Prevalence of detectable abnormal prion protein in persons incubating vCJD: plausible incubation periods and cautious inference.

Abstract

Background: Both small and large variant Creutzfeldt Jakob disease (vCJD) epidemics are consistent with the current observed incidence. Uncertainty in vCJD projections could potentially be reduced by incorporating information on the prevalence of the infectious agent in persons incubating vCJD. The prospect of vCJD prevalence studies has been raised by detection of abnormal prion protein, thought to be the infectious agent, in appendices and tonsils removed from vCJD patients. Although unlinked anonymous testing of stored operative tissues for abnormal prion protein is very appealing, the design and interpretation of such prevalence studies is complicated by the lack of information on how early in the incubation period of vCJD the abnormal prion protein becomes detectable.

Methods: We simulate a range of vCJD epidemics, consistent with the limited available information on the incidence of vCJD, to illustrate some of the potential problems encountered when interpreting the results from prevalence studies of detectable abnormal prion protein. We assume plausible incubation period distributions and dietary exposure patterns.

Results: We demonstrate, in the context of our simulated epidemics, that prevalence studies of detectable abnormal prion protein would require the testing of tens of thousands of operative specimens and, even then, that unlinked anonymous testing positives would be unexpected.