Date: Sat, 03 Jul 2010 08:49:04 -0400
Today at 10:56am
Researchers at the U.S. Centers for Disease
Control and Prevention (CDC), along with
collaborators in California and Germany,
published a paper in the journal Retrovirology
titled, Absence of evidence of Xenotropic
Murine Leukemia Virus-related virus infection in
persons with Chronic Fatigue Syndrome and
healthy controls in the United States. Blood
samples from people with CFS, matched controls
and 41 healthy blood donors were tested for
antibodies to XMRV using a western blot assay
and for XMRV DNA using a nested PCR assay. Three
independent laboratories, including the
retrovirus lab at CDC, Blood Systems Research
Institute (BSRI) and the Robert Koch-Institute
lab tested coded samples. There is no doubt of
the technical competence of these laboratories
to conduct these assays to detect XMRV
antibodies and DNA. So why wasnt XMRV detected?
If the rate of XMRV in the healthy blood supply
is 0.1% (or 1 person out of 1000), then there is
a slim chance of detecting XMRV DNA among 41
healthy blood donor samples. So, no surprise there.
What about the CFS cases and controls? First, I
would like to make a request of all authors of
scientific papers please provide a table that
describes the subject and sample cohort! Combing
back and forth in a paper to figure out who is
who and what is what is frustrating! From what I can decipher,
the samples were drawn from 18 people identified
through a Georgia registry who met criteria
described in the paper that is different from 1994 international CFS criteria.
Eleven CFS cases and matched controls were
identified from the Wichita studies, although it
is not clear if these samples came from the
longitudinal studies or the clinical study,
and 22 CFS cases and controls from the Georgia community-based study.
There is little indication that these three
cohorts are comparable in regard to CFS
definition, as each cohort was selected using different definition.
The authors strenuously object to application of
the Canadian case definition in other studies,
stating that, physical findings in persons
meeting the Canadian definition may signal the
presence of a neurological condition considered exclusionary for CFS.
Yet the physical findings listed are those
commonly experienced by CFS patients,
and one (tender lymphadenopathy) is a
case-defining symptom of the 1994 criteria.
Further, the samples from these three study
cohorts were collected using different types of
tubes, each of which has a distinct way of being processed.
As if this werent bad enough, none of the blood
tubes used were of the same type used in the Lombardi study.
(They used tubes containing sodium heparin that
are intended for use with virus isolation). The
blood tubes from the 18 Georgia registry
patients are designed to collect whole blood and
preserve nucleic acid; it is not clear where the
plasma came from for these subjects since plasma
cannot be obtained using these blood tube types.
So the explanation for not finding XMRV in these
samples is simple this was a study designed to
not detect XMRV using a hodge-podge sample set.
Detecting XMRV is hard. Replication of the
Science paper will be hard because of the
exacting methods required and because of the
heterogeneity and complexity of CFS. Regardless
of the outcome of any single study, it is
critical that a valid replication study be
designed and implemented by multiple
laboratories, using standard and optimized
techniques and testing split samples collected
appropriately from adequate numbers of well-characterized cases and controls.
Studies such as this one from Switzer, et al.,
continue to absorb time, divert precious
resources and fuel controversy instead of consensus.
References:
Absence of evidence of Xenotropic Murine
Leukemia Virus-related virus infection in
persons with Chronic Fatigue Syndrome and
healthy controls in the United States. Switzer
WM, Jia H, Hohn O, Zheng H, Tang S, Shankar A,
Bannert N, Simmons G, Hendry RM, Falkenberg VR,
Reeves WC, Heneine W. Retrovirology 1 July 2010.
Detection of an infectious retrovirus, XMRV, in
blood cells of patients with chronic fatigue
syndrome. Lombardi VC, Ruscetti FW, Gupta JD,
Pfost MA, Hagen KS, Peterson DL, Ruscetti SK,
Bagni RK, Petrow-Sadowski C, Gold B, Dean M,
Silverman RH, Mikovits JA. Science 8 October 2009. 1179052.
For more information about the CDCs cohorts
from the Wichita, Georgia and registry studies
visit:
<
http://www.cdc.gov/cfs/publications/surveillance.htm>http://www.cdc.go...
Suzanne D. Vernon, PhD
Scientific Director
The CFIDS Association of America
July 1, 2010
<
http://www.cfids.org/xmrv/070110study.asp>http://www.cfids.org/xmrv/07...
Lydia E. Neilson, M.S.M., Founder
Chief Executive Officer
National ME/FM Action Network
512 - 33 Banner Road
Nepean, ON K2H 8V7 Canada
Tel. (613) 829-6667 Fax (613) 829-8518
E-mail: ag922(a)ncf.ca
Web: