Elsevier

The Lancet

Volume 351, Issue 9109, 11 April 1998, Pages 1081-1085
The Lancet

Articles
Case-control study of risk factors of Creutzfeldt-Jakob disease in Europe during 1993-95*

https://doi.org/10.1016/S0140-6736(97)09468-3Get rights and content

Summary

Background

Creutzfeldt-Jakob disease (CJD) is a transmissible spongiform encephalopathy. Genetic and iatrogenic forms have been recognised but most are sporadic and of unknown cause. We have studied risk factors for CJD as part of the 1993-95 European Union collaborative studies of CJD in Europe.

Methods

The 405 patients with definite or probable CJD who took part in our study had taken part in population-based studies done between 1993 and 1995 in Belgium, France, Germany, Italy, the Netherlands, and the UK. Data on putative risk factors from these patients were compared with data from 405 controls.

Findings

We found evidence for familial aggregation of CJD with dementia due to causes other than CJD (relative risk [RR] 2·26, 95% CI 1·31-3·90). No significant increased risk of CJD in relation to a history of surgery and blood tranfusion was shown. There was no evidence for an association between the risk of CJD and the consumption of beef, veal, lamb, cheese, or milk. No association was found with occupational exposure to animals or leather. The few positive findings of the study include increased risk in relation to consumption of raw meat (RR 1·63 [95% CI 1·18-2·23]) and brain (1·68 [1·18-2·39]), frequent exposure to leather products (1·94 [1·13-3·33]), and exposure to fertiliser consisting of hoofs and horns (2·32 [1·38-2·91]). Additional analyses, for example stratification by country and of exposures pre-1985 and post-1985, suggest that these results should be interpreted with great caution.

Interpretation

Within the limits of the retrospective design of the study, our findings suggest that genetic factors other than the known CJD mutations may play an important part in CJD. Iatrogenic transmission of disease seems rare in this large population-based sample of patients with CJD. There is little evidence for an association between the risk of CJD and either animal exposure, or consumption of processed bovine meat or milk products for the period studied.

Introduction

Creutzfeldt-Jakob disease (CJD) is the most clinically significant spongiform encephalopathy in man.1, 2 Although the disease is rare,3 the rapid development of bovine spongiform encephalopathy (BSE) from a sporadic to an endemic disease in cattle in the UK4 underscores the potential transmissibility of these diseases. The discovery of a new variant (nv) of CJD in the UK following the BSE5 epidemic has re-opened discussion on whether spongiform encephalopathies may be transmitted from animals to man. Also, the potential of iatrogenic transmission of CJD remains a matter of concern. CJD has been transmitted from person to person through human pituitary derived growth and gonadotropin hormones,6, 7, 8, 9 neurosurgery and electroencephalography electrode implantation,10, 11, 12, 13 and corneal transplantation.14 Up until now there has been no epidemiological evidence of transmission through blood transfusion,15 but research in animal models indicates that this possibility cannot be excluded.16, 17 Here, we present the findings of a collaborative study of risk factors for CJD in Europe, in which genetic factors, medical history, occupational history, animal exposure, and diet were studied.

Section snippets

Patients and methods

The study was embedded within the European Union (EU) collaborative studies monitoring the incidence of CJD in Belgium (Flanders only), France, Germany, Italy, the Netherlands, and the UK.3 The registers aimed to ascertain all patients diagnosed with definite or probable CJD living in a defined geographical area, mainly at the national level. A standardised diagnostic protocol was used according to the criteria of Masters and colleagues.18 The pooled data set of 613 cases of CJD described

Results

54 cases and 22 controls had a positive family history of dementia other than CJD. In the cases of CJD the frequency of dementia in first degree relatives proved to be 2·26 (95% CI 1·31-3·90) that of the controls. Table 1 shows the medical history in patients and controls. Surgery of the vertebral column was found less often among cases, whereas there was a non-significant increase in the risk of CJD associated with surgery of the brain. A history of blood transfusion, electromyography, and

Discussion

In our collaborative study of risk factors of CJD, we found evidence for familial aggregation of CJD with dementia due to causes other than CJD. We did not find significant evidence for iatrogenic transmission of CJD. With regard to the exposures to animals and animal products studied, a significant increase in risk of CJD was found for cases exposed to leather products and fertiliser containing hoofs and horns. Of the dietary factors studied, the consumption of brain and raw meat were

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    *

    Members of the EU Collaborative Study Group of CJD are listed at end of paper

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