M19 - Prions (sterilisation)

Question 1

Name prion based diseases.

Answer 1

• Scrapie (BSE of cattle)
• Creutzfeldt- Jakob disease
  (sporadic / inherited)
• Gerstmann- straussler- Schenker
  -Kuru
  -New variant CJD

Question 2

what is the most common type of Creutzfeldt- Jacob disease (CJD)

Answer 2

Sporadic

Question 3

who is most effective by sporadic CJD?

Answer 3

patient over 60 years old (elderly)

Question 4

what happens in sporadic CJD?

Answer 4

rapid dementia to death (4.5 months)

Question 5

where are the highest levels of prions in sporadic CJD?

Answer 5

in CNS , also retina and sensory ganglia, but not in blood

Question 6

what is the other type of CJD which effects younger patient in their 30s?

Answer 6

Variant

Question 7

what is variant CJD?

Answer 7

fatal Human neurodegenerative condition classified as transmissible spongiform encephalopathy

Question 8

what is the risk of variant CJD?

Answer 8

Risk of person to person spread by contaminated surgical- instruments that have not been cleaned, disinfected

Question 9

what prion protein is found in vCJD?

Answer 9

PrPsc

Question 10

what is important in CJD?

Answer 10

PRNP codon 129 of Prion Protein

Question 11

what Amino acids are found are position 129?

Answer 11

methionine or valine

Question 12

What are the different genotypes of vCJD

Answer 12

• Homozygous MM
• Homozygous VV
• Heterozygous MV

Question 13

what is the genotype of 177 of 178 cases of vCJD?

Answer 13

MM

Question 14

what gene appears significant in CJD?

Answer 14

PrP gene

-amino acid variants

Question 15

what are the symptoms of vCJD?

Answer 15

-Average age 28 (65) -progressive dementia, sensory symptoms, unsteadiness,
involuntary movements, immobile & mute
death <14 mths

Question 16

what happens in the brain in vCJD?

Answer 16

• Brain vacuolation, neural apoptosis
• Accumulate misfolded protease- resistant prion protein
• Protease Resistant Prion protein PrPSc

Question 17

what is vCJD linked to?

Answer 17

BSE

Question 18

what is BSE?

Answer 18

infectious agent for scrapie resistant to treatments that destroy DNA

Question 19

what is a prion?

Answer 19

• Proteinaceous infectious particle

- a protein that can replicate itself within the body

Question 20

Critically what are the 2 forms?

Answer 20

PrP^C , PrP ^Sc

Question 21

what is PrP^C converted to?

Answer 21

PrP^Sc

Question 22

what is PrP^Sc resistant to?

Answer 22

protease

Question 23

what does prions accumulate as?

Answer 23

Plaques

Question 24

what does newly converted PrP^Sc convert?

Answer 24

more PrP^C

Question 25

Describe PrP^C.

Answer 25

- made normally by body - preferentially produced in neurons - functions in stability of myelin sheath and memory - chemically identical to PrP^Sc

Question 26

what is the amount of PrP^Sc proportional to?

Answer 26

infectivity

Question 27

what reduces infectivity of prions?

Answer 27

- agents that destroy protein function | - antibodies to PrP^Sc

Question 28

what is the difference between prion and virus?

Answer 28

``` Prion -NO Virus - YES • Immune response • Disinfection by – Formaldehyde – Proteases – Heat (80 ̊ C) – Ionizing & UV radiati ```

Question 29

Describe the life cycle of prion in the body.

Answer 29

* Uptake via Peyers Patches (intestine) * Circulates in blood * Accumulates (replicates?) in Lymphoid Tissue * Enters nerve or crosses blood/brain barrier * Accumulates in brain

Question 30

Describe the peripheral distribution of vCJD.

Answer 30

• Lymphoid tissue – Tonsil,lymph node, spleen (unique to vCJD) – Not salivary gland tissue • Neural Tissue – Trigeminal ganglion but not cranial nerve • Blood – 4 confirmed transfusion cases

Question 31

Assaying infective risk.

Answer 31

* Use & reuse of surgical instruments * Standard ‘decontamination’ reduces risk * Risk (of contamination)

Question 32

what does the risk of contamination depend on?

Answer 32

- number of infected people - length of incubation period - levels present in tissues - infective dose

Question 33

when can contamination and transmission occur?

Answer 33

- surgery (CNS, eye, lymphoid tissue) - Dentistry - Inwards routes for transmission (tonsils , gums, tongue, dental pulp)

Question 34

Describe decontamination.

Answer 34

``` • Cleaning – removing mass of material • Autoclaving – partially deactivates material • Files&ReamersProblem; – difficulty removing material – Average 8-10 patients before discarded – USA single use – Contamination with dental pulp (?) ```

Question 35

How is there a new emphasis on removing prion material?

Answer 35

* Washer-disinfectors automate process * Robust cleaning * Reduced exposure to sharp implements

Question 36

What decontamination is involved in vCJD patient?

Answer 36

dispose of instruments & avoid retraction of oral fluids

Question 37

What decontamination is involved in general patients?

Answer 37

autoclaving at 134 ̊C & immersion in 1M NaOH, or 1M NaOCl

Question 38

When assessing the risk of transmission by new infectious agent, what is unlikely?

Answer 38

• Damage epithelial of infected patient (tonsil). Human dental pulp not yet shown to contain prions • Survive cleaning/autoclaving. • Come into contact with receptive surface on next patient.

Question 39

When assessing the risk of transmission by new infectious agent, what is likely?

Answer 39

• Limits to detection, scale of problem unknown sub-clinical carriers • Ability to survive autoclaving/ cleaning files/reamers difficult to remove dental pulp • Infective dose unknown Large amount of endodontic surgery

Question 40

What are some prion research involving field?

Answer 40

- model for neurodegenerative disorders - improved testing - treatments possible (drugs)