Cost benefit analysis of the development and use of ante-mortem tests for
transmissible spongiform encephalopathiesProject Code: M03067
The FSA’s Strategic Plan for 2005–2010 committed the Agency to promote and
aid the development of a sensitive, rapid live test for TSEs by 2010. This study
carried out a cost-benefit analysis of the implementation of such tests.
The review of the state of the science has not identified any ante-mortem
test for BSE that is currently ready for use or for approval. Taking into
account the likely timescale for approval and modification of policy to enable
the introduction of live animal tests, and the attitude of commercial companies
to the challenges and risks involved, there appears to be little scope for their
introduction in the foreseeable future.
This study has demonstrated that although desirable, it is not necessary to
have a live animal test that works at all stages of incubation. It has been
shown that improving sensitivity from 3 to 12 months before clinical onset has a
real impact, and potential benefits. This could help to define the minimum
specification for a live animal test, i.e. 100% specificity and 95% sensitivity
within 12 months of clinical onset, at least for the protection of the food
chain. Applying an ante-mortem test to all cattle slaughtered increases the
costs significantly with no additional benefit in terms of TSE exposure,
resulting in a cost effectiveness value of 0.4.
Reference to part of this report which may lead to misinterpretation is not
permissible
This report presents the results of a study carried out by Det Norske
Veritas (DNV) for the Food Standards Agency (FSA) to assess the cost
effectiveness of the introduction of ante-mortem tests for Transmissible
Spongiform Encephalopathies (TSEs) in the United Kingdom. The study has focused
on the implementation of ante-mortem tests for BSE in cattle at the current
stage of the BSE epidemic, when prevalence levels are low.
The study has included a review of the state of the science relating to the
development and approval of ante-mortem TSE tests. This included a review of the
literature intended to inform the development of possible test scenarios, and
consultation with scientists and companies known to be involved in the research
and development of ante-mortem tests. This review led to the definition of a set
of possible scenarios for the introduction of live animal tests for TSEs. These
were discussed and reviewed at an Expert Workshop held in September 2009 and
involving experts from a range of stakeholders, including regulators, the meat
industry, veterinarians and people involved in test development. The outcome of
the Expert Workshop was that the cost effectiveness assessment should focus on
the introduction of a live test on healthy cattle carried out on farm before
being sent for slaughter and involve either all cattle sent for slaughter or
just adult cattle (over 48 months old at slaughter) as currently tested
post-mortem. Testing of healthy cattle pre-slaughter at abattoirs was also
considered, but it was felt that this would only be possible if the test
provided an almost instant result and that this was unlikely to be
achieved.
The cost effectiveness of the introduction of an ante-mortem TSE test has
been evaluated by considering the range of costs that would be associated with
implementing ante-mortem testing for the agreed scenarios compared with the
benefit, measured as the estimated change in exposure to TSE infectivity
resulting from the use of the test. The potential for TSE infectivity to enter
the human food supply has been evaluated using a model based on the DNV SRM
Controls Model that was developed for the FSA and used to estimate the impact of
alternative supervision strategies for SRM Controls. The DNV SRM Controls Model
has been previously reviewed by the Spongiform Encephalopathy Advisory Committee
(SEAC) and the results for assessing alternative options for supervision of SRM
controls accepted.
1. The review of the state of the science has not identified any
ante-mortem test for BSE that is currently ready for use or for approval. Taking
into account the likely timescale for approval and modification of policy to
enable the introduction of live animal tests, and the attitude of commercial
companies to the challenges and risks involved, there appears to be little scope
for their introduction in the foreseeable future.
2. Test specificity is likely to be critical to the acceptance of live
animal testing, by both industry and consumers. The prospect of substantial
numbers of false positive results that perpetuate fear of undetected or
unconfirmed infection may undermine any attempts to introduce such tests.
3. Assuming that an ante-mortem test would be able to detect infectivity
for a wider range of the incubation period than is currently possible with the
present post-mortem tests, at least for the last 12 months of the incubation
period, then it is estimated that the median exposure would reduce from 3 bovine
oral ID50 units with the present post-mortem testing programme (range 0.2 to 52)
to 0.02 bovine oral ID50 units (range <0 .01="" 0.5="" 100="" 48="" a="" and="" animals="" ante-mortem="" applied="" div="" food="" for="" months="" older="" only="" sensitivity.="" slaughtered="" test="" than="" the="" to="" with="">
July 2010
Cost Effectiveness Study of the use of Ante-mortem TSE Tests
Food Standards Agency
Page ii
DNV
Final Report v 4 M03067 21-07-10
Reference to part of this report which may lead to misinterpretation is not
permissible
4. The estimated exposure for an ante-mortem test with 95% sensitivity is a
median value of 0.3 (range 0.02 to 6) bovine oral ID50 units; this is still
significantly less than the exposure with the present post-mortem test.
5. Testing the prime beef cattle in addition to those over 48 months of age
at slaughter, does not result in any significant further reduction in exposure
to TSE infectivity, as the untested prime beef animals contribute only 3% of the
total exposure.
6. The cost of applying an ante-mortem test to over 48 month old cattle on
farm prior to being sent for slaughter is estimated to be only slightly greater
than that for the present post-mortem test; £6.9 million per year as opposed to
£6.2 million. The higher costs of sampling on farm with the need for cattle
handling and for a veterinarian to take the sample is partly off set by a
reduction in MHS supervision costs.
7. The higher cost for ante-mortem testing is balanced by the additional
reduction in TSE exposure, so that the cost effectiveness of the ante-mortem
test applied to over 48 month animals is estimated to be 2.1 bovine oral ID50
units per £million spent as opposed to 0.9 for the post-mortem test. However,
the significance of this increase in cost effectiveness needs to take into
account the fact that the TSE exposure to the UK population from beef
consumption is already at a very low level.
8. Applying an ante-mortem test to all cattle slaughtered increases the
costs significantly with no additional benefit in terms of TSE exposure,
resulting in a cost effectiveness value of 0.4.
9. With no data on the actual cost of an ante-mortem test it has been
assumed that this would be the same as for the post-mortem test. If this cost
were higher it would reduce the cost effectiveness of the ante-mortem test;
however it has been shown that the ante-mortem test remains more cost effective
provided that the cost of the test is no more than 3 times that of the
post-mortem test.
10. The sampling costs for the ante-mortem test could be reduced by using a
technical officer rather than a veterinarian to take the sample. It has been
shown that this would increase the cost effectiveness only slightly from 2.1 to
2.4 Bovine oral ID50 units per million GBP.
11. If the introduction of a reliable ante-mortem test were to enable a
change in the EU requirements for removing and disposing of SRM, this could
result in a substantial cost saving, estimated to be £16 million. This estimated
cost saving is greater than the cost of the test. However, discussions with the
EU indicate that rapid ante-mortem tests will never be accepted as alternatives
to the removal of SRM.
12. This study has demonstrated that although desirable, it is not
necessary to have a live animal test that works at all stages of incubation. It
has been shown that improving sensitivity from 3 to 12 months before clinical
onset has a real impact, and potential benefits. This could help to define the
minimum specification for a live animal test, i.e., 100% specificity and 95%
sensitivity within 12 months of clinical onset, at least for the protection of
the food chain.
13. This study has focussed on the application of TSE testing in cattle.
Whilst there are grounds for greater optimism for the development of ante-mortem
tests in small ruminants, there is currently little evidence of a test approach
that could be used in a similar way as that investigated for bovines in this
study.
July 2010
Cost Effectiveness Study of the use of Ante-mortem TSE Tests
Food Standards Agency
SNIP...
2.2.5 Lymphoreticular biopsies
Despite the extensive body of evidence that lymphoreticular biopsies can be
used for the screening of sheep exposed to scrapie (Espenes et al, 2006;
Gonzalez et al, 2005, 2006, 2008, a, b; O’Rourke et al, 1998, 2000, 2002), or
farmed and wild cervids infected with CWD (Keane et al, 2009; Spraker et al,
2009; Wild et al, 2002), there is no published evidence of any attempt to use
lymphoid biopsies as a matrix for testing in bovines. Nevertheless, in the
context of BSE, where testing of cattle must provide equivalent protection to
the removal of SRM, none of the evidence from sheep and cervids suggests that
satisfactory levels of sensitivity and specificity would have been achieved,
even if bovine LRS had been found to be PrPres–positive.
2.3 Consultations
2.3.1 Consultation with test-developers
A questionnaire was sent via the Veterinary Laboratories Agency (VLA) to 23
companies or institutes that had requested materials from the VLA TSE archive in
the past for the purposes of test development or validation, with particular
emphasis on live tests. Another company known to be involved in both research
and continued test development, but which had not received materials from the
VLA, was approached directly. In addition, some scientists funded by the FSA and
Defra in recent years under the banner of “diagnostics” were sent an equivalent
questionnaire, either via their funding body (FSA), or directly in the case of
staff at the VLA and the Roslin Biocentre. Four detailed questionnaires, and one
background note, were received from scientists contacted via the FSA or
directly. Two commercial companies, currently involved in marketing post-mortem
tests for BSE and scrapie, responded with a completed questionnaire. Three
July 2010 Cost Effectiveness Study of the use of Ante-mortem TSE Tests Food
Standards Agency Page 6 DNV Final Report v 4 M03067 21-07-10 Reference to part
of this report which may lead to misinterpretation is not permissible
others confirmed their withdrawal from this field of development. Many
others are known, on the basis of historical personal contact, to have
re-directed their activities.
The following represents a summary of relevant detail provided in the six
completed questionnaires. All six confirmed a desire to develop a test for use
on blood, while two also expressed an interest in testing milk, and one also
targeted CSF. Four approaches involved the detection of PrPSc, one used
proteomics while the fifth targeted up-regulation of ERAF. The latter approach
has since been abandoned because of the considerable variability in results from
healthy large animals and humans which confounded discrimination between
infected and healthy individuals.
Only three of the six responses indicated a desire or scope to test
bovines; these three did not include the commercial companies. All six were
interested in testing sheep both as an end in itself and as a model for test
development. Only three groups had an immediate interest in developing a test
for humans, while two felt there was scope for testing cervids (but subsequently
abandoned by one).
It was suggested that a test for BSE in bovines could possibly be available
within two to three years, but only if it was firstly demonstrated that test
methodology that worked on sheep could actually detect PrPSc in bovine blood.
The key challenge to test development was the continuing lack of understanding
of pathogenesis.
The commercial companies confirmed that the absence of national and
international policy for the future use of live tests was a factor that hindered
test development. Because of the inability to define a future market, the costs
of developing a test could not be compared with potential future income in order
to offer confidence that there would be returns on investment.
In summary, none of the respondents indicated that a live test for BSE was
likely to be available in the immediate future. Nevertheless, it is known that
at least three commercial companies that were not amongst the respondents are
still interested in marketing a test for CJD in humans, and can legitimately be
considered to have a real interest in the testing of bovines. This is no longer
a priority for them however, and will probably not be progressed if they fail to
gain approval for the testing of human blood.
2.4 Consultation with the European Commission/EFSA
The European Commission was consulted with respect to its medium term
expectations, in the context of the TSE RoadMap (EC, 2005), which acknowledges a
need to de-regulate with time, and its open-call for test developers to submit
tests for approval. The benchmark of 100% sensitivity and specificity
established in the first evaluation of post-mortem tests conducted in 1999
remains a serious challenge to the approval of any live animal test. The absence
of a definitive gold standard to confirm the status of preclinical animals
irrespective of stage of incubation remains a major obstacle to evaluating the
true performance of ante-mortem tests. At present the EFSA guidelines for the
evaluation of a live animal test are limited to a preliminary evaluation of
sensitivity and specificity (EFSA, 2007b). How a formal evaluation of
suitability for use on a wider scale will be conducted is partly dependent on
the analyte to be measured, and whether appropriate test materials are available
to enable such studies to be carried out. It is not however expected that rapid
ante-mortem tests will ever be accepted as alternatives to the removal of SRM.
It is also clear that tests will be expected to have diagnostic sensitivity not
less than 100% (95% confidence limit not less than 98.5%)(EFSA 2007a).
July 2010
Cost Effectiveness Study of the use of Ante-mortem TSE Tests Food Standards
Agency Page 7 DNV Final Report v 4 M03067 21-07-10 Reference to part of this
report which may lead to misinterpretation is not permissible
The Commission cannot offer a forward plan for the integration of live
animal testing within the EU programme of statutory testing.
Although it has no plans to extend the call for test evaluations any
further than 2012, and cannot confirm its policy regarding the likely context in
which such a test might be introduced, much will inevitably depend on timing,
the prevalence of infection and costs of introduction at the time. If live
animal tests are not available until such time as the EU testing programme has
been reduced significantly, because of the low prevalence of BSE, the issue of
equivalence with SRM removal will be less of an issue, and may enable a flexible
and positive approach to application for herd certification if such a demand
exists.
2.5 Consultation with the OIE
The OIE confirmed that although it could accommodate live animal tests
within guidelines for international trade, and for diagnosis of BSE, it has not
yet drafted protocols for the evaluation of live-animal tests, and has no plans
to draft any at present. Consequently it has no proposals for the context in
which it may accept the introduction of live tests, and will no doubt await
evidence of successful development before taking this issue forward.
2.6 Small Ruminants
With respect to small ruminants it is clear that while there are grounds
for greater optimism than with bovines, significant challenges remain. There is
a need for clarity on the extent to which genotype confers resistance to
infection with specific strains (absolute or relative) when exposed by natural
routes. Within specific breed/genotype/scrapie strain combinations there is a
need to confirm the performance of putative tests. Finally there will be
difficulties in confirming the effectiveness of a test with respect to all
strain/genotype combinations present within a national flock. Where there may
only be a limited number of strains involved, there may be scope for live tests
to be used in specific scenarios, such as flock/herd certification or culling of
exposed animals. At the moment there is little evidence of a test approach that
can be used for scenarios equivalent to those discussed for cattle in this
study.
2.7 Conclusion
The review of the state of the science identified no test for BSE that is
currently ready for use or for approval. Taking into account the likely
timescale for approval and modification of policy to enable the introduction of
live animal tests, and the attitude of commercial companies to the challenges
and risks involved, there appears to be little scope for their use in the
foreseeable future.
An issue that has also been highlighted by the review and the stakeholder
consultation is that test specificity is likely to be critical to the acceptance
of live animal testing, by both industry and consumers. While test sensitivity
is already recognised as important when perception of risk is so important in
determining the climate of national and international acceptability, the
prospect of substantial numbers of false positive results that perpetuate fear
of undetected or unconfirmed infection may undermine any attempts to introduce
such tests. Realistically there is a need for not one but two tests that are
capable of detecting infected animals at any stage of incubation, one for
screening and one for confirmation. Failure to confirm the results of a primary
positive result will critically undermine confidence in any screening programme.
It will also be important to ensure that approaches to diagnosis in the
screening and confirmatory tests are sufficiently different to ensure that they
are not compromised for the same reason, in order to discriminate between false
and true positives.
July 2010
Cost Effectiveness Study of the use of Ante-mortem TSE Tests
Food Standards Agency
SNIP...
PLEASE SEE FULL TEXT ;
BOTTOM LINE $$$
IF YOU TEST, YOU FIND, and the more you test, the more you will find.
HUMANS ARE EXPENDABLE WITH A SLOW, LONG INCUBATING, 100% FATAL DISEASE,
ONCE CLINICAL DISEASE...tss
Transmissible Spongiform Encephalopathy TSE Prion Disease North America
2014
Transmissible Spongiform Encephalopathy TSE Prion Disease have now been
discovered in a wide verity of species across North America. typical C-BSE,
atypical L-type BASE BSE, atypical H-type BSE, atypical H-G BSE, of the bovine,
typical and atypical Scrapie strains, in sheep and goats, with atypical Nor-98
Scrapie spreading coast to coast in about 5 years. Chronic Wasting Disease CWD
in cervid is slowly spreading without any stopping it in Canada and the USA and
now has mutated into many different strains. Transmissible Mink Encephalopathy
TME outbreaks. These Transmissible Spongiform Encephalopathy TSE Prion Disease
have been silently mutating and spreading in different species in North America
for decades.
The USDA, FDA, et al have assured us of a robust Triple BSE TSE prion
Firewall, of which we now know without a doubt, that it was nothing but ink on
paper. Since the 1997 mad cow feed ban in the USA, literally tons and tons of
banned mad cow feed has been put out into commerce, never to return, as late as
December of 2013, serious, serious breaches in the FDA mad cow feed ban have
been documented. The 2004 enhanced BSE surveillance program was so flawed, that
one of the top TSE prion Scientist for the CDC, Dr. Paul Brown stated ; Brown,
who is preparing a scientific paper based on the latest two mad cow cases to
estimate the maximum number of infected cows that occurred in the United States,
said he has "absolutely no confidence in USDA tests before one year ago" because
of the agency's reluctance to retest the Texas cow that initially tested
positive.
see ;
The BSE surveillance and testing have also been proven to be flawed, and
the GAO and OIG have both raised serious question as to just how flawed it has
been (see GAO and OIG reports). North America has more documented TSE prion
disease, in different documented species (excluding the Zoo BSE animals in the
EU), then any other place on the Globe. This does not include the very
likelihood that TSE prion disease in the domestic feline and canine have been
exposed to high doses of the TSE prion disease vid pet food. To date, it’s still
legal to include deer from cwd zone into pet food or deer food. Specified Risk
Material i.e. SRM bans still being breach, as recently as just last month.
nvCJD or what they now call vCJD, another case documented in Texas last
month, with very little information being released to the public on about this
case? with still the same line of thought from federal officials, ‘it can’t
happen here’, so another vCJD blamed on travel of a foreign animal disease from
another country, while ignoring all the BSE TSE Prion risk factors we have here
in the USA and Canada, and the time that this victim and others, do spend in the
USA, and exposed to these risk factors, apparently do not count in any way with
regard to risk factor. a flawed process of risk assessment.
sporadic CJD, along with new TSE prion disease in humans, of which the
young are dying, of which long duration of illness from onset of symptoms to
death have been documented, only to have a new name added to the pot of prion
disease i.e. sporadic GSS, sporadic FFI, and or VPSPR. I only ponder how a
familial type disease could be sporadic with no genetic link to any family
member? when the USA is the only documented Country in the world to have
documented two different cases of atypical H-type BSE, with one case being
called atypical H-G BSE with the G meaning Genetic, with new science now showing
that indeed atypical H-type BSE is very possible transmitted to cattle via oral
transmission (Prion2014). sporadic CJD and VPSPR have been rising in Canada,
USA, and the UK, with the same old excuse, better surveillance. You can only use
that excuse for so many years, for so many decades, until one must conclude that
CJD TSE prion cases are rising. a 48% incease in CJD in Canada is not just a
blip or a reason of better surveillance, it is a mathematical rise in numbers.
More and more we are seeing more humans exposed in various circumstance in the
Hospital, Medical, Surgical arenas to the TSE Prion disease, and at the same
time in North America, more and more humans are becoming exposed to the TSE
prion disease via consumption of the TSE prion via deer and elk, cattle, sheep
and goats, and for those that are exposed via or consumption, go on to further
expose many others via the iatrogenic modes of transmission of the TSE prion
disease i.e. friendly fire. I pondered this mode of transmission via the victims
of sporadic FFI, sporadic GSS, could this be a iatrogenic event from someone
sub-clinical with sFFI or sGSS ? what if?
Two decades have passed since Dr. Ironside first confirmed his first ten
nvCJD victims in 1995. Ten years later, 2005, we had Dr. Gambetti and his first
ten i.e. VPSPR in younger victims. now we know that indeed VPSPR is
transmissible. yet all these TSE prion disease and victims in the USA and Canada
are being pawned off as a spontaneous event, yet science has shown, the
spontaneous theory has never been proven in any natural case of TSE prion
disease, and scientist have warned, that they have now linked some sporadic CJD
cases to atypical BSE, to atypical Scrapie, and to CWD, yet we don’t here about
this in the public domain. We must make all human and animal TSE prion disease
reportable in every age group, in ever state and internationally, we must have a
serious re-evaluation and testing of the USA cattle herds, and we must ban
interstate movement of all cervids. Any voluntary effort to do any of this will
fail. Folks, we have let the industry run science far too long with regards to
the TSE prion disease. While the industry and their lobbyist continues to funnel
junk science to our decision policy makers, Rome burns. ...end
REFERENCES
Sunday, June 29, 2014
*** Transmissible Spongiform Encephalopathy TSE Prion Disease North America
2014
Wednesday, August 27, 2014
Highly sensitive detection of small ruminant BSE within TSE mixes by serial
Protein Misfolding Cyclic Amplification
Tuesday, September 2, 2014
*** COOL UPDATE September 2, 2014
Tuesday, August 12, 2014
*** MAD COW USDA TSE PRION COVER UP or JUST IGNORANCE, for the record
AUGUST 2014
Monday, July 28, 2014
Mitigating the Risk of Transmission and Environmental Contamination of
Transmissible Spongiform Encephalopathies 2013 Annual Report
Sunday, August 24, 2014
*** USAHA 117TH ANNUAL MEETING USDA-APHIS–VS CWD Herd Certification Program
Goals TSE PRION October 17 – 23, 2013
Monday, May 05, 2014
*** Member Country details for listing OIE CWD 2013 against the criteria of
Article 1.2.2., the Code Commission recommends consideration for listing
*** OIE GROUP RECOMMENDS THAT SCRAPE PRION DISEASE BE DELISTED, WISHES TO
CONTINUE SPREADING IT AROUND THE GLOBE
Monday, November 30, 2009
*** USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL
HEALTH CODE, DOES NOT SURPRISE ME $
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly would likely
create alarm in some circles even if the result could not be interpreted for
man. I have a view that all these agents could be transmitted provided a large
enough dose by appropriate routes was given and the animals kept long enough.
Until the mechanisms of the species barrier are more clearly understood it might
be best to retain that hypothesis.
snip...
R. BRADLEY
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to
nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep
and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were
exposed to the infectious agents only by their nonforced consumption of known
infectious tissues. The asymptomatic incubation period in the one monkey exposed
to the virus of kuru was 36 months; that in the two monkeys exposed to the virus
of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the
two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively.
Careful physical examination of the buccal cavities of all of the monkeys failed
to reveal signs or oral lesions. One additional monkey similarly exposed to kuru
has remained asymptomatic during the 39 months that it has been under
observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie
by natural feeding to squirrel monkeys that we have reported provides further
grounds for concern that scrapie-infected meat may occasionally give rise in
humans to Creutzfeldt-Jakob disease.
PMID: 6997404
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
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC.
Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK
National Institute of Neurological Diseases and Stroke, National Institutes
of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey
(Macaca fascicularis) with an incubation period of more than 5 yr from the time
of intracerebral inoculation of scrapie-infected mouse brain. The animal
developed a chronic central nervous system degeneration, with ataxia, tremor and
myoclonus with associated severe scrapie-like pathology of intensive astroglial
hypertrophy and proliferation, neuronal vacuolation and status spongiosus of
grey matter. The strain of scrapie virus used was the eighth passage in Swiss
mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral
passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton,
Berkshire).
Wednesday, February 16, 2011
IN CONFIDENCE
SCRAPIE TRANSMISSION TO CHIMPANZEES
IN CONFIDENCE
Sunday, December 12, 2010
EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2
December 2010
Sunday, April 18, 2010
SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010
Thursday, December 23, 2010
Molecular Typing of Protease-Resistant Prion Protein in Transmissible
Spongiform Encephalopathies of Small Ruminants, France, 2002-2009
Volume 17, Number 1 January 2011
Thursday, November 18, 2010
Increased susceptibility of human-PrP transgenic mice to bovine spongiform
encephalopathy following passage in sheep
Monday, April 25, 2011
Experimental Oral Transmission of Atypical Scrapie to Sheep
Volume 17, Number 5-May 2011
Friday, February 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
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
*** Canada 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.
Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine
(reticular) deposits, see also ; All of the Heidenhain variants were of the
methionine/ methionine type 1 molecular subtype.
P.5.21 Parallels between different forms of sheep scrapie and types of
Creutzfeldt-Jakob disease (CJD)
Wiebke M. Wemheuer1, Sylvie L. Benestad2, Arne Wrede1, Wilhelm E.
Wemheuer3, Tatjana Pfander1, Bjørn Bratberg2, Bertram Brenig3,Walter J.
Schulz-Schaeffer1 1University Medical Center Goettingen, Germany; 2Institute of
Veterinary Medicine Oslo, Norway; 3Institute of Veterinary Medicine Goettingen,
Germany
Background: Scrapie in sheep and goats is often regarded as the archetype
of prion diseases. In 1998, a new form of scrapie - atypical/Nor98 scrapie - was
described that differed from classical scrapie in terms of epidemiology, Western
blot profile, the distribution of pathological prion protein (PrPSc) in the body
and its stability against proteinase K. In a similar way, distinct disease types
exist in sporadic Creutzfeldt-Jakob disease (CJD). They differ with regard to
their clinical outcome, Western blot profile and PrPSc deposition pattern in the
central nervous system (CNS). Objectives: The comparison of PrPSc deposits in
sheep scrapie and human sporadic CJD.
Methods: Tissues of the CNS of sheep with classical scrapie, sheep with
atypical/Nor98 scrapie and 20 patients with sporadic CJD were examined using the
sensitive Paraffin Embedded Tissue (PET) blot method. The results were compared
with those obtained by immunohistochemistry. With the objective of gaining
information on the protein conformation, the PrPSc of classical and
atypical/Nor98 sheep scrapie and sporadic CJD was tested for its stability
against denaturation with guanidine hydrochloride (GdnHCl) using a Membrane
Adsorption Assay.
Results: The PrPSc of atypical/Nor98 scrapie cases and of CJD prion type 1
patients exhibits a mainly reticular/synaptic deposition pattern in the brain
and is relatively sensitive to denaturation with GdnHCl. In contrast classical
scrapie cases and CJD prion type 2 patients have a more complex PrPSc deposition
pattern in common that consists of larger PrPSc aggregates and the PrPSc itself
is comparatively stable against denaturation.
Discussion: The similarity between CJD types and scrapie types indicates
that at least two comparable forms of the misfolded prion protein exist beyond
species barriers and can elicit prion diseases. It seems therefore reasonable to
classify classical and atypical/Nor98 scrapie - in analogy to the existing CJD
types - as different scrapie types.
What if you can catch old-fashioned CJD by eating meat from a sheep
infected with scrapie?
28 Mar 01
Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine
issue 2284. Subscribe and get 4 free issues. FOUR years ago, Terry Singeltary
watched his mother die horribly from a degenerative brain disease. Doctors told
him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit
her violent symptoms, and he demanded an autopsy. It showed she had died of
sporadic Creutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming by
chance into a killer. But Singeltary thinks otherwise. He is one of a number of
campaigners who say that some sCJD, like the variant CJD related to BSE, is
caused by eating meat from infected animals. Their suspicions have focused on
sheep carrying scrapie, a BSE-like disease that is widespread in flocks across
Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight
to the campaigners' fears. To their complete surprise, the researchers found
that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by
some strains of scrapie," says team member Jean-Philippe Deslys of the French
Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses,
south-west of Paris. Hans Kretschmar of the University of Göttingen, who
coordinates CJD surveillance in Germany, is so concerned by the findings that he
now wants to trawl back through past sCJD cases to see if any might have been
caused by eating infected mutton or lamb.
Scrapie has been around for centuries and until now there has been no
evidence that it poses a risk to human health. But if the French finding means
that scrapie can cause sCJD in people, countries around the world may have
overlooked a CJD crisis to rival that caused by BSE.
Deslys and colleagues were originally studying vCJD, not sCJD. They
injected the brains of macaque monkeys with brain from BSE cattle, and from
French and British vCJD patients. The brain damage and clinical symptoms in the
monkeys were the same for all three. Mice injected with the original sets of
brain tissue or with infected monkey brain also developed the same
symptoms.
As a control experiment, the team also injected mice with brain tissue from
people and animals with other prion diseases: a French case of sCJD; a French
patient who caught sCJD from human-derived growth hormone; sheep with a French
strain of scrapie; and mice carrying a prion derived from an American scrapie
strain. As expected, they all affected the brain in a different way from BSE and
vCJD. But while the American strain of scrapie caused different damage from
sCJD, the French strain produced exactly the same pathology.
"The main evidence that scrapie does not affect humans has been
epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute
for Animal Health in Edinburgh, who was a member of the same team as Deslys.
"You see about the same incidence of the disease everywhere, whether or not
there are many sheep, and in countries such as New Zealand with no scrapie." In
the only previous comparisons of sCJD and scrapie in mice, Bruce found they were
dissimilar.
But there are more than 20 strains of scrapie, and six of sCJD. "You would
not necessarily see a relationship between the two with epidemiology if only
some strains affect only some people," says Deslys. Bruce is cautious about the
mouse results, but agrees they require further investigation. Other trials of
scrapie and sCJD in mice, she says, are in progress.
People can have three different genetic variations of the human prion
protein, and each type of protein can fold up two different ways. Kretschmar has
found that these six combinations correspond to six clinical types of sCJD: each
type of normal prion produces a particular pathology when it spontaneously
deforms to produce sCJD.
But if these proteins deform because of infection with a disease-causing
prion, the relationship between pathology and prion type should be different, as
it is in vCJD. "If we look at brain samples from sporadic CJD cases and find
some that do not fit the pattern," says Kretschmar, "that could mean they were
caused by infection."
There are 250 deaths per year from sCJD in the US, and a similar incidence
elsewhere. Singeltary and other US activists think that some of these people
died after eating contaminated meat or "nutritional" pills containing dried
animal brain. Governments will have a hard time facing activists like Singeltary
if it turns out that some sCJD isn't as spontaneous as doctors have
insisted.
Deslys's work on macaques also provides further proof that the human
disease vCJD is caused by BSE. And the experiments showed that vCJD is much more
virulent to primates than BSE, even when injected into the bloodstream rather
than the brain. This, says Deslys, means that there is an even bigger risk than
we thought that vCJD can be passed from one patient to another through
contaminated blood transfusions and surgical instruments.
Monday, December 1, 2008
When Atypical Scrapie cross species barriers
Thursday, December 20, 2012
OIE GROUP RECOMMENDS THAT SCRAPE PRION DISEASE BE DELISTED, WISHES TO
CONTINUE SPREADING IT AROUND THE GLOBE
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH
CODE, DOES NOT SURPRISE ME $
Saturday, August 02, 2014
*** Structural effects of PrP polymorphisms on intra- and inter-species
prion transmission
In contrast, the scrapie prions used in the deer transmission studies of
Greenlee and colleagues were isolated from a sheep encoding A136, ***raising the
possibility that deer may be susceptible to multiple scrapie strains.
snip...
Significance
The unpredictable recurrences of prion epidemics, their incurable
lethality, and the capacity of animal prions to infect humans, provide
significant motivation to ascertain the parameters governing disease
transmission. The unprecedented spread, and uncertain zoonotic potential of
chronic wasting disease (CWD), a contagious epidemic among deer, elk, and other
cervids, is of particular concern. Here we demonstrate that naturally occurring
primary structural differences in cervid PrPs differentially impact the
efficiency of intra- and interspecies prion transmission. Our results not only
deliver new information about the role of primary structural variation on prion
susceptibility, but also provide functional support to a mechanism in which
plasticity of a tertiary structural epitope governs prion protein conversion and
intra- and inter-species susceptibility to prions.-
snip...
*** 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.
see ;
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 to better
understand the potential host range and origins of prion diseases. We inoculated
white-tailed deer intracranially (IC) and by a natural route of exposure
(concurrent oral and intranasal inoculation) with a US scrapie isolate. All deer
inoculated by the intracranial route had evidence of PrPSc accumulation and
those necropsied after 20 months post-inoculation (PI) (3/5) had clinical signs,
spongiform encephalopathy, and widespread distribution of PrPSc in neural and
lymphoid tissues. A single deer that was necropsied at 15.6 months PI did not
have clinical signs, but had widespread distribution of PrPSc. This highlights
the facts that 1) prior to the onset of clinical signs PrPSc is widely
distributed in the CNS and lymphoid tissues and 2) currently used diagnostic
methods are sufficient to detect PrPSc prior to the onset of clinical signs. The
results of this study suggest that there are many similarities in the
manifestation of CWD and scrapie in white-tailed deer after IC inoculation
including early and widespread presence of PrPSc in lymphoid tissues, clinical
signs of depression and weight loss progressing to wasting, and an incubation
time of 21-23 months. Moreover, western blots (WB) done on brain material from
the obex region have a molecular profile consistent with CWD and distinct from
tissues of the cerebrum or the scrapie inoculum. However, results of microscopic
and IHC examination indicate that there are differences between the lesions
expected in CWD and those that occur in deer with scrapie: amyloid plaques were
not noted in any sections of brain examined from these deer and the pattern of
immunoreactivity by IHC was diffuse rather than plaque-like. After a natural
route of exposure, 100% of 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.
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 ;
Infectivity and abnormal prion protein in tissues from sheep exposed to
atypical scrapie (ongoing)
Last updated: 22 July 2007
This project will establish distribution of abnormal PrP and infectivity in
sheep tissues, such as blood, muscle, central nervous system(CNS) and milk.
Study Duration: July 2007 to June 2013
Contractor: ENVT
Project Code: FS231050 (M03058)
Background
Recently identified atypical scrapie cases in sheep represent an emerging
TSE of which little is known. Incidence in EU countries seems to vary between 3
and 11 per 10,000 tested animals. However, because there is probably a lack of
sensitivity in screening tests towards this particular TSE, this value is likely
to be an underestimation. There is no consistent information concerning the
abnormal PrP or infectivity distribution in peripheral tissues of atypical
cases. This absence of data, combined with the involvement of ARR/ARR (genotype
most resistant to BSE) animals that were believed to be resistant to TSE,
represent a major concern with regards to the efficiency of the current food
protection policy against TSE.
Research Approach
This project will establish distribution of abnormal PrP using various
tools including Immunohistochemistry, and infectivity (using transgenic mice
model) in sheep tissues such as blood, muscle, central nervous system(CNS) and
milk. The research will give consideration to the fact that atypical cases could
be either a spontaneous affection from CNS origin or an acquired infectious
disease resulting from an oral contamination.
Andréoletti, O., Orge, L., Benestad, S.L., Beringue, V., Litaise, C.,
Simon, S., Le Dur, A., Laude, H., Simmons, H., Lugan, S., Corbière, F., Costes,
P., Morel, N., Schelcher, F. & Lacroux, C. (2011) Atypical/Nor98 scrapie
infectivity in sheep peripheral tissues. Published online PLoS Pathogens 7:
e1001285
Exploring permeability of human species barrier to circulating TSE agent
(ongoing)
Last updated: 17 March 2007
This research project aims to explore the abilities of a number of
different TSE isolates including cattle BSE, atypical BSE in cattle, atypical
scrapie in sheep and chronic wasting disease in deer. It will also examine the
potential alteration of permeability of human species barrier for prions that
have adapted to a species other than their natural host, for example
experimental BSE in sheep.
Study Duration: March 2007 to February 2013
Contractor: ENVT
Project Code: FS231051 (M03043)
Background
The species barrier has appeared to be efficient for limiting propagation
of the TSE agent between animal species. One consequence of such a barrier is
the apparent absence of natural transmission from a number of animal TSE agents
to humans, however, that statement remains essentially based on epidemiological
observations. Very little data is available in this field, however, in the case
of cattle BSE its ability to cross the species barrier has been demonstrated.
The recent discovery of atypical forms of BSE in cattle as well as atypical
forms of scrapie in sheep raise the question of their transmissibility to
humans.
Research Approach
The research will use Enzyme-Linked ImmunoSorbent Assays and western blot
techniques to characterisation phenotypic features that are linked to a strain
of TSE agent.
Padilla, D., Béringue, V., Espinosa, J.C., Andréoletti, O., Jaumain, E.,
Reine, F., Herzog, L., Gutierrez-Adan, A., Pintado B., Laude H. & Torres
J.M. (2011) Sheep and goat BSE propagate more efficiently than cattle BSE in
human PrP transgenic mice. Published online PLoS Pathogens 7: e1001319 Espinosa,
J.C., Herva, M.E., Andréoletti, O., Padilla, D., Lacroux,C., Cassard, H.,
Lantier, I., Castilla, J. & Torres, J.M. (2009) Transgenic mice expressing
porcine prion protein resistant to classical scrapie but susceptible to sheep
bovine spongiform encephalopathy and atypical scrapie. Emerging Infectious
Diseases, 15, 1214-21
Occurrence and quantification of CNS contamination on bovine head meat
after slaughter (ongoing)
Last updated: 12 October 2008
This project aims to asses the risk of CNS contamination of head meat from
cattle slaughtered in UK abattoirs should a slaughtered animal be infected with
BSE.
Study Duration: October 2008 to March 2013
Contractor: Department of clinical veterinary science, University of
Bristol
Project Code: FS235009 (M03066)
Background
During the slaughter and dressing of bovines, there are several
conventional practices that disrupt the integrity of the central nervous system,
(CNS) and have the potential to disseminate it on edible meat. This applies not
only to carcass meat, but also to head meat, possibly contaminated by brain
material (which is specified risk material) at, or following, stunning an animal
with a captive bolt gun.
Head removal also is an invasive procedure, as the spinal cord is severed,
and there may be leakage of brain tissue through the foramen magnum. There is no
information on the prevalence or amount of CNS contamination of head meat from
cattle slaughtered in UK abattoirs and therefore no basis for an assessment of
public health risk from these sources should a slaughtered animal be infected
with BSE.
There are many factors that have potential to introduce substantial
variability in the degree of contamination of head meat, including abattoir
practices and subsequent moving and storage of heads if harvesting meat is
performed off-line or in separate premises.
Research Approach A comprehensive evaluation of the contamination of bovine
heads and head meat by CNS material will be based on current industry practices
and on a simulation of procedures that would be used if heads were processed at
cutting plants.
Contamination will be quantified using CNS marker protein(s) and will be
measured on head meat after different handling and harvesting methods currently
used. The effects of bunging the captive bolt shooting hole and the foramen
magnum (including after brain stem sampling) on contamination of heads will be
determined. The effects of surface dehydration of heads during storage on the
detection and amount of CNS material will be measured. Two options to simulate
loading, within-plant/road transport, and unloading of heads being transferred
to a cutting plant will be explored.
A best practice for the procedures involved in shipping heads will be
identified and contamination levels after transfer will be compared with that on
heads harvested on-line.
Results Additional Info Dissemination Published Papers
Thursday, February 27, 2014
BEEF, CANCER, PRIONS, AND OTHER DANGEROUS AND DEADLY PATHOGENS, APPARENTLY,
IT'S WHAT'S FOR DINNER
Thursday, March 6, 2014
TEXAS RECALL LIST MASSIVE FROM DEAD STOCK DOWNER CANCER COWS OFFAL from
Class I Recall 002-2014 and 013-2014 Health Risk: High Jan 13, 2014 and Feb 8,
2014 shipped to Texas, Florida, and Illinois UPDATE FEBRUARY 14, 2014
Thursday, March 20, 2014
JACK IN THE BOX NOW CAUGHT UP IN MASSIVE RANCHO DEAD STOCK DOWNER CANCER
COW RECALL
Thursday, June 12, 2014
Missouri Firm Recalls Ribeye and Carcass Products That May Contain
Specified Risk Materials 4,012 pounds of fresh beef products because the dorsal
root ganglia may not have been completely removed
Saturday, June 14, 2014
Rep. Rosa DeLauro (D-CT) Calls for Briefing on Beef Recalled for Mad Cow
Potential Rep. Rosa DeLauro (D-CT)
Tuesday, August 19, 2014
Former Rancho Employees Charged With 11 Felonies processed meat from 101
condemned cattle, including 79 with “cancer eye''
Thursday, November 28, 2013
Department of Justice Former Suppliers of Beef to National School Lunch
Program Settle Allegations of Improper Practices and Mistreating Cows
seems USDA NSLP et al thought that it would be alright, to feed our
children all across the USA, via the NSLP, DEAD STOCK DOWNER COWS, the most high
risk cattle for mad cow type disease, and other dangerous pathogens, and they
did this for 4 years, that was documented, then hid what they did by having a
recall, one of the largest recalls ever, and they made this recall and masked
the reason for the recall due to animal abuse (I do not condone animal abuse),
not for the reason of the potential for these animals to have mad cow BSE type
disease (or other dangerous and deadly pathogens). these TSE prion disease can
lay dormant for 5, 10, 20 years, or longer, WHO WILL WATCH OUR CHILDREN FOR THE
NEXT 5 DECADES FOR CJD ???
Saturday, September 21, 2013
Westland/Hallmark: 2008 Beef Recall A Case Study by The Food Industry
Center January 2010 THE FLIM-FLAM REPORT
DID YOUR CHILD CONSUME SOME OF THESE DEAD STOCK DOWNER COWS, THE MOST HIGH
RISK FOR MAD COW DISEASE ??? this recall was not for the welfare of the animals.
...tss you can check and see here ; (link now dead, does not work...tss)
try this link ;
Sunday, November 13, 2011
*** California BSE mad cow beef recall, QFC, CJD, and dead stock downer
livestock
Thursday, February 13, 2014
HSUS VS USDA ET AL BAN DOWNER CALVES FOR HUMAN CONSUMPTION (*veal) and
potential BSE risk factor there from
what’s the big secret about the age and history of this poor gentleman ???
MAD COW COVER UP USA, THE EVIDENCE MOUNTS $$$
Monday, June 02, 2014
Confirmed Human BSE aka mad cow Variant CJD vCJD or nvCJD Case in Texas
*** Infectious agent of sheep scrapie may persist in the environment for at
least 16 years
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
New studies on the heat resistance of hamster-adapted scrapie agent:
Threshold survival after ashing at 600°C suggests an inorganic template of
replication
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel
Production
Detection of protease-resistant cervid prion protein in water from a
CWD-endemic area
A Quantitative Assessment of the Amount of Prion Diverted to Category 1
Materials and Wastewater During Processing
Rapid assessment of bovine spongiform encephalopathy prion inactivation by
heat treatment in yellow grease produced in the industrial manufacturing process
of meat and bone meals
PPo4-4:
Survival and Limited Spread of TSE Infectivity after Burial
AD.63:
Susceptibility of domestic cats to chronic wasting disease
Amy V.Nalls,1 Candace Mathiason,1 Davis Seelig,2 Susan Kraft,1 Kevin
Carnes,1 Kelly Anderson,1 Jeanette Hayes-Klug1 and Edward A. Hoover1 1Colorado
State University; Fort Collins, CO USA; 2University of Minnesota; Saint Paul, MN
USA
Domestic and nondomestic cats have been shown to be susceptible to feline
spongiform encephalopathy (FSE), almost certainly caused by consumption of
bovine spongiform encephalopathy (BSE)-contaminated meat. Because domestic and
free-ranging nondomestic felids scavenge cervid carcasses, including those in
areas affected by chronic wasting disease (CWD), we evaluated the susceptibility
of the domestic cat (Felis catus) to CWD infection experimentally. Cohorts of 5
cats each were inoculated either intracerebrally (IC) or orally (PO) with
CWD-infected deer brain. At 40 and 42 mo post-inoculation, two IC-inoculated
cats developed signs consistent with prion disease, including a stilted gait,
weight loss, anorexia, polydipsia, patterned motor behaviors, head and tail
tremors, and ataxia, and progressed to terminal disease within 5 mo. Brains from
these two cats were pooled and inoculated into cohorts of cats by IC, PO, and
intraperitoneal and subcutaneous (IP/SC) routes. Upon subpassage, feline-adapted
CWD (FelCWD) was transmitted to all IC-inoculated cats with a decreased
incubation period of 23 to 27 mo. FelCWD was detected in the brains of all the
symptomatic cats by western blotting and immunohistochemistry and abnormalities
were seen in magnetic resonance imaging, including multifocal T2 fluid
attenuated inversion recovery (FLAIR) signal hyper-intensities, ventricular size
increases, prominent sulci, and white matter tract cavitation. Currently, 3 of 4
IP/SQ and 2 of 4 PO inoculared cats have developed abnormal behavior patterns
consistent with the early stage of feline CWD.
*** These results demonstrate that CWD can be transmitted and adapted to
the domestic cat, thus raising the issue of potential cervid-to- feline
transmission in nature.
www.landesbioscience.com
PO-081: Chronic wasting disease in the cat— Similarities to feline
spongiform encephalopathy (FSE)
FELINE SPONGIFORM ENCEPHALOPATHY FSE
Chronic Wasting Disease Susceptibility of Four North American Rodents
Chad J. Johnson1*, Jay R. Schneider2, Christopher J. Johnson2, Natalie A.
Mickelsen2, Julia A. Langenberg3, Philip N. Bochsler4, Delwyn P. Keane4, Daniel
J. Barr4, and Dennis M. Heisey2 1University of Wisconsin School of Veterinary
Medicine, Department of Comparative Biosciences, 1656 Linden Drive, Madison WI
53706, USA 2US Geological Survey, National Wildlife Health Center, 6006
Schroeder Road, Madison WI 53711, USA 3Wisconsin Department of Natural
Resources, 101 South Webster Street, Madison WI 53703, USA 4Wisconsin Veterinary
Diagnostic Lab, 445 Easterday Lane, Madison WI 53706, USA *Corresponding author
email: cjohnson@svm.vetmed.wisc.edu
We intracerebrally challenged four species of native North American rodents
that inhabit locations undergoing cervid chronic wasting disease (CWD)
epidemics. The species were: deer mice (Peromyscus maniculatus), white-footed
mice (P. leucopus), meadow voles (Microtus pennsylvanicus), and red-backed voles
(Myodes gapperi). The inocula were prepared from the brains of hunter-harvested
white-tailed deer from Wisconsin that tested positive for CWD. Meadow voles
proved to be most susceptible, with a median incubation period of 272 days.
Immunoblotting and immunohistochemistry confirmed the presence of PrPd in the
brains of all challenged meadow voles. Subsequent passages in meadow voles lead
to a significant reduction in incubation period. The disease progression in
red-backed voles, which are very closely related to the European bank vole (M.
glareolus) which have been demonstrated to be sensitive to a number of TSEs, was
slower than in meadow voles with a median incubation period of 351 days. We
sequenced the meadow vole and red-backed vole Prnp genes and found three amino
acid (AA) differences outside of the signal and GPI anchor sequences. Of these
differences (T56-, G90S, S170N; read-backed vole:meadow vole), S170N is
particularly intriguing due its postulated involvement in "rigid loop" structure
and CWD susceptibility. Deer mice did not exhibit disease signs until nearly 1.5
years post-inoculation, but appear to be exhibiting a high degree of disease
penetrance. White-footed mice have an even longer incubation period but are also
showing high penetrance. Second passage experiments show significant shortening
of incubation periods. Meadow voles in particular appear to be interesting lab
models for CWD. These rodents scavenge carrion, and are an important food source
for many predator species. Furthermore, these rodents enter human and domestic
livestock food chains by accidental inclusion in grain and forage. Further
investigation of these species as potential hosts, bridge species, and
reservoirs of CWD is required.
please see ;
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 Professor
Department of Chemical Engineering University of Delaware
===========END...TSS==============
> First transmission of CWD to transgenic mice over-expressing bovine
prion protein gene (TgSB3985)
PRION 2014 - PRIONS: EPIGENETICS and NEURODEGENERATIVE DISEASES – Shaping
up the future of prion research
Animal TSE Workshop 10.40 – 11.05 Talk Dr. L. Cervenakova First
transmission of CWD to transgenic mice over-expressing bovine prion protein gene
(TgSB3985)
Thursday, November 21, 2013
*** Assessing the susceptibility of transgenic mice over-expressing deer
prion protein to bovine spongiform encephalopathy
The present study was designed to assess the susceptibility of the
prototypic mouse line, Tg(CerPrP)1536+/- to bovine spongiform encephalopathy
(BSE) prions, which have the ability to overcome species barriers.
Tg(CerPrP)1536+/- mice challenged with red deer-adapted BSE resulted in a
90-100% attack rates, BSE from cattle failed to transmit, indicating agent
adaptation in the deer.
P.126: Successful transmission of chronic wasting disease (CWD) into mice
over-expressing bovine prion protein (TgSB3985)
Larisa Cervenakova,1 Christina J Sigurdson,2 Pedro Piccardo,3 Oksana
Yakovleva,1 Irina Vasilyeva,1 Jorge de Castro,1 Paula Saá,1 and Anton Cervenak1
1American Red Cross, Holland Laboratory; Rockville, MD USA; 2University of
California; San Diego, CA USA; 3Lab TSE/OBRR /CBER/FDA; Rockville, MD USA
Keywords: chronic wasting disease, transmission, transgenic mouse, bovine
prion protein
Background. CWD is a disease affecting wild and farmraised cervids in North
America. Epidemiological studies provide no evidence of CWD transmission to
humans. Multiple attempts have failed to infect transgenic mice expressing human
PRNP gene with CWD. The extremely low efficiency of PrPCWD to convert normal
human PrPC in vitro provides additional evidence that transmission of CWD to
humans cannot be easily achieved. However, a concern about the risk of CWD
transmission to humans still exists. This study aimed to establish and
characterize an experimental model of CWD in TgSB3985 mice with the following
attempt of transmission to TgHu mice.
Materials and Methods. TgSB3985 mice and wild-type FVB/ NCrl mice were
intracranially injected with 1% brain homogenate from a CWD-infected Tga20 mouse
(CWD/Tga20). TgSB3985 and TgRM (over-expressing human PrP) were similarly
injected with 5% brain homogenates from CWD-infected white-tailed deer (CWD/WTD)
or elk (CWD/Elk). Animals were observed for clinical signs of neurological
disease and were euthanized when moribund. Brains and spleens were removed from
all mice for PrPCWD detection by Western blotting (WB). A histological analysis
of brains from selected animals was performed: brains were scored for the
severity of spongiform change, astrogliosis, and PrPCWD deposition in ten brain
regions.
Results. Clinical presentation was consistent with TSE. More than 90% of
TgSB3985 and wild-type mice infected with CWD/Tga20, tested positive for PrPres
in the brain but only mice in the latter group carried PrPCWD in their spleens.
We found evidence for co-existence or divergence of two CWD/ Tga20 strains based
on biochemical and histological profiles. In TgSB3985 mice infected with CWD-elk
or CWD-WTD, no animals tested positive for PrPCWD in the brain or in the spleen
by WB. However, on neuropathological examination we found presence of amyloid
plaques that stained positive for PrPCWD in three CWD/WTD- and two
CWD/Elk-infected TgSB3985 mice. The neuropathologic profiles in CWD/WTD- and
CWD/Elkinfected mice were similar but unique as compared to profiles of BSE,
BSE-H or CWD/Tg20 agents propagated in TgSB3985 mice. None of CWD-infected TgRM
mice tested positive for PrPCWD by WB or by immunohistochemical detection.
Conclusions. To our knowledge, this is the first established experimental
model of CWD in TgSB3985. We found evidence for co-existence or divergence of
two CWD strains adapted to Tga20 mice and their replication in TgSB3985 mice.
Finally, we observed phenotypic differences between cervid-derived CWD and
CWD/Tg20 strains upon propagation in TgSB3985 mice. Further studies are underway
to characterize these strains.
P.89: Prions survive long-term burial in soil with some groundwater
dissemination
Allister JA Smith,1 Karen Fernie,1 Ben Maddison,2 Keith Bishop,2 Kevin
Gough,3 and Robert A Somerville1 1The Roslin Institute; University of Edinburgh;
Edinburgh, UK; 2ADAS Biotechnology Group, University of Nottingham; Nottingham,
UK; 3University of Nottingham; Nottingham, UK
An intrinsic property of prions is their extreme resistance to degradation.
When they are deposited within the environment, whether from inappropriate
disposal by man or from fallen diseased livestock, there is the potential to
further propagate cases of disease for many years. It is evidenced that the
spread of scrapie in sheep and chronic wasting disease in deer have occurred in
this manner.
We mimicked such scenarios under large-scale field conditions to determine
the extent to which TSE infectivity survives or disseminates in soil and soil
water over five years. The mouse passaged BSE strain, 301V, was used to spike
buried bovine heads, or was buried as an uncontained bolus in large soil-filled
lysimeters. Two soils were examined, a free-draining sandy loam and a
water-retentive clay loam.
Infectivity, determined by bioassay in mice, was recovered from all heads
exhumed annually for 5 years from both soil types, with little reduction in the
amount of infectivity over time. Small amounts of infectivity were found in soil
samples immediately surrounding the heads but not in samples remote from them.
Commensurate with this there was no evidence of significant lateral movement of
infectivity from the bolus buried in a large soil mass. However large amounts of
infectivity were recovered at the original bolus burial site in both soils.
There was limited vertical upward movement of infectivity from the bolus buried
in clay and downward movement from the bolus buried in sand perhaps reflecting
the clay soils propensity to flood.
Throughout the course of the experiment rainwater particulate from several
lysimeters was trapped on glass-fibre filters. Extracts from these filters were
subject to serial PMCA (protein misfolding cyclic amplification) which was
optimised using 301V-spiked samples and blinded controls. All positive and
negative control samples were correctly determined. We have tested 44 samples
from rainwater passed through the clay lysimeter filters, and found 9 positive
samples, mainly from the initial 8 months of the experiment.
We conclude that TSE infectivity is likely to survive burial for long time
periods with minimal loss of infectivity and limited movement from the original
burial site. However PMCA results have shown that there is the potential for
rainwater to elute TSErelated material from soil which could lead to the
contamination of a wider area. These experiments reinforce the importance of
risk assessment when disposing of TSE risk materials.
P.121: Efficient transmission of prion disease through environmental
contamination
Sandra Pritzkow, Rodrigo Morales, and Claudio Soto Mitchell Center for
Alzheimer’s disease and related Brain disorders; University of Texas Medical
School at Houston; Hourston, TX USA
Chronic wasting disease (CWD) is a prion disorder effecting captive and
free-ranging deer and elk. The efficient propagation suggests that horizontal
transmission through contaminated environment may play an important role. It has
been shown that infectious prions enter the environment through saliva, feces,
urine, blood or placenta tissue from infected animals, as well as by carcasses
from diseased animals and can stay infectious inside soil over several
years.
82 Prion Volume 8 Supplement
We hypothesize that environmental components getting in contact with
infectious prions can also play a role for the horizontal transmission of prion
diseases. To study this issue, surfaces composed of various environmentally
relevant materials were exposed to infectious prions and the attachment and
retention of infectious material was studied in vitro and in vivo. We analyzed
polypropylene, glass, stainless steel, wood, stone, aluminum, concrete and brass
surfaces exposed to 263K-infected brain homogenate. For in vitro analyses, the
material was incubated in serial dilutions of 263K-brain homogenate, washed
thoroughly and analyzed for the presence of PrPSc by PMCA. The results show that
even highly diluted PrPSc can bind efficiently to polypropylene, stainless
steel, glass, wood and stone and propagate the conversion of normal prion
protein. For in vivo experiments, hamsters were ic injected with implants
incubated in 1% 263K-infected brain homogenate. Hamsters, inoculated with
263K-contaminated implants of all groups, developed typical signs of prion
disease, whereas control animals inoculated with non-contaminated materials did
not.
In addition, in order to study the transmission in a more natural setting,
we exposed a group of hamster to habit in the presence of spheres composed of
various materials that were pretreated with 263K prions. Many of the hamsters
exposed to these contaminated materials developed typical signs of the disease
that were confirmed by immunohistological and biochemical analyses.
These findings suggest that various surfaces can efficiently bind
infectious prions and act as carriers of infectivity, suggesting that diverse
elements in the environment may play an important role in horizontal prion
transmission.
P.138: Phenotypic diversity in meadow vole (Microtus pennsylvanicus) prion
diseases following challenge with chronic wasting disease isolates
Christopher J Johnson,1 Christina M Carlson,1,2 Jay R Schneider,1 Jamie K
Wiepz,1 Crystal L Meyerett-Reid,3 Mark D Zabel,3 Joel A Pedersen,2 and Dennis M
Heisey1 1USGS National Wildlife Health Center; Madison, WI USA; 2University of
Wisconsin— Madison; Madison, WI USA; 3Colorado State University; Fort Collins,
CO USA
Chronic wasting disease (CWD), a prion disease of cervids (deer, elk and
moose), is spreading unchecked through large sections of North America.
Transmission of CWD among cervids is especially facile and can occur through
direct animal-toanimal contact and indirectly through contact with prions shed
from infected animals. The disease transmission threat posed by CWD to other
wildlife species remains unknown, but other species are inevitably exposed to
CWD by consumption of infectious materials and through contact with
environmental CWD contamination.
In this study, we investigated the transmission and adaptation of various
white-tailed deer CWD isolates in the meadow vole (Microtus pennsylvanicus), a
native North American rodent that is sympatric with current CWD epizootics that
we have previously established is susceptible to CWD. We found that serial
subpassage of CWD from white-tailed deer homozygous for glycine at position 96
(96GG) of the prion protein in meadow voles resulted in the selection of a
single prion strain that was characterized by homogeneity in incubation period,
abnormal prion protein (PrPTSE) glycoform ratio, lesion profile and PrPTSE
deposition pattern. In contrast, passage of CWD from heterozygous 96GS genotype
deer produced four unique disease phenotypes upon first passage. Subpassage of
these types ultimately resulted in selection of a single strain by third passage
that was distinct from the 96GG genotype CWD-derived strain.
We also establish that meadow voles are susceptible to CWD via peripheral
challenge, albeit with lower attack rates and longer incubation periods.
Interestingly, oral challenge of meadow voles with CWD resulted in subclinical
infection in primary passage animals, but manifested as clinical prion disease
upon subpassage.
Our data establish that meadow voles are permissive to CWD via peripheral
exposure route, suggesting they could serve as an environmental reservoir for
CWD. Additionally, our data are consistent with the hypothesis that at least two
strains of CWD circulate in naturally-infected cervid populations and provide
evidence that meadow voles are a useful tool for CWD strain typing.
P.141: Abundant prion shedding in CWD-infected deer revealed by Realtime
conversion
Edward A Hoover,1 Davin M Henderson,1 Nathaniel D Denkers,1 Candace K
Mathiason,1 Matteo Manca,2,3 and Byron Caughey2 1Prion Research Center, Colorado
State University; Fort Collins, CO USA; 2Laboratory of Persistent Viral
Diseases, NI AID; Hamilton, MT USA; 3Department of Biomedical Sciences,
University of Cagliari; Monserrato, Italy
Background/Introduction. Chronic wasting disease (CWD) is unique among
prion diseases in its efficient lateral transmission in nature. While the
presence of infectious prions in body fluids and excreta of infected cervids has
been demonstrated by bioassay, the dynamics, magnitude, and consequences of
prion shedding remain unknown. The present studies were undertaken to determine
the kinetics, duration, and magnitude of prion shedding in infected white-tailed
deer.
Materials and Methods. Longitudinal samples were collected from
white-tailed deer over a 2-year span after either oral (n=11)] aerosol (n = 6)
CWD exposure. The assay protocol employed phosphotungstic acid precipitation of
either whole saliva or the pelleted fraction of urine to seed recombinant Syrian
hamster prion PrP substrate in RT-QuIC reactions. Prion seeding activity was
assayed in 8 replicates of each sample employing thioflavin T detection in a
96-well plate-based fluorometer. Prion seeding reaction rate was determined by
taking the inverse of the time at which samples exceeded a threshold of 5
standard deviations above the mean fluorescence of negative controls (1/time to
threshold). Seeding activity was quantitated by comparing the realtime
conversion reaction rate to a standard curve derived from a reference bioassayed
brain pool homogenate from deer with terminal CWD.
Results. We analyzed >200 longitudinally collected, blinded, then
randomized saliva and urine samples from 17 CWDinfected and 3 uninfected
white-tailed deer. We detected prion shedding as early as 3 months post exposure
and sustained thereafter throughout the disease course in both aerosol and
orally exposed deer. The incidence of non-specific false positive results from
>500 saliva and urine samples from negative control deer was 0.8%. By
comparing real-time reaction rates for these body fluids to a bioassayed
serially diluted brain control, we estimated that ≤1 ml of saliva or urine from
pre-symptomatic infected deer constitutes a lethal infectious prion dose.
Conclusion. CWD prions are shed in saliva and urine of infected deer as
early as 3 months post infection and throughout the subsequent >1.5 year
course of infection. In current work we are examining the relationship of
prionemia to excretion and the impact of excreted prion binding to surfaces and
particulates in the environment.
Acknowledgments. Support: NIH-RO1-NS-061902; Morris Animal Foundation
D12ZO-045
P.154: Urinary shedding of prions in Chronic Wasting Disease infected
white-tailed deer
Nathaniel D Denkers,1 Davin M Henderson, 1 Candace K Mathiason,1 and Edward
A Hoover1 1Prion Research Center, Department of Microbiology, Immunology, and
Pathology, Colorado State University; Fort Collins, CO USA
Background/Introduction. Chronic wasting disease (CWD) is unique among
prion diseases in its efficient lateral transmission in nature, yet the dynamics
and magnitude of shedding and its immediate and long term consequences remain
unknown. The present study was designed to determine the frequency and time span
in which CWD prions are shed in urine from infected white-tailed deer using
adapted real-time quaking-induced conversion (RT-QuIC) methodology.
Materials and Methods. Longitudinal urine samples were collected by free
catch or catheterization over a 2-year period from oral-route infected [CWD+ (n
= 11)] and aerosol-route-infected [CWD+ (n = 6); CWD- (n = 3)] white-tailed
deer. High speed centrifugation pelleted material from 500 µl of urine was
treated with sodium phosphotungstic acid (Na-PTA), resuspended in 0.05% SDS
buffer, and used as seed in RT-QuIC assays employing recombinant Syrian hamster
prion PrP substrate. Eight (8) replicates of each sample were run and prion
seeding activity was recorded as thioflavin T binding fluorescence (480 nm
emission) using a fluorimeter-shaker. Samples were considered positive if they
crossed an established threshold (5 standard deviations above the negative mean
fluorescence).
Results. In our oral-route inoculation studies, prion seeding activity has
been demonstrated in urine collected at 6 months post-inoculation in 6 of 10
deer (11 of 80 replicates; 14%), and intermittently at later time points in all
11 CWD+ exposed deer. Our aerosol-route inoculation studies also showed prion
seeding activity in urine collected at 6 months post-inoculation in 1 of 2 deer
(3 of 16 replicates; 19%), and intermittently at later time points in 4 of 6
CWD+ exposed deer. Urine from sham-inoculated control deer and all baseline
samples yielded 3 false-positive prion seeding activities (3 of 352 replicates;
0.8%).
Conclusion. CWD prions (as inferred by prion seeding activity by RT-QuIC)
are shed in urine of infected deer as early as 6 months post inoculation and
throughout the subsequent disease course. Further studies are in progress
refining the real-time urinary prion assay sensitivity and we are examining more
closely the excretion time frame, magnitude, and sample variables in
relationship to inoculation route and prionemia in naturally and experimentally
CWD-infected cervids.
Acknowledgments. Support: NIH: RO1-NS-061902 and Morris Animal Foundation:
D12ZO-045
P.158: Structurally and phenotypically different prions in CWD-infected
white-tailed deer
Martin L Daus, Peter Lasch, and Michael Beekes Robert Koch-Institut;
Berlin, Germany
Prions can exist as multiple strains within mammals. We could detect, for
the first time, two distinct chronic wasting disease (CWD) isolates in
white-tailed deer (WTD).
WTD had been challenged with CWD from either mule deer (MD) or WTD.
Brain-derived prions from MD-infected WTD and WTD-infected WTD could be
distinguished by biochemical, biophysical and biological methods. PK-mediated
limited proteolysis at different pH-values indicated conformational differences
between pathological prion proteins (PrPTSE) from MD-infected WTD and
WTD-infected WTD. More specifically, Fouriertransform infrared microspectroscopy
revealed secondary structure differences between highly purified PrPTSE extracts
from MD-infected WTD and WTD-infected WTD. Different sedimentation velocities of
PrPTSE in gradient centrifugations provided additional evidence for structure
differences between prions from MD-infected WTD and WTD-infected WTD. Brain
homogenate from WTD-infected WTD showed a substantially lower seeding activity
on cellular prion protein (PrPC) of Syrian hamsters in protein misfolding cyclic
amplification (PMCA) than its conformationally distinct counterpart from
MD-infected WTD. When hamsters were intracerebrally inoculated with brain tissue
from MD-infected WTD disease could be transmitted, which was not observed after
similar inoculation with brain homogenate from WTD-infected WTD. In an ongoing
macaque-study both CWD-isolates are currently being further tested for their
transmissibility to primates.
P.163: Bayesian hierarchical modeling of chronic wasting disease in
free-ranging white-tailed deer in the eastern U.S.
Tyler S Evans1 and W David Walter2 1Pennsylvania Cooperative Fish and
Wildlife Research Unit; The Pennsylvania State University; University Park, PA
USA; 2US Geological Survey; Pennsylvania Cooperative Fish and Wildlife Research
Unit; The Pennsylvania State University; University Park, PA USA
Introduction. Chronic wasting disease (CWD) is a prion disease that affects
both free-ranging and captive cervid populations. In the past 45 years, CWD has
spread from a single region in Colorado to all bordering states, as well as
Canada, the Midwest and the northeastern United States. In 2005, CWD was
detected in the eastern U.S. in a free-ranging white-tailed deer (Odocoileus
virginianus) killed by a vehicle in West Virginia followed by positives from
Virginia, Maryland, and Pennsylvania. Although considerable information has been
learned about CWD in wildlife from several areas of the U.S. and Canada, little
information is available on spatial epidemiology of disease in the eastern
U.S.
Materials and Methods. In order to develop a CWD surveillance plan for the
region, we determined covariates and the best scale for analysis by exploring
habitat use and estimating the mean size of home range for deer in the central
Appalachian region (6 km2). We conducted Bayesian hierarchical modeling in
WinBUGS on 24 a priori models using 11,320 free-ranging white-tailed deer (69
positive, 11,251 negative) that have been tested for CWD since 2005. Testing for
CWD was conducted using standard protocols on a variety of tissues extracted
from hunter-harvested deer that included retropharyngeal lymph nodes, tonsil
lymph nodes, and the medulla oblongata sectioned at the obex.
Results. We found 94% of models weights were accounted for in our top model
that identified habitats such as developed and open as covariates that increased
the odds of infection for CWD in this region. Contrary to research in the
endemic area of Colorado, we did not identify clay soil as a significant
predictor of disease even though clay soil ranged from 9% to 19% in our study
samples. Furthermore, contrary to results from the recent expansion of CWD into
the agricultural Midwestern U.S. (Wisconsin, Illinois), we identified developed
and open habitats were better predictors of disease occurrence compared to
forest habitat considered more critical to deer population dynamics in the
U.S.
Conclusions. Our results suggested that the odds of infection for CWD is
likely controlled by areas that congregate deer thus increasing direct
transmission (deer-to-deer interactions) or indirect transmission
(deer-to-environment) by sharing or depositing infectious prion proteins in
these preferred habitats. Epidemiology of CWD in the eastern U.S. is likely
controlled by separate factors than found in the Midwestern and endemic areas
for CWD and can assist in performing more efficient surveillance efforts for the
region.
P.178: Longitudinal quantitative analysis of CWD prions shed in saliva of
deer
Davin M Henderson, Nina Garbino, Nathaniel D Denkers, Amy V Nalls, Candace
K Mathiason, and Edward A Hoover Prion Research Center, College of Veterinary
Medicine and Biomedical Sciences, Colorado State University; Fort Collins, CO
USA
Background/Introduction. Chronic Wasting Disease (CWD) is an emergent
rapidly spreading fatal prion disease of cervids (deer, elk and moose). CWD has
now been identified in 22 States (including two new states within the last
year), 2 Canadian provinces, and South Korea. Shedding of infectious prions in
excreta (saliva, urine, feces) may be an important factor in CWD transmission.
Here we apply an adapted version of a rapid in vitro assay [real-time
quaking-induced conversion (RT-QuIC)] to determine the time of onset, length,
pattern, and magnitude of prion shedding in saliva of infected deer.
Materials and Methods. The RT-QuIC assay was performed as previously
described in Henderson et al. PLoS-One (2013). Saliva samples were quantitated
by comparison to a RT-QuIC reaction rate standard curve of a bioassayed obex
sample from a terminally ill cervid.
Results. To better understand the onset and length of CWD prion shedding we
analyzed >150 longitudinally collected, blinded, then randomized saliva
samples from 17 CWD-infected and 3 uninfected white-tailed deer. We observed
prion shedding, as detected by the RT-QuIC assay, as early as 3 months from
inoculation and sustained shedding throughout the disease course in both aerosol
and orally exposed deer. We estimated the infectious lethal dose of prions shed
in saliva from infected deer by comparing real-time reaction rates of saliva
samples to a bioassayed serially diluted brain control. Our results indicate
that as little as 1 ml of saliva from pre-symptomatic infected deer constitutes
a lethal CWD prion dose.
Conclusions. During the pre-symptomatic stage of CWD infection and
throughout the course of disease deer may be shedding multiple LD50 doses per
day in their saliva. CWD prion shedding through saliva and excreta may account
for the unprecedented spread of this prion disease in nature.
Acknowledgments. Supported by NIH grant RO1-NS-061902 and grant D12ZO-045
from the Morris Animal Foundation.
PRION 2014 CONFERENCE
CHRONIC WASTING DISEASE CWD
A FEW FINDINGS ;
Conclusions. To our knowledge, this is the first established experimental
model of CWD in TgSB3985. We found evidence for co-existence or divergence of
two CWD strains adapted to Tga20 mice and their replication in TgSB3985 mice.
Finally, we observed phenotypic differences between cervid-derived CWD and
CWD/Tg20 strains upon propagation in TgSB3985 mice. Further studies are underway
to characterize these strains.
We conclude that TSE infectivity is likely to survive burial for long time
periods with minimal loss of infectivity and limited movement from the original
burial site. However PMCA results have shown that there is the potential for
rainwater to elute TSE related material from soil which could lead to the
contamination of a wider area. These experiments reinforce the importance of
risk assessment when disposing of TSE risk materials.
The results show that even highly diluted PrPSc can bind efficiently to
polypropylene, stainless steel, glass, wood and stone and propagate the
conversion of normal prion protein. For in vivo experiments, hamsters were ic
injected with implants incubated in 1% 263K-infected brain homogenate. Hamsters,
inoculated with 263K-contaminated implants of all groups, developed typical
signs of prion disease, whereas control animals inoculated with non-contaminated
materials did not.
Our data establish that meadow voles are permissive to CWD via peripheral
exposure route, suggesting they could serve as an environmental reservoir for
CWD. Additionally, our data are consistent with the hypothesis that at least two
strains of CWD circulate in naturally-infected cervid populations and provide
evidence that meadow voles are a useful tool for CWD strain typing.
Conclusion. CWD prions are shed in saliva and urine of infected deer as
early as 3 months post infection and throughout the subsequent >1.5 year
course of infection. In current work we are examining the relationship of
prionemia to excretion and the impact of excreted prion binding to surfaces and
particulates in the environment.
Conclusion. CWD prions (as inferred by prion seeding activity by RT-QuIC)
are shed in urine of infected deer as early as 6 months post inoculation and
throughout the subsequent disease course. Further studies are in progress
refining the real-time urinary prion assay sensitivity and we are examining more
closely the excretion time frame, magnitude, and sample variables in
relationship to inoculation route and prionemia in naturally and experimentally
CWD-infected cervids.
Conclusions. Our results suggested that the odds of infection for CWD is
likely controlled by areas that congregate deer thus increasing direct
transmission (deer-to-deer interactions) or indirect transmission
(deer-to-environment) by sharing or depositing infectious prion proteins in
these preferred habitats. Epidemiology of CWD in the eastern U.S. is likely
controlled by separate factors than found in the Midwestern and endemic areas
for CWD and can assist in performing more efficient surveillance efforts for the
region.
Conclusions. During the pre-symptomatic stage of CWD infection and
throughout the course of disease deer may be shedding multiple LD50 doses per
day in their saliva. CWD prion shedding through saliva and excreta may account
for the unprecedented spread of this prion disease in nature.
see full text and more ;
Monday, June 23, 2014
*** PRION 2014 CONFERENCE CHRONIC WASTING DISEASE CWD
*** 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.
First Live Test for Chronic Wasting Disease Last Modified: Jan 30, 2014
NWRC researchers and partners recently completed their third year of evaluating
and validating the first live rectal-tissue biopsy method for detecting chronic
wasting disease (CWD) in captive and wild elk. To date, researchers have
collected over 1,500 biopsies from captive elk in Colorado and used the
technique to find 15 elk that were positive for CWD. As compared to proven
post-mortem diagnostic tests, this live test appears to be nearly as
accurate.
“The key advantage to the rectal biopsy test is that it can be performed on
live animals. Until now, there was no practical live test for CWD in elk,” said
NWRC's Dr. Kurt VerCauteren. “With this technique we can detect CWD in animals
not showing any signs of the disease and, thus, remove them so they are not left
to infect other individuals and further contaminate the environment.”
The research is a collaborative effort between APHIS' WS and Veterinary
Services programs, the Agricultural Research Service, and the Colorado State
University Veterinary Diagnostic Laboratory within the College of Veterinary
Medicine and Biomedical Sciences. The majority of the research was conducted on
the Velvet Ridge Elk Ranch, owned by Dennis and Stephanie White, near Fort
Collins, Colorado. In 2002, an elk on the ranch was confirmed to have CWD and
since that time the Whites have worked closely with NWRC and other collaborators
to learn more about CWD and to develop methods to manage it in captive and wild
settings.
“The use of this new live test in the initial screening, surveillance and
monitoring of CWD will greatly aid in the management and control of the disease
in the wild, as well as in captive settings,” said VerCauteren. More studies are
needed before the live rectal test can be used on a large scale. For more
information, please contact nwrc@aphis.usda.gov.
Monday, May 05, 2014
cwd tse prion testing PMCA , IHC, tonsil, rectal, biopsy ???
Thursday, July 03, 2014
*** How Chronic Wasting Disease is affecting deer population and what’s the
risk to humans and pets?
Tuesday, July 01, 2014
*** CHRONIC WASTING DISEASE CWD TSE PRION DISEASE, GAME FARMS, AND
POTENTIAL RISK FACTORS THERE FROM
Wednesday, September 17, 2014
Cervid Health Business Plan Fiscal Years 2014 to 2018 Animal and Plant
Health Inspection Service Veterinary Services
what is the BIG SECRET about this recent case of nvCJD in Texas ???
Monday, June 02, 2014
*** Confirmed Human BSE aka mad cow Variant CJD vCJD or nvCJD Case in Texas
Tuesday, April 01, 2014
*** Questions linger in U.S. CJD cases 2005, and still do in 2014 ***
Sunday, March 09, 2014
A Creutzfeldt-Jakob Disease (CJD) Lookback Study: Assessing the Risk of
Blood Borne Transmission of Classic Forms of Creutzfeldt-Jakob Disease
FDA TSEAC CIRCUS AND TRAVELING ROAD SHOW FOR THE TSE PRION DISEASES
Sunday, April 06, 2014
SPORADIC CJD and the potential for zoonotic transmission there from, either
directly or indirectly via friendly fire iatrogenic mode, evidence to date
Wednesday, December 11, 2013
*** Detection of Infectivity in Blood of Persons with Variant and Sporadic
Creutzfeldt-Jakob Disease ***
Wednesday, September 10, 2014
Creutzfeldt-Jakob disease (CJD) biannual update (August 2014), with updated
guidance on decontamination of gastrointestinal endoscopy equipment
Research and analysis
Tuesday, September 16, 2014
mad cow scaremongers consumerfreedom.com December 20, 2003 article and a
2014 review
tss
