An overview on BSE and CJD.

1. SHUMAILA TASKEEN

2.  Proteinaceous Infection particles
 Abnormal proteins
 Neurotropic
 Resistant to heating
 Radiation resistant
 Not destroyed by enzymes that destroy
DNA or RNA
 Resistant to protein denaturing agents
What is Prion???

3. (Aguzzi and Heikenwalder, 2006

6. Prion an Abnormal /Normal
protein

7. Lacks nucleic acid, which was deemed essential to copy and
propagate biological information (Liberski 2012)
In 1980s, Stanley Prusiner & co.  Prion diseases are caused by
A dominant, self-templating amyloidogenic form
of a normal cellular protein  PrP
- Term prion- proteinacious infectious particle (Prusiner, 1991)
- Zoonotic potential
- Protracted incubation period (Aguzzi & Weissmann 1998, Prusiner 1991)
The Fascinating Agent

8. • The highest level of expression of PrP protein CNS pathological
deposits most evident.
• Usually associated topographically with neuronal vacuolation 
often described as spongiform encephalopathies (Bruce et al., 1989)
• Since spongiform vacuolation is not always present  these diseases are
described as transmissible degenerative encephalopathies
(Taylor, 1991)
Pathogenesis
Cerebral cortex (CJD)

9.  PrPc binds with Cu ( copper)
 Anti –oxidant property
 Resistant to oxidative stess ( mediator of copper superoxide
dismutase)
 Prevents neuronal dysfunction
Abnormality of prion proteins can induce apoptosis of neurons.
(Brown et al.,2002)
Functions of PrPc

10.  PrPc
 Monomeric
 Soluble
 Protease sensitive
 Predominantly
alpha helix
 PrPsc
 Multimeric
 Insoluble
 Protease
resistant
 Beta pleated
Conformational differences

12. BSE/Mad Cow Disease
•Etiology – prion protein
•Fatal neurodegenerative disease
(encephalopathy) in cattle.
•Causes spongy degeneration of
brain and spinal cord.
•Long Incubation period 2.5-5
years.

13.  1985 - 1st case discovered in UK
 1986 - Officially confirmed
 BSE epizootic - United Kingdom peaked in January 1993
(1,000 new cases /week)
Since then, the annual numbers dropped sharply:
 2 cases in 2015
 11 cases in 2010
 225 cases in 2005
 1,443 cases in 2000
 14,562 cases in 1995
UK alone, At end of 2015: >1,84,500 cases of confirmed
BSE (>35,000 herds) (CDC, 2018)
History of BSE

14. Hypothesis for Origin of Prion Protein in
Cattle
I. It may have jumped species from the disease Scrapie in sheep
OR
II. It evolved from a spontaneous form of MAD COW
DISEASE that has been seen occasionally in cattle for many
centuries.

15. • Huge setback to the affected economy in terms of food safety & food
security (UK DEFRA, 2004)
“Accidental experiment on the dietary transmissibility of prion
between sheep & cows” (Harrison & Roberts, 1992)
• 165 human cases of vCJD (Bruce et al., 1997)
• U.K lost approx. $ 6 bn (Davis and Lederberg, 2001)
vCJD Only BSE
BSE: “an accidental experiment”

16. 1) Classical BSE
Contaminated animal
feed containing meat or
bone meal
2) Atypical BSE
Not associated with
contaminated feed
Both forms are
contagious
Transmitted Spontaneous change in
Prion proteins in older adult
cattle
Types

17. (CDC,2018)

19. Clinical signs
 Animal seeks solitude
 Progressively deteriorating
behavioural and neurological signs.
 First notable sign increase in
aggression, hyperaesthetic to noise
& touch and later gets ataxic.
 Systemic signs- drop in milk
production, anorexia and lethargy.

20.  High incubation period difficulty in diagnosis.
 Presently virtually no known way to detect PrPsc reliably except
by examining post mortem brain tissue using neuropathological
and immunohistochemistry.
 Histopathological examination of medulla oblongata and other
tissues.
 Real time Quaking Induced- fluorescent technique
 ELISA, Immunohistochemistry, Western Blotting

22. Prevention & Control
Ban - feeding meat and bone meal to cattle decreased
incidence in endemic countries
In U.K & U.S slaughter houses- brain, spinal cord, trigeminal
ganglia, intestine, eye, tonsils from cattle are classified as specified
risk material
STOP

23. CREUTZFELDT-JAKOB DISEASE

24. Source: Journal of Archives in Military
Medicine, 2017
World Distribution Human Prion Disease

25. History
 Early 1920s – 1st rapidly progressive neurodegenerative
illnesses- 22-year-old woman - German
neurologists Creutzfeldt and Jakob
1930 - Early description of familial CJD - German
psychiatrist & neurologist Friedrich Meggendorfer
 1968 to 1997 - Bengaluru - 69 cases are reported
(Shankar et
al., 1997)
 Mumbai - seven cases (Mehndiratta et al.,
2001)

27.  Estimated incidence - 1/million/yr
 Sporadic variety - most common
 Familial - Suspected on family history - confirmed by genetic
testing
 USA - 492 deaths - 2016 (CDC, 2017)
 Biggest cluster related to contaminated Dural grafts - Japan
 Human growth hormone therapy – France (Brown, 2006)
Epidemiology

29. Classic CJD vs vCJD
29
Characteristic Classic CJD Variant CJD
Median age of death 68 years 28 years
Median duration of
illness
4-5 months 13-14 months
Clinical signs and
symptoms
Dementia; early
neurological signs
Prominent
psychiatric/behavioral
symptoms; painful dysesthesias;
delayed neurological signs
Presence of “Florid
plaques” on
neuropathology
Rare or absent Present in large numbers
Presence of agent in
lymphoid tissue
Not readily
detected
Readily detected
(CDC,
2015)

30. CJD Symptoms

31. Diagnosis
Source; Nature Reviews

32. Histopathological lesions

33. Probable Sporadic CJD

34. Mortality attributed to CJD in US
Source: CDC, 2018

35. Diagnosis

36. • Brain biopsy – the GOLD STANDARD
• MRI
• EEG-Suggestive but not definitive evidence for
CJD.
• Spinal fluid aspiration-14-3-3 protein; specific but
low sensitivity.
TREATMENT
Antipsychotic drugs and supportive therapy is somewhat
effective.

37.  Prions are resistant to most of common sterilization procedures
 Autoclaving at 134ᵒc for 18min can deactivate
 Treatment with 1N NaOH for 1 hour
 Treatment with 0.5% sodium hypochlorite for 2 hours
 If the Prions bound to the stainless steel should be treated with an
acidic detergent solution prior to autoclaving; rendering them
susceptible to inactivation
Decontamination