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I tested Negative

Discussion in 'XMRV Testing, Treatment and Transmission' started by imready, Dec 16, 2009.

  1. kurt

    kurt Senior Member

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    I read a study a few years back that said 40% of PWC have Lyme, so it is not everyone with CFS. Also, Lyme is hard to treat if you have bad detox genetics, as most PWC have. Probably we need to get the CFS managed and our immune system working again before we are likely to make much of a dent in Lyme.

    True, that culture of the 30/33 was interesting, but the culture uses antibodies, which has some issues: 1) WPI used MuLV antibodies and according to one review of research, some MuLV antibodies cross-react with some HERV types, and PWC have high rates of activated HERV per the WPI May presentation and also per research at Tufts; 2) WPI did not publish their results of the antibody study for the control group, so we do not know whether that 30/33 is unique for CFS, or whether the MuLV antibody would have also found an antigen at that rate in the controls. They can cite the literature for standard control rates of positive on MuLV antibodies, but that does not validate their antibody test, they have to run controls in their lab using their reagents, the same test must be run on both the CFS samples and controls. Maybe WPI did that but it was not reported in their Science article.

    Yes, too early to be making assumptions.

    Also, a negative result on a standard PCR is pretty strong. False positives are more common than false negatives for the type of PCR test that WPI used. I have heard that VIP is using one of the original prostate cancer tests, which I believe was standard PCR.

    We do need to keep hope alive. But hope should always be based on what is or can be reality. We do not yet know if XMRV is reality for CFS. So for me anyway my hope is that regardless of the outcome of the XMRV replications, more productive CFS research is in our future.
  2. fresh_eyes

    fresh_eyes happy to be here

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    Amen to that.
  3. CBS

    CBS Senior Member

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    Hi Kurt,

    I don't know if you saw it, and I have forgotten the thread, but another question I posted earlier was; "Did the WPI go back and do what they would probably characterize as the more sensitive tests (XMRV cultures) on the controls?"

    Good points to keep in mind.

    Shane
  4. cfs since 1998

    cfs since 1998 *****

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    http://www.davidsbell.com/PrintLynNewsV6N3.htm

    "That leaves 33 patients with CFS who were negative. But on further testing 19 of these 33 are XMRV antibody positive, 30 of these 33 had transmissible virus in the plasma, and 10 of these 33 had protein expression."
  5. Alesh

    Alesh Senior Member

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    In my opinion based on my personal experience with CFS, my illness is a kind of viral encephalitis. And as brain is the best place for a virus to hide against immune system, since brain lacks immune-competent cells, for me it is perfectly plausible that someone with XMRV encephalitis tests negative for the presence of XMRV in blood cells. What would be necessary is to test cerebrospinal fluid or eventually to perform a brain biopsy. The best strategy now is to survive to the point when more about XMRV is known. I contacted my distant fellow, who happens to be our national coordinator for testing of the prion diseases and he told me that he performed or supervised during his carrier more than 10000 brain autopsies but has never done an autopsy of a brain of a CFS patient. He also told me that if AIDS weren't lethal and thus autopsy impossible it would not be possible to identify HIV as a cause of AIDS. I think it is a striking fact-whatever that means-and we will know more in near future.
  6. sunshine722

    sunshine722

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    Good post. And so true how difficult testing for in HIV was at first. Nancy said this in lecture: "When the first HIV blood test came out it wasnt any good either. You know, it went through stages and stages and stages before we got a really good one. "
  7. kurt

    kurt Senior Member

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    Different PCR tests have different risks of false findings. The standard type of PCR has some risk of false positive, but low risk of false negative. So that means a negative finding is the strongest.

    The replication studies will most likely be using the more current real-time PCR method, and the risks are reversed, more risk of false negative, but low risk of false positive.

    There is some question about what test VIP is using right now, I believe though it is one of the original prostate cancer tests, which is a standard test. The Science article described a standard PCR, which means more risk of false positive than false negative.

    As for the antibody and culture studies there is an extensive research literature from attempts to link retroviral infections to other illnesses, particularly auto-immune conditions. And that literature reveals a significant risk of false positive (cross-reactions) using an MuLV antibody due to its ability to react with HERV retroviruses, endogenous forms that are known to be present in PWC (per WPI as well as research at Tufts).

    One study showed 40% of PWC have Lyme, so it is not true for 'everyone' with CFS, but certainly for some of us. And not all cases of Lyme are easily treated, particularly with CFS, due to our intolerance of die-off. Also, Lyme bugs burrow in to our bones, really there is almost no way to eradicate that infection if it is long-standing, just have to find a way to manage it and try to keep it in remission. Besides, based on experience, I suspect Lyme can not be successfully treated in CFS until the underlying CFS pathologies are under control, due to the toxic nature of the flare-ups of the Lyme co-infections.

    Exactly. I would even say the science of XMRV in CFS is not even finished with the first essential step yet.
  8. CBS

    CBS Senior Member

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    W. Churchill: "Now this is not the end. It is not even the beginning of the end. but it is, perhaps, the end of the beginning"

    It may be even more accurate to say that we are at somewhere between the beginning and the middle of the beginning.
  9. Robin

    Robin Guest

    If Lyme tests are valueless after a certain point, I've always been confused at how Lyme literate doctors can arrive at a diagnosis of Lyme vs. CFS. Was the study based on lab work? If so, were the infected-but-testing-negative included?
  10. anne_likes_red

    anne_likes_red Senior Member

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    And that "extra test" the plasma culture test - that is not currently provided as part of public XMRV testing right, not by any lab?

    Therefore, if I am understanding correctly, you have a 1 in 3 chance of a false (or a not yet) negative.
  11. fresh_eyes

    fresh_eyes happy to be here

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    anne_likes_red, could you spell out how you got to that, for the non-math-minded among us? :)
  12. anne_likes_red

    anne_likes_red Senior Member

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    ...well I may not be understanding this right but the first tests that tested 67% positive - they are the tests offered currently?

    If the plasma culture test, the one that scooped up the extra 30 showing evidence of infection (the one that has not been published yet) is not currently being offered as part of testing* then only 2/3 approx of positives are currently being detected. That's where I get 1 in 3 not currently being tested positive...but who may in fact test to be so with further testing.

    *That's what I'm understanding from Nancy Klimas's talk. However that was a month ago and may be out of date. Also I'm not clear on which tests are in fact being offered as part of the general public testing, I asked in another thread, so don't take my word for it. I'm confused...I don't think you need to take much notice of my maths ;)
  13. fresh_eyes

    fresh_eyes happy to be here

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    @ anne - Thank you! That makes sense. I guess my only question remaining is the same as yours - are the 2 tests currently offered the ones that resulted in the 67%. Anyone?
  14. anne_likes_red

    anne_likes_red Senior Member

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    I've been asking that all over...

    ...it's what I'm understanding from other things I've read and heard. But it may just be plain wrong.

    Nancy Klimas says in her lecture "So, there are some issues here. That blood test only identified 67% so if I ordered a blood test on you right now and it was negative, what would happen to your soul? You know, and yet it might not really be negative, in fact it’s got a one chance in three of being wrong. The blood test that we don’t have yet that we will have very shortly, those tests are going to be improved on."
    However...that lecture was last month, and things are moving on fast...
  15. spit

    spit Senior Member

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    WPI used a nested PCR, I believe, which uses two sets of primers -- essentially, two PCR assays, the second acting on the product from the first -- to cut down on the chances of poor specificity of either primer leading to false positives. There was also some sequencing, but I'd have to reread with more brain power than I've got at the moment to figure out how many samples were sequenced, either gag or env or whole genome.

    I'm not sure what VIP is doing, specifically.

    Specificity and sensitivity in PCR always depend, so far as I'm aware, on the particular assay -- primers used, sequence targeted, etc.

    Overall, we agree that the testing has a while before the results are really solid, and of course we don't know what to do with the results yet anyway.
  16. Cort

    Cort Phoenix Rising Founder

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    Dr. Bateman mirrored Dr. Klimas' suggestion regarding testing - she advised patients not to get to tested yet. Enough interest has been generated in the research community that it won't be long for a test that's been independently validated and standardized to appear. Right now you could falsely test negative or falsely test positive.

    So many labs are working on this that we should pretty soon (6 months?) have a standardized test that insurance will hopefully cover.

    I imagine the VIP dx test is a very good test and it will be accurate for many people - but not for everybody; that test will take some time to come out. IMReady could have XMRV with a slightly different sequence which the test simply didn't pick up. Someone just noted that XMRV envelope is quite variable genetically and the protein VIP dx tests for, I believe, is in the viral coat. (If I got all that right!)
  17. anne_likes_red

    anne_likes_red Senior Member

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    The "Discussion on XMRV" Lucinda Bateman, M.D. clip I just watched (from December 2) http://www.offerutah.org/batemanxmrv.htm - she seems to suggest the same. (So encouraging to see another doctor so excited on our behalf. :D)

    A standardised test sounds like a very good thing to look forward to.
  18. Cort

    Cort Phoenix Rising Founder

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    She's just fantastic; I love her cool, lucid approach to all this.
  19. spit

    spit Senior Member

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    anne likes red -- your analysis appears to me to be absolutely correct. WPI got positive results from their initial PCR testing in about 2/3 of the sample. Further testing gave much higher results. That would indicate that their initial PCR testing missed nearly 1/3 of the positive samples.

    That's a very low sensitivity.

    I will caution, though, that the higher results are still unpublished, so peer reviewers haven't had a chance to poke holes in them yet. That doesn't mean they're wrong, it just means they're shakier until they're reviewed. The incredibly strong unpublished correlation is one of the things I'd most like to see replicated, and soon -- you just don't typically see that kind of correlation without it meaning something, so it's essential to confirm it in published results.
  20. kurt

    kurt Senior Member

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    There are very different clinical pictures for Lyme vs. CFS. CFS includes significant PEM (post-exertional malaise) and Lyme does not always have PEM. Some Lyme positives can still exercise, in fact for some PWL exercise helps them keep their Lyme under control. For real PWC the ability to exercise is like a memory from a prior life. There are some other differences, and certainly there are many similarities, and some of us have both so pretty hard to tell them apart.

    This is under the assumption that the culture and WB antibody test are not also producing false positives, but as I tried to explain in an earlier post, that has not yet been validated. So right now it is hard to say if there are ANY false negatives in the testing. I suspect that VIP is unlikely to produce a false negative finding if they are still using a standard PCR and the reactive MuLV antibody. But a false positive is certainly possible.

    They are using a real-time PCR design for their main commercial test.

    I was told by CD that in their study (not yet reported) they ran both types of PCR, the WPI-style straight from the Science article, and their advanced RT PCR design.

    CD used that standard PCR test only in their study, their commercial test is RT-PCR.

    You would have to ask VIP what specific test they are using. I suspect VIP may have switched to the more accurate RT-PCR, just a hunch because WPI has said they want standardized testing and most other labs will be using RT-PCR.

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