Finding XMRV in a CFS cluster

Many people don't realize that CFS (Chronic Fatigue Syndrome), and the other names by which this disease is known such as Atypical Poliomyelitis and Myalgic Encephalomyelitis, is a cluster illness, meaning that there are outbreaks of many cases close together in a geographical area.  This aspect of this illness (or variations of an illness) has been downplayed, perhaps because it strongly implies a contagious etiology. 

The Wall Street Journal recently did a piece about Lyndonville, a town in upstate New York that was epicenter to an outbreak of CFS back in the 1980s (a decade that saw many outbreaks).  This outbreak has been studied because it was a very large relative to the small population of the town, it struck many young people, and the same small town doctor has been seeing these people for 25 years.  It was found recently that 70% of the people in that outbreak tested positive for XMRV.  Here is the WSJ piece:



The following video (although overly melodramatic) lists many of the outbreaks of the 20th century that are believed to be ME/CFS.  While undoubtedly some of these clusters were other illnesses, and in many cases so much time has passed that there is no way to go back and verify that it is indeed ME/CFS that occurred, I think it is still interesting to see the dates and locations of these outbreaks.  The ones that interest me the most are the one in Sacramento, CA in 1975, San Francisco Ca in 1984, and the series of outbreaks around Lake Tahoe and central California beginning in 1984 as it is plausible that I was infected in one of these outbreaks.  The sources for the epidemiological data are listed at the end of the video.

Journal of Infectious Diseases Reports on the Status of XMRV Research

As those of you who follow developments in the progress of research into the recently discovered retrovirus XMRV and human disease are aware, lately there has been a great deal of confusion about what the correlation is if any.  The original Lombardi et al paper that came out of the Whittemore Peterson Institute, and was published in the journal Science, made a strong case that XMRV is associated with human disease. Several follow up studies did not corroborate this finding, but have numerous methodological errors and serious conflicts of interest.  Much of the confusion in the mainstream media seems to have arisen because they received PR announcements when these studies were published (after a delay), but did not do research to understand what has transpired during the delay nor to establish the context of these studies, and they are unaware of the Harvard/NIH study that supports the original WPI findings.  As a result, there has been widespread dismissal of the original research as being nothing more than contamination from mouse genes.

Ongoing research will hopefully clarify the (probably complex) relationship between XMRV and other murine retrovirsus with their potential to cause disease in humans.  In the meantime, the Journal of Infectious Diseases has written up a summary of the research so far and what the implications may be.  Although this summary is conservative, it is a fairly helpful guide.  This summary gives more background of the research involving prostate cancer, which may be more relevant to ME/CFS then it seems at first glance since ME/CFS leads to an elevated risk of cancer (often lymphomas or brain tumors), so the possible cancer connection is interesting to me.  The research so far on XMRV's role in prostate cancer seems to indicate that the mechanism by which XMRV acts to promote cancer is complex rather than the simple triggering of an oncogene, or insertion of a DNA strand to trigger the cancer, that some retroviruses are known to do. 

This report sheds some light on why the findings of XMRV ( and other MLVs) in the human population may vary so much.  "Several factors may contribute to the varied detection of XMRV in different populations, including geographic distribution, patient selection, analyte choice (DNA, RNA, antigen), and detection methodology."  Additionally, they add "viremia may be chronically low (as it is in HTLV), transient, or episodic, complicating detection."  The Journal then proceeds to list out measures that would help in the future to resolve the issues caused by the variability of detection so far including standardized assays, independently confirming results by sharing and retesting the same samples, doing prospective studies to asses which populations should be studied, and figuring out how the various Murine endogenous retroviruses are related to each other.  They also point out that when it comes to the challenge of finding and confirming specific disease causation, this is much more challenging to do with retroviruses than it is with other pathogens that have a more basic mechanism for causing disease.

This blog post entitled "The XMRV Hunt and Me" explores some of the possible reasons why a very sick patient may test negative but still have disease caused by this retrovirus.  Mary Schweitzer (a particularly knowledgeable patient and advocate) has pointed out on her blog that HIV was first detected in lymph tissue rather than blood, and as chronically swollen lymph nodes is a classic sign of ME/CFS, it might make sense to look there.  She also points out that evidence from France indicates that the virus may pool in the lungs.  The NICEGUIDELINES blog points out that because XMRV is slow-replicating it is important to locate reservoirs and the virus may need to be brought out of latency.

Here are some other interesting tidbits from the report:

"Analyses of XMRV sequences from different sources have revealed limited genetic diversity among patients. Because retrovirus diversity is dependent on cycles of error prone viral replication, the absence of XMRV genetic variability suggests that multiple cycles of infection are not taking place in humans."

"these data suggest that XMRV had zoonotic origins in mice but has replicated to only to a limited degree in humans."

 "With respect to therapeutics, XMRV is sensitive to some antiretrovirals in vitro [11, 20, 29], and there are calls for use of antiretroviral agents for therapy, even though early observations suggest XMRV replication may be minimal in humans."  This statement is followed by an admonition NOT to use these drugs on patients outside of carefully controlled clinical trials.  This idea has been hotly argued within the ME/CFS patient population for many reasons.

New Developments in XMRV 1/19/11

This piece by Paula Carnes, called "Testing Negative, Staying Positive" gives a lot of new information about being tested for XMRV.  She elaborates on why some people are testing negative, how the disease seems to be working in the body, and some promising leads for treating it.   Here are a few highlights:

"-XMRV leaves the blood and hides out elsewhere in the body until you are stimulated with another infection. [This could explain that the early outbreaks at Incline Village, NV, Lyndonville, NY and Raleigh, NC were caused by a secondary contagious infection superimposed on an existing XMRV infection.] Replication of XMRV is stimulated by inflammation and hormones.

-The retrovirus(s) has a high level of sequence diversity or different strains. The NIH (Alter and Lo) found a P (polytropic) MRV strain. This means that if you are infected with the PMRV strain you will currently test negative at The Whittemore Peterson Institute (WPI). Mikovits is working to develop more accurate testing for both strains. She hopes to have a test for PMRV by June 1, 2011.

-Possible infections that enable XMRV to multiply would include EBV, HHV6, borrelia, babesia, bartonella, other?

-In chimp studies the virus very quickly left the blood and went into reservoirs, lymph node, spleen, liver – maybe thyroid, sex organs, adrenal glands, salivary glands, brain.

-Stress elevates cortisol levels which would in turn activate XMRV.

-Some patients have a positive culture test but no antibodies. If they are treated and begin to get better antibodies for XMRV will show up.
     

That article mentions another blog post in which a study is discussed showing evidence that XMRV may be a tick borne disease, here's a quote:

"Recently, a small study has revealed that ticks might be one way XMRV is passed on.  The study is being done by Dr. Eva Sapi and Dr. Joe Brewer.  The connection was discovered with a sample of chronic lyme disease patients showing 90% infectivity rates with XMRV and MLV's.  It is coincidental that the symptoms of Chronic Lyme, and Chronic fatigue syndrome are almost impossible to differentiate.  It also explains why despite antibiotic treatments, these patients fail to show improvements.  Ticks are already known to carry a form of viral encephalitis."

Dr Katz presents a webinar about XMRV in the blood supply

The first quarter of the webinar is more about details of blood banking and testing that are not specific to XMRV or ME/CFIDS.  After that, he turns his attention to both the disease and the virus.  Here are some points of interest:

Here is the link:
http://www.youtube.com/solvecfs#p/a/u/0/ex6iS_2RqiY

He notes that the more names there are for a given illness, the less well understood that illness is.  CFS has had many names, including Chronic Fatigue Syndrome, Post Viral Fatigue Syndrome, Myalgic Encephalomyelitis, and XAND which stands for X-associated Neuro-Immune Disease.  The name XAND was proposed by people at the Whittemore Peterson Institute because of the suspected association with the XMRV virus.

Prevalence of CFS in US is estimated between 0.4 and 1 percent of population.

A study published in the Journal of Infectious Diseases found that there are a number of genes expressed differently in people with CFS then in healthy controls.  These abnormal gene expressions are similar to those found in diseases of the hemenologic system, cancer, autoimmune disease,

XMRV is a gammaretrovirus that causes leukemias and sarcomas in other animals, including primates.

XMRV is closely related to xenotropic MLVs, which are murine leukemia viruses found in mice.  These viruses can be isolated from the genomes of mice and are then able to cause disease in other animals (this makes me wonder if XMRV came from biologics grown in animal tissue in the lab, such as vaccines?).

In 2009, a paper was published in the Journal Science that found XMRV in 67% of patients.  Dr Katz points out that the study looked for evidence of infection in several different ways, which makes the evidence stronger.  It was found in 3.7% of healthy controls.  Four further independent studies have not fund XMRV (although at least in some cases, they used very different methodology and looked in different places) in CFS patients.  Another study is expected imminently and is expected to confirm the WPI findings. 

The CFIDS Association of America has advised against people with CFS donating blood or organs because of the possibility of a virus such as  XMRV being transmitted.