Transcript Slide 1

CJD Overview
Bob Will, National CJD Surveillance Unit, Edinburgh, UK
Associazione Italiana Encefalopatie da Prion
Milano 3 Ottobre 2009
Hans Creutzfeldt
Alfons Jakob
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
Country
Period
Austria
1969-1985
1986-1994
1995-2001
1970-1980
1987-1996
1997-2001
1955-1972
1973-1977
1978-1983
1972-1986
0.18
0.67
1.15
0.66
1.07
1.39
0.10
0.31
0.69
0.66
1968-1977
1978-1982
1993-2001
0.34
0.58
1.52
Australia
Chile
Czechoslovakia
France
Incidence:
Country
cases/million
Germany
1979-1990
1993a2001
0.31
1.14
Israel
1963-1972
1963-1987
0.75
0.91
Period
Incidence:
cases/million
Italy
1958-1971
1993-2001
0.05
1.10
Japan
1975-1977
1985-1996
0.45
0.58
Netherlands
1993-2001
1.00
New Zealand
Slovakia
1989-1989
1993-2001
0.88
1.17
Switzerland
1995-2001
1.50
UK
1964-1973
1970-1979
1980-1984
1985-1989
1993-2001
1973-1977
1983-1990b
1991-1998b
0.09
0.31
0.47
0.46
0.99
0.26
1.10
1.10
US
a Extrapolated from part-year data
b Age-adjusted to the standard US projected 2000 population
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
DISEASE
CAUSE
Sporadic Creutzfeldt-Jakob
disease (CJD)
Unknown
Iatrogenic CJD
Kuru
Human to human transmission
Variant CJD
Transmission of BSE to humans
Familial CJD
Gerstmann-Straussler syndrome Mutations of prion protein gene
Fatal Familial Insomnia
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
sCJD AD
vCJD
Dr Alison Green, The National CJD Surveillance Unit
SpCJD
ECDC funded meeting, 10th March 2009
MRI brain scan in sporadic CJD
MRI brain scan in variant CJD
MORTALITY RATES PER COUNTRY - (EUROCJD) 1993-2000)
FIGURE 2
Sporadic CJD
Genetic CJD
0.00 - 0.50
0.51 - 1.00
1.01 - 1.50
Iatrogenic CJD
0.00
0.01 - 0.05
0.07
0.17
0.00 - 0.10
0.11 - 0.15
0.16 - 0.80
Variant CJD
0.00
0.05
0.20
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
20
18
16
14
12
10
8
6
4
2
0
69
-
-
- 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96
Year
Operation
Onset
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/ Jan1990
DIFFERENCES BETWEEN SPORADICAND VARIANT CJD
SPORADIC CJD
VARIANT CJD
Mean age at death
66 years
29 years
Median duration of
illness
Thalamic MRI high
signal
4 months
13 months
Caudate/Putamen
60%
EEG
"Typical" 70%
Pulvinar
90%
"Typical" 0%
Neuropathology
Plaques
10%
Florid plaques
100%
180
160
140
120
100
sCJD
vCJD
Age Group
90+
85-89
80-84
75-79
70-74
65-69
60-64
55-59
50-54
45-49
40-44
35-39
30-34
25-29
20-24
80
60
40
20
0
15-19
Number of cases
AGE AT DEATH FOR SPORADIC CJD CASES
AND vCJD CASES
BY 5-YEAR AGE GROUP
Results
Temporal distribution of vCJD cases in France and UK
35
29
number of cases
30
24
25
20
17
vCJD in France
16
14
15
11
10
10
vCJD in UK
13
9
8
7
4
5
1
0
0
0
1995
1996
1997
1
1
1
1998
1999
2000
2
4
5
2
4
2
0
00
0
1994
2001
2002
2003
2004
2005
2006
2007
year of onset
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
YEAR OF ONSET OF ILLNESS OF vCJD 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
Nether
-lands
Portugal
Spain
1
1
1
1
1
1
1
1
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.
vCJD case
(Case 1)
Donor
onset
Donation (RBC)
90
Donor
death
80
Transfusion
to recipient
vCJD
70 case
(Case 3)
Recipient
onset
Donor
onset
Donation 1 (RBC)
Recipient
death
Donor
death
60
Transfusion to recipient
50
vCJD case
40 4)
(Case
30
Recipient Recipient
onset
death
Donor
onset
Donation 2 (RBC)
Donor
death
Transfusion to recipient
Pre-clinical
infection
20
(Case 2)
Donor
onset
Donation (RBC)
Recipient
onset
Donor
death
Recipient
death
10
Years shown by quarter
RBC=red blood cells
07-1
06-3
06-1
05-3
05-1
04-3
04-1
03-3
03-1
02-3
02-1
01-3
01-1
Recipient death
00-3
00-1
99-3
99-1
98-3
98-1
97-3
97-1
96-3
0
96-1
Transfusion to recipient
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
Number of Reported BSE cases,
vCJD Deaths (Probable & Definite) and vCJD Onsets
in the EC & the UK 1988-2008
40
50
35
45
30
35
25
30
20
25
15
20
15
10
10
5
5
0
0
1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008
Year
No. vCJD deaths
No. BSE cases ('000s)
40
UK BSE cases
('000s)
UK vCJD deaths
EC BSE cases
(x 100)
EC vCJD deaths
EUROCJD & NEUROCJD
Joint Meeting
Lake Garda, Italy May 2003