Canada's National Collaborating Centre for Infectious Disease(NCCID) summary of XMRV

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This was on the ESME facebook page.
Canada's National Collaborating Centre for Infectious Disease(NCCID) has put out a nice overview and summary of XMRV in their 'Purple Paper', which was originally created to 'summarize peer-reviewed H1N1 literature pertinent to public health. This new project by NCCID aims to contextualize research findings to shed light on the Canadian situation in a usable accessible format.'
link here
http://www.nccid.ca/en/xmrv
 
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The link say's it's a Purple paper, like the one they had for H1N1. Can any Canadian's tell me what that is?

Purple Paper
XMRV: A Virus in Search of a Disease or A Novel Virus that Causes Prostate Cancer and/or Chronic Fatigue Syndrome?

Key Points

• Xenotropic Murine leukemia virus-Related Virus
(XMRV) is a gammaretrovirus that was first
described in 2006. It has been isolated from
human biological samples.

• Several reports have associated the virus with
familial and sporadic prostate cancer but other
reports do not find a link.

• Similarly, a possible association with chronic
fatigue syndrome has been reported but other
studies find no evidence of an association.

• XMRV has not been established as a cause of
either prostate cancer or chronic fatigue
syndrome.

• XMRV may be transmitted sexually.

• Because XMRV may be a blood-borne pathogen,
Canadian Blood Services and Australian Red
Cross Blood Service indefinitely defer individuals
with a history of chronic fatigue syndrome from
donating blood.

• The real population prevalence remains unclear.
 
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What is the Evidence for
the Causal Relationship between XMRV and
Chronic Fatigue Syndrome?

Chronic fatigue syndrome (CFS), also named myalgic encephalitis, is a complex, debilitating illness that likely encompasses more than one entity. CFS is characterized by persistent disabling physical and mental fatigue – lasting for at least six months and without apparent physical cause – that is not improved by bed rest [Prins et al., 2006]. According to the CFS definition from the Centers for Disease Control and Prevention (CDC), in addition to unexplained chronic fatigue, the sufferer may also experience impaired memory or concentration, sore throat, tender cervical or axillary lymph nodes, muscle pain, pain in several joints, new headaches, unrefreshing sleep, or malaise after exertion [CDC, 2006]. A viral origin of the disorder has long been suspected as three-quarters of patients have reported having an infection, such as an acute influenza-like illness or infectious mononucleosis, before the onset of CFS [Prins et al., 2006]. Because RNase L dysfunction has also been implicated as a potential cause of CFS [Suhadolnik RJ et al., 1997; Nijs and De Meirleir K, 2005], shortly after the discovery of XMRV among prostate cancer patients, scientists began their search for the same gammaretrovirus in CFS patients [Lombardi et al., 2009].

In the American study by Lombardi and colleagues [2009], investigators detected XMRV genetic sequences in the blood samples of 68 of 101 (68%) CFS patients, compared to only 8 of 218 (3.7%) healthy controls. Using antibody reagents that recognize a broad spectrum of common elements shared among all xenotropic MuLV (of which XMRV is a member), investigators found indirect evidence for the presence of XMRV proteins within the blood cells of CFS patients. Cell culture experiments revealed that patient-derived XMRV was infectious. By directly exposing uninfected permissive cell lines (that are susceptible to infection by XMRV) to infected blood cells or cell-free plasma from CFS patients, it was shown that cell-associated and cell- free transmission of XMRV were possible. This study also provided indirect evidence for the development of an XMRV-specific antibody response in CFS patients, but not in healthy controls [Lombardi et al., 2009].

The study by Lombardi and colleagues [2009] has generated much interest, concern and criticism. For example, the report has been criticized for not providing adequate description of the CFS patients in question, despite the complexity of the disorder [van Kuppeveld et al., 2010]. Some experts also queried whether it is biologically plausible for a single infectious agent to trigger two-thirds of CFS cases [McClure, 2010]. Previously unreported information has recently surfaced in an editorial from the British Medical Journal that the patients in the Lombardi study came from a suspected outbreak of CFS at a village near Lake Tahoe in the mid-1980’s [McClure, 2010]. Hence, even if the XRMV cause of CFS is real, the prevalence of XMRV among these CFS patients might have been overestimated when the finding is extrapolated to the general population. Following the initial publication of the Lombardi study, three independent studies from the UK and the Netherlands found no evidence of XMRV in their CFS patients [Erlwein et al., 2010; Groom et al., 2010; van Kuppeveld et al., 2010], thus injecting further doubt about the validity of the American findings.
At this juncture, there is no conclusive evidence supporting XMRV as the causative agent of CFS. The mechanism by which XMRV triggers CFS continues to be a mystery.
Not impressed with this!
 
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How is XMRV transmitted?
XMRV may be transmitted sexually. This is based on the finding that XMRV genetic material has been found in the semen of men with prostate cancer. Protein fragments originated from the prostate appeared to enhance XMRV infectivity in cell culture experiments [Hong et al., 2009]. In addition, given that XMRV was detected in the blood samples of CFS patients [Lombardi et al., 2009], XMRV may also be spread by contact with blood and blood products.

What are the implications if XMRV is Proven to Cause Disease?
The discovery of XMRV has very important implications for medicine, health care and public health, especially if the prevalence of the new human retrovirus is as high as the American studies have suggested. The fact that XMRV may be a blood-borne pathogen has already alerted officials from Canadian Blood Services and Australian Red Cross Blood Service to indefinitely defer individuals with a history of CFS from donating blood [Canadian Blood Services, 2010; Australian Red Cross Blood Service; 2010]. In the USA, agencies within the Department of Health and Human Services (HHS) are working to find the most sensitive and reliable method for XMRV detection, to determine the prevalence of XMRV in the blood supply and to determine the transmissibility of XMRV by blood transfusion [CDC, 2010]. Contaminated organs donated for transplantation will also become an issue if XMRV is transmissible by blood.

If XMRV is confirmed to be the causative agent of prostate cancer and CFS, more options will become available for prevention, screening and diagnosis, and treatment of the disease. For instance, preventive measures may involve a vaccine targeting XMRV. Assuming that XMRV is sexually transmitted, barrier methods and preventive precautions used for other STIs could be applied to the prevention of XMRV. Screening and diagnosis of prostate cancer and CFS may rely on molecular identification of XMRV. Treatment options may include the use of antivirals for other human retrovirus infections. In fact, nucleoside reverse transcriptase inhibitors, zidovudine and tenofovir, and integrase inhibitor, raltegravir medication used for HIV treatment have already been shown to be effective against XMRV in cell culture experiments [Sakuma et al., 2010; Singh et al., 2010; Paprotka et al., 2010].
 
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What are some Unresolved Issues?
Many questions are still unanswered.

Why is XMRV seemingly geographically confined
to the USA? Is it an artefact as a result of differences in experimental protocols or reagents? Or, is the disparity in the geographical distribution of XMRV between European countries and the USA a real phenomenon?

What is preventing XMRV spread from North America to Europe?

If a causal link between XMRV and prostate cancer does exist, what is the mechanism for disease initiation and progression?

If a causal link between XMRV and CFS does exist, what is the mechanism for disease initiation and progression?

Since prostate cancer affects only males and CFS affects mostly females, is it possible that the illnesses experienced by the two sexes are just different manifestation of the same disease caused by XMRV infection?

What is the role of RNase L in the relationship between XMRV and prostate cancer, and between XMRV and CFS?

How is the immune response of individuals who can control and eliminate XMRV different from the immune response of those who succumb to disease?

How is XMRV transmitted? At what age does one become prone to infection by XMRV?

Is it possible to transmit XMRV from mother to child?

Does XMRV have the potential to become stably integrated into the human genome such that individuals can inherit the virus from his/her parents as a "genetic trait"?

What is the prevalence of XMRV in Canada? Can a vaccine be developed against XMRV?
Would it be useful in preventing XMRV given its prevalence in Canada?

At present, it is apparent that there are more questions than answers. As scientists continue to work through some of these outstanding issues, a clearer picture related to the burden of XMRV on the Canadian population, health care, and public health will gradually emerge. Until then, health care and public health officials must be vigilant and respond accordingly as more information becomes available.