Question: what do you think is a reasonable time that passes between an infection and ME/CFS onset?

[Wyva]

Discussion moved from
ME Epidemiology - prevalence, peak ages of onset and gender ratio

Question: what do you think is a reasonable time that passes between an infection and ME/CFS onset?

For some people the ME/CFS symptoms don't start straight away after an infection and there seems to be a delay, a few weeks or months. I think this is also acknowledged in connection with long covid. Recently there was someone in my group who had covid and then started to have ME/CFS-like symptoms 9 months later. She got a long covid diagnosis but she wasn't really convinced because of the long time that passed since the infection.

So that got me wondering about this. I know there are no real answers I'm just curious what everyone thinks.

 

[Florence]

Question: what do you think is a reasonable time that passes between an infection and ME/CFS onset?

I think this is an interesting question.

My own experience could be regarded as immediate or delayed onset post viral infection, depending on how you view things.

Both prior to original ME onset, and then when I dropped down to a more severe level of ME seventeen years later, I experienced three or four fairly severe viral infections in relatively quick succession. Each time I would slowly and laboriously recover from the infection over a period of weeks or months and return to my original level of functioning, until the final infection, when I failed to recover. So if the 'original' virus is regarded as the trigger, then onset is delayed, and if the final one is viewed as such, then onset is immediate.

 

[Trish]

I think if someone has been completely well for many months after an infection, then gets ME symptoms, there is no way at the moment of knowing whther there is any connection between them, and it seems unlikely to me that there would be such a long delay, though the Covid could be one of a series of factors that cumulatively lead to ME perhaps.

 

[Midnattsol]

I think if someone has been completely well for many months after an infection, then gets ME symptoms, there is no way at the moment of knowing whther there is any connection between them, and it seems unlikely to me that there would be such a long delay, though the Covid could be one of a series of factors that cumulatively lead to ME perhaps.

As has been discussed on here before, those of us with a gradual onset might have had something going on in our bodies in advance of symptoms occuring. Maybe an infection weeks/months prior started it all, and it took a while for the cummulative effects of activity to show? It's difficult to know what is meant by "completely well" also, just look at the number of people who have "recovered" but are still very much limited in their daily life.

 

[Milo]

I think if someone has been completely well for many months after an infection, then gets ME symptoms, there is no way at the moment of knowing whther there is any connection between them, and it seems unlikely to me that there would be such a long delay, though the Covid could be one of a series of factors that cumulatively lead to ME perhaps.

It may have been my experience, but who knows for sure? The year I got sick, I went on a trip to Mexico and I got violently ill (GI) for 48 hours. That was January. In the months following, I started gaining weight and had energy issues (Had to lay down at lunch time at work)- Then in the fall I got a saliva exposure and got EBV. That was November. I was too sick (exhaustion) to return to work and then I developed a necrotic gallbladder and large ovarian cyst- It was during the surgery recovery that I started developing OI, then POTS, than heat intolerance, then depth perception issues, and so on. So in retrospect there were multiple hits.

Note: I consider myself being a sudden onset from the EBV infection, because that's how everything started.

 

[duncan]

Delayed onset may ultimately reduce down to delayed onset of ME/CFS symptoms - not necessarily delayed onset of disease or infection.

Two broad examples that come to mind are asymptomatic disease and relapsing remitting disease.

Also, now that I think about it, "packaged" diseases that sometimes come from vectors could explain a subset of delayed onset ME/CFS.

 

[Peter T]

For me there was no gap at all between the ending of the trigger infection(s) and the onset of my ME.

My initial onset was associated with an active EBV infection, but subjectively I had no clear point where I could say that the glandular fever (mononucleosis) ended and the ME began, the same symptoms continued through both.

Over a number of years I gradually improved and I did believe myself recovered, however I then had a bad dose of influenza (virus not formally confirmed/identified) which was associated with an immediate reappearance of my previous ME symptoms, so again it was not subjectively possible to say where my bout of flue ended and my ME relapse began.

Though obviously I can not be certain that the EBV caused my ME I am quite ready to believe that was the case, however given over my life pre ME I had had several bouts of flue, I must have after the EBV been primed in some way such that this particular bout was able to trigger my second onset/relapse.

Presumably the longer the gap between a proposed trigger infection and the apparent ME onset the harder it is to assume a causal relationship, however it is still possible that the initial virus primed in some way the person to subsequently develop full blown ME, though presumably in response to a further trigger of some sort. However, I have no sense of what that further trigger might be, unless when we understand the underlying biological mechanism, the idea of a non symptomatic stage of ME emerges, with the delayed onset being in fact being the cumulative effect of the person’s activity, so the delayed onset is in fact the first experience of PEM.

 

[LarsSG]

My own experience suggests a long delay between some event, probably an infection, and becoming significantly ill. As a teenager, there was something off for about a year before I suddenly became ill. Basically, it felt like I had recurring colds plus very mild PEM (I could do fine in a cross-country ski race one day and then I performed poorly and felt weak in a race a day or two later). This condition worsened over the year, then I suddenly became quite ill after a major exertion.

Then after significant recovery and many years of very mild symptoms (so mild that I sometimes didn't even think I had ME anymore, though I would now say I definitely did), I suddenly felt a familiar kind of weakness while out for a bike ride. From then, it took three months or so of gradual decline before I became significantly ill again. I think this decline was triggered by an infection because two of my siblings who were with me at the time also developed ME within about six months.

It's only in retrospect that this is all clear to me.

 

[Jonathan Edwards]

I think there are two different questions here.

One is what is a plausible lag period for an environmentally triggered condition.
The other is what lag period for an individual is likely to be more than coincidence.

Most diseases triggered by environmental agents (assuming brief exposure) come on within about three weeks. Not all, but the majority do. On the other hand for some of these the presentation of symptoms can be very delayed. So for rheumatic fever cardiac symptoms may come on thirty years after the infection, owing to long term scarring and stenosis of a mitral valve.

What may help the analysis is that by and large time frames tend to be characteristic. So even if rheumatic mitral valve disease has a long lag phase, Reiter's syndrome seems to have a very standard lag phase of no more than three weeks.

So if we accept that ME/CFS is quite often triggered with a brief lag phase - either just never feeling better after an infection or maybe feeling a bit better briefly but crashing within a fortnight - then it is pretty likely that this is the norm for ME/CFS. A lag of nine months then seems unlikely to be significant. So my intuition is that it is reasonable to link ME/CFS to an infection if the lag is three weeks or less but beyond that becomes increasingly uncertain.

I also think one would take into account whether or not the infection was a recognised common trigger. Illness following severe EBV infection would be more plausibly linked if a month later than illness following flu or food poisoning.

 

[hibiscuswahine]

I think there are many pwME/CFS who can’t recall a definite precipitant or have delayed onset and is the result of a multitude of unknown but suspected vulnerabilities outside the classic infectious onset

So from my clinical perspective, I would include any anaesthetics, history of brain injury/insult at any age, including antenatal (and that can be tricky if carers not alive/available to question or person has difficult recall), family history of ME-like illnesses (genetic vulnerability) etc. I would also be interested to know if they have any significant insults to brain development in childhood/adolescence. Because it might be in the brain and it might be inflammatory, endothelial, mitochondrial, peripheral neurological etc etc or might be all of them or a combination or something else medical science hasn’t discovered.

In the end, if they have the symptoms and duration matching the criteria for ME/CFS and other medical diagnoses excluded, they have the diagnosis until proven otherwise.

 

[Sean]

Delayed onset may ultimately reduce down to delayed onset of ME/CFS symptoms - not necessarily delayed onset of disease or infection.

Indeed. There is an important distinction between a disease process being in place and active, and it reaching the level of sufficient harm or consequences where the symptoms become expressed at a clinical level.

I have osteoarthritis, currently with a moderate level of symptom expression, mainly in the hands and hips at this stage. But the symptoms did not suddenly appear one day, they gradually came on, becoming more obvious and definite over time. Clearly the disease process was active at least some time before the symptoms became noticeable.

Other examples include post-polio syndrome and variant CJD, both of which can take decades to start reaching the clinical level of expression.

 

[Hutan]

Yes, re a threshold that might be crossed to reach a clinically observable level.

For example, if ME/CFS operated like my idea of how ciguatera poisoning works, or some other neurotoxins might work, then a single exposure can be enough to cause acute disease and subsequently some people have ongoing symptoms. A smaller proportion of these never stop having the symptoms.

But, it's also possible to have disease as a result of multiple low level exposures.

What seems to be happening is the neurotoxin is locking onto a receptor, inactivating a process. Over time, the neurotoxin molecules might be displaced. But, if there is a lot of neurotoxin all at once, or further exposures to the toxin, and/or perhaps some people are less efficient or incapable of clearing the toxin, and/or the body's demand for the biological process that is crippled increases, then the threshold is reached, and symptoms are experienced.

 

[duncan]

So if we accept that ME/CFS is quite often triggered with a brief lag phase - either just never feeling better after an infection or maybe feeling a bit better briefly but crashing within a fortnight - then it is pretty likely that this is the norm for ME/CFS.

Yes, but ME/CFS is quite often triggered after an elongated lag phase, so then by your logic it is pretty likely that this is the norm for ME/CFS.

A lag of nine months then seems unlikely to be significant.

On the contrary, I think it can be telling and help with the diagnosis, that is, help determine which infection brought on ME/CFS. I think this will prove to be even more so the case as our diagnostics improve, and perhaps will assist in distinguishing subsets.

So my intuition is that it is reasonable to link ME/CFS to an infection if the lag is three weeks or less but beyond that becomes increasingly uncertain.

Perhaps if you widened the net?

I also think one would take into account whether or not the infection was a recognised common trigger. Illness following severe EBV infection would be more plausibly linked if a month later than illness following flu or food poisoning.

Well, okay, sure. That's all very neat, but I worry it threatens to pre-emptively shut out too many additional pathogens and contributors that don't conform to the Wham-Bam subset. Perhaps even worse, today, after 40+ years of ME/CFS "research", saying something is a "recognised common trigger" is not saying much at all since we haven't really looked closely at a lot of possible triggers in any meaningful, controlled fashion.

ME/CFS presents with all sorts of peculiararities. It is a pain in that just when I think I've got it characterized, something fractures that confidence.

 

[Mij]

Question: what do you think is a reasonable time that passes between an infection and ME/CFS onset?

Sudden viral onset-->6 months was able to go to school and do some exercise (no PEM) but losing stamina-->'recovered' after 3 months, went back to work-->relapsed less than one month later--> was still able to do some light exercise without delayed typical PEM.

My guess is that M.E was already in the cards even before delayed PEM onset. I started running again to find that out 6-7 years later

 

[LarsSG]

There seem to be quite a few people who describe a series of colds or other infections or a period of poor health before they become seriously ill. I don't think it is unreasonable to say that maybe people can have ME very mildly and then get significantly worse. In that case, the trigger (either infectious or otherwise) could be a long time before they become ill enough to seek medical attention or even believe themselves to have ME. It could be that the initial trigger causes very mild ME that then resolves or gets worse due to some factors we don't understand or it could be that a mild ME state can be worsened by repeated infection or other triggers.

We just don't know much except that there is clearly some kind of infectious trigger in a significant number of cases. There are definitely people reporting onset of LC symptoms delayed by months. It seems premature at this point to rule anything out.

 

[Jonathan Edwards]

Yes, but ME/CFS is quite often triggered after an elongated lag phase, so then by your logic it is pretty likely that this is the norm for ME/CFS.

What evidence do we have for that?
We don't know what triggers any individual case.

Perhaps if you widened the net?

I am not sure what you mean by that. I am talking about a probabilistic analysis of how confident one might be that an environmental event was relevant.


I think an important point to make here is that there does not need to be any triggering environmental event. The popular idea that disease is caused by a combination of genetics and environment is wrong and the epidemiology textbooks say so. The psychologists assume that one can track some environmental event but there is no basis for thinking that. Biological systems are inherently unstable and events that initiate disease can be largely random and internal. Lymphoma is the obvious example.

That's all very neat, but I worry it threatens to pre-emptively shut out too many additional pathogens and contributors that don't conform to the Wham-Bam subset.

Yes, I know you have a penchant for there being a hidden infection but I am shutting out nothing here, just working on the basis of reasonable probabilities. If there was a hidden infection it ought to have some form of epidemiological signature that would have showed itself by now.

 

[duncan]

Yes, I know you have a penchant for there being a hidden infection but I am shutting out nothing here, just working on the basis of reasonable probabilities. If there was a hidden infection it ought to have some form of epidemiological signature that would have showed itself by now.

Infectious diseases have an entire discipline dedicated to them for a reason - and still they proliferate. Many of them - many - have little in the way of a signature, and many have no way of diagnosing them serologically. There arguably may be a clinical signature, but who are we kidding? This generation of clinicians is as inept at diagnostics are they are at pharmacology, and it cannot help that they too often are working with the additional handicaps of medical politics and ludicrously flawed definitions.

I wish it were not so, but I fear you are overreaching when you suggest there should be some sort of epidemiological signature by now.

 

[NelliePledge]

There seem to be quite a few people who describe a series of colds or other infections or a period of poor health before they become seriously ill. I don't think it is unreasonable to say that maybe people can have ME very mildly and then get significantly worse. In that case, the trigger (either infectious or otherwise) could be a long time before they become ill enough to seek medical attention or even believe themselves to have ME. It could be that the initial trigger causes very mild ME that then resolves or gets worse due to some factors we don't understand or it could be that a mild ME state can be worsened by repeated infection or other triggers.

We just don't know much except that there is clearly some kind of infectious trigger in a significant number of cases. There are definitely people reporting onset of LC symptoms delayed by months. It seems premature at this point to rule anything out.

At least 10 years in my case

 

[RedFox]

I think if someone has been completely well for many months after an infection, then gets ME symptoms, there is no way at the moment of knowing whther there is any connection between them, and it seems unlikely to me that there would be such a long delay, though the Covid could be one of a series of factors that cumulatively lead to ME perhaps.

Perhaps prior infections could set someone up for getting ME later. I consider it a highly speculative possibility that Lyme disease may have led to me ME years later. This wasn't a typical case of Lyme--I ended up with permanent neurological sequelae.

Treatment was months delayed because I had a confusing presentation. I had no bullseye rash, and all the other symptoms occurred one by one instead of together. Eventually it progressed to neurological manifestations. I got allodynia all over my upper body to the extent that riding in the car was painful. (That went away fortunately) I finally got diagnosed and started antibiotics when I got Bell's Palsy, sudden-onset one-sided facial paralysis triggered by inflammation of the facial nerve. It healed but now the right side of my face is slightly weaker and I have slight synkinesis. (For example, my eye twitches slightly as I talk.)

 

[Mithriel]

We are having to reconsider disease caused by parasites. The insights into infectious disease from nineteenth and early twentieth century researchers were stunning and led to a miraculous release from the burden of infections - to the extent that people have forgotten how devastating they can be so are easily persuaded that covid is nothing much.

As modern techniques were developed research into microbes fell out of favour but covid has changed that. It should be no surprise that biology is not as simple as we believed. The more we discover the more complexity we find.

Covid has been found in lots of tissues months after infection, even in people who feel completely recovered. It makes sense when you think about it. The immune system works really well at making us better but missing a few viruses here and there is not a problem. If they multiply enough to become a threat, the immune system will flare up again and get rid of most of them again. Maybe the third cold you get one winter is actually a flare up of the first! It makes sense from an evolutionary viewpoint. 100% efficiency is not needed to prevent death.

This is all just speculation, but there are already cases. The chickenpox virus persists for decades until it returns as shingles. Herpes retreats and evades the immune system until it appears as another cold sore then it gets chased back like a Russian plane over Britain in the 80s.

HIV infection could not even be detected for 6 months and only starts causing disease years later. Syphilis has different characteristic diseases over a lifetime of infection. These have been discovered because of research but how do we know that MUS is not caused by other microbes which have ways of evading the immune system?

Enteroviruses have a very complicated mechanism for avoiding the immune system so it makes no sense if they do not use it to persist in the system. If covid can do it can other corona viruses? If they had used all the money given to psychological research into looking at viruses we might have had answers by now.
Every virus that lives in the body gets on with its life there and if that life makes our bodies work less efficiently we will have low grade ill health.

Then again, even viruses which are eliminated can leave permanent damage behind. More species attack the immune system than we thought. leaving us susceptible to other invaders. Every advance in knowledge of the genetic systems opens another realm of complexity so I doubt disease biology is any simpler.

A delay of a few months or years from initial infection to ME is very possible from what we already know about biology.

One of the failings of science is how often they say "This is not possible". I have watched that be wrong all my life. There will always be more to learn and it will all seem obvious when we know.