Variant Creutzfeldt-Jakob Disease, fifteen years on

March 31 2009

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Variant Creutzfeldt-Jakob Disease, fifteen years on The epidemic of variant Creutzfeldt-Jakob Disease in France and in the United Kingdom involves the same disease, suggesting infection by the same strain of prion and shared risks of secondary transmission, notably post transfusion. This is what has been shown by the work by Jean-Philippe Brandel and Stéphane Haïk, researchers at the Prion Disease Team - Alzheimer's Disease from the Research Centre at the Brain and Spinal Cord Institute (Inserm - Pierre et Marie Curie University - CNRS) and neurologists from the national reference CJD unit in collaboration with researchers from Inserm Unit 708 "Neuroepidemiology" and the National CJD Surveillance Unit from the United Kingdom. The results of these works are published in the journal Annals of Neurology, on line today.

The epidemic of variant Creutzfeldt-Jakob Disease (vMCJ) began in France and in the United Kingdom in 1994 and now affects a large number of countries in the European Union and the rest of the world. It was very quickly linked to the epidemic of bovine spongiform encephalopathy or mad cow disease which emerged in the United Kingdom in the 1908s. Very widespread exposure of the population to the bovine prion from eating products from infected animals entering the food chain led to an initial fear of a large epidemic, particularly as many unknown factors (length of the incubation period, minimum affecting dose, etc.) made it difficult to model the epidemic precisely.

In recent years, forms of the disease associated with infection from blood transfusion have emerged in the United Kingdom, confirming the increased risk of secondary transmission, the fear of which arose from the replication of this specific source of prion in lymphoid tissue seen in affected subjects.

Fifteen years after the start of the epidemic, Jean-Philippe Brandel and his co-workers felt that it was important to make a direct comparison of French and British patients. The work published today reviews the evolution of the epidemic.

Clinical and epidemiological data were collected similarly from the 23 patients affected in France and the 162 British patients. Similar methods were used in both countries for the biochemical and neuropathological studies.

The data obtained in this study co-ordinated by Stéphane Haïk showed that:

  • The clinical presentation, progression time, cerebral lesions, replication in lymphoid tissue and biochemical signature of the abnormal form of the prion protein which accumulates in affected organisms are identical in French and British patients.
  • The evolution of the epidemic in the two countries (beginning in 1994 in both countries, peak occurring five years later in France) and the published data on estimated exposure of theFrench and British population to at risk products from British beef carcases suggest an incubation period of approximately ten years. T
  • There is no mutation in the prion protein gene although all patients are "methionine codon 129 homozygous" for the gene coding for the prion protein (1), whereas in the general population, 50% homozygotes and 50% heterozygotes are usually found.

The set of results reported by MM. Brandel and Haik suggest that in both countries the disease is related to a single and the same strain of prion from a common infection source, with similar risks of secondary transmission. The disease has until now only been seen in people with a specific genetic make-up: the homozygous for codon 129 methionine.

The researchers, however, cannot exclude the development of cases of variant Creutzfeldt-Jakob Disease in people with different genotypes in the future, as has been seen in other epidemics such as kuru (a historical prion disease associated with ritual cannibalism practices) and the iatrogenic form of Creutzfeldt-Jakob Disease secondary to treatment with growth hormone of human origin.

The authors also believe that it is possible, for these genotypes, that the infection is limited to that of asymptomatic carriage of the pathogenic agents with risks of secondary transmission following blood transfusion or invasive medical or surgical procedures. This last point justifies the precautionary measures which have been used for several years.

(1) A polymorphism of codon 129 of the prion protein gene exists which can code for two different amino acids: either a methionine or a valine. Each person has two versions (or alleles) of the same gene and can therefore either be homozygote (the two alleles are identical) for methionine or homozygote for valine or heterozygote (the two alleles are different) for methionine-valine. In France, and more generally in Europe, the distribution of codon 129 genotypes in the general population is 50% heterozygotes, 40% methionine homozygotes, 10% valine homozygotes.

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"Variant Creutzfeldt-Jakob Disease in France and the United Kingdom: Evidence for the Same Agent Strain"

Jean-Philippe Brandel, MD,1-3 C. A. Heath, MD,4 M. W. Head, PhD,5 E. Levavasseur, PhD,2 R. Knight, MD,5 J. L. Laplanche, PharmD, PhD,6 J. P. Langeveld, PhD,7 J. W. Ironside, MD,5 J. J. Hauw, MD,2,8 J. Mackenzie,5 A. Alpérovitch, MD,1 R. G. Will, MD,5 S. Haïk, MD, PhD2,3,8

1Institut National de la Sante et de la Recherche Médicale, U 708;
2. Institut National de la Sante et de la Recherche Médicale, Equipe Avenir Human Prion Diseases;
3. AP-HP, Hôpital de la Salpêtrière, Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob, Paris, France;
4. Department of Neurology, Ninewells Hospital, Dundee;
5. National Creutzfeldt-Jakob Disease Surveillance Unit, Western General Hospital, Edinburgh, United Kingdom;
6. AP-HP, Hôpital Lariboisière, Service de Biochimie et de Biologie Moléculaire, Paris, France;
7. Central Veterinary Institute of Wageningen UR (CVI), Lelystad, the Netherlands; and
8. AP-HP, Hôpital de la Salpêtrière, Laboratoire Raymond Escourolle, Paris

Annals of Neurology, March issue

Researcher contacts

Jean-Philippe Brandel
Tel.: 01 42 16 26 26

Stéphane Haïk
Tel.: 01 42 16 26 26

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