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Assessment of the prevalence of vCJD through testing tonsils and appendices for abnormal prion protein
A C Ghani1, C A Donnelly, N M Ferguson
1Wellcome Trust Centre for the Epidemiology of Infectious Disease, University of Oxford, UK. azra.ghani@ceid.ox.ac.uk
Insights
Testing appendix or tonsil tissue from individuals aged 25-29 can best inform the potential size of the vCJD epidemic. Early detection of abnormal prion protein (PrP(Sc)) is crucial for accurate epidemic forecasting.
Area of Science:
- Epidemiology
- Prion Diseases
- Public Health
Background:
- Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative disorder.
- Accurate estimation of the vCJD epidemic size is crucial for public health planning.
- Detecting abnormal prion protein (PrP(Sc)) in accessible tissues can aid in surveillance.
Purpose of the Study:
- To identify optimal age groups for vCJD surveillance through tissue sampling.
- To determine the most informative tissue types (tonsil or appendix) for PrP(Sc) detection.
- To assess how testing reduces uncertainty in future vCJD epidemic size predictions.
Main Methods:
- A cohort- and time-stratified model was employed to simulate vCJD epidemic scenarios.
- Data on tonsillectomy and appendectomy age distributions were integrated.
- The model evaluated the informativeness of different age groups and tissue types for PrP(Sc) detection.
Main Results:
- The 25-29 year age group is optimal for tonsil testing; appendix testing across all ages is nearly as informative.
- Tonsil testing is less informative overall but improves with age restriction (>10 years).
- Zero detected infections in 1000 samples suggest <870,000 cases, with specific case numbers predicted based on detected infections.
Conclusions:
- Appendix or tonsil tissue sampling (age >10) is most informative for vCJD surveillance.
- Excluding large epidemics requires early detection of few infections.
- Informed surveillance strategies are vital for managing the vCJD public health threat.
Abstract:
The objective of this study was to determine the age group or groups which will provide the most information on the potential size of the vCJD epidemic in Great Britain via the sampling of tonsil and appendix material to detect the presence of abnormal prion protein (PrP(Sc)). A subsidiary aim was to determine the degree to which such an anonymous age-stratified testing programme will reduce current uncertainties in the size of the epidemic in future years. A cohort- and time-stratified model was used to generate epidemic scenarios consistent with the observed vCJD case incidence. These scenarios, together with data on the age distribution of tonsillectomies and appendectomies, were used to evaluate the optimal age group and calendar time for undertaking testing and to calculate the range of epidemic sizes consistent with different outcomes. The analyses suggested that the optimal five-year age group to test is 25-29 years, although a random sample of appendix tissue from all age groups is nearly as informative. A random sample of tonsil tissue from all age groups is less informative, but the information content is improved if sampling is restricted to tissues removed from those over ten years of age. Based on the assumption that the test is able to detect infection in the last 75% of the incubation period, zero detected infections in an initial random sample of 1000 tissues would suggest that the epidemic will be less than 870,000 cases. If infections are detected, then the model prediction suggests that both relatively small epidemics (800+ cases if one is detected or 8300+ if two are detected) and larger epidemics (21,000+ cases if three or more are detected) are possible. It was concluded that testing will be most informative if undertaken using appendix tissues or tonsil tissues removed from those over ten years of age. Large epidemics can only be excluded if a small number of infections are detected and the test is able to detect infection early in the incubation period.