORSE
You will wish to be aware that on Thursday afternoon 25 June the T/DVO
Powys received a phone call from a veterinary Surgeon reporting his suspicion
that a horse had ___contracted BSE after having been fed cattle cake___.
The clinical symptoms described were similar to those shown by cattle there
___being a similar case some months ago on the same premises___.
The owner' s name and address is:
Irene Thomas J Thomas & Company Riding Stables Penybryn Llangorse
Brecon
The horse is a 12 year old gelding used for pony trekking.
By yesterday evening the horse was in a comatose state and on humane
grounds was destroyed by the veterinary Surgeon. At his request a full post
mortem and laboratory investigation will be carried out at the Carmarthen
Veterinary Investigation Centre this morning to ascertain the exact cause; I
have been told this will take at least two weeks. Charges to the veterinary
Surgeon have been waived in this instance.
I will inform you immediately I receive a diagnosis.
26 June 1990
D SUMMERS DRVO
cc
Mr D R Williams, RVO
Mr A R Hunter, SVIO
90/06.26/10.1
Mr A Huws Principal WOAD2A CP2
SUSPECT BSE IN A HORSE
You will wish to be aware that on Thursday afternoon 25 June the T/DVO
Powys received a phone call from a veterinary Surgeon reporting his suspicion
that a horse had contracted BSE after having been fed cattle cake. The clinical
symptoms described were similar to those shown by cattle there being a similar
case some months ago on the same premises.
The owner' s name and address is:
Irene Thomas J Thomas & Company Riding Stables Penybryn Llangorse
Brecon
The horse is a 12 year old gelding used for pony trekking.
By yesterday evening the horse was in a comatose state and on humane
grounds was destroyed by the veterinary Surgeon. At his request a full post
mortem and laboratory investigation will be carried out at the Carmarthen
Veterinary Investigation Centre this morning to ascertain the exact cause; I
have been told this will take at least two weeks. Charges to the veterinary
Surgeon have been waived in this instance.
I will inform you immediately I receive a diagnosis.
26 June 1990
D SUMMERS DRVO
cc
Mr D R Williams, RVO
Mr A R Hunter, SVIO
90/06.26/10.1
see full text and more here ;
>>> The most widely accepted hypothesis at this time is that CWD
may have originated from an interspecies transmission of scrapie. It is worth
noting that experimental transmission of scrapie into elk via IC inoculation is
clinically and neuropathologically indistinguishable from CWD with currently
available experimental methods.44 <<<
pens, pens, PENS ???
*** Spraker suggested an interesting explanation for the occurrence of CWD.
The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr.
Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at
this site. When deer were introduced to the pens they occupied ground that had
previously been occupied by sheep.
now, decades later ;
2012
PO-039: A comparison of scrapie and chronic wasting disease in white-tailed
deer
snip...
After a natural route of exposure, 100% of WTD were susceptible to scrapie.
Deer developed clinical signs of wasting and mental depression and were
necropsied from 28 to 33 months PI. Tissues from these deer were positive for
PrPSc by IHC and WB. Similar to IC inoculated deer, samples from these deer
exhibited two different molecular profiles: samples from obex resembled CWD
whereas those from cerebrum were similar to the original scrapie inoculum. On
further examination by WB using a panel of antibodies, the tissues from deer
with scrapie exhibit properties differing from tissues either from sheep with
scrapie or WTD with CWD. Samples from WTD with CWD or sheep with scrapie are
strongly immunoreactive when probed with mAb P4, however, samples from WTD with
scrapie are only weakly immunoreactive. In contrast, when probed with mAb’s 6H4
or SAF 84, samples from sheep with scrapie and WTD with CWD are weakly
immunoreactive and samples from WTD with scrapie are strongly positive. This
work demonstrates that WTD are highly susceptible to sheep scrapie, but on first
passage, scrapie in WTD is differentiable from CWD.
2011
*** After a natural route of exposure, 100% of white-tailed deer were
susceptible to scrapie.
Scrapie in Deer: Comparisons and Contrasts to Chronic Wasting Disease (CWD)
Justin J. Greenlee of the Virus and Prion Diseases Research Unit, National
Animal Disease Center, ARS, USDA, Ames, IA provided a presentation on scrapie
and CWD in inoculated deer. Interspecies transmission studies afford the
opportunity
After a natural route of exposure, 100% of white-tailed deer were
susceptible to scrapie. Deer developed clinical signs of wasting and mental
depression and were necropsied from 28 to 33 months PI. Tissues from these deer
were positive for scrapie by IHC and WB. Tissues with PrPSc immunoreactivity
included brain, tonsil, retropharyngeal and mesenteric lymph nodes, hemal node,
Peyer’s patches, and spleen. While two WB patterns have been detected in brain
regions of deer inoculated by the natural route, unlike the IC inoculated deer,
the pattern similar to the scrapie inoculum predominates.
2011 Annual Report
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research
Unit 2011 Annual Report
In Objective 1, Assess cross-species transmissibility of transmissible
spongiform encephalopathies (TSEs) in livestock and wildlife, numerous
experiments assessing the susceptibility of various TSEs in different host
species were conducted. Most notable is deer inoculated with scrapie, which
exhibits similarities to chronic wasting disease (CWD) in deer suggestive of
sheep scrapie as an origin of CWD.
snip...
4.Accomplishments 1. Deer inoculated with domestic isolates of sheep
scrapie. Scrapie-affected deer exhibit 2 different patterns of disease
associated prion protein. In some regions of the brain the pattern is much like
that observed for scrapie, while in others it is more like chronic wasting
disease (CWD), the transmissible spongiform encephalopathy typically associated
with deer. This work conducted by ARS scientists at the National Animal Disease
Center, Ames, IA suggests that an interspecies transmission of sheep scrapie to
deer may have been the origin of CWD. This is important for husbandry practices
with both captive deer, elk and sheep for farmers and ranchers attempting to
keep their herds and flocks free of CWD and scrapie.
White-tailed Deer are Susceptible to Scrapie by Natural Route of Infection
snip...
This work demonstrates for the first time that white-tailed deer are
susceptible to sheep scrapie by potential natural routes of inoculation.
In-depth analysis of tissues will be done to determine similarities between
scrapie in deer after intracranial and oral/intranasal inoculation and chronic
wasting disease resulting from similar routes of inoculation.
see full text ;
CWD, SCRAPIE, CATTLE, TSE ???
"CWD has been transmitted to cattle after intracerebral inoculation,
although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This
finding raised concerns that CWD prions might be transmitted to cattle grazing
in contaminated pastures."
Please see ;
Within 26 months post inoculation, 12 inoculated animals had lost weight,
revealed abnormal clinical signs, and were euthanatized. Laboratory tests
revealed the presence of a unique pattern of the disease agent in tissues of
these animals. These findings demonstrate that when CWD is directly inoculated
into the brain of cattle, 86% of inoculated cattle develop clinical signs of the
disease.
"although the infection rate was low (4 of 13 animals [Hamir et al.
2001])."
shouldn't this be corrected, 86% is NOT a low rate. ...
kindest regards,
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
UPDATED CORRESPONDENCE FROM AUTHORS OF THIS STUDY I.E. COLBY, PRUSINER ET
AL, ABOUT MY CONCERNS OF THE DISCREPANCY BETWEEN THEIR FIGURES AND MY FIGURES OF
THE STUDIES ON CWD TRANSMISSION TO CATTLE ;
----- Original Message -----
From: David Colby
Cc: stanley@XXXXXXXX
Sent: Tuesday, March 01, 2011 8:25 AM
Subject: Re: FW: re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 +
Author Affiliations
Dear Terry Singeltary,
Thank you for your correspondence regarding the review article Stanley
Prusiner and I recently wrote for Cold Spring Harbor Perspectives. Dr. Prusiner
asked that I reply to your message due to his busy schedule. We agree that the
transmission of CWD prions to beef livestock would be a troubling development
and assessing that risk is important. In our article, we cite a peer-reviewed
publication reporting confirmed cases of laboratory transmission based on
stringent criteria. The less stringent criteria for transmission described in
the abstract you refer to lead to the discrepancy between your numbers and ours
and thus the interpretation of the transmission rate. We stand by our assessment
of the literature--namely that the transmission rate of CWD to bovines appears
relatively low, but we recognize that even a low transmission rate could have
important implications for public health and we thank you for bringing attention
to this matter.
Warm Regards, David Colby
--
David Colby, PhDAssistant ProfessorDepartment of Chemical
EngineeringUniversity of Delaware
====================END...TSS==============
SNIP...SEE FULL TEXT ;
UPDATED DATA ON 2ND CWD STRAIN
Wednesday, September 08, 2010
CWD PRION CONGRESS SEPTEMBER 8-11 2010
*** The potential impact of prion diseases on human health was greatly
magnified by the recognition that interspecies transfer of BSE to humans by beef
ingestion resulted in vCJD. While changes in animal feed constituents and
slaughter practices appear to have curtailed vCJD, there is concern that CWD of
free-ranging deer and elk in the U.S. might also cross the species barrier.
Thus, consuming venison could be a source of human prion disease. Whether BSE
and CWD represent interspecies scrapie transfer or are newly arisen prion
diseases is unknown. Therefore, the possibility of transmission of prion disease
through other food animals cannot be ruled out. There is evidence that vCJD can
be transmitted through blood transfusion. There is likely a pool of unknown size
of asymptomatic individuals infected with vCJD, and there may be asymptomatic
individuals infected with the CWD equivalent. These circumstances represent a
potential threat to blood, blood products, and plasma supplies.
The chances of a person or domestic animal contracting CWD are “extremely
remote,” Richards said. The possibility can’t be ruled out, however. “One could
look at it like a game of chance,” he explained. “The odds (of infection)
increase over time because of repeated exposure. That’s one of the downsides of
having CWD in free-ranging herds: We’ve got this infectious agent out there that
we can never say never to in terms of (infecting) people and domestic
livestock.”
P35
ADAPTATION OF CHRONIC WASTING DISEASE (CWD) INTO HAMSTERS, EVIDENCE OF A
WISCONSIN STRAIN OF CWD
Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of
Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2
Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary
Research Institute, 4.Center for Prions and Protein Folding Diseases, 5
Department of Biological Sciences, University of Alberta, Edmonton AB, Canada
T6G 2P5
The identification and characterization of prion strains is increasingly
important for the diagnosis and biological definition of these infectious
pathogens. Although well-established in scrapie and, more recently, in BSE,
comparatively little is known about the possibility of prion strains in chronic
wasting disease (CWD), a disease affecting free ranging and captive cervids,
primarily in North America. We have identified prion protein variants in the
white-tailed deer population and demonstrated that Prnp genotype affects the
susceptibility/disease progression of white-tailed deer to CWD agent. The
existence of cervid prion protein variants raises the likelihood of distinct CWD
strains. Small rodent models are a useful means of identifying prion strains. We
intracerebrally inoculated hamsters with brain homogenates and phosphotungstate
concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD
endemic area) and experimentally infected deer of known Prnp genotypes. These
transmission studies resulted in clinical presentation in primary passage of
concentrated CWD prions. Subclinical infection was established with the other
primary passages based on the detection of PrPCWD in the brains of hamsters and
the successful disease transmission upon second passage. Second and third
passage data, when compared to transmission studies using different CWD inocula
(Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin
white-tailed deer population is different than the strain(s) present in elk,
mule-deer and white-tailed deer from the western United States endemic region.
PPo3-7:
Prion Transmission from Cervids to Humans is Strain-dependent
Qingzhong Kong, Shenghai Huang,*Fusong Chen, Michael Payne, Pierluigi
Gambetti and Liuting Qing Department of Pathology; Case western Reserve
University; Cleveland, OH USA *Current address: Nursing Informatics; Memorial
Sloan-Kettering Cancer Center; New York, NY USA
Key words: CWD, strain, human transmission
Chronic wasting disease (CWD) is a widespread prion disease in cervids
(deer and elk) in North America where significant human exposure to CWD is
likely and zoonotic transmission of CWD is a concern. Current evidence indicates
a strong barrier for transmission of the classical CWD strain to humans with the
PrP-129MM genotype. A few recent reports suggest the presence of two or more CWD
strains. What remain unknown is whether individuals with the PrP-129VV/MV
genotypes are also resistant to the classical CWD strain and whether humans are
resistant to all natural or adapted cervid prion strains. Here we report that a
human prion strain that had adopted the cervid prion protein (PrP) sequence
through passage in cervidized transgenic mice efficiently infected transgenic
mice expressing human PrP, indicating that the species barrier from cervid to
humans is prion strain-dependent and humans can be vulnerable to novel cervid
prion strains. Preliminary results on CWD transmission in transgenic mice
expressing human PrP-129V will also be discussed.
Acknowledgement Supported by NINDS NS052319 and NIA AG14359.
PPo2-27:
Generation of a Novel form of Human PrPSc by Inter-species Transmission of
Cervid Prions
Marcelo A. Barria,1 Glenn C. Telling,2 Pierluigi Gambetti,3 James A.
Mastrianni4 and Claudio Soto1 1Mitchell Center for Alzheimer's disease and
related Brain disorders; Dept of Neurology; University of Texas Houston Medical
School; Houston, TX USA; 2Dept of Microbiology, Immunology & Molecular
Genetics and Neurology; Sanders Brown Center on Aging; University of Kentucky
Medical Center; Lexington, KY USA; 3Institute of Pathology; Case western Reserve
University; Cleveland, OH USA; 4Dept of Neurology; University of Chicago;
Chicago, IL USA
Prion diseases are infectious neurodegenerative disorders affecting humans
and animals that result from the conversion of normal prion protein (PrPC) into
the misfolded and infectious prion (PrPSc). Chronic wasting disease (CWD) of
cervids is a prion disorder of increasing prevalence within the United States
that affects a large population of wild and captive deer and elk. CWD is highly
contagious and its origin, mechanism of transmission and exact prevalence are
currently unclear. The risk of transmission of CWD to humans is unknown.
Defining that risk is of utmost importance, considering that people have been
infected by animal prions, resulting in new fatal diseases. To study the
possibility that human PrPC can be converted into the infectious form by CWD
PrPSc we performed experiments using the Protein Misfolding Cyclic Amplification
(PMCA) technique, which mimic in vitro the process of prion replication. Our
results show that cervid PrPSc can induce the pathological conversion of human
PrPC, but only after the CWD prion strain has been stabilized by successive
passages in vitro or in vivo. Interestingly, this newly generated human PrPSc
exhibits a distinct biochemical pattern that differs from any of the currently
known forms of human PrPSc, indicating that it corresponds to a novel human
prion strain. Our findings suggest that CWD prions have the capability to infect
humans, and that this ability depends on CWD strain adaptation, implying that
the risk for human health progressively increases with the spread of CWD among
cervids.
PPo2-7:
Biochemical and Biophysical Characterization of Different CWD
Isolates
Martin L. Daus and Michael Beekes Robert Koch Institute; Berlin,
Germany
Key words: CWD, strains, FT-IR, AFM
Chronic wasting disease (CWD) is one of three naturally occurring forms of
prion disease. The other two are Creutzfeldt-Jakob disease in humans and scrapie
in sheep. CWD is contagious and affects captive as well as free ranging cervids.
As long as there is no definite answer of whether CWD can breach the species
barrier to humans precautionary measures especially for the protection of
consumers need to be considered. In principle, different strains of CWD may be
associated with different risks of transmission to humans. Sophisticated strain
differentiation as accomplished for other prion diseases has not yet been
established for CWD. However, several different findings indicate that there
exists more than one strain of CWD agent in cervids. We have analysed a set of
CWD isolates from white-tailed deer and could detect at least two biochemically
different forms of disease-associated prion protein PrPTSE. Limited proteolysis
with different concentrations of proteinase K and/or after exposure of PrPTSE to
different pH-values or concentrations of Guanidinium hydrochloride resulted in
distinct isolate-specific digestion patterns. Our CWD isolates were also
examined in protein misfolding cyclic amplification studies. This showed
different conversion activities for those isolates that had displayed
significantly different sensitivities to limited proteolysis by PK in the
biochemical experiments described above. We further applied Fourier transform
infrared spectroscopy in combination with atomic force microscopy. This
confirmed structural differences in the PrPTSE of at least two disinct CWD
isolates. The data presented here substantiate and expand previous reports on
the existence of different CWD strains.
2012
Envt.06:
Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates
Emmanuel Comoy,1,† Valérie Durand,1 Evelyne Correia,1 Aru Balachandran,2
Jürgen Richt,3 Vincent Beringue,4 Juan-Maria Torres,5 Paul Brown,1 Bob Hills6
and Jean-Philippe Deslys1
1Atomic Energy Commission; Fontenay-aux-Roses, France; 2Canadian Food
Inspection Agency; Ottawa, ON Canada; 3Kansas State University; Manhattan, KS
USA; 4INRA; Jouy-en-Josas, France; 5INIA; Madrid, Spain; 6Health Canada; Ottawa,
ON Canada
†Presenting author; Email: emmanuel.comoy@cea.fr
The constant increase of chronic wasting disease (CWD) incidence in North
America raises a question about their zoonotic potential. A recent publication
showed their transmissibility to new-world monkeys, but no transmission to
old-world monkeys, which are phylogenetically closer to humans, has so far been
reported. Moreover, several studies have failed to transmit CWD to transgenic
mice overexpressing human PrP. Bovine spongiform encephalopathy (BSE) is the
only animal prion disease for which a zoonotic potential has been proven. We
described the transmission of the atypical BSE-L strain of BSE to cynomolgus
monkeys, suggesting a weak cattle-to-primate species barrier. We observed the
same phenomenon with a cattleadapted strain of TME (Transmissible Mink
Encephalopathy). Since cattle experimentally exposed to CWD strains have also
developed spongiform encephalopathies, we inoculated brain tissue from
CWD-infected cattle to three cynomolgus macaques as well as to transgenic mice
overexpressing bovine or human PrP. Since CWD prion strains are highly
lymphotropic, suggesting an adaptation of these agents after peripheral
exposure, a parallel set of four monkeys was inoculated with CWD-infected cervid
brains using the oral route. Nearly four years post-exposure, monkeys exposed to
CWD-related prion strains remain asymptomatic. In contrast, bovinized and
humanized transgenic mice showed signs of infection, suggesting that CWD-related
prion strains may be capable of crossing the cattle-to-primate species barrier.
Comparisons with transmission results and incubation periods obtained after
exposure to other cattle prion strains (c-BSE, BSE-L, BSE-H and cattle-adapted
TME) will also be presented, in order to evaluate the respective risks of each
strain.
Envt.07:
Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free
Ranging White-Tailed Deer Infected with Chronic Wasting Disease
Martin L. Daus,1,† Johanna Breyer,2 Katjs Wagenfuehr,1 Wiebke Wemheuer,2
Achim Thomzig,1 Walter Schulz-Schaeffer2 and Michael Beekes1 1Robert Koch
Institut; P24 TSE; Berlin, Germany; 2Department of Neuropathology, Prion and
Dementia Research Unit, University Medical Center Göttingen; Göttingen, Germany
†Presenting author; Email: dausm@rki.de
Chronic wasting disease (CWD) is a contagious, rapidly spreading
transmissible spongiform encephalopathy (TSE) occurring in cervids in North
America. Despite efficient horizontal transmission of CWD among cervids natural
transmission of the disease to other species has not yet been observed. Here, we
report a direct biochemical demonstration of pathological prion protein PrPTSE
and of PrPTSE-associated seeding activity in skeletal muscles of CWD-infected
cervids. The presence of PrPTSE was detected by Western- and postfixed frozen
tissue blotting, while the seeding activity of PrPTSE was revealed by protein
misfolding cyclic amplification (PMCA). The concentration of PrPTSE in skeletal
muscles of CWD-infected WTD was estimated to be approximately 2000- to
10000-fold lower than in brain tissue. Tissue-blot-analyses revealed that PrPTSE
was located in muscle- associated nerve fascicles but not, in detectable
amounts, in myocytes. The presence and seeding activity of PrPTSE in skeletal
muscle from CWD-infected cervids suggests prevention of such tissue in the human
diet as a precautionary measure for food safety, pending on further
clarification of whether CWD may be transmissible to humans.
Friday, November 09, 2012
*** Chronic Wasting Disease CWD in cervidae and transmission to other
species
Sunday, November 11, 2012
*** Susceptibilities of Nonhuman Primates to Chronic Wasting Disease
November 2012
Friday, December 14, 2012
*** Susceptibility Chronic Wasting Disease (CWD) in wild cervids to Humans
2005 - December 14, 2012
Saturday, March 09, 2013
Chronic Wasting Disease in Bank Voles: Characterisation of the Shortest
Incubation Time Model for Prion Diseases
Tuesday, April 16, 2013
Cervid Industry Unites To Set Direction for CWD Reform and seem to ignore
their ignorance and denial in their role in spreading Chronic Wasting
Disease
Tuesday, June 11, 2013
CWD GONE WILD, More cervid escapees from more shooting pens on the loose in
Pennsylvania
Sunday, June 09, 2013
Missouri House forms 13-member Interim Committee on the Cause and Spread of
Chronic Wasting Disease CWD
Saturday, June 08, 2013
The battle against Chronic Wasting Disease continues in Southeast
Iowa
Tuesday, May 28, 2013
Chronic Wasting Disease CWD quarantine Louisiana via CWD index herd
Pennsylvania Update May 28, 2013
6 doe from Pennsylvania CWD index herd still on the loose in Louisiana,
quarantine began on October 18, 2012, still ongoing, Lake Charles premises.
Wednesday, June 12, 2013
CWD now waltzing into Texas from Pennsylvania CWD index herd, via
Louisiana, or Missouri now ?
please see what the U.K. DEFRA recently said ABOUT CWD RISK FACTORS ;
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced
into Great Britain? A Qualitative Risk Assessment October 2012
snip...
In the USA, under the Food and Drug Administration’s BSE Feed Regulation
(21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin)
from deer and elk is prohibited for use in feed for ruminant animals. With
regards to feed for non-ruminant animals, under FDA law, CWD positive deer may
not be used for any animal feed or feed ingredients. For elk and deer considered
at high risk for CWD, the FDA recommends that these animals do not enter the
animal feed system. However, this recommendation is guidance and not a
requirement by law.
Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD
eradication zones and
2) deer and elk that at some time during the 60-month period prior to
slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive
animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from
the USA to GB can not be determined, however, as it is not specified in TRACES.
It may constitute a small percentage of the 8412 kilos of non-fish origin
processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible
risk___ that (nonruminant) animal feed and pet food containing deer and/or elk
protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data
on the amount of deer and/or elk protein possibly being imported in these
products.
snip...
36% in 2007 (Almberg et al., 2011). In such areas, population declines of
deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of
Colorado, the prevalence can be as high as 30% (EFSA, 2011).
The clinical signs of CWD in affected adults are weight loss and
behavioural changes that can span weeks or months (Williams, 2005). In addition,
signs might include excessive salivation, behavioural alterations including a
fixed stare and changes in interaction with other animals in the herd, and an
altered stance (Williams, 2005). These signs are indistinguishable from cervids
experimentally infected with bovine spongiform encephalopathy (BSE).
Given this, if CWD was to be introduced into countries with BSE such as GB,
for example, infected deer populations would need to be tested to differentiate
if they were infected with CWD or BSE to minimise the risk of BSE entering the
human food-chain via affected venison.
snip...
The rate of transmission of CWD has been reported to be as high as 30% and
can approach 100% among captive animals in endemic areas (Safar et al., 2008).
snip...
In summary, in endemic areas, there is a medium probability that the soil
and surrounding environment is contaminated with CWD prions and in a
bioavailable form. In rural areas where CWD has not been reported and deer are
present, there is a greater than negligible risk the soil is contaminated with
CWD prion.
snip...
In summary, given the volume of tourists, hunters and servicemen moving
between GB and North America, the probability of at least one person travelling
to/from a CWD affected area and, in doing so, contaminating their clothing,
footwear and/or equipment prior to arriving in GB is greater than negligible.
For deer hunters, specifically, the risk is likely to be greater given the
increased contact with deer and their environment. However, there is significant
uncertainty associated with these estimates.
snip...
Therefore, it is considered that farmed and park deer may have a higher
probability of exposure to CWD transferred to the environment than wild deer
given the restricted habitat range and higher frequency of contact with tourists
and returning GB residents.
snip... see full text report here ;
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced
into Great Britain? A Qualitative Risk Assessment October 2012
A kind greetings from Bacliff, Texas !
I have often pondered if the whole damn mad cow follies started over here
in the USA, and somehow, the USA shipped it over to the UK ?
It happened with S. Korea and CWD, via Canada. see ;
The disease was confirmed only in elk in the Republic of Korea in 2001,
2004 and 2005. Epidemiological investigations showed that CWD was introduced via
importation of infected elk from Canada between 1994 and 1997.
but I still am not so sure that the mad cow follies did not start long ago
right here in the USA i.e. Richard Marsh and deadstock downer cattle to those
mink, and then the USA shipped it to hell and back. just pondering out loud
here. ...tss
The exact same recipe for B.S.E. existed in the U.S. for years
and years. In reading over the Qualitative Analysis of BSE
Risk Factors-1, this is a 25 page report by the
USDA:APHIS:VS. It could have been done in one page. The
first page, fourth paragraph says it all;
"Similarities exist in the two countries usage of continuous
rendering technology and the lack of usage of solvents,
however, large differences still remain with other risk factors
which greatly reduce the potential risk at the national level."
Then, the next 24 pages tries to down-play the high risks of
B.S.E. in the U.S., with nothing more than the cattle to sheep
ratio count, and the geographical locations of herds and flocks.
That's all the evidence they can come up with, in the next 24
pages.
Something else I find odd, page 16;
"In the United Kingdom there is much concern for a specific
continuous rendering technology which uses lower
temperatures and accounts for 25 percent of total output. This
technology was _originally_ designed and imported from the
United States. However, the specific application in the
production process is _believed_ to be different in the two
countries."
A few more factors to consider, page 15;
"Figure 26 compares animal protein production for the two
countries. The calculations are based on slaughter numbers,
fallen stock estimates, and product yield coefficients. This
approach is used due to variation of up to 80 percent from
different reported sources. At 3.6 million tons, the United
States produces 8 times more animal rendered product than
the United Kingdom."
"The risk of introducing the BSE agent through sheep meat and
bone meal is more acute in both relative and absolute terms in
the United Kingdom (Figures 27 and 28). Note that sheep
meat and bone meal accounts for 14 percent, or 61 thousand
tons, in the United Kingdom versus 0.6 percent or 22 thousand
tons in the United States. For sheep greater than 1 year, this is
less than one-tenth of one percent of the United States supply."
"The potential risk of amplification of the BSE agent through
cattle meat and bone meal is much greater in the United States
where it accounts for 59 percent of total product or almost 5
times more than the total amount of rendered product in the
United Kingdom."
Considering, it would only take _one_ scrapie infected sheep
to contaminate the feed. Considering Scrapie has run rampant
in the U.S. for years, as of Aug. 1999, 950 scrapie infected
flocks. Also, Considering only one quarter spoonful of scrapie
infected material is lethal to a cow. Considering all this, the
sheep to cow ration is meaningless. As I said, it's 24 pages of
B.S.e.
To be continued...
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA
_____________________________________________________________________
Qualitative Assessment Considering the comparative factors presented, with
the exception of some similarities in rendering practices, epidemiologic factors
believed conducive to the introduction of BSE in the United Kingdom are
significantly different in the United States. This is supported by the following
points: Similar changes in the rendering practices have occurred in both
countries. Continuous rendering accounts for the vast majority of all product
produced. From 1977 to 1982, the portion of United Kingdom product rendered
using hydrocarbon solvents dropped from 70 per-cent to 10 percent. Within the
United States the decline was at least 5 years earlier with very little if any
solvent in current use.
see full text ;
TME in mink was documented in the early 1960s. it was first thought that
the TME out break was from scrapie infected sheep, until a investigation was
done on feed practices at these mink facilities, and it was later found that the
mink had been fed 95%+ dead stock downer cows. and later, the Late Richard Marsh
tried to warn the feds of the pending mad cow debacle. they refused to listen.
... some interesting reading on pages 26 to 33
1979
TME originates from feeding mink, scrapie infected materials...
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...
Tuesday, July 21, 2009
Transmissible mink encephalopathy - review of the etiology
Folia Neuropathologica 2/2009
full text of the article:
Transmissible mink encephalopathy – review of the etiology
Folia Neuropathol 2009; 47 (2): 195-204
snip...
A possible clue was provided during the Stetsonville TME outbreak in which
the rancher fed his mink commercial feed (e.g., poultry, fish, cereal) and fresh
meat primarily from sick or downer dairy cattle within a 50-mile radius of his
ranch [37]. He did not recall including sheep products in his homemade feed
ration. Upon reviewing prior TME outbreaks in the U.S. and Canada, in all four
cases in which records were available and were not linked to a commercial feed
plant, downer cattle were also included in the mink diet. The Stetsonville TME
isolate, and subsequently additional TME isolates, were transmitted to cattle by
intracerebral inoculation and the Stetsonville TME isolate was the first
confirmed case of experimental transmission of a TSE/prion disease to cattle.
What was striking was that upon experimental transmission of cattle TME back
into mink by the oral and intracerebral routes, the incubation periods were
similar to that found for mink passaged TME. Hence, the pathogenicity of the
Stetsonville TME agent in mink was not altered upon passage into cattle,
suggesting that a previously unrecognized TSE/prion disease in cattle may be the
source of TME infection. Additional studies strongly suggest that TME has
similarities to L-type BSE in transgenic mice compared to H-type or classical
BSE [2]. Since the L-type BSE does not appear to be an infectious form of
TSE/prion disease, the proposal by Marsh [35,37] that a rare TSE in cattle may
be the source of TME infection seems plausible. This is particularly the case in
Wisconsin, which has had the majority of TME in the USA and is a prominent dairy
state with aged cattle being a primary source of fresh meat for mink ration.
Since mink are a sentinel host it is not surprising that they may have been a
key host in amplifying a rare cattle TSE disease. Another possible explanation
for the high incidence of TME in Wisconsin is based on the recent identification
of a mutation in the prion protein gene in cattle with atypical BSE. There may
be cattle breeding stock in Wisconsin that carry a mutation in the prion protein
gene that is linked to late onset disease and are also the source of TSE
infection for mink TME outbreaks described in the 1960s and 1985.
snip...
To this end, mink were shown to be sensitive to scrapie [23,24]. Of
interest, following i.c. inoculation with the UK source of scrapie from a
Suffolk sheep only a single animal developed the disease. In contrast, American
sources B-834 and B-957 from Suffolk sheep readily transmitted to mink. Also, in
another outbreak of TME in Stetsonville, Wisconsin, USA, the affected mink were
apparently fed with downer cattle but not scrapie-affected sheep [32], and thus
TME may result from BSE transmission from cattle to mink [37]. TME is readily
transmitted to cattle [26]. The suggestion that TME may result from transmission
from infected cattle but not sheep was supported by recent data on phenotypic
similarities of TME in cattle and L-type bovine spongiform encephalopathy (BSE)
transmitted to ovine transgenic mice (TgOvPrP4) [2]. To this end, L-type of BSE
and TME in TgOvPrP4 presented similar molecular mass of all 3 bands of PrPd.
Unglycosylated PrPd in L-type BSE, bovine TME and typical BSE has the same
molecular mass of approximately 18 kDa in contrast to that of diglycosylated
PrPd species which was lower by 0.5-0.8 kDa in L-type BSE and bovine TME as
compared to typical BSE. Furthermore, L-type BSE and bovine TME transmitted to
TgOvPrP4 mice presented spongiform change of low intensity but PrPd was strongly
expressed including amyloid plaques. Mink were also susceptible to BSE [44]. ...
snip...
please see full text and more here;
http://transmissible-mink-encephalopathy.blogspot.com/2009/07/transmissible-mink-encephalopathy.html
Saturday, December 01, 2007
Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and
L-type Bovine Spongiform Encephalopathy in a Mouse Model
Volume 13, Number 12–December 2007 Research
Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and
L-type Bovine Spongiform Encephalopathy in a Mouse Model
Thierry Baron,* Anna Bencsik,* Anne-Gaëlle Biacabe,* Eric Morignat,*
andRichard A. Bessen†*Agence Française de Sécurité Sanitaire des Aliments–Lyon,
Lyon, France; and†Montana State University, Bozeman, Montana, USA
Abstract
Transmissible mink encepholapathy (TME) is a foodborne transmissible
spongiform encephalopathy (TSE) of ranch-raised mink; infection with a ruminant
TSE has been proposed as the cause, but the precise origin of TME is unknown. To
compare the phenotypes of each TSE, bovine-passaged TME isolate and 3 distinct
natural bovine spongiform encephalopathy (BSE) agents (typical BSE, H-type BSE,
and L-type BSE) were inoculated into an ovine transgenic mouse line (TgOvPrP4).
Transgenic mice were susceptible to infection with bovine-passaged TME, typical
BSE, and L-type BSE but not to H-type BSE. Based on survival periods, brain
lesions profiles, disease-associated prion protein brain distribution, and
biochemical properties of protease-resistant prion protein, typical BSE had a
distint phenotype in ovine transgenic mice compared to L-type BSE and bovine
TME.The similar phenotypic properties of L-type BSE and bovine TME in TgOvPrP4
mice suggest that L-type BSE is a much more likely candidate for the origin of
TME than is typical BSE.
snip...
Conclusion
These studies provide experimental evidence that the Stetsonville TME agent
is distinct from typical BSE but has phenotypic similarities to L-type BSE in
TgOvPrP4 mice. Our conclusion is that L-type BSE is a more likely candidate for
a bovine source of TME infection than typical BSE. In the scenario that a
ruminant TSE is the source for TME infection in mink, this would be a second
example of transmission of a TSE from ruminants to non-ruminants under natural
conditions or farming practices in addition to transmission of typical BSE to
humans, domestic cats, and exotic zoo animals(37). The potential importance of
this finding is relevant to L-type BSE, which based on experimental transmission
into humanized PrP transgenic mice and macaques, suggests that L-type BSE is
more pathogenic for humans than typical BSE (24,38).
Saturday, June 25, 2011
Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus
Macaque
"BSE-L in North America may have existed for decades"
Emmanuel Comoy,1,† Valérie Durand,1 Evelyne Correia,1 Sophie Freire,1
Jürgen Richt,2 Justin Greenlee,3 Juan-Maria Torres,4 Paul Brown,1 Bob Hills5 and
Jean-Philippe Deslys1
1Atomic Energy Commission; Fontenay-aux-Roses, France; 2Kansas State
University; Manhattan, KS USA; 3USDA; Ames, IA USA; 4INIA; Madrid, Spain;
5Health Canada; Ottawa, ON Canada†Presenting author; Email:
emmanuel.comoy@cea.fr
The epidemiology of Transmissible mink encephalopathy (TME) indicates an
alimentary origin. Several inter-species transmission experiments have not
succeeded in establishing with certainty any natural reservoir of this prion
strain, although both ovine and bovine sources have been suspected. Cattle
exposed to TME develop a spongiform encephalopathy that is distinct from
classical Bovine Spongiform Encephalopathy (c-BSE).
Inoculation of c-BSE to cynomolgus macaque provided early evidence of a
possible risk to humans, and remains an important model to define the risk of
both primary (oral transmission from cattle to primate) and secondary
(intravenous intra-species transmission) exposures. We have also evaluated the
transmissibility of other cattle prion strains to macaques, including L- and H-
atypical forms of BSE, namely BSE-L and BSE-H, and cattle-adapted TME.
BSE-L induced a neurological disease distinct from c-BSE. Peripheral
exposures demonstrate the transmissibility of BSE-L by oral, intravenous, and
intra-cerebral routes, with incubation periods similar to c-BSE. Cattle-adapted
TME also induced a rapid disease in cynomolgus macaque. The clinical features,
lesion profile, and biochemical signature of the induced disease was similar to
the features observed in animals exposed to BSE-L, suggesting a link between the
two prion strains. Secondary transmissions to a common host (transgenic mouse
overexpressing bovine PrP) of cattle-TME and BSE-L before or after passage in
primates induced diseases with similar incubation periods: like the c-BSE
strain, these cattle strains maintained their distinctive features regardless of
the donor species and passages.
If the link between TME and BSE-L is confirmed, our results would suggest
that BSE-L in North America may have existed for decades, and highlight a
possible preferential transmission of animal prion strains to primates after
passage in cattle.
=====================end...tss====================
link url not available, please see PRION 2011 ;
ALSO, SEE Scrapie Mission, Texas, did not produce _typical_ BSE...
see page 17 here ;
3.57 The experiment which might have determined whether BSE and scrapie
were caused by the same agent (ie, the feeding of natural scrapie to cattle) was
never undertaken in the UK. It was, however, performed in the USA in 1979, when
it was shown that cattle inoculated with the scrapie agent endemic in the flock
of Suffolk sheep at the United States Department of Agriculture in Mission,
Texas, developed a TSE quite unlike BSE.339 The findings of the initial
transmission, though not of the clinical or neurohistological examination, were
communicated in October 1988 to Dr Watson, Director of the CVL, following a
visit by Dr Wrathall, one of the project leaders in the Pathology Department of
the CVL, to the United States Department of Agriculture.340 The results were not
published at this point, since the attempted transmission to mice from the
experimental cow brain had been inconclusive. The results of the clinical and
histological differences between scrapie-affected sheep and cattle were
published in 1995. Similar studies in which cattle were inoculated
intracerebrally with scrapie inocula derived from a number of scrapie-affected
sheep of different breeds and from different States, were carried out at the US
National Animal Disease Centre.341 The results, published in 1994, showed that
this source of scrapie agent, though pathogenic for cattle,
*** did not produce the same clinical signs of brain lesions characteristic
of BSE. ***
3.58 There are several possible reasons why the experiment was not
performed in the UK. It had been recommended by Sir Richard Southwood (Chairman
of the Working Party on Bovine Spongiform Encephalopathy) in his letter to the
Permanent Secretary of MAFF, Mr (now Sir) Derek Andrews, on 21 June 1988,342
though it was not specifically recommended in the Working Party Report or indeed
in the Tyrrell Committee Report (details of the Southwood Working Party and the
Tyrell Committee can be found in vol. 4: The Southwood Working Party, 1988–89
and vol. 11: Scientists after Southwood respectively). The direct inoculation of
scrapie into calves was given low priority, because of its high cost and because
it was known that it had already taken place in the USA.343 It was also felt
that the results of such an experiment would be hard to interpret. While a
negative result 337 Fraser, H., Bruce, M., Chree, A., McConnell, I. and Wells,
G. (1992) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice,
Journal of General Virology, 73, 1891–7; Bruce, M., Chree, A., McConnell, I.,
Foster, J., Pearson, G. and Fraser, H. (1994) Transmission of Bovine Spongiform
Encephalopathy and Scrapie to Mice: Strain Variation and the Species Barrier,
Philosophical Transactions of the Royal Society of London, Series B, Biological
Sciences, 343, 405–11 338 Bruce, M., Will, R., Ironside, J., McConell, I.,
Drummond, D., Suttie, A., McCordie, L., Chree, A., Hope, J., Birkett, C.,
Cousens, S., Fraser, H. and Bostock, C. (1997) Transmissions to Mice Indicate
that ‘New Variant’ CJD is Caused by the BSE Agent, Nature, 389, 498–501 339
Clark, W., Hourrigan, J. and Hadlow, W. (1995) Encephalopathy in Cattle
Experimentally Infected with the Scrapie Agent, American Journal of Veterinary
Research, 56, 606–12 340 YB88/10.00/1.1 341 Cutlip, R., Miller, J., Race, R.,
Jenny, A., Katz, J., Lehmkuhl, H., Debey, B. and Robinson, M. (1994)
Intracerebral Transmission of Scrapie to Cattle, Journal of Infectious Diseases,
169, 814–20 342 YB88/6.21/1.2 343 YB88/11.17/2.4 SCIENCE 84 would be
informative, a positive result would need to demonstrate that when scrapie was
transmitted to cattle, the disease which developed in cattle was the same as
BSE.344 Given the large number of strains of scrapie and the possibility that
BSE was one of them, it would be necessary to transmit every scrapie strain to
cattle separately, to test the hypothesis properly. Such an experiment would be
expensive. Secondly, as measures to control the epidemic took hold, the need for
the experiment from the policy viewpoint was not considered so urgent. It was
felt that the results would be mainly of academic interest.345 3.59
Nevertheless, from the first demonstration of transmissibility of BSE in 1988,
the possibility of differences in the transmission properties of BSE and scrapie
was clear. Scrapie was transmissible to hamsters, but by 1988 attempts to
transmit BSE to hamsters had failed. Subsequent findings increased that
possibility.
1992
NEW BRAIN DISORDER
3. WHAT ABOUT REPORTS OF NEW FORM OF BSE ?
THE VETERINARY RECORD HAS PUBLISHED AN ARTICLE ON A NEW BRAIN DISORDER OF
CATTLE DISCOVERED THROUGH OUR CONTROL MEASURES FOR BSE. ALTHOUGH IT PRESENTS
SIMILAR CLINICAL SIGNS TO BSE THERE ARE MAJOR DIFFERENCES IN HISTOPATHOLOGY AND
INCUBATION PERIODS BETWEEN THE TWO. MUST EMPHASISE THAT THIS IS _NOT_ BSE.
4. IS THIS NEW BRAIN DISORDER A THREAT ?
WE DO NOT EVEN KNOW WHETHER THE AGENT OF THIS DISEASE IS TRANSMISSIBLE. IN
ANY CASE, CASES SO FAR IDENTIFIED HAD SHOWN SIMILAR SYMPTOMS TO THOSE OF BSE,
AND THEREFORE HAVE BEEN SLAUGHTERED AND INCINERATED, SO THAT IF A TRANSMISSIBLE
AGENT WERE INVOLVED IT WOULD HAVE BEEN ELIMINATED. ...
Tuesday, November 17, 2009
SEAC NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS (IBNC) FROM
THE VETERINARY LABORATORIES AGENCY (VLA) SEAC 103/1
NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS
"All of the 15 cattle tested showed that the brains had abnormally
accumulated PrP"
2009
''THE LINE TO TAKE'' ON IBNC $$$ 1995 $$$
1995
page 9 of 14 ;
30. The Committee noted that the results were unusual. the questioned
whether there could be coincidental BSE infection or contamination with scrapie.
Dr. Tyrell noted that the feeling of the committee was that this did not
represent a new agent but it was important to be prepared to say something
publicly about these findings. A suggested line to take was that these were
scientifically unpublishable results but in line with the policy of openness
they would be made publicly available and further work done to test their
validity. Since the BSE precautions were applied to IBNC cases, human health was
protected. Further investigations should be carried out on isolations from
brains of IBNC cases with removal of the brain and subsequent handling under
strict conditions to avoid the risk of any contamination.
31. Mr. Bradley informed the Committee that the CVO had informed the CMO
about the IBNC results and the transmission from retina and he, like the
Committee was satisfied that the controls already in place or proposed were
adequate. ...
snip... see full text
http://web.archive.org/web/20030327015011/http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
Wednesday, July 28, 2010
Atypical prion proteins and IBNC in cattle DEFRA project code SE1796 FOIA
Final report
IN CONFIDENCE
BSE ATYPICAL LESION DISTRIBUTION
http://web.archive.org/web/20041226015813/http://www.bseinquiry.gov.uk/files/yb/1993/03/14001001.pdf
Tuesday, November 02, 2010
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only)
diagnostic criteria CVL 1992
Thursday, May 02, 2013
Chronic Wasting Disease (CWD) Texas Important Update on OBEX ONLY TEXTING
OBEX ONLY
USDA 2003
We have to be careful that we don't get so set in the way we do things that
we forget to look for different emerging variations of disease. We've gotten
away from collecting the whole brain in our systems. We're using the brain stem
and we're looking in only one area. In Norway, they were doing a project and
looking at cases of Scrapie, and they found this where they did not find lesions
or PRP in the area of the obex. They found it in the cerebellum and the
cerebrum. It's a good lesson for us. Ames had to go back and change the
procedure for looking at Scrapie samples. In the USDA, we had routinely looked
at all the sections of the brain, and then we got away from it. They've recently
gone back. Dr. Keller: Tissues are routinely tested, based on which tissue
provides an 'official' test result as recognized by APHIS.
Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't
they still asking for the brain? But even on the slaughter, they're looking only
at the brainstem. We may be missing certain things if we confine ourselves to
one area.
snip.............
Dr. Detwiler: It seems a good idea, but I'm not aware of it. Another
important thing to get across to the public is that the negatives do not
guarantee absence of infectivity. The animal could be early in the disease and
the incubation period. Even sample collection is so important. If you're not
collecting the right area of the brain in sheep, or if collecting
lymphoreticular tissue, and you don't get a good biopsy, you could miss the area
with the PRP in it and come up with a negative test. There's a new, unusual form
of Scrapie that's been detected in Norway. We have to be careful that we don't
get so set in the way we do things that we forget to look for different emerging
variations of disease. We've gotten away from collecting the whole brain in our
systems. We're using the brain stem and we're looking in only one area. In
Norway, they were doing a project and looking at cases of Scrapie, and they
found this where they did not find lesions or PRP in the area of the obex. They
found it in the cerebellum and the cerebrum. It's a good lesson for us. Ames had
to go back and change the procedure for looking at Scrapie samples. In the USDA,
we had routinely looked at all the sections of the brain, and then we got away
from it. They've recently gone back.
Dr. Keller: Tissues are routinely tested, based on which tissue provides an
'official' test result as recognized by APHIS .
Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't
they still asking for the brain? But even on the slaughter, they're looking only
at the brainstem. We may be missing certain things if we confine ourselves to
one area.
snip...
FULL TEXT;
Completely Edited Version PRION ROUNDTABLE
Accomplished this day, Wednesday, December 11, 2003, Denver, Colorado
END...TSS
snip...see ;
Tuesday, November 02, 2010
IN CONFIDENCE
The information contained herein should not be disseminated further except
on the basis of "NEED TO KNOW".
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only)
diagnostic criteria CVL 1992
In Confidence - Perceptions of unconventional slow virus diseases of
animals in the USA - APRIL-MAY 1989 - G A H Wells
snip...
PAGE 31
Appendix I
VISIT TO USA - DR A E WRATHALL - INFO ON BSE AND SCRAPIE
1. 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 emhryos from naturally infected sheep (cf SPA).
3. Prof. A Robertson gave a brief account of BSE. The US approach was to
PAGE 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.
please see ;
In Confidence - Perceptions of unconventional slow virus diseases of
animals in the USA - APRIL-MAY 1989 - G A H Wells
SNIP...
see full text;
Monday, June 3, 2013
Unsuccessful oral transmission of scrapie from British sheep to
cattle
Thursday, February 14, 2013
The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE and
TSE prion disease
SUMMARY REPORT CALIFORNIA BOVINE SPONGIFORM ENCEPHALOPATHY CASE
INVESTIGATION JULY 2012
Summary Report BSE 2012
Executive Summary
Saturday, August 4, 2012
Update from APHIS Regarding Release of the Final Report on the BSE
Epidemiological Investigation
Saturday, August 4, 2012
*** Final Feed Investigation Summary - California BSE Case - July 2012
Saturday, December 15, 2012
Bovine spongiform encephalopathy: the effect of oral exposure dose on
attack rate and incubation period in cattle -- an update 5 December 2012
Tuesday, June 4, 2013
INTERPRETING RESULTS OF FSIS VERIFICATION SAMPLING OF DOMESTIC BEEF PRODUCT
DERIVED FROM ADVANCED MEAT RECOVERY SYSTEMS (AMR01/FAMR01) FSIS Notice
38-12
Tuesday, June 11, 2013
Weld County Bi-Products dba Fort Morgan Pet Foods 6/1/12 significant
deviations from requirements in FDA regulations that are intended to reduce the
risk of bovine spongiform encephalopathy (BSE) within the United States
Thursday, June 6, 2013
BSE TSE PRION USDA FDA MAD COW FEED COMPLIANCE REPORT and NAI, OAI, and VAI
ratings as at June 5, 2013
Greetings,
since our fine federal friends have decided not to give out any more
reports on the USA breaches of the feed ban and surveillance etc. for the BSE
TSE prion mad cow type disease in the USDA livestock, I thought I might attempt
it. I swear, I just don’t understand the logic of the SSS policy, and that
includes all of it. I assure you, it would be much easier, and probably better
for the FDA and the USDA INC., if they would simply put some kind of report out
for Pete’s sake, instead of me doing it after I get mad, because I am going to
put it all out there. the truth.
PLEASE BE ADVISED, any breach of any of the above classifications OAI, VAI,
RTS, CAN lead to breaches into the feed BSE TSE prion protocols, and CAN lead to
the eventual suspect tainted feed reaching livestock. please, if any USDA
official out there disputes this, please explain then how they could not.
paperwork errors can eventually lead to breaches of the BSE TSE prion mad cow
feed ban reaching livestock, or contamination and exposure there from, as well.
I would sure like to see the full reports of just these ;
4018 CHI-DO 3007091297 Rancho Cantera 2866 N Sunnyside Rd Kent IL
61044-9605 OPR FR, OF HP 11/26/2012 OAI Y
9367 3008575486 Rocky Ford Pet Foods 21693 Highway 50 East Rocky Ford CO
81067 OPR RE, TH HP 2/27/2013 OAI N
9446 DEN-DO 1713202 Weld County Bi Products, Inc. 1138 N 11th Ave Greeley
CO 80631-9501 OPR RE, TH HP 10/12/2012 OAI N
9447 DEN-DO 3002857110 Weld County Bi-Products dba Fort Morgan Pet Foods
13553 County Road 19 Fort Morgan CO 80701-7506 OPR RE HP 12/7/2011 OAI N
see full list of the fda mad cow bse feed follies, toward the bottom, after
a short brief update on the mad cow bse follies, and our good friend Lester
Crawford that was at the FDA.
ALSO, I would kindly like to comment on this FDA BSE/Ruminant Feed
Inspections Firms Inventory (excel format)4 format, for reporting these breaches
of BSE TSE prion protocols, from the extensive mad cow feed ban warning letters
the fda use to put out for each violations. simply put, this excel format sucks,
and the FDA et al intentionally made it this difficult to follow the usda fda
mad cow follies. this is an intentional format to make it as difficult as
possible to follow these breaches of the mad cow TSE prion safety feed
protocols. to have absolutely no chronological or numerical order, and to format
such violations in a way that they are almost impossible to find, says a lot
about just how far the FDA and our fine federal friends will go through to hide
these continued violations of the BSE TSE prion mad cow feed ban, and any
breaches of protocols there from. once again, the wolf guarding the henhouse $$$
NAI = NO ACTION INDICATED
OAI = OFFICIAL ACTION INDICATED
VAI = VOLUNTARY ACTION INDICATED
RTS = REFERRED TO STATE
Inspections conducted by State and FDA investigators are classified to
reflect the compliance status at the time of the inspection, based upon whether
objectionable conditions were documented. Based on the conditions found,
inspection results are recorded in one of three classifications:
OAI (Official Action Indicated) when inspectors find significant
objectionable conditions or practices and believe that regulatory sanctions are
warranted to address the establishment’s lack of compliance with the regulation.
An example of an OAI classification would be findings of manufacturing
procedures insufficient to ensure that ruminant feed is not contaminated with
prohibited material. Inspectors will promptly re-inspect facilities classified
OAI after regulatory sanctions have been applied to determine whether the
corrective actions are adequate to address the objectionable conditions.
VAI (Voluntary Action Indicated) when inspectors find objectionable
conditions or practices that do not meet the threshold of regulatory
significance, but warrant an advisory to inform the establishment that
inspectors found conditions or practices that should be voluntarily corrected.
VAI violations are typically technical violations of the 1997 BSE Feed Rule.
These violations include minor recordkeeping lapses or conditions involving
non-ruminant feeds.
NAI (No Action Indicated) when inspectors find no objectionable conditions
or practices or, if they find objectionable conditions, those conditions are of
a minor nature and do not justify further actions.
when sound science was bought off by junk science, in regards to the BSE
TSE prion mad cow type disease, by the USDA, CFIA, WHO, OIE, et al. $$$
when the infamous, and fraudulently USDA, FSIS, APHIS, FDA, gold card was
taken away that infamous day in December of 2003, all cards were off the table,
it was time to change the science, and change they did. ...tss
snip. ...please see full text ;
Thursday, June 6, 2013
BSE TSE PRION USDA FDA MAD COW FEED COMPLIANCE REPORT and NAI, OAI, and VAI
ratings as at June 5, 2013
Thursday, May 30, 2013
World Organization for Animal Health (OIE) has upgraded the United States'
risk classification for mad cow disease to "negligible" from "controlled", and
risk further exposing the globe to the TSE prion mad cow type disease
U.S. gets top mad-cow rating from international group and risk further
exposing the globe to the TSE prion mad cow type disease
Monday, December 31, 2012
Creutzfeldt Jakob Disease and Human TSE Prion Disease in Washington State,
2006–2011-2012
Thursday, February 21, 2013
National Prion Disease Pathology Surveillance Center Cases Examined January
16, 2013
16 YEAR OLD SPORADIC FFI ?
Monday, January 14, 2013
Gambetti et al USA Prion Unit change another highly suspect USA mad cow
victim to another fake name i.e. sporadic FFI at age 16 CJD Foundation goes
along with this BSe
Monday, December 31, 2012
Creutzfeldt Jakob Disease and Human TSE Prion Disease in Washington State,
2006–2011-2012
Tuesday, December 25, 2012
CREUTZFELDT JAKOB TSE PRION DISEASE HUMANS END OF YEAR REVIEW DECEMBER 25,
2012
Tuesday, June 26, 2012
Creutzfeldt Jakob Disease Human TSE report update North America, Canada,
Mexico, and USDA PRION UNIT as of May 18, 2012
type determination pending Creutzfeldt Jakob Disease (tdpCJD), is on the
rise in Canada and the USA
Wednesday, June 13, 2012
MEXICO IS UNDER or MIS DIAGNOSING CREUTZFELDT JAKOB DISEASE AND OTHER PRION
DISEASE SOME WITH POSSIBLE nvCJD
Thursday, April 4, 2013
Variably protease-sensitive prionopathy in the UK: a retrospective review
1991–2008
Brain (2013) 136 (4): 1102-1115. doi: 10.1093/brain/aws366
Sunday, March 31, 2013
Creutzfeldt Jakob Disease CJD worlds youngest documented victim, 11 years
old, shall we pray
Tuesday, March 05, 2013
A closer look at prion strains Characterization and important implications
Prion
7:2, 99–108; March/April 2013; © 2013 Landes Bioscience
Tuesday, May 28, 2013
Late-in-life surgery associated with Creutzfeldt-Jakob disease: a
methodological outline for evidence-based guidance
Wednesday, May 16, 2012
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Proposal ID: 29403
Saturday, May 25, 2013
Brain homogenates from human tauopathies induce tau inclusions in mouse
brain
Tuesday, May 21, 2013
IS ALZHEIMER’S DISEASE A PRION DISEASE? the possible secondary transmission
by blood transfusion are posed
Tuesday, May 7, 2013
Proteinopathies, a core concept for understanding and ultimately treating
degenerative disorders?
Monday, September 26, 2011
Variably Protease-Sensitive Prionopathy, Prionpathy, Prionopathy, FFI, GSS,
gCJD, hvCJD, sCJD, TSE, PRION, update 2011
Friday, September 3, 2010
Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids,
Prionpathy, Prionopathy, TSE
still pondering...TSS
