on a wing and a prayer, and over 100-year modeled timeframes...
Chronic wasting disease model of genetic selection favoring prolonged
survival in Rocky Mountain elk (Cervus elaphus)
A. L. WILLIAMS,1, T. J. KREEGER,2,3 AND B. A. SCHUMAKER 1
1Department of Veterinary Sciences, University of Wyoming, Laramie, Wyoming
82070 USA 2Wyoming Game and Fish Department, Thorne-Williams Wildlife Research
Unit, Wheatland, Wyoming 82201 USA Citation: Williams, A. L., T. J. Kreeger, and
B. A. Schumaker. 2014. Chronic wasting disease model of genetic selection
favoring prolonged survival in Rocky Mountain elk (Cervus elaphus). Ecosphere
5(5):60.
http://dx.doi.org/10.1890/
ES14-00013.1
Abstract.
As the area where chronic wasting disease (CWD) has been found continues to
expand, there is concern over the impact it may have on elk (Cervus elaphus)
populations that congregate on winter feedgrounds in Wyoming. A stochastic
simulation model was created to determine the effect that genotype-specific CWD
mortality rates had on a hypothetical free-ranging elk population. Life table
data gathered from captive elk held in a CWD-contaminated facility was used to
parameterize the model. Modeling the free-ranging elk herd without hunting or
differences in survival by genotype resulted in a near extinction decrease in
elk numbers over a 100-year period. However, incorporating differences in
CWD-mortality by genotype into the model allowed the population to stabilize if
hunting was modified to harvest only antlered elk. Our results indicate that,
with flexible hunting management, elk populations could adapt to CWD through
changes in the frequency of genotypes associated with the incubation time for
CWD.
snip...
All possible levels of hunting were not analyzed.
An antlered-only management option that maintained current high levels of
bull harvest caused a decrease in the population well below the population
objective. However, the downward trend stabilized and suggested that if the time
frame was drawn out, the population may begin to rebound. The antlered only
strategy was included because it is one method that is highly likely to be
incorporated in an area where the population is a concern to managers who want
to continue hunting (Wyoming Game and Fish Department 2009). The model showed
that in an environment without harvest, CWD was not limiting enough to keep this
population from rising to higher than desired numbers (i.e., three times the
proposed population objective of 1,900 elk; Wyoming Game and Fish Department
2012). Our models indicated that elk populations exposed to PrPCWD could respond
through changes in frequency of genotypes with varying incubation times. Also,
changes in hunting strategies of elk populations could help maintain numbers
through these transitional periods. A reduction in hunting would likely be
necessary; however, eliminating harvest of all elk would allow this population
to exceed population objectives over time. Experimentation with hunting levels
likely would be required to determine what level of elk harvest is most likely
to maintain desired numbers. Additionally, monitoring genotypic frequencies in
conjunction with fecundity and recruitment are highly warranted.
According to our models and assumptions and considering prolonged
incubation times associated with certain genotypes, CWD alone was not enough to
cause extinction of elk herds that congregate on winter feedgrounds. While CWD
can negatively impact wildlife populations (Miller et al. 2008), our results
indicated that, with flexible management, elk populations could adapt to CWD
through increases in the frequency of genotypes over 100-year modeled
timeframes.
Key words: Cervus elaphus; chronic wasting disease; elk; feedgrounds;
genetics; model; prion; Wyoming, USA.
Article Citation: Lisa L. Wolfe, Karen A. Fox, and Michael W. Miller (2014)
“Atypical” Chronic Wasting Disease in PRNP Genotype 225FF Mule Deer.
Ahead of Print “Atypical” Chronic Wasting Disease in PRNP Genotype 225FF
Mule Deer Lisa L. Wolfe 1,2, Karen A. Fox 1, and Michael W. Miller 1 1 Colorado
Division of Parks and Wildlife, Wildlife Research Center, 317 West Prospect
Road, Fort Collins, Colorado 80526-2097, USA
Abstract
We compared mule deer (Odocoileus hemionus) of two different PRNP genotypes
(225SS, 225FF) for susceptibility to chronic wasting disease (CWD) in the face
of environmental exposure to infectivity. All three 225SS deer had
immunohistochemistry (IHC)-positive tonsil biopsies by 710 days postexposure
(dpe), developed classic clinical signs by 723–1,200 dpe, and showed gross and
microscopic pathology, enzyme-linked immunosorbent assay (ELISA) results, and
IHC staining typical of prion disease in mule deer. In contrast, although all
three 225FF deer also became infected, the two individuals surviving >720 dpe
had consistently negative biopsies, developed more-subtle clinical signs of CWD,
and died 924 or 1,783 dpe. The 225FF deer were “suspect” by ELISA postmortem but
showed negative or equivocal IHC staining of lymphoid tissues; both clinically
affected 225FF deer had spongiform encephalopathy in the absence of IHC staining
in the brain tissue. The experimental cases resembled three cases encountered
among five additional captive 225FF deer that were not part of our experiment
but also died from CWD. Aside from differences in clinical disease presentation
and detection, 225FF mule deer also showed other, more-subtle, atypical traits
that may help to explain the rarity of this genotype in natural populations,
even in the presence of enzootic CWD.
Key words: Chronic wasting disease, genotype, mule deer, Odocoileus
hemionus, prion, PRNP
Received: October 21, 2013; Accepted: January 22, 2014 ;Published Online:
May 7, 2014
2 Corresponding author (email: lisa.wolfe@state.co.us)
Immunity No immune response to the CWD prion protein has been
detected.
Background: Transmissible spongiform encephalopathies (TSEs) are a group of
related diseases that include Creutzfeldt-Jakob disease (CJD) and its new
variant (vCJD), kuru, scrapie, bovine spongiform encephalopathy (BSE; “mad cow
disease”), chronic wasting disease (CWD) in deer and elk, and others. These
diseases have incubation periods of years or decades, cause progressive
neurological degeneration, evoke no obvious immune response, and are invariably
fatal.
Our earlier work demonstrated that elk with the prion genotype 132LL were
underrepresented in infected elk *** although the genotype is not fully
protective in captive elk. We have now demonstrated that the 132L allele extends
the incubation time in elk, resulting in a doubling of the preclinical
incubation period. This finding is important for regulatory agencies and
producers in states in which clinical disease is considered in selection of
animals for surveillance testing.
Further, although our earlier work demonstrated that elk with the prion
genotype 132LL were underrepresented in infected elk, *** we confirmed one case
of CWD in an elk of this genotype, demonstrating that these elk are not
invariably resistant to disease.
However, we demonstrated that a relatively high percentage of elk with
positive tests on brain tissue have negative tests of the retropharyngeal lymph
node. Therefore, accurate diagnosis of elk requires examination of both the
brain and the lymph node.
This report serves to document research conducted under a specific
cooperative agreement between ARS and Colorado State University. Additional
details of research can be found in the report for the parent project
5348-32000-021-00D Animal Health.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Title: Prolonged CWD incubation time
and unique PrP**d profile in Prnp 132LL elk
Authors
item Greenlee, Justin item O'Rourke, Katherine item Hamir, Amirali item
Gidlewski, Thomas - USDA-VS-APHIS, FT COLLINS item Zhuang, Dongyue item Spraker,
Terry - COLORADO STATE UNIVERSITY
Submitted to: United States Animal Health Association Proceedings
Publication Type: Abstract Only Publication Acceptance Date: October 20, 2007
Publication Date: October 20, 2007 Repository URL:
http://www.usaha.org/meetings/proceedings.shtml
Citation: Greenlee, J.J., O'Rourke, K.I., Hamir, A.N., Gidlewski, T., Zhuang,
D., Spraker, T. 2007. Prolonged CWD Incubation Time and Unique PrP**d Profile in
Prnp 132LL Elk. In: Proceedings of the U.S. Animal Health Association 111th
Annual Meeting, Captive Wildlife and Alternative Livestock Committee, October
20, 2007, Reno, Nevada. p. 264-265.
Technical Abstract:
The transmissible spongiform encephalopathies including chronic wasting
disease (CWD) in deer and elk invariably result in fatal neurodegeneration and
accumulation of PrP**d, an abnormal form of the host prion protein PrP**c. In
some species, polymorphisms in the open reading frame of the Prnp gene are
associated with differences in the manifestation of prion disease including
relative susceptibility, clinical signs, incubation time, and neuropathology.
The polymorphism (M to L) at Prnp 132 in Rocky Mountain Elk (Cervus elaphus
nelsoni) corresponds to the human (M to V) polymorphism at Prnp 129, which has
been associated with susceptibility to vCJD. Elk with 132 M alleles are
predisposed to CWD and heterozygosity is associated with a prolonged incubation
time following experimental challenge. Previous studies suggest that elk
homozygous for 132 L occur rarely and make up the extreme minority of elk
affected with CWD. The effect of the 132 LL genotype on the development of CWD
post-exposure was previously unknown. The purpose of this study was to define
the course of disease in elk with various Prnp 132 allele combinations. Elk
(n=8; 2MM, 2LM, 4LL) were orally inoculated at 8 months of age with 15 ml of
pooled brain homogenate from one 132 MM and one 132 LM elk. Elk were observed
daily after inoculation and necropsies were done when clinical signs became
unequivocal. Immunohistochemistry (IHC), western blot, and microscopic
examination were used to confirm infection. Incubation time was dependent on
genotype. Clinical signs were apparent in 132 MM elk after 23 months and 132 LM
elk after 40 months. Rectal biopsies were done on the remaining 132 LL elk with
3 of 4 testing positive for PrP**d by IHC indicating peripheral distribution of
PrP**d is apparent prior to the onset of clinical disease. Clinical signs were
apparent in 132 LL elk after 59-63 months. One elk was euthanized 63 months
post-inoculation without exhibiting clinical signs, but had PrP**d accumulation
in CNS and peripheral lymphoid tissues. Differences between genotype were
apparent after western blot analysis. The molecular weight of the proteinase K
resistant bands of PrP**d is lower in the 132LL elk compared to 132MM or 132LM
elk.
***In summary, LL elk are susceptible to CWD, but have a prolonged
incubation time and western blot profile unique from other genotypes of elk with
CWD. Additional studies are planned to determine the mechanisms responsible for
the distinct presentation of CWD in 132 LL elk.
every time someone claims a certain species or type of species resistant to
a TSE prion, years later they are proven wrong, as with the rabbit and the tse
prion.
SEE;
“Our results confirm previous studies shattering the myth that rabbits are
resistant to prion infection and this should be taken into account when choosing
protein sources to feed rabbits.”
THERE are many reasons in the cwd study quoted, why 41 percent percent
tested negative, and them being resistant would be the last. it’s only wishful
thinking folks, wishful thinking to dream that ;
‘’see a CWD-resistant deer herd as soon as 50 years’’ but dream on if you
must $$$
there is nothing to date that is even close to producing any TSE prion free
herd of any species, but yet some are willing to risk the entire Wisconsin deer
herd on a whelm and a dream $$$ good luck with that. ...
If we let nature take its course, won’t deer become completely resistant to
CWD?
Researchers have investigated for genetic resistance to this disease within
white-tailed deer.
***Unfortunately, no white-tailed deer genotypes have been identified with
complete resistance to CWD.
Researchers have found an uncommon genotype that appears to allow deer to
survive longer with CWD than other genetic types, but they still eventually die
from CWD. This research also implies that deer with this genotype also have more
time to expose other healthy deer to CWD.
see;
‘’Furthermore, the prevalence of the disease and risk factors are not well
understood. According to CWD specialists, there is small hope that CWD will run
its course and leave behind a generation of CWD resistant deer; *** however,
many scientists do not believe this is the case for CWD.’’
P.159: Transgenic mice overexpressing rabbit prion protein are susceptible
to BSE, BASE and scrapie prion strains but resistant to CWD and atypical scrapie
Natalia Fernández-Borges,1 Enric Vidal,2 Belén Pintado,4 Hasier Eraña,1
Montserrat Ordóñez,3 Mercedes Márquez,5 Francesca Chianini,6 Dolors Fondevila,5
Manuel A Sánchez-Martín,7 Olivier Andréoletti,8 Mark P Dagleish,6 Martí
Pumarola,5 and Joaquín Castilla1,3 1CIC bioGUNE; Parque tecnológico de Bizkaia;
Derio; Bizkaia, Spain; 2Centre de Recerca en Sanitat Animal (CReSA); UAB-IR TA,
Campus de la Universitat Autònoma de Barcelona; Bellaterra; Barcelona,
Catalonia, Spain; 3IKERBASQUE; Basque Foundation for Science; Bilbao, Bizkaia,
Spain; 4Centro Nacional de Biotecnología (CNB), Campus de Cantoblanco;
Cantoblanco; Madrid, Spain; 5Department of Animal Medicine and Surgery;
Veterinary faculty; Universitat Autònoma de Barcelona (UAB); Bellaterra
(Cerdanyola del Vallès); Barcelona, Catalonia, Spain; 6Moredun Research
Institute; Bush Loan, Penicuik, Scotland, UK; 7Unidad de Generación de OMGs.
S.E.A. Department of Medicine; University of Salamanca; Salamanca, Spain; 8Ecole
Nationale du Veterinaire; Service de Pathologie du Bétail; Toulouse, France
Interspecies transmission of prions is a well established phenomenon, both
experimentally and in field conditions. Upon passage through new hosts prion
strains have proven their capacity to change their properties. It is, in fact, a
source of strain diversity which needs to be considered when assessing the
potential risks associated with consumption of prion contaminated protein
sources.
Rabbits were considered for decades a prion resistant species until proven
recently otherwise. To determine the extent of rabbit susceptibility to prions
and to assess their effects on the passage of different prion strains through
this species, a transgenic mouse model overexpressing rabbit PrPC was developed
(TgRab). Intracerebral challenges with prion strains originating from a variety
of species including field isolates (SSBP1 scrapie, Nor98-like scrapie, BSE,
BASE and CWD), experimental murine strains (ME7 and RML), experimentally
obtained strains (sheepBSE) and strains obtained by in vitro crossing of the
species barrier using saPMCA (BSE-RabPrPres, SSBP1-RabPrPres and CWD-RabPrPres)
have been performed.
Interestingly, on first passage, TgRab were susceptible to the majority of
prions tested with the exception of SSBP1 scrapie, CWD and Nor98 scrapie.
Furthermore TgRab were capable of propagating strain-specific features such as
differences in incubation periods, brain lesion and PrPd deposition profiles and
PK resistant western blotting band patterns. Our results confirm previous
studies shattering the myth that rabbits are resistant to prion infection and
this should be taken into account when choosing protein sources to feed rabbits.
Research Project: TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES: THE ROLE OF
GENETICS, STRAIN VARIATION, AND ENVIRONMENTAL CONTAMINATION IN DISEASE CONTROL
Location: Animal Diseases Research
Title: Resistance of fallow deer (dama dama) to chronic wasting disease
under natural exposure in a heavily contaminated environment
Authors
item Rhyan, J - item Spraker, T - item Mccollum, M - item Nol, P - item
Wolfe, L - item Miller, M - item Davis, T - item Creekmore, L - item O'Rourke,
Katherine
Submitted to: Journal of Wildlife Diseases Publication Type: Peer Reviewed
Journal Publication Acceptance Date: April 3, 2011 Publication Date: November
25, 2009 Citation: Rhyan, J.C., Spraker, T.R., Mccollum, M., Nol, P., Wolfe, L.,
Miller, M.W., Davis, T., Creekmore, L., Orourke, K.I. 2009. Resistance of fallow
deer (dama dama) to chronic wasting disease under natural exposure in a heavily
contaminated environment. Journal of Wildlife Diseases. 47(3):739-744.
Interpretive Summary: Chronic wasting disease or CWD is a fatal
neurodegenerative disease of deer and elk in North America. The disease is a
member of the prion family of disorders and is associated with misfolding of a
normal host prion protein. Detection of the misfolded protein is a useful
diagnostic test, particularly for animals in early disease. CWD has been
diagnosed in wild mule deer (Odocoileus hemionus), white-tailed deer (O.
virginianus), Rocky Mountain elk (Cervus elaphus), and Shira's moose (Alces
alces). Disease outbreaks in farmed cervids in the US and Canada have
demonstrated some differences in relative disease susceptibility associated with
changes in the gene for the normal prion protein ***but no genotype has been
linked to disease resistance. However, CWD has not been diagnosed in farmed
fallow deer (Dama dama) on farms with infected deer or elk. Fallow deer are
susceptible to direct inoculation of infected material into the brain, but the
levels of abnormal prion protein in the experimentally infected fallow deer were
low. In this study, we investigated the susceptibility of fallow deer to natural
disease transmission by housing fallow deer for up to 7 years in pens with mule
deer, a highly susceptible species showing strong evidence of prion shedding
into the environment. There was no evidence of disease or abnormal prion protein
in any of the fallow deer in this study. DNA analysis of the deer in the study
demonstrated a naturally occurring genetic mutation that may confer resistance
to CWD. If confirmed in follow up studies, fallow deer would be the first CWD
resistant cervid species. Technical Abstract: Chronic wasting disease or CWD is
a transmissible spongiform encephalopathy or prion disorder of cervid ruminants
in several regions of the US and Canada. The prion disorders are characterized
by misfolding of the host cellular prion protein into a relatively protease
resistant and potentially neurotoxic disease-associated isoform. CWD is highly
transmissible in mule deer (Odocoileus hemionus) with evidence for horizontal
transmission and environmental persistence of the infectious agent in the
environment. Examination of tissues from depopulated infected herds in the US
and Canada has not yet shown evidence of CWD in farmed fallow deer (Dama dama),
an imported species raised for meat, antlers, and exhibition purposes. In this
study, fallow deer were held in pens with a succession of CWD-infected mule deer
for 7 years. Mule deer losses were 100% during that time, with an average
incubation time of less than 3 years. In spite of this persisent natural
exposure, no evidence of abnormal prion protein was found in the tissues of the
fallow deer following 7 years of exposure. Resistance to prion disease in sheep
and possibly in goats in associated with single amino acid changes in the normal
prion protein. All fallow deer examined to date are homozygous for asparagine
(N) at residue 138. Mule deer, white-tailed deer, Rocky Mountain elk, and
Shira's moose are all homozygous for serine (S) at that site, although the
unexpressed cervid pseudogene encodes 138N. This finding represents the first
possible evidence for genetic resistance to CWD in cervids.
***but no genotype has been linked to disease resistance.
*** This finding represents the first possible evidence for genetic
resistance to CWD in cervids. ...NOT!!!
SEE ;
Experimental transmission of chronic wasting disease (CWD) from elk and
white-tailed deer to fallow deer by intracerebral route: Final report
Amir N. Hamir, Justin J. Greenlee, Eric M. Nicholson, Robert A. Kunkle,
Juergen A. Richt, Janice M. Miller, Mark Hall
Ab s t r a c t
Final observations on experimental transmission of chronic wasting disease
(CWD) from elk (Cervus elaphus nelsoni) and whitetailed deer (Odocoileus
virginianus) to fallow deer (Dama dama) are reported herein. During the 5-year
study, 13 fawns were inoculated intracerebrally with CWD-infected brain material
from white-tailed deer (n = 7; Group A) or elk (n = 6; Group B), and 3 other
fawns were kept as uninoculated controls (Group C). As described previously, 3
CWD-inoculated deer were euthanized at 7.6 mo post-inoculation (MPI). None
revealed presence of abnormal prion protein (PrPd) in their tissues. At 24
(Group A) and 26 (Group B) MPI, 2 deer were necropsied. Both animals had a small
focal accumulation of PrPd in their midbrains. Between 29 and 37 MPI, 3 other
deer (all from Group A) were euthanized. The 5 remaining deer became sick and
were euthanized between 51 and 60 MPI (1 from Group A and 4 from Group B).
Microscopic lesions of spongiform encephalopathy (SE) were observed in only
these 5 animals; however, PrPd was detected in tissues of the central nervous
system by immunohistochemistry, Western blot, and by commercial rapid test in
all animals that survived beyond 24 MPI. This study demonstrates that
intracerebrally inoculated fallow deer not only amplify CWD prions, but also
develop lesions of spongiform encephalopathy.
Voluntary Report - public distribution Date: 6/17/2003 GAIN Report Number:
E23101 E23101 European Union Sanitary/Phytosanitary/Food Safety Chronic Wasting
Disease 2003
Approved by: Justina Torry U.S. Mission to the European Union, Brussels
Prepared by: Sandie Kipe
Report Highlights: On March 7, 2003 the Scientific Steering Committee (SSC)
of the European Commission Health and Consumer Protection Directorate General
issued an opinion on Chronic Wasting Disease. However, the United States
currently does not export significant quantities of live deer to the EU.
Includes PSD Changes: No Includes Trade Matrix: No Unscheduled Report
Brussels USEU [BE2] [E2]
Summary On March 7, 2003 the Scientific Steering Committee (SSC) of the
European Commission Health and Consumer Protection Directorate General the
issued an opinion on Chronic Wasting Disease.
The opinion indicates that the early and widespread involvement of tissues
in CWD infected animals does not allow the definition of a specified risk
material list. However, due to the theoretical possibility of transmission to
humans, livestock, or other domestic animals, the SSC concludes that it is
important to ensure that no infectivity to the EU occurs through trade in live
cervids. Currently, exports to the EU of deer and deer products are minimal.
Background Chronic wasting disease is predominately found in deer, and is
caused by protein prions in the brain that are malformed. The malformed prion
protein becomes a pathogen capable of killing the diseased animal. The pathogen
peppers neutral tissue full of microscopic holes and gums up the brain with
toxic clumps of protein called amyloid plaques, eventually causing enough damage
to kill the animal. The malformed prion is extremely resistant, requiring
extensive heating or corrosive chemicals to disinfect the prion.
CWD is in the same family as better-known bovine spongiform encepalopathy
(BSE), or mad cow disease. BSE was spread by animal based feed inadvertently
containing tissue from sick cows and sheep in the early 1980s in the U.K. BSE
continues to persist in the U.K. but at a lower level relative to the earlier
outbreak. In 1996 scientists realized that BSE could pass to humans who have
consumed infected meat, leading to the fatal condition of Crueutzfeldt-Jakob
disease (vCJD).
Researchers are currently working to determine if CWD could infect humans.
A test tube study mixed CWD prions with healthy prions from cervids, humans,
cows, and sheep. The CWD prions did have difficulty converting normal human
prion proteins; only less than 7 percent were changed. However, this rate is
relatively the same as that of BSE, which is known to affect humans leaving
researchers to conclude that CWD may pose a similar health risk to humans.
The SSC report states that the disease is easily communicable from deer to
deer, in experimental studies oral exposure to only small dosages resulted in
infection. No practical live test exists to check whether an apparently healthy
wild animal is infected with CWD, only a brain sample test can determine if CWD
is present. Furthermore, the prevalence of the disease and risk factors are not
well understood. According to CWD specialists, there is small hope that CWD will
run its course and leave behind a generation of CWD resistant deer; ***however,
many scientists do not believe this is the case for CWD.
During the March 6-7 meeting of the SSC, the recommendation was issued that
no live cervids from North America be imported into Europe, since it is still
unknown if the disease can spread to humans, livestock, or other domesticated
animals. The SSC also recommended that a surveillance program is necessary to
monitor any possible occurrence of CWD in Europe.
The full opinion may be viewed at:
Visit our website: our website www.useu.be/agri/usda.html provides a broad
range of useful information on EU import rules and food laws and allows easy
access to USEU reports, trade information and other practical information. More
information on animal diseases can be found at
http://www.fas.usda.gov/dlp/BSE/bse.html.
E-mail: AgUSEUBrussels@fas.usda.gov
Related reports from USEU Brussels:
Report Number Title Date Released E23012 EU Veterinary Legislation Guide
01/28/2003
UNCLASSIFIED USDA FOREIGN AGRICULTURAL SERVICE
Classic Scrapie in Sheep with the ARR/ARR Prion Genotype in Germany and
France
Martin H. Groschup,*1 Caroline Lacroux,†1 Anne Buschmann,* Gesine Lühken,‡
Jacinthe Mathey,† Martin Eiden,* Séverine Lugan,† Christine Hoffmann,* Juan
Carlos Espinosa,§ Thierry Baron,¶ Juan Maria Torres,§ Georg Erhardt,‡ and
Olivier Andreoletti†
In the past, natural scrapie and bovine spongiform encephalopathy (BSE)
infections have essentially not been diagnosed in sheep homozygous for the
A136R154R171 haplotype of the prion protein. This genotype was therefore assumed
to confer resistance to BSE and classic scrapie under natural exposure
conditions. Hence, to exclude prions from the human food chain, massive breeding
efforts have been undertaken in the European Union to amplify this gene. We
report the identifi cation of 2 natural scrapie cases in ARR/ARR sheep that have
biochemical and transmission characteristics similar to cases of classic
scrapie, although the abnormally folded prion protein (PrPSc) was associated
with a lower proteinase-K resistance. PrPSc was clearly distinct from BSE prions
passaged in sheep and from atypical scrapie prions. These findings strongly
support the idea that scrapie prions are a mosaic of agents, which harbor
different biologic properties, rather than a unique entity.
snip...
The discovery of these 2 cases clearly indicates that the genetic
resistance of ARR/ARR sheep to the so-called clas-
sic scrapie agent is not absolute. It also provides evidence that, rather
than being a single entity, scrapie is a mosaic of infectious agents harboring
different biologic properties in its natural host....
A ProMED-mail post
ProMED-mail is a program of the International Society for Infectious
Diseases
[1] Date: Fri 12 Mar 2010 Source: The Australian [edited]
A West Australian sheep has been found to have signs characteristic of the
fatal brain disease atypical scrapie. It comes as Australia faces growing anger
from its trade partners over the Rudd government's surprise decision to extend a
ban on the importation of beef from countries exposed to mad cow disease for a
further 2 years.
Australia's chief veterinarian, Andy Carroll, told the ABC an indicative
case of the atypical scrapie had been confirmed but said it posed no risk to
human or animal health or the safety of eating meat and animal products.
Nor does atypical scrapie carry the dire trade consequences associated with
classical scrapie.
Classical scrapie is in the same transmissible spongiform encephalopathies
(TSE) family as BSE, better known as mad cow disease, from which humans can be
fatally infected.
Dr Carroll said samples from the sheep's brain were being sent to the World
Reference Laboratory in Britain.
Neither atypical scrapie nor classical scrapie has been seen in Australia
before, but a sheep in New Zealand tested positive to the atypical form last
year [2009].
Atypical scrapie is a relatively recently discovered disease and the common
scientific view is that it occurs spontaneously or naturally in very small
numbers of older sheep in countries all over the world.
[Byline: Jodie Minus]
-- Communicated by: Sabine Zentis Castleview Pedigree English Longhorns Gut
Laach 52385 Nideggen Germany
****** [2] Date: Wed 10 Mar 2010 Source: ABC News (Australian Broadcasting
Corporation) [edited]
Animal health authorities are testing a sheep's brain for what could be
Australia's 1st case of the disease atypical scrapie.
Although not confirmed, the sheep is thought to be from Western
Australia.
This type of scrapie is described as a sporadic degenerative brain
condition affecting older sheep, and is not contagious.
Ed Klim, from national advisory group SafeMeat, says a 2nd round of testing
is now taking place. "We've been made aware that the Australian Animal Health
Laboratory is conducting further routine testing on a sheep sample," he
says.
"The disease isn't considered a health risk nor should have any impact on
food safety or export markets for sheep meat of live sheep."
Australia's chief veterinarian and WA's Department of Agriculture of Food
are both aware of the testing but will not comment.
-- Communicated by: Terry S Singeltary Sr
[Although atypical scrapie is not yet ruled out, it is important to realize
this is a type of scrapie that thus far has only tended to appear as a sporadic
condition in older animals. Currently it has not been shown to follow the same
genetic tendencies for propagation as the usual scrapie.
However, the atypical phenotypic appearance has been shown to be preserved
on experimental passage.
Atypical scrapie was first identified in Norwegian sheep in 1998 and has
subsequently been identified in many countries, as Australia may join that list.
It is likely that this case will be sent to the UK for definitive
conformation.
[Ref: M Simmons, T Konold, L Thurston, et al. BMC Veterinary Research 2010,
6:14 [provisional abstract available at ]
"Background ----------- "Retrospective studies have identified cases
predating the initial identification of this form of scrapie, and
epidemiological studies have indicated that it does not conform to the behaviour
of an infectious disease, giving rise to the hypothesis that it represents
spontaneous disease. However, atypical scrapie isolates have been shown to be
infectious experimentally, through intracerebral inoculation in transgenic mice
and sheep. [Many of the neurological diseases can be transmitted by
intracerebral inoculation, which causes this moderator to approach intracerebral
studies as a tool for study, but not necessarily as a direct indication of
transmissibility of natural diseases. - Mod.TG]
"The 1st successful challenge of a sheep with 'field' atypical scrapie from
an homologous donor sheep was reported in 2007.
"Results -------- "This study demonstrates that atypical scrapie has
distinct clinical, pathological, and biochemical characteristics which are
maintained on transmission and sub-passage, and which are distinct from other
strains of transmissible spongiform encephalopathies in the same host
genotype.
"Conclusions ------------ Atypical scrapie is consistently transmissible
within AHQ homozygous sheep, and the disease phenotype is preserved on
sub-passage."
Lastly, this moderator wishes to thank Terry Singletary for some of his
behind the scenes work of providing citations and references for this posting. -
Mod.TG]
The HealthMap/ProMED-mail interactive map of Australia is available at . -
Sr.Tech.Ed.MJ]
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to
nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep
and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were
exposed to the infectious agents only by their nonforced consumption of known
infectious tissues. The asymptomatic incubation period in the one monkey exposed
to the virus of kuru was 36 months; that in the two monkeys exposed to the virus
of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the
two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively.
Careful physical examination of the buccal cavities of all of the monkeys failed
to reveal signs or oral lesions. One additional monkey similarly exposed to kuru
has remained asymptomatic during the 39 months that it has been under
observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie
by natural feeding to squirrel monkeys that we have reported provides further
grounds for concern that scrapie-infected meat may occasionally give rise in
humans to Creutzfeldt-Jakob disease.
PMID: 6997404
Recently the question has again been brought up as to whether scrapie is
transmissible to man. This has followed reports that the disease has been
transmitted to primates. One particularly lurid speculation (Gajdusek 1977)
conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and
transmissible encephalopathy of mink are varieties of a single "virus". The U.S.
Department of Agriculture concluded that it could "no longer justify or permit
scrapie-blood line and scrapie-exposed sheep and goats to be processed for human
or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is
emphasised by the finding that some strains of scrapie produce lesions identical
to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be
transmissible to man raises two considerations. First, the safety of laboratory
personnel requires prompt attention. Second, action such as the "scorched meat"
policy of USDA makes the solution of the acrapie problem urgent if the sheep
industry is not to suffer grievously.
snip...
76/10.12/4.6
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC.
Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK
National Institute of Neurological Diseases and Stroke, National Institutes
of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey
(Macaca fascicularis) with an incubation period of more than 5 yr from the time
of intracerebral inoculation of scrapie-infected mouse brain. The animal
developed a chronic central nervous system degeneration, with ataxia, tremor and
myoclonus with associated severe scrapie-like pathology of intensive astroglial
hypertrophy and proliferation, neuronal vacuolation and status spongiosus of
grey matter. The strain of scrapie virus used was the eighth passage in Swiss
mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral
passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton,
Berkshire).
Wednesday, February 16, 2011
IN CONFIDENCE
SCRAPIE TRANSMISSION TO CHIMPANZEES
IN CONFIDENCE
*** FINALLY, in making such absolute statements such as any species being
absolutely resistant to TSE prion disease, without final proof, I remind you of
;
5. A positive result from a chimpanzee challenged severly would likely
create alarm in some circles even if the result could not be interpreted for
man. I have a view that all these agents could be transmitted provided a large
enough dose by appropriate routes was given and the animals kept long enough.
Until the mechanisms of the species barrier are more clearly understood it might
be best to retain that hypothesis.
snip...
R. BRADLEY
never say never in relations to TSE prion disease. ...TSS
Implications and Opportunities for Future Research Disease risk. There is
much debate over whether a partial genetic resistance to CWD infection, or
delayed progression, might have positive or negative effects on disease dynamics
on the landscape. On the one hand, CWD infection rates may be substantially
lower in some genotypes, reducing the prevalence of CWD and disease impacts on
the affected population. These less-susceptible genotypes may gain a survival
advantage over other genotypes.20 Yet, because the infectious state may be
prolonged, these animals could disproportionately contribute to environmental
contamination and transmission to susceptible animals.18,81 Future research is
needed to determine whether all genotypes shed infectious material at similar
rates. We currently understand little about the relative importance of direct
vs. environmental routes of transmission in wild cervid populations. It will be
important to understand the ways in which these routes interact with Prnp types
to influence CWD infection and progression of disease. In addition to the mode
of contact, the biological source of infectious material may have an impact on
infectivity. It is unknown whether cervid species have different sensitivities
to particular agent conformations, genotypes or strains. Additionally, though we
know that cross-species infection is possible between elk, mule deer and
white-tailed deer, we do not understand the level of transmissibility of agent
between these species, or to other mammals in the ecosystem.82 Newly developed
laboratory methods including PMCA,27,83 shaking assays,84 and cell-free
conversions32 may provide insights on this question.
snip...
Survival and selection. The survival advantage conferred by decreased CWD
susceptibility can be sufficient to alter population dynamics and provide
selective pressure favoring disease resistance (demonstrated for the 96S allele
in white-tailed deer, in press20). Such selective pressure is rarely measurable
in wild populations, and indicates the potential for CWD to impact cervid
populations. Additional genetic work will be needed to evaluate potential
selective pressure on other loci and in other species to understand future
trends in CWD epidemics and deer populations. Further, we currently lack
information about nondisease related fitness characteristics associated with
Prnp genetics. This is fertile ground for future selection studies. Future
research such as simulation modeling might be used to address questions of how
selective pressure could change as disease prevalence alters infection hazard,
as agent strains shift, or how animal movement affects disease dynamics in
wildlife populations.
PRION 2014 CONFERENCE
CHRONIC WASTING DISEASE CWD
A FEW FINDINGS ;
Conclusions. To our knowledge, this is the first established experimental
model of CWD in TgSB3985. We found evidence for co-existence or divergence of
two CWD strains adapted to Tga20 mice and their replication in TgSB3985 mice.
Finally, we observed phenotypic differences between cervid-derived CWD and
CWD/Tg20 strains upon propagation in TgSB3985 mice. Further studies are underway
to characterize these strains.
We conclude that TSE infectivity is likely to survive burial for long time
periods with minimal loss of infectivity and limited movement from the original
burial site. However PMCA results have shown that there is the potential for
rainwater to elute TSE related material from soil which could lead to the
contamination of a wider area. These experiments reinforce the importance of
risk assessment when disposing of TSE risk materials.
The results show that even highly diluted PrPSc can bind efficiently to
polypropylene, stainless steel, glass, wood and stone and propagate the
conversion of normal prion protein. For in vivo experiments, hamsters were ic
injected with implants incubated in 1% 263K-infected brain homogenate. Hamsters,
inoculated with 263K-contaminated implants of all groups, developed typical
signs of prion disease, whereas control animals inoculated with non-contaminated
materials did not.
Our data establish that meadow voles are permissive to CWD via peripheral
exposure route, suggesting they could serve as an environmental reservoir for
CWD. Additionally, our data are consistent with the hypothesis that at least two
strains of CWD circulate in naturally-infected cervid populations and provide
evidence that meadow voles are a useful tool for CWD strain typing.
Conclusion. CWD prions are shed in saliva and urine of infected deer as
early as 3 months post infection and throughout the subsequent >1.5 year
course of infection. In current work we are examining the relationship of
prionemia to excretion and the impact of excreted prion binding to surfaces and
particulates in the environment.
Conclusion. CWD prions (as inferred by prion seeding activity by RT-QuIC)
are shed in urine of infected deer as early as 6 months post inoculation and
throughout the subsequent disease course. Further studies are in progress
refining the real-time urinary prion assay sensitivity and we are examining more
closely the excretion time frame, magnitude, and sample variables in
relationship to inoculation route and prionemia in naturally and experimentally
CWD-infected cervids.
Conclusions. Our results suggested that the odds of infection for CWD is
likely controlled by areas that congregate deer thus increasing direct
transmission (deer-to-deer interactions) or indirect transmission
(deer-to-environment) by sharing or depositing infectious prion proteins in
these preferred habitats. Epidemiology of CWD in the eastern U.S. is likely
controlled by separate factors than found in the Midwestern and endemic areas
for CWD and can assist in performing more efficient surveillance efforts for the
region.
Conclusions. During the pre-symptomatic stage of CWD infection and
throughout the course of disease deer may be shedding multiple LD50 doses per
day in their saliva. CWD prion shedding through saliva and excreta may account
for the unprecedented spread of this prion disease in nature.
see full text and more ;
Monday, June 23, 2014
PRION 2014 CHRONIC WASTING DISEASE CWD
Thursday, July 03, 2014
How Chronic Wasting Disease is affecting deer population and what’s the
risk to humans and pets?
Tuesday, July 01, 2014
CHRONIC WASTING DISEASE CWD TSE PRION DISEASE, GAME FARMS, AND POTENTIAL
RISK FACTORS THERE FROM
Monday, June 23, 2014
PRION 2014 TYPICAL AND ATYPICAL BSE AND CJD REPORT UPDATES
Sunday, June 29, 2014
Transmissible Spongiform Encephalopathy TSE Prion Disease North America
2014
TSS
