Let's start by questioning your assumptions:
1) I don't think it's just been the last fifty years. Yes, there was a noted global pandemic in the 1980s, but there also was one in the 1950s as well that was arguably worse.
2) I don't think they are more prone to get it, they are more prone to not recover. In several outbreaks, the strike ratio was 1:1, but it was noted that the ratio rises to 5:1 over time.
3) This does seem to be true in many cases.
4) The evidence for this is extremely limited and what exists is not very convincing for these agents as a cause of literal ME. Do they both cause a prolonged fatigue syndrome consistent with CFS? Most likely. Is this the same exact thing as ME? Unlikely, I think.
Think of the bullet point list as "what any ME/CFS hypothesis must seek to explain". Whether that be a hypothesis focusing on methylation or XMRV or HPA axis or whatever. Take the XMRV hypothesis for example. It would be a strech to say why such an hypothesis could explain all the four points.
Don't put too much emphasis on fifty years. It said fifty years or so. So where I was going was "more prevelant now than long ago". If you have a suggestion for an alternative phrasing, then let me know. Here are some:
"Why we now have many more new incidences than decades ago"
"Why we have many more incidences in our time than a century ago"
If you have hard statistics on this, then that would be the best. (The prevalence increases when patients add up, so it's really incidence that's interesting.)
I've now changed point 2 to "Why ME/CFS affects more women than men".
Like I wrote earlier, my impression is that the majority of ME/CFS patients haven't been sick following some specific outbreak. Correct me if I am wrong. By far the most common trigger of ME/CFS seems to be mononucleosis, which is more of a regular thing.
Yes, there is scant data on how Giardia can trigger ME/CFS. But I see the data we have as sound. I have seen the patients that were ill following the outbreak on the news, in the living room of one of them. Everything that were told about the symptoms seemed like a textbook case of ME/CFS.
Here's a study on it. Although it's a rare way to get ME/CFS, I think such cases offers a key to understanding the disease.
This is a side note. But I think of it just like
these incidences. Almost no one who have narcolepsy get it following a vaccine. But the fact that it's happened gives us a clue to understanding narcolepsy, which is also a disease where causal mechanisms are unknown. What I am saying is that case reports can give insight.
redo said:
The common denominator of giardiasis and mononucleosis is that they get the immune system going. Could it be that small "triggers" kick-starts an immune reaction that never stops?
I don't think so, no. Why is it that the various cold viruses, influenza, etc. have never been convincingly linked to ME or CFS then? The immune cascade requires constant antigen stimulation to keep going (and even then, there are built in feedback mechanisms to stop a runaway reaction.) So far, ME and CFS have only been linked with pathogens that can persist indefinitely in the body or GI tract.
Generally, if we assume these diseases are caused by persistent immune stimulation, then it isn't surprising that there will also be increased histamine release as the cells that release it will also be recruited by the immune response and take part in it. I also think a major part of it is caused by persistent increased sympathetic autonomic outflow. This is either a result of dysautonomia caused by damage or dysfunction in the brain, or as a normal response to infection, or both.
I don't think long term high doses of antihistamines is a safe route to take. You're not getting at the root cause and you might also be making the original problem worse in the long run due to the anticholingeric effects of most antihistamines. People like Michael VanElzakker recommend against it, see this thread:
I have changed my original post now, so now it reads:
"The common denominator of extreme stress, giardiasis and mononucleosis is that they all affect our immune system. Could it be that such "triggers" kick-start an immune reaction that never stops?"
So, these are vastly different triggers, and I am hard pressed to find another common denominator of extreme stress, giardiasis and mononucleosis than having "an effect on the immune system". I'm not sure whether there is sound data to back up the claim that extreme stress can trigger ME/CFS, but I've seen it mentioned many times and take it in good faith.
You raise a good question, writing "Why is it that the various cold viruses, influenza, etc. have never been convincingly linked to ME or CFS then?" What I think is that mononucleosis is especially good at causing ME/CFS, and with regards to other triggers they only cause it rarely. So rarely that there aren't epidemiological studies, but rather just case reports. That doesn't mean that case reports are invalid, or that other things can't trigger ME/CFS.
To your last point, "I don't think long term high doses of antihistamines is a safe route to take". Well neither do I, and I don't propose it. I am curious about Xolair though, especially since there are ME/CFS patients writing about how it changed their life.