Unsuccessful oral transmission of scrapie from British sheep to cattle
T. Konold, J. Spiropoulos, M. J. Chaplin, M. J. Stack, S. A. C. Hawkins, J.
W. Wilesmith, G. A. H. Wells
Following the detection of bovine spongiform encephalopathy (BSE) in the
UK, epidemiological studies identified a foodborne source with meat and bone
meal (MBM) as the likely vehicle of infection (Wilesmith and others 1988).
Subsequent studies demonstrated that the infectious agent is a transmissible
spongiform encephalopathy (TSE) strain with uniform neuropathological, molecular
and biological properties (Simmons and others 1996, Bruce 2003, Vidal and others
2005, Green and others 2005a, Stack and others 2011a). Furthermore, transmission
studies implicated the BSE agent as the cause of variant Creutzfeldt-Jakob
disease in human beings (Bruce and others 1997). However, the origin of the
agent remains unknown. One hypothesis suggests that it was a strain of sheep
scrapie in the UK (Wilesmith and others 1988). Recycling of this agent in MBM,
and inclusion of MBM in ruminant feed prior to control measures, would
inevitably have resulted in exposure of sheep, raising concerns that the BSE
agent may have been established in the sheep population, possibly manifesting in
disease indistinguishable from scrapie (Schreuder and Somerville 2003). The
present study was initiated in 1997 to determine the susceptibility of cattle to
the oral exposure of scrapie-affected brain by using pools of brains from
scrapie-affected British sheep sourced during the BSE epidemic.
All procedures were carried out in accordance with the Animal (Scientific
Procedures) Act 1986, under licence from the UK Government Home Office.
snip...
Within the constraints of the study design, the results do not support the
hypothesis of potential pathogenicity of scrapie agents or the BSE agent in
British sheep, to cattle by oral exposure. However, this negative finding does
not refute the possibility of a sheep origin of the BSE agent. That scrapie
strains are pathogenic for cattle by intracerebral inoculation has been shown
previously in the USA (Cutlip and others 1994, Clark and others 1995, Robinson
and others 1995) and from scrapie brain pools sourced from British sheep culled
prior to and during the BSE epidemic (Konold and others 2006). While the cattle
in these studies developed a TSE the resulting disease phenotypes did not
resemble BSE (Konold and others 2006). Oral dosing of cattle with US isolates of
scrapie (raw brain and brain processed to MBM) failed to produce disease in
cattle kept up to eight years postdosing (Cutlip and others 2001). Although not
addressed in the present study, it is possible, nevertheless, that the rendering
processes used previously in the production of MBM in Britain, might have
modified a scrapie agent to become pathogenic for cattle by the oral route.
snip...
Cattle may be susceptible to other scrapie strains not present in the
pools, and these might include atypical scrapie, which has been retrospectively
diagnosed in a sheep culled in the UK in 1987 (Webb and others 2009), and is
likely to have been present in the British sheep population prior to the
discovery of BSE in cattle. As cattle were exposed to a pool of scrapie-affected
sheep brains, we also cannot exclude the possibility of interaction between
strains, which may prevent the detection of supposedly more pathogenic strains
for cattle like the BSE agent, as demonstrated by testing a mix of scrapie and
BSE agents by WB (Baron and Biacabé 2001) or wild-type mouse bioassay (Green and
others 2005b). Transgenic mice expressing the ovine or bovine prion protein
gene, which were not available when the project was initiated, were used
successfully to differentiate BSE from scrapie strains in mixed infections of
sheep by intracerebral inoculation (Lantier and others 2009), but nothing is
known about the potential for interaction of strains following oral exposure to
a mixture of agents.
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
see ;
EVIDENCE OF SCRAPIE IN SHEEP AS A
RESULT OF FOOD BORNE EXPOSURE
This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies.
THE RISK OF TRANSMISSION OF BSE TO SHEEP VIA FEED
Prusiner vs Maff on BSE brains, and delaying science for profits $
BSE TRANSMISSION STUDIES
Furthermore, we showed that the strain responsible for iCJD is closely
related to that of one patient with sCJD, and, more unexpectedly, that these
agents were similar to the French scrapie strain studied (but different from the
U.S. scrapie strain). This finding requires a cautious interpretation for
several reasons, not least because of the inevitably limited number of TSE
strains that can be studied by such a cumbersome method as strain typing.
Nonetheless, it also prompts reconsideration of the possibility that, in some
instances, sheep and human TSEs can share a common origin.
snip...
Friday, April 19, 2013
APHIS 2013 Stakeholder Meeting (March 2013) BSE TSE PRION
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
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
http://bse-atypical.blogspot.com/2012/12/bovine-spongiform-encephalopathy-effect.html
Thursday, February 14, 2013
The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE and TSE prion disease
http://bse-atypical.blogspot.com/2013/02/the-many-faces-of-mad-cow-disease.html
2012 atypical L-type BSE BASE California reports
Saturday, August 4, 2012
*** Final Feed Investigation Summary - California BSE Case - July 2012
atypical L-type BASE BSE California
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
*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.
http://cdmrp.army.mil/prevfunded/nprp/NPRP_Summit_Final_Report.pdf
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
Journal of Veterinary Diagnostic Investigation 23(3) 407– 420 © 2011 The
Author(s) Reprints and permission: sagepub.com/journalsPermissions.nav DOI:
10.1177/1040638711403404 http://jvd.sagepub.com
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...
Atypical bovine spongiform encephalopathy cases: H-type and L-type BSE
Bovine spongiform encephalopathies with molecular profiles different from that
of C-type BSE have been reported since 2004 by investigators from several
countries. To date, 2 molecular types of atypical BSE have been described, and a
summary was published on the Internet in 2007 by the Spongiform Encephalopathy
Advisory Committee (http://www.seac.gov.uk/statements/newformsbse.
htm). One molecular type is the L-type, which has been found in cattle in
Italy,20 Japan,117 Germany,16 Belgium,27 and Canada.28 Western blot analysis
demonstrates the L-type form to have a lower molecular mass of the
unglycosylated PrPd isoform when compared with C-type BSE. The second type of
atypical BSE is the H-type, characterized by Western blot analysis to have a
higher molecular mass of the unglycosylated isoform. To date, the H-type has
been described in cattle from France,11 Germany,16 Japan,101 the Netherlands,55
Poland,55 Switzerland,103 the United Kingdom99 and the United States.86 The
unusual molecular phenotype of the H-type BSE cases was characterized by 1) a
higher molecular mass of the unglycosylated PrPd isoform, 2) a strong labeling
of all 3 PrPd polypeptides (unglycosylated, monoglycosylated and diglycosylated
isoforms) with the PrP-specific monoclonal antibodies 6H4 (amino acid epitope
consisting of DYEDRYYRE) and P4 (amino acid epitope consisting of
GGGWGQGGTHGQWNK), and 3) a glycoform profile with a less prominent
diglycosylated PrPd isoform (French and U.S. cases). Some, but not all H-type
BSE cases were positive by immunohistochemistry (IHC) because in some cases
tissues were not available for immunohistochemical testing. In contrast, L-type
cases were characterized by 1) a lower molecular mass of the unglycosylated PrPd
isoform, 2) a strong labeling of all 3 PrPd polypeptides with the PrP-specific
monoclonal antibody 6H4 but not P4, and 3) a glycoform profile with a
monoglycosylated PrPd band at least equally as intense as the diglycosylated
PrPd isoform. Epitope mapping with monoclonal antibodies as mentioned above is
used as one tool to differentiate TSE strains by IHC57,59 and Western blot.100
Until these recent atypical BSE reports, BSE has been shown to be very
consistent and uniform in appearance, even after transmission to other species.
There are several hypotheses proposed to explain atypical BSE cases.11 One
theory proposes that there are variants of BSE with different molecular features
in cattle; a second theory proposes that cattle may have been affected by
another TSE (e.g., scrapie or CWD); a third theory proposes that a rare sporadic
or genetic form of TSE disease could exist in cattle as described for human
TSEs. Recently a new PRNP allele (E211K)85 was reported in a cow with H-type BSE
indicating a possible genetic form of BSE that is heritable.77 Research on
atypical BSE, first reported in 2004,11 has investigated intra- and interspecies
transmissibility, influence of host genotype, PrPd tissue distribution, and
incidence rate of atypical BSE.* Both H- and L-type BSE cases have occurred in
different breeds and PRNP genotypes. The majority of cases were in older cattle
(>10 yrs of age) and very few of the animals had typical clinical signs of
C-type BSE. Importantly, experimental transmission of selected H- and L-type BSE
cases, into cattle, mice, and nonhuman primates has been
reported.7,16,18,23,63,68 Relatively less is known about the histopathological
and immunohistochemical characteristics of atypical BSE. Microscopic examination
of L-type BSE cases revealed prion deposition in the brain that differed in
distribution from C-type BSE cases and included amyloid plaques and increased
PrPd immunoreactivity in the olfactory bulbs,19 *References 6, 9, 15, 16, 18,
23, 55, 63, 68, 77, 79, 85, 93 although PrPRes immunoreactivity has been
detected by Western blot in olfactory bulbs of cattle with C-type BSE.104 The
investigators designated this newly identified disease phenotype “bovine
amyloidotic spongiform encephalopathy” or BASE.20 The morphological PrPd
deposition of BASE cases differed from that observed in C-type BSE cases:
relatively few deposits were found in the obex region but much more occurred in
the more rostral structures of the brain, namely in the thalamus and the
olfactory bulb. The PrPd-positive deposits were predominantly in the form of
amyloid-like plaques.20 The latter has been reported for TSEs in human beings,
but not for BSE in cattle. Less is known about the microscopic appearance of
H-type BSE, but recent unpublished findings (Chiara Porcario, et al., submitted
to BMC Vet Res) comparing the Italian and the U.S. IHC confirmatory methods for
BSE differentiated the different phenotypes (C-, H-, and L-type BSE) as each
appearing to be characterized by distinctive features of PrPd deposition.
Granular and linear tract PrPd deposits were a distinct feature of C-type BSE
cases, whereas intraglial and intraneuronal PrPd deposition appeared as the most
representative trait of H-type BSE as reported previously,16 and the presence of
PrPd deposits organized as plaques was a distinguishing hallmark of L-type BSE
(BASE) cases, also as previously reported with a preferential distribution in
more rostral brain regions.18,20
Transmissible mink encephalopathy Transmissible mink encephalopathy has
been sporadically identified in ranch-raised mink (Neovison vison). It was first
documented in Wisconsin in 194729 and the last reported outbreak in the United
States was in 1985.70 Like BSE, TME is a food borne disease that has been
experimentally transmitted to a variety of animal species, including cattle,
sheep, goats, monkeys, hamsters, mink, American sable (pine marten), beech
marten, skunks, ferrets, and raccoons. 29,30 Reported histopathological findings
in mink with TME indicate detectable lesions limited to the CNS with
microvacuolation of the gray matter, reactive astrocytosis in the cerebral
cortex, and neuronal degeneration.69 Microscopic lesions were reported as a
scrapie-like spongiform encephalopathy, which preceded clinical disease by
approximately 6 weeks.69 Weeks before microscopic lesions were visible,
ultrastructural alterations were recognized when assessed by electron microscopy
and included loss of normal ultrastructure of nerve endings, larger dendritic
segments, and variously shaped vesicles and vacuoles in the neuropil. 119 A
review of published literature on TME found no descriptions of PrPd distribution
patterns in mink as studies in mink were completed prior to development of
current diagnostic methods including IHC and Western blotting. Moreover, the
lack of natural cases of TME for the past several decades and the advent of the
hamster model83 made the mink a less desirable animal model for study. The
origin of TME is unknown, but it is speculated to have been derived from sheep
scrapie or from an unknown TSE in cattle.70,71
Experimental interspecies transmission of transmissible spongiform
encephalopathies into cattle Experimental scrapie transmission to cattle During
the 1990s the possibility that U.S. strains of sheep scrapie might cause BSE
following transmission to cattle was assessed experimentally through both IC and
oral inoculations. Intracerebral inoculations resulted in a 100% transmission of
a prion disease to cattle between 14–18 months following inoculation.26 A
separate study using multiple simultaneous routes of inoculation (including IC)
found only 20–40% transmission depending on the source of inoculum and a longer
incubation period of 24–48 months following inoculation.22 Although the affected
cattle exhibited anorexia, weight loss, leg and back stiffness, incoordination,
and rear leg weakness eventually leading to severe lethargy and ataxia, they did
not show signs of hyperactivity, one of the characteristic clinical signs of
BSE. To differentiate scrapie in cattle from BSE, there was no microscopic
evidence of spongiform changes in the scrapie-affected cattle. Neuropathological
changes were not present in the CNS of scrapie-affected cattle whereas
spongiform changes are usually observed in clinical BSE cases.91
Immunoreactivity for PrPd in scrapie-affected cattle was observed predominately
in neuronal cell bodies with relatively little accumulation in the
neuropil,25,26 in contrast to BSE where there is a diffuse distribution of PrPd
in the CNS.91 Following oral ingestion of the scrapie agent, cattle did not
develop symptoms of neurological disease nor did they develop spongiform lesions
nor PrPd deposits in the CNS after eight years post inoculation.24 Such
experiments demonstrate that IC inoculation of the U.S. scrapie agent into
cattle results in a disease with clinicopathologic hallmarks that differ
significantly from cattle with BSE. Whereas oral BSE inoculation into cattle is
a highly efficient means of transmission,107 this is not the case for scrapie.
24 Despite the proposed linkage of the BSE epidemic initiation to scrapie,114
scrapie isolates from U.S. sheep could only be transmitted to cattle by IC
inoculation, and the pathology and clinical disease differed from both BSE in
cattle and scrapie in sheep.25,26 The results were later corroborated by
inoculation of cattle with scrapie isolates from the United Kingdom.64
Therefore, current experimental evidence from scrapie transmission studies into
cattle does not support the hypothesis that the U.K. BSE epidemic originated
from feeding of scrapie PrPd to cattle. However, no experimental transmission
studies of atypical scrapie into cattle have been reported to date.
Experimental chronic wasting disease transmission to cattle The recognition
of CWD116 in captive and free-ranging cervids in the United States raised
questions about the possible transmissibility of such agent to other ruminant
species that may contact affected cervids or their carcasses on pasturelands or
farms. In 2001, preliminary findings of IC inoculation of cattle with the CWD
agent from mule deer tissue were published.37 Although brains of the animals
showed no significant histopathologic changes, PrPd was detected by IHC and
Western blot, indicating that amplification of the abnormal CWD prion had
occurred. In cattle inoculated with CWD, the consistent and sentinel finding of
localization of PrPd to multifocal and distinct aggregates confined to glial
cells and associated neuropil clearly distinguished this IHC pattern from that
seen in scrapie- and BSE-affected cattle, and for that matter, any other TSE.
Another distinct feature of the distribution of immunoreactivity for PrPd in CWD
of cattle was the infrequent finding of small (≤40 μm) plaques in the cerebrum.
Although the characteristic pattern of distinct multifocal aggregates of PrPd
predominated, in some white-tailed CWD inoculated cattle labeling in obex and
midbrain appeared as coalescing foci. Unlike BSE- and TME-inoculated cattle,
PrPd labeling of retina was not present.38,45 On the other hand, in an ongoing
study, none of the cattle given the same inoculum orally (50 g of pooled
brain/animal) have shown any evidence of prion disease up to 9 years after
inoculation.115 In contrast to the current authors’ first study,38 which
demonstrated a low attack rate of mule deer CWD upon first passage, subsequent
IC inoculation of mule deer CWD passed once in cattle (i.e., cattle-adapted mule
deer CWD), showed clinicopathological findings (similar to first passage) in all
inoculated cattle within 16.5 months postinoculation. 39 This increased attack
rate with shorter incubation periods may indicate adaptation of the mule deer
CWD agent to the new cattle host. However, it could also be argued that the
inoculum used for the primary passage simply had a lower infectivity titer than
that used for the second passage. 37–39 Recent findings of IC inoculation of CWD
from white-tailed deer into cattle showed that the white-tailed deer inoculum
had a higher attack rate (86%) in cattle than the mule deer CWD inoculum used
previously; however, microscopic lesions typical of BSE were still not
observed.45 While cattle inoculated with CWD from white-tailed deer and mule
deer CWD had similar Western blot molecular profile results, there was no change
between first and second passage of mule deer CWD in cattle.39 A recent study
(Greenlee JJ, Nicholson EM, Kunkle RA, Hamir AN: 2009, Susceptibility of cattle
to first-passage intracerebral inoculation with chronic wasting disease agent
from elk. In: Proceedings of the American College of Veterinary Pathologists
Annual Meeting, p. 1058) assessing transmissibility of CWD derived from elk to
cattle also found a low rate of transmission. Clinical signs of poor appetite,
weight loss, circling, and bruxism occurred in 2 out of 16 cattle at 16 and 17
months post-inoculation. No spongiform lesions were detected; however, in the 2
diseased cattle, PrPd was detected and confined to the CNS and was similar in
distribution to cattle inoculated with CWD from mule deer with the most
prominent immunoreactivity in midbrain, brainstem, and hippocampus with lesser
immunoreactivity in the cervical spinal cord. The lack of spongiform lesions in
any of the IC CWD-inoculated cattle (first or second passage of mule deer CWD)
and no change in PrPd deposition patterns suggests the differences in attack
rate between elk CWD, mule deer CWD, and white-tailed deer CWD upon first
passage are likely a difference in interspecies transmission susceptibility
(i.e., a species barrier), although differences in infectivity titer of each
inoculum cannot be excluded. Additional studies are required to fully assess the
potential for cattle to develop CWD through a more natural route of exposure,
but the cumulative evidence, thus far, of the lack of spongiform lesions and the
differences from BSE in PrPd distribution after IC inoculation, along with no
evidence of transmission following oral exposure, suggests that risk of
transmission through routes other than IC is low.
Experimental transmissible mink encephalopathy transmission to cattle In
1995, 3 different sources of TME were tested in cattle and in all instances the
animals developed clinical disease and severe spongiform encephalopathy.88 The
spongiform changes and astrocytic responses were considered more pronounced than
those of natural BSE, but similar to the pathology observed after experimental
IC BSE inoculations. This work confirmed an earlier report of TME transmission
to cattle,70 which lent strength to the proposal that TME outbreaks in the
United States were caused by contaminations of feed with a TSE agent present in
“downer” cows. This hypothesis was also partially supported by subsequent
experiments that showed that the BSE agent produced spongiform encephalopathy in
mink after oral exposure.87 However, clinical signs and histopathologic lesions
were reported to be distinguishable from natural TME.87 Subsequent IC
inoculations of cattle with first and second cattle-passaged TME confirmed the
earlier findings and also described for the first time the immunohistochemical
and Western blot characteristics (lower molecular weight of cattle-adapted TME
vs. C-type BSE by Western blot) of the accumulated PrPd, which indicated further
similarities between TME and BSE in cattle40 and accentuated their
dissimilarities from experimental scrapie and experimental CWD in cattle. A 2007
study lends further to the relationship between TME and L-type BSE, where in an
ovinized transgenic mouse model, cattle-passaged TME presented with the same
phenotypic characteristics as atypical L-type BSE.5 With TME in cattle, the
predominant pattern of immunohistochemical labeling was diffuse, evenly
distributed, punctuate and coarse granules that involved most areas of the
neuropil. Perineuronal labeling of PrPd was regularly noted, in contrast to its
non-presence in scrapie- and CWDinoculated cattle. However, to the authors’
knowledge, experimental studies investigating the oral route of transmission of
TME to cattle have as yet not been conducted.
Host species exerts influence over PrPd tissue distribution A consistent
finding from the experimental interspecies transmission studies of scrapie, CWD,
and TME into cattle is the observation that the PrPd tissue distribution in
cattle remains essentially restricted to the CNS and, aside from the
distinctions noted above regarding PrPd immunoreactivity distribution within the
CNS, it is no more extensive than naturally occurring BSE in cattle.24–26,37,40
Importantly, cattle inoculated with TME,40 scrapie,24–26 and CWD37,38,40 have no
evidence of a lymphoid or blood phase of PrPd; which is a distinction from
classical scrapie and CWD in their natural hosts. Although detectable PrPd has
been reported in the distal ileum following experimental oral BSE challenge in
cattle and occasionally in the tonsil, nictitating membrane, or bone
marrow,106,109 studies of naturally occurring clinical cases of BSE have found
infectivity only in the CNS tissue using conventional mouse bioassays.12 A
recent experiment on bone marrow infectivity of cattle orally inoculated with
BSE used IC inoculation of cattle as a bioassay with sternal bone marrow
collected at 22, 26, 32, and 36 months after exposure and found no evidence of
BSE in cattle 70–91 months post inoculation, suggesting that disease-causing BSE
material in bone marrow is either a rare event or that it may be consistently
present but at levels undetectable by what is perhaps considered the most
sensitive bioassay (i.e., IC inoculation of cattle).97 The consistent detectable
tissue distribution of PrPd in cattle experimentally inoculated with BSE, TME,
CWD, or scrapie is essentially restricted to the bovine nervous
system,24–26,37,38,40,42,94 as has been reported in naturally occurring cases of
BSE.17 Bovine tissue infectivity studies in transgenic mice that are highly
sensitive to BSE have confirmed the essential restriction of infectivity to the
nervous system in clinically diseased BSE cattle.17 Collectively, these results
indicate that the distribution of PrPd of BSE in cattle is fundamentally
different from TSEs in sheep, cervids, or mice.17 In contrast, sheep and cervids
appear to have extensive lymphoid tissue involvement with PrPd deposition,
regardless of the TSE with which they are inoculated.38,41,44,59 The only
exceptions to this paradigm have been studies where lymphoid involvement in elk
or European red deer experimentally inoculated with scrapie or BSE,
respectively, was not observed.43,44,72 Up to 15% of elk with naturally
occurring CWD show PrPd in the CNS and not in the lymphoid tissues.98
It can be concluded that the animal host, especially cattle, exerts
considerable influence over the pathogenesis of a prion disease in terms of what
tissues are involved and what can be seen in one animal species does not always
extrapolate to another. In particular, no evidence exists to suggest that
infectivity can be found in the blood of cattle with BSE as tested by bioassay
of spleen and/or blood in bovinized transgenic mice,17,34 whereas lines of
evidence exist that suggest that infectivity can be found in the blood of
cervids with CWD, scrapie in sheep, and vCJD in human beings. Whole blood
transfusion studies in sheep using donor sheep with experimental BSE or with
natural scrapie have shown that infectivity resides in the blood of sheep.51–54
Similarly, transmissibility by blood transfusion has been reported for deer with
experimental CWD.73
Differential diagnosis and conclusions
Over the past 20 years, several interspecies transmissibility studies of
various endemic TSEs (scrapie, CWD, and TME) to various livestock hosts have now
been completed. A limitation of the published research on experimental
interspecies TSE transmissions to cattle is the possibility that IC
inoculation results in the various clinical, histological, and diagnostic test
differences observed between scrapie and CWD in cattle versus BSE. However,
arguing against those findings being an artifact of the experimental design is
the fact that oral challenge studies with both CWD and scrapie into cattle have
failed to cause a TSE, and the differences in pathology, IHC, and Western blot
that have been observed are in keeping with a species barrier for cattle against
these two prion diseases. Moreover, the similarities of experimental BSE
transmission to mink by oral or IC challenge support the IC route as a valid
experimental approach.87 A brief description of clinical, histopathological, and
immunohistochemical findings, and molecular phenotype in cattle is summarized in
Table 1. Figure 1 illustrates histological changes in the brain of cattle with
the selected TSEs. Figure 2 illustrates the immunohistochemical immunoreactivity
differences of cattle from these same studies and Figure 3 illustrates the
Western blot molecular profile differences. Although the scrapie and CWD
transmission to cattle studies failed to reproduce a prion disease exactly like
BSE, they are important in that no reported bovine TSE cases to date appear
similar to experimental CWD or scrapie in cattle, thus providing evidence that
cattle seem naturally resistant to CWD and scrapie. In contrast to
cattle-passaged scrapie and CWD, which are phenotypically distinct from BSE in
the natural host, cattle-passaged TME shows intriguing phenotypic similarities
with the L-type BSE. It is critical to note these findings give further
scientific assurance that the confirmatory histological, immunohistochemical and
Western blot tests employed in the current international TSEs surveillance
programs are capable of detecting different prion strains in cattle and would
implicate their origin, should such a cross-species transmission occur naturally
in the future. Finally, these studies provide valuable confirmatory information
regarding the range of tissues to include as specified risk material and have
established an archive of tissues available to the greater scientific community
for prion research.
Key words: Bovine spongiform encephalopathy; cattle; chronic wasting
disease, prion diseases; PrP immunohistochemistry; PrP Western blot; spongiform
encephalopathy; transmissible mink encephalopathy; variant Creutzfeldt-Jakob
disease.
"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
To: flounder9@verizon.net
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
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
http://creutzfeldt-jakob-disease.blogspot.com/2013/03/a-closer-look-at-prion-strains.html
Tuesday, May 28, 2013
Late-in-life surgery associated with Creutzfeldt-Jakob disease: a methodological outline for evidence-based guidance
Monday, April 15, 2013
Dr. Stephen B. Thacker Director Centers for Disease Control and
Prevention′s Office of Science, Epidemiology and Laboratory Services (OSELS)
dies from Creutzfeldt Jakob Disease CJD
Sunday, February 10, 2013
Creutzfeldt-Jakob disease (CJD) biannual update (February 2013) Infection
report/CJD
Thursday, January 17, 2013
TSE guidance, surgical, dental, blood risk factors, Part 4 Infection
control of CJD, vCJD and other human prion diseases in healthcare and community
settings (updated January 2013)
Tuesday, May 21, 2013
CJD, TSE, PRION, BLOOD Abstracts of the 23rd Regional Congress of the
International Society of Blood Transfusion, Amsterdam, The Netherlands, June
2-5, 2013
Tuesday, March 5, 2013
Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening
of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)
FDA believes current regulation protects the public from BSE but reopens
comment period due to new studies
***!!!***
see steady increase of the sporadic CJD’s. ...
The Akron, Ohio-based CJD Foundation said the Center for Disease Control
revised that number in October of 2004 to about one in 9,000 CJD cases per year
in the population group age 55 and older.
Provider Details
Creutzfeldt-jakob Disease Foundation
Description:
CJD is a rare, fatal brain disorder. The statistical incidence of CJD cases
in the US has been revised to reflect that there is one case per 9000 in adults
age 55 and older. Eighty five percent of the cases are sporadic, meaning there
is no known cause at present.Toll free in state: (800) 659-1991, Main: (330)
665-5590
Service Categories Brain Injury, Dementia/Alzheimer's, Donations, Mental
Health
Contact Information: Phone: (330) 665-5590
Last Update Date: 07/23/2010
UK SEE STEADY INCREASE OF THE SPORADIC CJD’S AND THE VPSPR’S (sporadic
CJD’s). ...tss
CREUTZFELDT-JAKOB DISEASE IN THE UK (By Calendar Year)
1990 – 28 cases
(with steady increase in the years from 1990 to 2011. ...tss)
2011 – 90 cases
1 in addition, the NCJDRSU has identified a total of 9 cases of VPSPr.
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
CANADA SEE STEADY INCREASE OF THE SPORADIC CJD’S AND THE VPSPR’S (sporadic
CJD’s). ...tss
PLEASE NOTE, type determination pending Creutzfeldt Jakob Disease (tdpCJD)
in Canada is also on a steady increase.
please see ;
> 3. Final classification of 50 cases from 2009, 2010, 2011 and 2012 is
pending.
CJD Deaths Reported by CJDSS1, 1994-20122
As of May 31, 2012
Deaths of Definite and Probable CJD
Year Sporadic Iatrogenic Familial GSS FFI vCJD Total
1994 2 0 0 1 0 0 3
1995 3 0 0 0 0 0 3
1996 13 0 0 0 0 0 13
1997 16 0 1 1 0 0 18
1998 22 1 0 1 0 0 24
1999 26 2 2 1 0 0 31
2000 32 0 0 3 0 0 35
2001 27 0 2 1 0 0 30
2002 31 0 2 2 0 1 36
2003 27 1 1 0 0 0 29
2004 42 0 1 0 0 0 43
2005 42 0 0 2 0 0 44
2006 39 0 1 3 1 0 44 2007 35 0 0 4 0 0 39
2008 48 0 1 0 0 0 49
2009 48 0 3 2 0 0 53
2010 34 0 3 0 0 0 37
2011 37 0 2 1 0 1 41
2012 1 0 0 0 0 0 1
Total 525 4 19 22 1 2 573
1. CJDSS began in 1998
2. Data before 1998 are retrospective and partial, data from 1998 to 2008
are complete, and data for 2009 - 2012 are provisional
3. Final classification of 50 cases from 2009, 2010, 2011 and 2012 is
pending.
CJD Deaths Reported by CJDSS1, 1994-20122
As of May 31, 2012
USA SEE STEADY INCREASE OF THE SPORADIC CJD’S AND THE VPSPR’S (sporadic
CJD’s). ...tss
National Prion Disease Pathology Surveillance Center
Cases Examined1
(May 18, 2012)
Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD
1996 & earlier 50 32 28 4 0 0
1997 114 68 59 9 0 0
1998 88 52 44 7 1 0
1999 123 74 65 8 1 0
2000 145 103 89 14 0 0
2001 210 120 110 10 0 0
2002 248 149 125 22 2 0
2003 266 168 137 31 0 0
2004 326 187 164 22 0 13
2005 344 194 157 36 1 0
2006 382 196 166 28 0 24
2007 377 213 185 28 0 0
2008 396 232 206 26 0 0
2009 423 256 212 43 1 0
2010 413 257 216 41 0 0
2011 410 257 213 43 0 0
2012 153 82 51 15 0 0
TOTAL 44685 26406 2227 387 6 3
1 Listed based on the year of death or, if not available, on year of
referral;
2 Cases with suspected prion disease for which brain tissue and/or blood
(in familial cases) were submitted;
3 Disease acquired in the United Kingdom;
4 Disease was acquired in the United Kingdom in one case and in Saudi
Arabia in the other case;
5 Includes 14 cases in which the diagnosis is pending, and 18 inconclusive
cases;
6 Includes 17 (16 from 2012) cases with type determination pending in which
the diagnosis of vCJD has been excluded. The Sporadic cases include 16 cases of
sporadic Fatal Insomnia (sFI) and 42 cases of Variably Protease-Sensitive
Prionopathy (VPSPr) and 2118 cases of sporadic Creutzfeldt-Jakob disease (sCJD).
Rev 5/18/2012
> 6 Includes
> 17 (16 from 2012) cases with type determination pending in which the
diagnosis of vCJD has been excluded.
> The Sporadic cases include 16 cases of sporadic Fatal Insomnia (sFI)
and 42 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 2118 cases
of sporadic Creutzfeldt-Jakob disease (sCJD).
WELL, it seems the USA mad cow strains in humans classified as type
determination pending tdpCJD, VPSPr, sFFI, and sCJD) have steadily increased
over the years, and the same old song and dance continues with sporadic CJD
cases $$$
*** The discovery of previously unrecognized prion diseases in both humans
and animals (i.e., Nor98 in small ruminants) demonstrates that the range of
prion diseases might be wider than expected and raises crucial questions about
the epidemiology and strain properties of these new forms. We are investigating
this latter issue by molecular and biological comparison of VPSPr, GSS and
Nor98.
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion
poker goes up again $
OR-10: Variably protease-sensitive prionopathy is transmissible in bank
voles
Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1
Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan
Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome,
Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna,
Italy; 3Case Western Reserve University; Cleveland, OH USA
Background. Variably protease-sensitive prionopathy (VPSPr) is a recently
described “sporadic”neurodegenerative disease involving prion protein
aggregation, which has clinical similarities with non-Alzheimer dementias, such
as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in
Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the
prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is
the electrophoretic pattern of PrPSc after digestion with proteinase K (PK).
After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern
similar to that described in GSS cases. The clinical and pathological features
of VPSPr raised the question of the correct classification of VPSPr among prion
diseases or other forms of neurodegenerative disorders. Here we report
preliminary data on the transmissibility and pathological features of VPSPr
cases in bank voles.
Materials and Methods. Seven VPSPr cases were inoculated in two genetic
lines of bank voles, carrying either methionine or isoleucine at codon 109 of
the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases
selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical
diagnosis in voles was confirmed by brain pathological assessment and western
blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.
Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission
in BvM109. Overall, 3 voles were positive with survival time between 290 and 588
d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form
of the typical PrP27–30, which was indistinguishable to that previously observed
in BvM109 inoculated with sCJDMM1 cases.
In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission
until now. Overall, 5 voles were positive with survival time between 281 and 596
d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like
PrPSc electrophoretic pattern, characterized by low molecular weight PrPres.
These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative
with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus
and the N-terminus. Second passages are in progress from these first successful
transmissions.
Conclusions. Preliminary results from transmission studies in bank voles
strongly support the notion that VPSPr is a transmissible prion disease.
Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of
voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109.
The discovery of previously unrecognized prion diseases in both humans and
animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion
diseases might be wider than expected and raises crucial questions about the
epidemiology and strain properties of these new forms. We are investigating this
latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.
Wednesday, March 28, 2012
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE, price of prion
poker goes up again $
*** The discovery of previously unrecognized prion diseases in both humans
and animals (i.e., Nor98 in small ruminants) demonstrates that the range of
prion diseases might be wider than expected and raises crucial questions about
the epidemiology and strain properties of these new forms. We are investigating
this latter issue by molecular and biological comparison of VPSPr, GSS and
Nor98.
EFSA Journal 2011 The European Response to BSE: A Success Story
snip...
EFSA and the European Centre for Disease Prevention and Control (ECDC)
recently delivered a scientific opinion on any possible epidemiological or
molecular association between TSEs in animals and humans (EFSA Panel on
Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical
BSE prions as the only TSE agents demonstrated to be zoonotic so far but the
possibility that a small proportion of human cases so far classified as
"sporadic" CJD are of zoonotic origin could not be excluded. Moreover,
transmission experiments to non-human primates suggest that some TSE agents in
addition to Classical BSE prions in cattle (namely L-type Atypical BSE,
Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic
wasting disease (CWD) agents) might have zoonotic potential.
snip...
Thursday, August 12, 2010
Seven main threats for the future linked to prions
First threat
The TSE road map defining the evolution of European policy for protection
against prion diseases is based on a certain numbers of hypotheses some of which
may turn out to be erroneous. In particular, a form of BSE (called atypical
Bovine Spongiform Encephalopathy), recently identified by systematic testing in
aged cattle without clinical signs, may be the origin of classical BSE and thus
potentially constitute a reservoir, which may be impossible to eradicate if a
sporadic origin is confirmed.
***Also, a link is suspected between atypical BSE and some apparently
sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases
constitute an unforeseen first threat that could sharply modify the European
approach to prion diseases.
Second threat
snip...
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
TSS
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.