prions: proteins gone bad karen moody, pt, ms creutzfeldt-jakob disease surveillance coordinator...
TRANSCRIPT
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
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
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)