RESEARCH

XMRV - Hope and Caution: A Laymen's Guide to Chronic Fatigue Syndrome

Who Are Those Guys?  -  Gazing at the distant cloud of dust raised by his dogged but mysterious pursuers Butch Cassidy turned to the Sundance Kid and with some awe muttered “Who are those guys?” Despite all  their tricks that posse had stuck on their trail like glue. Has the Whittemore Peterson Institute’s posse caught one of  the slippiest preys in all medicine? Or will a significant subset of ME/CFS patients slither through their hands?

A good part of that answer depends on “Who are those guys?” Specifically when WPI researchers called the subjects of their study chronic fatigue syndrome (ME/CFS) patients just who were they talking about? Answering that question may determine if the WPI posse can corral  the whole disease or just a portion of it.

Lets take a close look at just who was in the little study that shook the ME/CFS world.

"When scientists want to find a virus, we look for it in the sickest individuals because often this is where there is likely to be the highest levels of a virus, if present." Dr. Suzanne Vernon

Stacking the Deck - The WPI did not choose your garden-variety chronic fatigue syndrome patients for their first study. They kind of stacked the deck. Stacking the deck ior putting your best foot forward is actually standard procedure in the research world. In their first study  researchers usually include patients they think will best make their case.

Those patients still fit the definition of the disease but they’ll often have less than subtle differences.  (Given the vague definition of this disease make that very large differences. This is presumably one reason the CDC went to a random sampling scheme.)

An immune researcher would probably try to include pathogen loaded, cytokine upregulated, fluey patients. A endocrine researcher might fit in patients with hormonal problems. Perhaps not surprisingly that first study usually works out pretty well but the second one by an independent researcher who didn’t try and gild the lily, so to speak, often doesn’t.

A Special Group of Patients - In this case Whittemore Peterson Institute was refreshingly direct in how they ’stacked the deck’. They stated  the study participants had ’severe disability’, low natural killer cell functioning, increased pro-inflammatory cytokine levels (primarily IL-6, IL-8), ‘extremely low’ VO2 max during exercise testing and RNase L dysfunction. During a radio interview we learned that 20% of the patients had lymphoma. (The Whittemore-Peterson Institute later stated that that was not true) Without knowing their functional status it sounds like they are housebound and many very well may have been bedridden.

Outbreaks! (Outbreaks?) - They also came from areas where ‘outbreaks’ had occurred. The WPI took a page from  the distant past when they included outbreaks in the parameters. No one to my knowledge has officially reported an ‘outbreak’ in several decades. Why therefore specifically go back to where ‘outbreaks’ had begun (and therefore not include ‘non-outbreak’ areas)?

Was this to highlight the possibly infectious nature of this pathogen or to draw attention to an important but mostly forgotten era of ME/CFS thinking? Or was it central to their case? Was limiting the participants of the study to known infectious events one way the WPI gilded their lily? (Will ‘non-outbreak’ patients fit the WPI’s  scenario?)

Whatever the answer to  that question its clear that these do  not appear to be your normal chronic fatigue syndrome patients. A recent Pacific Fatigue Lab study, for instance, found low VO2 max levels in about half their participants. A considerable number of those participants came from Dr. Montoya’s and Dr. Peterson’s pathogen studded patients. Given that the patients in all had  extremely low VO2 max levels study it’s possible that a significant number of even pathogen ridden patients might not have gotten into this study.

This was clearly a special subset; a patients; one that Dr.  Peterson says he believes makes up somewhere around 25% of all ME/CFS patients. Again this is expected but it does make it difficult to interpolate the results to other types of patients. Annette Whittemore has stated that she's committed to the entire ME/CFS group and the  WPI will certainly broaden its testing procedures to include more types of patients in the future.

The Big Question - Do I have an XMRV infection? Taking a very conservative view of this question and going strictly off this paper you’d have a good chance of testing positive for it if you had the following characteristics; an infectious onset, extremely low VO2 max levels, low natural killer cell functioning, RNase L. problems and increased inflammatory cytokines. (If you have all of those plus lymphoma you’re almost certainly in - but in a very bad way). Even in these very poorly off patients only two thirds of them tested positive for the virus (but that appears to be more a function of a less than accurate test than anything else).

Room  For Hope -  If you go strictly by the study you may begin to wonder if its going apply to the ‘average’ ME/CFS patient.  There is considerable room for hope, however, that it will  Dr. Mikovits reported that 95% of a larger set of patients (n=330) tested positive to an antibody tests. The antibody test did not measure active infection but it did indicate that these patients have been exposed to the pathogen.  Dr. Mikovits also stated that she expects most ‘ME/CFS’ patients to test positive for the virus. Dr. Cheney is our only independent guide to the prevalence question right now. He contributed 14 patients to  the study and reported that his results were similar to the group as a whole.  That is encouraging.

 It's also encouraging that  the patients came from me areas across the US.The virus has also been found in some FM patients, autism patients and atypical MS patients which suggests that the number of people with this virus will broaden not diminish.

Just like you cannot have AIDS without HIV, I believe you won't be able to find a case of chronic fatigue syndrome without XMRV," Dr. Judy Mikovits

Thankfully the number of healthy controls testing positive has remained very low throughout; this pathogen - in contrast to all the others associated with ME/CFS - appears to to be quite rare in the general population - an important finding.

Plus the WPI recently stated that not all the people in the study had abnormal RNase L/NK cell results thus it doesn't appear that you need to have these immune dysfunctions in order for the virus to be present. More and more it's looking like the broad group of ME/CFS patients may have this virus. Still the only thing that will seal that deal are studies showing that moderately ill patients are infected.

Professional Recomendations  - It wasn’t surprising, therefore, that the first recommendation from the ME Association was for the WPI to begin

"Carrying out further and larger studies using different populations of people with ME/CFS, including people at different stages of the illness (to see if the virus is present in the same percentages in both early and late cases) and in all degrees of severity."

 

Dr. Vernon echoed this when she stated that

“Independent replication studies should also include patients with mild and moderate CFS, at least one chronic disease control group (e.g., multiple sclerosis, lupus) and sex and age-matched healthy controls.”

Who Are Those Guys? So we don’t really know who ‘those guys’ - the ones with the virus - are  yet. We certainly have some tantalizing hints that the virus is  found in more types of patients than the Science paper can show but patients might want to wait pop the bubbly until they see studies that contain patients that look like them. The good news is that those studies should already be underway.

Beachhead Established - the Jungle Awaits - This is not to criticize the Whittemore Peterson Institute. It’s about being wary in the face of  a complex issue. Given how research happens these problems are inevitable. The WPI’s first job was to establish a beachhead and they’ve established the most biggest beachhead yet in this disease. Their next job is even more difficult - to try and work their way deeper into the jungle that has been ME/CFS. Hopefully they’ll be able to.

The Phoenix Rising website is compiled by a layman. It is not a substitute for a physician and is for informational uses only.