One in 2000 Brits carry brain disease protein – experts respond

A large-scale survey in the UK suggests around one in 2,000 people carry an abnormal prion —  a mis-folded brain protein — associated with mad cow disease and Creutzfeldt-Jakob disease (CJD).

NeuronsVariant Creutzfeldt-Jakob disease (vCJD) is a degenerative brain disease – often called the human form of bovine spongiform encephalopathy (BSE) or “mad cow disease.” It emerged in the UK after widespread exposure to BSE prions in the late 1980s and early 1990s through contaminated meat products in the food chain.

A new study published this week on examined over 32,000 anonymous appendix samples (from patients who had their appendix removed), identifying samples which carried vCJD prions. The researchers estimate a prevalence of 493 per million population – equating to one in  every 2,000 people carrying the misfolded protein.

An accompanying editorial says that although the disease remains rare, “infection” may be relatively common and doctors need to understand the public health measures that are in place to protect patients.

The University of Otago’s Prof Martin Pollock runs the New Zealand CJD registry and estimates that around five New Zealanders die every year from sporadic (i.e. non-variant) CJD.

Our colleagues at the UK SMC collected the following expert commentary. Feel free to use these quotes in your reporting. If you would like to contact a New Zealand expert, please contact the SMC (04 499 5476;

Dr Graham Jackson, MRC Prion Unit, UCL Institute of Neurology, said:

“Whilst the study is much needed and offers both confirmation and refinement of previous studies, further work is still required.  Given the high levels of infection indicated by this research It is now crucial we establish how many people in the UK harbour that infection in their bloodstream in order to adequately assess the risks of transmission through contaminated blood donations.  Studies to develop new blood tests for CJD must remain a priority to assist with screening and protecting the UK blood supply.”

Prof David Brown, Professor of Biochemistry at the University of Bath and former member of SEAC, the British government advisory board on BSE, said:

“This large-scale study has been planned for a very long time and examines 32,000 samples – a very large number.  Of those 32,000, 16 individuals were found to carry abnormal proteins in their appendix, which is where the 1 in 2000 figure comes from.

“This is an interesting result and suggests that it was important to carry out the study.  But this abnormal protein is not only present in vCJD but in all CJD – i.e. even that which has nothing to do with BSE.”

“It is important to note that the presence of the abnormal protein in the appendix does not confirm an individual will develop vCJD.  As the authors themselves point out, the incidence of vCJD is very small in relation to those who were exposed to BSE.

“Therefore this result does not indicate that 1 in 2000 people carry vCJD, and it could just be down to people who (for some other reason) carry the abnormal protein in their appendix.

“This study suggests that people from different age groups and from anywhere in the UK could get vCJD.  However, there is nothing to substantiate this in the study.  vCJD is limited to a percentage of the population that are both susceptible and within a certain age range.  At most the report suggests that a broad range of people could be carriers of a prion disease, which was suspected anyway.”

Prof Sheila Bird, Programme Leader at the MRC Biostatistics Unit, said:

“UK’s first appendix surveillance of sub-clinical carriage of vCJD by Hilton et al tested 12 674 samples, most from 20-29 year olds, and found three positives; two of the three were valine valine (VV) at codon 129 of the prion protein – but only 13% of the UK population is VV.

“We needed to know more, by birth-cohort and gender, as well as by genotype; and more precisely.  Hence, HPE’s denominator is 32,000 appendix samples.

“Males and females are equally represented in HPE’s surveillance study, but 10 of the 16 samples positive for abnormal prior came from males: 10/14,444 versus 6/14,351.  HPE dismisses the possibility that subclinical carriage is higher in males than females – which dietary consumption of BSE has predicted.  Apparent dismissal on the basis of ‘not significantly different’ is perhaps unwise.  Instead, UK should consider the merits of further enhancing its surveillance of subclinical vCJD so that male and female denominators were more substantial: around 50,000 samples each.  After all, we’ve done BSE-testing in millions of cattle across Europe but not yet surveillance in 100,000 UK human appendices.

“The HPE surveillance also shows 6 positives in its 8181 samples from persons born in 1941-60: around 730 per million.  Again, BSE consumption data pointed to this birth-cohort as having had greater dietary consumption.  But the uncertainty interval, based on testing fewer than 10,000 samples, remains wide at 270 to 1600 per million.  The HPE results are an endorsement of prior expectations, and a strong reason to continue UK’s surveillance to get firmer knowledge.

“The BMJ paper discloses that, of the HPE’s 16 positives, four (all female) were valine valine (VV) at codon 129 of the prion protein.  (We do not know the gender of the two earlier VV positive surveillance cases.).  The genotype data are a third reason for continued surveillance of appendix samples from those potentially BSE-exposed.

“Another aspect of UK surveillance needs to be revisited to learn more about the potential for vCJD transmission by blood transfusion from those who are subclinical carriers.  Persons who have been exposed to multiple transfusions might be approached in life to give permission for vCJD-informative testing to be done in the event of their death.

“However, as Gill et al point out in their BMJ article, we would not need either of the above approaches (enhanced surveillance in appendices or permission-in-life for vCJD informative testing at autopsy) if we had a validated test that detected abnormal PrP in blood – which is a key research goal of the MRC’s Prion Unit.”

Prof Azra Ghani, Professor of Infectious Disease Modelling at Imperial College London, said:

“The results from this large-scale survey are important in confirming the presence of a higher prevalence of abnormal prion protein compared with the 177 confirmed cases of vCJD. Whilst the lack of new cases remains reassuring, these results highlight the need to maintain both case surveillance, and precautionary measures to prevent onward transmission, over the coming decade.”

From the AusSMC:

Professor Colin Masters, Executive Director of The Mental Health Research Institute, Senior Deputy Director, The Florey Institute of Neuroscience and Mental Health and Laureate Professor at The University of Melbourne, comments:

“These data underscore the need for continued vigilance, especially in maintaining the restrictions on blood donors who lived in the UK at the critical time. It also emphasises the need for sensitive blood screening assays which are currently in development”