Wednesday, August 16, 2017

OHIO Chronic Wasting Disease CWD TSE Prion UPDATE?

Subject: OHIO Chronic Wasting Disease CWD TSE Prion UPDATE?

OHIO CWD holmes and wayne counties, 2 cwd facilities depopulated, DSA cwd killed 700 tested not detected, they believe cwd was contained to those two facilities. they hope. not very many cwd tests. surveillance and testing there from seem to be lacking, considering about 750,000. head of deer in Ohio... imo...terry

Ohio Deer Hunting Season 2017-2018 Today, the deer population in Ohio exceeds 750,000.


see map;



WEDNESDAY, AUGUST 05, 2015

Ohio confirms to me Chronic Wasting Disease 

CWD Spreads 19 confirmed cases to date Just got off the phone with Christy Clevenger of Ohio

Ohio Department of Agriculture March 2012 – Present (3 years 6 months) Reynoldsburg, Ohio CWD program

Ms. Clevenger confirmed, to date, from the Yoder debacle, 1 confirmed case of CWD from the Hunting Preserve, 2 confirmed cases from the Breeding Farm, and 16 confirmed cases of CWD from the Breeder Depopulation, with a total to date of 19 cases of CWD in Ohio...with sad regards, Terry






DISEASE UPDATE

Chronic wasting disease (CWD) is a fatal disease of the central nervous system of mule deer, white-tailed deer, elk, and moose. CWD is disease caused by abnormal proteins, or prions (not a bacteria or virus), that ultimately destroy brain tissue. This type of disease is known as a transmissible spongiform encephalopathy (TSE). This family of diseases includes bovine spongiform encephalopathy (“mad cow disease”), scrapie in sheep, and Creutzfeldt-Jacob Disease (CJD) in humans.

Since 2002 the Division of Wildlife has conducted statewide CWD surveillance, testing more than 14,500 free-ranging deer. To date, there has yet to be a wild, free-ranging deer test positive for the disease in Ohio. In 2015, Division of Wildlife staff collected 824 road-killed deer from 57 counties. An additional 1,000 deer harvested by hunters during the 2015-16 season (752 submitted by hunters and 248 collected from taxidermists) and 51 deer that either appeared to be in poor condition or were displaying abnormal behavior were also collected and tested for the disease. As in previous years, CWD was not detected in any of the wild deer tested. However, in October of 2014, a mature buck from a shooting preserve in Holmes County tested positive for CWD, becoming the first-ever CWD-positive deer in Ohio. The shooting preserve was depopulated in April of 2015, and testing revealed no additional CWD-positive animals. Subsequent testing of nearly 300 free-ranging deer in an 8-township area around the shooting preserve failed to detect any CWD-positive deer as well. However, in spring of 2015, two more CWD-positive deer were reported from a captive white-tailed deer breeding pen in Holmes County. This herd was depopulated in June 2015, and 16 additional deer tested positive for the disease, bringing the grand total of CWD-positive animals found in Ohio to 19 (all in captive herds). In response to these findings, the Division of Wildlife conducted targeted surveillance in the immediate vicinity of the infected facility during the summer of 2015. Staff collected 18 deer, including two that had escaped from captive facilities, with none testing positive for CWD.

Additionally, the focus area in 2015 was expanded to include two townships in southern Wayne County, and the 10-township focus area was declared a Disease Surveillance Area (DSA, Figure 10). This DSA designation will remain in effect for a minimum of three years and the following regulations apply: 1) required submission of deer harvested within the DSA to Division of Wildlife inspection stations for sampling during the gun and muzzleloader seasons, 2) prohibit the placement of or use of salt, mineral supplement, grain, fruit, vegetables or other feed to attract or feed deer within the DSA boundaries, 3) prohibit the hunting of deer by the aid of salt, mineral supplement, grain, fruit, vegetables or other feed within the DSA boundaries, and 4) prohibit the removal of a deer carcass killed by motor vehicle within the DSA boundaries unless the carcass complies with the cervidae carcass regulations (see wildohio.gov for additional information on carcass regulations). Under the new rule requiring mandatory submission of deer harvested in the DSA, hunters presented nearly 550 deer for testing at inspection stations during the gun, bonus gun, and muzzleloader seasons this past year. Combining all methods of sample collection (roadkill, mandatory submission of hunter harvests during the gun seasons, voluntary submission of hunter harvests during the archery season, and targeted surveillance), 752 deer were tested from the DSA.



July 30, 2015 

Chronic Wasting Disease Spreads in Ohio by Kristen A. Schmitt

There’s a problem in Holmes County, Ohio, and the state's Division of Wildlife (ODW) is going door-to-door to solve it:

Nineteen confirmed cases of Chronic Wasting Disease (CWD) can be traced to a single location in the area, World Class Whitetails of Ohio, a deer hunting preserve-and-breeding facility, which officials first quarantined last fall.

Because of CWD’s severity, wildlife officials are now covering ground on foot, hoping to harvest and sample whitetails within a three-mile radius of the preserve to see how far the disease has spread.

According to The Daily Record, last October World Class Whitetails owner Daniel Yoder disobeyed orders from the Ohio Department of Agriculture—which oversees deer farming—to isolate his deer, as the fatal disease, the state's first case of which in either wild or farm-raised deer, seems to have originated at the facility. So far this summer, 500 deer have been euthanized and tested for CWD at Yoder's facility to contain the disease.

"We've drawn a three-mile circle around the breeding pen and divided it up into 1-, 2-, and 3-mile zones," said Dennis Solon, an ODW manager for the Killbuck Marsh Wildlife Area. "We've contacted all the landowners who have a decent amount of land within those zones, and asked them if we can sample wild deer from their property."

The deer harvest is voluntary, but if landowners consent, they can specify the sex of the deer taken. Officials hope to obtain one or two deer from each parcel before October 1 for testing. "We don't want to look back and say, 'what could we have done?'" Solon said. "We're trying to do what's best for the deer population and the people of Ohio."


FRIDAY, NOVEMBER 20, 2015

ODNR Takes Action to Monitor Chronic Wasting Disease in Ohio's Deer Herd


Friday, October 23, 2015

Ohio Wildlife Council Passes Rule to Help Monitor CWD


Thursday, April 02, 2015

OHIO CONFIRMS SECOND POSTIVE CHRONIC WASTING DISEASE CWD on Yoder's properties near Millersburg


Wednesday, February 11, 2015

World Class Whitetails quarantined CWD deer Daniel M. Yoder charged with two counts of tampering with evidence



Thursday, October 23, 2014

*** FIRST CASE OF CHRONIC WASTING DISEASE CONFIRMED IN OHIO ON PRIVATE PRESERVE


Monday, June 11, 2012

*** OHIO Captive deer escapees and non-reporting ***


Chronic Wasting Disease 

 What is Chronic Wasting Disease?

The Ohio Department of Agriculture Division of Animal Health's Disease Diagnostics Laboratory is working with the Ohio Departments of Natural Resources and Health and the USDA to test and monitor Ohio's deer herd for evidence of Chronic Wasting Disease (CWD).

CWD is a progressive, fatal, degenerative disease of the brain affecting elk, mule deer, moose and white-tailed deer. CWD belongs to a group of related diseases called TransmissibleSpongiformEncephalopathies (TSE's), which includes diseases such as Scrapie in sheep and goats,Bovine Spongiform Encephalopathy (BSE) in cattle and Creutzfeldt-Jakob Disease (CJD) in humans. There is no evidence that CWD affects humans. CWD is not the same as CJD or BSE (Mad Cow Disease). TSE's are thought to be caused by abnormal proteins, called prions inthe brain. There is currently no treatment or vaccine available.

For the sixth year in a row, testing of Ohio's deer herd has found no evidence of CWD. State officials collected samples from hunter-harvested deer during the 2002-2008 deer-gun season. The samples were then tested by the Animal Disease Diagnostic laboratory. Hunter surveillance testing is completed for the 2009 CWD survey. All samples tested negative for both CWD and bovine tuberculosis. 

CWD Resources

2010 CWD Results 


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



Chronic Wasting Disease CWD TSE Prion to Humans, who makes that final call, when, or, has it already happened?

SATURDAY, JULY 29, 2017

Risk Advisory Opinion: Potential Human Health Risks from Chronic Wasting Disease CFIA, PHAC, HC (HPFB and FNIHB), INAC, Parks Canada, ECCC and AAFC


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


TUESDAY, JUNE 13, 2017

PRION 2017 CONFERENCE ABSTRACT Chronic Wasting Disease in European moose is associated with PrPSc features different from North American CWD


TUESDAY, JULY 04, 2017

*** PRION 2017 CONFERENCE ABSTRACTS ON CHRONIC WASTING DISEASE CWD TSE PRION ***


URINE

SUNDAY, JULY 16, 2017

*** Temporal patterns of chronic wasting disease prion excretion in three cervid species ***



> > > Two of the six fawns with CWD detected were 5 to 6 months old. < < <

Wisconsin : Six White-Tailed Deer Fawns Test Positive for CWD 

Date: May 13, 2003 Source: Wisconsin Department of Natural Resources 

Contacts: Julie Langenberg Wildlife Veterinarian 608-266-3143 Tom Hauge Director, Bureau of Wildlife Management 608-266-2193 

MADISON -- Six fawns in the area of south central Wisconsin where chronic wasting disease has been found in white-tailed deer have tested positive for the disease, according to Department of Natural Resources wildlife health officials. These are the youngest wild white-tailed deer detected with chronic wasting disease (CWD) to date. 

Approximately 4,200 fawns, defined as deer under 1 year of age, were sampled from the eradication zone over the last year. The majority of fawns sampled were between the ages of 5 to 9 months, though some were as young as 1 month. Two of the six fawns with CWD detected were 5 to 6 months old. All six of the positive fawns were taken from the core area of the CWD eradication zone where the highest numbers of positive deer have been identified. 

"This is the first intensive sampling for CWD in fawns anywhere," said Dr. Julie Langenberg, Department of Natural Resources wildlife veterinarian, "and we are trying to learn as much as we can from these data". 

"One noteworthy finding is simply the fact that we found positive fawns," Dr. Langenberg said. "These results do show us that CWD transmission can happen at a very young age in wild white-tailed deer populations. However, we found that the percentage of fawns infected with CWD is very low, in the area of 0.14 percent. If there was a higher rate of infection in fawns, then fawns dispersing in the spring could be much more worrisome for disease spread." 

Dr. Langenberg noted that while the youngest CWD-positive fawns had evidence of disease-causing prions only in lymph node tissue, several of the older CWD-positive fawns had evidence of CWD prions in both lymph node and brain tissues -- suggesting further progression of the disease. 

"Finding CWD prions in both lymph and brain tissues of deer this young is slightly surprising," said Langenberg, "and provides information that CWD infection and illness may progress more rapidly in a white-tailed deer than previously suspected. Published literature suggests that CWD doesn't cause illness in a deer until approximately 16 months of age. Our fawn data shows that a few wild white-tailed deer may become sick from CWD or may transmit the disease before they reach that age of 16 months." 

One of the positive fawns was shot with a doe that was also CWD positive. Information about these fawn cases combined with will help researchers who are studying the age and routes of CWD transmission in wild deer populations. "More data analysis and ongoing deer movement studies should give us an even better understanding of how this disease moves across the landscape", said Langenberg. 

"Thanks to eradication zone hunters who submitted deer of all ages for sampling, we have a valuable set of fawn data that is contributing to our state's and the nation's understanding about CWD," Langenberg said. 



SATURDAY, FEBRUARY 04, 2012

Wisconsin 16 MONTH age limit on testing dead deer Game Farm CWD Testing Protocol Needs To Be Revised


Most research has shown that the appearance of the misfolded PrPSc isoform in peripheral tissues and the onset of shedding may take place months or perhaps years before the appearance of clinical signs.


 IHC analysis, the gold standard for CWD regulatory testing in the United States, has identified prion infection in the deer RLN as early as 3 to 6 months into the course of the disease and in the brainstem as soon as 6 to 9 months postexposure (14)


3.5.2.2 Studies of PrPCWD in experimentally infected animals The pathogenesis of CWD has also been studied in experimentally infected mule deer via oral exposure to brain homogenate from clinical case of CWD (Sigurdson et al, 1999). PrPCWD was detected in alimentary-tract-associated lymphoid tissues (one or more 19 of the following: retropharyngeal lymph node, tonsil, Peyer’s patches and ileocaecal lymph node) as early as 42 days p.i. and in all fawns examined thereafter (53 through to 80 days p.i when the study was terminated). No PrPCWD was detectable in neural tissue in any fawn. In ongoing pathogenesis studies (Williams et al., unpublished) in deer brain, PrPCWD has been found at the age of 5-6 months when it was also found in lymphoid tissues. 

3.5.3 Conclusions In deer and elk, PrPCWD has a very wide and early tissue distribution, which resembles the distribution of scrapie and BSE agents in tissues in TSE-susceptible sheep and is different to that seen in BSE in cattle. However, tissue distribution is not identical for deer4 and elk. In the latter species it accumulates later in the incubation period into detectable levels. This widespread distribution of PrPCWD early in the incubation period presents significant, if not insurmountable, difficulty with respect to the potential for decisions on the removal of specified risk materials (SRM) in CWD.

The incubation period range in naturally occurring CWD is not known. Evidence of CWD infection (not clinical disease) has been seen in deer fawns and elk calves by about 6 months of age (Dr. Spraker). The youngest naturally infected mule deer diagnosed with clinical disease was 17 month of age suggesting 16 to 17 months as an approximate minimum incubation. CWD has been diagnosed in a 24 months old Rocky Mountain elk (Ball, 2002). Clinical disease in experimentally infected elk was observed by 12 months (range 12-34 months) post-exposure. In experimentally infected deer, minimum incubation was approximately 15 months and mean time from oral infection to death was approximately 23 months (20->25 months).



PAGE 25 
Transmission Studies 
Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases 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 inoculam (?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. 

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).***

Molecular Barriers to Zoonotic Transmission of Prions
*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.
 *** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.

*** 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 ;
you can see more evidence here ;

*** 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 

PRION 2016 TOKYO 
Zoonotic Potential of CWD Prions: An Update 
Chronic wasting disease (CWD) is a widespread and highly transmissible prion disease in free-ranging and captive cervid species in North America. The zoonotic potential of CWD prions is a serious public health concern, but the susceptibility of human CNS and peripheral organs to CWD prions remains largely unresolved. We reported earlier that peripheral and CNS infections were detected in transgenic mice expressing human PrP129M or PrP129V. Here we will present an update on this project, including evidence for strain dependence and influence of cervid PrP polymorphisms on CWD zoonosis as well as the characteristics of experimental human CWD prions. 
PRION 2016 TOKYO In Conjunction with Asia Pacific Prion Symposium 2016 PRION 2016 Tokyo Prion 2016 
PRION 2016 TOKYO In Conjunction with Asia Pacific Prion Symposium 2016 PRION 2016 Tokyo Prion 2016 

Monday, May 02, 2016 
*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo *** 

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. 

Key Molecular Mechanisms of TSEs 
Zabel, Mark D. 
Colorado State University-Fort Collins, Fort Collins, CO, United States 
Abstract Prion diseases, or transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative diseases affecting humans, cervids, bovids, and ovids. The absolute requirement of PrPC expression to generate prion diseases and the lack of instructional nucleic acid define prions as unique infectious agents. Prions exhibit species-specific tropism, inferring that unique prion strains exist that preferentially infct certain host species and confront transmission barriers to heterologous host species. However, transmission barriers are not absolute. Scientific consensus agrees that the sheep TSE scrapie probably breached the transmission barrier to cattle causing bovine spongiform encephalopathy that subsequently breached the human transmission barrier and likely caused several hundred deaths by a new-variant form of the human TSE Creutzfeldt-Jakob disease in the UK and Europe. The impact to human health, emotion and economies can still be felt in areas like farming, blood and organ donations and the threat of a latent TSE epidemic. This precedent raises the real possibility of other TSEs, like chronic wasting disease of cervids, overcoming similar human transmission barriers. A groundbreaking discovery made last year revealed that mice infected with heterologous prion strains facing significant transmission barriers replicated prions far more readily in spleens than brains6. Furthermore, these splenic prions exhibited weakened transmission barriers and expanded host ranges compared to neurogenic prions. These data question conventional wisdom of avoiding neural tissue to avoid prion xenotransmission, when more promiscuous prions may lurk in extraneural tissues. Data derived from work previously funded by NIH demonstrate that Complement receptors CD21/35 bind prions and high density PrPC and differentially impact prion disease depending on the prion isolate or strain used. Recent advances in live animal and whole organ imaging have led us to generate preliminary data to support novel, innovative approaches to assessing prion capture and transport. We plan to test our unifying hypothesis for this proposal that CD21/35 control the processes of peripheral prion capture, transport, strain selection and xenotransmission in the following specific aims. 
1. Assess the role of CD21/35 in splenic prion strain selection and host range expansion. 
2. Determine whether CD21/35 and C1q differentially bind distinct prion strains 
3. Monitor the effects of CD21/35 on prion trafficking in real time and space 
4. Assess the role of CD21/35 in incunabular prion trafficking 
Public Health Relevance Transmissible spongiform encephalopathies, or prion diseases, are devastating illnesses that greatly impact public health, agriculture and wildlife in North America and around the world. The impact to human health, emotion and economies can still be felt in areas like farming, blood and organ donations and the threat of a latent TSE epidemic. This precedent raises the real possibility of other TSEs, like chronic wasting disease (CWD) of cervids, overcoming similar human transmission barriers. Early this year Canada reported its first case of BSE in over a decade audits first case of CWD in farmed elk in three years, underscoring the need for continued vigilance and research. Identifying mechanisms of transmission and zoonoses remains an extremely important and intense area of research that will benefit human and other animal populations. 

PMCA Detection of CWD Infection in Cervid and Non-Cervid Species 
Hoover, Edward Arthur 
Colorado State University-Fort Collins, Fort Collins, CO, United States 

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).*** 


Molecular Barriers to Zoonotic Transmission of Prions
*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.
*** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.

SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY
***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.***

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. 
 
***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. 
 
 
 
In conclusion, the results in the current study indicate that removal of furniture that had been in contact with scrapie-infected animals should be recommended, particularly since cleaning and decontamination may not effectively remove scrapie infectivity (31), even though infectivity declines considerably if the pasture and the field furniture have not been in contact with scrapie-infected sheep for several months. As sPMCA failed to detect PrPSc in furniture that was subjected to weathering, even though exposure led to infection in sheep, this method may not always be reliable in predicting the risk of scrapie infection through environmental contamination. These results suggest that the VRQ/VRQ sheep model may be more sensitive than sPMCA for the detection of environmentally associated scrapie, and suggest that extremely low levels of scrapie contamination are able to cause infection in susceptible sheep genotypes. 
 
Keywords: classical scrapie, prion, transmissible spongiform encephalopathy, sheep, field furniture, reservoir, serial protein misfolding cyclic amplification 
 
 
Wednesday, December 16, 2015 
 
*** Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission *** 
 
 
*** Infectious agent of sheep scrapie may persist in the environment for at least 16 years *** 
 
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3 
 
 
with CWD TSE Prions, I am not sure there is any absolute yet, other than what we know with transmission studies, and we know tse prion kill, and tse prion are bad. science shows to date, that indeed soil, dirt, some better than others, can act as a carrier. same with objects, farm furniture. take it with how ever many grains of salt you wish, or not. if load factor plays a role in the end formula, then everything should be on the table, in my opinion...tss
 
 
 Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil Particles
 
Author Summary
 
Transmissible spongiform encephalopathies (TSEs) are a group of incurable neurological diseases likely caused by a misfolded form of the prion protein. TSEs include scrapie in sheep, bovine spongiform encephalopathy (‘‘mad cow’’ disease) in cattle, chronic wasting disease in deer and elk, and Creutzfeldt-Jakob disease in humans. Scrapie and chronic wasting disease are unique among TSEs because they can be transmitted between animals, and the disease agents appear to persist in environments previously inhabited by infected animals. Soil has been hypothesized to act as a reservoir of infectivity and to bind the infectious agent. In the current study, we orally dosed experimental animals with a common clay mineral, montmorillonite, or whole soils laden with infectious prions, and compared the transmissibility to unbound agent. We found that prions bound to montmorillonite and whole soils remained orally infectious, and, in most cases, increased the oral transmission of disease compared to the unbound agent. The results presented in this study suggest that soil may contribute to environmental spread of TSEs by increasing the transmissibility of small amounts of infectious agent in the environment.
 
 
tse prion soil
 
 
 
 
 
Wednesday, December 16, 2015
 
Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission
 
 
The sources of dust borne prions are unknown but it seems reasonable to assume that faecal, urine, skin, parturient material and saliva-derived prions may contribute to this mobile environmental reservoir of infectivity. This work highlights a possible transmission route for scrapie within the farm environment, and this is likely to be paralleled in CWD which shows strong similarities with scrapie in terms of prion dissemination and disease transmission. The data indicate that the presence of scrapie prions in dust is likely to make the control of these diseases a considerable challenge.
 
 
>>>Particle-associated PrPTSE molecules may migrate from locations of deposition via transport processes affecting soil particles, including entrainment in and movement with air and overland flow. <<<
 
Fate of Prions in Soil: A Review
 
Christen B. Smith, Clarissa J. Booth, and Joel A. Pedersen*
 
Several reports have shown that prions can persist in soil for several years. Significant interest remains in developing methods that could be applied to degrade PrPTSE in naturally contaminated soils. Preliminary research suggests that serine proteases and the microbial consortia in stimulated soils and compost may partially degrade PrPTSE. Transition metal oxides in soil (viz. manganese oxide) may also mediate prion inactivation. Overall, the effect of prion attachment to soil particles on its persistence in the environment is not well understood, and additional study is needed to determine its implications on the environmental transmission of scrapie and CWD.
 
 
P.161: Prion soil binding may explain efficient horizontal CWD transmission
 
Conclusion. Silty clay loam exhibits highly efficient prion binding, inferring a durable environmental reservoir, and an efficient mechanism for indirect horizontal CWD transmission.
 
 
>>>Another alternative would be an absolute prohibition on the movement of deer within the state for any purpose. While this alternative would significantly reduce the potential spread of CWD, it would also have the simultaneous effect of preventing landowners and land managers from implementing popular management strategies involving the movement of deer, and would deprive deer breeders of the ability to engage in the business of buying and selling breeder deer. Therefore, this alternative was rejected because the department determined that it placed an avoidable burden on the regulated community.<<<
 
Wednesday, December 16, 2015
 
Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission
 
Timm Konold1*, Stephen A. C. Hawkins2, Lisa C. Thurston3, Ben C. Maddison4, Kevin C. Gough5, Anthony Duarte1 and Hugh A. Simmons1
 
1 Animal Sciences Unit, Animal and Plant Health Agency Weybridge, Addlestone, UK, 2 Pathology Department, Animal and Plant Health Agency Weybridge, Addlestone, UK, 3 Surveillance and Laboratory Services, Animal and Plant Health Agency Penrith, Penrith, UK, 4 ADAS UK, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK, 5 School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK
 
Classical scrapie is an environmentally transmissible prion disease of sheep and goats. Prions can persist and remain potentially infectious in the environment for many years and thus pose a risk of infecting animals after re-stocking. In vitro studies using serial protein misfolding cyclic amplification (sPMCA) have suggested that objects on a scrapie affected sheep farm could contribute to disease transmission. This in vivo study aimed to determine the role of field furniture (water troughs, feeding troughs, fencing, and other objects that sheep may rub against) used by a scrapie-infected sheep flock as a vector for disease transmission to scrapie-free lambs with the prion protein genotype VRQ/VRQ, which is associated with high susceptibility to classical scrapie. When the field furniture was placed in clean accommodation, sheep became infected when exposed to either a water trough (four out of five) or to objects used for rubbing (four out of seven). This field furniture had been used by the scrapie-infected flock 8 weeks earlier and had previously been shown to harbor scrapie prions by sPMCA. Sheep also became infected (20 out of 23) through exposure to contaminated field furniture placed within pasture not used by scrapie-infected sheep for 40 months, even though swabs from this furniture tested negative by PMCA. This infection rate decreased (1 out of 12) on the same paddock after replacement with clean field furniture. Twelve grazing sheep exposed to field furniture not in contact with scrapie-infected sheep for 18 months remained scrapie free. The findings of this study highlight the role of field furniture used by scrapie-infected sheep to act as a reservoir for disease re-introduction although infectivity declines considerably if the field furniture has not been in contact with scrapie-infected sheep for several months. PMCA may not be as sensitive as VRQ/VRQ sheep to test for environmental contamination.
 
snip...
 
Discussion
 
Classical scrapie is an environmentally transmissible disease because it has been reported in naïve, supposedly previously unexposed sheep placed in pastures formerly occupied by scrapie-infected sheep (4, 19, 20). Although the vector for disease transmission is not known, soil is likely to be an important reservoir for prions (2) where – based on studies in rodents – prions can adhere to minerals as a biologically active form (21) and remain infectious for more than 2 years (22). Similarly, chronic wasting disease (CWD) has re-occurred in mule deer housed in paddocks used by infected deer 2 years earlier, which was assumed to be through foraging and soil consumption (23).
 
Our study suggested that the risk of acquiring scrapie infection was greater through exposure to contaminated wooden, plastic, and metal surfaces via water or food troughs, fencing, and hurdles than through grazing. Drinking from a water trough used by the scrapie flock was sufficient to cause infection in sheep in a clean building. Exposure to fences and other objects used for rubbing also led to infection, which supported the hypothesis that skin may be a vector for disease transmission (9). The risk of these objects to cause infection was further demonstrated when 87% of 23 sheep presented with PrPSc in lymphoid tissue after grazing on one of the paddocks, which contained metal hurdles, a metal lamb creep and a water trough in contact with the scrapie flock up to 8 weeks earlier, whereas no infection had been demonstrated previously in sheep grazing on this paddock, when equipped with new fencing and field furniture. When the contaminated furniture and fencing were removed, the infection rate dropped significantly to 8% of 12 sheep, with soil of the paddock as the most likely source of infection caused by shedding of prions from the scrapie-infected sheep in this paddock up to a week earlier.
 
This study also indicated that the level of contamination of field furniture sufficient to cause infection was dependent on two factors: stage of incubation period and time of last use by scrapie-infected sheep. Drinking from a water trough that had been used by scrapie sheep in the predominantly pre-clinical phase did not appear to cause infection, whereas infection was shown in sheep drinking from the water trough used by scrapie sheep in the later stage of the disease. It is possible that contamination occurred through shedding of prions in saliva, which may have contaminated the surface of the water trough and subsequently the water when it was refilled. Contamination appeared to be sufficient to cause infection only if the trough was in contact with sheep that included clinical cases. Indeed, there is an increased risk of bodily fluid infectivity with disease progression in scrapie (24) and CWD (25) based on PrPSc detection by sPMCA. Although ultraviolet light and heat under natural conditions do not inactivate prions (26), furniture in contact with the scrapie flock, which was assumed to be sufficiently contaminated to cause infection, did not act as vector for disease if not used for 18 months, which suggest that the weathering process alone was sufficient to inactivate prions.
 
PrPSc detection by sPMCA is increasingly used as a surrogate for infectivity measurements by bioassay in sheep or mice. In this reported study, however, the levels of PrPSc present in the environment were below the limit of detection of the sPMCA method, yet were still sufficient to cause infection of in-contact animals. In the present study, the outdoor objects were removed from the infected flock 8 weeks prior to sampling and were positive by sPMCA at very low levels (2 out of 37 reactions). As this sPMCA assay also yielded 2 positive reactions out of 139 in samples from the scrapie-free farm, the sPMCA assay could not detect PrPSc on any of the objects above the background of the assay. False positive reactions with sPMCA at a low frequency associated with de novo formation of infectious prions have been reported (27, 28). This is in contrast to our previous study where we demonstrated that outdoor objects that had been in contact with the scrapie-infected flock up to 20 days prior to sampling harbored PrPSc that was detectable by sPMCA analysis [4 out of 15 reactions (12)] and was significantly more positive by the assay compared to analogous samples from the scrapie-free farm. This discrepancy could be due to the use of a different sPMCA substrate between the studies that may alter the efficiency of amplification of the environmental PrPSc. In addition, the present study had a longer timeframe between the objects being in contact with the infected flock and sampling, which may affect the levels of extractable PrPSc. Alternatively, there may be potentially patchy contamination of this furniture with PrPSc, which may have been missed by swabbing. The failure of sPMCA to detect CWD-associated PrP in saliva from clinically affected deer despite confirmation of infectivity in saliva-inoculated transgenic mice was associated with as yet unidentified inhibitors in saliva (29), and it is possible that the sensitivity of sPMCA is affected by other substances in the tested material. In addition, sampling of amplifiable PrPSc and subsequent detection by sPMCA may be more difficult from furniture exposed to weather, which is supported by the observation that PrPSc was detected by sPMCA more frequently in indoor than outdoor furniture (12). A recent experimental study has demonstrated that repeated cycles of drying and wetting of prion-contaminated soil, equivalent to what is expected under natural weathering conditions, could reduce PMCA amplification efficiency and extend the incubation period in hamsters inoculated with soil samples (30). This seems to apply also to this study even though the reduction in infectivity was more dramatic in the sPMCA assays than in the sheep model. Sheep were not kept until clinical end-point, which would have enabled us to compare incubation periods, but the lack of infection in sheep exposed to furniture that had not been in contact with scrapie sheep for a longer time period supports the hypothesis that prion degradation and subsequent loss of infectivity occurs even under natural conditions.
 
In conclusion, the results in the current study indicate that removal of furniture that had been in contact with scrapie-infected animals should be recommended, particularly since cleaning and decontamination may not effectively remove scrapie infectivity (31), even though infectivity declines considerably if the pasture and the field furniture have not been in contact with scrapie-infected sheep for several months. As sPMCA failed to detect PrPSc in furniture that was subjected to weathering, even though exposure led to infection in sheep, this method may not always be reliable in predicting the risk of scrapie infection through environmental contamination. These results suggest that the VRQ/VRQ sheep model may be more sensitive than sPMCA for the detection of environmentally associated scrapie, and suggest that extremely low levels of scrapie contamination are able to cause infection in susceptible sheep genotypes.
 
Keywords: classical scrapie, prion, transmissible spongiform encephalopathy, sheep, field furniture, reservoir, serial protein misfolding cyclic amplification
 
 
Wednesday, December 16, 2015
 
*** Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission ***
 
 
*** Infectious agent of sheep scrapie may persist in the environment for at least 16 years ***
 
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
 
 
MONDAY, JUNE 12, 2017
 
Rethinking Major grain organizations opposition to CFIA's control zone approach to Chronic Wasting CWD TSE Prion Mad Deer Type Disease 2017?
 
 
WEDNESDAY, MAY 17, 2017
 
*** Chronic Wasting Disease CWD TSE Prion aka Mad Deer Disease and the Real Estate Market Land Values ***
 


*** Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep. 


*** After a natural route of exposure, 100% of WTD were susceptible to scrapie.

TUESDAY, MARCH 28, 2017 

*** Passage of scrapie to deer results in a new phenotype upon return passage to sheep ***


MONDAY, AUGUST 14, 2017

WEDNESDAY, JULY 26, 2017

Chronic wasting disease continues to spread Disease of cervids causing local population declines


WEDNESDAY, AUGUST 16, 2017
ARKANSAS CWD TSE PRION 214 CASES CONFIRMED TO DATE AS OF AUGUST 9, 2017
THURSDAY, AUGUST 03, 2017
Wisconsin CWD Showing Up in Northern Wisconsin Deer Farms
Wednesday, February 10, 2016
*** Wisconsin Two deer that escaped farm had chronic wasting disease CWD ***


SATURDAY, AUGUST 12, 2017

Pennsylvania 27 deer from Bedford County farm test positive for chronic wasting disease


Iowa Supreme Court rules law allows quarantine of CWD deer, not land

This is very, very concerning imo. 

IF this ruling is upheld as such ;

''The Iowa Supreme Court upheld the district court ruling — saying the law gives the DNR only the authority to quarantine the deer — not the land. The ruling says if the Iowa Legislature wants to expand the quarantine powers as suggested by the DNR, then it is free to do so.''

IF a 'precedent' is set as such, by the Legislature not intervening to expand quarantine powers to the DNR for CWD TSE Prion, and the precedent is set as such that the cervid industry and land there from, once contaminated with the CWD TSE Prion, are free to repopulate, sell the land, etc, imo, this will blow the lid off any containment efforts of this damn disease CWD TSE Prion. The Iowa Supreme Court did not just pass the cwd buck down the road, the Supreme Court of Iowa just threw the whole state of Iowa under the bus at 100 MPH. i remember the litigation that took place and the fuss over all those 'healthy' looking deer standing out in the pasture, i remember the photo postings and thread on the web on the deer farmers board, of all those healthy looking deer. the big rally behind the owners on the web, how they were going to come and cut the fences, folks liking the comments, 100 deer farmers were going to show up and stop the officials from coming in to test the deer. yep, it was on the www. all those healthy deer, while the litigation was going on, well, they were incubating the cwd tse prion, loading up the land even more, and in the end, 79.8% of those healthy looking deer had CWD TSE Prion. what about the exposure to the other species that come across that land, and then off to some other land? this makes no sense to me, if this is set in stone and the Legislation does not stop it, and stop if fast, any containment of the cwd tse prion will be futile, imo...terry

FRIDAY, JUNE 16, 2017

Iowa Supreme Court rules law allows quarantine of CWD deer, not land


MONDAY, AUGUST 14, 2017

Texas Chronic Wasting Disease CWD TSE Prion History



SUNDAY, AUGUST 06, 2017 

USA Chronic Wasting Disease CWD TSE Prion Emergency Response Plan Singeltary et al 




Terry S. Singeltary Sr.