Characterisation of an Unusual TSE in a Goat by Transmission in Knock-in
Transgenic Mice
Rona Wilson, Declan King, Nora Hunter, Wilfred Goldmann and Rona M. Barron1
+ Author Affiliations
Neurobiology Division, The Roslin Institute and R(D)SVS, University of
Edinburgh, Roslin, Midlothian ↵1 E-mail: rona.barron@roslin.ed.ac.uk Received 18
January 2013. Accepted 24 May 2013.
Abstract
Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative
disorder of cattle, and its transmission to humans through contaminated food is
thought to be the cause of the variant form of Creutzfeldt-Jakob disease (vCJD).
BSE is believed to have spread from the recycling in cattle of ruminant tissue
in meat and bone meal (MBM), however during this time sheep and goats were also
exposed to BSE-contaminated MBM. Both sheep and goats are experimentally
susceptible to BSE, and while there have been no reported natural BSE cases in
sheep, two goat BSE field cases have been documented. While cases of BSE are
rare in small ruminants, the existence of scrapie in both sheep and goats is
well established. In the UK, during 2006-2007, a serious outbreak of clinical
scrapie was detected in a large dairy goat herd. Subsequently, 200 goats were
selected for post-mortem examinations, one of which showed biochemical and
immunohistochemical features of the disease associated prion protein (PrPTSE)
which differed from all other infected goats. In the present study we
investigated this unusual case by performing bioassays into a panel of mouse
lines. Following characterisation, we found that strain properties such as the
ability to transmit to different mouse lines, lesion profile pattern, degree of
PrP deposition in the brain and biochemical features of this unusual goat case
were neither consistent with goat BSE nor with a goat scrapie herdmate control.
However our results suggest this unusual case has BSE-like properties and
highlights the need for continued surveillance.
Published Date: 2012-01-04 17:44:07 Subject: PRO/AH/EDR> Prion Disease
update 2012 (01) Archive Number: 20120104.0027
PRION DISEASE UPDATE 2012 (01) ******************************
[2] UK: caprine BSE
Date: Sat 3 Dec 2011
Source: Emerging Infectious Diseases 17(12) 12 [edited] http://wwwnc.cdc.gov/eid/article/17/12/11-0333_article.htm
Isolation of prion with BSE properties from farmed goat
-------------------------------------------------------
[Authors: Spiropoulos J, Lockey R, Sallis RE, Terry LA, Thorne L, Holder
TM, et al. Animal Health and Veterinary Laboratories Agency, Weybridge, Surrey,
UK]
Abstract
--------
Transmissible spongiform encephalopathies are fatal neurodegenerative
diseases that include variant Creutzfeldt-Jakob disease in humans, scrapie in
small ruminants, and bovine spongiform encephalopathy (BSE) in cattle. Scrapie
is not considered a public health risk, but BSE has been linked to variant
Creutzfeldt-Jakob disease. Small ruminants are susceptible to BSE, and in 2005
BSE was identified in a farmed goat in France. We confirm another BSE case in a
goat in which scrapie was originally diagnosed and retrospectively identified as
suspected BSE. The prion strain in this case was further characterized by mouse
bioassay after extraction from formaldehyde-fixed brain tissue embedded in
paraffin blocks. Our data show that BSE can infect small ruminants under natural
conditions and could be misdiagnosed as scrapie. Surveillance should continue so
that another outbreak of this zoonotic transmissible spongiform encephalopathy
can be prevented and public health safeguarded.
Transmissible spongiform encephalopathies (TSEs) are fatal diseases
characterized by neurodegenerative changes in the central nervous system that
include vacuolation, gliosis, and accumulation of an abnormal isoform (PrPSc) of
a naturally occurring host-encoded protein (PrPC) (1). According to the prion
hypothesis, PrPSc is the major or the sole infectious agent (1). Although this
hypothesis has not received universal acceptance, PrPScis ubiquitous in all
known naturally occurring TSEs, and its detection is widely used for their
diagnosis.
Bovine spongiform encephalopathy (BSE), a TSE of cattle, was first detected
in 1986 (2) and has since been linked with emerging TSEs in other species (3,4)
including humans (5,6). Because of its ability to cross species barriers and
particularly its zoonotic potential, BSE is considered a public health risk, and
extensive measures have been established to detect and eliminate the disease.
Scrapie, a naturally occurring TSE affecting small ruminants, has been
known for centuries (7) and is not considered to pose a public health risk (8).
Under experimental conditions, however, small ruminants are susceptible to BSE,
with pathogenesis and clinical signs that are not readily distinguishable from
scrapie (9-12). Additionally, the fact that small ruminants were exposed to
BSE-contaminated food before the exclusion of meat and bone meal from ruminant
feedstuffs led to the possibility that sheep and goats on commercial farms could
be affected by BSE that could be misdiagnosed as scrapie (13,14). The response
to this potential risk was the implementation of extensive statutory active
surveillance, elimination, and breeding for resistance programs in the European
Union (EU).
In 2005, as part of a review of historical TSE-positive cases of sheep and
goats in France, a specimen from a goat slaughtered for human consumption in
2002 was reported to be "indistinguishable from a BSE isolate on the basis of
all identification criteria available." (15). In response to this report, 2
retrospective studies were initiated in the United Kingdom to analyze archived
samples from goat cases that were initially diagnosed as scrapie (16,17).
Because only fixed material was available, both studies had to use differential
immunohistochemical analysis (D-IHC), a technique that can discriminate scrapie
from experimentally induced BSE in sheep (18). These studies identified a single
case, originally diagnosed in 1990 as scrapie, that had a D-IHC signature
indistinguishable from BSE (16).
Given the wide phenotypic variance of scrapie in sheep and our limited
knowledge of this variance in goats, the D-IHC result on its own was
insufficient for an unequivocal diagnosis. In accordance with EU regulation
36/2005 (19), the case was referred to the EU Reference Laboratory Strain Typing
Expert Group, which recommended further investigation by bioassay.
Bioassay is conventionally undertaken by using unfixed tissues to prepare
inocula. Much historical tissue is available only as formalin fixed or formalin
fixed and paraffin wax embedded. TSE infectivity persists in such material but
with a lower infectious titer than with unfixed frozen tissue (20). However, the
potential effects on biological activity, and therefore strain characterization,
of fixation and processing are unknown. Thus, further investigation of this case
required an extensive panel of controls. We report the results of the bioassay
analysis and confirm the diagnosis of BSE in a goat in the United Kingdom.
-- Communicated by: Terry S Singeltary Sr flounder9@verizon.net
[Interested readers should access the original text via the source URL
above to view the full text an the references cited. The following has been
extracted from the Discussion.
"The 2 cases of naturally occurring BSE in small ruminants, the one
reported here and the one identified in France (15), occurred in different
countries, during different time periods, and before strict BSE control measures
were fully implemented. Therefore, the most likely origin of these 2 cases would
be exposure to BSE-contaminated food supplements. Although in France goats
constitute 14.3 percent of the small ruminant population, in the United Kingdom
they account for only 0.3 percent of small ruminants. It is intriguing,
therefore, that the only naturally occurring BSE cases in small ruminants in
France and particularly in the United Kingdom were detected in goats and not in
sheep, although they have also been exposed to contaminated food supplements. A
possible explanation could be that goats are generally managed more intensively
than sheep and thus might have been exposed to higher doses of the infectious
agent because of the more frequent use of concentrates in intensive dairy
farming. Similar observations have been reported in cattle, in which the
incidence of BSE was significantly higher in dairy herds and in which management
is much more intensive than in beef herds (34). In the United Kingdom, most of
the commercial goat herds are kept for milk production in a typically intensive
production system, similar to dairy cattle.
The BSE case we have confirmed was 1 of 26 historic goat samples examined
in the United Kingdom collected during 1984-2002 (16,17). Since 1993, scrapie in
goats has been a notifiable disease in the United Kingdom, and since 2005,
samples from all suspected cases of TSE in small ruminants are required to be
tested for BSE-like features by using Western blotting (WB) (19). No BSE cases
have been identified, although an intermediate case in a goat was reported and
is under investigation by bioassay for final resolution (35,36). This screening
of brain samples from all small ruminant cases offers reassurance that BSE is
not present in the contemporary small ruminant population. However, application
of WB to sheep experimentally co-infected with BSE and scrapie detected only the
scrapie agent (37). Also, in contrast to BSE, where infectivity is mainly
confined to the nervous system, in small ruminants the BSE agent is widely
distributed in peripheral tissues and can be transmitted horizontally (11,38).
Therefore, feed ban measures alone would be inadequate to control a BSE outbreak
in small ruminants. Also, it would be impossible to prevent BSE from entering
the human food chain through consumption of food products derived from small
ruminants.
Because TSEs in goats are still a problem, particularly in Mediterranean
countries, our data suggest that extensive surveillance and breeding schemes
must remain in place to prevent a BSE outbreak in small ruminants and to
safeguard public health. This report also highlights several issues regarding
the use of mouse bioassay to identify TSE strains. As governing bodies seek
confirmation of equivocal cases that are identified worldwide, they must be
aware of the limitations, cost, and timescale demands of confirming such cases."
- Mod.CP]
[See http://healthmap.org/r/1lNY
for the interactive HealthMap/ProMED map of the United Kingdom. - Mod.MPP]
******
snip...
******
[5]
Switzerland: BSE Date: Fri 16 Dec 2011 Source: Prionics AG, e-scope
newsletter [edited] http://escope.prionics.com/issue/2011-december-4/
In spring 2011, 2 new cases of BSE were discovered in Switzerland [see
ProMED-mail posting Prion disease update 2011 (10) 20111107.3317]. Both cases
were detected using the Prionics(R)-Check BSE tests. A report has now been
published showing that these cases represent a novel type of BSE. What are the
consequences of these new BSE cases?
After a period of 4 years without BSE positive cows, in spring this year
[2011] Switzerland was shaken by the discovery of 2 new BSE cases detected only
one month apart from each other. The cases appeared in different areas of
Switzerland and involved animals aged 8 and 15 years, which were tested with the
Prionics(R)-Check BSE tests as part of the active disease surveillance program.
Bettina Bernhard, Head of the Prionics diagnostic laboratory reported that: "It
was the 1st time in 4.5 years that we had found a BSE positive sample in our
laboratory. Based on the results from the Prionics(R)-Check WESTERN, we
immediately saw that the fingerprint of the prion protein was not that of the
classical BSE cases we have detected before. We then informed the Swiss National
Reference Laboratory and veterinary authorities and the positive result was
confirmed with the Prionics(R)-Check PrioSTRIP."
Novel type of BSE?
------------------
BSE cases that differ from the classical BSE strain have been detected
before, however, with low incidence. These atypical strains, designated
BASE/L-BSE and H-BSE, were first reported in 2004 in Italy and France. Both
strains were detected as part of routine surveillance using the
Prionics(R)-Check WESTERN and ELISA tests. The recent publication by Torsten
Seuberlich of the Swiss National and OIE [World Organisation for Animal Health]
Reference Laboratories for BSE and Scrapie and his colleagues, is showing that
these 2 Swiss cases not only differ from classical BSE, but also from the
atypical BSE cases found in other countries. It appears that the 2 BSE cases
detected in Switzerland seem to represent a novel type of atypical BSE. Dr
Seuberlich explains: "We are now undertaking further investigations into these 2
cases and until there is more clarity, surveillance should continue to be
carried out at a high level and disease awareness should be increased.
Furthermore, we have to ensure that diagnostic techniques are applied that
identify such cases."
Continued vigilance needed
--------------------------
Whereas consumption of meat from cows affected by classical BSE has been
associated with vCJD, the public health hazard from atypical BSE is unclear.
Little is known about its origin and whether it can be transmitted to other
animals. These cases show, however, that BSE has not been completely eradicated
and that the disease can continue to occur even with current preventive measures
(such as the meat-and-bone meal ban) in place. The appearance of new strains of
the prion protein could also indicate that BSE is still evolving. Continuous
monitoring will be needed to keep these new strains under surveillance.
-- Communicated by: Terry S Singeltary Sr flounder9@verizon.net
[[See http://healthmap.org/r/1AFv for the
interactive HealthMap/ProMED map of Switzerland. - Mod.MPP]
Wednesday, January 18, 2012
BSE IN GOATS CAN BE MISTAKEN FOR SCRAPIE February 1, 2012
Saturday, December 3, 2011
Isolation of Prion with BSE Properties from Farmed Goat Volume 17, Number
12—December 2011
Sunday, October 3, 2010
Scrapie, Nor-98 atypical Scrapie, and BSE in sheep and goats North America,
who's looking ?
Tuesday, February 01, 2011
Sparse PrP-Sc accumulation in the placentas of goats with naturally
acquired scrapie
Research article
Thursday, June 2, 2011
USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES
Pennsylvania AND California
UPDATE PLEASE NOTE ;
AS of June 30, 2011,
snip...
INCLUDING 10 POSITIVE GOATS FROM THE SAME HERD (FIGURE 7).
snip...
see updated APHIS scrapie report ;
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
Thursday, January 07, 2010
Scrapie and Nor-98 Scrapie November 2009 Monthly Report Fiscal Year 2010
and FISCAL YEAR 2008
In FY 2010, 72 cases of classical Scrapie and 5 cases of Nor-98 like
Scrapie were confirmed...
Scrapie Nor-98 like case in California FY 2011 AS of December 31,
2010.
Scrapie cases in goats FY 2002 - 2011 AS of December 31, 2010 Total goat
cases = 21 Scrapie cases, 0 Nor-98 like Scrapie cases (21 field cases, 0 RSSS
cases)
Last herd with infected goats disignated in FY 2008 Michigan 8 cases
Tuesday, February 01, 2011
Sparse PrP-Sc accumulation in the placentas of goats with naturally
acquired scrapie
Research article
"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...
Scrapie Nor-98 like case in California FY 2011 AS of December 31,
2010.
Scrapie cases in goats FY 2002 - 2011 AS of December 31, 2010 Total goat
cases = 21 Scrapie cases, 0 Nor-98 like Scrapie cases (21 field cases, 0 RSSS
cases)
Last herd with infected goats disignated in FY 2008 Michigan 8 cases
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
Scrapie Nor-98 like case in California FY 2011 AS of December 31, 2010.
Scrapie cases in goats FY 2002 - 2011 AS of December 31, 2010 Total goat
cases = 21 Scrapie cases, 0 Nor-98 like Scrapie cases (21 field cases, 0 RSSS
cases)
Last herd with infected goats disignated in FY 2008 Michigan 8 cases
Thursday, November 18, 2010
Increased susceptibility of human-PrP transgenic mice to bovine spongiform
encephalopathy following passage in sheep
Monday, March 21, 2011
Sheep and Goat BSE Propagate More Efficiently than Cattle BSE in Human PrP
Transgenic Mice
*** Most recent positive goat confirmed in April 2013.
Scrapie Cases in Goats FY 2002 – FY 2013 As of April 30, 2013
***SCRAPIE GOATS CALIFORNIA 13 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 ??? )
Thursday, November 18, 2010
Increased susceptibility of human-PrP transgenic mice to bovine spongiform
encephalopathy following passage in sheep
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH
CODE
Thursday, December 20, 2012
OIE GROUP RECOMMENDS THAT SCRAPE PRION DISEASE BE DELISTED AND SAME OLD BSe
WITH BOVINE MAD COW DISEASE
*** The discovery of previously unrecognized prion diseases in both humans
and animals (i.e., Nor98 in small ruminants) demonstrates that the range of
prion diseases might be wider than expected and raises crucial questions about
the epidemiology and strain properties of these new forms. We are investigating
this latter issue by molecular and biological comparison of VPSPr, GSS and
Nor98.
Tuesday, April 30, 2013
Transmission of classical scrapie via goat milk
Veterinary Record2013;172:455 doi:10.1136/vr.f2613
ALSO, SEE CALIFORNIA AND MICHIGAN FOR THE HIGH SCRAPIE RATE IN GOATS
???
THIS needs to be addressed immediately, as to find the source, route,
cause, from this unusual event...tss
Wednesday, November 28, 2012
Scientific and technical assistance on the provisional results of the study
on genetic resistance to Classical scrapie in goats in Cyprus 1
SCIENTIFIC REPORT OF EFSA
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
*** The discovery of previously unrecognized prion diseases in both humans
and animals (i.e., Nor98 in small ruminants) demonstrates that the range of
prion diseases might be wider than expected and raises crucial questions about
the epidemiology and strain properties of these new forms. We are investigating
this latter issue by molecular and biological comparison of VPSPr, GSS and
Nor98.
OR-10: Variably protease-sensitive prionopathy is transmissible in bank
voles
Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1
Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan
Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome,
Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna,
Italy; 3Case Western Reserve University; Cleveland, OH USA
Background. Variably protease-sensitive prionopathy (VPSPr) is a recently
described “sporadic”neurodegenerative disease involving prion protein
aggregation, which has clinical similarities with non-Alzheimer dementias, such
as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in
Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the
prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is
the electrophoretic pattern of PrPSc after digestion with proteinase K (PK).
After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern
similar to that described in GSS cases. The clinical and pathological features
of VPSPr raised the question of the correct classification of VPSPr among prion
diseases or other forms of neurodegenerative disorders. Here we report
preliminary data on the transmissibility and pathological features of VPSPr
cases in bank voles.
Materials and Methods. Seven VPSPr cases were inoculated in two genetic
lines of bank voles, carrying either methionine or isoleucine at codon 109 of
the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases
selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical
diagnosis in voles was confirmed by brain pathological assessment and western
blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.
Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission
in BvM109. Overall, 3 voles were positive with survival time between 290 and 588
d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form
of the typical PrP27–30, which was indistinguishable to that previously observed
in BvM109 inoculated with sCJDMM1 cases.
In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until
now. Overall, 5 voles were positive with survival time between 281 and 596
d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like
PrPSc electrophoretic pattern, characterized by low molecular weight PrPres.
These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative
with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus
and the N-terminus. Second passages are in progress from these first successful
transmissions.
Conclusions. Preliminary results from transmission studies in bank voles
strongly support the notion that VPSPr is a transmissible prion disease.
Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of
voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109.
The discovery of previously unrecognized prion diseases in both humans and
animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion
diseases might be wider than expected and raises crucial questions about the
epidemiology and strain properties of these new forms. We are investigating this
latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.
Wednesday, March 28, 2012
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE, price of prion
poker goes up again $
*** The discovery of previously unrecognized prion diseases in both humans
and animals (i.e., Nor98 in small ruminants) demonstrates that the range of
prion diseases might be wider than expected and raises crucial questions about
the epidemiology and strain properties of these new forms. We are investigating
this latter issue by molecular and biological comparison of VPSPr, GSS and
Nor98.
Increased Atypical Scrapie Detections
Press reports indicate that increased surveillance is catching what
otherwise would have been unreported findings of atypical scrapie in sheep. In
2009, five new cases have been reported in Quebec, Ontario, Alberta, and
Saskatchewan. With the exception of Quebec, all cases have been diagnosed as
being the atypical form found in older animals. Canada encourages producers to
join its voluntary surveillance program in order to gain scrapie-free status.
The World Animal Health will not classify Canada as scrapie-free until no new
cases are reported for seven years. The Canadian Sheep Federation is calling on
the government to fund a wider surveillance program in order to establish the
level of prevalence prior to setting an eradication date. Besides long-term
testing, industry is calling for a compensation program for farmers who report
unusual deaths in their flocks.
Thursday, March 29, 2012
atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012
NIAA Annual Conference April 11-14, 2011San Antonio, Texas
Monday, April 25, 2011
Experimental Oral Transmission of Atypical Scrapie to Sheep
Volume 17, Number 5-May 2011 However, work with transgenic mice has
demonstrated the potential susceptibility of pigs, with the disturbing finding
that the biochemical properties of the resulting PrPSc have changed on
transmission (40).
***The pathology features of Nor98 in the cerebellum of the affected sheep
showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.
*** Intriguingly, these conclusions suggest that some pathological features
of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.
119
*** These observations support the view that a truly infectious TSE agent,
unrecognized until recently, infects sheep and goat flocks and may have
important implications in terms of scrapie control and public health.
Surprisingly the TSE agent characteristics were dramatically different
v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and
biochemical characteristics similar to those of atypical BSE L in the same mouse
model. Moreover, whereas no other TSE agent than BSE were shown to transmit into
Tg porcine mice, atypical scrapie was able to develop into this model, albeit
with low attack rate on first passage.
Furthermore, after adaptation in the porcine mouse model this prion showed
similar biological and biochemical characteristics than BSE adapted to this
porcine mouse model. Altogether these data indicate.
(i) the unsuspected potential abilities of atypical scrapie to cross
species barriers
(ii) the possible capacity of this agent to acquire new characteristics
when crossing species barrier
These findings raise some interrogation on the concept of TSE strain and on
the origin of the diversity of the TSE agents and could have consequences on
field TSE control measures.
Friday, February 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
RESEARCH
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 5, May 2011
Experimental Oral Transmission of Atypical Scrapie to Sheep
Marion M. Simmons, S. Jo Moore,1 Timm Konold, Lisa Thurston, Linda A.
Terry, Leigh Thorne, Richard Lockey, Chris Vickery, Stephen A.C. Hawkins,
Melanie J. Chaplin, and John Spiropoulos
To investigate the possibility of oral transmission of atypical scrapie in
sheep and determine the distribution of infectivity in the animals’ peripheral
tissues, we challenged neonatal lambs orally with atypical scrapie; they were
then killed at 12 or 24 months. Screening test results were negative for
disease-specifi c prion protein in all but 2 recipients; they had positive
results for examination of brain, but negative for peripheral tissues.
Infectivity of brain, distal ileum, and spleen from all animals was assessed in
mouse bioassays; positive results were obtained from tissues that had negative
results on screening. These fi ndings demonstrate that atypical scrapie can be
transmitted orally and indicate that it has the potential for natural
transmission and iatrogenic spread through animal feed. Detection of infectivity
in tissues negative by current surveillance methods indicates that diagnostic
sensitivity is suboptimal for atypical scrapie, and potentially infectious
material may be able to pass into the human food chain.
SNIP...
Although we do not have epidemiologic evidence that supports the effi cient
spread of disease in the fi eld, these data imply that disease is potentially
transmissible under fi eld situations and that spread through animal feed may be
possible if the current feed restrictions were to be relaxed. Additionally,
almost no data are available on the potential for atypical scrapie to transmit
to other food animal species, certainly by the oral route. However, work with
transgenic mice has demonstrated the potential susceptibility of pigs, with the
disturbing fi nding that the biochemical properties of the resulting PrPSc have
changed on transmission (40). The implications of this observation for
subsequent transmission and host target range are currently unknown.
How reassuring is this absence of detectable PrPSc from a public health
perspective? The bioassays performed in this study are not titrations, so the
infectious load of the positive gut tissues cannot be quantifi ed, although
infectivity has been shown unequivocally. No experimental data are currently
available on the zoonotic potential of atypical scrapie, either through
experimental challenge of humanized mice or any meaningful epidemiologic
correlation with human forms of TSE. However, the detection of infectivity in
the distal ileum of animals as young as 12 months, in which all the tissues
tested were negative for PrPSc by the currently available screening and confi
rmatory diagnostic tests, indicates that the diagnostic sensitivity of current
surveillance methods is suboptimal for detecting atypical scrapie and that
potentially infectious material may be able to pass into the human food chain
undetected.
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 5, May 2011
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly would likely
create alarm in some circles even if the result could not be interpreted for
man. I have a view that all these agents could be transmitted provided a large
enough dose by appropriate routes was given and the animals kept long enough.
Until the mechanisms of the species barrier are more clearly understood it might
be best to retain that hypothesis.
snip...
R. BRADLEY
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to
nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep
and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were
exposed to the infectious agents only by their nonforced consumption of known
infectious tissues. The asymptomatic incubation period in the one monkey exposed
to the virus of kuru was 36 months; that in the two monkeys exposed to the virus
of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the
two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively.
Careful physical examination of the buccal cavities of all of the monkeys failed
to reveal signs or oral lesions. One additional monkey similarly exposed to kuru
has remained asymptomatic during the 39 months that it has been under
observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie
by natural feeding to squirrel monkeys that we have reported provides further
grounds for concern that scrapie-infected meat may occasionally give rise in
humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
Recently the question has again been brought up as to whether scrapie is
transmissible to man. This has followed reports that the disease has been
transmitted to primates. One particularly lurid speculation (Gajdusek 1977)
conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and
transmissible encephalopathy of mink are varieties of a single "virus". The U.S.
Department of Agriculture concluded that it could "no longer justify or permit
scrapie-blood line and scrapie-exposed sheep and goats to be processed for human
or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is
emphasised by the finding that some strains of scrapie produce lesions identical
to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be
transmissible to man raises two considerations. First, the safety of laboratory
personnel requires prompt attention. Second, action such as the "scorched meat"
policy of USDA makes the solution of the acrapie problem urgent if the sheep
industry is not to suffer grievously.
snip...
76/10.12/4.6
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC.
Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK
National Institute of Neurological Diseases and Stroke, National Institutes
of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey
(Macaca fascicularis) with an incubation period of more than 5 yr from the time
of intracerebral inoculation of scrapie-infected mouse brain. The animal
developed a chronic central nervous system degeneration, with ataxia, tremor and
myoclonus with associated severe scrapie-like pathology of intensive astroglial
hypertrophy and proliferation, neuronal vacuolation and status spongiosus of
grey matter. The strain of scrapie virus used was the eighth passage in Swiss
mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral
passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton,
Berkshire).
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. Subscribe and get 4 free issues. FOUR years ago, Terry Singeltary
watched his mother die horribly from a degenerative brain disease. Doctors told
him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit
her violent symptoms, and he demanded an autopsy. It showed she had died of
sporadic Creutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming by
chance into a killer. But Singeltary thinks otherwise. He is one of a number of
campaigners who say that some sCJD, like the variant CJD related to BSE, is
caused by eating meat from infected animals. Their suspicions have focused on
sheep carrying scrapie, a BSE-like disease that is widespread in flocks across
Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight
to the campaigners' fears. To their complete surprise, the researchers found
that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by
some strains of scrapie," says team member Jean-Philippe Deslys of the French
Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses,
south-west of Paris. Hans Kretschmar of the University of Göttingen, who
coordinates CJD surveillance in Germany, is so concerned by the findings that he
now wants to trawl back through past sCJD cases to see if any might have been
caused by eating infected mutton or lamb.
Scrapie has been around for centuries and until now there has been no
evidence that it poses a risk to human health. But if the French finding means
that scrapie can cause sCJD in people, countries around the world may have
overlooked a CJD crisis to rival that caused by BSE.
Deslys and colleagues were originally studying vCJD, not sCJD. They
injected the brains of macaque monkeys with brain from BSE cattle, and from
French and British vCJD patients. The brain damage and clinical symptoms in the
monkeys were the same for all three. Mice injected with the original sets of
brain tissue or with infected monkey brain also developed the same
symptoms.
As a control experiment, the team also injected mice with brain tissue from
people and animals with other prion diseases: a French case of sCJD; a French
patient who caught sCJD from human-derived growth hormone; sheep with a French
strain of scrapie; and mice carrying a prion derived from an American scrapie
strain. As expected, they all affected the brain in a different way from BSE and
vCJD. But while the American strain of scrapie caused different damage from
sCJD, the French strain produced exactly the same pathology.
"The main evidence that scrapie does not affect humans has been
epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute
for Animal Health in Edinburgh, who was a member of the same team as Deslys.
"You see about the same incidence of the disease everywhere, whether or not
there are many sheep, and in countries such as New Zealand with no scrapie." In
the only previous comparisons of sCJD and scrapie in mice, Bruce found they were
dissimilar.
But there are more than 20 strains of scrapie, and six of sCJD. "You would
not necessarily see a relationship between the two with epidemiology if only
some strains affect only some people," says Deslys. Bruce is cautious about the
mouse results, but agrees they require further investigation. Other trials of
scrapie and sCJD in mice, she says, are in progress.
People can have three different genetic variations of the human prion
protein, and each type of protein can fold up two different ways. Kretschmar has
found that these six combinations correspond to six clinical types of sCJD: each
type of normal prion produces a particular pathology when it spontaneously
deforms to produce sCJD.
But if these proteins deform because of infection with a disease-causing
prion, the relationship between pathology and prion type should be different, as
it is in vCJD. "If we look at brain samples from sporadic CJD cases and find
some that do not fit the pattern," says Kretschmar, "that could mean they were
caused by infection."
There are 250 deaths per year from sCJD in the US, and a similar incidence
elsewhere. Singeltary and other US activists think that some of these people
died after eating contaminated meat or "nutritional" pills containing dried
animal brain. Governments will have a hard time facing activists like Singeltary
if it turns out that some sCJD isn't as spontaneous as doctors have
insisted.
Deslys's work on macaques also provides further proof that the human
disease vCJD is caused by BSE. And the experiments showed that vCJD is much more
virulent to primates than BSE, even when injected into the bloodstream rather
than the brain. This, says Deslys, means that there is an even bigger risk than
we thought that vCJD can be passed from one patient to another through
contaminated blood transfusions and surgical instruments.
Monday, December 14, 2009
Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease
Are Encoded by Distinct Prion Types
(hmmm, this is getting interesting now...TSS)
Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine
(reticular) deposits,
see also ;
All of the Heidenhain variants were of the methionine/ methionine type 1
molecular subtype.
see full text ;
Monday, December 14, 2009
Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease
Are Encoded by Distinct Prion Types
Friday, March 09, 2012
Experimental H-type and L-type bovine spongiform encephalopathy in cattle:
observation of two clinical syndromes and diagnostic challenges
Research article
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by
plaques and glial- and stellate-type prion protein deposits
Thursday, February 14, 2013
*** The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE
and TSE prion disease
Tuesday, March 5, 2013
Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening
of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)
FDA believes current regulation protects the public from BSE but reopens
comment period due to new studies
Tuesday, March 05, 2013
A closer look at prion strains Characterization and important implications
Prion 7:2, 99–108; March/April 2013; © 2013 Landes Bioscience
Tuesday, May 28, 2013
Late-in-life surgery associated with Creutzfeldt-Jakob disease: a
methodological outline for evidence-based guidance
Thursday, May 30, 2013
World Organization for Animal Health (OIE) has upgraded the United States'
risk classification for mad cow disease to "negligible" from "controlled", and
risk further exposing the globe to the TSE prion mad cow type disease
U.S. gets top mad-cow rating from international group and risk further
exposing the globe to the TSE prion mad cow type disease
TSS
