CJD Overview Bob Will National CJD Surveillance Unit

CJD Overview Bob Will, National CJD Surveillance Unit, Edinburgh, UK Associazione Italiana Encefalopatie da Prion Milano 3 Ottobre 2009

Science 1968

Questions • What is the origin of infection in CJD? • Is there a link to scrapie in sheep? • What are the clinical and pathological characteristics of CJD? • What are the epidemiological characteristics of CJD?

SYSTEMATIC STUDIES OF CJD WORLDWIDE

DISTRIBUTION OF SPORADIC CJD IN THE UK: 1990 -2002

SIGNIFICANT RISK FACTORS IN CONTROLLED STUDIES AUTHOR Bobowick et al. (1973) Kondo & Kuroiwa (1982) Kondo (1985) METHOD 38 “selected” cases; healthy controls. RISK FACTORS None. Population study: 60 cases, healthy controls trauma in males. 88 autopsied cases; autopsied controls organ resection. Davanipour et al (1985) 26 cases; 40 controls trauma or surgery to head or neck; other trauma; surgery needing sutures; tonometry Davanipour et al (1985) 26 cases; 40 controls roast pork, ham, underdone meat, hot dogs. Davanipour et al (1985) 26 cases; 40 controls contact with fish, rabbits, squirrels. Harries-Jones et al (1980) 92 cases; 184 controls Herpes Zoster; keeping cats; contact with pets other than cats/dogs; dementia in family Van Duijn et al (1998) 405 cases; 405 controls consumption of raw meat; consumption of brain; frequent exposure to leather products, exposure to fertilizer consisting of hoof and horn. Collins et al (1999) 241 cases; 784 controls number of surgical procedures; residence or employment on a farm or market garden. Ward et al (2002) 326 cases; 326 controls surgery, especially in females; ear piercing, psychiatric consultation.

HUMAN TSEs (Prion diseases

SPORADIC CJD : EEG PERIODIC TRIPHASIC DISCHARGES • 60 -80% SENSITIVITY (TESTING POLICY) • ? SPECIFICITY (? 74%) (CONTEXT DEPENDENT) • ‘SUBJECTIVITY’ OF REPORTING NO EEG CRITERIA PROSPECTIVELY VALIDATED IN LARGE NUMBERS OF CASES

CSF Analysis 14 -3 -3 Western Blot s. CJD AD v. CJD Dr Alison Green, The National CJD Surveillance Unit Sp. CJD ECDC funded meeting, 10 th March 2009

MRI brain scan in sporadic CJD

MRI brain scan in variant CJD

IATROGENIC CREUTZFELDT-JAKOB DISEASE WORLDWIDE Mode of infection No. of patients Agent entry into brain Mean incubation period (range) Clinical signs on presentation Corneal transplant 2 Optic nerve 18, 320 mo Dementia, cerebellar Stereotactic EEG 2 Intra-cerebral 16, 20 mo Dementia, cerebellar Neurosurgery 4 Intra-cerebral 17 mo (12 -28) Visual/dementia/cerebellar Dura mater graft 209 Cerebellar surface 11 yr (1. 5 -23) Cerebellar (visual, dementia) Growth hormone 203 Hematogenous(? ) 15 yr (4 -36) Cerebellar 4 Hematogenous (? ) 13 yr (12 -16) Cerebellar Hematogenous 6. 5, 7. 5, 8. 5 yr Sensory, psychiatric Gonadotrophin Blood transfusion 3 (+1)

DURA MATER CASES WORLDWIDE SHOWN BY YEAR OF OPERATION AND YEAR OF ONSET OF SYMPTOMS FOR CJD Mean incubation period from operation to onset of symptoms: 6. 8 years (range 1 -16)

THE HUMAN PRION PROTEIN GENE Mutations and polymorphisms • Clinical diagnosis • Screening of family members • Pre-natal testing • Influence on phenotype

The UK BSE epidemic ‘BSE posed the greatest political and economic challenge to the EU since its foundation’ The specified bovine offal ban UK Dec 1989/ Jan 1990

DIFFERENCES BETWEEN SPORADICAND VARIANT CJD

Number of cases AGE AT DEATH FOR SPORADIC CJD CASES AND v. CJD CASES BY 5 -YEAR AGE GROUP Age Group

Results Temporal distribution of v. CJD cases in France and UK According to the year of onset, the number of v. CJD cases in France reached a peak of incidence in 2004, five years after the peak observed in the UK in 1999

YEAR OF ONSET OF ILLNESS OF v. CJD WORLDWIDE Year Onset UK France Ireland 1994 8 1 1995 10 1996 11 1997 14 1998 17 1 1999 29 1 2000 24 1 2001 17 2 2002 14 2003 5 2 2004 9 7 2 2005 5 4 1 2006 3 4 2007 1 2008 2 2 Total 169 25 Italy USA Canada 1 1 1 Saudi Arabia Japan Netherlands Portugal Spain 1 1 1 3 1 4 1 3 1 1 1 3 2 5

CHARACTERISTICS OF TSEs • • • Prolonged incubation periods. Uniformly fatal neurological diseases. Causal agents (prions) resistant to sterilisation. No serological test for infection. Infection may be present in tissues (LRS) during the incubation period.

v. CJD case (Case 1) Donor onset Donation (RBC) Donor death Transfusion to recipient v. CJD case (Case 3) Donor onset Donation 1 (RBC) Recipient onset Donor death Recipient death Transfusion to recipient v. CJD case (Case 4) Donor onset Donation 2 (RBC) Recipient onset death Donor death Transfusion to recipient Pre-clinical infection (Case 2) Donation (RBC) Donor onset Donor death Transfusion to recipient RBC=red blood cells Recipient onset Years shown by quarter Recipient death

There is no evidence of transmission of any form of CJD through: • • • Social contact Treating minor injuries Occupational contact Maternal transmission Sexual transmission General surgery

EUROCJD & NEUROCJD Joint Meeting Lake Garda, Italy May 2003