De ontwikkelingen rond de XMRV-studies in de VS stapelen zich op.
Vandaag verscheen,
in strijd met de melding dat de positieve FDA/NIH-studie én de negatieve CVS-studie voorlopig niet gepubliceerd zouden worden,
toch de studie van het CDC.
Op zijn zachtst gezegd zeer merkwaardig...
Wellicht hebben de mensen van het CDC, "gedwongen" door het
nieuws van de positieve FDA/NIH-studie,
besloten de studie versneld te doen publiceren om het FDA/NIH voor te zijn.
Ben benieuwd of de positieve FDA/NIH-studie ooit nog verschijnt...
[Naschrift:
Volgens Science Insider (zie onder) worden momenteel aanvullende experimenten uitgevoerd,
die tegen het eind van 2010 afgerond zullen zijn, zodat de studie pas in 2011 zal verschijnen.]
Samenvatting van de studie
- Patiënten:
"chronisch vermoeiden" die voldoen aan de nietszeggende CDC/Reeves-kriteria.
bij slechts 11,8% was sprake van "sudden onset": beduidend lager dan het percentage
CVS-patiënten in andere studies, vaak de overgrote meerderheid (zoals bijvoorbeeld hier).
In de Canadese kriteria voor ME/CVS (die toegepast zijn in de
XMRV-Mikovits-studie
om patiënten te selekteren) wordt aangegeven dat ME/CVS meest "sudden onset" is.
In de XMRV-studie van van Kuppeveld et al.
werd "postvirale ME/CVS"-patiënten
(eveneens een grote groep patiënten:
klik hier) min of meer bij voorbaat uitgesloten.
- Monsters:
plasma t.b.v. antistoffen-testen en
DNA van afweercellen (mononucleaire cellen) t.b.v. PCR.
- Techniek:
De technieken die gebruikt zijn voldoen, volgens de kenners, aan de kwaliteitseisen.
Echter het zijn technieken die afwijken van de door Mikovits et al. gebruikte technieken.
Men heeft géén positieve en negatieve controlemonsters gebruikt (bijv. van het WPI).
Experts, bijv. Vernon, zetten ook vraagtekens bij de gebruikte materialen (bloedbuisjes etc.).
De vraag is: Waarom is dit gebeurd?
Waarom is er niet één patient met een XMRV-infektie gevonden?
Het antwoord van Vernon (CAA) hieronder laat niets aan duidelijkheid te wensen over:
het CDC wilde géén XMRV vinden én men heeft de aanpak hierop afgestemd.
Getuige het feit dat
men géén ME/CVS-patiënten, maar "chronisch vermoeiden" onderzocht heeft,
men niet de door het WPI beschikbaar gestelde laboratoriumtechnieken (zie verklaring WPI hieronder) gebruikt heeft,
maar een eigen, niet gevalideerde laboratoriummethode én
niet de 10 positieve monsters van het WPI gebruikt heeft om de eigen techniek te toetsen,
moet je wel bijna tot die konklusie komen....
Tot slot wil ik U wijzen op de volgende citaten uit deze studie:
CFS is a diagnosis of exclusion
based on self-reported symptoms and
requires careful medical and psychiatric evaluations
to rule out conditions with similar clinical presentation.
Our study and the negative reports from the UK and the Netherlands
evaluated patients for exclusionary conditions and
defined CFS
according to criteria of
the 1994 International CFS Research Case Definition [23] or
the earlier Oxford case definition [24].
The Lombardi et al. study specifies that samples were selected from
patients fulfilling
the 1994 international CFS case definition [23] and
the 2003 Canadian Consensus Criteria for CFS/ME [25].
Lombardi et al. did not specify
if patients were evaluated for exclusionary conditions, or
if the study subjects met both definitions, or
which patients met either CFS definition.
The 1994 International CFS case definition and
the Canadian Consensus Criteria are different and
do not necessarily identify similar groups of ill persons.
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 [11].
Wat kunnen we vaststellen uit bovenstaande citaten?
1.
De CDC geeft toe dat "CVS" een vergaarbak is en de definitie van "CVS" een cirkelredenering:
Als je iets vindt dat de ziekte kan verklaren, was het (met terugwerkende kracht) géén CVS.
Over 30 jaar stellen we dus vast dat niemand ooit CVS heeft gehad...
2.
Patiënten die voldoen aan de Canadese kriteria voor ME/CVS
zijn in de optiek van het CDC mogelijk mensen met een neurologische ziekte, die niet onder de vlag CVS thuishoren
(alhoewel de laatste bijzin dit weer deels tegenspreekt, waarschijnlijk voor het geval dat ....)
Zoals al jaren betoogd, is het van het grootste belang dat ME-én-CVS-belangengroepen,
zoals de ME/CVS stichting en ME/CVS vereniging, een duidelijke keuze maken:
appels: "ME" (Canadese kriteria) of (gebakken) peren: "CVS" (Reeveskriteria).
Doen ze dat niet dan zijn ze er medeverantwoordelijk voor dat al het fruit wordt aangetast:
"CVS" verdwijnt namelijk in de nieuwe versie van de bijbel voor psychiaters/psychologen
(DSM-V) per definitie op de psychische composthoop van "medisch onverklaarbare syndromen".
"ME" (gedefinieerd op basis van de Canadese kriteria) wordt dan wellicht weer wat het ooit was:
een (neurologische?) ziekte die niets met "CVS" te maken heeft (de politieke uitweg van het CDC).
In de media:
Klik op een van de onderstaande afbeeldingen om het bijbehorende artikel te kunnen lezen:
Whittemore Peterson Institute Statement
regarding Centers for Disease Control XMRV Study
Contrary to the WPI study published in Science in October, 2009,
as well as studies done by others, including the NIH and FDA,
Mr. William Switzer of the Centers for Disease Control reported
that his research team was unable to detect XMRV in CFS patient
samples.
This negative finding is in contrast to the WPI study
in which we detected XMRV in 67% of CFS patient samples.
To correctly replicate scientific studies
it is imperative that
researchers use the same methods and patient criteria
to ensure accurate results.
The methodology used by the CDC
was not the same as that used in the WPI study
nor was the patient selection criteria.
In September 2009, WPI sent the CDC twenty confirmed positive samples and
the appropriate methodology to help them develop a clinically validated test.
However, this team chose not to do this.
Until researchers use clinically validated tests to detect XMRV in patient samples,
as WPI and their collaborators have successfully done,
an accurate association of XMRV to any diseased population cannot be made.
For this reason, WPI researchers and many others
are currently validating more sensitive clinical assays
to assist federal agencies in their search for
the true prevalence of XMRV in the human population.
WPI will continue its core mission to deliver answers
to patients with neuro-immune diseases
by supporting the development of accurate diagnostics and
providing effective therapeutics and clinical care.
http://www.wpinstitute.org/news/docs/XMRV-CDC%20Statementrevisedawfinalawfinal.pdf
Blood from a Stone
Suzanne D. Vernon, PhD
Scientific Director
The CFIDS Association of America
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 wasn’t 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 weren’t 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 CDC’s cohorts from the Wichita, Georgia and registry studies visit:
http://www.cdc.gov/cfs/publications/surveillance.htm
http://www.cfids.org/xmrv/070110study.asp
Absence of evidence of Xenotropic Murine Leukemia Virus-related virus infection
in persons with Chronic Fatigue Syndrome and healthy controls in the United States
Retrovirology 2010, 7:57. doi:10.1186/1742-4690-7-57.
William M Switzer, Hongwei Jia, Oliver Hohn, HaoQiang Zheng, Shaohua Tang, Anupama Shankar,
Norbert Bannert, Graham Simmons, R Michael Hendry, Virginia R Falkenberg, William C Reeves and Walid Heneine.
Published: 1 July 2010
Background
XMRV, a xenotropic murine leukemia virus (MuLV)-related virus,
was recently identified by PCR testing
in 67% of persons with chronic fatigue syndrome (CFS) and
in 3.7% of healthy persons from the United States.
To investigate the association of
XMRV with CFS
we tested blood specimens from 51 persons with CFS and 56 healthy persons from the US
for evidence of XMRV infection by using serologic and molecular assays.
Blinded PCR and serologic testing were performed
at the US Centers for Disease Control and Prevention (CDC) and at two additional laboratories.
Results
Archived blood specimens were tested from
persons with CFS defined by the revised 1994 CDC case definition and
matched healthy controls
from Wichita, Kansas and metropolitan, urban, and rural Georgia populations.
Serologic testing at CDC utilized
a Western blot (WB) assay that showed
excellent sensitivity to MuLV and XMRV
polyclonal or monoclonal antibodies, and
no reactivity on sera from 121 US blood donors or 26 HTLV-and HIV-infected sera.
Plasma from 51 CFS cases and
plasma from 53 controls
were all WB negative.
Additional blinded screening of
the 51 cases and 53 controls
at the Robert Koch Institute
using an ELISA employing recombinant Gag and Env XMRV proteins
identified weak seroreactivity
in one CFS case and a healthy control,
which was not confirmed by immunofluorescence.
PCR testing at CDC
employed a gag and a pol nested PCR assay
with a detection threshold of 10 copies in 1 ug of human DNA.
DNA specimens from
50 CFS patients and 56 controls and 41 US blood donors
were all PCR-negative.
Blinded testing by a second nested gag PCR assay
at the Blood Systems Research Institute
was also negative
for DNA specimens from the 50 CFS cases and 56 controls.
Conclusions
We did not find
any evidence of infection with XMRV
in our U.S. study population of CFS patients or healthy controls
by using multiple molecular and serologic assays.
These data do not support an association of XMRV with CFS.
http://www.retrovirology.com/content/7/1/57
full-text:
http://www.retrovirology.com/content/pdf/1742-4690-7-57.pdf
Met dank aan Erik, Dean, Mirande en anderen.
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