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

3. Science 1968

4. 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?

5. SYSTEMATIC STUDIES OF CJD WORLDWIDE

7. DISTRIBUTION OF SPORADIC CJD IN THE UK: 1990-2002

8. AUTHORMETHODRISK FACTORS Bobowick et al. (1973)38 “selected” cases; healthy controls.None. Kondo & Kuroiwa (1982)Population study: 60 cases, healthy controls trauma in males. Kondo (1985)88 autopsied cases; autopsied controls organ resection. Davanipour et al (1985)26 cases; 40 controlstrauma or surgery to head or neck; other trauma; surgery needing sutures; tonometry Davanipour et al (1985)26 cases; 40 controlsroast pork, ham, underdone meat, hot dogs. Davanipour et al (1985)26 cases; 40 controlscontact with fish, rabbits, squirrels. Harries-Jones et al (1980)92 cases; 184 controlsHerpes Zoster; keeping cats; contact with pets other than cats/dogs; dementia in family Van Duijn et al (1998)405 cases; 405 controlsconsumption 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 controlsnumber of surgical procedures; residence or employment on a farm or market garden. Ward et al (2002)326 cases; 326 controlssurgery, especially in females; ear piercing, psychiatric consultation. SIGNIFICANT RISK FACTORS IN CONTROLLED STUDIES

9. HUMAN TSEs (Prion diseases HUMAN TSEs (Prion diseases

10. 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

11. CSF Analysis Dr Alison Green, The National CJD Surveillance Unit ECDC funded meeting, 10 th March 2009 sCJD AD vCJD SpCJD 14-3-3 Western Blot

12. MRI brain scan in sporadic CJD

13. MRI brain scan in variant CJD

15. IATROGENIC CREUTZFELDT-JAKOB DISEASE WORLDWIDE Mode of infection No. of patients Agent entry into brain Mean incubation period (range) Clinical signs on presentation Corneal transplant2Optic nerve18, 320 moDementia, cerebellar Stereotactic EEG2Intra-cerebral16, 20 moDementia, cerebellar Neurosurgery4Intra-cerebral17 mo (12-28)Visual/dementia/cerebellar Dura mater graft209Cerebellar surface11 yr (1.5-23)Cerebellar (visual, dementia) Growth hormone203Hematogenous(?)15 yr (4-36)Cerebellar Gonadotrophin4Hematogenous (?)13 yr (12-16)Cerebellar Blood transfusion3 (+1)Hematogenous6.5, 7.5, 8.5 yrSensory, psychiatric

16. 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)

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

19. ‘BSE posed the greatest political and economic challenge to the EU since its foundation’ The specified bovine offal ban UK Dec 1989/ Jan1990 The UK BSE epidemic

21. DIFFERENCES BETWEEN SPORADICAND VARIANT CJD

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

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

24. YEAR OF ONSET OF ILLNESS OF vCJD WORLDWIDE Year Onset UKFranceIrelandItalyUSACanadaSaudi Arabia JapanNether -lands PortugalSpain 199481 199510 199611 199714 1998171 19992911 2000241 20011721111 200214 2003521 2004972111 200554111 200634111 200713 2008221 Total16925413111325

25. 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.

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

28. 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

30. EUROCJD & NEUROCJD Joint Meeting Lake Garda, Italy May 2003