Wisconsin Second CWD-positive deer found in Oneida County 5-year-old buck shot at Three Lakes Trophy Ranch LLC agency received the CWD-positive report on the animal Dec. 29
Second CWD-positive deer found in Oneida County By Paul A. Smith of the
Journal Sentinel
Jan. 18, 2016
A second CWD-positive deer has been reported at an Oneida County shooting
preserve, according to the Department of Agriculture, Trade and Consumer
Protection.
The 5-year-old buck was shot at Three Lakes Trophy Ranch LLC in Three
Lakes. The agency received the CWD-positive report on the animal Dec. 29.
A 3-year-old buck at the facility also tested positive for the disease in
November, initiating a baiting and feeding ban in Oneida, Forest and Vilas
counties.
Officials with DATCP said Friday there was no plan to depopulate the
facility since "none of the deer are removed alive and all are tested as they
leave."
At least some residents in the area, however, are concerned about the
potential for the disease to spread to wild deer if animals were to escape the
captive facility or come into contact along the facility's perimeter.
The recent CWD-positive findings, as well as other deer management issues,
will be discussed Thursday evening at a special meeting of the Vilas County Deer
Advisory Council.
According to records from December, Three Lakes Trophy Ranch had about 425
deer on 570 acres.
Note: Oneida,
Forest and Vilas counties have been added to the CWD-affected counties effective
Jan. 11, 2016
As of 2015 there were 421 registered deer
farms in Wisconsin. White-tailed deer farming is regulated and licensed by the
Wisconsin Department of Agriculture, Trade and Consumer
Protection (DATCP) [exit DNR]. However the Department of Natural Resources (DNR) is
responsible for regulating white-tailed deer farm fencing. Before you can register your farm with DATCP you must
have your fence inspected and receive a deer farm fence certificate from the
DNR.
State pays farmer $298,000 for infected deer herd
By Paul A. Smith of the Journal Sentinel
Jan. 16, 2016 8:05 p.m.
The State of Wisconsin paid nearly $300,000 to the Eau Claire County farmer
whose deer herd was depopulated after it was found to be infected with chronic
wasting disease.
Rick Vojtik, owner of Fairchild Whitetails in Fairchild, received an
indemnity payment of $298,770 for 228 white-tailed deer killed on his farm,
according to officials with the Department of Agriculture, Trade and Consumer
Protection.
The money was taken from the agency's general program revenue funded by
Wisconsin taxpayers.
The state has a maximum payment of $1,500 per animal in such cases; Vojtik
received $1,310 each.
The adult deer killed at Fairchild Whitetails were tested for disease.
Including those tested before depopulation, 33 deer at the facility were
CWD-positive, according to the DATCP.
The CWD-positive deer on Vojtik's farm were the first and only detected to
date in Eau Claire County and triggered a deer baiting and feeding ban in Eau
Claire, Clark and Jackson counties.
More than a dozen deer escaped the facility last year but all were captured
or killed, according to Rick Rosen, regional warden supervisor for the
Department of Natural Resources.
In Wisconsin, the DATCP has authority over deer and elk farms while the DNR
has authority over the fences at such facilities and deer and elk outside
them.
Under an agreement with state officials, Vojtik will maintain the farm's
fences for five years and not put deer or other cervids in the area. Agents with
the DATCP will disinfect the property, said Paul McGraw, DATCP
veterinarian.
The 228 deer had been held in an enclosure of about 10 acres.
Chronic wasting disease has been found at 13 captive cervid facilities in
Wisconsin, according to DATCP records.
Second CWD finding in Oneida County: A second CWD-positive deer has been
reported at an Oneida County shooting preserve, according to the DATCP.
The 5-year-old buck was shot at Three Lakes Trophy Ranch LLC in Three
Lakes. The agency received the CWD-positive report on the animal Dec. 29.
A 3-year-old buck at the facility also tested positive for the disease in
November, initiating a baiting and feeding ban in Oneida, Forest and Vilas
counties.
Officials with the DATCP said Friday there was no plan to depopulate the
facility. According to records from December, Three Lakes Trophy Ranch had about
425 deer on 570 acres.
The captive animals are the only deer to test positive for CWD in that
portion of the Northwoods, including the Upper Peninsula of Michigan.
Last year, Michigan officials unveiled a campaign called "Keep the U.P. CWD
Free!" It is illegal to bring whole deer carcasses from Wisconsin into
Michigan.
Chronic wasting disease was identified in Colorado in 1967. The disease,
among a family of transmissible spongiform encephalopathies including Mad Cow
Disease and Creutzfeldt-Jakob, is fatal to deer, elk and moose. The disease was
first detected in Wisconsin in 2002 near Mount Horeb. As of this month, 41 of
the state's 72 counties are considered "CWD-affected" by the DNR.
Meat from a CWD-positive animal should not be eaten, according to health
officials.
DNR hiring for creel survey: The DNR is accepting applications for three
fisheries technicians to conduct creel surveys on Lake Michigan.
The limited-term employee positions will run from about March 7 to Oct. 31;
the jobs will be based in Mishicot, Plymouth and Sturtevant.
According to the job description, candidates must be able to accurately
identify common Lake Michigan fish; have good oral and written communication
skills; be able to work independently with limited supervision; be able to
approach anglers on piers and breakwaters, rocky shorelines, open sand, cobble
beaches and along streams and rivers over uneven terrain; and be willing to work
in inclement weather.
The jobs will pay $11.50 to $12.50 per hour depending on experience and
training. Work is required on weekends and holidays.
For application materials and more information, visit
dnr.wi.gov/employment. The application deadline is Feb. 2.
Interviews are planned the week of Feb. 8 at the DNR's Plymouth Service
Center.
© 2016, Journal Sentinel Inc. All rights reserved.
About Paul A. Smith Paul A. Smith covers outdoors and conservation
issues.
@mjsps psmith@journalsentinel.com 414-224-2313
CHRONIC WASTING DISEASE CWD WISCONSIN Almond Deer (Buckhorn Flats) Farm
Update DECEMBER 2011
The CWD infection rate was nearly 80%, the highest ever in a North American
captive herd.
RECOMMENDATION: That the Board approve the purchase of 80 acres of land for
$465,000 for the Statewide Wildlife Habitat Program in Portage County and
approve the restrictions on public use of the site.
SUMMARY:
$298,770 + $465,000
Friday, December 04, 2015
Wisconsin CWD-positive white-tailed deer found on Oneida County hunting
preserve December 3, 2015
Thursday, November 19, 2015
Wisconsin Eau Claire Co. deer herd two day round of depopulation CWD
testing shows 23 positive
Wednesday, December 16, 2015
Wisconsin Chronic wasting disease confirmed in Crawford County buck
harvested on private land
Tuesday, February 11, 2014
Wisconsin tracks 81 deer from game farm with CWD buck to seven other states
Tuesday, December 17, 2013
Wisconsin Second CWD positive deer found in Grant County
Monday, December 02, 2013
WISCONSIN CHRONIC WASTING DISEASE CWD DISCOVERED MARATHON COUNTY HUNTING
PRESERVE
Sunday, November 03, 2013
Wisconsin Second CWD deer found in Portage County
Wisconsin : 436 Deer Have Escaped From Farms to Wild
Date: March 18, 2003 Source: Milwaukee Journal Sentinel snip...
Sunday, November 03, 2013
Wisconsin Second CWD deer found in Portage County
Second CWD deer found in Portage County
News Release
Published: November 1, 2013 by the Northwest Region Contact(s): Kris
Johansen, DNR area wildlife supervisor, 715-284-1430; Ed Culhane,
DNR communications, 715-781-1683 WISCONSIN RAPIDS – A deer harvested by a
bow hunter in southeast Portage County has tested positive for chronic wasting
disease, the state Department of Natural Resources reports. This is the second
CWD-positive wild deer found in the county. Wildlife biologists in central
Wisconsin now are asking bow hunters to assist with increased surveillance for
the disease in four separate areas where positives have been confirmed outside
the CWD management zone.
CWD is contagious and fatal for deer, elk and moose. “Last fall CWD was
discovered for the first time in three wild, white-tailed deer in Adams, Juneau
and Portage counties” said DNR area wildlife supervisor Kris Johansen. “Now we
have a second positive in a different area of Portage County. To better define
the geographic extent of CWD in central Wisconsin, we are focusing additional
surveillance around each of these four locations.”
The latest CWD positive deer was harvested Oct. 6 just northwest of Almond
in Portage County.
To view where the surveillance focus areas are located, hunters can go to
the DNR website and enter “CWD registration” in the key word search, then click
on “CWD registration and sampling.” On this page – http://dnr.wi.gov/topic/wildlifehabitat/registersample.html
– detailed maps show the precise location of these surveillance circles for the
first three positives, the ones in Adams and Juneau counties and the first find
in Portage County, located in the northwest corner of the county.
There is also a map showing the two Portage County locations. A new map,
showing the precise surveillance area for the fourth positive, in southeast
Portage County, will be added to the web page as soon as it is prepared. This
page also links to a list of cooperating taxidermists and meat processors where
samples can be collected.
The DNR is asking hunters to work with these cooperators to have head and
lymph node samples from adult deer – harvested within the four focus areas –
removed for testing. To have the sample removed, the hunter can bring the whole
deer to one of the listed cooperators or just remove the head with at least
three inches of neck attached and bring that in for sampling.
“Please call ahead to set up an appointment,” Johansen said. “These are
private business operators who are helping us out, and we want to respect their
time and their schedules.” This list will be updated online as new cooperators
join the surveillance effort:
• Wisconsin River Meats, N5340 County HH, Mauston 608-847-7413
• A&B Butchering, 6971 Hwy 34, Rudolph 715-435-3893
• Strickly Wild Processing, 140 Buffalo St, Wisconsin Rapids 715-421-0587
• Hartnell's Wild Game Processing, 1925 Cypress Ave., Arkdale 608-339-7288
• Trevor Athens Taxidermy, 982 15th Ave., Arkdale 608-547-6117
• Tall Tines Taxidermy, N2621 Cassidy Road, Mauston 608-547-0818
• Todd's Wildlife Taxidermy, N2148 State 58, Mauston 608-847-7693
• Vollmer Taxidermy, 3631 Plover Road, Plover 715-345-1934
• Field and Stream Taxidermy, 217 S. Front St., Coloma 608-547-1565
• DNR Service Center, 473 Griffith Ave., Wisconsin Rapids 715-421-7813
• Mead Wildlife Area, S2148 County S, Milladore 715-457-6771
• Adams Ranger Station, 532 N. Adams St., Adams 608-339-4819
• Almond Market, 111 Main St., Almond 715-366-2002
Hunters may also have deer from any of the four focus areas tested for CWD
by contacting one of these DNR offices:
• Mead Wildlife Area headquarters, S2148 County S, Milladore –
715-457-6771
• WI Rapids Service Center, 473 Griffith Avenue, Wisconsin Rapids –
715-421-7813
• Adams-Friendship Ranger Station, 532 N. Main Street, Adams –
608-339-4819
On the weekends or during warm periods, hunters should remove the deer
head with at least three inches of neck attached, freeze the head and then
contact the DNR to arrange a drop off. DNR staff will also collect samples from
hunter-harvested deer on the opening weekend of the gun deer season. Collection
stations and hours will be published prior to the gun deer season. The CWD tests
are free to hunters. Each person who submits a head for testing will receive lab
results within three or four weeks. http://dnr.wi.gov/news/BreakingNews_Lookup.asp?id=2996
Friday, February 03, 2012
*** Wisconsin Farm-Raised Deer Farms and CWD there from 2012 report
Singeltary et al
THE YEAR 2000
Stop the madness: CWD threatens Wisconsin's elk, deer and, ultimately,
people.
15 July 00
The Isthmus magazine By BRIAN McCOMBIE
Imagine a disease worse than AIDS rippling through Wisconsin's deer herd.
One that's always fatal, cannot be tested for in live animals, and has the
chance of spreading to anyone who eats the infected venison. Sound like the
premise for Michael Crichton's next apocalyptic thriller?
Unfortunately, such a disease already exists in epidemic levels in the
wilds of Colorado and Wyoming. It's infected some game farms, too, and Wisconsin
game farmers have imported more than 350 elk with the potential for this
disease, including elk from farms known to be infected.
"If most people knew what kind of risk this disease poses to free-ranging
deer in the state, they'd be very concerned," says Dr. Sarah Hurley, Lands
Division administrator for the Department of Natural Resources. The DNR is now
testing free-ranging deer around these game farms for the disease: "We're
focusing our energies on those areas where we think there's the greatest
possibility of transmission."
The malady the DNR's looking for is chronic wasting disease (CWD)--better
known, to the extent it is known at all, as mad elk disease. It's a form of the
mad cow disease that devastated Britain's cattle industry in the 1980s, scared
the bejesus out of the populace, and is believed to have killed at least 70
people to date. An elk or deer with CWD can be listless, may walk in circles,
will lose weight and interact progressively less with fellow animals.
The corresponding human affliction is called Creutzfeldt-Jakob disease
(pronounced Croytz-feld Yawkob) or CJD. People with CJD experience symptoms
similar to Alzheimer's, including memory loss and depression, followed by
rapidly progressive dementia and death, usually within one year. While CJD is
rare (literally one in a million odds of getting it), over the last few years at
least three deer hunters have died of it. There is no proof either way whether
they contracted the disease from CWD-infected venison, but new research says it
is possible.
All three varieties--mad cow, mad elk and CJD--belong to a family of
diseases called transmissible spongiform encephalopathy. These diseases alter
the conformation of proteins in the brain called prions; after-death brain
samples usually show a series of microscopic holes in and around brain cells.
No one is exactly sure how mad elk disease spreads. At first, transmittal
through blood seemed likely, as from mother to fawn. But CWD has moved between
adult animals at game farms, leading scientists to conclude that it can be
spread through saliva or simple contact. Also, the rates of transmission are
higher in areas where animals have the most opportunities for contact.
Wisconsin's concentrated population of 1.7 million deer interact freely with
each other, and scientific modeling suggests CWD could tear through our deer
herd devastatingly fast. Despite the danger, Wisconsin and other states are
relying on only sporadic testing and a system of voluntary compliance. It's a
system that some say has more holes in it than a CWD-infected brain.
At present, Wisconsin game farm owners, even those harboring elk and deer
brought in from farms with known cases of CWD, do not have to call a
veterinarian if a deer or elk suddenly dies or acts strange. They're also not
required to inform the state Department of Natural Resources (DNR) or the
Department of Agriculture, Trade and Consumer Protection (DATCP) if animals
escape into the wild.
"The lax attitude is pretty shocking," says John Stauber, a Madison
activist and co-author of Mad Cow U.S.A. To protect people and deer, Stauber
argues for an immediate importation ban for game farms, plus programs of testing
and surveillance. He suggests both DATCP and DNR aren't taking such measures
because, as the regulators in charge, they don't want to find the CWD he thinks
is likely already in state. "It's in their bureaucratic interest to not
[actively] look for CWD in the game farms," says Stauber. "Because if they find
it, who's to blame?"
In the wild and especially out west, chronic wasting disease is spreading
fast. Northeastern Colorado documented its first case in 1981. By the mid-1990s,
samplings of mule deer brains showed 3% to 4% testing positive for CWD. Within a
few years, the rate was 8%, and now Larimer County, the center of the endemic
area, has a 15% rate of infection among mule deer. It's also being found in deer
and elk in Wyoming.
"Fifteen percent of a wild population of animals with this disease is
staggering," says Dr. Thomas Pringle, who tracks CWD-type diseases for the
Sperling Biomedical Foundation in Eugene, Ore. "It's basically unheard of. This
appears to be an unusually virulent strain. with highly efficient horizontal
transmission mechanisms."
CWD could eventually spread to Wisconsin on its own, animal to animal. But
that would take decades. Game farms, though, provide a mechanism to cut through
all that time and distance and drop CWD smack in the middle of the state.
An open-records search by Isthmus reveals that the first shipment of farm
elk from areas with CWD in the wild occurred in 1992, with 66 Colorado elk going
to a game farm in Plymouth. In April 1998, DATCP was informed that a Bloomer
game farm had purchased one elk from a Nebraska farm later found to be
CWD-infected. This prompted a Sept. 15, 1998, memo from Steven Miller, head of
the DNR's Lands Division, to Secretary George Meyer, with copies to DATCP chief
Ben Brancel and Gov. Tommy Thompson. In it, Miller recommends that Wisconsin
follow the lead of Montana (which found CWD on two game farms) and place "a
moratorium on the importation of all game farm animals.... At present it appears
the only way to help assure the disease does not spread into Wisconsin."
But the moratorium was never put in place, so it's possible that even more
elk potentially carrying CWD are now in state.
Instead of a moratorium, Wisconsin has opted for testing. It is among 12
states and two Canadian provinces that currently test deer for CWD. Last year,
the Wisconsin DNR began testing road- and hunter-killed deer in 1999 within a
five-mile radius of game farms that have brought in elk from CWD-infected areas.
Test areas include all or part of Fond du Lac, Dodge, Jefferson, Sheboygan and
Washington counties. All of the approximately 250 brains examined in 1999 came
back negative; this year, 500 to 600 deer will be tested.
Meanwhile, DATCP is asking owners of game farms that have animals from
herds known to have cases of CWD infection to voluntarily enter a surveillance
program. The agency's top veterinarian, Dr. Clarence Siroky, argues that
voluntary compliance makes more sense than a moratorium because, ban or no ban,
game farm operators "are going to find a way to bring these animals into the
state. We don't have police patrols and impregnable borders to keep anything in
or out."
With voluntary compliance, Siroky says, at least there are records of
animals entering the state. So if CWD or other diseases are discovered, the
animals can be traced back to their original herds and other farms they may have
been at. "It's better to know where the animals are coming in from," he insists.
Siroky may be right that an importation ban would result in some game
farms smuggling in animals. But currently, game farmers can bring in any deer or
elk, even those from known CWD-infected areas, so long as they can produce a
health certificate showing the animal's been tested. The problem is that no test
exists to find CWD in live animals. Animals can carry CWD for years and still
look healthy, so some of the 370 elk shipped into Wisconsin between 1996 and
1999 from CWD areas could have the disease. The odds are even higher for animals
purchased from farms later found to have CWD.
Wisconsin has approximately 100 deer or elk farms and they're big
business. On the Internet, prices for elk calves start at $1,500, and breeding
bulls go for up to $20,000. Some farms sell venison and the velvet that peels
from new elk antlers (considered an aphrodisiac in Asia). Others offer "hunts"
costing between $1,000 and $5,000 for trophy deer, to more than $10,000 for bull
elk with massive antlers.
Given these economics, it's reasonable to question why anyone with a
suspicion of CWD in his or her herd would call in state regulators or a vet. A
farm with a proven CWD case, confirms Dr. Robert Ehlenfeldt, DATCP's director of
Animal Disease Control, would be shut down indefinitely.
And if a problem develops on a Wisconsin game farm, there's no guarantee
that's where it will stay. Dr. Hurley says even fenced-in animals have easy
nose-to-nose contact with wild and other farmed animals. Besides, as the DNR's
chief of special operations Thomas Solin has documented, many game farms are not
secure. Gates are sometimes left open. Fences rust and break, rot and topple,
get crushed by fallen trees. Even if game farm animals don't escape, such
breaches allow wild deer to get in, mingle with the farmed deer and elk, then
leave.
Unlike other diseases, there's no test for CWD in living animals because
it doesn't create an immune system counter-response, detectable through blood
analysis. You can't kill CWD and related diseases by cooking the meat. One test
Stauber recounts in Mad Cow U.S.A. found that scrapie, a sheep form of CWD,
stayed viable after a full hour at 680 degrees Fahrenheit. Most disinfectants
don't kill these diseases, either, and they can exist in the soil for years.
And while diseases like mad cow and mad elk do have some trouble jumping
from species to species, it can happen. This May, Byron Caughey of the National
Institutes of Health announced that he had converted human brain materials with
mad-elk-contaminated brain matter at rates roughly equal to the transfer between
mad cow and humans.
Says Dr. Pringle, referring to Caughey's work, "CWD may not transmit that
easily, but the rate isn't zero." Pringle notes that the test Caughey used has
been a very reliable proxy in the past in determining transmission possibilities
for other diseases, including mad cow.
Once they jump the species barrier, transmissible spongiform
encephalopathy diseases adapt to fit the new host and are then passed on rather
easily within that species. Unfortunately, says Pringle, no one is trying to
determine if CWD has jumped into people as Creutzfeldt-Jakob disease. Making
matters more difficult is the fact that the disease can incubate for decades
before symptoms are seen.
In states with CWD-infected deer, thousands of people have undoubtedly
been exposed to CWD-infected venison. A February 1998 Denver Post article tells
of one hunter who's venison tested positive for CWD. By the time he was
notified, his meat had already been ground up and mixed with meat from hundreds
of other deer for venison sausage.
With AIDS, Pringle notes, there was a definite overreaction, with people
initially afraid to even shake hands with people infected with the virus.
Looking at the CWD situation in Colorado, he says there's been complete
underreaction. "It's like, oh, what the hell. Nobody's died yet--so keep eating
the venison!'" Pringle worries that if the disease is found in humans, it will
be so only after years of spreading through the human community.
Looking over documents obtained by Isthmus through its open-records
request, Stauber says DATCP is behaving more like a lobbyist for the game farm
industry than an agency bent on protecting Wisconsin's people from CWD. He
points to DATCP's Cervidae Advisory Committee as a prime example. In a Nov. 11,
1998, memo from Siroky to DATCP secretary Ben Brancel, Siroky notes that the
committee is needed to "obtain information from the public concerning disease
regulation" of farmed deer and elk, and "to help formulate action plans for
importation requirements, prevention and control" of CWD. But of the 12 people
Siroky nominates, one's a DNR warden, one's a DATCP employee, and the other 10
are game farm owners. And two of these owners were among those DATCP knew had
purchased elk from farms at high risk of having CWD.
"There's no significant input from anyone else," says Stauber. "Farmers,
deer hunters and consumers are all left out. Meanwhile, the government's failing
to take all necessary precautions to alert the public to this potential health
threat."
Sunday, January 17, 2016
Texas 10,000 deer in Texas tested for deadly disease CWD TSE, but not
tested much in the most logical place, the five-mile radius around the Medina
County captive-deer facility where it was discovered
Friday, January 15, 2016
TEXAS PARKS & WILDLIFE CWD Ante-Mortem Testing Symposium Texas Disposal
Systems Events Pavilion January 12, 2016
DNR to hold CWD meeting in DeWitt Township Tuesday
Tom Thelen, Lansing State Journal 12:13 p.m. EST January 11, 2016
Tests confirm deer taken in Watertown Twp. positive for CWD
Wednesday, December 30, 2015
Michigan Deer suspected positive for CWD found in Watertown Township; Jan.
12 public meeting set
Thursday, December 10, 2015
Wyoming Game and Fish seeks public comment on draft of updated CWD plan
Tuesday, December 08, 2015
Wyoming Game and Fish finds CWD in new elk hunt area in Johnson County
Friday, November 27, 2015
Wyoming Game and Fish finds CWD in new Deer Hunt Area near Sheridan
Monday, November 16, 2015
*** Wyoming Latest round of testing CWD surveillance program has found the
disease in three new hunt areas
Wyoming WGF Commission Meeting 11/6/2015 Afternoon Edition Vidoe
CWD starts at minute 58:51 of first hour of meeting discussion of previous
models predicting extinction of deer population and elk population.
please mark hour 1:02 where remarks were made about potential resistant
genes and prolonged survival, however a recent study (I posted directly next
after youtube link) where it states ;
‘’Our study also demonstrates that mice expressing the deer S96-PRNP
allele, previously shown to be resistant to various cervid prions, are
susceptible to H95+ CWD prions. The potential for the generation of novel
strains raises the possibility of an expanded host range for CWD. ‘’
hour minute mark 1:03
captive Elk study
39 femail elk calves captured on National Elk Refuge In Jackson, WY
Transported to WGFD Thorne-Williams Wildlife Research Unit (Sybille,
TWWRU)
Worst-case scenario for prion exposure
Genotypes
-27 M/M132 (69.2%)
-11 M/L132 (28.2%)
-1 L/L132 (2.6%)
38 of 39 elk died over 10-year study
1 remaining elk was L/L132
still alive and remained negative for PrPCWD by rectal biopsy
Appears healthy, weighs 242kg, and bore healthy calf in May, 2012
CWD infection rate in this study ???
> During the analysis, 37 of 39 elk died, all of which were positive for
CWD.
*** Our study also demonstrates that mice expressing the deer S96-PRNP
allele, previously shown to be resistant to various cervid prions, are
susceptible to H95+ CWD prions. ***
*** The potential for the generation of novel strains raises the
possibility of an expanded host range for CWD. ***
Deer Prion Proteins Modulate the Emergence and Adaptation of Chronic
Wasting Disease Strains
Camilo Duque Velásqueza,b, Chiye Kima,c, Allen Herbsta,b, Nathalie
Daudea,d, Maria Carmen Garzaa,e, Holger Willea,e, Judd Aikena,b and Debbie
McKenziea,c aCentre for Prions and Protein Folding Diseases, University of
Alberta, Edmonton, Alberta, Canada bDepartment of Agricultural, Food and
Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
cDepartment of Biological Sciences, University of Alberta, Edmonton, Alberta,
Canada dDepartment of Medicine, University of Alberta, Edmonton, Alberta, Canada
eDepartment of Biochemistry, University of Alberta, Edmonton, Alberta, Canada
B. Caughey, Editor
+ Author Affiliations
ABSTRACT
Transmission of chronic wasting disease (CWD) between cervids is influenced
by the primary structure of the host cellular prion protein (PrPC). In
white-tailed deer, PRNP alleles encode the polymorphisms Q95 G96 (wild type
[wt]), Q95 S96 (referred to as the S96 allele), and H95 G96 (referred to as the
H95 allele), which differentially impact CWD progression. We hypothesize that
the transmission of CWD prions between deer expressing different allotypes of
PrPC modifies the contagious agent affecting disease spread. To evaluate the
transmission properties of CWD prions derived experimentally from deer of four
PRNP genotypes (wt/wt, S96/wt, H95/wt, or H95/S96), transgenic (tg) mice
expressing the wt allele (tg33) or S96 allele (tg60) were challenged with these
prion agents. Passage of deer CWD prions into tg33 mice resulted in 100% attack
rates, with the CWD H95/S96 prions having significantly longer incubation
periods. The disease signs and neuropathological and protease-resistant prion
protein (PrP-res) profiles in infected tg33 mice were similar between groups,
indicating that a prion strain (Wisc-1) common to all CWD inocula was amplified.
In contrast, tg60 mice developed prion disease only when inoculated with the
H95/wt and H95/S96 CWD allotypes. Serial passage in tg60 mice resulted in
adaptation of a novel CWD strain (H95+) with distinct biological properties.
Transmission of first-passage tg60CWD-H95+ isolates into tg33 mice, however,
elicited two prion disease presentations consistent with a mixture of strains
associated with different PrP-res glycotypes. Our data indicate that H95-PRNP
heterozygous deer accumulated two CWD strains whose emergence was dictated by
the PrPC primary structure of the recipient host. These findings suggest that
CWD transmission between cervids expressing distinct PrPC molecules results in
the generation of novel CWD strains.
IMPORTANCE CWD prions are contagious among wild and captive cervids in
North America and in South Korea. We present data linking the amino acid variant
Q95H in white-tailed deer cellular prion protein (PrPC) to the emergence of a
novel CWD strain (H95+). We show that, upon infection, deer expressing H95-PrPC
molecules accumulated a mixture of CWD strains that selectively propagated
depending on the PRNP genotype of the host in which they were passaged. Our
study also demonstrates that mice expressing the deer S96-PRNP allele,
previously shown to be resistant to various cervid prions, are susceptible to
H95+ CWD prions. The potential for the generation of novel strains raises the
possibility of an expanded host range for CWD.
*** Our study also demonstrates that mice expressing the deer S96-PRNP
allele, previously shown to be resistant to various cervid prions, are
susceptible to H95+ CWD prions. ***
*** The potential for the generation of novel strains raises the
possibility of an expanded host range for CWD. ***
UPDATE CWD VACCINE ELK minute mark 1:22:00
VACCINE
RECOMBINANT PROTEIN FUSION VACCINE
Hedlin, PD et al ‘’Design and delivery of a cryptic PrP c epitope for
induction of Prp Sc-specific antibody responses.’’ Vaccine 28.4 (2010)
981-988.
PAN-PROVINCIAL VACCINE ENTERPRISES (PREVENT)
Dose: 2ml IM CWD VACCINE UPDATE IS A FAILURE, I REPEAT, A NEGATIVE RESULTS
FOR CWD VACCINE. .tss
Subject: Bayesian Modeling of Prion Disease Dynamics in Mule Deer Using
Population Monitoring and Capture-Recapture Data
To date, we are unaware of a study that documents a decrease in CWD
prevalence over time in mule deer, white-tailed deer or elk. We briefly consider
three plausible explanations for our findings: a) that natural oscillations
occur in CWD outbreaks; b) that the outbreak has peaked and is declining to a
lower endemic level; or c) that previous management actions were more successful
at suppressing the outbreak than originally believed.
Sharp & Pastor [41] illustrated that CWD outbreaks may play out as a
series of reoccurring epidemics characterized by either stable limit cycles or
oscillations that may dampen or amplify as a function of deer density. If this
is the case, we would expect today’s declining deer population to feedback on
conditions–lowering transmission rates leading to reduced CWD effects and a
growing population. Increasing abundance would support higher transmission
rates, deer decline, and oscillations of CWD prevalence and deer. Alternatively,
Almberg et al. [21] (see also [22–24,41,42]) suggested that CWD outbreaks could
reach endemic equilibrium characterized by coexistence of a smaller deer
population and CWD. Under these scenarios, population prevalence would reach a
lower, constant level after a period of high prevalence and deer decline.
Although neither of the foregoing scenarios can be dismissed completely,
invoking them ignores the extensive management of this deer population that
occurred in the years between the two time points we chose as the basis for our
analyses. Management aimed to reduce CWD transmission between 2000 and 2005,
which included a combination of (crude and unpopular) focal culling and a
broader increase in female harvest, decreased overall deer abundance by about
25%. Analyses carried out shortly after suggested that reductions in deer
density had made little impact on CWD prevalence [10]. However, our current
findings suggest that these management actions may indeed have attenuated the
outbreak. Observed dynamics over the last decade closely approximate those
predicted from models by Wild et al. [42] that included a substantial amount of
selective predation on CWD-infected individuals. That harvest could be a source
of selective mortality is supported by an early notion that CWD-infected deer
might be more vulnerable to harvest [43], just as infected deer also appear to
be more vulnerable to vehicle collisions and predation [20,33,44]. This offers
the possibility that hunting could be used as a more tightly controlled
substitute for predation in studies of system responses with CWD and perhaps
other similar diseases.
The protracted time-scale of the CWD outbreak is much longer than the
timespan of our research, which limits our ability to identify the true
explanation of our findings. Nonetheless, our research suggests that, at least
for the foreseeable future (e.g., decades), mule deer populations sharing the
overall survival and infection probabilities estimated from our analyses may
persist but likely will not thrive where CWD becomes established as an endemic
infectious disease.
‘’Nonetheless, our research suggests that, at least for the foreseeable
future (e.g., decades), mule deer populations sharing the overall survival and
infection probabilities estimated from our analyses may persist but likely will
not thrive where CWD becomes established as an endemic infectious disease. ‘’
*** Bayesian Modeling of Prion Disease Dynamics in Mule Deer Using
Population Monitoring and Capture-Recapture Data
‘’Mountain lions prey selectively on CWD infected deer [33] and CWD could
result in an abundance of vulnerable prey, thereby enhancing mountain lion
survival and reproduction [20].’’
please see ;
‘’preliminary results suggesting that bobcats (Lynx rufus) may be
susceptible to white-tailed deer (Odocoileus virginianus) chronic wasting
disease agent.’’
references on Feline Spongiform Encephalopathy FSE toward the bottom, see
;
Assessing Transmissible Spongiform Encephalopathy Species Barriers with an
In Vitro Prion Protein Conversion Assay
Friday, January 01, 2016
Bayesian Modeling of Prion Disease Dynamics in Mule Deer Using Population
Monitoring and Capture-Recapture Data
Tuesday, December 15, 2015
Chronic Wasting Disease will cause a Wyoming deer herd to go virtually
extinct in 41 years, a five-year study predicts
Study: Chronic Wasting Disease kills 19% of deer herd annually
Saturday, December 12, 2015
CHRONIC WASTING DISEASE CWD TSE PRION REPORT DECEMBER 14, 2015
Monday, January 11, 2016
INDIANA SB109 HIGH FENCE HUNTING LEGISLATION AND RISK FACTORS FOR CHRONIC
WASTING DISEASE CWD TSE PRION
Disease in Deer and Elk
Chris Siepker1, Nicholas Haley1, W. David Walter2, Matteo Manca3, Laura
Hoon-Hanks4, Ryan Monello5, Jenny Powers5, Justin Greenlee6 , Bruce Thomsen7 ,
Aaron Lehmkuhl7, Gordon Mitchell8, Tracy Nichols9,Byron Caughey3, Edward
Hoover4, and Juergen Richt1.
1. Department of Diagnostic Medicine and Pathobiology, Kansas State
University, Manhattan KS USA 2. United States G e o l o g i c a l Survey, P e n
n s y l v a n i a Cooperative Fish and Wildlife Research Unit, University Park
PA USA 3. TSE/Prion Biochemistry Section, Rocky Mountain Laboratories, National
Institutes of Health, Hamilton, MT USA 3. Department of MIP, Colorado State
University, Fort Collins CO USA 4. National Park Service, Wildlife Health
Branch, Fort Collins CO USA 5. Virus and Prion Research Unit, National Animal
Disease Center, ARS, USDA, Ames IA USA 6. USDA, APHIS, VS, STAS, National
Veterinary Service Laboratories, Ames IA USA 7. National and OIE Reference
Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa ON
Canada 8. National Wildlife Research Center Wildlife Services, APHIS, USDA, Fort
Collins CO USA
Chronic wasting disease (CWD) is an e f f i c i e n t l y t r a n smi t t e
d s p o n g i f o r m encephalopathy of cervids (e.g. deer, elk, and moose), and
is the only known prion disease affecting both free-ranging wildlife and captive
animals. The antemortem detection of CWD and other prion diseases has proven
difficult, due in part to difficulties in identifying an appropriate peripheral
tissue specimen and complications with conventional test sensitivity. At
present, biopsies of the recto-
Prion2015 Program Guide 22
anal mucosal-associated lymphoid tissues (RAMALT) have shown promising
sensitivity and are not impractical to collect in live animals. Nasal brush
collections have likewise proven both sensitive and practical for identification
of prion infections in humans. In this study, we evaluated both RAMALT and nasal
brush collections by real time quaking-induced conversion (RT-QuIC), and
compared our findings to RAMALT immu n o h i s t o c h emi s t r y a s we l l a
s conventional postmortem evaluation of obex and retropharyngeal lymph node
tissues from over 700 captive and free-ranging deer and elk in areas with
endemic CWD. We correlated our results with various clinical findings, including
pathological stage of infection as determined by obex scoring, PrP genotype,
age, and sex. While the sensitivity of RAMALT RT-QuIC analyses exceeded that of
RAMALT IHC (69-80% vs. >44%) and nasal brush collections (15-30%), the
sensitivity of both biopsy and nasal brush analyses were dependent primarily on
clinical stage of disease, although PrP genotype was also an important predictor
of sample positivity. Our findings further demonstrate the potential and
limitations of antemortem sample analyses by RT-QuIC in the identification and
management of prion diseases.
==================
P200 Clinical Stage of Infection is Critical in the Antemortem Diagnosis of
Chronic Wasting Disease in Deer and Elk.
Chris Siepker1, Nicholas Haley1, W. David Walter2, Laura Hoon-Hanks7, Ryan
Monello3, Jenny Powers3, Bruce Thomsen4, Justin Greenlee4, Aaron Lehmkuhl4,
Gordon Mitchell5, Tracy Nichols6, Edward Hoover7, Juergen Richt1
1Department of Diagnostic Medicine and Pathobiology, Kansas State
University, Manhattan, KS, USA, 2United States G e o l o g i c a l Survey, P e n
n s y l v a n i a Cooperative Fish & Wildlife Research Unit, Pennsylvania
State University, University Park, PA 16802, USA, 3National Park Service,
Wildlife Health Branch, Fort Collins, CO, USA, 4USDA, APHIS, VS, STAS, National
Veterinary Service Laboratories, Ames, IA, USA, 5National and OIE Reference
Laboratory for Scrapie and CWD Ottawa Laboratory Fallowfield Canadian Food
Inspection Agency, Ottawa, ON, Canada, 6National Wildlife Research Center
Wildlife Services APHIS, USDA, Fort Collins, CO, USA, 7Department of MIP,
Colorado State University, Fort Collins, CO, USA
Chronic wasting disease (CWD) is an e f f i c i e n t l y t r a n smi t t e
d s p o n g i f o r m encephalopathy of cervids (e.g. deer, elk, and moose), and
is the only known prion disease affecting both free-ranging wildlife and captive
animals. The antemortem detection of CWD and other prion diseases has proven
difficult, due in part to difficulties in identifying an appropriate peripheral
tissue specimen and complications with conventional test sensitivity. At
present, biopsies of the rectoanal mucosal-associated lymphoid tissues (RAMALT)
have shown promising sensitivity and are not impractical to collect in live
animals. Nasal brush collections have likewise proven both sensitive and
practical for identification of prion infections in humans. In this study, we
evaluated both RAMALT and nasal brush collections by real time quaking-induced
conversion (RT-QuIC), and compared our findings to RAMALT immu n o h i s t o c h
emi s t r y a s we l l a s conventional postmortem evaluation of obex and
retropharyngeal lymph node tissues from over 700 captive and free-ranging deer
and elk in areas with endemic CWD. We correlated our results with various
clinical findings, including pathological stage of infection as determined by
obex scoring, PrP genotype, age, and sex. While the sensitivity of RAMALT
RT-QuIC analyses exceeded that of RAMALT IHC (69-80% vs. >44%) and nasal
brush collections (15-30%), the sensitivity of both biopsy and nasal brush
analyses were dependent primarily on clinical stage of disease, although PrP
genotype was also an important predictor of sample positivity. Our findings
further demonstrate the potential and limitations of antemortem sample analyses
by RT-QuIC in the identification and management of prion diseases.
Research Project: Mitigating the Risk of Transmission and Environmental
Contamination of Transmissible Spongiform Encephalopathies Location: Animal
Diseases Research
2015 Annual Report
1a.Objectives (from AD-416): Objective 1: Determine whether goats are a
transmission reservoir for ovine scrapie by developing and validating diagnostic
methods for detecting goat scrapie. Determine the genetic predisposition and
transmission route(s) of goat scrapie.
Subobjective 1.1: Improve eradication efforts by developing improved
methods for antemortem scrapie diagnosis.
Subobjective 1.2: Determine if placenta and milk from goats are potential
sources of scrapie to sheep.
Objective 2: Develop methods to mitigate infectivity of soil-associated
prions by screening soil microbes for potential candidates for bioremediation.
1b.Approach (from AD-416): Scrapie is a complex and rare disorder affecting
outbred farm animals held under a wide variety of husbandry conditions and
exposed to an agent for which the transmissible and pathogenic events remain
largely unknown. The work described in the research plan is an extension of the
previous highly productive studies by this research group, addressing the need
for implementation of federal regulations based on the best available science,
often in the face of relatively small sample numbers in the natural host. The
work includes development of specific management and diagnostic tools and is
presented as an integrated series of research objectives. This approach was
selected over a hypothesis based approach. After consulting Glass and Hall, the
group determined that the work presented in the following plan was best
represented by goal statements rather than hypotheses because the work increases
the density of data necessary for progress and for support of current and
proposed federal regulations. This project addresses only scrapie, the TSE of
sheep and goats. Chronic wasting disease (CWD) is the TSE of North America
cervids (deer and elk). ***No live animal work with CWD is included in this
project plan since CWD is not endemic in Washington State, the disease appears
to be highly communicable, the modes of transmission are unknown, and we do not
have suitable biocontainment facilities to conduct CWD studies in large animals.
3.Progress Report: The National Scrapie Eradication program in the U.S. is
conducted by the state and federal animal disease health regulatory agencies,
with research support by ARS and several land grant universities, in a joint
endeavor with the sheep and goat industries. The comprehensive program of animal
identification, surveillance and genetic selection has resulted in a decrease of
scrapie prevalence by 88%. As prevalence falls, remaining potential sources of
infection will be monitored. The transmissible spongiform encephalopathies (TSE)
project at the Animal Disease Research Unit, Pullman, Washington, includes an
integrated examination of modes of transmission (both intraspecies and
interspecies), diagnostic test development and refinement, and delineation of
species-specific and genetically controlled differences in pathogenesis. In
FY15, progress was reported in each of these research areas.
Objective 1: Transmission of scrapie by placenta, blood and milk. Exposure
of the newborn lamb or kid to infectious prions shed by the postparturient
ewe/doe is probably the most efficient route of transmission in the field. Our
earlier work demonstrated the role of fetal genotype on transmission by the
ovine placenta. In this Fiscal Year (FY), we completed a study demonstrating
that the caprine placenta, while containing sparse amounts of detectable PrP-Sc,
is infectious to lambs and kids by oral exposure. Experimental oral exposure of
lambs and kids to milk from infected does during the first 2 to 3 days of life
was performed last year and the recipient animals are monitored for evidence of
disease. With an incubation period of 24-36 months, the study is expected to
yield useful information in FY16. These studies of experimental disease are
complemented by ongoing observations on transmission in our mixed herd of
infected goats and sheep.
Objective 2: Diagnosis and genetics of the TSEs in ruminant animals: Gold
standard testing of scrapie is performed by immunohistochemistry of formalin
fixed tissues, using lymphoid tissue to detect early disease and brain tissue to
detect advanced disease. Antemortem tissue based testing requires expertise in
the field and in the laboratory. We are completing a study examining the effects
of host and biopsy handling on lymphoid follicle frequency and detection of
PrP-Sc. Similarly, immunohistochemistry has been applied to determine the
effects of these factors on the frequency of observing two major cell types
known to accumulate PrPSc in lymphoid tissues—namely, macrophages and follicular
dendritic cells. These studies will be completed in FY16 and will provide
information on any needed refinements in the antemortem testing of sheep and
goats, with possible application to the evolving program of live animal testing
of captive deer and elk.
Genetic variation among animals within each species affects disease
resistance and incubation time: We have previously reported the effect of
genotype on diagnostic accuracy in white tailed deer. We have now completed a
study examining the role of a prion gene polymorphism at residue 127 in goats on
incubation time (reported in accomplishments) and in FY16 will perform studies
on diagnostic accuracy of the current testing modes in goats with this genotype.
Polymorphisms at additional sites (146 and 222) have been reported to be
associated with reduced susceptibility to caprine scrapie. Goat kids were
exposed to scrapie by the oral route on day 1 of life and are being monitored.
Goats with the potentially resistant allele have remained clinically normal for
more than 7 years after oral challenge; control goats lacking this allele
developed disease at 2-3 years of age. We will continue to monitor the 222K
goats for their natural lifespan and will perform extensive necropsy
examinations upon termination to determine whether these animals are a benefit
to the industry or represent a long lived source of prions in goat herds. The
polymorphism at residue 222, while potentially conferring resistance to scrapie,
also presents a diagnostic challenge. Residue 222 is included in the epitope
recognized by the monoclonal antibody used in gold standard diagnostic testing
in the U.S. We have reported the effect of this polymorphism on test sensitivity
(reported in accomplishments). We have previously reported that this
polymorphism is rare in U.S. goats, but in the current work, we presented some
alternatives to testing should this genotype be selected by breeders in the
future.
Examination of the prion distribution in fixed tissues is the basis for
diagnostic testing. In addition, the distribution and intensity of the
immunohistochemical staining are also useful indirect measures of disease
progression. We have reported this effect in our studies of genetics and
diagnosis of chronic wasting disease in white tailed deer. We have now extended
those studies to include Rocky Mountain elk, which have a unique prion
distribution pattern. We continue to work with state and federal agencies
monitoring the effects of genotype on prion disease captive and free-ranging
Rocky Mountain elk, as components of species-specific control programs.
While antemortem and postmortem tissue-based testing is sensitive and
specific, collection of tissues is inconvenient and testing is expensive.
Development of a blood based test might alleviate those problems. We are
conducting a systematic examination of prion-bearing cell types in sheep and
goats and have reported that all three major types of peripheral blood
mononuclear cells—B lymphocytes, T lymphocytes, and monocytes, can harbor prions
and are thus reasonable targets on which to base development of a diagnostic
platform for use during preclinical infection. We have recently reported that
relatively small amounts of blood contain infectious prions and continue to
examine methods for more sensitive and specific detection of PrP-Sc in
circulating cells.
Objective 3: Introduction of disease by novel routes: While direct contact
with prion-bearing tissues remains the most likely source of infection in sheep
and goats, the introduction of disease through fomites or through contact with
other species has not been ruled out. We originally intended to examine the role
of soil or premise contamination with prions after removal of infected sheep.
However, the success of the eradication program at reducing scrapie prevalence
to nearly undetectable levels over a relatively short amount of time suggests
that environmental routes are not highly efficient. ***However, prevalence of
chronic wasting disease in farmed and free-ranging cervids continues to climb
and as the disease is discovered in an increasing number of states and
provinces, the threat of transmission to sheep remains under investigation. In
conjunction with the Canadian Food Inspection Agency, we are completing a study
delineating methods for discriminating between a TSE of ovine and cervid origin
in sheep, using both conventional in vitro prion characterization methods and in
vivo studies with a panel of transgenic mice. The study will be concluded in
FY16; preliminary findings show differences in incubation time and molecular
folding patterns that may be useful in determining the origin of TSEs of sheep
in the CWD endemic zones.
In a continued effort to reduce research dependence on bioassay, work
continued on the creation of cultured cell lines with robust permissiveness to
natural isolates of prions. Work continued on the immortalization of caprine
microglia cell lines with different prion genotypes of interest. Studies also
continued in the optimization of the scrapie permissiveness of a caprine prion
protein-transfected rabbit kidney epithelial cell line. Factors associated with
cellular permissiveness to infection were also determined in a study that
compared the transcriptomes of clones from an immortalized ovine microglia cell
line but that differ greatly in permissiveness to natural source isolates (i.e.,
hindbrain) of classical scrapie prions.
4.Accomplishments 1. The placenta of goats with scrapie is infectious to
goat kids and lambs. The placenta of sheep is a highly infectious source of
scrapie prions and is well known to play a major role in natural transmission.
Goats, too, are a natural host of classical scrapie and are frequently raised
with sheep, but the potential routes of natural transmission from goats to sheep
have not been studied. ARS researchers at the Animal Disease Research Unit in
Pullman, Washington, have now demonstrated that the placenta shed from a goat,
despite its relatively sparse accumulation of the disease-associated form of the
prion protein, is infectious to newborn lambs and goat kids by oral exposure.
This accomplishment provides a scientific basis for regulatory and veterinary
consideration as to the possible modes of transmission risk of scrapie from
goats to sheep.
2. Prions were detected in small volume blood samples obtained from sheep
with preclinical scrapie. Initial studies that demonstrated the potential for
developing a blood-based live animal diagnostic test for classical scrapie in
sheep were based on blood sample volumes many times more than routinely used in
the practice of veterinary medicine. ARS researchers at the Animal Disease
Research Unit in Pullman, Washington, have now demonstrated that infectious
prions can be detected from much smaller blood sample volumes, even during
preclinical infection. This study supports further development of a safe and
highly efficient blood-based diagnostic test for preclinical scrapie infection
in sheep. It demonstrates the utility of using the small blood sample volumes
already routinely collected for diagnostic purposes.
3. A prion gene polymorphism that prolongs scrapie incubation in goats.
Scrapie eradication in sheep is based in part on strong genetic resistance to
classical scrapie infection. However, knowledge regarding the implications of
differing genotypes in goats is incomplete. ARS researchers at the Animal
Disease Research Unit in Pullman, Washington, have now demonstrated that the
appearance of clinical signs associated with scrapie can be significantly
delayed in goats with a prion gene polymorphism at codon 127. This
accomplishment helps explain why goats with this polymorphism may be
underrepresented in surveys of scrapie infected goat herds. Additionally, this
accomplishment suggests that scrapie eradication programs might need to include
longer trace-back histories when investigating scrapie-exposed goats of this
genotype.
4. A prion gene polymorphism that reduces the sensitivity of some
diagnostic tests for caprine scrapie. Gold standard diagnostic testing for
caprine scrapie is performed by monoclonal antibody immunohistochemistry. While
this assay is highly specific, the sensitivity of the assay is limited by the
use of a single monoclonal antibody directed to a variable portion of the prion
molecule. ARS researchers at the Animal Disease Research Unit in Pullman,
Washington, have confirmed that the monoclonal antibody currently used for
testing in the U.S. fails to detect prions in goats homozygous for a prion
polymorphism at codon 222. The study was performed by developing a digital image
segmentation and analysis algorithm to objectively measure spatially diverse
PrPSc accumulation profiles in the hindbrain of goats with naturally acquired
classical scrapie. Comparisons were also made under the standardized conditions
and reagents currently utilized by regulatory agencies. This accomplishment
provides the scientific basis for modification of the assay should this prion
genotype become more prevalent in the U.S. goat herd.
***5. Delineation of the progression of abnormal prion accumulation in the
brain of elk with chronic wasting disease. Diagnostic testing for the
transmissible spongiform encephalophathies (TSE) of elk is performed by
examination of a single section of brain, using a monoclonal antibody that
detects the abnormal prion protein. Collaborative research including scientists
from the Colorado State University Diagnostic Laboratory, the U.S. Department of
Agriculture Animal Health Inspection Service, the Canadian Food Inspection
Agency, and the ARS Animal Disease Research Unit in Pullman, Washington, has
demonstrated that the abnormal prion in this section of brain has a unique and
relatively consistent pattern of accumulation as disease progresses. The study
complements the earlier work performed by ARS and others on the effect of prion
genotype on disease progression in elk and in white tailed deer. The scoring
system described in these studies may be useful for estimating prion
distribution throughout the infected animal and potentially for estimating the
duration of infection, facilitating epidemiologic studies in infected herds.
Review Publications Schneider, D.A., Madsen-Bouterse, S.A., Zhuang, D.,
Truscott, T.C., Dassanayake, R.P., O'Rourke, K.I. 2015. The placenta shed from
goats with classical scrapie is infectious to goat kids and lambs. Journal of
General Virology. doi: 10.1099/vir.0.000151.
Munoz-Gutierrez, J.F., Schneider, D.A., Baszler, T.V., Dinkel, K.D.,
Greenlee, J.J., Nicholson, E.M., Stanton, J.J. 2015. hTERT-immortalized ovine
microglia propagate natural scrapie isolates. Virus Research. 198:35-43.
Dassanayake, R.P., White, S.N., Madsen-Bouterse, S.A., Schneider, D.A.,
O'Rourke, K.I. 2015. Role of PRNP S127 allele in experimental goat infection
with classical caprine scrapie. Animal Genetics. doi: 10.1111/age.12291.
Dassanayake, R.P., Truscott, T.C., Zhuang, D., Schneider, D.A.,
Madsen-Bouterse, S.A., Young, A.J., Stanton, J.B., Davis, W.C., O’Rourke, K.I.
2015. Classical natural ovine scrapie prions are detected in practical volumes
of blood by lamb and transgenic mouse bioassay. Journal of Veterinary Science.
16(2):179-186.
Madsen-Bouterse, S.A., Schneider, D.A., Dassanayake, R.P., Truscott, T.C.,
Zhuang, D., Kumpula-Mcwhirter, N., O'Rourke, K.I. 2015. PRNP variants in goats
reduce sensitivity of detection of PrPSc by immunoassay. Journal of Veterinary
Diagnostic Investigation. 27(3):332-343.
Spraker, T.R., Gidlewski, T., Powers, J.G., Nichols, T., Balachandran, .A.,
Cummins, B., Wild, M.A., Vercauteren, K., O'Rourke, K. 2015. Progressive
accumulation of the abnormal conformer of the prion protein and spongiform
encephalopathy in the obex of nonsymptomatic and symptomatic Rocky Mountain elk
(Cervus elaphus nelsoni) with chronic wasting disease. Journal of Veterinary
Diagnostic Investigation. doi: 10.117/1040638715593368.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Title: Antemortem detection of chronic
wasting disease prions in nasal brush collections and rectal biopsies from
white-tailed deer by real time quaking-induced conversion
Authors
item Haley, Nicholas - item Siepker, Chris - item Walter, W. David - item
Thomsen, Bruce - item Greenlee, Justin item Lehmkuhl, Aaron - item Richt, Jürgen
-
Submitted to: Journal of Clinical Microbiology Publication Type: Peer
Reviewed Journal Publication Acceptance Date: November 27, 2015 Publication
Date: N/A
Interpretive Summary: Chronic Wasting Disease (CWD), a fatal
neurodegenerative disease that occurs in farmed and wild cervids (deer and elk)
of North America, is a transmissible spongiform encephalopathy (TSE). TSEs are
caused by infectious proteins called prions that are resistant to various
methods of decontamination and environmental degradation. Early diagnosis of CWD
in wild and captive herds would be very helpful to controlling the spread of
CWD, for which there are not yet any preventative or treatment measures
available. The purpose of this study was to test a laboratory method of prion
detection (real-time Quaking Induced Conversion; RT-QuIC) that has the potential
to detect very low levels of infectious prions in samples collected from live
animals against the gold standard diagnostic where abnormal prion in tissues is
stained on a microscope slide. This study reports that RT-QuIC detects more
cases of CWD than standard methods, but also can identify a small number of
animals without CWD as being positive. In the case of CWD, where it is likely
that large numbers of animals within a herd may be positive, misidentifying a
negative as a positive may have less of an impact than in the case of other
prion diseases such as bovine spongiform encephalopathy considering that this
test allows testing much larger numbers of samples with a faster turn around
time than traditional methods. This information could have an impact on
regulatory and wildlife officials developing plans to reduce or eliminate CWD
and cervid farmers that want to ensure that their herd remains CWD-free.
Technical Abstract: Chronic wasting disease (CWD), a transmissible spongiform
encephalopathy of cervids, was first documented nearly fifty years ago in
Colorado and Wyoming and has since spread to cervids in 23 states, 2 Canadian
provinces, and the Republic of Korea. The increasing expansion of this disease
makes the development of sensitive diagnostic assays and antemortem sampling
techniques crucial for the mitigation of spread; this is especially true in
cases of relocation/reintroduction of farmed or free-ranging deer and elk, or
surveillance studies in private or protected herds where depopulation may be
contraindicated. This study sought to evaluate the sensitivity of the real-time
quaking-induced conversion (RT-QuIC) assay in samples collected antemortem.
Antemortem findings were then compared to results from ante- and postmortem
samples evaluated using the current gold standard diagnostic assay,
immunohistochemistry (IHC). Recto-anal mucosal associated lymphoid tissue
(RAMALT) biopsies and nasal brush collections from three separate herds of
farmed white-tailed deer (n=409) were evaluated, along with standard postmortem
microscopic analysis of brainstem at the level of the obex and retropharyngeal
lymph nodes. We hypothesized the sensitivity of RT-QuIC would be comparable to
IHC in antemortem tissues, and would correlate with both genotype and stage of
clinical disease. ***Our results showed that RAMALT testing by RT-QuIC had the
highest sensitivity (69.8%) when compared to postmortem testing. This data
suggests that RT-QuIC, like IHC, is a fairly sensitive assay for detection of
CWD prions in rectal biopsies and other antemortem samples, and with further
investigation has potential for large scale and rapid automated testing for CWD
diagnosis.
Research Project: Transmission, Differentiation, and Pathobiology of
Transmissible Spongiform Encephalopathies 2015 Annual Report
1a.Objectives (from AD-416): 1. Investigate the pathobiology of atypical
transmissible spongiform encephalopathies (TSEs) in natural hosts. A.
Investigate the pathobiology of atypical scrapie. B. Investigate the
pathobiology of atypical bovine spongiform encephalopathy (BSE). 2. Investigate
the horizontal transmission of TSEs. A. Assess the horizontal transmission of
sheep scrapie in the absence of lambing. B. Determine routes of transmission in
chronic wasting disease (CWD) infected premises. C. Assess oral transmission of
CWD in reindeer. 3. Investigate determinants of CWD persistence. A. Determine
CWD host range using natural routes of transmission. B. Investigate the
pathobiology of CWD.
1b.Approach (from AD-416): The studies will focus on three animal
transmissible spongiform encephalopathy (TSE) agents found in the United States:
bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; and chronic
wasting disease (CWD) of deer, elk, and moose. The research will address sites
of accumulation, routes of infection, environmental persistence, and ante mortem
diagnostics with an emphasis on controlled conditions and natural routes of
infection. Techniques used will include clinical exams, histopathology,
immunohistochemistry and biochemical analysis of proteins. The enhanced
knowledge gained from this work will help mitigate the potential for
unrecognized epidemic expansions of these diseases in populations of animals
that could either directly or indirectly affect food animals.
3.Progress Report: Research efforts directed toward meeting objective 1 of
our project plan include work in previous years starting with the inoculation of
animals for studies designed to address the pathobiology of atypical scrapie,
atypical bovine spongiform encephalopathy (BSE), as well as a genetic version of
BSE. Post-mortem examination of the animals inoculated with atypical scrapie has
been initiated and laboratory analysis of the tissues is ongoing. Atypical BSE
animals have developed disease and evaluation of the samples is currently
underway. Animals inoculated with a genetic version of BSE have developed
disease with a manuscript reporting these results was published (2012), and
additional laboratory comparisons of genetic BSE to atypical and classical BSE
are ongoing. In addition, we have investigated the possibility that atypical
scrapie was present earlier than previously detected in the national flock by
analyzing archived field isolates using methods that were unavailable at the
time of original diagnosis. Sample quality was sufficiently degraded that modern
methods, beyond those applied to the tissues at the time the tissues were
archived, were not suitable for evaluation. In research pertaining to objective
2, "Investigate the horizontal transmission of TSEs", we have initiated a study
to determine if cohousing non-lambing scrapie inoculated sheep is sufficient to
transmit scrapie to neonatal lambs. At this time, scrapie free ewes have lambed
in the presence of scrapie inoculated animals and the lambs are cohoused with
these inoculated animals.
4.Accomplishments 1. Changes in retinal function in cattle can be used to
identify different types of bovine spongiform encephalopathy (BSE). BSE belongs
to a group of fatal, transmissible protein misfolding diseases known as
transmissible spongiform encephalopathies (TSEs). Like other protein misfolding
diseases including Parkinson's disease and Alzheimer's disease, TSEs are
generally not diagnosed until the onset of disease after the appearance of
unequivocal clinical signs. As such, identification of the earliest clinical
signs of disease may facilitate diagnosis. The retina is the most accessible
part of the central nervous system. ARS scientist in Ames IA described
antemortem changes in retinal function and thickness that are detectable in BSE
inoculated animals up to 11 months prior to the appearance of any other signs of
clinical disease. Differences in the severity of these clinical signs reflect
the amount of PrPSc accumulation in the retina and the resulting inflammatory
response of the tissue. These results are the earliest reported clinical signs
associated with TSE infection and provide a basis for understanding the
pathology and evaluating therapeutic interventions. Further, this work shows
that High-type BSE and classical BSE can be differentiated by eye examination
alone, the first time BSE strains have been differentiable in a live animal.
2. Sheep genetics influences the susceptibility of sheep to scrapie. Sheep
scrapie is a transmissible spongiform encephalopathy that can be transmitted
between affected animals resulting in significant economic losses in affected
flocks. The prion protein gene (PRNP) profoundly influences the susceptibility
of sheep to the scrapie agent and the tissue levels and distribution of PrPSc in
affected sheep. In this study, sheep of 3 different prion genetic types (denoted
VRQ/VRQ, VRQ/ARR and ARQ/ARR) were inoculated and subsequently euthanized upon
onset of disease. Disease aspects were uniform across genotypes and consistent
with manifestations of classical scrapie. Mean survival time differences were
associated with the genetic type such that VRQ/VRQ sheep survived 18 months,
whereas VRQ/ARR and ARQ/ARR sheep survived 60 and 56 months, respectively.
Microscopic evaluation revealed similar accumulations in central nervous system
tissues regardless of host genetic type. PrPSc in lymphoid tissue was
consistently abundant in VRQ/VRQ, present but confined to tonsil or
retropharyngeal lymph node in 4/5 VRQ/ARR, and totally absent in ARQ/ARR sheep.
The results of this study demonstrate the susceptibility of sheep with the
ARQ/ARR genotype to scrapie by the intracranial inoculation route with PrPSc
accumulation in CNS tissues, but prolonged incubation times and lack of PrPSc in
lymphoid tissue. These results are important for science based policy with
regard to testing of sheep for scrapie where some live animal testing is
conducted using lymphoid tissues which would not detect scrapie in some specific
genetic types which could limit the national scrapie eradication program.
Review Publications Greenlee J.J. 2014. The prion diseases of animals. In:
McManus, L.M., Mitchell, R.N., editors. Pathobiology of Human Disease. San
Diego: Elsevier. p. 1124-1133.
Greenlee, J.J., Kunkle, R.A., Richt, J.A., Nicholson, E.M., Hamir, A.N.
2014. Lack of prion accumulation in lymphoid tissues of PRNP ARQ/ARR sheep
intracranially inoculated with the agent of scrapie. PLoS One. 9(9):e108029.
Greenlee, J.J., West Greenlee, M.,H. 2015. The transmissible spongiform
encephalopathies of livestock. ILAR Journal. 56(1):7-25.
Munoz-Gutierrez, J.F., Schneider, D.A., Baszler, T.V., Dinkel, K.D.,
Greenlee, J.J., Nicholson, E.M., Stanton, J.J. 2015. hTERT-immortalized ovine
microglia propagate natural scrapie isolates. Virus Research. 198:35-43.
Nicholson, E.M. 2015. Detection of the disease-associated form of the prion
protein in biological samples. Bioanalysis. 7(2):253-261.
West Greenlee, M.H., Smith, J.D., Platt, E.M., Juarez, J.R., Timms, L.L,
Greenlee, J.J. 2015. Changes in retinal function and morphology are early
clinical signs of disease in cattle with bovine spongiform encephalopathy. PLoS
ONE. 10(3):e0119431.
Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E.,
Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C.,
Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J.
2015. Transmission of scrapie prions to primate after an extended silent
incubation period. Scientific Reports. 5:11573.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
***Title: Transmission of chronic wasting disease to sentinel reindeer
(Rangifer tarandus tarandus)
Authors
item Moore, S - item Kunkle, Robert item Nicholson, Eric item Richt,
Juergen item Hamir, Amirali item Waters, Wade item Greenlee, Justin
Submitted to: American College of Veterinary Pathologists Meeting
Publication Type: Abstract Only Publication Acceptance Date: August 12, 2015
Publication Date: N/A
Technical Abstract:
Chronic wasting disease (CWD) is a naturally-occurring, fatal
neurodegenerative disease of North American cervids. Reindeer (Rangifer tarandus
tarandus) are susceptible to CWD following oral challenge, but CWD has not been
reported in free-ranging caribou (Rangifer tarandus caribou) or farmed reindeer.
Potential contact between CWD-affected cervids and Rangifer species that are
free-ranging or co-housed on farms presents a potential risk of CWD
transmission. The aims of this study were to 1) investigate the transmission of
CWD from white-tailed deer (Odocoileus virginianus; CWD-wtd), mule deer
(Odocoileus hemionus; CWD-md), or elk (Cervus elaphus nelsoni; CWD-elk) to
reindeer via the intracranial route, and 2) to assess for direct and indirect
horizontal transmission to non-inoculated sentinels. Three groups of 5 reindeer
fawns were challenged intracranially with CWD-wtd, CWD-md, or CWD-elk. Two years
after challenge of inoculated reindeer, non-inoculated control reindeer were
introduced into the same pen as the CWD-wtd inoculated reindeer (n=4) or into a
pen adjacent to the CWD-md inoculated reindeer (n=2). Reindeer were allowed to
develop clinical disease. At death/euthanasia a complete necropsy examination
was performed, including immunohistochemical testing of tissues for
disease-associated CWD prion protein (PrP-CWD). Intracranially challenged
reindeer developed clinical disease from 21 months post-inoculation (MPI).
PrP-CWD was detected in 5/6 sentinel reindeer although only 2/6 developed
clinical disease during the study period (<57 div="" mpi="">
***We have shown that reindeer are susceptible to CWD from various cervid
sources and can transmit CWD to naive reindeer both directly and indirectly.
Last Modified: 12/3/2015
***PrP-CWD was detected in 5/6 sentinel reindeer although only 2/6
developed clinical disease during the study period (<57 div="" mpi="">
***We have shown that reindeer are susceptible to CWD from various cervid
sources and can transmit CWD to naive reindeer both directly and indirectly.
Tuesday, September 29, 2015
*** Transmission of chronic wasting disease to sentinel reindeer (Rangifer
tarandus tarandus) can transmit CWD to naive reindeer both directly and
indirectly
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
*** Infectious agent of sheep scrapie may persist in the environment for at
least 16 years ***
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
*** Spraker suggested an interesting explanation for the occurrence of CWD.
The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr.
Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at
this site. When deer were introduced to the pens they occupied ground that had
previously been occupied by sheep.
PL1
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 ;
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 ***
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.
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced
into Great Britain? A Qualitative Risk Assessment October 2012
snip...
In the USA, under the Food and Drug Administration’s BSE Feed Regulation
(21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin)
from deer and elk is prohibited for use in feed for ruminant animals. With
regards to feed for non-ruminant animals, under FDA law, CWD positive deer may
not be used for any animal feed or feed ingredients. For elk and deer considered
at high risk for CWD, the FDA recommends that these animals do not enter the
animal feed system. However, this recommendation is guidance and not a
requirement by law.
Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD
eradication zones and
2) deer and elk that at some time during the 60-month period prior to
slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive
animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from
the USA to GB can not be determined, however, as it is not specified in TRACES.
It may constitute a small percentage of the 8412 kilos of non-fish origin
processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible
risk___ that (nonruminant) animal feed and pet food containing deer and/or elk
protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data
on the amount of deer and/or elk protein possibly being imported in these
products.
snip...
36% in 2007 (Almberg et al., 2011). In such areas, population declines of
deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of
Colorado, the prevalence can be as high as 30% (EFSA, 2011). The clinical signs
of CWD in affected adults are weight loss and behavioural changes that can span
weeks or months (Williams, 2005). In addition, signs might include excessive
salivation, behavioural alterations including a fixed stare and changes in
interaction with other animals in the herd, and an altered stance (Williams,
2005). These signs are indistinguishable from cervids experimentally infected
with bovine spongiform encephalopathy (BSE). Given this, if CWD was to be
introduced into countries with BSE such as GB, for example, infected deer
populations would need to be tested to differentiate if they were infected with
CWD or BSE to minimise the risk of BSE entering the human food-chain via
affected venison.
snip...
The rate of transmission of CWD has been reported to be as high as 30% and
can approach 100% among captive animals in endemic areas (Safar et al.,
2008).
snip...
In summary, in endemic areas, there is a medium probability that the soil
and surrounding environment is contaminated with CWD prions and in a
bioavailable form. In rural areas where CWD has not been reported and deer are
present, there is a greater than negligible risk the soil is contaminated with
CWD prion.
snip...
In summary, given the volume of tourists, hunters and servicemen moving
between GB and North America, the probability of at least one person travelling
to/from a CWD affected area and, in doing so, contaminating their clothing,
footwear and/or equipment prior to arriving in GB is greater than negligible.
For deer hunters, specifically, the risk is likely to be greater given the
increased contact with deer and their environment. However, there is significant
uncertainty associated with these estimates.
snip...
Therefore, it is considered that farmed and park deer may have a higher
probability of exposure to CWD transferred to the environment than wild deer
given the restricted habitat range and higher frequency of contact with tourists
and returning GB residents.
snip...
Saturday, January 31, 2015
European red deer (Cervus elaphus elaphus) are susceptible to Bovine
Spongiform Encephalopathy BSE by Oral Alimentary route
I strenuously once again urge the FDA and its industry constituents, to
make it MANDATORY that all ruminant feed be banned to all ruminants, and this
should include all cervids as soon as possible for the following
reasons...
======
In the USA, under the Food and Drug Administrations BSE Feed Regulation (21
CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from
deer and elk is prohibited for use in feed for ruminant animals. With regards to
feed for non-ruminant animals, under FDA law, CWD positive deer may not be used
for any animal feed or feed ingredients. For elk and deer considered at high
risk for CWD, the FDA recommends that these animals do not enter the animal feed
system.
***However, this recommendation is guidance and not a requirement by law.
======
31 Jan 2015 at 20:14 GMT
*** Ruminant feed ban for cervids in the United States? ***
31 Jan 2015 at 20:14 GMT
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Scrapie transmits to white-tailed deer by the oral route and has a
molecular profile similar to chronic wasting disease
Authors
item Greenlee, Justin item Moore, S - item Smith, Jodi - item Kunkle,
Robert item West Greenlee, M -
Submitted to: American College of Veterinary Pathologists Meeting
Publication Type: Abstract Only Publication Acceptance Date: August 12, 2015
Publication Date: N/A Technical Abstract: The purpose of this work was to
determine susceptibility of white-tailed deer (WTD) to the agent of sheep
scrapie and to compare the resultant PrPSc to that of the original inoculum and
chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure
(concurrent oral and intranasal (IN); n=5) with a US scrapie isolate. All
scrapie-inoculated deer had evidence of PrPSc accumulation. PrPSc was detected
in lymphoid tissues at preclinical time points, and deer necropsied after 28
months post-inoculation had clinical signs, spongiform encephalopathy, and
widespread distribution of PrPSc in neural and lymphoid tissues. Western
blotting (WB) revealed PrPSc with 2 distinct molecular profiles. WB on cerebral
cortex had a profile similar to the original scrapie inoculum, whereas WB of
brainstem, cerebellum, or lymph nodes revealed PrPSc with a higher profile
resembling CWD. Homogenates with the 2 distinct profiles from WTD with clinical
scrapie were further passaged to mice expressing cervid prion protein and
intranasally to sheep and WTD. In cervidized mice, the two inocula have distinct
incubation times. Sheep inoculated intranasally with WTD derived scrapie
developed disease, but only after inoculation with the inoculum that had a
scrapie-like profile. The WTD study is ongoing, but deer in both inoculation
groups are positive for PrPSc by rectal mucosal biopsy. In summary, this work
demonstrates that WTD are susceptible to the agent of scrapie, two distinct
molecular profiles of PrPSc are present in the tissues of affected deer, and
inoculum of either profile readily passes to deer.
White-tailed Deer are Susceptible to Scrapie by Natural Route of Infection
Jodi D. Smith, Justin J. Greenlee, and Robert A. Kunkle; Virus and Prion
Research Unit, National Animal Disease Center, USDA-ARS
Interspecies transmission studies afford the opportunity to better
understand the potential host range and origins of prion diseases. Previous
experiments demonstrated that white-tailed deer are susceptible to sheep-derived
scrapie by intracranial inoculation. The purpose of this study was to determine
susceptibility of white-tailed deer to scrapie after a natural route of
exposure. Deer (n=5) were inoculated by concurrent oral (30 ml) and intranasal
(1 ml) instillation of a 10% (wt/vol) brain homogenate derived from a sheep
clinically affected with scrapie. Non-inoculated deer were maintained as
negative controls. All deer were observed daily for clinical signs. Deer were
euthanized and necropsied when neurologic disease was evident, and tissues were
examined for abnormal prion protein (PrPSc) by immunohistochemistry (IHC) and
western blot (WB). One animal was euthanized 15 months post-inoculation (MPI)
due to an injury. At that time, examination of obex and lymphoid tissues by IHC
was positive, but WB of obex and colliculus were negative. Remaining deer
developed clinical signs of wasting and mental depression and were necropsied
from 28 to 33 MPI. Tissues from these deer were positive for scrapie by IHC and
WB. Tissues with PrPSc immunoreactivity included brain, tonsil, retropharyngeal
and mesenteric lymph nodes, hemal node, Peyer’s patches, and spleen. This work
demonstrates for the first time that white-tailed deer are susceptible to sheep
scrapie by potential natural routes of inoculation. In-depth analysis of tissues
will be done to determine similarities between scrapie in deer after
intracranial and oral/intranasal inoculation and chronic wasting disease
resulting from similar routes of inoculation.
see full text ;
PO-039: A comparison of scrapie and chronic wasting disease in white-tailed
deer
Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture;
Agricultural Research Service, National Animal Disease Center; Ames, IA USA
White-tailed deer are susceptible to the agent of sheep scrapie by
intracerebral inoculation
snip...
It is unlikely that CWD will be eradicated from free-ranging cervids, and
the disease is likely to continue to spread geographically [10]. However, the
potential that white-tailed deer may be susceptible to sheep scrapie by a
natural route presents an additional confounding factor to halting the spread of
CWD. This leads to the additional speculations that
1) infected deer could serve as a reservoir to infect sheep with scrapie
offering challenges to scrapie eradication efforts and
2) CWD spread need not remain geographically confined to current endemic
areas, but could occur anywhere that sheep with scrapie and susceptible cervids
cohabitate.
This work demonstrates for the first time that white-tailed deer are
susceptible to sheep scrapie by intracerebral inoculation with a high attack
rate and that the disease that results has similarities to CWD. These
experiments will be repeated with a more natural route of inoculation to
determine the likelihood of the potential transmission of sheep scrapie to
white-tailed deer. If scrapie were to occur in white-tailed deer, results of
this study indicate that it would be detected as a TSE, but may be difficult to
differentiate from CWD without in-depth biochemical analysis.
2012
PO-039: A comparison of scrapie and chronic wasting disease in white-tailed
deer
Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture;
Agricultural Research Service, National Animal Disease Center; Ames, IA USA
snip...
The results of this study suggest that there are many similarities in the
manifestation of CWD and scrapie in WTD after IC inoculation including early and
widespread presence of PrPSc in lymphoid tissues, clinical signs of depression
and weight loss progressing to wasting, and an incubation time of 21-23 months.
Moreover, western blots (WB) done on brain material from the obex region have a
molecular profile similar to CWD and distinct from tissues of the cerebrum or
the scrapie inoculum. However, results of microscopic and IHC examination
indicate that there are differences between the lesions expected in CWD and
those that occur in deer with scrapie: amyloid plaques were not noted in any
sections of brain examined from these deer and the pattern of immunoreactivity
by IHC was diffuse rather than plaque-like.
*** After a natural route of exposure, 100% of WTD were susceptible to
scrapie.
Deer developed clinical signs of wasting and mental depression and were
necropsied from 28 to 33 months PI. Tissues from these deer were positive for
PrPSc by IHC and WB. Similar to IC inoculated deer, samples from these deer
exhibited two different molecular profiles: samples from obex resembled CWD
whereas those from cerebrum were similar to the original scrapie inoculum. On
further examination by WB using a panel of antibodies, the tissues from deer
with scrapie exhibit properties differing from tissues either from sheep with
scrapie or WTD with CWD. Samples from WTD with CWD or sheep with scrapie are
strongly immunoreactive when probed with mAb P4, however, samples from WTD with
scrapie are only weakly immunoreactive. In contrast, when probed with mAb’s 6H4
or SAF 84, samples from sheep with scrapie and WTD with CWD are weakly
immunoreactive and samples from WTD with scrapie are strongly positive. This
work demonstrates that WTD are highly susceptible to sheep scrapie, but on first
passage, scrapie in WTD is differentiable from CWD.
2011
*** After a natural route of exposure, 100% of white-tailed deer were
susceptible to scrapie.
White-tailed Deer are Susceptible to Scrapie by Natural Route of Infection
Jodi D. Smith, Justin J. Greenlee, and Robert A. Kunkle; Virus and Prion
Research Unit, National Animal Disease Center, USDA-ARS
Interspecies transmission studies afford the opportunity to better
understand the potential host range and origins of prion diseases. Previous
experiments demonstrated that white-tailed deer are susceptible to sheep-derived
scrapie by intracranial inoculation. The purpose of this study was to determine
susceptibility of white-tailed deer to scrapie after a natural route of
exposure. Deer (n=5) were inoculated by concurrent oral (30 ml) and intranasal
(1 ml) instillation of a 10% (wt/vol) brain homogenate derived from a sheep
clinically affected with scrapie. Non-inoculated deer were maintained as
negative controls. All deer were observed daily for clinical signs. Deer were
euthanized and necropsied when neurologic disease was evident, and tissues were
examined for abnormal prion protein (PrPSc) by immunohistochemistry (IHC) and
western blot (WB). One animal was euthanized 15 months post-inoculation (MPI)
due to an injury. At that time, examination of obex and lymphoid tissues by IHC
was positive, but WB of obex and colliculus were negative. Remaining deer
developed clinical signs of wasting and mental depression and were necropsied
from 28 to 33 MPI. Tissues from these deer were positive for scrapie by IHC and
WB. Tissues with PrPSc immunoreactivity included brain, tonsil, retropharyngeal
and mesenteric lymph nodes, hemal node, Peyer’s patches, and spleen. This work
demonstrates for the first time that white-tailed deer are susceptible to sheep
scrapie by potential natural routes of inoculation. In-depth analysis of tissues
will be done to determine similarities between scrapie in deer after
intracranial and oral/intranasal inoculation and chronic wasting disease
resulting from similar routes of inoculation.
see full text ;
PL1
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 ;
98 | Veterinary Record | January 24, 2015
EDITORIAL
Scrapie: a particularly persistent pathogen
Cristina Acín
Resistant prions in the environment have been the sword of Damocles for
scrapie control and eradication. Attempts to establish which physical and
chemical agents could be applied to inactivate or moderate scrapie infectivity
were initiated in the 1960s and 1970s,with the first study of this type focusing
on the effect of heat treatment in reducing prion infectivity (Hunter and
Millson 1964). Nowadays, most of the chemical procedures that aim to inactivate
the prion protein are based on the method developed by Kimberlin and
collaborators (1983). This procedure consists of treatment with 20,000 parts per
million free chlorine solution, for a minimum of one hour, of all surfaces that
need to be sterilised (in laboratories, lambing pens, slaughterhouses, and so
on). Despite this, veterinarians and farmers may still ask a range of questions,
such as ‘Is there an official procedure published somewhere?’ and ‘Is there an
international organisation which recommends and defines the exact method of
scrapie decontamination that must be applied?’
From a European perspective, it is difficult to find a treatment that could
be applied, especially in relation to the disinfection of surfaces in lambing
pens of affected flocks. A 999/2001 EU regulation on controlling spongiform
encephalopathies (European Parliament and Council 2001) did not specify a
particular decontamination measure to be used when an outbreak of scrapie is
diagnosed. There is only a brief recommendation in Annex VII concerning the
control and eradication of transmissible spongiform encephalopathies (TSE
s).
Chapter B of the regulation explains the measures that must be applied if
new caprine animals are to be introduced to a holding where a scrapie outbreak
has previously been diagnosed. In that case, the statement indicates that
caprine animals can be introduced ‘provided that a cleaning and disinfection of
all animal housing on the premises has been carried out following
destocking’.
Issues around cleaning and disinfection are common in prion prevention
recommendations, but relevant authorities, veterinarians and farmers may have
difficulties in finding the specific protocol which applies. The European Food
and Safety Authority (EFSA ) published a detailed report about the efficacy of
certain biocides, such as sodium hydroxide, sodium hypochlorite, guanidine and
even a formulation of copper or iron metal ions in combination with hydrogen
peroxide, against prions (EFSA 2009). The report was based on scientific
evidence (Fichet and others 2004, Lemmer and others 2004, Gao and others 2006,
Solassol and others 2006) but unfortunately the decontamination measures were
not assessed under outbreak conditions.
The EFSA Panel on Biological Hazards recently published its conclusions on
the scrapie situation in the EU after 10 years of monitoring and control of the
disease in sheep and goats (EFSA 2014), and one of the most interesting findings
was the Icelandic experience regarding the effect of disinfection in scrapie
control. The Icelandic plan consisted of: culling scrapie-affected sheep or the
whole flock in newly diagnosed outbreaks; deep cleaning and disinfection of
stables, sheds, barns and equipment with high pressure washing followed by
cleaning with 500 parts per million of hypochlorite; drying and treatment with
300 ppm of iodophor; and restocking was not permitted for at least two years.
Even when all of these measures were implemented, scrapie recurred on several
farms, indicating that the infectious agent survived for years in the
environment, even as many as 16 years after restocking (Georgsson and others
2006).
In the rest of the countries considered in the EFSA (2014) report,
recommendations for disinfection measures were not specifically defined at the
government level. In the report, the only recommendation that is made for sheep
is repopulation with sheep with scrapie-resistant genotypes. This reduces the
risk of scrapie recurrence but it is difficult to know its effect on the
infection.
Until the EFSA was established (in May 2003), scientific opinions about TSE
s were provided by the Scientific Steering Committee (SSC) of the EC, whose
advice regarding inactivation procedures focused on treating animal waste at
high temperatures (150°C for three hours) and high pressure alkaline hydrolysis
(SSC 2003). At the same time, the TSE Risk Management Subgroup of the Advisory
Committee on Dangerous Pathogens (ACDP) in the UK published guidance on safe
working and the prevention of TSE infection. Annex C of the ACDP report
established that sodium hypochlorite was considered to be effective, but only if
20,000 ppm of available chlorine was present for at least one hour, which has
practical limitations such as the release of chlorine gas, corrosion,
incompatibility with formaldehyde, alcohols and acids, rapid inactivation of its
active chemicals and the stability of dilutions (ACDP 2009).
In an international context, the World Organisation for Animal Health (OIE)
does not recommend a specific disinfection protocol for prion agents in its
Terrestrial Code or Manual. Chapter 4.13 of the Terrestrial Code, General
recommendations on disinfection and disinsection (OIE 2014), focuses on
foot-and-mouth disease virus, mycobacteria and Bacillus anthracis, but not on
prion disinfection. Nevertheless, the last update published by the OIE on bovine
spongiform encephalopathy (OIE 2012) indicates that few effective
decontamination techniques are available to inactivate the agent on surfaces,
and recommends the removal of all organic material and the use of sodium
hydroxide, or a sodium hypochlorite solution containing 2 per cent available
chlorine, for more than one hour at 20ºC.
The World Health Organization outlines guidelines for the control of TSE s,
and also emphasises the importance of mechanically cleaning surfaces before
disinfection with sodium hydroxide or sodium hypochlorite for one hour (WHO
1999).
Finally, the relevant agencies in both Canada and the USA suggest that the
best treatments for surfaces potentially contaminated with prions are sodium
hydroxide or sodium hypochlorite at 20,000 ppm. This is a 2 per cent solution,
while most commercial household bleaches contain 5.25 per cent sodium
hypochlorite. It is therefore recommended to dilute one part 5.25 per cent
bleach with 1.5 parts water (CDC 2009, Canadian Food Inspection Agency
2013).
So what should we do about disinfection against prions? First, it is
suggested that a single protocol be created by international authorities to
homogenise inactivation procedures and enable their application in all
scrapie-affected countries. Sodium hypochlorite with 20,000 ppm of available
chlorine seems to be the procedure used in most countries, as noted in a paper
summarised on p 99 of this issue of Veterinary Record (Hawkins and others 2015).
But are we totally sure of its effectiveness as a preventive measure in a
scrapie outbreak? Would an in-depth study of the recurrence of scrapie disease
be needed?
What we can conclude is that, if we want to fight prion diseases, and
specifically classical scrapie, we must focus on the accuracy of diagnosis,
monitoring and surveillance; appropriate animal identification and control of
movements; and, in the end, have homogeneous and suitable protocols to
decontaminate and disinfect lambing barns, sheds and equipment available to
veterinarians and farmers. Finally, further investigations into the resistance
of prion proteins in the diversity of environmental surfaces are required.
References
snip...
98 | Veterinary Record | January 24, 2015
Persistence of ovine scrapie infectivity in a farm environment following
cleaning and decontamination
Steve A. C. Hawkins, MIBiol, Pathology Department1, Hugh A. Simmons, BVSc
MRCVS, MBA, MA Animal Services Unit1, Kevin C. Gough, BSc, PhD2 and Ben C.
Maddison, BSc, PhD3 + Author Affiliations
1Animal and Plant Health Agency, Woodham Lane, New Haw, Addlestone, Surrey
KT15 3NB, UK 2School of Veterinary Medicine and Science, The University of
Nottingham, Sutton Bonington, Loughborough, Leicestershire LE12 5RD, UK 3ADAS
UK, School of Veterinary Medicine and Science, The University of Nottingham,
Sutton Bonington, Loughborough, Leicestershire LE12 5RD, UK E-mail for
correspondence: ben.maddison@adas.co.uk Abstract Scrapie of sheep/goats and
chronic wasting disease of deer/elk are contagious prion diseases where
environmental reservoirs are directly implicated in the transmission of disease.
In this study, the effectiveness of recommended scrapie farm decontamination
regimens was evaluated by a sheep bioassay using buildings naturally
contaminated with scrapie. Pens within a farm building were treated with either
20,000 parts per million free chorine solution for one hour or were treated with
the same but were followed by painting and full re-galvanisation or replacement
of metalwork within the pen. Scrapie susceptible lambs of the PRNP genotype
VRQ/VRQ were reared within these pens and their scrapie status was monitored by
recto-anal mucosa-associated lymphoid tissue. All animals became infected over
an 18-month period, even in the pen that had been subject to the most stringent
decontamination process. These data suggest that recommended current guidelines
for the decontamination of farm buildings following outbreaks of scrapie do
little to reduce the titre of infectious scrapie material and that environmental
recontamination could also be an issue associated with these premises.
SNIP...
Discussion
Thorough pressure washing of a pen had no effect on the amount of
bioavailable scrapie infectivity (pen B). The routine removal of prions from
surfaces within a laboratory setting is treatment for a minimum of one hour with
20,000 ppm free chlorine, a method originally based on the use of brain
macerates from infected rodents to evaluate the effectiveness of decontamination
(Kimberlin and others 1983). Further studies have also investigated the
effectiveness of hypochlorite disinfection of metal surfaces to simulate the
decontamination of surgical devices within a hospital setting. Such treatments
with hypochlorite solution were able to reduce infectivity by 5.5 logs to lower
than the sensitivity of the bioassay used (Lemmer and others 2004). Analogous
treatment of the pen surfaces did not effectively remove the levels of scrapie
infectivity over that of the control pens, indicating that this method of
decontamination is not effective within a farm setting. This may be due to the
high level of biological matrix that is present upon surfaces within the farm
environment, which may reduce the amount of free chlorine available to
inactivate any infectious prion. Remarkably 1/5 sheep introduced into pen D had
also became scrapie positive within nine months, with all animals in this pen
being RAMALT positive by 18 months of age. Pen D was no further away from the
control pen (pen A) than any of the other pens within this barn. Localised hot
spots of infectivity may be present within scrapie-contaminated environments,
but it is unlikely that pen D area had an amount of scrapie contamination that
was significantly different than the other areas within this building.
Similarly, there were no differences in how the biosecurity of pen D was
maintained, or how this pen was ventilated compared with the other pens. This
observation, perhaps, indicates the slower kinetics of disease uptake within
this pen and is consistent with a more thorough prion removal and
recontamination. These observations may also account for the presence of
inadvertent scrapie cases within other studies, where despite stringent
biosecurity, control animals have become scrapie positive during challenge
studies using barns that also housed scrapie-affected animals (Ryder and others
2009). The bioassay data indicate that the exposure of the sheep to a farm
environment after decontamination efforts thought to be effective in removing
scrapie is sufficient for the animals to become infected with scrapie. The main
exposure routes within this scenario are likely to be via the oral route, during
feeding and drinking, and respiratory and conjunctival routes. It has been
demonstrated that scrapie infectivity can be efficiently transmitted via the
nasal route in sheep (Hamir and others 2008), as is the case for CWD in both
murine models and in white-tailed deer (Denkers and others 2010, 2013).
Recently, it has also been demonstrated that CWD prions presented as dust when
bound to the soil mineral montmorillonite can be infectious via the nasal route
(Nichols and others 2013). When considering pens C and D, the actual source of
the infectious agent in the pens is not known, it is possible that biologically
relevant levels of prion survive on surfaces during the decontamination regimen
(pen C). With the use of galvanising and painting (pen D) covering and sealing
the surface of the pen, it is possible that scrapie material recontaminated the
pens by the movement of infectious prions contained within dusts originating
from other parts of the barn that were not decontaminated or from other areas of
the farm.
Given that scrapie prions are widespread on the surfaces of affected farms
(Maddison and others 2010a), irrespective of the source of the infectious prions
in the pens, this study clearly highlights the difficulties that are faced with
the effective removal of environmentally associated scrapie infectivity. This is
likely to be paralleled in CWD which shows strong similarities to scrapie in
terms of both the dissemination of prions into the environment and the facile
mode of disease transmission. These data further contribute to the understanding
that prion diseases can be highly transmissible between susceptible individuals
not just by direct contact but through highly stable environmental reservoirs
that are refractory to decontamination.
The presence of these environmentally associated prions in farm buildings
make the control of these diseases a considerable challenge, especially in
animal species such as goats where there is lack of genetic resistance to
scrapie and, therefore, no scope to re-stock farms with animals that are
resistant to scrapie.
Scrapie Sheep Goats Transmissible spongiform encephalopathies (TSE)
Accepted October 12, 2014. Published Online First 31 October 2014
Monday, November 3, 2014
Persistence of ovine scrapie infectivity in a farm environment following
cleaning and decontamination
PPo3-22:
Detection of Environmentally Associated PrPSc on a Farm with Endemic
Scrapie
Ben C. Maddison,1 Claire A. Baker,1 Helen C. Rees,1 Linda A. Terry,2 Leigh
Thorne,2 Susan J. Belworthy2 and Kevin C. Gough3 1ADAS-UK LTD; Department of
Biology; University of Leicester; Leicester, UK; 2Veterinary Laboratories
Agency; Surry, KT UK; 3Department of Veterinary Medicine and Science; University
of Nottingham; Sutton Bonington, Loughborough UK
Key words: scrapie, evironmental persistence, sPMCA
Ovine scrapie shows considerable horizontal transmission, yet the routes of
transmission and specifically the role of fomites in transmission remain poorly
defined. Here we present biochemical data demonstrating that on a
scrapie-affected sheep farm, scrapie prion contamination is widespread. It was
anticipated at the outset that if prions contaminate the environment that they
would be there at extremely low levels, as such the most sensitive method
available for the detection of PrPSc, serial Protein Misfolding Cyclic
Amplification (sPMCA), was used in this study. We investigated the distribution
of environmental scrapie prions by applying ovine sPMCA to samples taken from a
range of surfaces that were accessible to animals and could be collected by use
of a wetted foam swab. Prion was amplified by sPMCA from a number of these
environmental swab samples including those taken from metal, plastic and wooden
surfaces, both in the indoor and outdoor environment. At the time of sampling
there had been no sheep contact with these areas for at least 20 days prior to
sampling indicating that prions persist for at least this duration in the
environment. These data implicate inanimate objects as environmental reservoirs
of prion infectivity which are likely to contribute to disease transmission.
HIGHEST INFECTION RATE ON SEVERAL CWD CONFIRMED CAPTIVES
CHRONIC WASTING DISEASE CWD WISCONSIN Almond Deer (Buckhorn Flats) Farm
Update DECEMBER 2011
The CWD infection rate was nearly 80%, the highest ever in a North American
captive herd.
RECOMMENDATION: That the Board approve the purchase of 80 acres of land for
$465,000 for the Statewide Wildlife Habitat Program in Portage County and
approve the restrictions on public use of the site.
SUMMARY:
For Immediate Release Thursday, October 2, 2014
Dustin Vande Hoef 515/281-3375 or 515/326-1616 (cell) or
Dustin.VandeHoef@IowaAgriculture.gov
*** TEST RESULTS FROM CAPTIVE DEER HERD WITH CHRONIC WASTING DISEASE
RELEASED 79.8 percent of the deer tested positive for the disease
DES MOINES – The Iowa Department of Agriculture and Land Stewardship today
announced that the test results from the depopulation of a quarantined captive
deer herd in north-central Iowa showed that 284 of the 356 deer, or 79.8% of the
herd, tested positive for Chronic Wasting Disease (CWD).
*** see history of this CWD blunder here ;
On June 5, 2013, DNR conducted a fence inspection, after gaining approval
from surrounding landowners, and confirmed that the fenced had been cut or
removed in at least four separate locations; that the fence had degraded and was
failing to maintain the enclosure around the Quarantined Premises in at least
one area; that at least three gates had been opened;and that deer tracks were
visible in and around one of the open areas in the sand on both sides of the
fence, evidencing movement of deer into the Quarantined Premises.
The overall incidence of clinical CWD in white-tailed deer was 82%
Species (cohort) CWD (cases/total) Incidence (%) Age at CWD death (mo)
”The occurrence of CWD must be viewed against the contest of the locations
in which it occurred. It was an incidental and unwelcome complication of the
respective wildlife research programmes. Despite it’s subsequent recognition as
a new disease of cervids, therefore justifying direct investigation, no specific
research funding was forthcoming. The USDA veiwed it as a wildlife problem and
consequently not their province!” page 26.
Sunday, January 06, 2013
USDA TO PGC ONCE CAPTIVES ESCAPE
*** "it‘s no longer its business.”
CWD, spreading it around...
for the game farm industry, and their constituents, to continue to believe
that they are _NOT_, and or insinuate that they have _NEVER_ been part of the
problem, will only continue to help spread cwd. the game farming industry, from
the shooting pens, to the urine mills, the antler mills, the sperm mills, velvet
mills, shooting pens, to large ranches, are not the only problem, but it is
painfully obvious that they have been part of the problem for decades and
decades, just spreading it around, as with transportation and or exportation and
or importation of cervids from game farming industry, and have been proven to
spread cwd. no one need to look any further than South Korea blunder ;
===========================================
spreading cwd around...
Between 1996 and 2002, chronic wasting disease was diagnosed in 39 herds of
farmed elk in Saskatchewan in a single epidemic. All of these herds were
depopulated as part of the Canadian Food Inspection Agency’s (CFIA) disease
eradication program. Animals, primarily over 12 mo of age, were tested for the
presence CWD prions following euthanasia. Twenty-one of the herds were linked
through movements of live animals with latent CWD from a single infected source
herd in Saskatchewan, 17 through movements of animals from 7 of the secondarily
infected herds.
***The source herd is believed to have become infected via importation of
animals from a game farm in South Dakota where CWD was subsequently diagnosed
(7,4). A wide range in herd prevalence of CWD at the time of herd depopulation
of these herds was observed. Within-herd transmission was observed on some
farms, while the disease remained confined to the introduced animals on other
farms.
spreading cwd around...
Friday, May 13, 2011
Chronic Wasting Disease (CWD) outbreaks and surveillance program in the
Republic of Korea
Hyun-Joo Sohn, Yoon-Hee Lee, Min-jeong Kim, Eun-Im Yun, Hyo-Jin Kim,
Won-Yong Lee, Dong-Seob Tark, In- Soo Cho, Foreign Animal Disease Research
Division, National Veterinary Research and Quarantine Service, Republic of Korea
Chronic wasting disease (CWD) has been recognized as an important prion
disease in native North America deer and Rocky mountain elks. The disease is a
unique member of the transmissible spongiform encephalopathies (TSEs), which
naturally affects only a few species. CWD had been limited to USA and Canada
until 2000.
On 28 December 2000, information from the Canadian government showed that a
total of 95 elk had been exported from farms with CWD to Korea. These consisted
of 23 elk in 1994 originating from the so-called “source farm” in Canada, and 72
elk in 1997, which had been held in pre export quarantine at the “source
farm”.Based on export information of CWD suspected elk from Canada to Korea, CWD
surveillance program was initiated by the Ministry of Agriculture and Forestry
(MAF) in 2001.
All elks imported in 1997 were traced back, however elks imported in 1994
were impossible to identify. CWD control measures included stamping out of all
animals in the affected farm, and thorough cleaning and disinfection of the
premises. In addition, nationwide clinical surveillance of Korean native
cervids, and improved measures to ensure reporting of CWD suspect cases were
implemented.
Total of 9 elks were found to be affected. CWD was designated as a
notifiable disease under the Act for Prevention of Livestock Epidemics in 2002.
Additional CWD cases - 12 elks and 2 elks - were diagnosed in 2004 and
2005.
Since February of 2005, when slaughtered elks were found to be positive,
all slaughtered cervid for human consumption at abattoirs were designated as
target of the CWD surveillance program. Currently, CWD laboratory testing is
only conducted by National Reference Laboratory on CWD, which is the Foreign
Animal Disease Division (FADD) of National Veterinary Research and Quarantine
Service (NVRQS).
In July 2010, one out of 3 elks from Farm 1 which were slaughtered for the
human consumption was confirmed as positive. Consequently, all cervid – 54 elks,
41 Sika deer and 5 Albino deer – were culled and one elk was found to be
positive. Epidemiological investigations were conducted by Veterinary
Epidemiology Division (VED) of NVRQS in collaboration with provincial veterinary
services.
Epidemiologically related farms were found as 3 farms and all cervid at
these farms were culled and subjected to CWD diagnosis. Three elks and 5
crossbreeds (Red deer and Sika deer) were confirmed as positive at farm 2.
All cervids at Farm 3 and Farm 4 – 15 elks and 47 elks – were culled and
confirmed as negative.
Further epidemiological investigations showed that these CWD outbreaks were
linked to the importation of elks from Canada in 1994 based on circumstantial
evidences.
In December 2010, one elk was confirmed as positive at Farm 5.
Consequently, all cervid – 3 elks, 11 Manchurian Sika deer and 20 Sika deer –
were culled and one Manchurian Sika deer and seven Sika deer were found to be
positive. This is the first report of CWD in these sub-species of deer.
Epidemiological investigations found that the owner of the Farm 2 in CWD
outbreaks in July 2010 had co-owned the Farm 5.
In addition, it was newly revealed that one positive elk was introduced
from Farm 6 of Jinju-si Gyeongsang Namdo. All cervid – 19 elks, 15 crossbreed
(species unknown) and 64 Sika deer – of Farm 6 were culled, but all confirmed as
negative.
New studies on the heat resistance of hamster-adapted scrapie agent:
Threshold survival after ashing at 600°C suggests an inorganic template of
replication
The infectious agents responsible for transmissible spongiform
encephalopathy (TSE) are notoriously resistant to most physical and chemical
methods used for inactivating pathogens, including heat. It has long been
recognized, for example, that boiling is ineffective and that higher
temperatures are most efficient when combined with steam under pressure (i.e.,
autoclaving). As a means of decontamination, dry heat is used only at the
extremely high temperatures achieved during incineration, usually in excess of
600°C. It has been assumed, without proof, that incineration totally inactivates
the agents of TSE, whether of human or animal origin.
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel
Production
Histochemical analysis of hamster brains inoculated with the solid residue
showed typical spongiform degeneration and vacuolation. Re-inoculation of these
brains into a new cohort of hamsters led to onset of clinical scrapie symptoms
within 75 days, suggesting that the specific infectivity of the prion protein
was not changed during the biodiesel process. The biodiesel reaction cannot be
considered a viable prion decontamination method for MBM, although we observed
increased survival time of hamsters and reduced infectivity greater than 6 log
orders in the solid MBM residue. Furthermore, results from our study compare for
the first time prion detection by Western Blot versus an infectivity bioassay
for analysis of biodiesel reaction products. We could show that biochemical
analysis alone is insufficient for detection of prion infectivity after a
biodiesel process.
Detection of protease-resistant cervid prion protein in water from a
CWD-endemic area
The data presented here demonstrate that sPMCA can detect low levels of
PrPCWD in the environment, corroborate previous biological and experimental data
suggesting long term persistence of prions in the environment2,3 and imply that
PrPCWD accumulation over time may contribute to transmission of CWD in areas
where it has been endemic for decades. This work demonstrates the utility of
sPMCA to evaluate other environmental water sources for PrPCWD, including
smaller bodies of water such as vernal pools and wallows, where large numbers of
cervids congregate and into which prions from infected animals may be shed and
concentrated to infectious levels.
A Quantitative Assessment of the Amount of Prion Diverted to Category 1
Materials and Wastewater During Processing
Keywords:Abattoir;bovine spongiform encephalopathy;QRA;scrapie;TSE
In this article the development and parameterization of a quantitative
assessment is described that estimates the amount of TSE infectivity that is
present in a whole animal carcass (bovine spongiform encephalopathy [BSE] for
cattle and classical/atypical scrapie for sheep and lambs) and the amounts that
subsequently fall to the floor during processing at facilities that handle
specified risk material (SRM). BSE in cattle was found to contain the most oral
doses, with a mean of 9864 BO ID50s (310, 38840) in a whole carcass compared to
a mean of 1851 OO ID50s (600, 4070) and 614 OO ID50s (155, 1509) for a sheep
infected with classical and atypical scrapie, respectively. Lambs contained the
least infectivity with a mean of 251 OO ID50s (83, 548) for classical scrapie
and 1 OO ID50s (0.2, 2) for atypical scrapie. The highest amounts of infectivity
falling to the floor and entering the drains from slaughtering a whole carcass
at SRM facilities were found to be from cattle infected with BSE at rendering
and large incineration facilities with 7.4 BO ID50s (0.1, 29), intermediate
plants and small incinerators with a mean of 4.5 BO ID50s (0.1, 18), and
collection centers, 3.6 BO ID50s (0.1, 14). The lowest amounts entering drains
are from lambs infected with classical and atypical scrapie at intermediate
plants and atypical scrapie at collection centers with a mean of 3 × 10−7 OO
ID50s (2 × 10−8, 1 × 10−6) per carcass. The results of this model provide key
inputs for the model in the companion paper published here.
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.
==========================================
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.
now, let’s see what the authors said about this casual link, personal
communications years ago. see where it is stated NO STRONG evidence. so, does
this mean there IS casual evidence ???? “Our conclusion stating that we found no
strong evidence of CWD transmission to humans”
From: TSS (216-119-163-189.ipset45.wt.net)
Subject: CWD aka MAD DEER/ELK TO HUMANS ???
Date: September 30, 2002 at 7:06 am PST
From: "Belay, Ermias"
To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"
Sent: Monday, September 30, 2002 9:22 AM
Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Dear Sir/Madam,
In the Archives of Neurology you quoted (the abstract of which was attached
to your email), we did not say CWD in humans will present like variant CJD. That
assumption would be wrong. I encourage you to read the whole article and call me
if you have questions or need more clarification (phone: 404-639-3091). Also, we
do not claim that "no-one has ever been infected with prion disease from eating
venison." Our conclusion stating that we found no strong evidence of CWD
transmission to humans in the article you quoted or in any other forum is
limited to the patients we investigated.
Ermias Belay, M.D. Centers for Disease Control and Prevention
-----Original Message-----
From: Sent: Sunday, September 29, 2002 10:15 AM
To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV
Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS
Thursday, April 03, 2008
A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008
Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ.
snip...
*** twenty-seven CJD patients who regularly consumed venison were reported
to the Surveillance Center***,
snip... full text ;
CJD is so rare in people under age 30, one case in a billion (leaving out
medical mishaps), that four cases under 30 is "very high," says Colorado
neurologist Bosque. "Then, if you add these other two from Wisconsin [cases in
the newspaper], six cases of CJD in people associated with venison is very, very
high." Only now, with Mary Riley, there are at least seven, and possibly eight,
with Steve, her dining companion. "It's not critical mass that matters,"
however, Belay says. "One case would do it for me." The chance that two people
who know each other would both contact CJD, like the two Wisconsin sportsmen, is
so unlikely, experts say, it would happen only once in 140 years.
Given the incubation period for TSEs in humans, it may require another
generation to write the final chapter on CWD in Wisconsin. "Does chronic wasting
disease pass into humans? We'll be able to answer that in 2022," says Race.
Meanwhile, the state has become part of an immense experiment.
I urge everyone to watch this video closely...terry
*** you can see video here and interview with Jeff's Mom, and scientist
telling you to test everything and potential risk factors for humans ***
*** 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).***
***This information will have a scientific impact since it is the first
study that demonstrates the transmission of scrapie to a non-human primate with
a close genetic relationship to humans. This information is especially useful to
regulatory officials and those involved with risk assessment of the potential
transmission of animal prion diseases to humans.
***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.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Evaluation of the zoonotic potential of transmissible mink
encephalopathy
Authors
item Comoy, Emmanuel - item Mikol, Jacqueline - item Ruchoux,
Marie-Madeleine - item Durand, Valerie - item Luccantoni-Freire, Sophie - item
Dehen, Capucine - item Correia, Evelyne - item Casalone, Cristina - item Richt,
Juergen item Greenlee, Justin item Torres, Juan Maria - item Brown, Paul - item
Deslys, Jean-Philippe -
Submitted to: Pathogens Publication Type: Peer Reviewed Journal Publication
Acceptance Date: July 30, 2013 Publication Date: July 30, 2013 Citation: Comoy,
E.E., Mikol, J., Ruchoux, M., Durand, V., Luccantoni-Freire, S., Dehen, C.,
Correia, E., Casalone, C., Richt, J.A., Greenlee, J.J., Torres, J.M., Brown, P.,
Deslys, J. 2013. Evaluation of the zoonotic potential of transmissible mink
encephalopathy. Pathogens. 2:(3)520-532.
Interpretive Summary: Cases of bovine spongiform encephalopathy (BSE) or
mad cow disease can be subclassified into at least 3 distinct disease forms with
the predominate form known as classical BSE and the others collectively referred
to as atypical BSE. Atypical BSE can be further subdivided into H-type and
L-type cases that are distinct from classical BSE and from each other. Both of
the atypical BSE subtypes are believed to occur spontaneously, whereas classical
BSE is spread through feeding contaminated meat and bone meal to cattle.
Transmissible mink encephalopathy (TME) is another prion disease that transmits
to cattle and show similarities to L-type BSE when subjected to laboratory
testing. The purpose of this study was to use non-human primates (cynomologous
macaque) and transgenic mice expressing the human prion protein to determine if
TME could represent a potential risk to human health. TME from two sources
(cattle and raccoons) was able to infect non-human primates and transgenic mice
after exposure by the intracranial route. This result suggest that humans may be
able to replicate TME prions after an exposure that allows infectious material
access to brain tissue. At this time, it is unknown whether non-human primates
or transgenic mice would be susceptible to TME prions after oral exposure. The
results obtained in these animal models were similar to those obtained for
L-type BSE. Although rare, the existence of TME and that it transmits to cattle,
non-human primates, and transgenic mice suggest that feed bans preventing the
feeding of mammalian tissues to cattle should stay in place and that regular
prion surveillance during the slaughter should remain in place. Parties with
interest in the cattle and beef industries and regulatory officials responsible
for safe feeding practices of cattle will be interested in this work. Technical
Abstract: Successful transmission of Transmissible Mink Encephalopathy (TME) to
cattle supports the bovine hypothesis to the still controversial origin of TME
outbreaks. Human and primate susceptibility to classical Bovine Spongiform
Encephalopathy (c-BSE) and the transmissibility of L-type BSE to macaques assume
a low cattle-to-primate species barrier: we therefore evaluated the zoonotic
potential of cattle-adapted TME. In less than two years, this strain induced in
cynomolgus macaques a neurological disease similar to L-BSE and distinct from
c-BSE. TME derived from another donor species (raccoon) induced a similar
disease with shorter incubation periods.
*** L-BSE and cattle-adapted TME were also transmissible to transgenic mice
expressing human PrP. Interestingly, secondary transmissions to transgenic mice
expressing bovine PrP showed the maintenance of prion strain features for the
three tested bovine prion strains (cattle TME, c-BSE and L-BSE) regardless of
intermediate host.
*** Thus, TME is the third animal prion strain transmissible to both
macaques and humanized transgenic mice, suggesting zoonotic potentials that
should be considered in the risk analysis of animal prion diseases for human
health.
*** Moreover, the similarities between TME and L-BSE are highly suggestive
of a link between those strains, and of the presence of L-BSE decades prior to
its identification in USA and Europe.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Scrapie transmits to white-tailed deer by the oral route and has a
molecular profile similar to chronic wasting disease
Authors
item Greenlee, Justin item Moore, S - item Smith, Jodi - item Kunkle,
Robert item West Greenlee, M -
Submitted to: American College of Veterinary Pathologists Meeting
Publication Type: Abstract Only Publication Acceptance Date: August 12, 2015
Publication Date: N/A Technical Abstract: The purpose of this work was to
determine susceptibility of white-tailed deer (WTD) to the agent of sheep
scrapie and to compare the resultant PrPSc to that of the original inoculum and
chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure
(concurrent oral and intranasal (IN); n=5) with a US scrapie isolate. All
scrapie-inoculated deer had evidence of PrPSc accumulation. PrPSc was detected
in lymphoid tissues at preclinical time points, and deer necropsied after 28
months post-inoculation had clinical signs, spongiform encephalopathy, and
widespread distribution of PrPSc in neural and lymphoid tissues. Western
blotting (WB) revealed PrPSc with 2 distinct molecular profiles. WB on cerebral
cortex had a profile similar to the original scrapie inoculum, whereas WB of
brainstem, cerebellum, or lymph nodes revealed PrPSc with a higher profile
resembling CWD. Homogenates with the 2 distinct profiles from WTD with clinical
scrapie were further passaged to mice expressing cervid prion protein and
intranasally to sheep and WTD. In cervidized mice, the two inocula have distinct
incubation times. Sheep inoculated intranasally with WTD derived scrapie
developed disease, but only after inoculation with the inoculum that had a
scrapie-like profile. The WTD study is ongoing, but deer in both inoculation
groups are positive for PrPSc by rectal mucosal biopsy. In summary, this work
demonstrates that WTD are susceptible to the agent of scrapie, two distinct
molecular profiles of PrPSc are present in the tissues of affected deer, and
inoculum of either profile readily passes to deer.
Monday, November 16, 2015
*** Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats Terry Singeltary
Sr. Submission ***
Wednesday, December 16, 2015
Objects in contact with classical scrapie sheep act as a reservoir for
scrapie transmission
Thursday, January 14, 2016
EMERGING ANIMAL DISEASES Actions Needed to Better Position USDA to Address
Future Risks Report to the Chairman, Committee on Energy and Commerce, House of
Representatives December 2015 GAO-16-132
GAO
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
12:55 PM
0 Comments:
Post a Comment
Subscribe to Post Comments [Atom]
<< Home