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AFNS 416 > 9 - Prion Diseases > Flashcards

9 - Prion Diseases Flashcards

1
Q

Why is BSE a one health issue? CWD?

A

BSE: agricultural, industry generation, distribution of infectious prions

CWD: transport of infectious animals, environmental reservoir of infectivity

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2
Q

How are prions unique pathogens?

A

They are acellular, non-living and are disease-specific protein structure (do not have their own genome)

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3
Q

The cellular prion protein is present in… What gene is it encoded by?

A

in all mammals

Encoded by prion protein gene (PRNP)

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4
Q

What happens when there is a prion infection? How (3)

A

Conversion of normal to misfolded (abnormal) prion protein

  • presence of misfolded (prion mechanism)
  • spontaneously
  • PRNP gene alterations
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5
Q

How can the PRNP gene alteration affect likelihood of misfolding?

A

Changes in normal prion protein
Makes conversion to misfolded more or less likely depending

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6
Q

Healthy vs disease-causing prion protein

A

PRP^c (healthy): enriched in a-helices, glycoprotein cell surface, metal homeostasis, necessary for prion infection

PRP^TSE: same a.a. sequence, enriched in B-sheets, partially resistant to proteinase K digfestion

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7
Q

What is the difference between a prion and a prion protein?

A

Prion: infectious, transmissible protein agent

Prion protein: non-infectious form (PrP^C), infectious form (PrP^TSE, Sc, etc)

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8
Q

Slides 9-12

A

Look

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9
Q

What species can be affected by prion diseases? Which are not?

A

Sheep, cervids, mink, camel, cats, humans, cows, mice

Not: horses, dogs

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10
Q

Three categories of human prion diseases

A
  1. Acquired:
    - kuru
    - variant creutzfeldt jakob disease (vCJD)
    - Iatrogenic CJD
  2. Familial:
    - familial CJD
    - fatal familial insomnia
    - gerstmann-straussler-scheinker syndrome
  3. Idiopathic (sporadic)(85%):
    - sporadic CJD
    - sporadic fatal insomnia
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11
Q

Explain the basic of prion diseases

A
  • spongiform degeneration
  • transmissible (not all contagious)
  • infection highest in brain and spinal cord. Also lymphatic
  • accumulation of PrP^TSE, BSE, etc
  • long incubation period
  • extended preclinical stage
  • fatal, no cure
  • resistant to inactivation
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12
Q

Prion infectivity in hamsters, cattle, deer

A

Hamsters: 1-10 billion infectious units

Cattle: 1-10 million infectious units/gram of brain tissue

Deer: unknown

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13
Q

What are prions resistant to?

A
  • chemical inactivation (acids, base, detergent)
  • standard sterilization methods (autoclaving/medical sterilization: 120C 20 min)
  • common UV and gamma irradiation levels
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14
Q

How do we inactivate prions?

A

Extreme conditions
- 1 N NaOH
- autoclaving at 134C for 1 hour

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15
Q

How do we detect prion diseases

A
  • postmortem
  • brain tissue
  • distinguish abnormal protein from normal (infectious agent)
  • clinical behaviour / characteristics (but occur late in disease)

Antibody response not useful

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16
Q

How long is the preclinical stage in deer? Cattle? Sheep? Humans

A

Deer (CWD) = years
Cattle (BSE) = years
Sheep (scrapie) = years

Humans (CJD) = decades

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17
Q

How do you distinguish normal from abnormal prions

A

Expose them to proteinase K, abnormal form is resistant

Slides 23-27**

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18
Q

Commercial detection kits for prions

A

Western blot or ELISA

government restrictions in place on purchase

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19
Q

What are PMCA and RT QuIC

A

PMCA: protein misfolding cyclic amplification

RT QuIC: real time quaking induced conversion

Highly sensitive technologies for detection of PrP^SC. Required expensive equipment and lab expertise.

Slide 30

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20
Q

Similarities and differences between PMCA and RT QuIC

A

Both can amplify detectable levels of abnormal prion proteins form small amounts of starting material
Both require PrP^c

PMCA uses PrP^c source from brain homogenate whereas RT-QuIC uses PrP^c from recombinant sources

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21
Q

Which prion diseases are transmissible? Contagious?

A

Transmissible: all
Contagious: scrapie & CWD

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22
Q

Characteristics that distinguish diff prion diseases

A
  • contagious?
  • length of incubation period
  • clinical symptoms
  • PK resistance
  • size of PK resistant proteins
  • distribution and size of spongiform lesions in brain
  • interspecies transmission
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23
Q

Sheep scrapie vs BSE

A

Both transmissible from brain tissue

Sheep scrapie also contagious (sheep to sheep)

24
Q

First recorded scrapie case in UK? Canada?

A

UK: ~1700
Canada: 1938

25
Q

Scrapie transmission

A

Contagious
Infectivity present in fluid and tissue from placentas of infected ewes
Environmentally persistent

26
Q

Variations in PRNP Gene leading to susceptibility or resistance to scrapie

A

ARR = resistance to scrapie
VRQ = susceptible

ARR/ARR = highly resistant
VRQ/VRQ = highly susceptible

27
Q

How are we trying to control scrapie

A
  • reportable disease (suspect cases must be reported to CFIA vet immediately)
  • sheep documented with scrapie and all animals exposed to same birthing environment must be destroyed (producers compensated)
  • selective breeding for genetic resistance to minimize risk
28
Q

What is atypical scrapie

A

Abnormal protein more sensitive to PK than classical
Gets digested away = hard to identify
More abundant in cerebellum & cortex than brain stem
Identified in “scrapie resistant” sheep

29
Q

How many BSE+ cattle in GB? North America? Cost of BSE to canadian cattle industry?

A

~200,000 in GB

26 in NA

~$7 billion dollar cost to industry

30
Q

How does BSE propagate in cow populations

A

Animal carcasses, slaughter facility waste and unused meat products are sent to rendering facilities, cooked at high temps into meat and bone meal, then fed back to cattle

If prions are in the carcasses, they are resistant to rendering temperatures

31
Q

How much animal carcass/animal by-products are processed in rendering plants yearly in NA

A

50 billion pounds converted into 18 billion pounds of product

Value $3 billion

32
Q

How much of every cow/pig is not consumed by humans

A

Half of every cow, a third of every pig

33
Q

When did BSE spike in the UK? What was done to control it? What about vCJD deaths?

A

Spiked from 1990-1995

Feed ban implemented in 1988 (no m&b meal to cattle)
Enhanced ban in 1996

vCJD cases spiked from 1995-2000 (BSE is zoonotic = variant CJD)

34
Q

What codon is important in CJD? How?

A

Codon 129 of prion protein

met/val (50% of pop) and val/val (10% of pop) are safe

met/met (40%) of pop died

35
Q

When were feed bans implemented in Canada for BSE?

A

1997: Ruminant feed ban
- prohibit feeding of most mammalian derived proteins to ruminants
- prohibit feeding of poultry litter and restaurant waste to ruminants

2007: Feed ban
- SRM banned from all animal feeds, pet foods, fertilizers

36
Q

Political pressures were coming from who when the feed bans were implemented in canada

A

From the rendering industry, arguing we had not yet seen BSE in Canada

37
Q

What is SRM? Banned…

A

Specified risk material
- skull, brain, eyes, spinal cord, etc

SRM from cattle 30 months or older banned from human food supply
SRM banned from all animal feeds, fertilizers and pet foods

38
Q

Distribution of the 26 NA cases of BSE

A

1 imported from GB
5 US
20 Canada

39
Q

Classical vs atypical BSE

A

Classical: caused by feeding cattle MBM, solution = stop feeding cattle infected material

Atypical: heavy (H) and light (L) migration of abnormal protein, NOT linked to feed, very old cattle (>10 years). Spontaneous?

40
Q

Which of scrapie, BSE and CWD are zoonotic?

A

Scrapie = no
BSE = yes
CWD = ?

41
Q

CWD facts (8)

A
  • contagious brain disease
  • always fatal (no treatment or cure)
  • complicated detection
  • many strains
  • environmental contamination
  • long preclinical
  • slow spread
  • zoonotic?
42
Q

Where did CWD begin in NA in 2000? How

A

Colorado, Nebraska, Wyoming

Animal to animal, animal to environmental (transport trucks: game farms) to animal

43
Q

Slides 64-67

A

Spread of CWD

44
Q

How did CWD get to Saskatchewan

A

in 1996, preclinical farmed elk moved from south dakota to sask

45
Q

% of mule deer, white tailed deer, elk and moose positive for CWD in AB

A

23.4% mule
8.3% white
1.6% elk
2.9% moose

46
Q

How did CWD get to South Korea?

A

In 2000, captive elk moved from Sask

47
Q

Is CWD in Europe?

A

Norway 2016, Finland 2018, Sweden 2019

48
Q

How did Norway try to stop CWD spread

A

Culled thousands of reindeer

49
Q

When do infected deer become contagious?

A

Lymph tissue positive for PrP^CWD as early as 3 months post oral infection (shedding)

50
Q

What tissues are low-moderately infective during early preclinical? Clinical?

A

Lymphatic, tonsil, saliva

Brain & spinal cord

Slide 77***

51
Q

How do you control CWD?

A
  • no drugs/vaccines/cures
  • depopulation?
  • reduce population?
52
Q

White tailed deer and CWD

A
  • very susceptible
  • numerous strains
  • free-ranging and captive
53
Q

Mule deer and CWD

A
  • very susceptible
  • AB and Sask more prevalent than white-tailed
54
Q

Elk and CWD

A
  • susceptible
  • free ranging and game farms
55
Q

Moose and CWD

A
  • relatively rare in NA (Colorado, Wyoming, AB)
  • environmental transmission likely route
  • more common in europe
56
Q

Caribou and CWD

A
  • no cases to date in NA
  • present in Norway
  • considered very susceptible
  • range of disease in deer is starting to grow into areas with caribou

AFNS 416 (22 decks)

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