Chronic fatigue syndrome after Giardia enteritis (Naess et al., 2012)

Free full text: http://www.biomedcentral.com/1471-230X/12/13

* I gave each sentence its own paragraph.

Yes getting to/understaning slowly - it is after 12 years evident to me of persistant gastro/genital infection (undiagnosed UK - but they are good at that).

Pre-publication history

One of the interesting things about this paper is the Pre-publication history: http://www.biomedcentral.com/1471-230X/12/13/prepub

Peter White wants to try to break the connection that this shows Giardia enteritis can cause CFS. He may have minor technical points but he could have suggested the authors mention limitations and provisos.

Simon Wessely is called in to act as another reviewer to try to break the impasse, it seems.
Amongst other things, he says:

He eventually lets it through saying:

SW also says:

which is interesting given some other studies such as by the CDC on childhood factors.

I agree with the reviewers that it would have been interesting if they had sampled some of the other 1100-odd initial giardia patients as some of them could also have CFS.
It would have been interesting if the group had been looked* at at 6 months or 1 year as the prevalence of CFS might have been higher. The mean duration of the illness was 2.7 years.

* I can't remember what other papers on the giardia outbreak found - I think they might not have reported CFS specifically??

Table 1 is at least a little interesting as it doesn't just include the 8 Fukuda criteria.

Based on that, the fatigue scores, the fact that all those working and studying have reduced their output or were classified as "sickness absence" as well as the pattern of SF-36 subscale scores suggests CFS (and probably ME/CFS and ME) is a reasonable diagnosis.

I find myself agreeing with Simon Wessely, how bizarre. I've highlighted his comment about the worthlessness of retropsective measures on another thread where you had brought up the exact same issue (Birth cohorts).

Giardia Lamblia is the first Protozoan associated with triggering CFS, as far as I know (others are viruses of bacteria).

Great! I hope there are confirmations of their results soon, more different studies are sparked by it.

Splitting the sentences helped. Thanks.

This is probably going to end in another multifactorial origin hypothesis, especially for the people with 'late' onset(months) vs 'short' onset (weeks) CFS after Gardia enteritis. But I'm especially trouble by this quote:

It's interesting that one of the researchers behind the Gardia-CFS connection, Knut-Arne Wensaas, had a pretty rough (to put it mildly!) discussion with Mella and Fluge about the rituximab paper: (http://www.plosone.org/annotation/l...notation/b3d77c11-5f3c-447c-ae74-a38aa62cf101)

This lead to these quotes from Fluge and Mella:

I think anyone can guess now what the results of that follow-up study will be......

Blastocystis hominis

http://en.wikipedia.org/wiki/Blastocystosis

"Blastocystis is a protozoal, single-celled parasite"

"Variation in severity
Researchers have sought to develop models to understand the variety of symptoms seen in humans. Some patients do not have symptoms, while others report severe diarrhea and fatigue."

One of my first CFS symptoms, circa 1991, was diarrhea. Great Smokies Lab found B. hominis in my stools.

There were several newspaper articles (not peer reviewed of course!) in the early to mid 90s that associated B. hominis with CFS. Northern California near Incline Village and Oregon are all that come to this old and fading mind.

A pity that they did not test these patients for ME or at least latent herpes infection.

I'm not sure what test for ME you mean.

Thanks for that. According to that well-referenced Wikipedia article there is some doubt about whether or not B.hominis is a pathogen at all (ie it may be present but does it cause disease?), but the consensus was that it probably is, or can be in some circumstances. Couldn't find any publisehd research linking it to CFS though those newspaper reports are interesting. Like giardiasis B.hominis is not only a protozoan but a gut protozoan which makes the link more intriguing.

There is, it turns out. one report much earlier report, from 1992, of Giardiasis being linked with CFS.

Problems with diagnosis

I was very impressed when I first read this study: a post-infectious rate of 5%+ CFS cases after 2.7 years is very high. Typically for glandular fever etc it's around 10% after just 6 months and I seem to recall it drops to around 6% after 12 months in prospective studies.

However, there are 2 serious issues around the diagnosis of CFS:

1. The Fukuda case definition wasn't applied properly with no pyschiatric interview and apparently no physical examination or required lab tests. The last time I saw an implementation this weak was in Simon Wessely's 1997 prevalence paper that found a 2.6% rate for Fukuda CFS (see post #10).

2. In the majority of cases (58%) the onset of fatigue was months after the acute illness, which could include more than a year after the acute illness.

As ever, the situation isn't clear-cut so I'll spell out the issues as I see them and hope others will chip in with comments.

Specific issues with diagnosis

There is clearly a thorough medical history. However, a neurologist interviewing patients about psychiatirc diagnoses is not the same as a psychiatric evaluation; there is no mention of a physical examination or the lab tests required by Fukuda. In pre-publication comments, the authors don't explain why they didn't implement Fukuda properly, despite being challenged about it by reviewers, though they do say "The patients were classified as CFS based on the CDC criteria for CFS (see reference 10- [Fukuda]) by a specialist on chronic fatigue in our department".

Mean SF-36 Physical Function score was 60, pretty high even for an outpatient group (I think). No SD is given but probably a good chunk of this group would have not been impaired enough to meet the PACE trial entry criteria of 65 or less. The mean FSS fatigue score was 6.6/7, which is pretty high, though I'm not sure if FSS has a ceiling effect like the Chalder Scale.

There is also no explicit exclusion of patients who were fatigued before the Giardia infection, though you like to think this was covered by the medical history.

So fatigue onset for 58% of CFS diagnoses could be many months or even over a year after enteritis. The authors do add that they "excluded patients with an interval free of symptoms between the giardiasis enteritis and the development of CFS." Nonetheless, if patients have enteritis for 6 months without fatigue, and then develop fatigue, that fatigue may not be a consequence of the enteritis. The authors suggest

but i don't think you can be ill for 6 months without noticing you are fatigued.

On the other hand, I would be pretty confident that patients whose fatigue started within weeks of the onset of enteritis did have fatigue as a consequence of the illness and in their case the lack of proper psychiatric interview etc doesn't bother me as much. It would be a freaky conincidence if so many patients spontaneously developed CFS or another fatiguing illness within weeks of gardiasis.

Putting some guesstimates together

For the reasons above, I don't accept the authors findings that the 5% prevalence of CFS

42% of CFS diagnoses (24/58) had rapid onset of fatigue [within weeks] , which works out as 1.9% (24 ex 1,262 lab confirmed Giardia cases) as pretty certain CFS cases after Giardiasis. That leaves some doubt over the remaining CFS diagnoses (34/58, or 2.5% of the original Giarida cases).

However, some of the 'dodgy 2.5%' are probably genuine Post-Infectious CFS cases. Simon Wessely's 1997 study only found 2.5% of CFS cases of any duration, wheras the dodgy 2.5% must have occurred within a couple of years of the initial infection. Lets conservatively assume just 1 in 5 of these (ie 0.5% of all cases) are post-infectous cases which bumps the total of 'real' cases up from 1.9% to 2.4%. That excludes any cases of post-giardiasis CFS cases that hadn't reached the referral clinic in this study, and there must have been some of these (sadly the authors didn't attempt to take a random sample of the original infected patients who didn't wind up in their clinic).

So a true 'lower limit' to the rate of CFS post-giardiasis is probably around 2.5%, and with an average duration of 2.7 years that is still a pretty high rate.

Comments welcome... I've made numerous assumptions along the way, feel free to challenge any and all of them. As if you need permission.

I emailed the lead author and he confirmed they were excluded, so there were no pre-existing cases of CFS in this cohort.

Hi oceanblue. I haven't read the paper and don't intend to so I can't make any more comments on your estimates.

All I want to say is that I wouldn't discount 'delayed' fatigue emerging following enteritis.

My own experience (now meeting the CCC and ICC criteria) was initially gastro symptoms and PEM but I didn't start to experience generalised 'fatigue', either physical or cognitive until over 10 years after onset.

Given that my various doctors approached the problem on a symptom by symptom basis, I was initially given a full gastro work over and PEM wouldn't have even entered into the conversation.

It was some 12 years or so before a ME diagnosis was suggested.

My case may be unusual but I wouldn't be surprised if some symptoms necessary for a 'CFS' diagnosis don't present simultaneously with the initial trigger.

The best would be if they'd use the CCC criteria, but none the less, this is good news. The first study of the outbreak only looked at "chronic fatigue". I think giardiasis plays exactly the same triggering role as EBV, borreliosis, the flu and so forth. Giving the immune system more to handle for a short period of time. That's the only common nominator I can find of the various triggers.

Thanks for that, Marco & Snow Leopard.I agree that many cases with delayed onset fatigue could be linked to the intial Giardia infection, but we can't be sure, particularly as the CFS cases were not properly diagnosed. What I have tried to do is to tease out what we can confidently deduce (i.e. a minimum incidence of 1.9% CFS more than 2 years on, as a direct result of the Giardia infection) as opposed to what is likely (a much higher incidence, perhaps 5% or more).

I, like you Snow Leopard, see vaccines as one of many in the list of CFS triggers. There are several I've been in contact with which have got it triggered by just that. Since you're pretty updated on the litterature, I've got a question for you: Besides EBV and now giardisis, do you know which stressors which have been scientifically linked to CFS as a trigger? I am not talking about large peer reviewed studies only, but also smaller case series etc.

I don't know. Like Marco, PEM rather than fatigue was more my main symptom for a long time. Once I avoided sports, the fatigue wasn't particularly noticeable, more the muscle problems. Cognitive problems weren't so noticeable initially. Looking back, I was maybe down 5% in the first 12 months (approx.) and maybe 10% after that, in terms of quantity I could learn with a period, say (v. approximate figures). Clerical errors probably crept in over a similar period.

Thanks for going to all this trouble, oceanblue.

However, I don't see it as that close to that Wessely study. I think making diagnoses using written records alone is at a different level to how these patients were assessed. For example, they may not have explicitly said they use all the Fukuda blood tests, but I imagine a consultant running a service for such patients would run most indicated tests.

My guess is that if one looked at a lot of CFS cohorts not all of the following are done exactly: