Chronic Wasting Disease: April 2023

TEXAS REPUBLICAN SB 1372 TAXPAYERS TO PAY FOR GAME FARMS CWD DEPOPULATION?

SB 1372

A BILL TO BE ENTITLED

AN ACT relating to costs associated with the destruction of certain deer.

BE IT ENACTED BY THE LEGISLATURE OF THE STATE OF TEXAS:

SECTION 1. Section 43.955, Parks and Wildlife Code, is amended to read as follows:

Sec. 43.955. COST OF ASSESSMENT AND DESTRUCTION OF DEER [RECOVERY]. (a) The applicable permit holder shall pay all costs associated with:

(1) an epidemiological assessment conducted under this subchapter to the animal health commission; and

(2) except as provided by Subsection (b), the destruction of deer under this subchapter to the department.

(b) Except as provided by Subsection (c), the department shall waive the costs associated with the destruction under this subchapter of breeder deer at a facility covered by a permit issued under Subchapter L where a breeder deer has tested positive for chronic wasting disease in a test performed by a testing laboratory accredited by the Animal and Plant Health Inspection Service of the United States Department of Agriculture.

(c) The department may not waive costs under Subsection (b) if the department determines that the permit holder or an agent of the permit holder, in violation of this chapter or a regulation of the commission, caused:

(1) the introduction of chronic wasting disease into the facility; or

(2) a delay in the detection of chronic wasting disease at the facility.

SECTION 2. Section 43.955, Parks and Wildlife Code, as amended by this Act, applies only to the payment of costs arising from the destruction of deer commenced on or after the effective date of this Act.

SECTION 3. This Act takes effect immediately if it receives a vote of two-thirds of all the members elected to each house, as provided by Section 39, Article III, Texas Constitution. If this Act does not receive the vote necessary for immediate effect, this Act takes effect September 1, 2023.

https://legiscan.com/TX/text/SB1372/2023

That can mean the killing of hundreds of expensive animals, and the financial ruin of their rancher.

snip...

In order to become law, the CWD bill still has to pass the House chamber with a majority vote and then be signed by Gov. Greg Abbott. The chair of the House committee that most recently approved the bill, Rep. Trent Ashby, said in an emailed statement that he was pleased to see the bill making its way through the legislature.

TEXAS REPUBLICAN SB 1372 TAXPAYERS TO PAY FOR CWD TSE PRION DEPOPULATION OF GAME FARMSg Abbott. The chair of the House committee that most recently approved the bill, Rep. Trent Ashby, said in an emailed statement that he was pleased to see the bill making its way through the legislature.

https://www.star-telegram.com/news/state/texas/article274737181.html

SO, the taxpayers will have the burden of paying for deer breeders cost of depopulation of their CWD deer herd?...that's crazy, and everyone should write Governor Abbott and tell him...taxpayers should not have to pay for game farms cwd depopulation...IMO...terry

what's Governor Abbott history with supporting deer farms?

Governor Abbott on HOW TO LEGISLATE SPREADING CWD TO HELL AND BACK IN TEXAS $$$

i picked up on something that was said, there were several folks complaining that the breeders were getting picked on, and someone said something about trying to 'legislate' there way out of this. folks, this is terrible, i have seen this in other states, and it just spreads cwd even more. hell, it happened right here in Texas in the early days, that's why we are where were at now, you cannot let a bunch of Austin Legislative Socialites regulate CWD, just look what happened in Wisconsin. but i bet this attempted swaying of regulatory power shift from TPWD et al to the Texas Legislature in Austin is happening as we speak. we can't let this happen...

SUNDAY, JANUARY 22, 2017

Texas 85th Legislative Session 2017 Chronic Wasting Disease CWD TSE Prion Cervid Captive Breeder Industry

http://chronic-wasting-disease.blogspot.com/2017/01/texas-85th-legislative-session-2017.html

FRIDAY, JANUARY 27, 2017

TEXAS, Politicians, TAHC, TPWD, and the spread of CWD TSE Prion in Texas

http://chronic-wasting-disease.blogspot.com/2017/01/texas-politicians-tahc-tpwd-and-spread.html

SUNDAY, MAY 14, 2017

85th Legislative Session 2017 AND THE TEXAS TWO STEP Chronic Wasting Disease CWD TSE Prion, and paying to play $$$

http://chronic-wasting-disease.blogspot.com/2017/05/85th-legislative-session-2017-and-texas.html

Powerful Abbott appointee's lobbying sparks blowback in Legislature

In an ironic twist for Gov. Greg Abbott, who has made ethics reform an urgent political priority, the Texas House is taking aim at what critics call a "pay to play" culture among his appointees.

BY JAY ROOT MAY 12, 2017 12 AM

Houston billionaire Dan Friedkin is chairman of the Texas Parks and Wildlife Commission.

Texas Parks and Wildlife Commission

When Gov. Greg Abbott tapped one of his top campaign donors to become chairman of the Texas Parks and Wildlife Commission, he didn’t get a part-time appointee who would merely draft rules and implement conservation laws passed by the Legislature.

In Dan Friedkin, the governor got a Houston billionaire — with a team of privately funded lobbyists — willing to use his influence to ensure his wildlife interests are taken into account by the Legislature before they pass those laws, interviews and records show.

On the receiving end of that influence, and not in a happy way, is state Rep. Chris Paddie, R-Marshall. Paddie said a lobbyist working for Friedkin’s business empire, which includes a massive South Texas hunting ranch, has been working against his deer breeder management bill, which many large ranchers oppose. The state Parks and Wildlife Department oversees deer breeding regulations in Texas.

“Many times these appointees are well-heeled, very influential people,” Paddie said. “Overall, I feel that it’s inappropriate for an appointee of a board or commission to have personal lobbyists lobbying on issues related to that board or commission.”

Under Texas law, state agencies are barred from lobbying the Legislature. But the powerful people who oversee them aren’t.

If Paddie and dozens of his colleagues get their way, that practice soon will be a Class A misdemeanor.

Last weekend, Paddie attached a ban on appointee lobbying — which would apply to any issues intersecting with their state responsibilities — to an ethics bill that already had powerful friends of the governor in its crosshairs. The provision was adopted unanimously and the bill sailed out of the Texas House on a 91-48 vote Saturday.

The ethics bill, authored by Rep. Lyle Larson, R-San Antonio, would bar big campaign donors from getting appointed by governors in the first place. Anyone who contributed over $2,500 would be barred from serving on state boards and commissions.

Larson pointed to news articles documenting the amount of campaign money appointees have collectively given governors. Last year the San Antonio Express-News calculated that Abbott had received nearly $9 million from people he’s picked for appointed office; before that, a widely cited report from Texans for Public Justice found former Gov. Rick Perry had received $17 million from his own appointees.

Larson said 20 years from now, Texans will be reading the same stories about a future governor unless the Legislature does something about it now.

“We’ve read that article for the last three decades,” Larson said during a brief floor speech. “This is your opportunity to say, 'We need to stop this.' The most egregious ethics violation we’ve got in the state is the pay to play in the governor’s office.”

A prodigious fundraiser, Abbott has put plenty of big donors on prestigious boards and commissions. On the Parks and Wildlife Commission alone, he has installed three mega-donors — pipeline mogul Kelcy Warren, who’s given Abbott more than $800,000 over his statewide political career; Houston businessman S. Reed Morian, who has given $600,000; and Friedkin, who personally donated more than $700,000 — while his Gulf States Toyota PAC gave Abbott another $100,000, according to Ethics Commission records.

Passage of Larson’s HB 3305 represents an ironic twist for Abbott, who for the second session in a row has made ethics reform an urgent political priority — resulting in a bill that's now taking aim at his gubernatorial appointments. Abbott, who has made a habit of ignoring tough questions, hasn't made any public statements about the bill, and his office did not respond to multiple requests for comment.

Friedkin — whose wealth is estimated at $3.4 billion by Forbes — is the owner and CEO of Gulf States Toyota, founded in 1969, which has had the exclusive rights to distribute new Toyotas in Texas and four nearby states. He’d also been a mega-donor to former Gov. Rick Perry, who first appointed Friedkin to the Parks and Wildlife Commission in 2005. Abbott made Friedkin chairman of the commission in 2015.

Requests for comment from Friedkin's office went unanswered.

In addition to his public role as parks and wildlife chairman, a perch that gives him significant influence over deer management issues, Friedkin has private wildlife interests. He owns the sprawling Comanche Ranch in South Texas, according to published news accounts.

The January 2014 edition of Texas Wildlife, published by the Texas Wildlife Association, described Friedkin’s Comanche Ranch as “privately owned and privately hunted” and said it’s “in the business to produce as many trophy bucks as possible, without damaging the native habitat.”

The association, which advocates for private landowners and hunting rights, has locked horns with deer breeding interests at Parks and Wildlife and the Capitol. They compete against each other in the lucrative trophy deer hunting market — and the battle between them perennially spills into the rule-making process at the Parks and Wildlife Commission.

One of their battles centers on how captive deer are tagged so that game wardens and others can distinguish them from native deer. Current law requires a combination of tags and tattoos, and the ranchers and large landowners want to keep it that way. The breeders, meanwhile, favor tagging deer with microchips, which they contend are more accurate and foolproof.

The Wildlife Association said in a Facebook post that removing visible tag or tattoo requirements and allowing microchip tracking “creates real biosecurity risks and blurs ethical lines in the hunting community, as captive deer breeders are allowed to transport and release these animals to be co-mingled with pasture-born deer.” Proponents of the current system say tough rules on breeders are needed to keep out imported deer that may carry Chronic Wasting Disease, which has been found in Texas.

On the other side of the issue is the Texas Deer Association, which represents breeder interests. Executive Director Patrick Tarlton said opposition to his $1.6 billion industry stems less from environmental and health concerns and more from wealthy ranch owners who want to boost profits from trophy-seeking hunters. He notes that Chronic Wasting Disease has been found in both free range and captive deer.

Paddie sided with the breeders by filing House Bill 2855, which would allow breeders to track their deer with microchips instead of relying on physical tags that they say can be torn off.

No one identifying themselves as a Friedkin corporate lobbyist opposed the deer breeding bills during public hearings, according to House and Senate committee records published online.

Behind the scenes, it was a different story.

Paddie said his chief of staff reached out to Laird Doran, one of several lobbyists for Friedkin’s Gulf States Toyota, after hearing that he was trying to convince other legislators to help defeat Paddie's deer microchip bill.

“My chief called him and said, 'Hey, if you’ve got a problem with our bill why aren’t you talking to us?’ ” Paddie said. “He said he represented the Friedkin Group when that happened.”

According to an email from an aide to Sen. Craig Estes, R-Wichita Falls, who is carrying the deer breeding bill in the Senate, Doran also identified himself as a representative of the “Friedkin Group.” That’s the name of the consortium that contains Friedkin's Gulf States Toyota, according to the company’s Linked-In page. He told Estes’ aide that the Friedkin group was opposed to any bill that would “remove requirements for (deer) ear tags,” the senator’s office confirmed.

It’s not clear exactly which Friedkin interests Doran was advancing. Doran is registered at the Texas Ethics Commission with a single entity — Gulf States Toyota — and the agency has no record of a lobbyist working for an entity or individual with the name Friedkin in it, the commission confirmed Wednesday afternoon.

However, Doran checked a variety of non-automotive subject areas in which he is lobbying during this legislative session on behalf of Friedkin’s lucrative distributorship, including “animals,” “parks & wildlife,” “state agencies, boards & commissions,” “environment” and more, his detailed lobby disclosures show.

Doran, director of government relations and senior counsel at the Friedkin Group, did not return phone and email messages left by The Texas Tribune.

Estes said he didn’t have a problem with a governor's appointee engaging in lobbying on issues that affected their private interests, as long as they keep that separate from their state roles.

“I don’t think they should be barred from expressing their views as long as they’re careful to say these are my views, not the views of the agency I’m representing,” Estes said.

But Tarlton, the deer association director, said Friedkin’s use of lobbyists to oppose deer breeders in the Legislature gives the breeders' opponents a huge advantage.

“I think that if the commissioner of Texas Parks and Wildlife is actively lobbying against an industry which his department directly oversees, it absolutely sets up an unfair and closed system of government,” Tarlton said. “The commission is supposed to be the unbiased and equitable oversight for everything wildlife.”

Paddie hopes his amendment to Larsen's ethics bill will even the playing field. He referred to the wealthy Parks and Wildlife chairman (see the 2:29:00 mark in this recorded exchange) when he tacked the appointee-lobbying provision onto Larson’s bill.

Paddie said he’s not singling out anyone. He said it would apply to other powerful gubernatorial appointees in a position to do the same.

“I could have named any number of examples as far as the agencies in particular,” Paddie said. “I want to stop it if anyone serving on any agency is doing this.”

Ryan Murphy contributed to this report.

Disclosure: The Texas Wildlife Association, Texas Parks and Wildlife Department and Gulf States Toyota have been financial supporters of The Texas Tribune. A complete list of Tribune donors and sponsors is available here.

https://www.texastribune.org/2017/05/12/powerful-abbott-appointees-lobbying-sparks-blowback-legislature/

TUESDAY, AUGUST 02, 2016

TEXAS TPWD Sets Public Hearings on Deer Movement Rule Proposals in Areas with CWD Rule Terry S. Singeltary Sr. comment submission

http://chronic-wasting-disease.blogspot.com/2016/08/texas-tpwd-sets-public-hearings-on-deer.html

SUNDAY, MAY 22, 2016

TEXAS CWD DEER BREEDERS PLEA TO GOVERNOR ABBOTT TO CIRCUMVENT TPWD SOUND SCIENCE TO LET DISEASE SPREAD

http://chronic-wasting-disease.blogspot.com/2016/05/texas-cwd-deer-breeders-plea-to.html

Wednesday, May 04, 2016

TPWD proposes the repeal of §§65.90 -65.94 and new §§65.90 -65.99 Concerning Chronic Wasting Disease - Movement of Deer Singeltary Comment Submission

http://chronic-wasting-disease.blogspot.com/2016/05/tpwd-proposes-repeal-of-6590-6594-and_4.html

Terry S. Singeltary Sr.

Your opinions and comments have been submitted successfully. Thank you for participating in the TPWD regulatory process.

Wednesday, October 28, 2015

Interim Chronic Wasting Disease Response Rules Comment online through 07:00 a.m. November 5, 2015

http://chronic-wasting-disease.blogspot.com/2015/10/interim-chronic-wasting-disease.html

SUNDAY, AUGUST 23, 2015

Subject: Chronic Wasting Disease CWD TSE Prion and how to put lipstick on a pig and take her to the dance in Texas

I was listening to a radio show the other day here in the Galveston bay area, and outdoor show, they had a breeder or someone from the industry on, and I was amazed at the false information he was spewing. the part about the poor little girl with her pet deer crying in the breeder pen, ......

cry me a friggen river, they are raising the damn deer to put in a pen to slaughter, or to breed for that purpose, AND you ought to see a human die from this shit. my mother did everything Linda Blair did in that movie the exorcist except spin her head 360 degrees. she DID levitate in bed because she would jerk so bad, where it took three grown strong adults to hold her down to keep her from hurting herself, all the while screaming God why can’t I stop this. so cry me a fucking river on a damn deer they are raising to have slaughtered, but whine because the TPWD et al are going to kill it to try and prevent the spread of disease cwd. if the TPWD et al had a better way of confirming or not whether those cervid had CWD, they would do it. the live tests they have to date do not work 100%, so there for they have not been validated. oh that’s fine with the pen owners, but it’s not fine for Texas. you don’t want a cwd test that just works part of the time. it’s total ignorance out there now, and they will put lipstick on this pig and take her to the dance, just like TAHC did with mad cow disease, and that’s well documented. they will change what ever law to meet their needs$$$ I will agree with this much of what the industry said this morning, that cwd has been in Texas for a long time, and in the pens to, and that the TAHC has not tested enough, that much he got correct. I have been saying this year, after year, after year, since back to 2001, to the TAHC, and told them exactly where they should be testing back in 2001, and then year after year after year, up and until 2012, where they finally did test there in enough numbers to find it a decade later, exactly where I been saying it was. the cwd deer have been waltzing across Texas from there for over a decade. it does not matter if I am pro-pen or not. that will not and does not change the science. why in the hell did they speak about the 4 confirmed deer from that index herd, yes, I said 4 now. why is not the TAHC TPWD telling that to the public now. why did not that guy today speak of 4? all the newspapers are reporting it, and I ask about the 4th case weeks and weeks ago? where is that information at on TAHC site? I am a meat eater, I am pro-hunt, and extremely pro-gun, I am however anti-stupid and anti-prion, prions can kill you, I don’t want to eat prions, you should not either. but here is the kicker, you eat meat infected with CWD TSE prion, your exposed, however you never go clinical in your life........BBBUT, your exposed and if you go on to have surgical, dental, tissue, blood donations, etc. you risk exposing my family and others...I will simply post this one short abstract of an old study the late great Dr. Gibbs...

http://chronic-wasting-disease.blogspot.com/2015/08/tahc-chronic-wasting-disease-cwd-tse.html

Texas 84th Legislative Session Sunday, December 14, 2014

*** TEXAS 84th Legislature commencing this January, deer breeders are expected to advocate for bills that will seek to further deregulate their industry

http://chronic-wasting-disease.blogspot.com/2014/12/texas-84th-legislature-commencing-this.html

TUESDAY, DECEMBER 16, 2014

Texas 84th Legislature 2015 H.R. No. 2597 Kuempel Deer Breeding Industry TAHC TPWD CWD TSE PRION

http://chronic-wasting-disease.blogspot.com/2014/12/texas-84th-legislature-2015-hr-no-2597.html

expand this to see all breeder cwd, and then think of what they have released at release sites... https://tpwd.texas.gov/huntwild/wild/diseases/cwd/tracking/

“Regrettably, the gravity of this situation continues to mount with these new CWD positive discoveries, as well as with the full understanding of just how many other facilities and release sites across Texas were connected to the CWD positive sites in Uvalde and Hunt Counties,” said Carter Smith, Executive Director of TPWD.

https://tpwd.texas.gov/huntwild/wild/diseases/cwd/tracking/

TAHC Chapter 40, Chronic Wasting Disease Terry Singeltary Comment Submission

https://chronic-wasting-disease.blogspot.com/2021/08/tahc-chapter-40-chronic-wasting-disease.html

***> TEXAS HISTORY OF CWD <***

Singeltary telling TAHC, that CWD was waltzing into Texas from WSMR around Trans Pecos region, starting around 2001, 2002, and every year, there after, until New Mexico finally shamed TAHC et al to test where i had been telling them to test for a decade. 2012 cwd was detected first right there where i had been trying to tell TAHC for 10 years.

***> Singeltary on Texas Chronic Wasting Disease CWD TSE Prion History <***

http://chronic-wasting-disease.blogspot.com/2017/08/texas-chronic-wasting-disease-cwd-tse.html

Control of Chronic Wasting Disease OMB Control Number: 0579-0189 APHIS-2021-0004 Singeltary Submission

Greetings APHIS et al, i would kindly like to comment on Control of Chronic Wasting Disease OMB Control Number: 0579-0189 APHIS-2021-0004.

***> 1st and foremost your biggest problem is 'VOLUNTARY'! AS with the BSE 589.2001 FEED REGULATIONS, especially since it is still voluntary with cervid, knowing full well that cwd and scrapie will transmit to pigs by oral route. VOLUNTARY DOES NOT WORK! all animal products should be banned and be made mandatory, and the herd certification program should be mandatory, or you don't move cervid. IF THE CWD HERD CERTIFICATION IS NOT MANDATORY, it will be another colossal tse prion failure from the start.

***> 2nd USA should declare a Declaration of Extraordinary Emergency due to CWD, and all exports of cervid and cervid products must be stopped internationally, and there should be a ban of interstate movement of cervid, until a live cwd test is available.

***> 3rd Captive Farmed cervid ESCAPEES should be made mandatory to report immediately, and strict regulations for those suspect cwd deer that just happen to disappear. IF a cervid escapes and is not found, that farm should be indefinitely shut down, all movement, until aid MIA cervid is found, and if not ever found, that farm shut down permanently.

***> 4th Captive Farmed Cervid, INDEMNITY, NO MORE Federal indemnity program, or what i call, ENTITLEMENT PROGRAM for game farm industry. NO MORE BAIL OUTS FROM TAX PAYERS. if the captive industry can't buy insurance to protect not only themselves, but also their customers, and especially the STATE, from Chronic Wasting Disease CWD TSE Prion or what some call mad deer disease and harm therefrom, IF they can't afford to buy that insurance that will cover all of it, then they DO NOT GET A PERMIT to have a game farm for anything. This CWD TSE Prion can/could/has caused property values to fall from some reports in some places. roll the dice, how much is a state willing to lose?

***> 5th QUARANTINE OF ALL FARMED CAPTIVE, BREEDERS, URINE, ANTLER, VELVET, SPERM, OR ANY FACILITY, AND THEIR PRODUCTS, that has been confirmed to have Chronic Wasting Disease CWD TSE Prion, the QUARANTINE should be for 21 years due to science showing what scrapie can do. 5 years is NOT near long enough. see; Infectious agent of sheep scrapie may persist in the environment for at least 16 to 21 years.

***> 6th America BSE 589.2001 FEED REGULATIONS CWD TSE Prion

***> 7TH TRUCKING TRANSPORTING CERVID CHRONIC WASTING DISEASE TSE PRION VIOLATING THE LACEY ACT

***> 8TH ALL CAPTIVE FARMING CERVID OPERATIONS MUST BE INSURED TO PAY FOR ANY CLEAN UP OF CWD AND QUARANTINE THERE FROM FOR THE STATE, NO MORE ENTITLEMENT PROGRAM FOR CERVID GAME FARMING PAY TO PLAY FOR CWD TSE PRION OFF THE TAX PAYERS BACK.

***> 9TH ANY STATE WITH DOCUMENTED CWD, INTERSTATE, NATIONAL, AND INTERNATIONAL MOVEMENT OF ALL CERVID, AND ALL CERVID PRODUCTS MUST BE HALTED!

***> 10TH BAN THE SALE OF STRAW BRED BUCKS AND ALL CERVID SEMEN AND URINE PRODUCTS

***> 11th ALL CAPTIVE FARMED CERVID AND THEIR PRODUCTS MUST BE CWD TSE PRION TESTED ANNUALLY AND BEFORE SALE FOR CWD TSE PRION

SEE FULL SCIENCE REFERENCES AND REASONINGS ;

***> 1st and foremost your biggest problem is 'VOLUNTARY'!

''APHIS created a cooperative, voluntary Federal-State-private sector CWD Herd Certification Program designed to identify farmed or captive herds infected with CWD.''

key word failure is 'voluntary'.

WE know for a fact now that voluntary does NOT WORK!

AS with the BSE 589.2001 FEED REGULATIONS (see , another colossal failure, and proven to be a sham, especially since it is still voluntary with cervid, knowing full well that cwd and scrapie will transmit to pigs by oral route. VOLUNTARY DOES NOT WORK! all animal products should be banned and be made mandatory, and the herd certification program should be mandatory, or you don't move cervid. IF THE CWD HERD CERTIFICATION IS NOT MANDATORY, it will be another colossal tse prion failure from the start.

Control of Chronic Wasting Disease OMB Control Number: 0579-0189 APHIS-2021-0004 Singeltary Submission

https://www.regulations.gov/comment/APHIS-2021-0004-0002

https://downloads.regulations.gov/APHIS-2021-0004-0002/attachment_1.pdf

Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification

https://www.regulations.gov/document/APHIS-2018-0011-0003

https://downloads.regulations.gov/APHIS-2018-0011-0003/attachment_1.pdf

TUESDAY, APRIL 11, 2023

Texas TAHC Chronic Wasting Disease Discovered in Deer Breeding Facilities in Frio and Hamilton Counties

https://chronic-wasting-disease.blogspot.com/2023/04/texas-tahc-chronic-wasting-disease.html

TUESDAY, MARCH 21, 2023

Texas CWD seven new cases three separate deer-breeding facilities in Zavala, Washington and Gonzales counties 471 confirmed to date

https://chronic-wasting-disease.blogspot.com/2023/03/texas-cwd-seven-new-cases-three.html

TEXAS CWD TRACKER HAS NOT BEEN UPDATED IN SOME TIME NOW. TEXAS CWD TOTALS ARE AROUND 473 TO DATE. SEE CWD POSITIVIES TO DATE;

449 Pending Breeder Deer Hunt Facility #9 White-tailed Deer F 2.5

448 Pending Breeder Deer Hunt Facility #9 White-tailed Deer M 2.5

447 Pending Breeder Deer Hunt Facility #9 White-tailed Deer M 2.6

446 Pending Breeder Deer Hunt Facility #9 White-tailed Deer F 2.5

445 2023-01-03 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.4

444 2022-12-30 Breeder Release Site Uvalde Facility #3 White-tailed Deer Unknown Unknown

443 2022-12-30 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.5

442 2023-01-03 Free Range Hartley N/A Mule Deer M 5.5

441 2023-01-03 Free Range Hartley N/A Mule Deer M 4.5

440 2023-01-03 Free Range Dallam N/A Mule Deer M 1.5

439 2023-01-03 Free Range Hartley N/A Mule Deer M 4.5

438 2023-01-03 Free Range Hartley N/A Mule Deer M 4.5

437 2023-01-03 Free Range Hartley N/A Mule Deer M 4.5

436 2023-01-03 Free Range Hartley N/A Mule Deer M 4.5

435 2022-12-22 Breeder Deer Hunt Facility #9 White-tailed Deer M 4.5

434 2022-12-22 Breeder Deer Hunt Facility #9 White-tailed Deer F 4.5

433 2022-12-22 Breeder Deer Hunt Facility #9 White-tailed Deer M 4.5

432 2022-12-30 Free Range Medina N/A White-tailed Deer M 4.5

431 2022-12-09 Free Range Medina N/A White-tailed Deer M 4.5

430 2022-12-15 Breeder Release Site Uvalde Facility #3 White-tailed Deer Unknown 5.5

429 2022-12-15 Breeder Release Site Uvalde Facility #3 White-tailed Deer Unknown 5.5

428 2022-12-15 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.4

427 2022-12-15 Breeder Deer Gillespie Facility #14 White-tailed Deer F 6.4

426 2022-12-15 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.4

425 2022-12-15 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.5

424 2022-12-15 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.5

423 2022-12-16 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.5

422 2022-12-15 Breeder Release Site Uvalde Facility #3 White-tailed Deer Unknown 5.0

421 2022-12-16 Breeder Release Site Uvalde Facility #3 White-tailed Deer Unknown 6.0

420 2022-12-15 Breeder Release Site Medina N/A White-tailed Deer F 6.5

419 2022-11-29 Free Range El Paso N/A Mule Deer F 3.5

418 2022-11-29 Breeder Deer Hunt Facility #9 White-tailed Deer M 1.2

417 2022-11-17 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.3

416 2022-11-17 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.4

415 2022-11-07 Breeder Deer Hunt Facility #9 White-tailed Deer F 4.5

414 2022-12-16 Breeder Deer Hunt Facility #9 White-tailed Deer F 4.5

413 2022-11-17 Breeder Deer Hunt Facility #9 White-tailed Deer F 2.4

412 2022-11-17 Breeder Deer Hunt Facility #9 White-tailed Deer F 2.3

411 2022-11-17 Breeder Deer Hunt Facility #9 White-tailed Deer F 4.4

410 2022-11-11 Breeder Release Site Kaufman Facility #9 White-tailed Deer M 4.5

409 2022-11-16 Breeder Release Site Medina Facility #3 Elk M 7.0

408 2022-10-31 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.3

407 2022-10-31 Breeder Deer Hunt Facility #9 White-tailed Deer F 2.4

406 2022-10-31 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.4

405 2022-10-31 Breeder Deer Hunt Facility #9 White-tailed Deer F 2.3

404 2022-10-31 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.1

403 2022-10-21 Free Range El Paso N/A Mule Deer M 7.5

402 2022-10-28 Breeder Deer Hunt Facility #9 White-tailed Deer M 1.2

401 2022-10-28 Breeder Deer Hunt Facility #9 White-tailed Deer F 3.3

400 2022-10-28 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.3

399 2022-10-13 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.3

398 2022-10-13 Breeder Deer Hunt Facility #9 White-tailed Deer F 4.2

397 2022-10-13 Breeder Deer Hunt Facility #9 White-tailed Deer F 2.3

396 2022-10-13 Breeder Deer Hunt Facility #9 White-tailed Deer M 1.2

395 2022-10-12 Breeder Deer Limestone Facility #15 White-tailed Deer F 3.3

394 2022-09-30 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.3

393 2022-09-30 Breeder Deer Hunt Facility #9 White-tailed Deer F 2.3

392 2022-09-28 Breeder Deer Hunt Facility #9 White-tailed Deer F 2.2

391 2022-09-20 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.2

390 2022-09-20 Breeder Deer Hunt Facility #9 White-tailed Deer F 6.2

389 2022-09-20 Breeder Deer Hunt Facility #9 White-tailed Deer F 4.2

388 2022-09-20 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.3

387 2022-09-20 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.2

386 2022-09-20 Breeder Deer Hunt Facility #9 White-tailed Deer F 2.2

385 2022-09-20 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.2

384 2022-09-20 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.2

383 2022-09-20 Breeder Deer Hunt Facility #9 White-tailed Deer F 2.2

382 2022-09-20 Breeder Deer Gillespie Facility #14 White-tailed Deer M 1.2

381 2022-09-12 Breeder Deer Limestone Facility #15 White-tailed Deer F 3.2

380 2022-09-12 Breeder Deer Limestone Facility #15 White-tailed Deer F 3.2

379 2022-09-13 Breeder Deer Limestone Facility #15 White-tailed Deer F 3.2

378 2022-11-07 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.2

377 2022-09-13 Breeder Deer Limestone Facility #15 White-tailed Deer F 3.2

376 2022-08-30 Breeder Deer Gillespie Facility #14 White-tailed Deer M 1.0

375 2022-08-15 Breeder Deer Hunt Facility #9 White-tailed Deer F 2.2

374 2022-08-30 Free Range Dallam N/A Mule Deer M 5.5

373 2022-08-10 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.1

372 2022-08-30 Free Range El Paso N/A Mule Deer M 2.5

371 2022-07-19 Breeder Deer Hunt Facility #9 White-tailed Deer M 2.1

370 2022-07-19 Breeder Deer Hunt Facility #9 White-tailed Deer M 1.8

369 2022-07-19 Breeder Deer Hunt Facility #9 White-tailed Deer F 3.9

368 2022-06-09 Breeder Deer Duval Facility #13 White-tailed Deer F 1.8

367 2022-05-27 Free Range El Paso N/A Mule Deer M 3.5

366 2022-05-25 Free Range El Paso N/A Mule Deer M 4.5

365 2022-04-21 Breeder Release Site Medina Facility #4 White-tailed Deer M 4.5

364 2022-04-21 Breeder Release Site Medina Facility #4 White-tailed Deer M 4.5

363 2022-04-07 Free Range Hudspeth N/A Mule Deer M 8.5

362 2022-04-07 Free Range El Paso N/A Mule Deer F 4.5

361 2022-02-28 Breeder Deer Hunt Facility #9 White-tailed Deer M 1.9

360 2022-02-18 Breeder Deer Kimble Facility #6 White-tailed Deer Unknown 3.5

359 2022-01-25 Free Range Medina N/A White-tailed Deer F 5.5

358 2022-01-12 Free Range Hartley N/A Mule Deer M 7.5

357 2022-01-12* Free Range Hartley N/A Mule Deer M 5.5

356 2022-01-12 Free Range Hartley N/A Mule Deer M 3.5

355 2022-01-12 Breeder Deer Kimble Facility #6 White-tailed Deer Unknown 5.5

354 2022-01-12 Free Range Hartley N/A Mule Deer F 3.5

353 2022-01-12 Free Range Hartley N/A Mule Deer M 5.5

352 2022-01-12 Free Range Hartley N/A Mule Deer M 4.5

351 2022-01-12 Free Range Hartley N/A Mule Deer M 5.5

350 2022-01-12 Free Range Hartley N/A White-tailed Deer M 3.5

349 2022-01-12 Breeder Release Site Medina Facility #3 Red Deer F 4.5

348 2022-01-12 Breeder Deer Hunt Facility #9 White-tailed Deer F 3.5

347 2022-01-12 Breeder Deer Hunt Facility #9 White-tailed Deer M 1.5

346 2022-01-10 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

345 2022-01-10 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.3

344 2022-01-10 Free Range Medina N/A White-tailed Deer M 4.5

343 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 5.4

342 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

341 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

340 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4

339 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4

338 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4

337 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4

336 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

335 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

334 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

333 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

332 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

331 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

330 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

329 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

328 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

327 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4

326 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

325 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

324 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

323 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 2.4

322 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 3.4

321 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

320 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

319 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

318 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

317 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

316 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

315 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

314 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4

313 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4

312 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4

311 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4

310 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 3.4

309 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 3.4

308 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 3.4

307 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 3.4

306 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4

305 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4

304 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

303 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4

302 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4

301 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4

300 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

299 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

298 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

297 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

296 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

295 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

294 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 5.4

293 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

292 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

291 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4

290 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

289 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

288 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4

287 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

286 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

285 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

284 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

283 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

282 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

281 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

280 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

279 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

278 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

277 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.4

276 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.4

275 2022-01-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.4

274 2022-01-06 Free Range Medina N/A White-tailed Deer M 2.5

273 2021-12-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 3.4

272 2021-12-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 3.4

271 2021-12-13 Free Range El Paso N/A Mule Deer F 4.5

270 2021-12-13 Breeder Deer Duval Facility #13 White-tailed Deer F 4.4

269 2021-12-13 Free Range Medina N/A White-tailed Deer M 3.5

268 2021-10-18 Breeder Deer Medina Facility #4 White-tailed Deer M 4.0

267 2021-10-12 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.1

266 2021-10-12 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.2

265 2021-10-12 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.2

264 2021-10-12 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.2

263 2021-10-12 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.2

262 2021-10-12 Breeder Deer Hunt Facility #9 White-tailed Deer F 8.2

261 2021-10-08 Breeder Deer Duval Facility #13 White-tailed Deer F 3.2

260 2021-10-08 Breeder Deer Medina Facility #4 White-tailed Deer F 2.3

259 2021-09-14 Breeder Deer Medina Facility #4 White-tailed Deer F 6.2

258 2021-07-07 Free Range El Paso N/A Mule Deer F 6.5

257 2021-06-30 Breeder Deer Hunt Facility #9 White-tailed Deer F 2.2

256 2021-06-30 Breeder Deer Hunt Facility #9 White-tailed Deer F 3.2

255 2021-06-30 Breeder Deer Hunt Facility #9 White-tailed Deer F 3.2

254 2021-06-30 Breeder Deer Hunt Facility #9 White-tailed Deer F 3.3

253 2021-06-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 7.9

252 2021-06-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 4.9

251 2021-06-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 3.9

250 2021-06-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 11.0

249 2021-06-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.9

248 2021-06-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 4.9

247 2021-06-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 6.0

246 2021-06-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 3.9

245 2021-06-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 3.9

244 2021-06-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 6.9

243 2021-06-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 11.0

242 2021-06-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 4.9

241 2021-06-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 1.9

240 2021-06-28 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 4.9

239 2021-06-21 Breeder Deer Medina Facility #4 White-tailed Deer M 2.5

238 2021-06-21 Breeder Deer Medina Facility #4 White-tailed Deer M 2.5

237 2021-06-21 Breeder Deer Medina Facility #4 White-tailed Deer M 5.5

236 2021-06-21 Breeder Deer Medina Facility #4 White-tailed Deer M 5.5

235 2021-06-21 Breeder Deer Medina Facility #4 White-tailed Deer F 9.5

234 2021-06-16 Breeder Deer Medina Facility #4 White-tailed Deer M 2.0

233 2021-06-16 Breeder Deer Medina Facility #4 White-tailed Deer F 6.0

232 2021-06-16 Breeder Deer Medina Facility #4 White-tailed Deer F 6.0

231 2021-06-16 Breeder Deer Medina Facility #4 White-tailed Deer F 9.9

230 2021-06-16 Breeder Deer Medina Facility #4 White-tailed Deer M 1.0

229 2021-06-16 Breeder Deer Medina Facility #4 White-tailed Deer M 8.0

228 2021-06-16 Breeder Deer Medina Facility #4 White-tailed Deer M 2.0

227 2021-06-16 Breeder Deer Medina Facility #4 White-tailed Deer F 12.0

226 2021-06-16 Breeder Deer Medina Facility #4 White-tailed Deer F 1.0

225 2021-06-15 Breeder Deer Uvalde Facility #12 White-tailed Deer M 3.9

224 2021-06-07 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 7.7

223 2021-05-13 Free Range El Paso N/A Mule Deer F 4.5

222 2021-04-27 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.6

221 2021-04-27 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.6

220 2021-04-27 Breeder Deer Mason Facility #11 White-tailed Deer M 2.8

219 2021-04-20 Breeder Deer Matagorda Facility #10 White-tailed Deer F 1.8

218 2021-03-29 Breeder Deer Hunt Facility #9 White-tailed Deer F 2.7

217 2021-03-29 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 3.4

216 2021-03-29 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.2

215 2021-03-29 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer F 3.5

214 2021-03-29 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 2.5

213 2021-03-29 Breeder Deer Uvalde Facilities #7 & 8 White-tailed Deer M 1.5

212 2021-03-25 Free Range El Paso N/A Mule Deer M 7.5

211 2021-02-26 Free Range Lubbock N/A Mule Deer M 8.5

210 2021-02-26 Free Range Hudspeth N/A Mule Deer M 6.5

209 2021-02-26 Free Range Hudspeth N/A Mule Deer M 6.5

208 2021-01-08 Breeder Release Site Medina Facility #3 Elk M Unknown

207 2021-01-07 Free Range Medina N/A White-tailed Deer M 4.5

206 2021-01-05 Free Range Hudspeth N/A Mule Deer M 6.5

205 2021-01-05 Breeder Release Site Medina N/A White-tailed Deer M 6.5

204 2020-12-22 Free Range Dallam N/A Mule Deer F 2.5

203 2020-12-22 Free Range Hudspeth N/A Mule Deer M 3.5

202 2020-12-22 Free Range Hartley N/A White-tailed Deer M 3.5

201 2020-12-22 Free Range Dallam N/A Mule Deer M 3.5

200 2020-12-11 Free Range Medina N/A White-tailed Deer M 3.5

199 2020-12-11 Free Range Medina N/A White-tailed Deer M 3.5

198 2020-11-19 Free Range El Paso N/A Mule Deer M 5.5

197 2020-11-19 Free Range Hudspeth N/A Mule Deer M 3.5

196 2020-11-19 Free Range Hartley N/A Mule Deer M 3.5

195 2020-11-03 Breeder Release Site Medina Facility #3 Red Deer F 4.0

194 2020-09-23 Free Range Val Verde N/A White-tailed Deer F 2.5

193 2020-08-17 Breeder Deer Kimble Facility #6 White-tailed Deer M 1.0

192 2020-08-17 Breeder Deer Kimble Facility #6 White-tailed Deer F 4.0

191 2020-08-17 Breeder Deer Kimble Facility #6 White-tailed Deer F 6.0

190 2020-08-17 Breeder Deer Kimble Facility #6 White-tailed Deer F 1.0

189 2020-08-17 Breeder Deer Kimble Facility #6 White-tailed Deer M 1.0

188 2020-08-17 Breeder Deer Kimble Facility #6 White-tailed Deer M 1.0

187 2020-08-17 Breeder Deer Kimble Facility #6 White-tailed Deer M 3.0

186 2020-08-17 Breeder Deer Kimble Facility #6 White-tailed Deer M 1.0

185 2020-08-04 Free Range El Paso N/A Mule Deer M 2.5

184 2020-07-30 Breeder Deer Kimble Facility #6 White-tailed Deer M 3.0

183 2020-06-25 Free Range El Paso N/A Mule Deer F 5.5

182 2020-06-16 Free Range El Paso N/A Mule Deer M 5.5

181 2020-06-11 Breeder Deer Uvalde Facility #3 White-tailed Deer M 4.0

180 2020-06-10 Breeder Release Site Uvalde Facility #3 White-tailed Deer F 5.5

179 2020-06-10 Breeder Release Site Medina Facility #3 White-tailed Deer M 3.5

178 2020-06-10 Breeder Release Site Medina Facility #3 White-tailed Deer F 5.5

177 2020-06-09 Breeder Release Site Uvalde Facility #3 White-tailed Deer F 4.5

176 2020-06-09 Breeder Release Site Uvalde Facility #3 White-tailed Deer F 2.5

175 2020-05-22 Free Range Hartley N/A Mule Deer M 5.5

174 2020-05-22 Free Range Hartley N/A Mule Deer M 5.5

173 2020-05-22 Free Range Dallam N/A Mule Deer M 2.5

172 2020-05-22 Free Range Hartley N/A Mule Deer F 5.5

171 2020-05-22 Free Range Hartley N/A Mule Deer M 4.5

170 2020-05-22 Free Range Hartley N/A Mule Deer M 4.5

169 2020-02-26 Breeder Deer Kimble Facility #6 White-tailed Deer F 5.5

168 2020-02-25 Free Range Val Verde N/A White-tailed Deer M 1.5

167 2020-01-28 Free Range Hudspeth N/A Mule Deer M 8.5

166 2020-01-28 Free Range Medina N/A White-tailed Deer M 4.5

165 2020-01-28 Free Range Medina N/A White-tailed Deer F 3.5

164 2020-01-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 4.5

163 2020-01-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 4.5

162 2020-01-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 4.5

161 2020-01-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 4.5

160 2020-01-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 4.5

159 2020-01-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 8.0

158 2020-01-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 3.0

157 2020-01-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 4.0

156 2020-01-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 4.0

155 2020-01-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 4.0

154 2019-12-18 Free Range Val Verde N/A White-tailed Deer F 5.5

153 2019-12-06 Breeder Deer Medina Facility #4 White-tailed Deer M 0.5

152 2019-12-06 Breeder Deer Medina Facility #4 White-tailed Deer F 9.0

151 2019-11-26 Breeder Release Site Medina Facility #3 Red Deer Unknown Unknown

150 2019-11-01 Free Range El Paso N/A Mule Deer M 4.5

149 2019-10-08 Breeder Deer Medina Facility #4 White-tailed Deer M 3.0

148 2019-10-08 Breeder Deer Medina Facility #4 White-tailed Deer F 4.0

147 2019-09-27 Breeder Deer Uvalde Facility #3 White-tailed Deer M 4.0

146 2019-09-27 Breeder Deer Uvalde Facility #3 White-tailed Deer M 4.0

145 2019-08-28 Free Range El Paso N/A Mule Deer M 3.0

144 2019-02-15 Free Range Medina N/A White-tailed Deer M 8.5

143 2019-01-30 Breeder Deer Uvalde Facility #3 White-tailed Deer M 3.5

142 2019-01-30 Breeder Release Site Uvalde Facility #3 White-tailed Deer M 5.5

141 2019-01-25 Free Range Hartley N/A Mule Deer M 3.5

140 2019-01-23 Free Range El Paso N/A Mule Deer M 6.5

139 2018-12-31 Free Range Medina N/A White-tailed Deer M 4.5

138 2018-12-31 Free Range Hartley N/A White-tailed Deer M 3.5

137 2018-12-31 Free Range Hudspeth N/A Mule Deer M 6.5

136 2018-12-31 Free Range Dallam N/A White-tailed Deer M 5.5

135 2018-12-31 Free Range El Paso N/A Mule Deer M 3.5

134 2018-12-31 Free Range Hartley N/A Mule Deer M 4.5

133 2018-11-30 Breeder Release Site Medina Facility #4 White-tailed Deer M 3.5

132 2018-11-20 Breeder Release Site Uvalde Facility #3 White-tailed Deer M 5.0

131 2018-10-11 Breeder Deer Uvalde Facility #3 White-tailed Deer M 3.0

130 2018-10-11 Breeder Deer Uvalde Facility #3 White-tailed Deer M 4.0

129 2018-09-17 Breeder Deer Uvalde Facility #3 White-tailed Deer F 10.0

128 2018-09-17 Breeder Deer Uvalde Facility #3 White-tailed Deer F 10.0

127 2018-09-17 Breeder Deer Uvalde Facility #3 White-tailed Deer F 9.0

126 2018-09-17 Breeder Deer Uvalde Facility #3 White-tailed Deer F 4.0

125 2018-09-17 Breeder Deer Uvalde Facility #3 White-tailed Deer F 2.0

124 2018-09-17 Breeder Deer Uvalde Facility #3 White-tailed Deer F 4.0

123 2018-09-17 Breeder Deer Uvalde Facility #3 White-tailed Deer F 8.0

122 2018-09-17 Breeder Deer Uvalde Facility #3 White-tailed Deer F 5.0

121 2018-09-17 Breeder Deer Uvalde Facility #3 White-tailed Deer F 2.0

120 2018-09-17 Breeder Deer Uvalde Facility #3 White-tailed Deer F 4.0

119 2018-08-30 Breeder Deer Uvalde Facility #3 White-tailed Deer M 3.0

118 2018-08-30 Breeder Deer Uvalde Facility #3 White-tailed Deer M 6.0

117 2018-08-02 Free Range El Paso N/A Mule Deer M 3.0

116 2018-07-03 Free Range Hartley N/A White-tailed Deer M 2.5

115 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer F 2.0

114 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer F 0.9

113 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer F 0.9

112 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer F 4.0

111 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer F 4.0

110 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer F 6.0

109 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer F 3.0

108 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer F 4.0

107 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer F 5.0

106 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer F 9.0

105 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 3.0

104 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 3.0

103 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 3.0

102 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 3.0

101 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 2.5

100 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 2.5

99 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 2.5

98 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 2.5

97 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 2.5

96 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 2.5

95 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer F 4.5

94 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer F 2.5

93 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer F 1.5

92 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer F 3.5

91 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer M 7.5

90 2018-06-13 Breeder Deer Uvalde Facility #3 White-tailed Deer F 7.5

89 2018-03-30 Breeder Deer Uvalde Facility #3 White-tailed Deer M 2.5

88 2018-03-27 Breeder Deer Uvalde Facility #3 White-tailed Deer M 2.5

87 2018-03-27 Breeder Deer Uvalde Facility #3 White-tailed Deer M 2.5

86 2018-03-27 Breeder Deer Uvalde Facility #3 White-tailed Deer M 2.5

85 2018-03-27 Breeder Deer Uvalde Facility #3 White-tailed Deer M 2.5

84 2018-03-09 Breeder Release Site Uvalde Facility #3 Elk F 4.5

83 2018-02-28 Breeder Deer Uvalde Facility #3 White-tailed Deer M 2.5

82 2018-02-13 Free Range Hudspeth N/A Mule Deer M 4.5

81 2018-01-31 Breeder Release Site Uvalde Facility #3 White-tailed Deer M 2.5

80 2018-01-29 Breeder Release Site Uvalde Facility #3 White-tailed Deer F 6.5

79 2018-01-08 Breeder Deer Uvalde Facility #3 White-tailed Deer M 3.5

78 2018-01-08 Breeder Deer Uvalde Facility #3 White-tailed Deer F 3.5

77 2018-01-08 Breeder Deer Uvalde Facility #3 White-tailed Deer F 8.5

76 2018-01-08 Breeder Deer Uvalde Facility #3 White-tailed Deer F 4.5

75 2018-01-08 Breeder Deer Uvalde Facility #3 White-tailed Deer F 5.5

74 2018-01-08 Breeder Deer Uvalde Facility #3 White-tailed Deer F 6.5

73 2018-01-08 Breeder Deer Uvalde Facility #3 White-tailed Deer M 3.5

72 2018-01-08 Breeder Deer Uvalde Facility #3 White-tailed Deer F 4.5

71 2018-01-08 Breeder Release Site Uvalde Facility #3 White-tailed Deer F 4.5

70 2018-01-08 Breeder Release Site Uvalde Facility #3 White-tailed Deer F 5.5

69 2017-12-29 Free Range Hartley N/A White-tailed Deer M 2.5

68 2017-12-22 Free Range Hartley N/A Mule Deer M 4.5

67 2017-12-22 Free Range Hartley N/A Mule Deer M 2.5

66 2017-12-18 Free Range El Paso N/A Mule Deer M 5.5

65 2017-11-29 Breeder Release Site Medina Facility #3 White-tailed Deer M 4.5

64 2017-11-27 Breeder Release Site Medina Facility #4 White-tailed Deer M 4.5

63 2017-10-25 Breeder Deer Medina Facility #5 White-tailed Deer F 3.0

62 2017-10-11 Breeder Deer Medina Facility #4 White-tailed Deer F 4.0

61 2017-10-11 Breeder Deer Medina Facility #4 White-tailed Deer F 4.0

60 2017-10-11 Breeder Deer Medina Facility #4 White-tailed Deer F 4.0

59 2017-10-11 Breeder Deer Medina Facility #4 White-tailed Deer M 4.0

58 2017-10-11 Breeder Deer Medina Facility #4 White-tailed Deer F 6.0

57 2017-10-11 Breeder Deer Medina Facility #4 White-tailed Deer F 4.0

56 2017-10-11 Breeder Deer Medina Facility #4 White-tailed Deer F 9.0

55 2017-10-11 Breeder Deer Medina Facility #4 White-tailed Deer F 9.0

54 2017-10-11 Breeder Deer Medina Facility #4 White-tailed Deer M 7.0

53 2017-10-06 Breeder Deer Medina Facility #3 White-tailed Deer F 1.0

52 2017-10-06 Breeder Release Site Medina Facility #3 Elk F 4.0

51 2017-09-13 Breeder Deer Medina Facility #3 White-tailed Deer F 5.0

50 2017-07-06 Breeder Deer Medina Facility #5 White-tailed Deer M 4.0

49 2017-02-28 Breeder Release Site Medina Facility #4 White-tailed Deer M 3.5

48 2017-02-17 Free Range Hudspeth N/A Mule Deer M 5.5

47 2017-02-17 Free Range Hudspeth N/A Mule Deer M 7.5

46 2017-02-09 Free Range Hudspeth N/A Mule Deer M 7.5

45 2017-02-09 Free Range Hudspeth N/A Mule Deer M 3.5

44 2017-01-24 Free Range Medina N/A White-tailed Deer M 1.5

43 2017-01-18 Free Range Hartley N/A Mule Deer M 4.5

42 2017-01-18 Breeder Release Site Uvalde Facility #3 White-tailed Deer M 3.5

41 2017-01-18 Breeder Release Site Uvalde Facility #3 White-tailed Deer M 5.5

40 2017-01-06 Free Range El Paso N/A Mule Deer M 4.5

39 2017-01-06 Free Range Dallam N/A Mule Deer M 2.5

38 2016-12-06 Free Range Dallam N/A Elk M 8.5

37 2016-10-28 Breeder Deer Uvalde Facility #3 White-tailed Deer F 4.5

36 2016-10-28 Breeder Deer Uvalde Facility #3 White-tailed Deer M 5.5

35 2016-09-21 Breeder Release Site Medina Facility #3 White-tailed Deer M 3.5

34 2016-06-29 Breeder Deer Medina Facility #4 White-tailed Deer F 4.0

33 2016-06-29 Breeder Deer Medina Facility #4 White-tailed Deer F 4.0

32 2016-06-29 Breeder Deer Medina Facility #4 White-tailed Deer F 4.0

31 2016-06-29 Breeder Deer Medina Facility #4 White-tailed Deer F 4.0

30 2016-06-29 Breeder Deer Medina Facility #4 White-tailed Deer F 4.0

29 2016-06-29 Breeder Deer Medina Facility #4 White-tailed Deer F 4.0

28 2016-06-29 Breeder Deer Medina Facility #4 White-tailed Deer F 4.0

27 2016-06-29 Breeder Deer Medina Facility #4 White-tailed Deer F 4.0

26 2016-06-29 Breeder Deer Medina Facility #4 White-tailed Deer F 4.0

25 2016-06-29 Breeder Deer Medina Facility #4 White-tailed Deer M 1.0

24 2016-06-29 Breeder Deer Medina Facility #4 White-tailed Deer F 1.0

23 2016-06-29 Breeder Deer Medina Facility #4 White-tailed Deer M 1.0

22 2016-06-29 Breeder Deer Medina Facility #4 White-tailed Deer F 1.0

21 2016-04-13 Breeder Deer Lavaca Facility #2 White-tailed Deer M 3.0

20 2016-04-13 Breeder Deer Lavaca Facility #2 White-tailed Deer M 3.0

19 2016-04-13 Breeder Deer Lavaca Facility #2 White-tailed Deer M 3.0

18 2016-04-13 Breeder Deer Lavaca Facility #2 White-tailed Deer M 3.0

17 2016-04-01 Breeder Deer Medina Facility #4 White-tailed Deer F 4.5

16 2016-03-29 Breeder Deer Medina Facility #3 White-tailed Deer M 3.0

15 2016-03-25 Free Range Hartley N/A Mule Deer M 3.5

14 2016-03-18 Free Range Hudspeth N/A Mule Deer M 5.5

13 2016-02-04 Breeder Release Site Medina Facility #3 White-tailed Deer M 3.0

12 2015-09-14 Breeder Deer Lavaca Facility #2 White-tailed Deer M 3.0

11 2015-08-12 Breeder Deer Medina Facility #1 White-tailed Deer M 2.5

10 2015-08-06 Breeder Deer Medina Facility #1 White-tailed Deer M 2.5

9 2015-08-06 Breeder Deer Medina Facility #1 White-tailed Deer M 2.5

8 2015-06-30 Breeder Deer Medina Facility #1 White-tailed Deer M 2.5

7 2014-12-04 Free Range Hudspeth N/A Mule Deer M 4.5

6 2012-12-28 Free Range Hudspeth N/A Mule Deer M 3.5

5 2012-12-10 Free Range Hudspeth N/A Mule Deer M 4.5

4 2012-12-02 Free Range Hudspeth N/A Mule Deer M 5.5

3 2012-12-01 Free Range Hudspeth N/A Mule Deer M 4.5

2 2012-07-12 Free Range Hudspeth N/A Mule Deer F 4.5

1 2012-07-12 Free Range Hudspeth N/A Mule Deer F 6.5

https://tpwd.texas.gov/huntwild/wild/diseases/cwd/tracking/#texasCWD

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 https://orcid.org/0000-0003-2042-3492, Lech Kaczmarczyk https://orcid.org/0000-0003-2747-3134, Doris Zeng https://orcid.org/0009-0002-2512-6227, +7, and Sabine Gilch https://orcid.org/0000-0001-5923-3464 sgilch@ucalgary.caAuthors Info & Affiliations Edited by Reed Wickner, NIH, Bethesda, MD;

received December 12, 2022; accepted March 6, 2023

April 4, 2023

120 (15) e2221060120

https://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.

https://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)

HIGHLIGHTS

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.

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.

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

Prion Disease Cell and Tissue Research Special Issue

Volume 392, issue 1, April 2023 Special Issue on Prion Diseases Issue editor Sabine Gilch 26 articles in this issue.

https://link.springer.com/journal/441/volumes-and-issues/392-1

Wild Science Webinar: March 2023 - CWD Research... here's an update on Arkansas CWD. runs about 23 minutes for the CWD, in the first part. Take note of the CWD maps for the USA overlay, from inception of cwd to today. starts at 3:25 minute mark to about the 4:15 rather remarkable, and frightening, considering they have found no way to stop it or slow cwd down, to date. the speaker said that CWD is HIGHLY UNDERESTIMATED. then another map shows populations declines and it shows those states, but then it draws attention to a spot i did not know about in TEXAS, and you can see this at about the 4:55 minute mark. something about Texas Based Metrics or Metrix study, i never heard of it, and then shows a spot in south Texas showing a -10.3%. thought some of you folks might find interest...terry Wild Science Webinar: March 2023 - CWD Research and Evaluating Florida Bass in Lake Ouachita

Arkansas Game and Fish Commission

https://www.youtube.com/watch?v=jj0ujdTqhys

https://www.agfc.com/en/hunting/big-game/deer/cwd/cwd-arkansas/

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

https://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 Conference abstracts: pushing the boundaries

https://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

https://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.

https://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.

https://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.

https://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

https://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

https://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 https://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.

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

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

https://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

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

Front. Vet. Sci., 14 September 2015 | https://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.

http://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.

https://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]

https://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

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

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

http://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) ???

https://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

http://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

https://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

https://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...

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

Dr. Paul Brown Scrapie Soil Test BSE Inquiry Document

https://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)

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

CHRONIC WASTING DISEASE CWD TSE PRION ZOONOSIS ZOONOTIC UPDATE

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

Samia Hannaoui1 · Irina Zemlyankina1 · Sheng Chun Chang1 · Maria Immaculata Arifin1 · Vincent Béringue2 · Debbie McKenzie3 · Hermann M. Schatzl1 · Sabine Gilch1

Received: 24 May 2022 / Revised: 5 August 2022 / Accepted: 7 August 2022 / Published online: 22 August 2022 © The Author(s) 2022

Abstract

Prions cause infectious and fatal neurodegenerative diseases in mammals. 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 provide evidence for a zoonotic potential of CWD prions, and its probable signature using mice expressing human prion protein (PrP) as an infection model. 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. Intriguingly, the protease-resistant PrP in the brain resembled that found in a familial human prion disease and was transmissible upon second passage. Our results suggest that CWD might infect humans, although the transmission barrier is likely higher compared to zoonotic transmission of cattle prions. Notably, our data suggest a different clinical presentation, prion signature, and tissue tropism, which causes challenges for detection by current diagnostic assays. 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.

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 Gerst-mann-Sträussler-Scheinker syndrome (GSS) is defined 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 profile and the N-terminal cleavage site.

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 pas-sage (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 3tg650 mice inoculated with Wisc-1- or 116AG-CWD and the presence of abnormal PrP (Western blot, IHC or RT-QuIC) might be explained by the presence of heterogeneous prions in the brains of infected mice with different seeding properties in vitro. Indeed, such heterogeneity and distinct seeding activities and infectivity of abnormal PrP fragments was observed in VPSPr cases [20, 43]. We could not establish a correlation between the presence of PrPSc deposits in mouse #328 and the absence of resist-ant PrP in Western blot even though prions present in the brain of this animal seeded the conversion of rPrP sub-strate very well (Fig. 1). Mouse #321 was not available for IHC; therefore, we cannot draw a conclusion about abnormal PrP deposits in the brain of this animal, but we can conclude that there is a correlation between level of prion seeding activity (Fig. 1) and the detection of atypical PrPres fragments (Fig. 2) present in the brain of this animal. We can only speculate that transmission of Wisc-1 to tg650 mice generated prions with characteristics that render them less prone to be unveiled with conventional methods. However, 77.7% of these mice showed prion seeding activity despite the absence of PK-resistant PrPSc for most of them, suggesting that protease-sensitive prions could be involved in these transmissions like it was shown in human prion diseases [54]. Further analyses such as conformation-dependent immunoassay [54] and in vivo sub-passages will be required to resolve these questions.

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 dis-ease 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 over-come 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 sub-clinical and atypical infections that are/might be transmissible, undetected by the gold standard tests, i.e., Western blot, ELISA, and IHC.

Ideally, an oral inoculation of mice with CWD prions would have mimicked best the natural route of exposure to acquired prion diseases like CWD. However, in our case, an oral inoculation would have been impossible considering the lifespan of the rodent models. It took us an extended amount of time, over two years and a half, to have a better idea of the extent of CWD transmission in the tg650 model, even with intracerebral inoculation, usually the fastest way to induce prion disease in a rodent model. Taking this into consideration, our study is the strongest proof-of-principle that CWD might be transmissible to humans. The overall risk for zoonotic transmission of CWD is likely lower than that for BSE; however, rather than predicting the absolute zoonotic risk for CWD, our study indicates the possibility of atypical features in humans. Furthermore, our findings provide striking insights into how CWD might manifest in humans and the impact it may have on human health. We have used Wisc-1/CWD1, one of the most common CWD strains, notably white-tailed deer prions, which have been shown to be more prone to generate human prions in vitro [47]. 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 surveil-lance in humans should encompass a wider spectrum of tissues/organs tested and include new criteria in the diagnosis of potential patients.

https://doi.org/10.1007/s00401-022-02482-9

https://link.springer.com/epdf/10.1007/s00401-022-02482-9?sharing_token=Vrc9lVnCx6nATJCPtcFbwPe4RwlQNchNByi7wbcMAY4BjPjkpxdzH-iFThODxSPKAK1QgQ-_2ZGPNoYIZyD3IDH8BQbGxEd1NHRwsyD-plz3_gnMpuGB-13C4DkxsBjdAJb3TEqBq0mBLdO-wl3E0flYPQbhh654WM_ijkAKt_U=&fbclid=IwAR0urg8a9eojZqpU6GePUgt5fQxsWqxsxwTzF_E_MktS3jf11wDxZP9Jy10

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.

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

Canada Creutzfeldt-Jakob disease surveillance system (CJDSS) report steady rise in cases as of January 2023 and STILL NO CASES REPORTED OF VPSPr CJD

wow, just wow, i don't know where to start with Canada and CJD and strange neurological conditions mounting.

seems the New Brunswick cases just sill not go away, and CJD cases in Canada keep rising.

Canada Creutzfeldt-Jakob disease surveillance system (CJDSS) report Update January 2023

(PLEASE NOTE, ''The increase in sCJD mortality can be at least partly attributed to increased awareness of CJD among referring clinicians.'' HAS BEEN USED 'ad nauseam' YEAR, AFTER YEAR, AFTER YEAR, OF RISKING CJD CASES.)

(PLEASE NOTE, OCTOBER OF 2022 THERE WERE 65 CJD CASES REPORTED, TWO MONTHS LATER, DECEMBER 2022, CJD CASES JUMPED TO 154 CASES REPORTED...tss)

(PLEASE NOTE, STILL, CANADA DOES NOT REPORT VPSPr CJD TSE Prion Cases to the public, see links below for this explanation and discussion. tss)

PLEASE NOTE, Canada does not mention VPSPr Variably protease-sensitive prionopathy and you can read why here ;

WHY do some countries count vpspr as sporadic cjd tse prion, and some countries don't?

THIS problem must be addressed immediately imo.

WE have the USA classifying Variably protease-sensitive prionopathy (VPSPr) (formerly known as Protease Sensitive Prionopathy) as sporadic Creutzfeldt Jakob Disease sCJD, and we have Canada not even mentioning in on there statistics links, like vpspr does not even exist, so this is a problem for any valid surveillance imo. IN fact, personal communication from Canada Surveillance et al;

QUOTE;

''Well Terry, we have the data. We simply do not report it separately because we do not believe it has any specific epidemiologic significance, including zoonotic transmission (this opinion is shared unanimously by the international CJD surveillance community, and was established very quickly after the discovery of VPSPr). The key reason in my mind why the US system reports it – in a footnote to their sporadic CJD data – is that they discovered it, and want to follow up on it publicly to validate the reality of their finding scientifically (which is distinct from its significance).''

''The simple answer to your question is that we do not track VPSPr separately, as we view is as a form of sporadic CJD with an unusual phenotype but no specific epidemiological significance. Even the USA surveillance figures do not report it separately.''

end

https://vpspr.blogspot.com/2022/04/phenotypic-heterogeneity-of-variably.html

https://vpspr.blogspot.com/

Hell of a way for a surveillance system for any country to look for any suspect unusual zoonosis zoonotic disease from any mutated TSE Prion strain from any species. ...terry

SNIP...SEE FULL POST HERE;

SUNDAY, APRIL 9, 2023

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

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

Case report: Two clusters of Creutzfeldt-Jakob disease cases within 1 year in West Michigan

“We do not have enough evidence to conclude that our two clusters are purely due to heightened awareness, more sensitive tests, and better ascertainment, nor could we be certain that they just simultaneously occurred (55).”

''However, families of patients 1, 2, and 4 reported consuming venison. More intriguingly, families and relatives of these three patients reported additional (at least four) possible or probable CJD cases occurring between 2007 and 2022 in their friends or communities (unpublished data).''

see;

Case report: Two clusters of Creutzfeldt-Jakob disease cases within 1 year in West Michigan

Front Neurol. 2023 Mar 20;14:1134225. doi: 10.3389/fneur.2023.1134225.eCollection 2023.

Case report: Two clusters of Creutzfeldt-Jakob disease cases within 1 year in West Michigan

Ling Ling Rong 1, Nicholas J Lannen 1, Evan C Tank 1, Jessica L Feistel 1, Christopher J Therasse 2, Anvita Potluri 1, Muhib Khan 1, Jiangyong Min 1

Affiliations

1Department of Neurosciences, Corewell Health West, Michigan State University, Grand Rapids, MI, United States.

2Department of Radiology, Corewell Health West, Michigan State University, Grand Rapids, MI, United States.

PMID: 37021286 PMCID: PMC10067729 DOI: 10.3389/fneur.2023.1134225

Abstract

Background: Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, and uniformly fatal neurodegenerative disease. The reported incidence of CJD is 1 to 2 per million people worldwide annually, with fewer than 1,000 cases in the United States per year. In this study, we report a unique case series on temporo-spatial clusters of CJD cases in West Michigan.

Methods: A total of five CJD cases consisting of two temporal clusters were seen from July 2021 to June 2022 at Corewell Health West hospitals. All patients had brain MRI, EEG, and CSF tests. Four patients underwent autopsies.

Results: All patients' MRIs showed characteristic CJD patterns. Four patients had positive CJD panels in CSF. One patient had typical CJD EEG findings. Four patients were confirmed as sporadic CJD by autopsy. All patients died within 3 months after CJD was suspected.

Discussion: All patients lived within a 90-mile radius of Grand Rapids, MI, and two lived in the same county. West Michigan has a population of 1.6 million people, and the four counties where five patients lived have a combined population of 395,104, indicating CJD's new case rate of 3.1 and 12.5 per million people, respectively. Corewell Health is one of the three major healthcare systems in West Michigan. The actual incidence of CJD in West Michigan is likely even higher. This dense temporal and spatial cluster of CJD cases poses a serious public health challenge and warrants urgent investigation.

Keywords: Creutzfeldt-Jacob disease; West Michigan; cluster; prion; rapidly progressive dementia; real-time quaking-induced conversion.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Introduction

Creutzfeldt–Jakob disease (CJD) is a transmissible, rapidly progressive neurological disease, caused by misfolded prion protein in the brain (1). The reported prevalence of CJD is 1 to 2 per million people worldwide annually and less than 1,000 cases in the United States per year (2–5)1 CJD subtypes include sporadic, genetic, iatrogenic, and variant CJD with 85–90% of cases being sporadic (2, 6, 7). sCJD can further be divided into subtypes including MM/(MV)1, MM2, VV1, VV2, and MV2 based on disease-related prion protein features and prion protein genotype in the host at the methionine (M) and valine (V) polymorphic codon 129 (8–11)1. The clinical diagnostic criteria for probable sCJD are rapidly progressive dementia plus at least two of the following: myoclonus, visual or cerebellar signs, pyramidal/extrapyramidal signs, and akinetic mutism. Vertigo, headache, and neuropsychiatric symptoms can also present. Patients gradually lose mobility, speech, and progress into a comatose state (2, 6, 7, 12, 13). Despite extensive research since its initial description 100 years ago, CJD remains an incurable disease with a survival of 4–12 months from symptom onset in the vast majority of patients (2, 6, 7).

Over the past few decades, there have been increased reports on sCJD. Some studied regional or national geographical distribution or temporal occurrence, but their cases occurred during periods of 9 to 15 years (14–18). Few case series focused on cases with similar clinical presentation without patients' geographic information (19, 20), or on cases over 5 years in the same region (21).

Our case series includes two temporal clusters of CJD cases in one region. Within 1 year from July 2021 to June 2022, we observed five CJD cases at Corewell Health West Butterworth (BW) and Blodgett (BL) Hospitals in Grand Rapids, Michigan (MI). These two hospitals are 3 miles apart. All five cases had supportive brain magnetic resonance imaging (MRI), four of them had supportive cerebrospinal fluid (CSF) findings, and one case had a characteristic electroencephalogram (EEG) pattern. All patients died within 3 months after CJD was suspected. We report this dense temporo-spatial cluster of CJD cases to call for an urgent investigation by public health officials.

Case series

Patient 1: A 67-year-old white woman who worked as a clinic manager was admitted on 14 July 2021 to BW due to rapid neurological decline. Her initial symptom was severe insomnia starting in mid-January 2021. By February 2021, her symptoms progressed to vertigo, diplopia, and imbalance. By May 2021, she was not able to function at work due to cognitive impairment. Her family noticed intermittent “childlike” behavior. On admission, she was fully alert, awake, and oriented with normal cranial nerves. Montreal Cognitive Assessment (MoCA) testing revealed profound deficits with a corrected score of 17/30.

Patient 2: A 78-year-old white man who was a semi-retired funeral home director was admitted on 31 July 2021 to BW for rapidly progressive cognitive decline along with dysfunctional gait, abnormal speech, and intermittent body jerking. In early May 2021, he started to have intermittent hand weakness, paresthesia, and forgetfulness. Due to unsteadiness, he began using a cane in June 2021 but quickly progressed to a walker. Outpatient electromyography and nerve conduction velocity (EMG/NCV) studies were unrevealing. MRI brain reported a 3-mm subacute infarct in left caudate head and ventriculomegaly. In the same month, he developed expressive aphasia progressing to a paucity of speech. Over 2 weeks, he had a catastrophic decline with excessive daytime somnolence. He was unable to perform activities of daily living and developed alternating urinary incontinence and retention. On admission, he was somnolent but easily startled by auditory stimuli. He followed limited, one-step commands and moved all extremities but was oriented to self only.

Patient 3: A 77-year-old white man who was a semi-retired attorney was transferred to BL for continuous video EEG monitoring on 03 May 2022 from an outside hospital (OSH), which was 75 miles east of Grand Rapids. In mid-March 2022, he complained of “brain fog” after he started medication for his newly diagnosed hypertension. The dyscognia persisted despite discontinuation of the anti-hypertensive. He developed visual disturbance and reported seeing his own fingers abnormally elongated, and his legs were fat and bowed. He was able to provide a full history and had an intact neurological examination on admission at the OSH 6 days before transfer to our facility. Brain MRI at OSH reported subtle cortical restricted diffusion involving both posterior temporoparietal and occipital regions. Levetiracetam was initiated after a 1-h EEG captured intermittent delta slowing over the left frontal region without rhythmicity. CSF at OSH was unremarkable except pending the CJD panel. Upon transfer to BL, he was awake and alert but with limited orientation, verbal output, and impaired abstraction. His motor and sensory examinations were intact.

Patient 4: A 78-year-old white woman and homemaker presented to the local emergency department on 03 June 2022 for cognitive decline over several months, accelerating over a few weeks before presentation. Her brain MRI reported multiple infarcts in different territories concerning global hypoxic ischemia; the on-call tele-stroke physician requested transfer to BW for further evaluation as the MRI pattern suggested CJD rather than hypoxic ischemia. The patient's initial symptom was intermittent forgetfulness, which started in August 2021 and had worsened since late December 2021. In March 2022, she developed “pressure in head” and complained “I do not feel my brain work.” The patient was diagnosed with anxiety and treated with anxiolytics without benefit. In late April 2022, gait abnormality and word-finding difficulties arose, and in May 2022, she developed auditory hallucinations. By June 2022, jerks in her upper extremities were noticed. Upon admission, she was oriented to person only and had impaired attention, reasoning, and verbal expression but had preserved motor strength and sensation.

Patient 5: A 64-year-old white woman who worked as a nurse was admitted to BL on 17 June 2022 for rapidly progressive cognitive decline. Her initial symptoms were “brain fog,” dizziness, and fatigue, starting in January 2022. By late April 2022, she endorsed imbalance, diplopia, and multiple falls along with visual hallucinations, paranoia, and memory dysfunctions. On admission, she was awake, alert, oriented to self and could only recognize her close friends. Her cranial nerves were intact. She had mild proximal weakness in both bilateral upper and lower extremities. The vibratory sensation of bilateral lower extremities was impaired in a length-dependent distribution. She required stabilization on standing (Figure 1).

Laboratory testing and results

All five patients had initial or repeated 1.5 or 3 Tesla brain MRI with and without contrast (w/wo) at BW or BL, respectively, revealing restricted diffusion and corresponding hyperintense T2 FLAIR signal involving bilateral caudate nuclei and putamina in a symmetric pattern (patient 1); asymmetric diffusion restriction signals in the cerebral cortex of cingulum, left temporoparietal lobes, and caudate nucleus (patient 2); prominent multifocal diffusion restriction involving the bi-hemispheric cerebral cortex, more posteriorly and on the left compared to the right (patient 3); symmetric cortical diffusion restriction involving paramedian, lateral parietal cortices, temporal cortices, and to a lesser extent in the frontal lobe with involvement of left greater than the right (patient 4); restricted diffusion in the bilateral caudate nuclei (left > right) and the left mesial temporal lobe, including the amygdala, the hippocampus, and the forniceal column (patient 5) (Figure 2).

EEG was performed on all patients. The EEG of patient 3 showed periodic sharp wave complexes (PSWC), a characteristic CJD pattern. Other patients' EEGs were unremarkable (patient 5), had non-specific rare generalized periodic discharges with triphasic morphology (patients 1 and 4); moderate bitemporal slowing with a right predominance (patient 1); generalized rhythmic delta activity (patient 2) (Figure 3). Blood, CSF basic tests, and Mayo Clinic autoimmune encephalopathy panel in serum (ENS2) were negative. The autoimmune encephalopathy panel and paraneoplastic panel in CSF were all negative. All patients' CSF CJD panels from the National Prion Disease Pathology Surveillance Center (NPDPSC) reported >98% likelihood of prion disease except patient 4 whose CJD likelihood and 14-3-3 proteins were inconclusive, RT-QuIC was negative, and T-tau level was high (19937 pg/ml) (Table 1).

Treatment and final diagnosis

All patients (except patient 4) received empirical treatment: five doses of 1,000 mg methylprednisolone intravenously daily, followed by five rounds of plasma exchange (patient 1); one dose of 400 mg/kg intravenous immunoglobulin (IVIg) (patient 2); five doses of 400 mg/kg IVIg alone daily (patient 3); or with five doses of IV methylprednisolone daily (patient 5). Patients did not have any benefits from the aforementioned treatment. Patients died in October 2021, August 2021, May 2022, July 2022, and July 2022, respectively. Four patients underwent autopsy and genetic analysis (the family of patient 2 declined autopsy). No gene mutation was detected in any patient. Except for codon 129 polymorphism, no other polymorphism was found in any patient. The final diagnosis was as follows: patients 1 and 5 were sCJD-VV2, and patients 3 and 4 were sCJD-MM1 (Table 1).

Discussion

All patients in this case series had a rapid cognitive decline. Two patients also had visual disturbances (particularly patient 3 who presented with impaired visual perception at an early stage), and the illness progressed rapidly, possibly representing the Heidenhain variant of CJD (12, 22). On admission, the patients were 67, 78, 77, 78, and 64 years of age, and the durations from the time of symptoms onset to death were 8, 4, 3, 11, and 6 months, respectively. This is mostly consistent with sporadic CJD, which has reported a range of 55–75 years of peak onset age and a median survival duration of 4–12 months (2, 5, 7, 23). The durations from the time when positive CJD in CSF was reported (in patients 1, 2, 3, and 5) or from the time when brain MRI showed typical CJD patterns (patient 4) to death were 72, 10, 2, 26, and 43 days, respectively. All were shorter than the reported typical 4 to 6 months from diagnosis to death (5, 23).

Brain MRI, EEG, and advanced CSF studies are the most utilized diagnostic tests for CJD (7, 24–26). Brain MRI with diffusion-weighted imaging (DWI) has a sensitivity of 67–91% (27, 28) and a specificity of 97% for diagnosing sCJD (27). With increased awareness of sCJD, its diagnostic criteria, and improvement in MRI accessibility and scan quality, the sensitivity of MRI for CJD could reach 99% (28). Our five patients' brain MRI revealed typical sCJD patterns, that is hyperintensities in the cortical gray matter (cortical ribboning sign) and the deep nuclei (basal ganglia and thalamus). The cortical ribboning sign was proposed to be the biomarker in the prodromal phase of sCJD diagnosis (29, 30). The MRI of patient 1 demonstrated a symmetric pattern of bilateral DWI and T2 FLAIR correlated signal in caudate nuclei and putamina. MRIs of patients 2, 4, and 5 revealed asymmetric, cortically based DWI changes in the cingulate, the caudate nuclei, and the left temporoparietal cortex, and the MRI of patient 3 showed multifocal cortically based DWI pattern, more on the left. Park et al. found that being greater than 60 years of age and diffusion restriction in the caudate nucleus and putamen were independent prognostic factors of shorter survival duration in patients with sCJD (27) with median overall survival of 1.7 months compared to 14.2 months in the intermediate risk group. Radiographically, our five patients belong to the high-risk group.

RT-QuIC is a breakthrough technology for diagnosing CJD with specificity reaching 99–100% (31–33). Its sensitivity can increase from 77 to 96% after modified techniques (31). Patients' (1, 2, 3, and 5) CSF CJD panel reported a likelihood of CJD of more than 98%, positive RT-QuIC, high T-tau protein, and positive 14-3-3 protein (more than 71,000 Au/ml in patients 3 and 5, and no titer reported in patient 1 and 2). The CSF of patient 4 was inconclusive for CJD likelihood and 14-3-3 proteins. Her RT-QuIC was negative, but T-tau protein was 19,937 pg/ml. As per NPDPSC test report, the sensitivity of RT-QuIC is lower when specimens are discolored by blood. Shir et al. reported that elevated CSF 14-3-3 and T-tau proteins as well as clinical symptoms such as myoclonus and visual or cerebellar abnormalities are associated with shorter disease duration (7), which held true for patient 3.

EEG has a lower diagnostic value when compared to brain MRI and CJD panel in CSF. The reported sensitivity of EEG-specific abnormalities to diagnose probable sCJD ranged from 38.2 to 68.75% (34, 35). However, the characteristic EEG finding in CJD, periodic sharp wave complexes (PSWCs), has 86% specificity (36) and 95% positive predictive value (37). Our case series confirmed low sensitivity and high specificity of EEG for diagnosing CJD. Of the five patients, four patients showed EEG abnormality (80%) with 20% specific (patient 3 showed characteristic periodic sharp wave complexes PSWC at 1 Hz, bi-hemispheric with left predominance) and 60% non-specific abnormalities (patients 1, 2, and 5). Mundlamurri et al. reported that in the early stage of sCJD, patients' EEGs can be normal or non-specifically abnormal (35). In very early phases (1.67 months after onset and before the emergence of generalized PSWC) of sCJD, the predominant findings of EEG can be (1) lateralized periodic discharges (LPDs), (2) central sagittal sporadic epileptiform discharges (CSSEDs), and (3) focal epileptiform discharges (38). It is suggested that the early presence of the PSWC pattern has a prognostic value because these patients have significantly lower average survival time (39). The EEG of patient 3 captured PSWC on day 48 after the illness onset. He died 19 days after the EEG was done and 2 days after positive CJD in CSF was reported.

Brain biopsy or autopsy remains the gold standard for final diagnosis. Four patients underwent autopsy and genetic analysis. All four patients had sporadic CJD, of the two most common subtypes, sCJD-VV2 in Patients 1 and 5, and sCJD-MM1 in patients 3 and 4. Different subtypes have different clinical and neuropathological features, as well as survival times and test results (8, 40, 41). The sensitivity of RT-QuIC for detecting MM1 and VV2 is high (96.3%) but can be negative for MM2 and VV1 subtypes (33, 42). Younes et al. reported that MM1, MV1, and VV2 are related to short duration/fast progression, while MV2, VV1, and MM2 are associated with long duration/slow progression (43). Our case series revealed that patients 3 and 4 were sCJD-MM1 but with an 8-month difference in survival length; patients 1 and 5 were diagnosed with sCJD-VV2 with similar survival durations, 8 vs. 6 months. Patient 2 had a short survival duration; unfortunately, his family declined an autopsy.

Geographical clusters of sCJD have been reported, but most clusters contained cases distributed over many years (14, 17, 18, 44–48), and few were temporo-spatial clusters. A French cluster of three cases of CJD occurring in 1998 reported that two of the patients lived in the same village. Molecular and phenotypic analyses showed both patients were homozygous for methionine at the polymorphic codon 129 but one patient was MM1 while another had mixed features of MM1 and MM2 both clinically and histo-pathologically (48). RT-QuIC was not yet invented. A Japanese cluster of three CJD cases occurred between 1988 and 1989 near Fukuoka city; no hospitalization time was mentioned in the report, nor were CSF studies or codon 129 polymorphism analyses done on these patients (49). A cluster of four cases in Burlington, Ontario, Canada, between April 1989 and April 1990 with two additional cases on further inquiry, and a cluster of seven cases in Nassau County, New York, between mid-June 1999 and mid-June 2000 (50, 51) were reported without genetic studies. Some clustering was found later to be an aggregation of genetic CJD cases (52, 53).

Our five cases in two clusters were seen within 1 year in Grand Rapids, Michigan. Cluster one included patients 1 and 2, seen within 1 month from July to August of 2021; cluster two included patients 3, 4, and 5, observed within 1 month between May and June of 2022. All patients lived within a 90-mile radius of Grand Rapids. No interpersonal connections were identified among them. All patients were white with differing professions (Table 1). None of them had a family history of Creutzfeldt–Jakob disease, or personal history of corneal transplants, craniotomy, administration of human growth hormone derived from pools of pituitary glands, or surgical procedure at the same facility. However, families of patients 1, 2, and 4 reported consuming venison. More intriguingly, families and relatives of these three patients reported additional (at least four) possible or probable CJD cases occurring between 2007 and 2022 in their friends or communities (unpublished data). One of the patients was a 63-year-old white woman and mayor, who lived 35 miles from patient 2, and died of CJD in March 2022. Thus, such a wave of dense temporo-spatial clustering of CJD in West Michigan is very unusual and alarming.

Our case series does not support that CJD incidence has no geographical differences (4, 54). West Michigan has 1.6 million people, and the combined population of four counties where five patients lived is 395,104 in 2022, which makes the CJD new case rate 3.1 and 12.5 per million people in West Michigan and combined four counties, respectively, which is higher than reported 1 to 2 per million people worldwide and 350–710 cases in the United States annually (2–5)1. Adding the cases reported by our three patients' families, the new case occurrence would be even higher. Michigan disease surveillance system (MDSS) reported 19 CJD cases by 31 December 2022 and only 12 cases in 2018, and this reflects a 58% increase2 We do not have enough evidence to conclude that our two clusters are purely due to heightened awareness, more sensitive tests, and better ascertainment, nor could we be certain that they just simultaneously occurred (55). Our study has several limitations, including an observational study, a limited time period, not using the conventionally used solar year period, and a relatively small population and area in West Michigan. As such, this case series highlights only a possible trend. More research and evidence are certainly required to reach a conclusion. We have planned additional retrospective studies, which we expect will surmount these shortcomings. Epidemiological surveillance, research, development of new diagnostic technologies, and public health endeavors are critical (4, 56).

Conclusion

For five sCJD cases in two dense clusters within 1 year in Grand Rapids, MI is more than expected. Extensive screening in West Michigan may eventually arrive at a reliable incidence rate of CJD in this region. These two clusters along with additional cases reported by our patients' families warrant urgent investigation. Further research including epidemiological study regarding possible transmission events, common environmental factors that trigger CJD occurrence as well as continuous surveillance, and further improving diagnostic techniques are critical and necessary.

Data availability statement The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics statement Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

Author contributions LR: writing the original draft, selecting MRI images, and finalizing the manuscript. NL, JF, AP, MK, and JM: reviewing and editing. ET: selecting EEG pictures, draft reviewing, and editing. CT: selecting MRI images. All authors contributed to the article and approved the submitted version.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Footnotes

snip...

https://pubmed.ncbi.nlm.nih.gov/37021286/

https://www.frontiersin.org/articles/10.3389/fneur.2023.1134225/full

Extremely disturbing to say the least.

WAS CJD Questionnaires asking real questions for potential routes and sources, were they given out and filled out by Family et al? This is Extremely important, and should happen with all victims of any human TSE Prion, due to the iatrogenic threat i.e. friendly fire, or pass it forward TSE Prion. See history of USA CJD Questionnaire, and why it's so important to be asking all the questions;

FRIDAY, JANUARY 15, 2021

CJD TSE Prion Questionnaire USA, UK, and the history there from, have you filled out this questionnaire?

if not, why not?

CJD TSE Prion Questionnaire USA, UK, Singeltary

CJD FOUNDATION Questionnaire

https://cjdfoundation.org/files/pdf/Patient%20Questionnaire%202016.pdf

UK CJD Questionnaire

http://web.archive.org/web/20090506075100/http://www.bseinquiry.gov.uk/files/mb/m26/tab04.pdf

NOT to open up old wounds, but here is my 23 years of endeavors to get the USA to have a CJD Questionnaire for every family of a person whom died of cjd tse prion in the USA in every State, pertaining to real questions of all the potential routes of CJD in that questionnaire. seems i have failed terribly. there was great debate, much anguish, and i did take it personally, when others took credit for what i had been trying to get done. but this was long ago, and today the CJD Foundation seems to be working hard to change there old ways, and seem to be looking to find the routes of sporadic cjd as well. this is just that history, like it or not...kind regards, terry

THE MAKING OF THE USA CJD QUESTIONNAIRE

https://beta.regulations.gov/document/FDA-2012-D-0307-0035

https://cjdquestionnaire.blogspot.com/2015/10/cjd-foundation-creutzfeldt-jakob.html

https://creutzfeldt-jakob-disease.blogspot.com/2012/03/cjd-foundation-cwru-gambetti-familial.html

http://cjdquestionnaire.blogspot.com/2007/11/cjd-questionnaire.html

https://cjdquestionnaire.blogspot.com/2009/

https://cjdquestionnaire.blogspot.com/2007/11/cjd-questionnaire.html

http://cjdquestionnaire.blogspot.com/

snip...see full history of the USA CJD Questionnaire here;

https://cjdquestionnaire.blogspot.com/2021/01/cjd-tse-prion-questionnaire-usa-uk-and.html

zoonotic transmission of CWD to Humans has not been _documented_, yet, does not mean it has not already happened. science has shown by transmission studies that CWD transmission to humans is very likely, if it has not happened already. so, what would iatrogenic transmission to humans from CWD look like? Consumption, CWD exposure to humans, and friendly fire there from, what if?

let's look at the science shall we.

1st, what about CWD TSE Prion in the area of Grand Rapids;

CHRONIC WASTING DISEASE OF CERVID is in Michigan, and it has been documented in this area around Grand Rapids.

''All patients lived within a 90-mile radius of Grand Rapids, MI, and two lived in the same county''

Chronic wasting disease found in deer at West Michigan farm

Published: Jan. 14, 2020, 2:32 p.m.

By Justin P. Hicks | jhicks3@mlive.com

NEWAYGO COUNTY, MI -- Three white-tailed deer have tested positive for chronic wasting disease at a deer farm in Newaygo County.

The Michigan Department of Agriculture and Rural Development reported Tuesday, Jan. 14 that samples from three 4-year-old deer tested positive for CWD during routine testing under the state’s surveillance program for farmed deer.

Officials said the disease still hasn’t been detected in free-ranging deer in Newaygo County. An investigation will be conducted to rule out exposure of any other farmed deer.

“Chronic wasting disease is a serious disease affecting both farmed and free-ranging deer,” State Veterinarian Nora Wineland said in a prepared statement. “MDARD and the Michigan Department of Natural Resources work together, in partnership with the state’s deer farmers, to ensure the protection of all of Michigan’s deer.”

CWD is a fatal neurological disease that affects white-tailed deer, mule deer, elk and moose. It can be transmitted directly from animal to animal or indirectly through the environment.

Since 2008, the disease has been detected in four other privately-owned deer facilities from Kent, Mecosta and Montcalm counties. Last year, 83 deer in Montcalm County were confirmed to have CWD.

There have been no reported cases of chronic wasting disease infection in humans. As a precaution, the U.S. Centers for Disease Control and the World Health Organization recommend that infected animals not be consumed by humans or domestic animals.

https://www.mlive.com/news/grand-rapids/2020/01/chronic-wasting-disease-found-in-deer-at-west-michigan-farm.html

MICHIGAN 25 Michigan deer test positive for CWD in 2021 by: Matt Jaworowski

Posted: Apr 21, 2022 / 01:01 PM EDT

Updated: Apr 21, 2022 / 01:01 PM EDT

SHARE GRAND RAPIDS, Mich. (WOOD) — The latest data from the Michigan Department of Natural Resources shows that 25 deer tested positive for chronic wasting disease in 2021.

The DNR said a little over 7,200 deer were tested last year: a low number for pre-pandemic standards but triple the number of tests run in 2020. In that year, the agency recorded 20 deer with CWD. But the department warns comparing year-to-year data loses a lot of context due to its testing strategy.

“Some years we’ve intensified surveillance in known hot spots, and other years (including 2021) we have looked elsewhere trying to find the disease, specifically avoiding those hot spots,” Chad Stewart, a DNR Deer, Elk and Moose Management Specialist, told News 8. “With that, it’s not really possible to compare the numbers between years at face value.”

Of the 25 CWD-positive deer, three cases of chronic wasting disease were detected in Isabella County, the first cases were found there.

Michigan’s first confirmed case of CWD was found in 2015 and has since been found in Clinton, Dickinson, Eaton, Gratiot, Ingham, Jackson, Kent and Montcalm counties, with Montcalm County, northeast Kent County and southern Jackson County showing the highest concentration of cases.

CWD testing peaked in 2018 and 2019, with a combined 50,000 deer tested and 127 positive tests. Stewart warned that hunters shouldn’t dismiss CWD as a threat despite the lower numbers.

“The distribution of our samples greatly affects the number of positives we expect to find. Intensive collection of samples in known CWD locations like Montcalm and Kent counties would certainly lead to a high number of positives being detected,” Stewart said in a news release. “Our goal this year was to begin to understand what CWD looks like in areas that are historically under-sampled, and we made a lot of strides on that front.”

Stewart also warned that, as of now, there’s no easy way to eradicate the disease completely.

“Once it becomes established, it is unlikely that we can reverse course on the disease. Prevention and early detection remain our best options for CWD management,” Stewart said.

https://www.wlns.com/news/michigan/25-michigan-deer-test-positive-for-cwd-in-2021/

SUNDAY, JANUARY 22, 2023

Michigan Chronic Wasting Disease CWD TSE Prion Totals Since 2015 To Present 242 Confirmed Cases

https://chronic-wasting-disease.blogspot.com/2023/01/michigan-chronic-wasting-disease-cwd.html

TUESDAY, FEBRUARY 28, 2023

Michigan MDARD Captive CWD Positives depopulated and quarantined

https://chronic-wasting-disease.blogspot.com/2023/02/michigan-mdard-captive-cwd-positives.html

MICHIGAN CWD Map

https://www.michigan.gov/dnr/managing-resources/wildlife/cwd/hunters/cwd-testing-results-for-deer-harvested-in-2021

THE exposure rate of Cervid CWD exposure via consumption, then going on to have surgical, medical, dental, tissue donations, blood donations, there from, then tracing back CJD TSE Prion victims there from, would be impossible to traceback with todays surveillance traceback efforts, especially when the USDA et al can't even traceback BSE cattle to date (i will spare you those details, but will be in a url link at the bottom.).

2nd iatrogenic CJD

iatrogenic CJD TSE PrP

least we forget...

*** 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.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract

Friendly fire, pass it forward, they call it iatrogenic cjd, or what i call 'tse prion poker', are you all in $$$

all iatrogenic cjd is, is sporadic cjd, before the iatrogenic event is discovered, traced back, proven, documented, put into the academic domain, and then finally the public domain, this very seldom happens, thus problem solved, it's all sporadic cjd...

Friday, March 11, 2022

Prevalence of Surgical Procedures at Symptomatic Onset of Prion Disease

Research Letter Surgery

March 9, 2022

https://itseprion.blogspot.com/2022/03/prevalence-of-surgical-procedures-at.html

https://itseprion.blogspot.com/

3rd CWD Zoonosis Zoonotic Science To Date

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.

https://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.''

https://thescipub.com/pdf/ajidsp.2021.43.48.pdf

https://creutzfeldt-jakob-disease.blogspot.com/2021/05/a-unique-presentation-of-creutzfeldt.html

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 ;

http://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

http://www.fda.gov/ohrms/dockets/ac/cber01.htm

http://web.archive.org/web/20110616141110/http://www.fda.gov/ohrms/dockets/ac/cber01.htm

see actual paper;

http://web.archive.org/web/20110616141110/http://www.fda.gov/ohrms/dockets/ac/01/transcripts/3681t2.rtf

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

http://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.

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

http://www.gao.gov/highlights/d03494high.pdf

see updated url link;

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

GREETINGS GAO:

i was suprised 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 ;

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

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 tg650brain 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

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

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

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)

https://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.

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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.

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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)

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.

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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:

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

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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.

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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.

Chronic Wasting Disease

Thursday, April 27, 2023

TEXAS REPUBLICAN SB 1372 TAXPAYERS TO PAY FOR GAME FARMS CWD DEPOPULATION?

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