Monday, November 26, 2018

Wisconsin CWD spreads on deer and elk farms as control efforts stumble

CWD spreads on deer and elk farms as Wisconsin’s control efforts stumble

By Rich Kremer Wisconsin Public Radio Nov 25, 2018

Rapidly growing numbers of cases of chronic wasting disease are appearing on deer and elk farms and hunting ranches in Wisconsin at the same time the state has pulled back on rules and procedures designed to limit the spread of the fatal brain disease among its captive and wild deer.

Since 2013, when the Department of Agriculture, Trade and Consumer Protection (DATCP) began to let some captive deer facilities with infected animals continue operating, additional cases of CWD have developed within those facilities, according to interviews and documents obtained under the state’s Open Records Law.

After Gov. Scott Walker announced “aggressive new actions” against CWD, lawmakers rejected an emergency rule to limit hunters from moving deer carcasses from counties affected by the fatal brain disorder.

Meanwhile, enhanced fencing requirements are under consideration for captive white-tailed deer and other cervids including elk — but those proposals face heavy opposition from facility owners who say such a requirement is not guaranteed to halt CWD spread and could put them out of business.

National CWD expert Bryan Richards said Wisconsin’s current approach of allowing facilities with CWD-infected animals to continue operating poses a serious threat to the state’s wild deer population, which has seen more than 4,400 infected deer since the first CWD case in 2002.

Wisconsin now has more CWD-positive deer farms in operation than any other state in the nation, said Richards, who works for the U.S. Geological Survey at the National Wildlife Health Center in Madison.

There are nine CWD-positive deer facilities still in business — seven of which have seen additional cases of CWD on their properties, according to DATCP records.

“The existence of CWD in these facilities constitutes a clear, persistent and likely escalating risk to the integrity of the wild deer on the other side of the fence,” Richards said.

But a top DATCP official said the goal of the approach is to keep CWD contained and away from the wild deer population. Until 2013, herds at CWD-positive facilities in Wisconsin were killed and the sites were disinfected.

The new approach “is meant to mitigate risk of moving the disease … outside of the fence,” said Amy Horn-Delzer, veterinary program manager.

Horn-Delzer added that it is up to facility owners to manage the spread of the disease within their own properties.

“We don’t want to put any other breeding farms at risk,” she said. “We don’t want to put the wild deer population at risk. So, that’s the risk that we look at.”

The federal Centers for Disease Control and Prevention says it is unclear whether this always fatal disease can be passed to humans, although research has shown eating meat from CWD-positive deer can infect macaque monkeys. Signs of the disease, which affects deer and elk, include weight loss, stumbling, drooling and aggression.

There are 380 registered commercial deer and elk operations in Wisconsin spread across nearly every county in the state. Some of them have been in operation since the 1970s and are generally broken down into two categories: breeding farms and hunting ranches.

Breeding farms raise deer to sell to slaughter and to ranches that sell hunting experiences at fenced-in properties. They also sell deer to other breeding farms looking to introduce new genetic lines into their herd. The industry has long been the subject of criticism from some hunters who feel keeping and hunting animals behind a fence gives hunters an unfair advantage over their prey.

There have been 300 CWD-positive tests at 24 deer farms and hunting ranches in Wisconsin, according to state records. Most of those have been found since 2013 — the same year that DATCP, which shares regulation of deer farms with the state Department of Natural Resources, began allowing hunting ranches and breeding farms to continue operating despite having the disease on their premises.

Prior to 2013, all animals on commercial deer operations testing positive for CWD were killed. State law allows authorities to test animals and, if warranted, kill the herd to avoid the spread of disease. Owners can receive up to $3,000 in state and federal funding for each animal that is euthanized.

DATCP acting state veterinarian Darlene Konkle said the agency has decided to take an individualized approach rather than a blanket policy of depopulating entire herds after a detection.

“Since 2013, we have been looking at each of these (CWD) positive facilities on a case-by-case basis and just looking at risk,” Konkle said.

Konkle said her agency keeps close tabs on them.

“In any of these cases in a positive CWD facility, they’re immediately quarantined as soon as we have confirmation of the disease,” she said. “So, they are not allowed to move live animals on or off. So, there’s that method of control that’s put into place immediately.”

Hunting ranch open despite 84 CWD cases

But there are exceptions to the rule.

Wilderness Game Farm Inc. operates two breeding farms and a hunting ranch in Portage County, and hunting ranches in Marathon and Shawano counties. Since 2013, there have been 84 cases of CWD on the Marathon County hunting ranch called Wilderness North.

Despite having more positive cases than any other captive deer operation in Wisconsin, the ranch continues to sell hunts priced at between $4,000 and $9,000 each, with an option for a “Gold Hunt” — no price listed — that promises deer with antlers measuring 200 inches, including all points.

Emails from Wilderness Game Farm owner Greg Flees, then-DATCP state veterinarian Paul McGraw and program manager Horn-Delzer show mandatory quarantines issued after the 2013 detection allow Flees to move deer from his breeding farms, which had no CWD detections, to his hunting ranches. One of them, Comet Creek in Shawano County, has had six deer test positive for CWD since 2017.

This April, McGraw and Horn-Delzer also approved Flees’ request to move deer that he said carried markers for genetic resistance to CWD to the heavily infected Wilderness North property to test whether they develop the disease. It is part of a research project in collaboration with a researcher from Midwestern University in Glendale, Arizona.

DATCP’s quarantine policy change was celebrated by Whitetails of Wisconsin (WOW), the state’s deer farming lobby group. On Jan. 21, 2014, then-WOW president Shannon Thiex alerted members that their lobbying on the matter had paid off.

"Last week we felt we had a case to fight to get the herds in this state reduced from herd quarantines to individual animal quarantines,” wrote Thiex. “After some great teamwork on the quarantine issue we were notified today that DATCP would indeed be working this week to change these quarantines to individual animals only.”

Flees is a second-generation deer farmer. He said his family has been breeding whitetails since the 1970s. Since then, Flees has become one of the best known names in the deer farming industry both in Wisconsin and nationwide. Flees said when test results came back positive from his Marathon County hunting ranch, he did not believe it.

“OK, we fenced in that property and we moved a bunch of these deer, we never took a deer from anywhere else other than this farm that’s never had a positive,” Flees said. “We put them onto that property, and once they were on that landscape, for awhile all of a sudden we started getting some positives.”

Flees said it is possible that CWD was already on the property or that it was brought in by scavengers, birds or feed products such as corn or alfalfa. A 2015 study shows that the misfolded protein that causes CWD, known as a prion, can be taken up from the soil into plants and infect deer.

Another potential method of transmission is deer that escape from CWD-positive facilities. DATCP records show that 67 deer escaped from Fairchild Whitetails in Eau Claire County between 2009 and 2015, before the 228-head herd was killed. Among the escapees were two bucks shot by hunters that tested positive for CWD, the Eau Claire Leader-Telegram reported.

Owner Rick Vojtik, who is also the president of Whitetails of Wisconsin, was paid $298,770 by DATCP for the animals that were killed; he told the Leader-Telegram the herd was worth about $1 million. In all, 34 animals tested positive for CWD.

According to USGS figures, nearly a quarter of all deer farms that have tested positive for CWD nationwide have been in Wisconsin. Richards said the state set a precedent five years ago when it allowed Flees’ Wilderness North hunting preserve to continue operating after deer started getting sick.

“So that was a very interesting change in philosophy and quite different to what had been done previously across the rest of the country,” he said.

Emergency rules proposed — then dropped

In May, Walker announced a series of actions aimed at slowing the spread of CWD. He called on DATCP to draw up an emergency rule requiring enhanced fencing and banning the movement of live deer from the state’s 55 counties listed as CWD affected, meaning either an infected deer had been detected there or within 10 miles of the county.

The Republican governor also called on the state DNR to create emergency rules that would have banned hunters from transporting deer carcasses out of counties listed as CWD affected to non-affected counties.

Walker issued his directives just before speaking to the Wisconsin Conservation Congress, the state’s official citizen advisory group on natural resource issues. At the time, he said the goal was to safeguard whitetail deer hunting.

“We need to protect Wisconsin’s hunting traditions and long-standing heritage by working together to contain the spread of chronic wasting disease in deer,” Walker said.

Despite that, DATCP’s citizen board, made up of Walker appointees, voted to take no action on the governor’s request for emergency rules. Now, the agency is pursuing the longer, regular rulemaking process to require double or enhanced fencing for elk and other non-whitetail farms and prohibiting farms from transporting live animals out of CWD-affected counties.

The Natural Resources Board, also staffed by Walker appointees, did proceed with an emergency rule to require enhanced fencing, including a second 8-foot tall fence or an electric fence for whitetail deer farms.

In October, the Legislature’s Republican-controlled Joint Committee for Review of Administrative Rules, which reviews agency regulations, voted to keep fencing requirements for deer farms but eliminated the DNR’s emergency rule that would have limited the movement of deer carcasses from CWD affected counties this hunting season.

While it survived the committee, the DNR fencing rule had already been amended by the agency’s citizen board to give the industry until September 2019 to comply with the new regulation.

That timing is significant because the emergency rule is set to expire Feb. 27, 2019. When DNR staff were asked whether that means deer farmers could simply wait until the rule expires to avoid enhanced fencing requirements, DNR policy initiatives advisor Scott Loomans said in an email that the agency is working on a permanent rule to avoid that.

“We are working on a companion permanent version of the CWD rule, and the goal is to have that rule in effect before or very close to when the emergency rule expires,” Loomans wrote. “Yes, the longer period of time that people have to come into compliance, under the amendment, does make the timeline for the permanent rule more important.”

The state DNR has estimated the total cost for all deer farms currently without double or enhanced fencing to be about $2.1 million. Whitetails of Wisconsin, whose members strongly oppose the requirement, has estimated the cost at more than 10 times that.

Woods and Meadow Hunting Preserve owner Scott Goetzka of Warrens, Wisconsin, said the cost of complying is too much for him and other deer farmers in the state.

“Because I feel this is politically driven — not science or veterinary science driven — two years from now, if they don’t like it or CWD keeps spreading, they’re going to come up with something else that you have to do,” Goetzka said. “They basically legislate you out of business.”

Even if farms are required to install additional fencing, that may not stop the spread, Richards said. He noted that CWD has been detected in Wisconsin inside a double-fenced facility.

“So, it’s pretty clear that even a double fence does not constitute a complete barrier to the movement of an infectious agent with CWD,” Richards said. “So, if that infectious agent can move from the outside into a captive facility across two fences, I see no reason to suspect that it could not move the other direction as well.”

Counties step in

As the state debates how to slow the spread of CWD, some local governments in Wisconsin are taking action.

This year, Bayfield and Douglas counties passed moratoriums that block new captive deer operations for one year while local officials study the industry and consider new rules.

Al Horvath of Superior, a lifelong hunter and delegate to the Wisconsin Conservation Congress, said the moratoriums were written after a deer farm in Bayfield County was found to have been stocked with animals from a farm that tested positive for the disease.

Horvath said it has been frustrating to see the lack of cooperation between DNR and DATCP — which share regulation of deer facilities — in attacking chronic wasting disease.

“It’s a state issue,” Horvath said. “They’re state entities. Yet, they’re each operating independently and acting like they’re only responsible for a certain part of it. They’re responsible to the citizens of the state for all of it. And if they can’t get together, if they can’t work with one another, they’re not going to work efficiently and get things done they need.”

Horvath, who considers himself pro-business, said he understands that many families have poured their entire life savings into the operations.

“I think that someone’s profit potential — their individual profit potential — is not sufficient to jeopardize a tradition and an entire population of animals,” Horvath said. “I just think it’s wrong.”

Hunter Paul Boehnlein of Madison was registering two deer for testing for CWD on Nov. 17, the first day of the gun-deer season, at the self-service station in Fitchburg, Wisconsin. The young doe and buck were taken in Iowa County, which has been ground zero for CWD in the state. He favors double fencing for deer farms, adding, “I don’t really understand why people are farming deer in the first place.”

Deer farmers seek answers

No matter how it got to his hunting ranches — or the state for that matter — Flees said he and other deer farmers in Wisconsin are looking to genetics to combat chronic wasting disease.

For the past year, Flees said he has been working with a researcher to breed deer with genetic markers that show resistance to CWD. Flees hopes in five years, he could have a resistant herd.

“Let us deer farmers do our work, and if we nail this resistance thing, let’s figure out how the state can maybe do the same thing in their herd.”

Other research suggests it could be quite a while until such answers are available.

“We don’t know how the CWD prion proteins might change over time to influence both the infection and mortality of different genotypes and deer populations,” according to an article co-written in June by Michael Samuel, an emeritus professor of wildlife ecology at the University of Wisconsin-Madison. “There are still many unknowns that make clear predictions about the longer-term evolution of CWD resistance difficult.”

Meanwhile, the spread of CWD across Wisconsin continues. On Nov. 15, another deer hunting ranch tested positive for the disease in Portage County, bringing the total number of facilities that have tested positive since 2002 to 24.

“I think the challenge with CWD is it’s been found both in the wild and on farms,” said Konkle, the acting state veterinarian. “We don’t know which came first and, at this point, I’m not sure it necessarily matters. It’s a challenge for both our agencies that deal with farm-raised deer and wild deer to try to manage.”

This report was collaboratively produced by Wisconsin Public Radio and the Wisconsin Center for Investigative Journalism. The nonprofit Center (www.WisconsinWatch.org) collaborates with WPR, Wisconsin Public Television, other news media and the University of Wisconsin-Madison School of Journalism and Mass Communication. All works created, published, posted or disseminated by the Center do not necessarily reflect the views or opinions of UW-Madison or any of its affiliates.

Zoology Deer Politics Economics Chronic Wasting Disease Medicine Board Farmer Farm State White-tailed Deer Elk Greg Flees




Cervid to human prion transmission 5R01NS088604-04 Update

Cervid to human prion transmission 

Kong, Qingzhong 

Case Western Reserve University, Cleveland, OH, United States

Abstract 

Prion disease is transmissible and invariably fatal. Chronic wasting disease (CWD) is the prion disease affecting deer, elk and moose, and it is a widespread and expanding epidemic affecting 22 US States and 2 Canadian provinces so far. CWD poses the most serious zoonotic prion transmission risks in North America because of huge venison consumption (>6 million deer/elk hunted and consumed annually in the USA alone), significant prion infectivity in muscles and other tissues/fluids from CWD-affected cervids, and usually high levels of individual exposure to CWD resulting from consumption of the affected animal among often just family and friends. However, we still do not know whether CWD prions can infect humans in the brain or peripheral tissues or whether clinical/asymptomatic CWD zoonosis has already occurred, and we have no essays to reliably detect CWD infection in humans. 

We hypothesize that: 

(1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues; 

(2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence; 

(3) Reliable essays can be established to detect CWD infection in humans; and 

(4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches. 

Aim 1 will prove that the classical CWD strain may infect humans in brain or peripheral lymphoid tissues at low levels by conducting systemic bioassays in a set of humanized Tg mouse lines expressing common human PrP variants using a number of CWD isolates at varying doses and routes. Experimental human CWD samples will also be generated for Aim 3. 

Aim 2 will test the hypothesis that the cervid-to-human prion transmission barrier is dependent on prion strain and influenced by the host (human) PrP sequence by examining and comparing the transmission efficiency and phenotypes of several atypical/unusual CWD isolates/strains as well as a few prion strains from other species that have adapted to cervid PrP sequence, utilizing the same panel of humanized Tg mouse lines as in Aim 1. 

Aim 3 will establish reliable essays for detection and surveillance of CWD infection in humans by examining in details the clinical, pathological, biochemical and in vitro seeding properties of existing and future experimental human CWD samples generated from Aims 1-2 and compare them with those of common sporadic human Creutzfeldt-Jakob disease (sCJD) prions. 

Aim 4 will attempt to detect clinical CWD-affected human cases by examining a significant number of brain samples from prion-affected human subjects in the USA and Canada who have consumed venison from CWD-endemic areas utilizing the criteria and essays established in Aim 3. The findings from this proposal will greatly advance our understandings on the potential and characteristics of cervid prion transmission in humans, establish reliable essays for CWD zoonosis and potentially discover the first case(s) of CWD infection in humans.

Public Health Relevance

There are significant and increasing human exposure to cervid prions because chronic wasting disease (CWD, a widespread and highly infectious prion disease among deer and elk in North America) continues spreading and consumption of venison remains popular, but our understanding on cervid-to-human prion transmission is still very limited, raising public health concerns. This proposal aims to define the zoonotic risks of cervid prions and set up and apply essays to detect CWD zoonosis using mouse models and in vitro methods. The findings will greatly expand our knowledge on the potentials and characteristics of cervid prion transmission in humans, establish reliable essays for such infections and may discover the first case(s) of CWD infection in humans.

 Funding Agency

Agency

National Institute of Health (NIH)

Institute

National Institute of Neurological Disorders and Stroke (NINDS)

Type

Research Project (R01)

Project #

5R01NS088604-04

Application #

9517118

Study Section

Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)

Program Officer Wong, May

Project Start 2015-09-30 Project End 2019-07-31 Budget Start 2018-08-01 Budget End 2019-07-31 Support Year 4 Fiscal Year 2018 Total Cost Indirect Cost Institution Name Case Western Reserve University Department Pathology Type Schools of Medicine DUNS # 077758407 City Cleveland State OH Country United States Zip Code 44106

 Related projects

NIH 2018 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University 

NIH 2017 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University 

NIH 2016 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University 

NIH 2015 R01 NS Cervid to human prion transmission Kong, Qingzhong / Case Western Reserve University $337,507




ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE

here is the latest;

PRION 2018 CONFERENCE
 
Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice 
 
Hermann M. Schatzl, Samia Hannaoui, Yo-Ching Cheng, Sabine Gilch (Calgary Prion Research Unit, University of Calgary, Calgary, Canada) Michael Beekes (RKI Berlin), Walter Schulz-Schaeffer (University of Homburg/Saar, Germany), Christiane Stahl-Hennig (German Primate Center) & Stefanie Czub (CFIA Lethbridge). 
 
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 detected in spinal cord and brain of some 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 pre-clinical 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.
 
***> 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. <***
 

READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT from this study ;
 
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. 
 
SEEMS THAT THEY FOUND Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states.
 
AND ANOTHER STUDY;
 
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..
 
IN THIS STUDY, THERE WERE autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017, AND included 104 patients.
 
SEEMS THEY FOUND THAT The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%), AND THAT The Majority of cases were male (60%), AND half of them had exposure to wild game.
 
snip...see more on Prion 2017 Macaque study from Prion 2017 Conference and other updated science on cwd tse prion zoonosis below...terry
 
 

 
just out CDC...see;


Volume 24, Number 8—August 2018

 
Research
 
Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions
 
Marcelo A. BarriaComments to Author , Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell)
 
M. A. Barria et al.
 
snip...see;
 



Molecular Barriers to Zoonotic Transmission of Prions 
 
Marcelo A. Barria, Aru Balachandran, Masanori Morita, Tetsuyuki Kitamoto, Rona Barron, Jean Manson, Richard Knight, James W. Ironside, and Mark W. Headcorresponding author 
 
snip... 
 
The conversion of human PrPC by CWD brain homogenate in PMCA reactions was less efficient when the amino acid at position 129 was valine rather than methionine. 
 
***Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype. 
 
snip... 
 
However, we can say with confidence that under the conditions used here, none of the animal isolates tested were as efficient as C-type BSE in converting human PrPC, which is reassuring. 
 
***Less reassuring is the finding that there is no absolute barrier to the conversion of human PrPC by CWD prions in a protocol using a single round of PMCA and an entirely human substrate prepared from the target organ of prion diseases, the brain. 


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884726/


THURSDAY, OCTOBER 04, 2018 

Cervid to human prion transmission 5R01NS088604-04 Update



SATURDAY, NOVEMBER 10, 2018 

cwd, bse, scrapie, cjd, tse prion updated November 10 2018



THURSDAY, OCTOBER 25, 2018 

***> Norway New additional requirements for imports of hay and straw for animal feed from countries outside the EEA due to CWD TSE Prion



Prion 2017 
 
Conference Abstracts CWD 2017 PRION CONFERENCE 
 
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress 
 
Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 
 
University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen 
 
This is a progress report of a project which started in 2009. 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation. 
 
PRION 2017 
 
DECIPHERING NEURODEGENERATIVE DISORDERS 
 
Subject: PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS VIDEO 
 
PRION 2017 
 
CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS 
 
*** PRION 2017 CONFERENCE VIDEO 
 
 

TUESDAY, JUNE 13, 2017 
 
PRION 2017 CONFERENCE ABSTRACT 
 
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress 
 
 
 
Risk Advisory Opinion: Potential Human Health Risks from Chronic Wasting Disease CFIA, PHAC, HC (HPFB and FNIHB), INAC, Parks Canada, ECCC and AAFC 
 
http://chronic-wasting-disease.blogspot.com/2017/07/risk-advisory-opinion-potential-human.html


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

***> SEE;

***> These observations strongly suggest that the spectrum of human prion diseases may extend the current field restricted to the phenotypes associated to protease-resistant PrP, and may notably include spinal cord diseases. <***


Unexpected prion phenotypes in experimentally transfused animals: predictive models for humans? 

Emmanuel E. Comoy, Jacqueline Mikol & Jean-Philippe Deslys 

Pages 162-169 | Received 06 Jul 2018, Accepted 24 Jul 2018, Accepted author version posted online: 06 Aug 2018, Published online: 16 Aug 2018

ABSTRACT 

The recently reevaluated high prevalence of healthy carriers (1/2,000 in UK) of variant Creutzfeldt-Jakob Disease (v-CJD), whose blood might be infectious, suggests that the evolution of this prion disease might not be under full control as expected. 

After experimental transfusion of macaques and conventional mice with blood derived from v-CJD exposed (human and animal) individuals, we confirmed in these both models the transmissibility of v-CJD, but we also observed unexpected neurological syndromes transmissible by transfusion: despite their prion etiology confirmed through transmission experiments, these original cases would escape classical prion diagnosis, notably in the absence of detectable abnormal PrP with current techniques. 

It is noteworthy that macaques developed an original, yet undescribed myelopathic syndrome associating demyelination and pseudo-necrotic lesions of spinal cord, brainstem and optical tract without affecting encephalon, which is rather evocative of spinal cord disease than prion disease in human medicine. 

These observations strongly suggest that the spectrum of human prion diseases may extend the current field restricted to the phenotypes associated to protease-resistant PrP, and may notably include spinal cord diseases.

KEYWORDS: (5-10): prion, vCJD, macaque, mouse, spinal cord disease, myelopathy, transfusion, abnormal PrP, demyelination, spongiform change

This article refers to:

Additional information

Funding

The original laboratory work was funded by European Commission [Fifth Framework Programme, QLK1-CT-2002-01096], French Research Funding Agency (Agence Nationale de la Recherche, ANR) [ANR-10-BLAN-1330 01], Health Canada [4500216567] and MacoPharma.



WEDNESDAY, OCTOBER 17, 2018 

PRICE OF TSE PRION POKER GOES UP spectrum of human prion diseases may extend the current field and may notably include spinal cord diseases



ZOONOTIC, ZOONOSIS, CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION 

10. ZOONOTIC, ZOONOSIS, CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION AKA MAD DEER ELK DISEASE IN HUMANS, has it already happened, that should be the question... 

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

EFSA Panel on Biological Hazards (BIOHAZ) Antonia Ricci Ana Allende Declan Bolton Marianne Chemaly Robert Davies Pablo Salvador Fernández Escámez ... See all authors 

First published: 17 January 2018 https://doi.org/10.2903/j.efsa.2018.5132 ;

also, see; 

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

snip... 

The tissue distribution of infectivity in CWD‐infected cervids is now known to extend beyond CNS and lymphoid tissues. While the removal of these specific tissues from the food chain would reduce human dietary exposure to infectivity, exclusion from the food chain of the whole carcass of any infected animal would be required to eliminate human dietary exposure. 
https://efsa.onlinelibrary..wiley.com/doi/full/10.2903/j.efsa.2018.5132

zoonosis zoonotic cervid tse prion cwd to humans, preparing for the storm 

***An alternative to modeling the species barrier is the cell-free conversion assay which points to CWD as the animal prion disease with the greatest zoonotic potential, after (and very much less than) BSE.116*** 
https://www.tandfonline.com/doi/pdf/10.4161/pri.29237
 
To date there is no direct evidence that CWD has been or can be transmitted from animals to humans. 

However, initial findings from a laboratory research project funded by the Alberta Prion Research Institute (APRI) and Alberta Livestock Meat Agency (ALMA), and led by a Canadian Food Inspection Agency (CFIA) scientist indicate that CWD has been transmitted to cynomolgus macaques (the non-human primate species most closely related to humans that may be used in research), through both the intracranial and oral routes of exposure. 

Both infected brain and muscle tissues were found to transmit disease. 

Health Canada’s Health Products and Food Branch (HPFB) was asked to consider the impact of these findings on the Branch’s current position on CWD in health products and foods. 

Summary and Recommendation: 

snip...

Health Portfolio partners were recently made aware of initial findings from a research project led by a CFIA scientist that have demonstrated that cynomolgus macaques can be infected via intracranial exposure and oral gavage with CWD infected muscle. 

These findings suggest that CWD, under specific experimental conditions, has the potential to cross the human species barrier, including by enteral feeding of CWD infected muscle. 
https://www.thetyee.ca/Documents/2017/06/24/Risk-Advisory-Opinion-CWD-2017.pdf


*** WDA 2016 NEW YORK *** 

We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. 

In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. 

***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. 

Student Presentations Session 2 

The species barriers and public health threat of CWD and BSE prions 

Ms. Kristen Davenport1, Dr. Davin Henderson1, Dr. Candace Mathiason1, Dr. Edward Hoover1 1Colorado State University 

Chronic wasting disease (CWD) is spreading rapidly through cervid populations in the USA. Bovine spongiform encephalopathy (BSE, mad cow disease) arose in the 1980s because cattle were fed recycled animal protein. 

These and other prion diseases are caused by abnormal folding of the normal prion protein (PrP) into a disease causing form (PrPd), which is pathogenic to nervous system cells and can cause subsequent PrP to misfold. CWD spreads among cervids very efficiently, but it has not yet infected humans. On the other hand, BSE was spread only when cattle consumed infected bovine or ovine tissue, but did infect humans and other species. 

The objective of this research is to understand the role of PrP structure in cross-species infection by CWD and BSE. To study the propensity of each species’ PrP to be induced to misfold by the presence of PrPd from verious species, we have used an in vitro system that permits detection of PrPd in real-time. 

We measured the conversion efficiency of various combinations of PrPd seeds and PrP substrate combinations. 

We observed the cross-species behavior of CWD and BSE, in addition to feline-adapted CWD and BSE. We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. 

***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. CWD is unique among prion diseases in its rapid spread in natural populations. BSE prions are essentially unaltered upon passage to a new species, while CWD adapts to the new species. This adaptation has consequences for surveillance of humans exposed to CWD. Wildlife Disease Risk Communication Research Contributes to Wildlife Trust Administration Exploring perceptions about chronic wasting disease risks among wildlife and agriculture professionals and stakeholders
http://www.wda2016.org/uploads/5/8/6/1/58613359/wda_2016_conference_proceedings_low_res.pdf
 

CDC CWD 2018 TRANSMISSION
https://www.cdc.gov/prions/cwd/transmission.html


TUESDAY, SEPTEMBER 12, 2017 

CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat 
http://chronic-wasting-disease.blogspot.com/2017/09/cdc-now-recommends-strongly-consider.html


SATURDAY, JANUARY 27, 2018 

CDC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE REPORT USA JANUARY 2018
http://chronic-wasting-disease.blogspot.com/2018/01/cdc-chronic-wasting-disease-cwd-tse.html


Subject: CDC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE REPORT USA JANUARY 2018

CHRONIC WASTING DISEASE CWD TSE PRION IS THE USA AND NORTH AMERICA'S MAD COW DISEASE. 

THE USDA INC ET AL WORKED VERY HARD CONCEALING BSE TSE PRION IN CATTLE. they almost succeeded $$$

BUT CWD TSE PRION IN CERVIDS IS A DIFFERENT BEAST, THE COVER UP THERE, USDA INC COULD NOT CONTAIN.

SPORADIC CJD IS 85%+ OF ALL HUMAN TSE PRION DISEASE.

SPORADIC CJD HAS NOW BEEN LINKED TO TYPICAL AND ATYPICAL BSE, SCRAPIE, AND CWD.

SPORADIC/SPONTANEOUS TSE HAS NEVER BEEN PROVEN.

***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
https://www.nature.com/articles/srep11573 


CDC CWD TSE PRION UPDATE USA JANUARY 2018

As of January 2018, CWD in free-ranging deer, elk and/or moose has been reported in at least 22 states in the continental United States, as well as two provinces in Canada. In addition, CWD has been reported in reindeer and moose in Norway, and a small number of imported cases have been reported in South Korea. The disease has also been found in farmed deer and elk. CWD was first identified in captive deer in the late 1960s in Colorado and in wild deer in 1981. By the 1990s, it had been reported in surrounding areas in northern Colorado and southern Wyoming. Since 2000, the area known to be affected by CWD in free-ranging animals has increased to at least 22 states, including states in the Midwest, Southwest, and limited areas on the East Coast.. It is possible that CWD may also occur in other states without strong animal surveillance systems, but that cases haven’t been detected yet. Once CWD is established in an area, the risk can remain for a long time in the environment. The affected areas are likely to continue to expand. Nationwide, the overall occurrence of CWD in free-ranging deer and elk is relatively low. However, in several locations where the disease is established, infection rates may exceed 10 percent (1 in 10), and localized infection rates of more than 25 percent (1 in 4) have been reported. The infection rates among some captive deer can be much higher, with a rate of 79% (nearly 4 in 5) reported from at least one captive herd. As of January 2018, there were 186 counties in 22 states with reported CWD in free-ranging cervids... 

Chronic Wasting Disease Among Free-Ranging Cervids by County, United States, January 2018 

snip.... 
https://www.cdc.gov/prions/cwd/occurrence.html


*** 2017-2018 CWD TSE Prion UPDATE
https://www.cdc.gov/prions/cwd/occurrence.html


*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies. 
http://cdmrp.army.mil/prevfunded/nprp/NPRP_Summit_Final_Report.pdf


Transmission Studies

Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}....TSS

resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.

snip...
https://web.archive.org/web/20090506002237/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf


Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿ 

Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations

In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.
http://jvi.asm.org/content/83/18/9608.full


Prions in Skeletal Muscles of Deer with Chronic Wasting Disease 

Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.
http://science.sciencemag.org/content/311/5764/1117.long


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

see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ???? “Our conclusion stating that we found no strong evidence of CWD transmission to humans”

From: TSS (216-119-163-189.ipset45.wt.net)

Subject: CWD aka MAD DEER/ELK TO HUMANS ???

Date: September 30, 2002 at 7:06 am PST

From: "Belay, Ermias"

To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"

Sent: Monday, September 30, 2002 9:22 AM

Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Dear Sir/Madam,

In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.

Ermias Belay, M.D. Centers for Disease Control and Prevention

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

From: Sent: Sunday, September 29, 2002 10:15 AM

To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV

Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS

Thursday, April 03, 2008

A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008 Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ.

snip...

*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,

snip... full text ;
http://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html


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


key word here is 'reported'. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can't, and it's as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it's being misdiagnosed as sporadic CJD. ...terry 


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

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).*** 

http://www.tandfonline.com/doi/full/10.4161/pri.28124?src=recsys
http://www.tandfonline.com/doi/pdf/10.4161/pri.28124?needAccess=true
https://wwwnc.cdc.gov/eid/article/20/1/13-0858_article


SEE; Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Monday, May 23, 2011

CDC Assesses Potential Human Exposure to Prion Diseases Travel Warning

Public release date: 23-May-2011

Contact: Francesca Costanzo adajmedia@elsevier.com 215-239-3249 Elsevier Health Sciences

CDC assesses potential human exposure to prion diseases Study results reported in the Journal of the American Dietetic Association Philadelphia, PA, May 23, 2011 – Researchers from the Centers for Disease Control and Prevention (CDC) have examined the potential for human exposure to prion diseases, looking at hunting, venison consumption, and travel to areas in which prion diseases have been reported in animals. Three prion diseases in particular – bovine spongiform encephalopathy (BSE or “Mad Cow Disease”), variant Creutzfeldt-Jakob disease (vCJD), and chronic wasting disease (CWD) – were specified in the investigation. The results of this investigation are published in the June issue of the Journal of the American Dietetic Association.

“While prion diseases are rare, they are generally fatal for anyone who becomes infected. More than anything else, the results of this study support the need for continued surveillance of prion diseases,” commented lead investigator Joseph Y. Abrams, MPH, National Center for Emerging and Zoonotic Infectious Diseases, CDC, Atlanta.”But it’s also important that people know the facts about these diseases, especially since this study shows that a good number of people have participated in activities that may expose them to infection-causing agents.”

Although rare, human prion diseases such as CJD may be related to BSE. Prion (proteinaceous infectious particles) diseases are a group of rare brain diseases that affect humans and animals. When a person gets a prion disease, brain function is impaired. This causes memory and personality changes, dementia, and problems with movement. All of these worsen over time. These diseases are invariably fatal. Since these diseases may take years to manifest, knowing the extent of human exposure to possible prion diseases could become important in the event of an outbreak.

CDC investigators evaluated the results of the 2006-2007 population survey conducted by the Foodborne Diseases Active Surveillance Network (FoodNet). This survey collects information on food consumption practices, health outcomes, and demographic characteristics of residents of the participating Emerging Infections Program sites. The survey was conducted in Connecticut, Georgia, Maryland, Minnesota, New Mexico, Oregon, and Tennessee, as well as five counties in the San Francisco Bay area, seven counties in the Greater Denver area, and 34 counties in western and northeastern New York.

Survey participants were asked about behaviors that could be associated with exposure to the agents causing BSE and CWD, including travel to the nine countries considered to be BSE-endemic (United Kingdom, Republic of Ireland, France, Portugal, Switzerland, Italy, the Netherlands, Germany, Spain) and the cumulative length of stay in each of those countries. Respondents were asked if they ever had hunted for deer or elk, and if that hunting had taken place in areas considered to be CWD-endemic (northeastern Colorado, southeastern Wyoming or southwestern Nebraska). They were also asked if they had ever consumed venison, the frequency of consumption, and whether the meat came from the wild.

The proportion of survey respondents who reported travel to at least one of the nine BSE endemic countries since 1980 was 29.5%. Travel to the United Kingdom was reported by 19.4% of respondents, higher than to any other BSE-endemic country. Among those who traveled, the median duration of travel to the United Kingdom (14 days) was longer than that of any other BSE-endemic country. Travelers to the UK were more likely to have spent at least 30 days in the country (24.9%) compared to travelers to any other BSE endemic country. The prevalence and extent of travel to the UK indicate that health concerns in the UK may also become issues for US residents.

The proportion of survey respondents reporting having hunted for deer or elk was 18.5% and 1.2% reported having hunted for deer or elk in CWD-endemic areas. Venison consumption was reported by 67.4% of FoodNet respondents, and 88.6% of those reporting venison consumption had obtained all of their meat from the wild. These findings reinforce the importance of CWD surveillance and control programs for wild deer and elk to reduce human exposure to the CWD agent. Hunters in CWD-endemic areas are advised to take simple precautions such as: avoiding consuming meat from sickly deer or elk, avoiding consuming brain or spinal cord tissues, minimizing the handling of brain and spinal cord tissues, and wearing gloves when field-dressing carcasses.

According to Abrams, “The 2006-2007 FoodNet population survey provides useful information should foodborne prion infection become an increasing public health concern in the future. The data presented describe the prevalence of important behaviors and their associations with demographic characteristics. Surveillance of BSE, CWD, and human prion diseases are critical aspects of addressing the burden of these diseases in animal populations and how that may relate to human health.”

###

The article is “Travel history, hunting, and venison consumption related to prion disease exposure, 2006-2007 FoodNet population survey” by Joseph Y. Abrams, MPH; Ryan A. Maddox, MPH; Alexis R Harvey, MPH; Lawrence B. Schonberger, MD; and Ermias D. Belay, MD. It appears in the Journal of the American Dietetic Association, Volume 111, Issue 6 (June 2011) published by Elsevier.

In an accompanying podcast CDC’s Joseph Y. Abrams discusses travel, hunting, and eating venison in relation to prion diseases. It is available at http://adajournal.org/content/podcast.
http://www.eurekalert.org/pub_releases/2011-05/ehs-cap051811.php


Thursday, May 26, 2011

Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.

Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Joseph Y. Abrams, MPH, Ryan A. Maddox, MPH , Alexis R. Harvey, MPH , Lawrence B. Schonberger, MD , Ermias D. Belay, MD

Accepted 15 November 2010. Abstract Full Text PDF References .

Abstract

The transmission of bovine spongiform encephalopathy (BSE) to human beings and the spread of chronic wasting disease (CWD) among cervids have prompted concerns about zoonotic transmission of prion diseases. Travel to the United Kingdom and other European countries, hunting for deer or elk, and venison consumption could result in the exposure of US residents to the agents that cause BSE and CWD. The Foodborne Diseases Active Surveillance Network 2006-2007 population survey was used to assess the prevalence of these behaviors among residents of 10 catchment areas across the United States. Of 17,372 survey respondents, 19.4% reported travel to the United Kingdom since 1980, and 29.5% reported travel to any of the nine European countries considered to be BSE-endemic since 1980. The proportion of respondents who had ever hunted deer or elk was 18.5%, and 1.2% had hunted deer or elk in a CWD–endemic area. More than two thirds (67.4%) reported having ever eaten deer or elk meat. Respondents who traveled spent more time in the United Kingdom (median 14 days) than in any other BSE-endemic country. Of the 11,635 respondents who had consumed venison, 59.8% ate venison at most one to two times during their year of highest consumption, and 88.6% had obtained all of their meat from the wild. The survey results were useful in determining the prevalence and frequency of behaviors that could be important factors for foodborne prion transmission.
http://www.adajournal.org/article/S0002-8223(11)00278-1/abstract


PLUS, THE CDC DID NOT PUT THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ; 

Thursday, May 26, 2011

Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/travel-history-hunting-and-venison.html


NOR IS THE FDA recalling this CWD positive elk meat for the well being of the dead elk ;

Wednesday, March 18, 2009

Noah's Ark Holding, LLC, Dawson, MN RECALL Elk products contain meat derived from an elk confirmed to have CWD NV, CA, TX, CO, NY, UT, FL, OK RECALLS AND FIELD CORRECTIONS: FOODS CLASS II
http://chronic-wasting-disease.blogspot.com/2009/03/noahs-ark-holding-llc-dawson-mn-recall.html

 Transmissible Spongiform Encephalopathies

Spongiform Encephalopathy in Captive Wild ZOO BSE INQUIRY
https://web.archive.org/web/20090506001201/http://www.bseinquiry.gov.uk/files/mb/m09a/tab03.pdf


BSE INQUIRY

CJD9/10022

October 1994

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane 

BerksWell Coventry CV7 7BZ

Dear Mr Elmhirst,

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.

The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended.. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.

The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.

The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.

I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.
http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf


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

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

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

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

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

snip...

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

snip...

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

snip...

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

snip...see full report ;

https://web.archive.org/web/20170126073306/http://collections..europarchive..org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf


THURSDAY, OCTOBER 04, 2018 

***> Cervid to human prion transmission 5R01NS088604-04 Update




ALSO, I FIND THIS VERY DISTURBING...SEE;


***> Prion 2018 P74 High Prevalence of CWD prions in male reproductive samples 

Carlos Kramm (1,2), Ruben Gomez-Gutierrez (1,3), Tracy Nichols (4), Claudio Soto (1) and Rodrigo Morales (1) 




READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT Protein Misfolding Cyclic Amplification PMCA results showed positive CWD prion detection in testes, epididymis and seminal fluid samples. seems also the scientists are worried about any potential mechanisms of CWD spreading and they want to decrease putative interindividual transmission associated to insemination using CWD contaminated specimens, if that might occur under natural conditions. i have been concerned about this for some time with BSE super-ovulation and since;

 PrPSc detection and infectivity in semen from scrapie-infected sheep




PITUITARY EXTRACT

This was used to help cows super ovulate. This tissue was considered to be of greatest risk of containing BSE and consequently transmitting the disease...








MANAGEMENT IN CONFIDENCE

CERTIFIED BSE-FREE HERDS FOR SOURCE OF MATERIAL FOR BIOLOGICAL PRODUCTS



Singeltary ***> U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001



HAVE YOU BEEN THUNDERSTRUCK? 

SUNDAY, AUGUST 02, 2015 

TEXAS CWD, Have you been ThunderStruck, deer semen, straw bred bucks, super ovulation, and the potential TSE Prion connection, what if?

Court papers state that in February 2007, Favero acquired 184 straws of whitetail deer semen valued at about $92,000 from a buck named “Diablo'” that he knew had been illegally taken out of Texas, and again in January 2008 took another 110 straws of semen from a buck named “Thunderstruck.” (Read more in the court paper posted at the bottom of this entry.)



SUNDAY, AUGUST 19, 2018 

Texas Deer Farms, Growing Freakish Antlers, and CWD TSE Prion aka mad deer disease



FRIDAY, MARCH 30, 2018 

Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification Program Standards Singeltary Submission March 30, 2018

Terry S. Singeltary Sr., Bacliff, Texas USA 77518 flounder9@verizon....net 

Attachments (1) Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification Program Standards Singeltary View Attachment:View as format pdf 



https://www.regulations.gov/docketBrowser?rpp=25&so=DESC&sb=commentDueDate&po=0&dct=PS&D=APHIS-2018-0011



Friday, December 14, 2012

DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012

snip.....

In the USA, under the Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law.

Animals considered at high risk for CWD include:

1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and

2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.

Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants.

The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES. It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011.

Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB.

There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.

snip.....

36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011).

The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE).

Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison.

snip.....

The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008).

snip.....

In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion.

snip.....

In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible... For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates.

snip.....

Therefore, it is considered that farmed and park deer may have a higher probability of exposure to CWD transferred to the environment than wild deer given the restricted habitat range and higher frequency of contact with tourists and returning GB residents.

snip.....



TUESDAY, APRIL 18, 2017 

*** EXTREME USA FDA PART 589 TSE PRION FEED LOOP HOLE STILL EXIST, AND PRICE OF POKER GOES UP ***



TUESDAY, JANUARY 17, 2017 

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION



THIS April, 4, 2017 

violation of the mad cow 21 CFR 589.2000 OAI is very serious for the great state of Michigan, some 20 years post FDA mad cow feed of August 1997. if would most likely take a FOIA request and a decade of wrangling to find out more. 

TUESDAY, JANUARY 17, 2017

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEEDVIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE 2016 to 2017 BSE TSE PRION 

I would kindly like to comment on this FDA BSE/Ruminant Feed Inspections Firms Inventory (excel format)4 format, for reporting these breaches of BSE TSE prion protocols, from the extensive mad cow feed ban warning letters the fda use to put out for each violations. simply put, this excel format sucks, and the FDA et al intentionally made it this difficult to follow the usda fda mad cow follies. this is an intentional format to make it as difficult as possible to follow these breaches of the mad cow TSE prion safety feed protocols. to have absolutely no chronological or numerical order, and to format such violations in a way that they are almost impossible to find, says a lot about just how far the FDA and our fine federal friends will go through to hide these continued violations of the BSE TSE prion mad cow feed ban, and any breaches of protocols there from. once again, the wolf guarding the henhouse $$$

NAI = NO ACTION INDICATED

OAI = OFFICIAL ACTION INDICATED

VAI = VOLUNTARY ACTION INDICATED

RTS = REFERRED TO STATE

OAI (Official Action Indicated) when inspectors find significant objectionable conditions or practices and believe that regulatory sanctions are warranted to address the establishment’s lack of compliance with the regulation. An example of an OAI classification would be findings of manufacturing procedures insufficient to ensure that ruminant feed is not contaminated with prohibited material. Inspectors will promptly re-inspect facilities classified OAI after regulatory sanctions have been applied to determine whether the corrective actions are adequate to address the objectionable conditions. 

2016



ONE more thing, please remember, the label does not have to say ''deer ration'' for cervid to be pumped up with. you can get the same ''high protein'' from many sources of high protein feed for animals other than cattle, and feed them to cervid...

Saturday, August 29, 2009

FOIA REQUEST FEED RECALL 2009 Product may have contained prohibited materials Bulk Whole Barley, Recall # V-256-2009



Friday, September 4, 2009

FOIA REQUEST ON FEED RECALL PRODUCT 429,128 lbs. feed for ruminant animals may have been contaminated with prohibited material Recall # V-258-2009



WEDNESDAY, JULY 11, 2018 

CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS FDA EMERGENCY REQUEST FOR RULE CHANGE USA Section 21 C.F.R. 589.2000

http://transmissiblespongiformencephalopathy.blogspot.com/2018/07/confidential-in-confidence-spongiform.html


TUESDAY, JULY 10, 2018
 
CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS
 
*** ''but feeding of other ruminant protein, including scrapie-infected sheep, can continue to pigs.''
 
CONFIDENTIAL SPONGIFORM ENCEPHALOPATHY OF PIGS
 
http://madporcinedisease.blogspot.com/2018/07/confidential-in-confidence-spongiform.html


O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations 

Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France 

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). 

Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods. 

*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period, 

***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014), 

***is the third potentially zoonotic PD (with BSE and L-type BSE), 

***thus questioning the origin of human sporadic cases. 

We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health. 

=============== 

***thus questioning the origin of human sporadic cases*** 

=============== 

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals. 

============== 
https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf 

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

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

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20 


PRION 2016 TOKYO

Saturday, April 23, 2016

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

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

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,

Natalia Fernandez-Borges a. and Alba Marin-Moreno a

"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France

Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion.. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.

To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.

These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.

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

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

These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20


why do we not want to do TSE transmission studies on chimpanzees $

5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

snip...

R. BRADLEY
https://web.archive.org/web/20170126051158/http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf


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

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

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

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains. 
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160


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

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

Emmanuel E. Comoy, Jacqueline Mikol, Sophie Luccantoni-Freire, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Valérie Durand, Capucine Dehen, Olivier Andreoletti, Cristina Casalone, Juergen A. Richt, Justin J. Greenlee, Thierry Baron, Sylvie L. Benestad, Paul Brown & Jean-Philippe Deslys Scientific Reports volume 5, Article number: 11573 (2015) | Download Citation

Abstract 

Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie.

SNIP...

Discussion We describe the transmission of spongiform encephalopathy in a non-human primate inoculated 10 years earlier with a strain of sheep c-scrapie. Because of this extended incubation period in a facility in which other prion diseases are under study, we are obliged to consider two alternative possibilities that might explain its occurrence. We first considered the possibility of a sporadic origin (like CJD in humans). Such an event is extremely improbable because the inoculated animal was 14 years old when the clinical signs appeared, i.e. about 40% through the expected natural lifetime of this species, compared to a peak age incidence of 60–65 years in human sporadic CJD, or about 80% through their expected lifetimes. Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.

The second possibility is a laboratory cross-contamination. Three facts make this possibility equally unlikely. First, handling of specimens in our laboratory is performed with fastidious attention to the avoidance of any such cross-contamination. Second, no laboratory cross-contamination has ever been documented in other primate laboratories, including the NIH, even between infected and uninfected animals housed in the same or adjacent cages with daily intimate contact (P. Brown, personal communication). Third, the cerebral lesion profile is different from all the other prion diseases we have studied in this model19, with a correlation between cerebellar lesions (massive spongiform change of Purkinje cells, intense PrPres staining and reactive gliosis26) and ataxia. The iron deposits present in the globus pallidus are a non specific finding that have been reported previously in neurodegenerative diseases and aging27. Conversely, the thalamic lesion was reminiscent of a metabolic disease due to thiamine deficiency28 but blood thiamine levels were within normal limits (data not shown). The preferential distribution of spongiform change in cortex associated with a limited distribution in the brainstem is reminiscent of the lesion profile in MM2c and VV1 sCJD patients29, but interspecies comparison of lesion profiles should be interpreted with caution. It is of note that the same classical scrapie isolate induced TSE in C57Bl/6 mice with similar incubation periods and lesional profiles as a sample derived from a MM1 sCJD patient30.

We are therefore confident that the illness in this cynomolgus macaque represents a true transmission of a sheep c-scrapie isolate directly to an old-world monkey, which taxonomically resides in the primate subdivision (parvorder of catarrhini) that includes humans. With an homology of its PrP protein with humans of 96.4%31, cynomolgus macaque constitutes a highly relevant model for assessing zoonotic risk of prion diseases. Since our initial aim was to show the absence of transmission of scrapie to macaques in the worst-case scenario, we obtained materials from a flock of naturally-infected sheep, affecting animals with different genotypes32. This c-scrapie isolate exhibited complete transmission in ARQ/ARQ sheep (332 ± 56 days) and Tg338 transgenic mice expressing ovine VRQ/VRQ prion protein (220 ± 5 days) (O. Andreoletti, personal communication). From the standpoint of zoonotic risk, it is important to note that sheep with c-scrapie (including the isolate used in our study) have demonstrable infectivity throughout their lymphoreticular system early in the incubation period of the disease (3 months-old for all the lymphoid organs, and as early as 2 months-old in gut-associated lymph nodes)33. In addition, scrapie infectivity has been identified in blood34, milk35 and skeletal muscle36 from asymptomatic but scrapie infected small ruminants which implies a potential dietary exposure for consumers.

Two earlier studies have reported the occurrence of clinical TSE in cynomolgus macaques after exposures to scrapie isolates. In the first study, the “Compton” scrapie isolate (derived from an English sheep) and serially propagated for 9 passages in goats did not transmit TSE in cynomolgus macaque, rhesus macaque or chimpanzee within 7 years following intracerebral challenge1; conversely, after 8 supplementary passages in conventional mice, this “Compton” isolate induced TSE in a cynomolgus macaque 5 years after intracerebral challenge, but rhesus macaques and chimpanzee remained asymptomatic 8.5 years post-exposure8. However, multiple successive passages that are classically used to select laboratory-adapted prion strains can significantly modify the initial properties of a scrapie isolate, thus questioning the relevance of zoonotic potential for the initial sheep-derived isolate. The same isolate had also induced disease into squirrel monkeys (new-world monkey)9. A second historical observation reported that a cynomolgus macaque developed TSE 6 years post-inoculation with brain homogenate from a scrapie-infected Suffolk ewe (derived from USA), whereas a rhesus macaque and a chimpanzee exposed to the same inoculum remained healthy 9 years post-exposure1. This inoculum also induced TSE in squirrel monkeys after 4 passages in mice. Other scrapie transmission attempts in macaque failed but had more shorter periods of observation in comparison to the current study. Further, it is possible that there are differences in the zoonotic potential of different scrapie strains.

The most striking observation in our study is the extended incubation period of scrapie in the macaque model, which has several implications. Firstly, our observations constitute experimental evidence in favor of the zoonotic potential of c-scrapie, at least for this isolate that has been extensively studied32,33,34,35,36. The cross-species zoonotic ability of this isolate should be confirmed by performing duplicate intracerebral exposures and assessing the transmissibility by the oral route (a successful transmission of prion strains through the intracerebral route may not necessarily indicate the potential for oral transmission37). However, such confirmatory experiments may require more than one decade, which is hardly compatible with current general management and support of scientific projects; thus this study should be rather considered as a case report.

Secondly, transmission of c-BSE to primates occurred within 8 years post exposure for the lowest doses able to transmit the disease (the survival period after inoculation is inversely proportional to the initial amount of infectious inoculum). The occurrence of scrapie 10 years after exposure to a high dose (25 mg) of scrapie-infected sheep brain suggests that the macaque has a higher species barrier for sheep c-scrapie than c-BSE, although it is notable that previous studies based on in vitro conversion of PrP suggested that BSE and scrapie prions would have a similar conversion potential for human PrP38.

Thirdly, prion diseases typically have longer incubation periods after oral exposure than after intracerebral inoculations: since humans can develop Kuru 47 years after oral exposure39, an incubation time of several decades after oral exposure to scrapie would therefore be expected, leading the disease to occur in older adults, i.e. the peak age for cases considered to be sporadic disease, and making a distinction between scrapie-associated and truly sporadic disease extremely difficult to appreciate.

Fourthly, epidemiologic evidence is necessary to confirm the zoonotic potential of an animal disease suggested by experimental studies. A relatively short incubation period and a peculiar epidemiological situation (e.g., all the first vCJD cases occurring in the country with the most important ongoing c-BSE epizootic) led to a high degree of suspicion that c-BSE was the cause of vCJD. Sporadic CJD are considered spontaneous diseases with an almost stable and constant worldwide prevalence (0.5–2 cases per million inhabitants per year), and previous epidemiological studies were unable to draw a link between sCJD and classical scrapie6,7,40,41, even though external causes were hypothesized to explain the occurrence of some sCJD clusters42,43,44. However, extended incubation periods exceeding several decades would impair the predictive values of epidemiological surveillance for prion diseases, already weakened by a limited prevalence of prion diseases and the multiplicity of isolates gathered under the phenotypes of “scrapie” and “sporadic CJD”.

Fifthly, considering this 10 year-long incubation period, together with both laboratory and epidemiological evidence of decade or longer intervals between infection and clinical onset of disease, no premature conclusions should be drawn from negative transmission studies in cynomolgus macaques with less than a decade of observation, as in the aforementioned historical transmission studies of scrapie to primates1,8,9. Our observations and those of others45,46 to date are unable to provide definitive evidence regarding the zoonotic potential of CWD, atypical/Nor98 scrapie or H-type BSE. The extended incubation period of the scrapie-affected macaque in the current study also underscores the limitations of rodent models expressing human PrP for assessing the zoonotic potential of some prion diseases since their lifespan remains limited to approximately two years21,47,48. This point is illustrated by the fact that the recently reported transmission of scrapie to humanized mice was not associated with clinical signs for up to 750 days and occurred in an extreme minority of mice with only a marginal increase in attack rate upon second passage13. The low attack rate in these studies is certainly linked to the limited lifespan of mice compared to the very long periods of observation necessary to demonstrate the development of scrapie. Alternatively, one could estimate that a successful second passage is the result of strain adaptation to the species barrier, thus poorly relevant of the real zoonotic potential of the original scrapie isolate of sheep origin49. The development of scrapie in this primate after an incubation period compatible with its lifespan complements the study conducted in transgenic (humanized) mice; taken together these studies suggest that some isolates of sheep scrapie can promote misfolding of the human prion protein and that scrapie can develop within the lifespan of some primate species.

In addition to previous studies on scrapie transmission to primate1,8,9 and the recently published study on transgenic humanized mice13, our results constitute new evidence for recommending that the potential risk of scrapie for human health should not be dismissed. Indeed, human PrP transgenic mice and primates are the most relevant models for investigating the human transmission barrier. To what extent such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. During the past decades, many protective measures have been successfully implemented to protect cattle from the spread of c-BSE, and some of these measures have been extended to sheep and goats to protect from scrapie according to the principle of precaution. Since cases of c-BSE have greatly reduced in number, those protective measures are currently being challenged and relaxed in the absence of other known zoonotic animal prion disease. We recommend that risk managers should be aware of the long term potential risk to human health of at least certain scrapie isolates, notably for lymphotropic strains like the classical scrapie strain used in the current study. Relatively high amounts of infectivity in peripheral lymphoid organs in animals infected with these strains could lead to contamination of food products produced for human consumption. Efforts should also be maintained to further assess the zoonotic potential of other animal prion strains in long-term studies, notably lymphotropic strains with high prevalence like CWD, which is spreading across North America, and atypical/Nor98 scrapie (Nor98)50 that was first detected in the past two decades and now represents approximately half of all reported cases of prion diseases in small ruminants worldwide, including territories previously considered as scrapie free.. Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.


Singeltary on Scrapie and human transmission way back, see;



***> CONGRESSIONAL ABSTRACTS PRION CONFERENCE 2018 <***

***> P69 Experimental transmission of CWD from white-tailed deer to co-housed reindeer 

Mitchell G (1), Walther I (1), Staskevicius A (1), Soutyrine A (1), Balachandran A (1) 

(1) National & OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada. 

Chronic wasting disease (CWD) continues to be detected in wild and farmed cervid populations of North America, affecting predominantly white-tailed deer, mule deer and elk. Extensive herds of wild caribou exist in northern regions of Canada, although surveillance has not detected the presence of CWD in this population. Oral experimental transmission has demonstrated that reindeer, a species closely related to caribou, are susceptible to CWD. Recently, CWD was detected for the first time in Europe, in wild Norwegian reindeer, advancing the possibility that caribou in North America could also become infected. Given the potential overlap in habitat between wild CWD-infected cervids and wild caribou herds in Canada, we sought to investigate the horizontal transmissibility of CWD from white-tailed deer to reindeer. 

Two white-tailed deer were orally inoculated with a brain homogenate prepared from a farmed Canadian white-tailed deer previously diagnosed with CWD. Two reindeer, with no history of exposure to CWD, were housed in the same enclosure as the white-tailed deer, 3.5 months after the deer were orally inoculated. The white-tailed deer developed clinical signs consistent with CWD beginning at 15.2 and 21 months post-inoculation (mpi), and were euthanized at 18.7 and 23.1 mpi, respectively. Confirmatory testing by immunohistochemistry (IHC) and western blot demonstrated widespread aggregates of pathological prion protein (PrPCWD) in the central nervous system and lymphoid tissues of both inoculated white-tailed deer. Both reindeer were subjected to recto-anal mucosal associated lymphoid tissue (RAMALT) biopsy at 20 months post-exposure (mpe) to the white-tailed deer. The biopsy from one reindeer contained PrPCWD confirmed by IHC. This reindeer displayed only subtle clinical evidence of disease prior to a rapid decline in condition requiring euthanasia at 22.5 mpe. Analysis of tissues from this reindeer by IHC revealed widespread PrPCWD deposition, predominantly in central nervous system and lymphoreticular tissues. Western blot molecular profiles were similar between both orally inoculated white-tailed deer and the CWD positive reindeer. Despite sharing the same enclosure, the other reindeer was RAMALT negative at 20 mpe, and PrPCWD was not detected in brainstem and lymphoid tissues following necropsy at 35 mpe. Sequencing of the prion protein gene from both reindeer revealed differences at several codons, which may have influenced susceptibility to infection. 

Natural transmission of CWD occurs relatively efficiently amongst cervids, supporting the expanding geographic distribution of disease and the potential for transmission to previously naive populations. The efficient horizontal transmission of CWD from white-tailed deer to reindeer observed here highlights the potential for reindeer to become infected if exposed to other cervids or environments infected with CWD. 




TITLE: PATHOLOGICAL FEATURES OF CHRONIC WASTING DISEASE IN REINDEER AND DEMONSTRATION OF HORIZONTAL TRANSMISSION 



 *** DECEMBER 2016 CDC EMERGING INFECTIOUS DISEASE JOURNAL CWD HORIZONTAL TRANSMISSION 



 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

Gudmundur Georgsson,1 Sigurdur Sigurdarson2 and Paul Brown3

Correspondence Gudmundur Georgsson ggeorgs@hi.is

1 Institute for Experimental Pathology, University of Iceland, Keldur v/vesturlandsveg, IS-112 Reykjavı´k, Iceland

2 Laboratory of the Chief Veterinary Officer, Keldur, Iceland

3 Bethesda, Maryland, USA Received 7 March 2006 Accepted 6 August 2006

In 1978, a rigorous programme was implemented to stop the spread of, and subsequently eradicate, sheep scrapie in Iceland. Affected flocks were culled, premises were disinfected and, after 2–3 years, restocked with lambs from scrapie-free areas. Between 1978 and 2004, scrapie recurred on 33 farms. 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. Of special interest was one farm with a small, completely self-contained flock where scrapie recurred 18 years after culling, 2 years after some lambs had been housed in an old sheephouse that had never been disinfected. Epidemiological investigation established with near certitude that the disease had not been introduced from the outside and it is concluded that the agent may have persisted in the old sheep-house for at least 16 years.

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

Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3 




Using in vitro Prion replication for high sensitive detection of prions and prionlike proteins and for understanding mechanisms of transmission. 

Claudio Soto Mitchell Center for Alzheimer's diseases and related Brain disorders, Department of Neurology, University of Texas Medical School at Houston. 

Prion and prion-like proteins are misfolded protein aggregates with the ability to selfpropagate to spread disease between cells, organs and in some cases across individuals. I n T r a n s m i s s i b l e s p o n g i f o r m encephalopathies (TSEs), prions are mostly composed by a misfolded form of the prion protein (PrPSc), which propagates by transmitting its misfolding to the normal prion protein (PrPC). The availability of a procedure to replicate prions in the laboratory may be important to study the mechanism of prion and prion-like spreading and to develop high sensitive detection of small quantities of misfolded proteins in biological fluids, tissues and environmental samples. Protein Misfolding Cyclic Amplification (PMCA) is a simple, fast and efficient methodology to mimic prion replication in the test tube. PMCA is a platform technology that may enable amplification of any prion-like misfolded protein aggregating through a seeding/nucleation process. In TSEs, PMCA is able to detect the equivalent of one single molecule of infectious PrPSc and propagate prions that maintain high infectivity, strain properties and species specificity. Using PMCA we have been able to detect PrPSc in blood and urine of experimentally infected animals and humans affected by vCJD with high sensitivity and specificity. Recently, we have expanded the principles of PMCA to amplify amyloid-beta (Aβ) and alphasynuclein (α-syn) aggregates implicated in Alzheimer's and Parkinson's diseases, respectively. Experiments are ongoing to study the utility of this technology to detect Aβ and α-syn aggregates in samples of CSF and blood from patients affected by these diseases.

=========================

***>>> Recently, we have been using PMCA to study the role of environmental prion contamination on the horizontal spreading of TSEs. These experiments have focused on the study of the interaction of prions with plants and environmentally relevant surfaces. Our results show that plants (both leaves and roots) bind tightly to prions present in brain extracts and excreta (urine and feces) and retain even small quantities of PrPSc for long periods of time. Strikingly, ingestion of prioncontaminated leaves and roots produced disease with a 100% attack rate and an incubation period not substantially longer than feeding animals directly with scrapie brain homogenate. Furthermore, plants can uptake prions from contaminated soil and transport them to different parts of the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety of environmentally relevant surfaces, including stones, wood, metals, plastic, glass, cement, etc. Prion contaminated surfaces efficiently transmit prion disease when these materials were directly injected into the brain of animals and strikingly when the contaminated surfaces were just placed in the animal cage. These findings demonstrate that environmental materials can efficiently bind infectious prions and act as carriers of infectivity, suggesting that they may play an important role in the horizontal transmission of the disease.

========================

Since its invention 13 years ago, PMCA has helped to answer fundamental questions of prion propagation and has broad applications in research areas including the food industry, blood bank safety and human and veterinary disease diagnosis. 



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



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



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



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



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 



PPo4-4: 

Survival and Limited Spread of TSE Infectivity after Burial 




Discussion Classical scrapie is an environmentally transmissible disease because it has been reported in naïve, supposedly previously unexposed sheep placed in pastures formerly occupied by scrapie-infected sheep (4, 19, 20). 

Although the vector for disease transmission is not known, soil is likely to be an important reservoir for prions (2) where – based on studies in rodents – prions can adhere to minerals as a biologically active form (21) and remain infectious for more than 2 years (22). 

Similarly, chronic wasting disease (CWD) has re-occurred in mule deer housed in paddocks used by infected deer 2 years earlier, which was assumed to be through foraging and soil consumption (23). 

Our study suggested that the risk of acquiring scrapie infection was greater through exposure to contaminated wooden, plastic, and metal surfaces via water or food troughs, fencing, and hurdles than through grazing. 

Drinking from a water trough used by the scrapie flock was sufficient to cause infection in sheep in a clean building. 

Exposure to fences and other objects used for rubbing also led to infection, which supported the hypothesis that skin may be a vector for disease transmission (9). 

The risk of these objects to cause infection was further demonstrated when 87% of 23 sheep presented with PrPSc in lymphoid tissue after grazing on one of the paddocks, which contained metal hurdles, a metal lamb creep and a water trough in contact with the scrapie flock up to 8 weeks earlier, whereas no infection had been demonstrated previously in sheep grazing on this paddock, when equipped with new fencing and field furniture. 

When the contaminated furniture and fencing were removed, the infection rate dropped significantly to 8% of 12 sheep, with soil of the paddock as the most likely source of infection caused by shedding of prions from the scrapie-infected sheep in this paddock up to a week earlier. 

This study also indicated that the level of contamination of field furniture sufficient to cause infection was dependent on two factors: stage of incubation period and time of last use by scrapie-infected sheep. 

Drinking from a water trough that had been used by scrapie sheep in the predominantly pre-clinical phase did not appear to cause infection, whereas infection was shown in sheep drinking from the water trough used by scrapie sheep in the later stage of the disease. 

It is possible that contamination occurred through shedding of prions in saliva, which may have contaminated the surface of the water trough and subsequently the water when it was refilled. 

Contamination appeared to be sufficient to cause infection only if the trough was in contact with sheep that included clinical cases. 

Indeed, there is an increased risk of bodily fluid infectivity with disease progression in scrapie (24) and CWD (25) based on PrPSc detection by sPMCA. 

Although ultraviolet light and heat under natural conditions do not inactivate prions (26), furniture in contact with the scrapie flock, which was assumed to be sufficiently contaminated to cause infection, did not act as vector for disease if not used for 18 months, which suggest that the weathering process alone was sufficient to inactivate prions. 

PrPSc detection by sPMCA is increasingly used as a surrogate for infectivity measurements by bioassay in sheep or mice. 

In this reported study, however, the levels of PrPSc present in the environment were below the limit of detection of the sPMCA method, yet were still sufficient to cause infection of in-contact animals. 

In the present study, the outdoor objects were removed from the infected flock 8 weeks prior to sampling and were positive by sPMCA at very low levels (2 out of 37 reactions). 

As this sPMCA assay also yielded 2 positive reactions out of 139 in samples from the scrapie-free farm, the sPMCA assay could not detect PrPSc on any of the objects above the background of the assay. 

False positive reactions with sPMCA at a low frequency associated with de novo formation of infectious prions have been reported (27, 28). 

This is in contrast to our previous study where we demonstrated that outdoor objects that had been in contact with the scrapie-infected flock up to 20 days prior to sampling harbored PrPSc that was detectable by sPMCA analysis [4 out of 15 reactions (12)] and was significantly more positive by the assay compared to analogous samples from the scrapie-free farm. 

This discrepancy could be due to the use of a different sPMCA substrate between the studies that may alter the efficiency of amplification of the environmental PrPSc. 

In addition, the present study had a longer timeframe between the objects being in contact with the infected flock and sampling, which may affect the levels of extractable PrPSc. 

Alternatively, there may be potentially patchy contamination of this furniture with PrPSc, which may have been missed by swabbing. 

The failure of sPMCA to detect CWD-associated PrP in saliva from clinically affected deer despite confirmation of infectivity in saliva-inoculated transgenic mice was associated with as yet unidentified inhibitors in saliva (29), and it is possible that the sensitivity of sPMCA is affected by other substances in the tested material. 

In addition, sampling of amplifiable PrPSc and subsequent detection by sPMCA may be more difficult from furniture exposed to weather, which is supported by the observation that PrPSc was detected by sPMCA more frequently in indoor than outdoor furniture (12). 

A recent experimental study has demonstrated that repeated cycles of drying and wetting of prion-contaminated soil, equivalent to what is expected under natural weathering conditions, could reduce PMCA amplification efficiency and extend the incubation period in hamsters inoculated with soil samples (30). 

This seems to apply also to this study even though the reduction in infectivity was more dramatic in the sPMCA assays than in the sheep model. 

Sheep were not kept until clinical end-point, which would have enabled us to compare incubation periods, but the lack of infection in sheep exposed to furniture that had not been in contact with scrapie sheep for a longer time period supports the hypothesis that prion degradation and subsequent loss of infectivity occurs even under natural conditions. 

In conclusion, the results in the current study indicate that removal of furniture that had been in contact with scrapie-infected animals should be recommended, particularly since cleaning and decontamination may not effectively remove scrapie infectivity (31), even though infectivity declines considerably if the pasture and the field furniture have not been in contact with scrapie-infected sheep for several months. As sPMCA failed to detect PrPSc in furniture that was subjected to weathering, even though exposure led to infection in sheep, this method may not always be reliable in predicting the risk of scrapie infection through environmental contamination. 

These results suggest that the VRQ/VRQ sheep model may be more sensitive than sPMCA for the detection of environmentally associated scrapie, and suggest that extremely low levels of scrapie contamination are able to cause infection in susceptible sheep genotypes. 

Keywords: classical scrapie, prion, transmissible spongiform encephalopathy, sheep, field furniture, reservoir, serial protein misfolding cyclic amplification 


 
Wednesday, December 16, 2015 

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



CWD, Wisconsin, Texas, and Dr. James Kroll

OPINION BLOG 

These are just two insights into the man who has been asked to provide analysis and recommended changes to Wisconsin’s deer management program. 

Kroll’s insights are from an article entitled “Which Side of the Fence Are You On?” 

by Joe Nick Patoski for a past edition of Texas Monthly. 

If nothing more, the article gives an unabashed look into the mind-set that will be providing the Wisconsin DNR with recommendations on how to change their deer management practices. 

James Kroll (also known as “Deer Dr.”) was appointed to the Wisconsin “deer czar” position last fall. 

He was hired by the Department of Administration and instructed to complete a review of the state’s deer management program. 

 Here’s a sample of the article: 

“Game Management,” says James Kroll, driving to his high-fenced, two-hundred-acre spread near Nacogdoches, “is the last bastion of communism.” 

Kroll, also known as Dr. Deer, is the director of the Forestry Resources Institute of Texas at Stephen F. Austin State University, and the “management” he is referring to is the sort practiced by the State of Texas. 

The 55-year-old Kroll is the leading light in the field of private deer management as a means to add value to the land. 

His belief is so absolute that some detractors refer to him as Dr. Dough, implying that his eye is on the bottom line more than on the natural world. 

Kroll, who has been the foremost proponent of deer ranching in Texas for more than thirty years, doesn’t mind the controversy and certainly doesn’t fade in the heat. 

People who call for more public lands are “cocktail conservationists,” he says, who are really pining for socialism. 

He calls national parks “wildlife ghettos” and flatly accuses the government of gross mismanagement. 

He argues that his relatively tiny acreage, marked by eight-foot fences and posted signs warning off would-be poachers, is a better model for keeping what’s natural natural while making money off the land. 

snip...

It is interesting to note that, in 2001, the State of Texas shifted its deer management strategies toward the same leanings that Kroll has suggested for Wisconsin. 

In Texas, the change was brought about via heavy lobbying from the high-fence deer ranching industry. This pressure helped convince the Texas Parks and Wildlife to change their regulations and allow private landowners to select the own deer biologists.


FRIDAY, JUNE 01, 2012 

TEXAS DEER CZAR TO WISCONSIN ASK TO EXPLAIN COMMENTS


THURSDAY, MARCH 29, 2012 

TEXAS DEER CZAR SAYS WISCONSIN DNR NOT DOING ENOUGH ABOUT CWD LIKE POT CALLING KETTLE BLACK


WEDNESDAY, OCTOBER 03, 2018 

WISCONSIN CAVES TO GAME FARM INDUSTRY AGAIN WHILE STATE FALLS FURTHER INTO THE ABYSS OF MAD DEER DISEASE CWD TSE PRION


TUESDAY, NOVEMBER 20, 2018 

WISCONSIN Captive CWD TSE Prion Lotto Entitlement Program Pays Out Again Indemnity From Taxpayers $330,000 To Farmers So Far This Year


TUESDAY, SEPTEMBER 25, 2018 

Wisconsin CWD TSE PRION PLAN preferred option disposal in a landfill OR public land is acceptable to leave the carcass in the spot of the kill

stupid is, as stupid does, sometimes you can't fix stupid...tss


WEDNESDAY, JUNE 13, 2018 

Wisconsin DATCP NVSL confirmed 21 WTD from a deer farm Iowa County tested positive for chronic wasting disease (CWD)


FRIDAY, FEBRUARY 16, 2018 

Wisconsin Deer from Now-Quarantined PA Lancaster County Farm Tests Positive for Chronic Wasting Disease CWD TSE Prion


FRIDAY, FEBRUARY 16, 2018 

Wisconsin Stop private deer industry from trucking CWD across state Durkin: Stop private deer industry from trucking CWD across state


MONDAY, MARCH 05, 2018 

TRUCKING AROUND AND SPREADING CHRONIC WASTING DISEASE CWD TSE PRION VIA MOVEMENT OF CERVID AND TRANSPORTATION VEHICLES


MONDAY, MARCH 20, 2017 

Wisconsin CWD TSE Prion Annual Roundup 441 positive 


Sunday, May 08, 2016

*** WISCONSIN CHRONIC WASTING DISEASE CWD TSE PRION SPIRALING FURTHER INTO THE ABYSS UPDATE ***

Wisconsin Chronic Wasting Disease CWD TSE Prion


Wednesday, February 10, 2016

*** Wisconsin Two deer that escaped farm had chronic wasting disease CWD ***


Sunday, January 17, 2016

*** Wisconsin Captive CWD Lotto Pays Out Again indemnity payment of $298,770 for 228 white-tailed deer killed on farm ***


WEDNESDAY, OCTOBER 03, 2018 

Texas Reports 13 more cases of Chronic Wasting Disease CWD TSE Prion in Breeder Deer state total jumps to 130 Confirmed to date


Tuesday, June 05, 2012

Captive Deer Breeding Legislation Overwhelmingly Defeated During 2012 Legislative Session


MONDAY, APRIL 01, 2013 

Dr. Deer/Dough from Texas on Wisconsin’s CWD implementation survey, is now available


MONDAY, AUGUST 14, 2017 

Singeltary on Texas Chronic Wasting Disease CWD TSE Prion History


THURSDAY, OCTOBER 04, 2018 

Cervid to human prion transmission 5R01NS088604-04 Update


SATURDAY, NOVEMBER 10, 2018 

cwd, bse, scrapie, cjd, tse prion updated November 10 2018


THURSDAY, OCTOBER 25, 2018 

***> Norway New additional requirements for imports of hay and straw for animal feed from countries outside the EEA due to CWD TSE Prion



JUST OUT CDC;


Tuesday, November 20, 2018

Eyes of CJD patients show evidence of prions Finding could help early diagnosis, raise concern for eye exams and transplants.



Singeltary 1999


 ***> THE EYES HAVE IT, CJD, AND THEY COULD BE STEALING THEM FROM YOUR LOVED ONE!...year 1999


i said that 20 years ago about this very thing. but did anyone listen...no!

prepare for the storm...terry

year 1999 to 2000

Subject: RE-The Eyes Have It (cjd) and they could be stealing them from your loved one... "pay back time" 

Date: Sat, 16 Sep 2000 10:04:26 -0700 

From: "Terry S. Singeltary Sr." 

Reply-To: Bovine Spongiform Encephalopathy 

To: BSE-L@uni-karlsruhe.de

######### Bovine Spongiform Encephalopathy #########

Greetings List Members,

I hate to keep kicking a madcow, but this still is very disturbing to me. Not only for the recipient of the cornea's, but as well, for the people whom would be operated on, using the same tools that were used to put those stolen cornea's in the recipient with. No history of this donor or his family (re-ffi), or anything would be known, using stolen organs and or tissue's. I just think this is not only wrong, but very dangerous to a great many other people, as this is one of the most infectious tissues of TSE's. It seems that this practice of stealing organ/tissue happens more than we think. Anyway, the family of the victim which had their cornea's stolen, are now suing. In the example I used with my Mother, if 3 months before, she would have been in a catastrophic accident (car wreck, whatever), no autopsy (for whatever reason), no family (for whatever reason), she lay in the morgue, and after 4 hours, they come steal the cornea's, lot of people could have been infected, just because of lack of medical history of donor/family. It may be hypothetical, but very real. We need to stop the spread of this disease.

kind regards, Terry S. Singeltary Sr., Bacliff, Texas USA 

===========================================

Previous story--

Cadaver corneal transplants -- without family permission...

Cadaver corneal transplants -- without family permission Houston, Texas channel 11 news 28 Nov 99

Reported by Terry S. Singeltary Sr.son of CJD victim

"It was a story about how the Lions eye bank were harvesting corneas from victims in the Morgue, without their consent. Under Texas law, this appears to be legal (remember Texas has the Veggie liable law). Even if Family says no, this appears to happen, from what the news story said.

They said the only way to prevent this, is to fill out a form, stating not to have this done. So if you don't fill out the form, they can do this. How many people don't know about the form? 

 This is not only disgusting and appalling, it could be highly infectious. Without proper background checking of the donors, on their physical history, checking on past dementia, and/or family history, some of these unfortunate victims, could be passing a human TSE. 

 Response Jill Spitler Clevelland Eye Bank: 

 "No, we are not stealing.........Yes, you do have such a law in the state of Texas, but not all your state Eye Banks utilize the law. The Eye Bank that you're speaking of is only one of 43 certified Eye Bank throughout the USA. 

 And there are measure taken per the Medical Standards of the Eye Bank Association of America, the certifying body for eye banks and per FDA regulations to address those concerns that you speak of. 

 I would suggest that those interested/concern with transplant contact their local agencies. The Eye Bank Association of America has a web. site . Further if anyone has problems contacting or finding out about their local organization(s), call me or e-mail me I would be glad to help. My e-mail address is jill@clevelandeyebank.org" 

 Terry Singeltary responds: 

 "Explain this to the family in Houston who went to their loved ones funeral, only to find out that the loved one that was in the casket, had their corneas removed without their permission, without the consent of the victim or it's family. They would not have known it, only for the funny look the victim had. So, they questioned, only to find out, the corneas, had in fact, been removed without consent. 

 I call that stealing, regardless what the law states. This type of legal grave robbing is not a logical thing to do without knowing any type of background of the victims medical past, which really will not prove anything due to the incubation period. Eye tissue being potentially a highly infective source, there are risks here. 

 Should they not at least know of the potential ramifications of TSE's (the person receiving the corneas)? 

 Should there not be some sort of screening? 

 Should there be some sort of moral issue here? 

 If this is the case, and in fact, they can come take your corneas, without your consent, then what will they start taking next, without your consent? 

 Lets look at a hypothetical situation: 

 What would happen if my Mom (DOD 12-14-97 hvCJD) would have gotten into a car wreck and died, before the symptoms of CJD appeared. Not much money, so there was no autopsy. What would have happened to that recipient of those infecting corneas?" 

 Comment (webmaster): Actual transmission of CJD by means of corneal transplant may or may not be rare. The incidence of infectivity in older people could be fairly high; this is not to be confused with the lower incidence of symptomatic (clinical) CJD. It is very unlikely that familial CJD would have been diagnosed in earlier generations; however, without interviewing the family even known kindreds would not be excluded. 

 In blood donation, a much stricter policy is followed, even though corneal transplant may be far more dangerous (being a direct link to the brain and not going through purification steps). 

 Since highly sensitive tests for pre-clinical CJD are now available, it would make sense to screen corneas for CJD, just as they are screened for AIDS, hepatitus, and a host of other conditions. 



Eye procedure raises CJD concerns

BySTEVE MITCHELL, Medical Correspondent

WASHINGTON, Nov. 18 (UPI) -- A New York man who died from a rare brain disorder similar to mad cow disease in May underwent an eye procedure prior to his death that raises concerns about the possibility of transmitting the fatal disease to others, United Press International has learned.

The development comes on the heels of the announcement Thursday by U.S. Department of Agriculture officials of a possible second case of mad cow disease in U.S. herds.

Richard Da Silva, 58, of Orange County, N.Y., died from Creutzfeldt Jakob disease, an incurable brain-wasting illness that strikes about one person per million.

Richard's wife Ann Marie Da Silva told UPI he underwent a check for the eye disease glaucoma in 2003, approximately a year before his death. The procedure involves the use of a tonometer, which contacts the cornea -- an eye tissue that can contain prions, the infectious agent thought to cause CJD.

Ann Marie's concern is that others who had the tonometer used on them could have gotten infected.

A 2003 study by British researchers suggests her concerns may be justified. A team led by J.W. Ironside from the National Creutzfeldt-Jakob Disease Surveillance Unit at the University of Edinburgh examined tonometer heads and found they can retain cornea tissue that could infect other people -- even after cleaning and decontaminating the instrument.

"Retained corneal epithelial cells, following the standard decontamination routine of tonometer prisms, may represent potential prion infectivity," the researchers wrote in the British Journal of Ophthalmology last year. "Once the infectious agent is on the cornea, it could theoretically infect the brain."

Prions, misfolded proteins thought to be the cause of mad cow, CJD and similar diseases, are notoriously difficult to destroy and are capable of withstanding most sterilization procedures.

Laura Manuelidis, an expert on these diseases and section chief of surgery in the neuropathology department at Yale University, agreed with the British researchers that tonometers represent a potential risk of passing CJD to other people.

Manuelidis told UPI she has been voicing her concern about the risks of corneas since 1977 when her own study, published in the New England Journal of Medicine, showed the eye tissue, if infected, could transmit CJD.

At the time the procedure was done on Richard Da Silva, about a year before he died, she said it was "absolutely" possible he was infectious.

The CJD Incidents Panel, a body of experts set up by the U.K. Department of Health, noted in a 2001 report that procedures involving the cornea are considered medium risk for transmitting CJD. The first two patients who have a contaminated eye instrument used on them have the highest risk of contracting the disease, the panel said.

In 1999, the U.K. Department of Health banned opticians from reusing equipment that came in contact with patients' eyes out of concern it could result in the transmission of variant CJD, the form of the disease humans can contract from consuming infected beef products.

Richard Da Silva was associated with a cluster of five other cases of CJD in southern New York that raised concerns about vCJD.

None of the cases have been determined to stem from mad cow disease, but concerns about the cattle illness in the United States could increase in light of the USDA announcement Thursday that a cow tested positive on initial tests for the disease. If confirmed, this would be the second U.S. case of the illness; the first was detected in a Washington cow last December. The USDA said the suspect animal disclosed Thursday did not enter the food chain. The USDA did not release further details about the cow, but said results from further lab tests to confirm the initial tests were expected within seven days.

Ann Marie Da Silva said she informed the New York Health Department and later the eye doctor who performed the procedure about her husband's illness and her concerns about the risk of transmitting CJD via the tonometer.

The optometrist -- whom she declined to name because she did not want to jeopardize his career -- "didn't even know what this disease was," she said.

"He said the health department never called him and I called them (the health department) back and they didn't seem concerned about it," she added. "I just kept getting angrier and angrier when I felt I was being dismissed."

She said the state health department "seems to have an attitude of don't ask, don't tell" about CJD.

"There's a stigma attached to it," she said. "Is it because they're so afraid the public will panic? I don't know, but I don't think that the answer is to push things under the rug."

New York State Department of Health spokeswoman Claire Pospisil told UPI she would look into whether the agency was concerned about the possibility of transmitting CJD via tonometers, but she had not called back prior to story publication.

Disposable tonometers are readily available and could avoid the risk of transmitting the disease, Ironside and colleagues noted in their study. Ann Marie Da Silva said she asked the optometrist whether he used disposable tonometers and "he said 'No, it's a reusable one.'"

Ironside's team also noted other ophthalmic instruments come into contact with the cornea and could represent a source of infection as they are either difficult to decontaminate or cannot withstand the harsh procedures necessary to inactivate prions. These include corneal burrs, diagnostic and therapeutic contact lenses and other coated lenses.

Terry Singletary, whose mother died from a type of CJD called Heidenhain Variant, told UPI health officials were not doing enough to prevent people from being infected by contaminated medical equipment.

"They've got to start taking this disease seriously and they simply aren't doing it," said Singletary, who is a member of CJD Watch and CJD Voice -- advocacy groups for CJD patients and their families.

U.S. Centers for Disease Control and Prevention spokeswoman Christine Pearson did not return a phone call from UPI seeking comment. The agency's Web site states the eye is one of three tissues, along with the brain and spinal cord, that are considered to have "high infectivity."

The Web site said more than 250 people worldwide have contracted CJD through contaminated surgical instruments and tissue transplants. This includes as many as four who were infected by corneal grafts. The agency noted no such cases have been reported since 1976, when sterilization procedures were instituted in healthcare facilities.

Ironside and colleagues noted in their study, however, many disinfection procedures used on optical instruments, such as tonometers, fail. They wrote their finding of cornea tissue on tonometers indicates that "no current cleaning and disinfection strategy is fully effective."

Singletary said CDC's assertion that no CJD cases from infected equipment or tissues have been detected since 1976 is misleading.

"They have absolutely no idea" whether any cases have occurred in this manner, he said, because CJD cases often aren't investigated and the agency has not required physicians nationwide report all cases of CJD.

"There's no national surveillance unit for CJD in the United States; people are dying who aren't autopsied, the CDC has no way of knowing" whether people have been infected via infected equipment or tissues, he said.

Ann Marie Da Silva said she has contacted several members of her state's congressional delegation about her concerns, including Rep. Sue Kelly, R-N.Y., and Sen. Charles Schumer, D-N.Y.

"Basically, what I want is to be a positive force in this, but I also want more of a dialogue going on with the public and the health department," she said.


Friday, December 04, 2009

New guidance on decontamination of trial contact lenses and other contact devices has been revealed for CJD AND vCJD


SUNDAY, JANUARY 17, 2016 

Of Grave Concern Heidenhain Variant Creutzfeldt Jakob Disease



TUESDAY, NOVEMBER 20, 2018 

CDC Eyes of CJD patients show evidence of prions concerns for iatrogenic transmission


MONDAY, NOVEMBER 19, 2018 

Benefit cuts hit mad cow disease sufferer A girl born severely disabled from vCJD may lose her home under universal credit

https://creutzfeldt-jakob-disease.blogspot.com/2018/11/benefit-cuts-hit-mad-cow-disease.html

HUMAN MAD COW DISEASE nvCJD TEXAS CASE NOT LINKED TO EUROPEAN TRAVEL CDC Sunday, November 23, 2014

Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas

Updated: October 7, 2014

CDC and the Texas Department of State Health Services (DSHS) have completed the investigation of the recently reported fourth vCJD case in the United States. It confirmed that the case was in a US citizen born outside the Americas and indicated that the patient's exposure to the BSE/vCJD agent most likely occurred before he moved to the United States; the patient had resided in Kuwait, Russia and Lebanon. The completed investigation did not support the patient's having had extended travel to European countries, including the United Kingdom, or travel to Saudi Arabia. The specific overseas country where this patient’s infection occurred is less clear largely because the investigation did not definitely link him to a country where other known vCJD cases likely had been infected.

https://www.cdc.gov/ncidod/dvrd/vcjd/other/confirmed-case-in-texas.htm

https://vcjd.blogspot.com/2014/11/confirmed-variant-creutzfeldt-jakob.html

Sunday, September 16, 2018 

Mother to Offspring Transmission of TSE PRION DISEASE and risk factors there from

http://prionprp.blogspot.com/2018/09/mother-to-offspring-transmission-of-tse.html

WEDNESDAY, SEPTEMBER 05, 2018 

*** Edmonton woman one of the youngest diagnosed with CJD at 35 years old and pregnant

http://creutzfeldt-jakob-disease.blogspot.com/2018/09/edmonton-woman-one-of-youngest.html

FRIDAY, OCTOBER 05, 2018 

More Politicians and Very Young People Struck Down With Creutzfeldt Jakob Disease CJD mad cow type TSE Prion USA

http://creutzfeldt-jakob-disease.blogspot.com/2018/10/more-politicians-and-very-young-people.html

SUNDAY, NOVEMBER 04, 2018 

Heidenhain variant of Creutzfeldt-Jakob disease in a patient who had bovine bioprosthetic valve implantation


TUESDAY, JULY 31, 2018 

USA CJD TSE Tables of Cases Examined National Prion Disease Pathology Surveillance Center Cases Examined May 1, 2018

http://prionunitusaupdate.blogspot.com/2018/07/usa-cjd-tse-tables-of-cases-examined.html


2006-2007

HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory

TSEs have been rampant in the USA for decades in many species, and they all have been rendered and fed back to animals for human/animal consumption. I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2007. With all the science to date refuting it, to continue to validate this myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, surgical, blood, medical, cosmetics etc. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route. This would further have to be broken down to strain of species and then the route of transmission would further have to be broken down. Accumulation and Transmission are key to the threshold from subclinical to clinical disease, and of that, I even believe that physical and or blunt trauma may play a role of onset of clinical symptoms in some cases, but key to all this, is to stop the amplification and transmission of this agent, the spreading of, no matter what strain. BUT, to continue with this myth that the U.K. strain of BSE one strain in cows, and the nv/v CJD, one strain in humans, and that all the rest of human TSE is one single strain i.e. sporadic CJD (when to date there are 6 different phenotypes of sCJD), and that no other animal TSE transmits to humans, to continue with this masquerade will only continue to spread, expose, and kill, who knows how many more in the years and decades to come. ONE was enough for me, My Mom, hvCJD, DOD 12/14/97 confirmed, which is nothing more than another mans name added to CJD, like CJD itself, Jakob and Creutzfeldt, or Gerstmann-Straussler-Scheinker syndrome, just another CJD or human TSE, named after another human. WE are only kidding ourselves with the current diagnostic criteria for human and animal TSE, especially differentiating between the nvCJD vs the sporadic CJD strains and then the GSS strains and also the FFI fatal familial insomnia strains or the ones that mimics one or the other of those TSE? Tissue infectivity and strain typing of the many variants of the human and animal TSEs are paramount in all variants of all TSE. There must be a proper classification that will differentiate between all these human TSE in order to do this. With the CDI and other more sensitive testing coming about, I only hope that my proposal will some day be taken seriously.

My name is Terry S. Singeltary Sr. and I am no scientist, no doctor and have no PhDs, but have been independently researching human and animal TSEs since the death of my Mother to the Heidenhain Variant of Creutzfeldt Jakob Disease on December 14, 1997 'confirmed'. ...END

Diagnosis and Reporting of Creutzfeldt-Jakob Disease 

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA Diagnosis and Reporting of Creutzfeldt-Jakob Disease 

To the Editor: 

In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally. 

Terry S. Singeltary, Sr Bacliff, Tex 

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. 


Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734.


BRITISH MEDICAL JOURNAL

BMJ

U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well....

02 January 2000

Terry S Singeltary

retired


US scientists develop a possible test for BSE

BMJ 1999; 319 doi: https://doi.org/10.1136/bmj.319.7220.1312b (Published 13 November 1999) Cite this as: BMJ 1999;319:1312

Rapid responses Response

Re: vCJD in the USA * BSE in U.S.

15 November 1999

Terry S Singeltary

NA

medically retired


January 28, 2003; 60 (2) VIEWS & REVIEWS

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States

Ermias D. Belay, Ryan A. Maddox, Pierluigi Gambetti, Lawrence B. Schonberger

First published January 28, 2003, DOI: https://doi.org/10.1212/01.WNL.0000036913.87823.D6

Abstract

Transmissible spongiform encephalopathies (TSEs) attracted increased attention in the mid-1980s because of the emergence among UK cattle of bovine spongiform encephalopathy (BSE), which has been shown to be transmitted to humans, causing a variant form of Creutzfeldt-Jakob disease (vCJD). The BSE outbreak has been reported in 19 European countries, Israel, and Japan, and human cases have so far been identified in four European countries, and more recently in a Canadian resident and a US resident who each lived in Britain during the BSE outbreak. To monitor the occurrence of emerging forms of CJD, such as vCJD, in the United States, the Centers for Disease Control and Prevention has been conducting surveillance for human TSEs through several mechanisms, including the establishment of the National Prion Disease Pathology Surveillance Center. Physicians are encouraged to maintain a high index of suspicion for vCJD and use the free services of the pathology center to assess the neuropathology of clinically diagnosed and suspected cases of CJD or other TSEs.

Received May 7, 2002. Accepted August 28, 2002.


RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 

Terry S. Singeltary, retired (medically) 

Published March 26, 2003

26 March 2003

Terry S. Singeltary, retired (medically) CJD WATCH

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?


Reply to Singletary Ryan A. Maddox, MPH Other Contributors: Published March 26, 2003 

Mr. Singletary raises several issues related to current Creutzfeldt- Jakob disease (CJD) surveillance activities. Although CJD is not a notifiable disease in most states, its unique characteristics, particularly its invariably fatal outcome within usually a year of onset, make routine mortality surveillance a useful surrogate for ongoing CJD surveillance.[1] In addition, because CJD is least accurately diagnosed early in the course of illness, notifiable-disease surveillance could be less accurate than, if not duplicative of, current mortality surveillance.[1] However, in states where making CJD officially notifiable would meaningfully facilitate the collection of data to monitor for variant CJD (vCJD) or other emerging prion diseases, CDC encourages the designation of CJD as a notifiable disease.[1] Moreover, CDC encourages physicians to report any diagnosed or suspected CJD cases that may be of special public health importance (e.g., vCJD, iatrogenic CJD, unusual CJD clusters).

As noted in our article, strong evidence is lacking for a causal link between chronic wasting disease (CWD) of deer and elk and human disease,[2] but only limited data seeking such evidence exist. Overall, the previously published case-control studies that have evaluated environmental sources of infection for sporadic CJD have not consistently identified strong evidence for a common risk factor.[3] However, the power of a case-control study to detect a rare cause of CJD is limited, particularly given the relatively small number of subjects generally involved and its long incubation period, which may last for decades. Because only a very small proportion of the US population has been exposed to CWD, a targeted surveillance and investigation of unusual cases or case clusters of prion diseases among persons at increased risk of exposure to CWD is a more efficient approach to detecting the possible transmission of CWD to humans. In collaboration with appropriate local and state health departments and the National Prion Disease Pathology Surveillance Center, CDC is facilitating or conducting such surveillance and case- investigations, including related laboratory studies to characterize CJD and CWD prions.

Mr. Singletary also expresses concern over a recent publication by Asante and colleagues indicating the possibility that some sporadic CJD cases may be attributable to bovine spongiform encephalopathy (BSE).[4] The authors reported that transgenic mice expressing human prion protein homozygous for methionine at codon 129, when inoculated with BSE prions, developed a molecular phenotype consistent with a subtype of sporadic CJD. Although the authors implied that BSE might cause a sporadic CJD-like illness among persons homozygous for methionine, the results of their research with mice do not necessarily directly apply to the transmission of BSE to humans. If BSE causes a sporadic CJD-like illness in humans, an increase in sporadic CJD cases would be expected to first occur in the United Kingdom, where the vast majority of vCJD cases have been reported. In the United Kingdom during 1997 through 2002, however, the overall average annual mortality rate for sporadic CJD was not elevated; it was about 1 case per million population per year. In addition, during this most recent 6-year period following the first published description of vCJD in 1996, there was no increasing trend in the reported annual number of UK sporadic CJD deaths.[3, 5] Furthermore, surveillance in the UK has shown no increase in the proportion of sporadic CJD cases that are homozygous for methionine (Will RG, National CJD Surveillance Unit, United Kingdom, 2003; personal communication).

References

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Diagnosis and reporting of Creutzfeldt-Jakob disease. JAMA 2001;285:733-734.

2. Belay ED, Maddox RA, Gambetti P, Schonberger LB. Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States. Neurology 2003;60:176-181.

3. Belay ED. Transmissible spongiform encephalopathies in humans. Annu Rev Microbiol 1999;53:283-314.

4. Asante EA, Linehan JM, Desbruslais M, et al. BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J 2002;21:6358-6366.

5. The UK Creutzfeldt-Jakob Disease Surveillance Unit. CJD statistics. Available at: http://www.cjd.ed.ac.uk/figures.htm. Accessed February 18, 2003.

Competing Interests: None declared.


Volume 2: Science 

4. The link between BSE and vCJD 

Summary 

4.29 The evidence discussed above that vCJD is caused by BSE seems overwhelming. Uncertainties exist about the cause of CJD in farmers, their wives and in several abattoir workers. It seems that farmers at least might be at higher risk than others in the general population. 1 Increased ascertainment (ie, increased identification of cases as a result of greater awareness of the condition) seems unlikely, as other groups exposed to risk, such as butchers and veterinarians, do not appear to have been affected. 

***The CJD in farmers seems to be similar to other sporadic CJD in age of onset, in respect to glycosylation patterns, and in strain-typing in experimental mice. 

***Some farmers are heterozygous for the methionine/valine variant at codon 129, and their lymphoreticular system (LRS) does not contain the high levels of PrPSc found in vCJD. 

*** It remains a remote possibility that when older people contract CJD from BSE the resulting phenotype is like sporadic CJD and is distinct from the vCJD phenotype in younger people.

BSEINQUIRY


***>Some farmers are heterozygous for the methionine/valine variant at codon 129, and their lymphoreticular system (LRS) does not contain the high levels of PrPSc found in vCJD.<***


SATURDAY, JUNE 23, 2018

***> Diagnosis of Methionine/Valine Variant Creutzfeldt-Jakob Disease by Protein Misfolding Cyclic Amplification

Volume 24, Number 7—July 2018



doi:10.1016/S1473-3099(03)00715-1 Copyright © 2003 Published by Elsevier Ltd. Newsdesk

Tracking spongiform encephalopathies in North America

Xavier Bosch

Available online 29 July 2003. 

Volume 3, Issue 8, August 2003, Page 463 

“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem.” ............................ 





THURSDAY, NOVEMBER 22, 2018 

Nebraska NEFGA Chronic Wasting Disease CWD TSE Prion 02106-19-40 North Platte River 279 NPR279 Lymph node sample Positive



WEDNESDAY, OCTOBER 03, 2018 

Texas Reports 13 more cases of Chronic Wasting Disease CWD TSE Prion in Breeder Deer state total jumps to 130 Confirmed to date



SATURDAY, NOVEMBER 10, 2018 

Pennsylvania Thirty-Eight Deer Test Positive for Chronic Wasting Disease on Fulton and Bedford County Deer Farms



FRIDAY, NOVEMBER 16, 2018 

Montana three deer harvested in Blaine County have tested positive for chronic wasting disease



FRIDAY, NOVEMBER 09, 2018 

Minnesota CWD TSE Prion detected four harvested samples from farmed deer quarantined farm Crow Wing County



Board of Animal Health’s Oversight of Deer and Elk Farms 2018

EVALUATION REPORT

Program Evaluation Division Office of the Legislative Auditor State of Minnesota

snip...

Since 2002, CWD has been identified on eight Minnesota deer and elk farms and in wild deer in two Minnesota counties. (pp. 40-41) 

From 2014 to 2017, about one-third of producers that reported dead deer or elk failed to submit tissues from at least one of those animals for CWD testing. (p. 26) 

(this is called SSS Shoot Shovel, and Shut the Hell Up Program for Captive Game Farms, works very well for cattle, sheep, and cervid, and it works very well in the USA and Canada with mad cow disease, and proven to be so, just ask ex Alberta Premier Ralph Klein..tss)

 BAH and the Department of Natural Resources (DNR) have struggled to appropriately share the information they both require to respond to CWD outbreaks. (p. 47)  While Minnesota’s CWD regulations are among the most rigorous in the nation, there are some areas where other states’ policies better protect deer and elk against the disease. (pp. 49-50) 

Summary Key Facts and Findings: 

 The Board of Animal Health (BAH) is responsible for protecting the health of Minnesota’s domestic animals, including deer and elk. (p. 3) 

 The board has five members, but not one who represents the general public. (pp. 11, 12-13) 

 As of April 2018, Minnesota had 398 registered herds, consisting of about 9,300 deer, elk, and other similar species. (p. 4) 

 Minnesota law does not require that deer and elk identification tags be read and recorded when completing an animal inventory. (pp. 21-22) 

 Chronic wasting disease (CWD) is an always fatal, neurodegenerative disease found in both farmed and wild deer and elk. (p. 6) 

 Since 2002, CWD has been identified on eight Minnesota deer and elk farms and in wild deer in two Minnesota counties. (pp. 40-41) 

 BAH staff do not systematically analyze whether deer and elk producers submit tissue samples for CWD testing for all deceased animals. (p. 25) 

 From 2014 to 2017, about one-third of producers that reported dead deer or elk failed to submit tissues from at least one of those animals for CWD testing. (p. 26) 

 BAH has, in some instances, failed to enforce deer and elk regulations. However, the board has improved its deer and elk program over the past several months. (pp. 30-34) 

 BAH and the Department of Natural Resources (DNR) have struggled to appropriately share the information they both require to respond to CWD outbreaks. (p. 47) 

 While Minnesota’s CWD regulations are among the most rigorous in the nation, there are some areas where other states’ policies better protect deer and elk against the disease. (pp. 49-50) 

Key Recommendations: 

 The Legislature should consider expanding the number of board members and adding at least one member of the general public. (p. 14) 

 BAH should clarify expectations of whether and how often producers must verify their herd inventory on an animal-by-animal basis. (pp. 23-24) 

 BAH should (1) systematically analyze CWD-testing compliance, and (2) appropriately penalize those producers who fail to submit CWD testing samples. (p. 27) 

 BAH should develop an approval program for deer and elk producers who wish to collect their own CWD test samples. (p. 30) 

 BAH should (1) ensure producers follow Minnesota deer and elk laws, (2) strengthen consequences for producers, and (3) monitor field staff performance. (p. 33) 

 BAH and DNR should draft a memorandum of understanding outlining each agencies’ responsibilities with respect to data sharing. (pp. 47-48) 

 The Legislature should convene an advisory task force to evaluate the state’s regulations related to deer feeding and live-animal imports. (p. 51)

snip...

Report Summary

Minnesota statutes charge the Board of Animal Health (BAH) with protecting the health of Minnesota’s domestic animals, including members of the family cervidae.1

 The cervidae family

includes deer, elk, and similar species, which may be collectively referred to as “cervids.” As of April 2018, Minnesota producers were raising more than 9,300 cervids in 398 registered herds.

Deer and elk health is threatened by chronic wasting disease (CWD), an always fatal, neurodegenerative disease found among wild and farmed cervids. CWD is difficult to manage because there is no live-animal diagnostic test approved for routine herd monitoring. Further, infected animals may not show clinical signs until the disease is quite advanced. The only way to definitively diagnose CWD is to analyze specific tissues from a dead deer or elk. CWD has been found on eight Minnesota deer and elk farms since 2002. It has also been detected in wild deer in two Minnesota counties.

BAH is smaller than other states’ animal health boards. The board is made up of three livestock producers and two veterinarians practicing in Minnesota. Members are appointed by the governor. BAH’s dayto-day work is performed by 41 staff members.

Minnesota’s structure for overseeing farmed deer and elk is unlike those in most other states. Only six states give the responsibility to an entity like BAH. In most states, farmed deer and elk oversight falls to a natural resources department, an agriculture department, or a combination of the two.

1 Minnesota Statutes 2017, 35.03.. BAH is smaller than other state’s animal health boards, which range in size from 7 to 16 members. BAH is also smaller than other Minnesota boards that license, permit, or register professions or entities. While BAH’s composition (three livestock producers and two veterinarians) is similar to other states’ boards, BAH is unlike most Minnesota boards in that it lacks a public member. We recommend expanding the size of the board and adding a member of the general public, in order to diversify the perspectives represented.

The law does not require that deer and elk identification tags be read regularly, calling into question the accuracy of cervid farm inventories. Annual inventories are an important tool for BAH. In the event that CWD is detected on a deer or elk farm, BAH uses the inventories that producers submit to track animal locations and movements and determine which other farms to investigate for possible CWD exposure.

By law, producers must submit annually to the board inventories that are verified by an accredited veterinarian.2

However, the law does not require that the producers or their veterinarians physically read the tags on their deer and elk in order to complete these inventories. As such, the inventories producers submit may not accurately reflect the animals on the farm, which could complicate the investigation that BAH must conduct if CWD is discovered among farmed cervids.

We recommend that BAH clarify its expectations for how often deer and elk identification tags are read. For example, the United States Department of Agriculture requires that deer and elk producers who move animals to other

2 Minnesota Statutes 2017, 35.155, subd. 11(a)

states read and record identification tags once every three years. BAH does not systematically analyze whether producers submit CWD testing samples for all deer and elk that they report as deceased, and many do not.

Deer and elk producers are required by law to submit specific tissues for CWD testing for all deer and elk that die at age 12 months or older.3

 BAH staff do not currently analyze CWD-testing compliance, unless they have a specific reason to manually evaluate the records associated with a particular herd. We analyzed BAH data and found that an estimated one-third of deer and elk producers failed to submit tissue samples for CWD testing from 2014 to 2017. We recommend that BAH create a report that identifies producers that have missed CWD tests. Further, we recommend that BAH penalize producers who do not submit the required samples.

Another issue with respect to CWD sample submission is sample quality. If producers submit the wrong type of tissue or a sample that is otherwise unreadable, the deer or elk in question will not be tested for CWD. From 2014 to 2017, the percentage of unreadable samples increased from 2 percent to 11 percent. In 2017, BAH began retraining producers who had submitted poor-quality samples. As a result, sample quality began to improve during the latter half of 2017. We recommend that BAH develop a standardized training and approval program for deer and elk producers who wish to collect their own CWD test samples.

3 Minnesota Rules, 1721.0420, subp. 1(D), published electronically April 4, 2013. Producers must submit part of the brainstem and lymph nodes from the head of a dead deer or elk. While BAH has had some issues enforcing cervid regulations in the past, its deer and elk program has improved over the past several months.

It was recently reported that a Winona County cervid farm that tested positive for CWD also had fences in poor repair.4

 Despite the fact that the fences (by the owner’s own admission) had been sagging for years, BAH had never mentioned fence issues on the farm’s annual inspection reports.

We do not know the degree to which this type of apparent enforcement error has occurred, and this lapse in oversight is concerning. However, the new director of the deer and elk program has made numerous changes over the past several months that will hopefully improve BAH’s enforcement of deer and elk regulations going forward.

Recent BAH changes include improved communication, through the development of a cervid-farming handbook and a CWD-testing guide. The new director has also placed a renewed emphasis on enforcement, putting in place the expectation that the field staff inspecting cervid farms give warnings and reinspect farms when they note violations. We recommend that the board fully enforce Minnesota cervid laws and that they consider strengthening the penalties for producers who fail to comply. Further, the board should monitor the performance of field staff conducting inspections.

The strained relationship between BAH and DNR has led to problems with data sharing.

BAH responds when CWD is detected on deer or elk farms; DNR leads the

4

 Tony Kennedy, “‘Hunters should be…afraid,’” Star Tribune, March 7, 2018. 

response when the disease is found in the wild. Both agencies, however, take certain actions when CWD is detected in the other agency’s jurisdiction, which means that the two must coordinate to a certain extent.

In order to respond to CWD outbreaks, each agency, at a minimum, must know the precise location where the infected animal was found. The tension between the two agencies, however, has resulted in poor communication and complaints from both sides with respect to sharing information.

DNR staff have complained that BAH refuses to share information about infected farms in a timely fashion. BAH staff allege that DNR has not adequately protected producer contact information, which is classified by law as not public data.5

 We recommend that the two agencies draft a memorandum of understanding making clear what information should be shared between agencies in the event of CWD outbreak, in what timeframe, and the measures the receiving agency should take to protect the data. BAH and DNR finalized an agreement on April 10, 2018, which focuses on protecting not public data. We think this is a good first step. There are some states with policies for managing farmed deer and elk that may better protect their animals from CWD.

We compared several of Minnesota’s cervid regulations to those from other U.S. states. We found that some Minnesota policies—such as its statewide deer-baiting ban, wholecarcass importation ban, and mandatory CWD testing of farmed cervids—are among the most rigorous in the nation.

5 Minnesota Statutes 2017, 13.643, subd. 6.

In other areas, however, Minnesota policies were less rigorous than those of other states. Deer feeding encourages animals to congregate artificially, facilitating disease transmission. Minnesota currently allows deer feeding, unless DNR has banned feeding in a particular area as part of its CWD response. Thirty-two percent of states also ban deer feeding only in certain parts of the state, but 18 percent of states ban deer feeding statewide.

The movement of live deer and elk from one place to another may facilitate the spread of CWD if one of the animals being moved happens to be infected. Minnesota bans live-cervid imports from counties in other states where CWD has been found in the wild. Half the states, however, have stricter standards for live-cervid imports.

Forty percent of states do not allow the importation of any live deer or elk. An additional 10 percent of states ban imports from entire states in which CWD has been detected.

We recommend that the Legislature establish an advisory task force to evaluate Minnesota’s policies related to deer feeding and live-cervid imports. 

Exhibit 3.2: Since 2002, Minnesota has had eleven chronic wasting disease events. 

see chart below;

snip...see full text 76 pages;



captive game farms and 100% testing...LOL!


FRIDAY, NOVEMBER 09, 2018 

Minnesota Chronic Wasting Disease CWD TSE Prion Captive Cervid Farming SSS testing policy



FRIDAY, NOVEMBER 16, 2018 

Illinois CWD in FY2018 Fifty-one CWD-positive deer were identified from 8,665 usable WT deer samples collected statewide



THURSDAY, OCTOBER 25, 2018 

***> Norway New additional requirements for imports of hay and straw for animal feed from countries outside the EEA due to CWD TSE Prion



FRIDAY, NOVEMBER 16, 2018 

Norway atypical TSE Prion found in Fourth Moose



SATURDAY, NOVEMBER 10, 2018 

Canada Saskatchewan New Case Of CWD TSE PRION Detected Near Melfort Released on November 7, 2018



SUNDAY, OCTOBER 28, 2018 

Alberta, Canada 2017 Fall CWD TSE Prion Surveillance Results



WEDNESDAY, SEPTEMBER 19, 2018 

CHRONIC WASTING DISEASE CWD TSE PRION Detection of a first case in Quebec Canada



MONDAY, OCTOBER 01, 2018

Minnesota Deer tests positive for CWD in disease management zone



FRIDAY, NOVEMBER 09, 2018 

Mississippi MDWFP Third CWD TSE Prion Suspected in Second Issaquena County White-tailed Deer 11/9/2018

https://chronic-wasting-disease.blogspot.com/2018/11/mississippi-mdwfp-third-cwd-tse-prion.html


THURSDAY, NOVEMBER 08, 2018 

Montana Testing confirms chronic wasting disease in deer harvested in Liberty and Carbon counties 



TUESDAY, NOVEMBER 20, 2018 

Michigan DNR reports 5 more cases of CWD TSE Prion with 75 total to date




SATURDAY, NOVEMBER 03, 2018 

Michigan DNR reports 70 case of CWD while michigan-sportsman.com otcarcher still spreading fake news blaming the poor squirrels



WEDNESDAY, OCTOBER 31, 2018 

Michigan Chronic Wasting Disease CWD TSE Prion Cases Jump To 69 to Date



Michigan adds another CWD TSE Prion case, total at 63 to date



THURSDAY, OCTOBER 04, 2018 

Michigan adds another CWD TSE Prion case, total at 63 to date



WEDNESDAY, SEPTEMBER 26, 2018 

Michigan adds another CWD TSE Prion case, total at 62 to date



MONDAY, AUGUST 27, 2018 

Michigan Adds Another CWD TSE Prion Case Total Increases To 61 to date



WEDNESDAY, SEPTEMBER 19, 2018 

Michigan Department of Natural Resources Slowing the spread of CWD UPDATE Sept 19 2018



THURSDAY, JUNE 21, 2018 

Michigan First case of chronic wasting disease suspected in Jackson County



THURSDAY, JUNE 07, 2018 

Michigan DNR to present chronic wasting disease recommendations to Natural Resources Commission Singeltary submission 



WEDNESDAY, MARCH 07, 2018 

***> Michigan DNR CWD National Perspective: Captive Herd Certification Program - Dr. Tracy Nichols

***> CURRENT STATUS OF CWD IN CAPTIVE CERVID HERDS IN 16 STATES AS OF MAY 2017

43 ELK HERDS

37 WTD HERDS

1 RED DEER HERD

6 MIX SPECIES HERDS

85 CWD-POSITIVE CAPTIVE HERDS 

snip...see



TUESDAY, MARCH 27, 2018 

Hunters and citizens invited to collaborate on Michigan's chronic wasting disease response



FRIDAY, MARCH 30, 2018 

Michigan Mecosta County man sentenced following DNR investigation Game ranch owner falsified information related to chronic wasting disease testing



ONE more thing, please remember, the label does not have to say ''deer ration'' for cervid to be pumped up with. you can get the same ''high protein'' from many sources of high protein feed for animals other than cattle, and feed them to cervid...

Saturday, August 29, 2009

FOIA REQUEST FEED RECALL 2009 Product may have contained prohibited materials Bulk Whole Barley, Recall # V-256-2009


Friday, September 4, 2009

FOIA REQUEST ON FEED RECALL PRODUCT 429,128 lbs. feed for ruminant animals may have been contaminated with prohibited material Recall # V-258-2009



WEDNESDAY, JULY 11, 2018 

CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS FDA EMERGENCY REQUEST FOR RULE CHANGE USA Section 21 C.F.R. 589.2000


TUESDAY, JULY 10, 2018 

CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS 

*** ''but feeding of other ruminant protein, including scrapie-infected sheep, can continue to pigs.'' 

CONFIDENTIAL SPONGIFORM ENCEPHALOPATHY OF PIGS 



New Outbreak of TSE Prion in NEW LIVESTOCK SPECIES

Mad Camel Disease

Our identification of this prion disease in a geographically widespread livestock species requires urgent enforcement of surveillance and assessment of the potential risks to human and animal health.



***> IMPORTS AND EXPORTS <***

***SEE MASSIVE AMOUNTS OF BANNED ANIMAL PROTEIN AKA MAD COW FEED IN COMMERCE USA DECADES AFTER POST BAN ***




O3 Experimental studies on prion transmission barrier and TSE pathogenesis in large animals 

 
Rosa Bolea(1), Acín C(1)Marín B(1), Hedman C(1), Raksa H(1), Barrio T(1), Otero A(1), LópezPérez O(1), Monleón E(1),Martín-Burriel(1), Monzón M(1), Garza MC(1), Filali H(1),Pitarch JL(1), Garcés M(1), Betancor M(1), GuijarroIM(1), GarcíaM(1), Moreno B(1),Vargas A(1), Vidal E(2), Pumarola M(2), Castilla J(3), Andréoletti O(4), Espinosa JC(5), Torres JM(5), Badiola JJ(1). 

1Centro de Investigación en Encefalopatías y Enfermedades Transmisibles Emergentes, VeterinaryFaculty, Universidad de Zaragoza; Zaragoza,Spain.2 RTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB) 3 4 INRA, ÉcoleVétérinaire, Toulouse, France.5CIC bioGUNE, Prion researchlab, Derio, Spain CISA- INIA, Valdeolmos, Madrid 28130, Spain. 

Experimental transmission of Transmissible Spongiform Encephalopathies (TSE) has been understood and related with several factors that could modify the natural development of these diseases. In fact, the behaviour of the natural disease does not match exactly in each animal, being modified by parameters such as the age at infection, the genotype, the breed or the causative strain. Moreover, different TSE strains can target different animal species or tissues, what complicate the prediction of its transmissibility when is tested in a different species of the origin source. The aim of the experimental studies in large animals is to homogenize all those factors, trying to minimize as much as possible variations between individuals. These effects can be flattened by experimental transmission in mice, in which a specific strain can be selected after several passages. With this objective, several experimental studies in large animals have been developed by the presenter research team. 

Classical scrapie agent has been inoculated in cow, with the aim of demonstrate the resistance or susceptibility of this species to the first well known TSE; Atypical scrapie has been inoculated in sheep (using several routes of infection), cow and pig, with the objective of evaluating the potential pathogenicity of this strain; Classical Bovine Spongiform Encephalopathy (BSE) has been inoculated in goats aiming to demonstrate if the genetic background of this species could protect against this strain; goat BSE and sheep BSE have been inoculated in goats and pigs respectively to evaluate the effect of species barrier; and finally atypical BSE has been inoculated in cattle to assess the transmissibility properties of this newly introduced strain. 

Once the experiments have been carried out on large animal species, a collection of samples from animals studied were inoculated in different types of tg mice overexpressing PrPcin order to study the infectivity of the tissues, and also were studied using PMCA. 

In summary, the parameters that have been controlled are the species, the strain, the route of inoculation, the time at infection, the genotype, the age, and the environmental conditions. 

To date, 

***> eleven of the atypical scrapie intracerebrally inoculated sheep have succumbed to atypical scrapie disease; 

***> six pigs to sheep BSE; 

***> one cow to classical scrapie; 

***> nine goats to goat BSE and 

***> five goats to classical BSE. 

***> PrPSC has been demonstrated in all cases by immunohistochemistry and western blot. 


=====> PRION CONFERENCE 2018




Terry S. Singeltary Sr. 

posted by Terry S. Singeltary Sr. at 9:11 AM

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