In humans

Sporadic CJD
- Occurs worldwide at an incidence of 1 /1000000
Familial disease
- Familial CJG
- Gerstmann-Straussler-Scheinker syndrome 1/10000000
- Fatal familial insomnia
- Atypical prion disease
Acquired disease
- Kuru
- Iatrogenic
- vCJD

In Animals

Scrapie

Disease of sheep and goats
Characterised by
- Ataxia
- Tremors
- Rubbing/scratching
- Loss of condition
- Death in 1-3 months
Endemic in UK
Incubation period of 2-5 yrs
Varied transmission
- Adult animals can transmit it to other animals
- Lamb exposed to prions in birth tissue shortly after birth.
  - Can also spread this way to other ewes
- Inoculation
- Agent can remain in environment (up to 50yrs)- don't know how
Progression to disease is under strong genetic control
- Up to 15 genetic types of PrP gene with varied susceptibility scrapie
  - Genetic breeding programme
Varied strains

Bovine Spongiformform encephalopathy

Disease of cattle
Characterised by
- Ataxia
- Nervous or Aggressive behaviour
- Loss of condition
- Death in 1-6 months
Highly infectious
Can be spread to many other animals
- Humans
- Sheep
- Goats
- Cats
Epidemic in UK from 1985
- Caused by contaminated feed
Incubation period of 5 years or more
Oral transmission (MBM) only
- No transmission form cow to cow/ cow to calf
Little evidence of host genetic effect
Occurs as 2 different strains

MBM= meat and bonemeal

Chronic wasting disease (CWD)

variant Creutzfeldt-Jakob Disease

1996 UK government announced that vCJD had been detected in 10 people over 14 months
Clinical signs
- Psychiatric
  - Depression
  - Anxiety
  - Delusions
  - Hallucinations
- Neurological
  - Ataxia
  - Chorea
  - Myoclonus
  - Dementia
Pathology: Spongiform change and PrP-containind 'florid plaques' throughout the brain. In human prion diseases, plaques of this type are unique to vCJD
Mean duration of illness 14 months
Young age of onset: mean = 28 yrs (Range 12-74)
Prevalence of infection: 1 in 3000 (spleens)
Genetic control: All non-surgical human cases so far MM not MV or VV

Kuru

Background
- Described in 1957 but may have started 1920
- Shiver, trembling or laughing disease
- Restricted to the Foré linguistic group in the highlands of New Guinea
Natural transmission
- Foré ate their dead
  - Women and children ate internal organs and brains , men ate muscle
- Cannibalism stopeed in 1957 encouraged by the governing Australian administration
- Incidence of the disease declined from the 1960s, especially in cases of young children

Characteristics of TSE diseases

Causes

Partial purification of brain tissue of scrapie infected hamsters revealed that a certain protein was essential for infectivity
Procedures that destroy nucleic acid don't alter infectivity, unlike those that denature protein
Stanley prisoner suggested that infectious agents are proteinaceous: devoid of nucleic acid but capable of replication. He called them prions (proteinaceous infectious particles)
The prion protein is a host protein, encoded by the PrP (Protease-resistant protein) gene. It occurs in at least two form PrP^c is normal, PrP^Sc is infectious and associated with disease
PrP^c and PrP^Sc have an identical amino acid sequence but the differ in conformation
Prisoner suggested that PrP^Sc converts PrP^c to itself
PrP^Sc is partially resistant to digestion. In a normal cell PrP^c is constantly made and digested; PrP^Sc is not digested PrP^Sc is not digested and sos accumulates leading to disease
Can take years/decades

NB this is a hypothesis!

c=cellular

Sc=Scrapie

Uniqueness of prion diseases

Some prion diseases originate sporadically by mutation and are then transmissible

Pathogenesis

Neuropathology

	Erstellt von Alice Butterworth vor fast 9 Jahre

Vet Med 1 (ID) Notiz am TSEs, erstellt von Alice Butterworth am 02/02/2018.