Minnesota Tests confirm 2 CWD-positive deer near Lanesboro
Tests confirm 2 CWD-positive deer near Lanesboro
November 22, 2016
DNR initiates disease response plan; offers hunters information on field dressing
Test results show two deer harvested by hunters in southeastern Minnesota were infected with Chronic Wasting Disease, according to the Department of Natural Resources.
One deer has been confirmed as CWD-positive. Confirmation of the second is expected later this week. The deer, both male, were killed near Lanesboro in Fillmore County during the first firearms deer season.
The two deer were harvested approximately 1 mile apart. These are the only deer to test positive from 2,493 samples collected Nov. 5-13. Results are still pending from 373 additional test samples collected during the opening three days of the second firearms season, Nov. 19-21.
CWD is a fatal brain disease to deer, elk and moose but is not known to affect human health. While it is found in deer in states bordering southeastern Minnesota, it was only found in a single other wild deer in Minnesota in 2010.
The DNR discovered the disease when sampling hunter-killed deer this fall in southeastern Minnesota as part of its CWD surveillance program. Dr. Lou Cornicelli, DNR wildlife research manager, said hunter and landowner cooperation on disease surveillance is the key to keeping the state’s deer herd healthy.
“We were proactively looking for the disease, a proven strategy that allows us to manage CWD by finding it early, reacting quickly and aggressively to control it and hopefully eliminating its spread,” he said.
It is unknown how the two CWD-positive deer, which were harvested 4 miles west of Lanesboro in deer permit area 348, contracted the disease, Cornicelli said.
“We want to thank hunters who have brought their deer to our check stations for sampling,” he said. “While finding CWD-positive deer is disappointing, we plan to work with hunters, landowners and other organizations to protect the state’s deer herd and provide hunters the opportunity to pass on their deer hunting traditions.”
These are the first wild deer found to have CWD since a deer harvested in fall 2010 near Pine Island tested positive. It was found during a successful disease control effort prompted by the detection in 2009 of CWD on a domestic elk farm. The DNR, landowners and hunters worked together to sample more than 4,000 deer in the Pine Island area from 2011 to 2013, and no additional infected deer were found.
The National Centers for Disease Control and Prevention as well as the World Health Organization have found no scientific evidence that the disease presents a health risk to humans who come in contact with infected animals or eat infected meat. Still, the CDC advises against eating meat from animals known to have CWD.
With the muzzleloader deer season stretching into mid-December and archery season open through Saturday, Dec. 31, hunters should take these recommended precautions when harvesting deer:
- Do not shoot, handle or consume any animal that is acting abnormally or appears to be sick.
- Wear latex or rubber gloves when field dressing your deer.
- Bone out the meat from your animal. Don’t saw through bone, and avoid cutting through the brain or spinal cord (backbone).
- Minimize the handling of brain and spinal tissues.
- Wash hands and instruments thoroughly after field dressing is completed.
- Avoid consuming brain, spinal cord, eyes, spleen, tonsils and lymph nodes of harvested animals. Normal field dressing coupled with boning out a carcass will remove most, if not all, of these body parts. Cutting away all fatty tissue will remove remaining lymph nodes.
- If you have your deer or elk commercially processed, request that your animal is processed individually, without meat from other animals being added to meat from your animal.
The DNR already has begun implementing the state’s CWD response plan. Three additional CWD testing stations were opened in Fillmore County last weekend and electronic registration was turned off in two additional deer permit areas.
“We’ll wait until the late 3B firearms season concludes this weekend and analyze test results from all the samples we collect from hunters,” Cornicelli said. “That will provide a better indication of the potential prevalence and distribution of CWD so we can determine boundaries for a disease management zone and the actions we’ll take to manage the disease and limit its spread.”
The DNR began CWD testing in southeastern Minnesota again this fall in response to expanded CWD infections in Wisconsin, Illinois, and northeast Iowa, as well as new and growing infections in Arkansas and Missouri. The increasing prevalence and geographic spread of the disease also prompted an expanded carcass import restriction that does not allow whole carcasses of deer, elk, moose and caribou to be brought into Minnesota.
The discovery of CWD in wild deer reinforces the need for the vigilance that disease surveillance and carcass import restrictions provide. Although inconvenient, hunter cooperation with these measures help protect Minnesota’s deer herd.
“Working with landowners and hunters to better protect deer from disease is vital to Minnesota’s hunting tradition and economy and most important, the deer population in general,” Cornicelli said. “In states where CWD has become well-established in wild deer, efforts at elimination have been unsuccessful. Research has shown that if established, the disease will reduce deer populations in the long term. Nobody wants this to happen in Minnesota.”
Because much of southeastern Minnesota’s land is privately owned, the DNR will work with landowners when collecting additional samples to assess disease distribution and reduce the potential for CWD to spread. Sample collection could take the form of a late winter deer hunt, landowner shooting permits and sharpshooting in conjunction with cooperating landowners who provide permission.
“Those decisions will be made after surveillance is done this hunting season,” Cornicelli said.
The DNR has been on the lookout for CWD since 2002, when the disease first was detected at a domestic elk farm in central Minnesota. In recent years it has put additional focus on southeastern Minnesota; the region abuts Wisconsin and northeastern Iowa. Wisconsin has 43 counties affected by CWD and the disease has been detected in northeastern Iowa’s Allamakee County.
Since 2002, the DNR has tested approximately 50,000 deer, elk, and moose for CWD.
CWD is transmitted primarily from animal-to-animal by infectious agents in feces, urine or saliva. The disease also can persist for a long time in the environment and may be contracted from contaminated soil. The movement of live animals is one of the greatest risk factors in spreading the disease to new areas.
For more information, including maps of CWD surveillance areas, frequently asked questions, hunter information and venison processing, visit the DNR’s CWD homepage. Landowners, hunters and citizens can stay engaged and informed by visiting the CWD page and signing up to receive an email automatically when new information on CWD management becomes available.
http://news.dnr.state.mn.us/2016/11/22/tests-confirm-2-cwd-positive-deer-near-lanesboro/
some history on Minnesota and CWD and then the latest…
Thursday, September 19, 2013
Chronic Wasting Disease CWD surveillance, deer feeding ban continues in southeastern Minnesota
http://chronic-wasting-disease.blogspot.com/2013/09/chronic-wasting-disease-cwd.html
Friday, September 28, 2012
Stray elk renews concerns about deer farm security Minnesota
Friday, May 25, 2012
Chronic Wasting Disease CWD found in a farmed red deer from
Ramsey County Minnesota
Saturday, March 17, 2012
Minnesota CWD DNR, Can chronic wasting disease jump from
deer to humans? yes, maybe some day YOUTUBE
Tuesday, January 25, 2011
Minnesota, National Veterinary Services Laboratory in Ames,
Iowa, has confirmed CWD case near Pine Island
Friday, January 21, 2011
MINNESOTA HIGHLY SUSPECT CWD POSITIVE WILD DEER FOUND NEAR
PINE ISLAND
Saturday, October 31, 2009
Elk from Olmsted County herd depopulated to control CWD
Three additional elk from the 558-head herd tested positive
Tuesday, January 27, 2009
Chronic Wasting Disease found in a farmed elk from Olmsted
County ST. PAUL, Minn.
CHRONIC WASTING DISEASE UPDATE September 6, 2002
Minnesota has announced the finding of CWD in a captive elk
in Aitkin County. The animal was a five-year-old male. It had been purchased
from a captive facility in Stearns County in August of 2000. The herd where the
elk was found has been placed under quarantine as has two additional facilities
where the infected elk had resided prior to it coming to the farm in Aitkin
County. Minnesota DNR officials will test wild deer in the area to determine if
there is any sign of CWD in the free-ranging population. This is the first case
of CWD in either captive or freeranging cervids in Minnesota. Several more
states have passed bans on the importation of deer and elk carcasses from
states where CWD has been found in wild animals. Previously the states of Colorado,
Illinois and Iowa and the province of Manitoba had passed such bans. The states
of Vermont, Oregon and Missouri have enacted similar bans. Numerous states have
issue voluntary advisories to their out-of-state hunters encouraging them not
to bring the carcass or carcass parts of deer and elk into their state. The
bans do permit the importation of boned out meat, hides or cape with no meat
attached, clean skull cap with antler attached, finished taxidermy heads or the
ivories of elk. The state of Georgia has recently banned the importation of
live cervids into that state also. Some citizens of Colorado have formed a new
political action group called Colorado Wildlife Defense (just happens that the
acronym is CWD). The stated goal of this group are; Elimination of big game
diseases, especially CWD; promotion of healthy wildlife habitat; promotion of
scientifically sound wildlife research; promotion of a discussion of the ethics
of hunting and wildlife management; education of the hunting and non hunting
public. Their action plan calls for; requiring double fencing of all game farms
at owners expense; all game farmers provide annual proof of bonding; prohibit
new licenses for deer and elk farms; prohibit expansion in acreage of existing
game farms; prohibit the transfer of game farm licenses; prohibit charging for
hunting behind high wire; prohibit blocking of traditional migratory paths by
high fences; requiring game farms to maintain environmental controls and
prohibit the escape of contaminated water or soil; requiring immediate
reporting of missing deer or elk from game farms; and requiring all game farm
deer and elk to be tested for brucellosis and TB. Wisconsin has announced that
7 more free-ranging deer have tested positive for CWD. They have expanded their
eradication zone by an additional 15 square miles to cover these findings. The
total number of free-ranging CWD positive in Wisconsin is now 31 white-tail
deer.
In 2000, a elk farmer in Wisconsin received elk from a
CWD exposed herd in Colorado. At that time, the farmer advised the Wisconsin
Department of Agriculture that both animals from the exposed herd in Colorado
were dead. He has now advised Wisconsin Ag. that he was mistaken and that one
of the animals is still alive in his herd. The second draft of the
implementation documents for the National CWD Plan was distributed to committee
members and others on Friday, August 30. The final documents are due to APHIS
and USFWS on Friday, September 13. The herd of captive elk in Oklahoma that had
been exposed to CWD will be destroyed this week. This herd had an elk test
positive for CWD in 1997 but the depopulation of the herd was not agreed to by
the owners and federal representatives until this week. Since the discovery of
CWD in the herd, the remaining animals have been under quarantine, however, in
the meantime the herd has dropped from 150 animals to 74. Due to a lack of
communication, not all of the 76 animals that died in the interim were tested
for CWD. All remaining animals will be tested but the true degree of infection
rate of the herd will never be known.
The owners of the facility will not be permitted to restock
the area with cervids for a period of five years. A New York based
organization, BioTech Research Fund I LLC has committed a $1 million line of
credit to fund commercialization of tests for brain-wasting disorders and
production of various vaccines to Gene-Thera of Wheat Ridge, Colorado.
Gene-Thera has spent three years developing new ways not only to diagnose CWD,
but create vaccines for mad cow disease, E. coli contaminants and
foot-and-mouth disease. Its tests for CWD have been successful in more than 100
samples from Colorado and Wisconsin according to company officials. Gene-Thera
plans to license and market some o fits disease test kits by the end of the
year, then begin volume distribution by mid-2003. The abstracts of the
presentations from the CWD Conference in Denver August 6 and 7 have been posted
on the Colorado Division of Wildlife web site. You will need adobe acrobat reader
to read them.
The Division web site is: http://wildlife.state.co.us/CWD/Symposium_booklet.pdf
Minnesota: Second case in a game farmed elk discovered
in Stearns Co.
This is a trace forward from the previously affected game
farm in Aitkins Co. An additional game farm in Benton Co is under quarantine.
snip...
Supporting Documents: Colorado: CWD-Exposed Elk Used in 1990
Study- Wildlife officials call W. Slope move a mistake Date: January 17, 2003
Source: Denver Post Contacts: Theo Stein Environment Writer
The Colorado Division of Wildlife knowingly used a herd of
captive elk exposed to chronic wasting disease in a grazing study on the
Western Slope in January 1990, possibly introducing the disease to the elk-rich
area. "It was a bad call," said Jeff Ver Steeg, the division's top
game manager. "I can't deny it." About 150 wild elk were allowed to
graze in the same pens near Maybell after the research herd was removed and may
have picked up the abnormal protein that causes the disease from the feces and
urine left by the captive elk. While the Division of Wildlife has expressed
concern before that its animals might have helped spread CWD, this is the first
time the agency has acknowledged it knowingly moved elk exposed to CWD deep
into an area where the disease was not known to already exist. Studies that
could help determine the source of CWD on the Western Slope are incomplete, and
officials say what data that do exist are so new and so spotty they may not
provide all the answers. So far, it appears that less than 1 percent of deer
and elk in the area are infected, compared with as much as 15 to 20 percent in
hotspots in northeastern Colorado. But as wildlife officials grapple with CWD's
appearance in northwestern Colorado, officials now admit the decision to
continue the grazing study over the objections of some biologists was an error.
At the time, biologists wanted to see whether elk grazing on winter range depleted
forage that ranchers wanted for fattening cattle in spring. "I think in
hindsight a lot of good people probably did some dumb things, myself
included," said Bruce Gill, a retired wildlife manager who oversaw
research efforts and remembers the debate over the project. "Had we known
CWD would explode into such a potentially volatile ecologic and economic issue,
we wouldn't have done it." Elk ranchers, who have been blamed for
exporting the disease from its stronghold on the Colorado and Wyoming plains to
seven states and two Canadian provinces, say the agency's belated disclosure
smacks of a coverup. "It's pure negligence," said Jerry Perkins, a
Delta banker and rancher who is now demanding a legislative inquiry. "If
I'd have moved animals I knew to be infected around like that, I'd be in
jail." Grand Junction veterinarian and sportsman Dick Steele said he
faults the agency for not disclosing information about CWD-exposed research
animals before October, when information was posted on the Division of Wildlife
website. "This went way beyond poor judgment," he said. "My main
concern is that this has been hidden for the last 12 years. It would have been
real important to our decision-making process on how to deal with CWD."
While the Maybell information is new, Perkins and other ranchers have long
suspected Division of Wildlife research facilities near Meeker and Kremmling,
which temporarily housed mule deer kept in heavily infected pens at the Fort
Collins facility, have leaked CWD to the wild. Fear of an outbreak led the
agency to sample 450 deer around the Meeker and Kremmling facilities. None
tested positive, but the sample size was only large enough to detect cases if
the infection rate was greater than 1 percent. This fall, tests on 23,000 deer
and elk submitted by hunters statewide have revealed 48 CWD cases north of
Interstate 70 and west of the Continental Divide. Biologists believe the
infection rate in that area, which includes the Maybell, Meeker and Kremmling
sites, is still well below 1 percent. But CWD has never been contained in a
wild population, so experts fear the problem will grow worse.
The Division of Wildlife says it will be months before
a statistical analysis of the fall's sampling results can be completed, an
exercise that may shed light on the disease's origin on the Western Slope.
"We're just not going to speculate at this point," said Ver Steeg of
the possible Maybell connection. "This is one possibility, but certainly
not the only possibility." Some biologists think a defunct elk ranch near
Pagoda, which had dozens of unexplained deaths in the mid-'90s, is another, a
suggestion Perkins rejects. "It may be inconclusive to them," said
Perkins. "It isn't inconclusive to us."
To date, 19 CWD-positive animals have been found on
six Wisconsin farms. All have been white-tailed deer except for one elk
imported from a Minnesota herd later found to be infected. More than 8,000
farm-raised deer and elk have been tested in Wisconsin, and about 540 herds are
enrolled in the CWD monitoring program.
CWD disease detected on Lac qui Parle County cervid
farm southwestern Minnesota (2006-03-15)
Date: March 15, 2006 at 12:36 pm PST
Chronic wasting disease detected on Lac qui Parle
County cervid farm (2006-03-15) The Board of Animal Health announced today that
chronic wasting disease (CWD) has been detected in one domestic white-tailed
deer on a cervid farm in Lac qui Parle County, which is located in southwestern
Minnesota.
Immediately, DNR officials will conduct a local deer
survey to determine the number of wild deer in the area. It is expected that
not many deer will be found because the area is highly agricultural, with
little deer habitat surrounding the farm. DNR will conduct opportunistic
sampling of deer, like road kills, in the immediate area now and will conduct
intensive hunter-harvested surveillance during the 2006 firearm deer season.
Although this positive animal is a captive deer, DNR
has conducted surveillance for CWD in wild deer in the area. The farm is
located near the northern boundary of deer permit area 447, where wild deer
surveillance for CWD last occurred in 2003.
Lou Cornicelli, DNR big game program coordinator,
said, "In 2003, we conducted wild deer CWD surveillance in adjoining
permit areas 433, 446 and 447. In total, we collected 392 samples from those
permit areas during the regular firearm deer season and CWD was not
detected."
The sampling of wild deer was designed statistically
to have a 95 percent confidence of detecting a 1 percent infection rate,
according to Mike DonCarlos, DNR wildlife programs manager.
"This situation is very similar to the positive
elk farm discovered in Stearns County in 2003, which followed the first
discovery of CWD in an Aitkin County elk farm," DonCarlos said. “The DNR
response will be similar to the Stearns County action and will include an
initial assessment of wild deer populations in the area and development of a
surveillance program for next fall."
From 2002 to 2004, DNR staff collected nearly 28,000
CWD samples statewide and no disease found in the wild herd.
"The intensive surveillance conducted in 2003
indicated CWD was not present in wild deer," Cornicelli said. “In
addition, all indications are that this positive captive deer has not contacted
any wild deer, but we will conduct additional surveillance this fall to be
sure."
CWD disease detected on Lac qui Parle County cervid
farm southwestern Minnesota (2006-03-15) Date: March 15, 2006 at 12:36 pm PST
Chronic wasting disease detected on Lac qui Parle
County cervid farm (2006-03-15) The Board of Animal Health announced today that
chronic wasting disease (CWD) has been detected in one domestic white-tailed
deer on a cervid farm in Lac qui Parle County, which is located in southwestern
Minnesota.
Immediately, DNR officials will conduct a local deer
survey to determine the number of wild deer in the area. It is expected that
not many deer will be found because the area is highly agricultural, with
little deer habitat surrounding the farm. DNR will conduct opportunistic
sampling of deer, like road kills, in the immediate area now and will conduct
intensive hunter-harvested surveillance during the 2006 firearm deer season.
Although this positive animal is a captive deer, DNR
has conducted surveillance for CWD in wild deer in the area. The farm is
located near the northern boundary of deer permit area 447, where wild deer
surveillance for CWD last occurred in 2003.
Lou Cornicelli, DNR big game program coordinator,
said, "In 2003, we conducted wild deer CWD surveillance in adjoining
permit areas 433, 446 and 447. In total, we collected 392 samples from those
permit areas during the regular firearm deer season and CWD was not detected."
The sampling of wild deer was designed statistically
to have a 95 percent confidence of detecting a 1 percent infection rate,
according to Mike DonCarlos, DNR wildlife programs manager.
"This situation is very similar to the positive
elk farm discovered in Stearns County in 2003, which followed the first
discovery of CWD in an Aitkin County elk farm," DonCarlos said. “The DNR
response will be similar to the Stearns County action and will include an
initial assessment of wild deer populations in the area and development of a
surveillance program for next fall."
From 2002 to 2004, DNR staff collected nearly 28,000
CWD samples statewide and no disease found in the wild herd.
"The intensive surveillance conducted in 2003
indicated CWD was not present in wild deer," Cornicelli said. “In
addition, all indications are that this positive captive deer has not contacted
any wild deer, but we will conduct additional surveillance this fall to be
sure."
IT is my opinion, that these states are going to have
to significantly increase their CWD TSE PRION testing, in order to truly know
what the rate of cwd tse prion is in that state. Minnesota seems to be another
state that needs to do this...imo...terry
Friday, August 05, 2016
MINNESOTA CHRONIC WASTING DISEASE SURVEILLANCE AND TESTING
CWD TSE PRION UPDATE
Sunday, November 13, 2016
Horizontal Transmission of Chronic Wasting
Disease in Reindeer CDC Volume 22, Number 12—December 2016
Wednesday, November 09, 2016
Chronic Wasting Disease (CWD) Program Standards
- Review and Comment By Terry S Singeltary Sr. November 9, 2016
Friday, November 18, 2016
IMPORTANT: SAWCorp CWD Test is NOT APHIS Approved
Monday, May 02, 2016
*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo
***
Saturday, April 23, 2016
PRION 2016 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 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 ef?ciency comparable to that of cattle BSE.
While the ef?ciency 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
*** 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.
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.
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential
2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Volume 22, Number 12—December 2016
Dispatch
Horizontal
Transmission of Chronic Wasting Disease in Reindeer
S. Jo
Moore, Robert Kunkle, M. Heather West Greenlee, Eric Nicholson, Jürgen Richt,
Amir Hamir1, W.
Ray Waters, and Justin Greenlee(http://wwwnc.cdc.gov/eid/article/22/12/16-0635_article#comment)
Author affiliations: US Department of Agriculture, Ames, Iowa,
USA (S.J. Moore, R. Kunkle, E. Nicholson, J. Richt, A. Hamir, W.R. Waters, J.
Greenlee):; Iowa State University, Ames (M.H. West Greenlee)
Abstract
We challenged reindeer by the intracranial route with the agent
of chronic wasting disease sourced from white-tailed deer, mule deer, or elk
and tested for horizontal transmission to naive reindeer. Reindeer were
susceptible to chronic wasting disease regardless of source species. Horizontal
transmission occurred through direct contact or indirectly through the
environment.
Reindeer are susceptible to chronic wasting disease (CWD) after
experimental oral challenge (1), and
recently, CWD was identified in a free-ranging reindeer in Norway (2,3).
Horizontal transmission is the primary mode of CWD transmission in deer. Direct
horizontal transmission occurs when naive animals are exposed to infectious
excreta (i.e., saliva, urine, feces) during close contact with CWD-affected
animals (reviewed in 4). Indirect
horizontal transmission occurs through exposure to environments contaminated
with infectious material (e.g., excreta or decomposed carcasses) (5,6).
The Eurasian reindeer (Rangifer tarundus tarundus) is closely
related to the North American caribou (R. t. caribou, R. t. granti, R. t.
groenlandicus). In North America, overlapping geographic ranges of
free-ranging populations of potentially CWD-infected white-tailed deer (Odocoileus
virginianus), mule deer (O. hemionus), or elk (Cervus elaphus
nelsoni) present a risk for horizontal transmission to caribou.
Exposure also could occur in farmed populations where contact occurs between
reindeer and captive and/or free-ranging CWD-affected cervids. We investigated
the transmission of CWD from white-tailed deer, mule deer, or elk to reindeer
through the intracranial route and assessed them for direct and indirect
horizontal transmission to uninoculated sentinels.
Figure
1
Figure 1(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-f1).
Immunohistochemical analysis for the prion protein showing scrapie prion
protein (PrPSc) deposits in brains (A–D) and retinas (E, F) from reindeer (Rangifer
tarandus tarandus) with chronic wasting disease. PrPSc
immunodetection using...
In 2005, we challenged reindeer fawns from a farm in Alaska,
USA, where CWD had never been reported, by intracranial inoculation (7) with
pooled brain material from CWD-affected elk from South Dakota (CWDelk),
CWD-affected mule deer from Wyoming (CWDmd), or CWD
from white-tailed deer from Wisconsin combined with brain material from
experimentally challenged white-tailed deer (CWDwtd) (Table 1(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t1); Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)).
Additional uninoculated fawns served as negative controls, controls for
indirect transmission, and controls for direct transmission (Table 1(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t1); online
Technical Appendix). We determined the prion protein gene (PRNP) genotype
of each fawn (Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)), and we
tried to ensure that each PRNP genotype
was present in each group (Table 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2)). Control
reindeer were housed in the same barn as inoculated reindeer but in separate
pens that prevented direct physical contact (i.e., nose-to-nose) between
control and inoculated animals (Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf) Figure 1). Indirect and direct contact control groups
were formed 25 months after intracranially challenged reindeer were inoculated
(Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf) Figure 1, panel B).
Clinical signs consistent with CWD were first observed 20.9
months after inoculation (Table 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2)). Common
clinical features included found dead without clinical signs noted, loss of
body condition, recumbency, and lethargy (Table 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2); online
Technical Appendix).
At death, a full necropsy was performed on all reindeer. Two
sets of tissue samples were collected: 1 set was fixed in 10% buffered
formalin, embedded in paraffin wax, sectioned at 5 μm for microscopy
examination after hematoxylin and eosin staining or immunohistochemical
staining using primary antibody F99/96.7.1 (Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)). A second
set of tissues was frozen, and selected tissues were used for immunodetection
of scrapie prion protein (PrPSc) by Western
blot (brain tissue only) as described previously (7) but with
some modifications, or an ELISA (brainstem and/or retropharyngeal lymph node)
using a commercial kit (IDEXX HerdChek BSE-Scrapie Antigen ELISA; IDEXX,
Westbrook, ME, USA) according to the manufacturers’ instructions (Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)).
In the intracranially inoculated groups, when intercurrent
deaths were excluded, reindeer with the NN138 polymorphism (reindeer nos. 2, 6,
and 12) had the shortest survival times in each group (Table 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2)). Different
inocula did not produce significantly different survival times (log-rank test,
p = 0.0931), but we observed differences in the amount of vacuolation and PrPSc in the
brain at the clinical stages of disease in CWDwtd- and CWDelk-inoculated
reindeer, compared with CWDmd-inoculated reindeer (Table 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2); Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)). In the
indirect contact animals, PrPSc was present
in the brain but restricted to the dorsal motor nucleus of the vagus nerve and
area postrema.
We observed different patterns of PrPSc deposition
in the brain (Figure 1, panels A–D; Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)), the most
striking of which was dominated by aggregated deposits of various sizes,
including plaque-like deposits (Figure 1, panels A,B). This pattern was seen in reindeer
with the NS138 NN176 (no. 8, CWDelk; no. 13,
CWDmd) or SS138 DD176 (no. 4, CWDwtd) genotypes.
With regard to immunoreactivity in the retina (Figure 1, panels E, F; online Technical Appendix), in 2
of 3 reindeer with aggregated deposits in the brain (nos. 8 and 13), aggregated
immunoreactivity also was observed in the inner plexiform layer of the retina (Figure 1, panel f).
Figure
2
Figure 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-f2). Western
blot characterization of the inocula used to inoculate reindeer and brainstem
samples from representative reindeer from each experimental group in study of
chronic wasting disease transmission. Scrapie prion protein (PrPSc)...
Reindeer that were negative by immunohistochemical analysis in
brain also were negative by Western blot and ELISA. Different Western blot
migration patterns were observed in PrPSc-positive
animals (Figure 2), but we found no clear association between
migration pattern and challenge group or PRNP genotype.
PrPSc was widespread in lymphoid tissues from most reindeer (Table 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2); online
Technical Appendix). Reindeer with the NS138 genotype had a significantly lower
average percentage of lymphoid follicles positive than did reindeer with NN138
(analysis of variance, p = 0.003) or SS138 (p = 0.003) deer. Excluding
intercurrent deaths, PrPSc was detected in all 4 CWDwtd-challenged
reindeer, all 5 CWDelk-challenged reindeer, all 4 CWDmd-challenged
reindeer, both indirect contact reindeer, and 2 of 4 direct contact reindeer (Table 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2)).
Potential sources of infectivity for direct contact animals
include urine, feces, and saliva from their CWDwtd-challenged
pen-mates, as has been shown for CWD-affected white-tailed deer (6,8,9).
Pinpointing the source of infectivity in the indirect contact group is more
difficult. Infectious prions can travel at least 30 m in airborne particulate (10), but
because the negative control reindeer in the pen adjacent to the indirect
contact reindeer did not become positive, a more direct route of transmission
is likely in this case. Penning, feeding, and watering protocols were designed
to prevent exposure of negative control and indirect contact reindeer to
potential infectivity on feed and water buckets, bedding, or fencing (6,11). However,
reindeer might have had access to bedding from adjacent pens that had spread
into the central alleyway.
During the 5-year course of this study, reindeer were moved
between pens several times to maintain an optimal number of animals per pen (Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf) Figure 1). Prolonged persistence of prion infectivity in
the natural environment has been documented for both CWD (2 years [5]) and
scrapie (up to 16 years [12]). In
addition, thorough cleaning and disinfection might not be sufficient to remove
all infectivity from the environment, leading to persistence of infectivity
under experimental housing conditions (13).
In reindeer challenged orally with the agent of CWD, the SS138
genotype (serine/serine at PRNP codon 138)
has been associated with susceptibility to disease and the NS138
(asparagine/serine) genotype with resistance (1). In the
study we report, disease developed in reindeer with the NS138 genotype after
intracranial inoculation, although the extent of lymphoreticular system
involvement was significantly lower than in NN138 and SS138 reindeer. The
potential association of the NN138 polymorphism with shorter survival times is
interesting. However, as with all potential genotype versus phenotype
interactions, care should be taken not to over-interpret these results given
the small group sizes and the large number of PRNP genotype
groups in this study.
Our results demonstrate that reindeer are susceptible to the
agent of CWD from white-tailed deer, mule deer, and elk sources after
intracranial inoculation. Furthermore, naive reindeer are susceptible to the
agent of CWD after direct and indirect exposure to CWD-infected reindeer,
suggesting a high potential for horizontal transmission of CWD within and
between farmed and free-ranging reindeer (and caribou) populations.
Dr. Moore is a postdoctoral research associate at the National
Animal Disease Center, US Department of Agriculture, Ames, Iowa. Her research
interests include pathogenesis and pathology of animal diseases with a special
interest in neuropathology and prion diseases.
On This Page
Figures
Tables
Technical Appendices
Downloads
We thank Martha Church, Robyn Kokemuller, Joe Lesan, Virginia
Montgomery, Dennis Orcutt, and Trudy Tatum for excellent technical support.
1.
Mitchell GB, Sigurdson
CJ, O’Rourke KI, Algire J, Harrington NP, Walther I, Experimental oral
transmission of chronic wasting disease to reindeer (Rangifer tarandus tarandus). PLoS One. 2012;7:e39055.DOIPubMed
2.
Norwegian Veterinary
Institute. The first detection of chronic wasting disease (CWD) in Europe. 2016
April 4 [cited 2016 Apr 5]. http://www.vetinst.no/sykdom-og-agens/chronic-wasting-disease/the-first-detection-of-chronic-wasting-disease-cwd-in-europe
3.
Becker R. Deadly
animal prion disease appears in Europe. 2016 [cited 2016 Jun 16]. http://www.nature.com/news/deadly-animal-prion-disease-appears-in-europe-1.19759
4.
Haley NJ, Hoover EA.
Chronic wasting disease of cervids: current knowledge and future perspectives.
Annu Rev Anim Biosci. 2015;3:305–25.DOIPubMed
5.
Miller MW, Williams
ES, Hobbs NT, Wolfe LL. Environmental sources of prion transmission in mule
deer. Emerg Infect Dis. 2004;10:1003–6.DOIPubMed
6.
Henderson DM, Denkers
ND, Hoover CE, Garbino N, Mathiason CK, Hoover EA. Longitudinal detection of
prion shedding in saliva and urine by CWD-infected deer by real-time
quaking-induced conversion. J Virol. 2015;89:9338–47.DOIPubMed
7.
Greenlee JJ, Smith JD,
Kunkle RA. White-tailed deer are susceptible to the agent of sheep scrapie by
intracerebral inoculation. Vet Res. 2011;42:107.DOIPubMed
8.
Mathiason CK, Hays SA,
Powers J, Hayes-Klug J, Langenberg J, Dahmes SJ, Infectious prions in
pre-clinical deer and transmission of chronic wasting disease solely by
environmental exposure. PLoS One. 2009;4:e5916.DOIPubMed
9.
Tamgüney G, Richt JA,
Hamir AN, Greenlee JJ, Miller MW, Wolfe LL, Salivary prions in sheep and deer.
Prion. 2012;6:52–61.DOIPubMed
10.
Gough KC, Baker CA,
Simmons HA, Hawkins SA, Maddison BC. Circulation of prions within dust on a
scrapie affected farm. Vet Res. 2015;46:40.DOIPubMed
11.
Maddison BC, Baker CA,
Terry LA, Bellworthy SJ, Thorne L, Rees HC, Environmental sources of scrapie
prions. J Virol. 2010;84:11560–2.DOIPubMed
12.
Georgsson G,
Sigurdarson S, Brown P. Infectious agent of sheep scrapie may persist in the
environment for at least 16 years. J Gen Virol. 2006;87:3737–40.DOIPubMed
13.
Hawkins SA, Simmons
HA, Gough KC, Maddison BC. Persistence of ovine scrapie infectivity in a farm
environment following cleaning and decontamination. Vet Rec. 2015;176:99.DOIPubMed
Figures
Tables
Technical Appendix
Suggested citation for this article: Moore SJ,
Kunkle R, West Greenlee MH, Nicholson E, Richt J, Hamir et al. Horizontal
transmission of chronic wasting disease in reindeer. Emerg Infect Dis. 2016 Dec
[date
cited]. http://dx.doi.org/10.3201/eid2212.160635
DOI: 10.3201/eid2212.160635
1Deceased.
Wednesday, November 09,
2016
Norway and Finland Rule
Changes for importation and exportation of deer to limit the spread of skrantesjuke
(CWD)
Title: Pathological features
of chronic wasting disease in reindeer and demonstration of horizontal
transmission
Monday, September 05,
2016
Pathological features of
chronic wasting disease in reindeer and demonstration of horizontal
transmission Major Findings for
Norway
Thursday, September 22,
2016
NORWAY DETECTS 5TH CASE
OF CHRONIC WASTING DISEASE CWD TSE PRION Skrantesjuke
SUNDAY, OCTOBER 02, 2016
*** What is the risk of
a cervid TSE being introduced from Norway into Great Britain? Qualitative Risk
Assessment September 2016
Wednesday, September 7,
2016
*** An assessment of the
long-term persistence of prion infectivity in aquatic environments
Friday, September 02,
2016
*** Chronic Wasting
Disease Drives Population Decline of White-Tailed Deer
*** Infectious agent of
sheep scrapie may persist in the environment for at least 16 years ***
Gudmundur Georgsson1,
Sigurdur Sigurdarson2 and Paul Brown3
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 ***
*** Infectious agent of
sheep scrapie may persist in the environment for at least 16 years ***
Gudmundur Georgsson1,
Sigurdur Sigurdarson2 and Paul Brown3
2016 Comment from Terry
Singeltary Sr.
The is a Comment on the
Food and Drug Administration (FDA) Notice: 158 Guidance for Industry Use of
Material from Deer and Elk in Animal Feed
DOCKET-- 03D-0186 -- FDA
Issues Draft Guidance on Use of Material From Deer and Elk in Animal Feed;
Availability Date: Fri, 16 May 2003 11:47:37 0500 EMC 1 Terry S. Singeltary Sr.
Vol #: 1
PLEASE SEE FULL TEXT
SUBMISSION ;
*** 2001 Terry S.
Singeltary Sr. comment submission ***
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.
Saturday, December 12,
2015
NOTICE: Environmental Impact Statement on Large Livestock
Carcasses TSE Prion REPORT December 14, 2015
Friday, August 14, 2015
Carcass Management During a Mass Animal Health Emergency Draft
Programmatic Environmental Impact Statement—August 2015
Wednesday, November 09,
2016
Chronic Wasting Disease
(CWD) Program Standards - Review and Comment By Terry S Singeltary Sr.
November 9, 2016
***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.***
***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 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
Monday, May 02, 2016
*** Zoonotic Potential
of CWD Prions: An Update Prion 2016 Tokyo ***
*** 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
Saturday, April 23, 2016
PRION 2016 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 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 ef?ciency
comparable to that of cattle BSE. While the ef?ciency 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
*** 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.
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.
==============
SCRAPIE WS-01: Prion
diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016
ISSN: 1933-6896 printl 1933-690X online
***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.
please see file
attachment for full submission and recent science and my deep concerns on the
TSE Prion disease... No documents available. AttachmentsView All (1)
scrapie-usa-blogspot-com View Attachment:
Saturday, November 12, 2016
Maine Medical Center received confirmation patient treated at the hospital has Creutzfeldt-Jakob disease
http://creutzfeldt-jakob-disease.blogspot.com/2016/11/maine-medical-center-received.html
Terry S. Singeltary Sr.
Volume 22, Number 12—December 2016
Dispatch
Horizontal
Transmission of Chronic Wasting Disease in Reindeer
S. Jo
Moore, Robert Kunkle, M. Heather West Greenlee, Eric Nicholson, Jürgen Richt,
Amir Hamir1, W.
Ray Waters, and Justin Greenlee(http://wwwnc.cdc.gov/eid/article/22/12/16-0635_article#comment)
Author affiliations: US Department of Agriculture, Ames, Iowa,
USA (S.J. Moore, R. Kunkle, E. Nicholson, J. Richt, A. Hamir, W.R. Waters, J.
Greenlee):; Iowa State University, Ames (M.H. West Greenlee)
Abstract
We challenged reindeer by the intracranial route with the agent
of chronic wasting disease sourced from white-tailed deer, mule deer, or elk
and tested for horizontal transmission to naive reindeer. Reindeer were
susceptible to chronic wasting disease regardless of source species. Horizontal
transmission occurred through direct contact or indirectly through the
environment.
Reindeer are susceptible to chronic wasting disease (CWD) after
experimental oral challenge (1), and
recently, CWD was identified in a free-ranging reindeer in Norway (2,3).
Horizontal transmission is the primary mode of CWD transmission in deer. Direct
horizontal transmission occurs when naive animals are exposed to infectious
excreta (i.e., saliva, urine, feces) during close contact with CWD-affected
animals (reviewed in 4). Indirect
horizontal transmission occurs through exposure to environments contaminated
with infectious material (e.g., excreta or decomposed carcasses) (5,6).
The Eurasian reindeer (Rangifer tarundus tarundus) is closely
related to the North American caribou (R. t. caribou, R. t. granti, R. t.
groenlandicus). In North America, overlapping geographic ranges of
free-ranging populations of potentially CWD-infected white-tailed deer (Odocoileus
virginianus), mule deer (O. hemionus), or elk (Cervus elaphus
nelsoni) present a risk for horizontal transmission to caribou.
Exposure also could occur in farmed populations where contact occurs between
reindeer and captive and/or free-ranging CWD-affected cervids. We investigated
the transmission of CWD from white-tailed deer, mule deer, or elk to reindeer
through the intracranial route and assessed them for direct and indirect
horizontal transmission to uninoculated sentinels.
The Study
Figure 1
Figure 1(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-f1). Immunohistochemical
analysis for the prion protein showing scrapie prion protein (PrPSc) deposits
in brains (A–D) and retinas (E, F) from reindeer (Rangifer
tarandus tarandus) with chronic wasting disease. PrPSc
immunodetection using...
In 2005, we challenged reindeer fawns from a farm in Alaska,
USA, where CWD had never been reported, by intracranial inoculation (7) with
pooled brain material from CWD-affected elk from South Dakota (CWDelk),
CWD-affected mule deer from Wyoming (CWDmd), or CWD
from white-tailed deer from Wisconsin combined with brain material from
experimentally challenged white-tailed deer (CWDwtd) (Table 1(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t1); Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)).
Additional uninoculated fawns served as negative controls, controls for
indirect transmission, and controls for direct transmission (Table 1(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t1); online
Technical Appendix). We determined the prion protein gene (PRNP) genotype
of each fawn (Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)), and we
tried to ensure that each PRNP genotype
was present in each group (Table 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2)). Control
reindeer were housed in the same barn as inoculated reindeer but in separate
pens that prevented direct physical contact (i.e., nose-to-nose) between
control and inoculated animals (Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf) Figure 1). Indirect and direct contact control groups
were formed 25 months after intracranially challenged reindeer were inoculated
(Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf) Figure 1, panel B).
Clinical signs consistent with CWD were first observed 20.9
months after inoculation (Table 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2)). Common
clinical features included found dead without clinical signs noted, loss of
body condition, recumbency, and lethargy (Table 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2); online
Technical Appendix).
At death, a full necropsy was performed on all reindeer. Two
sets of tissue samples were collected: 1 set was fixed in 10% buffered formalin,
embedded in paraffin wax, sectioned at 5 μm for microscopy examination after
hematoxylin and eosin staining or immunohistochemical staining using primary
antibody F99/96.7.1 (Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)). A second
set of tissues was frozen, and selected tissues were used for immunodetection
of scrapie prion protein (PrPSc) by Western
blot (brain tissue only) as described previously (7) but with
some modifications, or an ELISA (brainstem and/or retropharyngeal lymph node)
using a commercial kit (IDEXX HerdChek BSE-Scrapie Antigen ELISA; IDEXX,
Westbrook, ME, USA) according to the manufacturers’ instructions (Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)).
In the intracranially inoculated groups, when intercurrent
deaths were excluded, reindeer with the NN138 polymorphism (reindeer nos. 2, 6,
and 12) had the shortest survival times in each group (Table 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2)). Different
inocula did not produce significantly different survival times (log-rank test,
p = 0.0931), but we observed differences in the amount of vacuolation and PrPSc in the
brain at the clinical stages of disease in CWDwtd- and CWDelk-inoculated
reindeer, compared with CWDmd-inoculated reindeer (Table 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2); Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)). In the
indirect contact animals, PrPSc was present
in the brain but restricted to the dorsal motor nucleus of the vagus nerve and
area postrema.
We observed different patterns of PrPSc deposition
in the brain (Figure 1, panels A–D; Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf)), the most
striking of which was dominated by aggregated deposits of various sizes,
including plaque-like deposits (Figure 1, panels A,B). This pattern was seen in reindeer
with the NS138 NN176 (no. 8, CWDelk; no. 13,
CWDmd) or SS138 DD176 (no. 4, CWDwtd) genotypes.
With regard to immunoreactivity in the retina (Figure 1, panels E, F; online Technical Appendix), in 2
of 3 reindeer with aggregated deposits in the brain (nos. 8 and 13), aggregated
immunoreactivity also was observed in the inner plexiform layer of the retina (Figure 1, panel f).
Figure 2
Figure 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-f2). Western
blot characterization of the inocula used to inoculate reindeer and brainstem
samples from representative reindeer from each experimental group in study of
chronic wasting disease transmission. Scrapie prion protein (PrPSc)...
Reindeer that were negative by immunohistochemical analysis in
brain also were negative by Western blot and ELISA. Different Western blot
migration patterns were observed in PrPSc-positive
animals (Figure 2), but we found no clear association between
migration pattern and challenge group or PRNP genotype.
PrPSc was widespread in lymphoid tissues from most reindeer (Table 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2); online
Technical Appendix). Reindeer with the NS138 genotype had a significantly lower
average percentage of lymphoid follicles positive than did reindeer with NN138
(analysis of variance, p = 0.003) or SS138 (p = 0.003) deer. Excluding
intercurrent deaths, PrPSc was detected in all 4 CWDwtd-challenged
reindeer, all 5 CWDelk-challenged reindeer, all 4 CWDmd-challenged
reindeer, both indirect contact reindeer, and 2 of 4 direct contact reindeer (Table 2(http://wwwnc.cdc.gov/eid/article/22/12/16-0635-t2)).
Conclusions
Potential sources of infectivity for direct contact animals
include urine, feces, and saliva from their CWDwtd-challenged
pen-mates, as has been shown for CWD-affected white-tailed deer (6,8,9).
Pinpointing the source of infectivity in the indirect contact group is more
difficult. Infectious prions can travel at least 30 m in airborne particulate (10), but
because the negative control reindeer in the pen adjacent to the indirect
contact reindeer did not become positive, a more direct route of transmission
is likely in this case. Penning, feeding, and watering protocols were designed
to prevent exposure of negative control and indirect contact reindeer to
potential infectivity on feed and water buckets, bedding, or fencing (6,11). However,
reindeer might have had access to bedding from adjacent pens that had spread
into the central alleyway.
During the 5-year course of this study, reindeer were moved
between pens several times to maintain an optimal number of animals per pen (Technical Appendix[PDF - 251 KB - 7
pages](http://wwwnc.cdc.gov/eid/article/22/12/16-0635-techapp1.pdf) Figure 1). Prolonged persistence of prion infectivity in
the natural environment has been documented for both CWD (2 years [5]) and
scrapie (up to 16 years [12]). In
addition, thorough cleaning and disinfection might not be sufficient to remove
all infectivity from the environment, leading to persistence of infectivity
under experimental housing conditions (13).
In reindeer challenged orally with the agent of CWD, the SS138
genotype (serine/serine at PRNP codon 138)
has been associated with susceptibility to disease and the NS138
(asparagine/serine) genotype with resistance (1). In the
study we report, disease developed in reindeer with the NS138 genotype after
intracranial inoculation, although the extent of lymphoreticular system
involvement was significantly lower than in NN138 and SS138 reindeer. The
potential association of the NN138 polymorphism with shorter survival times is
interesting. However, as with all potential genotype versus phenotype
interactions, care should be taken not to over-interpret these results given
the small group sizes and the large number of PRNP genotype
groups in this study.
Our results demonstrate that reindeer are susceptible to the
agent of CWD from white-tailed deer, mule deer, and elk sources after intracranial
inoculation. Furthermore, naive reindeer are susceptible to the agent of CWD
after direct and indirect exposure to CWD-infected reindeer, suggesting a high
potential for horizontal transmission of CWD within and between farmed and
free-ranging reindeer (and caribou) populations.
Dr. Moore is a postdoctoral research associate at the National
Animal Disease Center, US Department of Agriculture, Ames, Iowa. Her research
interests include pathogenesis and pathology of animal diseases with a special
interest in neuropathology and prion diseases.
On This Page
Figures
Tables
Technical Appendices
Downloads
Acknowledgment
We thank Martha Church, Robyn Kokemuller, Joe Lesan, Virginia
Montgomery, Dennis Orcutt, and Trudy Tatum for excellent technical support.
References
14.
Mitchell GB, Sigurdson
CJ, O’Rourke KI, Algire J, Harrington NP, Walther I, Experimental oral
transmission of chronic wasting disease to reindeer (Rangifer tarandus tarandus). PLoS One. 2012;7:e39055.DOIPubMed
15.
Norwegian Veterinary
Institute. The first detection of chronic wasting disease (CWD) in Europe. 2016
April 4 [cited 2016 Apr 5]. http://www.vetinst.no/sykdom-og-agens/chronic-wasting-disease/the-first-detection-of-chronic-wasting-disease-cwd-in-europe
16.
Becker R. Deadly
animal prion disease appears in Europe. 2016 [cited 2016 Jun 16]. http://www.nature.com/news/deadly-animal-prion-disease-appears-in-europe-1.19759
17.
Haley NJ, Hoover EA.
Chronic wasting disease of cervids: current knowledge and future perspectives.
Annu Rev Anim Biosci. 2015;3:305–25.DOIPubMed
18.
Miller MW, Williams
ES, Hobbs NT, Wolfe LL. Environmental sources of prion transmission in mule
deer. Emerg Infect Dis. 2004;10:1003–6.DOIPubMed
19.
Henderson DM, Denkers
ND, Hoover CE, Garbino N, Mathiason CK, Hoover EA. Longitudinal detection of
prion shedding in saliva and urine by CWD-infected deer by real-time
quaking-induced conversion. J Virol. 2015;89:9338–47.DOIPubMed
20.
Greenlee JJ, Smith JD,
Kunkle RA. White-tailed deer are susceptible to the agent of sheep scrapie by
intracerebral inoculation. Vet Res. 2011;42:107.DOIPubMed
21.
Mathiason CK, Hays SA,
Powers J, Hayes-Klug J, Langenberg J, Dahmes SJ, Infectious prions in
pre-clinical deer and transmission of chronic wasting disease solely by
environmental exposure. PLoS One. 2009;4:e5916.DOIPubMed
22.
Tamgüney G, Richt JA,
Hamir AN, Greenlee JJ, Miller MW, Wolfe LL, Salivary prions in sheep and deer.
Prion. 2012;6:52–61.DOIPubMed
23.
Gough KC, Baker CA,
Simmons HA, Hawkins SA, Maddison BC. Circulation of prions within dust on a
scrapie affected farm. Vet Res. 2015;46:40.DOIPubMed
24.
Maddison BC, Baker CA,
Terry LA, Bellworthy SJ, Thorne L, Rees HC, Environmental sources of scrapie
prions. J Virol. 2010;84:11560–2.DOIPubMed
25.
Georgsson G, Sigurdarson
S, Brown P. Infectious agent of sheep scrapie may persist in the environment
for at least 16 years. J Gen Virol. 2006;87:3737–40.DOIPubMed
26.
Hawkins SA, Simmons
HA, Gough KC, Maddison BC. Persistence of ovine scrapie infectivity in a farm
environment following cleaning and decontamination. Vet Rec. 2015;176:99.DOIPubMed
Figures
Tables
Technical Appendix
Suggested citation for this article: Moore SJ,
Kunkle R, West Greenlee MH, Nicholson E, Richt J, Hamir et al. Horizontal
transmission of chronic wasting disease in reindeer. Emerg Infect Dis. 2016 Dec
[date
cited]. http://dx.doi.org/10.3201/eid2212.160635
DOI: 10.3201/eid2212.160635
1Deceased.
Wednesday, November 09,
2016
Norway and Finland Rule
Changes for importation and exportation of deer to limit the spread of skrantesjuke
(CWD)
Title: Pathological features
of chronic wasting disease in reindeer and demonstration of horizontal
transmission
Monday, September 05,
2016
Pathological features of
chronic wasting disease in reindeer and demonstration of horizontal
transmission Major Findings for
Norway
Thursday, September 22,
2016
NORWAY DETECTS 5TH CASE
OF CHRONIC WASTING DISEASE CWD TSE PRION Skrantesjuke
SUNDAY, OCTOBER 02, 2016
*** What is the risk of
a cervid TSE being introduced from Norway into Great Britain? Qualitative Risk
Assessment September 2016
Wednesday, September 7,
2016
*** An assessment of the
long-term persistence of prion infectivity in aquatic environments
Friday, September 02,
2016
*** Chronic Wasting
Disease Drives Population Decline of White-Tailed Deer
*** Infectious agent of
sheep scrapie may persist in the environment for at least 16 years ***
Gudmundur Georgsson1,
Sigurdur Sigurdarson2 and Paul Brown3
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 ***
*** Infectious agent of
sheep scrapie may persist in the environment for at least 16 years ***
Gudmundur Georgsson1,
Sigurdur Sigurdarson2 and Paul Brown3
2016 Comment from Terry
Singeltary Sr.
The is a Comment on the
Food and Drug Administration (FDA) Notice: 158 Guidance for Industry Use of
Material from Deer and Elk in Animal Feed
DOCKET-- 03D-0186 -- FDA
Issues Draft Guidance on Use of Material From Deer and Elk in Animal Feed;
Availability Date: Fri, 16 May 2003 11:47:37 0500 EMC 1 Terry S. Singeltary Sr.
Vol #: 1
PLEASE SEE FULL TEXT
SUBMISSION ;
*** 2001 Terry S.
Singeltary Sr. comment submission ***
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.
Saturday, December 12,
2015
NOTICE: Environmental Impact Statement on Large Livestock
Carcasses TSE Prion REPORT December 14, 2015
Friday, August 14, 2015
Carcass Management During a Mass Animal Health Emergency Draft
Programmatic Environmental Impact Statement—August 2015
Wednesday, November 09,
2016
Chronic Wasting Disease
(CWD) Program Standards - Review and Comment By Terry S Singeltary Sr. November
9, 2016
***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.***
***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 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
Monday, May 02, 2016
*** Zoonotic Potential
of CWD Prions: An Update Prion 2016 Tokyo ***
Saturday, April 23, 2016
PRION 2016 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 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 ef?ciency
comparable to that of cattle BSE. While the ef?ciency 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
*** 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.
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.
==============
SCRAPIE WS-01: Prion
diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016
ISSN: 1933-6896 printl 1933-690X online
***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.
please see file
attachment for full submission and recent science and my deep concerns on the
TSE Prion disease... No documents available. AttachmentsView All (1)
scrapie-usa-blogspot-com View Attachment:
Saturday, November 12, 2016
Maine Medical Center received confirmation patient treated at the hospital has Creutzfeldt-Jakob disease
http://creutzfeldt-jakob-disease.blogspot.com/2016/11/maine-medical-center-received.html
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
10:41 AM
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