New XMRV Fact Sheet from AABB

[jspotila]

The AABB (formerly the American Association of Blood Banks) has issued a revised fact sheet on XMRV. The pdf link to the fact sheet is here: http://www.aabb.org/documents/About_Blood/EID/xmrvfactsheet.pdf

Bottom line looks to me like they are not banning CFS donors, except for those who are known XMRV positive. Someone with more functioning brain cells than me will have to parse all the differences out. I tried to catch all the places things were changed or reworded from the January AABB statement. Hopefully I got them all. Here is Before and After of each change:

Before, under Disease Name: Evidence of association, but not causation, has been reported for XMRV infection with the following conditions: Prostate cancer; Chronic Fatigue Syndrome (CFS)

After, under Disease Name: No confirmed disease associations

Before, under Background: In 2009, a statistical association of XMRV infection with CFS was reported. Peripheral blood mononuclear cells (PBMC) from 67% of stringently defined CFS patients contained the proviral DNA of XMRV compared to 3.7% of healthy controls. These patients did not have the RNase L polymorphism mentioned above. Secondary infections in tissue culture could be established from PBMCs, B and T cells and plasma of patients. The study concluded, (T)hese findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS.

After, under Background: First paragraph is same as above. The section then continues:

• 186 CFS patients from a UK cohort who had been described as being unwell for a median of 4 years were screened for XMRV provirus and the closely related murine leukemia virus (MLV) from whole blood preparations. Neither XMRV nor MLV sequences were detected from any of the CFS cases.
• Another UK study tested 170 CFS patients from two cohorts (one with long-term established CFS and the other with samples collected 1.5-4 years after a CFS diagnosis) and 395 controls including 157 blood donors. DNA was extracted from PBMC and tested by RT-PCR targeting two envelope regions (sensitivity of 16 copies). No XMRV sequences were identified from 142 CFS cases and 157 controls tested. However, 26 of 565 (4.6%) samples had XMRV neutralizing antibody activity but only one of the 26 was from a CFS patient. Four samples were XMRV specific but most of the remaining antibody reactivity was due to cross-reactivity with other viruses. The authors note that XMRV infection may occur in the general population, although with currently uncertain outcomes.
• In a Dutch cohort, PBMC cryopreserved in 1991-1992 from 32 CFS patients and 43 healthy controls tested by RT-PCR targeting the integrase gene and/or a nested PCR assay targeting the gag gene and having a sensitivity of 10 XMRV sequence copies per 105 PBMC failed to detect XMRV sequences in any sample.
• Reasons for the discordant findings are not clear but may include differences in the cohorts studied or selection of patients from cohorts for testing, variable assay procedures, differences in prevalence in different geographic areas, varying properties of XMRV or other factors.

Before, under Blood Phase: A perspective accompanying the original CFS study concluded (G)iven that infectious virus is present in plasma and in blood cells, blood-borne transmission is a possibility.

After, under Blood Phase: The first published XMRV-CFS study found culturable virus in plasma and PBMC.

Before, under Case/Frequency in Population: In the CFS study referred to above, 3.7% of healthy controls harbored viral DNA sequences in PBMCs; however, the expression pattern of viral genes in the infected controls appeared to differ from those among the CFS population so the relevance of the observation must be explored.

After, under Case/Frequency in Population: In one CFS study, 3.7% of healthy controls harbored viral DNA sequences in PBMC; however, the expression pattern of viral genes in the infected controls appeared to differ from those among the CFS population so the relevance of the observation must be explored. Preliminary data from another study using developmental serological methods in a small sample of US blood donors found a seroprevalence of -0.1%.
The population prevalence of XMRV infection is unknown and rates may vary in different regions.

Before, under Primary Disease Symptoms: Many prostate cancers are asymptomatic, but symptoms of urinary obstruction and metastatic spread occur with advancing disease. CFS (also called, more descriptively, myalgic encephalitis) is characterized by persistent or recurrent fatigue, diffuse musculoskeletal pain, sleep disturbances, and subjective cognitive impairment of 6 months duration or longer. Symptoms are not caused by ongoing exertion, are not relieved by rest, and result in a substantial reduction of previous levels of occupational, educational, social, or personal activities. Alterations of immune, neuroendocrine, and autonomic function may be associated with this syndrome, but none is diagnostic. There is considerable overlap between this condition, fibromyalgia, and some affective disorders.

After, under Primary Disease Symptoms: Many prostate cancers are asymptomatic, but symptoms of urinary obstruction and metastatic spread occur with advancing disease. CFS (also called, more descriptively, myalgic encephalomyelitis) is characterized by new onset, unexplained, persistent or recurrent fatigue, diffuse post-exertional malaise and/or fatigue, myalgia, sleep dysfunction, and neurological/cognitive impairment with immune, autonomic and/or neuroendocrine manifestations of 6 months duration or longer (3 months in children). Symptoms are not caused by ongoing exertion, are not relieved by rest, and result in a substantial reduction of previous levels of occupational, educational, social, or personal activities. Co-morbid conditions, such as fibromyalgia syndrome and irritable bowel syndrome may overlap with CFS. The clinical case definition includes a list of exclusionary conditions.

Before, under Agent Specific Screening Question(s): No specific question is in use for blood donors and is not indicated because transfusion transmission has not been demonstrated.

• No sensitive or specific question is feasible.
• The high apparent prevalence of infection reported in healthy control subjects and the high prevalence of chronic fatigue in the population are expected to make donor history screening unreliable. The rate at which potential donors carrying a criteria- based diagnosis of CFS present to donor centers is unknown, but probably low in light of the associated disability.

After, under Agent Specific Screening Question(s): No specific question is in use for blood donors and is not indicated because transfusion transmission has not been demonstrated.

• No XMRV-specific question is feasible in the absence of any established risk factors for XMRV infection and the experimental nature and limited availability of diagnostic tests.
• No sensitive or specific question is feasible for CFS.
• If the high apparent prevalence of XMRV infection reported in healthy control subjects in the original CFS study is confirmed, and given the high prevalence of chronic fatigue in the population, donor history screening would not be expected to be effective.
• The rate at which potential donors carrying a criteria- based diagnosis of CFS would present to donor centers is unknown, but probably low in light of the associated disability.

Before, under Laboratory Tests: Research assays include PCR, cell culture, flow cytometry-based immunoassay, and immunohistochemical analyses.

After, under Laboratory Tests: Research assays include RT-PCR, cell culture, flow cytometry-based immunoassay, chemiluminescent immunoassay and immunohistochemical analyses.

Before, under Currently Recommeded Donor Deferral Period:

• No FDA Guidance or AABB Standard exists for blood donors.
• Current practice is to accept donors who are healthy at the time of donation.
• Pending the availability of further data, prudent practice would be indefinite deferral of donors who have received a diagnosis of XMRV infection.

After, under Currently Recommended Donor Deferral Period:

• No FDA Guidance or AABB Standard exists regarding XMRV infection.
• Pending the availability of further data, prudent practice would be indefinite deferral of donors who have received a diagnosis of XMRV infection.
• Current practice per FDA Guidance and AABB Standards is to accept donors who are healthy at the time of donation.
• CFS advocacy organizations and the National Cancer Institute have historically discouraged blood donation by CFS patients.
• Blood collection facilities should follow established SOPs regarding donors with cancer.

 

[Gerwyn]

The AABB (formerly the American Association of Blood Banks) has issued a revised fact sheet on XMRV. The pdf link to the fact sheet is here: http://www.aabb.org/documents/About_Blood/EID/xmrvfactsheet.pdf

Bottom line looks to me like they are not banning CFS donors, except for those who are known XMRV positive. Someone with more functioning brain cells than me will have to parse all the differences out. I tried to catch all the places things were changed or reworded from the January AABB statement. Hopefully I got them all. Here is Before and After of each change:

developmental serological methods is a posh way of saying speculative and unproven Any chance of any details?

 

[jackie]

Thank you Jennie! I think your "take" on this is correct! (in other words..."no big whoop!" - because of the inherent disabilities associated with being ill with me/cfs...the percentage of (infected) donors will be low? "we" (me/cfs) are already "discouraged" from being donors...and it will be up to individuals to decide...is that right?)

I have an interest in this topic, as my husband (who appears to be free of me/cfs at this time) has the rarest blood type and previously donated blood quite frequently - and is now being asked by the Red Cross (several times) to donate platelets as well. Neither of us have been tested for xmrv.

Thanks again for posting this! jackie

 

[V99]

Off topic a little, but why the change from:

Alterations of immune, neuroendocrine, and autonomic function may be associated with this syndrome, but none is diagnostic. There is considerable overlap between this condition, fibromyalgia, and some affective disorders.

to

Co-morbid conditions, such as fibromyalgia syndrome and irritable bowel syndrome may overlap with CFS. The clinical case definition includes a list of exclusionary conditions.

 

[fred]

Study of blood donors

"Preliminary data from another study using developmental serological methods in a small sample of US blood donors found a seroprevalence of -0.1%."

Which study was this?

 

[jspotila]

Off topic a little, but why the change from:

Alterations of immune, neuroendocrine, and autonomic function may be associated with this syndrome, but none is diagnostic. There is considerable overlap between this condition, fibromyalgia, and some affective disorders.

to

Co-morbid conditions, such as fibromyalgia syndrome and irritable bowel syndrome may overlap with CFS. The clinical case definition includes a list of exclusionary conditions.

I thought is was very interesting that the reference to "affective disorders" (translation depression and emotional problems) was deleted.

 

[gracenote]

Thanks so much, jspotila, for doing the side by side comparisons. That is so very helpful.

 

[fred]

I thought is was very interesting that the reference to "affective disorders" (translation depression and emotional problems) was deleted.

And IBS added, another illness that is dismissed as being 'all in the mind' and not related to CFS.

 

[natasa778]

"Preliminary data from another study using developmental serological methods in a small sample of US blood donors found a seroprevalence of -0.1%."

Which study was this?

Could be the one presented at CROI by Abbotts Labs?

 

[ixchelkali]

I find this both encouraging and discouraging

There are things to like about it. My absolute favorite bit is where it says "CFS (also called, more descriptively, myalgic encephalitis)."

The symptoms list is better than most; it mentions post-exertional malaise, and overall makes it sound serious. In the severity section it says CFS produces very significant disability with substantial disruption of activities of daily living among those meeting strict case definitions, so at least theyre not saying its too trivial to worry about.

However, in the section on screening questions, it says No sensitive or specific question is feasible for CFS. How about, Have you been diagnosed with CFS?
And then they say The rate at which potential donors carrying a criteria based diagnosis of CFS would present to donor centers is unknown, but probably low in light of the associated disability. In other words, theyre probably too sick to get to the donor center anyway. Thats probably an accurate guess, but I wouldnt want to bet the blood bank on it.

And of course, the most discouraging part is that, while they do say that it would be prudent to defer those with an XMRV diagnosis, they dont think that prudence dictates deferring those with ME/CFS. It makes it seem as though they are more concerned with whether they could be held responsible for someone contracting the disease than they are about whether someone contracts it.

In a way, I shouldnt mind; being deferred from donating blood might just add to the stigma ME/CFS patients already face. But I hate the thought of even one more person getting this, if it could be prevented. Couldn't they act, as the politicians say, "out of an abundance of caution"?

 

[Esther12]

developmental serological methods is a posh way of saying speculative and unproven Any chance of any details?

I think that refers to the one from this thread:

http://www.forums.aboutmecfs.org/sh...-Tissue-Tropism-and-Ser.-Markers-of-Infection

 

[usedtobeperkytina]

Did I catch a subtle reference at the very end that CFS patients who are not healthy shouldn't donate? I think it says something about only healthy people should donate, which is their standard policy.

So is this the way they will cover themselves? "Those CFS people shouldn't have been donating all the time, they were unhealthy."

I also notice some reference to possibly that the virus is sensitive to heat. If that is the case, could this be part of the wait? They will announce it is in blood supply when they can announce they can eliminate it from blood supply?

Am I just overly suspicious tonight?

Tina

 

[CBS]

My favorite:

Reasons for the discordant findings are not clear but may include differences in the cohorts studied or selection of patients from cohorts for testing, variable assay procedures, differences in prevalence in different geographic areas, varying properties of XMRV or other factors.

No mention of contamination or lab error (unless that goes under'other factors').

 

[JT1024]

Good catch CBS! That tells me that they know XMRV is real and a potential threat to the blood supply.

 

[Gerwyn]

"Preliminary data from another study using developmental serological methods in a small sample of US blood donors found a seroprevalence of -0.1%."

Which study was this?

It appears to be data on file using a highly suspect method which has not been validated in any way.strange that they chose to include this!