J D Cooper1, S M Bird. 1. MRC Biostatistics Unit and Department of Medical Genetics, Cambridge, UK.
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.
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 vCJDpatients 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 vCJDpatients 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.