I often see patients in my practice who have chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Over the years several candidate viral triggers for the condition have been proposed, including EBV, HHV-6, HTLVs and various enteroviruses (including CMV). Every few years or so, some research group whose heads are stuck firmly in the clouds comes out with a hyped-up revelation that the one and true “cause” of CFS/ME has been discovered.
Invariably these pronouncements are followed by cycles of expectation, then disappointment and eventual despair, as patients’ hopes for a meaningful answer to their problems are dashed once again. Part of the problem is that there is never likely to be a single “one size fits all” cause for the problem; and only a small minority of cases fitting the syndrome’s rather vague definition are likely be caused by chronic viral infections and perpetuated by abnormal immunological responses to them.
Last year a new candidate virus hit the scene – a retrovirus called XMRV (Xenotropic murine leukemia virus-related virus). This one seemed a real doozy – the initial reported study in Science indicated it was present in 67% of CFS patients. This “good” news went figuratively viral and soon the web was bursting with speculation about XMRV and how it could be diagnosed and treated.
However, despite this hype, there has been a spectacular failure to replicate the original study. Several groups have since tried and failed. Judy Mikovits, the lead author of the Science XMRV study, blames this on the other laboratories’ methodology and patient selection (even though one study used similar protocols), and she refuses to accept there is a chance her own study might be flawed.
Her centre even has marketed a test for the virus, so CFS patients on this side of the pond can avail themselves of it too (for the mere sum of $450). And not content with confining herself to CFS and the role XMRV might play in it (according to her it will be the next “AIDS” and become “the worst epidemic in US history”), Mikovitz has now proposed that the virus may play a part in multiple sclerosis and in autism too.
What has been interesting to me is the way in which patient groups have responded to the available research and information about XMRV. Most appear to remain firmly wedded to the idea that it is the real deal, and many ME/CFS forums are discussing research and treatment in great detail. Perhaps not mindful of previous false hopes in this area of medicine, some are obtaining, at great expense, complex experimental drug treatments via the Internet or from compliant doctors.
Since XMRV is a retrovirus, anti-retroviral drugs like those used to treat HIV/AIDS have been tried. Logically, this might make some sense, but only if XMRV infection actually is present in the first place, that is actively replicating and that it has a genuine role in the pathogenesis of real physical illness. Currently, those are all massive “ifs”, and it would be a foolhardy (and not to mention brave) individual who would recommend or try antiretroviral drugs on such a speculative basis.
Such people exist though. One of them is Jamie Deckoff-Jones, a Harvard educated doctor whose family has been struck down with not only Lyme disease but CFS/ME. Her tale is related in her blog, which describes how she started self prescribing combination antiretroviral drugs (ARVs) earlier this year and how she has also put her daughter on them. Dr Deckoff-Jones is clearly not stupid, but speaking as one who is very familiar with the problems of ARV drug toxicity, I shudder at the idea that someone should chose to take them on the basis of such paltry evidence.
The drugs she and her daughter are taking are Zidivodine (AZT) a nucleoside analogue which inhibits reverse transcriptase, Tenofovir, a nucleotide which works in a similar fashion, and Raltegravir, one of the newer ARVs which inhibits integration of proviral DNA into the host cell genome.
All ARVs have significant side effects. Most are fairly well tolerated in the short term, but there is major concern about their longer term use because of their numerous cumulative metabolic effects. Their use is entirely justified in a syndrome such as AIDS which if left untreated would soon result in an unpleasant death, but their use in CFS/ME must be decried as completely irresponsible.
Zidovudine is rarely used now – it was a very useful antiretroviral, but its cumulative toxicity was too great and there are better alternatives. It can cause anaemia and bone marrow damage, and in the longer term can induce mitochondrial toxicity which causes nerve and muscle damage, liver damage and a wasting form of lipodystrophy in the majority of its recipients.
Tenofovir is relatively new. It is well tolerated, but prone to cause chronic renal tubular damage and can result in metabolic disturbances which can result in osteopenia/osteoporosis. Hardly the sort of drug I would chose to give long-term to a young woman.
Raltegravir is newer still, so its full side effect profile has not been fully determined. Even so, it can cause rashes and liver dysfunction among other effects.
One major concern about ARVs is their propensity to affect metabolism in a way that causes “premature aging” (for want of a better term). Patients with HIV are now unlikely to die from their HIV, but more likely to die as a result of either overt or subtle accumulated metabolic effects - insulin resistance, hyperlipidemia, cardiovascular disease and liver disease.
Treating HIV is a not easy, and is a job best left to experts who know exactly what they are doing and who know what the drugs can and can’t do. ARVs are also very prone to significant drug interactions. It is crucial that those prescribing them have intimate knowledge of the potential problems and have gained sufficient hands on expertise in their use. It looks very much as though Dr Deckoff-Jones lacks this knowledge, relying instead on Google University for her information. I hope that she and her daughter come to no harm from her misjudged experiment.
But dabbling in ARVs is not the only aberrant form of prescription negligence. There are other marvellous, sciencey-sounding drugs to tempt the supposedly XRMV-infected CFS sufferer. Rituximab, one of the potent new monoclonal antibody immunomodulating drugs is being touted as one such treatment. Not only are these drugs very expensive, but they have considerable toxicities and like ARVs their use requires considerable skill and constant complex monitoring. They are entirely unsuited to be used as experimental anecdotal remedies for patients with fatigue.
To see CFS sufferers discussing these powerful drugs in the manner of kids choosing pick and mix at a candy store is rather alarming. On the Phoenix Rising forums, anonymous posters give each other tips about their ARV drugs which rank from the injudicious to the frankly dangerous. It seems as though many are deciding for themselves, pretty much at random, what to take, when and how much:
“June 3rd I will ask my doctor to either add Tenofovir, or if he refuses, to replace RAL with Tenofovir 300 mg/day. Also I will ask to increase AZT”
If there is one thing that my experience with treating patients with ARVs has taught me, it’s that strict adherence to a proper scientifically-structured regimen is necessary. Different ARV drug combinations, sequences and dosages have been meticulously studied in formal pharmacokinetic and clinical trials over many years before they achieve regulatory approval, and problems of ARV resistance are a major worry if patients deviate from the recommended course.
Part of the problem is that patients with CFS/ME tend to be quite self-reliant and have little faith in orthodox medicine. They have been so used to determining their own therapeutic options and managing their condition for themselves over the years that they are taking the same attitude with the new drug combinations. Now it’s one thing to up the dose of a harmless supplement, or take less Coenzyme Q10, but quite another to chop and change drugs and doses of what are often toxic and potentially lethal treatments with multiple drug interaction concerns as are seen with ARVs.
I might well tut and sigh, but all this foolishness does bring home one fact very clearly, namely that CFS/ME patients are despairing for answers and solutions to their plight, and will try almost anything. I can only hope that they don’t fall into the trap of being maliciously exploited by the snake oil salesmen and drug suppliers that are popping up trying to make a fast buck off the back of their misery.
I also hope that those scientists who have a personal stake in the XMRV story can be more objective and refrain from believing their own hype. Perhaps they will reconsider the evidence base and stop marketing their patent “test” for XMRV? I can but dream. Pharma companies who develop ARVs would be well advised to steer clear of what must appear to them to be a new and lucrative market.
After all, we don’t even know if XMRV is the problem, and all the indications are that it will prove to be just another false dawn in the long night that CFS patients are currently enduring.
This is a guest post by British doctor DeeTee.
There is *so much* wrong with using antiretrovirals for 'XMRV infection' I dont even know where to start. Ive been wanting to write a post on this topic for weeks (since a reader sent me a link to Deckoff-Joness blog), but again, I dont know where to start.
Im horrified.
And the fact Mikovits is supporting this (but 'not really' **WINK!!**)...
This article hardly addresses the problem. Who cares what a few patients are taking on their own? Many people take all sorts of crap, legal and illegal drugs, tobacco, alcohol, off-label drugs, all with serious health consequences. Are we to believe that this writer is trying to help us, trying to make the world a better place?
No, this writer is interested in abusing CFS/ME patients with this non-sensical concern. Perhaps you would be better served if you tried to channel your hostilities into a more palatable form and proposed some path of action in moving forward for the victim of this unfortunate illness.
Perhaps you would be more effective if you gave a better picture of this illness, which is worse than AIDS in many ways. Perhaps you could elucidate the scientific research that is being done by labs such as WPI and others. Perhaps you could write on potential ways out of this problem.
In the meantime I suggest that yo stop writing this crap. It is really demented for you to do this and it is an abuse.
Chris
Dr. Deckoff-Jones does not use "Google University" for information on treating XMRV with HAART. She goes to an infectious disease doctor who is familiar with HIV and its treatment. You need to do better research.
Chris, you ask "Who cares what a few patients are taking?"
Me for one.
Especially when the drugs involved are so complex and potentialy very toxic.
Especialy when there is no evidence base for their use.
Especially when people like me are left to pick up the pieces when things go wrong.
Especially when use of these drugs is encouraged or tolerated by those in positions of influence and who have set themselves up as opinion leaders in the field.
Especially when those who claim this cause is real also have a huge lucrative stake in demonstrating its existence and in offering expensive tests for its diagnosis.
Especially when pharma companies or shady suppliers of drugs will leap at the chance to exploit the vulnerable for a quick buck.
I am on the side of those with CFS/ME here, believe me.
I don't know why Chris thinks this is an attacking article. To me, and I do have ME, it is a really supportive article. It is not abusing! It is saying we need to hang on before we make assumptions and how dangerous the drugs that people are talking about using as treatments are! Nowhere does it even mention anything about the lack of biological evidence!
Aren't we trying to get people talking about CFS/ME not discouraging them!
If XMRV isn't the answer, and we don't know if it is or isn't yet, then I for one would like to think people are keeping an open mind at this stage and looking into other possibilities rather that waiting to we no for sure either way. That could add years to our suffering.
You wrote: "Most appear to remain firmly wedded to the idea that it is the real deal.."
Yet the link you provided was to a poll with less than a quarter of patients saying they absolutely believe XMRV is a major cause of CFS. 50% think there's a good chance, but need more evidence, with the rest being very sceptical, or thinking XMRV might just be a co-factor for CFS.
Considering the difficulty of living with the uncertainty of a condition like CFS I'm surprised that patients, as a group, have been able to maintain such a reasonable assessment of the current evidence. There is a hunger for understanding that will make patients more willing to jump onto any passing theory that can help them make sense of the hardships they face - this is the same for any serious chronic health condition; yet it seems that CFS patients are surprisingly detached and cynical about the claims made in Science.
This article does create the impression of whacky patients going against the reason of science, and I do not think this is fair. It's not surprising that there are some who are so desperate that they are willing to take risks for even a tiny hope of recovery - given their situation, it may even be reasonable for them to do so.
Gargle - some good points too!
DT,
I am sorry but I am not convinced. The fact remains that a few desperate patients taking toxic drug does not distinguish itself from many other situations. I had friends in the mid-1980’s who took all sorts of things to try to keep from dying (They didn’t work). In this current situation, it is not likely that this practice is going to spread and everyone will be dropping Raltegravir. Statistically you can rest assured that the chances are of you having to pick up the pieces of even one patient are infinitely low.
Most CFS patients and practitioners are waiting to see what happens, and are seriously afraid of the toxicity of these drugs.
These very sick patients with impossibly truncated lives have serious issues. The lymphoma risk is very real. Lymphoma is no joke. Some of these long-timers have no time with which to play around. Heart attack and stroke, and premature death, also awaits many patients. This is what propels a few to take these antiretroviral drugs – desperation in the face of this nasty illness.
But this is not really what your post is about.
The rest of your post is just rot – and it exposes your prejudices. All that crap about important people making wild claims and advocating a short-circuited means of research and treatment would be best left unsaid - as none of it is true. Of course, these arguments are thinly veiled attacks against a small group of researchers who have stumbled upon something that everyone knew was there - in one form or another. The research needs to play out without your premature announcement of its demise. Your statements mask an intent to sink these researchers with innuendo and heavy-handed character attacks. I like character attacks as well as the next person but yours are not very good.
Chris
Does it not cross your mind Chris, that the reason that WPI's results are not being replicated is that they are not valid?
" I like character attacks as well as the next person but yours are not very good."
Ok, this worries me! why any character attacks at all? Why not just debate the science. why is someone who says "let's just wait and see" ( my summery) anti anything in particular? aren't they just saying... wait for it... " let's just wait and see"
"...some research group whose heads are stuck firmly in the clouds..." -DeeTee
I hesitate to speculate where your head is firmly stuck...where the sun doesn't shine, for sure. This blog is full of disdain and disrespect for anyone with ME/CFS and for those who sincerely are trying to find the cause and a cure/treatment. This blog is full of errors.
Dr Deckoff-Jones is not "self-prescribing". She has a doctor who is prescribing and monitoring the whole process. You dismiss the trial of antiretroviral drugs as too extreme a medicine for "fatigue". If that is what you think ME/CFS is, you shouldn't even be writing about it...it reveals your ignorance of the facts. ME/CFS is a neuroimmune disease which has fatigue as ONE of it many symptoms.
Dr John Coffin, respected retrovirologist, has said clinical trials of antiretrovirol drugs would be the quickest way to figure out whether XMRV is a/the cause. Is he "crazy", too?
The Failure to Replicate studies have been "spectacular" alright. Spectacular Failures, done by groups who want desperately to prove there is no biomedical cause. (That apparently includes you...are you a psychiatrist?) That they found ZERO XMRV is a clue to any thinking person that they either don't know how to find it, or they didn't want to.
Of course patients are used to looking after themselves! With Drs like you promoting the idea that they are "crazy" - a very professional choice of words on your part - or malingerers, remaining so ignorant that you would cite "fatigue" as a reason not to choose those drugs, patients have had to educate themselves. They certainly don't get any help from the likes of you.
You disdain patients throughout your blog and then at then end you try to give the impression that you are just trying to save them from themselves. Please!
"...XMRV... all the indications are that it will prove to be just another false dawn in the long night..."
You have absolutely no basis in truth or logic for that statement. This discovery is not yet proven or disproven, but people like you would like it to be ignored before it can be fully researched. Why?
Uh-Oh
Anonymousity - DeeTee is a doctor specialising in infectious diseases. As such he probably sees CFS/ME patients who have been referred for investigation to look for infectious disease causes for their problems. So no, not a psychiatrist... and indeed, just the kind of specialist some CFS/ME folk are often insisting should be investigating their cases, at least as I understand it.
I note DeeTee said:
"Part of the problem [with hunting for causes of ME/CFS] is that there is never likely to be a single “one size fits all” cause for the problem; and only a small minority of cases fitting [CFS/ME's] rather vague definition are likely be caused by chronic viral infections and perpetuated by abnormal immunological responses to them."
That is actually a common view among the doctors I have met that see CFS/ME patients. Again, none of these doctors is a psychiatrist.
Re the subsequent XMRV studies failing to replicate the WPI's findings; you see conspiracy theories. Other people might see medical science testing a new idea to see if it pans out. That is the normal process, after all. And there are, to other people in the trade, worrying signs in the way the WPI people have gone about things, and the pattern of results.
Like you say, the question remains unresolved. But with the recent example of Andrew Wakefield and the MMR/autism hoax in everyone's minds, and the many earlier false dawns for viral causation theories for CFS/ME that DeeTee mentions, it is hardly a surprise if people want to be cautious about the XMRV story.
"... is prescribing and monitoring the whole process..."
Currently impossible. Reason #986159245 this is a Very Bad Idea. There is *no* quantifiable way of assessing the effectiveness of antiretrovirals in 'XMRV positive' individuals.
With HIV-1 patients, we monitor viral load (no one has isolated free virus in 'XMRV positive' individuals). We monitor CD4 counts (no one has correlated XMRV with any particular, measurable effect on infected individuals).
Cant assay for drug resistance.
Of course there is lipid/sugar/etc tests for monitoring side-effects, but a perfectly healthy person would have the same side-effects as an 'infected' person.
The irresponsible physician prescribing these medications to her is in no way in control of the situation. He/She has no idea what they are doing. They are monitoring jack squat.
You are entitled to your opinion, but try to get your facts straight. I am not prescribing for myself or my daughter.
Jamie Deckoff-Jones MD
Dr Deckoff Jones- Is your blog wrong, or are you and your daughter taking anti- retroviral treatments with known serious side effects for a virus that a) has very weak if any evidence that it causes your symptoms, and b) where you cannot even measure whether it is having any effect.
Whether it is you or someone else doing the prescribing is immaterial- the problem remains that this is a very dangerous strategy, with no way of telling whether you are poisoning yourself and your daughter for any gain whatsoever.
Science bloggers never mentioned ME when multiple patient surveys have shown substantial risk of harm from the graded exercise enshrined in NICE guidelines. Not a peep about the MRC's systematic refusal to fund basic research, due to peer review by psychiatrists. The medical profession has thrown so much crap at them that patients are desperate and will try anything, including unproven or quack treatments, surprise, surprise. All of a sudden, science bloggers come over all concerned. Pass the sick bucket.
I agree with the tone of the article, and think its a pretty clear summary of the current situation. However, I can see where some irate CF/ME sufferers are getting their cue from: the title can easily be (mis-) read to imply that people suffering from the condition are 'crazy and getting crazier', rather than the situation is escalating. Much as i hate post-hoc edits, I really think it might be worth re-titling the article.
RE: Oryx, would you prefer it if no-one gave a shit?
Sincere apologies to Dr Deckoff-Jones. I did read your blog but didn't pick up on the fact that you were not prescribing the drugs for yourself and your daughter.
My opinions about the dangers of this strategy are unaltered. I think by your actions and by publicising them you are fostering a potentially very dangerous concept.
Thanks for the butt-kick I needed to finally write a post on XMRV and antiretrovirals :)
Watching this story unfold has kinda been a retrovirologists version of the SAW movies...
So when DT wrote 'the mad just got madder' those irritating ME patients misread it, and should have known she meant 'the madness'. Nice try, Eleanor. In reply to your question, they don't. DT's chum ERV wrote she doesn't give a **** about ME.
Draust said,
"Anonymousity - DeeTee is a doctor specialising in infectious diseases."
How do you know, draust? Do you know where Dr DeeTee plies his infectious trade?
Shabby
The answer is "yes", as you well know. So that was another of your no-point points. Really, why do you bother?
In respect of Oryx's point, there has been plenty of coverage of CFS/ME on scientific and medical blogs, both before the XMRV story broke and since. However, it is true that some bloggers have steered clear of the subject because of the "antibodies" that commenting on CFS/ME raises. See any of ERV's blogposts on XMRV for a bunch of examples of the kind of stuff I mean.
The thing about the MRC "refusing to fund basic research in CFS/ME" is pure conspiracy theory. You can tell this in part because the key "Evil Psychiatrist" in the demonology of the people who believe this, Simon Wessely, has actually published several papers searching very carefully for underlying biochemical/immunological abnormalities in CFS/ME patients. So there would appear to be no block to people doing "non-psychiatric" research on CFS/ME. However, like every other sort of medical research, CFS/ME stuff has to compete for funding with other pressing priorities. It is also hard, in any field, to get lousy poor-quality research funded - which is as it should be.
However, despite this hype, there has been a spectacular failure to replicate the original study. Several groups have since tried and failed
Lets keep it simple as the general population is repeatedly been misinformed.
One simple question - NAME ONE REPLICATION STUDY?
Obviously those people who are saying that what Dr. Jamie Deckoff-Jones is doing is wrong, have never suffered from Chronic Fatigue.
As someone suffering with this dreaded syndrome, I for one would and have taken anything prescribed to alleviate or eradicate the symptoms, some have worked to a small degree and some have not.
This is a most horrific thing to deal with, I know, I have it. I have been dealing with it for 15 or 16 years now, I have dealt with the prejudice that ignorance breeds, both from doctors that I have seen and from "loved" ones. I went thru a divorce partly because of this disease and was told by the judge presiding over my divorce to " get a job" when ever I brought up the fact that I was not a wage earner and needed support from my ex-wife.
Ignorance is all around us, we should be used to it by now, but sometimes its hard not to say something because we want answers, we want to feel like we once did, we want our lives back. Is that asking too much?
Dr Aust: I've just done a crash course in the abusive and defamatory world of Bad Science and sceptic bloggers such as ERV, so I can't say I'm surprised that you label Jonathan Kerr and the late David Tyrell as conspiracy theorists.
"As Dr Jonathan Kerr, Sir Joseph Hotung Senior Lecturer in Inflammation, Department of Cellular and Molecular Medicine, Hon. Consultant in Microbiology, St George’s University of London, stated at the Invest in ME Conference held in London in 2006:
'It is rather sad that the MRC does not fund any biological studies such as we are doing, and I think the current…consideration of grant applications to the MRC on CFS is currently with the Neurosciences and Mental Health Board…and I think that (this) immediately biases the decision-making process because that panel is made up predominantly I believe of psychiatrists. It would be desirable if this could be reclassified (by the MRC) such that there would be money available…for biological approaches…It is a fact that currently the MRC does not fund any biological approaches.'
"At the 2007 Invest in ME Conference, Dr Kerr repeated his message:
'We have applied several times to the MRC and on each occasion we were invited to submit those applications and on each occasion we got scores typically of 9, 8 and 3 – the 3 score was obviously from a psychiatrist who was complaining about our way of enrolling the patients, the criteria we had etc…David Tyrell told me the MRC will never fund biomedical research in CFS because they are in the thrall of the psychiatrists – so far, he has been right.'
"The late Dr David Tyrell, CBE, FRS, DSc, FRCP, FRCPath was Chairman of the UK National Task Force on CFS/PVFS/ME whose 1994 Westcare/DoH Report was rejected by the Wessely School and gave rise to their own 1996 Joint Royal College’s Report (CR54) that denied the existence of ME."
These verbatim quotes from public conferences appear on what can be dismissed as a conspiracy theory page, but that is irrelevant to a discussion of vested interests and research scoring anomalies and outliers at the MRC. It's our money the MRC hand out, after all.
http://www.meactionuk.org.uk/The-MRC-secret-files-on-ME.htm
Oryx, I have applied a number of times to the MRC, and have been unsuccessful. Without knowing whether I am proposing a biological explanation of CFS/ME, can you tell me if I am the victim of a conspiracy, or if my grant applications just were not up to scratch?
The truth is, the great majority of grant applications are unsuccessful. Often it is because of deficiencies in the protocol compared to other applications (i.e. the application is not absolutely bad, but there are better ones in that round). I have also acted as a reviewer for the MRC, and the process is very difficult. The unsuccessful candidates often feel very bad - after all, they did their best in making the application, and invested a great deal of time and effort, yet it was turned down. It is quite common for retrospective accusations of bias and prejudice to be made. On the other hand, those who are successful never commend the reviewers, who merely saw the self evident merits of the proposal....so self-reports of bias are almost universal.
A very dear friend has severe CFS/ME, and no psychiatric conspiracy on earth would prevent me exploring biological causes in order to help her. Sadly, there are as yet none. I had hopes of XMRV, but these are now disappointed. I had a mild form myself once, so I can dimly appreciate what it is like. I still recognise that Mikovits is now making statements which are insupportable to the point of absurdity. Any lab which showed the initial XMRV hypothesis to be correct could expect praise and further funding, since at last a CFS/ME aetiology might be emerging, which is a necessary first step to a cure.
Up to this date, no-one has carried out a true replication study.
All the other studies have tried to find XMRV there own way and have failed.
You have to admit it is very strange that no-one has carried out a true replication study.
I have read all the papers and its very clear how much they differ.
I can understand why Mikovits WPI must be getting very frustrated.
Please take some time and compare these studies.
Allo v psycho: Sorry about your funding problems. I'm familiar with how it works, having gone through it successfully and unsuccessfully with a variety of official agencies, although not the MRC. I will guess that if you wanted psychiatric funding, lack of success means you were pipped at the post. If your studies were biological, then we need to know if the score range was similar to Kerr's. He repeatedly got high scores (80-90%) from two reviewers plus a spoiler (30%) from the psychiatrist on the panel. That should ring alarm bells, but I suspect the good old MRC just adds up the scores mechanically, regardless of the turf wars.
You might also have proposed quasi-biological research, maybe similar to some of Wessely's, mentioned by Dr Aust. He has typically looked for stress-related physiology, designed to underpin his somatization theory. I think they would bend over backwards to fund that, so it's a bit unlikely.
XMRV does not fulfil Koch's postulates for causing CFS/ME (at least not yet). Unaccountably, Dr Deckoff-Jones feels it does. Let's see what she says:
1. Isolate the organism from every case. The WPI has verified XMRV in 99 of 101 of the original samples from the Science paper.
(So they say, but has anyone independently verified this claim?)
2. Propagate in pure culture in vitro. Done.
(Again, this is in Mikovitz's lab only, but even were it to be done it demonstrates nothing other than the virus can replicate under lab conditions (as can thousands of other viruses), and says nothing about it's role in any particular disease.)
3. Reproduce disease by injecting the organism into a suitable recipient. Accomplished in tissue culture. Also lots of epidemiological evidence for vertical transmission.
(Errr, No. How does one determine a "tissue culture" is suffering from ME? This Koch postulate requires that XMRV is experimentally transmitted to a new uninfected host in vivo, who then goes on to reproduce the clinical disease, namely CFS/ME. This has not been done. Not to say it can't necessarily be done in time, but it has not been done.)
4. Re-isolate the organism. Accomplished in tissue culture.
(Again, the postulate requires the newly infected host is demonstrated to have productive XMRV infection, not a cell in a lab dish.)
This is a Koch postulate fail, unequivocally. More reason not to jump into empirical treatment for it.
"...the long night that CFS patients are currently enduring."
My 'long night' has seen me housebound, often bed bound and in dreadful pain for over two decades now - and yes, I've considered buying antiretrovirals from the internet. I'm grateful for articles such as yours that point out the dangers, but despair at the lack of research into the biological cause of my illness.
The psychiatric profession have grabbed all the research and treatment funding for themselves since the 1980s, despite the fact that M.E. has been classified as a neurological illness by the WHO since 1969. They have muddled us up with people with psychological disorders that cause fatigue, who need totally different treatments, under the meaningless umbrella term 'chronic fatigue syndrome'.
The ONLY treatments we are offered are useless cognitive behaviour therapy and (often) harmful graded exercise, given by staff who are trained to believe we are somatizing when we are not, and that exercise will cure us when it makes us worse - sometimes permanently. This is abuse, not medical treatment.
You sound an enlightened doctor; there are not many like you. What would you suggest we do? If we speak out we are branded 'militant loonies'. If we say nothing we continue to be invisible and to be offered mainly contempt, ridicule and abuse.If we try to treat ourselves at least we have a little hope.
There's new news about XMRV today:
http://www.virology.ws/
To amplify what JK said, independent confirmation of the WPI Science paper, by the FDA and NIH, is in press.
http://www.mmdnewswire.com/xmrv-9040.html
Original Press Release from the Netherlands: FDA and NIH confirm 'XMRV findings'
Gendringen, NL (MMD Newswire) June 22, 2010 -- The FDA and the NIH have independently confirmed the XMRV findings as published in Science, October last. This confirmation was issued by Dr. Harvey Alter of the NIH during a closed workshop on blood transfusion held on May 26-27 in Zagreb. Two journalists from the Dutch magazine for health professionals, ORTHO, who have been working on XMRV stories for several months, were able to obtain a copy of the Alter lecture.
In the October 8, 2009 issue of Science Express, the Lombardi-Mikovits group at the Whittemore Peterson Institute (WPI), the Cleveland Clinic and the National Cancer Institute (NCI) reported that 67% of 101 chronic fatigue syndrome (CFS) patients tested positive for infection with xenotropic murine retrovirus (XMRV). Only 3.7% of 218 healthy subjects tested were positive for this gammaretrovirus. Since that time, a number of research groups have proved unable to independently confirm these findings.
On Friday last, the AABB released an Association Bulletin recommending that its member blood collectors actively discourage potential donors who have been diagnosed with CFS from donating blood or blood components. This interim measure was proposed by the AABB Interorganizational Task Force on XMRV. This Task Force includes representatives from several government agencies, including the Center for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA) and the National Institutes of Health (NIH).
The fact that the measure was introduced suggests the presence of information not yet published. The ORTHO journalists were able to obtain a pdf document of the lecture given by Harvey Alter at the IPFA/PEI 17th Workshop on 'Surveillance and screening of Blood Borne Pathogens' in Zagreb. The International Plasma Fractionation Association (IPFA) represents the not-for-profit organizations around the world involved in plasma fractionation. The IPFA is based in Amsterdam, the Netherlands.
The highly-experienced Dr. Harvey Alter is Clinical Studies Chief at the Infectious Diseases and Immunogenetics Section of the Department of Transfusion Medicine at the NIH Clinical Center in Bethesda. "The data in the Lombardi, et al Science manuscript are extremely strong and likely true, despite the controversy", was one comment on the XMRV findings reported by Alter in Zagreb. "Although blood transmission to humans has not been proved, it is probable. The association with CFS is very strong, but causality not proved. XMRV and related MLVs are in the donor supply with an early prevalence estimate of 3%?7%. We (FDA & NIH) have independently confirmed the Lombardi group findings."
ORTHO contacted Dr. Harvey Alter today for a reaction. He did not want to comment, but confirmed that a paper is soon to be published.
A quick look at the beginning of your blog leads me to assume you are writing to inflame people in order to boost the readership of your column, not out of any knowledge base about ME/CFS and current research or concern for people who have ME/CFS.
1. The title “ the crazy just got crazier” – implying that people who try to treat ME/CFS are crazy as your main point – I should have known better and stopped reading here.
2. The unnecessary use of hyperbole “Every few years or so, some research group whose heads are stuck firmly in the clouds comes out with a hyped-up revelation that the one and true “cause” of CFS/ME has been discovered.”, trying to dismiss all past research with one broad brush stroke. Much of this research is valid, much has not been followed up as research dollars for ME/CFS have been scarce, and the few that there were were spent by the CDC on office furniture etc, or on quack psychiatric papers.
3. And your opinion for the following dismissive remark is based on what research?
“ Part of the problem is that there is never likely to be a single “one size fits all” cause for the problem; and only a small minority of cases fitting the syndrome’s rather vague definition are likely be caused by chronic viral infections and perpetuated by abnormal immunological responses to them.”
4. You state, “However, despite this hype, there has been a spectacular failure to replicate the original study. Several groups have since tried and failed.”, however, the facts are that not one replication study has been attempted yet.
I finally had the sense to stop reading seeing full well that I could expect every paragraph to have at least one major factual error, displaying an ignorance of the field, and to be smeared throughout with unfounded dismissive opinion.
Your blog post is full of misinformation, but the first wrong thing is you are from the UK, and goodness to me, you doctors of UK haven't figured out how to take care of ME patients with respect and dignity. CBT, GET and psychiatric hospitalization is barbaric and harmful.
I haven't been ill for very long, but I know some that have been in bed for decade, not because they chose it, but because they can't get up! Politics has made such that ME didn't deserve to be funded and has been an easy prey to ignore and sweep in a corner. After all, deaths can be camouflaged into heart attack, cancer, suicide or sepsis.
I'd be one of the first to enroll in clinical trials and give ART a chance. "Very toxic", well HIV patients on ART are working, must not be that bad huh? And that's why there is blood work, to monitor kidney and liver toxicity. And rituximab toxicity, honestly, is one of the most gentle drug I know in the cancer world. There is chances of rigors, fevers and allergic type of reaction and the patient is monitored for that while getting infused. Expensive, yeah maybe, but these patients deserve a chance at life. This disease could have been prevented so long ago. But some high up, stiff lip, insulting characters with interests with insurance companies have decided it was a psychiatric disorder.
I'd say you'd have to be in the middle of the disease to understand what it's like to have ME. You certainly have no clue.
Sooooo DT and all anti-ME'ites,
Where is all your invective against seriously ill and rightfully desperate patients, now that we have news that the FDA and NIH have replicated the Science paper... and that other MAJOR institutions are following suit? In fact, not only have EACH of the FDA and NIH independently replicated the Science work (using more than the one-shot, flimsy PCR used by the so-called "Failure Studies"), they are finding higher levels of XMRV in ME/CFS patients than reported by the original Science team. And of course they're actually looking at ME patients, not the trumped-up "tired/depressed" cohorts that Wessely et al are renowned for.
As a former healthcare professional myself with over a decade of disability from ME/CFS, I can attest to the flip indifference and rank unprofessionalism of my erstwhile colleagues on this disease. Thank heavens we have another generation of retrovirologists who "get it", and who are aggressively pursuing the connection between the XMRV retrovirus and CFS/ME.
I do find it laughable - in a rather tragic way - that the so-called "experts" on this disease such as Dr Aust are so woefully uninformed that they cannot differentiate the Oxford Criteria, which (surprise, surprise), fail to differentiate depressed patients from patients with ME/CFS; from the most rigorous Canadian Criteria for ME/CFS - which REQUIRE the hallmark "Post-exertional malaise" (to summarize: patients are profoundly fluey for at least 24 hrs after trivial activity); and which are noted for reproducible immune dysfunctions such as RNase-L antiviral pathway deficiency; NK cell dysfunction; signature cytokine abnormalities, etc. If you are so inclined – although evidence suggests otherwise – you might inform yourself by reading on the topic. A helpful primer on the importance of CFS criteria was recently made available by noted CFS psychologist, Dr Leonard Jason. His slides on how CFS cohort selection can bias research outcomes, can be seen at: www.cfids.org/webinar/jason-slides041410.pdf
Admittedly this is a complex disease which requires that specialists actually listen to their patients' symptoms - which are pathognomic - particularly post-exertional malaise. After all, that’s what the first “S” in SOAP format medical reporting is all about. And it does require that physicians learn to think independently when confronted with perplexing diseases - something that our paint-by-numbers medical community is loath to do. Suffice it to say that the loudest blowhards against the "ME/CFS troublemakers" tend to be the most ignorant of the abundant research on physical findings. Consider that the Journal of Pain featured on its cover last year the stunning post-exertional genetic signature of ME/CFS patients:
"In the laboratory they analyzed metabolite-detecting genes (ASIC3, P2X4, P2X5), adrenergic genes (A2A, B-1, B-2, COMT), and immune system genes (IL6, IL10, TNF alpha, TLR4 and CD14). When the investigators compared the activity of these genes before exercise, there was no difference between CFS patients and controls. But, as early as 30 minutes after exercise, there were significant increases in gene activity for the ASIC3, P2X4, P2X5 metabolite-detecting genes, the B-1, B-2 and COMT adrenergic genes, and the IL10, TLR4 and CD14 immune system genes. The gene activity increases persisted for up to 48 hours after exercise in the CFS patients. As anticipated with moderate exercise, there was no gene activity increase in the healthy subjects." This is what your patients have been saying for decades. Only braggadocios like you are too tone-deaf to deign to listen.
The minute the words "Chronic Fatigue Syndrome" are mentioned in a doc's office (many so-called professionals on our continent don't even know what Myalgic Encephalomyelitis is), the attending physicians' eyes roll back in their foreheads. It's nothing short of a perversion of the Hippocratic Oath and a massive cop-out that physicians - when confronted with a genuinely complex multi-system illness dominated 4:1 by females - would rather put the blame on seriously ill patients (calling us hypochondriacs), than say the dreaded words, "I don't know what's causing your illness". And so, we have a highly profitable industry of get-well-quick clinics championed by (you guessed it) psychiatrists.
DT, you are indeed a Lay Scientist extraordinaire, and I would suggest that you might direct your efforts to other derivations of "lay", rather than to the bastardization of the science on ME/CFS.
Similarly, you are clearly ignorant when it comes to knowledge of the cardiomyopathic changes in persistent viral infection - which (surprise, surprise) is so prevalent in female patients with "pain syndromes" such as ME/CFS. And you are clearly unaware of the dire stats that patients with a history of persistent chest pain are suddenly finding themselves in: falling dead at an alarming rate ~ 5 years after onset. Not surprisingly, Atypical Angina is associated with endothelial changes - one of the many findings in XMRV from the knowledgeable retrovirologists this side of the pond. Yet patients with Persistent Chest Pain (Cardiac Syndrome X; Atypical Angina) are being routinely laughed out of emergency departments, only to fall dead mysteriously a few years later – 20+ years before their “expiry date”. Similarly, many of the cardiotropic viruses such as EBV, HHV-6, and PVB19 – also associated with ME/CFS have a characteristic "signature" that requires "out of the box" cardiac diagnostics and targeted treatment (just look up myocarditis and virus on PubMed). Over here, we just get a diagnosis of “idiopathic cardiomyopathy”… when the Germans are a decade ahead, sensitively and specifically ferreting out and treating the heart viruses.
It doesn't take a rocket scientist to recognize that even HIV patients present uniquely - depending on the particular cocktail of opportunistic viruses they are growing. Why is the analogy of XMRV to ME/CFS too difficult to comprehend? After all, that’s what retroviruses DO – they potentiate opportunistic infections, and not always the same infections in every patient.
DT, you also display ignorance of abnormal neurological findings, which can be documented SPECT findings - rarely performed of course on all those malingering Brits with ME/CFS - which show profound perfusion abnormalities in the brain (also consistent with endothelial dysfunction). Again, as a former health professional I readily recognized my own onsets of TIA and stroke. However the "experts" I saw were woefully unequipped to diagnose subtle neurocognitive and neurological abnormalities, much less pervasive microvascular perfusion changes. This flies in the face of “early detection” mantras in medicine, and patients are left with progressive neuro/ neurocognitive signs and symptoms. Repeated visits as neuro pathology progresses, are met with derision and disdain: “Don’t waste our health resources” is the maxim.
It would be a gentle characterization to say that experts have traditionally used "blunt instruments" of diagnosis for ME/CFS - particularly when they metaphorically throw their hands up in the air the instant a history of Chronic Fatigue Syndrome is mentioned. If anyone is wasting health resources, it’s the club of physicians who are complicit for having allowed an unfortunate segment of the psychiatric profession to hijack promising biomedical research on ME/CFS.
If the FDA and NIH findings are reproduced internationally, we will be looking at a retrovirus in 3-7% of the population (much less the staggering % in ME/CFS patients) … and that should worry any thinking physician a LOT. Particularly since promising retroviral research in ME/CFS was snuffed out 2 decades ago by the CDC, as legions of patients have languished and died early deaths.
Suffice it to say that ME/CFS patients - particularly the ones who have been ill for one, two, three decades - have good reason to be anxious. It is an entirely normal reaction to being belittled, humiliated, and lectured at (even as you lose your career, your loved hobbies, your loved ones) by ignorant physicians who couldn't find an elephant in a haystack if their lives depended on it. That's the issue here. If your life depends on finding a cure - and you have a modicum of intelligence (something I'd credit far more of the assertive, pro-active, and enlightened ME/CFS patients with than the bigoted physicans many of us encounter), you will voraciously follow the research.
So DT, please spare me your pseudo-concern for ME/CFS patients. And while you're at it, you might get off your self-righteous high horse that "people like me are left to pick up the pieces when things go wrong." That's the whole point of the problem. NO ONE is picking up the pieces, even as ME/CFS patients stagnate for decades in dark rooms, in bed; and die early deaths from cancers and cardiomyopathic heart failure.
XMRV may not "be it" - but from what I have seen of the science, it indeed will be. And there will be many, many so-called "experts" around the world with egg on their faces. XMRV potentially represents a global health crisis of mammoth proportions that has been brought on by precisely the kind of indignant groupthink that you personify. If anything, ME/CFS patients should be lauded for speaking the truth and advocating for our care - when no one else wants to get their hands dirty by breaking the chain-letter cycle. We know how serious this disease is. Now how about informing yourself on this topic?
As a first step, you might wish to read the actual NIH/FDA papers, which will be imminently available. Or is the topic too complex for you?
The only this writer clearly establishes is that he knows very little about CFS. And by the way, CFS does kill people, and people that have it and friends and family of those people absolutely will do whatever they need to do to find a cure and treatment. No one else is going to do it for them. You statements above are just further confirmation of that.
Shame on you.
Thanks to all of you who have responded - I've not looked in for a few days so apologies for replying late. The recent posts cover a lot of ground on CFS/ME from diagnosis to treatment and I could not possibley respond in detail to you all.
However, to Oryx I would say that rumours of confirmation of the WPI Science findings remain just that - rumours. When the paper is published we can review what it says. Til then it is rather premature to comment. Harvey Alter's presentation is clearly based upon the precautionary principle with respect to blood transfusion - if anything might be in blood that is transmissable, even if it has not been shown to be linked to any medical illness, then protection of the blood supply is paramount. This hardly indicates verification that XMRV causes ME. Even were there to be independent verification and a consensus emerges to suggest active infection can provoke or perpetuate ME symptoms, there is still a huge gap between finding a probable cause and developing appropriate therapy. My concerns, which I have emphasised, are that unjustified, potentially very toxic drugs are or will be thrown around like smarties in misguided and unstructured attempts to treat this syndrome, often based upon patients' whims or based upon ideas they have gleaned from posters on the web. Is that really how you wish treatment for this condition to be developed and implemented? What would be required would be appropriate research studies in the fashion of ARV therapy for HIV - multiple, well controlled and randomised major trials of possible drugs shown in vitro and early phase 2/3 trials to be of benefit in ME. The approach currently being used and advocated is not in the interests of those with ME.
Anonymousity, where have I suggested that as a UK doctor I recommend barbaric psychiatric hospitalisation as treatment? I never mentioned GET or CBT either. And I fail to see how official definitions (psychiatric/psychosomatic/physical) could result in a situation where this disease could have been "prevented long ago". I resent suggestions that I have to have this disease in order to "have a clue". Medicine doesn't work that way, fortunately.
Givemeabreak, where have I used invective against ME patients? I genuinely am concerned for ME patients here in this mad rush for treatments at any cost and without any structured strategy in place. Dr Aust btw is not an expert, nor did he ever say he was. He is someone with a strong science background who is voicing his opinion (as we all are).
This is a blog, after all, not a commisioned expert review article on ME/CFS for the BMJ.
Many doctors actually are happy to admit they are stumped by patient's symptoms, but like most professionals in whatever job they may be reluctant to admit helplessness in their attempts to lessen patients symptoms.
For some, convincing themselves that the patient's symptoms are psychosomatic or the result of depression is a way of convincing themselves they have done all they can. And remember, of the dozens of patients that present to a GP with fatigue and symptoms consistent with CFS/ME or even presenting with a self diagnosis despite not having the case-defined symptoms, most may not have ME, and would not meet the Canadian criteria.
You claim I am "clearly ignorant when it comes to knowledge of the cardiomyopathic changes in persistent viral infection". What on earth do you base this claim upon? Is my post about this subject? Viral cardiomyopathy can causes sudden death. How many ME patients die in this way? Can you provide links to the evidence you say exists for XMRV causing atypical angina and early death?
So, the idea is that 7% of the population have XMRV, which is transmissable by blood, sexual contact and MTC transmission? As a retrovirus, human carriage is not something particularly unexpected. But what clinical correlates does it have? What proportion of the infected develop ME? According to Dr Deckoff-Jones, everyone will. How long has this been going on? Have 7% of us been dying from cardiomyopathy at an early age?
Let's see the science people, then we can move things forward in the most appropriate way posssible. Medical science accomplishes advances by careful, well planned and thoughtful epidemiology and clinical studies, not by letting our imaginations run riot.
And that's a name I've worked hard to earn. Pleased to meet you.
If the discussion is limited to criticism that patients are taking drugs that should only be issued in clinical trials, then perhaps some of the anger directed at you is harsh. If we move beyond that, it gets a little more complicated.
This is one of several blogs that has published pieces that are highly critical of WPI. They have certainly been clumsy in their PR, and perhaps in another area or two. But there's been a litany of talking points: they're selling tests; they're advocating ARV therapy; they're unprofessional in their criticism of other virologists; they're making irresponsible statements about autism. And on and on. And they kill kittens and puppies for fun, too.
Enough. We've been reminded enough times that This Is Not Done In Science. That is not the only talking point in this discussion.
What IS done in science when it comes to CFS/ME? What HAS been done in science when it comes to CFS/ME? The WPI and Jamie Deckoff-Jones are guilty of all these heinous crimes against science...but the status quo as it's been, that's somehow okay? I have yet to see anyone taking a position adversarial to the WPI say one word about how science has prioritized research when it comes to CFS/ME. About the numbers on CFS research funding.
http://report.nih.gov/rcdc/categories/
For any point you and others have made that I would grant as valid, there is a tremendous, ridiculous double standard. Do you not see it?
Besides which, as Hillary Johnson pointed out in her piece on the Chicago Tribune reporter...
http://www.oslersweb.com/blog.htm?post=710020
...does anyone know exactly how many patients are taking antiretrovirals? Does anyone know remotely?
Educated guess?
It would be folly to disagree that treatments outside of clinical trials are, at best, inappropriate, even taking people's desperation after decades with no treatments into account. But it strikes me that in this day and age, anyone who has a doctor willing to prescribe these meds is probably involved in some measure of discussion about it on the internet. Now, I haven't trolled patient forums looking for evidence of patient feedback, but it's not hard to come across them, especially since evidence of one is apparently taken as evidence of...many.
Outside of Deckoff-Jones and her daughter, I've seen one other person talking about this, and I presume you saw the reception she got when she dared to 'fess up on ERV (whose half-her-age persona is becoming increasingly bizarre; witness her attacks on Nancy Klimas). Again granting that there may well be discussions I have not seen and of course people who are not discussing, that is hardly even an educated guess. But it is a comment on the difficulty of even coming up with one, even with patients generally being VERY eager to share and communicate. So I would respectfully suggest that there are very, very few people currently taking these drugs in this manner (i.e. independently of clinical trials). But we don't know, and if you think there are hordes of people doing this...fair enough. Doesn't make sense to me, but whatever.
>And remember, of the dozens of patients that present to a GP with fatigue and symptoms consistent with CFS/ME or even presenting with a self diagnosis despite not having the case-defined symptoms, most may not have ME, and would not meet the Canadian criteria.
Canadian criteria? How many doctors would you say order the tests that allow for that criteria? On the entire planet? I'd be shocked if there are more than 100, probably more like a few dozen. If you disagree, I would ask if you could provide evidence to the contrary (an unreasonable request, granted, but the NICE guidelines & CDC both advise against such testing, at least for diagnosis, don't they? Oh, yeah--they don't recognize those criteria).
If you agree, then that speaks for itself as far as What Is (and is not) Done In Science.
I have to say that this is the most respectless post I have read about this. Who are you to say what is right for someone you don't know?
I'd rather not live, than live one more year with CFS. But I guess to you, I shouldn't be allowed to take a long shot, simply because it's a long shot.
I would say that rumours of confirmation of the WPI Science findings remain just that - rumours. When the paper is published we can review what it says. Til then it is rather premature to comment.
Looks like we'll have to wait a bit longer for any corroborative studies to be published.
The CDC study (see ref below) which has failed to confirm the Lombardi/Mikovits findings is being held back from formal publication just yet, while it is clarified as to what the apparently confirmatory NIH study shows.
http://www.retrovirology.com/content/7/1/57
http://www.nature.com/news/2010/100702/full/news.2010.332.html?s=news_rss
That last comment was from me - I forgot to log in.