mrmichaelfreedmen
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I was recently reading some of Dr John Chia's findings, and it suddenly occurred to me that his work and observations may have proved that enterovirus causes ME/CFS. The following explains my logic of why his observations provide proof.
Numerous studies dating back to the 1980s have demonstrated an association between enteroviruses and ME/CFS.
However, as we know, association does not by itself imply causation, and proving that enterovirus actually causes ME/CFS requires going further.
Research that has come tantalizing close to proving enterovirus causes ME/CFS is the data from interferon treatment studies. For ME/CFS patients with high antibody titers to enterovirus, intravenous interferon often results in major improvements in ME/CFS symptoms, and some patients experience full remission for up to a year or so (but most of these patients eventually relapse). And crucially, along with these symptomatic improvements and remissions, enteroviral load (enterovirus antibody titers and enteroviral RNA) goes down after the IV interferon treatment when symptoms improve; and enteroviral load goes back up again simultaneously with the relapse.
This suggests (but does not yet prove) that the ME/CFS improvements and remissions after interferon therapy are the result of the reduced enteroviral load, and that a high enteroviral load can cause ME/CFS.
There have been three published ME/CFS interferon therapy studies: one in 1993 (full paper here), one in 1996 (full paper here), and Dr John Chia's study in 2004. Some details of Dr Chia's further experiments with IV interferon are given in this 2011 article.
All of these studies found IV interferon treatment provided significant benefit in a subset of ME/CFS patients, and there were several cases of patients completely recovering (full remission) from ME/CFS after interferon treatment, and remaining in full remission for at least a year after the treatment.
In the 1993 study, 18 patients were treated with interferon alpha, and out of these, 5 patients improved. Of these 5 improved patients, 3 went into complete remission, and 2 of these 3 were still entirely recovered when checked 1 year later (they may have relapsed further down the line, but the study only followed them for a year).
Significantly, 4 out of the 5 patients who recovered or improved from interferon treatment had elevated coxsackievirus B IgM antibodies. Only one of the patients who did not improve had elevated coxsackievirus B IgM antibodies. So this study gives some indication that interferon often works for ME/CFS patients with active chronic enterovirus infections, but generally does not work for ME/CFS patients who do not have enterovirus infections. We will use this fact later.
In the 1996 study, 26 patients were treated with interferon alpha, and out of these 7 patients improved.
In Dr Chia's 2004 study, 5 patients who had chronically high antibody titers to CVB3 or CVB5 were treated with interferon alpha and the antiviral drug ribavirin. This combined interferon + ribavirin therapy resulted a significant symptomatic improvement in 4 of 5 patients. Concomitant to their symptomatic improvements was a disappearance of enteroviral RNA in all patients, and a decrease in enterovirus antibody titers in 4 of 5 patients.
However, relapse occurred about 4 months later in most patients, along with their antibody titers rising again to pre-treatment levels, and reappearance of enteroviral RNA.
The 2011 article details more of Dr Chia's experiments with interferon: for example: 8 of 14 severely ill ME/CFS patients with enteroviral RNA in their blood returned to part-time or full-time work after interferon-alpha plus interferon-delta combined therapy. Most however relapsed several months later (heavy exertion was a common trigger of relapse).
So we see in these interferon studies a general trend: patients improve or go into full remission as a result of interferon therapy, along with a concomitant reduction in enteroviral load (ie, reduced enterovirus antibody titers and disappearance of enteroviral RNA) while the patients are experiencing major improvements or full remission. Then when the patients relapse, the viral load also goes back up.
However, suggestive though it is, this evidence does not as it stands prove that enterovirus causes ME/CFS, because again, correlation does not imply causation, and there are alternative interpretations.
One alternative interpretation is if we assume ME/CFS is caused by an immune dysfunction or weakness, rather than a virus (let's say the viral infections in ME/CFS just arise from immune weakness, but do not cause ME/CFS): in this scenario, it is conceivable that interferon might rectify the immune dysfunction, and in that way ameliorate ME/CFS symptoms or bring on remission.
In other words, it is a logical possibility that the beneficial effects of interferon for ME/CFS come from its modulation of the immune system, rather than from its antiviral effects in reducing enteroviral load.
Thus the crux of the issue here is trying to determine whether interferon's highly beneficial effects for ME/CFS are the direct result of its antiviral action on enteroviruses, or the result of its immunomodulatory effects (or the result of some other disease-modifying effects interferon may have, that are unrelated to viruses).
If we can prove that the beneficial effects arise from interferon's antiviral action on enteroviruses, then we have more-or-less proven that enteroviruses can cause ME/CFS. So I am now going to attempt to prove this.
The proof starts with a statement made by Dr Chia in his presentation at the Invest in ME 2009 London Conference. At timecode 42:31 of this video, Dr Chia talks about his interferon-alpha + ribavirin combination therapy for enterovirus-associated ME/CFS. Dr Chia says:
Dr Chia is saying that he has found interferon-alpha is ineffective for coxsackievirus B4, ie, that interferon-alpha does not reduce CVB4 viral loads, although interferon is effective for other coxsackieviruses, such as CVB3.
Now Dr Chia has noted that CVB3 and CVB4 are the two most common enteroviruses he finds in ME/CFS patients as active infections (then less frequently, he finds CVB2, EV6, EV7 and EV9 as active infections).
So Dr Chia finds both CVB3 and CVB4 are strongly associated with ME/CFS; yet interferon is effective for fighting CVB3, but not CVB4.
Now comes the logical climax to my proposition that Chia's observations prove enterovirus causes ME/CFS:
If it were the case that interferon ameliorates ME/CFS not by any antiviral mechanism, but through modulating immune function (or via some other disease-modifying mechanism), then you would expect interferon treatment to have the same success rate for all classes of ME/CFS patient, irrespective of what active viral infections the patient has.
In particular, if interferon ameliorates ME/CFS via a non-antiviral mechanism, then you would expect interferon to work equally well for patients with active CVB3 and for patients with active CVB4. And indeed, equally well whether the patient has an enterovirus infection, or an infection with some other virus (or no viral infection at all).
However, Dr Chia found that interferon-alpha works for patients with CVB3, but not for patients with CVB4.
And furthermore, the 1993 study found that by and large, interferon-alpha only worked for patients with enterovirus infections. They found interferon-alpha rarely worked for ME/CFS patients without enterovirus infections.
So these findings clearly contradict the idea that interferon ameliorates ME/CFS by a mechanism unrelated to its antiviral effect. Because where interferon is ineffectual against a particular virus, it does not help ME/CFS patients with that virus.
Therefore we have to accept the explanation that interferon ameliorates ME/CFS via its antiviral action, an action which has been shown to significantly reduce enteroviral loads.
Thus this leads us to the conclusion that chronic active enteroviral infections are a cause of ME/CFS.
Note that in the above, I am not arguing that enterovirus is the only cause of ME/CFS. Other pathogens may well also cause this disease; and there may be non-pathogenic causes as well.
I am just suggesting that the status of enterovirus as merely an association of ME/CFS might be re-examined: I am questioning whether enterovirus can now be upgraded to a probable cause of ME/CFS.
Of course, there could be flaw in my argument. Please point it out if you find one.
Note also that Dr Chia does not use interferon much these days, due I believe to the cost (around $15,000 for a course of treatment), and the fact that relapse is the norm.
Virii and Cancer cells produce Nagalase(research it) - this would cause a self perpetual infection. I believe this is true for EV and has also been mentioned by Dr Chia as one of the reasons oxymatrine only works in 50% of cases.
I never visit these forums anymore. Good luck
