1. Prion Diseases = Transmissible Spongiform Encephalopathies (TSE)
Prion – Protinacious and infectious
a mis-folded protein
autocatalytic
self-propagating

2. genetic, sporadic, transmitted all prion diseases affect neural tissue
all are incurable and fatal
all mammals are susceptible
Creutzfeldt-Jakob (CJD)
Scrapie
Transmissible mink encephalopathy (TME)
Kuru
Bovine spongiform encephalopathy (BSE)
new variant (nv) CJD
Chronic wasting disease (CWD) ?

3. PrPC – endogenous conformer found in a variety of tissue
all associated with an abnormal protein conformer in the brain and subsequent neurodegeneration.
PrPC – endogenous conformer found in a variety of tissue
PrPSc- aka PrPRes - the misfolded conformer  neurodegenerative disease.
PrP – protease resistant protein
C – cellular; Sc – scrapie; Res – proteinase resistant

4. PrPC found on cell membranes binds copper
a copper-dependent anti-oxidant?
may have function in maintenance of long-term memory
nerve and immune cell

5. aa sequence is identical
PrPc
– a-helix-rich
susceptible to proteases
PrPSc
– b-pleated sheet-rich
not susceptible to proteases
aa sequence is identical

8. plaques of aggregated PrPSc and vacuolization in brain

9. TSE Transmission – oral – Ex. sheep  cow Animals slaughtered
Inedible materials go to rendering
Low temperature fat removal
Solvent extraction
Fat Steam strip
solvent
Dried = Meat and Bone Meal (MBM)
Used for feed

10. Chronic Wasting Disease
Pathogenesis
Likely route in infected animal
Oral  GI  tonsil & GALT  enteric nerves  obex of medulla oblongata  widespread distribution lymphoid tissue and CNS

11. Thalamus of white tail deer with CWD
Amyloid plaques in paraffin-embedded tissue Congo red-stained amyloid plaques
tonsil

12. Scrapie Great Britain and western Europe more than 250 years ago
1947 – scrapie found in domestic sheep in US (Michigan)
Primarily Suffolk breed
USDA APHIS survey ( )
1 positive out of 500 cull sheep positive
Probable transmission ewe to offspring and to other lambs through contact with the placenta and placental fluids
Signs usually appear 2 to 5 years after infection
Sheep may live 1 to 6 months or longer after the onset of clinical signs, but death is inevitable
Only Australia and New Zealand recognized scrapie-free

13. Scrapie
Irritation:
repeated rubbing of flanks and hindquarters against objects
repeated scratching of the flanks
nibbling or grinding teeth when rubbing
continued scratching of the shoulder or ear with a hind foot
unusual nibbling of the feet, legs or other parts of the body
excessive wool loss or skin damage

14. Scrapie Changes in behaviour (from normal):
excitable & increased nervousness
drooping ears
lagging behind
aggression
depression or vacant stare

15. Scrapie Changes in posture and movement: trembling
unusual high stepping trot, hopping like a rabbit or swaying back end
loss of coordination
stumbling
standing awkwardly
weak hind legs
unable to stand
Later signs:
weight loss
death

16. Management of Scrapie
USDA coordinates National Scrapie Eradication Program (NSEP)
participation by state governments and industry, specifically individual producers
Producers identify and keep detailed records on goats/sheep
Annual inspections by certified vet
Report suspect animals
Use genetic selection

17. Management of Scrapie Scrapie Flock Certification Program
Producer enrolls his/her flock.
Marketing advantage
Identify all animals over1 year of age
Maintain records
Flock/herd inspected annually
Report scrapie-suspect animals to proper animal health authorities
Submit tissue samples of any scrapie-suspect animals and from animals suspected of having other neurological or chronic, debilitating diseases
Report acquisitions of animals from flocks with a lower status or from flocks not participating in the program
Certified Scrapie-free after 5 years of closed flock

19. CWD

20. CWD Captive and wild cervids
white-tailed deer
mule deer
elk
moose
First observed, 1967, Colorado Division of Wildlife’s Research Facility in Fort Collins, CO (initially thought to be malnutrition)
1977 CWD determined to be TSE (mule deer)
1981, 1st wild animal (elk) from Rocky Mt. Nat’l Park, diagnosed
Models suggests may have been present in free-ranging populations of mule deer for more than 40 years

21. CWD Susceptibility of other cervids to CWD not known
Cattle and other domestic livestock appear to be resistant to natural infection (research continues)
Privately owned cervid facilities (POC) may allow spread

22. Origin of CWD Possible link to scrapie (derived from)?
Deer contact with scrapie agent either on shared pastures or in captivity somewhere along the front range of the Rocky Mountains (location of high levels of sheep grazing occurred in the early 1900s.) – sheep pasture at NWRC
In vitro models suggest less species barrier to interspecies TSE transmission between deer, elk, and sheep than between these cervids and either cattle or humans
Or CWD is independent origin specific to deer ?

23. Wildlife Fences
CWD transmission control by limiting contact between infected and non-infected animals
> 3 m woven wire
$10 to $20 per m
Cost:benefit ratio

24. Transmission Ecology - CWD
Elk Wallows as potential sites of transmission?
1-2 times per season
Low probability
Mineral licks might be more important (multi-spp.)

25. USDA APHIS WS National Wildlife Research Center (NWRC)
Congressional appropriations for research and management of CWD (and many other conflict issues)
Dr. Kurt VerCauteren

26. NWRC - CWD
Evaluation and Management of Chronic Wasting Disease Transmission PROJECT GOAL: Study ecology of CWD, assess the potential for CWD transmission at the interface between wild and domestic cervids, and develop methods that reduce or eliminate CWD transmission and spread.
Objective 1: Determine extent of interactions between domestic and wild cervids and develop cost-effective means of reducing interactions.
Objective 2: Explore a CWD vaccine.
Objective 3: Develop methods to detect CWD prions and decontaminate infected sites.
Objective 4: Assess the role of predators and scavengers in CWD epidemiology.
Objective 5: Develop improved cervid census and removal techniques.
Objective 6: Evaluate white-tailed deer and mule deer ecology along riparian areas relative to the transmission and spread of CWD.

27. NWRC - CWD
CWD Vaccine
Experimental vaccine trial in the widely used RML mouse scrapie model system yielded two promising candidates for further study. 
Currently, the two CWD vaccine candidates have been resynthesized, formulated, and used to vaccinate mule deer, making this the first known application of a CWD vaccine in the target species
Currently, prime and booster injections of the vaccine have been administered to mule deer housed at CSU’s Animal Population Health Institute paddocks, a CWD-free environment. 
Preliminary results show that the mule deer are producing good antibody titers to prion protein.
Deer passed more than 120 days since their disease challenge
Conclusive results on how well the CWD vaccine works in mule deer will not be known for another year to 18 months. 
Additional vaccine work on an oral CWD vaccine.

28. Testing of Hydrolysis and Rendering Effects on Prion Infectivity
How effective hydrolysis and rendering procedures are at destroying infectious prion material to determine if these methods are viable carcass waste-disposal options
Hydrolysis process using lye under increased pressure and temperature to degrade biological material 
Rendering process of cooking material in oil  
Using mouse model (injecting material into brain)
Six months after inoculation, some of the mice are showing signs of developing the disease. 
Preliminary results showed 0 of the 23 mice injected with hydrolyzed material died
16 out of 23 mice injected with rendered material died within about 244 days of injection

29. Validation of a Live Test for CWD
2006, a practical live test (rectal biopsy) for CWD in elk developed
Being tested in pen studies

30. CWD in WI Discovered wild deer in 2001/2002 >700,000 deer hunters
Avg 460,000 deer harvested
Generates >$500 million retail
~$1 billion impact to state’s economy

31. CWD in WI Discovered wild deer in 2001/2002
Spent $40+ million testing and drastically reducing deer populations since
Initially planned to kill all estimated 30,000 deer in focal area
Saskatchewan spent $30+ million

32. CWD in WI

33. CWD in WI

34. CWD in WI

35. CWD in WI

36. CWD in WI

37. CWD in WI Surveillance program to detect 1% prevalence
Difference in age/gender
0.16% fawns +
Increase prevalence with age (faster in males)
2-3% yearlings +
2+ yrs (M = 10%, F = 4-5% +)

38. CWD in Michigan February 28th, 2003
Governor Granholm signed an executive order creating a task force to address the threat of CWD in Michigan's deer and elk populations
Includes 5 voting members appointed by the Governor
Directors of the MDA, Community Health, DEQ, DNR, State Police, and Transportation = non-voting members of the task force

39. CWD in Michian
April 15, 2004
Granholm Signs Executive Order Transferring Regulation of Privately Owned Deer, Elk Facilities to DNR (from MDA)

40. CWD in Michigan
Michigan : Michigan's First Case of Chronic Wasting Disease Detected at Kent County Deer Breeding Facility Date: August 25, 2008
Source: Michigan Department of Natural Resources LANSING - The Michigan departments of Agriculture (MDA) and Natural Resources (DNR) today confirmed the state's first case of Chronic Wasting Disease (CWD) in a three-year old white-tailed deer from a privately owned cervid (POC) facility in Kent County. The state has quarantined all POC facilities, prohibiting the movement of all - dead or alive - privately-owned deer, elk or moose. Officials do not yet know how the deer may have contracted the disease. To date, there is no evidence that CWD presents a risk to humans.

41. CWD in Michigan
Michigan : Tests of More Than 1,000 Deer Find No More Cases of Chronic Wasting Disease Date: October 07, 2008
Source: The Grand Rapids Press Statewide, 1,095 deer have been tested, with 964 testing clean and 131 awaiting results. More than 300 wild Kent County deer have been tested and found to be clear of chronic wasting disease after the highly contagious disorder was found in one northern Kent County farm-raised deer in August.
Approximately $1 million spent on testing

42. CWD and Hunting No evidence of infection of humans Precautions:
Latex or rubber gloves when dressing/handling
Bone out meat, avoid cutting bone, spinal cord, into brain
General hygiene
Avoid consumption brain, spinal cord, eyes, spleen, tonsils, lymph nodes
Avoid consuming positive animal