Transcript Transmissible Spongiform Encephalopathies

Transmissible Spongiform
Encephalopathies
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Kuru
• Since the early 1900’s the Fore people of
New Guinea have honored their dead by
cooking and consuming the bodies of the
deceased.
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Kuru
• In the 1920’s a new disease appeared. It
killed primarily children and adult females.
• Symptoms were:
– Lack of coordination, staggering and slurred
speech
– Uncontrollable shivering
– Mood changes: euphoria to indifference
– Paralysis and death in a few months to a year
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By 1950’s kuru had become an epidemic
Not a psychological disease
Not a bacterial disease
Not a viral disease
Not a genetic disease
Not heavy metal or other poisoning
Not a vitamin deficiency
Brains full of sponge-like holes and
abnormal deposits of protein
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“Mad Cow Disease”
• Between 1984 and 1986 dairy cows in
England developed strange neurological
symptoms:
– Aggressive or apprehensive
– Muscle tremors
– Lost weight and coordination
– Fatal after a few months to a year
– Brains had holes and protein deposits
• Bovine spongiform encephalopathy (BSE)
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• BSE became an epidemic over the next 6
years, with 180,000 confirmed cases by
the year 2000.
• Cattle were being fed rendered cattle,
sheep and goats as a cheap source of
protein.
• More than 120 people have contracted
new variant Creutzfeldt-Jakob disease
from eating infected beef.
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Early Symptoms
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Confusion
Depression
Behavioral Changes
Impaired Vision
Impaired Coordination
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Later Symptoms
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Dementia: confusion and disorientation,
memory loss, personality loss, agitation,
and restlessness
Neuromuscular symptoms include
wasting, myoclonus, athetosis
Coma and increased susceptibility to
repiratory infections can occur.
Death can result within a year of
symptom onset.
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Transmissible Spongiform
Encephalopathies
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Long incubation periods
No inflammatory response
No antibody production
Sponge-like holes in brain and protein
deposits called plaques.
• Lose motor function, become demented
and die.
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Human TSE’s
• Kuru
• Creutzfeldt-Jakob disease (CJD)
• Gerstmann-Straussler-Scheinker
Syndrome (GSS)
• Fatal Familial Insomnia (FFI)
• New variant CJD (nvCJD)
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CJD Facts
No definitive diagnosis w/o brain biopsy or
autopsy
1/million affected: 250 - 300 new cases a year
Sporadic or classical (sCJD) - 85% of cases: no
known cause
Hereditary or familial - 15% of cases; autosomal
dominant
Aquired (aCJD) - contamination through medical
procedure
Variant (vCJD) - Beef tainted with BSE
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Animal TSE’s
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Scrapie in sheep
Bovine Spongiform Encephalopathy
Transmissible Mink Encephalopathy
Feline Spongiform Encephalopathy
Chronic Wasting Disease in deer and elk
Exotic Ungulate Encephalopathy –kudu,
orynx and nyala
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Prions
• Identified in 1982 by American scientist
Stanley Prusiner
• “Proteinaceous infectious particles”
• Nobel Prize in 1997
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Prion Hypothesis
• Normal nerve cells contain the normal
prion protein, a glycoprotein called PrPc
formed by the Prnp gene.
• TSE-infected cells contain the abnormal
form of the protein, called PrPsc. This
differs from the normal protein by having
beta-sheets instead of alpha-helices
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Prion hypothesis
• PrPsc interacts with PrPc, converting it into
another PrPsc
• Infectious PrPsc can come from inside or
outside the host.
– Taken in by injection or ingestion
– Random event, or mutation of Prnp gene that
makes protein susceptible to mis-folding.
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• Usually transmitted inefficiently between
species
– May be due to difference in amino acid
sequence in proteins
• Species barrier may be broken if passed
through an intermediate host.
• Mutations of Prnp gene linked to inherited
TSE’s
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Transmission
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Eating infected material
IV or IM injections
Tissue transplants
Contaminated surgical instruments
Blood???
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Decontamination
• Must be subjected to dry heat at least
600oC for one hour.
• Or be treated for one hour in a bleach
solution containing at least 2% chlorine.
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Restrictions
• On decontamination procedures for
surgical instruments
• Blood donations
• 200 patients world wide contracted CJD
through organ transplants and pituitary
gland extracts.
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Treatment
No cure
Opiate drugs can help relieve pain
Clonazepam and Sodium Valproate relieves
involunatary muscle jerks
Later stage involves catheter use, intravenous
fluid, feeding tubes
Pentosan Polysulphate (blood-thinning and
anti-inflammatory drug) - as of Dec 2004, 1
cure.
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Blood Test
• August 29, 2005 scientists developed a
blood test for vCJD.
• Could protect those receiving blood
transfusions and organ transplants
• Predict the size of future vCJD epidemics
• Test all the cows in the herd instead of
destroying them.
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