Pathological features of chronic wasting disease in reindeer and demonstration of horizontal transmission Major Findings for Norway
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research
Title: Pathological features of chronic wasting disease in reindeer and
demonstration of horizontal transmission
Author
item Moore, Sarah item Kunkle, Robert item West greenlee, Mary item
Nicholson, Eric item Richt, Juergen item Hamir, Amirali item Waters, Wade item
Greenlee, Justin
Submitted to: Emerging Infectious Diseases Publication Type: Peer reviewed
journal Publication Acceptance Date: 8/29/2016 Publication Date: N/A Citation:
Interpretive Summary: Chronic wasting disease (CWD) is a fatal
neurodegenerative disease that occurs in farmed and wild cervids (deer and elk)
of North America and was recently diagnosed in a single free-ranging reindeer
(Rangifer tarandus tarandus) in Norway. CWD is a transmissible spongiform
encephalopathy (TSE) that is caused by infectious proteins called prions that
are resistant to various methods of decontamination and environmental
degradation. Little is known about the susceptibility of or potential for
transmission amongst reindeer. In this experiment, we tested the susceptibility
of reindeer to CWD from various sources (elk, mule deer, or white-tailed deer)
after intracranial inoculation and tested the potential for infected reindeer to
transmit to non-inoculated animals by co-housing or housing in adjacent pens.
Reindeer were susceptible to CWD from elk, mule deer, or white-tailed deer
sources after experimental inoculation. Most importantly, non-inoculated
reindeer that were co-housed with infected reindeer or housed in pens adjacent
to infected reindeer but without the potential for nose-to-nose contact also
developed evidence of CWD infection. This is a major new finding that may have a
great impact on the recently diagnosed case of CWD in the only remaining
free-ranging reindeer population in Europe as our findings imply that horizontal
transmission to other reindeer within that herd has already occurred. Further,
this information will help regulatory and wildlife officials developing plans to
reduce or eliminate CWD and cervid farmers that want to ensure that their herd
remains CWD-free, but were previously unsure of the potential for reindeer to
transmit CWD.
Technical Abstract: Chronic wasting disease (CWD) is a naturally-occurring,
fatal prion disease of cervids. Reindeer (Rangifer tarandus tarandus) are
susceptible to CWD following oral challenge, and CWD was recently reported in a
free-ranging reindeer of Norway. Potential contact between CWD-affected cervids
and Rangifer species that are free-ranging or co-housed on farms presents a
potential risk of CWD transmission. The aims of this study were to 1)
investigate the transmission of CWD from white-tailed deer (Odocoileus
virginianus; CWDwtd), mule deer (Odocoileus hemionus; CWDmd), or elk (Cervus
elaphus nelsoni; CWDelk) to reindeer via the intracranial route, and 2) to
assess for direct and indirect horizontal transmission to non-inoculated
sentinels. Three groups of 5 reindeer fawns were challenged intracranially with
CWDwtd, CWDmd, or CWDelk. Two years after challenge of inoculated reindeer,
non-inoculated negative control reindeer were introduced into the same pen as
the CWDwtd inoculated reindeer (direct contact; n=4) or into a pen adjacent to
the CWDmd inoculated reindeer (indirect contact; n=2). Experimentally inoculated
reindeer were allowed to develop clinical disease. At death/euthanasia a
complete necropsy examination was performed, including immunohistochemical
testing of tissues for disease-associated CWD prion protein (PrPcwd).
Intracranially challenged reindeer developed clinical disease from 21 months
post-inoculation (months PI). PrPcwd was detected in 5 out of 6 sentinel
reindeer although only 2 out of 6 developed clinical disease during the study
period (< 57 months PI). We have shown that reindeer are susceptible to CWD
from various cervid sources and can transmit CWD to naïve reindeer both directly
and indirectly.
***Most importantly, non-inoculated reindeer that were co-housed with
infected reindeer or housed in pens adjacent to infected reindeer but without
the potential for nose-to-nose contact also developed evidence of CWD infection.
***This is a major new finding that may have a great impact on the recently
diagnosed case of CWD in the only remaining free-ranging reindeer population in
Europe as our findings imply that horizontal transmission to other reindeer
within that herd has already occurred.
***We have shown that reindeer are susceptible to CWD from various cervid
sources and can transmit CWD to naïve reindeer both directly and indirectly.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research
Title: Transmission of chronic wasting disease to sentinel reindeer
(Rangifer tarandus tarandus))
Author
item Moore, S item Kunkle, Robert item Nicholson, Eric item Richt, Juergen
item Hamir, Amirali item Waters, Wade item Greenlee, Justin
Submitted to: American College of Veterinary Pathologists Meeting
Publication Type: Abstract only Publication Acceptance Date: 8/12/2015
Publication Date: N/A Citation:
Interpretive Summary: Technical Abstract: Chronic wasting disease (CWD) is
a naturally-occurring, fatal neurodegenerative disease of North American
cervids. Reindeer (Rangifer tarandus tarandus) are susceptible to CWD following
oral challenge, but CWD has not been reported in free-ranging caribou (Rangifer
tarandus caribou) or farmed reindeer. Potential contact between CWD-affected
cervids and Rangifer species that are free-ranging or co-housed on farms
presents a potential risk of CWD transmission. The aims of this study were to 1)
investigate the transmission of CWD from white-tailed deer (Odocoileus
virginianus; CWD-wtd), mule deer (Odocoileus hemionus; CWD-md), or elk (Cervus
elaphus nelsoni; CWD-elk) to reindeer via the intracranial route, and 2) to
assess for direct and indirect horizontal transmission to non-inoculated
sentinels. Three groups of 5 reindeer fawns were challenged intracranially with
CWD-wtd, CWD-md, or CWD-elk. Two years after challenge of inoculated reindeer,
non-inoculated control reindeer were introduced into the same pen as the CWD-wtd
inoculated reindeer (n=4) or into a pen adjacent to the CWD-md inoculated
reindeer (n=2). Reindeer were allowed to develop clinical disease. At
death/euthanasia a complete necropsy examination was performed, including
immunohistochemical testing of tissues for disease-associated CWD prion protein
(PrP-CWD). Intracranially challenged reindeer developed clinical disease from 21
months post-inoculation (MPI). PrP-CWD was detected in 5/6 sentinel reindeer
although only 2/6 developed clinical disease during the study period (<57 and="" are="" both="" can="" cervid="" cwd="" directly="" div="" from="" have="" indirectly.="" mpi="" naive="" reindeer="" shown="" sources="" susceptible="" that="" to="" transmit="" various="" we="">
Wednesday, August 31, 2016
NORWAY CONFIRMS 4TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN SECOND
CARIBOU
Saturday, September 03, 2016
NORWAY Regulation concerning temporary measures to reduce the spread of
Chronic Wasting Disease (CWD) as 4th case of skrantesjuke confirmed in Sogn og
Fjordane
TSE PRIONS AKA MAD COW TYPE DISEASE, LIONS AND TIGERS AND BEARS, OH MY!
DEER BRAIN SURVEY
***5. Although the sample size would be too small to provide scientifically
valid evidence that there is no cervine spongiform encephalopathy in the UK
(4,000 odd brains would be necessary for that), a negative result would aid our
efforts to have trade in deer resumed. ...end...tss
Subject: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY
Date: Thu, 17 Oct 2002 17:04:51 –0700
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L
Greetings BSE-L,
is there any other CWD surveys/testing in the UK on their deer? what sort
of testing has been done to date on UK/EU deer? any input would be helpful...
thank you
DEER SPONGIFORM ENCEPHALOPATHY SURVEY
CVO BSE 1 28
DEER BRAIN SURVEY
1. The Parliamentary Secretary will wish to be aware of a survey of deer
brains for signs of a spongiform encephalopathy.
2. The purpose of the study will be to gather evidence of freedom from any
spongiform encephalopathy in the UK deer- population to support our efforts to
resume trade in deer with countries with which BSE has disrupted it.
3. This will be a low key study with no publicity to avoid unnecessary
media interest. It will be carried out in two stages:
(i) A small scale examination of around 30 deer brains to establish the
normal histology of the healthy brain; and
(ii) A larger scale random examination of 300 or more adult deer brains
drawn from both deer farms and parks to establish whether there is any evidence
of a cervine spongiform encephalopathy.
4. The industry have agreed to cooperate with the study and will supply the
necessary brain material. No compensation will be paid. The only cost to
Government will be for the laboratory examinations which will be borne within
existing resources.
*** 5. Although the sample size would be too small to provide
scientifically valid evidence that there is no cervine spongiform encephalopathy
in the UK (4,000 odd brains would be necessary for that), a negative result
would aid our efforts to have trade in deer resumed.
ROBERT LOWSON
Animal Health (Disease Control) Division
081 330 8042 - GTN 3836
Fax: 081 330 7862
Room 28A TOLB
20 November 1991
Mr Tanner - PS/Mr Maclean
c.c. PS/Minister Dr P Dawson Mr Lawrence PS/Permanent Secretary Mr Dugdalé
Dr Matthews Mr Capstick Mr Bradley — CVL Mr Maslin Mr MeldrumL Mr Wilesmith -
CVL Mr Thomson SOAFD Mr Haddon Mr Bell Mr Shannon DANI Mr X Taylor Mr Robertson
Mr Podmore WOAD
91/11.20/4.1
***5. Although the sample size would be too small to provide scientifically
valid evidence that there is no cervine spongiform encephalopathy in the UK
(4,000 odd brains would be necessary for that), a negative result would aid our
efforts to have trade in deer resumed.’’ LMAO...DOES THAT EVER SOUND
FAMILIAR...TSS
Wednesday, August 31, 2016
NORWAY CONFIRMS 4TH CASE OF CHRONIC WASTING DISEASE CWD TSE PRION IN SECOND
CARIBOU
Tuesday, August 02, 2016
Chronic wasting disease of deer – is the battle to keep Europe free already
lost?
Tuesday, April 12, 2016
The first detection of Chronic Wasting Disease (CWD) in Europe free-ranging
reindeer from the Nordfjella population in South-Norway.
Tuesday, June 14, 2016
*** Chronic Wasting Disease (CWD) in a moose from Selbu in Sør-Trøndelag
Norway ***
Thursday, July 07, 2016
Norway reports a third case Chronic Wasting Disease CWD TSE Prion in 2nd
Norwegian moose
14/06/2016 - Norway reports a third case
Saturday, July 16, 2016
Chronic wasting Disease in Deer (CWD or Spongiform Encephalopathy) The
British Deer Society 07/04/2016
Red Deer Ataxia or Chronic Wasting Disease CWD TSE PRION?
could this have been cwd in the UK back in 1970’S ???
SEE FULL TEXT ;
Sunday, August 28, 2016
CONFIDENTIAL
Transmissible Spongiform Encephalopathy TSE Prion and how Politics and
Greed by the Industry spread madcow type diseases from species to species and
around the globe
TSE PRIONS AKA MAD COW TYPE DISEASE, LIONS AND TIGERS AND BEARS, OH MY!
Please be assured, the USA does NOT have any clue as to what the real
perspective on the TSE prion disease in domestic feline and canine, much less
our big wild cats, OR any other species including humans for that matter, but
one thing for sure, the studies and history of the mad cow debacle below are
deeply concerning with regards, to humans and wild big cats like mountain lions,
cougars, lynx, Jaguar, and such, that feed on cervids that are infected with
CWD. one thing for sure, don’t kid yourselves, all are very much susceptible to
the TSE Prion disease, and if you don’t look, you don’t find, problems
solved$$$
Chronic Wasting Disease CWD TSE Prion Update
Subject: Stakeholder Perspectives on Chronic Wasting Disease Risk and
Management on the Canadian Prairies
research article
Stakeholder Perspectives on Chronic Wasting Disease Risk and Management on
the Canadian Prairies
Kari Amick, Douglas Clark & Ryan K. Brook
Page 408-424
Published online: 31 Aug 2015
Download citation http://dx.doi.org/10.1080/10871209.2015.1046095
Crossmark
Abstract
Chronic wasting disease (CWD) is an infectious disease caused by a prion
that results in neurodegeneration and death in cervids. This study uses Q
methodology to characterize stakeholder perspectives about CWD risk and
management on the Canadian prairies, and to understand the potential for CWD
management using an adaptive governance framework. Workshops and individual
interviews were conducted with 16 stakeholders in Saskatchewan and Manitoba.
Problem definitions framed CWD as a technical problem calling for technical
solutions. All perspectives on solutions focused on the importance of education
and the idea that management should fit within a national management strategy. A
unique Aboriginal perspective also emerged and warrants further exploration.
Results also indicated that although stakeholders wish to be involved with CWD
management, they trust and expect government leadership, and are disinterested
in adaptive governance. Challenges for stakeholder involvement in Canadian CWD
management include a lack of sufficient leadership and general ambivalence.
Keywords: adaptive governance, chronic wasting disease, Q methodology,
stakeholder perspectives, wildlife disease management,
Friday, September 02, 2016
Canada Chronic Wasting Disease CWD Surveillance Update 2016
Sunday, August 28, 2016
CONFIDENTIAL
Transmissible Spongiform Encephalopathy TSE Prion and how Politics and
Greed by the Industry spread madcow type diseases from species to species and
around the globe
TSE PRIONS AKA MAD COW TYPE DISEASE, LIONS AND TIGERS AND BEARS, OH MY!
Sunday, December 14, 2014
TEXAS 84th Legislature commencing this January, deer breeders are expected
to advocate for bills that will seek to further deregulate their industry
http://chronic-wasting-disease.blogspot.it/2014/12/texas-84th-legislature-commencing-this.html
Saturday, July 09, 2016
Texas Intrastate – within state movement of all Cervid or Trucking Chronic
Wasting Disease CWD TSE Prion Moratorium
Monday, July 18, 2016
Texas Parks Wildlife Dept TPWD HIDING TSE (CWD) in Deer Herds, Farmers
Sampling Own Herds, Rapid Testing, False Negatives, a Recipe for Disaster
http://chronic-wasting-disease.blogspot.com/2016/07/texas-parks-wildlife-dept-tpwd-hiding.html
Friday, July 01, 2016
*** TEXAS Thirteen new cases of chronic wasting disease (CWD) were
confirmed at a Medina County captive white-tailed deer breeding facility on June
29, 2016***
*** How Did CWD Get Way Down In Medina County, Texas?
DISCUSSION Observations of natural outbreaks of scrapie indicated that the
disease spread from flock to flock by the movement of infected, but apparently
normal, sheep which were incubating the disease.
There was no evidence that the disease spread to adjacent flocks in the
absent of such movements or that vectors or other host species were involved in
the spread of scrapie to sheep or goats; however, these possibilities should be
kept open...
Tuesday, August 02, 2016
TEXAS TPWD Sets Public Hearings on Deer Movement Rule Proposals in Areas
with CWD Rule Terry S. Singeltary Sr. comment submission
Thursday, August 25, 2016
TPWD Action Disease Detection and Response – Chronic Wasting Disease TPW
Commission Adopts New CWD Zones, Deer Movement Rules August 25, 2016
This map shows the recently imposed Surveillance Zone for CWD in portions
of Bandera, Medina and Uvalde counties.
http://chronic-wasting-disease.blogspot.com/2016/08/tpwd-action-disease-detection-and.html
Wednesday, August 10, 2016
Arkansas Chronic Wasting Disease CWD TSE Prion Potentially Trucked in from
Missouri, what about Florida and ?
Wednesday, July 27, 2016
Arkansas CWD 101 positive cases documented to date, Biologists to take
additional samples in in southern Pope County, Aug. 1-5
Tuesday, August 30, 2016
NEBRASKA CHRONIC WASTING DISEASE CWD TSE PRION UPDATE REPORT
Monday, August 29, 2016
*** NWHC USGS CHRONIC WASTING DISEASE CWD TSE PRION UPDATE ***
Friday, September 02, 2016
Chronic Wasting Disease Drives Population Decline of White-Tailed
Deer
Sunday, September 04, 2016
Stakeholder Perspectives on Chronic Wasting Disease Risk and Management on
the Canadian Prairies
research article
Tuesday, June 19, 2012
*** Experimental Oral Transmission of Chronic Wasting Disease to Reindeer
(Rangifer tarandus tarandus) ***
What is the risk of chronic wasting disease being introduced into Great
Britain? An updated Qualitative Risk Assessment March 2016
Summary
The previous assessment concentrated on the incursion of disease from North
America through the imports of animal feed or the movement of contaminated
clothing, footwear and equipment. The results suggested that import of pet feed
was a non-negligible risk, but given the unlikely contact of resident deer in GB
with such non-ruminant feed, this was considered overall a negligible to very
low risk. The movement of contaminated clothing, footwear or equipment
(particularly hunting equipment) could pose a very low risk, although the volume
of contaminated soil which would need to be ingested to give rise to an
infection is likely to be higher than would be present. There is a variable
level uncertainty in all these assessments.
The new assessment focuses on an additional potential route of entry: the
importation of natural deer urine lures. The main conclusions from this
assessment are:
In areas of North America where CWD has been reported, given that CWD is
excreted in faeces, saliva, urine and blood, and survives in the environment for
several years there is a medium probability that the deer urine in North America
contains CWD (high uncertainty; depends on the source of deer used for
production).
The risk of a deer in GB being infected per 30 ml bottle of urine imported
from the USA is very low, albeit with high uncertainty. Overall it is concluded
that the risk of at least one infection of deer in the UK with CWD per year from
deer urine lures imported from the USA is medium. This assumes a high number of
30 ml bottles imported per year from all areas of the USA.
None of the species affected by CWD in North America are present in GB. For
a British species to become infected with CWD following exposure, the dose and
inherent susceptibility of the species will be important. Based on current
scientific evidence Red deer (Cervus elaphus elaphus) are susceptible to CWD,
Fallow deer (Dama dama) are likely to be less susceptible and Roe deer
(Capreolus capreolus) have a gene conferring susceptibility. Therefore, it is
likely that given exposure to an infectious dose of CWD, deer in GB could become
infected with CWD.
Overall, the probability of importing CWD into GB from North America and
causing infection in British deer is uncertain but likely to be negligible to
very low via movement of deer hunters, other tourists and British servicemen and
very low via imported (non-
2
ruminant) animal feed and medium for the use of lures. However, if it was
imported and (a) deer did become infected with CWD, the consequences would be
severe as eradication of the disease is impossible, it is clinically
indistinguishable from BSE infection in deer (Dalgleish et al., 2008) and
populations of wild and farmed deer would be under threat.
The USA has implemented a Herd Certification Programme for farmed and
captive cervids. So far, 29 States are approved for HCP status (APHIS, 2015).
The list includes States such as Colorado, where CWD is present, therefore it is
recommended that any sourcing of such natural urine lures should be not only
from States with an HCP programme, but also from a herd which is registered as
being regularly tested free of CWD.
Animal urine is not considered a commodity which is subject to animal
by-products legislation for imports. Internet sales are common and although a
license would be required, there are no conditions for the safe sourcing of such
products. Deer urine lures are also available in Europe and may be produced from
carcases of hunted deer. The use of deer urine produced from a species not
present in Europe (such as white tailed deer) is questioned for its value with
native GB deer according to the British Deer Society survey.
Background
Thursday, April 07, 2016
What is the risk of chronic wasting disease being introduced into Great
Britain? An updated Qualitative Risk Assessment March 2016
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...
What is the risk of chronic wasting disease being introduced into Great
Britain? A Qualitative Risk Assessment October 2012
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 well as non-ruminants such as cats and dogs as
well, as soon as possible for the following reasons...
31 Jan 2015 at 20:14 GMT
*** Ruminant feed ban for cervids in the United States? ***
31 Jan 2015 at 20:14 GMT
Terry Singeltary Sr. comment ;
Tuesday, April 19, 2016
Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards
Singeltary Comment Submission
Thursday, August 25, 2016
FSIS Green Bay Dressed Beef Recalls Beef Products Due To Possible Specified
Risk Materials Contamination the most high risk materials for BSE TSE PRION AKA
MAD COW TYPE DISEASE
In the USA, USDA et al sometimes serves SRM’s up as appetizers or
horderves.
Monday, June 20, 2016
*** Specified Risk Materials SRMs BSE TSE Prion Program
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
*** Infectious agent of sheep scrapie may persist in the environment for at
least 16 years ***
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
CWD TSE PRION HUMAN ZOONOSIS POTENTIAL, has it already happened, and being
masked as sporadic CJD? and what about iatrogenic, or the pass if forward,
friendly fire mode of transmission of cwd to humans, same thing, sporadic cjd
?
*** WDA 2016 NEW YORK ***
We found that CWD adapts to a new host more readily than BSE and that human
PrP was unexpectedly prone to misfolding by CWD prions. In addition, we
investigated the role of specific regions of the bovine, deer and human PrP
protein in resistance to conversion by prions from another species. We have
concluded that the human protein has a region that confers unusual
susceptibility to conversion by CWD prions.
Student Presentations Session 2
The species barriers and public health threat of CWD and BSE prions
Ms. Kristen Davenport1, Dr. Davin Henderson1, Dr. Candace Mathiason1, Dr.
Edward Hoover1 1Colorado State University
Chronic wasting disease (CWD) is spreading rapidly through cervid
populations in the USA. Bovine spongiform encephalopathy (BSE, mad cow disease)
arose in the 1980s because cattle were fed recycled animal protein. These and
other prion diseases are caused by abnormal folding of the normal prion protein
(PrP) into a disease causing form (PrPd), which is pathogenic to nervous system
cells and can cause subsequent PrP to misfold. CWD spreads among cervids very
efficiently, but it has not yet infected humans. On the other hand, BSE was
spread only when cattle consumed infected bovine or ovine tissue, but did infect
humans and other species. The objective of this research is to understand the
role of PrP structure in cross-species infection by CWD and BSE. To study the
propensity of each species’ PrP to be induced to misfold by the presence of PrPd
from verious species, we have used an in vitro system that permits detection of
PrPd in real-time. We measured the conversion efficiency of various combinations
of PrPd seeds and PrP substrate combinations. We observed the cross-species
behavior of CWD and BSE, in addition to feline-adapted CWD and BSE. We found
that CWD adapts to a new host more readily than BSE and that human PrP was
unexpectedly prone to misfolding by CWD prions. In addition, we investigated the
role of specific regions of the bovine, deer and human PrP protein in resistance
to conversion by prions from another species. We have concluded that the human
protein has a region that confers unusual susceptibility to conversion by CWD
prions. CWD is unique among prion diseases in its rapid spread in natural
populations. BSE prions are essentially unaltered upon passage to a new species,
while CWD adapts to the new species. This adaptation has consequences for
surveillance of humans exposed to CWD.
Wildlife Disease Risk Communication Research Contributes to Wildlife Trust
Administration Exploring perceptions about chronic wasting disease risks among
wildlife and agriculture professionals and stakeholders
Ms. Alyssa Wetterau1, Dr. Krysten Schuler1, Dr. Elizabeth Bunting1, Dr.
Hussni Mohammed1 1Cornell University
Chronic wasting disease (CWD) is a fatal disease of North American
Cervidae. New York State (NYS, USA) successfully managed an outbreak of CWD in
2005 in both captive and wild white-tailed deer (Odocoileus virginianus) with no
reoccurrence of the disease as of 2015. To attain maximum compliance and
efficacy of management actions for prevention of CWD entry, understanding the
varied risk perceptions will allow for targeted, proactive communication efforts
to address divergences between expert-derived risk assessments and stakeholder
risk perceptions. We examined perceived risks associated with CWD introduction
and exposure among agricultural and wildlife agency professionals within and
outside of NYS, as well as stakeholder groups (e.g., hunters and captive cervid
owners). We measured perceived risk using a risk assessment questionnaire online
via Qualtrics survey software and evaluated similarities within, as well as
differences in, perception among participant groups. New York State biologists
employed by the Department of Environmental Conservation and independent non-NYS
wildlife and agricultural professionals thought CWD risks associated with
captive cervids were high; captive cervid owners thought risks for wild and
captive cervids were low. Agriculture and wildlife professional groups agreed on
general risk perceptions. We ranked 15 individual risk hazards into high and low
medium categories based on all responses. Differences between groups were most
evident in hypothetical disease pathways. Any pathway involving inter-state
import of live cervids received high ranking for all groups except captive
cervid owners. Comparatively low risk perceptions by captive cervid operators
may stem from misinformation, lack of understanding of testing programs, and
indemnity payments for animal depopulation. Communication and education directed
at areas of disagreement may facilitate effective disease prevention and
management.
* No evaluation of determination of CWD risk is required for alternative
livestock or captive wildlife shipped directly to slaughter or to a biosecure
facility approved by the Division and the Dept. of Agriculture.
*** We found that CWD adapts to a new host more readily than BSE and that
human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we
investigated the role of specific regions of the bovine, deer and human PrP
protein in resistance to conversion by prions from another species. We have
concluded that the human protein has a region that confers unusual
susceptibility to conversion by CWD prions. CWD is unique among prion diseases
in its rapid spread in natural populations. BSE prions are essentially unaltered
upon passage to a new species, while CWD adapts to the new species. This
adaptation has consequences for surveillance of humans exposed to CWD. ***
PRION 2016 TOKYO
Zoonotic Potential of CWD Prions: An Update
Ignazio Cali1, Liuting Qing1, Jue Yuan1, Shenghai Huang2, Diane Kofskey1,3,
Nicholas Maurer1, Debbie McKenzie4, Jiri Safar1,3,5, Wenquan Zou1,3,5,6,
Pierluigi Gambetti1, Qingzhong Kong1,5,6
1Department of Pathology, 3National Prion Disease Pathology Surveillance
Center, 5Department of Neurology, 6National Center for Regenerative Medicine,
Case Western Reserve University, Cleveland, OH 44106, USA.
4Department of Biological Sciences and Center for Prions and Protein
Folding Diseases, University of Alberta, Edmonton, Alberta, Canada,
2Encore Health Resources, 1331 Lamar St, Houston, TX 77010
Chronic wasting disease (CWD) is a widespread and highly transmissible
prion disease in free-ranging and captive cervid species in North America. The
zoonotic potential of CWD prions is a serious public health concern, but the
susceptibility of human CNS and peripheral organs to CWD prions remains largely
unresolved. We reported earlier that peripheral and CNS infections were detected
in transgenic mice expressing human PrP129M or PrP129V. Here we will present an
update on this project, including evidence for strain dependence and influence
of cervid PrP polymorphisms on CWD zoonosis as well as the characteristics of
experimental human CWD prions.
PRION 2016 TOKYO
In Conjunction with Asia Pacific Prion Symposium 2016
PRION 2016 Tokyo
Prion 2016
Prion 2016
Purchase options Price * Issue Purchase USD 198.00
Cervid to human prion transmission
Kong, Qingzhong
Case Western Reserve University, Cleveland, OH, United States
Abstract
Prion disease is transmissible and invariably fatal. Chronic wasting
disease (CWD) is the prion disease affecting deer, elk and moose, and it is a
widespread and expanding epidemic affecting 22 US States and 2 Canadian
provinces so far. CWD poses the most serious zoonotic prion transmission risks
in North America because of huge venison consumption (>6 million deer/elk
hunted and consumed annually in the USA alone), significant prion infectivity in
muscles and other tissues/fluids from CWD-affected cervids, and usually high
levels of individual exposure to CWD resulting from consumption of the affected
animal among often just family and friends. However, we still do not know
whether CWD prions can infect humans in the brain or peripheral tissues or
whether clinical/asymptomatic CWD zoonosis has already occurred, and we have no
essays to reliably detect CWD infection in humans. We hypothesize that:
(1) The classic CWD prion strain can infect humans at low levels in the
brain and peripheral lymphoid tissues;
(2) The cervid-to-human transmission barrier is dependent on the cervid
prion strain and influenced by the host (human) prion protein (PrP) primary
sequence;
(3) Reliable essays can be established to detect CWD infection in
humans;and
(4) CWD transmission to humans has already occurred. We will test these
hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in
vitro approaches.
Aim 1 will prove that the classical CWD strain may infect humans in brain
or peripheral lymphoid tissues at low levels by conducting systemic bioassays in
a set of "humanized" Tg mouse lines expressing common human PrP variants using a
number of CWD isolates at varying doses and routes. Experimental "human CWD"
samples will also be generated for Aim 3.
Aim 2 will test the hypothesis that the cervid-to-human prion transmission
barrier is dependent on prion strain and influenced by the host (human) PrP
sequence by examining and comparing the transmission efficiency and phenotypes
of several atypical/unusual CWD isolates/strains as well as a few prion strains
from other species that have adapted to cervid PrP sequence, utilizing the same
panel of humanized Tg mouse lines as in Aim 1.
Aim 3 will establish reliable essays for detection and surveillance of CWD
infection in humans by examining in details the clinical, pathological,
biochemical and in vitro seeding properties of existing and future experimental
"human CWD" samples generated from Aims 1-2 and compare them with those of
common sporadic human Creutzfeldt-Jakob disease (sCJD) prions.
Aim 4 will attempt to detect clinical CWD-affected human cases by examining
a significant number of brain samples from prion-affected human subjects in the
USA and Canada who have consumed venison from CWD-endemic areas utilizing the
criteria and essays established in Aim 3. The findings from this proposal will
greatly advance our understandings on the potential and characteristics of
cervid prion transmission in humans, establish reliable essays for CWD zoonosis
and potentially discover the first case(s) of CWD infection in humans.
Public Health Relevance There are significant and increasing human exposure
to cervid prions because chronic wasting disease (CWD, a widespread and highly
infectious prion disease among deer and elk in North America) continues
spreading and consumption of venison remains popular, but our understanding on
cervid-to-human prion transmission is still very limited, raising public health
concerns. This proposal aims to define the zoonotic risks of cervid prions and
set up and apply essays to detect CWD zoonosis using mouse models and in vitro
methods. The findings will greatly expand our knowledge on the potentials and
characteristics of cervid prion transmission in humans, establish reliable
essays for such infections and may discover the first case(s) of CWD infection
in humans.
Funding Agency Agency National Institute of Health (NIH)
Institute National Institute of Neurological Disorders and Stroke (NINDS)
Type Research Project (R01)
Project # 1R01NS088604-01A1
Application # 9037884
Study Section Cellular and Molecular Biology of Neurodegeneration Study
Section (CMND)
Program Officer Wong, May
Project Start 2015-09-30
Project End 2019-07-31
Budget Start 2015-09-30
Budget End 2016-07-31
Support Year 1
Fiscal Year 2015
Total Cost $337,507
Indirect Cost $118,756
Institution
Name Case Western Reserve University
Department Pathology
Type Schools of Medicine
DUNS # 077758407
City Cleveland
State OH
Country United States
Zip Code 44106
===========================================================
We hypothesize that:
(1) The classic CWD prion strain can infect humans at low levels in the
brain and peripheral lymphoid tissues;
(2) The cervid-to-human transmission barrier is dependent on the cervid
prion strain and influenced by the host (human) prion protein (PrP) primary
sequence;
(3) Reliable essays can be established to detect CWD infection in
humans;and
(4) *** CWD transmission to humans has already occurred. *** We will test
these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary
in vitro approaches.
============================================================
Key Molecular Mechanisms of TSEs
Zabel, Mark D.
Colorado State University-Fort Collins, Fort Collins, CO, United States
Abstract Prion diseases, or transmissible spongiform encephalopathies (TSEs),
are fatal neurodegenerative diseases affecting humans, cervids, bovids, and
ovids. The absolute requirement of PrPC expression to generate prion diseases
and the lack of instructional nucleic acid define prions as unique infectious
agents. Prions exhibit species-specific tropism, inferring that unique prion
strains exist that preferentially infct certain host species and confront
transmission barriers to heterologous host species. However, transmission
barriers are not absolute. Scientific consensus agrees that the sheep TSE
scrapie probably breached the transmission barrier to cattle causing bovine
spongiform encephalopathy that subsequently breached the human transmission
barrier and likely caused several hundred deaths by a new-variant form of the
human TSE Creutzfeldt-Jakob disease in the UK and Europe. The impact to human
health, emotion and economies can still be felt in areas like farming, blood and
organ donations and the threat of a latent TSE epidemic. This precedent raises
the real possibility of other TSEs, like chronic wasting disease of cervids,
overcoming similar human transmission barriers. A groundbreaking discovery made
last year revealed that mice infected with heterologous prion strains facing
significant transmission barriers replicated prions far more readily in spleens
than brains6. Furthermore, these splenic prions exhibited weakened transmission
barriers and expanded host ranges compared to neurogenic prions. These data
question conventional wisdom of avoiding neural tissue to avoid prion
xenotransmission, when more promiscuous prions may lurk in extraneural tissues.
Data derived from work previously funded by NIH demonstrate that Complement
receptors CD21/35 bind prions and high density PrPC and differentially impact
prion disease depending on the prion isolate or strain used. Recent advances in
live animal and whole organ imaging have led us to generate preliminary data to
support novel, innovative approaches to assessing prion capture and transport.
We plan to test our unifying hypothesis for this proposal that CD21/35 control
the processes of peripheral prion capture, transport, strain selection and
xenotransmission in the following specific aims. 1. Assess the role of CD21/35
in splenic prion strain selection and host range expansion. 2. Determine whether
CD21/35 and C1q differentially bind distinct prion strains 3. Monitor the
effects of CD21/35 on prion trafficking in real time and space 4. Assess the
role of CD21/35 in incunabular prion trafficking
Public Health Relevance Transmissible spongiform encephalopathies, or prion
diseases, are devastating illnesses that greatly impact public health,
agriculture and wildlife in North America and around the world. The impact to
human health, emotion and economies can still be felt in areas like farming,
blood and organ donations and the threat of a latent TSE epidemic. This
precedent raises the real possibility of other TSEs, like chronic wasting
disease (CWD) of cervids, overcoming similar human transmission barriers. Early
this year Canada reported its first case of BSE in over a decade audits first
case of CWD in farmed elk in three years, underscoring the need for continued
vigilance and research. Identifying mechanisms of transmission and zoonoses
remains an extremely important and intense area of research that will benefit
human and other animal populations.
Funding Agency Agency National Institute of Health (NIH)
Institute National Institute of Allergy and Infectious Diseases (NIAID)
Type High Priority, Short Term Project Award (R56)
Project # 1R56AI122273-01A1
Application # 9211114
Study Section Cellular and Molecular Biology of Neurodegeneration Study
Section (CMND)
Program Officer Beisel, Christopher E
Project Start 2016-02-16
Project End 2017-01-31
Budget Start 2016-02-16
Budget End 2017-01-31
Support Year 1
Fiscal Year 2016
Total Cost
Indirect Cost Institution Name Colorado State University-Fort Collins
Department Microbiology/Immun/Virology
Type Schools of Veterinary Medicine
DUNS # 785979618 City Fort Collins
State CO
Country United States
Zip Code 80523
PMCA Detection of CWD Infection in Cervid and Non-Cervid Species
Hoover, Edward Arthur
Colorado State University-Fort Collins, Fort Collins, CO, United States
Abstract Chronic wasting disease (CWD) of deer and elk is an emerging highly
transmissible prion disease now recognized in 18 States, 2 Canadian provinces,
and Korea. We have shown that Infected deer harbor and shed high levels of
infectious prions in saliva, blood, urine, and feces, and in the tissues
generating those body fluids and excreta, thereby leading to facile transmission
by direct contact and environmental contamination. We have also shown that CWD
can infect some non-cervid species, thus the potential risk CWD represents to
domestic animal species and to humans remains unknown. Whether prions borne in
blood, saliva, nasal fluids, milk, or excreta are generated or modified in the
proximate peripheral tissue sites, may differ in subtle ways from those
generated in brain, or may be adapted for mucosal infection remain open
questions. The increasing parallels in the pathogenesis between prion diseases
and human neurodegenerative conditions, such as Alzheimer's and Parkinson's
diseases, add relevance to CWD as a transmissible protein misfolding disease.
The overall goal of this work is to elucidate the process of CWD prion
transmission from mucosal secretory and excretory tissue sites by addressing
these questions: (a) What are the kinetics and magnitude of CWD prion shedding
post-exposure? (b) Are excreted prions biochemically distinct, or not, from
those in the CNS? (c) Are peripheral epithelial or CNS tissues, or both, the
source of excreted prions? and (d) Are excreted prions adapted for horizontal
transmission via natural/trans-mucosal routes? The specific aims of this
proposal are: (1) To determine the onset and consistency of CWD prion shedding
in deer and cervidized mice; (2); To compare the biochemical and biophysical
properties of excretory vs. CNS prions; (3) To determine the capacity of
peripheral tissues to support replication of CWD prions; (4) To determine the
protease- sensitive infectious fraction of excreted vs. CNS prions; and (5) To
compare the mucosal infectivity of excretory vs. CNS prions. Understanding the
mechanisms that enable efficient prion dissemination and shedding will help
elucidate how horizontally transmissible prions evolve and succeed, and is the
basis of this proposal. Understanding how infectious misfolded proteins (prions)
are generated, trafficked, shed, and transmitted will aid in preventing,
treating, and managing the risks associated with these agents and the diseases
they cause.
Public Health Relevance Chronic wasting disease (CWD) of deer and elk is an
emergent highly transmissible prion disease now recognized throughout the USA as
well as in Canada and Korea. We have shown that infected deer harbor and shed
high levels of infectious prions in saliva, blood, urine, and feces thereby
leading to transmission by direct contact and environmental contamination. In
that our studies have also shown that CWD can infect some non-cervid species,
the potential risk CWD may represents to domestic animal species and humans
remains unknown. The increasing parallels in the development of major human
neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, and
prion diseases add relevance to CWD as a model of a transmissible protein
misfolding disease. Understanding how infectious misfolded proteins (prions) are
generated and transmitted will aid in interrupting, treating, and managing the
risks associated with these agents and the diseases they cause.
Funding Agency Agency National Institute of Health (NIH)
Institute National Institute of Neurological Disorders and Stroke (NINDS)
Type Research Project (R01)
Project # 4R01NS061902-07
Application # 9010980
Study Section Cellular and Molecular Biology of Neurodegeneration Study
Section (CMND)
Program Officer Wong, May Project Start 2009-09-30
Project End 2018-02-28
Budget Start 2016-03-01
Budget End 2017-02-28
Support Year 7
Fiscal Year 2016
Total Cost $409,868
Indirect Cost $134,234 Institution Name Colorado State University-Fort
Collins
Department Microbiology/Immun/Virology
Type Schools of Veterinary Medicine
DUNS # 785979618 City Fort Collins
State CO
Country United States
Zip Code 80523
LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL
THE WRONG PLACES $$$
*** 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).***
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
*** 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
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.***
================
*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***
Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014
*** chronic wasting disease, there was no absolute barrier to conversion of
the human prion protein.
*** Furthermore, the form of human PrPres produced in this in vitro assay
when seeded with CWD, resembles that found in the most common human prion
disease, namely sCJD of the MM1 subtype.
*** 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).***
*** The potential impact of prion diseases on human health was greatly
magnified by the recognition that interspecies transfer of BSE to humans by beef
ingestion resulted in vCJD. While changes in animal feed constituents and
slaughter practices appear to have curtailed vCJD, there is concern that CWD of
free-ranging deer and elk in the U.S. might also cross the species barrier.
Thus, consuming venison could be a source of human prion disease. Whether BSE
and CWD represent interspecies scrapie transfer or are newly arisen prion
diseases is unknown. Therefore, the possibility of transmission of prion disease
through other food animals cannot be ruled out. There is evidence that vCJD can
be transmitted through blood transfusion. There is likely a pool of unknown size
of asymptomatic individuals infected with vCJD, and there may be asymptomatic
individuals infected with the CWD equivalent. These circumstances represent a
potential threat to blood, blood products, and plasma supplies.
***********CJD REPORT 1994 increased risk for consumption of veal and
venison and lamb***********
CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL
REPORT AUGUST 1994
Consumption of venison and veal was much less widespread among both cases
and controls. For both of these meats there was evidence of a trend with
increasing frequency of consumption being associated with increasing risk of
CJD. (not nvCJD, but sporadic CJD...tss)
These associations were largely unchanged when attention was restricted to
pairs with data obtained from relatives. ...
Table 9 presents the results of an analysis of these data.
There is STRONG evidence of an association between ‘’regular’’ veal eating
and risk of CJD (p = .0.01).
Individuals reported to eat veal on average at least once a year appear to
be at 13 TIMES THE RISK of individuals who have never eaten veal.
There is, however, a very wide confidence interval around this estimate.
There is no strong evidence that eating veal less than once per year is
associated with increased risk of CJD (p = 0.51).
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).
There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY
OF LAMB EATING (p = 0.02).
The evidence for such an association between beef eating and CJD is weaker
(p = 0.14). When only controls for whom a relative was interviewed are included,
this evidence becomes a little STRONGER (p = 0.08).
snip...
It was found that when veal was included in the model with another
exposure, the association between veal and CJD remained statistically
significant (p = < 0.05 for all exposures), while the other exposures ceased
to be statistically significant (p = > 0.05).
snip...
In conclusion, an analysis of dietary histories revealed statistical
associations between various meats/animal products and INCREASED RISK OF CJD.
When some account was taken of possible confounding, the association between
VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS
STATISTICALLY. ...
snip...
In the study in the USA, a range of foodstuffs were associated with an
increased risk of CJD, including liver consumption which was associated with an
apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3
studies in relation to this particular dietary factor, the risk of liver
consumption became non-significant with an odds ratio of 1.2 (PERSONAL
COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)
snip...see full report ;
CJD9/10022
October 1994
Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge
Spencers Lane BerksWell Coventry CV7 7BZ
Dear Mr Elmhirst,
CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT
Thank you for your recent letter concerning the publication of the third
annual report from the CJD Surveillance Unit. I am sorry that you are
dissatisfied with the way in which this report was published.
The Surveillance Unit is a completely independant outside body and the
Department of Health is committed to publishing their reports as soon as they
become available. In the circumstances it is not the practice to circulate the
report for comment since the findings of the report would not be amended. In
future we can ensure that the British Deer Farmers Association receives a copy
of the report in advance of publication.
The Chief Medical Officer has undertaken to keep the public fully informed
of the results of any research in respect of CJD. This report was entirely the
work of the unit and was produced completely independantly of the the
Department.
The statistical results reqarding the consumption of venison was put into
perspective in the body of the report and was not mentioned at all in the press
release. Media attention regarding this report was low key but gave a realistic
presentation of the statistical findings of the Unit. This approach to
publication was successful in that consumption of venison was highlighted only
once by the media ie. in the News at one television proqramme.
I believe that a further statement about the report, or indeed statistical
links between CJD and consumption of venison, would increase, and quite possibly
give damaging credence, to the whole issue. From the low key media reports of
which I am aware it seems unlikely that venison consumption will suffer
adversely, if at all.
http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf
Monday, May 02, 2016
*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***
*** PRION 2014 CONFERENCE CHRONIC WASTING DISEASE CWD
*** PPo3-7: Prion Transmission from Cervids to Humans is Strain-dependent
*** Here we report that a human prion strain that had adopted the cervid
prion protein (PrP) sequence through passage in cervidized transgenic mice
efficiently infected transgenic mice expressing human PrP,
*** indicating that the species barrier from cervid to humans is prion
strain-dependent and humans can be vulnerable to novel cervid prion strains.
PPo2-27:
Generation of a Novel form of Human PrPSc by Inter-species Transmission of
Cervid Prions
*** Our findings suggest that CWD prions have the capability to infect
humans, and that this ability depends on CWD strain adaptation, implying that
the risk for human health progressively increases with the spread of CWD among
cervids.
PPo2-7:
Biochemical and Biophysical Characterization of Different CWD Isolates
*** The data presented here substantiate and expand previous reports on the
existence of different CWD strains.
Envt.07:
Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free
Ranging White-Tailed Deer Infected with Chronic Wasting Disease
***The presence and seeding activity of PrPTSE in skeletal muscle from
CWD-infected cervids suggests prevention of such tissue in the human diet as a
precautionary measure for food safety, pending on further clarification of
whether CWD may be transmissible to humans.
>>>CHRONIC WASTING DISEASE , THERE WAS NO ABSOLUTE BARRIER TO
CONVERSION OF THE HUMAN PRION PROTEIN<<<
*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***
Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014
Wednesday, January 01, 2014
Molecular Barriers to Zoonotic Transmission of Prions
*** chronic wasting disease, there was no absolute barrier to conversion of
the human prion protein.
*** Furthermore, the form of human PrPres produced in this in vitro assay
when seeded with CWD, resembles that found in the most common human prion
disease, namely sCJD of the MM1 subtype.
Envt.07:
Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free
Ranging White-Tailed Deer Infected with Chronic Wasting Disease
***The presence and seeding activity of PrPTSE in skeletal muscle from
CWD-infected cervids suggests prevention of such tissue in the human diet as a
precautionary measure for food safety, pending on further clarification of
whether CWD may be transmissible to humans.
Yet, it has to be noted that our assessments of PrPTSE levels in skeletal
muscles were based on findings in presumably pre- or subclinically infected
animals. Therefore, the concentration of PrPTSE in skeletal muscles of WTD with
clinically manifest CWD may possibly exceed our estimate which refers to
clinically inconspicuous animals that are more likely to enter the human food
chain. Our tissue blot findings in skeletal muscles from CWD-infected WTD would
be consistent with an anterograde spread of CWD prions via motor nerve fibres to
muscle tissue (figure 4A). Similar neural spreading pathways of muscle infection
were previously found in hamsters orally challenged with scrapie [28] and
suggested by the detection of PrPTSE in muscle fibres and muscle-associated
nerve fascicles of clinically-ill non-human primates challenged with BSE prions
[29]. Whether the absence of detectable PrPTSE in myofibers observed in our
study is a specific feature of CWD in WTD, or was due to a pre- or subclinical
stage of infection in the examined animals, remains to be established. In any
case, our observations support previous findings suggesting the precautionary
prevention of muscle tissue from CWD-infected WTD in the human diet, and
highlight the need to comprehensively elucidate of whether CWD may be
transmissible to humans. While the understanding of TSEs in cervids has made
substantial progress during the past few years, the assessment and management of
risks possibly emanating from prions in skeletal muscles of CWD-infected cervids
requires further research.
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease Rachel C.
Angers1,*, Shawn R. Browning1,*,†, Tanya S. Seward2, Christina J. Sigurdson4,‡,
Michael W. Miller5, Edward A. Hoover4, Glenn C. Telling1,2,3,§ + Author
Affiliations
1 Department of Microbiology, Immunology and Molecular Genetics, University
of Kentucky, Lexington, KY 40536, USA. 2 Sanders Brown Center on Aging,
University of Kentucky, Lexington, KY 40536, USA. 3 Department of Neurology,
University of Kentucky, Lexington, KY 40536, USA. 4 Department of Microbiology,
Immunology and Pathology, Colorado State University, Fort Collins, CO 80523,
USA. 5 Colorado Division of Wildlife, Wildlife Research Center, Fort Collins, CO
80526, USA. ↵§ To whom correspondence should be addressed. E-mail:
gtell2@uky.edu ↵* These authors contributed equally to this work.
↵† Present address: Department of Infectology, Scripps Research Institute,
5353 Parkside Drive, RF-2, Jupiter, FL 33458, USA.
↵‡ Present address: Institute of Neuropathology, University of Zurich,
Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
Abstract The emergence of chronic wasting disease (CWD) in deer and elk in
an increasingly wide geographic area, as well as the interspecies transmission
of bovine spongiform encephalopathy to humans in the form of variant Creutzfeldt
Jakob disease, have raised concerns about the zoonotic potential of CWD. Because
meat consumption is the most likely means of exposure, it is important to
determine whether skeletal muscle of diseased cervids contains prion
infectivity. Here bioassays in transgenic mice expressing cervid prion protein
revealed the presence of infectious prions in skeletal muscles of CWD-infected
deer, demonstrating that humans consuming or handling meat from CWD-infected
deer are at risk to prion exposure.
Exotic Meats USA Announces Urgent Statewide Recall of Elk Tenderloin
Because It May Contain Meat Derived From An Elk Confirmed To Have Chronic
Wasting Disease
Contact: Exotic Meats USA 1-800-680-4375
FOR IMMEDIATE RELEASE -- February 9, 2009 -- Exotic Meats USA of San
Antonio, TX is initiating a voluntary recall of Elk Tenderloin because it may
contain meat derived from an elk confirmed to have Chronic Wasting Disease
(CWD). The meat with production dates of December 29, 30 and 31, 2008 was
purchased from Sierra Meat Company in Reno, NV. The infected elk came from Elk
Farm LLC in Pine Island, MN and was among animals slaughtered and processed at
USDA facility Noah’s Ark Processors LLC.
Chronic Wasting Disease (CWD) is a fatal brain and nervous system disease
found in elk and deer. The disease is caused by an abnormally shaped protein
called a prion, which can damage the brain and nerves of animals in the deer
family. Currently, it is believed that the prion responsible for causing CWD in
deer and elk is not capable of infecting humans who eat deer or elk contaminated
with the prion, but the observation of animal-to-human transmission of other
prion-mediated diseases, such as bovine spongiform encephalopathy (BSE), has
raised a theoretical concern regarding the transmission of CWD from deer or elk
to humans. At the present time, FDA believes the risk of becoming ill from
eating CWD-positive elk or deer meat is remote. However, FDA strongly advises
consumers to return the product to the place of purchase, rather than disposing
of it themselves, due to environmental concerns.
Exotic Meats USA purchased 1 case of Elk Tenderloins weighing 16.9 lbs. The
Elk Tenderloin was sold from January 16 – 27, 2009. The Elk Tenderloins was
packaged in individual vacuum packs weighing approximately 3 pounds each. A
total of six packs of the Elk Tenderloins were sold to the public at the Exotic
Meats USA retail store. Consumers who still have the Elk Tenderloins should
return the product to Exotic Meats USA at 1003 NE Loop 410, San Antonio, TX
78209. Customers with concerns or questions about the Voluntary Elk Recall can
call 1-800-680-4375. The safety of our customer has always been and always will
be our number one priority.
Exotic Meats USA requests that for those customers who have products with
the production dates in question, do not consume or sell them and return them to
the point of purchase. Customers should return the product to the vendor. The
vendor should return it to the distributor and the distributor should work with
the state to decide upon how best to dispose. If the consumer is disposing of
the product he/she should consult with the local state EPA office.
#
COLORADO: Farmer's market meat recalled after testing positive for
CWD
24.dec.08 9News.com Jeffrey Wolf
Elk meat that was sold at a farmer's market is being recalled because tests
show it was infected with chronic wasting disease. The Boulder County Health
Department and Colorado Department of Public Health and Environment issued the
recall Wednesday after the meat was sold at the Boulder County Fairgrounds on
Dec. 13. Although there isn't any human health risk connected with CWD, the
recalled was issued as a precaution. About 15 elk were bought from a commercial
ranch in Colorado in early December and processed at a licensed plant. All 15
were tested for CWD and one came up positive. The labeling on the product would
have the following information: *Seller: High Wire Ranch *The type of cut:
"chuck roast," "arm roast," "flat iron," "ribeye steak," "New York steak,"
"tenderloin," "sirloin tip roast," "medallions" or "ground meat." *Processor:
Cedaredge Processing *The USDA triangle containing the number "34645" People
with questions about this meat can contact John Pape, epidemiologist at the
Colorado Department of Public Health and Environment at 303-692-2628.
COULD NOT FIND any warning or recalls on these two sites confirming their
recall of CWD infected meat. ...TSS
Wednesday, April 06, 2011
Presence and Seeding Activity of Pathological Prion Protein (PrPTSE) in
Skeletal Muscles of White-Tailed Deer Infected with Chronic Wasting Disease
Prion Infectivity in Fat of Deer with Chronic Wasting Disease
Brent Race,# Kimberly Meade-White,# Richard Race, and Bruce Chesebro* Rocky
Mountain Laboratories, 903 South 4th Street, Hamilton, Montana 59840
Received 2 June 2009/ Accepted 24 June 2009
ABSTRACT Top ABSTRACT TEXT REFERENCES
Chronic wasting disease (CWD) is a neurodegenerative prion disease of
cervids. Some animal prion diseases, such as bovine spongiform encephalopathy,
can infect humans; however, human susceptibility to CWD is unknown. In
ruminants, prion infectivity is found in central nervous system and lymphoid
tissues, with smaller amounts in intestine and muscle. In mice, prion
infectivity was recently detected in fat. Since ruminant fat is consumed by
humans and fed to animals, we determined infectivity titers in fat from two
CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD
infectivity and might be a risk factor for prion infection of other
species.
snip...
The highest risk of human contact with CWD might be through exposure to
high-titer CNS tissue through accidental skin cuts or corneal contact at the
time of harvest and butchering. However, the likelihood of a human consuming fat
infected with a low titer of the CWD agent is much higher. It is impossible to
remove all the fat present within muscle tissue, and fat consumption is
inevitable when eating meat. Of additional concern is the fact that meat from an
individual deer harvested by a hunter is typically consumed over multiple meals
by the same group of people. These individuals would thus have multiple
exposures to the CWD agent over time, which might increase the chance for
transfer of infection.
In the Rocky Mountain region of North America, wild deer are subject to
predation by wolves, coyotes, bears, and mountain lions. Although canines such
as wolves and coyotes are not known to be susceptible to prion diseases, felines
definitely are susceptible to BSE (9) and might also be infected by the CWD
agent. Deer infected with the CWD agent are more likely to be killed by
predators such as mountain lions (11). Peripheral tissues, including lymph
nodes, muscle, and fat, which harbor prion infectivity are more accessible for
consumption than CNS tissue, which has the highest level of infectivity late in
disease. Therefore, infectivity in these peripheral tissues may be important in
potential cross-species CWD transmissions in the wild.
The present finding of CWD infectivity in deer fat tissue raises the
possibility that prion infectivity might also be found in fat tissue of other
infected ruminants, such as sheep and cattle, whose fat and muscle tissues are
more widely distributed in both the human and domestic-animal food chains.
Although the infectivity in fat tissues is low compared to that in the CNS,
there may be significant differences among species and between prion strains.
Two fat samples from BSE agent-infected cattle were reported to be negative by
bioassay in nontransgenic RIII mice (3, 6). However, RIII mice are
10,000-fold-less sensitive to BSE agent infection than transgenic mice
expressing bovine PrP (4). It would be prudent to carry out additional
infectivity assays on fat from BSE agent-infected cattle and scrapie
agent-infected sheep using appropriate transgenic mice or homologous species to
determine the risk from these sources.
0C7.04
North American Cervids Harbor Two Distinct CWD Strains
Authors
Angers, R. Seward, T, Napier, D., Browning, S., Miller, M., Balachandran
A., McKenzie, D., Hoover, E., Telling, G. 'University of Kentucky; Colorado
Division of Wildlife, Canadian Food Inspection Agency; University Of Wisconsin;
Colorado State University.
Content
Despite the increasing geographic distribution and host range of CWD,
little is known about the prion strain(s) responsible for distinct outbreaks of
the disease. To address this we inoculated CWD-susceptible Tg(CerPrP)1536+/·
mice with 29 individual prion samples from various geographic locations in North
America. Upon serial passage, intrastudy incubation periods consistently
diverged and clustered into two main groups with means around 210 and 290 days,
with corresponding differences in neuropathology. Prion strain designations were
utilized to distinguish between the two groups: Type I CWD mice succumbed to
disease in the 200 day range and displayed a symmetrical pattern of vacuolation
and PrPSc deposition, whereas Type II CWD mice succumbed to disease near 300
days and displayed a strikingly different pattern characterized by large local
accumulations of florid plaques distributed asymmetrically. Type II CWD bears a
striking resemblance to unstable parental scrapie strains such as 87A which give
rise to stable, short incubation period strains such as ME7 under certain
passage conditions. In agreement, the only groups of CWD-inoculated mice with
unwavering incubation periods were those with Type I CWD. Additionally,
following endpoint titration of a CWD sample, Type I CWD could be recovered only
at the lowest dilution tested (10-1), whereas Type II CWD was detected in mice
inoculated with all dilutions resulting in disease. Although strain properties
are believed to be encoded in the tertiary structure of the infectious prion
protein, we found no biochemical differences between Type I and Type II CWD. Our
data confirm the co·existence of two distinct prion strains in CWD-infected
cervids and suggest that Type II CWD is the parent strain of Type I CWD.
see page 29, and see other CWD studies ;
Sunday, November 23, 2008
PRION October 8th - 10th 2008 Book of Abstracts
ADAPTATION OF CHRONIC WASTING DISEASE (CWD) INTO HAMSTERS, EVIDENCE OF A
WISCONSIN STRAIN OF CWD
Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of
Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2
Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary
Research Institute, 4.Center for Prions and Protein Folding Diseases, 5
Department of Biological Sciences, University of Alberta, Edmonton AB, Canada
T6G 2P5
The identification and characterization of prion strains is increasingly
important for the diagnosis and biological definition of these infectious
pathogens. Although well-established in scrapie and, more recently, in BSE,
comparatively little is known about the possibility of prion strains in chronic
wasting disease (CWD), a disease affecting free ranging and captive cervids,
primarily in North America. We have identified prion protein variants in the
white-tailed deer population and demonstrated that Prnp genotype affects the
susceptibility/disease progression of white-tailed deer to CWD agent. The
existence of cervid prion protein variants raises the likelihood of distinct CWD
strains. Small rodent models are a useful means of identifying prion strains. We
intracerebrally inoculated hamsters with brain homogenates and phosphotungstate
concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD
endemic area) and experimentally infected deer of known Prnp genotypes. These
transmission studies resulted in clinical presentation in primary passage of
concentrated CWD prions. Subclinical infection was established with the other
primary passages based on the detection of PrPCWD in the brains of hamsters and
the successful disease transmission upon second passage. Second and third
passage data, when compared to transmission studies using different CWD inocula
(Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin
white-tailed deer population is different than the strain(s) present in elk,
mule-deer and white-tailed deer from the western United States endemic
region.
Tuesday, December 16, 2014
Evidence for zoonotic potential of ovine scrapie prions
Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves
Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle
Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia
Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier
Andréoletti1, Affiliations Contributions Corresponding author Journal name:
Nature Communications Volume: 5, Article number: 5821 DOI:
doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014
Published 16 December 2014 Article tools Citation Reprints Rights &
permissions Article metrics
Abstract
Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant
Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie
prions remains unknown. Mice genetically engineered to overexpress the human
prion protein (tgHu) have emerged as highly relevant models for gauging the
capacity of prions to transmit to humans. These models can propagate human
prions without any apparent transmission barrier and have been used used to
confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie
prions transmit to several tgHu mice models with an efficiency comparable to
that of cattle BSE. The serial transmission of different scrapie isolates in
these mice led to the propagation of prions that are phenotypically identical to
those causing sporadic CJD (sCJD) in humans. These results demonstrate that
scrapie prions have a zoonotic potential and raise new questions about the
possible link between animal and human prions.
Subject terms: Biological sciences• Medical research At a glance
*** In complement to the recent demonstration that humanized mice are
susceptible to scrapie, we report here the first observation of direct
transmission of a natural classical scrapie isolate to a macaque after a 10-year
incubation period. Neuropathologic examination revealed all of the features of a
prion disease: spongiform change, neuronal loss, and accumulation of PrPres
throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of
scrapie to humans, at a time when protective measures for human and animal
health are being dismantled and reduced as c-BSE is considered controlled and
being eradicated.
*** Our results underscore the importance of precautionary and protective
measures and the necessity for long-term experimental transmission studies to
assess the zoonotic potential of other animal prion strains.
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a.
Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos,
Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT.
Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas.
France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated
bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD)
disease in human. To date, BSE agent is the only recognized zoonotic prion.
Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that
have been circulating for centuries in farmed ruminants there is no apparent
epidemiological link between exposure to ruminant products and the occurrence of
other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD).
However, the zoonotic potential of the diversity of circulating TSE agents has
never been systematically assessed. The major issue in experimental assessment
of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the
biological phenomenon that limits TSE agents’ propagation from a species to
another. In the last decade, mice genetically engineered to express normal forms
of the human prion protein has proved essential in studying human prions
pathogenesis and modeling the capacity of TSEs to cross the human species
barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants,
we study their transmission ability in transgenic mice expressing human PrPC
(HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC
(129Met or 129Val) are used to determine the role of the Met129Val dimorphism in
susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to
propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be
susceptible to BSE in sheep or goat to a greater degree than the BSE agent in
cattle and that these agents can convey molecular properties and
neuropathological indistinguishable from vCJD. However homozygous 129V mice are
resistant to all tested BSE derived prions independently of the originating
species suggesting a higher transmission barrier for 129V-PrP variant.
Transmission data also revealed that several scrapie prions propagate in
HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the
efficiency of transmission at primary passage was low, subsequent passages
resulted in a highly virulent prion disease in both Met129 and Val129 mice.
Transmission of the different scrapie isolates in these mice leads to the
emergence of prion strain phenotypes that showed similar characteristics to
those displayed by MM1 or VV2 sCJD prion. These results demonstrate that scrapie
prions have a zoonotic potential and raise new questions about the possible link
between animal and human prions.
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly would likely
create alarm in some circles even if the result could not be interpreted for
man. I have a view that all these agents could be transmitted provided a large
enough dose by appropriate routes was given and the animals kept long enough.
Until the mechanisms of the species barrier are more clearly understood it might
be best to retain that hypothesis.
snip...
R. BRADLEY
1978 SCRAPIE IN CONFIDENCE SCJD
1979
SILENCE ON CJD AND SCRAPIE
1980
SILENCE ON CJD AND SCRAPIE
*** 1981 NOVEMBER
Thursday, August 04, 2016
*** MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON
CREUTZFELDT JAKOB DISEASE 1978 THE SCRAPIE FILES IN CONFIDENCE CONFIDENTIAL
SCJD
2016
SCRAPIE AND CWD ZOONOSIS
PRION 2016 CONFERENCE TOKYO
Saturday, April 23, 2016
*** SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
***
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X
Transmission of scrapie prions to primate after an extended silent
incubation period
***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. Comoy , Jacqueline Mikol , Sophie Luccantoni-Freire , Evelyne
Correia , Nathalie Lescoutra-Etchegaray , Valérie Durand , Capucine Dehen ,
Olivier Andreoletti , Cristina Casalone , Juergen A. Richt , Justin J. Greenlee
, Thierry Baron , Sylvie L. Benestad , Paul Brown & Jean-Philippe Deslys
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...
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.
***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.***
2015
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, Valerie 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 long 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***
===============
***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.
==============
Saturday, May 28, 2016
*** Infection and detection of PrPCWD in soil from CWD infected farm in
Korea Prion 2016 Tokyo ***
What is the risk of chronic wasting disease being introduced into Great
Britain? An updated Qualitative Risk Assessment March 2016
Summary
The previous assessment concentrated on the incursion of disease from North
America through the imports of animal feed or the movement of contaminated
clothing, footwear and equipment. The results suggested that import of pet feed
was a non-negligible risk, but given the unlikely contact of resident deer in GB
with such non-ruminant feed, this was considered overall a negligible to very
low risk. The movement of contaminated clothing, footwear or equipment
(particularly hunting equipment) could pose a very low risk, although the volume
of contaminated soil which would need to be ingested to give rise to an
infection is likely to be higher than would be present. There is a variable
level uncertainty in all these assessments.
The new assessment focuses on an additional potential route of entry: the
importation of natural deer urine lures. The main conclusions from this
assessment are:
In areas of North America where CWD has been reported, given that CWD is
excreted in faeces, saliva, urine and blood, and survives in the environment for
several years there is a medium probability that the deer urine in North America
contains CWD (high uncertainty; depends on the source of deer used for
production).
The risk of a deer in GB being infected per 30 ml bottle of urine
imported from the USA is very low, albeit with high uncertainty. Overall it is
concluded that the risk of at least one infection of deer in the UK with CWD per
year from deer urine lures imported from the USA is medium. This assumes a high
number of 30 ml bottles imported per year from all areas of the USA.
None of the species affected by CWD in North America are present in GB.
For a British species to become infected with CWD following exposure, the dose
and inherent susceptibility of the species will be important. Based on current
scientific evidence Red deer (Cervus elaphus elaphus) are susceptible to CWD,
Fallow deer (Dama dama) are likely to be less susceptible and Roe deer
(Capreolus capreolus) have a gene conferring susceptibility. Therefore, it is
likely that given exposure to an infectious dose of CWD, deer in GB could become
infected with CWD.
Overall, the probability of importing CWD into GB from North America and
causing infection in British deer is uncertain but likely to be negligible to
very low via movement of deer hunters, other tourists and British servicemen and
very low via imported (non-
2
ruminant) animal feed and medium for the use of lures. However, if it was
imported and (a) deer did become infected with CWD, the consequences would be
severe as eradication of the disease is impossible, it is clinically
indistinguishable from BSE infection in deer (Dalgleish et al., 2008) and
populations of wild and farmed deer would be under threat.
The USA has implemented a Herd Certification Programme for farmed and
captive cervids. So far, 29 States are approved for HCP status (APHIS, 2015).
The list includes States such as Colorado, where CWD is present, therefore it is
recommended that any sourcing of such natural urine lures should be not only
from States with an HCP programme, but also from a herd which is registered as
being regularly tested free of CWD.
Animal urine is not considered a commodity which is subject to animal
by-products legislation for imports. Internet sales are common and although a
license would be required, there are no conditions for the safe sourcing of such
products. Deer urine lures are also available in Europe and may be produced from
carcases of hunted deer. The use of deer urine produced from a species not
present in Europe (such as white tailed deer) is questioned for its value with
native GB deer according to the British Deer Society survey.
Background
Thursday, April 07, 2016
What is the risk of chronic wasting disease being introduced into Great
Britain? An updated Qualitative Risk Assessment March 2016
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...
What is the risk of chronic wasting disease being introduced into Great
Britain? A Qualitative Risk Assessment October 2012
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 well as non-ruminants such as cats and dogs as
well, as soon as possible for the following reasons...
31 Jan 2015 at 20:14 GMT
*** Ruminant feed ban for cervids in the United States? ***
31 Jan 2015 at 20:14 GMT
Terry Singeltary Sr. comment ;
Tuesday, April 19, 2016
Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards
Singeltary Comment Submission
*** Infectious agent of sheep scrapie may persist in the environment for at
least 16 years ***
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
Friday, August 14, 2015
*** Susceptibility of cattle to the agent of chronic wasting disease from
elk after intracranial inoculation ***
Saturday, May 28, 2016
*** Infection and detection of PrPCWD in soil from CWD infected farm in
Korea Prion 2016 Tokyo ***
Experimental Oral Transmission of Chronic Wasting Disease to Reindeer
(Rangifer tarandus tarandus)
Gordon B. Mitchell1, Christina J. Sigurdson2,3, Katherine I. O’Rourke4,
James Algire1, Noel P. Harrington1, Ines Walther1, Terry R. Spraker5, Aru
Balachandran1*
1 National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food
Inspection Agency, Ottawa Laboratory – Fallowfield, Ottawa, Ontario,
Canada,
2 Departments of Pathology and Medicine, University of California, San
Diego, La Jolla, California, United States of America, 3 Department of
Pathology, Microbiology and Immunology, University of California, Davis,
California, United States of America, 4 Animal Disease Research Unit,
Agricultural Research Service, United States Department of Agriculture, Pullman,
Washington, United States of America, 5 Veterinary Diagnostic Laboratory,
Colorado State University, Fort Collins, Colorado, United States of
America
Abstract
Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of
cervids, remains prevalent in North American elk, white-tailed deer and mule
deer. A natural case of CWD in reindeer (Rangifer tarandus tarandus) has not
been reported despite potential habitat overlap with CWD-infected deer or elk
herds. This study investigates the experimental transmission of CWD from elk or
white-tailed deer to reindeer by the oral route of inoculation. Ante-mortem
testing of the three reindeer exposed to CWD from white-tailed deer identified
the accumulation of pathological PrP (PrPCWD) in the recto-anal mucosa
associated lymphoid tissue (RAMALT) of two reindeer at 13.4 months
post-inoculation. Terminal CWD occurred in the two RAMALT-positive reindeer at
18.5 and 20 months post-inoculation while one other reindeer in the white-tailed
deer CWD inoculum group and none of the 3 reindeer exposed to elk CWD developed
disease. Tissue distribution analysis of PrPCWD in CWD-affected reindeer
revealed widespread deposition in central and peripheral nervous systems,
lymphoreticular tissues, the gastrointestinal tract, neuroendocrine tissues and
cardiac muscle. Analysis of prion protein gene (PRNP) sequences in the 6
reindeer identified polymorphisms at residues 2 (V/M), 129 (G/S), 138 (S/N) and
169 (V/M). These findings demonstrate that (i) a sub-population of reindeer are
susceptible to CWD by oral inoculation implicating the potential for
transmission to other Rangifer species, and (ii) certain reindeer PRNP
polymorphisms may be protective against CWD infection.
snip...
The importance of Rangifer species to the culture of aboriginal peoples
cannot be underestimated with many components of hunted animals being consumed
as food. Although relatively limited in comparison to elk and deer industries in
North America, reindeer and caribou farming does occur, producing consumables
such as meat, hides and antler velvet. The human health risks of consuming meat
or other products derived from CWD-infected animals remain uncertain, although
epidemiological evidence indicates transmission has not yet occurred [30,31,32]
and transgenic mouse studies suggest the risk is remote in humans expressing
common PRNP sequences [33,34,35]. The finding that CWD can be transmitted to
squirrel monkeys by intracranial inoculation [36] raises concern for human
transmissibility, however a study in macaques failed to demonstrate transmission
after 70 months [37]. Since prion strains may undergo changes in transmission
characteristics following passage through different species and strain selection
pressures can be exerted by host genetic factors during passage within a species
[24,38,39,40], caution is warranted when predicting the risks of CWD
transmission from reindeer to other species.
This is the first evidence of CWD transmission to the sub-species Rangifer
tarandus tarandus, implicating the potential for transmission to others in this
genus. Current diagnostic tests, including antemortem RAMALT testing, appear
capable of detecting CWD in Rangifer species and increased surveillance would be
required to determine if natural transmission has indeed occurred. Additional
studies are ongoing to chart the distribution of infectivity during the course
of disease and determine the influence of PRNP polymorphisms in disease
susceptibility.
Citation: Mitchell GB, Sigurdson CJ, O’Rourke KI, Algire J, Harrington NP,
et al. (2012) Experimental Oral Transmission of Chronic Wasting Disease to
Reindeer (Rangifer tarandus tarandus). PLoS ONE 7(6): e39055.
doi:10.1371/journal.pone.0039055
Editor: Anthony E. Kincaid, Creighton University, United States of
America
Received May 4, 2012; Accepted May 15, 2012; Published June 18, 2012
This is an open-access article, free of all copyright, and may be freely
reproduced, distributed, transmitted, modified, built upon, or otherwise used by
anyone for any lawful purpose. The work is made available under the Creative
Commons CC0 public domain dedication.
Funding: This work was supported by the Canadian Food Inspection Agency and
Agriculture and Agri-Food Canada under C00233, the United States
Department of Agriculture Agricultural Research Service under CRIS
5348-32000-026-00-D and the United States National Institutes of Health under
NS069566 and U54AI0359. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests
exist.
* E-mail: Aru.Balachandran@inspection.gc.ca
THANK YOU PLOS FOR OPEN ACCESS FOR THE LAYPEOPLE, such as myself. ...TSS
natural cases of CWD in eight Sika deer (Cervus nippon) and five Sika/red
deer crossbreeds Korea and Experimental oral transmission to red deer (Cervus
elaphus elaphus)
SCWDS BRIEFS
A Quarterly Newsletter from the Southeastern Cooperative Wildlife Disease
Study College of Veterinary Medicine The University of Georgia Athens, Georgia
30602
Volume 27 January 2012 Number 4
Red deer susceptibility to CWD via oral inoculation was demonstrated in a
study conducted by collaborators from the U.S. and Canada. Red deer developed
clinical signs and had spongiform changes in the brain when euthanatized at 20
MPI. The CWD prion was detectable in neural and lymphoid tissues, endocrine
organs, cardiac muscle, nasal mucosa, and other tissues. Although field cases of
CWD in red deer have not been reported, results of this study indicate that it
could occur, which is not surprising given that elk and red deer are subspecies
of Cervus elaphus. The results of this study can be found in the Canadian
Veterinary Journal 51: 169-178.
In addition, it was reported in May 2011 that natural cases of CWD were
found in eight Sika deer (Cervus nippon) and five Sika/red deer crossbreeds
during epidemiological investigations of CWD cases in captive elk in Korea.
May 2011 natural cases of CWD were found in eight Sika deer (Cervus nippon)
and five Sika/red deer crossbreeds during epidemiological investigations of CWD
cases in captive elk in Korea
Friday, May 13, 2011
Chronic Wasting Disease (CWD) outbreaks and surveillance program in the
Republic of Korea 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. : Corresponding author: Dr. Hyun-Joo Sohn (+82-31-467-1867, E-mail:
shonhj@korea.kr)
2011 Pre-congress Workshop: TSEs in animals and their environment 5
Friday, May 13, 2011
Chronic Wasting Disease (CWD) outbreaks and surveillance program in the
Republic of Korea
Tuesday, June 19, 2012
Experimental Oral Transmission of Chronic Wasting Disease to Reindeer
(Rangifer tarandus tarandus)
I urge everyone to watch this video closely...terry
*** you can see video here and interview with Jeff's Mom, and scientist
telling you to test everything and potential risk factors for humans ***
Using in vitro prion replication for high sensitive detection of prions and
prionlike proteins and for understanding mechanisms of transmission.
Claudio Soto
Mitchell Center for Alzheimer's diseases and related Brain disorders,
Department of Neurology, University of Texas Medical School at Houston.
Prion and prion-like proteins are misfolded protein aggregates with the
ability to selfpropagate to spread disease between cells, organs and in some
cases across individuals. I n T r a n s m i s s i b l e s p o n g i f o r m
encephalopathies (TSEs), prions are mostly composed by a misfolded form of the
prion protein (PrPSc), which propagates by transmitting its misfolding to the
normal prion protein (PrPC). The availability of a procedure to replicate prions
in the laboratory may be important to study the mechanism of prion and
prion-like spreading and to develop high sensitive detection of small quantities
of misfolded proteins in biological fluids, tissues and environmental samples.
Protein Misfolding Cyclic Amplification (PMCA) is a simple, fast and efficient
methodology to mimic prion replication in the test tube. PMCA is a platform
technology that may enable amplification of any prion-like misfolded protein
aggregating through a seeding/nucleation process. In TSEs, PMCA is able to
detect the equivalent of one single molecule of infectious PrPSc and propagate
prions that maintain high infectivity, strain properties and species
specificity. Using PMCA we have been able to detect PrPSc in blood and urine of
experimentally infected animals and humans affected by vCJD with high
sensitivity and specificity. Recently, we have expanded the principles of PMCA
to amplify amyloid-beta (Aβ) and alphasynuclein (α-syn) aggregates implicated in
Alzheimer's and Parkinson's diseases, respectively. Experiments are ongoing to
study the utility of this technology to detect Aβ and α-syn aggregates in
samples of CSF and blood from patients affected by these diseases.
=========================
***Recently, we have been using PMCA to study the role of environmental
prion contamination on the horizontal spreading of TSEs. These experiments have
focused on the study of the interaction of prions with plants and
environmentally relevant surfaces. Our results show that plants (both leaves and
roots) bind tightly to prions present in brain extracts and excreta (urine and
feces) and retain even small quantities of PrPSc for long periods of time.
Strikingly, ingestion of prioncontaminated leaves and roots produced disease
with a 100% attack rate and an incubation period not substantially longer than
feeding animals directly with scrapie brain homogenate. Furthermore, plants can
uptake prions from contaminated soil and transport them to different parts of
the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety
of environmentally relevant surfaces, including stones, wood, metals, plastic,
glass, cement, etc. Prion contaminated surfaces efficiently transmit prion
disease when these materials were directly injected into the brain of animals
and strikingly when the contaminated surfaces were just placed in the animal
cage. These findings demonstrate that environmental materials can efficiently
bind infectious prions and act as carriers of infectivity, suggesting that they
may play an important role in the horizontal transmission of the disease.
========================
Since its invention 13 years ago, PMCA has helped to answer fundamental
questions of prion propagation and has broad applications in research areas
including the food industry, blood bank safety and human and veterinary disease
diagnosis.
see ;
with CWD TSE Prions, I am not sure there is any absolute yet, other than
what we know with transmission studies, and we know tse prion kill, and tse
prion are bad. science shows to date, that indeed soil, dirt, some better than
others, can act as a carrier. same with objects, farm furniture. take it with
how ever many grains of salt you wish, or not. if load factor plays a role in
the end formula, then everything should be on the table, in my opinion. see
;
***Recently, we have been using PMCA to study the role of environmental
prion contamination on the horizontal spreading of TSEs. These experiments have
focused on the study of the interaction of prions with plants and
environmentally relevant surfaces. Our results show that plants (both leaves and
roots) bind tightly to prions present in brain extracts and excreta (urine and
feces) and retain even small quantities of PrPSc for long periods of time.
Strikingly, ingestion of prioncontaminated leaves and roots produced disease
with a 100% attack rate and an incubation period not substantially longer than
feeding animals directly with scrapie brain homogenate. Furthermore, plants can
uptake prions from contaminated soil and transport them to different parts of
the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety
of environmentally relevant surfaces, including stones, wood, metals, plastic,
glass, cement, etc. Prion contaminated surfaces efficiently transmit prion
disease when these materials were directly injected into the brain of animals
and strikingly when the contaminated surfaces were just placed in the animal
cage. These findings demonstrate that environmental materials can efficiently
bind infectious prions and act as carriers of infectivity, suggesting that they
may play an important role in the horizontal transmission of the disease.
Since its invention 13 years ago, PMCA has helped to answer fundamental
questions of prion propagation and has broad applications in research areas
including the food industry, blood bank safety and human and veterinary disease
diagnosis.
see ;
Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil
Particles
Author Summary
Transmissible spongiform encephalopathies (TSEs) are a group of incurable
neurological diseases likely caused by a misfolded form of the prion protein.
TSEs include scrapie in sheep, bovine spongiform encephalopathy (‘‘mad cow’’
disease) in cattle, chronic wasting disease in deer and elk, and
Creutzfeldt-Jakob disease in humans. Scrapie and chronic wasting disease are
unique among TSEs because they can be transmitted between animals, and the
disease agents appear to persist in environments previously inhabited by
infected animals. Soil has been hypothesized to act as a reservoir of
infectivity and to bind the infectious agent. In the current study, we orally
dosed experimental animals with a common clay mineral, montmorillonite, or whole
soils laden with infectious prions, and compared the transmissibility to unbound
agent. We found that prions bound to montmorillonite and whole soils remained
orally infectious, and, in most cases, increased the oral transmission of
disease compared to the unbound agent. The results presented in this study
suggest that soil may contribute to environmental spread of TSEs by increasing
the transmissibility of small amounts of infectious agent in the
environment.
tse prion soil
Wednesday, December 16, 2015
Objects in contact with classical scrapie sheep act as a reservoir for
scrapie transmission
The sources of dust borne prions are unknown but it seems reasonable to
assume that faecal, urine, skin, parturient material and saliva-derived prions
may contribute to this mobile environmental reservoir of infectivity. This work
highlights a possible transmission route for scrapie within the farm
environment, and this is likely to be paralleled in CWD which shows strong
similarities with scrapie in terms of prion dissemination and disease
transmission. The data indicate that the presence of scrapie prions in dust is
likely to make the control of these diseases a considerable challenge.
>>>Particle-associated PrPTSE molecules may migrate from locations
of deposition via transport processes affecting soil particles, including
entrainment in and movement with air and overland flow. <<<
Fate of Prions in Soil: A Review
Christen B. Smith, Clarissa J. Booth, and Joel A. Pedersen*
Several reports have shown that prions can persist in soil for several
years. Significant interest remains in developing methods that could be applied
to degrade PrPTSE in naturally contaminated soils. Preliminary research suggests
that serine proteases and the microbial consortia in stimulated soils and
compost may partially degrade PrPTSE. Transition metal oxides in soil (viz.
manganese oxide) may also mediate prion inactivation. Overall, the effect of
prion attachment to soil particles on its persistence in the environment is not
well understood, and additional study is needed to determine its implications on
the environmental transmission of scrapie and CWD.
P.161: Prion soil binding may explain efficient horizontal CWD transmission
Conclusion. Silty clay loam exhibits highly efficient prion binding,
inferring a durable environmental reservoir, and an efficient mechanism for
indirect horizontal CWD transmission.
>>>Another alternative would be an absolute prohibition on the
movement of deer within the state for any purpose. While this alternative would
significantly reduce the potential spread of CWD, it would also have the
simultaneous effect of preventing landowners and land managers from implementing
popular management strategies involving the movement of deer, and would deprive
deer breeders of the ability to engage in the business of buying and selling
breeder deer. Therefore, this alternative was rejected because the department
determined that it placed an avoidable burden on the regulated
community.<<<
Wednesday, December 16, 2015
Objects in contact with classical scrapie sheep act as a reservoir for
scrapie transmission
Objects in contact with classical scrapie sheep act as a reservoir for
scrapie transmission
Timm Konold1*, Stephen A. C. Hawkins2, Lisa C. Thurston3, Ben C. Maddison4,
Kevin C. Gough5, Anthony Duarte1 and Hugh A. Simmons1
1 Animal Sciences Unit, Animal and Plant Health Agency Weybridge,
Addlestone, UK, 2 Pathology Department, Animal and Plant Health Agency
Weybridge, Addlestone, UK, 3 Surveillance and Laboratory Services, Animal and
Plant Health Agency Penrith, Penrith, UK, 4 ADAS UK, School of Veterinary
Medicine and Science, University of Nottingham, Sutton Bonington, UK, 5 School
of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington,
UK
Classical scrapie is an environmentally transmissible prion disease of
sheep and goats. Prions can persist and remain potentially infectious in the
environment for many years and thus pose a risk of infecting animals after
re-stocking. In vitro studies using serial protein misfolding cyclic
amplification (sPMCA) have suggested that objects on a scrapie affected sheep
farm could contribute to disease transmission. This in vivo study aimed to
determine the role of field furniture (water troughs, feeding troughs, fencing,
and other objects that sheep may rub against) used by a scrapie-infected sheep
flock as a vector for disease transmission to scrapie-free lambs with the prion
protein genotype VRQ/VRQ, which is associated with high susceptibility to
classical scrapie. When the field furniture was placed in clean accommodation,
sheep became infected when exposed to either a water trough (four out of five)
or to objects used for rubbing (four out of seven). This field furniture had
been used by the scrapie-infected flock 8 weeks earlier and had previously been
shown to harbor scrapie prions by sPMCA. Sheep also became infected (20 out of
23) through exposure to contaminated field furniture placed within pasture not
used by scrapie-infected sheep for 40 months, even though swabs from this
furniture tested negative by PMCA. This infection rate decreased (1 out of 12)
on the same paddock after replacement with clean field furniture. Twelve grazing
sheep exposed to field furniture not in contact with scrapie-infected sheep for
18 months remained scrapie free. The findings of this study highlight the role
of field furniture used by scrapie-infected sheep to act as a reservoir for
disease re-introduction although infectivity declines considerably if the field
furniture has not been in contact with scrapie-infected sheep for several
months. PMCA may not be as sensitive as VRQ/VRQ sheep to test for environmental
contamination.
snip...
Discussion
Classical scrapie is an environmentally transmissible disease because it
has been reported in naïve, supposedly previously unexposed sheep placed in
pastures formerly occupied by scrapie-infected sheep (4, 19, 20). Although the
vector for disease transmission is not known, soil is likely to be an important
reservoir for prions (2) where – based on studies in rodents – prions can adhere
to minerals as a biologically active form (21) and remain infectious for more
than 2 years (22). Similarly, chronic wasting disease (CWD) has re-occurred in
mule deer housed in paddocks used by infected deer 2 years earlier, which was
assumed to be through foraging and soil consumption (23).
Our study suggested that the risk of acquiring scrapie infection was
greater through exposure to contaminated wooden, plastic, and metal surfaces via
water or food troughs, fencing, and hurdles than through grazing. Drinking from
a water trough used by the scrapie flock was sufficient to cause infection in
sheep in a clean building. Exposure to fences and other objects used for rubbing
also led to infection, which supported the hypothesis that skin may be a vector
for disease transmission (9). The risk of these objects to cause infection was
further demonstrated when 87% of 23 sheep presented with PrPSc in lymphoid
tissue after grazing on one of the paddocks, which contained metal hurdles, a
metal lamb creep and a water trough in contact with the scrapie flock up to 8
weeks earlier, whereas no infection had been demonstrated previously in sheep
grazing on this paddock, when equipped with new fencing and field furniture.
When the contaminated furniture and fencing were removed, the infection rate
dropped significantly to 8% of 12 sheep, with soil of the paddock as the most
likely source of infection caused by shedding of prions from the
scrapie-infected sheep in this paddock up to a week earlier.
This study also indicated that the level of contamination of field
furniture sufficient to cause infection was dependent on two factors: stage of
incubation period and time of last use by scrapie-infected sheep. Drinking from
a water trough that had been used by scrapie sheep in the predominantly
pre-clinical phase did not appear to cause infection, whereas infection was
shown in sheep drinking from the water trough used by scrapie sheep in the later
stage of the disease. It is possible that contamination occurred through
shedding of prions in saliva, which may have contaminated the surface of the
water trough and subsequently the water when it was refilled. Contamination
appeared to be sufficient to cause infection only if the trough was in contact
with sheep that included clinical cases. Indeed, there is an increased risk of
bodily fluid infectivity with disease progression in scrapie (24) and CWD (25)
based on PrPSc detection by sPMCA. Although ultraviolet light and heat under
natural conditions do not inactivate prions (26), furniture in contact with the
scrapie flock, which was assumed to be sufficiently contaminated to cause
infection, did not act as vector for disease if not used for 18 months, which
suggest that the weathering process alone was sufficient to inactivate prions.
PrPSc detection by sPMCA is increasingly used as a surrogate for
infectivity measurements by bioassay in sheep or mice. In this reported study,
however, the levels of PrPSc present in the environment were below the limit of
detection of the sPMCA method, yet were still sufficient to cause infection of
in-contact animals. In the present study, the outdoor objects were removed from
the infected flock 8 weeks prior to sampling and were positive by sPMCA at very
low levels (2 out of 37 reactions). As this sPMCA assay also yielded 2 positive
reactions out of 139 in samples from the scrapie-free farm, the sPMCA assay
could not detect PrPSc on any of the objects above the background of the assay.
False positive reactions with sPMCA at a low frequency associated with de novo
formation of infectious prions have been reported (27, 28). This is in contrast
to our previous study where we demonstrated that outdoor objects that had been
in contact with the scrapie-infected flock up to 20 days prior to sampling
harbored PrPSc that was detectable by sPMCA analysis [4 out of 15 reactions
(12)] and was significantly more positive by the assay compared to analogous
samples from the scrapie-free farm. This discrepancy could be due to the use of
a different sPMCA substrate between the studies that may alter the efficiency of
amplification of the environmental PrPSc. In addition, the present study had a
longer timeframe between the objects being in contact with the infected flock
and sampling, which may affect the levels of extractable PrPSc. Alternatively,
there may be potentially patchy contamination of this furniture with PrPSc,
which may have been missed by swabbing. The failure of sPMCA to detect
CWD-associated PrP in saliva from clinically affected deer despite confirmation
of infectivity in saliva-inoculated transgenic mice was associated with as yet
unidentified inhibitors in saliva (29), and it is possible that the sensitivity
of sPMCA is affected by other substances in the tested material. In addition,
sampling of amplifiable PrPSc and subsequent detection by sPMCA may be more
difficult from furniture exposed to weather, which is supported by the
observation that PrPSc was detected by sPMCA more frequently in indoor than
outdoor furniture (12). A recent experimental study has demonstrated that
repeated cycles of drying and wetting of prion-contaminated soil, equivalent to
what is expected under natural weathering conditions, could reduce PMCA
amplification efficiency and extend the incubation period in hamsters inoculated
with soil samples (30). This seems to apply also to this study even though the
reduction in infectivity was more dramatic in the sPMCA assays than in the sheep
model. Sheep were not kept until clinical end-point, which would have enabled us
to compare incubation periods, but the lack of infection in sheep exposed to
furniture that had not been in contact with scrapie sheep for a longer time
period supports the hypothesis that prion degradation and subsequent loss of
infectivity occurs even under natural conditions.
In conclusion, the results in the current study indicate that removal of
furniture that had been in contact with scrapie-infected animals should be
recommended, particularly since cleaning and decontamination may not effectively
remove scrapie infectivity (31), even though infectivity declines considerably
if the pasture and the field furniture have not been in contact with
scrapie-infected sheep for several months. As sPMCA failed to detect PrPSc in
furniture that was subjected to weathering, even though exposure led to
infection in sheep, this method may not always be reliable in predicting the
risk of scrapie infection through environmental contamination. These results
suggest that the VRQ/VRQ sheep model may be more sensitive than sPMCA for the
detection of environmentally associated scrapie, and suggest that extremely low
levels of scrapie contamination are able to cause infection in susceptible sheep
genotypes.
Keywords: classical scrapie, prion, transmissible spongiform
encephalopathy, sheep, field furniture, reservoir, serial protein misfolding
cyclic amplification
Wednesday, December 16, 2015
*** Objects in contact with classical scrapie sheep act as a reservoir for
scrapie transmission ***
New studies on the heat resistance of hamster-adapted scrapie agent:
Threshold survival after ashing at 600°C suggests an inorganic template of
replication
The infectious agents responsible for transmissible spongiform
encephalopathy (TSE) are notoriously resistant to most physical and chemical
methods used for inactivating pathogens, including heat. It has long been
recognized, for example, that boiling is ineffective and that higher
temperatures are most efficient when combined with steam under pressure (i.e.,
autoclaving). As a means of decontamination, dry heat is used only at the
extremely high temperatures achieved during incineration, usually in excess of
600°C. It has been assumed, without proof, that incineration totally inactivates
the agents of TSE, whether of human or animal origin.
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel
Production
Histochemical analysis of hamster brains inoculated with the solid residue
showed typical spongiform degeneration and vacuolation. Re-inoculation of these
brains into a new cohort of hamsters led to onset of clinical scrapie symptoms
within 75 days, suggesting that the specific infectivity of the prion protein
was not changed during the biodiesel process. The biodiesel reaction cannot be
considered a viable prion decontamination method for MBM, although we observed
increased survival time of hamsters and reduced infectivity greater than 6 log
orders in the solid MBM residue. Furthermore, results from our study compare for
the first time prion detection by Western Blot versus an infectivity bioassay
for analysis of biodiesel reaction products. We could show that biochemical
analysis alone is insufficient for detection of prion infectivity after a
biodiesel process.
Detection of protease-resistant cervid prion protein in water from a
CWD-endemic area
The data presented here demonstrate that sPMCA can detect low levels of
PrPCWD in the environment, corroborate previous biological and experimental data
suggesting long term persistence of prions in the environment2,3 and imply that
PrPCWD accumulation over time may contribute to transmission of CWD in areas
where it has been endemic for decades. This work demonstrates the utility of
sPMCA to evaluate other environmental water sources for PrPCWD, including
smaller bodies of water such as vernal pools and wallows, where large numbers of
cervids congregate and into which prions from infected animals may be shed and
concentrated to infectious levels.
A Quantitative Assessment of the Amount of Prion Diverted to Category 1
Materials and Wastewater During Processing
Keywords:Abattoir;bovine spongiform encephalopathy;QRA;scrapie;TSE
In this article the development and parameterization of a quantitative
assessment is described that estimates the amount of TSE infectivity that is
present in a whole animal carcass (bovine spongiform encephalopathy [BSE] for
cattle and classical/atypical scrapie for sheep and lambs) and the amounts that
subsequently fall to the floor during processing at facilities that handle
specified risk material (SRM). BSE in cattle was found to contain the most oral
doses, with a mean of 9864 BO ID50s (310, 38840) in a whole carcass compared to
a mean of 1851 OO ID50s (600, 4070) and 614 OO ID50s (155, 1509) for a sheep
infected with classical and atypical scrapie, respectively. Lambs contained the
least infectivity with a mean of 251 OO ID50s (83, 548) for classical scrapie
and 1 OO ID50s (0.2, 2) for atypical scrapie. The highest amounts of infectivity
falling to the floor and entering the drains from slaughtering a whole carcass
at SRM facilities were found to be from cattle infected with BSE at rendering
and large incineration facilities with 7.4 BO ID50s (0.1, 29), intermediate
plants and small incinerators with a mean of 4.5 BO ID50s (0.1, 18), and
collection centers, 3.6 BO ID50s (0.1, 14). The lowest amounts entering drains
are from lambs infected with classical and atypical scrapie at intermediate
plants and atypical scrapie at collection centers with a mean of 3 × 10−7 OO
ID50s (2 × 10−8, 1 × 10−6) per carcass. The results of this model provide key
inputs for the model in the companion paper published here.
*** Infectious agent of sheep scrapie may persist in the environment for at
least 16 years ***
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
>>>Another alternative would be an absolute prohibition on the
movement of deer within the state for any purpose. While this alternative would
significantly reduce the potential spread of CWD, it would also have the
simultaneous effect of preventing landowners and land managers from implementing
popular management strategies involving the movement of deer, and would deprive
deer breeders of the ability to engage in the business of buying and selling
breeder deer. Therefore, this alternative was rejected because the department
determined that it placed an avoidable burden on the regulated
community.<<<
Circulation of prions within dust on a scrapie affected farm
Kevin C Gough1, Claire A Baker2, Hugh A Simmons3, Steve A Hawkins3 and Ben
C Maddison2*
Abstract
Prion diseases are fatal neurological disorders that affect humans and
animals. Scrapie of sheep/goats and Chronic Wasting Disease (CWD) of deer/elk
are contagious prion diseases where environmental reservoirs have a direct link
to the transmission of disease. Using protein misfolding cyclic amplification we
demonstrate that scrapie PrPSc can be detected within circulating dusts that are
present on a farm that is naturally contaminated with sheep scrapie. The
presence of infectious scrapie within airborne dusts may represent a possible
route of infection and illustrates the difficulties that may be associated with
the effective decontamination of such scrapie affected premises.
snip...
Discussion
We present biochemical data illustrating the airborne movement of scrapie
containing material within a contaminated farm environment. We were able to
detect scrapie PrPSc within extracts from dusts collected over a 70 day period,
in the absence of any sheep activity. We were also able to detect scrapie PrPSc
within dusts collected within pasture at 30 m but not at 60 m distance away from
the scrapie contaminated buildings, suggesting that the chance of contamination
of pasture by scrapie contaminated dusts decreases with distance from
contaminated farm buildings. PrPSc amplification by sPMCA has been shown to
correlate with infectivity and amplified products have been shown to be
infectious [14,15]. These experiments illustrate the potential for low dose
scrapie infectivity to be present within such samples. We estimate low ng levels
of scrapie positive brain equivalent were deposited per m2 over 70 days, in a
barn previously occupied by sheep affected with scrapie. This movement of dusts
and the accumulation of low levels of scrapie infectivity within this
environment may in part explain previous observations where despite stringent
pen decontamination regimens healthy lambs still became scrapie infected after
apparent exposure from their environment alone [16]. The presence of sPMCA
seeding activity and by inference, infectious prions within dusts, and their
potential for airborne dissemination is highly novel and may have implications
for the spread of scrapie within infected premises. The low level circulation
and accumulation of scrapie prion containing dust material within the farm
environment will likely impede the efficient decontamination of such scrapie
contaminated buildings unless all possible reservoirs of dust are removed.
Scrapie containing dusts could possibly infect animals during feeding and
drinking, and respiratory and conjunctival routes may also be involved. It has
been demonstrated that scrapie can be efficiently transmitted via the nasal
route in sheep [17], as is also the case for CWD in both murine models and in
white tailed deer [18-20].
The sources of dust borne prions are unknown but it seems reasonable to
assume that faecal, urine, skin, parturient material and saliva-derived prions
may contribute to this mobile environmental reservoir of infectivity. This work
highlights a possible transmission route for scrapie within the farm
environment, and this is likely to be paralleled in CWD which shows strong
similarities with scrapie in terms of prion dissemination and disease
transmission. The data indicate that the presence of scrapie prions in dust is
likely to make the control of these diseases a considerable challenge.
***at present, no cervid PrP allele conferring absolute resistance to prion
infection has been identified.
P-145 Estimating chronic wasting disease resistance in cervids using real
time quaking- induced conversion
Nicholas J Haley1, Rachel Rielinqer2, Kristen A Davenport3, W. David
Walter4, Katherine I O'Rourke5, Gordon Mitchell6, Juergen A Richt2
1 Department of Microbiology and Immunology, Midwestern University, United
States; 2Department of Diagnostic Medicine and Pathobiology, Kansas State
University; 3Prion Research Center; Colorado State University; 4U.S. Geological
Survey, Pennsylvania Cooperative Fish and Wildlife Research Unit; 5Agricultural
Research Service, United States Department of Agriculture; 6Canadian Food
Inspection Agency, National and OlE Reference Laboratory for Scrapie and CWO
In mammalian species, the susceptibility to prion diseases is affected, in
part, by the sequence of the host's prion protein (PrP). In sheep, a gradation
from scrapie susceptible to resistant has been established both in vivo and in
vitro based on the amino acids present at PrP positions 136, 154, and 171, which
has led to global breeding programs to reduce the prevalence of scrapie in
domestic sheep. In cervids, resistance is commonly characterized as a delayed
progression of chronic wasting disease (CWD); at present, no cervid PrP allele
conferring absolute resistance to prion infection has been identified. To model
the susceptibility of various naturally-occurring and hypothetical cervid PrP
alleles in vitro, we compared the amplification rates and efficiency of various
CWD isolates in recombinant PrPC using real time quaking-induced conversion. We
hypothesized that amplification metrics of these isolates in cervid PrP
substrates would correlate to in vivo susceptibility - allowing susceptibility
prediction for alleles found at 10 frequency in nature, and that there would be
an additive effect of multiple resistant codons in hypothetical alleles. Our
studies demonstrate that in vitro amplification metrics predict in vivo
susceptibility, and that alleles with multiple codons, each influencing
resistance independently, do not necessarily contribute additively to
resistance. Importantly, we found that the white-tailed deer 226K substrate
exhibited the slowest amplification rate among those evaluated, suggesting that
further investigation of this allele and its resistance in vivo are warranted to
determine if absolute resistance to CWD is possible.
***at present, no cervid PrP allele conferring absolute resistance to prion
infection has been identified.
PRION 2016 CONFERENCE TOKYO
Prion protein gene sequence and chronic wasting disease susceptibility in
white-tailed deer (Odocoileus virginianus)
Adam L Brandt, Amy C Kelly, Michelle L Green, Paul Shelton, Jan Novakofski
& Nohra E Mateus-Pinilla To cite this article: Adam L Brandt, Amy C Kelly,
Michelle L Green, Paul Shelton, Jan Novakofski & Nohra E Mateus-Pinilla
(2015) Prion protein gene sequence and chronic wasting disease susceptibility in
white-tailed deer (Odocoileus virginianus), Prion, 9:6, 449-462, DOI:
10.1080/19336896.2015.1115179 To link to this article: http://dx.doi.org/10.1080/19336896.2015.1115179
Prion, 9:449–462, 2015 Published with license by Taylor & Francis
Group, LLC ISSN: 1933-6896 print / 1933-690X online DOI:
10.1080/19336896.2015.1115179
RESEARCH PAPER Prion protein gene sequence and chronic wasting disease
susceptibility in white-tailed deer (Odocoileus virginianus) Adam L Brandt1, Amy
C Kelly1, Michelle L Green1,2, Paul Shelton3, Jan Novakofski2,*, and Nohra E
Mateus-Pinilla1,2 1Illinois Natural History Survey; University of Illinois at
Urbana-Champaign; Urbana, IL USA; 2Department of Animal Sciences; University of
Illinois at Urbana-Champaign; Urbana, IL USA; 3Illinois Department of Natural
Resources; Division of Wildlife Resources; Springfield, IL USA
ABSTRACT.
The sequence of the prion protein gene (PRNP) affects susceptibility to
spongiform encephalopathies, or prion diseases in many species. In white-tailed
deer, both coding and noncoding single nucleotide polymorphisms have been
identified in this gene that correlate to chronic wasting disease (CWD)
susceptibility. Previous studies examined individual nucleotide or amino acid
mutations; here we examine all nucleotide polymorphisms and their combined
effects on CWD. A 626 bp region of PRNP was examined from 703 free-ranging
white-tailed deer. Deer were sampled between 2002 and 2010 by hunter harvest or
government culling in Illinois and Wisconsin. Fourteen variable nucleotide
positions were identified (4 new and 10 previously reported). We identified 68
diplotypes comprised of 24 predicted haplotypes, with the most common diplotype
occurring in 123 individuals. Diplotypes that were found exclusively among
positive or negative animals were rare, each occurring in less than 1% of the
deer studied. Only one haplotype (C, odds ratio 0.240) and 2 diplotypes (AC and
BC, odds ratios of 0.161 and 0.108 respectively) has significant associations
with CWD resistance. Each contains mutations (one synonymous nucleotide 555C/T
and one nonsynonymous nucleotide 286G/A) at positions reported to be
significantly associated with reduced CWD susceptibility. Results suggest that
deer populations with higher frequencies of haplotype C or diplotypes AC and BC
might have a reduced risk for CWD infection – while populations with lower
frequencies may have higher risk for infection. Understanding the genetic basis
of CWD has improved our ability to assess herd susceptibility and direct
management efforts within CWD infected areas.
Adam L Brandt, Amy C Kelly, Michelle L Green, Paul Shelton, Jan
Novakofski, and Nohra E Mateus-Pinilla *Correspondence to: Jan Novakofski;
Email: jnova@illinois.edu Received September 21, 2015; Revised October 23, 2015;
Accepted October 23, 2015. Color versions of one or more of the figures in the
article can be found online atwww.tandfonline.com/kprn. This is an Open Access
article distributed under the terms of the Creative Commons
Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/),
which permits unrestricted non-commercial use, distribution, and reproduction in
any medium, provided the original work is properly cited. The moral rights of
the named author(s) have been asserted.
DISCUSSION
In this study, we find reduced susceptibility to CWD infection among
white-tailed deer with haplotype C (Table 2). We still observed individual deer
positive for CWD with this haplotype, demonstrating a reduced susceptibility
rather than a complete genetic resistance as is seen with other TSEs (e.g.,
scrapie36,37). This haplotype had 2 different polymorphisms, 1 synonymous and 1
non-synonymous, both reported to be associated with decreased infection; nt286A
(aa96S) and nt555T.10,26,29,30 Other haplotypes have similar mutations at nt286
and nt555 (e.g., haplotypes I, Q, and S); though, within the CWD infection area
these haplotypes are not found at all (haplotype Q), occur infrequently (f <
0.01, haplotypes I and S), or are found exclusively among positive deer
(haplotype I). A number of other haplotypes have the same mutations at either
nt286 or nt555; again most are absent (haplotypes H, V, W and X), infrequent (f
< 0.01, haplotypes N and P), or are found abundantly among positive deer
(haplotype B) in the CWD infection area (Table 2). Rarity of these haplotypes
prevents any meaningful association with changes in susceptibility (Table 2).
The effects of mutations at nt286 and nt555 alone or in concert are unclear as
other haplotypes with these polymorphisms occur infrequently and with varied
susceptibility. An even larger sampling may be necessary to resolve this
interaction.
Neither haplotypes with aa95H (nt285C) had a significantly reduced
susceptibility to CWD (Table 2). Some previous studies reported the occurrence
of this mutation among CWD negative deer only, which was interpreted as CWD
resistance.26,29 In this study and in the study by Kelly et al.10 the aa95H
mutation was found among deer positive for CWD; however, we find in a larger
sampling (ND240) the frequency of aa95H to be lower than that found by Kelly et
al.10 and not significantly associated with resistance. We cannot preclude the
importance of this mutation given that a significant difference in disease
susceptibility may be possible with an even larger sample size providing greater
statistical power (data not shown).
The presence of aa96S has been associated with slowed disease progression,
longer life span among captive deer,26,27 and does not appear to affect the rate
at which prions are shed from infected individuals.38 Additionally, CWD infected
mule deer have been found to excrete pathogenic prions while asymptomatic. 39
This contributes to concerns that wild deer with aa96S may be shedding
infectious prions into the environment for longer periods of time than deer
lacking the mutation, but are not symptomatic or detectable by
immunohistochemical procedures. On the other hand, studies using epidemiological
modeling suggest that deer with aa96S under certain conditions may have a
selective advantage for CWD resistance over those without.40 With our data, we
are unable to make accurate conclusions about detection, longevity, or increased
risks of exposure to infectious prions. Nonetheless, our results do corroborate
the importance of the polymorphism at G96S in reduced CWD susceptibility (Table
5).26,30
Kelly et al.10 found a negative correlation between the number of
nucleotide deviations from the PRNP consensus sequence and CWD infection. The
database derived consensus sequence reported is the same as the most common
haplotype (haplotype A) in this study (Table 1). Haplotype C has 2 deviations
from haplotype A; other haplotypes were found containing more deviations but
were exceedingly rare (Table 1). These haplotypes (namely haplotypes I, N, Q, S,
and X) were largely absent among CWD positive deer (only 2 positive deer were
found each with a single copy of haplotype I) and their combined frequency was
less than 1%. An increased number of polymorphisms may improve resistance to
CWD, but the large sample size of this study (ND703) suggests that haplotypes
with more than 2 nucleotide deviations are rare and would not be likely to have
an appreciable effect on resistance or susceptibility within the
population.
Examination of PRNP diplotypes revealed that individuals with at least one
copy of haplotype C (specifically AC and BC) were less likely to test positive
for CWD (Table 4). Other diplotypes containing at least one copy of haplotype C
(mutations at aa96S and nt555T) had a low frequency of occurrence (<1 41="" a="" account="" additional="" address="" age="" all="" always="" analyses="" and="" animals.="" animals="" any="" are="" area.="" area="" as="" association="" at="" attempted="" available="" average="" avoid="" background.29="" basis="" be="" been="" between="" bias.="" but="" by="" c="" cases="" circumstances="" conditions="" confounding="" control="" controlled="" could="" counties="" county="" cwd.="" cwd="" decreasing="" deer43-45="" deer="" design="" determining="" diplotypes="" disease="" distances="" div="" due="" examined="" experimental="" exposed="" factor="" factors="" family="" for="" found="" free="" frequency="" frequent="" from="" genetic="" geographic="" greater="" groups="" haplotype="" harvest.="" have="" herd="" home="" hunter="" i.e.="" ideal="" identified="" illinois="" immunity="" in="" increase="" increasing="" indication="" individually="" infected="" infection="" inheritance="" is="" less="" likelihood="" likely="" locations="" low="" management="" match="" matched-case="" may="" minimize="" more="" multiple="" nature="" negative="" nonetheless="" not="" obtainable="" of="" on="" one="" or="" origin="" originating="" other="" outside="" over="" paired-case="" paired="" perfectly="" play="" population-level="" positive="" possible="" potential="" prnp="" randomly="" range="" ranging="" relatedness="" relationship="" resistance="" restricted="" results="" role="" samples="" sampling="" selected="" sequence="" sex="" significant="" similar="" spurious="" statistical="" status="" strong="" studies="" study="" studying="" suggesting="" susceptibility.="" susceptibility="" than="" that="" the="" therefore="" these="" they="" this="" though="" through="" throughout="" time="" to="" under="" use="" vital="" was="" were="" when="" whitetailed="" with="" without="">
The PRNP gene is variable within all species with some mutations affecting
susceptibility to TSEs.46-48 Scrapie infection in sheep is the classic example
of genetic resistance to a prion disease, where individuals with 2 copies of
amino acid sequence V136, R154, Q171 are susceptible to scrapie, and those with
2 copies of the sequence A136, R154, R171 are resistant. 36,37 Changes in the
protein coding sequence have been shown to affect the ability of pathogenic
prions to convert normal prion proteins31; accordingly, many studies have
heavily examined the amino acid variations associated with CWD. Synonymous or
silent mutations are often overlooked, but may have a greater effect on protein
expression and conformation than expected.49-53Other studies have found
significant associations between individual synonymous mutations and CWD
susceptibility. 10,28 The specific mechanisms involved between nucleotide
variation (specifically synonymous mutations) and CWD are not known, but the
rate at which PrPC conformations that are more favorable to PrPSC conversion are
produced may be slowed by the presence of certain synonymous mutations.51 Due to
the low frequency of haplotypes with similar mutations as haplotype C, we cannot
accurately conclude whether or not the specific combination of mutations or any
one mutation alone is responsible for reduced CWD susceptibility. Nevertheless,
haplotype and diplotype analyses provide more insight in gene-disease
association than those restricted to alleles and genotypes54 which are unable to
detect additive effects.
A solid understanding of the genetics of CWD in white-tailed deer is vital
to improve management of CWD on the landscape. Most TSEs are found in domestic
or captive animals where management of infected individuals is feasible. For
example, scrapie infected flocks can be handled through a process generally
involving genetic testing, removal and destruction of infected or suspect
animals, followed by decontamination of facilities and equipment.55 Containment
of free ranging deer in wild populations potentially infected with CWD and
decontamination of the environment is not reasonably possible. The long term
effects of CWD are not yet known but it is conceivable that an unmanaged
infected population would be gradually extirpated as the disease progresses
56,57 or at least reduced to low densities with high disease prevalence.58,59
Either outcome would have severe ecological effects (e.g., deer play a major
role in affecting plant communities60 and as a prey source61,62) as well as
negative economic impacts to hunting. Overall disease prevalence has remained at
relatively low levels in Illinois compared to Wisconsin. 11 It is important to
note that at the time of sampling, CWD had been found in 6 Illinois counties and
has since been detected in 14.9 Complete eradication of CWD among free ranging
white-tailed deer may not be possible; however, an active containment effort in
Illinois appears to have prevented significant increases in prevalence.9,11,12
Further examination of PRNP haplotype and diplotype frequencies across northern
Illinois and southern Wisconsin in conjunction with population structure and
movement45,63,64 will be useful in identifying localities with greater or
reduced susceptibility risk. Effectiveness of CWD containment efforts can be
aided through genetic testing and redirecting management resources.
snip...
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Comparison of two US sheep scrapie isolates supports identification
as separate strains
Authors
item Moore, Sarah - item Smith, Jodi item West Greenlee, Mary - item
Nicholson, Eric item Richt, Juergen item Greenlee, Justin
Submitted to: Veterinary Pathology Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 22, 2015 Publication Date: N/A
Interpretive Summary: Scrapie is a fatal disease of sheep and goats that
causes damaging changes in the brain. The infectious agent is an abnormal
protein called a prion that has misfolded from its normal state. Whether or not
a sheep will get scrapie is determined primarily by their genetics. Furthermore,
different scrapie strains exist that may result in a different expression of
disease such as shorter incubation periods, unusual clinical signs, or unique
patterns of lesions within the brain. This study evaluated two U.S. scrapie
isolates in groups of sheep with varying susceptibilities to scrapie. Our data
indicates that there are differences in incubation periods, sheep genotype
susceptibilities, and lesion profiles that support designating these scrapie
isolates as unique strains. The identification of a new scrapie strain in the
United States means that control measures, methods of decontamination, and the
potential for transmission to other species may need to be reevaluated. This
information is useful to sheep farmers and breeders that are selectively
breeding animals with genotypes resistant to the most prevalent strain of
scrapie and could impact future regulations for the control of scrapie in the
United States. Technical Abstract: Scrapie is a naturally occurring
transmissible spongiform encephalopathy (TSE) of sheep and goats. There are
different strains of sheep scrapie that are associated with unique molecular,
transmission, and phenotype characteristics, but very little is known about the
potential presence of scrapie strains within sheep in the US. Scrapie strain and
PRNP genotype could both affect susceptibility, potential for transmission,
incubation period, and control measures required for eliminating scrapie from a
flock. Here we evaluate two US scrapie isolates, No. 13-7 and x124, after
intranasal inoculation to compare clinical signs, incubation periods (IP),
spongiform lesions, and patterns of PrPSc deposition in sheep with
scrapie-susceptible PRNP genotypes (QQ171). After inoculation with x124,
susceptibility and IP were associated with valine at codon 136 (V136) of the
prion protein: VV136 had short IPs (6.9 months), AV136 sheep were 11.9 months,
and AA136 sheep did not develop scrapie. All No.13-7 inoculated sheep developed
scrapie with IP’s of 20.1 months for AA136 sheep, 22.8 months for AV136 sheep,
and 26.7 months for VV136 sheep. Patterns of immunoreactivity in the brain were
influenced by challenge isolate and host genotype. Differences in PrPSc profiles
versus isolate were most striking when examining brains from sheep with the
VV136 genotype. In summary, intranasal inoculation with isolates x124 and No.
13-7 resulted in differences in IP, sheep genotype susceptibility, and PrPSc
profile that support designation as separate strains.
Last Modified: 6/6/2016
PRION 2016 CONFERENCE TOKYO
IL-13 Transmission of prions to non human-primates: Implications for human
populations
Jean-Philippe Deslys, Emmanuel E. Comoy
CEW, Institute of Emerging Diseases and Innovative Therapies (iMETI),
Division of Prions and Related Diseases (SEPIA), Fontenay-aux-Roses, France
Prion diseases 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 prion
disease might be zoonotic under appropriate conditions. Contrarily, in the
absence of obvious (epidemiological or experimental) elements supporting a
transmission or genetic predispositions, prion diseases, like the other
proteinopathies, are reputed to occur spontaneously (atypical animal prion
strains, sporadic CJD summing 80 % of human prion cases).
Non-human primate models provided the first evidences supporting the
transmissibility of human prion strains and the zoonotic potential of BSE. Among
them, cynomolgus macaques brought major information for BSE risk assessment for
human health1, according to their phylogenetic proximity to humans and extended
lifetime. We used this model to assess the risk of primary (oral) and secondary
(transfusional) risk of BSE, and also the zoonotic potential of other animal
prion diseases 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' . longer incubation than BSE2. Scrapie, as recently evoked in
humanized mice3, is the third potentially zoonotic prion disease (with BSE and
L-type BSE4), thus questioning the origin of human sporadic cases. We also
observed hidden prions transmitted by blood transfusion in primate which escape
to the classical diagnostic methods and extend the field of healthy carriers. We
will present an updated panorama of our different long-term transmission studies
and discuss the implications on risk assessment of animal prion diseases for
human health and of the status of healthy carrier5.
1. Chen, C. C. & Wang, Y. H. Estimation of the Exposure of the UK
Population to the Bovine Spongiform Encephalopathy Agent through Dietary Intake
During the Period 1980 to 1996. PLoS One 9, e94020 (2014).
2. Comoy, E. E. et al. Transmission of scrapie prions to primate after an
extended silent incubation period. Sci Rep 5, 11573 (2015).
3. Cassard, H. et al. Evidence for zoonotic potential of ovine scrapie
prions. Nat Commun 5, 5821-5830 (2014).
4. Comoy, E. E. et al. Atypical BSE (BASE) transmitted from asymptomatic
aging cattle to a primate. PLoS One 3, e3017 (2008).
5. Gill O. N. et al. Prevalent abnormal prion protein in human appendixes
after bovine spongiform encephalopathy epizootic: large scale survey. BMJ. 347,
f5675 (2013).
Curriculum Vitae
Dr. Deslys co-authored more than one hundred publications in international
scientific journals on main aspects of applied prion research (diagnostic,
decontamination techniques, risk assessment, and therapeutic approaches in
different experimental models) and on underlying pathological mechanisms. He
studied the genetic of the first cases of iatrogenic CJD in France. His work has
led to several patents including the BSE (Bovine Spongiform Encephalopathy)
diagnostic test most widely used worldwide. He also wrote a book on mad cow
disease which can be downloaded here for free (http://www.neuroprion.org/pdf_docs/documentation/madcow_deslys.pdf).
His research group is Associate Laboratory to National Reference Laboratory for
CJD in France and has high security level microbiological installations
(NeuroPrion research platform) with different experimental models (mouse,
hamster, macaque). The primate model of BSE developed by his group with
cynomolgus macaques turned out to mimick remarkably well the human situation and
allows to assess the primary (oral) and secondary (transfusional) risks linked
to animal and human prions even after very long silent incubation periods. For
several years, his interest has extended to the connections between PrP and
Alzheimer and the prion mechanisms underlying neurodegenerative diseases. He is
coordinating the NeuroPrion international association (initially european
network of excellence now open to all prion researchers).
- 59-
P-088 Transmission of experimental CH1641-like scrapie to bovine PrP
overexpression mice
Kohtaro Miyazawa1, Kentaro Masujin1, Hiroyuki Okada1, Yuichi Matsuura1,
Takashi Yokoyama2
1Influenza and Prion Disease Research Center, National Institute of Animal
Health, NARO, Japan; 2Department of Planning and General Administration,
National Institute of Animal Health, NARO
Introduction: Scrapie is a prion disease in sheep and goats. CH1641-lke
scrapie is characterized by a lower molecular mass of the unglycosylated form of
abnormal prion protein (PrpSc) compared to that of classical scrapie. It is
worthy of attention because of the biochemical similarities of the Prpsc from
CH1641-like and BSE affected sheep. We have reported that experimental
CH1641-like scrapie is transmissible to bovine PrP overexpression (TgBoPrP) mice
(Yokoyama et al. 2010). We report here the further details of this transmission
study and compare the biological and biochemical properties to those of
classical scrapie affected TgBoPrP mice.
Methods: The details of sheep brain homogenates used in this study are
described in our previous report (Yokoyama et al. 2010). TgBoPrP mice were
intracerebrally inoculated with a 10% brain homogenate of each scrapie strain.
The brains of mice were subjected to histopathological and biochemical analyses.
Results: Prpsc banding pattern of CH1641-like scrapie affected TgBoPrP mice
was similar to that of classical scrapie affected mice. Mean survival period of
CH1641-like scrapie affected TgBoPrP mice was 170 days at the 3rd passage and it
was significantly shorter than that of classical scrapie affected mice (439
days). Lesion profiles and Prpsc distributions in the brains also differed
between CH1641-like and classical scrapie affected mice.
Conclusion: We succeeded in stable transmission of CH1641-like scrapie to
TgBoPrP mice. Our transmission study demonstrates that CH 1641-like scrapie is
likely to be more virulent than classical scrapie in cattle.
WS-02
Scrapie in swine: A diagnostic challenge
Justin J Greenlee1, Robert A Kunkle1, Jodi D Smith1, Heather W. Greenlee2
1National Animal Disease Center, US Dept. of Agriculture, Agricultural
Research Service, United States; 2Iowa State University College of Veterinary
Medicine
A naturally occurring prion disease has not been recognized in swine, but
the agent of bovine spongiform encephalopathy does transmit to swine by
experimental routes. Swine are thought to have a robust species barrier when
exposed to the naturally occurring prion diseases of other species, but the
susceptibility of swine to the agent of sheep scrapie has not been thoroughly
tested.
Since swine can be fed rations containing ruminant derived components in
the United States and many other countries, we conducted this experiment to test
the susceptibility of swine to U.S. scrapie isolates by intracranial and oral
inoculation. Scrapie inoculum was a pooled 10% (w/v) homogenate derived from the
brains of clinically ill sheep from the 4th passage of a serial passage study of
the U.S scrapie agent (No. 13-7) through susceptible sheep that were homozygous
ARQ at prion protein residues 136, 154, and 171, respectively. Pigs were
inoculated intracranially (n=19) with a single 0.75 ml dose or orally (n=24)
with 15 ml repeated on 4 consecutive days. Necropsies were done on a subset of
animals at approximately six months post inoculation (PI), at the time the pigs
were expected to reach market weight. Remaining pigs were maintained and
monitored for clinical signs of TSE until study termination at 80 months PI or
when removed due to intercurrent disease (primarily lameness). Brain samples
were examined by immunohistochemistry (IHC), western blot (WB), and
enzyme-linked immunosorbent assay (ELISA). Brain tissue from a subset of pigs in
each inoculation group was used for bioassay in mice expressing porcine PRNP.
At six-months PI, no evidence of scrapie infection was noted by any
diagnostic method. However, at 51 months of incubation or greater, 5 animals
were positive by one or more methods: IHC (n=4), WB (n=3), or ELISA (n=5).
Interestingly, positive bioassay results were obtained from all inoculated
groups (oral and intracranial; market weight and end of study).
Swine inoculated with the agent of scrapie by the intracranial and oral
routes do not accumulate abnormal prion protein (PrPSc) to a level detectable by
IHC or WB by the time they reach typical market age and weight. However, strong
support for the fact that swine are potential hosts for the agent of scrapie
comes from positive bioassay from both intracranially and orally inoculated pigs
and multiple diagnostic methods demonstrating abnormal prion protein in
intracranially inoculated pigs with long incubation times.
Curriculum Vitae
Dr. Greenlee is Research Veterinary Medical Officer in the Virus and Prion
Research Unit at the National Animal Disease Center, US Department of
Agriculture, Agricultural Research Service. He applies his specialty in
veterinary anatomic pathology to focused research on the intra- and interspecies
transmission of prion diseases in livestock and the development of antemortem
diagnostic assays for prion diseases. In addition, knockout and transgenic mouse
models are used to complement ongoing experiments in livestock species. Dr.
Greenlee has publications in a number of topic areas including prion agent
decontamination, effects of PRNP genotype on susceptibility to the agent of
sheep scrapie, characterization of US scrapie strains, transmission of chronic
wasting disease to cervids and cattle, features of H-BSE associated with the
E211 K polymorphism, and the development of retinal assessment for antemortem
screening for prion diseases in sheep and cattle. Dr. Greenlee obtained his DVM
degree and completed the PhD/residency program in Veterinary Pathology at Iowa
State University. He is a Diplomate of the American College of Veterinary
Pathologists.
Wednesday, May 25, 2016
USDA APHIS National Scrapie TSE Prion Eradication Program April 2016
Monthly Report Prion 2016 Tokyo Update
Saturday, April 23, 2016
Prion 2016 Tokyo Update
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Scrapie Sample Submission
Submit Samples to Test for Genetic Susceptibility to Scrapie
Genetic testing does NOT tell you whether or not a sheep is infected with
scrapie
Susceptibility to infection in sheep has been shown to vary according to
sheep genetics and breed. For classical scrapie in sheep, the codons at
positions 136 and 171 in the gene that codes for the amino acids in the prion
protein (PrP) have been highly associated with scrapie susceptibility and
resistance. At this time, no genes have been identified for goats that confer
significant resistance. Therefore, all goats must be assumed to be
susceptible.
The Genetics of Scrapie Susceptibility Information Sheet
Scrapie epidemic in a fully PrP-genotyped sheep flock
Authors: M. Baylis1, W. Goldmann2, F. Houston1, D. Cairns2, A. Chong2, A.
Ross2, A. Smith2, N. Hunter2, A. R. McLean3 VIEW AFFILIATIONS
Author for correspondence: Matthew Baylis. Fax +44 1635 577237. e-mail
matthew.baylis@bbsrc.ac.uk J. Gen. Virol., November 2002 83: 2907-2914, doi:
10.1099/0022-1317-83-11-2907 Subject: Other Agents Received: 26/03/2002
Accepted: 09/07/2002 Published Online: 01/11/2002
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Abstract
Fulltext Figs (1) References (17) Cited By (33) Supplementary Material (0)
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In scrapie-affected sheep flocks, host PrP genotype plays a vital role in
determining which sheep will succumb to scrapie and the incubation period.
Consequently, within-flock scrapie dynamics is best understood within the
context of the genotype profile of the flock. Here we describe a 17 month
epidemic of scrapie in a commercially farmed flock of 230 genotyped Texel sheep.
At the start of the study, 70% of the sheep were of three genotypes only:
ARR/ARQ, ARH/ARQ and ARQ/ARQ. Only 15% of sheep encoded the disease-associated
VRQ allele and only a single sheep (0·4%) was of the most susceptible VRQ/VRQ
genotype. For susceptible genotypes there was a marked deficit (P<0 13="" 17="" 18="" 2="" 3="" 4="" 55="" 86="" a="" ages="" analysis="" and="" animals="" arq="" as="" associated="" at="" be="" between="" but="" by="" cases="" causes="" cohorts="" confirmed="" death="" defined="" difference="" disease:="" div="" dying="" effect="" ensuing="" farm.="" for="" found="" genotype="" group="" had="" highly="" implying="" in="" known="" later="" median="" middle-="" months="" mortality="" negative="" no="" not="" occurred="" of="" older-age="" older="" on="" or="" positive="" previously.="" prp="" rates="" respectively.="" revealed="" risk="" scrapie="" seven="" sheep.="" sheep="" significant="" six="" some="" submission="" survival="" survivorship="" susceptible="" suspect="" that="" the="" there="" three="" to="" two="" unknown="" vrq="" was="" were="" with="" years="">
***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.***
Tuesday, July 12, 2016
Chronic Wasting Disease CWD, Scrapie, Bovine Spongiform Encephalopathy BSE,
TSE, Prion Zoonosis Science History
see history of NIH may destroy human brain collection
Friday, February 05, 2016
*** Report of the Committee on Wildlife Diseases FY2015 CWD TSE PRION
Detections in Farmed Cervids and Wild ***
Sunday, July 17, 2016
*** CHRONIC WASTING DISEASE CWD TSE PRION GLOBAL REPORT UPDATE JULY 17 2016
***
***at present, no cervid PrP allele conferring absolute resistance to prion
infection has been identified.
P-145 Estimating chronic wasting disease resistance in cervids using real
time quaking- induced conversion
Nicholas J Haley1, Rachel Rielinqer2, Kristen A Davenport3, W. David
Walter4, Katherine I O'Rourke5, Gordon Mitchell6, Juergen A Richt2
1 Department of Microbiology and Immunology, Midwestern University, United
States; 2Department of Diagnostic Medicine and Pathobiology, Kansas State
University; 3Prion Research Center; Colorado State University; 4U.S. Geological
Survey, Pennsylvania Cooperative Fish and Wildlife Research Unit; 5Agricultural
Research Service, United States Department of Agriculture; 6Canadian Food
Inspection Agency, National and OlE Reference Laboratory for Scrapie and CWO
In mammalian species, the susceptibility to prion diseases is affected, in
part, by the sequence of the host's prion protein (PrP). In sheep, a gradation
from scrapie susceptible to resistant has been established both in vivo and in
vitro based on the amino acids present at PrP positions 136, 154, and 171, which
has led to global breeding programs to reduce the prevalence of scrapie in
domestic sheep. In cervids, resistance is commonly characterized as a delayed
progression of chronic wasting disease (CWD); at present, no cervid PrP allele
conferring absolute resistance to prion infection has been identified. To model
the susceptibility of various naturally-occurring and hypothetical cervid PrP
alleles in vitro, we compared the amplification rates and efficiency of various
CWD isolates in recombinant PrPC using real time quaking-induced conversion. We
hypothesized that amplification metrics of these isolates in cervid PrP
substrates would correlate to in vivo susceptibility - allowing susceptibility
prediction for alleles found at 10 frequency in nature, and that there would be
an additive effect of multiple resistant codons in hypothetical alleles. Our
studies demonstrate that in vitro amplification metrics predict in vivo
susceptibility, and that alleles with multiple codons, each influencing
resistance independently, do not necessarily contribute additively to
resistance. Importantly, we found that the white-tailed deer 226K substrate
exhibited the slowest amplification rate among those evaluated, suggesting that
further investigation of this allele and its resistance in vivo are warranted to
determine if absolute resistance to CWD is possible.
***at present, no cervid PrP allele conferring absolute resistance to prion
infection has been identified.
PRION 2016 CONFERENCE TOKYO
Friday, August 26, 2016
Journal Journal of Toxicology and Environmental Health, Part A Volume 79,
2016 - Issue 16-17 Prion Research in Perspective IV CANADA BSE CWD SCRAPIE CJD
TSE Prion Disease
Monday, August 22, 2016
CREUTZFELDT JAKOB DISEASE USA 2015 SPORADIC CJD TOTAL FIGURES REACHES
HIGHEST ANNUAL COUNT TO DATE AT 239 CONFIRMED CASES
to be continued...
Terry S. Singeltary Sr, Bacliff, Texas USA 77518 flounder9@verizon.net
posted by Terry S. Singeltary Sr. at
4:16 PM
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