Prions: Proteins Gone Bad

Karen Moody, PT, MSCreutzfeldt-Jakob Disease Surveillance Coordinator

Texas Department of State Health ServicesDiseases in Nature – Ft Worth, TX

June 2, 2009

Outline• The Medical Mystery• Prions• Human Prion Disease• Animal Prion Disease• BSE – Mad Cow Disease• Variant CJD• Texas CJD Cases• Reporting and Investigating• Infection Control• Resources

Prion Disease - A Medical Mystery

• 1700s– Scrapie – sheep– Fatal Familial Insomnia (FFI)– Gerstmann-Straussler-Scheinker

• 1920s– Hans Gerhard Creutzfeldt and

Alfons Maria Jakob

Prion Disease – A Medical Mystery

• 1950s– Kuru – Fore Tribe - New Guinea

• 1980s– Bovine Spongiform Encephalopathy (BSE)– The Discovery of Prions – Stanley Prusiner

• 1990s– Prions are transmissible from cattle to

humans (variant CJD)

Prions – Proteins Gone Bad

• Not a bacterium or virus

• Misfolded protein

• Two stable conformations(PrPc vs. PrPsc)

• No nucleic acid

• Genetic mutations

• Survive routine disinfection & sterilization procedures

Human Prion Diseases• Sporadic

– Sporadic CJD (sCJD)

– Sporadic fatal insomnia

• Acquired (Infectious)– Variant CJD (vCJD)

– Iatrogenic CJD (iCJD)

• Genetic– Fatal Familial Insomnia– Familial CJD (fCJD)– Gertsmann-Straussler-Scheinker

Animal Prion Diseases

• Chronic Wasting Disease (CWD)– Mule deer, White tailed deer, Moose and Elk

• Bovine Spongiform Encephalopathy (BSE)– Cattle

• Scrapie– Sheep

Downloaded form http://www.cdc.gov

Bovine Spongiform Encephalopathy (BSE or Mad Cow Disease)

• 1985 – recognized progressive neurological disorder in two cattle

• 1986 – examination of cow brain indicate spongiform changes

• 1987 – meat-and-bone-meal feed

• 1988 – Feed ban enacted in UK

• 1993 – BSE epidemic in UK peaked with 1,000 cattle affected per week

• 2007 – 184,500 cattle confirmed in 35,000 herds

Cases of BSE in USA

• 2003 – Washington– Holstein imported from Canada

• 2005 – Texas – First endemic case of BSE in US

• 2006 - Alabama – Euthanized and buried on farm (herd of origin

not identified)

• April 25, 2009 – FDA issued regulation barring high risk material use in animal feed in USA.

vCJD

• 1990 – CJD surveillance unit in UK

• 1995 – Three CJD cases (ages 16, 19, 29)– 10 suspected CJD cases <50 years old

• 1996 – Identified first human case– Distinctive clinical syndrome associated with plaque

formation

– vCJD prion strain unique to humans

– Prion strain similar to BSE strain

• Clinical and pathological characteristics different from sCJD

Clinical and Pathological Characteristics of vCJD

• Pathological characteristics– Amyloid plaques with spongiform degeneration

• Clinical characteristics– Psychological / behavioral symptoms– Dysesthesias – Average age of patient – 28 years– Duration of illness – 12 to 14 months– No unique EEG findings– Positive pulvinar sign on MRI

Sporadic CJD vs. Variant CJD

Characteristics sCJD vCJD

Age 68 Years 28 Years

Duration 4-5 Months 13-14 Months

Clinical Presentation

DementiaPsychiatric / Behavioral Symptoms

MRI ‘Pulvinar Sign’

Not Reported Present (>75%)

Periodic Spikes on EEG

Often Present Often Absent

Downloaded http://www.cdc.gov

vCJD Worldwide

• As of 2008

– 208 cases (4 related to blood transfusions)

– Three cases identified in USA – likely exposure in UK

• Do genetics play a role in susceptibility?

– Polymorphic codon 129 PRNP gene

– 100% of cases have been Methionine-Methionine

• How many more cases might we see?

Reporting and Investigating

• CJD – reportable condition in Texas

• CSF – elevated 14-3-3 protein and positive Tau

protein = suspect case of CJD

• Medical records – signs and symptoms

• Arrange for autopsy (especially those suspected

of having vCJD)

• Under 55 years – suspect for vCJD

Type 2004 2005 2006 2007 2008

Sporadic

-Confirmed 8 9 5 10 12

-Probable 5 8 3 3 3

-Possible 1 0 1 0 1

Variant 0 0 1 0 0

Familial 0 1 1 0 0

Iatrogenic 0 0 0 0 0

Sporadic Fatal Insomnia

0 0 0 1 0

Total 14 18 11 14 16

CJD in Texas

CJD Cases by Age and Gender

2005 2006 2007 2008 Total

Gender

Male 7 7 5 8 27

Female 8 2 9 8 27

Age

<55 4 3 3 3 13

>55 11 6 11 13 41*Based on data as of March 30, 2009† Includes confirmed, probable, possible sporadic and familial CJD

iCJD and Infection Control

• iCJD risk – contaminated surgical instruments & certain medical procedures

• Incineration eliminates risk of infectivity

• Special procedures - heat resistant surgical devices

• Prions not transmissible by touching, kissing or bathing

• Possible transmission – ingest or transplant contaminated neural tissue

Resources• National Prion Disease Pathology

Surveillance Center (NPDPSC)– Free CSF testing and autopsy arrangement

• CJD Foundation– Family conference

• Centers for Disease Control and Prevention (CDC)– Quarterly conference calls

• World Health Organization (WHO)