Idaho Two more Chronic Wasting Disease cases detected in cow elk and white-tailed doe in Unit 14
Idaho Two more Chronic Wasting Disease cases detected in cow elk and white-tailed doe in Unit 14
Two more Chronic Wasting Disease cases detected in cow elk and white-tailed doe in Unit 14
By Roger Phillips, Public Information Supervisor Wednesday, January 12, 2022 - 4:01 PM MST Latest detections bring Idaho's total to six positive cases of CWD, all in Unit 14 Idaho Fish and Game received notice on Jan. 10 that two more animals, a cow elk and a white-tailed deer doe, have tested positive for Chronic Wasting Disease. Both animals were in Unit 14 in Idaho County. The whitetail was about 4 miles south of Slate Creek in the same area as other CWD-positive deer, and the elk was about 1.5 miles northeast of White Bird.
Two mule deer bucks taken by hunters in the Slate Creek area during October were the first-ever CWD detections in Idaho.
Through Jan. 11, Fish and Game officers and biologists collected samples from about 550 deer and elk in the CWD surveillance area, which includes Units 14 and 15 and portions of adjacent units. Six total animals have tested positive, including the two mule deer bucks, two whitetail bucks, one whitetail doe, and one cow elk. All were in Unit 14. Lab results are not back yet from 10 CWD samples collected in the surveillance area during the CWD surveillance hunts.
Fish and Game asks people to report any deer or elk showing signs of CWD, which includes extremely low body weight, wide stance, lowered head, droopy ears and excessive salivation. People can report online at idfg.idaho.gov/cwd.
With deer and elk on winter range, Fish and Game officials also remind people it is unlawful to feed deer and elk within the CWD management zone defined by the Fish and Game Commission, which is hunt units 14 and 15.
People collecting road-killed deer, elk or moose for consumption or bait for trapping must not take the head or spinal column out of units 14 or 15, unless taking a head to a Fish and Game regional office for testing.
Statewide, Fish and Game tested more than 2,500 animals for CWD in 2021. Fish and Game has been testing for the disease since 1997 and sampled more than 20,000 animals during that time.
CWD is a neurological disease that affects deer, elk, moose and caribou. There is no practical live test for the disease, so only samples taken from dead animals can be used.
Although new to Idaho, CWD is found in 27 U.S. states and four Canadian provinces, including neighboring states Montana, Wyoming and Utah. Learn more about CWD in Idaho at idfg.idaho.gov/cwd.
According to the U.S. Centers for Disease Control and Prevention, there have been no reports of CWD infection in people. However, in the interest of safety, public health officials encourage people to not eat meat from animals that test positive for CWD, and hunters should follow health agencies' precautions and recommendations.
CWD affects the nervous system in deer, elk, moose and caribou and is caused by abnormal, misfolded proteins called prions that accumulate within the spinal column and brain, causing progressive damage to those cells and brain damage.
CWD has a very long incubation period (time between infection and observable disease) that typically takes at least 10 months for a deer or elk to show signs of illness.
Idaho Two white-tailed deer test positive for Chronic Wasting Disease in same area as previous CWD cases
Two white-tailed deer test positive for Chronic Wasting Disease in same area as previous CWD cases
By Roger Phillips, Public Information Supervisor Thursday, December 30, 2021 - 4:16 PM MST Recent cases bring total to four deer testing positive for CWD with 72 samples awaiting lab results Idaho Fish and Game officials received notice on Dec. 29 that two white-tailed deer bucks from the Slate Creek area north of Riggins have tested positive for Chronic Wasting Disease. These are the third and fourth deer that have tested positive for CWD in the area. Idaho had its first CWD detections from two hunter-harvested mule deer bucks from the Slate Creek area in November.
“While unfortunate, these latest CWD detections show our surveillance efforts are working, and we greatly appreciate the assistance we’ve received from hunters and landowners to help us learn how widespread CWD may be, and what percentage of the deer population may be affected,” Fish and Game State Wildlife Manager Rick Ward said.
After the initial CWD detections in November, the Idaho Fish and Game Commission established a CWD management zone that includes all of hunting Units 14 and 15 and a surveillance area that encompasses Units 14 and 15 and portions of four other adjacent hunting units.
Fish and Game has been intensively monitoring harvested deer within those areas for the disease, and created 35 special CWD surveillance hunts in December to collect additional samples from hunter-harvested deer.
As of Dec. 29, Fish and Game has taken 448 samples in the CWD surveillance zone that tested negative. Four have tested positive – all of which were within the Slate Creek drainage. Samples collected from 72 deer are still pending lab results at the Colorado State University laboratory. Statewide, Fish and Game tested more than 2,500 animals for CWD in 2021.
Fish and Game biologists remain in the information-gathering stage, and are waiting for the results of all pending CWD tests.
“We still have test results pending from deer harvested within the surveillance zone,” Ward said. “When we get the results of all tests, we will then assess our management options. Hunters and the general public will be involved in this process as the Fish and Game Commission deliberates future CWD management actions.”
With deer and elk now on lower-elevation winter range in Unit 14 and 15, Fish and Game officials are reminding people that it is unlawful to feed deer and elk within the CWD management zone (Units 14 & 15). People salvaging road-killed deer, elk, or moose must not remove the head or spinal column from the area, unless bringing a head to a Fish and Game Regional office for CWD testing.
CWD is a neurological disease that affects deer, elk, moose and caribou. There is no practical live test for the disease, so the only way to determine how many animals may have it is to take samples from dead animals. Fish and Game has been testing for CWD since 1997 and sampled more than 20,000 animals since then.
Although new to Idaho, CWD is found in 27 U.S. states and four Canadian provinces. CWD was detected in Wyoming in the mid-1980s and first detected in Montana in 2017. Learn more about CWD in Idaho at idfg.idaho.gov/cwd.
According to the U.S. Centers for Disease Control and Prevention, there have been no reports of CWD infection in people. However, in the interest of safety, public health officials encourage people to not eat meat from animals that test positive for CWD, and hunters should follow these precautions and recommendations.
Idaho Chronic Wasting Disease detected in two mule deer first time ever detected there
Chronic Wasting Disease detected in two Idaho mule deer
By Roger Phillips, Public Information Supervisor
Wednesday, November 17, 2021 - 3:47 PM MST
These are the first confirmed positive tests for Chronic Wasting Disease in Idaho
Two mule deer bucks harvested during October in the Slate Creek drainage near Lucile in Idaho County tested positive for Chronic Wasting Disease, according to Idaho Fish and Game. Under Fish and Game’s CWD strategic plan, both hunters have been notified that their bucks tested positive.
Although CWD has been known to exist in the Western United States for over 40 years, this is the first time animals in Idaho have tested positive for the disease, which is fatal to deer, elk, moose and caribou. The Idaho Fish and Game Commission has been notified, as well as the Idaho Department of Agriculture, the Idaho Department of Health and Welfare and the U.S. Department of Agriculture.
Samples from the diseased mule deer were tested at the Colorado State University Veterinary Diagnostic Lab and are being verified by the National Veterinary Services Laboratories in Ames, Iowa.
Anyone hunting in Unit 14 is encouraged to have any harvested deer or elk tested. To sample for CWD, lymph node tissue from fresh or frozen harvested heads are extracted. Meat or muscle tissue cannot be used to test for CWD.
Fish and Game will continue to supply more information as it becomes available. Visit idfg.idaho.gov/cwd for more information.
Facts about CWD
What is CWD?
It is a contagious and always-fatal neurological disease that affects deer, elk, moose and reindeer. Fish and Game has been testing animals for CWD since 1997.
How can hunters have harvested animals tested?
Fish and Game staff will extract the lymph nodes from any harvested deer, elk or moose at any regional office. There is no cost to the hunter. To sample for CWD, hunters need to bring the fresh or frozen head to any Fish and Game regional office to have a lymph node extracted. Meat or muscle tissue cannot be used to test for CWD.
Turnaround time for Fish and Game’s CWD samples is about 4-6 weeks, and hunters can check Fish and Game’s website for results.
What are symptoms of CWD?
Symptoms in deer, elk, moose and caribou include excessive salivation, drooping head/ears, tremors, extremely low body weight, and unusual behavior, such as showing no fear of humans and lack of coordination. But CWD cannot be diagnosed strictly by symptoms because other diseases, or conditions, can also cause similar symptoms in an animal. Also, animals can be infected for months or years before showing symptoms.
What if someone sees an animal that appears to have CWD?
Fish and Game welcomes reports by hunters and citizens. A person should accurately document the location of the animal (GPS coordinates if possible) and report the species and gender, if known. Take pictures, if possible, and immediately contact the nearest Fish and Game regional office. Do not attempt to touch, disturb, kill or remove the animal.
CWD MAP
Idaho CWD
Idaho Department of Fish and Game
2021 STRATEGY FOR CHRONIC WASTING DISEASE PREVENTION, DETECTION, AND MANAGEMENT FOR IDAHO’S WILD CERVIDS (DEER, ELK, AND MOOSE)
Idaho White-tailed Deer Management Plan 2020-2025
There are currently 2 captive white-tailed deer facilities in Idaho. These facilities and continued importation of white-tailed deer represent potential sites for disease introductions and genetic contamination.
Although 1,932 white-tailed deer from Idaho were tested for CWD from 1998 to 2016, prior to 2019, only a small number of white-tailed deer were tested for other diseases.
THURSDAY, NOVEMBER 18, 2021
Idaho Chronic Wasting Disease detected in two mule deer first time ever detected there
SATURDAY, JULY 21, 2018
Idaho Fish and Game Commission Quarterly Meeting July 25 26, 2018 Chronic Wasting Disease CWD TSE Prion
Published: 06 September 2021
Chronic wasting disease: a cervid prion infection looming to spillover
Alicia Otero, Camilo Duque Velásquez, Judd Aiken & Debbie McKenzie
Veterinary Research volume 52, Article number: 115 (2021)
Voluntary Chronic Wasting Disease Herd Certification Program Annual Update, FY2020
Last Modified: Feb 9, 2021
U.S. Department of Agriculture
Animal and Plant Health Inspection Service (APHIS) Veterinary Services
Annual Update from the Cervid Health Team
Voluntary Chronic Wasting Disease Herd Certification Program (HCP)
The APHIS National CWD Herd Certification Program (HCP) was implemented in 2014. It is a voluntary Federal-State-industry cooperative program administered by APHIS and implemented by participating States. The program provides uniform national herd certification standards that minimize the risk of spreading CWD in farmed cervid populations. Participating States and herd owners must comply with requirements for animal identification, fencing, recordkeeping, inspections/inventories, as well as animal mortality testing and response to any CWD-exposed, suspect, and positive herds. APHIS monitors the Approved State HCPs to ensure consistency with Federal standards through annual reporting by the States.
With each year of successful surveillance, herds participating in the HCP will advance in status until reaching five years with no evidence of CWD, at which time herds are certified as being low risk for CWD. Only farmed cervids from enrolled herds certified as low risk for CWD may move interstate. FY 2020 marks the eighth year that Approved States have submitted their CWD HCP annual reports to APHIS.
The current Cervid Health Program staff officers are as follows: Dr. Mark Lyons, Dr. Jennifer Siembieda, and Dr. Tracy Nichols
Voluntary Herd Certification Participation Summary
Currently, 28 States participate in the voluntary CWD Herd Certification Program encompassing 2,145 enrolled herds, of which, 1,723 had the certified status in the program.
1,616 enrolled deer herds, of which, 1,297 were certified
371 enrolled elk herds, of which, 328 were certified
147 enrolled mixed species herds, of which, 98 were certified
CWD in Farmed Cervids Summary of CW Detections
There were 22 newly identified CWD positive herds in FY20
13 of these herds were not participants in the Federal HCP
2 herds were considered enrolled in the HCP
7 herds were certified in the HCP
Half of the herds were located within 20 miles of identified CWD in the wild, half were not CWD Herds by State
Pennsylvania: Eight new CWD positive herds
Breeding herd of 33 WTD, HCP certified, depopulated with Federal indemnity
Breeding herd of 6 WTD, not in HCP, depopulated with Federal indemnity
Breeding herd of 15 WTD, not in HCP, depopulated by owner\
Hunt preserve of 58 WTD, not in HCP, populated and under quarantine
Breeding herd of 75 WTD, not in HCP, populated and under quarantine
Breeding herd of WTD, not in HCP, populated and under quarantine
Breeding herd of 90 WTD, not in HCP, populated and under quarantine
Breeding herd of 4 WTD, not in HCP, populated and under quarantine
Iowa: Two new CWD positive herds
Breeding herd of 23 WTD, HCP certified, depopulated with Federal indemnity
Breeding herd of 13 WTD, HCP certified, depopulated with Federal indemnity
Minnesota: Two new CWD positive herds
Breeding herd of 3 WTD, enrolled in HCP, not certified, depopulated by owner
Breeding herd of 6 WTD, enrolled in HCP, not certified, depopulated with Federal indemnity
Colorado: Two new CWD positive herds
Breeding herd/hunt preserve of 9 elk, HCP certified, depopulated by owner
Breeding herd of 8 elk, HCP certified, populated and under quarantine
Utah: Two new CWD positive herds
Breeding herd of 465 elk, not in HCP, partial depopulation with Federal indemnity- removed purchased animals, populated-quarantine
Breeding herd of 103 elk, not in HCP, partial depopulation with Federal indemnity- removed purchased animals, populated-quarantine
Michigan: One new CWD positive herd
Hunt preserve of >600 WTD, not in HCP, populated and under quarantine
Montana: One new CWD positive herd
Breeding herd of 3 elk, not in HCP, populated and under quarantine
Texas: one new CWD positive herd
Breeding herd of 59 WTD, not in HCP, depopulated with Federal indemnity
Kansas: One new CWD positive herd
Breeding herd of 20 elk, HCP certified, depopulated with Federal indemnity
Ohio: Eight new CWD positive herd
Breeding herd of 138 WTD, HCP certified, depopulated with Federal indemnity
Research
Whole genome study investigating the association of genetics with CWD susceptibility has been published.
Blinded validation of the genetic predicative model is almost complete
A standardized protocol has been developed, in partnership with ARS, USGS, University of WI, and NIH for tissue sample testing using RT-QuIC
A study is starting shortly to determine the sensitivity and specify of RT-QuIC utilizing the standardized protocol
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Voluntary Chronic Wasting Disease Herd Certification Program Annual Update, FY2020
Cervids: CWD Voluntary Herd Certification Program
Last Modified: Jun 29, 2021
CWD status of captive herds
“Regarding the current situation involving CWD in permitted deer breeding facilities, TPWD records indicate that within the last five years, the seven CWD-positive facilities transferred a total of 2,530 deer to 270 locations in 102 counties and eight locations in Mexico (the destinations included 139 deer breeding facilities, 118 release sites, five Deer Management Permit sites, and three nursing facilities).'' ...
It is apparent that prior to the recent emergency rules, the CWD detection rules were ineffective at detecting CWD earlier in the deer breeding facilities where it was eventually discovered and had been present for some time; this creates additional concern regarding adequate mitigation of the risk of transferring CWD-positive breeder deer to release sites where released breeder deer come into contact with free-ranging deer...
Commission Agenda Item No. 5 Exhibit B
DISEASE DETECTION AND RESPONSE RULES
PROPOSAL PREAMBLE
1. Introduction.
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A third issue is the accuracy of mortality reporting. Department records indicate that for each of the last five years an average of 26 deer breeders have reported a shared total of 159 escapes. Department records for the same time period indicate an average of 31 breeding facilities reported a shared total of 825 missing deer (deer that department records indicate should be present in the facility, but cannot be located or verified).
Listen here;
Nov 3, 2021
Nov 4, 2021
Counties where CWD Exposed Deer were Released, September 2021
Number of CWD Exposed Deer Released by County, September 2021
Oh, Deer, CWD, Heading Off a Wildlife Epidemic Texas Real Estate Research Center TAMU
Texas A & M University
Texas Real Estate Research Center
Oh, Deer
Heading Off a Wildlife Epidemic
Charles E. Gilliland (Aug 18, 2021)
The Takeaway
Landowners in certain parts of the state need to be aware of chronic wasting disease, which can greatly reduce the number of deer. While there are no known cures or ways to eradicate the disease, the Texas Parks and Wildlife Department is taking measures to reduce its spread.
A multitude of risks threaten to undermine Texas landowners' efforts to manage their land. Some of those spring from past activities but can leave invisible living legacies behind. Anthrax, for example. An outbreak of anthrax in livestock leaves a scattering of spores across the countryside that can activate and infect replacement herds.
Chronic wasting disease (CWD) in wildlife poses a similar potential problem for landowners in certain parts of Texas. CWD infects members of the Cervidae family, namely deer, elk, moose, etc. CWD does not pose dangers to livestock, and scientists have not found evidence of the disease infecting humans. However, it is always fatal to stricken wildlife, threatening a destructive wave of infections among deer herds where the disease has spread. Therefore, CWD poses a direct threat to one of the primary motives for owning rural land: wildlife herd management.
Profiling CWD
CWD belongs to a family of disorders known as prion diseases, or transmissible spongiform encephalopathies (TSEs). It includes Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy, or mad cow disease, in cattle. The Centers for Disease Control and Prevention describes these maladies in detail:
The causative agents of TSEs are believed to be prions. The term “prions" refers to abnormal, pathogenic agents that are transmissible and are able to induce abnormal folding of specific normal cellular proteins called prion proteins that are found most abundantly in the brain. The functions of these normal prion proteins are still not completely understood. The abnormal folding of the prion proteins leads to brain damage and the characteristic signs and symptoms of the disease. Prion diseases are usually rapidly progressive and always fatal.
CWD symptoms include dramatic weight loss, stumbling, listlessness, decreased social interaction, loss of fear of humans, and excessive salivating. However, animals typically exhibit no symptoms until 18-24 months after contracting the disease. In addition, these symptoms could be caused by other conditions, so formal testing is needed to reliably diagnose CWD.
Obviously, an infected animal may spread the disease to other members of the herd during the nonsymptomatic phase of infection. Perhaps even worse, the body casts off prions, so an infected animal will cast off diseased prions. Therefore, an infected herd can leave infection in the soil and remain infectious to host animals, much like anthrax.
CWD Comes to Texas
Scientists first identified CWD in mule deer in Colorado in 1967. Since that time, CWD has spread to Wyoming, Montana, Wisconsin, Pennsylvania, and other states.
CWD first appeared in Hudspeth County in 2012 in free-ranging mule deer. In 2015, the Texas Parks and Wildlife Department (TPWD) found CWD in white-tailed deer in captive facilities in Medina County. By 2021, a total of 224 cases had been identified in 13 counties. Tests confirmed cases in two red deer, four elk, 49 mule deer, and 169 white-tailed deer.
See the TPWD site for details. Texas A&M AgriLife Extension provides a good overview of the disease in A Guide to Chronic Wasting Disease (CWD) in Texas Cervids.
Containing the Spread
Currently, there is no known cure for the disease nor any mechanism to eradicate it. Therefore, TPWD management of CWD seeks to contain the spread to areas of confirmed infections.
The plan has established five CWD zones with confirmed infections: Kimble County Zone, Trans-Pecos Zone, South Central Zone, Panhandle Zone, and Val Verde County Zone. The latest edition of the TPWD Outdoor Annual provides maps of each zone indicating official stations performing testing for CWD. All hunters harvesting animals in these zones must take them to one of these stations to have them tested for CWD within 48 hours of the harvest. In addition, hunters can transport carcasses out of the zones only after all brain and spinal cord tissue have been removed. TPWD will provide a receipt for the sample.
Because the spread of CWD is evolving, regulations can change quickly. Therefore, anyone involved in hunting activity should consult the most recent Outdoor Annual for the latest regulations. To reduce the chances of spreading the disease, TPWD regulations also restrict the movement of live deer from CWD zones.
Impact on Rural Landowners CWD poses a significant threat to the future of hunting in Texas. Deer population declines of 45 and 50 percent have been documented in Colorado and Wyoming. A broad infection of Texas deer populations resulting in similar population impacts would inflict severe economic damage to rural communities and could negatively impact land markets. Specifically, those landowners seeking to establish a thriving herd of deer could avoid buying in areas with confirmed CWD infections.
As they do with anthrax-susceptible properties, land brokers may find it advisable to inquire about the status of CWD infections on properties that they present for sale. Prospective buyers should also investigate the status of the wildlife on prospective properties. In addition, existing landowners should monitor developments as TPWD crafts management strategies to identify and contain this deadly disease.
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Dr. Gilliland (c-gilliland@tamu.edu) is a research economist with the Texas Real Estate Research Center at Texas A&M University.
Scrapie Agent (Strain 263K) Can Transmit Disease via the Oral Route after Persistence in Soil over Years
Published: May 9, 2007
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Our results showed that 263K scrapie agent can persist in soil at least over 29 months. Strikingly, not only the contaminated soil itself retained high levels of infectivity, as evidenced by oral administration to Syrian hamsters, but also feeding of aqueous soil extracts was able to induce disease in the reporter animals. We could also demonstrate that PrPSc in soil, extracted after 21 months, provides a catalytically active seed in the protein misfolding cyclic amplification (PMCA) reaction. PMCA opens therefore a perspective for considerably improving the detectability of prions in soil samples from the field.
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***> This is very likely to have parallels with control efforts for CWD in cervids. <***
Paper
Rapid recontamination of a farm building occurs after attempted prion removal
Kevin Christopher Gough BSc (Hons), PhD Claire Alison Baker BSc (Hons) Steve Hawkins MIBiol Hugh Simmons BVSc, MRCVS, MBA, MA Timm Konold DrMedVet, PhD, MRCVS … See all authors
First published: 19 January 2019 https://doi.org/10.1136/vr.105054
Abstract
The transmissible spongiform encephalopathy scrapie of sheep/goats and chronic wasting disease of cervids are associated with environmental reservoirs of infectivity. Preventing environmental prions acting as a source of infectivity to healthy animals is of major concern to farms that have had outbreaks of scrapie and also to the health management of wild and farmed cervids. Here, an efficient scrapie decontamination protocol was applied to a farm with high levels of environmental contamination with the scrapie agent. Post‐decontamination, no prion material was detected within samples taken from the farm buildings as determined using a sensitive in vitro replication assay (sPMCA). A bioassay consisting of 25 newborn lambs of highly susceptible prion protein genotype VRQ/VRQ introduced into this decontaminated barn was carried out in addition to sampling and analysis of dust samples that were collected during the bioassay. Twenty‐four of the animals examined by immunohistochemical analysis of lymphatic tissues were scrapie‐positive during the bioassay, samples of dust collected within the barn were positive by month 3. The data illustrates the difficulty in decontaminating farm buildings from scrapie, and demonstrates the likely contribution of farm dust to the recontamination of these environments to levels that are capable of causing disease.
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This study clearly demonstrates the difficulty in removing scrapie infectivity from the farm environment. Practical and effective prion decontamination methods are still urgently required for decontamination of scrapie infectivity from farms that have had cases of scrapie and this is particularly relevant for scrapiepositive goatherds, which currently have limited genetic resistance to scrapie within commercial breeds.24 This is very likely to have parallels with control efforts for CWD in cervids.
***>This is very likely to have parallels with control efforts for CWD in cervids.
***> Infectious agent of sheep scrapie may persist in the environment for at least 16 years
***> Nine of these recurrences occurred 14–21 years after culling, apparently as the result of environmental contamination, but outside entry could not always be absolutely excluded.
JOURNAL OF GENERAL VIROLOGY Volume 87, Issue 12
Infectious agent of sheep scrapie may persist in the environment for at least 16 years Free
Gudmundur Georgsson1, Sigurdur Sigurdarson2, Paul Brown3
Front. Vet. Sci., 14 September 2015 | https://doi.org/10.3389/fvets.2015.00032
Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission
imageTimm Konold1*, imageStephen A. C. Hawkins2, imageLisa C. Thurston3, imageBen C. Maddison4, imageKevin C. Gough5, imageAnthony Duarte1 and imageHugh A. Simmons1
1Animal Sciences Unit, Animal and Plant Health Agency Weybridge, Addlestone, UK
2Pathology Department, Animal and Plant Health Agency Weybridge, Addlestone, UK
3Surveillance and Laboratory Services, Animal and Plant Health Agency Penrith, Penrith, UK
4ADAS UK, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK
5School 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.
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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
***> CONGRESSIONAL ABSTRACTS PRION CONFERENCE 2018
P69 Experimental transmission of CWD from white-tailed deer to co-housed reindeer
Mitchell G (1), Walther I (1), Staskevicius A (1), Soutyrine A (1), Balachandran A (1)
(1) National & OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada.
Chronic wasting disease (CWD) continues to be detected in wild and farmed cervid populations of North America, affecting predominantly white-tailed deer, mule deer and elk. Extensive herds of wild caribou exist in northern regions of Canada, although surveillance has not detected the presence of CWD in this population. Oral experimental transmission has demonstrated that reindeer, a species closely related to caribou, are susceptible to CWD. Recently, CWD was detected for the first time in Europe, in wild Norwegian reindeer, advancing the possibility that caribou in North America could also become infected. Given the potential overlap in habitat between wild CWD-infected cervids and wild caribou herds in Canada, we sought to investigate the horizontal transmissibility of CWD from white-tailed deer to reindeer.
Two white-tailed deer were orally inoculated with a brain homogenate prepared from a farmed Canadian white-tailed deer previously diagnosed with CWD. Two reindeer, with no history of exposure to CWD, were housed in the same enclosure as the white-tailed deer, 3.5 months after the deer were orally inoculated. The white-tailed deer developed clinical signs consistent with CWD beginning at 15.2 and 21 months post-inoculation (mpi), and were euthanized at 18.7 and 23.1 mpi, respectively. Confirmatory testing by immunohistochemistry (IHC) and western blot demonstrated widespread aggregates of pathological prion protein (PrPCWD) in the central nervous system and lymphoid tissues of both inoculated white-tailed deer. Both reindeer were subjected to recto-anal mucosal associated lymphoid tissue (RAMALT) biopsy at 20 months post-exposure (mpe) to the white-tailed deer. The biopsy from one reindeer contained PrPCWD confirmed by IHC. This reindeer displayed only subtle clinical evidence of disease prior to a rapid decline in condition requiring euthanasia at 22.5 mpe. Analysis of tissues from this reindeer by IHC revealed widespread PrPCWD deposition, predominantly in central nervous system and lymphoreticular tissues. Western blot molecular profiles were similar between both orally inoculated white-tailed deer and the CWD positive reindeer. Despite sharing the same enclosure, the other reindeer was RAMALT negative at 20 mpe, and PrPCWD was not detected in brainstem and lymphoid tissues following necropsy at 35 mpe. Sequencing of the prion protein gene from both reindeer revealed differences at several codons, which may have influenced susceptibility to infection.
Natural transmission of CWD occurs relatively efficiently amongst cervids, supporting the expanding geographic distribution of disease and the potential for transmission to previously naive populations. The efficient horizontal transmission of CWD from white-tailed deer to reindeer observed here highlights the potential for reindeer to become infected if exposed to other cervids or environments infected with CWD.
SOURCE REFERENCE 2018 PRION CONFERENCE ABSTRACT
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research
Title: Horizontal transmission of chronic wasting disease in reindeer
Author
item MOORE, SARAH - ORISE FELLOW item KUNKLE, ROBERT item WEST GREENLEE, MARY - IOWA STATE UNIVERSITY item Nicholson, Eric item RICHT, JUERGEN item HAMIR, AMIRALI item WATERS, WADE item Greenlee, Justin
Submitted to: Emerging Infectious Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/29/2016
Publication Date: 12/1/2016
Citation: Moore, S., Kunkle, R., Greenlee, M., Nicholson, E., Richt, J., Hamir, A., Waters, W., Greenlee, J. 2016. Horizontal transmission of chronic wasting disease in reindeer. Emerging Infectious Diseases. 22(12):2142-2145. doi:10.3201/eid2212.160635.
Interpretive Summary: Chronic wasting disease (CWD) is a fatal neurodegenerative disease that occurs in farmed and wild cervids (deer and elk) of North America and was recently diagnosed in a single free-ranging reindeer (Rangifer tarandus tarandus) in Norway. CWD is a transmissible spongiform encephalopathy (TSE) that is caused by infectious proteins called prions that are resistant to various methods of decontamination and environmental degradation. Little is known about the susceptibility of or potential for transmission amongst reindeer. In this experiment, we tested the susceptibility of reindeer to CWD from various sources (elk, mule deer, or white-tailed deer) after intracranial inoculation and tested the potential for infected reindeer to transmit to non-inoculated animals by co-housing or housing in adjacent pens. Reindeer were susceptible to CWD from elk, mule deer, or white-tailed deer sources after experimental inoculation. Most importantly, non-inoculated reindeer that were co-housed with infected reindeer or housed in pens adjacent to infected reindeer but without the potential for nose-to-nose contact also developed evidence of CWD infection. This is a major new finding that may have a great impact on the recently diagnosed case of CWD in the only remaining free-ranging reindeer population in Europe as our findings imply that horizontal transmission to other reindeer within that herd has already occurred. Further, this information will help regulatory and wildlife officials developing plans to reduce or eliminate CWD and cervid farmers that want to ensure that their herd remains CWD-free, but were previously unsure of the potential for reindeer to transmit CWD.
Technical Abstract: Chronic wasting disease (CWD) is a naturally-occurring, fatal prion disease of cervids. Reindeer (Rangifer tarandus tarandus) are susceptible to CWD following oral challenge, and CWD was recently reported in a free-ranging reindeer of Norway. Potential contact between CWD-affected cervids and Rangifer species that are free-ranging or co-housed on farms presents a potential risk of CWD transmission. The aims of this study were to 1) investigate the transmission of CWD from white-tailed deer (Odocoileus virginianus; CWDwtd), mule deer (Odocoileus hemionus; CWDmd), or elk (Cervus elaphus nelsoni; CWDelk) to reindeer via the intracranial route, and 2) to assess for direct and indirect horizontal transmission to non-inoculated sentinels. Three groups of 5 reindeer fawns were challenged intracranially with CWDwtd, CWDmd, or CWDelk. Two years after challenge of inoculated reindeer, non-inoculated negative control reindeer were introduced into the same pen as the CWDwtd inoculated reindeer (direct contact; n=4) or into a pen adjacent to the CWDmd inoculated reindeer (indirect contact; n=2). Experimentally inoculated reindeer were allowed to develop clinical disease. At death/euthanasia a complete necropsy examination was performed, including immunohistochemical testing of tissues for disease-associated CWD prion protein (PrPcwd). Intracranially challenged reindeer developed clinical disease from 21 months post-inoculation (months PI). PrPcwd was detected in 5 out of 6 sentinel reindeer although only 2 out of 6 developed clinical disease during the study period (< 57 months PI). We have shown that reindeer are susceptible to CWD from various cervid sources and can transmit CWD to naïve reindeer both directly and indirectly.
***> Scrapie vs Chronic Wasting Disease CWD TSE Prion ???
172. Establishment of PrPCWD extraction and detection methods in the farm soil
Kyung Je Park, Hoo Chang Park, In Soon Roh, Hyo Jin Kim, Hae-Eun Kang and Hyun Joo Sohn
Foreign Animal Disease Division, Animal and Plant Quarantine Agency, Gimcheon, Gyeongsangbuk-do, Korea
Conclusions: Our studies showed that PrPCWD persist in 0.001% CWD contaminated soil for at least 4 year and natural CWD-affected farm soil. When cervid reintroduced into CWD outbreak farm, the strict decontamination procedures of the infectious agent should be performed in the environment of CWD-affected cervid habitat.
*** 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.
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.
Sheep and cattle may be exposed to CWD via common grazing areas with affected deer but so far, appear to be poorly susceptible to mule deer CWD (Sigurdson, 2008). In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006). It is not known how susceptible humans are to CWD but given that the prion can be present in muscle, it is likely that humans have been exposed to the agent via consumption of venison (Sigurdson, 2008). Initial experimental research suggests that human susceptibility to CWD is low and there may be a robust species barrier for CWD transmission to humans (Sigurdson, 2008), however the risk appetite for a public health threat may still find this level unacceptable.
2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains
Olivier Andreoletti, INRA Research Director, Institut National de la Recherche Agronomique (INRA) – École Nationale Vétérinaire de Toulouse (ENVT), invited speaker, presented the results of two recently published scientific articles of interest, of which he is co-author: ‘Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice’ (MarinMoreno et al., 2020) and ‘The emergence of classical BSE from atypical/Nor98 scrapie’ (Huor et al., 2019).
In the first experimental study, H-type and L-type BSE were inoculated into transgenic mice expressing all three genotypes of the human PRNP at codon 129 and into adapted into ARQ and VRQ transgenic sheep mice. The results showed the alterations of the capacities to cross the human barrier species (mouse model) and emergence of sporadic CJD agents in Hu PrP expressing mice: type 2 sCJD in homozygous TgVal129 VRQ-passaged L-BSE, and type 1 sCJD in homozygous TgVal 129 and TgMet129 VRQ-passaged H-BSE.
3.2.1.2 Non‐cervid domestic species
The remarkably high rate of natural CWD transmission in the ongoing NA epidemics raises the question of the risk to livestock grazing on CWD‐contaminated shared rangeland and subsequently developing a novel CWD‐related prion disease. This issue has been investigated by transmitting CWD via experimental challenge to cattle, sheep and pigs and to tg mouse lines expressing the relevant species PrP.
For cattle challenged with CWD, PrPSc was detected in approximately 40% of intracerebrally inoculated animals (Hamir et al., 2005, 2006a, 2007). Tg mice expressing bovine PrP have also been challenged with CWD and while published studies have negative outcomes (Tamguney et al., 2009b), unpublished data provided for the purposes of this Opinion indicate that some transmission of individual isolates to bovinised mice is possible (Table 1).
In small ruminant recipients, a low rate of transmission was reported between 35 and 72 months post‐infection (mpi) in ARQ/ARQ and ARQ/VRQ sheep intracerebrally challenged with mule deer CWD (Hamir et al., 2006b), while two out of two ARQ/ARQ sheep intracerebrally inoculated with elk CWD developed clinical disease after 28 mpi (Madsen‐Bouterse et al., 2016). However, tg mice expressing ARQ sheep PrP were resistant (Tamguney et al., 2006) and tg mice expressing the VRQ PrP allele were poorly susceptible to clinical disease (Beringue et al., 2012; Madsen‐Bouterse et al., 2016). In contrast, tg mice expressing VRQ sheep PrP challenged with CWD have resulted in highly efficient, life‐long asymptomatic replication of these prions in the spleen tissue (Beringue et al., 2012).
A recent study investigated the potential for swine to serve as hosts of the CWD agent(s) by intracerebral or oral challenge of crossbred piglets (Moore et al., 2016b, 2017). Pigs sacrificed at 6 mpi, approximately the age at which pigs reach market weight, were clinically healthy and negative by diagnostic tests, although low‐level CWD agent replication could be detected in the CNS by bioassay in tg cervinised mice. Among pigs that were incubated for up to 73 mpi, some gave diagnostic evidence of CWD replication in the brain between 42 and 72 mpi. Importantly, this was observed also in one orally challenged pig at 64 mpi and the presence of low‐level CWD replication was confirmed by mouse bioassay. The authors of this study argued that pigs can support low‐level amplification of CWD prions, although the species barrier to CWD infection is relatively high and that the detection of infectivity in orally inoculated pigs with a mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity.
Very low oral exposure to prions of brain or saliva origin can transmit chronic wasting disease
Nathaniel D. Denkers ,Clare E. Hoover ,Kristen A. Davenport,Davin M. Henderson,Erin E. McNulty,Amy V. Nalls,Candace K. Mathiason,Edward A. Hoover
Published: August 20, 2020
We report that oral exposure to as little as 300 nanograms (ng) of CWD-positive brain or to saliva containing seeding activity equivalent to 300 ng of CWD-positive brain, were sufficient to transmit CWD disease. This was true whether the inoculum was administered as a single bolus or divided as three weekly 100 ng exposures. However, when the 300 ng total dose was apportioned as 10, 30 ng doses delivered over 12 weeks, no infection occurred. While low-dose exposures to prions of brain or saliva origin prolonged the time from inoculation to first detection of infection, once infection was established, we observed no differences in disease pathogenesis. These studies suggest that the CWD minimum infectious dose approximates 100 to 300 ng CWD-positive brain (or saliva equivalent), and that CWD infection appears to conform more with a threshold than a cumulative dose dynamic.
ARS RESEARCH Generation of human chronic wasting disease in transgenic mice
Publication Acceptance Date: 9/8/2021
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
Title: Generation of human chronic wasting disease in transgenic mice
Author item WANG, ZERUI - Case Western Reserve University (CWRU) item QIN, KEFENG - University Of Chicago item CAMACHO, MANUEL - Case Western Reserve University (CWRU) item SHEN, PINGPING - Case Western Reserve University (CWRU) item YUAN, JUE - Case Western Reserve University (CWRU) item Greenlee, Justin item CUI, LI - Jilin University item KONG, QINGZHONG - Case Western Reserve University (CWRU) item MASTRIANNI, JAMES - University Of Chicago item ZOU, WEN-QUAN - Case Western Reserve University (CWRU)
Submitted to: Acta Neuropathologica Publication Type: Peer Reviewed Journal Publication Acceptance Date: 9/8/2021 Publication Date: N/A Citation: N/A
Interpretive Summary: Prion diseases are invariably fatal neurologic diseases for which there is no known prevention or cure. Chronic wasting disease (CWD) is the prion disease of deer and elk and is present in farmed and free ranging herds throughout North America. To date there is no clear evidence that the CWD agent could be transmitted to humans. This manuscript describes the use of an in vitro technique, cell-free serial protein misfolding cyclic amplification (sPMCA), to generate a CWD prion that is infectious to transgenic mice expressing the human prion protein. This study provides the first evidence that CWD prions may be able to cause misfolding in the human prion protein. This information will impact medical experts and those involved in making policy for farmed cervids and wildlife.
Technical Abstract: Chronic wasting disease (CWD) is a cervid spongiform encephalopathy or prion disease caused by the infectious prion or PrPSc, a misfolded conformer of cellular prion protein (PrPC). It has rapidly spread in North America and also has been found in Asia and Europe. In contrast to the zoonotic mad cow disease that is the first animal prion disease found transmissible to humans, the transmissibility of CWD to humans remains uncertain although most previous studies have suggested that humans may not be susceptible to CWD. Here we report the generation of an infectious human PrPSc by seeding CWD PrPSc in normal human brain PrPC through the in vitro cell-free serial protein misfolding cyclic amplification (sPMCA). Western blotting confirms that the sPMCA-induced proteinase K-resistant PrPSc is a human form, evidenced by a PrP-specific antibody that recognizes human but not cervid PrP. Remarkably, two lines of humanized transgenic (Tg) mice expressing human PrP-129Val/Val (VV) or -129Met/Met (MM) polymorphism develop prion disease at 233 ± 6 (mean ± SE) days post-inoculation (dpi) and 552 ± 27 dpi, respectively, upon intracerebral inoculation with the sPMCA-generated PrPSc. The brain of diseased Tg mice reveals the electrophoretic profile of PrPSc similar to sporadic Creutzfeldt-Jakob disease (sCJD) MM1 or VV2 subtype but different neuropathological patterns. We believe that our study provides the first evidence that CWD PrPSc is able to convert human PrPC into PrPSc in vitro and the CWD-derived human PrPSc mimics atypical sCJD subtypes in humanized Tg mice.
''The brain of diseased Tg mice reveals the electrophoretic profile of PrPSc similar to sporadic Creutzfeldt-Jakob disease (sCJD) MM1 or VV2 subtype but different neuropathological patterns.''
''We believe that our study provides the first evidence that CWD PrPSc is able to convert human PrPC into PrPSc in vitro and the CWD-derived human PrPSc mimics atypical sCJD subtypes in humanized Tg mice.''
Published: 26 September 2021
Generation of human chronic wasting disease in transgenic mice
Zerui Wang, Kefeng Qin, Manuel V. Camacho, Ignazio Cali, Jue Yuan, Pingping Shen, Justin Greenlee, Qingzhong Kong, James A. Mastrianni & Wen-Quan Zou
Acta Neuropathologica Communications volume 9, Article number: 158 (2021)
Abstract
Chronic wasting disease (CWD) is a cervid prion disease caused by the accumulation of an infectious misfolded conformer (PrPSc) of cellular prion protein (PrPC). It has been spreading rapidly in North America and also found in Asia and Europe. Although bovine spongiform encephalopathy (i.e. mad cow disease) is the only animal prion disease known to be zoonotic, the transmissibility of CWD to humans remains uncertain. Here we report the generation of the first CWD-derived infectious human PrPSc by elk CWD PrPSc-seeded conversion of PrPC in normal human brain homogenates using in vitro protein misfolding cyclic amplification (PMCA). Western blotting with human PrP selective antibody confirmed that the PMCA-generated protease-resistant PrPSc was derived from the human PrPC substrate. Two lines of humanized transgenic mice expressing human PrP with either Val or Met at the polymorphic codon 129 developed clinical prion disease following intracerebral inoculation with the PMCA-generated CWD-derived human PrPSc. Diseased mice exhibited distinct PrPSc patterns and neuropathological changes in the brain. Our study, using PMCA and animal bioassays, provides the first evidence that CWD PrPSc can cross the species barrier to convert human PrPC into infectious PrPSc that can produce bona fide prion disease when inoculated into humanized transgenic mice.
Snip...
It is worth noting that the annual number of sporadic CJD (sCJD) cases in the USA has increased, with the total number of suspected and confirmed sCJD cases rising from 284 in 2003 to 511 in 2017 (https://www.cdc.gov/prions/cjd/occurrence-transmission.html). The greatly enhanced CJD surveillance and an aging population in the USA certainly contributed to the observed increase in annual sCJD case numbers in recent years, but the possibility cannot be excluded that some of the increased sCJD prevalence is linked to CWD exposure.
In the present study, using serial protein misfolding cyclic amplification (sPMCA) assay we generate PrPSc by seeding CWD prions in normal human brain homogenates. Importantly, we reveal that two lines of humanized Tg mice expressing human PrP-129VV and 129MM develop prion diseases upon intracerebral inoculation of the abnormal PrP generated by sPMCA. We believe that our study provides the first opportunity to dissect the clinical, pathological and biochemical features of the CWD-derived human prion disease in two lines of humanized Tg mice expressing two major human PrP genotypes, respectively.
***> ''The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).''
***> In conclusion, sensory symptoms and loss of reflexes in Gerstmann-Sträussler-Scheinker syndrome can be explained by neuropathological changes in the spinal cord. We conclude that the sensory symptoms and loss of lower limb reflexes in Gerstmann-Sträussler-Scheinker syndrome is due to pathology in the caudal spinal cord. <***
***> The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.<***
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
***> All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals.<***
***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II) <***
***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.
https://www.nature.com/articles/srep11573
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases).
Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases.
We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases***
===============
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
==============
https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf
***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases).
Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases.
We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases***
===============
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
==============
https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf
***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
PRION 2016 TOKYO
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
Title: Transmission of scrapie prions to primate after an extended silent incubation period)
*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160
GAME FARM INDUSTRY WANTS TO COVER UP FINDINGS OF INCREASE RISK TO CJD FROM CERVID
BSE INQUIRY
CJD9/10022
October 1994
Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane
BerksWell Coventry CV7 7BZ
Dear Mr Elmhirst,
CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT
Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.
The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended.. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.
The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.
The statistical results regarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.
I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.
http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf
Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasized by the finding that some strains of scrapie produce lesions identical to the once which characterize the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the scrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
IN CONFIDENCE
SCRAPIE TRANSMISSION TO CHIMPANZEES
IN CONFIDENCE
reference...
RB3.20
TRANSMISSION TO CHIMPANZEES
1. Kuru and CJD have been successfully transmitted to chimpanzees but scrapie and TME have not.
2. We cannot say that scrapie will not transmit to chimpanzees. There are several scrapie strains and I am not aware that all have been tried (that would have to be from mouse passaged material). Nor has a wide enough range of field isolates subsequently strain typed in mice been inoculated by the appropriate routes (i/c, ilp and i/v) :
3. I believe the proposed experiment to determine transmissibility, if conducted, would only show the susceptibility or resistance of the chimpanzee to infection/disease by the routes used and the result could not be interpreted for the predictability of the susceptibility for man. Proposals for prolonged oral exposure of chimpanzees to milk from cattle were suggested a long while ago and rejected.
4. In view of Dr Gibbs' probable use of chimpazees Mr Wells' comments (enclosed) are pertinent. I have yet to receive a direct communication from Dr Schellekers but before any collaboration or provision of material we should identify the Gibbs' proposals and objectives.
5. A positive result from a chimpanzee challenged severely 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.
6. A negative result would take a lifetime to determine but that would be a shorter period than might be available for human exposure and it would still not answer the question regarding mans' susceptibility. In the meantime no doubt the negativity would be used defensively. It would however be counterproductive if the experiment finally became positive. We may learn more about public reactions following next Monday' s meeting.
R. Bradley
23 September 1990
CVO (+Mr Wells' comments)
Dr T W A Little
Dr B J Shreeve
90/9.23/1.1.
http://web.archive.org/web/20090506041740/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf
IN CONFIDENCE CHIMPANZEES
CODE 18-77 Reference RB3.46
Some further information that may assist in decision making has been gained by discussion with Dr Rosalind Ridley.
She says that careful study of Gajdusek's work shows no increased susceptibility of chimpanzees over New World Monkeys such as Squirrel Monkeys. She does not think it would tell you anything about the susceptibility to man. Also Gajdusek did not, she believes, challenge chimpanzees with scrapie as severely as we did pigs and we know little of that source of scrapie. Comparisons would be difficult. She also would not expect the Home Office to sanction such experiments here unless there was a very clear and important objective that would be important for human health protection. She doubted such a case could be made. If this is the case she thought it would be unethical to do an experiment abroad because we could not do it in our own country.
Retrospectively she feels they should have put up more marmosets than they did. They all remain healthy. They would normally regard the transmission as negative if no disease resulted in five years.
We are not being asked for a decision but I think that before we made one we should gain as much knowledge as we can. If we decided to proceed we would have to bear any criticisms for many years if there was an adverse view by scientists or media. This should not be undertaken lightly. There is already some adverse comment here, I gather, on the pig experiment though that will subside.
The Gibbs' (as' distinct from Schellekers') study is somewhat different. We are merely supplying material for comparative studies in a laboratory with the greatest experience of human SEs in the world and it has been sanctioned by USDA (though we do not know for certain yet if chimpanzees specifically will be used). This would keep it at a lower profile than if we conducted such an experiment in the UK or Europe.
I consider we must have very powerful and defendable objectives to go beyond Gibbs' proposed experiments and should not initiate others just because an offer has been made.
Scientists have a responsibility to seek other methods of investigative research other than animal experimentation. At present no objective has convinced me we need to do research using Chimpanzees - a species in need of protection. Resisting such proposals would enable us to communicate that information to the scientist and the public should the need arise. A line would have been drawn.
CVO cc Dr T Dr B W A Little Dr B J Shreeve
R Bradley
26 September 1990
90/9.26/3.2
http://web.archive.org/web/20090506041605/http://www.bseinquiry.gov.uk/files/yb/1990/09/26003001.pdf
this is tse prion political theater here, i.e. what i call TSE PRION POKER...tss
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.
snip...
PAGE 26
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.
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 its subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA viewed it as a wildlife problem and consequently not their province! ...page 26.
snip...see;
IN CONFIDENCE
PERCEPTIONS OF UNCONVENTIONAL SLOW VIRUS DISEASE OF ANIMALS IN THE USA
GAH WELLS
REPORT OF A VISIT TO THE USA
APRIL-MAY 1989
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...
1985
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...
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
10:11 AM
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