Susceptibility of cattle to the agent of chronic wasting disease from elk after intracranial inoculation
ARS VIRUS AND PRION RESEARCH / Research / Publication #277212
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Susceptibility of cattle to the agent of chronic wasting disease
from elk after intracranial inoculation
Authors
item Greenlee, Justin item Nicholson, Eric item Smith, Jodi item Kunkle,
Robert item Hamir, Amirali
Submitted to: Journal of Veterinary Diagnostic Investigation Publication
Type: Peer Reviewed Journal Publication Acceptance
Date: July 12, 2012
Publication Date: November 1, 2012
Citation: Greenlee, J.J., Nicholson, E.M., Smith, J.D., Kunkle, R.A.,
Hamir, A.N. 2012.
Susceptibility of cattle to the agent of chronic wasting disease from elk
after intracranial inoculation.
Journal of Veterinary Diagnostic Investigation. 24(6):1087-1093.
Interpretive Summary: Chronic Wasting Disease (CWD), a fatal
neurodegenerative disease that occurs in farmed and wild cervids (deer and elk)
of North America, is a transmissible spongiform encephalopathy (TSE). TSEs are
caused by infectious proteins called prions that are resistant to various
methods of decontamination and environmental degradation. Cattle could be
exposed to chronic wasting disease (CWD) by contact with infected farmed or
free-ranging cervids. The purpose of this study was to assess the potential
transmission of CWD from elk to cattle after intracranial inoculation, the most
direct route to test the potential of a host to replicate an isolate of the
prion agent. This study reports that only 2 of 14 calves inoculated with CWD
from elk had clinical signs or evidence of abnormal prion protein accumulation.
These results suggest that cattle are unlikely to be susceptible to CWD if
inoculated by a more natural route. This information could have an impact on
regulatory officials developing plans to reduce or eliminate TSEs and farmers
with concerns about ranging cattle on areas where CWD may be present.
Technical Abstract:
***Cattle could be exposed to the agent of chronic wasting disease (CWD) through contact with infected farmed or free-ranging cervids or exposure to contaminated premises. The purpose of this study was to assess the potential for CWD derived from elk to transmit to cattle after intracranial inoculation. Calves (n=14) were inoculated with brain homogenate derived from elk with CWD to determine the potential for transmission and define the clinicopathologic features of disease.
Technical Abstract:
***Cattle could be exposed to the agent of chronic wasting disease (CWD) through contact with infected farmed or free-ranging cervids or exposure to contaminated premises. The purpose of this study was to assess the potential for CWD derived from elk to transmit to cattle after intracranial inoculation. Calves (n=14) were inoculated with brain homogenate derived from elk with CWD to determine the potential for transmission and define the clinicopathologic features of disease.
Cattle were necropsied if clinical signs occurred or at the termination of
experiment (49 months post-inoculation (MPI)).
Clinical signs of poor appetite, weight loss, circling, and bruxism
occurred in two cattle (14%) at 16 and 17 MPI, respectively.
Accumulation of abnormal prion protein (PrP**Sc) in these cattle was
confined to the central nervous system with the most prominent immunoreactivity
in midbrain, brainstem, and hippocampus with lesser immunoreactivity in the
cervical spinal cord.
*** The rate of transmission was lower than in cattle inoculated with CWD
derived from mule deer (38%) or white-tailed deer (86%).
Additional studies are required to fully assess the potential for cattle to
develop CWD through a more natural route of exposure, but a low rate of
transmission after intracranial inoculation suggests that risk of transmission
through other routes is low.
***A critical finding here is that if CWD did transmit to exposed cattle, currently used diagnostic techniques would detect and differentiate it from other prion diseases in cattle based on absence of spongiform change, distinct pattern of PrP**Sc deposition, and unique molecular profile.
***A critical finding here is that if CWD did transmit to exposed cattle, currently used diagnostic techniques would detect and differentiate it from other prion diseases in cattle based on absence of spongiform change, distinct pattern of PrP**Sc deposition, and unique molecular profile.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Project Number: 5030-32000-103-00
Project Type: Appropriated
Start Date: Oct 01, 2011 End Date: Sep 30, 2016
Objective: 1. Investigate the pathobiology of atypical transmissible
spongiform encephalopathies (TSEs) in natural hosts. A. Investigate the
pathobiology of atypical scrapie. B. Investigate the pathobiology of atypical
bovine spongiform encephalopathy (BSE). 2. Investigate the horizontal
transmission of TSEs. A. Assess the horizontal transmission of sheep scrapie in
the absence of lambing. B. Determine routes of transmission in chronic wasting
disease (CWD) infected premises. C. Assess oral transmission of CWD in reindeer.
3. Investigate determinants of CWD persistence. A. Determine CWD host range
using natural routes of transmission. B. Investigate the pathobiology of CWD.
Approach: The studies will focus on three animal transmissible spongiform
encephalopathy (TSE) agents found in the United States: bovine spongiform
encephalopathy (BSE); scrapie of sheep and goats; and chronic wasting disease
(CWD) of deer, elk, and moose. The research will address sites of accumulation,
routes of infection, environmental persistence, and ante mortem diagnostics with
an emphasis on controlled conditions and natural routes of infection. Techniques
used will include clinical exams, histopathology, immunohistochemistry and
biochemical analysis of proteins. The enhanced knowledge gained from this work
will help mitigate the potential for unrecognized epidemic expansions of these
diseases in populations of animals that could either directly or indirectly
affect food animals.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES 2014 Annual Report
1a.Objectives (from AD-416): 1. Investigate the pathobiology of atypical
transmissible spongiform encephalopathies (TSEs) in natural hosts. A.
Investigate the pathobiology of atypical scrapie. B. Investigate the
pathobiology of atypical bovine spongiform encephalopathy (BSE). 2. Investigate
the horizontal transmission of TSEs. A. Assess the horizontal transmission of
sheep scrapie in the absence of lambing. B. Determine routes of transmission in
chronic wasting disease (CWD) infected premises. C. Assess oral transmission of
CWD in reindeer. 3. Investigate determinants of CWD persistence. A. Determine
CWD host range using natural routes of transmission. B. Investigate the
pathobiology of CWD.
1b.Approach (from AD-416): The studies will focus on three animal
transmissible spongiform encephalopathy (TSE) agents found in the United States:
bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; and chronic
wasting disease (CWD) of deer, elk, and moose. The research will address sites
of accumulation, routes of infection, environmental persistence, and ante mortem
diagnostics with an emphasis on controlled conditions and natural routes of
infection. Techniques used will include clinical exams, histopathology,
immunohistochemistry and biochemical analysis of proteins. The enhanced
knowledge gained from this work will help mitigate the potential for
unrecognized epidemic expansions of these diseases in populations of animals
that could either directly or indirectly affect food animals.
3.Progress Report: Research efforts directed toward meeting objective 1 of
our project plan, Investigate the pathobiology of atypical transmissible
spongiform encephalopathies (TSEs) in natural hosts, include work in previous
years starting with the inoculation of animals for studies designed to address
the pathobiology of atypical scrapie, atypical bovine spongiform encephalopathy
(BSE), as well as a genetic version of BSE. Animals inoculated with atypical
scrapie have not yet developed disease. Atypical BSE animals have developed
disease and evaluation of the samples is currently underway. Animals inoculated
with a genetic version of BSE have developed disease and the manuscript has been
published (2012). In addition, we have investigated the possibility that
atypical scrapie was present earlier than previously detected in the national
flock by analyzing archived field isolates using methods that were unavailable
at the time of original diagnosis. Sample quality was sufficiently degraded that
modern methods were not suitable for evaluation. In research pertaining to
objective 2, Investigate the horizontal transmission of TSEs, we have initiated
a study to determine if cohousing non-lambing scrapie inoculated sheep is
sufficient to transmit scrapie to neonatal lambs. At this time, scrapie free
ewes have lambed in the presence of scrapie inoculated animals and the lambs are
cohoused with these inoculated animals.
4.Accomplishments 1. Evaluated enzyme immunoassay for rapid identification
of prion disease in livestock. Scrapie of sheep and bovine spongiform
encephalopathy of cattle are diseases that cause damage to the central nervous
system including the retina in the eye. The infectious agent is an abnormal
protein called a prion that has misfolded from its normal state and is resistant
to breakdown by the host cells. Current diagnostic methods require the testing
of brain material, which can be difficult to collect and may lead to
contamination of the environment and exposure of personnel to the infectious
agent. Eyes can be readily collected without opening the skull. ARS researchers
at Ames, Iowa demonstrated that the enzyme immunoassay results using eyes of
negative controls or samples collected from sheep or cattle with clinical signs
were in agreement with approved confirmatory assays (western blot or
immunohistochemistry). These results indicate the retina is a useful tissue for
rapid diagnosis of prion disease in clinically ill sheep and cattle and could be
considered to greatly increase the number of samples submitted for prion disease
diagnosis with a minimal investment of time and limited exposure of personnel to
prion agents.
2. Evaluated E211K cattle as a model for inherited human prion disease.
Prion diseases cause damage to the central nervous system of animals and humans.
The infectious agent is an abnormal protein called a prion that has misfolded
from its normal state and is resistant to breakdown by the host cells and thus
accumulates and damages those cells. Some forms of prion disease are genetic and
can be inherited. Current models of genetic prion disease in humans rely on
mouse models expressing either the human prion protein (E200K) or a combination
of both mouse and human sequences. In addition to being an entirely artificial
system these mouse models have a short lifespan making them a less than ideal
system to study a naturally occurring genetic disorder with a long incubation
time and late onset of disease. Cattle, however, exhibit a number of
similarities to humans with regard to prion disease and perhaps most notable is
the late onset of genetic prion disease. ARS researchers at Ames, Iowa have
produced cattle containing both 1 and 2 chromosome copies of the cattle prion
gene (E211K) and evaluated many aspects of this prion protein from cattle
including protein stability, protein expression levels and ratios, as well as
evidence of oxidative stress. Taken together, these results highlight the
differences between mouse models of genetic prion disease and a naturally
occurring prion disease system in cattle and suggest that cattle will provide a
more relevant understanding of genetic prion disease in humans than do current
rodent models.
Review Publications Smith, J.D., Greenlee, J.J. 2014. Detection of
misfolded prion protein in retina samples of sheep and cattle by use of a
commercially available enzyme immunoassay. American Journal of Veterinary
Research. 75(3):268-272.
Haldar, S., Beveridge, A.J., Wong, J., Singh, A.J., Galimberti, D.,
Borroni, D., Zhu, X., Blevins, J., Greenlee, J., Perry, G., Mukhopadhyay, C.K.,
Schmotzer, C., Singh, N. 2014. A low-molecular-weight ferroxidase is increased
in the CSF of sCJD Cases: CSF ferroxidase and transferrin as diagnostic
biomarkers for sCJD. Antioxidants & Redox Signaling. 19(14):1662-1675.
*** P.126: Successful transmission of chronic wasting disease (CWD) into
mice over-expressing bovine prion protein (TgSB3985) ***
Larisa Cervenakova,1 Christina J Sigurdson,2 Pedro Piccardo,3 Oksana
Yakovleva,1 Irina Vasilyeva,1 Jorge de Castro,1 Paula Saá,1 and Anton Cervenak1
1American Red Cross, Holland Laboratory; Rockville, MD USA; 2University of
California; San Diego, CA USA; 3Lab TSE/OBRR /CBER/FDA; Rockville, MD USA
Keywords: chronic wasting disease, transmission, transgenic mouse, bovine
prion protein
Background. CWD is a disease affecting wild and farmraised cervids in North
America. Epidemiological studies provide no evidence of CWD transmission to
humans. Multiple attempts have failed to infect transgenic mice expressing human
PRNP gene with CWD. The extremely low efficiency of PrPCWD to convert normal
human PrPC in vitro provides additional evidence that transmission of CWD to
humans cannot be easily achieved. However, a concern about the risk of CWD
transmission to humans still exists. This study aimed to establish and
characterize an experimental model of CWD in TgSB3985 mice with the following
attempt of transmission to TgHu mice.
Materials and Methods. TgSB3985 mice and wild-type FVB/ NCrl mice were
intracranially injected with 1% brain homogenate from a CWD-infected Tga20 mouse
(CWD/Tga20). TgSB3985 and TgRM (over-expressing human PrP) were similarly
injected with 5% brain homogenates from CWD-infected white-tailed deer (CWD/WTD)
or elk (CWD/Elk). Animals were observed for clinical signs of neurological
disease and were euthanized when moribund. Brains and spleens were removed from
all mice for PrPCWD detection by Western blotting (WB). A histological analysis
of brains from selected animals was performed: brains were scored for the
severity of spongiform change, astrogliosis, and PrPCWD deposition in ten brain
regions.
Results. Clinical presentation was consistent with TSE. More than 90% of
TgSB3985 and wild-type mice infected with CWD/Tga20, tested positive for PrPres
in the brain but only mice in the latter group carried PrPCWD in their spleens.
We found evidence for co-existence or divergence of two CWD/ Tga20 strains based
on biochemical and histological profiles. In TgSB3985 mice infected with CWD-elk
or CWD-WTD, no animals tested positive for PrPCWD in the brain or in the spleen
by WB. However, on neuropathological examination we found presence of amyloid
plaques that stained positive for PrPCWD in three CWD/WTD- and two
CWD/Elk-infected TgSB3985 mice. The neuropathologic profiles in CWD/WTD- and
CWD/Elkinfected mice were similar but unique as compared to profiles of BSE,
BSE-H or CWD/Tg20 agents propagated in TgSB3985 mice. None of CWD-infected TgRM
mice tested positive for PrPCWD by WB or by immunohistochemical detection.
Conclusions. To our knowledge, this is the first established experimental
model of CWD in TgSB3985. We found evidence for co-existence or divergence of
two CWD strains adapted to Tga20 mice and their replication in TgSB3985 mice.
Finally, we observed phenotypic differences between cervid-derived CWD and
CWD/Tg20 strains upon propagation in TgSB3985 mice. Further studies are underway
to characterize these strains.
TSS
UPDATED CORRESPONDENCE FROM AUTHORS OF THIS STUDY I.E. COLBY, PRUSINER ET
AL, ABOUT MY CONCERNS OF THE DISCREPANCY BETWEEN THEIR FIGURES AND MY FIGURES OF
THE STUDIES ON CWD TRANSMISSION TO CATTLE ;
CWD to cattle figures CORRECTION
Greetings,
I believe the statement and quote below is incorrect ;
"CWD has been transmitted to cattle after intracerebral inoculation,
although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This
finding raised concerns that CWD prions might be transmitted to cattle grazing
in contaminated pastures."
Please see ;
Within 26 months post inoculation, 12 inoculated animals had lost weight,
revealed abnormal clinical signs, and were euthanatized. Laboratory tests
revealed the presence of a unique pattern of the disease agent in tissues of
these animals. These findings demonstrate that when CWD is directly inoculated
into the brain of cattle, 86% of inoculated cattle develop clinical signs of the
disease.
" although the infection rate was low (4 of 13 animals [Hamir et al.
2001]). "
shouldn't this be corrected, 86% is NOT a low rate. ...
kindest regards,
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
Thank you!
Thanks so much for your updates/comments. We intend to publish as rapidly
as possible all updates/comments that contribute substantially to the topic
under discussion.
re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author
Affiliations
1Institute for Neurodegenerative Diseases, University of California, San
Francisco, San Francisco, California 94143 2Department of Neurology, University
of California, San Francisco, San Francisco, California 94143 Correspondence:
stanley@ind.ucsf.edu
Mule deer, white-tailed deer, and elk have been reported to develop CWD. As
the only prion disease identified in free-ranging animals, CWD appears to be far
more communicable than other forms of prion disease. CWD was first described in
1967 and was reported to be a spongiform encephalopathy in 1978 on the basis of
histopathology of the brain. Originally detected in the American West, CWD has
spread across much of North America and has been reported also in South Korea.
In captive populations, up to 90% of mule deer have been reported to be positive
for prions (Williams and Young 1980). The incidence of CWD in cervids living in
the wild has been estimated to be as high as 15% (Miller et al. 2000). The
development of transgenic (Tg) mice expressing cervid PrP, and thus susceptible
to CWD, has enhanced detection of CWD and the estimation of prion titers
(Browning et al. 2004; Tamgüney et al. 2006). Shedding of prions in the feces,
even in presymptomatic deer, has been identified as a likely source of infection
for these grazing animals (Williams and Miller 2002; Tamgüney et al. 2009b). CWD
has been transmitted to cattle after intracerebral inoculation, although the
infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding
raised concerns that CWD prions might be transmitted to cattle grazing in
contaminated pastures.
snip...
----- Original Message -----
From: David Colby To: flounder9@verizon.net
Cc: stanley@XXXXXXXX
Sent: Tuesday, March 01, 2011 8:25 AM
Subject: Re: FW: re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 +
Author Affiliations
Dear Terry Singeltary,
Thank you for your correspondence regarding the review article Stanley
Prusiner and I recently wrote for Cold Spring Harbor Perspectives. Dr. Prusiner
asked that I reply to your message due to his busy schedule. We agree that the
transmission of CWD prions to beef livestock would be a troubling development
and assessing that risk is important. In our article, we cite a peer-reviewed
publication reporting confirmed cases of laboratory transmission based on
stringent criteria. The less stringent criteria for transmission described in
the abstract you refer to lead to the discrepancy between your numbers and ours
and thus the interpretation of the transmission rate. We stand by our assessment
of the literature--namely that the transmission rate of CWD to bovines appears
relatively low, but we recognize that even a low transmission rate could have
important implications for public health and we thank you for bringing attention
to this matter. Warm Regards, David Colby -- David Colby, PhDAssistant Professor
Department of Chemical Engineering University of Delaware
===========END...TSS==============
SNIP...SEE FULL TEXT ;
UPDATED DATA ON 2ND CWD STRAIN Wednesday, September 08, 2010 CWD PRION
CONGRESS SEPTEMBER 8-11 2010
Sunday, August 19, 2012
Susceptibility of cattle to the agent of chronic wasting disease from elk
after intracranial inoculation 2012
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research
Unit
Thursday, November 21, 2013
*** Assessing the susceptibility of transgenic mice over-expressing deer
prion protein to bovine spongiform encephalopathy
The present study was designed to assess the susceptibility of the
prototypic mouse line, Tg(CerPrP)1536+/- to bovine spongiform encephalopathy
(BSE) prions, which have the ability to overcome species barriers.
Tg(CerPrP)1536+/- mice challenged with red deer-adapted BSE resulted in a
90-100% attack rates, BSE from cattle failed to transmit, indicating agent
adaptation in the deer.
Thus far, among domestic animals, CWDmd has been transmitted by the
intracerebral route to a goat18 and cattle.5–7 The present findings demonstrate
that it is also possible to transmit CWDmd agent to sheep via the intracerebral
route.
Preliminary studies (Hamir et al., unpublished data, 2006) of intracerebral
inoculation of CWD from white-tailed deer into cattle suggests that this source
is much more efficient at causing disease (as indicated by the attack rate) than
CWDmd.
these cattle ranchers supporting these shooting pens, if there are any,
could be in terrible shape if a strain of cwd was to jump to cattle...just
saying.
Title: Transmission of Chronic Wasting Disease of Mule Deer to Suffolk
Sheep Following Intracerebral Inoculation
Authors
item Hamir, Amirali item Kunkle, Robert item Cutlip, Randall - ARS RETIRED
item Miller, Janice - ARS RETIRED item Williams, Elizabeth - UNIVERSITY OF
WYOMING item Richt, Juergen
Submitted to: Conference Research Workers Disease Meeting Publication Type:
Abstract Only Publication Acceptance Date: December 3, 2006 Publication Date:
December 3, 2006 Citation: Hamir, A.N., Kunkle, R.A., Cutlip, R.C., Miller,
J.M., Williams, E.S., Richt, J.A. 2006. Transmission of chronic wasting disease
of mule deer to Suffolk sheep following intracerebral inoculation [abstract].
Conference of Research Workers in Animal Diseases 87th Annual Meeting. Paper No.
P34. p. 108.
Technical Abstract: To determine the transmissibility of chronic wasting
disease (CWD) to sheep, 8 Suffolk lambs of various prion protein (PRNP) genotype
(4 ARQ/ARR, 3 ARQ/ARQ, 1 ARQ/VRQ at codons 136, 154 and 171, respectively) were
inoculated intracerebrally with brain suspension from mule deer with CWD
(CWD**md). Two other lambs were kept as non inoculated controls. Within 36
months post inoculation (MPI), 2 inoculated animals became sick and were
euthanized. Only 1 sheep (euthanized at 35 MPI) showed clinical signs that were
consistent with those described for scrapie. Microscopic lesions of spongiform
encephalopathy (SE) were only seen in this sheep and its tissues were positive
for the abnormal prion protein (PrP**res) by immunohistochemistry and Western
blot. Three other inoculated sheep were euthanized (36 to 60 MPI) because of
conditions unrelated to TSE. The 3 remaining inoculated sheep and the 2 control
sheep were non clinical at the termination of the study (72 MPI) and were
euthanized. One of the 3 remaining inoculated sheep revealed SE and its tissues
were positive for PrP**res. The sheep with clinical prion disease (euthanized at
35 MPI) was of the heterozygous genotype (ARQ/VRQ) and the sheep with the sub
clinical disease (euthanized at 72 MPI) was of the homozygous ARQ/ARQ genotype.
These findings demonstrate that transmission of the CWD**md agent to sheep via
the intracerebral route is possible. Interestingly, the host genotype may play a
significant part in successful transmission and incubation period of CWD**md.
Last Modified: 11/6/2014
I strenuously once again urge the FDA and its industry constituents, to
make it MANDATORY that all ruminant feed be banned to all ruminants, and this
should include all cervids as soon as possible for the following
reasons...
======
In the USA, under the Food and Drug Administrations BSE Feed Regulation (21
CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from
deer and elk is prohibited for use in feed for ruminant animals. With regards to
feed for non-ruminant animals, under FDA law, CWD positive deer may not be used
for any animal feed or feed ingredients. For elk and deer considered at high
risk for CWD, the FDA recommends that these animals do not enter the animal feed
system.
***However, this recommendation is guidance and not a requirement by law.
======
31 Jan 2015 at 20:14 GMT
*** Ruminant feed ban for cervids in the United States? ***
Singeltary et al
31 Jan 2015 at 20:14 GMT
HIGHEST INFECTION RATE ON SEVERAL CWD CONFIRMED CAPTIVES
CHRONIC WASTING DISEASE CWD WISCONSIN Almond Deer (Buckhorn Flats) Farm
Update DECEMBER 2011
The CWD infection rate was nearly 80%, the highest ever in a North American
captive herd.
RECOMMENDATION: That the Board approve the purchase of 80 acres of land for
$465,000 for the Statewide Wildlife Habitat Program in Portage County and
approve the restrictions on public use of the site.
SUMMARY:
For Immediate Release Thursday, October 2, 2014
Dustin Vande Hoef 515/281-3375 or 515/326-1616 (cell) or
Dustin.VandeHoef@IowaAgriculture.gov
*** TEST RESULTS FROM CAPTIVE DEER HERD WITH CHRONIC WASTING DISEASE
RELEASED 79.8 percent of the deer tested positive for the disease
DES MOINES – The Iowa Department of Agriculture and Land Stewardship today
announced that the test results from the depopulation of a quarantined captive
deer herd in north-central Iowa showed that 284 of the 356 deer, or 79.8% of the
herd, tested positive for Chronic Wasting Disease (CWD).
*** see history of this CWD blunder here ;
On June 5, 2013, DNR conducted a fence inspection, after gaining approval
from surrounding landowners, and confirmed that the fenced had been cut or
removed in at least four separate locations; that the fence had degraded and was
failing to maintain the enclosure around the Quarantined Premises in at least
one area; that at least three gates had been opened;and that deer tracks were
visible in and around one of the open areas in the sand on both sides of the
fence, evidencing movement of deer into the Quarantined Premises.
The overall incidence of clinical CWD in white-tailed deer was 82%
Species (cohort) CWD (cases/total) Incidence (%) Age at CWD death
(mo)
*** Spraker suggested an interesting explanation for the occurrence of CWD.
The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr.
Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at
this site. When deer were introduced to the pens they occupied ground that had
previously been occupied by sheep.
O.05: Transmission of prions to primates after extended silent incubation
periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Val erie Durand, Sophie Luccantoni,
Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys
Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies
reputed to be transmissible under field conditions since decades. The
transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that
an animal PD might be zoonotic under appropriate conditions. Contrarily, in the
absence of obvious (epidemiological or experimental) elements supporting a
transmission or genetic predispositions, PD, like the other proteinopathies, are
reputed to occur spontaneously (atpical animal prion strains, sporadic CJD
summing 80% of human prion cases). Non-human primate models provided the first
evidences supporting the transmissibiity of human prion strains and the zoonotic
potential of BSE. Among them, cynomolgus macaques brought major information for
BSE risk assessment for human health (Chen, 2014), according to their
phylogenetic proximity to humans and extended lifetime. We used this model to
assess the zoonotic potential of other animal PD from bovine, ovine and cervid
origins even after very long silent incubation periods. *** We recently observed
the direct transmission of a natural classical scrapie isolate to macaque after
a 10-year silent incubation period, ***with features similar to some reported
for human cases of sporadic CJD, albeit requiring fourfold longe incubation than
BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014), ***is the
third potentially zoonotic PD (with BSE and L-type BSE), ***thus questioning the
origin of human sporadic cases. We will present an updated panorama of our
different transmission studies and discuss the implications of such extended
incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases...TSS
===============
-------- Original Message --------
Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD
Date: Thu, 28 Nov 2002 10:23:43 -0000
From: "Asante, Emmanuel A" e.asante@ic.ac.uk
To: "'flounder@wt.net'" flounder@wt.net
Dear Terry,
I have been asked by Professor Collinge to respond to your request. I am a
Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have
attached a pdf copy of the paper for your attention.
Thank you for your interest in the paper.
In respect of your first question, the simple answer is, ***yes. As you
will find in the paper, we have managed to associate the alternate phenotype to
type 2 PrPSc, the commonest sporadic CJD. It is too early to be able to claim
any further sub-classification in respect of Heidenhain variant CJD or Vicky
Rimmer's version. It will take further studies, which are on-going, to establish
if there are sub-types to our initial finding which we are now reporting. The
main point of the paper is that, as well as leading to the expected new variant
CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an
alternate phenotype which is indistinguishable from type 2 PrPSc.
I hope reading the paper will enlighten you more on the subject. If I can
be of any further assistance please to not hesitate to ask. Best wishes.
Emmanuel Asante
<>
____________________________________
Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial
College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44
(0)20 7594 3794 Fax: +44 (0)20 7706 3272 email: e.asante@ic.ac.uk (until
9/12/02) New e-mail: e.asante@prion.ucl.ac.uk (active from now)
____________________________________
***Our study demonstrates susceptibility of adult cattle to oral
transmission of classical BSE. ***
***our findings suggest that possible transmission risk of H-type BSE to
sheep and human. ***
P.86: Estimating the risk of transmission of BSE and scrapie to ruminants
and humans by protein misfolding cyclic amplification
Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama
National Institute of Animal Health; Tsukuba, Japan
To assess the risk of the transmission of ruminant prions to ruminants and
humans at the molecular level, we investigated the ability of abnormal prion
protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical
scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to
proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding
cyclic amplification (PMCA).
Six rounds of serial PMCA was performed using 10% brain homogenates from
transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc
seed from typical and atypical BSE- or typical scrapie-infected brain
homogenates from native host species. In the conventional PMCA, the conversion
of PrPC to PrPres was observed only when the species of PrPC source and PrPSc
seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA
and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested
prion strains. On the other hand, human PrPC was converted by PrPSc from typical
and H-type BSE in this PMCA condition.
Although these results were not compatible with the previous reports
describing the lack of transmissibility of H-type BSE to ovine and human
transgenic mice, ***our findings suggest that possible transmission risk of
H-type BSE to sheep and human. Bioassay will be required to determine whether
the PMCA products are infectious to these animals.
================
***Our study demonstrates susceptibility of adult cattle to oral
transmission of classical BSE. ***
P.86: Estimating the risk of transmission of BSE and scrapie to ruminants
and humans by protein misfolding cyclic amplification
Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama
National Institute of Animal Health; Tsukuba, Japan
To assess the risk of the transmission of ruminant prions to ruminants and
humans at the molecular level, we investigated the ability of abnormal prion
protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical
scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to
proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding
cyclic amplification (PMCA).
Six rounds of serial PMCA was performed using 10% brain homogenates from
transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc
seed from typical and atypical BSE- or typical scrapie-infected brain
homogenates from native host species. In the conventional PMCA, the conversion
of PrPC to PrPres was observed only when the species of PrPC source and PrPSc
seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA
and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested
prion strains. On the other hand, human PrPC was converted by PrPSc from typical
and H-type BSE in this PMCA condition.
Although these results were not compatible with the previous reports
describing the lack of transmissibility of H-type BSE to ovine and human
transgenic mice, ***our findings suggest that possible transmission risk of
H-type BSE to sheep and human. Bioassay will be required to determine whether
the PMCA products are infectious to these animals.
===============
***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67
PrPsc was not detected using rapid tests for BSE.
***Subsequent testing resulted in the detection of pathologic lesion in
unusual brain location and PrPsc detection by PMCA only.
IBNC Tauopathy or TSE Prion disease, it appears, no one is sure
Posted by flounder on 03 Jul 2015 at 16:53 GMT
10 years post mad cow feed ban August 1997
10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN
COMMERCE USA 2007
Date: March 21, 2007 at 2:27 pm PST
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II
PRODUCT
Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried,
Recall # V-024-2007
CODE
Cattle feed delivered between 01/12/2007 and 01/26/2007
RECALLING FIRM/MANUFACTURER
Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.
Firm initiated recall is ongoing.
REASON
Blood meal used to make cattle feed was recalled because it was cross-
contaminated with prohibited bovine meat and bone meal that had been
manufactured on common equipment and labeling did not bear cautionary BSE
statement.
VOLUME OF PRODUCT IN COMMERCE
42,090 lbs.
DISTRIBUTION
WI
___________________________________
PRODUCT
Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot-
Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M
CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B
DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal,
JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT
Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral,
BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC
LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall #
V-025-2007
CODE
The firm does not utilize a code - only shipping documentation with
commodity and weights identified.
RECALLING FIRM/MANUFACTURER
Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm
initiated recall is complete.
REASON
Products manufactured from bulk feed containing blood meal that was cross
contaminated with prohibited meat and bone meal and the labeling did not bear
cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE
9,997,976 lbs.
DISTRIBUTION
ID and NV
END OF ENFORCEMENT REPORT FOR MARCH 21, 2007
16 years post mad cow feed ban August 1997
2013
Sunday, December 15, 2013
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED
VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE DECEMBER 2013 UPDATE
17 years post mad cow feed ban August 1997
Tuesday, December 23, 2014
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED
VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2014 BSE TSE PRION
Sunday, June 14, 2015
Larry’s Custom Meats Inc. Recalls Beef Tongue Products That May Contain
Specified Risk Materials BSE TSE Prion
DR. DEHAVEN:
snip...
*** As far as spontaneous cases, that is a very difficult issue.
***There is no evidence to prove that spontaneous BSE occurs in cattle; but
here again it's an issue of proving a negative.
*** We do know that CJD, the human version of the disease, does occur
spontaneously in humans at the rate of about 1 in 1 million.
*** We don't have enough data to definitively say that spontaneous cases of
BSE in cattle occur or do not occur.
“Again, it's a very difficult situation to prove a negative.
“So a lot of research is ongoing. Certainly if we do come up with any
positive samples in the course of this surveillance we will be looking at that
question in evaluating those samples but no scientifically hard evidence to
confirm or refute whether or not spontaneous cases of BSE occur.
snip...
http://www.usda.gov/wps/portal/!ut/p/_s.7_0_A/7_0_1OB?contentidonly=true&contentid=2004/03/0106.html
What irks many scientists is the USDA?s April 25 statement that the rare
disease is ?not generally associated with an animal consuming infected
feed.?
The USDA?s conclusion is a ?gross oversimplification,? said Dr. Paul Brown,
one of the world?s experts on this type of disease who retired recently from the
National Institutes of Health.
"(The agency) has no foundation on which to base that statement.?
?We can?t say it?s not feed related,? agreed Dr. Linda Detwiler, an
official with the USDA during the Clinton Administration now at Mississippi
State.
In the May 1 email to me, USDA?s Cole backed off a bit. ?No one knows the
origins of atypical cases of BSE,? she said
Few scientists would argue that the one California cow which never was
headed to the U.S. food supply represents a health hazard.
But many maintain that the current surveillance is insufficient.
Dr. Kurt Giles, an expert in neurogenerative diseases now at the University
of California, San Francisco, was at Oxford during the British outbreak.
He told me USDA?s assurances about safety today remind him of British
statements during the 1980s.
?It is so reminiscent of that absolute certainty,? he said.
Robert Bazell is NBC's chief science and medical correspondent. Follow him
on Facebook and on Twitter @RobertBazellNBC
http://www.nature.com/nature/report/index.html?comment=42931&doi=10.1038/485279b
http://bseusa.blogspot.com/2012/05/are-usda-assurances-on-mad-cow-case.html
THE USDA JUNE 2004 ENHANCED BSE SURVEILLANCE PROGRAM WAS TERRIBLY FLAWED ;
CDC DR. PAUL BROWN TSE EXPERT COMMENTS 2006
In an article today for United Press International, science reporter Steve
Mitchell writes:
Analysis: What that mad cow means
By STEVE MITCHELL UPI Senior Medical Correspondent
WASHINGTON, March 15 (UPI) -- The U.S. Department of Agriculture was quick
to assure the public earlier this week that the third case of mad cow disease
did not pose a risk to them, but what federal officials have not acknowledged is
that this latest case indicates the deadly disease has been circulating in U.S.
herds for at least a decade.
The second case, which was detected last year in a Texas cow and which USDA
officials were reluctant to verify, was approximately 12 years old.
These two cases (the latest was detected in an Alabama cow) present a
picture of the disease having been here for 10 years or so, since it is thought
that cows usually contract the disease from contaminated feed they consume as
calves. The concern is that humans can contract a fatal, incurable,
brain-wasting illness from consuming beef products contaminated with the mad cow
pathogen.
"The fact the Texas cow showed up fairly clearly implied the existence of
other undetected cases," Dr. Paul Brown, former medical director of the National
Institutes of Health's Laboratory for Central Nervous System Studies and an
expert on mad cow-like diseases, told United Press International. "The question
was, 'How many?' and we still can't answer that."
Brown, who is preparing a scientific paper based on the latest two mad cow
cases to estimate the maximum number of infected cows that occurred in the
United States, said he has "absolutely no confidence in USDA tests before one
year ago" because of the agency's reluctance to retest the Texas cow that
initially tested positive.
USDA officials finally retested the cow and confirmed it was infected seven
months later, but only at the insistence of the agency's inspector
general.
"Everything they did on the Texas cow makes everything they did before 2005
suspect," Brown said.
SNIP...
UPI requested detailed records about animals tested under the USDA's
surveillance plan via the Freedom of Information Act in May 2004 but nearly two
years later has not received any corresponding documents from the agency,
despite a federal law requiring agencies to comply within 30 days. This leaves
open the question of whether the USDA is withholding the information, does not
have the information or is so haphazardly organized that it cannot locate
it.
SNIP...
Markus Moser, a molecular biologist and chief executive officer of
Prionics, a Swiss firm that manufactures BSE test kits, told UPI one concern is
that if people are infected, the mad cow pathogen could become "humanized" or
more easily transmitted from person to person.
"Transmission would be much easier, through all kinds of medical
procedures" and even through the blood supply, Moser said.
© Copyright 2006 United Press International, Inc. All Rights Reserved
CDC - Bovine Spongiform Encephalopathy and Variant Creutzfeldt ... Dr. Paul
Brown is Senior Research Scientist in the Laboratory of Central Nervous System
... Address for correspondence: Paul Brown, Building 36, Room 4A-05, ...
PAUL BROWN COMMENT TO ME ON THIS ISSUE
Tuesday, September 12, 2006 11:10 AM
"Actually, Terry, I have been critical of the USDA handling of the mad cow
issue for some years, and with Linda Detwiler and others sent lengthy detailed
critiques and recommendations to both the USDA and the Canadian Food Agency."
........TSS
OR, what the Honorable Phyllis Fong of the OIG found ;
Audit Report Animal and Plant Health Inspection Service Bovine Spongiform
Encephalopathy (BSE) Surveillance Program  Phase II and Food Safety and
Inspection Service
Controls Over BSE Sampling, Specified Risk Materials, and Advanced Meat
Recovery Products - Phase III
Report No. 50601-10-KC January 2006
Finding 2 Inherent Challenges in Identifying and Testing High-Risk Cattle
Still Remain
FRANCE HAVE AN EPIDEMIC OF SPONTANEOUS ATYPICAL BSE ‘’LOL’’
spontaneous atypical BSE ???
if that's the case, then France is having one hell of an epidemic of
atypical BSE, probably why they stopped testing for BSE, problem solved $$$
As of December 2011, around 60 atypical BSE cases have currently been
reported in 13 countries, *** with over one third in France.
so 20 cases of atypical BSE in France, compared to the remaining 40 cases
in the remaining 12 Countries, divided by the remaining 12 Countries, about 3+
cases per country, besides Frances 20 cases. you cannot explain this away with
any spontaneous BSe. ...TSS
Sunday, October 5, 2014
France stops BSE testing for Mad Cow Disease
spontaneous TSE prion, that's wishful thinking. on the other hand, if
spontaneous did ever happen (never once documented in the field), it would be
our worst nightmare, due to feed. just saying.
*** We describe the transmission of spongiform encephalopathy in a
non-human primate inoculated 10 years earlier with a strain of sheep c-scrapie.
Because of this extended incubation period in a facility in which other prion
diseases are under study, we are obliged to consider two alternative
possibilities that might explain its occurrence. We first considered the
possibility of a sporadic origin (like CJD in humans). Such an event is
extremely improbable because the inoculated animal was 14 years old when the
clinical signs appeared, i.e. about 40% through the expected natural lifetime of
this species, compared to a peak age incidence of 60–65 years in human sporadic
CJD, or about 80% through their expected lifetimes. ***Moreover, sporadic
disease has never been observed in breeding colonies or primate research
laboratories, most notably among hundreds of animals over several decades of
study at the National Institutes of Health25, and in nearly twenty older animals
continuously housed in our own facility.***
>>> Moreover, sporadic disease has never been observed in breeding
colonies or primate research laboratories, most notably among hundreds of
animals over several decades of study at the National Institutes of Health25,
and in nearly twenty older animals continuously housed in our own facility.
<<<
Monday, June 23, 2014
PRION 2014 TYPICAL AND ATYPICAL BSE AND CJD REPORT UPDATES
***P.170: Potential detection of oral transmission of H type atypical BSE
in cattle using in vitro conversion
Sandor Dudas, John G Gray, Renee Clark, and Stefanie Czub Canadian Food
Inspection Agency; Lethbridge, AB Canada
Keywords: Atypical BSE, oral transmission, RT-QuIC
The detection of bovine spongiform encephalopathy (BSE) has had a
significant negative impact on the cattle industry worldwide. In response,
governments took actions to prevent transmission and additional threats to
animal health and food safety. While these measures seem to be effective for
controlling classical BSE, the more recently discovered atypical BSE has
presented a new challenge. To generate data for risk assessment and control
measures, we have challenged cattle orally with atypical BSE to determine
transmissibility and mis-folded prion (PrPSc) tissue distribution. Upon
presentation of clinical symptoms, animals were euthanized and tested for
characteristic histopathological changes as well as PrPSc deposition.
The H-type challenged animal displayed vacuolation exclusively in rostral
brain areas but the L-type challenged animal showed no evidence thereof. To our
surprise, neither of the animals euthanized, which were displaying clinical
signs indicative of BSE, showed conclusive mis-folded prion accumulation in the
brain or gut using standard molecular or immunohistochemical assays. To confirm
presence or absence of prion infectivity, we employed an optimized real-time
quaking induced conversion (RT-QuIC) assay developed at the Rocky Mountain
Laboratory, Hamilton, USA.
Detection of PrPSc was unsuccessful for brain samples tests from the orally
inoculated L type animal using the RT-QuIC. It is possible that these negative
results were related to the tissue sampling locations or that type specific
optimization is needed to detect PrPSc in this animal. We were however able to
consistently detect the presence of mis-folded prions in the brain of the H-type
inoculated animal. Considering the negative and inconclusive results with other
PrPSc detection methods, positive results using the optimized RT-QuIC suggests
the method is extremely sensitive for H-type BSE detection. This may be evidence
of the first successful oral transmission of H type atypical BSE in cattle and
additional investigation of samples from these animals are ongoing.
P.126: Successful transmission of chronic wasting disease (CWD) into mice
over-expressing bovine prion protein (TgSB3985)
Larisa Cervenakova,1 Christina J Sigurdson,2 Pedro Piccardo,3 Oksana
Yakovleva,1 Irina Vasilyeva,1 Jorge de Castro,1 Paula Saá,1 and Anton Cervenak1
1American Red Cross, Holland Laboratory; Rockville, MD USA; 2University of
California; San Diego, CA USA; 3Lab TSE/OBRR /CBER/FDA; Rockville, MD USA
Keywords: chronic wasting disease, transmission, transgenic mouse, bovine
prion protein
Background. CWD is a disease affecting wild and farmraised cervids in North
America. Epidemiological studies provide no evidence of CWD transmission to
humans. Multiple attempts have failed to infect transgenic mice expressing human
PRNP gene with CWD. The extremely low efficiency of PrPCWD to convert normal
human PrPC in vitro provides additional evidence that transmission of CWD to
humans cannot be easily achieved. However, a concern about the risk of CWD
transmission to humans still exists. This study aimed to establish and
characterize an experimental model of CWD in TgSB3985 mice with the following
attempt of transmission to TgHu mice.
Materials and Methods. TgSB3985 mice and wild-type FVB/ NCrl mice were
intracranially injected with 1% brain homogenate from a CWD-infected Tga20 mouse
(CWD/Tga20). TgSB3985 and TgRM (over-expressing human PrP) were similarly
injected with 5% brain homogenates from CWD-infected white-tailed deer (CWD/WTD)
or elk (CWD/Elk). Animals were observed for clinical signs of neurological
disease and were euthanized when moribund. Brains and spleens were removed from
all mice for PrPCWD detection by Western blotting (WB). A histological analysis
of brains from selected animals was performed: brains were scored for the
severity of spongiform change, astrogliosis, and PrPCWD deposition in ten brain
regions.
Results. Clinical presentation was consistent with TSE. More than 90% of
TgSB3985 and wild-type mice infected with CWD/Tga20, tested positive for PrPres
in the brain but only mice in the latter group carried PrPCWD in their spleens.
We found evidence for co-existence or divergence of two CWD/ Tga20 strains based
on biochemical and histological profiles. In TgSB3985 mice infected with CWD-elk
or CWD-WTD, no animals tested positive for PrPCWD in the brain or in the spleen
by WB. However, on neuropathological examination we found presence of amyloid
plaques that stained positive for PrPCWD in three CWD/WTD- and two
CWD/Elk-infected TgSB3985 mice. The neuropathologic profiles in CWD/WTD- and
CWD/Elkinfected mice were similar but unique as compared to profiles of BSE,
BSE-H or CWD/Tg20 agents propagated in TgSB3985 mice. None of CWD-infected TgRM
mice tested positive for PrPCWD by WB or by immunohistochemical detection.
Conclusions. To our knowledge, this is the first established experimental
model of CWD in TgSB3985. We found evidence for co-existence or divergence of
two CWD strains adapted to Tga20 mice and their replication in TgSB3985 mice.
Finally, we observed phenotypic differences between cervid-derived CWD and
CWD/Tg20 strains upon propagation in TgSB3985 mice. Further studies are underway
to characterize these strains.
P.150: Zoonotic potential of L-type BSE prions: A new prion disease in
humans?
Emilie Jaumain,1 Stéphane Haïk,2 Isabelle Quadrio,3 Laetitia Herzog,1
Fabienne Reine,1 Armand Perret-Liaudet,3 Human Rezaei,1 Hubert Laude,1 Jean-Luc
Vilotte,4 and Vincent Béringue1 1INR A (Institut National de la Recherche
Agronomique); UR892; Virologie Immunologie Moléculaires; Jouy-en-Josas, France;
2IN SERM; Equipe maladie d’Alzheimer et maladies à Prions; CRicm; UMRS 1127; CNR
S; UPMC. R.; ICM, Hôpital de la Salpêtrière; Paris, France; 3Neurobiologie, CMRR
, Gériatrie, Hospices Civils de Lyon, Université Lyon 1-CNR S UMR5292-IN SERM
U1028; Lyon, France; 3INR A; UMR1313; Génétique Animale et Biologie Intégrative;
Jouy-en-Josas, France
In summary, L-type prions can be passaged on the human PrP sequence without
any obvious transmission barrier. The phenotype obtained differs from the
classical CJD prion types known so far. Careful extrapolation would suggest that
the zoonotic transmission of this agent could establish a new prion disease type
in humans.
Wednesday, May 30, 2012
PO-028: Oral transmission of L-type bovine spongiform encephalopathy
(L-BSE) in primate model Microcebus murinus
Nadine Mestre-Frances,1 Simon Nicot,2 Sylvie Rouland,1 Anne-Gaëlle
Biacabe,2 Isabelle Quadrio,3 Armand Perret-Liaudet,3 Thierry Baron,2 Jean-Michel
Verdier1
1IN SER M UM2; Montpellier, France; 2Anses; Lyon, France; 3Hopitaux Civils
de Lyon; Lyon, France
Here, we demonstrate that the L-BSE agent can be transmitted by oral route
from cattle to young and adult mouse lemurs. In comparison to IC inoculated
animals, orally challenged lemurs were characterized by longer survival periods
as expected with this route of infection.
CJD toll among farmers `too high for mere chance'
August 15, 1997
PA News
John von Radowitz and Andrew Woodcock Microbiologist Richard Lacey, billed
in this story as the first to suggest a link between CJD and BSE seven years
ago, was cited in this story as saying that the number of cattle farmers falling
victim to Creutzfeld-Jakob Disease is much too high to be mere chance, adding
that, "Where the CJD Surveillance Unit come unstuck is in trying to explain what
happened to these six farmers. This is just too many to have occurred by chance.
Unfortunately they don't want to consider the possibility that these farmers in
this country and other countries were infected by cattle before BSE developed."
The story notes that professor Lacey believes sporadic CJD itself originates
from a cattle infection - possibly a precursor to BSE that has not yet been
detected, adding that,
"For years I have suggested that the cause is a rare disease in cattle
world wide. Both BSE and the new variant CJD are a new and different disease.
What has probably happened is that BSE is a variant of the old type of disease,
which could have been missed because it's symptom free. It would explain why
such an unusually high number of dairy farmers are being affected by CJD both
here and abroad." He also said that cases of sporadic CJD had been recorded as
far back as the 1920s. Professor Lacey went on to add that he thought the new
variant pattern was alarming, adding, "It's rising, and that is a concern.
Unfortunately we can't predict the scale of the problem. If the disease doubled
each year up to the year 2020 you'd have hundreds of thousands of cases."
.195 Among occupational groups exposed to BSE, farmers remain unusual in
having such an excess over the incidence of CJD for the population as a whole.
No cases of CJD have been reported amount veterinarians exposed to BSE. Four
people in the meat industry (butchers, abattoirs, rendering plants, etc) have
been reported to have vCJD.386 The present evidence has been accepted by some as
reassuring in that such occupations may not pose as serious a risk as might have
been expected.
This was not simply another farmer but the third farmer...
suspect case of CJD in a farmer who has had a case of BSE in his beef
suckler herd.
http://web.archive.org/web/20030331213802/http://www.bseinquiry.gov.uk/files/yb/1995/10/23006001.pdf
cover-up of 4th farm worker ???
http://web.archive.org/web/20030516083454/http://www.bseinquiry.gov.uk/files/yb/1995/10/23006001.pdf
http://web.archive.org/web/20030330175323/http://www.bseinquiry.gov.uk/files/yb/1995/10/20006001.pdf
CONFIRMATION OF CJD IN FOURTH FARMER
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://web.archive.org/web/20030728074919/http://www.bseinquiry.gov.uk/files/yb/1995/11/13010001.pdf
4th farmer, and 1st teenager
snip...
2. 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://web.archive.org/web/20030516181226/http://www.bseinquiry.gov.uk/files/yb/1995/01/31004001.pdf
CJD FARMERS WIFE 1989
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://web.archive.org/web/20030330212925/http://www.bseinquiry.gov.uk/files/yb/1995/10/04004001.pdf
Monday, May 19, 2008
SPORADIC CJD IN FARMERS, FARMERS WIVES, FROM FARMS WITH BSE HERD AND
ABATTOIRS
Monday, June 29, 2015
*** RESTRICTED – POLICY CJD IN ADOLESCENTS (16 year old Vickey Rimmer),
FARMERS WITH BSE HERDS, AND FARMERS WIFE with Sporadic CJD
Thursday, July 30, 2015
*** Professor Lacey believes sporadic CJD itself originates from a cattle
infection number of cattle farmers falling victim to Creutzfeld-Jakob Disease is
much too high to be mere chance
PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS
*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***
O18
Zoonotic Potential of CWD Prions
Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1,
Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve
University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy,
3Encore Health Resources, Houston, Texas, USA
Chronic wasting disease (CWD) is a widespread and expanding prion disease
in free-ranging and captive cervid species in North America. The zoonotic
potential of CWD prions is a serious public health concern. Current literature
generated with in vitro methods and in vivo animal models (transgenic mice,
macaques and squirrel monkeys) reports conflicting results. The susceptibility
of human CNS and peripheral organs to CWD prions remains largely unresolved. In
our earlier bioassay experiments using several humanized transgenic mouse lines,
we detected protease-resistant PrPSc in the spleen of two out of 140 mice that
were intracerebrally inoculated with natural CWD isolates, but PrPSc was not
detected in the brain of the same mice. Secondary passages with such
PrPSc-positive CWD-inoculated humanized mouse spleen tissues led to efficient
prion transmission with clear clinical and pathological signs in both humanized
and cervidized transgenic mice. Furthermore, a recent bioassay with natural CWD
isolates in a new humanized transgenic mouse line led to clinical prion
infection in 2 out of 20 mice. These results indicate that the CWD prion has the
potential to infect human CNS and peripheral lymphoid tissues and that there
might be asymptomatic human carriers of CWD infection.
==================
***These results indicate that the CWD prion has the potential to infect
human CNS and peripheral lymphoid tissues and that there might be asymptomatic
human carriers of CWD infection.***
==================
P.105: RT-QuIC models trans-species prion transmission
Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover
Prion Research Center; Colorado State University; Fort Collins, CO USA
The propensity for trans-species prion transmission is related to the
structural characteristics of the enciphering and heterologous PrP, but the
exact mechanism remains mostly mysterious. Studies of the effects of primary or
tertiary prion protein structures on trans-species prion transmission have
relied primarily upon animal bioassays, making the influence of prion protein
structure vs. host co-factors (e.g. cellular constituents, trafficking, and
innate immune interactions) difficult to dissect. As an alternative strategy, we
used real-time quakinginduced conversion (RT-QuIC) to investigate trans-species
prion conversion.
To assess trans-species conversion in the RT-QuIC system, we compared
chronic wasting disease (CWD) and bovine spongiform encephalopathy (BSE) prions,
as well as feline CWD (fCWD) and feline spongiform encephalopathy (FSE). Each
prion was seeded into each host recombinant PrP (full-length rPrP of
white-tailed deer, bovine or feline). We demonstrated that fCWD is a more
efficient seed for feline rPrP than for white-tailed deer rPrP, which suggests
adaptation to the new host.
Conversely, FSE maintained sufficient BSE characteristics to more
efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was
competent for conversion by CWD and fCWD. ***This insinuates that, at the level
of protein:protein interactions, the barrier preventing transmission of CWD to
humans is less robust than previously estimated.
================
***This insinuates that, at the level of protein:protein interactions, the
barrier preventing transmission of CWD to humans is less robust than previously
estimated.***
================
Thursday, August 12, 2010
Seven main threats for the future linked to prions
***Also, a link is suspected between atypical BSE and some apparently
sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases
constitute an unforeseen first threat that could sharply modify the European
approach to prion diseases.
Second threat
snip...
Monday, October 10, 2011
EFSA Journal 2011 The European Response to BSE: A Success Story
snip...
*** but the possibility that a small proportion of human cases so far
classified as "sporadic" CJD are of zoonotic origin could not be excluded.
Moreover, transmission experiments to non-human primates suggest that some TSE
agents in addition to Classical BSE prions in cattle (namely L-type Atypical
BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic
wasting disease (CWD) agents) might have zoonotic potential.
snip...
***In addition, non-human primates are specifically susceptible for
atypical BSE as demonstrated by an approximately 50% shortened incubation time
for L-type BSE as compared to C-type.
***Considering the current scientific information available, it cannot be
assumed that these different BSE types pose the same human health risks as
C-type BSE or that these risks are mitigated by the same protective measures.
From: Terry S. Singeltary Sr.
Sent: Saturday, November 15, 2014 9:29 PM
To: Terry S. Singeltary Sr.
Subject: THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE R. G. WILL
1984
THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE
R. G. WILL
1984
*** The association between venison eating and risk of CJD shows similar
pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK
OF CJD (p = 0.04). (SEE LINK IN REPORT HERE...TSS) PLUS, THE CDC DID NOT PUT
THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ;
snip...
Evidence That Transmissible Mink Encephalopathy Results from Feeding
Infected Cattle
Over the next 8-10 weeks, approximately 40% of all the adult mink on the
farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or
dead dairy cattle...
In Confidence - Perceptions of unconventional slow virus diseases of
animals in the USA - APRIL-MAY 1989 - G A H Wells
3. Prof. A. Robertson gave a brief account of BSE. The US approach was to
accord it a very low profile indeed. Dr. A Thiermann showed the picture in the
''Independent'' with cattle being incinerated and thought this was a fanatical
incident to be avoided in the US at all costs. ...
human cwd will NOT look like nvCJD. in fact, see ;
*** These results would seem to suggest that CWD does indeed have zoonotic
potential, at least as judged by the compatibility of CWD prions and their human
PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests
that if zoonotic CWD occurred, it would most likely effect those of the PRNP
codon 129-MM genotype and that the PrPres type would be similar to that found in
the most common subtype of sCJD (MM1).***
LET'S take a closer look at this new prionpathy or prionopathy, and then
let's look at the g-h-BSEalabama mad cow. This new prionopathy in humans? the
genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_
mad cow in the world to date like this, ......wait, it get's better. this new
prionpathy is killing young and old humans, with LONG DURATION from onset of
symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and
the plaques are very similar in some cases too, bbbut, it's not related to the
g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that
they claim is a genetic TSE, has no relation to any gene mutation in that
family. daaa, ya think it could be related to that mad cow with the same genetic
make-up ??? there were literally tons and tons of banned mad cow protein in
Alabama in commerce, and none of it transmitted to cows, and the cows to humans
there from ??? r i g h t $$$ ALABAMA MAD COW g-h-BSEalabama In this study, we
identified a novel mutation in the bovine prion protein gene (Prnp), called
E211K, of a confirmed BSE positive cow from Alabama, United States of America.
This mutation is identical to the E200K pathogenic mutation found in humans with
a genetic form of CJD. This finding represents the first report of a confirmed
case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We
hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in
"the approximately 10-year-old cow" carrying the E221K mutation.
Saturday, August 14, 2010
BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and
VPSPr PRIONPATHY (see mad cow feed in COMMERCE IN ALABAMA...TSS)
her healthy calf also carried the mutation
(J. A. Richt and S. M. Hall PLoS Pathog. 4, e1000156; 2008).
This raises the possibility that the disease could occasionally be genetic
in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the
UK epidemic had most likely originated from such a mutation and argued against
the scrapierelated assumption. Such rare potential pathogenic PRNP mutations
could occur in countries at present considered to be free of BSE, such as
Australia and New Zealand. So it is important to maintain strict surveillance
for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many
countries still feed ruminant proteins to pigs). Removal of specified risk
material, such as brain and spinal cord, from cattle at slaughter prevents
infected material from entering the human food chain. Routine genetic screening
of cattle for PRNP mutations, which is now available, could provide additional
data on the risk to the public. Because the point mutation identified in the
Alabama animals is identical to that responsible for the commonest type of
familial (genetic) CJD in humans, it is possible that the resulting infective
prion protein might cross the bovine-human species barrier more easily. Patients
with vCJD continue to be identified. The fact that this is happening less often
should not lead to relaxation of the controls necessary to prevent future
outbreaks.
Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary
Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen
A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier
Hall, Manhattan, Kansas 66506-5601, USA NATURE|Vol 457|26 February 2009
Thursday, July 24, 2014
*** Protocol for further laboratory investigations into the distribution of
infectivity of Atypical BSE SCIENTIFIC REPORT OF EFSA New protocol for Atypical
BSE investigations
Saturday, August 14, 2010
BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and
VPSPr PRIONPATHY (see mad cow feed in COMMERCE IN ALABAMA...TSS)
PLOS Singeltary Comment ;
*** ruminant feed ban for cervids in the United States ? ***
31 Jan 2015 at 20:14 GMT
19 May 2010 at 21:21 GMT
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics
of BSE in Canada Singeltary reply ;
*** ATYPICAL BSE AND POTENTIAL FOR ANIMAL PROTEIN FEED TO BE A LINK THERE
FROM ***
P.9.21 Molecular characterization of BSE in Canada
Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim
McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre,
Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of
Calgary, Canada
Background: Three BSE types (classical and two atypical) have been
identified on the basis of molecular characteristics of the misfolded protein
associated with the disease. To date, each of these three types have been
detected in Canadian cattle. Objectives: This study was conducted to further
characterize the 16 Canadian BSE cases based on the biochemical properties of
there associated PrPres.
Methods: Immuno-reactivity, molecular weight, glycoform profiles and
relative proteinase K sensitivity of the PrPres from each of the 16 confirmed
Canadian BSE cases was determined using modified Western blot analysis.
Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type
and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and
changes in glycosylation similar to other atypical BSE cases. PK digestion under
mild and stringent conditions revealed a reduced protease resistance of the
atypical cases compared to the C-type cases. N terminal- specific antibodies
bound to PrPres from H type but not from C or L type. The C-terminal-specific
antibodies resulted in a shift in the glycoform profile and detected a fourth
band in the Canadian H-type BSE.
Discussion: The C, L and H type BSE cases in Canada exhibit molecular
characteristics similar to those described for classical and atypical BSE cases
from Europe and Japan. This supports the theory that the importation of BSE
contaminated feedstuff is the source of C-type BSE in Canada. * It also suggests
a similar cause or source for atypical BSE in these countries.
*** It also suggests a similar cause or source for atypical BSE in these
countries. ***
Discussion: The C, L and H type BSE cases in Canada exhibit molecular
characteristics similar to those described for classical and atypical BSE cases
from Europe and Japan. *** This supports the theory that the importation of BSE
contaminated feedstuff is the source of C-type BSE in Canada. *** It also
suggests a similar cause or source for atypical BSE in these countries. ***
see page 176 of 201 pages...tss
Thursday, July 24, 2014
*** Protocol for further laboratory investigations into the distribution of
infectivity of Atypical BSE SCIENTIFIC REPORT OF EFSA New protocol for Atypical
BSE investigations
Guidance for Industry Ensuring Safety of Animal Feed Maintained and Fed
On-Farm Draft Guidance FDA-2014-D-1180 Singeltary Comment
Thursday, February 20, 2014
***Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate
Model
***Infectivity in skeletal muscle of BASE-infected cattle
***feedstuffs- It also suggests a similar cause or source for atypical BSE
in these countries. ***
***Also, a link is suspected between atypical BSE and some apparently
sporadic cases of Creutzfeldt-Jakob disease in humans.
full text ;
atypical L-type BASE BSE
Saturday, January 24, 2015
Bovine Spongiform Encephalopathy: Atypical Pros and Cons
Saturday, January 31, 2015
RAPID ADVICE 17-2014 : Evaluation of the risk for public health of casings
in countries with a “negligible risk status for BSE” and on the risk of
modification of the list of specified risk materials (SRM) with regard to BSE
Conclusion/Significance: Our results point to a possibly higher degree of
pathogenicity of BASE than classical BSE in primates and also raise a question
about a possible link to one uncommon subset of cases of apparently sporadic
CJD. Thus, despite the waning epidemic of classical BSE, the occurrence of
atypical strains should temper the urge to relax measures currently in place to
protect public health from accidental contamination by BSE-contaminated
products.
1. The BSE epidemic
1.1. The origin of the BSE epidemic will probably never be determined with
certainty.
1.2. We do not know whether or not some of the BARB cases represent truly
sporadic classical BSE. If there are spontaneous cases then BSE will never be
eradicated although reducing surveillance could make it appear that BSE has been
eradicated.
snip...
5.3. It was stated that the number of sporadic CJD cases was rising.
Participants were invited to discuss the reason for this. It was suggested that
this was likely to be due to improved surveillance with more cases of sporadic
CJD being detected (i.e. through MRI scans). There had been a similar increase
in sporadic CJD in countries which did not have a BSE epidemic but improved
their surveillance. This supported this theory and suggested that the increase
in sporadic CJD was not related to the BSE outbreak.
Atypical BSE: Transmissibility
Linda Detwiller, 5/10/2011
BASE (L) transmitted to: cattle (IC) - inc < 20 mos and oral?)
Cynomolgus macaques (IC)
Mouse lemurs (IC and oral)
wild-type mice (IC)
bovinized transgenic mice (IC and IP)
humanized transgenic mice (IC)
H cases transmitted to:
cattle – IC incubations < 20 months
bovinized transgenic mice (IC)
ovinized transgenic mice (IC)
C57BL mice (IC)
One study did not transmit to humanized PrP Met 129 mice
Evaluation of Possibility of Atypical
BSE Transmitting to Humans
Possble interpretation:
L type seems to transmit to nonhuman primates with greater ease than
classical BSE
L type also transmitted to humanized transgenic mice with higher attack
rate and shorter incubation period than classical?
H type did not transmit to Tg Hu transgenic mice
Linda Detwiller, 5/10/2011
I ask Professor Kong ;
Thursday, December 04, 2008 3:37 PM
Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform
Encephalopathies (BSE): Public Health Risk Assessment
IS the h-BSE more virulent than typical BSE as well, or the same as cBSE,
or less virulent than cBSE? just curious.....
Professor Kong reply ;
.....snip
As to the H-BSE, we do not have sufficient data to say one way or another,
but we have found that H-BSE can infect humans. I hope we could publish these
data once the study is complete. Thanks for your interest.
Best regards, Qingzhong Kong, PhD Associate Professor Department of
Pathology Case Western Reserve University Cleveland, OH 44106 USA
BSE-H is also transmissible in our humanized Tg mice. The possibility of
more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
P.4.23 Transmission of atypical BSE in humanized mouse models
Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw
Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1
1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale,
Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research
Institute, Poland; 5Kansas State University (Previously at USDA National Animal
Disease Center), USA
Background: Classical BSE is a world-wide prion disease in cattle, and the
classical BSE strain (BSE-C) has led to over 200 cases of clinical human
infection (variant CJD). Atypical BSE cases have been discovered in three
continents since 2004; they include the L-type (also named BASE), the H-type,
and the first reported case of naturally occurring BSE with mutated bovine PRNP
(termed BSE-M). The public health risks posed by atypical BSE were argely
undefined.
Objectives: To investigate these atypical BSE types in terms of their
transmissibility and phenotypes in humanized mice.
Methods: Transgenic mice expressing human PrP were inoculated with several
classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the
transmission rate, incubation time, characteristics and distribution of PrPSc,
symptoms, and histopathology were or will be examined and compared.
Results: Sixty percent of BASE-inoculated humanized mice became infected
with minimal spongiosis and an average incubation time of 20-22 months, whereas
only one of the C-type BSE-inoculated mice developed prion disease after more
than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse
brains was biochemically different from bovine BASE or sCJD. PrPSc was also
detected in the spleen of 22% of BASE-infected humanized mice, but not in those
infected with sCJD. Secondary transmission of BASE in the humanized mice led to
a small reduction in incubation time. The atypical BSE-H strain is also
transmissible with distinct phenotypes in the humanized mice, but no BSE-M
transmission has been observed so far.
Discussion: Our results demonstrate that BASE is more virulent than
classical BSE, has a lymphotropic phenotype, and displays a modest transmission
barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg
mice. The possibility of more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
14th International Congress on Infectious Diseases H-type and L-type
Atypical BSE January 2010 (special pre-congress edition)
18.173 page 189
Experimental Challenge of Cattle with H-type and L-type Atypical BSE
A. Buschmann1, U. Ziegler1, M. Keller1, R. Rogers2, B. Hills3, M.H.
Groschup1. 1Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany,
2Health Canada, Bureau of Microbial Hazards, Health Products & Food Branch,
Ottawa, Canada, 3Health Canada, Transmissible Spongiform Encephalopathy
Secretariat, Ottawa, Canada
Background: After the detection of two novel BSE forms designated H-type
and L-type atypical BSE the question of the pathogenesis and the agent
distribution of these two types in cattle was fully open. From initial studies
of the brain pathology, it was already known that the anatomical distribution of
L-type BSE differs from that of the classical type where the obex region in the
brainstem always displays the highest PrPSc concentrations. In contrast in
L-type BSE cases, the thalamus and frontal cortex regions showed the highest
levels of the pathological prion protein, while the obex region was only weakly
involved.
Methods:We performed intracranial inoculations of cattle (five and six per
group) using 10%brainstemhomogenates of the two German H- and L-type atypical
BSE isolates. The animals were inoculated under narcosis and then kept in a
free-ranging stable under appropriate biosafety conditions. At least one animal
per group was killed and sectioned in the preclinical stage and the remaining
animals were kept until they developed clinical symptoms. The animals were
examined for behavioural changes every four weeks throughout the experiment
following a protocol that had been established during earlier BSE pathogenesis
studies with classical BSE.
Results and Discussion: All animals of both groups developed clinical
symptoms and had to be euthanized within 16 months. The clinical picture
differed from that of classical BSE, as the earliest signs of illness were loss
of body weight and depression. However, the animals later developed hind limb
ataxia and hyperesthesia predominantly and the head. Analysis of brain samples
from these animals confirmed the BSE infection and the atypical Western blot
profile was maintained in all animals. Samples from these animals are now being
examined in order to be able to describe the pathoge esis and agent distribution
for these novel BSE types.
Conclusions: A pilot study using a commercially avaialble BSE rapid test
ELISA revealed an essential restriction of PrPSc to the central nervous system
for both atypical BSE forms. A much more detailed analysis for PrPSc and
infectivity is still ongoing.
*** We describe the transmission of spongiform encephalopathy in a
non-human primate inoculated 10 years earlier with a strain of sheep c-scrapie.
Because of this extended incubation period in a facility in which other prion
diseases are under study, we are obliged to consider two alternative
possibilities that might explain its occurrence. We first considered the
possibility of a sporadic origin (like CJD in humans). Such an event is
extremely improbable because the inoculated animal was 14 years old when the
clinical signs appeared, i.e. about 40% through the expected natural lifetime of
this species, compared to a peak age incidence of 60–65 years in human sporadic
CJD, or about 80% through their expected lifetimes.
***Moreover, sporadic disease has never been observed in breeding colonies
or primate research laboratories, most notably among hundreds of animals over
several decades of study at the National Institutes of Health25, and in nearly
twenty older animals continuously housed in our own facility.***
>>> Moreover, sporadic disease has never been observed in breeding
colonies or primate research laboratories, most notably among hundreds of
animals over several decades of study at the National Institutes of Health25,
and in nearly twenty older animals continuously housed in our own facility.
<<<
Transmission of scrapie prions to primate after an extended silent
incubation period
Emmanuel E. Comoy1 , Jacqueline Mikol1 , Sophie Luccantoni-Freire1 ,
Evelyne Correia1 , Nathalie Lescoutra-Etchegaray1 , Valérie Durand1 , Capucine
Dehen1 , Olivier Andreoletti2 , Cristina Casalone3 , Juergen A. Richt4 n1 ,
Justin J. Greenlee4 , Thierry Baron5 , Sylvie L. Benestad6 , Paul Brown1 […]
& Jean-Philippe Deslys1 - Show fewer authors Scientific Reports 5, Article
number: 11573 (2015) doi:10.1038/srep11573 Download Citation
Epidemiology | Neurological manifestations | Prion diseases Received: 16
February 2015 Accepted: 28 May 2015 Published online: 30 June 2015 ABSTRACT
Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion
disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD)
in humans and having guided protective measures for animal and human health
against animal prion diseases. Recently, partial transmissions to humanized mice
showed that the zoonotic potential of scrapie might be similar to c-BSE. We here
report the direct transmission of a natural classical scrapie isolate to
cynomolgus macaque, a highly relevant model for human prion diseases, after a
10-year silent incubation period, with features similar to those reported for
human cases of sporadic CJD. Scrapie is thus actually transmissible to primates
with incubation periods compatible with their life expectancy, although fourfold
longer than BSE. Long-term experimental transmission studies are necessary to
better assess the zoonotic potential of other prion diseases with high
prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98
scrapie.
snip...
Discussion
We describe the transmission of spongiform encephalopathy in a non-human
primate inoculated 10 years earlier with a strain of sheep c-scrapie. Because of
this extended incubation period in a facility in which other prion diseases are
under study, we are obliged to consider two alternative possibilities that might
explain its occurrence. We first considered the possibility of a sporadic origin
(like CJD in humans). Such an event is extremely improbable because the
inoculated animal was 14 years old when the clinical signs appeared, i.e. about
40% through the expected natural lifetime of this species, compared to a peak
age incidence of 60–65 years in human sporadic CJD, or about 80% through their
expected lifetimes. Moreover, sporadic disease has never been observed in
breeding colonies or primate research laboratories, most notably among hundreds
of animals over several decades of study at the National Institutes of Health25,
and in nearly twenty older animals continuously housed in our own
facility.
The second possibility is a laboratory cross-contamination. Three facts
make this possibility equally unlikely. First, handling of specimens in our
laboratory is performed with fastidious attention to the avoidance of any such
cross-contamination. Second, no laboratory cross-contamination has ever been
documented in other primate laboratories, including the NIH, even between
infected and uninfected animals housed in the same or adjacent cages with daily
intimate contact (P. Brown, personal communication). Third, the cerebral lesion
profile is different from all the other prion diseases we have studied in this
model19, with a correlation between cerebellar lesions (massive spongiform
change of Purkinje cells, intense PrPres staining and reactive gliosis26) and
ataxia. The iron deposits present in the globus pallidus are a non specific
finding that have been reported previously in neurodegenerative diseases and
aging27. Conversely, the thalamic lesion was reminiscent of a metabolic disease
due to thiamine deficiency28 but blood thiamine levels were within normal limits
(data not shown). The preferential distribution of spongiform change in cortex
associated with a limited distribution in the brainstem is reminiscent of the
lesion profile in MM2c and VV1 sCJD patients29, but interspecies comparison of
lesion profiles should be interpreted with caution. It is of note that the same
classical scrapie isolate induced TSE in C57Bl/6 mice with similar incubation
periods and lesional profiles as a sample derived from a MM1 sCJD
patient30.
We are therefore confident that the illness in this cynomolgus macaque
represents a true transmission of a sheep c-scrapie isolate directly to an
old-world monkey, which taxonomically resides in the primate subdivision
(parvorder of catarrhini) that includes humans. With an homology of its PrP
protein with humans of 96.4%31, cynomolgus macaque constitutes a highly relevant
model for assessing zoonotic risk of prion diseases. Since our initial aim was
to show the absence of transmission of scrapie to macaques in the worst-case
scenario, we obtained materials from a flock of naturally-infected sheep,
affecting animals with different genotypes32. This c-scrapie isolate exhibited
complete transmission in ARQ/ARQ sheep (332 ± 56 days) and Tg338 transgenic mice
expressing ovine VRQ/VRQ prion protein (220 ± 5 days) (O. Andreoletti, personal
communication). From the standpoint of zoonotic risk, it is important to note
that sheep with c-scrapie (including the isolate used in our study) have
demonstrable infectivity throughout their lymphoreticular system early in the
incubation period of the disease (3 months-old for all the lymphoid organs, and
as early as 2 months-old in gut-associated lymph nodes)33. In addition, scrapie
infectivity has been identified in blood34, milk35 and skeletal muscle36 from
asymptomatic but scrapie infected small ruminants which implies a potential
dietary exposure for consumers.
Two earlier studies have reported the occurrence of clinical TSE in
cynomolgus macaques after exposures to scrapie isolates. In the first study, the
“Compton” scrapie isolate (derived from an English sheep) and serially
propagated for 9 passages in goats did not transmit TSE in cynomolgus macaque,
rhesus macaque or chimpanzee within 7 years following intracerebral challenge1;
conversely, after 8 supplementary passages in conventional mice, this “Compton”
isolate induced TSE in a cynomolgus macaque 5 years after intracerebral
challenge, but rhesus macaques and chimpanzee remained asymptomatic 8.5 years
post-exposure8. However, multiple successive passages that are classically used
to select laboratory-adapted prion strains can significantly modify the initial
properties of a scrapie isolate, thus questioning the relevance of zoonotic
potential for the initial sheep-derived isolate. The same isolate had also
induced disease into squirrel monkeys (new-world monkey)9. A second historical
observation reported that a cynomolgus macaque developed TSE 6 years
post-inoculation with brain homogenate from a scrapie-infected Suffolk ewe
(derived from USA), whereas a rhesus macaque and a chimpanzee exposed to the
same inoculum remained healthy 9 years post-exposure1. This inoculum also
induced TSE in squirrel monkeys after 4 passages in mice. Other scrapie
transmission attempts in macaque failed but had more shorter periods of
observation in comparison to the current study. Further, it is possible that
there are differences in the zoonotic potential of different scrapie
strains.
The most striking observation in our study is the extended incubation
period of scrapie in the macaque model, which has several implications. Firstly,
our observations constitute experimental evidence in favor of the zoonotic
potential of c-scrapie, at least for this isolate that has been extensively
studied32,33,34,35,36. The cross-species zoonotic ability of this isolate should
be confirmed by performing duplicate intracerebral exposures and assessing the
transmissibility by the oral route (a successful transmission of prion strains
through the intracerebral route may not necessarily indicate the potential for
oral transmission37). However, such confirmatory experiments may require more
than one decade, which is hardly compatible with current general management and
support of scientific projects; thus this study should be rather considered as a
case report.
Secondly, transmission of c-BSE to primates occurred within 8 years post
exposure for the lowest doses able to transmit the disease (the survival period
after inoculation is inversely proportional to the initial amount of infectious
inoculum). The occurrence of scrapie 10 years after exposure to a high dose (25
mg) of scrapie-infected sheep brain suggests that the macaque has a higher
species barrier for sheep c-scrapie than c-BSE, although it is notable that
previous studies based on in vitro conversion of PrP suggested that BSE and
scrapie prions would have a similar conversion potential for human PrP38.
Thirdly, prion diseases typically have longer incubation periods after oral
exposure than after intracerebral inoculations: since humans can develop Kuru 47
years after oral exposure39, an incubation time of several decades after oral
exposure to scrapie would therefore be expected, leading the disease to occur in
older adults, i.e. the peak age for cases considered to be sporadic disease, and
making a distinction between scrapie-associated and truly sporadic disease
extremely difficult to appreciate.
Fourthly, epidemiologic evidence is necessary to confirm the zoonotic
potential of an animal disease suggested by experimental studies. A relatively
short incubation period and a peculiar epidemiological situation (e.g., all the
first vCJD cases occurring in the country with the most important ongoing c-BSE
epizootic) led to a high degree of suspicion that c-BSE was the cause of vCJD.
Sporadic CJD are considered spontaneous diseases with an almost stable and
constant worldwide prevalence (0.5–2 cases per million inhabitants per year),
and previous epidemiological studies were unable to draw a link between sCJD and
classical scrapie6,7,40,41, even though external causes were hypothesized to
explain the occurrence of some sCJD clusters42,43,44. However, extended
incubation periods exceeding several decades would impair the predictive values
of epidemiological surveillance for prion diseases, already weakened by a
limited prevalence of prion diseases and the multiplicity of isolates gathered
under the phenotypes of “scrapie” and “sporadic CJD”.
Fifthly, considering this 10 year-long incubation period, together with
both laboratory and epidemiological evidence of decade or longer intervals
between infection and clinical onset of disease, no premature conclusions should
be drawn from negative transmission studies in cynomolgus macaques with less
than a decade of observation, as in the aforementioned historical transmission
studies of scrapie to primates1,8,9. Our observations and those of others45,46
to date are unable to provide definitive evidence regarding the zoonotic
potential of CWD, atypical/Nor98 scrapie or H-type BSE. The extended incubation
period of the scrapie-affected macaque in the current study also underscores the
limitations of rodent models expressing human PrP for assessing the zoonotic
potential of some prion diseases since their lifespan remains limited to
approximately two years21,47,48. This point is illustrated by the fact that the
recently reported transmission of scrapie to humanized mice was not associated
with clinical signs for up to 750 days and occurred in an extreme minority of
mice with only a marginal increase in attack rate upon second passage13. The low
attack rate in these studies is certainly linked to the limited lifespan of mice
compared to the very long periods of observation necessary to demonstrate the
development of scrapie. Alternatively, one could estimate that a successful
second passage is the result of strain adaptation to the species barrier, thus
poorly relevant of the real zoonotic potential of the original scrapie isolate
of sheep origin49. The development of scrapie in this primate after an
incubation period compatible with its lifespan complements the study conducted
in transgenic (humanized) mice; taken together these studies suggest that some
isolates of sheep scrapie can promote misfolding of the human prion protein and
that scrapie can develop within the lifespan of some primate species.
In addition to previous studies on scrapie transmission to primate1,8,9 and
the recently published study on transgenic humanized mice13, our results
constitute new evidence for recommending that the potential risk of scrapie for
human health should not be dismissed. Indeed, human PrP transgenic mice and
primates are the most relevant models for investigating the human transmission
barrier. To what extent such models are informative for measuring the zoonotic
potential of an animal TSE under field exposure conditions is unknown. During
the past decades, many protective measures have been successfully implemented to
protect cattle from the spread of c-BSE, and some of these measures have been
extended to sheep and goats to protect from scrapie according to the principle
of precaution. Since cases of c-BSE have greatly reduced in number, those
protective measures are currently being challenged and relaxed in the absence of
other known zoonotic animal prion disease. We recommend that risk managers
should be aware of the long term potential risk to human health of at least
certain scrapie isolates, notably for lymphotropic strains like the classical
scrapie strain used in the current study. Relatively high amounts of infectivity
in peripheral lymphoid organs in animals infected with these strains could lead
to contamination of food products produced for human consumption. Efforts should
also be maintained to further assess the zoonotic potential of other animal
prion strains in long-term studies, notably lymphotropic strains with high
prevalence like CWD, which is spreading across North America, and atypical/Nor98
scrapie (Nor98)50 that was first detected in the past two decades and now
represents approximately half of all reported cases of prion diseases in small
ruminants worldwide, including territories previously considered as scrapie
free. Even if the prevailing view is that sporadic CJD is due to the spontaneous
formation of CJD prions, it remains possible that its apparent sporadic nature
may, at least in part, result from our limited capacity to identify an
environmental origin.
98 | Veterinary Record | January 24, 2015
EDITORIAL
Scrapie: a particularly persistent pathogen
Cristina Acín
Resistant prions in the environment have been the sword of Damocles for
scrapie control and eradication. Attempts to establish which physical and
chemical agents could be applied to inactivate or moderate scrapie infectivity
were initiated in the 1960s and 1970s,with the first study of this type focusing
on the effect of heat treatment in reducing prion infectivity (Hunter and
Millson 1964). Nowadays, most of the chemical procedures that aim to inactivate
the prion protein are based on the method developed by Kimberlin and
collaborators (1983). This procedure consists of treatment with 20,000 parts per
million free chlorine solution, for a minimum of one hour, of all surfaces that
need to be sterilised (in laboratories, lambing pens, slaughterhouses, and so
on). Despite this, veterinarians and farmers may still ask a range of questions,
such as ‘Is there an official procedure published somewhere?’ and ‘Is there an
international organisation which recommends and defines the exact method of
scrapie decontamination that must be applied?’
From a European perspective, it is difficult to find a treatment that could
be applied, especially in relation to the disinfection of surfaces in lambing
pens of affected flocks. A 999/2001 EU regulation on controlling spongiform
encephalopathies (European Parliament and Council 2001) did not specify a
particular decontamination measure to be used when an outbreak of scrapie is
diagnosed. There is only a brief recommendation in Annex VII concerning the
control and eradication of transmissible spongiform encephalopathies (TSE s).
Chapter B of the regulation explains the measures that must be applied if
new caprine animals are to be introduced to a holding where a scrapie outbreak
has previously been diagnosed. In that case, the statement indicates that
caprine animals can be introduced ‘provided that a cleaning and disinfection of
all animal housing on the premises has been carried out following destocking’.
Issues around cleaning and disinfection are common in prion prevention
recommendations, but relevant authorities, veterinarians and farmers may have
difficulties in finding the specific protocol which applies. The European Food
and Safety Authority (EFSA ) published a detailed report about the efficacy of
certain biocides, such as sodium hydroxide, sodium hypochlorite, guanidine and
even a formulation of copper or iron metal ions in combination with hydrogen
peroxide, against prions (EFSA 2009). The report was based on scientific
evidence (Fichet and others 2004, Lemmer and others 2004, Gao and others 2006,
Solassol and others 2006) but unfortunately the decontamination measures were
not assessed under outbreak conditions.
The EFSA Panel on Biological Hazards recently published its conclusions on
the scrapie situation in the EU after 10 years of monitoring and control of the
disease in sheep and goats (EFSA 2014), and one of the most interesting findings
was the Icelandic experience regarding the effect of disinfection in scrapie
control. The Icelandic plan consisted of: culling scrapie-affected sheep or the
whole flock in newly diagnosed outbreaks; deep cleaning and disinfection of
stables, sheds, barns and equipment with high pressure washing followed by
cleaning with 500 parts per million of hypochlorite; drying and treatment with
300 ppm of iodophor; and restocking was not permitted for at least two years.
Even when all of these measures were implemented, scrapie recurred on several
farms, indicating that the infectious agent survived for years in the
environment, even as many as 16 years after restocking (Georgsson and others
2006).
In the rest of the countries considered in the EFSA (2014) report,
recommendations for disinfection measures were not specifically defined at the
government level. In the report, the only recommendation that is made for sheep
is repopulation with sheep with scrapie-resistant genotypes. This reduces the
risk of scrapie recurrence but it is difficult to know its effect on the
infection.
Until the EFSA was established (in May 2003), scientific opinions about TSE
s were provided by the Scientific Steering Committee (SSC) of the EC, whose
advice regarding inactivation procedures focused on treating animal waste at
high temperatures (150°C for three hours) and high pressure alkaline hydrolysis
(SSC 2003). At the same time, the TSE Risk Management Subgroup of the Advisory
Committee on Dangerous Pathogens (ACDP) in the UK published guidance on safe
working and the prevention of TSE infection. Annex C of the ACDP report
established that sodium hypochlorite was considered to be effective, but only if
20,000 ppm of available chlorine was present for at least one hour, which has
practical limitations such as the release of chlorine gas, corrosion,
incompatibility with formaldehyde, alcohols and acids, rapid inactivation of its
active chemicals and the stability of dilutions (ACDP 2009).
In an international context, the World Organisation for Animal Health (OIE)
does not recommend a specific disinfection protocol for prion agents in its
Terrestrial Code or Manual. Chapter 4.13 of the Terrestrial Code, General
recommendations on disinfection and disinsection (OIE 2014), focuses on
foot-and-mouth disease virus, mycobacteria and Bacillus anthracis, but not on
prion disinfection. Nevertheless, the last update published by the OIE on bovine
spongiform encephalopathy (OIE 2012) indicates that few effective
decontamination techniques are available to inactivate the agent on surfaces,
and recommends the removal of all organic material and the use of sodium
hydroxide, or a sodium hypochlorite solution containing 2 per cent available
chlorine, for more than one hour at 20ºC.
The World Health Organization outlines guidelines for the control of TSE s,
and also emphasises the importance of mechanically cleaning surfaces before
disinfection with sodium hydroxide or sodium hypochlorite for one hour (WHO
1999).
Finally, the relevant agencies in both Canada and the USA suggest that the
best treatments for surfaces potentially contaminated with prions are sodium
hydroxide or sodium hypochlorite at 20,000 ppm. This is a 2 per cent solution,
while most commercial household bleaches contain 5.25 per cent sodium
hypochlorite. It is therefore recommended to dilute one part 5.25 per cent
bleach with 1.5 parts water (CDC 2009, Canadian Food Inspection Agency 2013).
So what should we do about disinfection against prions? First, it is
suggested that a single protocol be created by international authorities to
homogenise inactivation procedures and enable their application in all
scrapie-affected countries. Sodium hypochlorite with 20,000 ppm of available
chlorine seems to be the procedure used in most countries, as noted in a paper
summarised on p 99 of this issue of Veterinary Record (Hawkins and others 2015).
But are we totally sure of its effectiveness as a preventive measure in a
scrapie outbreak? Would an in-depth study of the recurrence of scrapie disease
be needed?
What we can conclude is that, if we want to fight prion diseases, and
specifically classical scrapie, we must focus on the accuracy of diagnosis,
monitoring and surveillance; appropriate animal identification and control of
movements; and, in the end, have homogeneous and suitable protocols to
decontaminate and disinfect lambing barns, sheds and equipment available to
veterinarians and farmers. Finally, further investigations into the resistance
of prion proteins in the diversity of environmental surfaces are required.
References
snip...
98 | Veterinary Record | January 24, 2015
Persistence of ovine scrapie infectivity in a farm environment following
cleaning and decontamination
Steve A. C. Hawkins, MIBiol, Pathology Department1, Hugh A. Simmons, BVSc
MRCVS, MBA, MA Animal Services Unit1, Kevin C. Gough, BSc, PhD2 and Ben C.
Maddison, BSc, PhD3 + Author Affiliations
1Animal and Plant Health Agency, Woodham Lane, New Haw, Addlestone, Surrey
KT15 3NB, UK 2School of Veterinary Medicine and Science, The University of
Nottingham, Sutton Bonington, Loughborough, Leicestershire LE12 5RD, UK 3ADAS
UK, School of Veterinary Medicine and Science, The University of Nottingham,
Sutton Bonington, Loughborough, Leicestershire LE12 5RD, UK E-mail for
correspondence: ben.maddison@adas.co.uk Abstract Scrapie of sheep/goats and
chronic wasting disease of deer/elk are contagious prion diseases where
environmental reservoirs are directly implicated in the transmission of disease.
In this study, the effectiveness of recommended scrapie farm decontamination
regimens was evaluated by a sheep bioassay using buildings naturally
contaminated with scrapie. Pens within a farm building were treated with either
20,000 parts per million free chorine solution for one hour or were treated with
the same but were followed by painting and full re-galvanisation or replacement
of metalwork within the pen. Scrapie susceptible lambs of the PRNP genotype
VRQ/VRQ were reared within these pens and their scrapie status was monitored by
recto-anal mucosa-associated lymphoid tissue. All animals became infected over
an 18-month period, even in the pen that had been subject to the most stringent
decontamination process. These data suggest that recommended current guidelines
for the decontamination of farm buildings following outbreaks of scrapie do
little to reduce the titre of infectious scrapie material and that environmental
recontamination could also be an issue associated with these premises.
SNIP...
Discussion
Thorough pressure washing of a pen had no effect on the amount of
bioavailable scrapie infectivity (pen B). The routine removal of prions from
surfaces within a laboratory setting is treatment for a minimum of one hour with
20,000 ppm free chlorine, a method originally based on the use of brain
macerates from infected rodents to evaluate the effectiveness of decontamination
(Kimberlin and others 1983). Further studies have also investigated the
effectiveness of hypochlorite disinfection of metal surfaces to simulate the
decontamination of surgical devices within a hospital setting. Such treatments
with hypochlorite solution were able to reduce infectivity by 5.5 logs to lower
than the sensitivity of the bioassay used (Lemmer and others 2004). Analogous
treatment of the pen surfaces did not effectively remove the levels of scrapie
infectivity over that of the control pens, indicating that this method of
decontamination is not effective within a farm setting. This may be due to the
high level of biological matrix that is present upon surfaces within the farm
environment, which may reduce the amount of free chlorine available to
inactivate any infectious prion. Remarkably 1/5 sheep introduced into pen D had
also became scrapie positive within nine months, with all animals in this pen
being RAMALT positive by 18 months of age. Pen D was no further away from the
control pen (pen A) than any of the other pens within this barn. Localised hot
spots of infectivity may be present within scrapie-contaminated environments,
but it is unlikely that pen D area had an amount of scrapie contamination that
was significantly different than the other areas within this building.
Similarly, there were no differences in how the biosecurity of pen D was
maintained, or how this pen was ventilated compared with the other pens. This
observation, perhaps, indicates the slower kinetics of disease uptake within
this pen and is consistent with a more thorough prion removal and
recontamination. These observations may also account for the presence of
inadvertent scrapie cases within other studies, where despite stringent
biosecurity, control animals have become scrapie positive during challenge
studies using barns that also housed scrapie-affected animals (Ryder and others
2009). The bioassay data indicate that the exposure of the sheep to a farm
environment after decontamination efforts thought to be effective in removing
scrapie is sufficient for the animals to become infected with scrapie. The main
exposure routes within this scenario are likely to be via the oral route, during
feeding and drinking, and respiratory and conjunctival routes. It has been
demonstrated that scrapie infectivity can be efficiently transmitted via the
nasal route in sheep (Hamir and others 2008), as is the case for CWD in both
murine models and in white-tailed deer (Denkers and others 2010, 2013).
Recently, it has also been demonstrated that CWD prions presented as dust when
bound to the soil mineral montmorillonite can be infectious via the nasal route
(Nichols and others 2013). When considering pens C and D, the actual source of
the infectious agent in the pens is not known, it is possible that biologically
relevant levels of prion survive on surfaces during the decontamination regimen
(pen C). With the use of galvanising and painting (pen D) covering and sealing
the surface of the pen, it is possible that scrapie material recontaminated the
pens by the movement of infectious prions contained within dusts originating
from other parts of the barn that were not decontaminated or from other areas of
the farm.
Given that scrapie prions are widespread on the surfaces of affected farms
(Maddison and others 2010a), irrespective of the source of the infectious prions
in the pens, this study clearly highlights the difficulties that are faced with
the effective removal of environmentally associated scrapie infectivity. This is
likely to be paralleled in CWD which shows strong similarities to scrapie in
terms of both the dissemination of prions into the environment and the facile
mode of disease transmission. These data further contribute to the understanding
that prion diseases can be highly transmissible between susceptible individuals
not just by direct contact but through highly stable environmental reservoirs
that are refractory to decontamination.
The presence of these environmentally associated prions in farm buildings
make the control of these diseases a considerable challenge, especially in
animal species such as goats where there is lack of genetic resistance to
scrapie and, therefore, no scope to re-stock farms with animals that are
resistant to scrapie.
Scrapie Sheep Goats Transmissible spongiform encephalopathies (TSE)
Accepted October 12, 2014. Published Online First 31 October 2014
PPo3-22:
Detection of Environmentally Associated PrPSc on a Farm with Endemic
Scrapie
Ben C. Maddison,1 Claire A. Baker,1 Helen C. Rees,1 Linda A. Terry,2 Leigh
Thorne,2 Susan J. Belworthy2 and Kevin C. Gough3 1ADAS-UK LTD; Department of
Biology; University of Leicester; Leicester, UK; 2Veterinary Laboratories
Agency; Surry, KT UK; 3Department of Veterinary Medicine and Science; University
of Nottingham; Sutton Bonington, Loughborough UK
Key words: scrapie, evironmental persistence, sPMCA
Ovine scrapie shows considerable horizontal transmission, yet the routes of
transmission and specifically the role of fomites in transmission remain poorly
defined. Here we present biochemical data demonstrating that on a
scrapie-affected sheep farm, scrapie prion contamination is widespread. It was
anticipated at the outset that if prions contaminate the environment that they
would be there at extremely low levels, as such the most sensitive method
available for the detection of PrPSc, serial Protein Misfolding Cyclic
Amplification (sPMCA), was used in this study. We investigated the distribution
of environmental scrapie prions by applying ovine sPMCA to samples taken from a
range of surfaces that were accessible to animals and could be collected by use
of a wetted foam swab. Prion was amplified by sPMCA from a number of these
environmental swab samples including those taken from metal, plastic and wooden
surfaces, both in the indoor and outdoor environment. At the time of sampling
there had been no sheep contact with these areas for at least 20 days prior to
sampling indicating that prions persist for at least this duration in the
environment. These data implicate inanimate objects as environmental reservoirs
of prion infectivity which are likely to contribute to disease transmission.
*** Approximately 4,200 fawns, defined as deer under 1 year of age, were
sampled from the eradication zone over the last year. The majority of fawns
sampled were between the ages of 5 to 9 months, though some were as young as 1
month. Two of the six fawns with CWD detected were 5 to 6 months old. All six of
the positive fawns were taken from the core area of the CWD eradication zone
where the highest numbers of positive deer have been identified.
"This is the first intensive sampling for CWD in fawns anywhere," said Dr.
Julie Langenberg, Department of Natural Resources wildlife veterinarian, "and we
are trying to learn as much as we can from these data".
Tuesday, July 21, 2015
Texas CWD Medina County Herd Investigation Update July 16, 2015
• 66 Texas sites, 2 Mexico sites
Wednesday, July 22, 2015
Texas Certified Chronic Wasting Disease CWD Sample Collector, like the Wolf
Guarding the Henhouse
Thursday, July 23, 2015
*** Chronic Wasting Disease (CWD) 101 Drs. Walter Cook & Donald S.
Davis
Sunday, July 26, 2015
*** TEXAS IN MELT DOWN MODE OVER CAPTIVE CWD AND THEY ARE PUTTING LIPSTICK
ON THAT PIG AND TAKING HER TO THE DANCE LIKE MAD COW DISEASE ***
Tuesday, July 28, 2015 TEXAS Kills 35 Deer at Medina County Ranch (Texas
Captive CWD)
Tuesday, August 11, 2015
Why Has the Federal Government Cut Funding for Chronic Wasting Disease
Research?
http://chronic-wasting-disease.blogspot.com/2015/08/why-has-federal-government-cut-funding.html
Tuesday, August 11, 2015
Wisconsin doing what it does best, procrastinating about CWD yet again
thanks to Governor Walker
IF the state of Texas does not get serious real fast with CWD, and test all
those deer, that 5 year plan is a ticking time bomb waiting to happen.
all cervid tested after slaughter, and test results must be released to the
public.
the tse prion aka mad cow type disease is not your normal pathogen.
The TSE prion disease survives ashing to 600 degrees celsius, that’s around
1112 degrees farenheit.
you cannot cook the TSE prion disease out of meat.
you can take the ash and mix it with saline and inject that ash into a
mouse, and the mouse will go down with TSE.
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel
Production as well.
the TSE prion agent also survives Simulated Wastewater Treatment Processes.
IN fact, you should also know that the TSE Prion agent will survive in the
environment for years, if not decades.
you can bury it and it will not go away.
The TSE agent is capable of infected your water table i.e. Detection of
protease-resistant cervid prion protein in water from a CWD-endemic area.
it’s not your ordinary pathogen you can just cook it out and be done with.
that’s what’s so worrisome about Iatrogenic mode of transmission, a simple
autoclave will not kill this TSE prion agent.
New studies on the heat resistance of hamster-adapted scrapie agent:
Threshold survival after ashing at 600°C suggests an inorganic template of
replication
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel
Production
Detection of protease-resistant cervid prion protein in water from a
CWD-endemic area
*** Infectious agent of sheep scrapie may persist in the environment for at
least 16 years***
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
Longitudinal Detection of Prion Shedding in Saliva and Urine by
CWD-Infected Deer by RT-QuIC
Davin M. Henderson1, Nathaniel D. Denkers1, Clare E. Hoover1, Nina
Garbino1, Candace K. Mathiason1 and Edward A. Hoover1# + Author Affiliations
1Prion Research Center, Department of Microbiology, Immunology, and
Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado
State University, Fort Collins, CO 80523
ABSTRACT Chronic Wasting Disease (CWD) is an emergent, rapidly spreading
prion disease of cervids. Shedding of infectious prions in saliva and urine is
thought to be an important factor in CWD transmission. To help elucidate this
issue, we applied an in vitro amplification assay to determine the onset,
duration, and magnitude of prion shedding in longitudinally collected saliva and
urine samples from CWD-exposed white-tailed deer. We detected prion shedding as
early as 3 months after CWD exposure and sustained shedding throughout the
disease course. We estimated that a 50% lethal dose (LD50) for cervidized
transgenic mice would be contained in 1 ml of infected deer saliva or 10 ml or
urine. Given the average course of infection and daily production of these body
fluids, an infected deer would shed thousands of prion infectious doses over the
course of CWD infection. The direct and indirect environmental impact of this
magnitude of prion shedding for cervid and non-cervid species is surely
significant.
Importance: Chronic wasting disease (CWD) is an emerging and uniformly
fatal prion disease affecting free ranging deer and elk and now recognized in 22
United States and 2 C anadian Provinces. It is unique among prion diseases in
that it is transmitted naturally though wild populations. A major hypothesis for
CWD's florid spread is that prions are shed in excreta and transmitted via
direct or indirect environmental contact. Here we use a rapid in vitro assay to
show that infectious doses of CWD prions are in fact shed throughout the
multi-year disease course in deer. This finding is an important advance in
assessing the risks posed by shed CWD prions to animals as well as humans.
FOOTNOTES
↵#To whom correspondence should be addressed: Edward A. Hoover, Prion
Research Center, Department of Microbiology, Immunology and Pathology, Colorado
State University, Fort Collins, Colorado, US Email: edward.hoover@colostate.edu
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced
into Great Britain? A Qualitative Risk Assessment October 2012
snip...
In the USA, under the Food and Drug Administration’s BSE Feed Regulation
(21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin)
from deer and elk is prohibited for use in feed for ruminant animals. With
regards to feed for non-ruminant animals, under FDA law, CWD positive deer may
not be used for any animal feed or feed ingredients. For elk and deer considered
at high risk for CWD, the FDA recommends that these animals do not enter the
animal feed system. However, this recommendation is guidance and not a
requirement by law.
Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD
eradication zones and
2) deer and elk that at some time during the 60-month period prior to
slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive
animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from
the USA to GB can not be determined, however, as it is not specified in TRACES.
It may constitute a small percentage of the 8412 kilos of non-fish origin
processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible
risk___ that (nonruminant) animal feed and pet food containing deer and/or elk
protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data
on the amount of deer and/or elk protein possibly being imported in these
products.
snip...
36% in 2007 (Almberg et al., 2011). In such areas, population declines of
deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of
Colorado, the prevalence can be as high as 30% (EFSA, 2011). The clinical signs
of CWD in affected adults are weight loss and behavioural changes that can span
weeks or months (Williams, 2005). In addition, signs might include excessive
salivation, behavioural alterations including a fixed stare and changes in
interaction with other animals in the herd, and an altered stance (Williams,
2005). These signs are indistinguishable from cervids experimentally infected
with bovine spongiform encephalopathy (BSE). Given this, if CWD was to be
introduced into countries with BSE such as GB, for example, infected deer
populations would need to be tested to differentiate if they were infected with
CWD or BSE to minimise the risk of BSE entering the human food-chain via
affected venison.
snip...
The rate of transmission of CWD has been reported to be as high as 30% and
can approach 100% among captive animals in endemic areas (Safar et al., 2008).
snip...
In summary, in endemic areas, there is a medium probability that the soil
and surrounding environment is contaminated with CWD prions and in a
bioavailable form. In rural areas where CWD has not been reported and deer are
present, there is a greater than negligible risk the soil is contaminated with
CWD prion.
snip...
In summary, given the volume of tourists, hunters and servicemen moving
between GB and North America, the probability of at least one person travelling
to/from a CWD affected area and, in doing so, contaminating their clothing,
footwear and/or equipment prior to arriving in GB is greater than negligible.
For deer hunters, specifically, the risk is likely to be greater given the
increased contact with deer and their environment. However, there is significant
uncertainty associated with these estimates.
snip...
Therefore, it is considered that farmed and park deer may have a higher
probability of exposure to CWD transferred to the environment than wild deer
given the restricted habitat range and higher frequency of contact with tourists
and returning GB residents.
snip...
CHRONIC WASTING DISEASE CWD TSE PRION, how much does it pay to find CWD $$$
CWD, spreading it around...
for the game farm industry, and their constituents, to continue to believe
that they are _NOT_, and or insinuate that they have _NEVER_ been part of the
problem, will only continue to help spread cwd. the game farming industry, from
the shooting pens, to the urine mills, the antler mills, the sperm mills, velvet
mills, shooting pens, to large ranches, are not the only problem, but it is
painfully obvious that they have been part of the problem for decades and
decades, just spreading it around, as with transportation and or exportation and
or importation of cervids from game farming industry, and have been proven to
spread cwd. no one need to look any further than South Korea blunder ;
===========================================
spreading cwd around...
Between 1996 and 2002, chronic wasting disease was diagnosed in 39 herds of
farmed elk in Saskatchewan in a single epidemic. All of these herds were
depopulated as part of the Canadian Food Inspection Agency’s (CFIA) disease
eradication program. Animals, primarily over 12 mo of age, were tested for the
presence CWD prions following euthanasia. Twenty-one of the herds were linked
through movements of live animals with latent CWD from a single infected source
herd in Saskatchewan, 17 through movements of animals from 7 of the secondarily
infected herds.
***The source herd is believed to have become infected via importation of
animals from a game farm in South Dakota where CWD was subsequently diagnosed
(7,4). A wide range in herd prevalence of CWD at the time of herd depopulation
of these herds was observed. Within-herd transmission was observed on some
farms, while the disease remained confined to the introduced animals on other
farms.
spreading cwd around...
Friday, May 13, 2011
Chronic Wasting Disease (CWD) outbreaks and surveillance program in the
Republic of Korea
Hyun-Joo Sohn, Yoon-Hee Lee, Min-jeong Kim, Eun-Im Yun, Hyo-Jin Kim,
Won-Yong Lee, Dong-Seob Tark, In- Soo Cho, Foreign Animal Disease Research
Division, National Veterinary Research and Quarantine Service, Republic of Korea
Chronic wasting disease (CWD) has been recognized as an important prion
disease in native North America deer and Rocky mountain elks. The disease is a
unique member of the transmissible spongiform encephalopathies (TSEs), which
naturally affects only a few species. CWD had been limited to USA and Canada
until 2000.
On 28 December 2000, information from the Canadian government showed that a
total of 95 elk had been exported from farms with CWD to Korea. These consisted
of 23 elk in 1994 originating from the so-called “source farm” in Canada, and 72
elk in 1997, which had been held in pre export quarantine at the “source
farm”.Based on export information of CWD suspected elk from Canada to Korea, CWD
surveillance program was initiated by the Ministry of Agriculture and Forestry
(MAF) in 2001.
All elks imported in 1997 were traced back, however elks imported in 1994
were impossible to identify. CWD control measures included stamping out of all
animals in the affected farm, and thorough cleaning and disinfection of the
premises. In addition, nationwide clinical surveillance of Korean native
cervids, and improved measures to ensure reporting of CWD suspect cases were
implemented.
Total of 9 elks were found to be affected. CWD was designated as a
notifiable disease under the Act for Prevention of Livestock Epidemics in 2002.
Additional CWD cases - 12 elks and 2 elks - were diagnosed in 2004 and
2005.
Since February of 2005, when slaughtered elks were found to be positive,
all slaughtered cervid for human consumption at abattoirs were designated as
target of the CWD surveillance program. Currently, CWD laboratory testing is
only conducted by National Reference Laboratory on CWD, which is the Foreign
Animal Disease Division (FADD) of National Veterinary Research and Quarantine
Service (NVRQS).
In July 2010, one out of 3 elks from Farm 1 which were slaughtered for the
human consumption was confirmed as positive. Consequently, all cervid – 54 elks,
41 Sika deer and 5 Albino deer – were culled and one elk was found to be
positive. Epidemiological investigations were conducted by Veterinary
Epidemiology Division (VED) of NVRQS in collaboration with provincial veterinary
services.
Epidemiologically related farms were found as 3 farms and all cervid at
these farms were culled and subjected to CWD diagnosis. Three elks and 5
crossbreeds (Red deer and Sika deer) were confirmed as positive at farm 2.
All cervids at Farm 3 and Farm 4 – 15 elks and 47 elks – were culled and
confirmed as negative.
Further epidemiological investigations showed that these CWD outbreaks were
linked to the importation of elks from Canada in 1994 based on circumstantial
evidences.
In December 2010, one elk was confirmed as positive at Farm 5.
Consequently, all cervid – 3 elks, 11 Manchurian Sika deer and 20 Sika deer –
were culled and one Manchurian Sika deer and seven Sika deer were found to be
positive. This is the first report of CWD in these sub-species of deer.
Epidemiological investigations found that the owner of the Farm 2 in CWD
outbreaks in July 2010 had co-owned the Farm 5.
In addition, it was newly revealed that one positive elk was introduced
from Farm 6 of Jinju-si Gyeongsang Namdo. All cervid – 19 elks, 15 crossbreed
(species unknown) and 64 Sika deer – of Farm 6 were culled, but all confirmed as
negative.
Friday, August 07, 2015
Texas CWD Captive, and then there were 4 ?
Thursday, August 06, 2015
WE HAVE LOST TEXAS TO CWD TASK FORCE CATERING TO INDUSTRY
HAVE YOU BEEN THUNDERSTRUCK ?
Thursday, July 24, 2014
*** Protocol for further laboratory investigations into the distribution of
infectivity of Atypical BSE SCIENTIFIC REPORT OF EFSA New protocol for Atypical
BSE investigations
Wednesday, July 15, 2015
*** Additional BSE TSE prion testing detects pathologic lesion in unusual
brain location and PrPsc by PMCA only, how many cases have we missed?
Wednesday, July 29, 2015
Further characterisation of transmissible spongiform encephalopathy
phenotypes after inoculation of cattle with two temporally separated sources of
sheep scrapie from Great Britain
Wednesday, July 29, 2015
Porcine Prion Protein Amyloid or mad pig disease PSE
Monday, August 10, 2015
Detection and Quantification of beta-Amyloid, Pyroglutamyl A beta, and Tau
in Aged Canines
http://caninespongiformencephalopathy.blogspot.com/2015/08/detection-and-quantification-of-beta.html
Friday, August 7, 2015
Transgenic Mouse Bioassay: Evidence That Rabbits Are Susceptible to a
Variety of Prion Isolates
Thursday, August 13, 2015
Iatrogenic CJD due to pituitary-derived growth hormone with genetically
determined incubation times of up to 40 years
Thursday, January 15, 2015
41-year-old Navy Commander with sporadic Creutzfeldt–Jakob disease CJD TSE
Prion: Case Report
Subject: *** Becky Lockhart 46, Utah’s first female House speaker, dies
diagnosed with the extremely rare Creutzfeldt-Jakob disease aka mad cow type
disease
what is CJD ? just ask USDA inc., and the OIE, they are still feeding the
public and the media industry fed junk science that is 30 years old.
why doesn’t some of you try reading the facts, instead of rubber stamping
everything the USDA inc says.
sporadic CJD has now been linked to BSE aka mad cow disease, Scrapie, and
there is much concern now for CWD and risk factor for humans.
My sincere condolences to the family and friends of the House Speaker Becky
Lockhart. I am deeply saddened hear this.
with that said, with great respect, I must ask each and every one of you
Politicians that are so deeply saddened to hear of this needless death of the
Honorable House Speaker Becky Lockhart, really, cry me a friggen river. I am
seriously going to ask you all this...I have been diplomatic for about 17 years
and it has got no where. people are still dying. so, are you all stupid or
what??? how many more need to die ??? how much is global trade of beef and other
meat products that are not tested for the TSE prion disease, how much and how
many bodies is this market worth?
Saturday, January 17, 2015
*** Becky Lockhart 46, Utah’s first female House speaker, dies diagnosed
with the extremely rare Creutzfeldt-Jakob disease
*** ALERT new variant Creutzfeldt Jakob Disease nvCJD or vCJD, sporadic CJD
strains, TSE prion aka Mad Cow Disease United States of America Update December
14, 2014 Report ***
*** Creutzfeldt-Jakob Disease Public Health Crisis VIDEO
Alzheimer’s, iatrogenic, what if ?
Friday, January 10, 2014
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type
prion disease, what it ???
iatrogenic TSE prion disease, at a hospital near you, what if ???
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
3:53 PM
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