Title: Prevalence of Abnormal Prion Protein in Appendix Tissue Collected from "Non-Exposed" Populations (Appendix 3)
Funder: Department of Health (England)

Abstract: The second unlinked anonymous survey of the prevalence of abnormal prion protein in archived appendix tissues (Appendix 2) was coordinated by the HPA and finished at the end of September 2012. Appendices from operations conducted between 2000 and 2012 were collected from 41 hospitals throughout England and tested for abnormal prion protein by immunohistochemistry (IHC). The testing was subcontracted to two collaborators, the Animal Health and Veterinary Laboratories Agency (AHVLA) and the UCL Institute of Neurology (UCL-IoN). Abnormal prion accumulation was detected within the follicular dendritic cells of 16 appendices out of 32,441 suitable samples examined. The final overall prevalence estimated from this survey, 493 per million (95% Confidence Interval (CI): 282 to 801 per million), is statistically consistent with results from an earlier appendix survey (237 per million, 95%CI 49 to 692 per million) which examined samples from operations performed between 1995 and 1999 and has been historically used as a precautionary figure for vCJD risk management purposes (Appendix 1). While the confidence intervals of the two studies overlap, the range of estimates from the recent survey is narrower with a higher central estimate for subclinical infection (approximately 1 in 2,000 in the UK population instead of 1 in 4,000). The hypothesis that the prevalence of abnormal prions found in both appendix surveys to date is linked to the epidemic of BSE in cattle in England can be tested directly by studying further appendix samples archived prior to the BSE outbreak and samples from those born in 1996 or later by which time measures had been put in place to protect the food chain. The ACDP TSE RA Group therefore recommended, as a high priority, the collection and testing of appendix samples taken from appendectomies carried out before 1980 ie. prior to the advent of the BSE epidemic. In addition, they also recommended testing of samples taken from appendectomies carried out between 2000 and the present day in the younger post-1996 birth cohort ie. those born after the BSE epidemic. The HPA are proposing to coordinate this prevalence survey over a 33 month period. The AHVLA and the UCL-IoN will be once again subcontracted in order to test the appendix samples by IHC. A current public health concern is that asymptomatically infected individuals may pass vCJD infection to others through surgical instruments, blood donation, or tissue and organ donations. Risk reduction interventions, rational planning of other CJD research priorities and care provision will be improved using the refined estimates of the prevalence of vCJD in the population from Appendix 2. The results from this proposed Appendix study will help clarify whether the prevalence seen is due to BSE exposure through eating beef after 1980 or actually reflects a ‘normal’ English population prevalence of abnormal prion protein. For this reason, this work is a high public health priority.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: NEUROLOGICAL