Research papers on type of onset (infectious, gradual etc)?

Simon M

Simon M

Senior Member (Voting Rights)
I am looking for any good data on the different types of onset.

Ideally, this should be from a large, representative sample. I'm pretty sure that no such study exists.

From memory, I think that the Chronic Fatigue Initiative, CFI, did publish something on this, possibly a paper by Dana March. I also thought there was something from the CDC multisite clinic study, with both studies having around 200+ people in them.

I'm not sure if there are any other studies, but I'd love to hear about them.

I'm afraid my memory is rubbish and my googling powers are limited due to migraines, so any help with this will be appreciated. Any discussion of the issue likeweise.

Thanks

Simon
 
Thanks, I really appreciate the information and suggestions.

I think it is amazing, though, that we don't have good data on onset type. It might provide powerful clues, as well as a useful tool for some grouping patients in research studies. Maybe those with an infectious onset are significantly different from those without?
 
Simon M said:
Thanks, I really appreciate the information and suggestions.

I think it is amazing, though, that we don't have good data on onset type. It might provide powerful clues, as well as a useful tool for some grouping patients in research studies. Maybe those with an infectious onset are significantly different from those without?
Click to expand...

It is certainly of interest getting a better handle on the factors associated with onset, and it may be that better studies/surveys will significantly advance our understanding, however it may be that there will always be grey areas.

For example my onset was presumed to be associated with EBV and there was no distinction in my symptoms from the end of the presumed viral infection and the start of my ME. My apparent onset indeed could be pinned down to within an hour, most definitely a sudden onset. However the link to EBV was only established later by the presence of EBV antibodies, that equally could have been due to an early sub clinical infection. So far we have evidence of associations, which are by themselves not sufficient evidence for causation. Conversely we can not rule out that gradual onset or onset related to other causes were not associated with sub clinical viral infections.
 
Simon M said:
Thanks, I really appreciate the information and suggestions.

I think it is amazing, though, that we don't have good data on onset type. It might provide powerful clues, as well as a useful tool for some grouping patients in research studies. Maybe those with an infectious onset are significantly different from those without?
Click to expand...


I wonder how accurate retrospective studies of onset would be? If someone is looking back it is easy to remember a small bug (particularly in the winter). Or in some cases I think people are (very) mildly effected and then something triggers a severe worsening and hence getting a diagnosis.

In the case of the UK I suspect there would be little evidence around what particular virus someone had that may trigger ME as I don't think that would be tested (but most people have EBV and CMV antibodies).

I wonder if an alternative is to look at previlence after a rise in particular viruses and I think there was some work in Spain and/or Norway that looked at this. Something looking at number of new diagnoses after a wide spread virus hence may suggest something about viral triggers (both when raised and when not) but it wouldn't say anything about gradual onset.
 
My mother developed it after a biphasic infection which she appeared to have caught from her friend who was very unwell and in bed. I was also infected but recovered normally. In the following years I began to have PEM episodes.

I'm not sure that the infection is of great importance. My mother already had health problems before that and we have symptoms in common. The infection may have made an already existing problem much worse.
 
Adrian said:
I think there was some work in Spain and/or Norway that looked at this. Something looking at number of new diagnoses after a wide spread virus hence may suggest something about viral triggers (both when raised and when not)
Click to expand...
There was a big Q-fever outbreak in the Netherlands and a Giardiasis outbreak in Norway which were investigated. In both cases there was an increased incidence of ME/CFS or ME/CFS-like symptoms.
 
Agree, this is a big hole in the ME/CFS research. I have often found myself scouring papers for this and exasperated when the information just isn't there.

Chu's paper that @Michiel Tack quoted above is helpful for pointing to relevant papers.

It might be worth contacting Leonard Jason as his team seem to have a nice big dataset from the US, UK and Norway.

Table 3 in Pendergrast et al's 2016 paper is interesting. The data is divided into housebound vs not housebound. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464362/

Sorry I don't know how to copy the table in here - would be grateful if someone could tell me for future!

Here's the text version:

Table 3. Illness experience of housebound (H) and not housebound (NH) patients.
H NH
N¼125 N¼411
N (%) N (%) Sig.
Illness began after
Infectious illness 95 (76.0) 272 (66.2) *
An accident 6 (4.8) 22 (5.4)
A trip or vacation 9 (7.2) 28 (6.8)
An immunization 17 (13.6) 41 (9.9)
Surgery 18 (14.4) 41 (9.9)
Severe stress 33 (26.4) 158 (38.4) *
Other 36 (28.8) 95 (23.1)
Illness developed
Rapidly (<1 month) 53 (42.4) 135 (32.9)
Gradually (<1 year) 28 (22.4) 115 (27.9)
Slowly (>1 year) 41 (31.8) 151 (36.7)
 
Adrian said:
I wonder how accurate retrospective studies of onset would be? If someone is looking back it is easy to remember a small bug (particularly in the winter). Or in some cases I think people are (very) mildly effected and then something triggers a severe worsening and hence getting a diagnosis.

In the case of the UK I suspect there would be little evidence around what particular virus someone had that may trigger ME as I don't think that would be tested (but most people have EBV and CMV antibodies).

I... looking at number of new diagnoses after a wide spread virus hence may suggest something about viral triggers..
Click to expand...
Peter Trewhitt said:
For example my onset was presumed to be associated with EBV and there was no distinction in my symptoms from the end of the presumed viral infection and the start of my ME. My apparent onset indeed could be pinned down to within an hour, most definitely a sudden onset. However the link to EBV was only established later by the presence of EBV antibodies, that equally could have been due to an early sub clinical infection. So far we have evidence of associations, which are by themselves not sufficient evidence for causation. Conversely we can not rule out that gradual onset or onset related to other causes were not associated with sub clinical viral infections.
Click to expand...

There is definitely a danger of some recall bias, however, in the case of ME/CFS, I do think we can learn a lot from these studies, for two reasons:
1. There is a proven causal link to CFS after a range of laboratory-proven infections. Dubbo looked at Ross River virus, Q fever and infectious mononucleosis. There's a good Peter White study on infectious mononucleosis alone (the lab test for mono does look for active infection, not just the presence of EBV antibodies). Plus the Norwegian giardia and Dutch Q fever studies already mentioned. Very likely, Covid 19 will be added to the list.
2. ME is a life-changing event and many people, myself included, had a bad infection at the start. That's not something that you recall later and make a false connection. It's something that slaps you in the face at the time.

strategist said:
I'm not sure that the infection is of great importance. My mother already had health problems before that and we have symptoms in common. The infection may have made an already existing problem much worse.
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However, this is also an important issue, particularly given Adrian's point about winter infections. There may be a trivial, unimportant associations that cloud the data.

Decodeme is planning to ask people a) if they have an infection and b) if it is lab confirmed (Covid, glandular fever, other). So there will be some data on this and the ability to compare lab confirmed with more general infectious onset.


Be very interested to know if Solve our collecting such data: they have more extensive surveys and Beeld explore the issue in more detail.

Michiel Tack said:
There are some additional references in the 2018 S4ME thread: https://www.s4me.info/threads/who-said-80-of-me-is-post-infectious.7320/#post-130742
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thanks again to everyone who has commented here. There is definitely a project here, compiling all the onset data. I think it would be very valuable and I'd love to do it myself, but am, unfortunately, much to ill.
 
Infectious mononucleosis: the Dubbo study and "Risks for Developing ME/CFS in College Students Following Infectious Mononucleosis: A Prospective Cohort Study, 2020, Jason et al"

H1N1 (in Norway): Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine

Data on gradual onset can likely be found in older papers by psychological/psychiatric research groups, but the samples would be contaminated by the use of loose diagnostic criteria (Oxford, Fukuda).
 
Simon M said:
2. ME is a life-changing event and many people, myself included, had a bad infection at the start. That's not something that you recall later and make a false connection. It's something that slaps you in the face at the time.
Click to expand...

I think here there may be a sudden vs gradual onset here. Clearly where onset is severe that probably isn't subject to recall bias issues. But I think there are a proportion of PwME (unknown size) who start off really mild and then something happens and the deteriate or deteriate gradually and here recall is much more difficult (which is the point I was trying to make). In some cases the 'something happens and the deteriate' event could be seen as the trigger.
 
Adrian said:
I think here there may be a sudden vs gradual onset here. Clearly where onset is severe that probably isn't subject to recall bias issues. But I think there are a proportion of PwME (unknown size) who start off really mild and then something happens and the deteriate or deteriate gradually and here recall is much more difficult (which is the point I was trying to make). In some cases the 'something happens and the deteriate' event could be seen as the trigger.
Click to expand...
That's a good point. What we really need are two questions:
— sudden (needs defining) versus gradual onset
— specific triggers: infectious and others.

Sudden onset and specific triggers are likely to give the most reliable data. I'm not sure how you would investigate triggers of gradual onset where it is likely to be harder for people to be clear what exactly it is that was the trigger and there is a danger recall bias.
 
Simon M said:
There may be a trivial, unimportant associations that cloud the data.
Click to expand...

I agree about the unimportant etc associations. Also, my observation in Facebook groups: EBV seems to be such a well-known trigger that a lot of people associate it with their disease, either based on the fact that they have antibodies (which I think most adults have) or that they had mononucleosis at some point but much earlier. For example I remember someone who said her mononucleosis 8 years before the onset of her ME/CFS was the trigger. I think this also complicates things.
 
Simon M said:
Thanks, I really appreciate the information and suggestions.

I think it is amazing, though, that we don't have good data on onset type. It might provide powerful clues, as well as a useful tool for some grouping patients in research studies. Maybe those with an infectious onset are significantly different from those without?
Click to expand...
What about those with two or more possibilities such as my wife? Infection during post-op recovery. Possibly less unusual than people might think. Although there may have been something going on before that, because bike balance had become a bit flaky.
 
It's very difficult to make a clear set of questions gathering onset information that work for everyone.

I agree that there needs to be multiple options - in my case, the onset when I was in my 40s involved an infectious illness, which was probably the main thing. But there was also possibly heat exposure (extended heatwave in a house with no air conditioning) while indoors with no ventilation with a container load of furniture and boxes that had been fumigated with methyl bromide (and, for good measure, was full of visible mildew, having been stored for some months in a tropical country). All in the same few weeks.

I've just completed Solve's survey and I found it very difficult to fit my experience into the boxes. In my case, I was diagnosed with ME when I was 10, I was sick for a year. I recovered and seemed perfectly well until my 40s. If I answered the questions with the childhood onset in mind, it would make it seem as though I have had ME/CFS when I was 10, and I can't recall a specific trigger, although there may well have been. Probably not many people will have my particular issue of two clear onsets, but they may well have other quirks that make answering a survey with rigid expectations of how the disease works very difficult.

If you are making a survey @Simon M, I think it's good if it is very robust, with questions able to stand alone where possible. For example, questions of 'is the onset of your ME/CFS best-described as gradual or well-defined?' 'what age(s) did your ME/CFS or relapse after a long period of wellness begin?', 'what cause(s) triggered your ME/CFS onset or major relapse?', each with multiple responses possible. If there are strings of questions that you can only access by giving a required answer on the first question, an inability to fit neatly in the box can result in the loss of useful information from subsequent questions.

Simon, if you are working on the DecodeME survey, I suggest you register with Solve and do their survey. I'm sure it would give you ideas about what works and what doesn't.
 
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