vCJD World situation and Updates RG Will National CJD Research and Surveillance Unit Edinburgh, UK TSEAC meeting 1 st August 2011

NUMBER OF DEATHS PER ANNUM OF vCJD IN THE UK

CASES OF vCJD OUTWITH THE UK WITH RESIDENCE IN UK > 6 MONTHS FROM 1980 ONWARD Year Period resident in the UK Onset to death further measures to reduce human exposure to BSE 14 years 7 years 17 years 16 years 13 years 16 years 15 years 12 years 15 years

vCJD – BLOOD DONORS Total number of vCJD cases in the UK175 Number who were eligible to donate (ie aged  17)165 Number reported by relatives to have been blood donors 32 Number of cases where donor records have been traced 24* Number of cases from whom components were actually issued 18 Number of recipients identified from 18 cases where recipient and component information is available 67 *Donor records were traced on four cases where the relatives had reported the case not to be a donor. One of these had donated while the other 3 were registered as donors but never donated

LEGEND: Red blood cells / Whole bloodPlasma (leucodepleted) Red blood cells (leucodepleted)Cryo Red blood cells (buffy coat depleted) Platelets PlasmaPlatelets (leucodepleted) TIME FROM DONATION TO ONSET OF CLINICAL SYMPTOMS IN DONOR (YEARS) RECIPIENT SURVIVAL TO DEATH (YEARS) vCJD case (No. 1) PrP positivity in spleen (No. 2) Survival period (transfusion to death, n=49) for recipients of vCJD components according to interval between donation and onset of clinical symptoms in the donor vCJD case (No. 3) vCJD case (No. 4)

LEGEND:Red blood cells / Whole blood Red blood cells (leucodepleted) Plasma TIME FROM DONATION TO ONSET OF CLINICAL SYMPTOMS IN DONOR (YEARS) RECIPIENT SURVIVAL (YEARS) Survival of live recipients (n=18) of components from vCJD donors according to interval between donation and onset of clinical symptoms in donor (as at 31 March 2011)

Volume 50, May 2010 TRANSFUSION

1 102 ‘AT RISK’ DONORS HOSPITAL X 1989 HOSPITAL Y 1993 CASE B CASE A ? 27 OTHER RECIPIENTS

Median and posterior distributions of projected time series Cases: A: Total number B: Transfusion associated C: Unidentifiable transfusion associated Genotypes: D: MM E: MV F: VV

Input data: Time-dependence of the exposure of the British population to the BSE agent

UK CASES OF vCJD BY YEAR OF BIRTH

PLASMA FROM vCJD DONORS SENT FOR FRACTIONATION WITHIN UK YEAR SENTNUMBER OF UNITS TOTAL25

Detection of PrP res in the spleen of an adult haemophilic patient in the UK James W Ironside, Alex Peden, Mark W Head National CJD Surveillance Unit, University of Edinburgh, UK David M Keeling, Carolyn M Millar, Frank GH Hill, UK Haemophilia Centre Doctors’ Organisation, UK 15 February 2009

Patients with inherited bleeding disorders registered in the National Haemophilia Database on by diagnosis and subgroups at risk of vCJD for public health purposes.

Distribution of patients with bleeding disorders by estimated lifetime cumulated vCJD infectivity received (n=787)

Zaman et al Haemophilia ‘604/787 patients were followed up for more than 13 years following exposure to an implicated batch’ ‘For these 604 patients, the estimated vCJD risk is’: <1% for 595 > 50% for % for 51 ‘94 (16%) received implicated batches from donations within 6 months of clinical onset in the donor’ ‘151 (25%) received their first dose under 10 years of age.’

UK vCJD cases: exposure to plasma products 9 cases received products on 12 occasions 1970 – 1998 Low risk products 5 cases anti D (4 at childbirth) 4 cases im immunoglobulin (travel) Low/medium risk product 1 case albumin (?%) Batch number known for 4 products None donated from a known vCJD case

VARIANT CREUTZFELDT-JAKOB DISEASE CURRENT DATA (MAY 2011) COUNTRYTOTAL NUMBER OF PRIMARY CASES (NUMBER ALIVE) TOTAL NUMBER OF SECONDARY CASES: BLOOD TRANSFUSION (NUMBER ALIVE) RESIDENCE IN UK > 6 MONTHS DURING PERIOD UK172 (4)3 (0)175 France25 (0)-1 R of Ireland4 (0)-2 Italy2 (0)-0 USA3† (0)-2 Canada2 (0)-1 Saudi Arabia1 (0)-0 Japan1* (0)-0 Netherlands3 (0)-0 Portugal2 (0)-0 Spain5 (0)-0 Taiwan1 (0)-1 *the case from Japan had resided in the UK for 24 days in the period †the third US patient with vCJD was born and raised in Saudi Arabia and has lived permanently in the United States since late According to the US case-report, the patient was most likely infected as a child when living in Saudi Arabia.

What is the source of infection in non-UK vCJD P Sanchez-Juan et al. Emerging Infectious Diseases Correlation with indigenous BSE: r s = 0.44 (p = 0.1) Correlation with carcasse meat imports: r s = 0.6 (p = 0.02) Correlation with live bovine imports r s = 0.80 (p = 0.002)

VARIANT CREUTZFELDT-JAKOB DISEASE CURRENT DATA (MAY 2011) COUNTRYTOTAL NUMBER OF PRIMARY CASES (NUMBER ALIVE) TOTAL NUMBER OF SECONDARY CASES: BLOOD TRANSFUSION (NUMBER ALIVE) RESIDENCE IN UK > 6 MONTHS DURING PERIOD UK172 (4)3 (0)175 France25 (0)-1 R of Ireland4 (0)-2 Italy2 (0)-0 USA3† (0)-2 Canada2 (1)-1 Saudi Arabia1 (0)-0 Japan1* (0)-0 Netherlands3 (0)-0 Portugal2 (0)-0 Spain5 (0)-0 Taiwan1 (0)-1 *the case from Japan had resided in the UK for 24 days in the period †the third US patient with vCJD was born and raised in Saudi Arabia and has lived permanently in the United States since late According to the US case-report, the patient was most likely infected as a child when living in Saudi Arabia.

vCJD case in Taiwan Male, aged 34 years Duration of illness 28 months Psychiatric onset, pain, ataxia, myoclonus, dementia Codon 129: MM Pulvinar sign + No tonsil biopsy or necropsy Diagnosis: probable vCJD

Taiwan vCJD case Lived in the UK No BSE identified in Taiwan Presumed exposed in the UK

UK Customs Excise Data

TOTAL IMPORTS FROM UK (BASED ON UK CUSTOMS AND EXCISE DATA) Number Mammalian flours, meals and pellets Carcass meat Live Bovines 0

TOTAL IMPORTS FROM UK (BASED ON UK CUSTOMS AND EXCISE DATA) Number (000s) Mammalian flours, meals and pellets Carcass meat Live Bovines

Total Exports of MBM No data 0 - < < < < < < > Legend: (in tonnes)

Acknowledgements Neurologists and Neuropathologists throughout the UK All our collaborators in the UK and internationally All the staff at the NCJDSU Patients and their families Funded by the Department of Health, the Scottish Government, the European Union