Incubation period of Creutzfeldt-Jakob disease in human growth hormone recipients in France.

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.

A statistical model to identify the contaminated lots implicated in iatrogenic transmission of Creutzfeldt-Jakob disease among French human growth hormone recipients.

From 1970 to 1988, thousands of children have been treated with human growth hormone (hGH) to supply pituitary gland deficiency. In France, 51 of the 968 children treated by hGH lots produced between January 1984 and March 1985 had developed Creutzfeldt-Jakob disease (CJD) by the end of 1996. The authors' objective was to investigate which of the 13 hGH lots produced during this period might be implicated in the iatrogenic transmission of CJD. In this paper, the authors describe a model that was developed to compute the probability for each lot of being contaminated. The validity of the model was assessed by a simulation study that showed a good agreement between the estimated and the simulated number of contaminated lots. The model suggested that about half of the lots distributed during this period might have been contaminated by the infectious agent that causes CJD. The risk of iatrogenic CJD for patients exposed to contaminated hGH lots was estimated to be 0.06 (95% confidence interval 0.05-0.07).