Predicting incidence of variant Creutzfeldt-Jakob disease from UK dietary exposure to bovine spongiform encephalopathy for the 1940 to 1969 and post-1969 birth cohorts

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Abstract
Background To investigate variant Creutzfeldt-Jakob disease (vCJD) incubation period, transmission barrier, and short-term vCJD predictions for methionine homozygotes in 1940–1969 and post-1969 birth cohorts by use of gender- and age-specific exposure intensities to bovine spongiform encephalopathy (BSE), based on consumption of beef mechanically recovered meat (MRM) and head meat. Methods Simulation (from vCJD infections generated randomly from gender and age-specific dietary exposure intensities to BSE), constrained to equal the 47 and 64 vCJD onsets before 2001 in 1940–1969 and post-1969 birth cohorts, was used to estimate lognormal (and other) incubation mean and standard deviation which fitted the calendar year distribution of observed vCJD onsets; and to explore exponential decay in susceptibility to infection with age above 15 years. Results For the post-1969 birth cohort, the best-fitting lognormal incubation period mean of 11 years (SD 1.5 years and 195 infections) was associated with 194 vCJD onsets (64 before 2001, 105 in 2001–2005, and 25 in 2006–2010). About one-fifth of simulated vCJD onsets before 2001 arose from infections in 1990–1996; age and gender of simulated and observed vCJD patients agreed closely. For the 1940–1969 birth cohort, well-fitting lognormal means ranged widely, the marginally best fitting being 26 years (SD 16.5 years and 382 infections; 47 vCJD onsets before 2001, 58 in 2001–2005, and 63 in 2006–2010). An age-dependent susceptibility function was required to match the age distribution of vCJD patients in the 1940–1969 birth cohort. Conclusions About three-fifths of predicted vCJD onsets are expected to be in males, and nearly two-thirds of vCJD onsets in 2001–2005 are expected to be in post-1969 birth cohort according to best-fitting predictions.