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Surprisingly good outcomes for people who get ME/CFS after Mononucleosis (Glandular Fever)

Discussion in 'Phoenix Rising Articles' started by Simon, Jan 20, 2015.

  1. Simon


    Monmouth, UK
    Simon submitted a new blog post:

    Surprisingly good outcomes for people who get ME/CFS after Mononucleosis (Glandular Fever)

    Sometimes ME/CFS emerges after mononucleosis, or glandular fever. Simon McGrath shares results from a long-term follow-up study from Haukeland University Hospital in Norway...

    "When will this end?" It's a question that most ME/CFS patients have probably asked themselves and their doctor many times. I certainly have.

    Yet there is astonishingly little hard data on recovery rates from this illness or on how much patients improve, and the evidence there is doesn't give too much hope.

    Step forward a long-term follow-up study that shows unexpectedly good rates of improvement for younger people who developed ME/CFS after infectious mononucleosis (glandular fever) – though the results are hardly spectacular.

    Around 11 years on from getting sick, just over half of all ME/CFS patients were able to work part or full-time, though fatigue levels remained high:

    The study was led by Dr. Morten Nyland and comes from the Neurology department of Haukeland University Hospital in Norway, site of the famed Rituximab pilot study. In fact two of the authors of this new paper were part of that pilot study. And although this wasn't a trial, patients were encouraged to use self-management (pacing/activity management), and the authors concluded that this probably contributed to the relatively good outcomes.

    How the study worked (important)

    An ideal study would take a bunch of patients and follow them at consistent time points, say the start of the illness, and then five and 10 years later. In this case, though, researchers made the most of pre-existing data to access a large group of patients who were followed up at very different times in their illness, an approach using two contact points that still yields invaluable results.

    "Contact 1" was the first time the patient was seen by the specialist ME/CFS clinic at Haukeland University Hospital, any time between 1996 and 2006.

    "Contact 2" was a follow-up questionnaire sent to all patiets in 2009, an average of 6.5 years later. There was huge variation in follow-up time between patients, for example at the second and final contact in 2009 one patient had been ill for 24 years and another only five years. The study had data at both contact points for 92 patients, making this one of the largest follow-up studies going.

    At the initial contact, patients had been ill for an average of nearly five years, and again that hides a lot of variation. Half had been ill for 3.2 years or less, a quarter for under two years. The higher average was because some had been ill for a very long time. The patients were also relatively young (the average age was 24 years), reflecting the age profile of infectious mononucleosis, the 'kissing disease', which particularly affects young adults and teens.

    Over half of all patients were employed at final contact

    Pleasingly, the study used employment status as the clear-cut, objective primary outcome -- and arguably the ability to earn a living is the outcome that matters most to patients. The graph below shows a lot of improvement between first and second contact, which an average gap of six years, though the gap will vary a lot between patients.

    Unemployment is in red while employment (full-time or part-time) or being a student is in green. Onset is when they got ill, Contact 1 is typically five years later, and Contact 2 typically another six years on.

    Clearly things have improved for many patients, but the overall situation at Contact 2 remains a great deal worse than onset.
    Note that half of those employed at Contact 2 were working full-time, compared with only 1 in 10 at Contact 1, so presumably there has been an increase in hours worked per person, as well as more people working.

    Caution: It's possible that 11 years from onset (age 35 vs. age 24 at onset) some people would not be working anyway due to raising families so unemployment might not be zero even for a healthy group. And employment at onset wasn't split into full-time/part-time.

    How patients said their overall health had changed

    The study also asked patients how their overall health had changed since Contact 1 (their first visit to the clinic). Most patients said they had improved, 12% reported they had got worse.


    Fatigue was also rated at both Contact 1 and Contact 2 using the Fatigue Severity Scale which gives an average score ranging from 1.0 (no fatigue) to 7.0 (maximum fatigue); any score of 5.0 or higher counts as severe fatigue. The average score at Contact 1 was 6.4, falling to 5.0 at Contact 2 -- so even after this improvement the group as a whole was right on the threshold of severe fatigue.

    Different degrees of improvement

    The study measured 'improvement' in several different ways. As well as change in employment status, they looked at self-rated improvement (including an option of 'recovered') and change in fatigue scores.

    You can see that 'improvement' ranged from 70% reporting any improvement, to 32% moving into employment, and 13% who rated themselves as recovered.

    Most people improved, even those who hadn't improved at Contact 1.

    Another encouraging point was that of the 26 people who said they had already improved at Contact 1, 25 improved again by Contact 2. And of the 38 who reported they hadn't improved before, 25 (66%) improved by Contact 2.

    Fatigue improved much less than employment status

    One slightly strange finding, which the authors didn't comment on, is that average fatigue levels fall rather modestly compared with the percentage improving in employment status. While 32% of patients were able to start working, fatigue scores only fell from 6.4 to 5.0.

    It seems likely that this in part is down to people getting back to work but still struggling, so that their level of fatigue doesn't improve as much as it might.

    Interestingly, although 28% were working full-time only 13% rated themselves as 'recovered', which supports the view that some people are improving and choosing to work full-time despite not being completely well, and may still be struggling quite a lot.

    What 'predicts' return to work/improvement over time? (not a lot)

    Overall, this important new study shows that outcomes for younger people who develop ME/CFS after mono are not great, but are probably better than expected. Around half were in work 11 years after onset, though fatigue remains high for most.

    What might be driving this improvement? The authors ran some fancy analysis to see what features (such as symptoms and age) predicted being in employment or an improved fatigue score at the final contact. It turned out that only lower joint pain at Contact 1 was associated with later employment, but the effect was small.

    Similarly, low joint pain and depression at Contact 1, and better eduction, were predictors of less fatigue at Contact 2 -- but again the effect was small.

    Surprisingly, length of illness was not an important predictor of employment or fatigue. Generally those with shorter illnesses are seen as having a better chance of recovery, but that doesn't appear to have been the case here.

    It's possible that outcomes for ME/CFS after mono are better than after other triggers. I'll give the last word to the authors themselves, who suggest that both pacing/activity management and financial support through sickness benefits were likely to have played an important role to improvements:

    "Self-management strategies, long-term sickness absence benefits providing a stable financial support, in addition to occupational interventions aimed at return to work were likely contributors to the generally positive, prolonged outcome."
    Simon McGrath tweets on ME/CFS research

    Phoenix Rising thread discussing this paper, including the more detailed post that led to this blog.

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    Continue reading the Original Blog Post

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    Last edited: Jan 25, 2015
    MeSci, Sean, Valentijn and 8 others like this.
  2. Marco

    Marco Grrrrrrr!

    Near Cognac, France
    Very interesting study and report Simon. Lots to dig into.
  3. Woolie

    Woolie Senior Member

    @Gingergrrl, did you see this?



    The average age of patients was 24, but this is hardly surprising, as most people get mono in their early tens or twenties.

    An important outcome of this study - where strict criteria were used to diagnose ME - is that full recovery does NOT mean you didn't have real ME in the first place!
    zzz likes this.
  4. Gingergrrl

    Gingergrrl Senior Member

    @Woolie I am taking a brief break from posting on PR (b/c I am so overwhelmed with other things I am needing to do) but felt I needed to respond to this and really appreciate you pointing it out to me. I do have a few questions in case you or @Simon know the answer.

    1) It says that the average age of patients was 24 when they got mono so wouldn't they have a greater chance of recovery than someone like myself who got severe mono at age 41?

    2) Did it specify if they all had mono from EBV? I know EBV is the most common cause of mono but that there are also a few other viruses that can lead to mono.

    3) Did all of these patients go directly from mono to ME/CFS with no recovery in between? I recovered from mono (and continued to work full-time and got married) but had a new infection or a viral activation of EBV ten months later from which I never recovered and now am very severely affected and basically housebound. So am I sort of in a weird outlier group?
    MeSci likes this.
  5. Esther12

    Esther12 Senior Member

    Ta Simon. Also, I can't remember if I said this in the thread where we discussed this study, but it is good to take the time to comment positively on studies that get important things right. So many papers are so poor that I can slip into only reading papers to find problems, quoting and commenting on only the things that piss me off.
    MeSci likes this.
  6. heapsreal

    heapsreal iherb 10% discount code OPA989,

    australia (brisbane)

    Im in your weird group, 31 when i got mono from both cmv and ebv as well as chickenpox(which i had as a kid). I initially had igg life long antibodies to ebv near the start of cfs but now dont have these?? so if i was tested for ebv now at 44, i would test negative? I think mono reactivation is alot more common than its realised. Theres something suppressing our immune systems??
    zzz, August59 and Gingergrrl like this.
  7. Woolie

    Woolie Senior Member

    Hi @Gingergrrl,

    The average age of the people at CFS onset was 24, but there seems to have been quite a range (looks like the range could be at least 17-31, just from the standard deviation). They did look at whether age at onset affect outcomes on a fatigue scale, and it didn't. Not at all. Not even a trend in that direction.

    It just chose people based on "physician report" of mono. Prof Edwards seems to think some doctors will diagnose mono without any EBV-positive testing, but I don't know how common that is. Without the confirmatory bloods, the doctors I've met would just send you home with a diagnosis of undetermined viral illness.

    I couldn't see any talk of CFS onset (after mono), sorry.

    I know lots of stuff suggests the younger you are, the better your prognosis, and that could well be true. But there's another possiblility: it could be if you're younger, the onset of your CFS is more likely to be acute EBV. And it could be that EBV-onset has a slightly better prognosis.

    One thing they did notice affected recovery was whether the person had arthralgia (joint pain). That was assocaited with poorer outcomes. Do you have that?
    Hip, MeSci, alex3619 and 1 other person like this.
  8. Gingergrrl

    Gingergrrl Senior Member


    But even 31 is ten years younger than the age that I got mono which seems to make my recovery harder. Also (and I apologize I didn't get to read the article yet) but were they only measuring fatigue or other symptoms (like autonomic issues, PEM, ability to create energy on demand, etc.)

    That is a good point that I had not thought of so I guess we don't know if the people involved had EBV (but can assume most probably did.)

    I'm not quite understanding this sentence and keep re-reading it. Do you mean if you are younger, your infection is more acute (meaning severe) or something else? If it is more acute or severe, why would that have a better prognosis? Mine was extremely acute and severe.

    I never had any joint pain at any time during my illness (mono or ME/CFS.) I had a muscle and tendon injury in my right arm due to Levaquin but that is a separate issue. Now my muscles are weak overall, but worse on the side with the Levaquin injury. When I overuse my right arm (I am right handed) the pain gets worse but it is muscle/tendon pain and never in the joints. Why would this factor matter? Just curious.
  9. Daffodil

    Daffodil Senior Member

    this study is a JOKE
  10. Research 1st

    Research 1st Severe ME, POTS & MCAS.

    Guys, One HUGE error in this upbeat study of no EBV in CFS is the recent science on EBV that contradicts it entirely. Take a look!

    So actually, the CFS patients lacked a correct immune response to it and thus would likely have a form of chronic mono. The reverse finding of this article saying the exact opposite.

    CFS patients were infected, when testing negative!

    Rule of thumb:
    Negative studies using antibodies (serology), don't rule out active infection in immune suppressed individuals!
    taniaaust1 and SOC like this.
  11. alex3619

    alex3619 Senior Member

    Logan, Queensland, Australia
    A negative study on some aspect does not necessarily mean that a study it contradicts is wrong. It does mean we have to look more carefully.

    Negative antibody titre findings in ME are not reliable. Period. Its only a weak indicator. We need viral titres, but this is more expensive usually.

    The other issue, including the T and B cells defect study, is that the problem is probably not active EBV. Its non-lytic EBV. Its not latent in the sense of not active, its just latent in the sense of not inducing lysis and an acute viral infection. Its still damaging. The research on this is only just getting started. PBMC viral levels are looking to be one thing they can test.

    The Haukeland study is an empirical outcome study, and much depends on the details of (especially)the methodology. There is already some suggestion on places like this forum, largely anecdotal, that teens get ME more severely but also have higher recovery. We have to keep an open mind until there is decent epidemiology. It could be right, only a slight trend, or wrong.

    This study is also not making grandiose claims, at least what I have seen so far as I have not read the paper yet. Recovery rate is about what some other studies have suggested. The range of recovery seems to be 1-14%, with this at the high end. Its also restricted to probable (not certain) EBV induced ME/CFS. If they used the CCC, which I presume is the case, then this is mostly about ME. If they used Fukuda its likely to have fewer ME patients.

    My computer is stuffed again and I am trying to function from my laptop, or I would be investigating this more.

    There are large numbers of us who can work for a while. I have a friend who is now severely disabled who was able to recover enough to work for a few years. This is not uncommon. Relapse is always possible though. I know lots of others who could recover enough to work, but still are quite sick. The working sick is perhaps a better description than recovered.

    The notion of recovery in ME is problematic, remission is perhaps a better word. If this is EBV related then remission is all that can be achieved, as we have no way to fully purge this virus with current technology.
    Last edited: Jan 21, 2015
    taniaaust1, Woolie, MeSci and 2 others like this.
  12. Simon


    Monmouth, UK
    That's a really interesting observation!

    These mono patients were part of a larger cohort so potentially could be investigated
    It's not clear if they have outcome data on non-mono patients; if so it would be interesting to compare results by type of patients and by age.

    edit, this ties in with the idea of an early 'mono/EBV' peak, and a separate, later adult peak, quite possibly with very different causes:
    Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008¿20127

    Figure One: twin age peaks:

    (this image may be copyright: it's from the linked open source paper above, but please don't reproduce without linking to the original paper and explaining it may be copyright).

    I haven't seen anything that says what proportion of adolescents with mecfs had it post mon/EBV, but get the impression it's most of them.
    Last edited: Jan 22, 2015
    Mel9, Snow Leopard and Woolie like this.
  13. Artstu

    Artstu Senior Member

    I had Glandular fever aged 20, then good health until aged 40 when I got CFS/ME. I'm looking forward to feeling much better in a couple of years at age 51.
  14. Lynn

    Lynn Senior Member

    I contracted Mono at age 19 in college. I then had the typical low grade fever and swollen lymph nodes for years afterwards. I was diagnosed as having Mono again by the University of Michigan almost 3 years after the original inset. I struggled with ME/CFS symptoms for years but I was very high functioning. I built a great career but finally crashed at age 36.

    I think this study would have put me in the category of recovered because I was employed. The reality was, like many of us I just kept pushing on until I could no longer do so. I wonder if this study continues following these people if the researchers will see something similar?

    Woolie, MeSci, Valentijn and 2 others like this.
  15. Hope123

    Hope123 Senior Member

    Haven't read the article but a few thoughts:

    1) I don't remember the details but age and severity of EBV infections are correlated. In the past and 3rd world countries, where kids get EBV early, even before the teenage years, they often don't have any symptoms. In first world countries, the age of getting EBV has risen to even late teens (and I didn't get it until much later). This goes back to the number of immune cells (I think it is B?) that are available and adaptable. Younger people have more of these cells and they are more flexible.

    2) I like that the authors looked at work as an important outcome and it's a good start but I would hesitate to say that is the most important outcome for everyone. Being able to take care of yourself, travel, ability to exercise, take care of family, etc. are also important. Being able to work doesn't mean that people are able to do these things. A more encompassing measure of function would be interesting to see in future studies.

    3) My guess is getting sick at a younger age may mean that people are able to adapt to work more easily than someone who gets sick later. For instance, I know someone who has been disabled since childhood but not with ME/CFS; this person was ambitious and starting from their teens, found and worked on a career path that would fit her disability successfully. One interesting aspect would have been to asked if people changed or curtailed their plans/ education because of illness. For instance, would that receptionist have been a scientist had she not been ill?

    4) The rate of employment for people with ME/CFS ranges from 25% to 70% depending on the study/ survey so 50% employment in this study -- I'm not sure if it's all that different from the average. It's hard to do a direct comparison because most studies of employment have used Fukuda.
  16. taniaaust1

    taniaaust1 Senior Member

    Sth Australia
    nods and something people should remember. I got attacked an ME website for severe ones with ME after I recovered from extremely severe ME over time. At the 1st follow up in this study had I been in it, I would of been one of those lucky 13% listed as fully recovered. Look where I am today thou, sick again to the point I need a wheelchair and a careworker to go out.

    Im finding this study a little strange in that the fact NO-ONE was unemployed at all on outset. For countries typical unemployment rates, you'd expect there would be some unemployment showing at the start, yet out of 92 patients, there wasnt any at all which were unemployed.

    I also dont think this study was from a typical percent of a population either seeing 53% were students. This makes me think thou the average age listed was 24 years, I personally think they must of had lots of younger ones in this study with the average age before pushed up by a few very oldies.

    I dont know if it tells in the full study or not (Im not up to reading it) but I'd like to know if only say 3 hrs work per week per week was counted as part time employment, I would guess that was so. Including part time study in things make things appear more positive then things really are. I would of found it even more interesting if they had an average amount of hours per week of work being done for the whole group.

    Still a very interesting study and Im glad they did it.
    Woolie likes this.
  17. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    The incidence graph in brown and blue seems to me to tell us more than almost everything else we know about ME/CFS. Epidemiology generally doesn't lie and it forces constraints on any hypothesis right at the start.

    My initial reactions are that:
    1. There are obviously two diseases. This is not a wobble.
    2. The first disease does NOT look like EBV, it starts too early.
    3. The first disease does not fit either with the 'high achiever crash/yuppie flu' concept, which ought to be more 18-28.
    4. The second disease is NOT a typical autoimmune disease because it tails off by 60. A purely B cell stochastic process should go on getting commoner with age until you start to exhaust the susceptible genetic pool (which happens for RA and breast cancer only around 85). The only autoimmune disease that has this sort of curve is lupus.
    5. The first disease could be a T cell disease such as type I diabetes or an adolescent immune disease like anti-DEK+ve oligoarthritis (one of the common childhood arthropathies).
    6. The early curves for boys and girls look more or less identical to what Esther Crawley reports, which gives reassurance that this is bona fide and not skewed by some local cultural factor.
    7. This is why we need more population based studies! And what we need is to have a population for which curves can be constructed for known T and B cell diseases, EBV, reactive affective disorders (i.e. depression, phobias etc.) and anything else relevant.

    As an aside in relation to a comment from Woolie: I think there may be a misunderstanding about mono diagnosis - I agree that the more or less all physicians would want specific evidence from tests to call it mono although I do not know how rigorously these get interpreted.
    Mel9, Battery Muncher, MeSci and 2 others like this.
  18. lansbergen

    lansbergen Senior Member

    It could be the same disease. In the aldult animals infection pressure was the main factor. In the young animals infection could not be prevented because the action that caused it was required by law.

    Does the age curve not reflect wpmen caring for infeced schoolchildren?

    Sidereal likes this.
  19. alex3619

    alex3619 Senior Member

    Logan, Queensland, Australia
    It might be two diseases, I have favoured that idea for some time. However it could also be two pathways to the same end state, perhaps with two different risk factor profiles, including hormonal changes.
  20. Simon


    Monmouth, UK
    I think I might have confused things slightly by posting about a separate Norwegian incidence study on this blog about the entirely Haukeland post-mono outcomes study. The study with the twin age peaks is discussed here
    CFS/ME starts most often age 10-19 & 30-39: Norwegian population study
    which might be the best place to continue this discussion about the meanings of the age peaks? I'll copy over the key points and respond there.

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