Scrapie (/ˈskreɪpi/) is a fatal, degenerative disease affecting the nervous systems of sheep and goats.[1] It is one of several transmissible spongiform encephalopathies (TSEs), and as such it is thought to be caused by a prion.[2][3] Scrapie has been known since at least 1732 and does not appear to be transmissible to humans.[4][5] However, new studies suggest a link between scrapie and sporadic CJD.[6] The name scrapie is derived from one of the clinical signs of the condition, wherein affected animals will compulsively scrape off their fleeces against rocks, trees or fences. The disease apparently causes an itching sensation in the animals. Other clinical signs include excessive lip smacking, altered gaits and convulsive collapse.[7] Scrapie is infectious and transmissible among conspecifics, so one of the most common ways to contain it (since it is incurable) is to quarantine and kill those affected. However, scrapie tends to persist in flocks and can also arise apparently spontaneously in flocks that have not previously had cases of the disease. The mechanism of transmission between animals and other aspects of the biology of the disease are only poorly understood, and are active areas of research. Recent studies suggest prions may be spread through urine and persist in the environment for decade

1. Presented by G.Vijayalakshmi B.Sc.,M.Sc., 20PY10
Ayya Nadr Janaki Ammal College,Sivakasi.
Presented to Dr.K.Nalini

2. WHAT IS PRIONS?
 Prions are infectious agents composed of protein in misfolded form
 Intially thought to be viruses which replicated slowly within their
hosts but no nucleic acid found associated with infectious material
 Shown to be abberent forms of normal cellular proteins which can
induce changes in the shape of their normal homologus with
castrophic consquences for the host.
 Normal form of protein called PrPc,while the infectious form is
PsPSc.
 Stanley prusiner discovered prion in 1982 won nobel prize in 1997
for physiology or medicine
 Prion don’t have DNA or RNA
 They are extremely resistant to heat and chemicals
 Prions are very difficult to decompose biologically they survive in
soil for many years

3. Cont……….
Affect both humans and
animals
Doesnot produces any
inflammatory or immune
reaction in the host
Spread to human by
infected meat products
Resistance to
ultraviolet,standard
disinfectant and protease K
Common form of prion that
affect human is Creutzfeldt
Jakob disease
Nature of prions challenges
for early diagnosis
Known as transmissable
spongy encephalopathy

4. History of prions
1730-scarpie in
english sheeP
1950-kuru
appear fore
people of new
Guinea
1960-
demonstarting
the
transmissible
nature of kuru
and CJD
1982-
Dr.Stankey
Prusiner coins
the term
“prion”
(1986-2000)-
180,000 cattle
become
infected by
BSE
1997-
Scientists
identify the
PrPgene

5. Characteristics of prions
• Characterized by “Spongiform change” caused by intracellular vacuoles in
neurons and glia
• Containing about 250 amino acids
• Abnormal variants of normal proteins
• Convert normal to abnormal forms
• No antibiotics can cure disease caused by prions
• Not typical of a prokaryotic or eukaryotic organism
• All that present in this pathogen is the protein PrPsc ,the mutation of PrPc
• PrPsc is resistant to any form of digestion
• It is non immunogens and do not induce an immune response
• Prions are not easy to decompose biologically
• They are resistant to high temperature and disinfectants

6. Normal protein(alpha
helix)
Secondary structure
dominated by alpha
helices
Easily soluble
Easily digested by
proteases
Encoded by PRNP
gene(in humans)
Located on human
chromosome 20
monomeric

7. Abnormal protein(beta
helix)
PrPsc(sc for scarpie)
Same amino acid sequence and
primary structure as normal
protein
Secondary structure dominated
by beta conformatiom
When PrPsc contacts PrPc
converts it to the abnormal form
Insoluble in all but strongest
solvent
Highly resistant to digestion by
proteases
Survives in tissues post –
mortem
Extremely resistant
(heat,normal sterilization
processes,sunlight)
No detectable immune response
multimeric

8. Prion biology

9. Characteristics of infection
• Loss of motor control
• Dementia
• Paralysis
• Encephalitis
• Widespread neuronal loss

10. TSE diseases

11. Prion
multiplication(heterodime
r model)
When a prion enters a healthy
organism,it induces existing ,
properly folded normal proteins to
convert into the disease-
associated ,prion form
The normal form of the protein
is called PrPc,while the infectious
form is PrPsc
These newly formed prions can
then go on to convert more
proteins themselves;this triggers a
chain reaction that large amounts
of the prion form (amyloid fibre)
Prions cause other similar
proteins to also misfold-lose
function ,cause disease

12. Scarpie(non conventional
disease agents)
In 1732,reported in
UK,affecting the wool
industry
Geographical distribution is
worldwide(expect Australia
and new zealand) and in
developing countries
Also known as rida
The name scarpie is derived
from one of the clinical signs
of the condition-itching
sensation in the animals
Their clinical sign are
excessive lip smacking
,altered gaits,convulsive
collapse

13. Cont……….
 It has a long incubation period
 100% fatal
 Cause no immune response
 Demonstrated to be transmissible in the 1930s,despite lack of inflammation whether is is
camouglaged virus
 1930-1950 numerous experiments demonstrated that scarpie agent is extraordinarily
resilient.It survives
 30min .of boiling
 60days of freezing
 Strong formaldehyde ,carboxylic acid,chloroform
 Dessication for 2 yrs
 Intense uv exposure
 Scarpie appears to have multiple “strains”(variants)which are transmissible and can compete
with each other
 It require information whether it is encoded by DN or RNA
 Scarpie disease of sheep had many similarities to kuri in terms of symtomatology and etiology
 Could be transmitted to hamsters and mice ,kuru could not

14. Size of the scarpie agent
• Passes through fine filters
• Stays in solution despite ultracentrifugation
• 1966:electron bombardment experiments demonstrate that if the scarpie
agent contains a DNA genome,it would have to be 1000times smaller than
the smallest known virus at the time
COMPOSITION OF SCARPIE AGENT
 UV damages DNA/RNA severely ,but not protein.Scarpie is resistant to
UV
 Late 1960s:Scarpie agent is treated with nucleases (DNAor RNA digesting
enzymes)and proteases (protein digesting enzymes).
 Scarpie agent is only damaged by the proteases

15. Symptoms of scarpie
• Symptoms may take 2-5 years to appear
• Head and neck tremors
• Skin itching
• As the disease progress animals have high-sleeping or trembling
• Convlusions
• Scraping body with the wall
• Drink small quantities of water often
• Blindness
• Inability to control legs(this attacks the nervous system)
• Good appetite accompained by weight loss
• Excessive lip smacking
• Altered traits

16. Transmission &pathogenesis
• Well understood in sheep
• Can transmit to goats if we keep them in the herd of sheep
• Can transmit to already present sheeps if we keep foreign
infected breed in our flock
• Can be transmitted to the race during pregnancy or at the
time of birth from dam through placenta or
reproductivetract because Prions may be present there
• Genetically transmitted or through urine of the sheep
• Prions &virons both can transmit into the race
• The pathogenesis of scarpie involves the lymphatic system
• The agents agent can also through cuts in the skin
• Parasympathetic nervous system

17. Diagnosis
• Clinical sign &symptoms
• Laboratory test
• Scarpie is usually confirmed bt detecting PrPSc(prions)in CNS
• Post mortem examination is important for the diagnosis of scarpie
• At present a reliable diagnosis of prion disease is possible only
through autopsy
• The standard diagnosis procedures for BSE suggested by the OIE are
• ELISA
• Western blotting
• Immunohistochemical method
• However smiple immunological tests to detect BSE cannot
distinguish PrPsc from PrPc.

18. Control measures
• Public health control measures ,such as
surveillance,culling sick animals,or banning
specified risk materials
• UK program that excludes all animals more
than 30 months of age.The program appears
to be highly effective
• Banning the use of meat from the veterbral
column of apparently recovered cattle,sheep
and goats for human food.

19. kuru
• Kuru is a rare and fatal nervous system disease
• Kuru is a disease of man
• Kuru –fore language –trembling associated with fear or cold
• It is transmitted by cannibalism in fore people in new guiena
• It is identified in new guinea by Robert and Louise Glasse in 1950’s
• Glasse suggested that endocannibalism was associated with disease
• Australian government supressed cannibalism among north fore in early 1950’s
• Soth fore were convinced to discontinue the pratice in 1950
• 1%of the fore tribe was afflicted;mostly women ,some children,few adult males.
• There is no evidence for transmission to fetus, transmission via milk or intimate
social contact
 Progressive cerebral ataxia
 3phases
 1-initial phase- ambulant with minimal truncal ataxia,dysarthria and tremor

20. Cont…..
2-sedentary phase-loss of ambulation
due to ataxia
cheoreoathetosis,worsening of tremor
and mood instability
3-terminal phase- generalized
hyperreflexia,progression of dysathria
and dysphagia
Muscle strength and sensorium
normal
Down hill course within 12 months
from onset.
It was the first neurodegenerative
disease resulting from an infectious
agent,it led to the creation of a new
class of disease including Creutzfeldt-
jakob disease,Gerstmann-Straussler-
Scheinkler disease and fatal insomnia

21. symptoms
• More common neurological disorders such as Parkinson’s disease or
stroke may resemble kuru symptoms .These include:
• Difficulty walking
• Poor coordination
• Difficulty swallowing
• Slurred speech
• Moodiness and behavioral changes
• Dementia
• Muscle twitching and tremors
• Inability to grasp objects
• Random ,complusive laughing or crying
• Headache and joint pain
• Loss of bodily control

22. Causes
• Belong to transmissible spongiform encephalopathies
• Primilarilly affects cerebellum –part of your brain
responsible for coordination and balance
• Kuru is not caused by a bacteria ,virus or fungus.
• Create sponge –like holes in your brain and are fatal
• The new Guinea government has discouraged the
practice of cannibalism
• Cases still appear given the disease’s long incubation
period ,but they are rare .

23. diagnosis
• During life a probable diagnosis is based on the clinical picture
• Electrodiagnostic test
• Neurological examnation
• Brain biopsy histology with western blot analysis of proteinase K
treated brain homogenate.
• Iq PCR as one of the choice methods for PrPres detection in brain
surgical biopsy and autopsy specimens.
• CSF ---14,3-3 protein and Tau protein.
• Senstively 94% and specifity ---93%in s CJD
• Less sensitive in v CJD &CJD ,rarely elevated in GSS,not in FFI.
• False positive in acute stroke,MS,encephalitis,AD ,FTD,HAD.

24. TREATMENT
• There is no successful treatment for kuru other
than discouraging the pratice of cannibalism
• Currently there are no cures or treatments for
any of the other TSE diseases.
• Brain contaminated with prions remain infectious
even when preserved in formaldehyde for years.

25. • Prion is not a virus
a)true
b)false
• PrPsc is monomeric
a) True
b) False
• Prion is a ------------model
a)Aliphatic model
b)Endodimeric model
c)Heterodimeric model
• Kuru identified in which year?
• Scarpie identified in which year?