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Creutzfeldt-Jakob Disease: results of an inquiry in the fifteen Member States of the European Union

L Chambaud¹, PWJ Peters ¹, BC Merkel ²
1 Expert National Détaché, Commission Européenne; Luxembourg
2 Agent temporaire, Commission Européenne; Luxembourg

Introduction

Creutzfeldt-Jakob Disease (CJD) was first described in 1920-1921. CJD is a rare disease with a reported incidence of 0.5 to 1 case per million people in Europe (1). This fatal dementia belongs to the category of Transmissible Spongiform Encephalopathies (TSE) whose human forms include Gerstmann-Sträussler-Scheinker syndrome, kuru and fatal familial insomnia, all of which are very rare. TSEs constitute “a group of subacute degenerative diseases of the brain, caused by ëunconventionalí filterable agents, with very long incubation periods and no demonstrable inflammatory or immune response” (2). CJD occurs most often in its sporadic form, although in about 10% of cases a genetic origin can be found. CJD has also developed after organ transplants or treatment with human growth hormone obtained from corpses infected with the agent.

Some TSEs also affect animal species. The oldest is Scrapie in sheep, which has been known in Europe since 1732. This can also occur in other animals, such as minks, elks and stags. Bovine spongiform encephalopathy (BSE) (3) was first described in the United Kingdom in 1987. Since then BSE has spread among British cattle, with the highest annual incidence reported being 36 681 confirmed cases in 1992. Concern has been growing about the possibility of transmission between species, and particularly of transmission of the agent from animals to humans (4).

A report in the Lancet of 6 April 1996 described 10 cases of new variant CJD (NV-CJD) discovered among cases diagnosed in recent years in the UK. This led to a huge crisis of confidence among the member states of the European Community over the safety of beef. With regard to the aetiology of the cases, the Lancet paper concluded, “That it is due to exposure to the BSE agent is perhaps the most plausible interpretation of our findings” (5).

The data available at European level have been mainly collected by means of a collaborative surveillance project established in 1993 which involves five member states: the UK, France, Germany, Italy and the Netherlands. In order to obtain information both on surveillance methods in Europe and on the epidemiological data collected, the European Commission (Public Health Unit) sent a questionnaire to the 15 member states. The data presented here come from the responses to that questionnaire.

Methods

A questionnaire was sent to each member state in April 1996. The recipients of the questionnaires were identified by means of the member statesí official representations to the European Community. All member states replied. To obtain further detail, a second questionnaire was sent out in July 1996, to which again all the states replied. This questionnaire sought information on centres of expertise in the fields of epidemiology and neuropathology, on the measures taken nationally to provide information to consumers and to prevent the disease, and on data on CJD since 1990. Only the replies on this last topic are presented here.

Results

The data collected concern the surveillance of CJD as a whole. The distribution of confirmed cases is set out in table 1. The cases are presented by year of diagnosis. When a case definition was detailed in the reply it was related to the definitions developed by the five country collaborative surveillance project mentioned above. This project drew a distinction between possible cases (clinical indications), probable cases (clinical indications and EEG evidence) and certain cases (cases confirmed by standard neuropathological techniques and/or other specific methods) (6).

From table 1 it is clear that there was a lack of consensus on the way to report confirmed cases in this survey although a consensus definition is given in the collaborative study; some countries included only certain cases, others both certain and probable cases, and the UK reported deaths only, although numbers of certain and probable cases have been published in that country.

The diversity of definitions is reinforced by table 2 on suspect cases. The questionnaire asked for data on cases that were suspected but not confirmed. Some member states provided all the cases referred to the surveillance unit, whether or not they had been investigated; others took as the only criterion the presence of clinical indications; still others included the presence of a characteristic EEG; Austria did not report suspected case; finally, some countries used the death certificate as a criterion without providing any other details.

Table 3 further strengthens the case for data to be presented in a standard form. In effect some member states calculate incidence on the basis of suspected cases, others on the basis of confirmed cases. There is no clear trend in the incidence of CJD in any of the countries able to supply data on incidence rates since 1990.

Only two member states (France and the UK) have encountered NV-CJD and incorporated it in the data for confirmed cases. Member states also differ in their policies on the inclusion of other TSEs. Thus France, Germany and the UK include these familial forms, but Austria and the Netherlands do not. France excludes cases of iatrogenic CJD resulting from the use of human growth hormone.

Discussion

Definitions used by the States vary, both for confirmed and suspected cases and in how the incidence of CJD is calculated. There are several reasons for the differences:

Several countries do not have yet a system enabling suspected cases to be confirmed and rely entirely on suspicions generated by death certificates.

Our questionnaire asked for suspected and confirmed cases to be differentiated, whereas the definitions proposed in the context of the five-state collaborative surveillance project distinguished three different levels (possible, probable and certain cases). Some of the disparities can therefore be explained by different interpretations of the question. Different interpretations of the term " suspected case " can partly explain why some countries, such as France and Italy, have fewer suspected than confirmed cases each year whereas with UK the reverse is true (table 2). Moreover, the differences seen could be due to different post mortem rates between countries leading to a classification bias, affecting both confirmed and suspected cases if other degenerative diseases (Alzheimerís, for example) are wrongly diagnosed as CJD.

The annual incidences of CJD in member states are generally between 0.5 and 1 case per million, the exceptions being Luxembourg and Belgium and to a lesser extent Austria and Sweden. However two points must be stressed:

The numerators used vary greatly depending on the nature of the data available and how cases are understood (suspected, confirmed or both).

Incidence is particularly inaccurate in countries where very few cases arise each year. This is well illustrated by the example of Luxembourg where one case each year produces an incidence of 2.5 per million.

These partial explanations still leave real doubts about the comparability of the data between member states. Harmonisation of surveillance would be very valuable for a disease whose reported incidence is very low and there would be clear advantages in analysing the data at a supranational level.

It is difficult to see a clear trend in the evolution of CJD since 1990 either in the total numbers or in the incidence data. The fact that no increase is apparent must be interpreted cautiously. Firstly it is difficult to verify that the methods of data collection and of case confirmation in each country have not changed since 1990. Secondly, in most countries surveillance began only recently (only seven states can provide data from 1992). Finally, a real increase could be disguised by the lengthy periods between the appearance of the first signs of the disease and its confirmation and between confirmation and notification.

The data presented for 1993 to 1995 show no change in the proportion of confirmed cases among people under 60 years of age. Cases of NV-CJD have been found among young people (aged from 16 to 39 in the first published set). If the age criterion remains, it will be important to be able to follow changes in the number of cases in the youngest age groups throughout Europe.

In the light of this inquiry, it therefore seems indispensable:

to draw up common criteria for the fifteen member states both for the collection of information on CJD surveillance and for the analysis and diffusion of the results of this surveillance. Such coordination throughout Europe would enable the surveillance of the incidence of CJD and its different forms, including NV-CJD, and to detect any unusual trends in one or more countries. It could also help to calculate a baseline of expected cases both in Europe as a whole and in individual countries considering the very few cases diagnosed and notified each year. In addition, in the light of the work confirming the connections between BSE and NV-CJD (7), this surveillance should be closely linked to surveillance of animal TSEs.

to set up a study to examine in each member state all the steps towards confirmation and notification of a CJD case. This would clarify our understanding of the population referred as suspected cases of CJD and enable the sensitivity of the surveillance systems to be evaluated.

The questionnaire of this study is available from the authors at the Commission of the European Communities, DGV - F/21, Bât. J. Monnet, C4/107 Plateau du Kirchberg, L 2920 Luxembourg.

References

1. Alperovitch A., Brown P., Weber T., Pocchiari M., Hofman A., Will R. Incidence of Creutzfeldt-Jakob disease in Europe in 1993. Lancet 1994; 343:918

2. Benenson A.S., Ed.: Control of Communicable Diseases Manual.. Washington: American Public Health Association, 1995

3. Patterson W.J.: Bovine spongiform encephalopathy and the public health. Journal of Public Health Medicine;17(3):261-268

4. Collee J.G.: BSE:stocktaking 1993. Lancet 1993; 342:790-3

5. Will R.G., Ironside J.W., Zeidler M., Cousens SN, Estibeiro A., Alperovitch A. et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996;347:921-25

6. World Health Organization. Division of Emerging and other communicable diseases surveillance and control: Report of a WHO consultation on clinical and neuropathological characteristics of the new variant of CJD and other human and animal transmissible spongiform encephalopathies. Geneva. WHO/EMC/ZOO/96.1

7. Collinge J., Sidle K.C.L., Meads J., Ironside J., Hill AF. Molecular analysis of prion strain variation and the aetiology of ënew variantí CJD. Nature 1996;383:685-90