Prion diseases are fatal neurodegenerative diseases caused by misfolded prion proteins. Some key points: - Prion diseases affect humans and animals like BSE in cattle and scrapie in sheep. Human forms include CJD and vCJD. - Prions resist heat and disinfectants and propagate through conversion of normal prion proteins into infectious forms. - BSE emerged in cattle in the 1980s due to feeding meat and bone meal and had severe economic impacts. It can cause vCJD in humans. - Diagnosis relies on brain examination, but prion detection tests continue to improve. Control focuses on banning risky animal feeds and removing high-risk tissues from the food chain.

1. PRION DISEASE: AN OVERVIEW
Dr. Gazanfar Abass
M.V.Sc. Scholar(VPH)
IVRI

2. Overview
Introduction OF PRIONS
HISTORY OF PRION DISEASE
PATHOGENESIS OF PRION DISEASE
HUMAN PRION DISEASE
ANIMAL PRION DISEASE
DIAGNOSIS
Conclusions

3. PRION
-Stanley prusiner discovered prion in 1982.
-Proteinaceous infective particles.
-Glycosylated specific protien of 30-KD.
-Doesnot produce any inflammatory or immune
reaction in the host.
-Resistance to ultraviolet ,standard disinfectant and
protease k.

4. THE HISTORY OF PRION
1730-Scrapie in English sheep
1950-Kuru appear Fore people
of New Guinea
1960-Demonstrating the
transmissible nature of kuru and
CJD.
1982-Dr. Stanley Prusiner coins the
term "prion" (Proteinaceous infectious
particle).
1997-Scientists identify the
PrP gene
(1986- 2000)-180,000
cattle become infected
by BSE

5. Functions of normal Prion
protein
PrPC + Cu (Copper)
Antioxidant
Resistance to oxidative stress
Prevent neuronal dysfunction
(Brown et al., 2002)

6. MECHANISM OF PRION
DISEASE
α-helix
converted to β-
sheet structure
Prion acts as a
template.
Triggers a
chain reaction
Amyloid fibers
plaques

7. Transformation
PrPC PrPSc

8. DIFFERENCE BETWEEN
PrPC and PrPSc
PrPC PrPSc
Solubility Soluble Non soluble
Structure Alpha-helix Beta-helix
Multimerisation Monomeric Multimeric
Infectivity Non infectious Infectious
Susceptibility to
Proteinase K
Susceptible Resistant

9. Pathogenisis of prion disease
(Adriano Aguzzi et al.,2012)

10. PRION DISEASE(TSE)
Transmissible, progressive and invariably fatal
neurodegenerative conditions associated with misfolding and
aggregation of a host-encoded cellular prion protein.
(Imran et al., 2011)
-Also known as transmissable spongy encephalopathy.
-They have occurred in a wide range of mammalian species including
human.
-Characterized by “Spongiform change” caused by
intracellular vacuoles in neurons and glia.

11. Human prion disease
Acquired
Hereditary
Sporadically
1-CJD
2-FATAL INSOMIA
3- variably
protease-sensitive
prionopathy
1-Familial CJD
2- Fatal familial
insomnia
3- Gerstmann-
Sträussler-Scheinker
syndrome
1-Kuru
2-Iatrogenic CJD
3-Variant form of
CJD .
(Bucelli RC et al.,2013)

12. Disease Host Etiology
Year of
Description
Scrapie Sheep, Goats
Infection with Prions of
unknown origin
Mid 18th century
TME Mink
Infection with Prions of
either sheep or cattle
origin
1947
CWD Cervids
Infection with Prions of
unknown origin
1967
BSE Cattle
Infection with Prions of
unknown origin
1986
FSE Cats
Infection with Prions of
BSE origin
1990
Animal prion diseases
(Jeongmin lee et al.,2013)

13. Scrapie
In 1732, scrapie—disease was first reported in the UK, affecting the wool industry.
The name scrapie is derived from one of the clinical signs of
the condition- itching sensation in the animals.
CLINICAL SIGN
-Excessive lip smacking.
-Altered gaits.
-Convulsive collapse .

14. In 1900s, farmers in the UK started to feed cows with internal
organs or bones of sheep to benefit economically from the increase
in milk and meat production.
By the 1930s, other European countries and the United States
(USA) had adopted this practice. Based on the findings of
epidemiological studies on the origin of BSE, this later became the
main cause of prion disease transmission from sheep to cows across
the species barrier.
( Wilesmith JW et
al.,1991)

15. BSE(bovine spongyform encephalopathy)
-Late 1985: Fatal neurodegenerative disease in
cattle.
-Long incubation period (2.5 to 8years).
-Insidious onset
 Irritabilty, aggression
 Motor system impairment
 Difficulty in rising
 Decreased milk production
 Wasting
 Death (Hope j et al.,1988)

16. Cause of BSE
Ruminant tissue in food
chain
Scrapie
Meat and bone meal
(MBM)
Sporadic BSE in cattle

17. BSE Epidemic
 ~180,000 cumulative cases in UK.
 Peaked at 37,000 cases per annum in 1992.
 Progressive decline with introduction of feed
bans.

18. Transmissible Spongiform Encephalopathy as a Zoonotic Disease, Brown, P., et. al. ILSI, March
2003
(mammals)

20. three phases of BSE in
cattle
First phase:
- Low infectivity rate.
-NO threat to human.
Second phase
-High infectivity rate
-Risk to public health
-Symptoms not evident
to public health
The third phase:
Clinical symptoms
Then death follows shortly.

21. Cattle affected by BSE
experience progressive
degeneration of the
nervous system

22. Creutzfeldt-Jakob disease (CJD)
Identified by Creutzfeldt and Jakob (1920)
A progressive fatal neurodegenerative disease of
unknown cause.
Characterized by seizures, massive incoordination,
dementia.
Sporadic Cruetzfeldt-Jacob disease accounts for
85% of all CJD cases with annual worldwide
incidence of 1-2 cases/million population.
(Mead S et al.,2003)

23.  Variant Creutzfeldtt-Jakob Disease (vCJD), is caused by the
consumption of BSE infected meat products.
 First 10 cases of variant CJD were observed in 1996,ten
years after the outbreak of BSE in the UK.
 Variant CJD seems to affect mostly young patients below
30 year.
Variant Creutzfeldtt-Jakob Disease (vCJD)

24. COUNTRY CDC REPORT (OCT. 2009) WHO REPORT(FEB.2012)
UNITED KINGDOM 170 175
FRANCE 25 25
ITALY 2 2
SPAIN 5 5
IRELAND 4 4
UNITED STATES 3 3
NETHERLAND 3 3
PORTUGAL 2 2
CANADA 1 2
JAPAN 1 1
SAUDI ARABIA 1 1
TAIWAN - 1
TOTAL-217 TOTAL-224
Epidemiology of VCJD

25. KURU
Kuru is the first human prion disease that was shown to be
transmissible to chimpanzees by intracerebral introduction of brain
homogenates from kuru patients.
(Gajdusek DC et al.,1966)
-Fore linguistic group of Papua New Guinea. .
-Transmission- ritualistic cannibalism.
-Women and young children were more exposed to the risk material
than adult man.
- Kuru epidemic killed 1-2% of the population at its peak.
-With a ban on ritualistic cannibalism in the mid-1950s imposed by
Australian authorities, the incidence of the disease started to
decline steadily.

26. Deaths from kuru 1957–1982. Courtesy of late D. Carleton Gajdusek.

27. Kuru has 3 clinical stages
-Ambulant
-Sedentary
-Terminal
clinical signs.
-Headache and pain usually in the joints of legs.
-Cerebellar ataxia, tremors and and athetoid
movements are distinctive.
-Shivering amplifiable by cold was the symptom
on the basis of which the disease was named
"kuru.

28. Different prions affect different regions of the
brain
Cerebral cortex: the symptoms include
loss of memory and mental acuity, also
visual imparement (CJD).
Thalamus: Fatal Familial Insomnia
(FFI).
Cerebellum: lose the control of body
movements and difficulties to walk
(kuru, GSS).
Brain stem: In the mad cow disease
(BSE), the brain stem is affected.

29. Diagnostic Methods
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, simple immunological tests to detect BSE cannot distinguish
PrPSc from PrPC.

30. Method
Specimen Detection of
Rapid test using ELISA Fresh brain tissue PrPSc antigen
Histopathological test Formalin fixed brain
tissue
Spongiform in brain
Immunohistochemistry FFB-tissue PrPSc antigen
Western blot Fresh brain tissue PrPSc antigen
Electron microscopy Fresh brain tissue Scrapie-associated fibril
Bioassay Fresh tissue PrPSc and infectivity
Prion detection methods for the diagnosis of BSE
(Gavier-Widen D et al.,2005)

31. 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 vertebral column
of apparently recovered cattle, sheep, and goats for
human food.
 BSE testing of all cattle more than 30 months of age.

32. CONCLUSION
BSE and vCJD are typical emerging epidemics.
SRM is the most important aspect in controlling.
Conditions or guidelines for trade” that can prevent the
disease from spreading from one country to another (SRM
standards set by the OIE ).
Risk reduction, strict precautionary principles should be
applied.
Ban on MBM and SBO.