A New Decade of ME Research: The 11th Invest in ME International ME Conference 2016
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Prolonged Fatigue [CFS] & cytokines post-West Nile Virus Infection, in USA

Discussion in 'Latest ME/CFS Research' started by Simon, Aug 29, 2014.

  1. Simon

    Simon

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    Evaluation of Prolonged Fatigue Post–West Nile Virus Infection and Association of Fatigue with Elevated Antiviral and Proinflammatory Cytokines
    Garcia, 2014
    What isn't obvious from the abstract is that most of the cases of post-viral fatigue met Fukuda CFS (though based on questionnaire only), and that this is a study in the USA, where 3 million people have been infected.

    It's not the most compelling study from a CFS perspective (more on this later) but could be yet another case where CFS develops at a high rate after an acute infection from particular pathogens. If so, it would join the club founded by EBV/Glandular Fever but also including the gut parasite Giardia, plus Ross River Virus and Q-Fever. It's in a similar mode to the Dubbo studies.
     
    Last edited: Aug 29, 2014
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  2. Simon

    Simon

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    Commentary
    - reading the research so you don't have to :) -

    West Nile Virus (WNV) was identified as a source of encephalitis in the USA by Ian Lipkin (who else?) in 1999. It's a mosquito-borne infection that causes no symptoms in most (estimated 3 million WNV cases in US), a more typical infection in about 20% of cases but neourological problems in around 1%. So far there have been around 1,000 documented deaths in the US from WNV, most in people who already had other health problems.

    This study follows a cohort of cases diagnosed in Houston, Texas between 2002 and 2011, with follow-up (when blood samples for cytokines and questionnaires were done), with follow-up ranging from 1-10 years ie different length of illness for different folk.

    Fatigue and 'CFS'
    It's important to understand how they defined fatigue:
    This is significant because chronic fatigue is fairly common - and this rules out those who were chronically fatigued before infection - ie it's 'new onset' fatigue as it's sometimes called in CFS definitions.

    All patients were fatigued at the time of the evaluation, but 30% did not experience fatigue immediately after the acute infectious illness - so this might be chronic fatigue from some other cause.

    31% of the cohort were fatigued at follow-up (44/140) and "Of those with fatigue postinfection, 28 (64%) met the CDC’s case definition of chronic fatigue syndrome (Fukuda)".

    Unfortunately, the rest of the data is for all fatigued patients, not only those who met Fukuda. Also note there were no lab tests or medical/psychiatric exam to confirm CFS diagnosis. So this study is only indicative of CFS post West Nile Virus, but is, I think, still of interest. Note that for all fatigued patients combined, 82% had cognitive problems, 75% had PEM and 75% sleep problems.

    The biggest predictor of developing fatigue after WNV infection was having a symptomatic infection (most infections produce no symptoms), and 42/44 or 95% of those fatigued at follow-up had symptoms on infection..The other predictors were being female and being younger (under 50 at infection).

    The average length of fatigue in the fatigued group was five years (which was probably nearly the average length of follow-up since infection, but they don't give that figure).

    Elevated cytokines
    They compared the blood levels of 20 cytokines in 25 fatigued cases vs 52 cases without fatigue.

    Interferon-gamma, Granulocyte macrophage-colony stimulating factor (GM-CSF) and Interleukins IL-2, IL26 and IL-2 were all significantly elevated in fatigue cases- and all are pro-inflammatory and/or antiviral.

    They found no significant reductions in any cytokine level.

    Chronic infection?
    One possibility for these elevated cytokines is an ongoing, chronic West Nile Virus infection. They didn't test for WNV directly, but they did look at IgM levels (antibodies against WNV). While IgG antibodies would be expected, given all subjects had a proven initial WNV infection, IgM indicates (though doesn't prove) a chronic infection.

    The authors found 23% of cases did have significant IgM levels, indicating a chronic WNV infection. However, they found no correlation between prolonged fatigue and IgM levels. Nonetheless, the authors suggest a chronic WNV infection could be causing the fatigue. As they conclude:
    Role in CFS?
    Finally, I expect a few people would agree with this:
     
    Last edited: Aug 29, 2014
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  3. aimossy

    aimossy Senior Member

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    Excellent, thanks @Simon :)
     
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  4. Bob

    Bob

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    Thanks for all of that, Simon. Very interesting. The symptoms, the course of the illness and the epidemiology (i.e. it being more frequent in women) do sound very much like ME. I wonder if Prof Lipkin has thought about, or would be interested in studying chronic cases. (He could perhaps apply for grants through the NIH's infectious disease budgets rather than through the CFS budget so grants might be more forthcoming!)
     
    Last edited: Aug 29, 2014
  5. SOC

    SOC Senior Member

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    Was it your understanding that the authors understood the difference between exercise intolerance and PEM, or are they conflating the two? If post-infection WMV patients do, in fact, get genuine PEM, this is very interesting. If they get exercise intolerance due to post-viral OI for example, it's not so interesting.
     
  6. Simon

    Simon

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    Just checked, and the actual wording in the table was "tired or unwell after exertion" so post-exertional, not all malaise (but note the Canadian Consensus use of "Post-Exertional Malaise and/or Fatigue" as it's second key symptom).
     
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  7. SOC

    SOC Senior Member

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    Thanks, Simon, that clears it up, I think. :) Post-exertional fatigue would indeed fit the CCC, but it doesn't necessarily indicate that the kind of PEM which would cause a failed 2-day CPET exists. Hopefully someone will test WNV patients, along with patients with other fatiguing illnesses, to determine if they also have abnormalities on the 2-day CPET. As we confirm more and more extended post-known-virus metabolic abnormalities, we may be able to hone in on the root of ME/CFS. Or at least gain more credibility in the medical world. ;)
     
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  8. Isabelle

    Isabelle

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    @Simon

    Hi, Was the initial WNV infection confirmed by rising antibody titres or real-time reverse transcription PCR (rRT-PCR)? Did they say why they only tested IgM? IgM may indicate an acute infection (IgG neg initially), though it will persist in some cases (IgG pos) and may occasionally be non-specific. If they suspected a chronic infection I don’t understand why they didn’t test for virus.

    Sorry, not well enough to read it myself.
     

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