NOTICE: National Scrapie Eradication Report - January 2015 USDA Animal and
Plant Health Inspection Service sent this bulletin at 03/03/2015 03:00 PM EST
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The monthly report for the National Scrapie Eradication Program for January
2015 is now available. The monthly reports are available in both PowerPoint and
PDF formats.
•PowerPoint Monthly Report
•PDF Monthly Report
Highlights of the January 2015 Report
One new scrapie infected flock and two new scrapie source flocks have been
designated in FY 2015. Since the beginning of FY 2015, 29 sheep have tested
positive for scrapie; 26 of these positives were from the same source flock. Two
goats have tested positive; both from the same herd.
As of January 31, for FY 2015, 11,011 sheep and 2,892 goats have been
tested for scrapie.
Scrapie/Scrapie Program Monthly Tidbit
Do you know how “scrapie” got its name? Sheep and goats affected by the
disease often scratch and rub against fixed objects, apparently to relieve
itching. Other signs are loss of coordination, weakness, weight loss despite a
healthy appetite, biting at feet or limbs, lip smacking, and abnormalities in an
animal’s gait or while walking (such as high-stepping of the forelegs, hopping
like a rabbit, and swaying of the back end). Death has been reported in sheep
and goats where clinical signs were not observed. Visit the APHIS Scrapie
Disease Information webpage to learn more.
Resources
•To report a sheep or goat with clinical signs of scrapie, please contact
your local VS office.
•To learn more about scrapie, the disease, and the national scrapie
eradication program visit the APHIS VS Scrapie Website and
www.eradicatescrapie.org.
Infected sheep may have come from U.S., not Ontario farm where officials
slaughtered flock, court hears
Adrian Humphreys | February 27, 2015 | Last Updated: Mar 1 5:07 PM ET
Friday, February 20, 2015
APHIS Freedom of Information Act (FOIA) Appeal Mouse Bio-Assays
2007-00030-A Sheep Imported From Belgium and the Presence of TSE Prion Disease
Kevin Shea to Singeltary 2015
Tuesday, December 16, 2014
Evidence for zoonotic potential of ovine scrapie prions
Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves
Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle
Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia
Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier Andréoletti1,
Affiliations Contributions Corresponding author Journal name: Nature
Communications Volume: 5, Article number: 5821 DOI: doi:10.1038/ncomms6821
Received 07 August 2014 Accepted 10 November 2014 Published 16 December 2014
Article tools Citation Reprints Rights & permissions Article metrics
Abstract
Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant
Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie
prions remains unknown. Mice genetically engineered to overexpress the human
prion protein (tgHu) have emerged as highly relevant models for gauging the
capacity of prions to transmit to humans. These models can propagate human
prions without any apparent transmission barrier and have been used used to
confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie
prions transmit to several tgHu mice models with an efficiency comparable to
that of cattle BSE. The serial transmission of different scrapie isolates in
these mice led to the propagation of prions that are phenotypically identical to
those causing sporadic CJD (sCJD) in humans. These results demonstrate that
scrapie prions have a zoonotic potential and raise new questions about the
possible link between animal and human prions.
Subject terms: Biological sciences• Medical research At a glance
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly would likely
create alarm in some circles even if the result could not be interpreted for
man. I have a view that all these agents could be transmitted provided a large
enough dose by appropriate routes was given and the animals kept long enough.
Until the mechanisms of the species barrier are more clearly understood it might
be best to retain that hypothesis.
snip...
R. BRADLEY
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep
infected with scrapie?
28 Mar 01 Most doctors believe that sCJD is caused by a prion protein
deforming by chance into a killer. But Singeltary thinks otherwise. He is one of
a number of campaigners who say that some sCJD, like the variant CJD related to
BSE, is caused by eating meat from infected animals. Their suspicions have
focused on sheep carrying scrapie, a BSE-like disease that is widespread in
flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight
to the campaigners' fears. To their complete surprise, the researchers found
that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by
some strains of scrapie," says team member Jean-Philippe Deslys of the French
Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses,
south-west of Paris. Hans Kretschmar of the University of Göttingen, who
coordinates CJD surveillance in Germany, is so concerned by the findings that he
now wants to trawl back through past sCJD cases to see if any might have been
caused by eating infected mutton or lamb...
2001
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep
infected with scrapie?
28 Mar 01
Like lambs to the slaughter
31 March 2001
by Debora MacKenzie Magazine issue 2284.
FOUR years ago, Terry Singeltary watched his mother die horribly from a
degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary
was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded
an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming by
chance into a killer. But Singeltary thinks otherwise. He is one of a number of
campaigners who say that some sCJD, like the variant CJD related to BSE, is
caused by eating meat from infected animals. Their suspicions have focused on
sheep carrying scrapie, a BSE-like disease that is widespread in flocks across
Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight
to the campaigners' fears. To their complete surprise, the researchers found
that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by
some strains of scrapie," says team member Jean-Philippe Deslys of the French
Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses,
south-west of Paris. Hans Kretschmar of the University of Göttingen, who
coordinates CJD surveillance in Germany, is so concerned by the findings that he
now wants to trawl back through past sCJD cases to see if any might have been
caused by eating infected mutton or lamb.
Scrapie has been around for centuries and until now there has been no
evidence that it poses a risk to human health. But if the French finding means
that scrapie can cause sCJD in people, countries around the world may have
overlooked a CJD crisis to rival that caused by BSE.
Deslys and colleagues were originally studying vCJD, not sCJD. They
injected the brains of macaque monkeys with brain from BSE cattle, and from
French and British vCJD patients. The brain damage and clinical symptoms in the
monkeys were the same for all three. Mice injected with the original sets of
brain tissue or with infected monkey brain also developed the same
symptoms.
As a control experiment, the team also injected mice with brain tissue from
people and animals with other prion diseases: a French case of sCJD; a French
patient who caught sCJD from human-derived growth hormone; sheep with a French
strain of scrapie; and mice carrying a prion derived from an American scrapie
strain. As expected, they all affected the brain in a different way from BSE and
vCJD. But while the American strain of scrapie caused different damage from
sCJD, the French strain produced exactly the same pathology.
"The main evidence that scrapie does not affect humans has been
epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute
for Animal Health in Edinburgh, who was a member of the same team as Deslys.
"You see about the same incidence of the disease everywhere, whether or not
there are many sheep, and in countries such as New Zealand with no scrapie." In
the only previous comparisons of sCJD and scrapie in mice, Bruce found they were
dissimilar.
But there are more than 20 strains of scrapie, and six of sCJD. "You would
not necessarily see a relationship between the two with epidemiology if only
some strains affect only some people," says Deslys. Bruce is cautious about the
mouse results, but agrees they require further investigation. Other trials of
scrapie and sCJD in mice, she says, are in progress.
People can have three different genetic variations of the human prion
protein, and each type of protein can fold up two different ways. Kretschmar has
found that these six combinations correspond to six clinical types of sCJD: each
type of normal prion produces a particular pathology when it spontaneously
deforms to produce sCJD.
But if these proteins deform because of infection with a disease-causing
prion, the relationship between pathology and prion type should be different, as
it is in vCJD. "If we look at brain samples from sporadic CJD cases and find
some that do not fit the pattern," says Kretschmar, "that could mean they were
caused by infection."
There are 250 deaths per year from sCJD in the US, and a similar incidence
elsewhere. Singeltary and other US activists think that some of these people
died after eating contaminated meat or "nutritional" pills containing dried
animal brain. Governments will have a hard time facing activists like Singeltary
if it turns out that some sCJD isn't as spontaneous as doctors have
insisted.
Deslys's work on macaques also provides further proof that the human
disease vCJD is caused by BSE. And the experiments showed that vCJD is much more
virulent to primates than BSE, even when injected into the bloodstream rather
than the brain. This, says Deslys, means that there is an even bigger risk than
we thought that vCJD can be passed from one patient to another through
contaminated blood transfusions and surgical instruments.
Friday, January 30, 2015
*** Scrapie: a particularly persistent pathogen ***
Wednesday, December 24, 2014
National Scrapie Eradication Program November 2014 Monthly Report Fiscal
Year 2015
RESEARCH ARTICLE
Phenotype Shift from Atypical Scrapie to CH1641 following Experimental
Transmission in Sheep
Marion M. Simmons*, S. Jo Moore¤a, Richard Lockey¤b, Melanie J. Chaplin,
Timm Konold, Christopher Vickery, John Spiropoulos
Animal and Plant Health Agency—Weybridge, Woodham Lane, Addlestone, Surrey,
KT15 3NB, United Kingdom
¤a Current address: School of Veterinary and Biomedical Sciences, Murdoch
University, South Street, Murdoch, Western Australia, 6150, Australia
¤b Current address: University of Southampton, Southampton, SO17 1BJ,
United Kingdom * marion.simmons@apha.gsi.gov.uk
Abstract
The interactions of host and infecting strain in ovine transmissible
spongiform encephalopathies are known to be complex, and have a profound effect
on the resulting phenotype of disease. In contrast to classical scrapie, the
pathology in naturally-occurring cases of atypical scrapie appears more
consistent, regardless of genotype, and is preserved on transmission within
sheep homologous for the prion protein (PRNP) gene. However, the stability of
transmissible spongiform encephalopathy phenotypes on passage across and within
species is not absolute, and there are reports in the literature where
experimental transmissions of particular isolates have resulted in a phenotype
consistent with a different strain. In this study, intracerebral inoculation of
atypical scrapie between two genotypes both associated with susceptibility to
atypical forms of disease resulted in one sheep displaying an altered phenotype
with clinical, pathological, biochemical and murine bioassay characteristics all
consistent with the classical scrapie strain CH1641, and distinct from the
atypical scrapie donor, while the second sheep did not succumb to challenge. One
of two sheep orally challenged with the same inoculum developed atypical scrapie
indistinguishable from the donor. This study adds to the range of transmissible
spongiform encephalopathy phenotype changes that have been reported following
various different experimental donor-recipient combinations. While these
circumstances may not arise through natural exposure to disease in the field,
there is the potential for iatrogenic exposure should current disease
surveillance and feed controls be relaxed. Future sheep to sheep transmission of
atypical scrapie might lead to instances of disease with an alternative
phenotype and onward transmission potential which may have adverse implications
for both public health and animal disease control policies.
snip...
Despite naturally-occurring atypical scrapie being observed in a range of
genotypes, successful experimental transmissions of clinical disease have so far
only been reported within a particular homologous donor-recipient genotype model
using sheep which are AHQ/AHQ homozygous [8,15,16]. These published
transmissions represent part of a large study at APHA which has been running
since 2004, investigating the potential transmissibility of atypical scrapie in
a range of both homologous and cross-genotype combinations. Here we describe an
unexpected and interesting finding from that study where one experimental
challenge in which atypical scrapie from an ARR/ARR donor was inoculated
intracerebrally into two AHQ/AHQ recipient sheep, and in one of them the
resulting disease had a phenotype that was indistinguishable from CH1641 [29], a
classical scrapie strain which has some BSE-like Western blot properties.
Subject: more on scrapie/BSE strain CH1641
From: tom
Reply-To: Bovine Spongiform Encephalopathy
Date: Sun, 10 Jan 1999 21:52:05 -0800
Content-Type: text/plain
Parts/Attachments: Parts/Attachments text/plain (37 lines) Reply Reply
Recall a forthcoming J Gen Virol Jan 1999 v80:1 - 4 says there are
similarities between BSE and an experimental isolate of natural scrapie, CH1641.
This might then be the long-sought missing scrapie strain that could have given
rise to the BSE epidemic. It would raise additional questions about the
harmlessness to humans of scrapie.
On the other hand, CH1641 happened to be one of the scrapie strains studied
very recently by Collinge's group, Neurosci Lett. 1998 Oct 23;255(3):159-62. It
did not have the prp-sc type identical to BSE passaged in sheep.
The CH1641 strain is mentioned only twice before in Medline abstracts
(though there could be many fulltext mentions), one of these being the original
naming of the strain in 1988:
The unusual properties of CH1641, a sheep-passaged isolate of
scrapie.
Foster JD, Dickinson AG Vet Rec 1988 Jul 2;123(1):5-8
An isolate of scrapie designated CH1641 was identified from a natural case
of scrapie in a Cheviot sheep by passage in sheep and goats. It has not been
possible to transmit scrapie to mice from this source. The Sip gene which
controls the incubation periods of experimental scrapie in Cheviot sheep has two
alleles; sA which shortens and pA which lengthens the incubation periods of most
strains of scrapie after the first experimental injection in sheep (the A group
of strains). The CH1641 isolate differs from them in that the alleles of Sip act
in the opposite way, with incubation being shorter in the pA homozygotes. There
is some evidence that one or more genes, in addition to Sip, may be implicated
in the control of scrapie incubation in sheep and the possibility of a carrier
infection with CH1641 is also discussed.
Novel polymorphisms in the caprine PrP gene: a codon 142 mutation
associated with scrapie incubation period.
J Gen Virol 1996 Nov;77 ( Pt 11):2885-91 Published erratum appears in J Gen
Virol 1997 Mar;78(Pt 3):697 Goldmann W, Martin T, Foster J, Hughes S, Smith G,
Hughes K, Dawson M, Hunter N
Age at disease onset and rate of progression of transmissible spongiform
encephalopathies in man, sheep and mice are modulated by the host genome, in
particular by the PrP gene and its allelic forms. Analysis of the caprine PrP
gene revealed several different alleles. Four PrP protein variants were found,
three of which were goat specific with single amino acid changes at codons 142,
143 and 240. The fourth was identical to the most common sheep PrP protein
variant (Ala136-Arg154-Gln171). The dimorphism at codon 142 (Ile --> Met)
appeared to be associated with differing disease incubation periods in goats
experimentally infected with isolates of bovine spongiform encephalopathy, sheep
scrapie CH1641 or sheep-passaged ME7 scrapie.
TSE PRION UPDATE USA 2012
re-BSE in goats can be mistaken for scrapie
Wednesday, January 18, 2012
BSE IN GOATS CAN BE MISTAKEN FOR SCRAPIE
February 1, 2012
Wednesday, January 18, 2012
Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural
Scrapie Isolates Similar to CH1641 Experimental Scrapie
Journal of Neuropathology & Experimental Neurology:
February 2012 - Volume 71 - Issue 2 - p 140–147
Monday, March 21, 2011
Sheep and Goat BSE Propagate More Efficiently than Cattle BSE in Human PrP
Transgenic Mice
snip...
On the other hand, this component would not be distinguishable from
bovine-passaged BSE prions due to the current limits of the standard biological
methods and/or the molecular tools employed here to characterize prion strains.
Whatever the mechanism, the notion that a passage through an intermediate
species can profoundly alter prion virulence for the human species has important
public-health issues, regarding emerging and/or expanding TSEs, like atypical
scrapie or CWD.
snip...
Taken all together, our results suggest that the possibility of a small
ruminant BSE prion as vCJD causal agent could not be ruled out, which has
important implications on public and animal health policies. On one hand,
although the exact magnitude and characteristic of the vCJD epidemic is still
unclear, its link with cattle BSE is supported by strong epidemiological ground
and several experimental data. On the other hand, the molecular typing performed
in our studies, indicates that the biochemical characteristics of the PrPres
detected in brains of our sheep and goat BSE-inoculated mice seem to be
indistinguishable from that observed in vCJD. Considering the similarity in
clinical manifestation of BSE- and scrapie-affected sheep [48], a masker effect
of scrapie over BSE, as well as a potential adaptation of the BSE agent through
subsequent passages, could not be ruled out. As BSE infected sheep PrPSc have
been detected in many peripheral organs, small ruminant-passaged BSE prions
might be a more widespread source of BSE infectivity compared to cattle [19],
[49], [50]. This fact is even more worrying since our transmission studies
suggest that apparently Met129 human PrP favours a BSE agent with ovine rather
than a bovine sequence. Finally, it is evident that, although few natural cases
have been described and so far we cannot draw any definitive conclusion about
the origin of vCJD, we can not underestimate the risk of a potential goat and/or
sheep BSE agent.
snip...
Technical Abstract:
Prion strains may vary in their ability to transmit to humans and animals.
Few experimental studies have been done to provide evidence of differences
between U.S. strains of scrapie, which can be distinguished by incubation times
in inbred mice, microscopic lesions, immunoreactivity to various antibodies, or
molecular profile (electrophoretic mobility and glycoform ratio). Recent work on
two U.S. isolates of sheep scrapie supports that at least two distinct strains
exist based on differences in incubation time and genotype of sheep affected.
One isolate (No. 13-7) inoculated intracerebrally caused scrapie in sheep AA at
codon 136 (AA136) and QQ at codon 171 (QQ171) of the prion protein in an average
of 19 months post-inoculation (PI) whereas a second isolate (No. x124) caused
disease in less than 12 months after oral inoculation in AV136/QQ171 sheep.
Striking differences were evident when further strain analysis was done in R111,
VM, C57Bl6, and C57Bl6xVM (F1) mice. No. 13-7 did not induce disease in any
mouse strain at any time post-inoculation (PI) nor were brain tissues positive
by western blot (WB). Positive WB results were obtained from mice inoculated
with isolate No. x124 starting at day 380 PI. Incubation times averaged 508,
559, 601, and 633 days PI for RIII, C57Bl6, VM, and F1 mice, respectively.
Further passage will be required to characterize these scrapie strains in mice.
This work provides evidence that multiple scrapie strains exist in U.S.
sheep.
One of these isolates (TR316211) behaved like the CH1641 isolate, with
PrPres features in mice similar to those in the sheep brain. From two other
isolates (O100 and O104), two distinct PrPres phenotypes were identified in
mouse brains, with either high (h-type) or low (l-type) apparent molecular
masses of unglycosylated PrPres, the latter being similar to that observed with
CH1641, TR316211, or BSE. Both phenotypes could be found in variable proportions
in the brains of the individual mice. In contrast with BSE, l-type PrPres from
"CH1641-like" isolates showed lower levels of diglycosylated PrPres. From one of
these cases (O104), a second passage in mice was performed for two mice with
distinct PrPres profiles. This showed a partial selection of the l-type
phenotype in mice infected with a mouse brain with predominant l-type PrPres,
and it was accompanied by a significant increase in the proportions of the
diglycosylated band. These results are discussed in relation to the diversity of
scrapie and BSE strains.
In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q
(AAQQ) and the disease phenotype is similar to that seen with experimental
strain CH1641.
snip...see ;
Thursday, July 14, 2011
Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical
Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)
SHEEP AND BSE
PERSONAL AND CONFIDENTIAL
SHEEP AND BSE
A. The experimental transmission of BSE to sheep.
Studies have shown that the ''negative'' line NPU flock of Cheviots can be
experimentally infected with BSE by intracerebral (ic) or oral challenge (the
latter being equivalent to 0.5 gram of a pool of four cow brains from animals
confirmed to have BSE).
RB264
BSE - TRANSMISSION STUDIES
Wednesday, January 18, 2012
Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural
Scrapie Isolates Similar to CH1641 Experimental Scrapie
Journal of Neuropathology & Experimental Neurology:
February 2012 - Volume 71 - Issue 2 - p 140–147
Tuesday, February 01, 2011
Sparse PrP-Sc accumulation in the placentas of goats with naturally
acquired scrapie
Research article
snip...
Date: Tuesday, February 01, 2011 5:03 PM
To: Mr Terry Singeltary
Subject: Your comment on BMC Veterinary Research 2011, 7:7
Dear Mr Singeltary
Thank you for contributing to the discussion of BMC Veterinary Research
2011, 7:7 .
Your comment will be posted within 2 working days, as long as it
contributes to the topic under discussion and does not breach patients'
confidentiality or libel anyone. You will receive a further notification by
email when the posting appears on the site or if it is rejected by the
moderator.
Your posting will read:
Mr Terry Singeltary,
retired
Scrapie cases Goats from same herd USA Michigan
Comment: " In spite of the poorly defined effects of PRNP genetics, scrapie
strain, dose, route and source of infection, the caprine placenta may represent
a source of infection to progeny and herd mates as well as a source of
persistent environmental contamination. "
Could this route of infection be the cause of the many cases of Goat
scrapie from the same herd in Michigan USA ?
Has this been investigated ?
(Figure 6) including five goat cases in FY 2008 that originated from the
same herd in Michigan. This is highly unusual for goats, and I strenuously urge
that there should be an independent investigation into finding the common
denominator for these 5 goats in the same herd in Michigan with Scrapie. ...
Kind Regards, Terry
snip...
UPDATED RESPONSE ON MY CONCERNS OF GOAT SCRAPIE IN MICHIGAN ;
----- Original Message -----
From: "BioMed Central Comments"
To:
Sent: Wednesday, February 16, 2011 4:13 AM
Subject: Your comment on BMC Veterinary Research 2011, 7:7
Your discussion posting "Scrapie cases Goats from same herd USA Michigan"
has been rejected by the moderator as not being appropriate for inclusion on the
site.
Dear Mr Singeltary,
Thank you for submitting your comment on BMC Veterinary Research article
(2011, 7:7). We have read your comment with interest but we feel that only the
authors of the article can answer your question about further investigation of
the route of infection of the five goats in Michigan. We advise that you contact
the authors directly rather than post a comment on the article.
With best wishes,
Maria
Maria Kowalczuk, PhD Deputy Biology Editor BMC-series Journals
BioMed Central 236 Gray's Inn Road London, WC1X 8HB
+44 20 3192 2000 (tel) +44 20 3192 2010 (fax)
W: www.biomedcentral.com E: Maria.Kowalczuk@biomedcentral.com
Any queries about this decision should be sent to
comments@biomedcentral.com
Regards
BMC Veterinary Research
SNIP...PLEASE SEE FULL TEXT ;
Tuesday, February 01, 2011
Sparse PrP-Sc accumulation in the placentas of goats with naturally
acquired scrapie
Research article
Thursday, March 29, 2012
atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012
NIAA Annual Conference April 11-14, 2011San Antonio, Texas
***SCRAPIE GOATS CALIFORNIA 13 CASES TO DATE ! ***
***SCRAPIE GOATS MICHIGAN 8 CASES TO DATE ! ***
(an unusually high amount of scrapie documented in goats for a happenstance
of bad luck, or spontaneous event, THAT DOES NOT HAPPEN IN OTHER STATES ??? )
TSS