Commentary
- reading the research so you don't have to 
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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:
fatigue postinfection was defined as fatigue that impaired one’s daily activities for 6 months or more following, but not prior to, infection with WNV.
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
We found that in our population of persons with a history of WNV, those reporting fatigue postinfection had a significant elevation of pro-inflammatory and antiviral cytokines compared to those without fatigue postinfection
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:
Further studies are needed to understand the immunologic and biomechanical factors underlying the debilitating fatigue in our study population.
Role in CFS?
The strong correlation of extended fatigue in our population suggests that prior WNV infection could be an influential factor in those with diagnosed chronic fatigue syndrome. If the underlying cause is not known, physicians should consider testing their patients with diagnosed chronic fatigue syndrome for previous WNV infection, particularly if the patient reports a history of febrile viral-like illness prior to the onset of fatigue.
Finally, I expect a few people would agree with this:
Understanding the mechanisms of fatigue are particularly important considering that chronic fatigue can result in an annual household income loss of $20,000 (34). The average length of fatigue duration was 5 years in our population, which if unresolved could result in substantial long-term personal and economic tolls.
