title: Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey.
abstract: OBJECTIVE
  To carry out a further survey of archived appendix samples to understand better the differences between existing estimates of the prevalence of subclinical infection with prions after the bovine spongiform encephalopathy epizootic and to see whether a broader birth cohort was affected, and to understand better the implications for the management of blood and blood products and for the handling of surgical instruments.
  
  
  METHODS
  Irreversibly unlinked and anonymised large scale survey of archived appendix samples.
  
  
  METHODS
  Archived appendix samples from the pathology departments of 41 UK hospitals participating in the earlier survey, and additional hospitals in regions with lower levels of participation in that survey.
  
  
  METHODS
  32,441 archived appendix samples fixed in formalin and embedded in paraffin and tested for the presence of abnormal prion protein (PrP).
  
  
  RESULTS
  Of the 32,441 appendix samples 16 were positive for abnormal PrP, indicating an overall prevalence of 493 per million population (95% confidence interval 282 to 801 per million). The prevalence in those born in 1941-60 (733 per million, 269 to 1596 per million) did not differ significantly from those born between 1961 and 1985 (412 per million, 198 to 758 per million) and was similar in both sexes and across the three broad geographical areas sampled. Genetic testing of the positive specimens for the genotype at PRNP codon 129 revealed a high proportion that were valine homozygous compared with the frequency in the normal population, and in stark contrast with confirmed clinical cases of vCJD, all of which were methionine homozygous at PRNP codon 129.
  
  
  CONCLUSIONS
  This study corroborates previous studies and suggests a high prevalence of infection with abnormal PrP, indicating vCJD carrier status in the population compared with the 177 vCJD cases to date. These findings have important implications for the management of blood and blood products and for the handling of surgical instruments.
authors.affiliation: HIV and STI Department, and CJD Section, National Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK.
authors.forename: O Noel
authors.initials: ON
authors.lastname: Gill
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Spencer
authors.forename: Angela
authors.initials: A
authors.lastname: Richard-Loendt
authors.forename: Carole
authors.initials: C
authors.lastname: Kelly
authors.forename: Reza
authors.initials: R
authors.lastname: Dabaghian
authors.forename: Lynnette
authors.initials: L
authors.lastname: Boyes
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Linehan
authors.forename: Marion
authors.initials: M
authors.lastname: Simmons
authors.forename: Paul
authors.initials: P
authors.lastname: Webb
authors.forename: Peter
authors.initials: P
authors.lastname: Bellerby
authors.forename: Nick
authors.initials: N
authors.lastname: Andrews
authors.forename: David A
authors.initials: DA
authors.lastname: Hilton
authors.forename: James W
authors.initials: JW
authors.lastname: Ironside
authors.forename: Jon
authors.initials: J
authors.lastname: Beck
authors.forename: Mark
authors.initials: M
authors.lastname: Poulter
authors.forename: Simon
authors.initials: S
authors.lastname: Mead
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandner
mesh_terms: D000818:Animals; D001065:Appendix / Q000737:chemistry*; D002353:Carrier State / Q000453:epidemiology* / Q000378:metabolism; D002417:Cattle; D003062:Codon / Q000235:genetics; D015331:Cohort Studies; D007562:Creutzfeldt-Jakob Syndrome / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism; D016643:Encephalopathy, Bovine Spongiform / Q000453:epidemiology* / Q000235:genetics / Q000635:transmission; D005260:Female; D005820:Genetic Testing; D006720:Homozygote; D006801:Humans; D008297:Male; D015995:Prevalence; D000072002:Prion Proteins; D011328:Prions / Q000032:analysis* / Q000235:genetics; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D003062:Codon; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions