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Difference between sudden and gradual onset XMRV

Discussion in 'XMRV Testing, Treatment and Transmission' started by RustyJ, Jul 10, 2010.

  1. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Not sure if anyone has gone down this track. If XMRV is propagated via immune system activation, possibly due to secondary virus or viral load, then could this be the major difference between sudden and gradual onset XMRV.

    If the Lake Tahoe cohort was also infected with a rapid onset virus which ignited XMRV replication, then what will be significant is not just that they had XMRV but what that secondary trigger virus was. Genetics as a determinant does not explain why everyone in the Tahoe group came down with rapid onset (unless they were all cousins, of course). Far more likely that the group already had XMRV which is slow to replicate under most circumstances, but the circumstance changed to induce rapid replication. And if not a secondary virus, perhaps some other trigger.

    Perhaps when the dust is settled on the XMRV issue someone will look closely at the triggers. Maybe categorise them according to how effectively they contribute to XMRV propagation. For example EBV may be a slow trigger or CMV a rapid trigger and so forth. Or a measles vaccination may be a rapid trigger.
     
  2. Angela Kennedy

    Angela Kennedy *****

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    Sorry people - got to put this spanner into the works - before any of this could be done, one has to effectively define 'gradual' and define 'sudden', in a way that is instantly recognisable and scientifically sound/safe, to all.
     
  3. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    I assumed the CAA had gone down this track with their initial restrictions for the BioBank, which seemed farcical to me. XMRV is XMRV. [Unless the different strains of XMRV are responsible for the onset time] Anyway, I think the terms 'gradual' and 'sudden' will become less relevant, and simply be the end points of a continuum, each point on that continuum dependent on a trigger or range of triggers.
     
  4. Hope123

    Hope123 Senior Member

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    Another possibility is that the outbreaks started when the virus first jumped from mice (or other carrier) to humans. Viruses can change over generations and perhaps it was more virulent at the beginning meaning it could infect just about anyone. Later on, over time, the virus changed and became weaker, not able to cause disease or persist in many people it infected. Or maybe some strains weaken their host gradually vs. suddenly. A successful bug might not kill or disable its host because killing or disabling the host might mean less chance for it to spread.

    This doesn't totally explain sudden vs. gradual onset but it's something I've thought about in terms of why CFS occurred in outbreaks then but not now.*

    *caveat being that no one has really looked for CFS clusters since the 1980s
     
  5. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Perhaps those that say they had sudden onset may have had intermittent symptoms over a long period of time.

    One thing I should say about my own experience. I definitely did have what I would describe as a sudden onset, but that may have been brought on by glandular fever.

    When I look back over my life things happened which I could probably pin down to ME. Eg, I had
    *Many dental fillings, yet my other family members had none, yet I probably cleaned my teeth more than my brothers and sisters.
    *Periods of prolonged colds or flu lasting most of the winter in the four or five years before the sudden onset.
    *Severe hayfever and consistent sore throats 3 years prior to the sudden onset and some fatigue.
    *An inexplicable loss of intelligence in Grade 11. I fell from top 0.5% in country to top 20%. Years before I came down with fully fledged ME I used to refer to this in wonder (and get weird looks, believe me). Of course, tests now show that my intelligence levels have dropped to below average.
    *Strange but infrequent episodes of energy drain while playing sport.
     
  6. Frickly

    Frickly Senior Member

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    This has always been confusing to me. I still don't know if I was sudden or gradual onset. Looking back....I see signs of this since I was in my early twenties (general fatigue and lymph node swelling, along with some cognitive issues). However, It was when I was 31, that it hit me hard and I could not get up my stairs. I went through a six month period of this. After that it came and went until it came and stayed. I may have had an illness that set it off as I was sick alot. However, I did not pay attention and just powered through these periods. I can't remember. What is that? Gradual or sudden? I don't know.
     
  7. ukxmrv

    ukxmrv Senior Member

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    Rusty,

    I am XMRV+ and was very well before the acute viral illness struck. No childhood diseases or problems, no fillings at all. No stress or illnesses. No allergies. Physically active.
    We are all different and when the survey of XMRV+ is published that I hope we will be in a better position to see a pattern.
     
  8. Adam

    Adam *****

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    This is a good point I can relate to. My sudden onset was Oct 1996. And yet, I could point to a number of possible symptoms prior to that. About 6 months before the onset I lost the use of my legs for about an hour. I was falling to the floor with every step and just gave up in the end and sat down. A total one-off I thought at the time. Wish it had have been.

    Oh well.
     
  9. darkrobot

    darkrobot

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    Rusty, apart from the glandular fever you have just described my life between the ages of 10-25, when I was finally given a "diagnosis" of ME/ CFS.

    I was also a very bright child,and was moved forward a year in primary school because I found the work in my class too easy. Soon after the brain fog began to set in, I passed an exam to get into one of the best high schools in the country (just- I turned over the exam paper after time was up and found a whole extra page of questions I hadn't answered! :eek:). This is my first really tangible memory of brainfog screwing things up for me. It was downhill from there, and from then on I struggled to get passable grades. This is the first time I've come across a kindred spirit. :D

    I am not sure whether this was gradual onset, or sudden but mild onset which steadily got worse over the years.

    I aslo have many fillings, frequent bouts of illness which seemed to last longer than anyone else's, sudden energy drain when playing sport, sore throats, respiratory symptoms, but it was all put down to depression and "allergies".

    I am currently on long term abx for borrelia and micrococci, and am also on LDN and various mito supplements. These have helped enormously, especially with the brain fog.
     
  10. dannybex

    dannybex Senior Member

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    I've said it before...

    and I'll say it again... :Retro smile:

    There should be at least a third category..."gradually sudden".

    I suggest that only after reading dozens of stories where the poster says they had sudden onset, but then goes into detail about multiple warnings and hints that something wasn't right, in the months or years leading up to a 'sudden' and deep crash or 'onset'.

    ???


    p.s. I probably would be considered gradual onset, but possibly "gradually sudden"... as I was working waaaaay too hard, too long, pushing myself too hard, was exposed to solvents, pesticides, fungicides, etc.. I knew something wasn't right, but would 'recover' for months, even a year, until I finally ended up at the ER and could barely function.
     
  11. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    How do you even explain the mechanisms involved in 'sudden' onset XMRV? According to WPI and just about everyone else, XMRV is very slow to replicate. I would have thought sudden onset was the least likely outcome. The immune system response should correspond with the level of infection. So does the virus replicate quickly in some people? Is the response delayed in some people? It seems that the time of reported sudden onset symptoms has very little to do with the time of the infection. For these reasons I think sudden onset is largely irrelevant with respect to XMRV and the fevers may be more indicative of the onset of a co-current, opportunistic, rapidly spreading viral infection.

    Anyone have a theory on this. I think it is important, because there has been a lot of emphasis placed on sudden onset. Are more sudden onset ME patients positive for XMRV or the reverse?
     
  12. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Adam, that has got to be the scariest thing I have ever heard. I have had a few mental blackouts (petite mals?) where I was driving along a road I travel 2 times a day. Suddenly couldn't recognise anything. Gradually, over the course of a couple of minutes things started coming back. It was very disconcerting.
     
  13. alex3619

    alex3619 Senior Member

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    Hi RustyJ

    I'll give this a go. Suppose someone already had XMRV. It has been slowly replicating, slowly making things worlse, but nothing that could be said to be ME or CFS. It is probably in the lymph nodes in large numbers, but also almost everywhere else. You then get another infection - something probably almost ordinary. It is perhaps a little more severe than normal. The immune system really kicks off. Suddenly XMRV is replicating like made. Twenty years of slow replication take place in just a few days. Viral load in the tissues goes from low to high. Now you have a real case of XAND, as the virus is now able to highly disturb the entire system, triggering major and prolgonged cytokine shifts, perhaps autoimmunity, and who knows what else? The immune system has become fully activated, finally recognises XMRV, but can't kill it. The immune system gradually becomes exhausted, but can't ever switch off until it clears the infection - which it never will. The triggering coinfection dies down as immunity kicks in, but XMRV can reactivate it at any time our immune system is weakened.

    Remember, a highly adapted virus wants its host weak and infective, not dead. That would make XMRV much more adapted in humans than, for example, HIV.

    This is only one of range of possible explanations - it would be good to hear more.

    Bye
    Alex

     
  14. alex3619

    alex3619 Senior Member

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    PS The preceding scenario relies on XMRV replicating in cells in which another virus is already replicating. The longer you have XMRV the more cells are infected, and the higher the risk of a coinfection triggering XMRV replication. Alex.
     
  15. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Hi Alex. Your assessment is probably correct. However this does not rule out the sudden onset symptoms being symptoms of the co-infection, not actually XMRV. Indeed, I have not heard of any scientific explanation of symptoms of sudden onset. Eg, fevers is not a normal symptom of ME (XMRV). Also raises some other interesting questions. Over the course of 20 years (to full XAND), some patients would have contracted many viruses, so why then does it still take 20 years? Maybe it is just a small number of viruses responsible. What about people carrying XMRV all their lives without having symptoms? All very intriguing.
     
  16. floydguy

    floydguy Senior Member

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    Another possibility might be acute (or maybe even gradual) onset with remission and then gradual worsening of symptoms years later. I got really sick in 1985 while in high school with a mono type illness but then recovered for 15 years or so.

    Interesting comments Rusty made about his symptoms before onset. One of the strange things that happened to me was a rapid deterioration of my gums just before I got ill. In 6 months I went from my gums being okay to needing immediate gum graft surgery. Also had others on his list like the occasional WTF energy drain during sport and awful cold/flu during winter months.
     
  17. slayadragon

    slayadragon Senior Member

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    twitpic.com/photos/SlayaDragon
    Incline Village Epidemic


    I've spent a lot of time trying to understand what happened in Incline Village and discussing the topic with Erik Johnson, a member of the cohort who has mostly recovered through what he calls "extreme avoidance" of mold and other biotoxins.

    This is my current understanding. Please note that it may not be exactly what he believes (he tends to share information rather than hypotheses).

    In 1984/85, a microcystis (poison cyanobacteria) bloom was especially problematic on Lake Tahoe. A bright green algae was notable throughout the area, especially on the beach and in the woods.

    Erik already was aware of his reactivity to toxic mold and other biotoxins. He thus noted that the "bright green not-grass" was having an effect on him. He also was reacting to various buildings in the area, including Truckee High School.

    At about that same time, he noted a stronger version of this "stuff" coming up through the sewer vents in Incline Village and (I believe) Truckee. It made him feel somewhat sick as well. He went to Dr. Cheney and complained of what he described as "Chronic Fatigue," though this also had a neurological component to it.

    Then the "Yuppie Flu" swept through the area. On August 5, 1985, Erik caught that "flu." After that, he became far more affected by the "whatever" that was coming up through the sewer vents. The "stuff" (apparently toxic mold) in his own house made him sick as well. His previously fairly mild reactions to these substances moved up to being "life threatening," constituting the symptoms he was experiencing.

    His observation was that people who were living/working in particularly bad buildings, or who were living in homes that were adjacent to sewer vents, were more likely to get the "flu" and much more likely to get what later was called Chronic Fatigue Syndrome subsequent to it.

    By scrupulously avoiding the "whatever" in buildings and outside, and by decontaminating (showering and changing clothes) after being hit with it, Erik managed to recover the majority of his health. He now works a full-time job, exercises vigorously and regularly, and lives a basically normal healthy life. He previously had all the Canadian Criteria symptoms except the bladder infection; now, he has only a few residual cognitive ones (including the disappearance of his formerly good math abilities). Having to be really careful about avoidance is annoying but better than living in agony, he has.

    I find this story interesting because it suggests that there were two new things that happened in 1984/1985 in the Lake Tahoe area. One was the "flu" that swept through. The second was the microcystis bloom and the "whatever" that established itself in the sewers.

    It's my tentative belief that the epidemic consisted of several components.

    1. Substantial previous exposure to very bad buildings (e.g. Truckee High School) or to the "whatever" coming through the sewer vents.

    2. Genetics predisposing people to being biotoxin responders. (However, as at Truckee High School, a particularly large exposure was capable of making anybody sick.)

    3. Exposure to the virus that ramped up reactivity to these biotoxins from mild-ish to severe.

    4. Possibly other factors (e.g. accumulated toxic burden of mercury, stress) were contributors increasing likelihood or severity.


    A question is what the "Yuppie Flu" was. One possibility is that it was XMRV. However, I'm of the impression that this virus may have a longer incubation period than was noted in the fast spread in the Lake Tahoe epidemic.

    If that's the case, then it could be that this was just an ordinary flu that triggered the XMRV to activate.

    It's also possible that it was not a viral infection at all, but rather a big biotoxin exposure that appeared to be a flu, that caused the XMRV to activate. (Ritchie Shoemaker describes certain biotoxin exposures that appear to be "flus" in Desperation Medicine.)

    Again though, much of this is speculative on my part. I am putting it here not because I am claiming to have the answer, but because it seems to me that more people should be considering the question.

    Best, Lisa
     
  18. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Thanks for that Lisa. If I understand what you are saying, according to Erik's experience it seems that his symptoms have dissipated although he still has XMRV (XMRV doesn't go away), hence it wasn't XMRV that caused his symptoms, but the biotoxin. So is XMRV causing any of our symptoms? Is it just allowing other viruses to continually affect us - the 30-40 or so we're supposed to have?
     
  19. slayadragon

    slayadragon Senior Member

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    Judy Mikovits states that at least four factors cause XMRV to (re)activate: inflammation, cortisol, androgens and estrogens.

    Biotoxins are extremely inflammatory. Those who are affected by them also tend to produce large amounts of cortisol in order to compensate for their effects.

    It thus seems reasonable to think that the decreases in cortisol and inflammation obtained as a result of biotoxin avoidance might eventually help the system to get the XMRV under control, thus allowing most or all of its effects to dissipate.

    Conversely, it seems that insofar as people's systems are being stressed by active infections of any pathogens (viral, bacterial, fungal, parastical, etc.), they are less able to effectively deal with new toxin exposures and thus are more affected by them.

    It's possible that active infections of XMRV make biotoxin exposures particularly damaging. However, especially since a course of Valcyte/Famvir caused my own mold reactivity to decrease substantially, I suspect that other pathogens have similar effects.

    A number of us with classic Canadian Criteria CFS have found that our symptoms have substantially disappeared or diminished as a result of pursuing "extreme avoidance." This generally takes a substantial amount of time though (approximately six months). This seems consistent with the idea that it takes time for pathogens to get under control and for the body to repair itself.

    So I'm seeing it as a vicious circle: the biotoxins cause the pathogens to become active, and the active pathogens cause the biotoxins to become more damaging.

    This is just my own current way of looking at it though.

    Best, Lisa
     
  20. aiden424

    aiden424

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    I've always wondered if it could be xmrv too because I had such a sudden onset. I worked the day before and was fine. I woke up April 16, 1986 with what first felt like the flu or strep throat. By the end of the day I was so sick I was bedridden. Have been in that state for the last 24 years. Antibiotics have helped some. Doctors at first thought viral menengitis, but spinal tap was negative. I just wonder if xmrv is slow to reproduce how I got so sick so fast.

    Kathy
     

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