Regarding the CDC XMRV Study

Absence of evidence of Xenotropic Murine Leukemia Virus-related virus infection in persons with Chronic Fatigue Syndrome and healthy controls in the <?xml:namespace prefix = st1 ns = "urn:schemas-microsoft-com:eek:ffice:smarttags" /><st1:place w:st="on"><st1:country-region w:st="on">United States</st1:country-region></st1:place>.
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
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http://www.retrovirology.com/content/pdf/1742-4690-7-57.pdf
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One assumes that the reviewers for the journal Retrovirology are retrovirologists, so they are probably not familiar with Chronic Fatigue Syndrome or its case definitions. That may explain why they apparently did not check the accuracy of the statements regarding patient cohorts in the Discussion section of this paper. I cant speak to the quality of the retrovirology, but I have some observations regarding the accuracy of the discussion of the patient cohort.
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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.
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The supporting online material for the Lombardi et al paper, published by Science magazine (http://www.sciencemag.org/cgi/data/328/5980/825-d/DC1/1), specifies that Samples banked in the WPI repository from 2006 to 2009 were selected for our study from patients who fulfilled both the 1994 CDC Fukuda Criteria for CFS as well asthe 2003 Canadian Consensus Criteria (CCC). It further specifies All known medical conditions causing severe fatigue were excluded. Thus the above criticism of the Lombardi et al studys patient cohort is inaccurate.
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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.
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All of the exclusionary conditions included in the 1994 CDC Fukuda Criteria for CFS (1) are also listed as exclusions in the 2003 Canadian Consensus Criteria (2). The Canadian definition actually excludes more neurologic (and other medical) conditions than the Fukuda Criteria.
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However, the 1994 CDC Fukuda Criteria for CFS specifically does not exclude anxiety disorders, somatoform disorders, nonpsychotic or melancholic depression, or neurasthenia, while the Canadian Consensus Criteria excludes primary psychiatric disorders. The 1994 CDC Fukuda Criteria for CFS also does not exclude any condition, such as Lyme disease or syphillis, that was treated with definitive therapy before development of chronic symptoms, while the Canadian Criteria does exclude infectious diseases such as tuberculosis, chronic hepatitis, Lyme disease, etc. So it is possible, perhaps even likely, that the patient cohort studied by Switzer et al included patients whose fatigue was the result of psychiatric conditions that would have been excluded in the Lombardi et al study.
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The authors of this study say of their patient cohort
These CFS cases are different from CFS patients seen in general practice and referral clinics; of the participants from the population based study in Georgia, only half had consulted a physician because of their fatigue, about 16% had been diagnosed with CFS.
This patient cohort is not similar to what is usually diagnosed as CFS. Only about half of them had felt ill enough to consult with a doctor. Thirty-three of the 51 patients had been found by a random telephone call process rather than being referred by a physician. The other 18 came from a registry study where health care workers were asked to refer anyone fatigued for more than a month who had one of the core CFS symptoms. They were then evaluated by the CDC, applying a case control definition which specifically doesnt exclude psychiatric disorders such as somatoform disorders or neurasthenia (aka hypochondriasis). Those who were found to meet a CDC-defined threshold of "unwellness" were diagnosed as having CFS for purposes of study.
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CFS is a complex disease with various clinical subtypes proposed which could also account for differences in the results obtained in each study.
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How does this account for the different rates of infection found in healthy controls? The Lombardi et al study found XMRV in 3.7% of healthy controls. Similar rates of XMRV infection in healthy controls or blood donors have been found in studies in <st1:country-region w:st="on">Germany</st1:country-region> (Fischer, 2-3%) and <st1:place w:st="on"><st1:country-region w:st="on">Japan</st1:country-region></st1:place> (Rika, 1.7%). Why did these studies find low rates of XMRV in the general population, while the CDC study found none?

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(1) Fukuda et al, Annals of Internal Medicine, Vol. 121, December 15, 1994, pp. 953-959.
(2) Carruthers B M, Jain A K, De Meirleir K L. et al Myalgic encephalomyelitis/chronic fatigue syndrome: clinical working case definition, diagnostic and treatment protocols. J Chronic Fatigue Syndr 2003. 117115

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