ArticleThe Lancet regional health. Europe2025
Estimating future variant Creutzfeldt-Jakob disease cases in the UK: a cohort-based probabilistic model.
Article in The Lancet regional health. Europe, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Variant Creutzfeldt-Jakob disease (vCJD) is a fatal prion disorder linked to dietary exposure to bovine spongiform encephalopathy (BSE). The epidemic peaked in the early 2000s, and no new cases have been reported in the UK since 2016. However, uncertainties remain regarding potential future cases, particularly in individuals with non-MM prion protein gene codon 129 genotypes, and possible secondary transmission via blood transfusion. We aimed to update risk estimates with recent data, informed by a probabilistic modelling approach. Methods: We developed a cohort-based probabilistic model for variant CJD incidence incorporating genotype-specific attack rates and incubation periods, accounting for competing mortality risks. Model parameters were calibrated using historical case data and life-table analyses. We explored multiple scenarios, including sensitivity analyses with alternative incubation period distributions and potential missed diagnoses. Secondary transmission risk was assessed using historical transfusion-linked cases and epidemiological data. Findings: In the base-case scenario, our model estimates a 48% probability that no further vCJD cases will occur, with a mean forecast of 2.7 additional cases. Allowing for missed past cases, estimates increased to a mean of 3.0 cases (one missed case) and 4.9 cases (four missed cases). Sensitivity analysis using a Cauchy incubation period distribution rather than a log-normal distribution increased estimates to 6.6, 9.4, and 17.9 cases, respectively. A plausible worse-case scenario, assuming very long incubation times and higher susceptibility in non-MM individuals, projected up to 65 cases of vCJD over coming decades, peaking in the 2030s. Secondary transmission risk remains negligible given transfusion safety measures, including leukodepletion since 1999. Interpretation: Our findings suggest that vCJD is unlikely to re-emerge at significant levels. However, ongoing case ascertainment and scrutiny remains critical due to uncertainties in non-MM incubation and potentially, the emergence of previously unrecognised prion strains. Continued neuropathological case investigation, maintenance of core blood safety policies, and periodic risk reassessments are essential to ensure public health preparedness and avoid unnecessary restrictions. Funding: No specific funding other than salaries of the authors.
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