October 15, 2013

expert reaction to new research estimating 1 in 2000 carry vCJD proteins

A survey in the BMJ found around one in 2,000 people in the UK may carry variant CJD proteins though uncertainty remains about how many people will eventually develop the disease.

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.

‘Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey’ by O Noel Gill et al., published in the BMJ on Tuesday 15th October.