Aug 10, 2000 - There is continued speculation about the likely number of cases of variant. CreutzfeldtâJakob disease (vCJD) that will occur in Great Britain in ...
brief communications
Predicted vCJD mortality in Great Britain Modelling the latest data puts a ceiling on the likely number of vCJD cases. here is continued speculation about the likely number of cases of variant Creutzfeldt–Jakob disease (vCJD) that will occur in Great Britain in the wake of the BSE epidemic in cattle and in light of a recent cluster of vCJD cases in Leicestershire, England. We show here that the current mortality data are consistent with between 63 and 136,000 cases among the population known to have a susceptible genotype (about 40% of the total population), with on average less than two cases of vCJD arising from the consumption of one infected bovine. Between 1980 and, roughly, 1996, about 750,000 cattle infected with BSE were slaughtered for human consumption in Great Britain1,2. The recent fall in the annual incidence of vCJD (3, 10, 10, 18 and 14 deaths in 1995–99, respectively) has been interpreted as showing the disease to be in decline3. However, the suggestion by the European Union Scientific Steering Committee that up to 500,000 people could have been exposed to BSE from a single infected bovine4 has fuelled speculation that millions of consumers are at risk. We used extensive scenario analyses to relate the number of infected cattle slaughtered for consumption1,2 to the incidence of vCJD stratified by time and age5, assuming that only those with the observed susceptible genotype (having two copies of the methionine codon at codon 129 of the PrP gene) are at risk (other genotypes may be resistant to infection or have longer average incubation periods). We explored a wide range of assumptions regarding the distribution of the vCJD incubation period, the relative infectivity of cattle by incubation stage, and the effectiveness of control measures at reducing human exposure to infected material5. The scenarios result from the exploration of over 5 million combinations of parameters. From the vCJD incidence in 1999, we can substantially reduce the uncertainty in the upper bound of the total number of cases among people with the susceptible genotype. Our earlier analyses showed that if
T
Figure 1 The range of vCJD epidemic scenarios consistent with the time- and age-stratified vCJD mortality data to the end of 1999. a, The age distribution (at death) of the 53 cases of vCJD confirmed to the end of 1999, as of 1 March 2000 (R. Will, personal communication). b, The relationship between mean incubation period (conditional on the incubation period being 91 years), the average number of vCJD cases arising from consumption of one late-stage (last 6 months of the incubation period) bovine and the total epidemic size. The probability that an individual develops clinical disease at time u and age a is u
p (u,a )4S(u,a)eu1a f (u1t,a1u& t t )I (t,a1u&t )exp(1e0 I(t8,a1u& t )dt8 )dt, with S(u,a) being the survival probability, f(u,a) the incubation period distribution and I (t,a8 )4n (t )bg(a8)eV (z )w (z,t )dz the infection hazard; n (t ) is the effectiveness of control measures, b the transmission coefficient, g(a) age-dependent susceptibility/ exposure, V(z ) the relative infectiousness of bovines time z before disease onset, and w (z,t ) the proportion of cattle slaughtered at time t and time z away from disease onset (estimates taken from ref. 2). We assume that the infectiousness of bovine tissues increases exponentially, doubling in the last 6 months of the bovine incubation period. We explored two forms for the age-dependent susceptibility/ exposure — a uniform distribution and a normal distribution truncated at zero. We modelled the age-dependent incubation period using the scaling f (u,a)4h (u )/s(a ), where h (u ) is an age-independent incubation period and s (a)4{a2exp(1a3a)&a1}/{exp(1a3a)&a1}. Each point represents a model scenario that is consistent at the 95% level with the marginal time- and age-stratified mortality data to the end of 1999 as of 1 March 2000.
fewer than 15 cases arose in 1999 in any age group, the upper bound on the number of cases in this population was approximately 500,000 (ref. 6). This is reduced to about 136,000 when the incidence in 1999 is combined with the observed stable age structure (Fig. 1a). Our model suggests that the age distribution of vCJD cases could not have arisen from an age-dependent incubation period alone (which would give rise to an increasing median age over time), and thus
Table 1 Projections for the eventual total number of vCJD cases Mean i.p. (years)
Number of cases in 2000
Average number of cases in 2000–02
10–14
15–19
20&
