M19 - Prions (sterilisation) Flashcards
Name prion based diseases.
- Scrapie (BSE of cattle)
- Creutzfeldt- Jakob disease
(sporadic / inherited) - Gerstmann- straussler- Schenker
-Kuru
-New variant CJD
what is the most common type of Creutzfeldt- Jacob disease (CJD)
Sporadic
who is most effective by sporadic CJD?
patient over 60 years old (elderly)
what happens in sporadic CJD?
rapid dementia to death (4.5 months)
where are the highest levels of prions in sporadic CJD?
in CNS , also retina and sensory ganglia, but not in blood
what is the other type of CJD which effects younger patient in their 30s?
Variant
what is variant CJD?
fatal Human neurodegenerative condition classified as transmissible spongiform encephalopathy
what is the risk of variant CJD?
Risk of person to person spread by contaminated surgical- instruments that have not been cleaned, disinfected
what prion protein is found in vCJD?
PrPsc
what is important in CJD?
PRNP codon 129 of Prion Protein
what Amino acids are found are position 129?
methionine or valine
What are the different genotypes of vCJD
- Homozygous MM
- Homozygous VV
- Heterozygous MV
what is the genotype of 177 of 178 cases of vCJD?
MM
what gene appears significant in CJD?
PrP gene
-amino acid variants
what are the symptoms of vCJD?
-Average age 28 (65) -progressive dementia, sensory symptoms, unsteadiness,
involuntary movements, immobile & mute
death <14 mths
what happens in the brain in vCJD?
- Brain vacuolation, neural apoptosis
- Accumulate misfolded protease- resistant prion protein
- Protease Resistant Prion protein PrPSc
what is vCJD linked to?
BSE
what is BSE?
infectious agent for scrapie resistant to treatments that destroy DNA
what is a prion?
- Proteinaceous infectious particle
- a protein that can replicate itself within the body
Critically what are the 2 forms?
PrP^C , PrP ^Sc
what is PrP^C converted to?
PrP^Sc
what is PrP^Sc resistant to?
protease
what does prions accumulate as?
Plaques
what does newly converted PrP^Sc convert?
more PrP^C
Describe PrP^C.
- made normally by body
- preferentially produced in neurons
- functions in stability of myelin sheath and memory
- chemically identical to PrP^Sc
what is the amount of PrP^Sc proportional to?
infectivity
what reduces infectivity of prions?
- agents that destroy protein function
- antibodies to PrP^Sc
what is the difference between prion and virus?
Prion -NO Virus - YES • Immune response • Disinfection by – Formaldehyde – Proteases – Heat (80 ̊ C) – Ionizing & UV radiati
Describe the life cycle of prion in the body.
- Uptake via Peyers Patches (intestine)
- Circulates in blood
- Accumulates (replicates?) in Lymphoid Tissue
- Enters nerve or crosses blood/brain barrier
- Accumulates in brain
Describe the peripheral distribution of vCJD.
• 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
Assaying infective risk.
- Use & reuse of surgical instruments
- Standard ‘decontamination’ reduces risk
- Risk (of contamination)
what does the risk of contamination depend on?
- number of infected people
- length of incubation period
- levels present in tissues
- infective dose
when can contamination and transmission occur?
- surgery (CNS, eye, lymphoid tissue)
- Dentistry
- Inwards routes for transmission (tonsils , gums, tongue, dental pulp)
Describe decontamination.
• 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 (?)
How is there a new emphasis on removing prion material?
- Washer-disinfectors automate process
- Robust cleaning
- Reduced exposure to sharp implements
What decontamination is involved in vCJD patient?
dispose of instruments & avoid retraction of oral fluids
What decontamination is involved in general patients?
autoclaving at 134 ̊C & immersion in 1M NaOH, or 1M NaOCl
When assessing the risk of transmission by new infectious agent, what is unlikely?
• 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.
When assessing the risk of transmission by new infectious agent, what is likely?
• 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
What are some prion research involving field?
- model for neurodegenerative disorders
- improved testing
- treatments possible (drugs)
