TSE and ANS cases

- give examples of TSEs - discuss role of prions in TSE development - describe pathology of TSE and current diagnostic procedures - clinical signs of diseases - transmission risk of TSE in context of public health - explain economic impact of TSEs in UK - relate clinical abnormalities in patients with dysfunction of the ANS to normal autonomic structure and function

give examples of TSEs in sheep and goats

scrapie and atypical scrapie

give examples of TSEs in mink

• mink spongiform encephalopathy

give examples of TSEs in deer and elk

• chronic wasting disease

give examples of TSEs in cattle

BSE

give example of TSE in cats

FSE (feline spongiform encephalopathy)

what is an example of a TSE disease affecting camels

camel prion disease

what are TSEs/prion diseases

• neurological disorders

• they have very long incubation periods

• neuronal loss

• invariably fatal

• caused by misfolded prion protein PrP^Sc (prion protein scabie - because scabie was the first prion disease found)

why does the histology of TSEs have the spongy appearance?

• prions cause neurone damage

• gives a spongy appearance

what is a prion

• a completely novel infectious agent

• they’re a misfolded protein that goes from primarily alpha structures to having more beta structures. It’s practically indestructible.

what is the role of prions in TSE disease development

it’s an autocatalytic protein, generates more of itself.

It has different shapes depending on the disease

Accumulates over time, especially in the brain which leads to the symptoms over time

• can be inherited which leads to faster misfolding and accumulation

what are the properties of prions

• relatively insoluble

• self catalytic conversion

• exceptionally high stability for a protein

• resistant to proteases

• resistant to heat treatment

• resistant to UV

what are the concerns with prion properties

• can’t easily decontaminate premises or in clinical setting

• can survive in environmental reservoirs for many years

how are genetics linked to TSEs?

• some animals are more genetically susceptible to PrP^Sc

• Some are exposed to the prion leading to spontaneous conversion - inherited

what is the pathology of TSEs

• prion is absorbed in the gut

• passes through Peyer’s patches (especially M cells)

• passes through gut associated lymphoid tissue

• passes through ENS

• goes to SLOs (spleen, lymph nodes, tonsils, appendix) or straight to CNS

• ends up in the brain

what is the pathology of TSEs dependant on?

• species

• shape of prion strain

What are the 2 places we test for prions in the brain and why

• just a brain stem sample post mortem

• a sample of the cerebrum and cortex as well as brain stem

why?

• classical scrapie accumulates in the brainstem (obex)

• atypical/Nor98 scrapie accumulates in the cerebrum and cerebellum

How do we test for what kind of strain of prion disease an animal has?

why do we do prion strain testing?

• we need to compare strains to existing ones to identify what kind of prion it is

• need to know if it’s zoonotic or not

how do we find out if a prion strain is zoonotic and therefore poses a threat?

• place the prion in with a mouse with a transgenic gene for the human prion.

• See if a disease develops

• if it does = zoonotic

what are clinical signs of TSE diseases?

• weight loss, subtle behavioural changes

• licking lips, grinding teeth, scratching

• pruritus (scrapie)

• posture, gait

• ataxia, tremors

• none, animal found dead

What are the 5 ways we can diagnose TSE diseases?

1. transfer brain extract to permissive experimental animal (susceptible mouse strain)

   • ethical issues

   • long incubation periods and cost

2. specific identification of PrP^Sc, disease specific protein

3. confirmatory tests e.g. histology, immunohistochemistry

4. Western blots

5. ELISAs

how do western blot tests and ELISAs work?

• rely on protease resistance of PrPSc compared to PrPC

  • sample is taken from obex and homognenised in buffer solution

  • sample is digested with protease

  • separated by size on a gel (proteins present), bound by an antibody against PrP

How are all TSE confirmatory tests conducted

• post mortem

what 2 groups do prions fall into in regards to transmission

1. very difficult to transmit b/w susceptible hosts:

   • all human TSEs including vCJD

   • BSE (& FSE) → zoonotic

   • MSE

   1. readily transmitted

      • scrapie in sheep/goats → non-zoonotic

      • CWD in cervids → unlikely to be zoonotic

how are the 2 groups of TSE transmitted?

Group 1: through medical procedure or ingestion of contaminated food/feed

Group 2: direct contact and environmental reservoirs

compare vCJD to CJD

variant:

• affects much younger age group

• different initial symptoms (psychiatric/behavioural vs dementia)

• causes death > 1 year after illness onset (vs 4-5 months)

How was the BSE epidemic controlled?

1. culling, cohort culling (animals born 2 years either side of the cow detected with BSE were culled)

2. feed ban for ruminant material

3. older cattle banned from human food chain

4. ban of specified-risk material from food chain

5. export ban

6. surveillance (veterinary profession)

7. plan to eradicate TSEs from sheep

outline the economic impact of TSEs in the UK

• BSE outbreak cost around £3.7bn

direct costs of BSE:

• loss of income for agriculture/government compensation

• culling and older cattle can’t be used

• export ban

• collapse of home market for beef

• lower market for milk, lamb

• cost of surveillance

• cost of research

• plan to eradicate all TSEs in sheep

what is the national scrapie plan (NSP)?

• suspect cases of scrapie: report to Animal health division office, farm visit by veterinary officer, compulsory slaughter and tests, movement restrictions until lab results available.

• Compulsory scrapie flocks scheme (CSFS) - any flock with suspected and positive scrapie test, will be registered automatically registered in CSFS, state veterinary service VO visit to identify all sheep and goats on holding (including embryos)

what are we trying to do to help improve genetic resistance to scrapie?

• genotyping

• sheep with required resistant genotypes (ARR/ARR = desirable, AHQ/VRZ or AHR/VRQ or VRQ/VRQ = undesirable)

• selected for breeding or culled/slaughtered for food chain as appropriate - 3 year testing

what is atypical scrapie?

• first identified in Norway in 1998

• all clinical cases presented with ataxia w/o pruritus or wool loss

• positive fro rapid screening ELISAs

• low molecular weight fragment on Western blot

• immunopathology in more rostral areas of brain including cerebellum

• immunostaining at obex distinct from classical scrapie

• in older animals

• spontaneous

what other new strains have been discovered?

• atypical BSE

• CWD - only affects free-ranging wildlife - chronic wasting disesase