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Large-Scale Tonsillectomy Would Quantify UK CJD Prevalence (pp 1196, 1260)

September 29, 2004

A study in this week's issue of THE LANCET describes how two different types of analysis used in conjunction on samples of tonsil tissue is the 'gold standard' method for confirming clinical variant CJD, and that a large-scale screening programme of tonsil tissue is the only way of identifying the true incidence of vCJD infection.

Variant Creutzfeldt-Jakob disease (vCJD) is thought to be caused by dietary or other exposure to bovine spongiform encephalopathy (BSE) prions; 142 people have died of vCJD, although the prevalence of preclinical or subclinical prion infection in the UK is currently unknown.

Since clinical variant CJD is uniformly associated with tonsillar prion infection, Adam Frosh, John Collinge (MRC Prion Unit, Institute of Neurology, London, UK) and colleagues screened 2000 anonymous surgical tonsillectomy specimens for the presence of the rogue prion protein that causes vCJD. The investigators used two techniques to assess each specimen for the abnormal prion.

Although no positive cases of vCJD were identified, the investigators caution that this negative result cannot provide reassurance that relevant community infection is unlikely because of the fairly small sample size, demographic and age-related factors, and unknown test sensitivity during the prolonged incubation period.

Professor Collinge comments: "Our findings suggest that a national large-scale prospective prevalence study of tonsillectomy specimens is necessary. This study should examine fresh frozen specimens since any positive findings can be confirmed by transmission studies to indicator mice. However, the proportion of tonsillectomies done in patients born before the specified bovine offal ban is falling, thus reducing the opportunity to derive meaningful results".

In an accompanying commentary (p 1196), Markus Glatzel (University Hospital of Zurich, Switzerland) concludes: "Previous vCJD prevalence studies, based solely on the histological detection of prion protein accumulation, have detected one positive out of 8318 tested samples, and three positives out of 12,674 tested samples, respectively, which gives estimated prevalences of 120 per million and 237 per million inhabitants. These projections caused substantial turmoil, not least because the lack of frozen tissue precluded further biochemical analysis and additional assays aimed at showing prion infectivity in samples that tested positive. With a protocol like the one used by Frosh and colleagues these difficulties could have been avoided. Therefore, Frosh's protocol should be viewed as the gold standard for vCJD prevalence studies, for now".

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