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.

3

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

6

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 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.

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 FactsNo definitive diagnosis w/o brain biopsy or autopsy1/million affected: 250 - 300 new cases a yearSporadic or classical (sCJD) - 85% of cases: no known causeHereditary or familial - 15% of cases; autosomal dominantAquired (aCJD) - contamination through medical procedureVariant (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

15

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 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

18

19

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.

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 600oC 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

TreatmentNo cureOpiate drugs can help relieve painClonazepam and Sodium Valproate relieves involunatary muscle jerksLater stage involves catheter use, intravenous fluid, feeding tubesPentosan 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.