Transmissible Spongiform Encephalopathies Flashcards
General on Transmissible Spongiform Encephalopathies
Infectious agents of uncertain structure
Spongiform degenerative lesions- no inflammation associated with lesions.
Slow, progresive onset of neurological disease (2-5 years before they show signs)- once they show signs they die relatively quickly
Uniformly fatal
Very atypical- most similar to viruses but are distinct
General on Transmissible Spongiform Encephalopathies
Infectious agents of uncertain structure
Spongiform degenerative lesions- no inflammation associated with lesions.
Slow, progresive onset of neurological disease (2-5 years before they show signs)- once they show signs they die relatively quickly
Uniformly fatal
Very atypical- most similar to viruses but are distinct
What diseases fall under Transmissible Spongiform Encephalopathies?
Scrapie, Bovine spongiform encephalopathy, Chronic Wasting disease, Transmissible mink encephalopathy, Kuru, Creutzfeldt-Jacob Disease, Familial Insomnia, and Gerstmann-Straussler Disease
What’s the problem with the lesions on the brain?
They happen normally with old age, so sometimes it is difficult to know if it occurred due to the disease or normal aging processes
Why is the agent unusual?
- Filterable (take infectious material- pass through a filter- removes infectivity of TSEs),
- about the same size as a virus, no virion-like structures * highly resistant to inactivation (tx with UV light, formalin, exposure to gamma radiation- much harder to kill off infectivity than any other virus)
- no nucleic acid identified, too small to encode protein * lipid associated
- Scrapie associated fibrils
- infectivity destroyed by protein disruption
Why is the agent unusual?
- Filterable (take infectious material- pass through a filter- removes infectivity of TSEs),
- about the same size as a virus, no virion-like structures * highly resistant to inactivation (tx with UV light, formalin, exposure to gamma radiation- much harder to kill off infectivity than any other virus)
- no nucleic acid identified, too small to encode protein
- lipid associated (concentrated in the fatty tissues of the brain, most viruses tend to be associated with aqueous parts)
- Scrapie associated fibrils (SAFs- associated but too big to be filtered)
- infectivity destroyed by protein disruption (might be infectious proteins)
Why is the agent unusual?
- Filterable (take infectious material- pass through a filter- removes infectivity of TSEs),
- about the same size as a virus, no virion-like structures * highly resistant to inactivation (tx with UV light, formalin, exposure to gamma radiation- much harder to kill off infectivity than any other virus)
- no nucleic acid identified, too small to encode protein
- lipid associated (concentrated in the fatty tissues of the brain, most viruses tend to be associated with aqueous parts)
- Scrapie associated fibrils (SAFs- associated but too big to be filtered)
- infectivity destroyed by protein disruption (might be infectious proteins)
Louping Ill Vaccine Contamination
One group of sheep they used to make vaccination were infected and they distributed Scrapie
Why are TSEs (the disease) unusual?
- Very long incubation period (2-5 years)
- No evidence of inflammation
- No apparent immune response
- Adaptation to the host species
- Effect of dose on incubation period
- Influenced by a single gene (PRP- prion protein gene)
- Strain characteristics
Why are TSEs (the disease) unusual?
- Very long incubation period (2-5 years)
- No evidence of inflammation
- No apparent immune response
- Adaptation to the host species
- Effect of dose on incubation period
- Influenced by a single gene (PRP- prion protein gene)
- Strain characteristics
How did they type different strains of Scrapie?
Imaging of the brain and mapping out the lesions and finding the pattern
How did they type different strains of Scrapie?
Imaging of the brain and mapping out the lesions and finding the pattern
What is the agent of TSE?
Prion hypothesis- infectious protein, post-translationally modified variant of host’s own PrP protein. Protein gets misfolded or refolded so it becomes much more resistant to destruction from proteases. So the cell has a hard time removing accumulation and eventually it messes up the function of the cell. PROPAGATES the CHANGE IN FOLDING- why it is INFECTIOUS. (there are some inheritable encephalopathies in humans which have a mutation in PrP gene)
What is the misfolded protein called in Scrapie?
PrPsc
What is the misfolded protein called in Scrapie?
PrPsc
What are the clinical signs and symptoms of Scrapie
Pruritis, tremors, ataxia, paralysis, wasting, subacute- most die in 4-6 weeks, generally 2-5 yo
Pathogenesis of Scrapie
Vacuolation and degeneration of neurones of CNS, hypertrophy of astrocytes; tonsils, spleen, lymph nodes, probably in dendritic cells, spinal cord, ascends the spinal cord to the brain
Pathogenesis of Scrapie
Vacuolation and degeneration of neurones of CNS, hypertrophy of astrocytes; tonsils, spleen, lymph nodes, probably in dendritic cells, spinal cord, ascends the spinal cord to the brain
Epi of Scrapie
Spread horizontally, vertically?, injection of infected material, new strain IDed in resistant sheep- unrecognized infected population or spontaneous disease
Epi of Scrapie
Spread horizontally, vertically?, injection of infected material, new strain IDed in resistant sheep- unrecognized infected population or spontaneous disease (called atypical Scrapie)
Diagnosis of Scrapie
Animal inoculation, histopathology, ELISAs, or Western Blots specific for protease resistant PrP
Control of Scrapie
Eradication by aggressive slaughter campaigns (i.e. NZ), quarantine regulations, failure in North America and Europe (long incubation period), breeding resistant sheep (select for resistant genetics), atypical scrapie
Bovine Spongiform Encephalopathy general (Mad Cow Disease)
Britain- 1986- 1994 peak of epidemic 30K cases in the UK
Hyperaesthetic (non-noxious stimulus causes pain), apprehensive, nervous, frenzied
Eventually ataxic, then debility, recumbency, and death
Death in weeks to months
Incubation period of several years
Typical spongiform lesions
Feline spongiform encephalopathy
Epi of BSE
In British dairy cattle, shift from batch to continuous processing of meat meal (takes less time, but the temperatures are lower)
- Temps were high enough to kill most agents, but not BSE
- Also reduced use of lipid solvents which allowed BSE to get through
- ban on feeding meat meal to cattle- so very little vertical or horizontal transmission since
Epi of BSE
In British dairy cattle, shift from batch to continuous processing of meat meal (takes less time, but the temperatures are lower)
- Temps were high enough to kill most agents, but not BSE
- Also reduced use of lipid solvents which allowed BSE to get through
- ban on feeding meat meal to cattle- so very little vertical or horizontal transmission since
Diagnosis of BSE
Histopathology- specific detection of PrPsc
Control of BSE
Ban on feeding meat meal, average age of infected cattle increased, numbers of cases declined dramatically, slaughter of all suspected cases
Transmissible Mink Encephalopathy
Rare outbreaks in farmed mink, feeding scrapie infected sheep meat to mink, experimental feeding of scrapie to mink, downer cows- BSE?
