THE CASE OF JOAN IRVINE

California resident Joan Irvine came down with ME/CFS the day after a blood transfusion during surgery to repair a shattered hip and thigh in 1987.  She sought treatment with Dr. Daniel Peterson.  Seeking answers, she wrote in 1992 to Dr. William Reeves, who was already heading up research into this disease at the CDC, as well as Dr. George Rutherford, then chief of the infectious disease branch of the California Department of Health.  Both men advised against donating blood. 

Two readers sent in Irvine's letters to Reeves and Rutherford today, as well as her synopsis of the events.  You can read them here: http://www.cfs-news.org/joan.htm

Irvine’s ME/CFS case was virulent, and she committed suicide in 1996.

NEXT:  What happened with the FDA/NIH study, and patients' call to action.

Q and A with CDC SCIENTISTS

Through emails, CDC scientists Bill Switzer, lead investigator of the CDC XMRV study, and Dr. Steve Monroe, director of the CDC’s division of High Consequence Pathogens and Pathology, discussed the agency's XMRV study, published in Retrovirology July 1.  The study found no evidence of the retrovirus in the CDC's Chronic Fatigue Syndrome patients and controls.

I also asked Switzer and Monroe questions about the FDA/NIH XMRV study, which found the virus in CFS patients and had been accepted by Proceedings of the National Academy of Sciences only to be put on hold, which was reported June 30 in the Wall Street Journal.

A CDC press officer emailed Switzer’s and Monroe’s replies on Friday at 5:10 p.m.  Monroe had already left for the day; Switzer for a week’s vacation. Thus, there could be no timely follow-up.

CFS Central:

“My sources tell me that there were at least 20 XMRV samples confirmed to be positive from several other labs that were sent to you for the CDC study.  Did you test these samples, and what were your results when you tested the samples? Did you find XMRV or not?”

Bill Switzer MPH, lead investigator of the CDC XMRV study:
“As reported in Retrovirology, this study used and tested samples that were collected in CDC-sponsored studies of CFS, as well a set of healthy blood donors.  Continued efforts are underway to learn more about XMRV, including work with other HHS [Health and Human Services] agencies and non-governmental organizations to standardize testing methods across all XMRV studies.”

CFS Central:

“Why did the CDC request the FDA/NIH study be put on hold pending more research?”

Dr. Steve Monroe, director of CDC’s division of High Consequence Pathogens and Pathology:
“When CDC, FDA, and NIH learned that separate studies had been conducted with differing results, a collective decision was made to try and account for these differences.”

CFS Central:

“Why couldn’t both the CDC and the FDA/NIH papers be published and then the agencies do follow-up research to resolve the differences in your findings?”

Monroe:
“Timely discussion among researchers regarding the specifics of scientific studies is common and can help them more readily account for the direction of further research.  Future research will benefit from the knowledge gained from the Retrovirology study and other studies that have attempted to learn more about this novel retrovirus.”
 
CFS Central:

“Why didn’t the CDC try to culture XMRV?  (That’s what the Lombardi study did.)” [Published in Science in October 2009, that study found XMRV in 67 percent of 101 CFS patients.]

Switzer:

“It is unclear whether or not performing culture on all samples would have improved the ability to detect XMRV. The CDC Retrovirology study used the same PCR testing methods of a previously published study that found an association between XMRV and CFS. While CDC could not confirm an association between XMRV and CFS, the method utilized in the study provided the best means of detecting XMRV if it was present.”

CFS Central:

“Why didn’t the CDC use blood tubes intended for use with virus isolation as the Lombardi study did?”

Switzer:
“Many blood collection tubes with a variety of anticoagulants can be used for virus isolation. The archived specimens we used were collected with anticoagulants that are not known to interfere with either PCR testing or virus isolation.”

CFS Central:

“According to your paper, the CDC used the ‘revised Fukuda’ AKA Empirical definition of CFS…. The CDC study cohort, as defined by the Empirical definition, includes many people who are simply depressed and tired but do not have Chronic Fatigue Syndrome. How can this CDC cohort be valid if it includes people who are just tired and depressed?”

Monroe:
“All subjects in the study met the 1994 International Research Case Definition for CFS. One aspect of the definition is its ability to distinguish between subjects who may suffer from CFS symptoms, such as tiredness or depression, but do not have CFS.  CDC used samples from CFS subjects who fully met the 1994 case definition and healthy controls that were collected from two previous population-based studies in Wichita, Kansas and metropolitan, urban and rural populations in Georgia. In addition, CFS patients from the CDC Health Care Provider-based Registry of Unexplained Fatiguing Illnesses and CFS were included.

“Thus, CDC used population-based and clinic referral samples. This enabled us to examine sudden onset cases and those that develop gradually. The use of both types of samples in this study helped us to more precisely examine whether or not infection, such as through XMRV, might have played a role in the onset of symptoms.”

***

Having had none of my questions answered by the CDC, I turned to other sources.

Coming up:  THE FDA/NIH XMRV PAPER—and ME/CFS PATIENTS—IN LIMBO.  Plus, one patient’s solution:  A united demonstration of solidarity at blood banks in every city, in every country, and on every continent to inform the public that Health and Human Services is withholding the publication of the FDA/NIH XMRV study and that the newly discovered retrovirus may be contaminating the blood supply and infecting millions of people.


This article, "Q and A with CDC Scientists," 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.

CDC and FDA/NIH STUDIES ON HOLD

On April 15, 2010, a government source told CFS Central that a soon-to-be-published CDC study hadn’t found the retrovirus XMRV in CFS patients but that another government agency had.  The agency that found XMRV in CFS patients—and up to 7 percent of the blood supply—turned out to be two agencies: the National Institutes of Health (NIH) and the FDA, as was leaked last week. 

Today the Wall Street Journal is reporting that the CDC paper, which was accepted at the journal Retrovirology, has been put on hold, as has the FDA/NIH paper, which was accepted at the Proceedings of the National Academy of Sciences.  The reason?  According to the Wall Street Journal, it’s because “senior public-health officials wanted to see consensus—or at least an explanation of how and why the papers reached different conclusions.”  In addition, the Wall Street Journal also reported that a spokesman for the Department of Health and Human Services said the research was being reviewed to ensure “accuracy” and “relevancy of the scientific information.”

Some insiders say that this is a face-saving move to come up with a plausible explanation for the disparate XMRV findings and to present a united front so as not to confuse the public about blood safety.

The CDC has had a problematic year where CFS is concerned.  The long-time CDC principal investigator for CFS research Dr. William Reeves was reassigned on February 14, which many critics believe was because the scientist was embarrassing the agency.  After Dr. Judy Mikovits's paper linking XMRV to Chronic Fatigue Syndrome was published in Science in October, Reeves 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.” 

If the CDC had found the retrovirus, it would have negated its 20-year affair with CFS as a psychological problem.  Now that two other government agencies have found XMRV and other studies due out this summer have also found the retrovirus, critics point out that the CDC is in a no-win situation and beginning to look like the odd man out.

 

DETERMINING XMRV'S MUTATION RATE

One concern during antiretroviral treatment is drug resistance. That’s why HIV patients are usually on a three-drug cocktail, known as HAART, which stands for Highly Active Antiretroviral Therapy.  HIV is a lively, rapidly replicating retrovirus, leading to a high mutation rate:  As in most arenas, mistakes occur more commonly in haste.  The more mutations, the greater the risk of a favorable mutation popping up that confers drug resistance.

But XMRV replicates slowly and doesn’t appear to mutate much.  If XMRV proves to be the cause of ME/CFS and patients begin antiretroviral therapy, will patients still require a triple cocktail?

At present, only three FDA-approved HIV drugs have been shown to have efficacy against XMRV in vitro (in the test tube): AZT, tenofovir and raltegravir.  One possible way to determine whether CFS patients need all three would be for researchers to conduct retrospective longitudinal studies.  Examining the banked blood of HIV patients who’ve been followed for years, they would locate the positive XMRV samples.

Even if HIV patients aren’t infected with XMRV in large numbers, there may be a background rate of 3 to 7 percent, as per the findings of the soon-to-be-published FDA and NIH study, or the more conservative 3.7 percent background rate found in a study by Dr. Judy Mikovits, published in Science in October.

While the HIV patients have been on any one of the three antiretrovirals that appear to be effective for XMRV, has XMRV mutated?  If XMRV hasn’t mutated over several years, a single drug might be sufficient.  If it has mutated, researchers could examine the mutation rates of patients on two of the drugs that appear to be active against XMRV, and so on.

It would also be helpful to examine the banked blood of ME/CFS patients who’ve been followed over many years to determine the natural XMRV mutation rate over time. Researchers may also discover that some strains of XMRV are less likely to mutate than others.

It would be risky for patients to go on monotherapy until more is known about drug resistance and XMRV.  Because once you developed resistance, the drug is essentially useless.