1. Lecture Week 11 Medical Microbiology SBM 2044
Prion
Lecture Week 11
Medical Microbiology SBM 2044

2. Prion Diseases
Prion diseases are associated with the accumulation in the CNS of an abnormal form of a host protein called the prion protein, PrP
Infectious agent = an abnormally folded, degradation-resistant form of the PrP protein
The disease is rare, fatal and rapidly progressive neurodegenerative diseases that occur in humans and other animal species
They share common recognisable neuropathologic features:
presence of small vacuoles within the neuropil, produces a spongiform appearance,
neuronal loss,
glial cell proliferation.

3. Human Prion Diseases Kuru Creutzfeldt-Jakob disease (CJD)
Variant Creutzfeldt-Jakob disease (variant CJD)
Gerstmann-Straussler-Scheinker syndrome (GSS)
Fatal familial insomnia (FFI)

4. Prions
Proteinaceous infectious particle = small infectious agent that consists of protein but lacks nucleic acid
PrP is a host protein, and the sole constituents of prions
The gene encoding PrP is found in the genomes of all humans and animals
expressed in most human tissues, mainly in the CNS
Function of PrP ? ?
copper-binding protein, in cellular response to oxidative stress
long-term memory

5. PrPSc PrPSc is a pathological protease-resistant form of PrP
First isolated from the brains of animals with scrapie
Prion diseases: PrP  PrPSc
a conformational change in PrP from a predominantly -helical form to -sheet

6. CJD 1 case per 1 million population worldwide each year
Sporadic disease
Age at onset usually years old
Mean survival of 5 months
Britain – patients in their 20s… variant CJD?
Clinical manifestations:
Rapidly progressive dementia and myoclonus,
memory loss, judgment difficulties
cognitive disturbances
death within 1 year

7. Diagnosing CJD
Magnetic resonance imaging of a patient with Creutzfeldt-Jacob disease. A. Increased signal intensity in the putamen and head of the caudate (arrows). B. Bilateral parieto-occipital cortical hyperintensity (arrows).

8. Diagnosing CJD
Pathologic specimen from a patient with CJD demonstrating spongiform changes and neuronal loss.

9. Treatment and Prevention
No specific treatment
Prions are resistant to routine sterilization and decontaminating procedures
PrPSc can be activated by
prolonged autoclaving (at 121°C and 15 psi for 4 ½ hours
immersion in 1 N NaOH (for 30 mins, repeat 3x)
Prohibition on ruminant-derived products for all animal feed

10. Variant CJD
Bovine-to-human transmission of bovine spongiform encephalopathy (BSE), known as “mad cow disease”.
PrP proteins show different glycosylation pattern and electrophoretic mobility, than other prion diseases
Appear in the late 1990s, following epizootic of BSE in Britain
may be caused by changes in the rendering process of bovine byproducts, use for cattle feed (cannibalism)
Average age at onset 30 years old, a mean survival of 14 months

11. Epidemiology of CJD
Annual frequency of bovine spongiform encephalopathy (BSE) and variant CJD (vCJD) in Great Britain, 1988–2003.

12. Damaging Effects of vCJD
Clinical manifestations depend of the locations of PrPSc accumulation in the NS
All forms of CJD are uniformly fatal
vCJD patients have:
prominent sensory disturbances (on the face, limbs and torso)
psychiatric symptoms – depression
apathy, anxiety, intermittent delusions and psychosis
abnormalities of gaze

13. Diagnosing vCJD Laboratory and imaging studies are unhelpful
CSF shows no cells, mild elevation of CSF protein
MRI can be normal. But many patients present with signal hyperintensity in the pulvinar
Presence of plaques which stain for PrPSc throughout cerebrum and cerebellum, basal ganglia and thalamus
PrPSc has also been identified in tonsil biopsy tissue (nonneural tissue! ! !)

14. Diagnosing vCJD
FIGURE Magnetic resonance imaging of a patient with variant CJD. A. Increased signal intensity in the pulvinar (“pulvinar sign”). B. Increased signal intensity in the pulvinar and dorsomedial thalamus (“hockey stick sign”).

15. Other Human Prion diseases
Gerstmann-Straussler-Scheinker syndrome (GSS)
autosomal dominant pattern of inheritance
progressive cerebellar degeneration accompanied by dementia
Fatal familial insomnia (FFI)
rapidly fatal midlife disease
a mean survival of 13 months
progressive insomnia, often with a dreamlike confusional state during waking hours
inattention, memory loss, confusion, hallucinations
myoclonus, ataxia and spasticity in later stage of disease
dysautonomia (hyperhidrosis, hyperthermia, tachycardia and hypertension) and endocrine disturbances ( adrenocorticotropic hormone secretion, cortisol secretion)

16. Review of the Course Content
Microbes – Man interactions Week 1-3
Medical Bacteriology Week 4-6
Medical Virology Week 7-10
Medical Mycology Week 11-12
Emerging infectious diseases & biological agents of warfare Week 13
Introduction to the medical diagnostics in microbiology Week 14

17. Quiz on all of the following topics:
Vaccines and Immunisations
Medical Diagnostics in Microbiology
Emerging and Reemerging Infectious Diseases
Biological Weapons
Prions
Day/Date: Thursday 13th March 2008,
Time: :30-3:30pm
Happy studying!!