Blood from a Stone: CAA Dr. Suzanne Vernon's Analysis of CDC Paper

Sean

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Let's just say that the prevalence of XMRV is about 4% (which I personally believe to be true) but the prevalence in the blood supply is only .1, as Dr. Vernon states. Dear forum scientists, is there a way both of these "facts" could be accurate?
Possible explanations include:

1. the standard treatment process for donor blood is enough to kill off most of the virus

2. the blood donor population is significantly different from the general population

I am sure there are other possible reasons.
 

Cort

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This also ties in with the fact that the CDC received 22 XMRV positive controls (from the NIH & elsewhere) and failed to detect XMRV in a single one of those controls. They obfuscate this fact in their paper by using the weasel-phrase "Bona fide" [controls]. This is bordering on academic fraud.
What does this refer to? Reading the paper I thought the testing was done very well. They used 'gag' sequences for antibody's - as Ruscetti recommends - and showed that antibodies to Env sequences will not show up. They used blinded positive control specimens and were able to pick them out of other samples. They received XMRV plasmid from Dr. Silverman spiked whole blood or PBMC's with them and showed they could find gag and pol sequences in them using PCR. They used nested PCR - as Ruscetti recommends - and again, looked at the right sequences - gag and pol - not env as some of the other studies have done.

Then they sent blinded samples to Robert Koch Labs in Germany and the BSRI at UCSF in California - who confirmed their results. At least from what I can tell the lab part of the study was done very well. Maybe someone with more knowledge will differ.

I don't see the inability to find XMRV in 22 positive controls. Can you point out where that is?

I thought they did a good job - until Dr. Vernon added her piece, and that, of course, changed things :)
 

garcia

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What does this refer to? Reading the paper I thought the testing was done very well. They used 'gag' sequences for antibody's - as Ruscetti recommends - and showed that antibodies to Env sequences will not show up. They used blinded positive control specimens and were able to pick them out of other samples. They received XMRV plasmid from Dr. Silverman spiked whole blood or PBMC's with them and showed they could find gag and pol sequences in them using PCR. They used nested PCR - as Ruscetti recommends - and again, looked at the right sequences - gag and pol - not env as some of the other studies have done.

Then they sent blinded samples to Robert Koch Labs in Germany and the BSRI at UCSF in California - who confirmed their results. At least from what I can tell the lab part of the study was done very well. Maybe someone with more knowledge will differ.

I don't see the inability to find XMRV in 22 positive controls. Can you point out where that is?

I thought they did a good job - until Dr. Vernon added her piece, and that, of course, changed things :)
Cort that information was deliberately left out of the paper by the CDC. Can you really see them admitting to the fact that their methods failed to detect *any* xmrv in known positives? Hardly likely. Instead they deliberately obfuscate the issue by hiding behind the weasel-phrase "Bona Fide [controls]". Apparently the controls sent to the CDC by NIH, WPI & others are not "Bona Fide" because the CDC test failed to detect any of them. As I said in my post on the CAA wall, this is bordering on academic fraud.

See Mindy Kitei's blog for the source on the 22 controls:

http://www.cfscentral.com/2010/06/embargoed-studies-redux.html
 
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If what Mindy says is true, and so far all she has reported has held up, even though she is not giving any indication of what type of sources she has (standard in journalism, she may be in a postition that if she gives even a general, vague attribution, she will jeopardize her sources), then what CDC did was similar to what the Dutch study did, publish a paper and not mention the ones they found negative were found to be positive in another lab.

Tina
 

VillageLife

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Dr Vernon was acting as the official messenger for the NIH Dr Alter study.

She is in the *Know* thats for sure.

For her to come out with such a strong statement about the CDC study, echoes so much.

I remember what Dr Coffin said back in October 2009, at the CFSAC meeting, he said the NIH are really pushing for more to be learned about XMRV.
NIH it seems have really been the positive leaders, they gave $1.6 Million award for ME/CFS Research for Drs. Mikovits/Dr Kerr and they got there best - DR ALTER to work on this.

I think it clearly has been about NIH/FDA Vs CDC.......remember good always wins in the end!

I think we should start cheering for NIH, they clearly are behind us!
 
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Possible explanations include:

1. the standard treatment process for donor blood is enough to kill off most of the virus

2. the blood donor population is significantly different from the general population

Thanks, Sean. For the sake of all those people who need transfusions, I hope the first one is right.
 

*GG*

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From Dr. Vernon's piece:


I'm perplexed as to why she assumes the rate of infectivity of XMRV in the blood supply is 0.1% It has been generally established as 2.2 - 7% of normals. Am I missing something?
A lower rate of infection would "help" in regards to the argument perhaps? If your sample size is only 41 people, then that is 4 percent of 1000 people, this combined with the "improper" methodology makes it highly unlikely that you would find XMRV!

You are going to need a much larger sample size in order to find it in the general population, assuming CFIDS sufferers have no higher an incidence of carrying the XMRV than the general population!

I think her quotes/statement are a slam against the CDC of, you were trying to find a "needle in a haystack" with fork? Not sure if this later part is the best analogy, but I think perhaps you get the point?!
 

*GG*

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Update on CAA website and Facebook:

At the 17th Conference on Retroviruses and Opportunistic Infections in February 2010, Qui, et al., reported that the rate of XMRV in U.S. blood donors was 0.1 percent, or 1 person out of 1000. There is a slim chance CDC would have detected XMRV DNA among just 41 healthy blood donor samples. So, no surprise there. Link: http://www.cfids.org/xmrv/070110study.asp

The CFIDS Association of America john: Documentation for 0.1% rate of XMRV in healthy blood donors: http://www.retroconference.org/2010/Abstracts/39393.htm. Blood donors are "healthier" than the general population and rates for many things -- not just XMRV -- differ between subjects drawn from the general population compared to blood donors. CDC tested blood donors, patients and matched controls. We have updated the online version of the article to clarify the source of this data: http://www.cfids.org/xmrv/070110study.asp

http://www.facebook.com/CFIDSAssn?v...d=132416646789815&comments=1#s132416646789815
 
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> [possibly] the standard treatment process for donor blood is enough to kill off most of the virus

Do y'all find any evidence that pathogen reduction is in place in the US? As I just said at Mindy's, I skimmed a review of Alter's on pathogen reduction and it seemed like one type of PR was in use in this country -- but only for plasma, not other products. There is more PR in Europe. I read a Wall St Journal article i searched up on here, which seemed consistent with the foregoing.

There are 5 million tranfusees per year in this country and I'm not sure how many receive only plasma. I'm guessing it's a minority.

This paper is a little opaque but seems to say that the point prevalence of having ever received a transfusion is 18% in Germany. We can assume that rates in the USA are similar. The lifetime prevalence will be higher than the point prevalence.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725807/

Basically, this looks bad. I did not realize this problem was so large quantitatively.
 
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> [possibility #]2. the blood donor population is significantly different from the general population

Different it may be - but definitely not 40-fold to 70-fold different in XMRV-positivity. I think about 3-fold would be the outside figure for what's plausible. There is about a 2-fold difference when you look at HHV-8 (I think it was HHV-8), if I recall, in the Alter paper I looked at.
 

dannybex

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When Coffin was asked about transmission/infectivity several months ago, he said of course that that's still an unanswered question and may take years to answer. So just because it's in the blood supply doesn't mean it will result in some huge pandemic. Here's a snippet of a quote from Coffin:

"if it is causal for the disease we don’t know what the attack rate is going to be, we don’t know what fraction of the people infected with this virus. Everybody infected with HIV eventually dies, almost everybody will die, 99 point something percent will eventually die of AIDS, if untreated. However everybody infected with another human retrovirus HTLV1, only a small fraction will actually get disease so we don’t know that for these viruses. I mean this list [of questions] could go on and on."

And on and on and on.....
 

gracenote

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This looks relevant to me.

http://www.mphtlvtesting.com/htlv-blood-screen.html

HTLV Blood Screening In Transfusion Services

In November 1988, the Food and Drug Administration (FDA) recommended that all blood donation centers screen blood supplies for HTLV-1 antibodies. This is to prevent the transmission of HTLV-1 infection to recipients of blood components.

A study of 39,898 random blood donors in eight US cities showed that 10 (0.025%) were found to have antibodies against HTLV-1 (Willams et al., 1988). This established the fact that HTLV-1 infection might be transmitted to recipients via transfusion of cellular blood products from infected donors (Okochi et al, 1984). Since the recommendation by FDA, approximately 2,000 HTLV-1/2-infected blood donors were identified during the first year of screening in the United States. Further confirmatory test such as PCR were performed to differentiate between HTLV-1 and HTLV-2 infections. The results showed up to be approximately 50% with HTLV-1 infections and 50% with HTLV-2 infections. These donors were subsequently counseled and permanently deferred from donating blood.

WHO Recommendations
The WHO recommendations to prevent the transmission of HTLV-1/2 through the route of transfusion:

1. In countries in which HTLV is endemic, decisions on introducing screening for HTLV-1 and HTLV-2 should take into consideration the impact on blood supply.

2. When implemented, screening for specific anti-HTLV-1/2 should be performed using a highly sensitive HTLV-1/2 antibody enzyme immunoassay.

3. Countries in which HTLV is non-endemic should consider screening for evidence of HTLV-1 and HTLV-2 infection prior to the release of blood and blood components for clinical use.
 
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> So just because it's in the blood supply doesn't mean it will result in some huge pandemic.

Well, maybe not, but maybe so. Over at Mindy's, using a 7% prevalence rate (which is the most pessimistic number) and some other crude and/or questionable assumptions, I found that 1.25% of Americans might have been exposed by transfusion (probably about 1/5 have had a transfusion). Of course, some of the 7%, particularly the asymptomatic ones, may not have enough virus in their blood to infect another person even by transfusion (even though it is a rather profuse exchange of bodily fluids). Not everyone exposed may get infected.

But, what it they all do, or half do? For example, the risk of HIV transmission in the case of transfusion with tainted blood is near 100%, even though it is not at all a breeze to catch this virus from a *few* accidental needlesticks or a *few* sexual exposures other than receptive anal sex (see http://www.medscape.com/viewarticle/531696_3). I think the prevalence of CFS in the US is around 0.45 - 0.7%, to make a crude estimate using my personal definition of what CFS is. So possibly around 1/10 of those with XMRV may have CFS (point prevalence). So, it *could* be, it seems to me -- as in, it is remotely possible and would not shock my down to the heels to learn -- that as much as 0.12% of Americans have gotten CFS from transfusion, or 0.36 million, about 300,000. That's a whoooooole lot of carnage. OK, what about autism? Who knows what causes it. It's also possible that Reeves disease and, who knows, maybe chronic (as in basically permanent) major depression, might be caused by XMRV.

Again all this depends on variables most of which we cannot begin to know, so I'm not saying any of the above is true, or even close to true. It *could* be, though, which is pretty amazing in itself. It looks like we are likely to be moving toward more use of universal pathogen reduction treatments (directed against nucleic acids) in this country! Certainly if this XMRV thing comes out true. Even if it doesn't, I bet it will inspire more openness to PR anyway, just because it *could* have been true. After all the safety questions with PR are pretty theoretical and the empirical data for its safety, from Europe where it is widely used, are substantial. And, PR is roughly cost-neutral according to Alter.
 
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Lest I be mis-interpreted about HIV... there is certainly a chance of catching it from a few accidental needle sticks or a few heterosexual episodes. It's just not that high. It's like a few percent. So, taking such risks is certainly not recommended. It's just that the risk of infection from a small number of such exposures will not be anywhere near 100%.

The point is that taking a transfusion of HIV+ blood is a way, waaaaay worse idea than say having unprotected heterosexual sex with an HIV+ person one time. The point I'm trying to make is that for at least one agent (HIV), blood transfusion is a far, far more efficient means of transmission than are other familiar ways of getting that virus.
 
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So anyway, I'm getting a better grasp here on why the government might be pretty flipped out. Namely, because something really bad may have happened! I wonder if there are some scholars who have thought all along that it has been totally insane not to use pathogen reduction on the blood supply.
 

alex3619

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Hi Eric

I am glad someone else is applying math to the problem. While math isn't always reliable, it does offer new insights. If the numbers are anything close to the truth, this is 100 times bigger than 9/11 although without the intentionally evil overtones. This is more evil by ignorance. Do you know the figures for how many might have been infected by HIV through blood transfusion? I don't recall ever reading the number. What about hep C etc? If we have numbers to compare it to we might have a better idea of the implications. I might go searching later, but my brain is not working in many ways st the moment, and I might not be able to read for much longer.

Looked at another way, if one in five CFS patients got XMRV from transfusion (this number is a little rubbery imo) then we could be talking about 240000 in the USA using very simplified math. Close enough to your figure to be very worried indeed. Unless we accept the rediculously high prevalence for CFS more recently quoted by the CDC of course.

Bye
Alex

So anyway, I'm getting a better grasp here on why the government might be pretty flipped out. Namely, because something really bad may have happened! I wonder if there are some scholars who have thought all along that it has been totally insane not to use pathogen reduction on the blood supply.
 
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Alex,
Alter writes:

"Historically, there has been a very long interval
between the first recognition that a disease is
transfusion-transmitted and the eventual implementation
of a donor-screening test to prevent that
transmission (Table 1). For the hepatitis B virus
(HBV), the interval between recognition of transfusion-
transmission and implementation of the first
assays for HBV, the Australia antigen, was
approximately 30 years; and for non-A, non-B/
HCV hepatitis, it was 15 years. For HIV, the
interval was reduced to 3 years; however, in that
comparatively brief interval, more than 14 000
transfusion-transmitted, predominantly fatal HIV
infections occurred in the United States alone."

HIV was recognized as a transfusion risk in '82, and began to be screened out in '85. There was certainly a potential for a lot more than 14,000 people to get it through the blood supply, especially because the transmission efficiency by blood transfusion is 90-100%, but really not very many people at all had it back then, compared to how many people had it later. For that reason not very much of the blood supply was tainted with it. I can't find a chart of how much the HIV+ percentage of the population grew, but you can basically see it by looking at this graph of the number of AIDS deaths in the USA. (You can see that deaths plummeted after HAART was invented, which is reason #27 why Deusberg and other HIV denialists are stark raving insane. Until then, they grew rapidly and regularly every year.)

http://en.wikipedia.org/wiki/File:AIDS_Deaths-US_1987-1997.gif

Of course, unlike some people on various forums, I don't believe CFS is very likely at all to be a growing thing, the way HIV was. I believe its prevalence is probably stable. In fact suspect pretty strongly that CFS is identical with the diagnosis "neurasthenia" which was used around 1900, and I suspect the prevalence is about the same as it was in 1900.
 

garcia

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> [possibility #]2. the blood donor population is significantly different from the general population

Different it may be - but definitely not 40-fold to 70-fold different in XMRV-positivity. I think about 3-fold would be the outside figure for what's plausible. There is about a 2-fold difference when you look at HHV-8 (I think it was HHV-8), if I recall, in the Alter paper I looked at.
I agree. Alter in his slide presentation says:

XMRV and related MLVs are in the donor supply with an early prevalence estimate of 3%‐7%.