OKLAHOMA CONFIRMS SECOND CWD POSITIVE WTD

[Terry S. Singeltary Sr.]

OKLAHOMA CONFIRMS SECOND CWD POSITIVE WTD

SECOND CWD-POSITIVE WILD DEER CONFIRMED IN OKLAHOMA

Jul 3, 2023 A second wild white-tailed deer has tested positive for chronic wasting disease (CWD) in Oklahoma.

The deer was located about 15 miles east of Woodward in Woodward County after a landowner reported the deer behaving abnormally.

Oklahoma's first case of a wild deer infected with CWD was confirmed the first week of June in Texas County, prompting the activation of the next stage in the state's CWD Response Strategy jointly produced by the Oklahoma Department of Wildlife Conservation and the Oklahoma Department of Agriculture, Food and Forestry.

“We will be working through our response plan implementing surveillance efforts and steps to monitor and slow the potential spread of this disease. Our ultimate goal is to ensure healthy and well-managed deer with as little impact to either the resource or our constituents as possible,” said Jerry Shaw, Wildlife Programs Supervisor with ODWC.

CWD is an always-fatal neurological disease that affects the brains of deer, elk, moose, and other members of the cervid family, creating holes resembling those in sponges. CWD transmission from wild animals to people or to livestock has never been documented.

The Wildlife Department has conducted CWD monitoring on hunter-harvested deer and elk, and road-killed deer, since 1999.

Department staff will continue monitoring for evidence of CWD within Oklahoma’s borders and will release additional information, including ways deer and elk hunters can help with detection and mitigation, as hunting seasons approach.

Additional guidelines or management plans will be distributed and well-advertised if determined necessary to further protect Oklahoma’s deer and elk populations.

Additional human health information relating to CWD is available at www.usgs.gov/centers/nwhc/science/chronic-wasting-disease#publications

For more information on the disease, hunting regulations, and proper disposal of infected animals, go to www.wildlifedepartment.com/hunting/resources/deer/cwd

www.wildlifedepartment.com/outdoor-news/second-cwd-positive-wild-deer-confirmed-oklahoma

Oklahoma Detects First Wild Deer Chronic Wasting Disease CWD TSE Prion

ODWC ACTIVATES CWD RESPONSE STRATEGY AFTER DISEASED WILD DEER FOUND IN PANHANDLE

Jun 6, 2023

A white-tailed deer in the Oklahoma Panhandle has tested positive for chronic wasting disease (CWD).

A Texas County landowner reported the deer to the Oklahoma Department of Wildlife Conservation after witnessing it behaving abnormally. The deer was recovered near Optima and testing was conducted.

This marks the first case of CWD in a wild deer in Oklahoma.

ODWC has activated the next stage of the CWD Response Strategy jointly produced with the Oklahoma Department of Agriculture, Food and Forestry.

“While this is unfortunate news, it is not unexpected since CWD has already been detected in every state that borders Oklahoma. We will be working through our response plan to ensure we can monitor potential spread and keep our state’s deer herd healthy,” said Jerry Shaw, Wildlife Programs Supervisor with ODWC.

CWD is an always-fatal neurological disease that affects the brains of deer, elk, moose, and other members of the cervid family, creating holes that resemble those in sponges. It’s important to note that CWD transmission from wild animals to people or to livestock has never been documented

The Wildlife Department has conducted CWD monitoring on hunter-harvested deer and elk, and road-killed deer, since 1999. This case marks the first time the disease has been detected in laboratory testing of tissue samples from more than 10,000 wild deer and elk from throughout Oklahoma.

The Wildlife Department will continue monitoring for evidence of this disease within Oklahoma’s borders and will release additional information, including ways deer and elk hunters can help with detection and mitigation, as hunting seasons approach.

Additional guidelines or management plans will be distributed and well-advertised if determined necessary to further protect Oklahoma’s deer and elk populations.

Additional human health information relating to CWD is available at www.usgs.gov/centers/nwhc/science/chronic-wasting-disease#publications

For more information on the disease, hunting regulations, and proper disposal of infected animals, go to

www.wildlifedepartment.com/hunting/resources/deer/cwd

www.wildlifedepartment.com/outdoor-news/odwc-activates-cwd-response-strategy-after-diseased-wild-deer-found-panhandle

Oklahoma Wild Deer Test Positive for CWD

www.wildlifedepartment.com/outdoor-news/odwc-activates-cwd-response-strategy-after-diseased-wild-deer-found-panhandle

MONDAY, SEPTEMBER 12, 2022

OKLAHOMA ODWC ACTIVATES CWD RESPONSE PLAN AFTER DISEASED DEER FOUND WITHIN MILES OF PANHANDLE OKLAHOMA ODWC ACTIVATES CWD RESPONSE PLAN AFTER DISEASED DEER FOUND WITHIN MILES OF PANHANDLE

ODWC ACTIVATES CWD RESPONSE PLAN AFTER DISEASED DEER FOUND WITHIN MILES OF PANHANDLE Sep 9, 2022

A white-tailed deer carcass recently recovered along a Texas road about 2.5 miles south of the Oklahoma border in the western Panhandle south of Felt, Okla., has tested positive for chronic wasting disease (CWD). The CWD positive deer was found in an area of Texas with a history of CWD detection dating back 3 years. Although not inside of our borders, due to the proximity of this finding to Oklahoma, the Oklahoma Department of Wildlife Conservation (ODWC) has activated the next stage of the CWD Response Plan that was jointly produced with the Oklahoma Department of Agriculture, Food and Forestry.

“With the ability of deer to easily travel many miles in a day, the CWD Response Plan dictates that we respond to this finding as if CWD has now been detected among free-roaming wild deer in Oklahoma,” said Jerry Shaw, Wildlife Programs Supervisor with ODWC.

CWD is an always-fatal neurological disease that affects the brains of deer, elk, moose, and other members of the cervid family, creating holes that resemble those in sponges. It’s important to note in this area of the state that CWD does not affect pronghorn antelope, and CWD transmission from wild animals to humans or livestock has never been documented either.

No CWD-positive wild deer have been found within Oklahoma’s borders. But CWD has been found in two captive elk herds in the state. CWD has been confirmed in wild cervids in every state surrounding Oklahoma. In total, 30 states now have detected CWD within their borders.

The Wildlife Department has conducted CWD monitoring on hunter-harvested deer and elk and road-killed deer since 1999. The disease has not been detected in laboratory testing of tissue samples from more than 10,000 wild deer and elk from throughout Oklahoma.

​The Wildlife Department will continue monitoring for evidence of this disease within Oklahoma’s borders and will release additional information, including ways deer and elk hunters can help with detection and mitigation as hunting seasons approach. Additional guidelines or restrictions will be distributed and well-advertised if determined necessary to further protect Oklahoma’s deer and elk populations.

Additional human health information relating to CWD is available at www.usgs.gov/centers/nwhc/science/chronic-wasting-disease#publications

For more information on the disease, how it could affect hunting, and proper disposal of infected animals, go to www.wildlifedepartment.com/hunting/resources/deer/cwd

www.wildlifedepartment.com/outdoor-news/odwc-activates-cwd-response-plan-after-diseased-deer-found-within-miles-panhandle

Oklahoma CWD Past History

TUESDAY, JANUARY 07, 2020

Oklahoma Farmed Elk Lincoln County CWD Depopulation 3 Positive Elk with 1 Additional Dead Trace Out Confirmed Positive

i was wondering what the results (if any), from all the other cervid that this Elk came into contact with, from any additional testing, was there any, from the existing herd, trace in and outs and such, and herds there from???

was that breeding farm completely depopulated yet, and if so, what are the numbers on any additional positives, if any?

PERSONAL COMMUNICATION @ag.ok.gov Tue, Jan 7, 2020 4:11 pm

We completed the depopulation of the elk herd.

Out of 250 head there were 3 positive elk.

We know of one trace out that died and was tested positive.

Many other trace outs (over 100) have been tested and are negative.

END...TSS

WEDNESDAY, APRIL 24, 2019

Oklahoma Farmed Elk Lincoln County has tested positive for chronic wasting disease CWD TSE Prion

JOINT RELEASE FROM THE OKLAHOMA DEPARTMENT OF AGRICULTURE, FOOD & FORESTRY AND THE OKLAHOMA DEPARTMENT OF WILDLIFE CONSERVATION

Chronic Wasting Disease Confirmed in One Farmed Oklahoma Elk

chronic-wasting-disease.blogspot.com/2019/04/oklahoma-farmed-elk-lincoln-county-has.html

re-Commission Hears Update on CWD Status in Oklahoma

Fri, May 10, 2019 4:19 pm

Terry Singeltary [e-mail]

To comdist1 [e-mail] Cc comdist2 [e-mail], comdist3 [e-mail], comdist4 [e-mail], comdist5 [e-mail], comdist6 [e-mail], comdist7 [e-mail], comdist8 [e-mail], micah.holmes [e-mail]

Commission Hears Update on CWD Status in Oklahoma

The Oklahoma Wildlife Conservation Commission on Monday authorized the Director of the Oklahoma Department of Wildlife Conservation to take reasonable steps to respond to future developments related to chronic wasting disease (CWD) in Oklahoma.

The authorization by a vote of 5-1 also instructed Director J.D. Strong to bring any such actions to the attention of the Commission as soon as possible after any actions are taken.

CWD is a fatal neurological disease that affects the brains of elk, deer and other cervid species.

No vaccine or treatment for the disease exists. Importantly, no health risk to humans or non-cervid livestock has been documented.

In late April, an elk from a farmed herd in Lincoln County tested positive for CWD.

Strong emphasized that any CWD response related to farmed cervids, cervid breeding facilities or the import and export of farmed cervids is under the jurisdiction of the state Department of Agriculture, Food and Forestry.

The Wildlife Department is responsible for managing the wild cervid populations and overseeing cervid hunting facilities.

Strong said the Wildlife Department’s goal is not to make any hasty, large-scale decisions right away in dealing with the threat of CWD, but to take a measured, scientific approach and collect all the information possible before deciding how to best respond to any possible confirmed cases in wild cervids.

He stressed the need for a team approach and expressed his continued willingness to work with the various stakeholder groups in finalizing a CWD action plan.

“At the end of the day, it’s all about hunting,” Strong said, whether CWD strikes farmed cervids or wild cervids. “One of the best ways is to enlist the help of hunters” in a strategy to minimize the spread of CWD.

snip...

content.govdelivery.com/accounts/OKDWC/bulletins/2434f4a

''In late April, an elk from a farmed herd in Lincoln County tested positive for CWD.

Strong emphasized that any CWD response related to farmed cervids, cervid breeding facilities or the import and export of farmed cervids is under the jurisdiction of the state Department of Agriculture, Food and Forestry. The Wildlife Department is responsible for managing the wild cervid populations and overseeing cervid hunting facilities.

Strong said the Wildlife Department’s goal is not to make any hasty, large-scale decisions right away in dealing with the threat of CWD, but to take a measured, scientific approach and collect all the information possible before deciding how to best respond to any possible confirmed cases in wild cervids.''

if you wait for cwd to find you, then you have lost the fight already imo.

Greetings ODWC et al,

i kindly wish to submit the following updated science on the chronic wasting disease cwd tse prion. you do know that the new strain of cwd in Texas is of a more virulent strain? see below......GOOD LUCK!

kindest regards, terry

snip...end...TSS

TUESDAY, JANUARY 07, 2020

Oklahoma Farmed Elk Lincoln County CWD Depopulation 3 Positive Elk with 1 Additional Dead Trace Out Confirmed Positive

chronic-wasting-disease.blogspot.com/2020/01/oklahoma-farmed-elk-lincoln-county-cwd.html

TUESDAY, MARCH 08, 2016

Oklahoma Chronic Wasting Disease CWD of Deer and Elk Surveillance, Testing, and Preparedness

Hunting: Oklahoma Department of Wildlife Conservation 2015-2016 Harvest Report is updated weekly. Sportsmen have the option to exclude their name; however, your deer harvest information will still appear on the ... www.wildlifedepartment.com www.wildlifedepartment.com/hunting/deer.htm

Oklahoma Chronic Wasting Disease (CWD) of Deer and Elk Surveillance, Testing, and Preparedness

Chronic Wasting Disease CWD of Deer and Elk

Key Points

1. At this point there is no known cases of CWD in wild deer and elk in Oklahoma.

2. There has been no known transmission of CWD from deer or elk to any other animals or people even in states where CWD is found.

3. It is always wise to use common sense when handling any meat or when dealing with sick or injured animals.

For more information about CWD log on to www.cwd-info.org

"In 2006 more than 1,626 hunter harvested deer and elk were sampled in Oklahoma and all tested negative for chronic wasting disease. To date, some 7,088 animals have been tested statewide as part of The Wildlife Department's monitoring program and all have tested negative for CWD. The Department will continue to monitor the state's deer and elk herds through additional testing."

What is Chronic Wasting Disease (CWD)?

It was 35 years ago and the biologists were baffled. Blood work showed nothing unusual, liver and kidney tests turned up negative for all known diseases, but the mule deer were still wasting away to skin and bones. It could have been straight out of an episode of “The X Files.”

A few of the captive deer at the Colorado Division of Wildlife’s research facilities in Fort Collins had begun to lose weight on a diet that sustained other deer. They drank incessantly and spent much of their time standing listlessly in their corrals. The biologists knew they had a unique syndrome on their hands, but it was like nothing they had ever seen before.

Captive deer at Wyoming Game and Fish Department's Sybille Research Unit were soon showing signs of the mystery disease. Because the Colorado and Wyoming facilities regularly traded deer and elk, the appearance of the disease in Wyoming came as no great surprise.

Over the next 10 years, researchers worked to understand the origin and causes of the affliction, but their studies led to more questions than answers.

One thing was certain, the disease was deadly. Between 1974 and 1979, 66 mule deer and one black-tailed deer were held captive in Colorado and Wyoming research corrals. Of those, 57 contracted the strange disease and not one survived.

The search went on for the cause of the disease. Viruses, bacteria and nutritional deficiencies were all ruled out. Biologists named it "chronic wasting disease” (CWD), identifying the disease’s most devastating outward symptom, irreversible weight loss.

The first break in the case came in 1978, when wildlife veterinarian Beth Williams began analyzing tissues of affected animals. She found microscopic holes in brain and nerve tissues of the deer. The disease was turning the brains of these deer into Swiss cheese.

This finding put Chronic Wasting Disease into a small category of diseases labeled transmissible spongiform encephalopathies (TSE). As pathologists looked into CWD further, they began to see similarities between it and scrapie, a TSE that affects sheep.

Sheep and goats have been affected by scrapie in Europe for centuries. In all those years, no other type of animal has ever come down with the disease, including generations of shepherds who work with their flocks daily and consumers who eat their meat and drink their milk.

Although they now knew CWD was related to scrapie and other TSEs, this helped little because at the time pathologists knew little about the cause of this disease either. The scientific camps began to stake their claim on the origins of these enigma diseases. Some thought it was a genetic illness, others assumed it was a virus too small to be detected by existing techniques. Several different scientists were pursuing proof of their favorite theories.

In the meantime, unsettling news was reported from the field. In March 1981, biologists in north Colorado brought in a sick elk that turned out to be suffering from chronic wasting disease. The disease had somehow spread from captive animals into free-ranging herds.

Cervids (animals such as white-tailed deer and elk ) seemed to be the target of CWD, no other animals including cattle, horses or humans have been affected by CWD. The disease spread incrementally through northcentral Colorado affecting mule deer, white-tailed deer and elk. In 1986, CWD claimed an elk in southeastern Wyoming, the first confirmed case of the disease in a wild animal outside of Colorado.

Although this was not exactly a raging disease outbreak, the spread of the disease had started and wildlife vets and biologists were concerned. They knew little about it, and knew nothing about how to stop it.

Today, 34 years since the disease was discovered, pathologists have learned more about the disease, but still have much to learn before they fully understand it. However slowly, CWD has continued to creep across the United States and Canada, currently impacting either captive or free-ranging deer in nine states and a pair of Canadian provinces. This includes a closely monitored captive elk herd in central Oklahoma.

It is now generally accepted that prions, naked proteins with the ability to duplicate and multiply, are the culprits to blame for CWD and other TSE’s. There remains no known cure or even a reliable method of disinfecting contaminated areas. Biologists in Fort Collins, Colorado, where the disease was first discovered, found out how resilient these prions can be. They set out in an intensive effort to rid the research facilities of CWD. All captive deer and elk were killed and buried. Personnel then plowed up the soil in the pens in an effort to bury possible disease organisms and structures and pastures were repeatedly treated with a powerful disinfectant. A year later, 12 elk calves from the wild were released in the sanitized holding areas. In the next five years, two of these elk died from chronic wasting disease.

Fortunately, Oklahoma’s free-ranging deer herd is not known to carry the disease. Over the past three years biologists and veterinarians have examined almost 400 deer and elk taken during Oklahoma's hunting seasons as part of the Department’s CWD monitoring program. All samples obtained from animals taken from the wild have tested negative and biologists will continue to closely monitor the deer and elk herd for signs of the disease.

Currently, detecting the disease is far from simple. The only acceptable test is a microscopic examination of an animal’s brain stem. There are no live animal tests and only a handful of laboratories and pathologists are qualified to administer the brain test.

If there is a bright side to chronic wasting disease it is that it reminds how valuable our deer are. It wasn’t that long ago that deer seemed headed down the same path as the buffalo and the passenger pigeon, over-exploited and pushed out by land-hungry settlers. Through the tireless work of biologists and sportsmen, deer have been restored to once unthinkable numbers in Oklahoma and across their native range.

A deer is a symbol of grace and it provides a succulent, nutritious meal. It is that and more, it is a wild animal that makes the woods a better place just for being there. It is as American as they come, inhabiting just about every ecotone on this continent.

To know that a disease as serious as CWD is spreading should pain everyone who has ever marveled at a deer slinking over a barbed wire fence. But it is no surprise that it was hunters who were the first to step up to the plate for the animals. In Oklahoma, a CWD monitoring program is in place thanks to funds provided through hunter’s licenses. In Wisconsin, it is hunters who have taken on the grim task of thinning out the deer herd to prevent the spread of CWD, and across the United States it is sportsmen who are carrying much of the financial burden to pay for biologists, veterinarians and pathologists to study the disease.

Is Venison Safe to Eat?

According to current research, there is no scientific evidence linking CWD to human diseases. It is recommended that hunters practice standard safety practices when handling any wild game, or any meat for that matter, as general precautionary measures.

These practices include washing your hands after handling raw meat and cooking the meat at an appropriate temperature.

"In my opinion, venison is just as safe as any other game meat," said Mike Shaw, head deer biologist for the Oklahoma Department of Wildlife Conservation.

Even in the parts of Wyoming and Colorado where chronic wasting disease is found, less than six percent of deer are infected.

A few precautions are recommended:

1) Don't shoot an animal that is acting abnormally or looks sick. 2) Wear rubber or latex gloves when you field-dress your animal. 3) Don't eat deer brains or spinal cord. 4) Bone out your deer meat and discard the brain, spinal cord, eyes, spleen, and lymph nodes.

Prions: New germs

In 1972 neurologist Stanley Prusiner lost a patient to Creutzfeldt-Jakob disease, a TSE that affect humans. Prusiner was serving his residency at the University of California’s School of Medicine and was astounded by the lack of information about the rare disease.

Two years later he set up his own laboratory at the University of California-San Francisco and set out to get to the root cause of scrapie, Creutzfeldt-Jakob and other TSE’s.

He took two known facts about the disease and came up with an astounding conclusion. He knew that scrapie infected tissue showed no signs of foreign DNA. He also knew that the only disinfectant techniques that affected the scrapie "germ" were those techniques that broke down not only DNA, but also proteins. From these two facts he assumed that the scrapie "germ" was a simple protein without DNA.

The notion seemed impossible in scientific circles. Since the 1950’s scientists had been working on the basis that proteins were duplicated using a blueprint provided by DNA. Prusiner was saying that these proteinaceous infectious particles, or prions for short, could recreate themselves without ever using DNA. His theory was accepted with just about the same enthusiasm that early mapmakers shared with Columbus when he told them the earth was round.

Prusiner spent the next two decades proving his theory and his efforts were rewarded in 1997 when he won the Nobel Prize for medicine. Although a few skeptics still remain, it is now generally accepted that prions play a causative role in CWD and other TSE’s.

The Worth of a Healthy Deer Herd

Wildlife agencies across the United States are scrambling to protect deer herds in their areas from the ravaging effects of CWD.

It is no wonder why. Not only are deer a beautiful natural resource and part of a rich hunting heritage, they also provide a significant economic impact. The annual pilgrimage of hunters into the woods each fall means big bucks, in more ways than one. In Oklahoma alone, 261,000 hunters, most of which are deer hunters, spent over $2.6 million on hunting expenditures according to a recent survey. While hunters are after deer, they spend money to gas their vehicles, eat meals and purchase equipment. These dollars go back into Oklahoma communities, particularly those in rural areas.

In an effort to keep Oklahoma’s deer safe from CWD, the Wildlife Conservation Commission has suspended the import of live deer and elk into the state from states that have CWD in their free-ranging deer herds. By suspending import of potentially infected animals, the Department hopes to avoid the consequences of the disease and the potential costs of controlling CWD. The detection of the disease has had immense economic impact on states such as Wisconsin where the disease was discovered last year. Within the first month after detection, the Wisconsin wildlife management agency spent approximately $250,000 in control and public information efforts and will spend upwards of $2.5 million this year as a result of CWD control efforts. The agency continues to try to control the spread of the disease and has publicly outlined plans to kill all 30,000 estimated animals in the focal area where infected animals have been found.

Wisconsin is not the only state fighting CWD. As an example, a supplemental appropriation of $300,143 has been made in Colorado to help combat the disease and more appropriations are being considered. Saskatchewan has spent approximately $30 million in attempts at eradicating the disease in infected commercially operated game farms.

www.wildlifedepartment.com/hunting/cwd.htm

*** While elk were historically found in Oklahoma, the majority of the current private lands elk population found in the state is the result of animals that were either intentionally liberated or escaped from a captive facility.

www.wildlifedepartment.com/media/proposed_changes.htm

*** Chronic Wasting Disease (CWD) in deer and elk – *** has been recently confirmed in a captive elk herd in Oklahoma County

FEBRUARY 2001 NEWS RELEASES

A degenerative brain disease similar to mad cow disease - called Chronic Wasting Disease (CWD) in deer and elk – *** has been recently confirmed in a captive elk herd in Oklahoma County, but has never been documented in wild deer or elk in Oklahoma. Even if the disease did exist in wild herds, there has never been a confirmed case of a hunter contracting it through hunting or eating venison.

www.wildlifedepartment.com/newsreleasearchive/2001/02-01nr.htm

Deer Management Assistance Program: Erik Bartholomew - [phone] [e-mail] [e-mail]; [e-mail] [e-mail]; [e-mail]

Oklahoma Chronic Wasting Disease CWD TSE Prion Surveillance and Testing History

Oklahoma

Chronic Wasting Disease Surveillance in Oklahoma: Chronic Wasting Disease (CWD) is a progressive, fatal, degenerative neurological disease that affects deer, elk, and moose.

First recognized in 1967 in captive mule deer in Colorado, CWD now affects free-ranging cervids in at least 15 states and 2 Canadian provinces. Research suggests that transmission may occur via several routes, with environmental contamination likely playing a significant role.

In 1998, a captive elk herd in central Oklahoma was diagnosed with CWD.

Infected animals in this herd originated in Montana, and although the herd was depopulated in September 2002, there remains the concern for possible exposure of native wild deer populations.

Since that time numerous captive cervid facilities have developed in Oklahoma.

Additionally, CWD has been located in free-ranging animals in multiple states including Texas, Kansas, Colorado, New Mexico, and Missouri.

From 1997 to 2012, the Oklahoma Department of Wildlife Conservation (ODWC) in cooperation with the U.S. Department of Agriculture (Animal and Plant Health Inspection Service) Veterinary Services, and the Oklahoma Department of Agriculture took a proactive approach to protect Oklahomas deer and elk resource.

This approach helped to reassure hunters, the general public, deer processors, taxidermists, rendering companies, and the states trading partners that Oklahomas wild deer population is free of CWD and to reduce the potential threat to human health concerns.

The U.S. Fish and Wildlife Service (USFWS) funding supplied to ODWC is to conduct surveillance for CWD in Oklahoma and at the Wichita Mountains National Wildlife Refuge (WMNWR).

Funding received during the first year of this project will focus on CWD surveillance in southwest Oklahoma, which includes the WMNWR.

Surveillance will shift to other regions of Oklahoma in subsequent years if funding is available.

Funding for this project was received through the USFWS National Wildlife Refuge System Wildlife Health Office.

As such, eligible entities for this funding are USFWS divisions and programs or State wildlife management agencies that form partnerships with one or more USFWS National Wildlife Refuges.

Hence, ODWC is one such entity and responsible for the management of white-tailed deer and elk populations in Oklahoma.

WMNWR and ODWC formed such a partnership in order to jointly utilize this funding and conduct CWD surveillance in Oklahoma and on the WMNWR.

Depending upon funding allocations, this project could be funded for up to 5 years.

Federal Grant Title: Chronic Wasting Disease Surveillance in Oklahoma Federal Agency Name: Fish and Wildlife Service Grant Categories: Natural Resources Type of Opportunity: Discretionary Funding Opportunity Number: F14AS00385 Type of Funding: Grant CFDA Numbers: 15.650 CFDA Descriptions: Research Grants (Generic) Current Application Deadline: Aug 14, 2014 Notice of Intent to Award Single Source Original Application Deadline: Aug 14, 2014 Notice of Intent to Award Single Source Posted Date: Aug 8, 2014 Creation Date: Aug 8, 2014 Archive Date: Aug 7, 2015 Total Program Funding: $32250 Maximum Federal Grant Award: $32250 Minimum Federal Grant Award: $6450 Expected Number of Awards: 1 Cost Sharing or Matching: No

Applicants Eligible for this Grant State governments Grant Announcement Contact Michelle L. Willcox, Grants Specialist, 505-248-7486 [e-mail] [e-mail]

Fish and Wildlife Service 703-358-2459

www.federalgrants.com/Chronic-Wasting-Disease-Surveillance-in-Oklahoma-47559.html

Ear tags had been discarded in the Oklahoma CWD elk case, causing uncertainty in trace-back (limited to Montana, Idaho, or Utah). Oklahoma:

-- In June,1998 CW) was diagnosed in a captive elk in Oklahoma.

-- The Oklahoma herd received more than 80 elk from commercial sources in Montana and Idaho.

-- Animals from the same origins as the Oklahoma herd went to 13 other ranches in Colorado, Idaho, Iowa, Montana, Nebraska, Alberta, and Saskatchewan in the past 11 years, plus many secondary movements. [8]

-- no control or surveillance program.

Utah:

-- one trace-back zoo in Salt Lake City from elk possibly associated to Oklahoma game farm.

-- One 30 year old hunter dying of CJD of unknown origin (not familial or iatrogenic).

-- 135 deer sampled in 1998, 90 tested, all negative so far, pathology done in-state. Unpublished UF&G.

Montana:

-- Single trace-back elk game farm under quarantine from Oklahoma case, though importer destroyed ear tag.

-- Single trace-forward elk game farm that had bought elk from trace-back game farm connected to Oklahoma

Iowa, Illinois, Texas, and Wisconsin:

-- These states have trace-forward herds from an infected herd in Nebraska.

-- Missouri also sold elk from this herd at auction to buyers in unknown states.

-- Wisconsin has additional trace-forward game farms from affected South Dakota game farms [7]

-- Michigan allows deer to concentrate at bait stations, spread of tuberculosis attributed to this in NE Lower Peninsula [7].

Vermont:

-- ancedotal trace-forward herds from Colorado and Wyoming

Idaho:

-- no reported CWD, possible trace-back herd based on Oklahoma case, hold order on elk farm.

-- elk ranchers forced regulatory change to ag department to avoid regs.

www.mad-cow.org/99feb_cwd_special.html

PROGRAM GUIDELINES FOR OKLAHOMA CHRONIC WASTING DISEASE (CWD) CERVID SURVEILLANCE AND CERTIFICATION STATUS PROGRAM

www.oda.state.ok.us/ais/aiscervidaemonitor.pdf

Dec. 19, 2013

A service of the Oklahoma Department of Wildlife Conservation

Wildlife Department offering online public comment period for proposed regulation changes

Sportsmen have the opportunity to log on to wildlifedepartment.com to voice their thoughts on a list of Oklahoma hunting and fishing related rule change proposals.

Most notable is a proposal to expand private lands elk hunting opportunity to statewide. For several years elk have been hunted on private lands in Caddo, Comanche, and Kiowa counties in southwest Oklahoma. More recently, Adair, Cherokee, Delaware, Mayes, Muskogee and Sequoyah counties in the northeast part of the state were added to the list of locations where these animals could be pursued by hunters.

While elk were historically found in Oklahoma, the majority of the current private lands elk population found in the state is the result of animals that were either intentionally liberated or ***escaped from a captive facility. A recent survey showed that at least 30 of the state's 77 counties are home to elk. The proposal will allow elk hunting opportunity in every county of the state. The popular controlled hunts program will not be affected by this proposal and will continue to offer hunters lucky enough to draw a permit the chance to pursue elk on certain state and federal managed areas.

www.wildlifedepartment.com/newsreleasearchive/2013/1213.htm

Monthly Activity Report Wildlife Division: February Alan Peoples, Chief Bill Dinkines, Assistant Chief Wildlife & Lands Management

CWD-95-12- Attended SE Deer Study Group meeting in Destin, FL. Reviewed literature from other states regarding new CWD cases in Virginia, Missouri, and West Virginia. Discussed CWD response plan with USDA HVIC. Provided CWD status update for Oklahoma at SEDSG meeting in Florida.

www.wildlifedepartment.com/employee/2012/april/wildlife.pdf

Monthly Activity Report Wildlife Division: March Alan Peoples, Chief Bill Dinkines, Assistant Chief Wildlife & Lands Management

CWD9512- Assisted with 2 roadkill deer in NW OKC for CWD samples. Removed obex from roadkilled deer. Disposed of heads. Traveled to reported roadkill location, evaluated deer for suitability. Removed unsuitable roadkill from roadway. Researched IR camera purchase. Researched and purchased digital camera.

www.wildlifedepartment.com/employee/2012/may/wildlife.pdf

Monthly Activity Report Wildlife Division: January, 2013 Alan Peoples, Chief Bill Dinkines, Assistant Chief Wildlife & Lands Management

095-CWD-13- Pulled CWD sample on road-killed deer. Prepared quarterly report, determined rollover/add-on for next budget cycle. Submitted paperwork to APHIS. Checked on and purchased equipment for CWD grant.

www.wildlifedepartment.com/employee/2013/March/Wildlife%20Feb.pdf

Monthly Activity Report Wildlife Division: April, 2013 Alan Peoples, Chief Bill Dinkines, Assistant Chief Wildlife & Lands Management

095-CWD-13- Held a meeting with ODAFF regarding captive cervid program and shared concerns regarding transmission of CWD from captive herds to native animals. Met with ODWC Wildlife Div. staff prior to ODAFF meeting to solidify Dept. position.

wildlifedepartment.com/employee/2013/July/Wildlife.pdf

Monthly Activity Report Wildlife Division: April, 2014 Alan Peoples, Chief Bill Dinkines, Assistant Chief Wildlife & Lands Management

F12AF00615- Big Game: Entered deer data from DMAP, DCAP and check station books onto spreadsheets. Entered student data for deer ages into spreadsheet. Completed DMAP summaries for each cooperator. Made copy of age sheets for each DMAP cooperator. Mailed DMAP summary packets. Sent DMAP summaries to each biologist for their properties. Bundled 10,000 carcass tags for 2014 season. Updated 2013 DMAP compliance spreadsheet. Made new 2014 spreadsheets for DMAP by biologists and by county. Aged deer jaws. Entered data, prepped data, edited data, and began SAS runs of data, started building tables for BGR. Research trailer and gun for SCI grant, prepped, and submitted grants request. Prep for field day in Okmulgee. Discuss CWD funding opportunity, responded to RMEF grant department on Dewey County survey, Send IE 2014-15 deer season dates. Submitted samples to SCWDS for testing. Discussions with supervisors about long range deer plan.

www.wildlifedepartment.com/employee/2014/may/wildlife.pdf

FEBRUARY 2001 NEWS RELEASES

> A degenerative brain disease similar to mad cow disease - called Chronic Wasting Disease (CWD) in deer and elk - has been recently confirmed in a captive elk herd in Oklahoma County Oklahoma Venison and Elk Safe To Eat

Recent media reports linking eating wild deer meat to a form of “mad cow disease” have been sensationalized, and hunters should not been worried about their venison, according to officials with the Oklahoma Department of Wildlife Conservation.

A degenerative brain disease similar to mad cow disease - called Chronic Wasting Disease (CWD) in deer and elk - has been recently confirmed in a captive elk herd in Oklahoma County, but has never been documented in wild deer or elk in Oklahoma. Even if the disease did exist in wild herds, there has never been a confirmed case of a hunter contracting it through hunting or eating venison.

“Chronic Wasting Disease has occurred in Colorado and Wyoming for 30 years, but nobody who has hunted there or eaten venison from those animals has come down with CWD,” said Mike Shaw, wildlife research supervisor for the Wildlife Department. “A hunter from Vinita contracted Creuztfelt-Jacob Disease (CJD), a related spongiform encephalopathy, in 1999, but the National Center for Disease Control never established a positive connection to his eating deer meat. We even investigated the possible link by sampling 16 deer from the area where the man hunted. None of the deer tested positive for Chronic Wasting Disease. In addition, we have tested more than 200 deer from other parts of the state, and those deer have all been negative for CWD.”

In fact, nationally there are over 11 million big game hunters, and only two confirmed reports of hunters contracting Creutzfeldt-Jacob Disease, Shaw said. The Center for Disease Control investigated both cases and concluded that their contracting CJD was coincidental to hunting.

“There is always a risk involved with handling any type of animals, domestic or wild, but that risk is very small,” he said. “The odds are many times greater that someone would be struck by lightning or die from a bee sting.”

Shaw said there are two precautions that anyone concerned about chronic wasting disease can take. Wearing protective gloves when dressing and butchering animals and avoiding consumption of brain and spinal cord tissue are good precautionary measures.

Dr. Gene Eskew, a veterinarian with the Oklahoma Department of Agriculture, said the captive elk in Oklahoma County are under quarantine, and they do not believe any infected elk have been killed for human consumption. Only four of the 140 elk have contracted the disease thus far. Agriculture Department officials will be watching for additional elk deaths, and will test the animals immediately through the National Veterinary Services Laboratory in Ames, Iowa.

“As a biological scientist who has studied deer most of my life, I can honestly say that I don’t see any danger in eating deer meat because there just isn’t any scientific evidence proving that Chronic Wasting Disease can cause Creutzfeldt-Jacob Disease,” Shaw said. “There are far too many other things to worry about; real dangers like driving to work, having a heart attack because you don’t exercise enough or getting stung by a bee.

www.wildlifedepartment.com/newsreleasearchive/2001/02-01nr.htm

FEBRUARY 2001 NEWS RELEASES

A degenerative brain disease similar to mad cow disease - called Chronic Wasting Disease (CWD) in deer and elk – *** has been recently confirmed in a captive elk herd in Oklahoma County, but has never been documented in wild deer or elk in Oklahoma. Even if the disease did exist in wild herds, there has never been a confirmed case of a hunter contracting it through hunting or eating venison.

www.wildlifedepartment.com/newsreleasearchive/2001/02-01nr.htm

soonersearch.ok.gov//agencies/wildlife/results.htm?cref=http%3A%2F%2Fwww.ok.gov%2Fsoonersearch%2Fxml%2Fcse_WilDep.xml&cof=FORID%3A9&q=chronic+wasting+disease+cwd&sa=Search&siteurl=www.wildlifedepartment.com%2Fsearch.htm&ref=www.wildlifedepartment.com%2Fchunt%2Fstep1.htm&ss=0j0j1

Farmed Cervidae

“Farmed Cervidae” are cervid species raised in captivity for the purpose of supplying the commercial hunting industry with livestock. In Oklahoma, the majority of this industry is whitetail deer with elk making up a smaller portion. These animals are intensively managed, fed, and selectively bred for antler mass, spread, and classification (typical vs. non-typical). Not all farmed cervidae are ultimately hunted, however. As global demand for venison rises, some animals are raised for slaughter, while other producers raise farmed cervidae for the sole purpose of hobby and enjoyment.

Current Topics

•License renewal applications for Farmed Cervidae Facilities will be mailed out in January and are due by April 1, 2016.

•Annual CWD Inventories and Triannual Tuberculosis/Brucellosis Testing is due between January 1, 2016 and April 1, 2016 for applicable herds.

•Cervid imports into Oklahoma from Missouri are once again permissible since Missouri is currently accepting cervid imports from Oklahoma.

Import Requirements

All cervidae imported into the state of Oklahoma must have the following: an approved permit application, valid certificate of veterinary inspection, proper identification, tuberculosis and brucellosis testing, and chronic wasting disease herd certification status. The permit application below explains these requirements in full. The veterinarian of the consignor in the exporting state completes and submits the permit application and certificate of veterinary inspection. The consignee of any import must hold a valid farmed cervidae facility license or commercial hunting area license. Cervidae imports are restricted from any county where Chronic Wasting Disease has been identified among free-ranging cervidae (map linked below).

•Cervidae Import Permit Application

•Import Requirements of Other States

• Map of CWD Positive Counties

Facility Licensing

Any farmed cervidae facility in Oklahoma maintaining whitetail deer, mule deer, red deer, or elk is required to be licensed by The Oklahoma Department of Agriculture. The purpose of facility licensing is multifold: to prevent the commingling of native cervidae with captive cervidae, to protect the farmed cervidae and hunting industries in Oklahoma from chronic wasting disease, and to protect the farmed cervidae and cattle industries of Oklahoma from the controlled diseases the two have in common. The Oklahoma Department of Wildlife Conservation licenses commercial hunting areas in Oklahoma where the majority of farmed cervidae are ultimately harvested.

•Farmed Cervidae License Application

•Oklahoma Farmed Cervidae Act & Rules

•Licensing Explained

• Carcass Disposal Regulations

Exotic Cervidae Species Registration

All species in the Cervidae Family (other than whitetail deer, mule deer, red deer, and elk) are currently considered “exotics” by Oklahoma regulations and are exempt from facility licensing. However, due to the concern of controlled diseases, owners of these species must register with the Oklahoma Department of Agriculture unless already licensed by the Oklahoma Department of Wildlife Conservation or USDA Animal Care. This registration will also help keep registrants informed of any emergency disease information.

Please submit the completed form below to [e-mail] or Fax [phone].

Exotic Cervidae Owner Registration Form

Chronic Wasting Disease (CWD) Herd Certification Program (HCP)

The CWD HCP is a voluntary surveillance program designed to verify that a cervidae herd is low risk for CWD. Federal rule and program standards for interstate transport of cervidae and a national CWD HCP were passed in August 2012 and implemented by ODAFF. Herds that complete five years of the program with no evidence of CWD are designated as “certified” and are allowed to transport cervidae species interstate. Producers can purchase CWD certified cervidae and “inherit” the status of the original herd or can start with non-monitored animals at year one and work their way up through the program year-by-year. CWD herd certification not only allows herds to be moved interstate, it also adds value to a herd while helping producers protect the health of their animals. A CWD HCP application must be submitted to ODAFF and approved for participation in the program.

•CWD HCP Application and Inventory Form

•CWD Inventory and Inspections Explained Presentation

•Map of CWD Certified Veterinarians

•CWD HCP Federal Rule

• CWD HCP Program Standards

• USDA CWD HCP WebPage

www.oda.state.ok.us/ais/farmedcervidae.htm

*** Oklahoma Captive figures for CWD testing and surveillance will come at a later date, and this url will but updated...tss ***

*** •Cervid imports into Oklahoma from Missouri are once again permissible since Missouri is currently accepting cervid imports from Oklahoma.

Sunday, March 06, 2016

Missouri 2015-2016 CWD Surveillance Summary to Date, with confirmed cases mounting

chronic-wasting-disease.blogspot.com/2016/03/missouri-2015-2016-cwd-surveillance.html

Snip...See full text;

Tuesday, March 08, 2016

Oklahoma Chronic Wasting Disease CWD of Deer and Elk Surveillance, Testing, and Preparedness

chronic-wasting-disease.blogspot.com/2016/03/oklahoma-chronic-wasting-disease-cwd-of.html

chronic-wasting-disease.blogspot.com/2022/09/oklahoma-odwc-activates-cwd-response.html

TEXAS CWD 2023

WEDNESDAY, JUNE 14, 2023

Texas TPWD CWD 508 Cases Confirmed To Date

chronic-wasting-disease.blogspot.com/2023/06/texas-tpwd-cwd-508-cases-confirmed-to.html

TUESDAY, JUNE 27, 2023

USAHA Report of the Subcommittee on Farmed Cervidae CWD TSE Prion Herds 2015 to 2023

chronic-wasting-disease.blogspot.com/2023/06/usaha-report-of-subcommittee-on-farmed.html

prpsc.proboards.com/thread/128/usaha-reports-farmed-cervidae-herds

2023 CWD ZOONOSIS

***> Currently, there is scientific evidence to suggest that CWD has zoonotic potential; however, no confirmed cases of CWD have been found in humans.<***

PART 2. TPWD CHAPTER 65. DIVISION 1. CWD

31 TAC §§65.82, 65.85, 65.88

The Texas Parks and Wildlife Commission in a duly noticed meeting on May 25, 2023 adopted amendments to 31 TAC §§65.82, 65.85, and §65.88, concerning Disease Detection and Response, without changes to the proposed text as published in the April 21, 2023, issue of the Texas Register (48 TexReg 2048). The rules will not be republished.

Currently, there is scientific evidence to suggest that CWD has zoonotic potential; however, no confirmed cases of CWD have been found in humans.

www.sos.texas.gov/texreg/archive/June302023/Adopted%20Rules/31.NATURAL%20RESOURCES%20AND%20CONSERVATION.html#57

U of M expert warns of increasing likelihood of CWD transmission to humans

Cathy Wurzer and Gretchen Brown June 5, 2023 1:30 PM

Minnesota scientists have watched chronic wasting disease (CWD) — a fatal, neurological illness — kill deer and elk.

Now, they’re studying its potential to jump to humans.

The University of Minnesota’s Center for Infectious Disease Research and Policy has received more than $1.5 million in state money to start prepping for the possibility of CWD spreading to cows, pigs and possibly humans.

Michael Osterholm, Ph.D. is a world-renowned epidemiologist who heads the center.

He said transmission to humans has not yet been confirmed, but research suggests it is increasingly likely — especially as the disease continues to spread among deer and elk.

“None of us want to believe this could happen,” he told MPR News host Cathy Wurzer. “But you know, as much as you hope it isn't going to happen, hope is not a strategy.”

Current testing can be done only if animals die or are killed, and lymph nodes or brain matter is removed for testing to verify the disease.

That means captive deer often aren’t tested until they die or show symptoms of the disease, and that’s often too late to stop the spread of the disease.

And there aren’t yet adequate tests for humans, Osterholm said — let alone protocols in place if a human were to test positive for the disease.

snip...see;

U of M expert warns of increasing likelihood of CWD transmission to humans

Published: 22 August 2022

www.mprnews.org/episode/2023/06/05/chronic-wasting-disease-in-humans-us-osterholm-prepares-for-whatif?

Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD

Samia Hannaoui, Irina Zemlyankina, Sheng Chun Chang, Maria Immaculata Arifin, Vincent Béringue, Debbie McKenzie, Hermann M. Schatzl & Sabine Gilch

Acta Neuropathologica volume 144, pages767–784 (2022)

Inoculation of these mice with deer CWD isolates resulted in atypical clinical manifestation with prion seeding activity and efficient transmissible infectivity in the brain and, remarkably, in feces, but without classical neuropathological or Western blot appearances of prion diseases.

In contrast, in cervids affected with CWD, infectivity has been found in the lymphatic system, salivary gland, intestinal tract, muscles, antler velvet, blood, urine, saliva, and feces [4], which have been demonstrated to be transmissible [57].

These data demonstrate that humanized tg650 mice inoculated with CWD prions shed prion infectivity in feces able to generate transmissible PrPSc in bank voles distinct from those generated by inoculation of the Wisc-1 deer isolate directly to bank voles.

Our findings strongly suggest that CWD should be regarded as an actual public health risk. Here, we use humanized mice to show that CWD prions can cross the species barrier to humans, and remarkably, infectious prions can be excreted in feces.

The presence of infectious prions shed in feces is one argument in favor of the existence of de novo generated PrPSc in these mice.

CWD in humans might remain subclinical but with PrPSc deposits in the brain with an unusual morphology that does not resemble the patterns usually seen in different prion diseases (e.g., mouse #328; Fig. 3), clinical with untraceable abnormal PrP (e.g., mouse #327) but still transmissible and uncovered upon subsequent passage (e.g., mouse #3063; Fig. 4), or prions have other reservoirs than the usual ones, hence the presence of infectivity in feces (e.g., mouse #327) suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable. Here, humanized mice inoculated with CWD deer isolates had an atypical onset of the disease with myoclonus (93.75%), before presenting typical clinical signs, generating prions that presented with either atypical biochemical signature (#321 and #3063), shed in feces (#327), or were undetectable by the classical detection methods.

The finding that infectious PrPSc was shed in fecal material of CWD-infected humanized mice and induced clinical disease, different tropism, and typical three banding pattern-PrPres in bank voles that is transmissible upon second passage is highly concerning for public health. The fact that this biochemical signature in bank voles resembles that of the Wisc-1 original deer isolate and is different from that of bvWisc-1, in the migration profile and the glyco-form-ratio, is valid evidence that these results are not a product of contamination in our study. If CWD in humans is found to be contagious and transmissible among humans, as it is in cervids [57], the spread of the disease within humans might become endemic. In contrast to bank voles inoculated with fecal homogenates from mouse #327, so far, we could not detect a PK-resistant PrPSc fragment in the brain homogenates of fecal homogenate-inoculated tg650 mice. The presence of PrPres in these mice will allow us to determine if the molecular signature of hCWD prions from the brain (mouse #321 and #3063) vs feces are the same. Previously, Beringue et al. found that extraneural prions, compared to neural prions, helped more to overcome the species barrier to foreign prions, in addition, different strain types emerged from such serial transmission [11]. Our data also suggest that prions found in the periphery may hold higher zoonotic potential than prions found in neural tissues. In fact, upon second passage, 50% of the tg650 mice inoculated with fecal homogenates from mouse #327 had succumbed with terminal disease compared to only 20% of brain/spinal cord homogenates inoculated-tg650 mice suggesting that hCWD prions found in feces transmit disease more efficiently. Our results also suggest that epidemiological studies [25] may have missed subclinical and atypical infections that are/might be transmissible, undetected by the gold standard tests, i.e., Western blot, ELISA, and IHC.

Overall, our findings suggest that CWD surveillance in humans should encompass a wider spectrum of tissues/organs tested and include new criteria in the diagnosis of potential patients.

Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD - Acta Neuropathologica

Therefore, although in vitro seeded PrPSc amplification by PMCA may not mimic all aspects of in vivo conversion of brain PrPC into PrPSc, our finding of the CWD-induced conversion of human brain PrPC into PrPSc suggests the potential of transmission of CWD to humans.

actaneurocomms.biomedcentral.com/counter/pdf/10.1186/s40478-021-01262-y.pdf

Transmission of Cervid Prions to Humanized Mice Demonstrates the Zoonotic Potential of CWD

Samia Hannaouia, Irina Zemlyankinaa, Sheng Chun Changa, Maria Immaculata Arifina, Vincent Béringueb, Debbie McKenziec, Hermann M. Schatzla, and Sabine Gilcha

aDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine; Hotchkiss Brain Institute; University of Calgary, Calgary, Canada; bUniversité Paris-Saclay, INRAE, UVSQ, VIM, Jouy-en-Josas, France; cDepartment of Biological Sciences, Center for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Canada

Aims: Chronic wasting disease (CWD), a prion disease of cervids, spreads efficiently among wild and farmed animals. Potential transmission to humans of CWD is a growing concern due to its increasing prevalence. Here, we aimed to determine the zoonotic potential of CWD using a mouse model for human prion diseases.

Material and Methods: Transgenic mice overexpressing human PrPChomozygous for methionine at codon 129 (tg650) were inoculated intracerebrally with brain homogenates of white-tailed deer infected with Wisc-1/CWD1 or 116AG CWD strains. Mice were monitored for clinical signs and were euthanized at terminal disease. Brains were tested by RT-QuIC, western blot upon PK digestion, and immunohistochemistry; fecal homogenates were analyzed by RT-QuIC. Brain/spinal cord and fecal homogenates of CWD-inoculated tg650 mice were inoculated into tg650 mice or bank voles. Brain homogenates of bank voles inoculated with fecal homogenates of CWD-infected tg650 mice were used for second passage in bank voles.

Results: Here, we provide the strongest evidence supporting the zoonotic potential of CWD prions, and their possible phenotype in humans. Inoculation of mice expressing human PrPCwith deer CWD isolates (strains Wisc-1 and 116AG) resulted in atypical clinical manifestations in > 75% of the mice, with myoclonus as leading clinical sign. Most of tg650 brain homogenates were positive for seeding activity in RT-QuIC. Clinical disease and presentation was transmissible to tg650 mice and bank voles. Intriguingly, protease-resistant PrP in the brain of tg650 mice resembled that found in a familial human prion disease and was transmissible upon passage. Abnormal PrP aggregates upon infection with Wisc-1 were detectable in thalamus, hypothalamus, and midbrain/pons regions.

Unprecedented in human prion disease, feces of CWD-inoculated tg650 mice harbored prion seeding activity and infectious prions, as shown by inoculation of bank voles and tg650 with fecal homogenates.

Conclusions: This is the first evidence that CWD can infect humans and cause disease with a distinctive clinical presentation, signature, and tropism, which might be transmissible between humans while current diagnostic assays might fail to detect it. These findings have major implications for public health and CWD-management.

Funded by: We are grateful for financial support from the Natural Sciences and Engineering Research Council of Canada, the National Institutes of Health, Genome Canada, and the Alberta Prion Research Institute. SG is supported by the Canada Research Chairs program.

Acknowledgement: We thank Dr. Trent Bollinger, WCVM, University of Saskatchewan, Saskatoon, Canada, for providing brain tissue from the WTD-116AG isolate, Dr. Stéphane Haïk, ICM, Paris, France, for providing brain tissue from vCJD and sCJD cases, and Dr. Umberto Agrimi, Istituto Superiore di Sanità, Italy, for the bank vole model. We thank animal facility staff for animal care, Dr. Stephanie Anderson for veterinary oversight, and Yo-Ching Cheng for preparing recombinant PrP substrates. Thank you to Dr. Stephanie Booth and Jennifer Myskiw, Public Health Agency of Canada, Canada.

www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286

P35

ADAPTATION OF CHRONIC WASTING DISEASE (CWD) INTO HAMSTERS, EVIDENCE OF A WISCONSIN STRAIN OF CWD

Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2 Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary Research Institute, 4.Center for Prions and Protein Folding Diseases, 5 Department of Biological Sciences, University of Alberta, Edmonton AB, Canada T6G 2P5

The identification and characterization of prion strains is increasingly important for the diagnosis and biological definition of these infectious pathogens. Although well-established in scrapie and, more recently, in BSE, comparatively little is known about the possibility of prion strains in chronic wasting disease (CWD), a disease affecting free ranging and captive cervids, primarily in North America. We have identified prion protein variants in the white-tailed deer population and demonstrated that Prnp genotype affects the susceptibility/disease progression of white-tailed deer to CWD agent. The existence of cervid prion protein variants raises the likelihood of distinct CWD strains. Small rodent models are a useful means of identifying prion strains. We intracerebrally inoculated hamsters with brain homogenates and phosphotungstate concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD endemic area) and experimentally infected deer of known Prnp genotypes. These transmission studies resulted in clinical presentation in primary passage of concentrated CWD prions. Subclinical infection was established with the other primary passages based on the detection of PrPCWD in the brains of hamsters and the successful disease transmission upon second passage. Second and third passage data, when compared to transmission studies using different CWD inocula (Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin white-tailed deer population is different than the strain(s) present in elk, mule-deer and white-tailed deer from the western United States endemic region.

www.istitutoveneto.it/prion_09/Abstracts_09.pdf

PRION CONFERENCE 2009

Prion special issue related to the III International Symposium on “The New Prion Biology

www.tandfonline.com/doi/pdf/10.4161/pri.3.4.10772?needAccess=true

www.tandfonline.com/toc/kprn20/3/4?nav=tocList

www.neuroprion.org/

www.certh.gr/dat/EED86597/file.pdf

UPDATE CWD ZOONOSIS AND THE WISCONSIN STRAIN

SUNDAY, APRIL 9, 2023

Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD

SEE A FEW HIGHLIGHTS;

''Here, we provide evidence for a zoonotic potential of CWD prions, and its probable signature using mice expressing human prion protein (PrP) as an infection model.''

''Furthermore, the presence of infectious prions in feces is concerning because if this occurs in humans, it is a source for human-to-human transmission.'' ''These findings have strong implications for public health and CWD management.''

''We demonstrate that this transgenic line was susceptible to infection with CWD prions and displayed a distinct leading clinical sign, an atypical PrPSc signature and unusual fecal shedding of infectious prions.''

''Importantly, these prions generated by the human PrP transgenic mice were transmissible upon passage.''

Our results are the first evidence of a zoonotic risk of CWD when using one of the most common CWD strains, Wisc-1/CWD1 for ''infection. ''

''Our findings strongly suggest that CWD should be regarded as an actual public health risk. Here, we use humanized mice to show that CWD prions can cross the species barrier to humans, and remarkably, infectious prions can be excreted in feces.''

''Indeed, such heterogeneity and distinct seeding activities and infectivity of abnormal PrP fragments was observed in VPSPr cases [20, 43].''

''This implies a high risk of exposure to this strain, e.g., through consumption or handling of infected carcasses, in contrast to rarer CWD strains, and therefore, an actual risk for human health.''

''Fecal shedding of infectious prions, if it occurs in humans, is particularly concerning because of potential human-to-human transmission and adaptation of hCWD.''

Overall, our findings suggest that CWD surveillance in humans should encompass a wider spectrum of tissues/organs tested and include new criteria in the diagnosis of potential patients.

***> PLEASE NOTE;

''Our results indicate that if CWD crosses the species-barrier to humans, it is unlikely to resemble the most common forms of human prion diseases with respect to clinical signs, tissue tropism and PrPSc signature. For instance, PrPSc in variable protease-sensitive prionopathy (VPSPr), a sporadic form of human prion disease, and in the genetic form Gerstmann-Sträussler-Scheinker syndrome (GSS) is defned by an atypical PK-resistant PrPSc fragment that is non-glycosylated and truncated at both C- and N-termini, with a molecular weight between 6 and 8 kDa [24, 44–46]. These biochemical features are unique and distinctive from PrPSc (PrP27-30) found in most other human or animal prion disease. The atypical PrPSc signature detected in brain homogenate of tg650 mice #321 (1st passage) and #3063 (2nd passage), and the 7–8 kDa fragment (Figs. 2, 4) are very similar to that of GSS, both in terms of migration profle and the N-terminal cleavage site.''

snip...

''CWD in humans might remain subclinical but with PrPSc deposits in the brain with an unusual morphology that does not resemble the patterns usually seen in different prion diseases (e.g., mouse #328; Fig. 3), clinical with untraceable abnormal PrP (e.g., mouse #327) but still transmissible and uncovered upon subsequent passage (e.g., mouse #3063; Fig. 4), or prions have other reservoirs than the usual ones, hence the presence of infectivity in feces (e.g., mouse #327) suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable. Here, humanized mice inoculated with CWD deer isolates had an atypical onset of the disease with myoclonus (93.75%), before presenting typical clinical signs, generating prions that presented with either atypical biochemical signature (#321 and #3063), shed in feces (#327), or were undetectable by the classical detection methods. The fact that we could not establish a strong correlation between disease manifestation in tg650 mice inoculated with Wisc-1- or 116AG-CWD and the presence of abnormal PrP (Western blot, IHC or RTQuIC) might be explained by the presence of heterogeneous prions in the brains of infected mice with diferent seeding properties in vitro. Indeed, such heterogeneity and distinct seeding activities and infectivity of abnormal PrP fragments was observed in VPSPr cases [20, 43].''

VPSPr, GSS, and CWD zoonosis, concerns there from, where did i hear this concern before?

1. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.

link.springer.com/article/10.1007/s00401-022-02482-9

efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2018.5132

transmissiblespongiformencephalopathy.blogspot.com/2023/04/transmission-of-cervid-prions-to.html

Heterozygosity for cervid S138N polymorphism results in subclinical CWD in gene-targeted mice and progressive inhibition of prion conversion

HIGHLIGHT

However, prion seeding activity was detected in spleens, brains, and feces of these mice, suggesting subclinical infection accompanied by prion shedding.

Infected animals accumulate prions in lymphoreticular and other peripheral tissues, e.g., skeletal muscle, and shed infectious prions in saliva, urine and feces, contributing to direct and environmental transmission and rapidly increasing geographic distribution of CWD (9–12).

However, prion-seeding activity was detectable in the brain, spleen, and feces, indicating subclinical infection and potential for contagiousness.

Heterozygosity for cervid S138N polymorphism results in subclinical CWD in gene-targeted mice and progressive inhibition of prion conversion

Maria I. Arifin orcid.org/0000-0003-2042-3492, Lech Kaczmarczyk orcid.org/0000-0003-2747-3134, Doris Zeng orcid.org/0009-0002-2512-6227, +7, and Sabine Gilch orcid.org/0000-0001-5923-3464 [e-mail] Info & Affiliations Edited by Reed Wickner, NIH, Bethesda, MD;

received December 12, 2022; accepted March 6, 2023

April 4, 2023

120 (15) e2221060120

doi.org/10.1073/pnas.2221060120

Significance

Amino acid substitutions within the cervid prion protein (PrP) can decrease susceptibility to chronic wasting disease, generally with more prominent effects in homozygous animals. Using novel gene-targeted mouse models expressing S138N reindeer/caribou PrP, we demonstrate subclinical infection with prion seeding activity in spleen and fecal prion shedding in heterozygous 138SN and homozygous 138NN mice. A lower percentage of heterozygous 138SN-PrP than homozygous 138NN-PrP expressing mice harbored seeding-efficient prions in tissues. This is caused by dominant-negative interference of the PrP variants occurring only if they are coexpressed. Our findings are relevant to inform conservation efforts for caribou, an endangered species in North America. Furthermore, our study provides new mechanistic insights into genetic resistance and dominant-negative interference of conversion-competent PrP variants.

Abstract

Prions are proteinaceous infectious particles that replicate by structural conversion of the host-encoded cellular prion protein (PrPC), causing fatal neurodegenerative diseases in mammals. Species-specific amino acid substitutions (AAS) arising from single nucleotide polymorphisms within the prion protein gene (Prnp) modulate prion disease pathogenesis, and, in several instances, reduce susceptibility of homo- or heterozygous AAS carriers to prion infection. However, a mechanistic understanding of their protective effects against clinical disease is missing. We generated gene-targeted mouse infection models of chronic wasting disease (CWD), a highly contagious prion disease of cervids. These mice express wild-type deer or PrPC harboring the S138N substitution homo- or heterozygously, a polymorphism found exclusively in reindeer (Rangifer tarandus spp.) and fallow deer (Dama dama). The wild-type deer PrP-expressing model recapitulated CWD pathogenesis including fecal shedding. Encoding at least one 138N allele prevented clinical CWD, accumulation of protease-resistant PrP (PrPres) and abnormal PrP deposits in the brain tissue. However, prion seeding activity was detected in spleens, brains, and feces of these mice, suggesting subclinical infection accompanied by prion shedding. 138N-PrPC was less efficiently converted to PrPres in vitro than wild-type deer (138SS) PrPC. Heterozygous coexpression of wild-type deer and 138N-PrPC resulted in dominant-negative inhibition and progressively diminished prion conversion over serial rounds of protein misfolding cyclic amplification. Our study indicates that heterozygosity at a polymorphic Prnp codon can confer the highest protection against clinical CWD and highlights the potential role of subclinical carriers in CWD transmission.

snip...

To conclude, our study demonstrates that CWD-infected animals harboring S138N PrP might be “silent spreaders” of CWD prions and highlights the importance of lymphatic tissues in the detection of CWD, particularly in caribou, even in the absence of clinical manifestation. It is important to keep in mind that even protective genotypes may be permissive to certain minor or newly emerging CWD strains. Our results provide new mechanistic insights into dominant-negative inhibition of prion conversion, the tissue specificity of this effect, and suggests that PrPC primary structure is a determinant for tissue-specific prion replication.

www.pnas.org/doi/10.1073/pnas.2221060120

A CAPTIVE QUARANTEENED CWD HERD IS A TIME BOMB WAITING TO GO OFF!

CHRONIC WASTING DISEASE CASESCWD STATUS OF CAPTIVE HERDS

www.aphis.usda.gov/animal_health/animal_diseases/cwd/downloads/status-of-captive-herds.pdf

Heterozygosity for cervid S138N polymorphism results in subclinical CWD in gene-targeted mice and progressive inhibition of prion conversion

HIGHLIGHT

However, prion seeding activity was detected in spleens, brains, and feces of these mice, suggesting subclinical infection accompanied by prion shedding.

Infected animals accumulate prions in lymphoreticular and other peripheral tissues, e.g., skeletal muscle, and shed infectious prions in saliva, urine and feces, contributing to direct and environmental transmission and rapidly increasing geographic distribution of CWD (9–12).

However, prion-seeding activity was detectable in the brain, spleen, and feces, indicating subclinical infection and potential for contagiousness.

Heterozygosity for cervid S138N polymorphism results in subclinical CWD in gene-targeted mice and progressive inhibition of prion conversion

Maria I. Arifin orcid.org/0000-0003-2042-3492, Lech Kaczmarczyk orcid.org/0000-0003-2747-3134, Doris Zeng orcid.org/0009-0002-2512-6227, +7, and Sabine Gilch orcid.org/0000-0001-5923-3464 [e-mail] Info & Affiliations Edited by Reed Wickner, NIH, Bethesda, MD;

received December 12, 2022; accepted March 6, 2023

April 4, 2023

120 (15) e2221060120

doi.org/10.1073/pnas.2221060120

Significance

Amino acid substitutions within the cervid prion protein (PrP) can decrease susceptibility to chronic wasting disease, generally with more prominent effects in homozygous animals. Using novel gene-targeted mouse models expressing S138N reindeer/caribou PrP, we demonstrate subclinical infection with prion seeding activity in spleen and fecal prion shedding in heterozygous 138SN and homozygous 138NN mice. A lower percentage of heterozygous 138SN-PrP than homozygous 138NN-PrP expressing mice harbored seeding-efficient prions in tissues. This is caused by dominant-negative interference of the PrP variants occurring only if they are coexpressed. Our findings are relevant to inform conservation efforts for caribou, an endangered species in North America. Furthermore, our study provides new mechanistic insights into genetic resistance and dominant-negative interference of conversion-competent PrP variants.

Abstract

Prions are proteinaceous infectious particles that replicate by structural conversion of the host-encoded cellular prion protein (PrPC), causing fatal neurodegenerative diseases in mammals. Species-specific amino acid substitutions (AAS) arising from single nucleotide polymorphisms within the prion protein gene (Prnp) modulate prion disease pathogenesis, and, in several instances, reduce susceptibility of homo- or heterozygous AAS carriers to prion infection. However, a mechanistic understanding of their protective effects against clinical disease is missing. We generated gene-targeted mouse infection models of chronic wasting disease (CWD), a highly contagious prion disease of cervids. These mice express wild-type deer or PrPC harboring the S138N substitution homo- or heterozygously, a polymorphism found exclusively in reindeer (Rangifer tarandus spp.) and fallow deer (Dama dama). The wild-type deer PrP-expressing model recapitulated CWD pathogenesis including fecal shedding. Encoding at least one 138N allele prevented clinical CWD, accumulation of protease-resistant PrP (PrPres) and abnormal PrP deposits in the brain tissue. However, prion seeding activity was detected in spleens, brains, and feces of these mice, suggesting subclinical infection accompanied by prion shedding. 138N-PrPC was less efficiently converted to PrPres in vitro than wild-type deer (138SS) PrPC. Heterozygous coexpression of wild-type deer and 138N-PrPC resulted in dominant-negative inhibition and progressively diminished prion conversion over serial rounds of protein misfolding cyclic amplification. Our study indicates that heterozygosity at a polymorphic Prnp codon can confer the highest protection against clinical CWD and highlights the potential role of subclinical carriers in CWD transmission.

snip...

To conclude, our study demonstrates that CWD-infected animals harboring S138N PrP might be “silent spreaders” of CWD prions and highlights the importance of lymphatic tissues in the detection of CWD, particularly in caribou, even in the absence of clinical manifestation. It is important to keep in mind that even protective genotypes may be permissive to certain minor or newly emerging CWD strains. Our results provide new mechanistic insights into dominant-negative inhibition of prion conversion, the tissue specificity of this effect, and suggests that PrPC primary structure is a determinant for tissue-specific prion replication.

www.pnas.org/doi/10.1073/pnas.2221060120

Published: 22 August 2022

Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD

Samia Hannaoui, Irina Zemlyankina, Sheng Chun Chang, Maria Immaculata Arifin, Vincent Béringue, Debbie McKenzie, Hermann M. Schatzl & Sabine Gilch

Acta Neuropathologica volume 144, pages767–784 (2022)

Inoculation of these mice with deer CWD isolates resulted in atypical clinical manifestation with prion seeding activity and efficient transmissible infectivity in the brain and, remarkably, in feces, but without classical neuropathological or Western blot appearances of prion diseases.

In contrast, in cervids affected with CWD, infectivity has been found in the lymphatic system, salivary gland, intestinal tract, muscles, antler velvet, blood, urine, saliva, and feces [4], which have been demonstrated to be transmissible [57].

These data demonstrate that humanized tg650 mice inoculated with CWD prions shed prion infectivity in feces able to generate transmissible PrPSc in bank voles distinct from those generated by inoculation of the Wisc-1 deer isolate directly to bank voles.

Our findings strongly suggest that CWD should be regarded as an actual public health risk. Here, we use humanized mice to show that CWD prions can cross the species barrier to humans, and remarkably, infectious prions can be excreted in feces.

The presence of infectious prions shed in feces is one argument in favor of the existence of de novo generated PrPSc in these mice.

CWD in humans might remain subclinical but with PrPSc deposits in the brain with an unusual morphology that does not resemble the patterns usually seen in different prion diseases (e.g., mouse #328; Fig. 3), clinical with untraceable abnormal PrP (e.g., mouse #327) but still transmissible and uncovered upon subsequent passage (e.g., mouse #3063; Fig. 4), or prions have other reservoirs than the usual ones, hence the presence of infectivity in feces (e.g., mouse #327) suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable. Here, humanized mice inoculated with CWD deer isolates had an atypical onset of the disease with myoclonus (93.75%), before presenting typical clinical signs, generating prions that presented with either atypical biochemical signature (#321 and #3063), shed in feces (#327), or were undetectable by the classical detection methods.

The finding that infectious PrPSc was shed in fecal material of CWD-infected humanized mice and induced clinical disease, different tropism, and typical three banding pattern-PrPres in bank voles that is transmissible upon second passage is highly concerning for public health. The fact that this biochemical signature in bank voles resembles that of the Wisc-1 original deer isolate and is different from that of bvWisc-1, in the migration profile and the glyco-form-ratio, is valid evidence that these results are not a product of contamination in our study. If CWD in humans is found to be contagious and transmissible among humans, as it is in cervids [57], the spread of the disease within humans might become endemic. In contrast to bank voles inoculated with fecal homogenates from mouse #327, so far, we could not detect a PK-resistant PrPSc fragment in the brain homogenates of fecal homogenate-inoculated tg650 mice. The presence of PrPres in these mice will allow us to determine if the molecular signature of hCWD prions from the brain (mouse #321 and #3063) vs feces are the same. Previously, Beringue et al. found that extraneural prions, compared to neural prions, helped more to overcome the species barrier to foreign prions, in addition, different strain types emerged from such serial transmission [11]. Our data also suggest that prions found in the periphery may hold higher zoonotic potential than prions found in neural tissues. In fact, upon second passage, 50% of the tg650 mice inoculated with fecal homogenates from mouse #327 had succumbed with terminal disease compared to only 20% of brain/spinal cord homogenates inoculated-tg650 mice suggesting that hCWD prions found in feces transmit disease more efficiently. Our results also suggest that epidemiological studies [25] may have missed subclinical and atypical infections that are/might be transmissible, undetected by the gold standard tests, i.e., Western blot, ELISA, and IHC.

Overall, our findings suggest that CWD surveillance in humans should encompass a wider spectrum of tissues/organs tested and include new criteria in the diagnosis of potential patients.

link.springer.com/article/10.1007/s00401-022-02482-9
Saturday, April 9, 2022

EFSA EU Request for a scientific opinion on the monitoring of Chronic Wasting Disease (CWD) EFSA-Q-2022-00114 M-2022-00040 Singeltary Submission

efsaopinioncwd.blogspot.com/2022/04/efsa-eu-request-for-scientific-opinion.html
Chronic wasting disease detection in environmental and biological samples from a taxidermy site
Paulina Sotoa,b, J. Hunter Reedc, Mitch Lockwoodc, and Rodrigo Moralesa,b
aDepartment of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA; bUniversidad Bernardo O’Higgins, Santiago, Chile; cTexas Parks and Wildlife Department, Texas, USA
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy affecting captive and free-ranging cervids (e.g., mule deer, white-tailed deer, elk, reindeer, and moose). Nowadays, CWD is widely distributed in North America. It is suggested that CWD spreads due to direct animal contact or through exposure to contaminated environments previously inhabited by infected animals. CWD may also be spread through the movement of infected animals and carcasses. Taxidermy practices involve processing deer tissues (or whole animal carcasses). In many cases, the CWD status of processed animals is unknown. This can generate risks of disease spread and transmission. Taxidermy practices include different steps involving physical, chemical, and biological procedures. Without proper tissue handling or disposal practices, taxidermist facilities may become a focus of prion infectivity.
Aims: In this study, we evaluated the presence of infectious prions in a taxidermy facility believed to be exposed to CWD. Detection was performed using the Protein Misfolding Cyclic Amplification (PMCA) technique in biological and inert environmental samples.
Methods: We collected biological and environmental samples (plants, soils, insects, excreta, and others) from a taxidermy facility, and we tested these samples using the PMCA technique. In addition, we swabbed different surfaces possibly exposed to CWD-infected animals. For the PMCA reaction, we directly used a swab piece or 10 µL of 20% w/v homogenized samples.
Results: The PMCA analysis demonstrated CWD seeding activity in some of the components of this facility, including insects involved in head processing, soils, and a trash dumpster.
Conclusions: Different areas of this property were used for various taxidermy procedures. We were able to detect the presence of prions in i) soils that were in contact with the heads of dead animals, ii) insects involved in the cleaning of skulls, and iii) an empty dumpster where animal carcasses were previously placed. This is the first report demonstrating that swabbing is a helpful method to screen for prion infectivity on surfaces potentially contaminated with CWD. These findings are relevant as this swabbing and amplification strategy may be used to evaluate the disease status of other free-ranging and captive settings where there is a concern for CWD transmissions, such as at feeders and water troughs with CWD-exposed properties. This approach could have substantial implications for free-ranging cervid surveillance as well as in epidemiological investigations of CWD.
Funded by: USDA
Grant number: AP20VSSPRS00C143
PRION 2022 ABSTRACTS, AND A BIG THANK YOU TO On behalf of the Prion2020/2022 Congress Organizing Committee and the NeuroPrion Association, we heartily invite you to join us for the International Conference Prion2020/2022 from 13.-16. September 2022 in Göttingen.

Prion 2022 Conference abstracts: pushing the boundaries

www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286

Large-scale PMCA screening of retropharyngeal lymph nodes and in white-tailed deer and comparisons with ELISA and IHC: the Texas CWD study

Rebeca Benaventea, Paulina Sotoa, Mitch Lockwoodb, and Rodrigo Moralesa aDepartment of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA; bTexas Park and Wildlife Department, Texas, USA

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy that affects various species of cervids, and both free-ranging and captive animals. Until now, CWD has been detected in 3 continents: North America, Europe, and Asia. CWD prevalence in some states may reach 30% of total animals. In Texas, the first case of CWD was reported in a free-range mule deer in Hudspeth and now it has been detected in additional 14 counties. Currently, the gold standard techniques used for CWD screening and detection are ELISA and immunohistochemistry (IHC) of obex and retropharyngeal lymph nodes (RPLN). Unfortunately, these methods are known for having a low diagnostic sensitivity. Hence, many CWD-infected animals at pre-symptomatic stages may be misdiagnosed. Two promising in vitro prion amplification techniques, including the real-time quaking-induced conversion (RT-QuIC) and the protein misfolding cyclic amplification (PMCA) have been used to diagnose CWD and other prion diseases in several tissues and bodily fluids. Considering the low cost and speed of RT-QuIC, two recent studies have communicated the potential of this technique to diagnose CWD prions in RPLN samples. Unfortunately, the data presented in these articles suggest that identification of CWD positive samples is comparable to the currently used ELISA and IHC protocols. Similar studies using the PMCA technique have not been reported.

Aims: Compare the CWD diagnostic potential of PMCA with ELISA and IHC in RPLN samples from captive and free-range white-tailed deer. Material and Methods: In this study we analyzed 1,003 RPLN from both free-ranging and captive white-tailed deer collected in Texas. Samples were interrogated with the PMCA technique for their content of CWD prions. PMCA data was compared with the results obtained through currently approved techniques.

Results: Our results show a 15-fold increase in CWD detection in free-range deer compared with ELISA. Our results unveil the presence of prion infected animals in Texas counties with no previous history of CWD. In the case of captive deer, we detected a 16% more CWD positive animals when compared with IHC. Interestingly, some of these positive samples displayed differences in their electroforetic mobilities, suggesting the presence of different prion strains within the State of Texas.

Conclusions: PMCA sensitivity is significantly higher than the current gold standards techniques IHC and ELISA and would be a good tool for rapid CWD screening.

Funded by: USDA

Grant number: AP20VSSPRS00C143

PRION 2022 ABSTRACTS, AND A BIG THANK YOU TO On behalf of the Prion2020/2022 Congress Organizing Committee and the NeuroPrion Association, we heartily invite you to join us for the International Conference Prion2020/2022 from 13.-16. September 2022 in Göttingen.

Prion 2022 Conference abstracts: pushing the boundaries

www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286

Shedding of Chronic Wasting Disease Prions in Multiple Excreta Throughout Disease Course in White-tailed Deer

Nathaniel D. Denkersa, Erin E. McNultya, Caitlyn N. Krafta, Amy V. Nallsa, Joseph A. Westricha, Wilfred Goldmannb, Candace K. Mathiasona, and Edward A. Hoovera

aPrion Research Center, College of Veterinary Medicine and Biological Sciences, Department of Microbiology, Immunology, and Pathology; Colorado State University, Fort Collins, CO, USA; bDivision of Infection and Immunity, The Roslin Institute and the Royal Dick School of Veterinary Studies, University of Edinburgh, Midlothian, UK

Aims: Chronic wasting disease (CWD) now infects cervids in South Korea, North America, and Scandinavia. CWD is unique in its efficient transmission and shedding of prions in body fluids throughout long course infections. Questions remain as to the magnitude of shedding and the route of prion acquisition. As CWD continues to expand, the need to better understand these facets of disease becomes more pertinent. The purpose of the studies described was to define the longitudinal shedding profile of CWD prions in urine, saliva, and feces throughout the course of infection in white-tailed deer.

Material and Methods: Twelve (12) white-tailed deer were inoculated with either 1 mg or 300ng of CWD. Urine, saliva, and feces were collected every 3-month post-inoculation (MPI) throughout the study duration. Cohorts were established based on PNRP genotype: codon 96 GG (n = 6) and alternate codons 96 GS (n = 5) & 103NT (n = 1). Urine and saliva were analyzed using iron-oxide magnetic extraction (IOME) and real-time quaking induced conversion (RT-QuIC)(IQ). Feces were subjected to IOME, followed by 4 rounds protein misfolding cyclic amplification (PMCA) with products analyzed by RT-QuIC (IPQ). To determine whether IPQ may be superior to IQ, a subset of urine and saliva were also tested by IPQ. Results were compared with clinical disease status.

Results: Within the 96 GG cohort, positive seeding activity was detected in feces from all deer (100%), in saliva from 5 of 6 (83%), and in urine from 4 of 6 (66%). Shedding in all excreta occurred at, or just after, the first positive tonsil biopsy result. In the 96 GS/103NT cohort, positive seeding activity could be detected in feces from 3 of 6 (50%) deer, saliva in 2 of 6 (33%), and urine in 1 of 6 (16%). Shedding in excreta was detected >5 months after the first tonsil positive result. Four of six 96 GG deer developed clinical signs of CWD, whereas only 2 of the 96 GS/103NT did. Shedding was more frequently detected in deer with clinical disease. The IPQ protocol did not significantly improve detection in saliva or urine samples, however, it significantly augmented detection in feces by eliminating non-specific background commonly experienced with IQ. Negative control samples remained negative in samples tested.

Conclusions: These studies demonstrate: (a) CWD prion excretion occurs throughout infection; (2) PRNP genotype (GG≫GS/NT) influences the excreta shedding; and (3) detection sensitivity in excreta can vary with different RT-QuIC protocols. These results provide a more complete perspective of prion shedding in deer during the course of CWD infection.

Funded by: National Institutes of Health (NIH)

Grant number: RO1-NS061902-09 R to EAH, PO1-AI077774 to EAH, and R01-AI112956-06 to CKM

Acknowledgement: We abundantly thank Sallie Dahmes at WASCO and David Osborn and Gino D’Angelo at the University of Georgia Warnell School of Forestry and Natural Resources for their long-standing support of this work through provision of the hand-raised, CWD-free, white-tailed deer used in these studies

Carrot plants as potential vectors for CWD transmission

Paulina Sotoa,b, Francisca Bravo-Risia,b, Claudio Sotoa, and Rodrigo Moralesa,b

aDepartment of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA; bUniversidad Bernardo O’Higgins, Santiago, Chile

Prion diseases are infectious neurodegenerative disorders afflicting humans and other mammals. These diseases are generated by the misfolding of the cellular prion protein into a disease-causing isoform. Chronic wasting disease (CWD) is a prevalent prion disease affecting cervids (captive and free-range). CWD is thought to be transmitted through direct animal contact or by indirect exposure to contaminated environments. Many studies have shown that infectious prions can enter the environment through saliva, feces, or urine from infected animals and decaying carcasses. However, we do not fully understand the specific contribution of each component to disease transmission events. Plants are logical environmental components to be evaluated since they grow in environments contaminated with CWD prions and are relevant for animal and human nutrition.

Aims: The main objective of this study is to study whether prions are transported to the roots and leaves of carrots, an edible plant commonly used in the human diet and as deer bait.

Methods: We have grown carrot plants in CWD-infected soils. After 90 days, we harvested the carrots and separated them from the leaves. The experiment was controlled by growing plants in soil samples treated with brain extracts from healthy animals. These materials were interrogated for their prion seeding activity using the Protein Misfolding Cyclic Amplification (PMCA) technique. Infectivity was evaluated in mouse bioassays (intracerebral injections in Tg1536 mice). The animals were sacrificed when they showed established signs of prion disease. Animals not displaying clinical signs were sacrificed at 600 days post-inoculation.

Results: The PMCA analysis demonstrated CWD seeding activity in soils contaminated with CWD prions, as well as in carrot plants (leaves and roots) grown on them. Bioassays demonstrated that both leaves and roots contained CWD prions in sufficient quantities to induce disease (92% attack rate). As expected, animals treated with prion-infected soils developed prion disease at shorter incubation periods (and complete attack rates) compared to plant components. Animals treated with soil and plant components exposed with CWD-free brain extracts did not display prion-associated clinical signs or evidence of sub-clinical prion infection.

Conclusions: We show that edible plant components can absorb prions from CWD contaminated soils and transport them to their aerial parts. Our results indicate that plants could participate as vectors of CWD transmission. Importantly, plants designated for human consumption represent a risk of introducing CWD prions into the human food chain.

Funded by: NIH

Grant number: R01AI132695

www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286

October 6th-12th, 126th Meeting 2022 Resolutions

RESOLUTION NUMBER: 30 Approved

SOURCE: COMMITTEE ON WILDLIFE

SUBJECT MATTER: Chronic Wasting Disease Carcass Disposal Dumpster Management and Biosecurity

BACKGROUND INFORMATION:

State and tribal wildlife agencies may identify collection points (dumpsters) within an identified chronic wasting disease (CWD) management zone for the disposal of hunter-harvested cervid carcasses to remove potentially infected carcasses off the landscape for disposal by an approved method (Gillin & Mawdsley, 2018, chap.14). However, depending on their placement and maintenance these dumpsters could potentially increase the risk of CWD transmission.

In several different states, photographic evidence has shown dumpsters in state identified CWD management zones overflowing with deer carcasses and limbs scattered on the land nearby. This could provide an opportunity for scavengers to potentially move infected carcass material to non-infected zones or increase contamination of the ground material around the dumpster’s location.

Federal guidance does not explicitly address uniform standards for collection locations for carcasses of free-ranging cervids; however, the United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services Program Standards on CWD outlines procedures for carcass disposal, equipment sanitation, and decontamination of premises for captive cervid facilities.

RESOLUTION:

The United States Animal Health Association urges the Association of Fish and Wildlife Agencies (AFWA), Wildlife Health Committee to further refine the AFWA Technical Report on Best Management Practices for Prevention, Surveillance, and Management of Chronic Wasting Disease; Chapter 14, Carcass Disposal to address the placement and management of chronic wasting disease carcass disposal dumpsters or other carcass collection containers.

Reference:

1. Gillin, Colin M., and Mawdsley, Jonathan R. (eds.). 2018. AFWA Technical Report on Best Management Practices for Surveillance, Management and Control of Chronic Wasting Disease. Association of Fish and Wildlife Agencies, Washington, D. C. 111 pp.

www.usaha.org/upload/Resolution/2022/2022_Resolution_30_CWD_Dumpste.pdf

ENVIRONMENT FACTORS FOR THE TRANSMISSION OF CWD TSE PRP

Sensitive detection of chronic wasting disease prions recovered from environmentally relevant surfaces

Environment International

Available online 13 June 2022, 107347

Environment International

Sensitive detection of chronic wasting disease prions recovered from environmentally relevant surfaces

Qi Yuana Gag e Rowdenb Tiffany M.Wolfc Marc D.Schwabenlanderb Peter A.LarsenbShannon L.Bartelt-Huntd Jason C.Bartza

a Department of Medical Microbiology and Immunology, Creighton University, Omaha, Nebraska, 68178, United States of America

b Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN, 55108, United States of America

c Department of Veterinary Population Medicine, University of Minnesota, Saint Paul, MN, 55108, United States of America

d Department of Civil and Environmental Engineering, Peter Kiewit Institute, University of Nebraska-Lincoln, Omaha, Nebraska, 68182, United States of America

Received 26 April 2022, Revised 8 June 2022, Accepted 9 June 2022, Available online 13 June 2022.

doi.org/10.1016/j.envint.2022.107347

Get rights and content

Under a Creative Commons license Open access

Highlights • An innovative method for prion recovery from swabs was developed.

• Recovery of prions decreased as swab-drying time was increased.

• Recovery of CWD prions from stainless steel and glass was approximately 30%.

• RT-QuIC enhanced CWD prion detection by 4 orders of magnitude.

• Surface-recovered CWD prion was sufficient for efficient RT-QuIC detection.

Abstract

Chronic wasting disease (CWD) has been identified in 30 states in the United States, four provinces in Canada, and recently emerged in Scandinavia. The association of CWD prions with environmental materials such as soil, plants, and surfaces may enhance the persistence of CWD prion infectivity in the environment exacerbating disease transmission. Identifying and quantifying CWD prions in the environment is significant for prion monitoring and disease transmission control. A systematic method for CWD prion quantification from associated environmental materials, however, does not exist. In this study, we developed an innovative method for extracting prions from swabs and recovering CWD prions swabbed from different types of surfaces including glass, stainless steel, and wood. We found that samples dried on swabs were unfavorable for prion extraction, with the greatest prion recovery from wet swabs. Using this swabbing technique, the recovery of CWD prions dried to glass or stainless steel was approximately 30% in most cases, whereas that from wood was undetectable by conventional prion immunodetection techniques. Real-time quake-induced conversion (RT-QuIC) analysis of these same samples resulted in an increase of the detection limit of CWD prions from stainless steel by 4 orders of magnitude. More importantly, the RT-QuIC detection of CWD prions recovered from stainless steel surfaces using this method was similar to the original CWD prion load applied to the surface. This combined surface swabbing and RT-QuIC detection method provides an ultrasensitive means for prion detection across many settings and applications.

snip...

5. Conclusions

Chronic wasting disease is spreading in North America and it is hypothesized that in CWD-endemic areas environmental persistence of CWD prions can exacerbate disease transmission. The development of a sensitive CWD prion detection method from environmentally relevant surfaces is significant for monitoring, risk assessment, and control of CWD. In this study, we developed a novel swab-extraction procedure for field deployable sampling of CWD prions from stainless steel, glass, and wood. We found that extended swab-drying was unfavorable for extraction, indicating that hydrated storage of swabs after sampling aided in prion recovery. Recoverable CWD prions from stainless steel and glass was approximately 30%, which was greater than from wood. RT-QuIC analysis of the swab extracts resulted in an increase of the detection limit of CWD prions from stainless steel by 4 orders of magnitude compared to conventional immunodetection techniques. More importantly, the RT-QuIC detection of CWD prions recovered from stainless steel surfaces using this developed method was similar to the original CWD prion load without surface contact. This method of prion sampling and recovery, in combination with ultrasensitive detection methods, allows for prion detection from contaminated environmental surfaces.

www.sciencedirect.com/science/article/pii/S0160412022002744?via%3Dihub

Research Paper

Cellular prion protein distribution in the vomeronasal organ, parotid, and scent glands of white-tailed deer and mule deer

Anthony Ness, Aradhana Jacob, Kelsey Saboraki, Alicia Otero, Danielle Gushue, Diana Martinez Moreno, Melanie de Peña, Xinli Tang, Judd Aiken, Susan Lingle & Debbie McKenzie ORCID Icon show less

Pages 40-57 | Received 03 Feb 2022, Accepted 13 May 2022, Published online: 29 May 2022

Download citation

doi.org/10.1080/19336896.2022.2079888

ABSTRACT

Chronic wasting disease (CWD) is a contagious and fatal transmissible spongiform encephalopathy affecting species of the cervidae family. CWD has an expanding geographic range and complex, poorly understood transmission mechanics. CWD is disproportionately prevalent in wild male mule deer and male white-tailed deer. Sex and species influences on CWD prevalence have been hypothesized to be related to animal behaviours that involve deer facial and body exocrine glands. Understanding CWD transmission potential requires a foundational knowledge of the cellular prion protein (PrPC) in glands associated with cervid behaviours. In this study, we characterized the presence and distribution of PrPC in six integumentary and two non-integumentary tissues of hunter-harvested mule deer (Odocoileus hemionus) and white-tailed deer (O. virginianus). We report that white-tailed deer expressed significantly more PrPC than their mule deer in the parotid, metatarsal, and interdigital glands. Females expressed more PrPC than males in the forehead and preorbital glands. The distribution of PrPC within the integumentary exocrine glands of the face and legs were localized to glandular cells, hair follicles, epidermis, and immune cell infiltrates. All tissues examined expressed sufficient quantities of PrPC to serve as possible sites of prion initial infection, propagation, and shedding.

KEYWORDS: Prion chronic wasting diseasesex differences species differences disease prevalence cervid protein expression glands

www.tandfonline.com/doi/full/10.1080/19336896.2022.2079888

Paper

Rapid recontamination of a farm building occurs after attempted prion removal

Kevin Christopher Gough BSc (Hons), PhD Claire Alison Baker BSc (Hons) Steve Hawkins MIBiol Hugh Simmons BVSc, MRCVS, MBA, MA Timm Konold DrMedVet, PhD, MRCVS … See all authors

First published: 19 January 2019 doi.org/10.1136/vr.105054

The data illustrates the difficulty in decontaminating farm buildings from scrapie, and demonstrates the likely contribution of farm dust to the recontamination of these environments to levels that are capable of causing disease.

snip...

This study clearly demonstrates the difficulty in removing scrapie infectivity from the farm environment. Practical and effective prion decontamination methods are still urgently required for decontamination of scrapie infectivity from farms that have had cases of scrapie and this is particularly relevant for scrapiepositive goatherds, which currently have limited genetic resistance to scrapie within commercial breeds.24 This is very likely to have parallels with control efforts for CWD in cervids.

bvajournals.onlinelibrary.wiley.com/doi/abs/10.1136/vr.105054

***>This is very likely to have parallels with control efforts for CWD in cervids.

pubmed.ncbi.nlm.nih.gov/30602491/

***> Infectious agent of sheep scrapie may persist in the environment for at least 16 years

***> Nine of these recurrences occurred 14–21 years after culling, apparently as the result of environmental contamination, but outside entry could not always be absolutely excluded.

JOURNAL OF GENERAL VIROLOGY Volume 87, Issue 12

Infectious agent of sheep scrapie may persist in the environment for at least 16 years Free

Gudmundur Georgsson1, Sigurdur Sigurdarson2, Paul Brown3

www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.82011-0

Front. Vet. Sci., 14 September 2015 | doi.org/10.3389/fvets.2015.00032

Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission

imageTimm Konold1*, imageStephen A. C. Hawkins2, imageLisa C. Thurston3, imageBen C. Maddison4, imageKevin C. Gough5, imageAnthony Duarte1 and imageHugh A. Simmons1

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

snip...

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.

journal.frontiersin.org/article/10.3389/fvets.2015.00032/full

***> 172. Establishment of PrPCWD extraction and detection methods in the farm soil

Kyung Je Park, Hoo Chang Park, In Soon Roh, Hyo Jin Kim, Hae-Eun Kang and Hyun Joo Sohn

Foreign Animal Disease Division, Animal and Plant Quarantine Agency, Gimcheon, Gyeongsangbuk-do, Korea

Conclusions: Our studies showed that PrPCWD persist in 0.001% CWD contaminated soil for at least 4 year and natural CWD-affected farm soil. When cervid reintroduced into CWD outbreak farm, the strict decontamination procedures of the infectious agent should be performed in the environment of CWD-affected cervid habitat.

www.tandfonline.com/doi/full/10.1080/19336896.2019.1615197

THE tse prion aka mad cow type disease is not your normal pathogen.

The TSE prion disease survives ashing to 600 degrees celsius, that’s around 1112 degrees farenheit.

you cannot cook the TSE prion disease out of meat.

you can take the ash and mix it with saline and inject that ash into a mouse, and the mouse will go down with TSE.

Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production as well.

the TSE prion agent also survives Simulated Wastewater Treatment Processes.

IN fact, you should also know that the TSE Prion agent will survive in the environment for years, if not decades.

you can bury it and it will not go away.

The TSE agent is capable of infected your water table i.e. Detection of protease-resistant cervid prion protein in water from a CWD-endemic area.

it’s not your ordinary pathogen you can just cook it out and be done with.

***> that’s what’s so worrisome about Iatrogenic mode of transmission, a simple autoclave will not kill this TSE prion agent.

1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8

***> Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.

Laboratory of Central Nervous System Studies, National Institute of

Neurological Disorders and Stroke, National Institutes of Health,

Bethesda, MD 20892.

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.

PMID: 8006664 [PubMed - indexed for MEDLINE]

www.ncbi.nlm.nih.gov/pubmed/8006664?dopt=Abstract

New studies on the heat resistance of hamster-adapted scrapie agent: Threshold survival after ashing at 600°C suggests an inorganic template of replication

www.pnas.org/content/97/7/3418.full

Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production

www.ncbi.nlm.nih.gov/pmc/articles/PMC2493038/

MONDAY, APRIL 19, 2021

Evaluation of the application for new alternative biodiesel production process for rendered fat including Category 1 animal by-products (BDI-RepCat® process, AT)

transmissiblespongiformencephalopathy.blogspot.com/2021/04/evaluation-of-application-for-new.html

Detection of protease-resistant cervid prion protein in water from a CWD-endemic area

https://www.ncbi...nlm.nih.gov/pmc/articles/PMC2802782/pdf/prion0303_0171.pdf

A Quantitative Assessment of the Amount of Prion Diverted to Category 1 Materials and Wastewater During Processing

onlinelibrary.wiley.com/doi/10.1111/j.1539-6924.2012.01922.x/abstract

Rapid assessment of bovine spongiform encephalopathy prion inactivation by heat treatment in yellow grease produced in the industrial manufacturing process of meat and bone meals

bmcvetres.biomedcentral.com/track/pdf/10.1186/1746-6148-9-134.pdf

THURSDAY, FEBRUARY 28, 2019

BSE infectivity survives burial for five years with only limited spread

link.springer.com/content/pdf/10.1007%2Fs00705-019-04154-8.pdf

5 or 6 years quarantine is NOT LONG ENOUGH FOR CWD TSE PRION !!!

QUARANTINE NEEDS TO BE 21 YEARS FOR CWD TSE PRION !

FRIDAY, APRIL 30, 2021

Should Property Evaluations Contain Scrapie, CWD, TSE PRION Environmental Contamination of the land?

***> Confidential!!!!

***> As early as 1992-3 there had been long studies conducted on small pastures containing scrapie infected sheep at the sheep research station associated with the Neuropathogenesis Unit in Edinburgh, Scotland. Whether these are documented...I don't know. But personal recounts both heard and recorded in a daily journal indicate that leaving the pastures free and replacing the topsoil completely at least 2 feet of thickness each year for SEVEN years....and then when very clean (proven scrapie free) sheep were placed on these small pastures.... the new sheep also broke out with scrapie and passed it to offspring. I am not sure that TSE contaminated ground could ever be free of the agent!! A very frightening revelation!!!

---end personal email---end...tss

and so it seems...

Scrapie Agent (Strain 263K) Can Transmit Disease via the Oral Route after Persistence in Soil over Years

Published: May 9, 2007

snip...

Our results showed that 263K scrapie agent can persist in soil at least over 29 months. Strikingly, not only the contaminated soil itself retained high levels of infectivity, as evidenced by oral administration to Syrian hamsters, but also feeding of aqueous soil extracts was able to induce disease in the reporter animals. We could also demonstrate that PrPSc in soil, extracted after 21 months, provides a catalytically active seed in the protein misfolding cyclic amplification (PMCA) reaction. PMCA opens therefore a perspective for considerably improving the detectability of prions in soil samples from the field.

snip...

journals.plos.org/plosone/article?id=10.1371/journal.pone.0000435

Dr. Paul Brown Scrapie Soil Test BSE Inquiry Document

web.archive.org/web/20090505211734/http://www.bseinquiry.gov.uk/files/sc/Seac07/tab03.pdf

Published: 06 September 2021

***> Chronic wasting disease: a cervid prion infection looming to spillover

Alicia Otero, Camilo Duque Velásquez, Judd Aiken & Debbie McKenzie

Veterinary Research volume 52, Article number: 115 (2021)

veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-021-00986-y

PRION CONFERENCE 2022 ABSTRACTS CWD TSE PrP ZOONOSIS

Transmission of prion infectivity from CWD-infected macaque tissues to rodent models demonstrates the zoonotic potential of chronic wasting disease.

Samia Hannaouia, Ginny Chenga, Wiebke Wemheuerb, Walter J. Schulz-Schaefferb, Sabine Gilcha, and Hermann M. Schätzla aDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine & Hotchkiss Brain Institute; University of Calgary, Calgary, Canada; bInstitute of Neuropathology, Medical Faculty, Saarland University, Homburg/Saar, Germany

Aims: Chronic wasting disease (CWD) is a prion disease of cervids. Its rapid geographic expansion, shedding of infectivity and persistence in the environment for many years are of concern for humans. Here, we provide the first evidence by transmission experiments to different transgenic mouse models and bank voles that Cynomolgus macaques inoculated via different routes with CWD-positive cervid tissues harbor infectious prions that elicit clinical disease in rodents.

Material and Methods: We used tissue materials from macaques inoculated with CWD to inoculate transgenic mice overexpressing cervid PrPCfollowed by transmission into bank voles. We used RT-QuIC, immunoblot and PET blot analysis to assess brains, spinal cords, and tissues of the gastrointestinal tract (GIT) for the presence of prions.

Results: Our results show that of the macaque materials that induced clinical disease in transgenic mice,73% were from the CNS (46% spinal cord and 27% brain), and 27% were from the spleen, although attack rates were low around 20%. Clinical mice did not display PK-resistant PrPSc(PrPres) in immunoblot, but showed low-levels of prion seeding activity. Transmission into bank voles from clinical transgenic mice led to a 100% attack rate with typical PrPressignature in immunoblot, which was different from that of voles inoculated directly with CWD or scrapie prions. High-level prion seeding activity in brain and spinal cord and PrPresdeposition in the brain were present. Remarkably, we also found prion seeding activity in GIT tissues of inoculated voles. Second passage in bank voles led to a 100% attack rate in voles inoculated with brain, spinal cord and small intestine material from first round animals, with PrPresin immunoblot, prion seeding activity, and PrPresdeposition in the brain. Shortened survival times indicate adaptation in the new host. This also shows that prions detected in GIT tissues are infectious and transmissible. Transmission of brain material from sick voles back to cervidized mice revealed transmission in these mice with a 100% attack rate, and interestingly, with different biochemical signature and distribution in the brain.

Conclusions: Our findings demonstrate that macaques, considered the best model for the zoonotic potential of prions, were infected upon CWD challenge, including oral one. The disease manifested as atypical in macaques and transgenic mice, but with infectivity present at all times, as unveiled in the bank vole model with an unusual tissue tropism.

Funded by: The National Institutes of Health, USA, and the Alberta Prion Research Institute/Alberta Innovates Canada. Grant number: 1R01NS121016-01; 201,600,023

Acknowledgement: We thank Umberto Agrimi, Istituto Superiore di Sanità, Rome, Italy, and Michael Beekes, Robert-Koch Institute Berlin, Germany, for providing the bank vole model. We thank the University of Calgary animal facility staff and Dr. Stephanie Anderson for animal care.

Transmission of Cervid Prions to Humanized Mice Demonstrates the Zoonotic Potential of CWD

Samia Hannaouia, Irina Zemlyankinaa, Sheng Chun Changa, Maria Immaculata Arifina, Vincent Béringueb, Debbie McKenziec, Hermann M. Schatzla, and Sabine Gilcha

aDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine; Hotchkiss Brain Institute; University of Calgary, Calgary, Canada; bUniversité Paris-Saclay, INRAE, UVSQ, VIM, Jouy-en-Josas, France; cDepartment of Biological Sciences, Center for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Canada

Aims: Chronic wasting disease (CWD), a prion disease of cervids, spreads efficiently among wild and farmed animals. Potential transmission to humans of CWD is a growing concern due to its increasing prevalence. Here, we aimed to determine the zoonotic potential of CWD using a mouse model for human prion diseases.

Material and Methods: Transgenic mice overexpressing human PrPChomozygous for methionine at codon 129 (tg650) were inoculated intracerebrally with brain homogenates of white-tailed deer infected with Wisc-1/CWD1 or 116AG CWD strains. Mice were monitored for clinical signs and were euthanized at terminal disease. Brains were tested by RT-QuIC, western blot upon PK digestion, and immunohistochemistry; fecal homogenates were analyzed by RT-QuIC. Brain/spinal cord and fecal homogenates of CWD-inoculated tg650 mice were inoculated into tg650 mice or bank voles. Brain homogenates of bank voles inoculated with fecal homogenates of CWD-infected tg650 mice were used for second passage in bank voles.

Results: Here, we provide the strongest evidence supporting the zoonotic potential of CWD prions, and their possible phenotype in humans. Inoculation of mice expressing human PrPCwith deer CWD isolates (strains Wisc-1 and 116AG) resulted in atypical clinical manifestations in > 75% of the mice, with myoclonus as leading clinical sign. Most of tg650 brain homogenates were positive for seeding activity in RT-QuIC. Clinical disease and presentation was transmissible to tg650 mice and bank voles. Intriguingly, protease-resistant PrP in the brain of tg650 mice resembled that found in a familial human prion disease and was transmissible upon passage. Abnormal PrP aggregates upon infection with Wisc-1 were detectable in thalamus, hypothalamus, and midbrain/pons regions.

Unprecedented in human prion disease, feces of CWD-inoculated tg650 mice harbored prion seeding activity and infectious prions, as shown by inoculation of bank voles and tg650 with fecal homogenates.

Conclusions: This is the first evidence that CWD can infect humans and cause disease with a distinctive clinical presentation, signature, and tropism, which might be transmissible between humans while current diagnostic assays might fail to detect it. These findings have major implications for public health and CWD-management.

Funded by: We are grateful for financial support from the Natural Sciences and Engineering Research Council of Canada, the National Institutes of Health, Genome Canada, and the Alberta Prion Research Institute. SG is supported by the Canada Research Chairs program.

Acknowledgement: We thank Dr. Trent Bollinger, WCVM, University of Saskatchewan, Saskatoon, Canada, for providing brain tissue from the WTD-116AG isolate, Dr. Stéphane Haïk, ICM, Paris, France, for providing brain tissue from vCJD and sCJD cases, and Dr. Umberto Agrimi, Istituto Superiore di Sanità, Italy, for the bank vole model. We thank animal facility staff for animal care, Dr. Stephanie Anderson for veterinary oversight, and Yo-Ching Cheng for preparing recombinant PrP substrates. Thank you to Dr. Stephanie Booth and Jennifer Myskiw, Public Health Agency of Canada, Canada.

The chronic wasting disease agent from white-tailed deer is infectious to humanized mice after passage through raccoons

Eric Cassmanna, Xu Qib, Qingzhong Kongb, and Justin Greenleea

aNational Animal Disease Center, Agricultural Research Service, US Department of Agriculture, Ames, IA, USA bDepartments of Pathology, Neurology, National Center for Regenerative Medicine, and National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio, USA

Aims: Evaluate the zoonotic potential of the raccoon passaged chronic wasting disease (CWD) agent in humanized transgenic mice in comparison with the North American CWD agent from the original white-tailed deer host.

Material and Methods: Pooled brain material (GG96) from a CWD positive herd was used to oronasally inoculate two white-tailed deer with wild-type prion protein genotype and intracranially inoculate a raccoon. Brain homogenates (10% w/v) from the raccoon and the two white-tailed deer were used to intracranially inoculate separate groups of transgenic mice that express human prion protein with methionine (M) at codon 129 (Tg40h). Brains and spleens were collected from mice at experimental endpoints of clinical disease or approximately 700 days post-inoculation. Tissues were divided and homogenized or fixed in 10% buffered neutral formalin. Immunohistochemistry, enzyme immunoassay, and western blot were used to detect misfolded prion protein (PrPSc) in tissue.

Results: Humanized transgenic mice inoculated with the raccoon passaged CWD agent from white-tailed deer exhibited a 100% (12/12) attack rate with an average incubation period of 605 days. PrPScwas detected in brain tissue by enzyme immunoassay with an average optical density of 3.6/4.0 for positive brains. PrPScalso was detected in brain tissue by western blot and immunohistochemistry. No PrPScwas detected in the spleens of mice inoculated with the raccoon passaged CWD agent. Humanized mice inoculated with the CWD agent from white-tailed deer did not have detectable PrPScusing conventional immunoassay techniques.

Conclusions: The host range of the CWD agent from white-tailed deer was expanded in our experimental model after one passage through raccoons.

Funded by: This research was funded in its entirety by congressionally appropriated funds to the United States Department of Agriculture, Agricultural Research Service. The funders of the work did not influence study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Acknowledgement: We thank Quazetta Brown, Lexi Frese, Rylie Frese, Kevin Hassall, Leisa Mandell, and Trudy Tatum for providing excellent technical support to this project.

Stable and highly zoonotic cervid prion strain is possible

Manuel Camacho, Xu Qi, Liuting Qing, Sydney Smith, Jieji Hu, Wanyun Tao, Ignazio Cali, and Qingzhong Kong Department of Pathology, Case Western Reserve University, Cleveland, USA

Aims: Whether CWD prions can infect humans remains unclear despite the very substantial scale and long history of human exposure of CWD in some areas. Multiple in vitro conversion experiments and in vivo animal studies suggest that the CWD-to-human transmission barrier is not unbreakable. A major public health concern on CWD zoonosis is the emergence of highly zoonotic CWD strains. We aim to address the question of whether highly zoonotic CWD strains are possible.

Material and Methods: We inoculated a few sCJD brain samples into cervidized transgenic mice, which were intended as negative controls for bioassays of brain tissues from sCJD cases who had hunted or consumed vension from CWD-endemic states. Some of these mice became infected and their brain tissues were further examined by serial passages in humanized or cervidized mice.

Results: Passage of sCJDMM1 in transgenic mice expressing elk PrP (Tg12) resulted in a ‘cervidized’ CJD strain that we termed CJDElkPrP. We observed 100% transmission of CJDElkPrPin transgenic mice expressing human PrP (Tg40h). We passaged CJDElkPrPtwo more times in the Tg12 mice. We found that such second and third passage CJDElkPrPprions also led to 100% infection in the Tg40h mice. In contrast, we and others found zero or poor transmission of natural elk CWD isolates in humanized mice, despite that natural elk CWD isolates and CJDElkPrPshare the same elk PrP sequence.

Conclusions: Our data demonstrate that highly zoonotic cervid prion strains are not only possible but also can be stably maintained in cervids and that CWD zoonosis is prion strain-dependent.

Funded by: NIH

Grant number: R01NS052319, R01NS088604, R01NS109532

Acknowledgement: We want to thank the National Prion Disease Pathology Surveillance Center and Drs. Allen Jenny and Katherine O’Rourke for providing the sCJD samples and the CWD samples, respectively.

Adaptation of chronic wasting disease (CWD) prion strains in hosts with different PRNP genotypes

Camilo Duque Velasqueza,c, Elizabeth Triscotta,c, Chiye Kima,c, Diana Morenoa,c, Judd Aikenb,c, and Debbie McKenziea,c

aDepartment of Biological Science, University of Alberta, Edmonton, AB T6G 2G8, Canada; bDepartment of Agriculture, Food & Nutritional Science, University of Alberta, Edmonton, AB T6G 2G8, Canada; cCentre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada

Aims: The contagious nature of CWD epizootics and the PrPCamino acid variation of cervids (and susceptible sympatric species) guarantee the expansion of prion conformational diversity and selective landscapes where new strains can arise. CWD strains can have novel transmission properties including altered host range that may increase zoonotic risk as circulating strains diversify and evolve. We are characterizing the host adaptability of characterized CWD strains as well as CWD isolates from different cervid species in various enzootic regions.

Material and Methods: Characterized CWD strains as well as a number of isolates from hunter-harvested deer were bioassayed in our rodent panel (transgenic mice expressing cervid alleles G96, S96 and H95-PrPC, elk PrPC, bovine PrPC, and both hamsters and non-transgenic laboratory mice). Strain characteristics were compared using computer based scoring of brain pathology (e.g. PrPCWDbrain distribution), western blot and protein misfolding cyclic amplification (PMCA).

Results: Transmission of various isolates resulted in the selection of strain mixtures in hosts expressing similar PrPC, particularly for polymorphic white-tailed deer and for Norwegian reindeer. As of the second passage, transmission of P153 moose prions from Norway has not resulted in emergence of strains with properties similar to any North American CWD strains in our taxonomic collection (Wisc-1, CWD2, H95+and 116AG).

Conclusions: Our data indicates polymorphic white-tailed deer can favor infection with more than one strain. Similar to transmission studies of Colorado CWD isolates from cervids expressing a single PrPCprimary structure, the isolate from Norway reindeer (V214) represents a strain mixture, suggesting intrinsic strain diversity in the Nordfjella epizootic. The diversity of CWD strains with distinct transmission characteristics represents a threat to wildlife, sympatric domestic animals and public health.

Funded by: Genome Canada and Genome Alberta (Alberta Prion Research Institute and Alberta Agriculture & Forestry); NSERC Grant number: #LSARP 10205; NSERC RGPIN-2017-05539

Acknowledgement: We would like to thank Margo Pybus (Alberta Environment and Parks) Trent Bollinger (University of Saskatchewan) for providing us with tissue samples from hunter-harvested deer and Sylvie Benestad for providing moose and reindeer samples.

Application of PMCA to understand CWD prion strains, species barrier and zoonotic potential

Sandra Pritzkowa, Damian Gorskia, Frank Ramireza, Fei Wanga, Glenn C. Tellingb, Justin J. Greenleec, Sylvie L. Benestadd, and Claudio Sotoa aDepartment of Neurology, University of Texas Medical School at Houston, Houston, Texas, USA; bDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA; cVirus and Prion Research Unit, United States Department of Agriculture, Ames, Iowa, USA; dNorwegian Veterinary Institute, OIE Reference Laboratory for CWD, Ås, Norway

Aims: Chronic wasting disease (CWD) is a prion disease affecting various species of cervids that continues to spread uncontrollably across North America and has recently been detected in Scandinavia (Norway, Sweden and Finland). The mechanisms responsible for the natural transmission of CWD are largely unknown. Furthermore, the risk of CWD transmission to other species, including humans, is also unknown and remains a dangerous enigma. In this study, we investigated the potential of CWD prions to infect several other animal species (sheep, cattle, pig, hamster, and mouse) including humans, by examining their capacity to convert the normal prion protein of distinct species in a PMCA reaction. Moreover, we also investigated whether the in vivo passage of CWD through intermediate species alters their capacity for zoonotic transmission, which may represent a major hazard to human health.

Material and Methods: For these studies, we used brain material from CWD-infected white-tailed deer (Odocoileus virginianus), elk (Cervus canadensis), and mule deer (Odocoileus hemionus) as species native to North America. We also used CWD-infected Moose (Alces alces), reindeer (Rangifer tarandus) and red deer (Cervus elaphus) as Norwegian cervids. We also used brains from cattle, sheep and pigs experimentally infected by CWD. To study interspecies-transmission and zoonotic potential, samples were tested via PMCA for the conversion of PrPCinto PrPScusing different combinations of inoculum and host species. Based on these analyses we estimated the spillover and zoonotic potential for different CWD isolates. We define and quantify spillover and zoonotic potential indices as the efficiency by which CWD prions sustain prion generation in vitro at the expense of normal prion proteins from various mammals and human, respectively.

Results: Our results show that prions from some cervid species, especially those found in Northern Europe, have a higher potential to transmit disease characteristics to other animals. Conversely, CWD-infected cervids originated in North America appear to have a greater potential to generate human PrPSc. We also found that in vivo transmission of CWD to cattle, but not to sheep or pigs substantially increases the ability of these prions to convert human PrPCby PMCA.

Conclusions: Our findings support the existence of different CWD prion strains with distinct spillover and zoonotic potentials. We also conclude that transmission of CWD to other animal species may increase the risk for CWD transmission to humans. Our studies may provide a tool to predict the array of animal species that a given CWD prion could affect and may contribute to understanding the risk of CWD for human health.

Funded by: National Institute of Health Grant number: P01 AI077774

Generation of human chronic wasting disease in transgenic mice

Zerui Wanga, Kefeng Qinb, Manuel V. Camachoa, Ignazio Cali a,c, Jue Yuana, Pingping Shena, Tricia Gillilanda, Syed Zahid Ali Shaha, Maria Gerasimenkoa, Michelle Tanga, Sarada Rajamanickama, Anika Yadatia, Lawrence B. Schonbergerd, Justin Greenleee, Qingzhong Konga,c, James A. Mastriannib, and Wen-Quan Zoua,c

aDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; bDepartment of Neurology and Center for Comprehensive Care and Research on Memory Disorders, the University of Chicago Pritzker School of Medicine, Chicago, USA; cNational Prion Disease Pathology Surveillance Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; dDivision of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA, USA; eVirus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, 1920 Dayton Avenue, Ames, IA, USA

Aims: Chronic wasting disease (CWD) results from the accumulation of an infectious misfolded conformer (PrPSc) of cellular prion protein (PrPC) in the brains of deer and elk. It has been spreading rapidly throughout many regions of North America, exported inadvertently to South Korea, and more recently identified in Europe. Mad cow disease has caused variant Creutzfeldt-Jakob disease (vCJD) in humans and is currently the only known zoonotic prion disease. Whether CWD is transmissible to humans remains uncertain. The aims of our study were not only to confirm whether CWD prion isolates can convert human brain PrPCinto PrPScin vitro by serial protein misfolding cyclic amplification (sPMCA) but also to determine whether the sPMCA-induced CWD-derived human PrPScis infectious.

Material and Methods: Eight CWD prion isolates from 7 elks and 1 deer were used as the seeds while normal human brain homogenates containing either PrP-129 MM (n = 2) or PrP-129 VV (n = 1) were used as the substrates for sPMCA assay. A normal elk brain tissue sample was used as a negative control seed. Two lines of humanized transgenic (Tg) mice expressing either human PrP-129VV or −129 MM polymorphism were included for transmission studies to determine the infectivity of PMCA-amplified PrPSc. Wester blotting and immunohistochemistry and hematoxylin & eosin staining were used for determining PrPScand neuropathological changes of inoculated animals.

Results: We report here the generation of the first CWD-derived infectious human PrPScusing elk CWD PrPScto initiate conversion of human PrPCfrom normal human brain homogenates with PMCA in vitro. Western blotting with a human PrP selective antibody confirmed that the PMCA-generated protease-resistant PrPScwas derived from the human brain PrPCsubstrate. Two lines of humanized transgenic mice expressing human PrPCwith either Val or Met at the polymorphic codon 129 developed clinical prion disease following intracerebral inoculation with the PMCA-generated CWD-derived human PrPSc. Diseased mice exhibited distinct PrPScpatterns and neuropathological changes in the brain.

Conclusions: Our study, using PMCA and animal bioassays, provides the first evidence that CWD PrPSchas the potential to overcome the species barrier and directly convert human PrPCinto infectious PrPScthat can produce bona fide prion disease when inoculated into humanized transgenic mice.

Funded by: CJD Foundation and NIH

Mortality surveillance of persons potentially exposed to chronic wasting disease

R.A. Maddoxa, R.F. Klosb, L.R. Willb, S.N. Gibbons-Burgenerb, A. Mvilongoa, J.Y. Abramsa, B.S. Applebyc, L.B. Schonbergera, and E.D. Belaya aNational Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, USA; bWisconsin Department of Health Services (WDHS), Division of Public Health, Madison, USA; cNational Prion Disease Pathology Surveillance Center (NPDPSC), Case Western Reserve University, Cleveland, USA

Aims: It is unknown whether chronic wasting disease (CWD), a prion disease of cervids, can infect people, but consumption of meat from infected animals would be the most likely route of transmission. Wisconsin Department of Health Services, Division of Public Health (WDHS) personnel maintain a database consisting of information collected from hunters who reported eating, or an intention to eat, venison from CWD-positive cervids. These data, collected since 2003, allow for the evaluation of causes of mortality in individuals potentially exposed to CWD.

Material and Methods: The WDHS database contains the name, date of birth, when available, year of CWD-positive deer harvest, and city and state of residence for each potentially exposed individual. The database also includes information on how the deer was processed (self-processed or by a commercial operator) and when applicable, names of others with whom the venison was shared. Duplicate entries (i.e., those who consumed venison from CWD-positive deer in multiple hunt years) are determined by first name, last name, and date of birth. All names in the database are cross-checked with reported cases of human prion disease in Wisconsin and cases in the National Prion Disease Pathology Surveillance Center (NPDPSC) diagnostic testing database. Persons with date of birth available are also cross-checked with prion disease decedents identified through restricted-use national multiple cause-of-death data via a data use agreement with the National Center for Health Statistics (NCHS).

Results: The database currently consists of 1561 records for hunt years 2003–2017 and 87 additional records for 2018–2019. Of these, 657 records have accompanying date of birth; 15 entries were removed as duplicates leaving 642 unique individuals. Of these individuals, 278 of 426 (66%) who ate venison from a CWD-positive deer and provided processing information reported self-processing. No matches were found among any persons in the database cross-checked with WDHS human prion disease surveillance data, NPDPSC data (February 2022 update), and NCHS data through 2020.

Conclusions: Because of the linkage of person and CWD-positive animal in the WDHS database, reviewing the cause of mortality in potentially exposed persons is possible. The number of individuals cross-checked so far is likely only a small percentage of those potentially exposed to CWD in Wisconsin, and many more years of vital status tracking are needed given an expected long incubation period should transmission to humans occur. Nevertheless, the findings of this ongoing review are thus far reassuring.

Prion disease incidence, United States, 2003–2020

R.A. Maddoxa, M.K. Persona, K. Kotobellib, A. Mvilongoa, B.S. Applebyb, L.B. Schonbergera, T.A. Hammetta, J.Y. Abramsa, and E.D. Belaya aNational Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, USA; bNational Prion Disease Pathology Surveillance Center (NPDPSC), Case Western Reserve University, Cleveland, USA

Aims: Mortality data, in conjunction with neuropathological and genetic testing results, are used to estimate prion disease incidence in the United States.

Material and Methods: Prion disease decedents for 2003–2020 were identified from restricted-use U.S. national multiple cause-of-death data, via a data use agreement with the National Center for Health Statistics, and from the National Prion Disease Pathology Surveillance Center (NPDPSC) database. NPDPSC decedents with neuropathological or genetic test results positive for prion disease for whom no likely match was found in the NCHS multiple cause-of-death data were added as cases for incidence calculations, while those with negative neuropathology results but with cause-of-death data indicating prion disease were removed. Unmatched cases in the NPDPSC database lacking neuropathological testing but with a positive real-time quaking-induced conversion (RT-QuIC) test result were additionally assessed. Age-specific and age-adjusted average annual incidence rates were calculated from the combined data; the year 2000 as the standard population and the direct method were used for age-adjustment.

Results: A total of 7,921 decedents were identified as having prion disease during 2003–2020 for an age-adjusted average annual incidence of 1.2 per million population. The age-adjusted incidence between males and females (1.3 and 1.1 per million, respectively) differed significantly (p < 0.0001). The age-specific average annual incidence among those <55 and ≥55 years of age was 0.2 and 4.8 per million, respectively; incidence among those ≥65 was 6.1 per million. Eighteen cases were <30 years of age for an age-specific incidence of 8.0 per billion; only 6 of these very young cases were sporadic (3 sporadic CJD, 3 sporadic fatal insomnia), with the rest being familial (9), variant (2), or iatrogenic (1). The age-adjusted annual incidence for the most recent year of data, 2020, was 1.3 per million. However, assessment of RT-QuIC positive cases lacking neuropathology in the NPDPSC database suggested that approximately 20% more cases may have occurred in that year; the addition of a subset of these cases that had date of death information available (n = 44) increased the 2020 rate to 1.4 per million.

Conclusions: Mortality data supplemented with the results of neuropathological, CSF RT-QuIC, and genetic testing can be used to estimate prion disease incidence. However, the identification in the NPDPSC database of RT-QuIC-positive cases lacking date of death information suggests that this strategy may exclude a number of probable prion disease cases. Prion disease cases <30 years of age, especially those lacking a pathogenic mutation, continue to be very rare.

Shedding of Chronic Wasting Disease Prions in Multiple Excreta Throughout Disease Course in White-tailed Deer

Nathaniel D. Denkersa, Erin E. McNultya, Caitlyn N. Krafta, Amy V. Nallsa, Joseph A. Westricha, Wilfred Goldmannb, Candace K. Mathiasona, and Edward A. Hoovera

aPrion Research Center, College of Veterinary Medicine and Biological Sciences, Department of Microbiology, Immunology, and Pathology; Colorado State University, Fort Collins, CO, USA; bDivision of Infection and Immunity, The Roslin Institute and the Royal Dick School of Veterinary Studies, University of Edinburgh, Midlothian, UK

Aims: Chronic wasting disease (CWD) now infects cervids in South Korea, North America, and Scandinavia. CWD is unique in its efficient transmission and shedding of prions in body fluids throughout long course infections. Questions remain as to the magnitude of shedding and the route of prion acquisition. As CWD continues to expand, the need to better understand these facets of disease becomes more pertinent. The purpose of the studies described was to define the longitudinal shedding profile of CWD prions in urine, saliva, and feces throughout the course of infection in white-tailed deer.

Material and Methods: Twelve (12) white-tailed deer were inoculated with either 1 mg or 300ng of CWD. Urine, saliva, and feces were collected every 3-month post-inoculation (MPI) throughout the study duration. Cohorts were established based on PNRP genotype: codon 96 GG (n = 6) and alternate codons 96 GS (n = 5) & 103NT (n = 1). Urine and saliva were analyzed using iron-oxide magnetic extraction (IOME) and real-time quaking induced conversion (RT-QuIC)(IQ). Feces were subjected to IOME, followed by 4 rounds protein misfolding cyclic amplification (PMCA) with products analyzed by RT-QuIC (IPQ). To determine whether IPQ may be superior to IQ, a subset of urine and saliva were also tested by IPQ. Results were compared with clinical disease status.

Results: Within the 96 GG cohort, positive seeding activity was detected in feces from all deer (100%), in saliva from 5 of 6 (83%), and in urine from 4 of 6 (66%). Shedding in all excreta occurred at, or just after, the first positive tonsil biopsy result. In the 96 GS/103NT cohort, positive seeding activity could be detected in feces from 3 of 6 (50%) deer, saliva in 2 of 6 (33%), and urine in 1 of 6 (16%). Shedding in excreta was detected >5 months after the first tonsil positive result. Four of six 96 GG deer developed clinical signs of CWD, whereas only 2 of the 96 GS/103NT did. Shedding was more frequently detected in deer with clinical disease. The IPQ protocol did not significantly improve detection in saliva or urine samples, however, it significantly augmented detection in feces by eliminating non-specific background commonly experienced with IQ. Negative control samples remained negative in samples tested.

Conclusions: These studies demonstrate: (a) CWD prion excretion occurs throughout infection; (2) PRNP genotype (GG≫GS/NT) influences the excreta shedding; and (3) detection sensitivity in excreta can vary with different RT-QuIC protocols. These results provide a more complete perspective of prion shedding in deer during the course of CWD infection.

Funded by: National Institutes of Health (NIH)

Grant number: RO1-NS061902-09 R to EAH, PO1-AI077774 to EAH, and R01-AI112956-06 to CKM

Acknowledgement: We abundantly thank Sallie Dahmes at WASCO and David Osborn and Gino D’Angelo at the University of Georgia Warnell School of Forestry and Natural Resources for their long-standing support of this work through provision of the hand-raised, CWD-free, white-tailed deer used in these studies

Large-scale PMCA screening of retropharyngeal lymph nodes and in white-tailed deer and comparisons with ELISA and IHC: the Texas CWD study

Rebeca Benaventea, Paulina Sotoa, Mitch Lockwoodb, and Rodrigo Moralesa

aDepartment of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA; bTexas Park and Wildlife Department, Texas, USA

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy that affects various species of cervids, and both free-ranging and captive animals. Until now, CWD has been detected in 3 continents: North America, Europe, and Asia. CWD prevalence in some states may reach 30% of total animals. In Texas, the first case of CWD was reported in a free-range mule deer in Hudspeth and now it has been detected in additional 14 counties. Currently, the gold standard techniques used for CWD screening and detection are ELISA and immunohistochemistry (IHC) of obex and retropharyngeal lymph nodes (RPLN). Unfortunately, these methods are known for having a low diagnostic sensitivity. Hence, many CWD-infected animals at pre-symptomatic stages may be misdiagnosed. Two promising in vitro prion amplification techniques, including the real-time quaking-induced conversion (RT-QuIC) and the protein misfolding cyclic amplification (PMCA) have been used to diagnose CWD and other prion diseases in several tissues and bodily fluids. Considering the low cost and speed of RT-QuIC, two recent studies have communicated the potential of this technique to diagnose CWD prions in RPLN samples. Unfortunately, the data presented in these articles suggest that identification of CWD positive samples is comparable to the currently used ELISA and IHC protocols. Similar studies using the PMCA technique have not been reported.

Aims: Compare the CWD diagnostic potential of PMCA with ELISA and IHC in RPLN samples from captive and free-range white-tailed deer. Material and Methods: In this study we analyzed 1,003 RPLN from both free-ranging and captive white-tailed deer collected in Texas. Samples were interrogated with the PMCA technique for their content of CWD prions. PMCA data was compared with the results obtained through currently approved techniques.

Results: Our results show a 15-fold increase in CWD detection in free-range deer compared with ELISA. Our results unveil the presence of prion infected animals in Texas counties with no previous history of CWD. In the case of captive deer, we detected a 16% more CWD positive animals when compared with IHC. Interestingly, some of these positive samples displayed differences in their electroforetic mobilities, suggesting the presence of different prion strains within the State of Texas.

Conclusions: PMCA sensitivity is significantly higher than the current gold standards techniques IHC and ELISA and would be a good tool for rapid CWD screening.

Funded by: USDA

Grant number: AP20VSSPRS00C143

ATYPRION project: assessing the zoonotic potential of interspecies transmission of CWD isolates to livestock (preliminary results).

Enric Vidala,b, Juan Carlos Espinosac, Samanta Gilera,b, Montserrat Ordóñeza,b, Guillermo Canteroa,b, Vincent Béringued, Justin J. Greenleee, and Juan Maria Torresc

aUnitat mixta d’Investigació IRTA-UAB en Sanitat Animal. Centre de Recerca en Sanitat Animal (CReSA). Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia; bIRTA. Programa de Sanitat Animal. Centre de Recerca en Sanitat Animal (CReSA). Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia; cCentro de Investigación en Sanidad Animal, CISA-INIA-CSIC, Valdeolmos, Madrid, Spain; dMolecular Virology and Immunology, French National Research Institute for Agriculture, Food and Environment (INRAE), Université Paris-Saclay, Jouy-en-Josas, France; eVirus and Prion Research Unit, National Animal Disease Center, ARS, United States Department of Agriculture, Ames, IA, USA

Aims: Since variant Creutzfeldt-Jackob disease was linked to the consumption of bovine spongiform encephalopathy prions, the study of the pathobiological features of animal prions, particularly their zoonotic potential, is of great concern to the scientific community and public health authorities. Furthermore, interspecies transmission of prions has been demonstrated as a putative evolutionary mechanism for prions, that can lead to the emergence of new features including the ability to infect humans. For instance, small ruminants’ atypical scrapie prions, when propagated in a bovine or porcine host, can shift to a classical BSE phenotype thus posing a potential risk in case of human exposure. So far, no hard evidence of zoonotic transmission of cervids’ chronic wasting disease (CWD) to humans has been published, however experimental transmission to bovine, ovine and caprine hosts has been achieved. Our goal is to investigate if, once passaged through these domestic species, CWD prions might become infectious to humans.

Material and Methods: Different CWD isolates experimentally adapted to cattle, sheep and goat (Hamir et al, 2005, 2006, 2007, Greenlee et al 2012) have been intracerebrally inoculated to transgenic mouse models expressing the human cellular prion protein either homozygous for methionine or valine at codon 129 (Tg340-Met129 and Tg362-Val129). Additionally, inocula obtained from experimental transmission of elk CWD to ovinized (Tg501) and bovinized (BoTg110) transgenic mice, as well as white-tailed deer CWD to BoTg110 mice, are currently being bioassayed in both human PrPCtransgenic models.

Results and conclusions: No evidence of transmission has been found on first passage for bovine adapted elk and mule deer CWD to none of the humanized models. The remaining bioassays are ongoing without showing clinical signs yet, as well as second passages for the negative 1stpassages.

Funded by: La Marató de TV3 foundation. Grant number: ATYPRION (201,821–30-31-32)

www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286

Prion 2022 Conference abstracts: pushing the boundaries

www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286

Prion Conference 2018 Abstracts

P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States

Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1)

(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.

Background

Chronic wasting disease (CWD) is a prion disease of deer and elk that has been identified in freeranging cervids in 23 US states. While there is currently no epidemiological evidence for zoonotic transmission through the consumption of contaminated venison, studies suggest the CWD agent can cross the species barrier in experimental models designed to closely mimic humans. We compared rates of human prion disease in states with and without CWD to examine the possibility of undetermined zoonotic transmission.

Methods

Death records from the National Center for Health Statistics, case records from the National Prion Disease Pathology Surveillance Center, and additional state case reports were combined to create a database of human prion disease cases from 2003-2015. Identification of CWD in each state was determined through reports of positive CWD tests by state wildlife agencies. Age- and race-adjusted mortality rates for human prion disease, excluding cases with known etiology, were determined for four categories of states based on CWD occurrence: highly endemic (>16 counties with CWD identified in free-ranging cervids); moderately endemic (3-10 counties with CWD); low endemic (1-2 counties with CWD); and no CWD states. States were counted as having no CWD until the year CWD was first identified. Analyses stratified by age, sex, and time period were also conducted to focus on subgroups for which zoonotic transmission would be more likely to be detected: cases <55 years old, male sex, and the latter half of the study (2010-2015).

Results

Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states (rate ratio [RR]: 1.12, 95% confidence interval [CI] = 1.01 - 1.23), as did low endemic states (RR: 1.15, 95% CI = 1.04 - 1.27). Moderately endemic states did not have an elevated mortality rate (RR: 1.05, 95% CI = 0.93 - 1.17). In age-stratified analyses, prion disease mortality rates among the <55 year old population were elevated for moderately endemic states (RR: 1.57, 95% CI = 1.10 – 2.24) while mortality rates were elevated among those ≥55 for highly endemic states (RR: 1.13, 95% CI = 1.02 - 1.26) and low endemic states (RR: 1.16, 95% CI = 1.04 - 1.29). In other stratified analyses, prion disease mortality rates for males were only elevated for low endemic states (RR: 1.27, 95% CI = 1.10 - 1.48), and none of the categories of CWD-endemic states had elevated mortality rates for the latter time period (2010-2015).

Conclusions

While higher prion disease mortality rates in certain categories of states with CWD in free-ranging cervids were noted, additional stratified analyses did not reveal markedly elevated rates for potentially sensitive subgroups that would be suggestive of zoonotic transmission. Unknown confounding factors or other biases may explain state-by-state differences in prion disease mortality.

=====

P172 Peripheral Neuropathy in Patients with Prion Disease

Wang H(1), Cohen M(1), Appleby BS(1,2)

(1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio.

Prion disease is a fatal progressive neurodegenerative disease due to deposition of an abnormal protease-resistant isoform of prion protein. Typical symptoms include rapidly progressive dementia, myoclonus, visual disturbance and hallucinations. Interestingly, in patients with prion disease, the abnormal protein canould also be found in the peripheral nervous system. Case reports of prion deposition in peripheral nerves have been reported. Peripheral nerve involvement is thought to be uncommon; however, little is known about the exact prevalence and features of peripheral neuropathy in patients with prion disease.

We reviewed autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017. We collected information regarding prion protein diagnosis, demographics, comorbidities, clinical symptoms, physical exam, neuropathology, molecular subtype, genetics lab, brain MRI, image and EMG reports. Our study included 104 patients. Thirteen (12.5%) patients had either subjective symptoms or objective signs of peripheral neuropathy. Among these 13 patients, 3 had other known potential etiologies of peripheral neuropathy such as vitamin B12 deficiency or prior chemotherapy. Among 10 patients that had no other clear etiology, 3 (30%) had familial CJD. The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%). The Majority of cases wasere male (60%). Half of them had exposure to wild game. The most common subjective symptoms were tingling and/or numbness of distal extremities. The most common objective finding was diminished vibratory sensation in the feet. Half of them had an EMG with the findings ranging from fasciculations to axonal polyneuropathy or demyelinating polyneuropathy.

Our study provides an overview of the pattern of peripheral neuropathy in patients with prion disease. Among patients with peripheral neuropathy symptoms or signs, majority has polyneuropathy. It is important to document the baseline frequency of peripheral neuropathy in prion diseases as these symptoms may become important when conducting surveillance for potential novel zoonotic prion diseases.

=====

P177 PrP plaques in methionine homozygous Creutzfeldt-Jakob disease patients as a potential marker of iatrogenic transmission

Abrams JY (1), Schonberger LB (1), Cali I (2), Cohen Y (2), Blevins JE (2), Maddox RA (1), Belay ED (1), Appleby BS (2), Cohen ML (2)

(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.

Background

Sporadic Creutzfeldt-Jakob disease (CJD) is widely believed to originate from de novo spontaneous conversion of normal prion protein (PrP) to its pathogenic form, but concern remains that some reported sporadic CJD cases may actually be caused by disease transmission via iatrogenic processes. For cases with methionine homozygosity (CJD-MM) at codon 129 of the PRNP gene, recent research has pointed to plaque-like PrP deposition as a potential marker of iatrogenic transmission for a subset of cases. This phenotype is theorized to originate from specific iatrogenic source CJD types that comprise roughly a quarter of known CJD cases.

Methods

We reviewed scientific literature for studies which described PrP plaques among CJD patients with known epidemiological links to iatrogenic transmission (receipt of cadaveric human grown hormone or dura mater), as well as in cases of reported sporadic CJD. The presence and description of plaques, along with CJD classification type and other contextual factors, were used to summarize the current evidence regarding plaques as a potential marker of iatrogenic transmission. In addition, 523 cases of reported sporadic CJD cases in the US from January 2013 through September 2017 were assessed for presence of PrP plaques.

Results

We identified four studies describing 52 total cases of CJD-MM among either dura mater recipients or growth hormone recipients, of which 30 were identified as having PrP plaques. While sporadic cases were not generally described as having plaques, we did identify case reports which described plaques among sporadic MM2 cases as well as case reports of plaques exclusively in white matter among sporadic MM1 cases. Among the 523 reported sporadic CJD cases, 0 of 366 MM1 cases had plaques, 2 of 48 MM2 cases had kuru plaques, and 4 of 109 MM1+2 cases had either kuru plaques or both kuru and florid plaques. Medical chart review of the six reported sporadic CJD cases with plaques did not reveal clinical histories suggestive of potential iatrogenic transmission.

Conclusions

PrP plaques occur much more frequently for iatrogenic CJD-MM cases compared to sporadic CJDMM cases. Plaques may indicate iatrogenic transmission for CJD-MM cases without a type 2 Western blot fragment. The study results suggest the absence of significant misclassifications of iatrogenic CJD as sporadic. To our knowledge, this study is the first to describe grey matter kuru plaques in apparently sporadic CJD-MM patients with a type 2 Western blot fragment.

=====

P180 Clinico-pathological analysis of human prion diseases in a brain bank series

Ximelis T (1), Aldecoa I (1,2), Molina-Porcel L (1,3), Grau-Rivera O (4), Ferrer I (5), Nos C (6), Gelpi E (1,7), Sánchez-Valle R (1,4)

(1) Neurological Tissue Bank of the Biobanc-Hospital ClÃnic-IDIBAPS, Barcelona, Spain (2) Pathological Service of Hospital ClÃnic de Barcelona, Barcelona, Spain (3) EAIA Trastorns Cognitius, Centre Emili Mira, Parc de Salut Mar, Barcelona, Spain (4) Department of Neurology of Hospital ClÃnic de Barcelona, Barcelona, Spain (5) Institute of Neuropathology, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona (6) General subdirectorate of Surveillance and Response to Emergencies in Public Health, Department of Public Health in Catalonia, Barcelona, Spain (7) Institute of Neurology, Medical University of Vienna, Vienna, Austria.

Background and objective:

The Neurological Tissue Bank (NTB) of the Hospital Clínic-Institut d‘Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain is the reference center in Catalonia for the neuropathological study of prion diseases in the region since 2001. The aim of this study is to analyse the characteristics of the confirmed prion diseases registered at the NTB during the last 15 years.

Methods:

We reviewed retrospectively all neuropathologically confirmed cases registered during the period January 2001 to December 2016.

Results:

176 cases (54,3% female, mean age: 67,5 years and age range: 25-86 years) of neuropathological confirmed prion diseases have been studied at the NTB. 152 cases corresponded to sporadic Creutzfeldt-Jakob disease (sCJD), 10 to genetic CJD, 10 to Fatal Familial Insomnia, 2 to GerstmannSträussler-Scheinker disease, and 2 cases to variably protease-sensitive prionopathy (VPSPr). Within sCJD subtypes the MM1 subtype was the most frequent, followed by the VV2 histotype.

Clinical and neuropathological diagnoses agreed in 166 cases (94%). The clinical diagnosis was not accurate in 10 patients with definite prion disease: 1 had a clinical diagnosis of Fronto-temporal dementia (FTD), 1 Niemann-Pick‘s disease, 1 Lewy Body‘s Disease, 2 Alzheimer‘s disease, 1 Cortico-basal syndrome and 2 undetermined dementia. Among patients with VPSPr, 1 had a clinical diagnosis of Amyotrophic lateral sclerosis (ALS) and the other one with FTD.

Concomitant pathologies are frequent in older age groups, mainly AD neuropathological changes were observed in these subjects.

Discussion:

A wide spectrum of human prion diseases have been identified in the NTB being the relative frequencies and main characteristics like other published series. There is a high rate of agreement between clinical and neuropathological diagnoses with prion diseases. These findings show the importance that public health has given to prion diseases during the past 15 years. Continuous surveillance of human prion disease allows identification of new emerging phenotypes. Brain tissue samples from these donors are available to the scientific community. For more information please visit:

www.clinicbiobanc.org/banc-teixits-neurologics/mostres/en_index.html

=====

P192 Prion amplification techniques for the rapid evaluation of surface decontamination procedures

Bruyere-Ostells L (1), Mayran C (1), Belondrade M (1), Boublik Y (2), Haïk S (3), Fournier-Wirth C (1), Nicot S (1), Bougard D (1)

(1) Pathogenesis and control of chronic infections, Etablissement Français du Sang, Inserm, Université de Montpellier, Montpellier, France. (2) Centre de Recherche en Biologie cellulaire de Montpellier, CNRS, Université de Montpellier, Montpellier, France. (3) Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.

Aims:

Transmissible Spongiform Encephalopathies (TSE) or prion diseases are a group of incurable and always fatal neurodegenerative disorders including Creutzfeldt-Jakob diseases (CJD) in humans. These pathologies include sporadic (sCJD), genetic and acquired (variant CJD) forms. By the past, sCJD and vCJD were transmitted by different prion contaminated biological materials to patients resulting in more than 400 iatrogenic cases (iCJD). The atypical nature and the biochemical properties of the infectious agent, formed by abnormal prion protein or PrPTSE, make it particularly resistant to conventional decontamination procedures. In addition, PrPTSE is widely distributed throughout the organism before clinical onset in vCJD and can also be detected in some peripheral tissues in sporadic CJD. Risk of iatrogenic transmission of CJD by contaminated medical device remains thus a concern for healthcare facilities. Bioassay is the gold standard method to evaluate the efficacy of prion decontamination procedures but is time-consuming and expensive. Here, we propose to compare in vitro prion amplification techniques: Protein Misfolding Cyclic Amplification (PMCA) and Real-Time Quaking Induced Conversion (RT-QuIC) for the detection of residual prions on surface after decontamination.

Methods:

Stainless steel wires, by mimicking the surface of surgical instruments, were proposed as a carrier model of prions for inactivation studies. To determine the sensitivity of the two amplification techniques on wires (Surf-PMCA and Surf-QuIC), steel wires were therefore contaminated with serial dilutions of brain homogenates (BH) from a 263k infected hamster and from a patient with sCJD (MM1 subtype). We then compared the different standard decontamination procedures including partially and fully efficient treatments by detecting the residual seeding activity on 263K and sCJD contaminated wires. We completed our study by the evaluation of marketed reagents endorsed for prion decontamination.

Results:

The two amplification techniques can detect minute quantities of PrPTSE adsorbed onto a single wire. 8/8 wires contaminated with a 10-6 dilution of 263k BH and 1/6 with the 10-8 dilution are positive with Surf-PMCA. Similar performances were obtained with Surf-QuIC on 263K: 10/16 wires contaminated with 10-6 dilution and 1/8 wires contaminated with 10-8 dilution are positive. Regarding the human sCJD-MM1 prion, Surf-QuIC allows us to detect 16/16 wires contaminated with 10-6 dilutions and 14/16 with 10-7 . Results obtained after decontamination treatments are very similar between 263K and sCJD prions. Efficiency of marketed treatments to remove prions is lower than expected.

Conclusions:

Surf-PMCA and Surf-QuIC are very sensitive methods for the detection of prions on wires and could be applied to prion decontamination studies for rapid evaluation of new treatments. Sodium hypochlorite is the only product to efficiently remove seeding activity of both 263K and sCJD prions.

=====

WA2 Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice

Schatzl HM (1, 2), Hannaoui S (1, 2), Cheng Y-C (1, 2), Gilch S (1, 2), Beekes M (3), SchulzSchaeffer W (4), Stahl-Hennig C (5) and Czub S (2, 6)

(1) University of Calgary, Calgary Prion Research Unit, Calgary, Canada (2) University of Calgary, Faculty of Veterinary Medicine, Calgary, Canada, (3) Robert Koch Institute, Berlin, Germany, (4) University of Homburg/Saar, Homburg, Germany, (5) German Primate Center, Goettingen, Germany, (6) Canadian Food Inspection Agency (CFIA), Lethbridge, Canada.

To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years. After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were found in spinal cord and brain of euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and preclinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles. Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate. The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology. Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP. The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.

See also poster P103

***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.

=====

WA16 Monitoring Potential CWD Transmission to Humans

Belay ED

Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA.

The spread of chronic wasting disease (CWD) in animals has raised concerns about increasing human exposure to the CWD agent via hunting and venison consumption, potentially facilitating CWD transmission to humans. Several studies have explored this possibility, including limited epidemiologic studies, in vitro experiments, and laboratory studies using various types of animal models. Most human exposures to the CWD agent in the United States would be expected to occur in association with deer and elk hunting in CWD-endemic areas. The Centers for Disease Control and Prevention (CDC) collaborated with state health departments in Colorado, Wisconsin, and Wyoming to identify persons at risk of CWD exposure and to monitor their vital status over time. Databases were established of persons who hunted in Colorado and Wyoming and those who reported consumption of venison from deer that later tested positive in Wisconsin. Information from the databases is periodically cross-checked with mortality data to determine the vital status and causes of death for deceased persons. Long-term follow-up of these hunters is needed to assess their risk of development of a prion disease linked to CWD exposure.

=====

P166 Characterization of CJD strain profiles in venison consumers and non-consumers from Alberta and Saskatchewan

Stephanie Booth (1,2), Lise Lamoureux (1), Debra Sorensen (1), Jennifer L. Myskiw (1,2), Megan Klassen (1,2), Michael Coulthart (3), Valerie Sim (4)

(1) Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg (2) Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg (3) Canadian CJD Surveillance System, Public Health Agency of Canada, Ottawa (4) Division of Neurology, Department of Medicine Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton.

Chronic wasting disease (CWD) is spreading rapidly through wild cervid populations in the Canadian provinces of Alberta and Saskatchewan. While this has implications for tourism and hunting, there is also concern over possible zoonotic transmission to humans who eat venison from infected deer. Whilst there is no evidence of any human cases of CWD to date, the Canadian CJD Surveillance System (CJDSS) in Canada is staying vigilant. When variant CJD occurred following exposure to BSE, the unique biochemical fingerprint of the pathologic PrP enabled a causal link to be confirmed. However, we cannot be sure what phenotype human CWD prions would present with, or indeed, whether this would be distinct from that see in sporadic CJD. Therefore we are undertaking a systematic analysis of the molecular diversity of CJD cases of individuals who resided in Alberta and Saskatchewan at their time of death comparing venison consumers and non-consumers, using a variety of clinical, imaging, pathological and biochemical markers. Our initial objective is to develop novel biochemical methodologies that will extend the baseline glycoform and genetic polymorphism typing that is already completed by the CJDSS. Firstly, we are reviewing MRI, EEG and pathology information from over 40 cases of CJD to select clinically affected areas for further investigation. Biochemical analysis will include assessment of the levels of protease sensitive and resistant prion protein, glycoform typing using 2D gel electrophoresis, testing seeding capabilities and kinetics of aggregation by quaking-induced conversion, and determining prion oligomer size distributions with asymmetric flow field fractionation with in-line light scattering. Progress and preliminary data will be presented. Ultimately, we intend to further define the relationship between PrP structure and disease phenotype and establish a baseline for the identification of future atypical CJD cases that may arise as a result of exposure to CWD.

=====

Source Prion Conference 2018 Abstracts

www.ncbi.nlm.nih.gov/pmc/articles/PMC6738495/

transmissiblespongiformencephalopathy.blogspot.com/2018/05/prion-2018-may-22-25-2018-santiago-de.html

chronic-wasting-disease.blogspot.com/2018/07/oral-transmission-of-cwd-into.html

prionconference.blogspot.com/2018/

Volume 24, Number 8—August 2018 Research Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions

Marcelo A. BarriaComments to Author , Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell)

Abstract Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form. We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted.

snip...

Discussion Characterization of the transmission properties of CWD and evaluation of their zoonotic potential are important for public health purposes. Given that CWD affects several members of the family Cervidae, it seems reasonable to consider whether the zoonotic potential of CWD prions could be affected by factors such as CWD strain, cervid species, geographic location, and Prnp–PRNP polymorphic variation. We have previously used an in vitro conversion assay (PMCA) to investigate the susceptibility of the human PrP to conversion to its disease-associated form by several animal prion diseases, including CWD (15,16,22). The sensitivity of our molecular model for the detection of zoonotic conversion depends on the combination of 1) the action of proteinase K to degrade the abundant human PrPC that constitutes the substrate while only N terminally truncating any human PrPres produced and 2) the presence of the 3F4 epitope on human but not cervid PrP. In effect, this degree of sensitivity means that any human PrPres formed during the PMCA reaction can be detected down to the limit of Western blot sensitivity. In contrast, if other antibodies that detect both cervid and human PrP are used, such as 6H4, then newly formed human PrPres must be detected as a measurable increase in PrPres over the amount remaining in the reaction product from the cervid seed. Although best known for the efficient amplification of prions in research and diagnostic contexts, the variation of the PMCA method employed in our study is optimized for the definitive detection of zoonotic reaction products of inherently inefficient conversion reactions conducted across species barriers. By using this system, we previously made and reported the novel observation that elk CWD prions could convert human PrPC from human brain and could also convert recombinant human PrPC expressed in transgenic mice and eukaryotic cell cultures (15).

A previous publication suggested that mule deer PrPSc was unable to convert humanized transgenic substrate in PMCA assays (23) and required a further step of in vitro conditioning in deer substrate PMCA before it was able to cross the deer–human molecular barrier (24). However, prions from other species, such as elk (15) and reindeer affected by CWD, appear to be compatible with the human protein in a single round of amplification (as shown in our study). These observations suggest that different deer species affected by CWD could present differing degrees of the olecular compatibility with the normal form of human PrP.

The contribution of the polymorphism at codon 129 of the human PrP gene has been extensively studied and is recognized as a risk factor for Creutzfeldt-Jakob disease (4). In cervids, the equivalent codon corresponds to the position 132 encoding methionine or leucine. This polymorphism in the elk gene has been shown to play an important role in CWD susceptibility (25,26). We have investigated the effect of this cervid Prnp polymorphism on the conversion of the humanized transgenic substrate according to the variation in the equivalent PRNP codon 129 polymorphism. Interestingly, only the homologs methionine homozygous seed–substrate reactions could readily convert the human PrP, whereas the heterozygous elk PrPSc was unable to do so, even though comparable amounts of PrPres were used to seed the reaction. In addition, we observed only low levels of human PrPres formation in the reactions seeded with the homozygous methionine (132 MM) and the heterozygous (132 ML) seeds incubated with the other 2 human polymorphic substrates (129 MV and 129 VV). The presence of the amino acid leucine at position 132 of the elk Prnp gene has been attributed to a lower degree of prion conversion compared with methionine on the basis of experiments in mice made transgenic for these polymorphic variants (26). Considering the differences observed for the amplification of the homozygous human methionine substrate by the 2 polymorphic elk seeds (MM and ML), reappraisal of the susceptibility of human PrPC by the full range of cervid polymorphic variants affected by CWD would be warranted.

In light of the recent identification of the first cases of CWD in Europe in a free-ranging reindeer (R. tarandus) in Norway (2), we also decided to evaluate the in vitro conversion potential of CWD in 2 experimentally infected reindeer (18). Formation of human PrPres was readily detectable after a single round of PMCA, and in all 3 humanized polymorphic substrates (MM, MV, and VV). This finding suggests that CWD prions from reindeer could be more compatible with human PrPC generally and might therefore present a greater risk for zoonosis than, for example, CWD prions from white-tailed deer. A more comprehensive comparison of CWD in the affected species, coupled with the polymorphic variations in the human and deer PRNP–Prnp genes, in vivo and in vitro, will be required before firm conclusions can be drawn. Analysis of the Prnp sequence of the CWD reindeer in Norway was reported to be identical to the specimens used in our study (2). This finding raises the possibility of a direct comparison of zoonotic potential between CWD acquired in the wild and that produced in a controlled laboratory setting. (Table).

The prion hypothesis proposes that direct molecular interaction between PrPSc and PrPC is necessary for conversion and prion replication. Accordingly, polymorphic variants of the PrP of host and agent might play a role in determining compatibility and potential zoonotic risk. In this study, we have examined the capacity of the human PrPC to support in vitro conversion by elk, white-tailed deer, and reindeer CWD PrPSc. Our data confirm that elk CWD prions can convert the human PrPC, at least in vitro, and show that the homologous PRNP polymorphisms at codon 129 and 132 in humans and cervids affect conversion efficiency. Other species affected by CWD, particularly caribou or reindeer, also seem able to convert the human PrP. It will be important to determine whether other polymorphic variants found in other CWD-affected Cervidae or perhaps other factors (17) exert similar effects on the ability to convert human PrP and thus affect their zoonotic potential.

Dr. Barria is a research scientist working at the National CJD Research and Surveillance Unit, University of Edinburgh. His research has focused on understanding the molecular basis of a group of fatal neurologic disorders called prion diseases.

Acknowledgments We thank Aru Balachandran for originally providing cervid brain tissues, Abigail Diack and Jean Manson for providing mouse brain tissue, and James Ironside for his critical reading of the manuscript at an early stage.

This report is independent research commissioned and funded by the United Kingdom’s Department of Health Policy Research Programme and the Government of Scotland. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health or the Government of Scotland.

Author contributions: The study was conceived and designed by M.A.B. and M.W.H. The experiments were conducted by M.A.B. and A.L. Chronic wasting disease brain specimens were provided by G.M. The manuscript was written by M.A.B. and M.W.H. All authors contributed to the editing and revision of the manuscript.

wwwnc.cdc.gov/eid/article/24/8/16-1888_article

www.ed.ac.uk/clinical-brain-sciences/news/news-jul-dec-2018/cwd-prions-human-conversion
Prion 2017 Conference Abstracts
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1
University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen
This is a progress report of a project which started in 2009.
21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves.
Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice.
At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation.
PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS ABSTRACTS REFERENCE
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.

efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2018.5132

SATURDAY, FEBRUARY 23, 2019

Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019

chronic-wasting-disease.blogspot.com/2019/02/chronic-wasting-disease-cwd-tse-prion.html

TUESDAY, NOVEMBER 04, 2014

Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011 Authors, though, acknowledged the study was limited in geography and sample size and so it couldn't draw a conclusion about the risk to humans. They recommended more study. Dr. Ermias Belay was the report's principal author but he said New York and Oneida County officials are following the proper course by not launching a study. "There's really nothing to monitor presently. No one's sick," Belay said, noting the disease's incubation period in deer and elk is measured in years. "

chronic-wasting-disease.blogspot.com/2014/11/six-year-follow-up-of-point-source.html

Transmission Studies Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}....TSS resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.

snip....

web.archive.org/web/20090506002237/http://www..bseinquiry.gov.uk/files/mb/m11b/tab01.pdf

Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿

Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.

jvi.asm.org/content/83/18/9608.full

Prions in Skeletal Muscles of Deer with Chronic Wasting Disease Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.

science.sciencemag.org/content/311/5764/1117..long

*** now, let’s see what the authors said about this casual link, personal communications years ago, and then the latest on the zoonotic potential from CWD to humans from the TOKYO PRION 2016 CONFERENCE. 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 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: [phone]).

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: [e-mail]; [e-mail]; [e-mail]

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 ;

chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html

> However, to date, no CWD infections have been reported in people.

sporadic, spontaneous CJD, 85%+ of all human TSE, did not just happen. never in scientific literature has this been proven. if one looks up the word sporadic or spontaneous at pubmed, you will get a laundry list of disease that are classified in such a way;

sporadic = 54,983 hits

www.ncbi.nlm.nih.gov/pubmed/?term=sporadic

spontaneous = 325,650 hits

www.ncbi.nlm.nih.gov/pubmed/?term=spontaneous

key word here is 'reported'. science has shown that CWD in humans will look like sporadic CJD.

SO, how can one assume that CWD has not already transmitted to humans? they can't, and it's as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it's being misdiagnosed as sporadic CJD. ...terry

*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***

> However, to date, no CWD infections have been reported in people.
key word here is ‘reported’. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can’t, and it’s as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it’s being misdiagnosed as sporadic CJD. …terry
*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***
*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***
www.tandfonline.com/doi/full/10.4161/pri.28124?src=recsys
www.tandfonline.com/doi/pdf/10.4161/pri.28124?needAccess=true
wwwnc.cdc.gov/eid/article/20/1/13-0858_article
CWD TSE PRION AND ZOONOTIC, ZOONOSIS, POTENTIAL

Subject: Re: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY

Date: Fri, 18 Oct 2002 23:12:22 +0100

From: Steve Dealler

Reply-To: Bovine Spongiform Encephalopathy Organization: Netscape Online member

To: BSE-L@ References:

Dear Terry,

An excellent piece of review as this literature is desperately difficult to get back from Government sites.

What happened with the deer was that an association between deer meat eating and sporadic CJD was found in about 1993. The evidence was not great but did not disappear after several years of asking CJD cases what they had eaten. I think that the work into deer disease largely stopped because it was not helpful to the UK industry...and no specific cases were reported. Well, if you dont look adequately like they are in USA currenly then you wont find any!

Steve Dealler ===============

caninespongiformencephalopathy.blogspot.com/2010/03/canine-spongiform-encephalopathy-aka.html

''The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).''

CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL REPORT AUGUST 1994

Consumption of venison and veal was much less widespread among both cases and controls. For both of these meats there was evidence of a trend with increasing frequency of consumption being associated with increasing risk of CJD. (not nvCJD, but sporadic CJD...tss) These associations were largely unchanged when attention was restricted to pairs with data obtained from relatives. ...

Table 9 presents the results of an analysis of these data.

There is STRONG evidence of an association between ‘’regular’’ veal eating and risk of CJD (p = .0.01).

Individuals reported to eat veal on average at least once a year appear to be at 13 TIMES THE RISK of individuals who have never eaten veal.

There is, however, a very wide confidence interval around this estimate. There is no strong evidence that eating veal less than once per year is associated with increased risk of CJD (p = 0.51).

The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).

There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02).

The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).

snip...

It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).

snip...

In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...

snip...

In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (...TSS)

snip...see full report ;

web.archive.org/web/20090506050043/http://www.bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf

web.archive.org/web/20090506050007/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf

web.archive.org/web/20090506050244/http://www.bseinquiry.gov.uk/files/yb/1994/07/00001001.pdf

Stephen Dealler is a consultant medical microbiologist [e-mail]

BSE Inquiry Steve Dealler

Management In Confidence

BSE: Private Submission of Bovine Brain Dealler

snip...see full text;

MONDAY, FEBRUARY 25, 2019

***> MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019

bseinquiry.blogspot.com/2019/02/mad-dogs-and-englishmen-bse-scrapie-cwd.html

***> ''The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).''

***> In conclusion, sensory symptoms and loss of reflexes in Gerstmann-Sträussler-Scheinker syndrome can be explained by neuropathological changes in the spinal cord. We conclude that the sensory symptoms and loss of lower limb reflexes in Gerstmann-Sträussler-Scheinker syndrome is due to pathology in the caudal spinal cord. <***

***> The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.<***

***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***

***> All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals.<***

***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II) <***

familialcjdtseprion.blogspot.com/2019/02/cwd-gss-tse-prion-spinal-cord-confucius.html

***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***

Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.

www.nature.com/articles/srep11573

i was following and posting about cwd, bse, scrapie, cjd, tse, prion, when some here were still probably in grade school, i don't make this up.

TUESDAY, MAY 11, 2021

> A Unique Presentation of Creutzfeldt-Jakob Disease in a Patient Consuming Deer Antler Velvet <

Conclusion

We believe that our patient’s case of CJD is highly suspicious for cervid etiology given the circumstances of the case as well as the strong evidence of plausibility reported in published literature. This is the first known case of CJD in a patient who had consumed deer antler velvet. Despite the confirmed diagnosis of CJD, a causal relationship between the patient’s disease and his consumption of deer antler velvet cannot be definitively concluded.

Supplemental data including molecular tissue sample analysis and autopsy findings could yield further supporting evidence. Given this patient’s clinical resemblance to CBD and the known histological similarities of CBD with CJD, clinicians should consider both diseases in the differential diagnosis of patients with a similarly esoteric presentation. Regardless of the origin of this patient’s disease, it is clear that the potential for prion transmission from cervids to humans should be further investigated by the academic community with considerable urgency.

thescipub.com/pdf/ajidsp.2021.43.48.pdf

''We believe that our patient’s case of CJD is highly suspicious for cervid etiology given the circumstances of the case as well as the strong evidence of plausibility reported in published literature. This is the first known case of CJD in a patient who had consumed deer antler velvet. Despite the confirmed diagnosis of CJD, a causal relationship between the patient’s disease and his consumption of deer antler velvet cannot be definitively concluded.''

thescipub.com/pdf/ajidsp.2021.43.48.pdf

CREUTZFELDT JAKOB DISEASE: A Unique Presentation of Creutzfeldt-Jakob Disease in a Patient Consuming Deer Antler Velvet

i was warning England and the BSE Inquiry about just this, way back in 1998, and was ask to supply information to the BSE Inquiry. for anyone that might be interested, see;

Singeltary submission to the BSE Inquiry on CJD and Nutritional Supplements 1998

ABOUT that deer antler spray and CWD TSE PRION... I have been screaming this since my neighbors mom died from cjd, and she had been taking a supplement that contained bovine brain, bovine eyeball, and other SRMs specified risk materials, the most high risk for mad cow disease. just saying...

I made a submission to the BSE Inquiry long ago during the BSE Inquiry days, and they seemed pretty interested.

Sender: "Patricia Cantos"

To: "Terry S Singeltary Sr. (E-mail)"

Subject: Your submission to the Inquiry

Date: Fri, 3 Jul 1998 10:10:05 +0100 3 July 1998

Mr Terry S Singeltary Sr. E-Mail: Flounder at wt.net Ref: E2979

Dear Mr Singeltary, Thank you for your E-mail message of the 30th of June 1998 providing the Inquiry with your further comments. Thank you for offering to provide the Inquiry with any test results on the nutritional supplements your mother was taking before she died. As requested I am sending you our general Information Pack and a copy of the Chairman's letter. Please contact me if your system cannot read the attachments. Regarding your question, the Inquiry is looking into many aspects of the scientific evidence on BSE and nvCJD.

I would refer you to the transcripts of evidence we have already heard which are found on our internet site at ;

www.bse.org.uk.

Could you please provide the Inquiry with a copy of the press article you refer to in your e-mail? If not an approximate date for the article so that we can locate it? In the meantime, thank you for you comments. Please do not hesitate to contact me on... snip...end...tss

everyone I tell this too gets it screwed up...MY MOTHER WAS NOT TAKING THOSE SUPPLEMENTS IPLEX (that I ever knew of). this was my neighbors mother that died exactly one year previously and to the day of sporadic CJD that was diagnosed as Alzheimer’s at first. my mother died exactly a year later from the Heidenhain Variant of Creutzfeldt Jakob Disease hvCJD, and exceedingly rare strains of the ever growing sporadic CJD’s. both cases confirmed. ...

kind regards, terry

TSEs i.e. mad cow disease's BSE/BASE and NUTRITIONAL SUPPLEMENTS IPLEX, mad by standard process; vacuum dried bovine BRAIN, bone meal, bovine EYE, veal Bone, bovine liver powder, bovine adrenal, vacuum dried bovine kidney, and vacuum dried porcine stomach. also; what about potential mad cow candy bars ? see their potential mad cow candy bar list too... THESE are just a few of MANY of just this ONE COMPANY...TSS

''So, in sum, dietary supplements sold in the United States often contain ruminant tissues from undisclosed sources. Personally, I am rather squeamish and I don't think I would be eating prostate or testicle or pituitary, but I am also a little bit wary of consuming products with those glands, not just out of personal repugnance but simply out of a health concern.'' DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION CENTER FOR BIOLOGICS EVALUATION AND RESEARCH TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES ADVISORY COMMITTEE Friday, January 19, 2001

snip...

15 Open Public Hearing

16 DR. FREAS: We are opening the open public hearing

17 now. We have received one response to speak in this

18 afternoon's open public hearing. That is from Dr. Scott

19 Norton. If Dr. Norton is here, would you please come

20 forward. You can either use the podium or the microphone,

21 whichever is your choice.

22 DR. NORTON: I am Scott Norton and I am a

23 physician in the Washington D.C. area. I am here speaking

24 as a private citizen today.

25 I first became concerned about the presence of 231

1 tissues from ruminant animals in dietary supplements about

2 six months ago and expressed my concern in a letter that was 3 published in New England Journal of Medicine in July of Year 4 2000. 5 A couple of the products that I had looked at, and 6 examined their labels, that raised these concerns I brought 7 in right here. I will just read some of the organs that are 8 found in one that is called Male Power. Deer antler, 9 pancreas, orchic--despite what we just heard that the FDA

10 prefers the term "testicular tissue" to be written on the

11 labels, I have never seen a dietary supplement say

12 "testicle." They always say "orchis" or "orchic" which may

13 sound rather flowery to the etymologically impaired--thymus,

14 adrenal, heart, lymph node, prostate, spleen and pituitary.

15 There are actually seventeen organs in that particular

16 product.

17 There is another product that is called Brain

18 Nutrition that tells us that it is vitamins and minerals

19 essential for important brain function. It does not mention

20 that there is any glandulars on at least the bold print. 21 But if you look at the small print on the back, we learn

22 that it has brain extract and pituitary extract, raw, in

23 there.

24 We know that many of the organs that can be found

25 in the dietary supplements do fall in that list of organs

232

1 that are suspect for contamination with TSEs, the labels, in 2 nearly all cases, identify neither the animal source nor the 3 geographic location from which the organs were derived. I 4 have seen one line that did specify from New Zealand cattle 5 but no other manufacturer will list either the species or 6 the geographic location. 7 The FDA's and the USDA's import alerts that we 8 just learned about prohibit the use of these organs in 9 foods, medicines and medical devices. But my reading of the

10 alert, 17-04, suggests that DSHEA does allow some loopholes

11 for these tissues to possible slip in.

12 I will just read from 17-04 that we heard. On the

13 first page, it says that, "This alert does not establish any

14 obligations on regulated entities." I love seeing

15 legislation that starts out with that caveat.

16 Then it says, further, "The USDA regulations do

17 not apply to bovine-derived materials intended for human

18 consumption as finished dietary supplements." We also learn

19 that the prohibition, or the import alert, is limited to

20 bulk lots of these tissues, completed tissues, from BSE-

21 derived countries. It does not mention if it is not a bulk

22 import or if it is raw materials rather than finished

23 materials.

24 Further, we know that it is strongly recommended

25 but not actually prohibited in the language here. So I have

233

1 not taken the assurances from that import alert that Dr. 2 Moore was trying to convey to us. 3 So, in sum, dietary supplements sold in the United 4 States often contain ruminant tissues from undisclosed 5 sources. Personally, I am rather squeamish and I don't 6 think I would be eating prostate or testicle or pituitary, 7 but I am also a little bit wary of consuming products with 8 those glands, not just out of personal repugnance but simply 9 out of a health concern.

10 So my question to the advisory committee is this;

11 is my caution reasonable and, if it is, should we take

12 further efforts to inform, or even protect, the American

13 public from such exposure.

14 I was curious about Dr. Moore's remarks. I sensed

15 two messages. One was the initial reassurance that FDA has

16 the regulatory authority but then I also learned that it is

17 the manufacturer's responsibility to provide those 18 assurances, that the FDA doesn't actually inspect.

19 I think that the FDA commissioners from Harvey

20 Wylie to David Kessler would say that that track record has

21 proven itself.

22 Thank you very much.

23 [Applause.]

24 DR. BROWN: Thanks, Dr. Norton. 25 Committee Discussion snip...

17 But I think that we could exhibit some quite 18 reasonable concern about blood donors who are taking dietary 19 supplements that contain a certain amount of unspecified- 20 origin brain, brain-related, brain and pituitary material. 21 If they have done this for more than a sniff or something 22 like that, then, perhaps, they should be deferred as blood 23 donors. 24 That is probably worse than spending six months in 25 the U.K. 1/19/01 3681t2.rtf(845) page 501 www.fda.gov/ohrms/dockets/ac/cber01.htm

Advisory Committees: CBER 2001 Meeting Documents

see actual paper;

web.archive.org/web/20110616...ov/ohrms/dockets/ac/01/transcripts/3681t2.rtf

www.fda.gov/ohrms/dockets/dailys/03/Mar03/031403/96N-0417-EC-2.htm

www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_07.pdf

-------- Original Message --------

Subject: METABOLIFE AND TSEs GAO-03-494 ''URGENT DATA''

Date: Thu, 01 May 2003 11:23:01 -0500

From: "Terry S. Singeltary Sr."

To: NelliganJ at gao.gov

The General Accounting Office (GAO) today released the following reports and testimonies:

REPORTS

1. Dietary Supplements: Review of Health-Related Call Records for Users of Metabolife 356. GAO-03-494, March 31.

www.gao.gov/cgi-bin/getrpt?GAO-03-494

www.gao.gov/highlights/d03494high.pdf

see updated url link;

web.archive.org/web/20050205084229/http://www.gao.gov/highlights/d03494high.pdf

GREETINGS GAO:

i was surprised that i did not see any listing of bovine tissue in metabolife on it's label. have they ceased using these desiccated tissues???

i see that the lable on this product METABOLIFE 356, does not state that it has any tissues of desiccated bovine organs? i no the product use to, so i am curious if they have ceased the use of the tissues of cattle they use to use (see below)

METABOLIFE 356 BOVINE COMPLEX/GLANDULAR SYSTEM OVARIES, PROSTATE, SCROTUM AND ADRENAL USDA SOURCE CATTLE

i tried warning them years ago of this potential threat of CJD/TSEs;

From: Randy Smith To: "'flounder at wt.net'" Subject: Metabolife Date: Mon, 7 Dec 1998 14:21:35 -0800

Dear Sir,

We are looking at reformulation. I agree that slow virus diseases present a problem in some areas of the world.

Our product uses healthy USDA inspected cattle for the glandular extract.

If you have any links to more information on this subject I would like to examine them.

Thank you for your interest and concern,

Dr. Smith ============

snip...

see full text links of this archived information ;

chronic-wasting-disease.blogspot.com/2009/03/chronic-wasting-disease-prions-in-elk.html

chronic-wasting-disease.blogspot.com/2023/05/ohio-division-of-wildlife-confirms.html

prpsc.proboards.com/thread/124/additional-cases-marion-wyandot-counties

with that, there is abundance of other scientific studies that show it's very likely CWD will or already has, transmit to humans, it's just that no one wants to believe it, they simply don't want it to happen, neither do i, but in the real world, imo, it's already happened and is being masked as sporadic CJD imo, you can see this science archived here, skroll down to about the halfway point of this blog on the recent cases of cwd in Texas;

see about half way down to;

***> PRION CONFERENCE 2022 ABSTRACTS CWD TSE PrP ZOONOSIS

chronic-wasting-disease.blogspot.com/2023/05/texas-cwd-now-confirmed-505-cervid-101.html

sad...terry

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

www.ncbi.nlm.nih.gov/pmc/articles/PMC5019500/

***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.

***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

PRION 2016 TOKYO

Saturday, April 23, 2016

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.

These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

Title: Transmission of scrapie prions to primate after an extended silent incubation period)

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.

www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160

efsaopinioncwd.blogspot.com/2022/04/efsa-eu-request-for-scientific-opinion.html

Terry S. Singeltary Sr.