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Prions: Proteins Gone Bad
Karen Moody, PT, MS
Creutzfeldt-Jakob Disease Surveillance Coordinator
Texas Department of State Health Services
Diseases in Nature – Ft Worth, TX
June 2, 2009
Outline
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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
Dementia
Psychiatric /
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
CJD in Texas
Type
2004
2005
2006
2007
2008
-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
Sporadic
CJD Cases by Age and Gender
2005
2006
2007
2008
Total
Male
7
7
5
8
27
Female
8
2
9
8
27
<55
4
3
3
3
13
>55
11
6
11
13
41
Gender
Age
*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)