FW: HAVE WE ALL GOT XMRV?

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Subject: ME/CFS, XMRV, DSM-V and the British Medical Journal - 6 March 2010

Hello all,

Following received from Dr Shepherd, via LocalME:

ME/CFS, XMRV, DSM-V and the British Medical Journal - 6 March 2010

Current issue contents:

http://www.bmj.com/current.dtl

This week's edition of the British Medical Journal is concentrating on ME/CFS

and XMRV.

Besides having XMRV on the front cover there are seven other items:

1 Editor's choice: 'Let's proceed with caution' by Fiona Godlee.

2 Editorial: 'Chronic fatigue syndrome and human retrovirus XMRV' by Simon

Wessely and Myra McClure (p489)

3 Letter: 'More than defeatism greets patients with ME' from Munn

(p495)

4 Letter: 'Severely affected, severely neglected' from Shepherd

(p495)

5 Observations/Medicine and the media: Science, chronic fatigue syndrome, and

ME by Cathie Sudlow (p510)

6 Research highlights: Chronic fatigue syndrome and XMRV - reasons why the BMJ

fast tracked the Dutch XMRV study and critical comments about the media

publicity that accompanied publication of the Science paper in October 2009

(p516)

7 Fast Track Research: Prevalence of XMRV in patients with chronic fatigue

syndrome in the Netherlands: retrospective analysis of samples from an

established cohort (summary of key points on p520)

Up until now many clinical doctors in the UK have not even heard of XMRV and

only a few knew about the possible link to ME/CFS.

Things are about to change....

There is also an editorial - 'If accepted, will fan the flames of false positive

diagnoses' - on the first draft of DSM-V (p492)

Post by The ME Association: http://www.meassociation.org.uk

XMRV and ME/CFS – Third negative study reported in the British Medical Journal

ME ASSOCIATION SUMMARY AND COMMENT

A third European XMRV study, which has attempted to find the human retrovirus

XMRV in people with ME/CFS, has failed to do so. Results from the case-control

study by Kuppeveld et al is reported today in the British Medical Journal:along

with an accompanying editorial from Professors Myra McClure and Simon Wessely.

BRIEF SUMMARY OF THE LATEST XMRV RESEARCH

This latest XMRV study was carried out by a research group based in the

Netherlands.

The virologists examined peripheral blood mononuclear cells in blood samples

that were taken from a cohort of Dutch ME/CFS patients whose diagnosis met with

(the very broad) Oxford research criteria for CFS. They also tested blood

samples from some neighbourhood controls. Blood samples were taken between

December 1991 and April 1992 and were cryopreserved.

The virologists used a polymerase chain reaction (PCR) assay to target the XMRV

integrase gene and/or a nested PCR assay targeting the XMRV gag gene. PCR is a

way of detecting viral genetic material in the blood samples. PCR testing was

carried out on 32 patient samples and 43 control samples - which are low numbers

for this type of scientific study. The authors state that their PCR technique is

sensitive enough to detect low virus copy numbers.

No XMRV sequences were detected in any of the patient or control samples in any

of the assays.

The authors conclude that their data casts doubt on the claim that XMRV is

associated with chronic fatigue syndrome in the majority of patients.

ME ASSOCIATION COMMENT

The first and so far only study to positively link XMRV to ME/CFS was reported

in October 2009 in Science by Lombardi et al.

Since then this is the third XMRV follow up study to be reported in the medical

literature. All three follow up studies have emphatically failed to confirm the

presence of XMRV in people with ME/CFS. The previous two studies involved much

larger CFS patient cohorts (meeting Fukuda research criteria) numbering 186

(Erlwein et al) and 170 (Groom et al).

This latest study, along with the other two negative studies from the UK, will

again be criticised for not being a true replication study because (a) the

patient cohort did not meet the same strict entry criteria as was used in the

American study (ie Fukuda CFS as well as Canadian clinical criteria) and (

differing laboratory protocols were used to try and identify the presence of

XMRV. These are perfectly valid criticisms regarding the interpretation of what

constitutes a replication study – an essential part of the scientific

evaluation of new findings and theories.

However, it should be noted that under the umbrella of either Oxford or Fukuda

CFS research criteria there are going to be a significant number of people who

will also meet Canadian clinical criteria if the patient cohorts from all three

negative studies are added together. In addition, Kuppeveld et al appear to be

unaware of the use of the Canadian criteria in the US study – probably because

this was not mentioned in the paper that appeared in Science. It also has to be

accepted that the various laboratory investigations for finding XMRV have been

carried out in very reputable microbiological research centres and involved

retrovirologists of international repute. So the scientific testing procedures

and results for XMRV must be taken seriously.

Overall, these three negative studies now place a very serious question mark

over the proposition that XMRV is present in a significant proportion of the

ME/CFS population and that the infection plays a significant role in most cases

of sporadic ME/CFS.

Various explanations are being put forward to explain the stark differences

between the US and European findings – including geographical variation in the

prevalence of XMRV and the possibility that the US patient cohort came from

geographical clusters of XMRV that are not representative of the wider and

sporadic ME/CFS population. But it seems more likely that the explanation lies

with the differing ways of testing for XMRV in the lab.

The MEA believes that it is vital to quickly resolve why these stark differences

are occurring. One small but important step we are discussing with both

researchers and people with ME/CFS is whether people in the UK who have sent

their blood to the US and tested positive would be willing to have it retested

by a UK research group. We also believe it would be helpful if a fresh cohort of

ME/CFS patients could be agreed by all and their blood tested for XMRV in the

different laboratories involved in these four studies. If the explanation does

appear to be with laboratory testing methods for XMRV we hope that the

international retrovirology experts will step in and help to achieve an agreed

position.

In the meantime we eagerly await the results of further XMRV studies and once

again point out that the MEA Ramsay Research Fund is very willing to consider

funding high quality research proposals relating to XMRV, especially any

proposal that would include the use of a fresh cohort of patients that would

meet Fukuda CFS research criteria and Canadian clinical criteria.

MEA SUMMARIES

The MEA has a very comprehensive XMRV website summary (>> Quick Links) covering

the publication of the Science study and events that followed publication.

Summaries covering the two follow up studies from the UK can be found in the MEA

website news archives for January and February 2010.

COMMERCIAL TESTS FOR XMRV

Our position on individual XMRV testing remains exactly the same. We do not see

any point in spending a large sum of money on a test that cannot, at present, be

used as a diagnostic marker or for the purpose of management.

Dr Shepherd

Hon Medical Adviser, ME Association

26 February 2010

ENDS

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