1 Transmissible Spongiform Encephalopathies

2 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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4 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

5 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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7 “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)

8 BSE became an epidemic over the next 6 years, with 180,000 confirmed cases by the year 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.

9 Confusion Depression Behavioral Changes Impaired Vision Impaired Coordination Early Symptoms

10 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.

11 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.

12 Human TSE’s Kuru Creutzfeldt-Jakob disease (CJD) Gerstmann-Straussler-Scheinker Syndrome (GSS) Fatal Familial Insomnia (FFI) New variant CJD (nvCJD)

13 CJD Facts No definitive diagnosis w/o brain biopsy or autopsy 1/million affected: 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

14 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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16 Prions Identified in 1982 by American scientist Stanley Prusiner “Proteinaceous infectious particles” Nobel Prize in 1997

17 Prion Hypothesis Normal nerve cells contain the normal prion protein, a glycoprotein called PrP c formed by the Prnp gene. TSE-infected cells contain the abnormal form of the protein, called PrP sc. This differs from the normal protein by having beta-sheets instead of alpha-helices

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19 Prion hypothesis PrP sc interacts with PrP c, converting it into another PrP sc Infectious PrP sc 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.

20 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

21 Transmission Eating infected material IV or IM injections Tissue transplants Contaminated surgical instruments Blood???

22 Decontamination Must be subjected to dry heat at least 600 o C for one hour. Or be treated for one hour in a bleach solution containing at least 2% chlorine.

23 Restrictions On decontamination procedures for surgical instruments Blood donations 200 patients world wide contracted CJD through organ transplants and pituitary gland extracts.

24 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.

25 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.