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Tuesday, July 12, 2016

Louisiana Notice of Intent Cervid Carcass Importation (LAC XIX.V.1.119) CWD TSE PRION

Subject: Louisiana Notice of Intent Cervid Carcass Importation (LAC XIX.V.1.119) CWD TSE PRION

Greetings Chairman Yakupzack, Louisiana Wildlife and Fisheries Officials and Hunters,
 
I kindly wish to submit the following Science on Chronic Wasting Disease CWD Transmissible Spongiform Encephalopathy TSE Prion disease, aka mad cow type disease in cervid. yes, it’s alright to say that, because that is what it is scientifically, like it or not. I have wasted what seems to be a lifetime, daily, my life researching as a layperson this damn disease. I lost my mother to the Heidenhain Variant of Creutzfeldt Jakob Disease hvCJD December of 1997, and just could never except the officials word of ‘it’s not here’. well, it’s been here, and I have proven this with my research of the history and science of the TSE prion disease. I kindly wish to submit this to you and the great state of Louisiana. please use as you wish, I do not advertise or make money from this, I just made a promise to mom. never forget, and never let them forget.
 
I understand fully that this is more information on the CWD Scrapie TSE prion than you want to know, but it’s not going anywhere, and it will find you eventually. I hope I am wrong there.
 
I hope you find this information useful in your future decisions and policy making with the CWD, Scrapie, TSE, Prion disease, and I truly hope that Louisiana is spared from the CWD Scrapie TSE Prion disease, but I have my doubts that this will happen, if it’s not there already. when you test to find, you find cwd tse prion. when you don’t test to find, you might or might not find it, until it gets real bad, then you can’t miss it. ...GOOD LUCK!
 
Thank You,
 
with kindest regards,
I am sincerely,
 
Terry S. Singeltary Sr.
 
Bacliff, Texas USA 77518
 
 
NOTICE OF INTENT
 
Department of Wildlife and Fisheries
 
Wildlife and Fishereies Commission
 
Cervid Carcass Importation
 
(LAC XIX.V.1.119)
 
The Department of Wildlife and Fisheries and the Wildlife and Fisheries Commission do hereby give notice of its intent to establish rules and regulations in relation to the importation of cervid carcasses.
 
Title 76
 
WILDLIFE AND FISHERIES
 
Part V. Wild Quadrupeds and Birds
 
Chapter 1. Wild Quadrupeds
 
§119 . Cervid Carcass Importation
 
A. Definitions
 
Cervid —any animal of the family Cervidae including but not limited to including but not limited to white -tailed deer, mule deer, elk, moose, caribou, fallow deer, axis deer, sika deer, red deer, and reindeer.
 
B. No person shall import, transport or possess any cervid carcass or part of a cervid carcass originating outside Louisiana, except: deboned meat, antlers, clean skull plates with antlers, clean skull plates without tissue attached, capes, tanned hides, finished taxidermy mounts, and cleaned cervid teeth. Approved parts or deboned meat transported from other states must be legally possessed from the state it was taken.
 
Approved parts and deboned meat from other states must contain a possession tag with the hunter’s name, out-of-state license number (if required), address, species, date and location (county and state) of harvest. All cervids transported into or through this state in violation of the provisions of this ban shall be seized and disposed of in accordance with Wildlife and Fisheries Commission Department of Wildlife and Fisheries rules regulations.
 
AUTHORITY NOTE: Promulgated in accordance with the Louisiana Constitution, Article IX, Section 7, R.S. 56:1, R.S. 56:5, R.S. 56:6(10), (13) and 15), R.S. 56:20, R.S. 56:112, R.S. 56:116.1 and R.S. 56:171 et seq.
 
The secretary of the Department of Wildlife and Fisheries is authorized to take any and all necessary steps on behalf of the Commission to promulgate and effectuate this Notice of Intent and the Final Rule, including but not limited to, the filing of the Fiscal and Economic Impact Statements, the filing of the Notice of Intent and final Rule and the preparation of reports and correspondence to other agencies of government.
 
Family Impact Statement
 
In accordance with Act #1183 of 1999 Regular Session of the Louisiana Legislature, the Department of Wildlife and Fisheries, Wildlife and Fisheries Commission hereby issues its Family Impact Statement in connection with the preceding Notice of Intent. This Notice of Intent will have no impact on the six criteria set out at R.S. 49:972(B).
 
Poverty Impact Statement
 
The proposed rulemaking will have no impact on poverty as described in R.S. 49:973.
 
Provider Impact Statement
 
This Rule has no known impact on providers as described in HCR 170 of the 2014 Regular Legislative Session.
 
Public Comments
 
Interested persons may submit written comments relative to the proposed Rule until 4:30 PM , Monday , August 22, 2016 to Johnathan Bordelon, Wildlife Division, Department of Wildlife and Fisheries, P.O. Box 98000, Baton Rouge, LA, 70898 -9000, or via email to jbordelon@wlf.la.gov or at the regularly scheduled August Wildlife and Fisheries Commission Meeting .
 
Bart Yakupzack Chairman
 
 
 
 
CWD FACT SHEET
 
What is Chronic Wasting Disease?
 
CWD is a neurodegenerative disease found in most deer species, including moose, elk, mule deer and white-tailed deer. It is infectious, always fatal and there is no known cure. It’s part of a group of diseases known as transmissible spongiform encephalopathies (TSEs) and is similar to BSE (mad cow disease) of cattle and scrapie in sheep. These diseases cause irreversible damage to brain tissue which leads to salivation, neurological symptoms, emaciation and death of the animal.
 
Has it been found in Louisiana’s white-tailed deer population?
 
No. But Texas and Arkansas have recorded it. The disease has been documented in 23 states and two Canadian provinces. The Louisiana Department of Wildlife and Fisheries has been monitoring and testing for CWD for more than 10 years and has checked more than 7,000 deer during that time period. The state has yet to test positive for it.
 
What causes CWD and how is it spread?
 
CWD is caused by prions, which are proteins normally found in the body that have mutated. These prions kill nerve cells and cause holes to develop in the brain tissue. They are spread through direct deer-to-deer contact or through contact with urine, feces, saliva and body parts of infected deer or infectious materials in the soil. It’s most commonly found in deer pens and captive facilities. It is different from hemorrhagic disease (epizootic hemorrhagic disease virus and/ or bluetongue virus), which is a virus spread by bites from infected insects.
 
What signs do deer with CWD display?
 
It can take one to two years for CWD to incubate and exhibit outward symptoms in the infected animal. When symptoms appear they can include emaciation, lethargy, abnormal behavior and loss of bodily functions. Other signs include excessive salivation, loss of appetite, progressive weight loss, excessive thirst and urination, teeth grinding and drooping ears.
 
Can humans contract CWD?
 
According to the Centers for Disease Control and Prevention (CDCP) there is no evidence that CWD can infect humans. However, the CDCP recommends caution in handling venison in the infected region and that deer be tested for CWD before consuming.
 
What is the plan of action the Louisiana Department of Wildlife and Fisheries has developed should CWD be discovered in Louisiana?
 
If it is discovered in Louisiana, LDWF will create a management zone, the size of which will depend on the locations and distribution of infected deer as well as the density, distribution and seasonal movements of the local deer population.
 
There will be feeding and baiting restrictions in the management zone where the disease is found. It may be necessary to reduce and maintain a lower deer density in that area. There also will be movement restrictions placed on deer body parts. Hunters will not be able to bring a whole deer out from the management zone. They’ll be restricted to deboned meat, a clean skull plate with the antlers, and the cape, which is the skin of the head and shoulders. Any deer harvested within the management zone will be tested. LDWF will maintain intensive surveillance in the management zone for an indefinite period of time.
 
 
 
NOW, let’s look at the scientific facts on Chronic Wasting Disease CWD, Scrapie, Transmissible Spongiform Encephalopathy TSE PRION disease, and what the latest sound science is saying from the PRION CONFERENCES OF 2014, 2015, and 2016. seems some states like to go by science that is 3 or 4 decades old about mad cow disease. let’s look at all the science shall we...
 
 
Thursday, April 14, 2016
 
*** Louisiana Chronic Wasting Disease CWD TSE Prion Surveillance and Testing Program? ***
 
 
*** 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.
 
 
see ;
 
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. see ;
 
***Recently, we have been using PMCA to study the role of environmental prion contamination on the horizontal spreading of TSEs. These experiments have focused on the study of the interaction of prions with plants and environmentally relevant surfaces. Our results show that plants (both leaves and roots) bind tightly to prions present in brain extracts and excreta (urine and feces) and retain even small quantities of PrPSc for long periods of time. Strikingly, ingestion of prioncontaminated leaves and roots produced disease with a 100% attack rate and an incubation period not substantially longer than feeding animals directly with scrapie brain homogenate. Furthermore, plants can uptake prions from contaminated soil and transport them to different parts of the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety of environmentally relevant surfaces, including stones, wood, metals, plastic, glass, cement, etc. Prion contaminated surfaces efficiently transmit prion disease when these materials were directly injected into the brain of animals and strikingly when the contaminated surfaces were just placed in the animal cage. These findings demonstrate that environmental materials can efficiently bind infectious prions and act as carriers of infectivity, suggesting that they may play an important role in the horizontal transmission of the disease.
 
Since its invention 13 years ago, PMCA has helped to answer fundamental questions of prion propagation and has broad applications in research areas including the food industry, blood bank safety and human and veterinary disease diagnosis.
 
 
see ;
 
 
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
 
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
 
 
>>>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.<<<
 
Circulation of prions within dust on a scrapie affected farm
 
Kevin C Gough1, Claire A Baker2, Hugh A Simmons3, Steve A Hawkins3 and Ben C Maddison2*
 
Abstract
 
Prion diseases are fatal neurological disorders that affect humans and animals. Scrapie of sheep/goats and Chronic Wasting Disease (CWD) of deer/elk are contagious prion diseases where environmental reservoirs have a direct link to the transmission of disease. Using protein misfolding cyclic amplification we demonstrate that scrapie PrPSc can be detected within circulating dusts that are present on a farm that is naturally contaminated with sheep scrapie. The presence of infectious scrapie within airborne dusts may represent a possible route of infection and illustrates the difficulties that may be associated with the effective decontamination of such scrapie affected premises.
 
snip...
 
Discussion
 
We present biochemical data illustrating the airborne movement of scrapie containing material within a contaminated farm environment. We were able to detect scrapie PrPSc within extracts from dusts collected over a 70 day period, in the absence of any sheep activity. We were also able to detect scrapie PrPSc within dusts collected within pasture at 30 m but not at 60 m distance away from the scrapie contaminated buildings, suggesting that the chance of contamination of pasture by scrapie contaminated dusts decreases with distance from contaminated farm buildings. PrPSc amplification by sPMCA has been shown to correlate with infectivity and amplified products have been shown to be infectious [14,15]. These experiments illustrate the potential for low dose scrapie infectivity to be present within such samples. We estimate low ng levels of scrapie positive brain equivalent were deposited per m2 over 70 days, in a barn previously occupied by sheep affected with scrapie. This movement of dusts and the accumulation of low levels of scrapie infectivity within this environment may in part explain previous observations where despite stringent pen decontamination regimens healthy lambs still became scrapie infected after apparent exposure from their environment alone [16]. The presence of sPMCA seeding activity and by inference, infectious prions within dusts, and their potential for airborne dissemination is highly novel and may have implications for the spread of scrapie within infected premises. The low level circulation and accumulation of scrapie prion containing dust material within the farm environment will likely impede the efficient decontamination of such scrapie contaminated buildings unless all possible reservoirs of dust are removed. Scrapie containing dusts could possibly infect animals during feeding and drinking, and respiratory and conjunctival routes may also be involved. It has been demonstrated that scrapie can be efficiently transmitted via the nasal route in sheep [17], as is also the case for CWD in both murine models and in white tailed deer [18-20].
 
The sources of dust borne prions are unknown but it seems reasonable to assume that faecal, urine, skin, parturient material and saliva-derived prions may contribute to this mobile environmental reservoir of infectivity. This work highlights a possible transmission route for scrapie within the farm environment, and this is likely to be paralleled in CWD which shows strong similarities with scrapie in terms of prion dissemination and disease transmission. The data indicate that the presence of scrapie prions in dust is likely to make the control of these diseases a considerable challenge.
 
 
***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.***
 
 
Saturday, April 16, 2016
 
APHIS [Docket No. APHIS-2016-0029] Secretary's Advisory Committee on Animal Health; Meeting May 2, 2016, and June 16, 2016 Singeltary Submission
 
 
Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle
 
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
 
snip...
 
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
 
 
 
 
In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells
 
3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ...
 
 
”The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite it’s subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province!” ...page 26.
 
 
*** 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.
 
 
Spongiform Encephalopathy in Captive Wild ZOO BSE INQUIRY
 
 
SCRAPIE AND CWD ZOONOSIS
 
PRION 2016 CONFERENCE 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
 
 
Transmission of scrapie prions to primate after an extended silent incubation period
 
***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.***
 
 
Wednesday, June 29, 2016
 
CWD, SCRAPIE, ZOONOSIS, it’s for real folks, the risk factors have increased greatly, and science has spoken, cwd and scrapie to humans as sporadic cjd may have already happened.
 
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
 
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...
 
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.
 
***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.***
 
 
 
2015
 
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.
 
==============
 
 
CHRONIC WASTING DISEASE TSE PRION
 
PRION 2016 TOKYO
 
Zoonotic Potential of CWD Prions: An Update
 
Ignazio Cali1, Liuting Qing1, Jue Yuan1, Shenghai Huang2, Diane Kofskey1,3, Nicholas Maurer1, Debbie McKenzie4, Jiri Safar1,3,5, Wenquan Zou1,3,5,6, Pierluigi Gambetti1, Qingzhong Kong1,5,6
 
1Department of Pathology, 3National Prion Disease Pathology Surveillance Center, 5Department of Neurology, 6National Center for Regenerative Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
 
4Department of Biological Sciences and Center for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada,
 
2Encore Health Resources, 1331 Lamar St, Houston, TX 77010
 
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
 
Purchase options Price * Issue Purchase USD 198.00
 
 
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 # 1R01NS088604-01A1
 
Application # 9037884
 
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 2015-09-30
 
Budget End 2016-07-31
 
Support Year 1
 
Fiscal Year 2015
 
Total Cost $337,507
 
Indirect Cost $118,756
 
Institution
 
Name Case Western Reserve University
 
Department Pathology
 
Type Schools of Medicine
 
DUNS # 077758407
 
City Cleveland
 
State OH
 
Country United States
 
Zip Code 44106
 
 
===========================================================
 
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.
 
============================================================
 
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.
 
Funding Agency Agency National Institute of Health (NIH)
 
Institute National Institute of Allergy and Infectious Diseases (NIAID)
 
Type High Priority, Short Term Project Award (R56)
 
Project # 1R56AI122273-01A1
 
Application # 9211114
 
Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)
 
Program Officer Beisel, Christopher E
 
Project Start 2016-02-16
 
Project End 2017-01-31
 
Budget Start 2016-02-16
 
Budget End 2017-01-31
 
Support Year 1
 
Fiscal Year 2016
 
Total Cost
 
Indirect Cost Institution Name Colorado State University-Fort Collins
 
Department Microbiology/Immun/Virology
 
Type Schools of Veterinary Medicine
 
DUNS # 785979618 City Fort Collins
 
State CO
 
Country United States
 
Zip Code 80523
 
 
PMCA Detection of CWD Infection in Cervid and Non-Cervid Species
 
Hoover, Edward Arthur
 
Colorado State University-Fort Collins, Fort Collins, CO, United States Abstract Chronic wasting disease (CWD) of deer and elk is an emerging highly transmissible prion disease now recognized in 18 States, 2 Canadian provinces, and Korea. We have shown that Infected deer harbor and shed high levels of infectious prions in saliva, blood, urine, and feces, and in the tissues generating those body fluids and excreta, thereby leading to facile transmission by direct contact and environmental contamination. We have also shown that CWD can infect some non-cervid species, thus the potential risk CWD represents to domestic animal species and to humans remains unknown. Whether prions borne in blood, saliva, nasal fluids, milk, or excreta are generated or modified in the proximate peripheral tissue sites, may differ in subtle ways from those generated in brain, or may be adapted for mucosal infection remain open questions. The increasing parallels in the pathogenesis between prion diseases and human neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, add relevance to CWD as a transmissible protein misfolding disease. The overall goal of this work is to elucidate the process of CWD prion transmission from mucosal secretory and excretory tissue sites by addressing these questions: (a) What are the kinetics and magnitude of CWD prion shedding post-exposure? (b) Are excreted prions biochemically distinct, or not, from those in the CNS? (c) Are peripheral epithelial or CNS tissues, or both, the source of excreted prions? and (d) Are excreted prions adapted for horizontal transmission via natural/trans-mucosal routes? The specific aims of this proposal are: (1) To determine the onset and consistency of CWD prion shedding in deer and cervidized mice; (2); To compare the biochemical and biophysical properties of excretory vs. CNS prions; (3) To determine the capacity of peripheral tissues to support replication of CWD prions; (4) To determine the protease- sensitive infectious fraction of excreted vs. CNS prions; and (5) To compare the mucosal infectivity of excretory vs. CNS prions. Understanding the mechanisms that enable efficient prion dissemination and shedding will help elucidate how horizontally transmissible prions evolve and succeed, and is the basis of this proposal. Understanding how infectious misfolded proteins (prions) are generated, trafficked, shed, and transmitted will aid in preventing, treating, and managing the risks associated with these agents and the diseases they cause.
 
Public Health Relevance Chronic wasting disease (CWD) of deer and elk is an emergent highly transmissible prion disease now recognized throughout the USA as well as in Canada and Korea. We have shown that infected deer harbor and shed high levels of infectious prions in saliva, blood, urine, and feces thereby leading to transmission by direct contact and environmental contamination. In that our studies have also shown that CWD can infect some non-cervid species, the potential risk CWD may represents to domestic animal species and humans remains unknown. The increasing parallels in the development of major human neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, and prion diseases add relevance to CWD as a model of a transmissible protein misfolding disease. Understanding how infectious misfolded proteins (prions) are generated and transmitted will aid in interrupting, treating, and managing the risks associated with these agents and the diseases they cause.
 
Funding Agency Agency National Institute of Health (NIH)
 
Institute National Institute of Neurological Disorders and Stroke (NINDS)
 
Type Research Project (R01)
 
Project # 4R01NS061902-07
 
Application # 9010980
 
Study Section Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)
 
Program Officer Wong, May Project Start 2009-09-30
 
Project End 2018-02-28
 
Budget Start 2016-03-01
 
Budget End 2017-02-28
 
Support Year 7
 
Fiscal Year 2016
 
Total Cost $409,868
 
Indirect Cost $134,234 Institution Name Colorado State University-Fort Collins
 
Department Microbiology/Immun/Virology
 
Type Schools of Veterinary Medicine
 
DUNS # 785979618 City Fort Collins
 
State CO
 
Country United States
 
Zip Code 80523
 
 
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).***
 
 
PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS
 
*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***
 
O18
 
Zoonotic Potential of CWD Prions
 
Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1, Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy, 3Encore Health Resources, Houston, Texas, USA
 
*** These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.
 
==================
 
***These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.***
 
==================
 
P.105: RT-QuIC models trans-species prion transmission
 
Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover Prion Research Center; Colorado State University; Fort Collins, CO USA
 
Conversely, FSE maintained sufficient BSE characteristics to more efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was competent for conversion by CWD and fCWD.
 
***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.
 
================
 
***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.***
 
================
 
 
*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***
 
Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014
 
*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.
 
*** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.
 
 
 
*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***
 
 
*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.
 
 
***********CJD REPORT 1994 increased risk for consumption of veal and venison and lamb***********
 
CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL REPORT AUGUST 1994
 
Consumption of venison and veal was much less widespread among both cases and controls. For both of these meats there was evidence of a trend with increasing frequency of consumption being associated with increasing risk of CJD. (not nvCJD, but sporadic CJD...tss)
 
These associations were largely unchanged when attention was restricted to pairs with data obtained from relatives. ...
 
Table 9 presents the results of an analysis of these data.
 
There is STRONG evidence of an association between ‘’regular’’ veal eating and risk of CJD (p = .0.01).
 
Individuals reported to eat veal on average at least once a year appear to be at 13 TIMES THE RISK of individuals who have never eaten veal.
 
There is, however, a very wide confidence interval around this estimate. There is no strong evidence that eating veal less than once per year is associated with increased risk of CJD (p = 0.51).
 
The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).
 
There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02).
 
The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).
 
snip...
 
It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).
 
snip...
 
In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...
 
snip...
 
In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)
 
snip...see full report ;
 
 
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.
 
 
Monday, May 02, 2016
 
*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***
 
 
*** PRION 2014 CONFERENCE CHRONIC WASTING DISEASE CWD
 
 
*** PPo3-7: Prion Transmission from Cervids to Humans is Strain-dependent
 
*** Here we report that a human prion strain that had adopted the cervid prion protein (PrP) sequence through passage in cervidized transgenic mice efficiently infected transgenic mice expressing human PrP,
 
*** indicating that the species barrier from cervid to humans is prion strain-dependent and humans can be vulnerable to novel cervid prion strains.
 
PPo2-27:
 
Generation of a Novel form of Human PrPSc by Inter-species Transmission of Cervid Prions
 
*** Our findings suggest that CWD prions have the capability to infect humans, and that this ability depends on CWD strain adaptation, implying that the risk for human health progressively increases with the spread of CWD among cervids.
 
PPo2-7:
 
Biochemical and Biophysical Characterization of Different CWD Isolates
 
*** The data presented here substantiate and expand previous reports on the existence of different CWD strains.
 
 
Envt.07:
 
Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free Ranging White-Tailed Deer Infected with Chronic Wasting Disease
 
***The presence and seeding activity of PrPTSE in skeletal muscle from CWD-infected cervids suggests prevention of such tissue in the human diet as a precautionary measure for food safety, pending on further clarification of whether CWD may be transmissible to humans.
 
 
>>>CHRONIC WASTING DISEASE , THERE WAS NO ABSOLUTE BARRIER TO CONVERSION OF THE HUMAN PRION PROTEIN<<<
 
*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***
 
Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014
 
Wednesday, January 01, 2014
 
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.
 
 
 
*** 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 ;
 
 
Monday, May 02, 2016
 
*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***
 
 
*** NIH awards $11 million to UTHealth researchers to study deadly CWD prion diseases Claudio Soto, Ph.D. ***
 
Public Release: 29-Jun-2016
 
 
I urge everyone to watch this video closely...terry
 
*** you can see video here and interview with Jeff's Mom, and scientist telling you to test everything and potential risk factors for humans ***
 
 
CWD TSE PRION CHRONIC WASTING DISEASE UPDATE
 
Friday, July 01, 2016
 
*** TEXAS Thirteen new cases of chronic wasting disease (CWD) were confirmed at a Medina County captive white-tailed deer breeding facility on June 29, 2016
 
 
*** Scrapie Field Trial Experiments Mission, Texas, The Moore Air Force Base Scrapie Experiment 1964 ***
 
How Did CWD Get Way Down In Medina County, Texas?
 
Confucius ponders...
 
Could the Scrapie experiments back around 1964 at Moore Air Force near Mission, Texas, could this area have been ground zero for CWD TSE Prion (besides the CWD cases that have waltzed across the Texas, New Mexico border near WSMR Trans Pecos region since around 2001)?
 
Epidemiology of Scrapie in the United States 1977
 
snip...
 
Scrapie Field Trial Experiments Mission, Texas
 
A Scrapie Field Trial was developed at Mission, Texas, to provide additional information for the eradication program on the epidemiology of natural scrapie. The Mission Field Trial Station is located on 450 acres of pastureland, part of the former Moore Air Force Base, near Mission, Texas. It was designed to bring previously exposed, and later also unexposed, sheep or goats to the Station and maintain and breed them under close observation for extended periods to determine which animals would develop scrapie and define more closely the natural spread and other epidemiological aspects of the disease.
 
The 547 previously exposed sheep brought to the Mission Station beginning in 1964 were of the Cheviot, Hampshire, Montadale, or Suffolk breeds. They were purchased as field outbreaks occurred, and represented 21 bloodlines in which scrapie had been diagnosed. Upon arrival at the Station, the sheep were maintained on pasture, with supplemental feeding as necessary. The station was divided into 2 areas: (1) a series of pastures and-pens occupied by male animals only, and (2) a series of pastures and pens occupied by females and young progeny of both sexes. ...
 
snip...see full text ;
 
 
Thursday, June 09, 2016
 
Scrapie Field Trial Experiments Mission, Texas, The Moore Air Force Base Scrapie TSE Prion Experiment 1964
 
How Did CWD Get Way Down In Medina County, Texas?
 
 
 
Friday, April 22, 2016
 
*** Texas Scrapie Confirmed in a Hartley County Sheep where CWD was detected in a Mule Deer
 
 
Wednesday, March 18, 2015
 
Chronic Wasting Disease CWD Confirmed Texas Trans Pecos March 18, 2015
 
 
Wednesday, March 25, 2015
 
Chronic Wasting Disease CWD Cases Confirmed In New Mexico 2013 and 2014 UPDATE 2015
 
 
very important ;
 
Sunday, July 10, 2016
 
>>>*** Primary transmission of CWD versus scrapie prions from small ruminants to ovine and cervid PrP transgenic mice ***<<<
 
 
Saturday, July 09, 2016
 
*** Texas Intrastate – within state movement of all Cervid or Trucking Chronic Wasting Disease CWD TSE Prion Moratorium
 
 
Tuesday, June 07, 2016
 
*** Comparison of two US sheep scrapie isolates supports identification as separate strains ***
 
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
 
 
Scrapie-like disorder in a Nyala (Tragelaphus angasi)
 
IN CONFIDENCE
 
 
 
 
Spongiform encephalopathy has so far only been recorded in the sheep and goat, man, mink, and several deer including the mule deer, black tailed deer and the elk (most, if not all, of the deer incidents occurred in wild life parts in Wyoming and Colorado). Clinical cases in deer all occurred from 3 1/2 to 5 years old and usually 60-80% losses occurred over a 4 year period...
 
 
The clinical and neuropathological findings in F22 are consistent with the spongiform encephalopathies of animals and man. The agents causing spongiform encephalopathy in various species cannot be unequivocally distinguished and some isolates of human agent cause neurologic disease in goats indistinguishable from scrapie. The spongiform encephalopathies are invariably fatal once clinical signs of disease are evident and as very high fatality rates (79% of 67 animals) are recorded in Mule deer it is important that an awareness of the disease is maintained at Marwell.
 
 
”The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite it’s subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province!” page 26.
 
 
Mission, Texas Scrapie transmission to cattle study
 
Wilbur Clarke (reference the Mission, Texas scrapie transmission transmission to cattle study) is now the State Veterinarian for Montana based at Helena.
 
I was given confidential access to sections from the Clarke scrapie-cattle transmission experiment. Details of the experimental design were as supplied previously by Dr. Wrathall (copy of relevant information appended). Only 3 animals (2 inoculated with 2nd pass Suffolk scrapie and 1 inoculated with Angora goat passaged scrapie) showed clinical signs. Clinical signs were characterised by weakness, ''a stilted hindlimb gait'', disorientation, ataxia and, terminally, lateral recumbency. The two cattle from which I examined material were inocluated at 8 months of age and developed signs 36 months pi (goat scrapie inoculum) and 49 months pi (one of the Suffolk scrapie inoculated) respectively. This latter animal was killed at 58 months of age and so the clinical duration was only 1 month. The neuropathology was somewhat different from BSE or the Stetsonville TME in cattle. Vacuolar changes were minimal, to the extent that detection REQUIRED CAREFUL SEARCHING. Conversely astrocyte hypertrophy was a widespread and prominent feature. The material requires DETAILED NEUROPATHOLOGICAL ASSESSMENT BUT WHETHER OR NOT THIS WILL BE DONE REMAINS A QUESTION.
 
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...
 
 
 
Spongiform Encephalopathy in Captive Wild ZOO BSE INQUIRY
 
 
 
***The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans.***
 
***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.***
 
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
 
 
It is clear that the designing scientists must also have shared Mr Bradleys surprise at the results because all the dose levels right down to 1 gram triggered infection.
 
 
it is clear that the designing scientists must have also shared Mr Bradleys surprise at the results because all the dose levels right down to 1 gram triggered infection.
 
 
Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle
 
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
 
snip...
 
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
 
 
In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells
 
3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ...
 
 
 
Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle
 
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
 
snip...
 
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
 
 
 
 
In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells
 
3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ...
 
 
”The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite it’s subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province!” ...page 26.
 
 
*** 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.
 
 
Limited amplification of chronic wasting disease prions in the peripheral tissues of intracerebrally inoculated cattle
 
Authors: Nicholas Haley1, Christopher Siepker2, Justin Greenlee3, Jürgen Richt4
 
VIEW AFFILIATIONS Affiliations: 1 1Midwestern Univerisity 2 2Kansas State University 3 3USDA, Agricultural Research Service 4 4Kansas State University
 
Published Ahead of Print: 31 March, 2016 Journal of General Virology doi: 10.1099/jgv.0.000438 Published Online: 31/03/2016
 
Chronic wasting disease (CWD) is a fatal neurodegenerative disease, classified as a prion disease or transmissible spongiform encephalopathy (TSE) similar to bovine spongiform encephalopathy (BSE). Cervids affected by CWD accumulate an abnormal protease resistant prion protein throughout the central nervous system (CNS), as well as in both lymphatic and excretory tissues - an aspect of prion disease pathogenesis not observed in cattle with BSE. Using seeded amplification through real time quaking induced conversion (RT-QuIC), we investigated whether the bovine host or prion agent was responsible for this aspect of TSE pathogenesis. We blindly examined numerous central and peripheral tissues from cattle inoculated with CWD for prion seeding activity. Seeded amplification was readily detected in the CNS, though rarely observed in peripheral tissues, with a limited distribution similar to that of BSE prions in cattle. This seems to indicate that prion peripheralization in cattle is a host-driven characteristic of TSE infection.
 
 
Friday, August 14, 2015
 
Susceptibility of cattle to the agent of chronic wasting disease from elk after intracranial inoculation
 
ARS VIRUS AND PRION RESEARCH / Research / Publication #277212
 
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
 
Title: Susceptibility of cattle to the agent of chronic wasting disease from elk after intracranial inoculation
 
Authors
 
item Greenlee, Justin item Nicholson, Eric item Smith, Jodi item Kunkle, Robert item Hamir, Amirali
 
Submitted to: Journal of Veterinary Diagnostic Investigation Publication
 
Type: Peer Reviewed Journal Publication Acceptance
 
Date: July 12, 2012
 
Publication Date: November 1, 2012
 
Citation: Greenlee, J.J., Nicholson, E.M., Smith, J.D., Kunkle, R.A., Hamir, A.N. 2012.
 
Susceptibility of cattle to the agent of chronic wasting disease from elk after intracranial inoculation.
 
Journal of Veterinary Diagnostic Investigation. 24(6):1087-1093.
 
Interpretive Summary: Chronic Wasting Disease (CWD), a fatal neurodegenerative disease that occurs in farmed and wild cervids (deer and elk) of North America, is a transmissible spongiform encephalopathy (TSE). TSEs are caused by infectious proteins called prions that are resistant to various methods of decontamination and environmental degradation. Cattle could be exposed to chronic wasting disease (CWD) by contact with infected farmed or free-ranging cervids. The purpose of this study was to assess the potential transmission of CWD from elk to cattle after intracranial inoculation, the most direct route to test the potential of a host to replicate an isolate of the prion agent. This study reports that only 2 of 14 calves inoculated with CWD from elk had clinical signs or evidence of abnormal prion protein accumulation. These results suggest that cattle are unlikely to be susceptible to CWD if inoculated by a more natural route. This information could have an impact on regulatory officials developing plans to reduce or eliminate TSEs and farmers with concerns about ranging cattle on areas where CWD may be present.
 
Technical Abstract:
 
***Cattle could be exposed to the agent of chronic wasting disease (CWD) through contact with infected farmed or free-ranging cervids or exposure to contaminated premises. The purpose of this study was to assess the potential for CWD derived from elk to transmit to cattle after intracranial inoculation. Calves (n=14) were inoculated with brain homogenate derived from elk with CWD to determine the potential for transmission and define the clinicopathologic features of disease.
 
Cattle were necropsied if clinical signs occurred or at the termination of experiment (49 months post-inoculation (MPI)).
 
Clinical signs of poor appetite, weight loss, circling, and bruxism occurred in two cattle (14%) at 16 and 17 MPI, respectively.
 
Accumulation of abnormal prion protein (PrP**Sc) in these cattle was confined to the central nervous system with the most prominent immunoreactivity in midbrain, brainstem, and hippocampus with lesser immunoreactivity in the cervical spinal cord.
 
*** The rate of transmission was lower than in cattle inoculated with CWD derived from mule deer (38%) or white-tailed deer (86%).
 
Additional studies are required to fully assess the potential for cattle to develop CWD through a more natural route of exposure, but a low rate of transmission after intracranial inoculation suggests that risk of transmission through other routes is low.
 
***A critical finding here is that if CWD did transmit to exposed cattle, currently used diagnostic techniques would detect and differentiate it from other prion diseases in cattle based on absence of spongiform change, distinct pattern of PrP**Sc deposition, and unique molecular profile.
 
 
*** P.126: Successful transmission of chronic wasting disease (CWD) into mice over-expressing bovine prion protein (TgSB3985) ***
 
Larisa Cervenakova,1 Christina J Sigurdson,2 Pedro Piccardo,3 Oksana Yakovleva,1 Irina Vasilyeva,1 Jorge de Castro,1 Paula Saá,1 and Anton Cervenak1 1American Red Cross, Holland Laboratory; Rockville, MD USA; 2University of California; San Diego, CA USA; 3Lab TSE/OBRR /CBER/FDA; Rockville, MD USA
 
Keywords: chronic wasting disease, transmission, transgenic mouse, bovine prion protein
 
Background. CWD is a disease affecting wild and farmraised cervids in North America. Epidemiological studies provide no evidence of CWD transmission to humans. Multiple attempts have failed to infect transgenic mice expressing human PRNP gene with CWD. The extremely low efficiency of PrPCWD to convert normal human PrPC in vitro provides additional evidence that transmission of CWD to humans cannot be easily achieved. However, a concern about the risk of CWD transmission to humans still exists. This study aimed to establish and characterize an experimental model of CWD in TgSB3985 mice with the following attempt of transmission to TgHu mice.
 
Materials and Methods. TgSB3985 mice and wild-type FVB/ NCrl mice were intracranially injected with 1% brain homogenate from a CWD-infected Tga20 mouse (CWD/Tga20). TgSB3985 and TgRM (over-expressing human PrP) were similarly injected with 5% brain homogenates from CWD-infected white-tailed deer (CWD/WTD) or elk (CWD/Elk). Animals were observed for clinical signs of neurological disease and were euthanized when moribund. Brains and spleens were removed from all mice for PrPCWD detection by Western blotting (WB). A histological analysis of brains from selected animals was performed: brains were scored for the severity of spongiform change, astrogliosis, and PrPCWD deposition in ten brain regions.
 
Results. Clinical presentation was consistent with TSE. More than 90% of TgSB3985 and wild-type mice infected with CWD/Tga20, tested positive for PrPres in the brain but only mice in the latter group carried PrPCWD in their spleens. We found evidence for co-existence or divergence of two CWD/ Tga20 strains based on biochemical and histological profiles. In TgSB3985 mice infected with CWD-elk or CWD-WTD, no animals tested positive for PrPCWD in the brain or in the spleen by WB. However, on neuropathological examination we found presence of amyloid plaques that stained positive for PrPCWD in three CWD/WTD- and two CWD/Elk-infected TgSB3985 mice. The neuropathologic profiles in CWD/WTD- and CWD/Elkinfected mice were similar but unique as compared to profiles of BSE, BSE-H or CWD/Tg20 agents propagated in TgSB3985 mice. None of CWD-infected TgRM mice tested positive for PrPCWD by WB or by immunohistochemical detection.
 
Conclusions. To our knowledge, this is the first established experimental model of CWD in TgSB3985. We found evidence for co-existence or divergence of two CWD strains adapted to Tga20 mice and their replication in TgSB3985 mice. Finally, we observed phenotypic differences between cervid-derived CWD and CWD/Tg20 strains upon propagation in TgSB3985 mice. Further studies are underway to characterize these strains.
 
TSS
 
UPDATED CORRESPONDENCE FROM AUTHORS OF THIS STUDY I.E. COLBY, PRUSINER ET AL, ABOUT MY CONCERNS OF THE DISCREPANCY BETWEEN THEIR FIGURES AND MY FIGURES OF THE STUDIES ON CWD TRANSMISSION TO CATTLE ;
 
CWD to cattle figures CORRECTION
 
Greetings,
 
I believe the statement and quote below is incorrect ;
 
"CWD has been transmitted to cattle after intracerebral inoculation, although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding raised concerns that CWD prions might be transmitted to cattle grazing in contaminated pastures."
 
Please see ;
 
Within 26 months post inoculation, 12 inoculated animals had lost weight, revealed abnormal clinical signs, and were euthanatized. Laboratory tests revealed the presence of a unique pattern of the disease agent in tissues of these animals. These findings demonstrate that when CWD is directly inoculated into the brain of cattle, 86% of inoculated cattle develop clinical signs of the disease.
 
 
" although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). "
 
shouldn't this be corrected, 86% is NOT a low rate. ...
 
kindest regards,
 
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
 
Thank you!
 
Thanks so much for your updates/comments. We intend to publish as rapidly as possible all updates/comments that contribute substantially to the topic under discussion.
 
 
re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations
 
1Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, California 94143 2Department of Neurology, University of California, San Francisco, San Francisco, California 94143 Correspondence: stanley@ind.ucsf.edu
 
 
Mule deer, white-tailed deer, and elk have been reported to develop CWD. As the only prion disease identified in free-ranging animals, CWD appears to be far more communicable than other forms of prion disease. CWD was first described in 1967 and was reported to be a spongiform encephalopathy in 1978 on the basis of histopathology of the brain. Originally detected in the American West, CWD has spread across much of North America and has been reported also in South Korea. In captive populations, up to 90% of mule deer have been reported to be positive for prions (Williams and Young 1980). The incidence of CWD in cervids living in the wild has been estimated to be as high as 15% (Miller et al. 2000). The development of transgenic (Tg) mice expressing cervid PrP, and thus susceptible to CWD, has enhanced detection of CWD and the estimation of prion titers (Browning et al. 2004; Tamgüney et al. 2006). Shedding of prions in the feces, even in presymptomatic deer, has been identified as a likely source of infection for these grazing animals (Williams and Miller 2002; Tamgüney et al. 2009b). CWD has been transmitted to cattle after intracerebral inoculation, although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding raised concerns that CWD prions might be transmitted to cattle grazing in contaminated pastures.
 
snip...
 
 
----- Original Message -----
 
From: David Colby To: flounder9@verizon.net
 
Cc: stanley@XXXXXXXX
 
Sent: Tuesday, March 01, 2011 8:25 AM
 
Subject: Re: FW: re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations
 
Dear Terry Singeltary,
 
Thank you for your correspondence regarding the review article Stanley Prusiner and I recently wrote for Cold Spring Harbor Perspectives. Dr. Prusiner asked that I reply to your message due to his busy schedule. We agree that the transmission of CWD prions to beef livestock would be a troubling development and assessing that risk is important. In our article, we cite a peer-reviewed publication reporting confirmed cases of laboratory transmission based on stringent criteria. The less stringent criteria for transmission described in the abstract you refer to lead to the discrepancy between your numbers and ours and thus the interpretation of the transmission rate. We stand by our assessment of the literature--namely that the transmission rate of CWD to bovines appears relatively low, but we recognize that even a low transmission rate could have important implications for public health and we thank you for bringing attention to this matter. Warm Regards, David Colby -- David Colby, PhDAssistant Professor Department of Chemical Engineering University of Delaware
 
===========END...TSS==============
 
SNIP...SEE FULL TEXT ;
 
 
Friday, August 14, 2015
 
*** Susceptibility of cattle to the agent of chronic wasting disease from elk after intracranial inoculation ***
 
 
Saturday, May 28, 2016
 
*** Infection and detection of PrPCWD in soil from CWD infected farm in Korea Prion 2016 Tokyo ***
 
 
Thursday, July 07, 2016
 
Norway reports a third case Chronic Wasting Disease CWD TSE Prion in 2nd Norwegian moose
 
14/06/2016 - Norway reports a third case
 
 
Tuesday, May 03, 2016
 
Arkansas Chronic Wasting Disease CWD TSE Prion and Elk Restoration Project and Hunkering Down in the BSE Situation Room USDA 1998
 
 
Friday, April 22, 2016
 
COLORADO CHRONIC WASTING DISEASE CWD TSE PRION SURVEILLANCE AND TESTING PROGRAM IS MINIMAL AND LIMITED
 
*** SEE CWD HIGH INFECTION RATE MAPS FOR COLORADO ! ***
 
 
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 ***
 
 
Sunday, May 08, 2016
 
WISCONSIN CHRONIC WASTING DISEASE CWD TSE PRION SPIRALING FURTHER INTO THE ABYSS UPDATE
 
 
Tuesday, May 03, 2016
 
Wednesday, May 11, 2016
 
PENNSYLVANIA TWELVE MORE CASES OF CWD FOUND: STATE GEARS UP FOR ADDITIONAL CONTROL MEASURES
 
 
Friday, April 22, 2016
 
Missouri MDC finds seven new cases of ChronicWasting Disease CWD during past‐season testing
 
 
KANSAS CWD CASES ALARMING
 
Wednesday, March 02, 2016 Kansas Chronic Wasting Disease CWD TSE Prion 52 cases 2015 updated report 'ALARMING'
 
 
Tuesday, February 02, 2016
 
Illinois six out of 19 deer samples tested positive for CWD in the Oswego zone of Kendall County
 
 
I could go on, for more see ;
 
Thursday, March 31, 2016
 
*** Chronic Wasting Disease CWD TSE Prion Roundup USA April 1, 2016 ***
 
 
Saturday, May 28, 2016
 
*** Infection and detection of PrPCWD in soil from CWD infected farm in Korea Prion 2016 Tokyo ***
 
 
What is the risk of chronic wasting disease being introduced into Great Britain? An updated Qualitative Risk Assessment March 2016
 
 
Summary
 
The previous assessment concentrated on the incursion of disease from North America through the imports of animal feed or the movement of contaminated clothing, footwear and equipment. The results suggested that import of pet feed was a non-negligible risk, but given the unlikely contact of resident deer in GB with such non-ruminant feed, this was considered overall a negligible to very low risk. The movement of contaminated clothing, footwear or equipment (particularly hunting equipment) could pose a very low risk, although the volume of contaminated soil which would need to be ingested to give rise to an infection is likely to be higher than would be present. There is a variable level uncertainty in all these assessments.
 
The new assessment focuses on an additional potential route of entry: the importation of natural deer urine lures. The main conclusions from this assessment are:
 
 In areas of North America where CWD has been reported, given that CWD is excreted in faeces, saliva, urine and blood, and survives in the environment for several years there is a medium probability that the deer urine in North America contains CWD (high uncertainty; depends on the source of deer used for production).
 
 The risk of a deer in GB being infected per 30 ml bottle of urine imported from the USA is very low, albeit with high uncertainty. Overall it is concluded that the risk of at least one infection of deer in the UK with CWD per year from deer urine lures imported from the USA is medium. This assumes a high number of 30 ml bottles imported per year from all areas of the USA.
 
 None of the species affected by CWD in North America are present in GB. For a British species to become infected with CWD following exposure, the dose and inherent susceptibility of the species will be important. Based on current scientific evidence Red deer (Cervus elaphus elaphus) are susceptible to CWD, Fallow deer (Dama dama) are likely to be less susceptible and Roe deer (Capreolus capreolus) have a gene conferring susceptibility. Therefore, it is likely that given exposure to an infectious dose of CWD, deer in GB could become infected with CWD.
 
Overall, the probability of importing CWD into GB from North America and causing infection in British deer is uncertain but likely to be negligible to very low via movement of deer hunters, other tourists and British servicemen and very low via imported (non-
 
2
 
ruminant) animal feed and medium for the use of lures. However, if it was imported and (a) deer did become infected with CWD, the consequences would be severe as eradication of the disease is impossible, it is clinically indistinguishable from BSE infection in deer (Dalgleish et al., 2008) and populations of wild and farmed deer would be under threat.
 
The USA has implemented a Herd Certification Programme for farmed and captive cervids. So far, 29 States are approved for HCP status (APHIS, 2015). The list includes States such as Colorado, where CWD is present, therefore it is recommended that any sourcing of such natural urine lures should be not only from States with an HCP programme, but also from a herd which is registered as being regularly tested free of CWD.
 
Animal urine is not considered a commodity which is subject to animal by-products legislation for imports. Internet sales are common and although a license would be required, there are no conditions for the safe sourcing of such products. Deer urine lures are also available in Europe and may be produced from carcases of hunted deer. The use of deer urine produced from a species not present in Europe (such as white tailed deer) is questioned for its value with native GB deer according to the British Deer Society survey.
 
Background
 
 
Thursday, April 07, 2016
 
What is the risk of chronic wasting disease being introduced into Great Britain? An updated Qualitative Risk Assessment March 2016
 
 
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...
 
What is the risk of chronic wasting disease being introduced into Great Britain? A Qualitative Risk Assessment October 2012
 
 
I strenuously once again urge the FDA and its industry constituents, to make it MANDATORY that all ruminant feed be banned to all ruminants, and this should include all cervids, as well as non-ruminants such as cats and dogs as well, as soon as possible for the following reasons...
 
31 Jan 2015 at 20:14 GMT
 
*** Ruminant feed ban for cervids in the United States? ***
 
31 Jan 2015 at 20:14 GMT
 
Terry Singeltary Sr. comment ;
 
 
 
Tuesday, April 19, 2016
 
Docket No. FDA-2013-N-0764 for Animal Feed Regulatory Program Standards Singeltary Comment Submission
 
 
 
 
Thursday, April 14, 2016
 
*** Louisiana Chronic Wasting Disease CWD TSE Prion Surveillance and Testing Program? ***
 
 
 
Terry S. Singeltary Sr.
 

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