flatfish
11-20-2006, 02:28 PM
Subject: Human transmissible spongiform encephalopathies in eleven countries: diagnostic pattern across time, 1993-2002
Date: November 18, 2006 at 9:22 am PST
Human transmissible spongiform encephalopathies in
eleven countries: diagnostic pattern across time, 1993-
2002
Jesús de Pedro-Cuesta1§, Markus Glatzel2, Javier Almazán1, Katharina Stoeck3, Vittorio
Mellina4, Maria Puopolo4, Mauricio Pocchiari4, Inga Zerr5, Hans A Kretszchmar6, Jean-
Philippe Brandel7, Nicole Delasnerie-Lauprętre7, Annick Alpérovitch7, Cornelia Van
Duijn8, Pascual Sanchez-Juan8, Steven Collins9, Victoria Lewis9, Gerard H. Jansen10,
Michael B. Coulthart10, Ellen Gelpi11, Herbert Budka11, Eva Mitrova12 .
1
Instituto de Salud Carlos III, Centro Nacional de Epidemiologia, Departamento de
Epidemiologia Aplicada, Calle Sinesio Delgado 6, 28029, Madrid, Spain.
2Institute of Neuropathology, University Medical Center Hamburg-Eppendorf,
Martinistraße 52, D-20246 Hamburg, Germany
3Institute of Neuropathology, University Hospital Zurich, Switzerland.
4Registry of Creutzfeldt-Jakob disease, ?Department of Cell.Biology and
Neurosciences, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome, Italy.
5Department of Neurology, Georg-August-Universität Göttingen, Robert-Koch Strasse
40, 37075 Gottingen, Germany.
6Department. of Neuropathology, Ludwig-Maximilian University, Munich, Germany
7U.708 INSERM, Hopital de la Salpetriere, 75651 Paris, Cedex 13, France.
8Department of Epidemiology and Biostatistics, Erasmus MC, PO Box 1738, 3000 DR
Rotterdam, The Netherlands
9Australian National Creutzfeldt-Jakob disease Registry, Department of Pathology, The
University of Melbourne, Parkville, Australia.
10CJD Surveillance System, Division of Host Genetics and Prion Diseases, Public
Health Agency of Canada, LCDC Building, AL 0601E2, Tunney's Pasture, Ottawa,
Ontario, K1A 0L2, Canada.
11Institute of Neurology, Medical University of Vienna, and Austrian Reference Centre
for Human Prion Diseases, AKH 4J, A-1097 Vienna, Austria.
12Research base of Slovak Medical University, Bratislava, Slovakia.
§
Corresponding author
Abstract
Background
The objective of this study was to describe the diagnostic panorama of human
transmissible spongiform encephalopathies across 11 countries.
Methods
>From data collected for surveillance purposes, we describe annual proportions of deaths
due to different human transmissible spongiform encephalopathies in eleven
EUROCJD-consortium countries over the period 1993-2002, as well as variations in the
use of diagnostic tests. Using logistic models we quantified international differences
and changes across time.
Results
In general, pre-mortem use of diagnostic investigations increased with time.
International differences in pathological confirmation of sporadic Creutzfeldt-Jakob
disease, stable over time, were evident. Compared to their counterparts, some countries
displayed remarkable patterns, such as: 1) the high proportion, increasing with time, of
variant Creutzfeldt-Jakob disease in the United Kingdom, (OR 607.99 95%CI 84.72-
4363.40), and France (OR 18.35, 95%CI 2.20-152.83); 2) high, decreasing proportions
of iatrogenic Creutzfeldt-Jakob disease in France, (OR 5.81 95%CI 4.09-8.24), and the
United Kingdom, (OR 1.54 95%CI 1.03-2.30); and, 3) high and stable ratios of genetic
forms in Slovakia (OR 21.82 95%CI 12.42-38.33) and Italy (OR 2.12 95%CI 1.69-
2.68).
Conclusions
Considerable international variation in aetiological subtypes of human transmissible
spongiform encephalopathies was evident over the observation period. With the
exception of variant Creutzfeldt-Jakob disease and iatrogenic Creutzfeldt-Jakob disease
in France and the United Kingdom , these differences persisted across time.
SNIP...
Discussion
In terms of case numbers, this study constitutes the largest-scale observation of HTSE
ever conducted. Prior reports on this clinical population are sparse [10]. Taking into
account that neither mortality of HTSE nor population denominators are considered in
this study, the results suggest that: 1) the panorama of HTSE, as seen from deaths for all
or part of the 1993-2002 period in 11 countries, varies within and between countries,
sometimes exhibiting characteristic features; 2) there is an expected, overall rising time
trend in annual deaths and proportions of patients studied using ancillary tests other than
EEG; 3) characteristic national patterns, as seen from the magnitude of and time-trends
for proportions of specific entities, were particularly relevant in the UK and France for
vCJD and iCJD, and in Slovakia and Italy for gHTSE; 4) pathological confirmation of
sCJD varied but international differences persisted across time; and, 5) the additional
contribution of ancillary tests to sCJD diagnosis decreased to almost nil for EEG,
increased to stable figures for the 14.3.3 test, and was high and stable across time for
genetic assay insofar as gHTSE was concerned. The interpretation of these results is
complicated by several parameters, due to the fact that use of methods for diagnosing
HTSE, particularly CSF 14.3.3 test and MRI, improved significantly over the course of
the study period.
The eligibility of cases for this study based on vital status after death proved most
appropriate, since diagnostic criteria for probable sCJD may require measurement of
disease duration, <2 years, and quality of diagnosis is frequently determined by postmortem
examination. Diagnosis classification for probable cases is therefore neither
conditional to a specific disease course nor provisory. A rising time-trend in sCJD
incidence or mortality has been observed over the last decade in Austria, France,
Germany, Italy, Switzerland, the UK, and other countries [9,23-25] and has mainly been
attributed to progressive, persistent, improvement in sCJD diagnostic ascertainment
[26,27] or has gone unexplained [9]. This large dataset makes the EUROCJD countries
the most stable reference population for comparing HTSE incidence, e.g., that of sCJD
in specific age-groups. Nonetheless, undercounts due to poor reporting or case
ascertainment before 1998, likely due to different awareness and clinical management
of dementia prior to 14.3.3 CSF test, and incomplete case-finding after 2001 by
observation at death, suggest that the optimal time interval for incidence measurements
using this material should be carefully selected, e.g., 2000-2001 for sCJD.
With regard to changes across time, differences due to the presence of vCJD in the UK
and France are most remarkable. Abrupt changes in 1997 and 1998 for sCJD suggest a
strong impact of the first vCJD report [4] on diagnostic practices and the updating of
diagnostic criteria. Yet, interpretation of comparative linear time trends can sometimes
prove problematic. For instance, changes in average age at death might reflect improved
ascertainment for sCJD and an exposure-related cohort effect with increasing duration
of incubation period for iCJD.
CONTINUED...............
Date: November 18, 2006 at 9:22 am PST
Human transmissible spongiform encephalopathies in
eleven countries: diagnostic pattern across time, 1993-
2002
Jesús de Pedro-Cuesta1§, Markus Glatzel2, Javier Almazán1, Katharina Stoeck3, Vittorio
Mellina4, Maria Puopolo4, Mauricio Pocchiari4, Inga Zerr5, Hans A Kretszchmar6, Jean-
Philippe Brandel7, Nicole Delasnerie-Lauprętre7, Annick Alpérovitch7, Cornelia Van
Duijn8, Pascual Sanchez-Juan8, Steven Collins9, Victoria Lewis9, Gerard H. Jansen10,
Michael B. Coulthart10, Ellen Gelpi11, Herbert Budka11, Eva Mitrova12 .
1
Instituto de Salud Carlos III, Centro Nacional de Epidemiologia, Departamento de
Epidemiologia Aplicada, Calle Sinesio Delgado 6, 28029, Madrid, Spain.
2Institute of Neuropathology, University Medical Center Hamburg-Eppendorf,
Martinistraße 52, D-20246 Hamburg, Germany
3Institute of Neuropathology, University Hospital Zurich, Switzerland.
4Registry of Creutzfeldt-Jakob disease, ?Department of Cell.Biology and
Neurosciences, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome, Italy.
5Department of Neurology, Georg-August-Universität Göttingen, Robert-Koch Strasse
40, 37075 Gottingen, Germany.
6Department. of Neuropathology, Ludwig-Maximilian University, Munich, Germany
7U.708 INSERM, Hopital de la Salpetriere, 75651 Paris, Cedex 13, France.
8Department of Epidemiology and Biostatistics, Erasmus MC, PO Box 1738, 3000 DR
Rotterdam, The Netherlands
9Australian National Creutzfeldt-Jakob disease Registry, Department of Pathology, The
University of Melbourne, Parkville, Australia.
10CJD Surveillance System, Division of Host Genetics and Prion Diseases, Public
Health Agency of Canada, LCDC Building, AL 0601E2, Tunney's Pasture, Ottawa,
Ontario, K1A 0L2, Canada.
11Institute of Neurology, Medical University of Vienna, and Austrian Reference Centre
for Human Prion Diseases, AKH 4J, A-1097 Vienna, Austria.
12Research base of Slovak Medical University, Bratislava, Slovakia.
§
Corresponding author
Abstract
Background
The objective of this study was to describe the diagnostic panorama of human
transmissible spongiform encephalopathies across 11 countries.
Methods
>From data collected for surveillance purposes, we describe annual proportions of deaths
due to different human transmissible spongiform encephalopathies in eleven
EUROCJD-consortium countries over the period 1993-2002, as well as variations in the
use of diagnostic tests. Using logistic models we quantified international differences
and changes across time.
Results
In general, pre-mortem use of diagnostic investigations increased with time.
International differences in pathological confirmation of sporadic Creutzfeldt-Jakob
disease, stable over time, were evident. Compared to their counterparts, some countries
displayed remarkable patterns, such as: 1) the high proportion, increasing with time, of
variant Creutzfeldt-Jakob disease in the United Kingdom, (OR 607.99 95%CI 84.72-
4363.40), and France (OR 18.35, 95%CI 2.20-152.83); 2) high, decreasing proportions
of iatrogenic Creutzfeldt-Jakob disease in France, (OR 5.81 95%CI 4.09-8.24), and the
United Kingdom, (OR 1.54 95%CI 1.03-2.30); and, 3) high and stable ratios of genetic
forms in Slovakia (OR 21.82 95%CI 12.42-38.33) and Italy (OR 2.12 95%CI 1.69-
2.68).
Conclusions
Considerable international variation in aetiological subtypes of human transmissible
spongiform encephalopathies was evident over the observation period. With the
exception of variant Creutzfeldt-Jakob disease and iatrogenic Creutzfeldt-Jakob disease
in France and the United Kingdom , these differences persisted across time.
SNIP...
Discussion
In terms of case numbers, this study constitutes the largest-scale observation of HTSE
ever conducted. Prior reports on this clinical population are sparse [10]. Taking into
account that neither mortality of HTSE nor population denominators are considered in
this study, the results suggest that: 1) the panorama of HTSE, as seen from deaths for all
or part of the 1993-2002 period in 11 countries, varies within and between countries,
sometimes exhibiting characteristic features; 2) there is an expected, overall rising time
trend in annual deaths and proportions of patients studied using ancillary tests other than
EEG; 3) characteristic national patterns, as seen from the magnitude of and time-trends
for proportions of specific entities, were particularly relevant in the UK and France for
vCJD and iCJD, and in Slovakia and Italy for gHTSE; 4) pathological confirmation of
sCJD varied but international differences persisted across time; and, 5) the additional
contribution of ancillary tests to sCJD diagnosis decreased to almost nil for EEG,
increased to stable figures for the 14.3.3 test, and was high and stable across time for
genetic assay insofar as gHTSE was concerned. The interpretation of these results is
complicated by several parameters, due to the fact that use of methods for diagnosing
HTSE, particularly CSF 14.3.3 test and MRI, improved significantly over the course of
the study period.
The eligibility of cases for this study based on vital status after death proved most
appropriate, since diagnostic criteria for probable sCJD may require measurement of
disease duration, <2 years, and quality of diagnosis is frequently determined by postmortem
examination. Diagnosis classification for probable cases is therefore neither
conditional to a specific disease course nor provisory. A rising time-trend in sCJD
incidence or mortality has been observed over the last decade in Austria, France,
Germany, Italy, Switzerland, the UK, and other countries [9,23-25] and has mainly been
attributed to progressive, persistent, improvement in sCJD diagnostic ascertainment
[26,27] or has gone unexplained [9]. This large dataset makes the EUROCJD countries
the most stable reference population for comparing HTSE incidence, e.g., that of sCJD
in specific age-groups. Nonetheless, undercounts due to poor reporting or case
ascertainment before 1998, likely due to different awareness and clinical management
of dementia prior to 14.3.3 CSF test, and incomplete case-finding after 2001 by
observation at death, suggest that the optimal time interval for incidence measurements
using this material should be carefully selected, e.g., 2000-2001 for sCJD.
With regard to changes across time, differences due to the presence of vCJD in the UK
and France are most remarkable. Abrupt changes in 1997 and 1998 for sCJD suggest a
strong impact of the first vCJD report [4] on diagnostic practices and the updating of
diagnostic criteria. Yet, interpretation of comparative linear time trends can sometimes
prove problematic. For instance, changes in average age at death might reflect improved
ascertainment for sCJD and an exposure-related cohort effect with increasing duration
of incubation period for iCJD.
CONTINUED...............