Projections of the future course of the primary vCJD epidemic in the UK: inclusion of subclinical infection and the possibility of wider genetic susceptibility

The incidence of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom appears to be in decline, with only four deaths reported this year (to 6 September 2004). However, results of a survey of lymphoreticular tissues have suggested a substantially higher prevalence of vCJD than expected from the clinical data alone. There are two plausible explanations for this discrepancy: first, a proportion of those infected will Hot develop clinical disease (subclinical infection); and second, the genetic group in which no clinical cases of vCJD have yet occurred is susceptible. Using mathematical models for the primary transmission of bovine spongiform encephalopathy to humans, we explore the impact of these hypotheses on case predictions. Under the first hypothesis, the results suggest relatively few future cases will arise via primary transmission, but that these cases are a small proportion of those infected, with most having subclinical infection. Under the second hypothesis, results suggest a maximum fivefold increase in cases, but this hypothesis is unable to account for the discrepancy between clinical cases and the estimated prevalence. Predictions of future cases of vCJD therefore remain uncertain, particularly given the recent identification of additional cases infected via blood transfusion.