TransmissibleSpongiformEncephalopathies

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Transmissible Spongiform Encephalopathies,Ryan Maddox, MPH,Creutzfeldt-Jakob Disease Surveillance Unit,Division of Viral and Rickettsial Diseases,National Center for Infectious Diseases,Centers for Disease Control and Prevention,1,Abbreviations,TSE Transmissible Spongiform Encephalopathy (prion disease),CJD Creutzfeldt-Jakob Disease,vCJD Variant Creutzfeldt-Jakob Disease,BSE Bovine Spongiform Encephalopathy (“mad cow” disease),CWD Chronic Wasting Disease,2,Transmissible Spongiform Encephalopathies (TSEs):,Neurodegenerative diseases,Rapidly progressive, always fatal,Affect humans and animals,Long incubation periods,Brain, spinal cord, and adjacent tissues are considered infectious,Prion theory widely accepted,3,TSEs are further characterized by:,Absence of immune response,Neuropathology may include:,Spongiform changes,Reactive gliosis,Neuronal loss,Amyloid plaques,No inflammatory reaction,4,Human TSEs,Kuru,Creutzfeldt-Jakob Disease (CJD),Variant Creutzfeldt-Jakob Disease (vCJD),Gerstmann-Str,ussler Scheinker Syndrome (GSS),Fatal Familial Insomnia (FFI),5,Animal TSEs,Scrapie,Bovine Spongiform Encephalopathy (BSE),Chronic Wasting Disease (CWD),6,Creutzfeldt-Jakob Disease (CJD),Occurs worldwide,Annual incidence (U.S.): 1 case per million population,Median age at death (U.S.): 68 years,7,CJD Clinical Features,Patients usually present with dementia, visual problems, or cerebellar dysfunction,Subsequent neurologic signs include myoclonus, tremors, and rigidity,Neurologic signs deteriorate very rapidly,akinetic mutism,8,CJD More Features,Rapidly progressive - over 50% of CJD patients die within 6 months and 85-90% within 12 months of illness onset (median illness duration: 4 months),CJD occurs in three different forms:,sporadic,familial,iatrogenic,9,Sporadic CJD,About 85% of CJD patients,No recognizable mode of transmission identified,May be caused by:,Age-related somatic mutation of the prion protein gene,Error in production of the normal prion protein,10,Familial CJD,About 10-15% of CJD patients,Autosomal dominant inheritance,Associated with prion protein gene abnormalities,Usually a family history of CJD is present,11,Iatrogenic CJD,30 months prevented from entering human or animal food chain - 1996,21,U.K. CJD Surveillance,Detected 10 CJD patients with:,Unusual clinical presentation,Young age: Median, 28 years (Range 16-39),Psychiatric presentation followed by cerebellar symptoms,Non-diagnostic, abnormal EEG,Prolonged duration of illness (Median: 14 months),22,U.K. CJD Surveillance (2),Unique neuropathology,Spongiform changes most evident in the basal ganglia and thalamus,Widespread kuru-type plaques in the cerebellum and cerebrum,The plaques had pale periphery and were surrounded by spongiform lesions,23,U.K. CJD Surveillance (3),U.K. surveillance unit reported that the 10 cases represented a distinct new entity, variant CJD (vCJD), based on:,The unique clinicopathological features,Absence of any known CJD risk factors,Absence of genetic abnormalities,Absence of similar cases in other countries,24,Variant Creutzfeldt-Jakob Disease (vCJD),U.K. government announced that the BSE agent may have spread to humans (probably through consumption of contaminated beef and beef products),Cluster in 10 young patients,Unique to the U.K.,Consistent incubation period (9 years after BSE outbreak),No other plausible explanation,25,Evidence for BSE-vCJD Link,Epidemiological evidence,Geographic clustering in the United Kingdom,Absence of vCJD cases in BSE-free countries,Laboratory evidence,Experimental study using macaques,Western blot analysis of infecting prions,Experimental study using panels of inbred and cross-bred mice,26,Variant CJD is different from CJD,Variant CJD patients tend to be much younger, present with behavioral or sensory problems, have a delayed onset of neurologic signs, and tend to have a longer duration of illness,Pathology differs between vCJD and CJD,27,USDA and FDA,USDA and FDA have taken measures to prevent the introduction of BSE into the U.S.,Importation of ruminants from BSE-endemic countries banned, and certain cattle products restricted (1989),Importation of live ruminants and most ruminant products from all of Europe prohibited (1997),Mammalian-to ruminant feed ban in the U.S. (1997),28,USDA Surveillance,USDA tests high-risk animals,176,468 cattle tested in 2004,29,FDA Regulations,Prohibited use of cattle materials at highest risk of BSE in human food, including dietary supplements, and cosmetics (2004),High risk includes,Material from non-ambulatory, disabled cattle,Material from organs of cattle = 30 months,Mechanically separated material,30,107 deaths from definite vCJD + 43 deaths from probable vCJD (no neuropathological confirmation) = 150,6 patients with probable vCJD alive; 156 vCJD cases total (definite/probable, dead/alive),Data from,31,Data from,32,Variant CJD Around the World,Cases have also been reported from Canada (1), Ireland (2), Italy (1), Japan (1), The Netherlands (1), Portugal (1), Saudi Arabia (1), and the United States (1),One of the Irish cases, the Canadian case, Japanese case, and the U.S. case were believed to have been exposed to the BSE agent in the United Kingdom,33,CDC CJD surveillance,Conducted active surveillance in 5 areas,Periodic review of national cause-of-death data,Potential cases (iatrogenic, vCJD, etc.) reported by doctors and state public health departments,Ongoing review of clinical and pathologic records of CJD decedents aged 3 years after donation; recipient developed vCJD 6.5 years after transfusion,Case 2: Donor developed vCJD 18 months after donation; recipient (methionine/valine) had subclinical infection,36,Chronic Wasting Disease (CWD),Known natural hosts: deer (,Odocoileus,species) and Rocky Mountain elk,Clinical symptoms,Weight loss,Behavioral changes,Excessive salivation,Difficulty swallowing,37,CWD,Most animals die within several months of onset,Wide range of ages affected,May be highly transmissible within a population, but mode of transmission is not fully understood,Direct: animal-to-animal contact,Indirect: causative agent in environment,38,Chronic Wasting Disease Among Free-Ranging Deer and Elk by County, United States,39,CWD transmissible to humans?,Belay ED, Maddox RA, Williams ES, Miller MW, Gambetti P, Schonberger LB. Chronic wasting disease and potential transmission to humans. Emerg Infect Dis 2004;10:977-84.,Investigation of “clusters” of CJD cases,Collaborative project with Wyoming,40,Case,Age,Year,Codon 129,Western Blot,Final diagnosis,Endemic?,1,25,2001,MV,Type 1,GSS 102,Yes,2,26,2001,MM,Type 2,CJD,No,3,28,2002,nd,nd,GSS 102,No,4,28,1997,MM,nd,CJD,No,5,28,2000,MV,Type 1,CJD,No,6,30,1999,VV,Type 1,CJD,No,7,54,2002,VV,Type 2,CJD,No,8,55,1999,MM,Type 1,CJD,No,9,61,2000,MM,Type 1,CJD,Yes,10,63,2002,VV,Type 1,CJD,No,11,64,2002,MM,Type 1,CJD,Yes,12,66,2001,MM,Type 1,CJD,No,41,Is CWD affecting humans?,Unique pathology among suspect cases?,More human TSE cases in endemic areas?,Common genetics among suspect cases?,History of exposure to deer and elk with CWD?,42,For more on prion diseases:,Information on National Prion Disease Pathology Surveillance Center (NPDPSC),established by CDC and AANP,NPDPSC provides free, state-of-the-art diagnostic testing,Links to various prion disease articles and sites,43,Acknowledgements,CDC,Dr. Larry Schonberger,Dr. Ermias Belay,Dr. Jim Sejvar,Mr. Bob Holman,Mr. Aaron Curns,NPDPSC,Dr. Pierluigi Gambetti,Ms. Carrie Harris,State health department personnel,44,