Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey.
OBJECTIVE
To establish with improved accuracy the prevalence of disease related prion protein (PrP(CJD)) in the population of Britain and thereby guide a proportionate public health response to limit the threat of healthcare associated transmission of variant Creutzfeldt-Jakob disease (vCJD).


METHODS
Cross sectional opportunistic survey. Study samples Anonymised tonsil pairs removed at elective tonsillectomy throughout England and Scotland.


METHODS
National anonymous tissue archive for England and Scotland.


METHODS
Presence of PrP(CJD) determined by using two enzyme immunoassays based on different analytical principles, with further investigation by immunohistochemistry or immunoblotting of any samples reactive in either assay.


RESULTS
Testing of 63 007 samples was completed by the end of September 2008. Of these, 12 753 were from the birth cohort in which most vCJD cases have arisen (1961-85) and 19 908 were from the 1986-95 cohort that would have been also exposed to bovine spongiform encephalopathy through infected meat or meat products. None of the samples tested was unequivocally reactive in both enzyme immunoassays. Only two samples were reactive in one or other enzyme immunoassay and equivocal in the other, and nine samples were equivocally reactive in both enzyme immunoassays. Two hundred and seventy six samples were initially reactive in one or other enzyme immunoassay; the repeat reactivity rate was 15% or less, depending on the enzyme immunoassay and cut-off definition. None of the samples (including all the 276 initially reactive in enzyme immunoassay) that were investigated by immunohistochemistry or immunoblotting was positive for the presence of PrP(CJD).


CONCLUSIONS
The observed prevalence of PrP(CJD) in tonsils from the 1961-95 combined birth cohort was 0/32 661 with a 95% confidence interval of 0 to 113 per million. In the 1961-85 cohort, the prevalence of zero with a 95% confidence interval of 0 to 289 per million was lower than, but still consistent with, a previous survey of appendix tissue that showed a prevalence of 292 per million with a 95% confidence interval of 60 to 853 per million. Continuing to archive and test tonsil specimens, especially in older birth cohorts, and other complementary large scale anonymous tissue surveys, particularly of post-mortem tissues, will further refine the calculated prevalence of PrP(CJD).
Clewley
Jonathan P
JP
Centre for Infections, Health Protection Agency, London NW9 5EQ. jonathan.clewley@hpa.org.uk
Kelly
Carole M
CM
Andrews
Nick
N
Vogliqi
Kelly
K
Mallinson
Gary
G
Kaisar
Maria
M
Hilton
David A
DA
Ironside
James W
JW
Edwards
Philip
P
McCardle
Linda M
LM
Ritchie
Diane L
DL
Dabaghian
Reza
R
Ambrose
Helen E
HE
Gill
O Noel
ON
D007562:Creutzfeldt-Jakob Syndrome / Q000453:epidemiology* / Q000821:virology; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D014066:Palatine Tonsil / Q000821:virology*; D018620:PrPSc Proteins / Q000302:isolation & purification*; D015995:Prevalence; D006113:United Kingdom / Q000453:epidemiology
D018620:PrPSc Proteins