Is BSE Caused by a VIRUS?

[Oldtimer]

Health/ScienceStudy challenges mad cow research
BLOOMBERG NEWS

January 31, 2007

Researchers have found more evidence that a virus may cause mad cow disease and a related brain disorder in humans, threatening to overturn 25 years of research focusing on malformed proteins called prions.

Nerve cells infected with the human form of mad cow disease contained a virus-sized particle that doesn't appear in uninfected cells, said Laura Manuelidis, a neuropathologist at Yale Medical School in New Haven, Conn. Cells infected with scrapie, a sheep disorder related to mad cow disease, contained the same germ.



The findings raise the possibility of vaccines against the diseases and challenge research showing the disorders are spread by prions, abnormal proteins that have also been detected in the brains of infected humans and animals.

Some scientists have questioned the prion research performed by Stanley Prusiner of the University of California, San Francisco, since he won the Nobel Prize in 1997, Manuelidis said.

"If you don't look for something, you're not going to find it," she said in a telephone interview. "If everyone believes the world is flat, no one will go out and try to find the end."

Mad cow disease, otherwise known as bovine spongiform encephalopathy, is one of a family of rare infections that cause slow, relentless brain damage in humans and animals. The disease often takes years to appear and develop, making research especially time-consuming.

Questions about whether prions cause the infections have arisen because people and animals are thought to catch the diseases by eating tainted meat. The human stomach and intestines would quickly break down any protein, normal or abnormal, before it reached the blood or brain, said Sheldon Penman, an emeritus professor of biology at Massachusetts Institute of Technology.

Proteins, the building blocks of cells and tissues, aren't normally considered carriers of infections, like bacteria and viruses, he said. The Nobel Prize-winning work by the University of California's Prusiner lacked the precision to show that injections of prions transmitted the disease, Penman said.

"He injected stuff that had prions in it, including a million other things," Penman said in an interview. "He never did the crucial experiment of injecting prion protein and inducing disease."

Prusiner won the Nobel in physiology or medicine in 1997 "for his discovery of prions - a new biological principle of infection." He declined an interview through a university spokeswoman.

Scientists have been trying to gain a better understanding of mad cow disease, or BSE, since it struck United Kingdom herds in the late 1980s. About 153 people have developed the human form, called variant Creutzfeldt-Jakob disease, or vCJD, and health officials have put restrictions on animal feeding practices to prevent infections.

Manuelidis published research in 2005 showing that infections with a mild form of vCJD protected mice against more severe infections with the same disease. The findings suggested that vaccines against such human and animal diseases might be possible, she said at the time.

In the study published Monday, she and her colleagues studied colonies of cells with and without the human and sheep infections. They found that only infected cells contained a particle at the smaller end of the range associated with viruses.

The particles were configured in rows and groupings that appear similar to the way viruses sometimes congregate in cells, Manuelidis said. Using immune proteins called antibodies, the Yale team determined that the particles are not made of prion protein. The findings appear online in the Proceedings of the National Academy of Sciences.

 

[skcatlman]

OT just a dream at this point. In an attempt to explain what a prion is it is called a protien, but if you have seen what a prion looks like under electronmicroscopy and compare it to a virus they are very different. The easiest way to explain it is a prion is like the attachment structure on an virus, made of animo acids which attaches and infilterates a cell and downloads it genetic code for replication.that is the easiest way for me to explain it.
So the chance of developing a vaccine are not realisticat this time, a prion is not like a bacteria or virus. it replicates similarly but there is no cell wall to attack like in a bacteria, it is a series of amino acids which would be tough create an immune reponse that won't kill the host oranism. i'm not saying it is impossible just very difficult and with variations even tougher. I am not a microbiologist but I have taken courses in university to have this basic knowledge. If you want to know more contact a serious scientis studying prions to explain it more comprehensively.

 

[Oldtimer]

Studies like this raises more questions- and brings many of the previous theories into doubt... Just shows there are still so many unanswered questions about cause and transmission of BSE/TSE's that we should not be weakening any of our firewalls and safeguards...And USDA has said over and over that the number 1 safeguard the US had against BSE was our import rule quarantine on cattle/beef ....

 

[skcatlman]

OT the horse was dead months ago, you have jerky, you can stop beating it anytime now!!!!!!! we all know you don't want to give any other country access to the US market. get on with it do you have anything new to say ,not about how other countries are sending unsafe beef to the US. And how importers are not shutting their borders because their rules are too strict not that they feel they product being sent over is unsafe.

 

[flounder]

CALL it what you want, transmission studies do not lie, and neither do the threshold of destruction i.e. 600 degrees c.
does not disprove what has already been proven about amplifications and transmissions of this agent. ...TSS


TSS



Subject: Cells infected with scrapie and Creutzfeldt–Jakob disease agents produce intracellular 25-nm virus-like particles
Date: January 31, 2007 at 10:28 am PST
Cells infected with scrapie and Creutzfeldt–Jakob

disease agents produce intracellular 25-nm

virus-like particles


Laura Manuelidis*, Zhoa-Xue Yu, Nuria Banquero, and Brian Mullins

Yale Medical School, 333 Cedar Street, New Haven, CT 06510

Communicated by Sheldon Penman, Massachusetts Institute of Technology, Cambridge, MA, December 11, 2006 (received for review October 10, 2006)

We had repeatedly found
25-nm-diameter virus-like particles in

highly infectious brain fractions with little prion protein (PrP), and

therefore we searched for similar virus-like particles in situ in

infected cell lines with high titers. Neuroblastoma cells infected

with the 22L strain of scrapie as well as hypothalamic GT cells

infected with the FU Creutzfeldt–Jakob disease agent, but not

parallel mock controls, displayed dense 25-nm virus-like particles in

orthogonal arrays. These particles had no relation to abnormal PrP

amyloid in situ, nor were they labeled by PrP antibodies that

faithfully recognized rough endoplasmic reticulum membranes

and amyloid fibrils, the predicted sites of normal and pathological

intracellular PrP. Additionally, phorbol ester stimulated the production

of abnormal PrP gel bands by>5-fold in infected N2a
22L

cells, yet this did not increase either the number of virus-like arrays

or the infectious titer of these cells. Thus, the 25-nm infectionassociated

particles could not be prions. Synaptic differentiation

and neurodegeneration, as well as retroviruses that populate the

rough endoplasmic reticulum of neuroblastoma cells, were not

required for particle production. The 25-nm particle arrays in

cultured cells strongly resembled those first described in 1968 in

synaptic regions of scrapie-infected brain and subsequently identified

in many natural and experimental TSEs. The high infectivity

of comparable, isolated virus-like particles that show no intrinsic

PrP by antibody labeling, combined with their loss of infectivity

when nucleic acid–protein complexes are disrupted, make it likely

that these 25-nm particles are the causal TSE virions that induce

late-stage PrP brain pathology.



snip.



In summation, all of this data provides a clear, consistent,

substantive, and logical alternative to the accepted prion hypothesis.

The causative TSE agent is most consistent with an

exogenous 25-nm virion without intrinsic host PrP. The stimulation

of host innate immune responses by these agents, a

complex set of molecular reactions that precedes the elaboration

of pathologic PrP (9) and one that is not provoked by PrP-res

itself (25), also point to a foreign pathogen rather than some

unpredictably spontaneous mutation in the host's PrP without

cause. The presence of these particles in many different species

infected with a wide variety of TSE strains is in accord with

Koch's first requirement (1). It is also improbable that an

identical virus-like structure would be a contaminant or a

secondary coincidental feature of all these different TSE models.

Nevertheless, a more detailed molecular analysis of these

particles will be required to substantiate their causal nature.

Purification of these
25-nm particles from productive tissue

cultures should be informative if the essential infectivity assays

are performed systematically with parallel ultrastructural and

molecular analyses. Animal titrations of infectivity are expensive

and prolonged. However, sustained and reproducible infection

of indicator GT cells by a variety of TSE agents already has

shown that they can rapidly authenticate the presence of agent

in disrupted samples as well as in living cells (4, 17). GT cells also

may be used for testing infectivity of viral nucleic acids as well

as PrP conformers. Rapid assays of infectivity in culture should

facilitate the isolation of infectious particles from host components,

and treatments that modify the production of these

particles in culture may resolve further the infectious structure

from the pathological disease processes it initiates.

Materials and Methods......snip......end........TSS


http://www.pnas.org/cgi/content/abstract/0610999104v1




New studies on the heat resistance of
hamster-adapted scrapie agent: Threshold
survival after ashing at 600°C suggests an
inorganic template of replication

Paul Brown*,, Edward H. Rau, Bruce K. Johnson*, Alfred E. Bacote*, Clarence J. Gibbs Jr.*, and D. Carleton Gajdusek§

http://www.pnas.org/cgi/content/full/97/7/3418





tss

 

[Beef11]

I'm no sheep man but it seems that some sheep have an RR Rr or rr genotypical status telling about their resitance to "scrapie"? Am i correct on this?

 

[SSAP]

Can we add Mr. Rick Fox's (an official with the South Dakota Stockgrowers Association and the Ranchers-Cattlemen Action Legal Fund) statement in here also;

"The prion, you know, is kind of like Superman - it's indestructible," Fox said. "So if one of these prions come in here, it's here in the United States forever."

From: Brownfield Ag News for America, Jan 30, 2007
http://www.brownfieldnetwork.com/gestal ... 576FF98E7C

Don't think that the anti-beef groups won't pick this up and use it in their agenda somehow ......

What are beef consumers to think when they read/hear this?

AND it does apply to American domestic beef as readers/consumers will recall the Texas and Alabama BSE cows.

We worry about anti-beef radical groups who undermine our industry, and here we have an American cattleman doing the same.

Is this how you want your cattleman groups to represent you?

 

[Beef11]

Nope bse is caused by a copper deficiency. There is a guy in england i cant recall his name that says every animal tested over there for bse was found to be copper deficient and that it was because they used organophosphates on the cattle. His reasoning behind it was that the prions good prions in the brain use copper to do whatever it is they do. Well he says that because they were copper deficient that the prions started using magnesium in place of the copper which made things get all out of whack. Basically kind of like getting grass tetanus. That was his reasoning. Sounds weird I know but the article made sense.

I'm not saying that copper has nothing to do with it. I am saying that it is highly unlikely that it is soley caused by a lack of copper.

 

[Oldtimer]

Can we add Mr. Rick Fox's (an official with the South Dakota Stockgrowers Association and the Ranchers-Cattlemen Action Legal Fund) statement in here also;

"The prion, you know, is kind of like Superman - it's indestructible," Fox said. "So if one of these prions come in here, it's here in the United States forever."

From: Brownfield Ag News for America, Jan 30, 2007
http://www.brownfieldnetwork.com/gestal ... 576FF98E7C

Don't think that the anti-beef groups won't pick this up and use it in their agenda somehow ......

What are beef consumers to think when they read/hear this?

AND it does apply to American domestic beef as readers/consumers will recall the Texas and Alabama BSE cows.

We worry about anti-beef radical groups who undermine our industry, and here we have an American cattleman doing the same.

Is this how you want your cattleman groups to represent you?

SSAP-- Well if you study the subject you will find it is true...Cannot be killed by normal sterilization methods- the reason for transmission by surgical equipment, survives rendering temperatures- the reason for transmission thru MBM feed...Lasts for years in the ground-just like anthrax spores....

And yes SSAP-that is how I want my cattle organization to represent me by being open and honest--and protecting me and my herd from more BSE entering this country...The USDA has said that the best safeguard we have against BSE is our import rule quarantine against countries that have BSE....

I think SDSGA deserves an ATTA BOY for standing up for its member and getting him paid the money he was owed...To me that is why you belong to cattlemens organizations- to represent and assist you when you need it....

And yes, there have been BSE cattle found in the US- but does that mean we should just open the border up to any country with diseased cattle and bring more in-- especially higher risk cattle that have new positives turning up recently with many being POST feedban, including one that was only 4 years old :roll: ...

 

[skcatlman]

I want to see this article, from everything i have read about BSE it is caused by a prion, not a mineral deficiency. And yes there are sheep that are scrapie resistant, but that hasn't been explained yet. Yes prions withstands traditional sterilization.
OT the horse has been dead for a year now, could you stop beating it, you are making too much dust. Boy are you good at insinuations, maybe i should try this. For those countries who can't trace cattle back to where they were born and raised, how do they know if there isn't a major problem with BSE if they can't find where the cows come from. The cows in those countries magically appear with BSE and there are not others. Amazing how that works, you can't find where an animal comes from ,but there are no other animals sick?????????? Must be those magical BSE cows that materialize from thin air. Those countries must have a good program for detection they can't find but only a couple of BSE positive cows so there should be no more testing because it seems like there are no more cows to be found that would test positive.LMAO LOL

 

[Beef11]

And yes there are sheep that are scrapie resistant, but that hasn't been explained yet.

So we can breed for a genetic profile that resists a BSE like disease. The big question now is why? what?

 

[Oldtimer]

Nope bse is caused by a copper deficiency. There is a guy in england i cant recall his name that says every animal tested over there for bse was found to be copper deficient and that it was because they used organophosphates on the cattle. His reasoning behind it was that the prions good prions in the brain use copper to do whatever it is they do. Well he says that because they were copper deficient that the prions started using magnesium in place of the copper which made things get all out of whack. Basically kind of like getting grass tetanus. That was his reasoning. Sounds weird I know but the article made sense.

You are talking about Dr. Prusiner-- the fellow that discovered the prion, also....And that is his theory on how BSE developed...

But his organophosphates theory doesn't answer the question of where all the other TSE's came from- like kuru in humans in New Guinea, and Chronic Wasting Disease in deer and elk in the US....

BSE didn't show up in Europe and England until after they lowered their rendering temperatures- and were rendering cattle parts and scrapie infected sheep into cattle feed-- which has led many to believe it developed from the scrapie mutating.....

But they are all theories....

And definitely there still are way too many unanswered questions to begin weaking our safeguards and firewalls that were put in place to protect the US consumer and US cattle herd....

 

[flounder]

Nope bse is caused by a copper deficiency. There is a guy in england i cant recall his name that says every animal tested over there for bse was found to be copper deficient and that it was because they used organophosphates on the cattle. His reasoning behind it was that the prions good prions in the brain use copper to do whatever it is they do. Well he says that because they were copper deficient that the prions started using magnesium in place of the copper which made things get all out of whack. Basically kind of like getting grass tetanus. That was his reasoning. Sounds weird I know but the article made sense.

EUROPEAN COMMISSION
HEALTH & CONSUMER PROTECTION DIRECTORATE-GENERAL
Scientific Steering Committee
OPINION ON
ORGANOPHOSPHATE (OP) POISONING AND
HYPOTHETICAL INVOLVEMENT IN THE ORIGIN OF BSE
Background
In its opinion on possible links between BSE and Organophosphates adopted on 25-26 June
1998 and in its opinion on Hypotheses on the origin and transmission of BSE adopted on 29-
30 November 2001 the SSC concluded that there is no scientific evidence in support of the
hypothesis of an OP origin of BSE.
The issue of organophosphate poisoning has not been dealt with by the SSC so far. The
concerns expressed in the enquiries cover mainly intoxication by occupational exposure of
shepherds and farmers to OPs upon use against ecto-parasites, especially in sheep dipping and
treatment of cattle against Warble Fly infestation. Risks from residues are addressed to a
lesser extend.
In early 2003, a large number of additional enquiries on the issue have been addressed to
European Commission's Health and Consumer Directorate General. Four of these with
substantial enclosures were by one person. Most of them are addressing both issues: chronic
organophosphate (OP) poisoning and the origin of BSE.
Information provided with the enquiries
In addition to numerous newspaper and magazine articles the enclosures to the enquiries
provide the Material Safety Data Sheet on diazinon, the OHSA Occupational Safety and
Health Guideline for Tetraethylpyrophosphate (TEPP), an US agency Hazardous Substances
Fact Sheet on crufomate, company safety information sheets, some correspondence with UK
authorities including their activities to improve safe use of these chemicals. The information
regarding claimed OP chronic poisoning of cases presented does not provide evidence, neither
for OPs being the cause for diseases nor for their exclusion (i.e., "very low" bloodcholinesterase
levels, provided without data or comparison with the normal distribution of
values; successful treatment of a patient for OP clearance without giving any OP data). It
C:\WINNT\Temporary Internet Files\SSC_Last_OP_Final.doc 2
seems however, that due to insufficient, non-prudent use of the safety requirements undue
exposures of shepherds and farmers have occurred.
There is no additional information on the claimed involvement of OPs in the origin of BSE.
This applies for both, the hypotheses on the direct effect of OPs as well as on their
hypothetical role for Cu-deficiency to be involved in the origin of BSE (Cu binding of prion
protein is known). New publications are mentioned in one enquiry but they have not yet been
provided. In an Internet search no recent scientifically valid publications were traceable. The
SSC had been informed that research would be launched on this hypothesis, but no
information has been provided so far on its status or on results.
Conclusions
a) As regards the involvement of organophosphates in the origin of BSE, no new scientific
information providing evidence or supporting the hypothesis by valid data became
available after the adoption of the last opinion of the SSC on this issue. Consequently
there is no reason for modifying the existing opinions.
b) Regarding the possibility of OP poisoning, the European legislation for registration of
plant protection products and veterinary medicines – addressed in the enquiries – provide
the basis for safe use of registered compounds and their formulations. Regarding the
alleged intoxication cases reported and OP exposure it must be concluded that safety
measures may not have been strictly followed.
References
Brown, D.R., Qin, K., Herms, J.W., Madlung, A., Manson, J., Strome, R., Fraser, P.E., Kruck, T., von
Bohlen, A., Schulz- Schaeffer, W., Giese, A., Westaway, D. and Kretzschmar, H. (1997) The Cellular
Prion Protein Binds Copper In Vivo, Nature, 390, 684-7.
Purdey, M. (2000) Ecosystems Supporting Clusters of Sporadic TSEs Demonstrate Excesses of the Radical-
Generating Divalent Cation Manganese and Deficiencies of Antioxidant Co-Factors Cu, Se, Fe, Zn Medical
Hypotheses, 54, 278-306.
Scientific Steering Committee, 1998. Opinion on possible links between BSE and Organophosphates. Adopted
on 25-26 June 1998
Scientific Steering Committee, 2001. Opinion on Hypotheses on the origin and transmission of BSE. Adopted
on 29-30 November 2001.

http://europa.eu.int/comm/food/fs/sc/ssc/out356_en.pdf



Studies on the Putative Interactions between the Organophosphorus Insecticide Phosmet and Recombinant Mouse PrP and its Implication in the BSE Epidemic
I. Shaw1, C. Berry2, E. Lane1, P. Fitzmaurice1, D. Clarke3 and A. Holden1

(1) Centre for Toxicology, University of Central Lancashire, Preston, UK
(2) Department of Morbid Anatomy, The Royal London Hospital, London, UK
(3) CLRC Daresbury Laboratory, Warrington, UK


Abstract It has been suggested that exposure of cattle to the ectoparasiticide Phosmet in the 1980s caused a conformational change in the cellular prion protein (PrPC) to form the BSE prion (PrPSC), which initiated the epidemic of bovine spongiform encephalopathy (BSE).
Recombinant mouse cellular prion (r[mouse]PrPC) was exposed to the organophosphorus pesticide Phosmet in vitro and the conformation of the prion before and after exposure was monitored using circular dichroism (CD) spectroscopy, utilizing synchrotron radiation at the Council for the Central Laboratory of the Research Councils (CLRC) facilities at Daresbury, UK. Metabolites of Phosmet, generated in situ by rat microsomes, were investigated in the same way, to determine whether they might initiate the conformational change due to their high chemical reactivity.
Our studies showed that exposure of r[mouse]PrPC to Phosmet or microsomes-generated metabolites of Phosmet did not result in the conformational change in the protein from -helix to -pleated sheet that is characteristic of the PrPC to PrPSC conversion and, therefore, Phosmet is very unlikely to have initiated the BSE epidemic by a simple direct mechanism of conformational change in the prion protein.
bovine spongiform encephalopathy - circular dichroism spectroscopy - insecticide - organophosphate - Phosmet - prion - protein conformation



http://www.springerlink.com/(bmbpjj55ksv02p2wiismj555)/app/home/contribution.asp?referrer=parent&backto=issue,3,9;journal,31,74;linkingpublicationresults,1:103009,1



transmission studies do not lie, amplification and transmission!


i see NO properties of high levels of Manganese in the diet, combined with low levels of copper, in any of these primate
transmission studies.

1: J Infect Dis 1980 Aug;142(2):205-8


Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to
nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of
sheep and goats were transmitted to squirrel monkeys (Saimiri
sciureus) that were exposed to the infectious agents only by their
nonforced consumption of known infectious tissues. The asymptomatic
incubation period in the one monkey exposed to the virus of kuru was
36 months; that in the two monkeys exposed to the virus of
Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and
that in the two monkeys exposed to the virus of scrapie was 25 and
32 months, respectively. Careful physical examination of the buccal
cavities of all of the monkeys failed to reveal signs or oral
lesions. One additional monkey similarly exposed to kuru has
remained asymptomatic during the 39 months that it has been under
observation.

PMID: 6997404

http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract


Oral Transmission And Early Lymphoid Tropism Of Chronic Wasting Disease
Prpres In Mule Deer Fawns

Publication: Journal Of General Virology
Publication Request Approval Date: June 25, 1999

Interpretive Summary: Chronic wasting disease is a transmissible
spongiform encephalopathy or prion disease of deer and elk. CWD is a
member of the family of diseases that includes sheep scrapie and bovine
spongiform encephalopathy (BSE). The natural route of transmission of
these diseases in ruminant animals is unknown but oral exposure to
contaminated feeds, bedding, or tissues is presumed to be a major source
of infection. In this study, mule deer fawns were orally fed an
infectious homogenate and sacrificed at intervals to examine the
lymphoid tissue of the alimentary tract for signs of infection. Prion
protein was detected as early as 42 days and was evident in all fawns
after 53 days. This paper provides an improved procedure for detecting
prions in early infection, establishes a protocol for accelerated study
of transmission routes, and supports the hypothesis that oral exposure
may reflect the initial pathway of CWD infection in deer.

Technical Abstract: Mule deer fawns were inoculated orally with a brain
homogenate prepared from mule deer with naturally occurring chronic
wasting disease (CWD), a prion induced transmissible spongiform
encephalopathy. Fawns were necropsies and examined for PrP-res, a
protein marker for infection, at 10, 42, 53, 77, 78 and 80 days post
inoculation using an immunohistochemistry assay modified to enhance
sensitivity. PrP-res was detected in alimentary-tract- associated
lymphoid tissues as early as 42 days post inoculation and in all fawns
after 53 days. These results indicated that CWD PrP-res can be detected
at least 16 months before clinical signs would be expected to appear and
may reflect the initial pathway of CWD infection in deer.

http://nps.ars.usda.gov/publication...gnum=0000103091

Establishing the transmission of BSE to mink

44. Transmissible mink encephalopathy ("TME") is a rare disease of ranch
reared mink, first recognised in the USA. It had been assumed to be
scrapie in mink and, like BSE, outbreaks have epidemiological
features consistent with a foodborne infection, but it has never been
possible to demonstrate that scrapie infected sheep brain tissue is
pathogenic to mink by oral exposure. In an incident of TME in
Stetsonville, Wisconsin, USA in 1985 Dr Richard Marsh observed that
although the rancher fed 'dead stock', mainly in the form of cattle
carcasses, sheep tissues had never been fed. Studies in the USA of
this incident showed not only that cattle inoculated intracerebrally
with the mink brain developed a fatal spongiform encephalopathy, but
also that the cattle passaged agent remained pathogenic for
mink by either intracerebral inoculation or feeding. In the absence of
reports of a clinical disease homologous to BSE in domestic cattle,
these findings prompted the suggestion that a rare or occult
form of such a disease might exist in the USA. Comparison of the
biological properties of the BSE
12
pathogen with those of the Stetsonville isolate was therefore of
considerable interest in relation to hypotheses concerning possible
origins of BSE and potential for subclinical infection in cattle.
45. Proposals to carry out studies with mink in the USA were developed
in collaboration with, the United States Department of Agriculture
("USDA") Agricultural Research Service ("ARS") and the
Department of Veterinary Science, University of Wisconsin, Madison,
Wisconsin, USA. On 30th October, 1990 I attended a CVL/NPU BSE R&D
meeting at the NPU in Edinburgh (YB90/10.30/1.1). I reported that brain
material from BSE affected cows and a control cow (not fed meat and
bonemeal) had been sent coded to Mr Mark Robinson (USDA) for
transmission studies in mink. The studies were conducted from February
1991 under the control and principal funding of USDA-ARS. The results,
discussed at the tenth CVL/NPU BSE R&D meeting on 27th April, 1993
(YB93/4.27/1.1) indicated that mink were indeed susceptible to BSE and,
in contrast to previous attempts to transmit scrapie to the species,
were susceptible by the oral route of inoculation. The collaboration
resulted in the publication of a paper: Robinson, M.M. et al (1994)
Experimental infection of mink with bovine spongiform encephalopathy.
Journal of General Virology 75, 2151-2155 (J/JVIR /75/2151).

snip...


http://www.bseinquiry.gov.uk/files/ws/s065a.pdf

BSE TO MINK CONFIRMED

http://www.bseinquiry.gov.uk/files/yb/1 ... 001001.pdf


1: Proc Natl Acad Sci U S A 2001 Mar 27;98(7):4142-7

Adaptation of the bovine spongiform encephalopathy agent to primates and
comparison with Creutzfeldt-- Jakob disease: implications for human health.

Lasmezas CI, Fournier JG, Nouvel V, Boe H, Marce D, Lamoury F, Kopp N,
Hauw JJ, Ironside J, Bruce M, Dormont D, Deslys JP.

Commissariat a l'Energie Atomique, Service de Neurovirologie, Direction
des Sciences du Vivant/Departement de Recherche Medicale, Centre de
Recherches du Service de Sante des Armees 60-68, Fontenay-aux-Roses,
France. [email protected]

There is substantial scientific evidence to support the notion that
bovine spongiform encephalopathy (BSE) has contaminated human beings,
causing variant Creutzfeldt-Jakob disease (vCJD). This disease has
raised concerns about the possibility of an iatrogenic secondary
transmission to humans, because the biological properties of the
primate-adapted BSE agent are unknown. We show that (i) BSE can be
transmitted from primate to primate by intravenous route in 25 months,
and (ii) an iatrogenic transmission of vCJD to humans could be readily
recognized pathologically, whether it occurs by the central or
peripheral route. Strain typing in mice demonstrates that the BSE agent
adapts to macaques in the same way as it does to humans and confirms
that the BSE agent is responsible for vCJD not only in the United
Kingdom but also in France. The agent responsible for French iatrogenic
growth hormone-linked CJD taken as a control is very different from vCJD
but is similar to that found in one case of sporadic CJD and one sheep
scrapie isolate. These data will be key in identifying the origin of
human cases of prion disease, including accidental vCJD transmission,
and could provide bases for vCJD risk assessment.


http://www.ncbi.nlm.nih.gov/entrez/...1&dopt=Abstract

this next one frightens me the most, you might want to read
it twice, and really think about it...TSS

1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8

Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes
contaminated during neurosurgery.

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.

Laboratory of Central Nervous System Studies, National Institute of
Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, MD 20892.

Stereotactic multicontact electrodes used to probe the cerebral cortex
of a middle aged woman with progressive dementia were previously
implicated in the accidental transmission of Creutzfeldt-Jakob disease
(CJD) to two younger patients. The diagnoses of CJD have been confirmed
for all three cases. More than two years after their last use in humans,
after three cleanings and repeated sterilisation in ethanol and
formaldehyde vapour, the electrodes were implanted in the cortex of a
chimpanzee. Eighteen months later the animal became ill with CJD. This
finding serves to re-emphasise the potential danger posed by reuse of
instruments contaminated with the agents of spongiform encephalopathies,
even after scrupulous attempts to clean them.

http://www.ncbi.nlm.nih.gov/entrez/...4&dopt=Abstract

Proc Natl Acad Sci U S A 1999 Mar 30;96(7):4046-51

Natural and experimental oral infection of nonhuman primates by bovine
spongiform encephalopathy agents.

Bons N, Mestre-Frances N, Belli P, Cathala F, Gajdusek DC, Brown P.

Ecole Pratique des Hautes Etudes, Laboratoire de Neuromorphologie
Fonctionnelle, Universite Montpellier II, 34095-Montpellier cedex 5, France.

Experimental lemurs either were infected orally with the agent of bovine
spongiform encephalopathy (BSE) or were maintained as uninfected control
animals. Immunohistochemical examination for proteinase-resistant
protein (prion protein or PrP) was performed on tissues from two
infected but still asymptomatic lemurs, killed 5 months after infection,
and from three uninfected control lemurs. Control tissues showed no
staining, whereas PrP was detected in the infected animals in tonsil,
gastrointestinal tract and associated lymphatic tissues, and spleen. In
addition, PrP was detected in ventral and dorsal roots of the cervical
spinal cord, and within the spinal cord PrP could be traced in nerve
tracts as far as the cerebral cortex. Similar patterns of PrP
immunoreactivity were seen in two symptomatic and 18 apparently healthy
lemurs in three different French primate centers, all of which had been
fed diets supplemented with a beef protein product manufactured by a
British company that has since ceased to include beef in its veterinary
nutritional products. This study of BSE-infected lemurs early in their
incubation period extends previous pathogenesis studies of the
distribution of infectivity and PrP in natural and experimental scrapie.
The similarity of neuropathology and PrP immunostaining patterns in
experimentally infected animals to those observed in both symptomatic
and asymptomatic animals in primate centers suggests that BSE
contamination of zoo animals may have been more widespread than is
generally appreciated.

http://www.ncbi.nlm.nih.gov/entrez/...0&dopt=Abstract

1: Vet Rec 1993 Apr 17;132(16):403-6

Experimental transmission of BSE and scrapie to the common marmoset.

Baker HF, Ridley RM, Wells GA.

Division of Psychiatry, Clinical Research Centre, Harrow, Middlesex.

Two young male common marmosets (Callithrix jacchus) were injected
intracerebrally and intraperitoneally with a crude brain homogenate
prepared from a cow with bovine spongiform encephalopathy (BSE). Two
other marmosets were similarly injected with brain homogenate from a
sheep with natural scrapie. The two animals injected with scrapie
material developed neurological signs 38 and 42 months after injection
and the two animals injected with BSE material developed neurological
signs after 46 and 47 months. Post mortem examination of the brains
revealed spongiform encephalopathy especially in the basal nuclei and
diencephalon of all the animals and, in addition, involvement of the
cerebral cortex of the marmosets injected with scrapie material. The
experiment extends the host range of experimental BSE to include a
primate species.

http://www.ncbi.nlm.nih.gov/entrez/...8&dopt=Abstract


1: J Gen Virol 1991 Mar;72 ( Pt 3):589-94

Epidemiological and experimental studies on a new incident of
transmissible mink encephalopathy.

Marsh RF, Bessen RA, Lehmann S, Hartsough GR.

Department of Veterinary Science, University of Wisconsin-Madison 53706.

Epidemiological investigation of a new incident of transmissible mink
encephalopathy (TME) in Stetsonville, Wisconsin, U.S.A. in 1985 revealed
that the mink rancher had never fed sheep products to his mink but did
feed them large amounts of products from fallen or sick dairy cattle. To
investigate the possibility that this occurrence of TME may have
resulted from exposure to infected cattle, two Holstein bull calves were
injected intracerebrally with mink brain from the Stetsonville ranch.
Each bull developed a fatal spongiform encephalopathy 18 and 19 months
after inoculation, respectively, and both bovine brains passaged back
into mink were highly pathogenic by either intracerebral or oral
inoculation. These results suggest the presence of a previously
unrecognized scrapie-like infection in cattle in the United States.

http://www.ncbi.nlm.nih.gov/entrez/...3&dopt=Abstract

1: Ital J Neurol Sci 1983 Apr;4(1):61-4

Creutzfeld-Jakob disease in the province of Siena: two cases transmitted
to monkeys.

Fieschi C, Orzi F, Pocchiari M, Nardini M, Rocchi F, Asher D, Gibbs C,
Gajdusek D.

Two cases of histopathologically documented Creutzfeldt-Jakob disease
were observed in the same area of the province of Siena in 1974-1975.
The transmission of the disease was obtained through brain homogenates
and lymphnodes in one of the two cases. This confirms that the agent is
present in other tissues besides the brain and underlines further the
analogies between Creutzfeld-Jakob disease and scrapie.

http://www.ncbi.nlm.nih.gov/entrez/...0&dopt=Abstract


1: Dev Biol Stand 1993;80:9-13

Transmission of human spongiform encephalopathies to experimental
animals: comparison of the chimpanzee and squirrel monkey.

Asher DM, Gibbs CJ Jr, Sulima MP, Bacote A, Amyx H, Gajdusek DC.

Laboratory of Central Nervous System Studies, National Institute of
Neurological Disorders and Stroke, NIH, Bethesda, MD 20992.

The agents of kuru and Creutzfeldt-Jakob disease have been consistently
transmitted from patients with those diseases to chimpanzees and
squirrel monkeys, as well as to other new-world primates, with average
incubation periods of two or three years. No other animals have been
found so consistently susceptible to the agents in human tissues. More
rapid and convenient assays for the infectious agents would greatly
facilitate research on the spongiform encephalopathies of humans.

http://www.ncbi.nlm.nih.gov/entrez/...9&dopt=Abstract


1: J Vet Diagn Invest 2001 Jan;13(1):91-6

Preliminary findings on the experimental transmission of chronic wasting
disease agent of mule deer to cattle.

Hamir AN, Cutlip RC, Miller JM, Williams ES, Stack MJ, Miller MW,
O'Rourke KI, Chaplin MJ.

National Animal Disease Center, ARS, USDA, Ames, IA 50010, USA.

To determine the transmissibility of chronic wasting disease (CWD) to
cattle and to provide information about clinical course, lesions, and
suitability of currently used diagnostic procedures for detection of CWD
in cattle, 13 calves were inoculated intracerebrally with brain
suspension from mule deer naturally affected with CWD. Between 24 and 27
months postinoculation, 3 animals became recumbent and were euthanized.
Gross necropsies revealed emaciation in 2 animals and a large pulmonary
abscess in the third. Brains were examined for protease-resistant prion
protein (PrP(res)) by immunohistochemistry and Western blotting and for
scrapie-associated fibrils (SAFs) by negative-stain electron microscopy.
Microscopic lesions in the brain were subtle in 2 animals and absent in
the third case. However, all 3 animals were positive for PrP(res) by
immunohistochemistry and Western blot, and SAFs were detected in 2 of
the animals. An uninoculated control animal euthanized during the same
period did not have PrP(res) in its brain. These are preliminary
observations from a currently in-progress experiment. Three years after
the CWD challenge, the 10 remaining inoculated cattle are alive and
apparently healthy. These preliminary findings demonstrate that
diagnostic techniques currently used for bovine spongiform
encephalopathy (BSE) surveillance would also detect CWD in cattle should
it occur naturally.

http://www.ncbi.nlm.nih.gov/entrez/...4&dopt=Abstract

P.S. the study above confirmed 5 cows and 1 goat transmission of CWD to cattle,
of the final stages of the study. ...tss

Published online before print March 20, 2001, 10.1073/pnas.041490898
Neurobiology
Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt- Jakob disease: Implications for human health
Corinne Ida Lasmézas*,dagger, Jean-Guy Fournier*, Virginie Nouvel*, Hermann Boe*, Domíníque Marcé*, François Lamoury*, Nicolas KoppDagger , Jean-Jacques Hauw§, James Ironside¶, Moira Bruce||, Dominique Dormont*, and Jean-Philippe Deslys*

snip...


Discussion

One aim of this study was to determine the risk of secondary transmission to humans of vCJD, which is caused not by a primarily human strain of TSE agent but by the BSE strain having passed the species barrier to humans. This risk is tightly linked to the capacity of the BSE agent to adapt to primates and harbor enhanced virulence (i.e., induce disease after a short incubation period and provoke disease even if highly diluted) and to its pathogenicity after inoculation by the peripheral route. With respect to the latter, there are huge variations between different TSE agent strains and hosts. For example, the BSE agent is pathogenic to pigs after i.c. inoculation but not after oral administration (23). Thus, we wanted to know to what extent the BSE/vCJD agent is pathogenic to humans by the i.c. and i.v. routes. To achieve this, we used the macaque model. To monitor the evolution of the BSE agent in primates, but also to verify the identity of French vCJD, we conducted parallel transmission to C57BL/6 mice, allowing strain-typing. The experimental scheme is depicted in Fig. 1.

Characterization of the BSE Agent in Primates. The identity of the lesion profiles obtained from the brains of the French patient with vCJD, two British patients with vCJD, and nonhuman primates infected with BSE provides experimental demonstration of the fact that the BSE agent strain has been transmitted to humans both in the U.K. and in France. Further, it lends support to the validity of the macaque model as a powerful tool for the study of vCJD. As far as the evolution of the BSE agent in primates is concerned, we observed an interesting phenomenon: at first passage of BSE in macaques and with vCJD, there was a polymorphism of the lesion profile in mice in the hippocampal region, with about half of them harboring much more severe vacuolation than the mice inoculated with cattle BSE. At second passage, the polymorphism tended to disappear, with all mice showing higher vacuolation scores in the hippocampus than cattle BSE mice. This observation suggests the appearance of a variant of the BSE agent at first passage in primates and its clonal selection during second passage in primates. The lesion profiles showed that it was still the BSE agent, but the progressive appearance of a "hippocampal signature" hallmarked the evolution toward a variant by essence more virulent to primates.

Characterization of the CJD and Scrapie Strains. Controls were set up by transmitting one French and one U.S. scrapie isolate from ruminants as well as French sCJD and iCJD cases from humans. None of these revealed a lesion profile or transmission characteristics similar or close to those of BSE or vCJD, respectively, thus extending to the present French scrapie isolate the previous observation that the BSE agent was different from all known natural scrapie strains (4, 24).
The lesion profiles of sCJD and iCJD differed only slightly in severity of the lesions, but not in shape of the profile, revealing the identity of the causative agents. One of us reported the absence of similarity between sCJD (six cases) and U.K. scrapie (eight cases) in transmission characteristics in mice (4). Herein, we made the striking observation that the French natural scrapie strain (but not the U.S. scrapie strain) has the same lesion profile and transmission times in C57BL/6 mice as do the two human TSE strains studied. This strain "affiliation" was confirmed biochemically. There is no epidemiological evidence for a link between sheep scrapie and the occurrence of CJD in humans (25). However, such a link, if it is not a general rule, would be extremely difficult to establish because of the very low incidence of CJD as well as the existence of different isolates in humans and multiple strains in scrapie. Moreover, scrapie is transmissible to nonhuman primates (26). Thus, there is still a possibility that in some instances TSE strains infecting humans do share a common origin with scrapie, as pointed out by our findings.

Transmission of vCJD and BSE to Nonhuman Primates. vCJD transmitted readily to the cynomolgus macaque after 2 years of incubation, which was comparable to the transmission obtained from first-passaged macaque BSE and much shorter than the interspecies transmission of BSE. Starting with 100 mg of BSE-macaque brain material, dilutions up to 4 µg still provoked disease. These data suggest that the BSE agent rapidly adapts to primates accompanied by enhanced virulence.
Examination of macaque brain inoculated with vCJD revealed a similar pathology to that with second-passage BSE. The distribution of vacuolation and gliosis, as well as the pattern of PrP deposition, including the dense, sometimes florid plaques, were similar to the human vCJD and the BSE hallmarks of the first passage (1, 2). These data show that the phenotype of BSE in primates is conserved over two passages. Moreover, they confirm that the BSE agent behaves similarly in humans and macaques, a precious finding that will prove useful in the near future for the design of pathogenesis or therapeutic studies. Because of the number of macaques examined in this study, we can now reliably state that the pathology, in particular the PrP deposition pattern provoked by BSE, is similar in older and very young animals. However, plaque deposition is greater, and mature florid plaques were more numerous, in the young, which may be correlated with a longer duration of the clinical phase observed in this animal (2). This is important with regard to the fact that vCJD has been diagnosed mainly in teenagers and young adults, which raises the concern that older patients may have been misdiagnosed because of an alternative phenotype of the disease. One should bear in mind, however, that cynomolgus macaques are all homozygotes for methionine at codon 129 of the PrP gene. Thus, our observations may not be relevant to humans carrying one or both valine alleles; however, all patients with vCJD reported to date have been M/M at this position (27).

Intravenous Transmissions to Nonhuman Primates. Brain pathology was identical in macaques inoculated i.c. and i.v. The i.v. route proved to be very efficient for the transmission of BSE, as shown by the 2-year survival of the animals, which is only 5 months longer than that obtained after inoculating the same amount of agent i.c. As the i.v. injection of the infectious agent implies per se a delayed neuroinvasion compared with a direct inoculation in the brain, this slight lengthening of the incubation period cannot, at this stage, be interpreted as a lower efficiency of infection as regards the i.c. route.
These data should be taken into account in the risk assessment of iatrogenic vCJD transmission by i.v. administration of biological products of human origin. They also constitute an incentive for a complete i.v. titration.
Conclusions

From BSE and vCJD transmissions in nonhuman primates, a number of conclusions can be drawn that are of major importance for human health: (i) human-adapted BSE appears to be a variant of the BSE agent that is more virulent for humans than cattle BSE and is efficiently transmitted by the peripheral route; (ii) the detection of vCJD in unusually young patients is probably not because of a lack of diagnosis of cases in older patients, thus raising the question of the source of human contamination with BSE early in life; and (iii) iatrogenic transmissions from patients with vCJD would be readily recognized by using the same diagnostic criteria as those applied to vCJD [clinical and pathological criteria (27) comprising neuronal loss and gliosis in the thalamus correlated with high MRI signal (28, 29)], whether such contaminations had occurred by the central or i.v. route. Primary and iatrogenic cases of vCJD could be distinguished on the basis of the patient's clinical history.

The risk assessment of biological products of human origin, notably those derived from blood, has been deeply modified by the appearance of vCJD. We confirm that the BSE agent has contaminated humans not only in the U.K. and the Republic of Ireland but also in France, and we show that its pathogenic properties for primates are being enhanced by a primary passage in humans. Considering the flow of potentially contaminated bovine-derived products between 1980 and 1996, it is obvious that further vCJD cases may occur outside the U.K. Thus, and in the light of the present study, it is necessary to sustain worldwide CJD surveillance regardless of national BSE incidence and to take all precautionary measures to avoid iatrogenic transmissions from vCJD.

snip...

http://www.pnas.org/cgi/content/full/041490898v1



MRC-43-00 [ ] [Text only version of this site] [Print this page]
Issued: Monday, 28 August 2000
NEW EVIDENCE OF SUB-CLINICAL PRION INFECTION: IMPORTANT RESEARCH FINDINGS RELEVANT TO CJD AND BSE

A team of researchers led by Professor John Collinge at the Medical Research Council Prion Unit1 report today in the Proceedings of the National Academy of Sciences, on new evidence for the existence of a ?sub-clinical? form of BSE in mice which was unknown until now.

The scientists took a closer look at what is known as the ?species barrier? - the main protective factor which limits the ability of prions2 to jump from one species to infect another. They found the mice had a ?sub-clinical? form of disease where they carried high levels of infectivity but did not develop the clinical disease during their normal lifespan. The idea that individuals can carry a disease and show no clinical symptoms is not new. It is commonly seen in conventional infectious diseases.

Researchers tried to infect laboratory mice with hamster prions3 called Sc237 and found that the mice showed no apparent signs of disease. However, on closer inspection they found that the mice had high levels of mouse prions in their brains. This was surprising because it has always been assumed that hamster prions could not cause the disease in mice, even when injected directly into the brain.

In addition the researchers showed that this new sub-clinical infection could be easily passed on when injected into healthy mice and hamsters.

The height of the species barrier varies widely between different combinations of animals and also varies with the type or strain of prions. While some barriers are quite small (for instance BSE easily infects mice), other combinations of strain and species show a seemingly impenetrable barrier. Traditionally, the particular barrier studied here was assumed to be robust.

Professor John Collinge said: "These results have a number of important implications. They suggest that we should re-think how we measure species barriers in the laboratory, and that we should not assume that just because one species appears resistant to a strain of prions they have been exposed to, that they do not silently carry the infection. This research raises the possibility, which has been mentioned before, that apparently healthy cattle could harbour, but never show signs of, BSE.

"This is a timely and unexpected result, increasing what we know about prion disease. These new findings have important implications for those researching prion disease, those responsible for preventing infected material getting into the food chain and for those considering how best to safeguard health and reduce the risk that theoretically, prion disease could be contracted through medical and surgical procedures."

ISSUED FRIDAY 25 AUGUST UNDER EMBARGO. PLEASE NOTE THAT THE EMBARGO IS SET BY THE JOURNAL.

FOR FURTHER INFORMATION CONTACT THE MRC PRESS OFFICE ON 020 7637 6011 (OFFICE HOURS) OR 07818 428297 OR 0385 774357 (OUT-OF-OFFICE-HOURS) OR PROFESSOR JOHN COLLINGE ON 020 7594 3760. PLEASE NOTE THAT OWING TO TRAVEL COMMITMENTS PROFESSOR COLLINGE WILL ONLY BE AVAILABLE UNTIL 16.30 ON FRIDAY 25 AUGUST AND CONTACTABLE AGAIN ON MONDAY 28 AUGUST VIA THE MRC PRESS OFFICE. DR ANDREW HILL (A CO-AUTHOR ON THE PAPER) FROM THE DEPARTMENT OF PATHOLOGY AT THE UNIVERSITY OF MELBOURNE WILL BE AVAILABLE ON 00 61 3 8344 3995 (DURING OFFICE HOURS) OR 00 61 3 9443 0009 (OUT-OF-OFFICE HOURS). PLEASE NOTE THAT AUSTRALIA IS TEN HOURS AHEAD OF UK TIME.

NOTES FOR EDITORS

Professor Collinge is a consultant neurologist and Director of the newly formed MRC Prion Unit based at The Imperial College School of Medicine at St Mary?s Hospital. He is also a member of the UK Government?s Spongiform Encephalopathy Advisory Committee (SEAC). The MRC prion unit is was set up in 1999, and its work includes molecular genetic studies of human prion disease and transgenic modelling of human prion diseases.

Prions are unique infectious agents that cause fatal brain diseases such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie and BSE (mad cow disease) in animals. In some circumstances prions from one species of animals can infect another and it is clear that BSE has done this to cause the disease variant CJD in the UK and France. It remains unclear how large an epidemic of variant CJD will occur over the years ahead.

The strain of prion used here to infect the mice is the Sc237 strain (also known as 263K) which infects hamsters, and until now was assumed not to infect mice.

This research was funded by the Medical Research Council and Wellcome Trust.

The Medical Research Council (MRC) is a national organisation funded by the UK tax-payer. Its business is medical research aimed at improving human health; everyone stands to benefit from the outputs. The research it supports and the scientists it trains meet the needs of the health services, the pharmaceutical and other health-related industries and the academic world. MRC has funded work which has led to some of the most significant discoveries and achievements in medicine in the UK. About half of the MRC?s expenditure of £345 million is invested in over 50 of its Institutes and Units, where it employs its own research staff. The remaining half goes in the form of grant support and training awards to individuals and teams in universities and medical schools.

The Wellcome Trust is the world's largest medical research charity with a spend of some £600 million in the current financial year 1999/2000. The Wellcome Trust supports more than 5,000 researchers, at 400 locations, in 42 different countries to promote and foster research with the aim of improving human and animal health. As well as funding major initiatives in the public understanding of science, the Wellcome Trust is the country's leading supporter of research into the history of medicine.

©2002 Medical Research Council

http://www.mrc.ac.uk/index/public_inter ... -43-00.htm


and for Gods sake, if someone is smearing this cr@p all over there kids
heads for lice and did not come up with a TSE, i would say this is good case study;


1) None of our animals that contracted BSE were treated with OP's, even
in utero.
2) My kids were treated with OP's as infants to control head lice. This
seems to be endemic as infection waves in UK primary schools (and
possibly elsewhere).
3) One might argue if the continued use of british beef in the UK was
ethical, none the less it happened. We have a duty to learn from it, not
least a duty to learn on behalf of those people who died so horribly....


NOPE, greed and money is the name of the game, they have known for decades;


STRICTLY PRIVATE AND CONFIDENTIAL 25, AUGUST 1995

snip...

To minimise the risk of farmers' claims for compensation from feed
compounders.

To minimise the potential damage to compound feed markets through adverse publicity.

To maximise freedom of action for feed compounders, notably by
maintaining the availability of meat and bone meal as a raw
material in animal feeds, and ensuring time is available to make any
changes which may be required.

snip...

THE FUTURE

4..........

MAFF remains under pressure in Brussels and is not skilled at
handling potentially explosive issues.

5. Tests _may_ show that ruminant feeds have been sold which
contain illegal traces of ruminant protein. More likely, a few positive
test results will turn up but proof that a particular feed mill knowingly
supplied it to a particular farm will be difficult if not impossible.

6. The threat remains real and it will be some years before feed
compounders are free of it. The longer we can avoid any direct
linkage between feed milling _practices_ and actual BSE cases,
the more likely it is that serious damage can be avoided. ...

SEE full text ;

http://www.bseinquiry.gov.uk/files/yb/1 ... 002001.pdf



BUT, i applaud ranchers that understand the TSE science and not the hype that surrounds it such as 'reader the second' ;


>>>Look, Mark Purdey, I applaud you for your perserverance, your bravery in taking on the establishment, and your creativity. It may well be that you were instrumental in bringing the familial and other genetic clusters in Slovenia to the attention of science.

I acknowledge that you suffered but your suffering sir is NOTHING compared to the suffering of the families afflicted with CJD and variant CJD and to the extent that your writings are used to ignore public health threats and to avoid taking public health measures that may well protect humans from CJD, then your writings are being ill used. You should acknowledge that and if you do not, I will pay no further attention to you.

Your supporters use your writings to (1) deny that CJD is transmissable from person to person, e.g., via contaminated surgical instruments or tissue or blood donations; (2) reject totally the strong hypothesis that variant CJD is due to the BSE epidemic in the UK being "pushed" over the species barrier. They claim that all cases of human CJD are due to metal contamination. It is they who are perverting your theories and therefore subjecting you to ridicule. Unless you deny these things as well and in which case, you should be ignored since in the case of (1) you deny fact and in the case of (2) you reject a hypothesis that must be accepted for the time being and must lead our public health measures given its strength.

NO ONE has denied that the ultimate cause of TSEs is unknown. However TSEs ARE transmissable between species, albeit not easily, and they are certainly transmissable among the same species. The suffering of the individual and his/her family who contracts CJD or variant CJD is hideous beyond description. If TSEs are your life work, you had better be taking that into consideration.<<<


>>>This is a danger to ranchers and to all humans<<<


INDEED there is;


CJD FARMERS WIFE 1989

http://www.bseinquiry.gov.uk/files/yb/1 ... 007001.pdf

http://www.bseinquiry.gov.uk/files/yb/1 ... 003001.pdf


20 year old died from sCJD in USA in 1980 and a 16 year
old in 1981. A 19 year old died from sCJD in
France in 1985. There is no evidence of an iatrogenic
cause for those cases....

http://www.bseinquiry.gov.uk/files/yb/1 ... 004001.pdf

cover-up of 4th farm worker ???

http://www.bseinquiry.gov.uk/files/yb/1 ... 006001.pdf

http://www.bseinquiry.gov.uk/files/yb/1 ... 006001.pdf

CONFIRMATION OF CJD IN FOURTH FARMER

http://www.bseinquiry.gov.uk/files/yb/1 ... 008001.pdf

now story changes from;

SEAC concluded that, if the fourth case were confirmed, it would be
worrying, especially as all four farmers with CJD would have had BSE
cases on their farms.

to;

This is not unexpected...

was another farmer expected?

http://www.bseinquiry.gov.uk/files/yb/1 ... 010001.pdf

4th farmer, and 1st teenager

http://www.bseinquiry.gov.uk/files/yb/1 ... 003001.pdf

2. snip...
Over a 5 year period, which is the time period on which the advice
from Professor Smith and Dr. Gore was based, and assuming a
population of 120,000 dairy farm workers, and an annual incidence
of 1 per million cases of CJD in the general population, a
DAIRY FARM WORKER IS 5 TIMES MORE LIKELY THAN
an individual in the general population to develop CJD. Using the
actual current annual incidence of CJD in the UK of 0.7 per
million, this figure becomes 7.5 TIMES.

3. You will recall that the advice provided by Professor Smith in
1993 and by Dr. Gore this month used the sub-population of dairy
farm workers who had had a case of BSE on their farms -
63,000, which is approximately half the number of dairy farm
workers - as a denominator. If the above sums are repeated using
this denominator population, taking an annual incidence in the general
population of 1 per million the observed rate in this sub-population
is 10 TIMES, and taking an annual incidence of 0.7 per million,
IT IS 15 TIMES (THE ''WORST CASE'' SCENARIO) than
that in the general population...

http://www.bseinquiry.gov.uk/files/yb/1 ... 004001.pdf



1: J Infect Dis 1980 Aug;142(2):205-8



Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract



TSS

 

[flounder]

I'm no sheep man but it seems that some sheep have an RR Rr or rr genotypical status telling about their resitance to "scrapie"? Am i correct on this?

yes, but these animals are not as resistant as they would like them to be, especially in the atypical strains. ...TSS


Subject: REPORT OF THE COMMITTEE ON SCRAPIE ANNUAL REPORT 2006
Date: January 15, 2007 at 7:53 pm PST

REPORT OF THE COMMITTEE ON SCRAPIE


snip...


Infected and Source Flocks

As of September 30, 2006, there were 85 scrapie-infected and source flocks (48 infected and 37

source). There were a total of 116 new infected and source flocks reported for FY 2006. Figure 1

shows the number of new infected and source flocks by year. The total infected and source flock

statuses that were released in FY 2006 was 100. A total of 343 positive scrapie cases were confirmed

and reported by the National Veterinary Services Laboratories (NVSL). Of these, 70 were RSSS cases,

(collected in FY 2006 and confirmed in FY 2006 or FY 2007), and 222 positive field necropsy cases

(most of these cases were found during depopulations of scrapie exposed animals in infected/source

flocks), 14 necropsies of field cases retained long term for test evaluation, and 37 third eyelid regulatory

tests confirmed in FY 2006. Three of the field cases were goats. One goat case, in Colorado, could not

be linked to exposure in sheep as a result Colorado goats no longer meet the requirements to be

classified as low-risk goats or low-risk commercial goats for interstate movement.

Approximately 3,822 animals were indemnified comprised of 62% non-registered sheep, 30%

registered sheep, 5% non-registered goats and 3% registered goats. This represents a 26% decrease

over FY 2005 with a significant shift from registered to grade animals.

Regulatory Scrapie Slaughter Surveillance (RSSS)

RSSS was designed based on the findings of the Center for Epidemiology and Animal Health

(CEAH) Scrapie: Ovine Slaughter Surveillance (SOSS) study. The results of SOSS can be found at

http://www.aphis.usda.gov/vs/ceah/cahm/Sheep/sheep.htm.

RSSS started April 1, 2003. It is a targeted slaughter surveillance program which is designed to

identify infected flocks for clean-up. During FY 2006, collections increased by 9% overall and by 16%

for black and mottled faced sheep compared to FY 2005. Improvement in the overall program

effectiveness and efficiency is demonstrated by the 33% decrease in percent positive black faced sheep

compared to FY 2005 (0.67 to 0.45%, based on test results posted before November 6, 2006). During

FY 2006, 37,167 samples were collected. The distribution of these samples is shown in figure 2. There

have been 70 NVSL confirmed positive cases that were collected in FY 2006. Face colors of these

positives were 62 black and eight mottled. The percent positive by face color is shown in the figure 3

below.

Scrapie Testing

In FY 2006, 42,823 animals were sampled for scrapie testing: 37,167 RSSS; 3,649 regulatory

field cases, 1,934 regulatory third eyelid biopsies, and 73 necropsy validations.

Animal ID

As of October 02, 2006, 118,668 sheep and goat premises have been assigned identification

numbers in the Scrapie National Generic Database. Official eartags have been issued to 96,755 of these

premises.

Note: report based on data available as of November 6, 2006


snip...


Descriptive Analysis and Scrapie Infected/Source Flocks and Investigations in FY 2006.

Dianne Norden and Charles Gaiser

Regional Epidemiologists

Veterinary Services

Infected and Source Flocks

On average, Scrapie Infected/Source flocks identified in FY 2006 had an inventory of 98 animals

(1,044), 23 animals indemnified on average (1-279), 3.45 positive animals found per flock upon flock

cleanup plans. Of all these Infected/Source flocks for which data are available, 4,441 animals were

involved in trace forward investigations. The primary breed of these flocks was predominantly blackfaced

breeds, however there were 12 white-faced flocks identified (one Shetland, four Polypay Cross,

four Southdown, three Dorset) and one flock whose primary breed was Dorper. Most of these flocks

(89.7%) underwent a standard genetics based flock plan (flock genotyped and QQ animals removed).

Other flock plans included variations on the standard genetics based flock plan (e.g. some high risk

animals retained separately from the genetically less susceptible or resistant animals after lid testing

"negative", other flocks removed QRAV animals in addition to all QQs, and four flocks underwent a

whole flock depopulation. These flocks were primarily identified because of a positive found at

slaughter (43%). Other detection methods included trace forward of exposed animals (30%), trace back

to birth flock of positive animals (19%), investigation of clinical suspects (7%) and voluntary

surveillance (1%).

Investigations

Attempts were made to trace 4,889 high risk sheep out of these Infected and Source flocks.

While some of these investigations are still ongoing (9%), 16% were untraceable and 75% were

traceable to a flock. Almost 30 (27) clinically suspicious sheep were investigated in FY 06. Seven of

these animals were ultimately diagnosed with scrapie resulting in five newly discovered Infected or

Source flocks. Nearly 37,000 (36,891) samples were collected at slaughter. Of these, 55 positive

animals were detected, and 31 were successfully traced back to their flock of origin, resulting in 27

newly discovered Infected or Source Flocks. Over 20 (22) traces are still ongoing, and two of these

positives were untraceable.

Scrapie positive animals

Of the Scrapie positive animals that were found, 75% (116) were female, and most (90%) had

lambed or aborted in their flock of origin. Most (65%) were still in their flock of birth at the time of

diagnosis. Nearly all (99.2%) of all positive animals found were QQ, of those that were QQ, most

(89.2% were QQAA). One animal has initially tested QRAA; the genotype of this animal is being

confirmed. One QRAV positive was detected in FY 2006. Most positive animals were found as part of

an Infected or Source flock depopulation (45%). Other methods of detection included RSSS traceback

(28%), traceforward investigations (20%), investigation of clinical suspects (5%), and Voluntary

Surveillance (2%). The breeds of these positives was predominantly black-faced breeds (99), but there

were 63 White-faced breeds identified (40 Southdown, 11 Polypay Cross, two Dorsets, and 10 nonspecified

white-faced or white-faced crosses). The average age of scrapie-positive animals was 3.9

years, ranging from six months to 12 years of age.


http://www.usaha.org/committees/reports ... r-2006.pdf



18 January 2007 - Draft minutes of the SEAC 95 meeting (426 KB) held on 7
December 2006 are now available.



64. A member noted that at the recent Neuroprion meeting, a study was
presented showing that in transgenic mice BSE passaged in sheep may be more
virulent and infectious to a wider range of species than bovine derived BSE.
Other work presented suggested that BSE and bovine amyloidotic spongiform
encephalopathy (BASE) MAY BE RELATED. A mutation had been identified in the
prion protein gene in an AMERICAN BASE CASE THAT WAS SIMILAR IN NATURE TO A
MUTATION FOUND IN CASES OF SPORADIC CJD. A study also demonstrated that in a
mouse model it was possible to alleviate the pathological changes of prion
disease by suppressing expression of the prion protein gene after infection.


http://www.seac.gov.uk/minutes/95.pdf


A case of scrapie in a sheep carrying the lysine-171 allele of the prion protein gene

P. L. Acutis1, F. Martucci1, M. Mazza1, S. Peletto1, B. Iulini1, C. Corona1, E. Bozzetta1, C. Casalone1 and M. Caramelli1

(1) CEA – Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Torino, Italy

Received: 29 July 2005 Accepted: 27 February 2006 Published online: 30 March 2006

Summary. Susceptibility to scrapie in sheep depends on the host PrP genotype. No data about the linkage of the rare ARK allele to differential scrapie susceptibility are currently available. Several tissues isolated from sheep from an Italian scrapie outbreak and carrying the ARK allele were examined for the presence of the pathological prion protein. A weak positivity was detected only by Western blot in the brainstem of one ARK/ARH sheep. This result shows that the ARK allele does not confer full resistance against scrapie and that the allele needs to be studied further before it can be considered for breeding purposes.


http://www.springerlink.com/content/084l832600t50j67/

Subject: Sheep-Passaged Bovine Spongiform Encephalopathy Agent Exhibits
Altered Pathobiological Properties in Bovine-PrP Transgenic Mice
Date: December 28, 2006 at 8:41 am PST
Journal of Virology, January 2007, p. 835-843, Vol. 81, No. 2
0022-538X/07/$08.00+0 doi:10.1128/JVI.01356-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Sheep-Passaged Bovine Spongiform Encephalopathy Agent Exhibits Altered
Pathobiological Properties in Bovine-PrP Transgenic Mice
Juan Carlos Espinosa,1 Olivier Andréoletti,2 Joaquín Castilla,1 María
Eugenia Herva,1 Mónica Morales,1 Elia Alamillo,1 Fayna Díaz San-Segundo,1
Caroline Lacroux,2 Séverine Lugan,2 Francisco Javier Salguero,1 Jan
Langeveld,3 and Juan María Torres1*
Centro de Investigación en Sanidad Animal, INIA, 28130 Valdeolmos, Madrid,
Spain,1 UMR INRA-ENVT 1225, Interactions Hôte Agent Pathogène, Ecole
Nationale Vétérinaire de Toulouse, Toulouse, France,2 CIDC-Lelystad, 8203 AA
Lelystad, The Netherlands3

Received 27 June 2006/ Accepted 22 October 2006

Sheep can be experimentally infected with bovine spongiform encephalopathy
(BSE), and the ensuing disease is similar to scrapie in terms of
pathogenesis and clinical signs. BSE infection in sheep is an animal and
human health concern. In this study, the transmission in BoPrP-Tg110 mice of
prions from BSE-infected sheep was examined and compared to the transmission
of original cattle BSE in cattle and sheep scrapie prions. Our results
indicate no transmission barrier for sheep BSE prions to infect BoPrP-Tg110
mice, but the course of the disease is accelerated compared to the effects
of the original BSE isolate. The shortened incubation period of sheep BSE in
the model was conserved in subsequent passage in BoPrP-Tg110 mice,
indicating that it is not related to infectious titer differences.
Biochemical signature, lesion profile, and PrPSc deposition pattern of both
cattle and sheep BSE were similar. In contrast, all three sheep scrapie
isolates tested showed an evident transmission barrier and further
adaptation in subsequent passage. Taken together, those data indicate that
BSE agent can be altered by crossing a species barrier, raising concerns
about the virulence of this new prion towards other species, including
humans. The BoPrP-Tg110 mouse bioassay should be considered as a valuable
tool for discriminating scrapie and BSE in sheep.


----------------------------------------------------------------------------
----
* Corresponding author. Mailing address: Centro de Investigación en Sanidad
Animal, INIA, 28130 Valdeolmos, Madrid, Spain. Phone: 34 91 620 23 00. Fax:
34 91 620 22 47. E-mail: [email protected] .

Published ahead of print on 1 November 2006.


http://jvi.asm.org/

Published online before print October 20, 2005

Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0502296102
Medical Sciences

A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes

( sheep prion | transgenic mice )

Annick Le Dur *, Vincent Béringue *, Olivier Andréoletti , Fabienne Reine *, Thanh Lan Laï *, Thierry Baron , Bjørn Bratberg ¶, Jean-Luc Vilotte ||, Pierre Sarradin **, Sylvie L. Benestad ¶, and Hubert Laude *
*Virologie Immunologie Moléculaires and ||Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway


Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved September 12, 2005 (received for review March 21, 2005)

Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.


--------------------------------------------------------------------------------

Author contributions: H.L. designed research; A.L.D., V.B., O.A., F.R., T.L.L., J.-L.V., and H.L. performed research; T.B., B.B., P.S., and S.L.B. contributed new reagents/analytic tools; V.B., O.A., and H.L. analyzed data; and H.L. wrote the paper.

A.L.D. and V.B. contributed equally to this work.

To whom correspondence should be addressed.

Hubert Laude, E-mail: [email protected]

http://www.pnas.org/cgi/doi/10.1073/pnas.0502296102


http://www.pnas.org/cgi/content/abstract/0502296102v1

PrPSc accumulation in fetal cotyledons of scrapie-resistant lambs is influenced by fetus location in the uterus
Janet Alverson1,2, Katherine I. O'Rourke1,2 and Timothy V. Baszler2,3

1 USDA, ARS, Animal Disease Research Unit, 3003 ADBF, Washington State University, Pullman, WA 99164, USA
2 Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA
3 Washington Animal Disease Diagnostic Laboratory, Washington State University, Pullman, WA 99164, USA


Correspondence
Janet Alverson
[email protected]


ABSTRACT

Placentae from scrapie-infected ewes have been shown to accumulate PrPSc when the genotype of the fetus is of a susceptible genotype (VRQ/VRQ, ARQ/VRQ or ARQ/ARQ). Cotyledons from fetuses of genotypes ARR/ARR, ARQ/ARR and ARQ/VRR have previously been shown to be resistant to PrPSc accumulation. By using ewes from a naturally infected scrapie flock, cotyledons from fetuses of multiple births of different genotypes were examined. PrPSc was detected in fetal cotyledons of genotype ARQ/ARQ, but not in cotyledons from their dizygotic twin of genotype ARQ/ARR. This confirms earlier reports of single fetuses of these genotypes, but is the first description of such a finding in twin fetuses, one of each genotype. It is also demonstrated that cotyledons from sibling fetuses of genotypes ARQ/VRQ and ARQ/ARQ have different patterns of PrPSc accumulation depending on whether the dam is of genotype ARQ/ARQ or ARQ/VRQ. Lastly, it is shown that cotyledons from fetuses with resistant genotypes are weakly positive for PrPSc when they have shared the same pregnant uterine horn with a fetus of a susceptible genotype with cotyledons positive for the detection of PrPSc. Additionally, a PCR product for the Sry gene, a product specific to males, was found in cotyledons from female fetuses that had shared a uterine horn with a male fetus. This indicates that some sharing of fetal blood occurs between placentomes and fetuses residing in the same uterine horn, which can result in PrPSc accumulation in cotyledons with resistant genotypes.


http://vir.sgmjournals.org/cgi/content/full/87/4/1035


Subject: REPORT OF THE COMMITTEE ON SCRAPIE November 9, 2005 USAHA
Date: February 12, 2006 at 1:03 pm PST

REPORT OF THE COMMITTEE ON SCRAPIE

Chair: Dr. Jim Logan, Cheyenne, WY

Vice Chair: Dr. Joe D. Ross, Sonora, TX

Dr. Deborah L. Brennan, MS; Dr. Beth Carlson, ND; Dr. John R. Clifford, DC; Dr. Thomas F. Conner, OH; Dr. Walter E. Cook, WY; Dr. Wayne E. Cunningham, CO; Dr. Jerry W. Diemer, TX; Dr. Anita J. Edmondson, CA; Dr. Dee Ellis, TX; Dr. Lisa A. Ferguson, MD; Dr. Keith R. Forbes, NY; Dr. R. David Glauer, OH; Dr. James R. Grady, CO; Dr. William L. Hartmann, MN; Dr. Carolyn Inch, CAN; Dr. Susan J. Keller, ND; Dr. Allen M. Knowles, TN; Dr. Thomas F. Linfield, MT; Dr. Michael R. Marshall, UT; Dr. Cheryl A. Miller, In; Dr. Brian V. Noland, CO; Dr. Charles Palmer, CA; Dr. Kristine R. Petrini, MN; Mr. Stan Potratz, IA; Mr. Paul E. Rodgers, CO; Dr. Joan D. Rowe, CA; Dr. Pamela L. Smith, IA; Dr. Diane L. Sutton, MD; Dr. Lynn Anne Tesar, SD; Dr. Delwin D. Wilmot, NE; Dr. Nora E. Wineland, CO; Dr. Cindy B. Wolf, MN.

The Committee met on November 9, 2005, from 8:00am until 11:55am, Hershey Lodge and Convention Center, Hershey, Pennsylvania. The meeting was called to order by Dr. Jim Logan, chair, with vice chairman Dr. Joe D. Ross attending. There were 74 people in attendance.

The Scrapie Program Update was provided by Dr. Diane Sutton, National Scrapie Program Coordinator, United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS), Veterinary Services (VS). The complete text of the Status Report is included in these Proceedings.

Dr. Patricia Meinhardt, USDA-APHIS-VS-National Veterinary Services Laboratory (NVSL) gave the Update on Genotyping Labs and Discrepancies in Results. NVSL conducts investigations into discrepancies on genotype testing results associated with the Scrapie Eradication Program. It is the policy of the Program to conduct a second genotype test at a second laboratory on certain individual animals. Occasionally, there are discrepancies in those results. The NVSL conducts follow-up on these situations through additional testing on additional samples from the field and archive samples from the testing laboratories.

For the period of time from January 1, 2005, until October 15, 2005, there were 23 instances of discrepancies in results from 35 flocks. Of those 23 instances, 14 were caused by laboratory error (paperwork or sample mix-up), 3 results from field error, 5 were not completely resolved, and 1 originated from the use of a non-approved laboratory for the first test. As a result of inconsistencies, one laboratory's certification was revoked by APHIS-VS.

To reduce/eliminate these problems, the Program has placed additional quality requirements on the testing laboratories: additional review of final reports, additional coding systems for testing operations, strict follow-up and reports to NVSL on corrective actions, dual data entry systems, and more frequent inspections.

The Agricultural Research Services (ARS) Scrapie Research Update was given by Janet Alverson, USDA- ARS. Dr. Alverson reported on the effect of multiple births and fetal position within the uterus on PrP-Sc accumulation in fetal cotyledons. Fetal cotyledons of fetuses with

resistant genotypes can accumulate PrP-Sc when positioned next to a fetus of susceptible genotype with cotyledons positive for PrP-Sc accumulation.

Scrapie Surveillance Evaluation Working Group Update was presented by Tracey Lynn, Epidemiologist with the National Surveillance Unit, Center for Epidemiology and Animal Health (CEAH). The presentation provided a background on evaluation, a quick review of analyses completed to date by the scrapie surveillance evaluation working group, and some of the preliminary findings. The process of surveillance system evaluation is undertaken to assist a disease control program with identifying possible improvements to their surveillance system, and includes an assessment of the overall utility of the system, identification of potential gaps in coverage, and an evaluation of the overall performance of the system. The scrapie surveillance evaluation working group reviewed the structure and processes of the scrapie surveillance program, as well as various quality and effectiveness measures.

Overall, 98-99% of surveillance samples come from the Regulatory Scrapie Surveillance System (RSSS), so the RSSS system has been the primary focus of the evaluation process. The working group developed a flow chart indicating the flow of sheep through RSSS, which identified potential gaps in surveillance coverage, including custom kill plants and sheep being exported to Mexico. Spatial analyses can assist in identifying areas with high density sheep populations with lower levels of RSSS sampling. Identification compliance is being evaluated by reviewing reports from slaughter plants on the proportion of animals with appropriate identification. Additional analyses remain, including defining the most appropriate economic analyses, and comparing the surveillance system with developing surveillance standards. The working group hopes to have a draft written report for review by the end of the year.

Giving the Update on Scrapie Diagnostics and Susceptibility was Katherine O'Roarke, Research Microbiologist, USDA-ARS. "What's New in Scrapie" -- Biopsy sampling of the third eyelid or tonsillar lymphoid tissue is a useful live animal test for scrapie. The biopsy sample is examined for accumulation of the abnormal prion protein using immunohistochemistry. A joint project conducted by the Veterinary Laboratory Agencies and the Moredun Institute in the United Kingdom has developed an alternative technique in which tissue is collected from the narrow band of lymphoid tissue near the rectal-anal junction. The morphology of the lymphoid follicles is similar in the tonsil, retropharyngeal lymph nodes, third eyelid, and rectal-anal mucosal tissue. A report on more than 300 sheep in the United Kingdom (UK), prepared by Drs. Lorenzo Gonzalez and Jeffrey Martin, will describe the sensitivity, specificity, and optimal collection interval for this technique in a variety of breeds of British sheep. ARS has done a preliminary evaluation of the technique in US sheep. Samples of third eyelid and rectal-mucosal tissue were collected from 56 sheep. Forty-two (42) sheep had negative biopsies at both sites; most of these sheep have been necropsied and no PrP-d was found in retropharyngeal lymph node or tonsil, showing good agreement with the antemortem biopsies. Fourteen (14) sheep had positive rectal biopsy samples; of those, only 12 had positive eyelid biopsies. These sheep will be monitored for disease development. However, the protocol is identical for all samples and it is probable that these sheep represent false negative third eyelid results. Abstracts of reports on the UK studies indicate that sensitivity of the test was 70% in the UK; similar large scale testing on US sheep is necessary. The biopsy tissue is somewhat difficult to handle in the tissue processing laboratory and adaptation to an ELISA format may improve test performance.

Alexia McKnight, Assistant Professor of Radiology, University of Pennsylvania, reviewed magnetic resonance imaging (MRI) diagnostics before the committee. A synopsis containing references is attached at the end of this report. Dr. McKnight asked the question, "could MRI be a cost-effective screening test, estimated at $25-30 each with results immediately available." The committee feels that it is not practical as compared to other alternatives currently available. However, the committee expressed interest in future reference to this technology.

Dr. Diane Sutton lead the Uniform Methods and Rules (UM&R) and Regulatory Issues Discussion. Several modifications to the UM&R were discussed. Eight issues were identified and communicated to the APHIS scrapie program coordinator. The committee acknowledged that APHIS and the industry is adequately addressing the year-to-year industry concerns.

Dr. Kris Petrini representing the North Central United States Animal Health Association District presented five recommendations to the Committee. During the discussions regarding these recommendations it was evident that all five issues had been addressed during the year at this Committee meeting.

The Committee approved a recommendation that USDA-APHIS-VS continue to provide indemnity funds for animals that have been designated for testing in Flocks Under Investigation as an alternative to third eyelid testing after consultation with the designated Scrapie Epidemiologist (DSE) and the Regional Area Epidemiologist (RAE).

The 2004 Resolutions along with their responses were reviewed by the Committee.

A Resolution concerning premises registration and identification was approved by the Committee and forwarded to the Committee on Nominations and Resolutions.

Committee on Scrapie

Status Report-Fiscal Year 2005: Cooperative State-Federal Scrapie Eradication Program

Submitted by Diane Sutton, DVM and Gary Ross, DVM

National Center for Animal Health Programs, APHIS, USDA

In Fiscal Year 2005 the Scrapie Eradication Program focused on: (1) utilization of a genetic based approach to flock clean-up plans; (2) cleaning up infected and source flocks; (3) tracing and testing exposed animals and flocks; (4) expansion of regulatory slaughter surveillance (RSSS); (5) conducting considtent state reviews, (6) producer education; (7) upgrading of the Scrapie National Generic Database and ( publishing the updated Scrapie Eradication Uniform Methods and Rules (UM&R). The current Scrapie Eradication UM&R is posted at http://www.aphis.usda.gov/vs/nahps/scra ... e-erad.pdf.

Consistent State Reviews

States must meet the requirements in 9 CFR 79.6 in order to move sheep and goats in interstate commerce with minimal restrictions. Twenty seven states have enacted the required identification rules, the remaining states have submitted a work plan that describes the steps that will be taken to comply and provided a timeline for completing significant milestones. USDA is conducting onsite scrapie program consistent state reviews and has completed reviews in 12 states. States must be in full compliance by the end of their current rule making cycle. States not in full compliance at that time will be removed from the consistent state list. Removal from the list would create a significant impact on the interstate movement of sheep and goats from those States.

Scrapie Flock Certification Program

As of September 30, 2005, there were 1,961 flocks participating in the Scrapie Flock Certification Program (SFCP). Of these flocks 188 were certified flocks, 1,770 were complete monitored flocks, and 3 were selective monitored flocks (figure 2). There were 209 flocks newly enrolled and 53 newly certified (13 with status dates in FY 2005 and 40 with status dates in previous years) in FY 2005 (figure 3).

Infected and Source Flocks

As of September 30, 2005, there were 105 scrapie infected and source flocks. There were a total of 165** new infected and source flocks reported for FY 2005. The total infected and source flocks that have been released in FY 2005 was 128. The ratio of infected and source flocks cleaned up or placed on clean up plans vs. new infected and source flocks discovered in FY 2005 was 1.03 : 1*. In addition 622 scrapie cases were confirmed and reported by the National Veterinary Services Laboratories (NVSL) in FY 2005, of which 130 were RSSS cases. Fifteen cases of scrapie in goats have been reported since 1990. The last goat case was reported in May 2005. Approximately 5,626 animals were indemnified comprised of 49% non-registered sheep, 45% registered sheep, 1.4% non-registered goats and 4.6% registered goats.

Regulatory Scrapie Slaughter Surveillance (RSSS)

RSSS was designed to utilize the findings of the Center for Epidemiology and Animal Health (CEAH) Scrapie: Ovine Slaughter Surveillance (SOSS) study. The results of SOSS can be found at http://www.aphis.usda.gov/vs/ceah/cahm/Sheep/sheep.htm . RSSS started April 1,

2003. It is a targeted slaughter surveillance program which is designed to identify infected flocks for clean-up. During FY 2005 collections increased by 32% overall and by 90% for black and mottled faced sheep improving overall program effectiveness and efficiency as demonstrated by the 26% decrease in percent positive black faced sheep compared to FY 2004. Samples have been collected from 62,864 sheep since April 1, 2003, of which results have been reported for 59,105 of which 209 were confirmed positive. During FY 2005, 33,137 samples were collected from 81 plants. There have been 130 NVSL confirmed positive cases (30 collected in FY 2004 and confirmed in FY 2005 and 100 collected and confirmed in FY 2005) in FY 2005. Face colors of these positives were 114 black, 14 mottled, 1 white and 1 unknown. The percent positive by face color is shown in the chart below.

Scrapie Testing

In FY 2005, 35,845 animals have been tested for scrapie: 30,192 RSSS; 4,742 regulatory field cases; 772 regulatory third eyelid biopsies; 10 third eyelid validations; and 129 necropsy validations (chart 9).

Animal ID

As of October 04, 2005, 103,580 sheep and goat premises have been assigned identification numbers in the Scrapie National Generic Database. Official eartags have been issued to 73,807 of these premises.

*This number based on an adjusted 12 month interval to accommodate the 60 day period for setting up flock plans.

http://www.usaha.org/committees/reports ... r-2005.pdf

PrP genotypes of atypical scrapie cases in Great Britain

G. C. Saunders, S. Cawthraw, S. J. Mountjoy, J. Hope and O. Windl

Department of TSE Molecular Biology, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey KT15 3NB, UK

Correspondence
G. C. Saunders
[email protected]

Great Britain and elsewhere have detected atypical scrapie infection in sheep with PrP genotypes thought to be genetically resistant to the classical form of scrapie. DNA sequencing of the PrP gene of British atypical scrapie cases (n=69), classical scrapie cases (n=59) and scrapie-free controls (n=138) was undertaken to identify whether PrP variants, other than the three well-characterized polymorphic codons, influenced susceptibility to atypical scrapie infection. Four non-synonymous changes, M112T, M137T, L141F and P241S, were detected that are most probably associated with the A136R154Q171 haplotype. Only the PrP variant containing a phenylalanine residue at amino acid position 141 was found to be associated more commonly with the atypical scrapie cases. In addition to the single nucleotide polymorphisms associated with the ARQ allele, two out of nine atypical scrapie cases with the ARR/ARR genotype were found to contain a 24 bp insertion, leading to an additional octapeptide repeat. In terms of PrP genetics, one classification of the GB scrapie cases examined in this study would place animals carrying any homozygous or heterozygous combination of ARR, AHQ or AF141RQ alleles, or any one of these alleles when paired with ARQ, as being susceptible to atypical scrapie infection, and animals heterozygous or homozygous for VRQ or homozygous for ARQ as being susceptible to classical scrapie disease. The AHQ PrP allele was associated with the highest incidence of atypical scrapie (263 per 100 000 alleles), whilst VRQ was associated with the lowest incidence (10 per 100 000 alleles).

Published online ahead of print on 11 August 2006 as DOI 10.1099/vir.0.81779-0.

http://vir.sgmjournals.org/

--------------------------------------------------------------------------------
Science 17 March 2000:
Vol. 287. no. 5460, p. 1907
DOI: 10.1126/science.287.5460.1907


News Focus
Writing Scrapie's Coda, Codon by Codon?
Michael Balter
Over the past decade, geneticists have begun to unravel why some sheep are more vulnerable than others to scrapie. They have found that different variations, or polymorphisms, in the gene coding for PrP--a cellular protein that many scientists believe becomes infectious when it converts to an abnormal form called a prion--seem to confer varying degrees of susceptibility. This correlation raises the possibility that genetically susceptible sheep could be bred out of the population, leaving only scrapie-resistant animals (see main text).

Studies of sheep experimentally infected with scrapie have shown that three codons, or positions, in the PrP gene--codons 136, 154, and 171--are critical in determining whether the animal comes down with the disease. Each codon gets translated into one of the 256 amino acids of the sheep PrP protein. Individuals most vulnerable to scrapie have the amino acids valine, arginine, and glutamine at the respective positions dictated by the three codons. Using the single-letter code for amino acids, this polymorphism is referred to as VRQ. At the other extreme, sheep with the polymorphism alanine-arginine-arginine (ARR) are the most resistant. Indeed, out of hundreds of scrapie-infected sheep tested worldwide, only one, in Japan, has turned out to be ARR. Three other polymorphisms (shown at below) apparently lead to intermediate levels of vulnerability to the disease.


Muddling this neat picture, however, are some bizarre differences in the effect of polymorphisms in different sheep breeds. For example, Suffolk sheep with the genotype ARQ are susceptible to scrapie, whereas ARQ Cheviot sheep are resistant. "We really don't understand this," says Nora Hunter, a geneticist at the Institute for Animal Health's Neuropathogenesis Unit in Edinburgh. Hunter and her colleagues are currently testing several hypotheses, including the possibility that the two breeds are being infected by different prion strains, or that Suffolk sheep may produce higher levels of PrP and thus have more protein available for conversion to the prion form.
More clear, however, is why PrP polymorphisms correlate with scrapie susceptibility in the first place. Findings reported in the 17 July 1997 issue of Nature and in the 13 May 1997 Proceedings of the National Academy of Sciences show that the VRQ version of normal PrP protein is easily converted into the prion form when mixed with other prions in the test tube. (Most researchers studying prion diseases believe this mechanism is responsible for the creation of new prions in infected animals.) The ARR polymorphism, on the other hand, strongly resists this conversion, while polymorphisms corresponding to intermediate scrapie susceptibility fall in between. This biochemical confirmation of the importance of PrP polymorphisms has bolstered the view that breeding VRQ and other susceptible genotypes out of the sheep population might be the best course toward eradication. Says Hunter: "At the moment, there really isn't any good alternative."

http://www.sciencemag.org/


Scrapie

The Countess of Mar asked Her Majesty's Government:

What have been the total costs, including the set-up cost and running costs, of the National Scrapie Plan since its inception; how many full-time posts are involved; and in which tasks. [HL4601]

The Parliamentary Under-Secretary of State, Department for Environment, Food and Rural Affairs (Lord Bach): The total cost of the National Scrapie Plan (NSP) since its inception in 2001 until the end of February 2006 is approximately £97 million. This figure is inclusive of set-up and running costs.

Currently, there are 84 full-time staff engaged on NSP activities. This includes staff at the State Veterinary Service's (SVS) National Scrapie Plan Administration Centre, who are responsible for service delivery aspects, and core Defra staff responsible for the NSP policy and programme management in partnership with the GB devolved administrations. In addition, farm-based activities are carried out by SVS field staff and local veterinary inspectors alongside their other duties.

22 Mar 2006 : Column WA65


The Countess of Mar asked Her Majesty's Government:

How many cases of (a) classical, and (b) atypical scrapie have been detected in sheep in the United Kingdom since the introduction of the National Scrapie Plan; what were the genotypes of the sheep; and which strains of scrapie were found. [HL4603]

Lord Bach: In the UK there are two forms of surveillance performed for the detection of TSEs in sheep, termed passive and active surveillance. Passive surveillance is where animals are reported to the State Veterinary Service (SVS) with clinical signs of disease, and the case is investigated. In 2002 the European Union launched a Europe-wide active TSE surveillance programme to establish the prevalence of TSEs in small ruminants. This has required the testing of sheep slaughtered for human consumption and fallen sheep over 18 months of age.

Table 1 shows the number of classical cases of scrapie detected in Great Britain through the passive surveillance from the beginning of the National Scrapie Plan in July 2001 until 15 March 2006. Diagnostic methods capable of detecting atypical cases of scrapie were introduced into the passive surveillance programme in July 2004, so the data presented for atypical cases of scrapie in the table are from July 2004 to 15 March 2006.
Genotype Classical Scrapie Atypical Scrapie
Unknown 152 0
ARR/ARR 0 0
ARR/AHQ 0 1
ARR/ARQ 3 0
ARR/ARH 0 0
AHQ/AHQ 8 0
AHQ/ARH 0 0
ARQ/ARH 25 0
ARH/ARH 13 0
AHQ/ARQ 26 2
ARQ/ARQ 289 0
ARR/VRQ 59 0
AHQNRQ 2 0
ARH/VRQ 68 0
ARQIVRQ 664 0
VRQ/VRQ 203 0
Total 1,512 3

Table 2 shows the number of confirmed classical and atypical scrapie cases detected in Great Britain through active surveillance of sheep at abattoirs and fallen stock since testing began in January 2002 until 15 March 2006. The active surveillance programme is an EU requirement. From January 2002 the Veterinary Laboratories Agency has tested over 140,000 sheep samples.
Genotype Classical Scrape Atypical Scrape
Unknown 1 0
ARR/ARR 0 15
ARR/AHQ 0 29
ARR/ARQ 1 13
ARR/ARH 0 1
AHQ/AHQ 1 13
AHQ/ARH 0 2
ARQ/ARH 1 0
ARH/ARH 0 0
AHQ/ARQ 3 21
ARQ/ARQ 23 13
ARR/VRQ 32 0
AHQ/VRQ 0 0
ARH/VRQ 12 0
ARQNRQ 76 1
VRQ/VRQ 15 0
Total 165 108


22 Mar 2006 : Column WA66


Information on the strains of scrapie present in a sample is not routinely collected.
Spongiform Encephalopathy Advisory Committee

The Countess of Mar asked Her Majesty's Government:

What have been the total funds allocated by them and by the research councils for research into transmissible spongiform encephalopathies in sheep, goats and cattle since the Spongiform Encephalopathy Advisory Committee was formed; and to which individuals or organisations those funds have been allocated. [HL4605]

The Parliamentary Under-Secretary of State, Department for Environment, Food and Rural Affairs (Lord Bach): The main funders of research into transmissible spongiform encephalopathies (TSEs) in sheep, goats and cattle are MAFF/Defra, the Biotechnology and Biological Sciences Research Council (BBSRC) and the Food Standards Agency (FSA).

MAFF/DEFRA

Since the Spongiform Encephalopathy Advisory Committee (SEAC) was formed in 1990, MAFF/Defra have funded or are currently funding 274 research projects in TSEs at a total cost of £182,600,992. The breakdown of MAFF/Defra funding per institution is as follows.

see full text;


http://www.publications.parliament.uk/p ... 2w04_sbhd1


New Zealand sheep with scrapie-susceptible PrP genotypes succumb to experimental challenge with a sheep-passaged scrapie isolate (SSBP/1)
E. F. Houston1, S. I. Halliday1, M. Jeffrey3, W. Goldmann2 and N. Hunter2

Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, UK1
BBSRC/MRC Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH9 3JF, UK2
VLA Lasswade, Pentlands Science Park, Bush Loan, Penicuik, Midlothian EH26 0PZ, UK3


Author for correspondence: Fiona Houston. Fax +44 1635 577263. e-mail [email protected]


Abstract

Scrapie does not occur in New Zealand (NZ), although PrP gene alleles associated with susceptibility to the disease are found at relatively high frequencies in NZ sheep. The hypothesis that scrapie is a genetic disease of sheep is thus unlikely to be true. To confirm that NZ sheep are actually susceptible to scrapie infection, NZ sheep of various PrP genotypes were challenged by subcutaneous inoculation with a sheep-passaged scrapie isolate (SSBP/1). Showing similar PrP genetics to that seen in UK sheep, all NZ sheep carrying the VRQ PrP allele developed clinical signs typical of scrapie, with characteristic neurodegenerative changes and PrPSc evident on histopathological examination of their brains and lymphoid tissues. The incubation periods recorded in NZ sheep were generally shorter than those found in UK sheep. The results confirm that New Zealand sheep are as susceptible as their UK counterparts to experimental scrapie infection by subcutaneous inoculation.

http://vir.sgmjournals.org/cgi/content/full/83/5/1247

355 Emerging traits of interest to the livestock industries: scrapie resistance

in sheep. R. M. Lewis*1 and B. Villanueva2, 1Virginia Polytechnic

Institute and State University, Blackburg, 2Scottish Agricultural College,

Edinburgh, UK.

Many loci with major effects on performance, including fitness, have been identified

in livestock. Where genotype tests characterizing polymorphisms at such

loci are available, breeders have opportunity to use such information to increase

the frequency of beneficial alleles. A clear example is the Prion Protein

(PrP) locus in sheep, which is associated with resistance to the fatal transmissible

spongiform (TSE) scrapie. Five main haplotypes have been identified for

this locus resulting from polymorphisms at codons 136, 154 and 171. Animals

homozygous for the ARR haplotype are considered resistant while animals carrying

the VRQ haplotype are considered highly susceptible. Genetic strategies

based on PrP genotyping have thus been adopted to eradicate scrapie in infected

flocks while increasing the resistance of national flocks. The voluntary

National Scrapie Plan (NSP) in Great Britain is one of the earliest PrP genotyping

programs. It began in 2001 by genotyping rams registered with breed societies

favoring rams with beneficial genotypes for breeding. Since other TSE diseases

may be present in sheep, another aim of NSP is to remove the theoretical risk of

bovine spongiform encephalopathy naturally affecting sheep. Although increasing

genetic resistance to TSEs is clearly important, the path to achieving resistance

requires care. For instance, limited evidence suggests ARR homozygosity

may not unequivocally result in scrapie resistance, perhaps reflecting variable

strains of scrapie. Semen banks designed to preserve alleles currently disfavored

are needed to ensure flexibility to manage future TSEs. Furthermore, if

favored alleles are antagonistic to other economically important traits or are

sufficiently rare that selection increases inbreeding and reduces genetic variability,

a focus on scrapie alone may prove risky. The careful integration of

scrapie resistance into the overall breeding goal is thus central.

http://www.fass.org/2005/abstracts/05abs230.pdf

7. The new research reports the experimental transmission of BSE

to ARR/ARR sheep following intracerebral challenge with 0.5ml

10% BSE-infected bovine brain homogenate. The incubation

period of disease is approximately twice the average incubation

period of 556 days reported in BSE susceptible genotypes

(ARQ/ARQ sheep) challenged by intracerebral inoculation with

BSE in the same study. Apart from a single unconfirmed report of

1 on inclusion of ruminant derived MBM in concentrate foodstuffs for ruminants (the feed ban).

© SEAC 2003

naturally occurring scrapie in Japan, this is the first record of a

TSE infection in ARR/ARR sheep.

http://www.seac.gov.uk/statements/sheep ... tement.pdf


TSS