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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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• Confusion• Depression• Behavioral Changes• Impaired Vision• Impaired Coordination

Early Symptoms

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Later Symptoms• 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

• 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

• 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

• 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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TreatmentNo 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.