vCJD World situation and Updates

RG WillNational CJD Research and Surveillance Unit

Edinburgh, UKr.g.will@ed.ac.uk

TSEAC meeting

1st August 2011

NUMBER OF DEATHS PER ANNUM OF vCJD IN THE UK

3

10 10

1815

28

2017 18

95 5 5

13 3

10

5

10

15

20

25

30

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

CASES OF vCJD OUTWITH THE UKWITH RESIDENCE IN UK > 6 MONTHS FROM 1980 ONWARD

YearPeriod 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 DONORSvCJD – BLOOD DONORS Total number of vCJD cases in the UK 175

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 blood Plasma (leucodepleted)Red blood cells (leucodepleted) CryoRed blood cells (buffy coat depleted) PlateletsPlasma Platelets (leucodepleted)

TIME FROM DONATION TO ONSET OF CLINICAL SYMPTOMS IN DONOR (YEARS)

REC

IPIE

NT

SUR

VIVA

L TO

DEA

TH (Y

EAR

S)

vCJD case (No. 1)

PrP positivity in spleen (No. 2)

Survival period (transfusion to death, n=49) for recipients of vCJDcomponents 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 bloodRed blood cells (leucodepleted)Plasma

TIME FROM DONATION TO ONSET OF CLINICAL SYMPTOMS IN DONOR (YEARS)

REC

IPIE

NT

SUR

VIVA

L (Y

EAR

S)

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 X1989

HOSPITAL Y1993

CASE B

CASE A

?

27 OTHER RECIPIENTS1989-2005

Median and posterior distributions of projected time series

Cases:A: Total numberB: Transfusion associated C: Unidentifiable transfusion associated

Genotypes:D: MME: MVF: VV

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

BSE agent

UK CASES OF vCJDBY YEAR OF BIRTH

PLASMA FROM vCJD DONORS SENT FOR FRACTIONATION WITHIN UK

YEAR SENT NUMBER OF UNITS1986 1

1987 4

1989 1

1990 2

1991 1

1992 3

1993 2

1994 2

1995 2

1996 4

1997 2

1998 1

TOTAL 25

Detection of PrPres 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, UKDavid 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 1.1.2009 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 164100% 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 product1 case albumin (?%)

Batch number known for 4 productsNone donated from a known vCJD case

European and International CJD Surveillance Network 1993-2009

2009: 34

2005: 322004: 312002: 261998: 21

1993: 71996: 11

2006: 33

Year/No. countries

Not to scale

VARIANT CREUTZFELDT-JAKOB DISEASECURRENT DATA (MAY 2011)

COUNTRY TOTAL NUMBER OF PRIMARY CASES

(NUMBER ALIVE)

TOTAL NUMBER OF SECONDARY CASES: BLOOD TRANSFUSION

(NUMBER ALIVE)

RESIDENCE IN UK > 6 MONTHS

DURING PERIOD 1980-1996

UK 172 (4) 3 (0) 175France 25 (0) - 1R of Ireland 4 (0) - 2Italy 2 (0) - 0USA 3† (0) - 2Canada 2 (0) - 1Saudi Arabia 1 (0) - 0Japan 1* (0) - 0Netherlands 3 (0) - 0Portugal 2 (0) - 0Spain 5 (0) - 0Taiwan 1 (0) - 1

* the case from Japan had resided in the UK for 24 days in the period 1980-1996.† the third US patient with vCJD was born and raised in Saudi Arabia and has lived permanently in the United States since late

2005. 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 vCJDP Sanchez-Juan et al. Emerging Infectious Diseases

• Correlation with indigenous BSE: rs = 0.44 (p = 0.1)

• Correlation with carcasse meat imports: rs = 0.6 (p = 0.02)

• Correlation with live bovine imports rs= 0.80 (p = 0.002)

VARIANT CREUTZFELDT-JAKOB DISEASECURRENT DATA (MAY 2011)

COUNTRY TOTAL NUMBER OF PRIMARY CASES

(NUMBER ALIVE)

TOTAL NUMBER OF SECONDARY CASES: BLOOD TRANSFUSION

(NUMBER ALIVE)

RESIDENCE IN UK > 6 MONTHS

DURING PERIOD 1980-1996

UK 172 (4) 3 (0) 175France 25 (0) - 1R of Ireland 4 (0) - 2Italy 2 (0) - 0USA 3† (0) - 2Canada 2 (1) - 1Saudi Arabia 1 (0) - 0Japan 1* (0) - 0Netherlands 3 (0) - 0Portugal 2 (0) - 0Spain 5 (0) - 0Taiwan 1 (0) - 1

* the case from Japan had resided in the UK for 24 days in the period 1980-1996.† the third US patient with vCJD was born and raised in Saudi Arabia and has lived permanently in the United States since late

2005. 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 1989-1997• 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)

100

200

300

400

500

600

700

800

Num

berM

amm

alia

n flo

urs,

mea

ls a

nd p

elle

tsC

arca

ss m

eat Live B

ovines

0

TOTAL IMPORTS FROM UK(BASED ON UK CUSTOMS AND EXCISE DATA)

0100

200

300

400

500

600

700

800

900

1000

1100

1200

13001400

1500

1600

1700

France Germany Netherlands Italy

Tonn

es (0

00s)

Mammalian flours, meals and pellets (1980-1997) Carcass Meat (1978-1999) Live Bovines (1980-1990)

100 200 300

400

500

600

700

800

Num

ber (000s)M

amm

alia

n flo

urs,

mea

ls a

nd p

elle

tsC

arca

ss m

eat

Live Bovines

0

90010001100

1200

130014001500

16001700

Total Exports of MBM 1986 -1995

No data

0 - < 5

5 - < 10

10 - < 20

20 - < 100

100 - < 1.000

1.000 - < 10.000

> 10.000

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