Transcript Prion Diseases

Prion Diseases = Transmissible Spongiform
Encephalopathies (TSE)
Prion – Protinacious and infectious
• a mis-folded protein
• autocatalytic
• self-propagating
•
•
•
•
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) ?
• 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
• PrPC
– found on cell membranes
– binds copper
– a copper-dependent anti-oxidant?
– may have function in maintenance of longterm memory
nerve and immune cell
• PrPc
– a-helix-rich
– susceptible to
proteases
• PrPSc
– b-pleated sheet-rich
– not susceptible to
proteases
• aa sequence is
identical
plaques of aggregated PrPSc and
vacuolization in brain
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
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
Thalamus of white tail deer with CWD
Amyloid plaques in paraffin-embedded tissue
Congo red-stained amyloid plaques
tonsil
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 (2002-2003)
– 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
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
Scrapie
• Changes in behaviour (from
normal):
– excitable & increased
nervousness
– drooping ears
– lagging behind
– aggression
– depression or vacant stare
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
http://www.youtube.com/watch?v=S4bhexPs1FA
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
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 scrapiesuspect 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
CWD
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
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
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 ?
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
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.)
USDA APHIS WS
• National Wildlife
Research Center
(NWRC)
• Congressional
appropriations for
research and
management of
CWD (and many
other conflict
issues)
Dr. Kurt VerCauteren
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.
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.
• 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
• Validation of a Live Test for CWD
– 2006, a practical live test (rectal biopsy) for
CWD in elk developed
– Being tested in pen studies
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
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
CWD in WI
CWD in WI
CWD in WI
CWD in WI
CWD in WI
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% +)
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 = nonvoting members of the task force
CWD in Michian
• April 15, 2004
– Granholm Signs Executive Order Transferring
Regulation of Privately Owned Deer, Elk
Facilities to DNR (from MDA)
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.
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 farmraised deer in August.
Approximately $1 million spent on testing
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