The prevalence of vCJD in Britain remains a subject of contention. Credit: PCL

Britain's epidemic of variant Creutzfeldt–Jakob disease (vCJD) could be worse than current death rates predict, a survey of a marker for the condition in body tissue suggests.

The disease, thought to be contracted by eating beef from cattle infected with mad cow disease, was first seen in Britain in 1995. Since then, 141 people have died, and government scientists have struggled to estimate the likely scale of the epidemic. vCJD can only be diagnosed after death, so previous estimates of its prevalence have been confined to projections from the known death statistics.

Now a study of around 13,000 tissue samples taken from hospital patients has found that three of them contained traces of a prion that is associated with vCJD (D. A. Hilton et al. J. Path. doi:10.1002/path.1580; 2004). The figure is surprisingly high: “Finding three cases in a sample this size is sobering stuff,” says John Collinge, a prion-disease researcher at University College London.

The study, led by pathologist David Hilton of Derriford Hospital in Plymouth, looked at tissues from tonsils and appendices removed in hospitals across Britain. vCJD is believed to be caused by the build-up in the brain of an abnormal form of a normally benign but little-understood type of protein called a prion. Abnormal prions are known to accumulate in tonsil and appendix tissue in vCJD sufferers. Hilton's team first removed the normal form of the prion and then used an antibody that binds to either form to search for the abnormal version.

James Ironside, an author on the paper and director of the National CJD Surveillance Unit at the Western General Hospital in Edinburgh, says that current estimates of the disease's prevalence would predict that none — or perhaps one — of the samples would test positive. But he cautions that the numbers involved are too small to allow new estimates of overall vCJD prevalence. There is also an unexpected feature of the results: the distribution of the abnormal prion in two of the three positive samples was different from that previously observed in vCJD patients.

One explanation for the result is that more people are carrying the disease than the death rates suggest. All known individuals with vCJD have a particular genotype, called MM. People with other genotypes may incubate the disease for even longer, and so haven't yet shown up in the death rates. “There could be a second wave of cases,” says Ironside. He would like to retest the two positive samples that show odd distributions to see if they are from people with different genotypes, but isn't sure if there is enough tissue to do so.

Another possibility is that the survey has unearthed a group of people who are infected with abnormal prion proteins, but who will not go on to develop vCJD.

One prion-disease expert, who declined to be named, questioned whether Hilton's team should have gone public with their potentially alarming results on the basis of so few data. This researcher noted that false positives have emerged in similar surveys and says Hilton should have run western blot tests, which are more sensitive than the antibody staining method used by Hilton's group. Ironside says the method used by hospitals to preserve tissue samples — immersion in paraffin — precluded the use of western blot tests.

The pattern of vJCD infection in Britain should become clearer in late 2006, when the Health Protection Agency is due to complete a study of 100,000 tonsil tissue samples. These are frozen, and therefore suitable for western blot analysis.