THE FDA/NIH/HARVARD “XMRV” STUDY: THE SAME THING, ONLY DIFFERENT

by Mindy Kitei 

The just-released study detects variants of the retrovirus XMRV in most CFS patients.  In addition, nearly 7 percent of the healthy U.S. controls—all of whom are blood donors—test positive, signaling the contamination of the U.S. blood supply. 

Patients, physicians and virologists have been anxiously awaiting the Proceedings of the National Academy of Sciences (PNAS) paper on Chronic Fatigue Syndrome and the retrovirus XMRV.  The paper, "Detection of MLV-related virus gene sequences in blood of patients with Chronic Fatigue Syndrome and healthy controls," was published today.  In it, the authors state that their conclusions “clearly support” the October 2009 Science study linking the retrovirus XMRV to the neuroimmune disease Chronic Fatigue Syndrome (CFS), which afflicts 17 million people worldwide, 1 million of them in the U.S.  XMRV has also been linked to a virulent form of prostate cancer.

Most surprising is that the PNAS study didn’t find XMRV, which stands for Xenotropic Murine Leukemia Virus-Related Virus, in any patients or controls.  Instead, researchers from the National Institutes of Health (NIH), the FDA, and Harvard Medical School detected novel close cousins to XMRV called MLVs—which stands for Murine Leukemia Viruses—in 86.5 percent of 37 patients and nearly 7 percent of 44 controls.

Seven percent is approximately 20 million people, a robust signal that these retroviruses have entered the blood supply. What makes this most likely a fait accompli is that the healthy controls in this study were all blood donors. Before the discovery of XMRV, there were only two known human retroviruses: HTLV and HIV.

A family of viruses
The NIH’s principal investigator on the study, Dr. Harvey Alter, believes his group and the earlier Science group are looking at the same retrovirus.  “Viruses tend not to be homogeneous,” Alter explained to CFS Central in a telephone interview. “The fact that we didn’t find XMRV doesn’t bother me because we already knew that retroviruses tend to be variable. They mutate a lot, basically. This is true of HIV and HCV [hepatitis C virus]. It’s not one virus. It’s a family of viruses.”

Dr. Judy Mikovits, principal investigator of the 2009 Science study, agrees. “We presented a paper at the Cold Spring Harbor RNA tumor virus meeting in May showing that patients reported in Lombardi [the Science paper] contained both X [XMRV] and P [polytropic MLV] variants as well as at least one other family member,” Mikovits told CFS Central.

The Murine Leukemia Viruses detected in the Alter paper have been studied for more than 40 years and are known to cause leukemias and neurological disease.  As documented in more than 2,500 studies, patients with CFS suffer from neurological symptoms, including seizures, short-term memory problems and abnormal brain scans, as well as cancers, particularly lymphomas. The "Murine" in Murine Leukemia Virus is another word for mouse. The last known retrovirus to jump species was HIV—from monkeys to humans.

Alter said that the paper’s conclusions haven’t changed since June. That’s when his paper was put on hold, along with a CDC XMRV paper that didn’t find the virus in CFS patients. Back then, a spokesperson for the Department of Health and Human Services (HHS) announced that the papers were pulled to reconcile or at least to understand why the CDC didn’t find XMRV, and the FDA and the NIH did. At that time, Alter’s paper not only had already been accepted by PNAS, it was in galleys—the final stage before being printed in the journal.

Scientists disagree all the time, particularly with new discoveries, so holding up the PNAS paper at that phase was surprising and unusual. PNAS Editor-in-Chief Dr. Randy Schekman told CFS Central in July that putting a paper on hold had occurred only one other time that he knew of in his nearly four-year tenure at the journal.

Science or spin

The HHS announcement of pulling both papers morphed into political spin when the CDC study was published in the journal Retrovirology a few days later, on the listless Friday before the July 4th holiday weekend. Meanwhile, the scientists on the FDA/NIH/Harvard study were sent back to the drawing board to do more work on their study.

Their study, said Alter, has only gotten stronger in the interim. “There were no changes in the conclusions, but we added data that made the conclusions stronger,” he explained. “For one thing, we did some further work to feel confidant that there was no contamination…. We had hundreds of negative controls, and every assay had negative controls. And then we used an assay from mouse mitochondrial DNA and found that there was no evidence of mouse contamination. We had variation in the viruses we were finding. If there was a contaminant, you’d find one species, not several.”

The key scientists

Along with Alter and fellow scientists at the NIH, researchers at the Food and Drug Administration led by Dr. Shyh-Ching Lo, and Professor of Medicine at Harvard Dr. Anthony Komaroff, conducted the PNAS study. Alter’s earlier NIH research led to the discovery of hepatitis C. Chief of the NIH’s infectious diseases section and associate director of research in the department of transfusion medicine, Alter developed methods to screen the blood for hepatitis, essentially eradicating the risk of acquiring hepatitis from donor blood.

The highly respected Lo is best known for isolating the pathogen mycoplasma fermentans from HIV patients. And Harvard’s Komaroff, senior physician at Brigham and Women’s Hospital in Boston, has been publishing steadily on a viral connection to CFS since 1987.

The researchers caution, as did the earlier Science researchers, that their study doesn’t prove these retroviruses cause CFS, only that they’re associated with CFS. The next step is to determine if they’re causative for the disease and transmissible by blood. The latter seems likely, based on a recent study by researchers at Emory University’s primate lab.

“I think these retroviruses are likely to be associated with a subset of cases,” wrote Harvard’s Komaroff in an email to CFS Central. “Until larger studies are done, we won’t know how large that subset is…. The two important questions at this stage are: 1) Based on larger studies from a broader geographic area, what fraction of cases are associated with these MLVs; 2) Are these MLVs a cause of CFS, or just ‘innocent bystanders.’ ”

Four MLVs

The FDA/NIH/Harvard researchers detected four MLVs, which they referred to as “CFS Type 1,” “CFS Type 2” and “CFS Type 3.” Type 4 was found only in one control. “Not that we can tell,” Komaroff replied when asked if the different types exhibited different symptoms, “but the total numbers are small: We need much larger studies to answer this important question.”

In addition, the blood from eight of the 25 patients Komaroff supplied from 15 years ago had blood draws again in March 2010.  Seven of the eight remained positive. According to Komaroff, the patient who became negative hadn’t recovered.

However, that doesn’t mean that this retrovirus doesn't cause CFS, and it doesn’t mean that the patient isn’t still infected with the MLV. Since the host’s DNA becomes inextricably intertwined with a retrovirus, infection lasts for life. Besides, as noted in both the Science study and in the PNAS study, finding this retrovirus in the blood is difficult. In fact, Emory University scientists who injected XMRV into macaques this past spring reported that even when the virus was undetectable in the blood, it thrived in the reproductive organs as well as the spleen, gut, bladder, lung, liver and lymph nodes. Explained Alter, “When viruses are in low titer, sometimes you can find them one day and not find them another day.”

Mutating MLVs
Important to note is the retroviruses detected in those seven patients in 2010 had mutated in the 15-year interim. “That’s just what you’d expect from a retrovirus,” said Alter. “That’s more evidence that this is a real agent, not a sequence floating around in the lab.”

What's next
Alter said he’ll look at other cohorts of CFS patients as well as patients with other diseases, including hepatitis C, HIV, fibromyalgia and autoimmune diseases to see if they harbor these MLVs. He’ll also be examining larger populations of blood donors to determine if the MLVs are transmitted by blood.

The 2009 Science XMRV study led to Australia, Canada and New Zealand banning patients with CFS from giving blood. And the Japanese Red Cross issued a disturbing report that XMRV has been detected in nearly 2 percent of Japan’s blood supply. The U.S. government has stopped short of prohibition, but the National Cancer Institute has advised CFS patients against blood donation. Will the U.S. be next?   “Our policy now is that if someone says they have Chronic Fatigue Syndrome, we will not use them as blood donors,” said Alter.

Judy Mikovits believes that the prevalence of MLVs in the healthy population—3.7 percent in her study and 6.8 percent in the FDA/NIH/Harvard study—“represents a serious public health threat that demands research dollars and clinical trials for those who are infected and ill.”

Researchers at several governmental agencies have formed a working group to examine the blood supply for XMRV.  Now that the FDA/NIH/Harvard study has found additional MLVs, that pursuit will be broadened. “The current assays are very difficult,” admitted Alter, one of the researchers looking at the blood supply.  “The viruses are present in very low titers so you need a very sensitive assay.  They will have to be broadened to more than just XMRV."  No easy task.  An antibody test, Alter explained, would be simpler than the current methods of PCR and culture. "It would be more broad, and it wouldn’t require amplification or sequencing. The NCI [National Cancer Institute] has been working on an [antibody] assay, but it’s not so robust yet.”

Bishop paper

Interestingly, a group of British researchers led by retrovirologist Dr. Kate Bishop reported in 2010 that 26 of their group of 170 patients and 395 controls exhibited antibodies to XMRV. The surprise came when the scientists unblinded the study and discovered that 25 of the 26 were controls. “I was quite shocked,” divulged Bishop to CFS Central in June. Bishop understandably expected that most of the 26 would be patients. However, she wasn’t convinced that the antibodies were caused by XMRV. That’s because the antibodies of all but three controls and one patient weren't specific for XMRV and neutralized other viruses as well as XMRV. In hindsight, could those antibodies have been mounted against the MLVs that Alter and Lo found? At this juncture, it’s anyone’s guess.

FDA/NIH versus CDC

In late June, when HHS spokesperson announced the unusual decision to pull the PNAS paper as well as the CDC XMRV paper to reconcile or at least to understand the disparate findings of XMRV studies by the CDC, it became nail-biting time for patients. Several 2010 European studies failed to find any evidence of XMRV in CFS patients, and without confirmatory news many feared the XMRV connection would be severed.

Many patients and researchers have been ruminating whether the FDA/NIH/Harvard paper would ever be published. Indeed, one highly placed CFS Central source believed the study would have been quashed had some of its findings not been leaked in June by Dutch journalists at a blood-borne pathogen conference in Zagreb, Croatia. Ever since, online forums have been rife with uneasy posts from patients speculating whether the findings would be changed to fall in line with the XMRV negative CDC study.

Byzantine history

Given the 26-year Byzantine history of the government response to Chronic Fatigue Syndrome (see sidebar for more, below), including a retroviral link to CFS first detected—and then ignored—nearly 20 years ago, it’s been an understandable concern.

In 1991, a young researcher at the University of Pennsylvania’s Wistar Institute named Dr. Elaine DeFreitas discovered a retrovirus in the blood of CFS patients and, ironically, published her findings in PNAS. (Whether XMRV and DeFreitas’s retrovirus are one and the same is not known with certainty.) When the CDC couldn’t reproduce the results, DeFreitas’s discovery was dismissed.

Tangling with the U.S. government proved costly to the researcher, which scared off likeminded scientists for nearly 20 years, silenced patients and split the research community into two nonintersecting camps: Those who championed a viral cause, and those—including the CDC, several British psychiatrists and Emory University psychologists—who championed a psychogenic cause.

The scales tipped in the viral direction when Dr. Judy Mikovits of the Whittemore-Peterson Institute in Reno, Nevada, led the U.S. group that connected XMRV to CFS in 2009. Longtime CFS viral researchers, physicians and patients were hopeful for the first time in nearly two decades that maybe, just maybe, their time had finally come.

But after the spate of European studies that didn’t find XMRV in 2010, and after the CDC didn’t either, there was an elegiac sense of déjà vu—that what happened with Wistar’s Elaine DeFreitas was about to happen all over again. Blogged one patient: “If anyone can put a positive spin on this then please post now. I sense defeat (in myself). And another 13 yrs (to life) in the wilderness.”

Given today’s findings in the FDA/NIH/Harvard paper and the studies by Alter and other scientists in the works, that scenario no longer seems likely.

###

This article and sidebar, below, are copyright CFS Central 2010. All Rights Reserved. You may quote up to 150 words from this article as long as you indicate in the body of your post (as opposed to a footnote or an endnote) that the excerpt is by Mindy Kitei for CFS Central. You may not reprint more than 150 words from this article on blogs, forums, websites or any other online or print venue. Instead, refer readers to this blog to read the article. 
 

SIDEBAR:

The CFS Political Backstory 

In 1984, Dr. Paul Cheney and Dr. Daniel Peterson dialed up the CDC for help with an outbreak of a flu-like illness that had hit their picturesque town of Incline Village, on beautiful Lake Tahoe, Nevada. When the epidemiologists arrived, they saw about 10 patients, and then went skiing. That outbreak turned out to be one of several outbreaks of Chronic Fatigue Syndrome seen worldwide in the 1980s.

In 1991, a young researcher at the University of Pennsylvania’s Wistar Institute named Dr. Elaine DeFreitas discovered a retrovirus in the blood of CFS patients. Twenty years ago, newspapers and TV news shows latched onto DeFreitas’s finding, spreading the word that the cause of the debilitating disease had, perhaps, been found.

The jubilant atmosphere was short-lived. The CDC failed to find DeFreitas’s retrovirus in patients and controls (without using DeFreitas’s protocol) and British researchers found the retrovirus in all the controls and the patients—again without using her protocol. Given the diametrically opposed findings, DeFreitas reasoned the problem was rooted in the methods. But by that time, retroviral disbelievers outnumbered believers, media interest had flagged and the CDC took the unusual step of publicly chastising DeFreitas, which halted retroviral research into CFS.

In 1996, a congressional investigation proved that CDC scientists siphoned millions of Congress-appropriated CFS dollars to what then-CDC director Jeffrey Koplan told the Washington Post were "more important" maladies, including measles and polio.

The first report of an association of XMRV with human disease came in 2006—from U.S. researchers at the Cleveland Clinic studying a virulent form of prostate cancer, not CFS. But then a German study found no such association, a harbinger of the conflicting findings of the CFS XMRV studies to come.

Dr. William Reeves and the CDC

After Dr. Judy Mikovits's paper linking XMRV to Chronic Fatigue Syndrome was published in Science in October 2009, Dr. William Reeves, the head of CFS research at the CDC for 20 years until February of this year, told the New York Times: “We and others are looking at our own specimens and trying to confirm it. If we validate it, great. My expectation is that we will not.” Reeves also told the Times that the culprits behind CFS were more likely sexual and emotional abuse and an inability to handle stress.

Privately, insiders have told CFS Central that they did not expect the CDC to find the retrovirus because the agency’s CFS definition has been watered down from one neuroimmune disease to five different combinations of depression, insomnia, obesity and “metabolic strain,” as Reeves himself explained in a 2009 paper. In a 2008 CDC paper, “An extended concept of altered self,” Dr. Jim Jones argued that illnesses such as CFS are “illness states” rather than “true diseases.” A CDC paper from 2006 on coping styles found CFS patients guilty of “maladaptive coping” and “escape-avoiding behavior.”

However, studies by Dr. Leonard Jason have shown that using the CDC’s latest definition of the disease, 38 percent of patients have major depression, not CFS, which is a serious neuroimmune disease, as shown in more than 2,500 peer-reviewed studies.

Though Reeves was transferred from CFS research to senior adviser for Mental Health Surveillance in February, he's still authoring studies on CFS. His latest, released in July, is “Personality Features and Personality Disorders in Chronic Fatigue Syndrome.”

For more information on the retroviral link to CFS, see "Blood Feud: Part 1" and "Blood Feud: Part 2" or contact CFS Central at mindykitei.cfscentral@comcast.net

THE JOURNAL RETROVIROLOGY RESPONDS

Retrovirology published the CDC XMRV study in July that didn't find any positives in the CFS patients tested.  CFS Central queried the journal for an interview with its editor, Dr. Kuan-Teh Jeang.  As requested, CFS Central furnished a list of questions: 

• One of the CDC slides from last week’s Blood Safety Advisory Committee meeting showed that the CDC tested 20 samples from Chronic Fatigue Syndrome (CFS) patients that the Whittemore Peterson Institute (WPI) found to be positive for the retrovirus XMRV.  But, according to the slide, the CDC didn’t find any positives among those 20.  WPI sent those samples last fall to the CDC, and the CDC tested the samples before submitting its paper to Retrovirology. Did Retrovirology know that the CDC had tested those WPI samples? 
  

• If Retrovirology did know, why was that information omitted from the CDC’s XMRV CFS paper?
  

• If Retrovirology didn’t know, will the CDC’s XMRV CFS paper be amended to include that the CDC didn’t find any positives in those WPI samples?
  

• Given that the CDC couldn’t confirm any of the Whittemore Peterson Institute’s 20 positive samples, why did the CDC scientists or Retrovirology conclude that the CDC’s methods were accurate?
  

• When the CDC posted the slide at the Blood Safety Advisory Committee meeting, the CDC put quotation marks around the word “positive,” implying, perhaps, that  the 20 samples the WPI sent to the CDC were contaminated.  Was this belief something that the CDC scientists shared with Retrovirology?
  

• In the CDC XMRV study, it says:  “The Lombardi et al. study specifies that samples were selected from patients fulfilling the 1994 international CFS case definition and the 2003 Canadian Consensus Criteria for CFS/ME…. Most notably, the Canadian Criteria include multiple abnormal physical findings such as spatial instability, ataxia, muscle weakness and fasciculation, restless leg syndrome, and tender lymphadenopathy. The physical findings in persons meeting the Canadian definition may signal the presence of a neurologic condition considered exclusionary for CFS and thus the XMRV positive persons in the Lombardi et al. study may represent a clinical subset of patients."

Dr. Jeang, not only the Canadian Consensus Criteria, but the 1994 Fukuda definition (AKA the 1994 International Case Definition of CFS), which is listed on the CDC’s website as the agency’s official definition for the disease (http://www.cdc.gov/cfs/general/symptoms/index.html) includes multiple physical findings.  Indeed “tender lymph nodes” is listed as a diagnostic criterion for CFS on the CDC website.  In addition, “difficulty  maintaining upright position, dizziness, balance problems or fainting” are neurological findings listed as common CFS symptoms on the CDC  website.

Is the CDC’s XMRV paper saying, then, that the patients who exhibit these physical and neurological symptoms may no longer meet the CDC’s very own case definition of Chronic Fatigue Syndrome?

Here is the reply from the press office:

"Sorry to take so long to get back to you. After reviewing these questions I feel it would be more appropriate for you to contact the NIAID [National Institute of Allergy and Infectious Disease] press office as these questions are more relevant for them than the journal.  Details can be found here: http://www.niaid.nih.gov/news/mediainquiries/Pages/contactinformation.aspx

"However, Retrovirology, has issued this statement:

"Retrovirology always evaluates all materials submitted to the journal through a stringent peer-review process. The confidentiality clause prevents us from providing any details of the peer-reviews. Retrovirology is not responsible for content that is not submitted to the journal, nor can it comment on anything that is not submitted for consideration to the journal."


This article is copyright CFS Central 2010. All Rights Reserved. You may quote up to 150 words from this article as long as you indicate in the body of your post (as opposed to a footnote or an endnote) that the excerpt is by Mindy Kitei for CFS Central. You may not reprint more than 150 words from this article on blogs, forums, websites or any other online or print venue. Instead, refer readers to this blog to read the article. 

FDA/NIH PAPER in PRESS

"The Alter paper is now in press, but I don't know when it will go online and until then there will be a press embargo," says Dr. Randy Schekman, editor of the journal Proceedings of the National Academy of Sciences, where the FDA/NIH XMRV paper on ME/CFS patients had been accepted and then pulled by higher-ups in the department of Health and Human Services.  The NIH's Dr. Harvey Alter is the principal investigator of the FDA/NIH study and one of the discoverers of hepatitis C.  

On Monday I emailed the CDC press office about this question that Dr. Monroe didn't answer in our interview:  "One of the CDC slides from this week’s Blood Safety Advisory Committee meeting showed that the CDC tested 20 samples from CFS patients that the Whittemore Peterson Institute found to be positive for XMRV.  But, according to the slide, the CDC didn’t find any positives among those 20. Why was this piece of information—that the agency was unable to find positives in any of those 20 samples—left out of the CDC’s XMRV study?"  No word back.  

Q & A with CDC's STEVE MONROE

The CDC says it's found XMRV in prostate tissue but omits a crucial fact from its XMRV study on CFS patients

Below are the emailed answers to the questions I posed, by email, to Dr. Stephan Monroe, head of the CDC’s division of High Consequence Pathogens and Pathology.  More problematic than the non-answers to most of the questions on the CDC's present and future course for CFS research is that Monroe didn’t answer one of my questions on the CDC study.

That question was why did the CDC XMRV scientists omit in their paper that they had tested 20 samples that the Whittemore Peterson Institute found to be XMRV positive but didn't find any positives themselves?  Rather than answer it, Monroe simply ran up the next question—deleting its bullet point, thereby altering the questions as posed.  The CDC press office sent Monroe’s responses at 4:42 p.m. Friday, making a Friday follow-up unfeasible.  However, I’m resubmitting the question to Dr. Monroe and will report his reply on CFS Central.

Published in July, the CDC's study failed to find the retrovirus in any CFS patients the researchers tested, unlike the October 2009 Science study by the Whittemore Peterson Institute, the National Cancer Institute and the Cleveland Clinic that found 67 percent of CFS patients positive for XMRV, and the as-of-yet unpublished FDA/NIH study, which reportedly found 80 percent of CFS patients positive for the retrovirus.  The 2010 XMRV studies in Europe have failed to find the retrovirus in patients with either CFS or prostate cancer, the two diseases in which U.S. scientists have reported an XMRV link.

Here are the two questions on the CDC’s XMRV study that CFS Central submitted to Monroe:

• One of the CDC slides from this week’s Blood Safety Advisory Committee meeting showed that the CDC tested 20 samples from CFS patients that the Whittemore Peterson Institute found to be positive for XMRV. But, according to the slide, the CDC didn’t find any positives among those 20. Why was this piece of information— that the agency was unable to find positives in any of those 20 samples—left out of the CDC’s XMRV study? 

• Given that the CDC couldn’t confirm any of the Whittemore Peterson Institute’s 20 positive samples, why did the CDC scientists conducting the study conclude that the CDC’s methods were accurate? My sources have confirmed that three independent labs found these samples to be positive.

Here is the one question and answer back from Monroe.  I've highlighted his reply in red: 

• One of the CDC slides from this week’s Blood Safety Advisory Committee meeting showed that the CDC tested 20 samples from CFS patients that the Whittemore Peterson Institute found to be positive for XMRV.  But, according to the slide, the CDC didn’t find any positives among those 20.  Why was this piece of information— that the agency was unable to find positives in any of those 20 samples—left out of the CDC’s XMRV study?  Given that the CDC couldn’t confirm any of the Whittemore Peterson Institute’s 20 positive samples, why did the CDC scientists conducting the study conclude that the CDC’s methods were accurate?  My sources have confirmed that three independent labs found these samples to be positive. 

The information in the Retrovirology paper was consistent with the specifics of the study design. The results, and methodology, have been confirmed by three different independent laboratories.

Below are the rest of the questions and answers.  I've deleted the bullets because editing with bullets has proved too problematic in Blogger.

CFS Central: Who decides what research the CDC will pursue when it comes to Chronic Fatigue Syndrome?  Is it you, Dr. Monroe?  Is it Mr. Bill Switzer [principal investigator of the CDC XMRV study]?  Is it Dr. William Reeves [who has long held that CFS is a psychogenic illness and served as the former head of CFS research for 20 years until his transfer in February to Mental Health Surveillance]?  Is it Dr. Elizabeth Unger [acting head of CFS research]? Is it Dr. Thomas Frieden [the head of the CDC]?  Or is it from higher-ups in the HHS organization?  Who decides?

Dr. Steve Monroe: As there is still much to learn about CFS, CDC pursues a broad approach to research related to CFS. Decisions about the direction of CFS research are primarily guided by the insights gained from our continued scientific investigations. 

CFS Central: There are one million people with HIV/AIDS in the U.S. There are one million people with CFS in the U.S. (using the original 1994 Fukuda definition, not the Empirical definition).  The two diseases became widespread in the 1980s.  Some believe that the CDC pursued psychiatric research where CFS is concerned because the agency had its hands full with HIV and didn’t want to deal with another infectious epidemic in this country.  And now decades later, the agency remains in that mode and will continue in that mode.  Do you believe there’s validity to this argument? Why or why not?

SM:  The direction of CFS research has, and will continue to be, based on the best available scientific information and insights gained from our research and the findings of others.

CFS Central: On patient forums in the U.S. and abroad, many bloggers voice that they have no confidence in the CDC’s CFS policies and research.  Patients post on my blog, CFS Central, or address emails to me directly about their disappointment and outrage when it comes to the CDC.  One of the most important reasons CFS patients say that they have no confidence in the CDC is because the agency is pursuing a psychological cause, when much of the evidence, including 2,500 journal articles, points to a physiological cause. Is the CDC aware that many patients have no confidence in the agency when it comes to CFS research and policy?  Does the CDC care that patients have lost confidence in the agency?

SM:  CDC is deeply committed to reducing the morbidity and societal costs associated with CFS to enable a better quality of life for CFS patients. 

CFS Central: As a follow-up to this question, three CFS patients whom I interviewed in 1994 for an investigative article on the experimental [HIV and CFS] drug Ampligen called “The AIDS Drug No One Can Have” for Philadelphia magazine have since died of the disease, including one at age 43, and another at 59 from mantle cell lymphoma, a rare cancer in the general population but one that’s remarkably common in CFS patients. While some patients are dying and many others are bed-bound or house-bound and experiencing seizures, chronic infections, heart failure and short-term memory loss, the CDC is advocating cognitive therapy, antidepressants and “sleep hygiene.”

These mild interventions may help the 38 percent of patients  with major depression who were misdiagnosed as having CFS under the Empirical definition, according to studies done by Dr. Leonard Jason.  These mild interventions, however, aren’t helping most patients who meet the original 1994, including three CFS patients whom I interviewed in 1994 who have since died of the disease: Nancy Kaiser, Jerry Crum and LeAnne Hyneman.  Does the CDC see the disconnect in what the CDC is advocating—antidepressants, “sleep hygiene” and cognitive therapy—and what patients, at least those who meet the original 1994 Fukuda definition—are experiencing? What should the CDC do to help these patients now and over the next five years?

SM: Unfortunately, there are very few double-blind, placebo-controlled studies of interventions for alleviating symptoms of CFS. CDC recommends that people with CFS work with a healthcare professional to develop a treatment plan that is highly individualized and addresses their particular constellation of symptoms. 

CFS Central: At the first international workshop on XMRV in September, the CDC’s William Switzer will be speaking on assay development to test for XMRV.  Has he ever found XMRV in any blood or tissue from any patients? 

SM: CDC has detected XMRV in samples from patients with prostate cancer.  Preliminary results were reported at a scientific conference and the findings are being prepared for publication in a peer-reviewed journal.

CFS Central: As I understand it from the CDC website, the foster-care study, which will begin in late 2010 and continue to 2013, will explore whether foster children are at higher risk for CFS than the general population of youths. 

What happens if a child doesn’t want to participate? What rights do the children have?

Who is advocating for these children? 

Will there be a court-appointed lawyer for these children? 

Or will it be only the state? 

Or will it be the foster parents plus the state? 

On the CDC website, it discusses “pharmacologic intervention trials” with these children. What kind of medications will be used? 

SM: The 5-year strategic research plan for CFS was developed in 2009 and is periodically updated. The foster-care study is not included in the current plan. 

CFS Central:  Dr. William Reeves, who was transferred from the head of CFS research to senior adviser for Mental Health Surveillance in February, is still authoring studies on CFS. His latest, released last week, is “Personality Features and Personality Disorders in Chronic Fatigue Syndrome.”  Will Dr. Reeves continue to do research into CFS over the next few years? 

SM:  CFS research will continue to be inclusive of many scientists, including those within and outside the agency, whose expertise can help us learn more about this illness.

CFS Central: The CDC says the revised 1994 Fukuda definition is the equivalent of the original 1994 Fukuda (AKA Empirical) definition. The CDC has been using the revised definition in its studies since 2005.  The CDC reported in 2003 that the estimated occurrence of CFS under the original definition in the U.S. was .23 percent.  In 2007, the CDC reported the occurrence with the new definition broadened to 2.5 percent, a 10-fold increase.  Likewise, Dr. Leonard Jason’s studies found the same 10-fold increase in the new definition over the old definition.  In addition, Jason found that in contrast to the original definition, 38 percent of patients characterized as having CFS under the revised definition actually had “major depression.”  Therefore, how can these two definitions of CFS be equivalent? 

SM:  The CDC uses quantitative assessment tools to reproducibly identify those individuals who meet the 1994 international research case definition of CFS.  The defining symptoms and criteria for exclusion have not changed. 

CFS Central:  The CDC devised the 1988 name Chronic Fatigue Syndrome to describe the symptoms of patients in the outbreak on Lake Tahoe, Nevada, among other clusters. Many of those patients had neurological symptoms and all had physical symptoms.  In the CDC’s XMRV study, it says: 

“The Lombardi et al. study [AKA the October 2009 Science study that found XMRV in 67 percent of CFS patients] specifies that samples were selected from patients fulfilling the 1994 international CFS case definition and the 2003 Canadian Consensus Criteria for CFS/ME…. Most notably, the Canadian Criteria include multiple abnormal physical findings such as spatial instability, ataxia, muscle weakness and fasciculation, restless leg syndrome, and tender lymphadenopathy. The physical findings in persons meeting the Canadian definition may signal the presence of a neurologic condition considered exclusionary for CFS and thus the XMRV positive persons in the Lombardi et al. study may represent a clinical subset of patients.”

Dr. Monroe, not only the Canadian Criteria, but the 1994 Fukuda definition—listed on the CDC’s website as the agency’s official definition for the disease—includes multiple physical findings.  Indeed “tender lymph nodes” is listed as a diagnostic criterion for CFS on the CDC website.  In addition, “difficulty maintaining upright position, dizziness, balance problems or fainting” are neurological findings listed as common CFS symptoms on the CDC website. 

Is the CDC now saying that the patients who exhibit these physical and neurological symptoms may no longer meet the CDC definition of the Chronic Fatigue Syndrome?

If the patients with physical and neurological symptoms who meet the original 1994 Fukuda definition of Chronic Fatigue Syndrome don’t have CFS, what, then, do they have?

SM:  People with CFS generally experience a variety of symptoms, many of which are consistent with other health conditions. 

Similarly, people who do not meet the diagnostic criteria for CFS may experience symptoms that are common among people who suffer from this illness.

Dr. Mary Schweitzer contributed to this post.

 

This article is copyright CFS Central 2010. All Rights Reserved. You may quote up to 150 words from this article as long as you indicate in the body of your post (as opposed to a footnote or an endnote) that the excerpt is by Mindy Kitei for CFS Central. You may not reprint more than 150 words from this article on blogs, forums, websites or any other online or print venue. Instead, refer readers to this blog to read the article.