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From the Unité de Recherches Epidémiologiques en Neurologie et Psychopathologie, INSERM U360 (Drs. Huillard d’Aignaux, Brandel, Hauw, and Alpérovitch), the Centre National de Référence de la Maladie de Creutzfeldt–Jakob Iatrogène (Drs. de Villemeur, Brandel, and Agid), the Laboratoire de Neuropathologie (Dr. Hauw), the Hôpital de la Salpêtrière, Paris; INSERM U444 and SC4 (Dr. Costagliola), Institut Saint-Antoine de Recherches en Santé, Université Pierre et Marie Curie, Paris; Unité de Recherches en Epidémiologie (Dr. Maccario), INSERM U472, Villejuif; the Laboratoire de Neurovirologie (Drs. Deslys and Dormont), C.E.A., Fontenay aux Roses; and the Hôpital Saint-Vincent de Paul (Dr. Chaussain), Paris, France.
Address correspondence and reprint requests to Dr. A. Alpérovitch, INSERM Unité 360, Hôpital de la Salpêtrière, 75651 Paris Cedex 13, France; e-mail: alperovi{at}vjf.inserm.fr
OBJECTIVE: To estimate the statistical distribution of the incubation period of Creutzfeldt–Jakob disease (CJD) in human growth hormone (hGH) recipients in France.
BACKGROUND: Published papers suggest that the median incubation period of hGH-related CJD is approximately 15 years, but there are as yet no statistical data that support this assertion.
METHODS: Of the 1,361 hGH recipients who were included in this study, 55 had developed CJD at the time of the study. Individual data on hGH treatment history were available. Different mathematical models were used to estimate the statistical distribution of the incubation period. One main feature of the models was to take into account the occurrence of future CJD cases.
RESULTS: Models showed that the mean incubation period was 9 to 10 years, and the 95th percentile of the distribution was 15 to 16 years. Data and models indicated that the incubation period was significantly shorter in homozygotes at codon 129 of the prion protein gene than in heterozygotes.
CONCLUSIONS: The short mean incubation period of CJD in French hGH recipients may be due to high infectivity in hormone lots. Estimates of the 95th percentile indicate that the number of hGH-related CJD cases may continue to increase in the coming years.
Key words: Creutzfeldt–Jakob disease—Incubation period—Hormone—Iatrogenic disease—Models—statistical.
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