Persistent fatigue induced by interferon-alpha: A novel, inflammation-based, proxy model of Chronic Fatigue Syndrome, 2018, Pariante et al

Just to add: The paper was first published in 2016:

https://journals.sagepub.com/doi/10.1177/1359105316658967

 

Am I just being really cynical here or does anyone else suspect that the hype surrounding this paper has nothing to do with importance of the results and is instead a scrambling attempt by those involved to gain some plausible deniability with regards to their previous disregard for bad research in this field?

I can't help thinking that with mounting pressure about the PACE trial and now the issues with Cochrane the BPSers, MRC, SMC, Kings etc. have concluded:

"Oh crap! This isn't going to go away and looks very bad for us. Oh I know! Let's use our collective resources to plug this paper; it doesn't directly contradict our work on psychological perpetuation but looks at biological triggers for fatigue. We can say: "Yes we supported the PACE trial - but look we also supported this quality piece of biomedical research. See there isn't bias towards psychological CFS research! What are those crazy patients on about?! "

Edit: Spelling mistake​

 

The SMC briefing on this paper has gone on line this morning, though dated last Saturday, have not read it yet.

http://www.sciencemediacentre.org/the-biology-of-chronic-fatigue/

The title alone seems to go well beyond what one can reasonably conclude from the research.

 

Not much to read, this is all there is on their website (as it's meant as a journalist briefing and is available publicly I have quoted the complete text, if the SMC feel that this is unfair use of their text then I'd be happy to edit it down).

Lack of capital letters and poor formatting are all the work of the SMC.

 

Clearly it is all rather semantic.

However, defining a syndrome like ME or CFS (in the sense of the same as ME) is based on the idea that a specific clinical pattern implies some at least partially unknown causal path. Having a virus at the start is part of the accepted syndrome. Having an injection or two of interferon is not - i.e. the subjects do not have 'wild type ME'. And if one allows interferon induced illness then one probably has to include chemotherapy induced fatigue, cancer in ducked fatigue and all the things that the syndrome of wild type ME is intended to exclude.

What is not clear to me is whether or not the subjects in this study do in fact fit with ME in other respects. Do we know they did not have PEM? The Oxford criteria are over inclusive but it might be that all the subjects would have fitted CCC?

 

Did anybody ever pose the question this way: Are there people experiencing debilitating persistent fatigue due to a known medical condition who display an illness pattern similar to ME, including having ME-typical PEM (that is more than just increased tiredness)?

The problem with the Pariante study to me appears to be that the investigators were not interested at all in the specifics of ME other than the two non-specific criteria persistent fatigue and no biomedically abnormal findings. In the manner they are applying their findings (eta: hypothetically) to ME, supported by the SMC, they are propagating the Oxford Criteria and the ME/CFS = chronic fatigue = persistent tiredness narrative.

(Edited for clarity.)

 

I don't think it is a matter of giving benefit of doubt. As indicated by Adam, the value of the study lies beyond that. Parent's claim that the subjects developed 'CFS' is at best confusing, but if they did have PEM they had PEM and that would be of interest. If Parent really wants to claim they have the same problem as is called CFS or ME then he needs to justify it but as indicated above, I still think it is irrelevant because it is not going to be 'wild type ME' even so.

 

I suspect there are because at regular intervals members of this and another forum have discovered that their illness is due to something specific, like a genetic or autoimmune disorder. They seem to have been happy that they had PEM. I would not be at all surprised if interferon induced fatigue included PEM. It would be worth knowing.

 

Given the comment in that book chapter by McDonald and Mann from 1991, which I referred to above, it might reasonably be expected that a PEM like fatigue would be encountered. "Patients...who suffer from this fatigue find that it is exacerbated by physical exercise."

it might be worth looking up the paper they refer to: McDonald EM, Mann A and Thomas HC (1987) Interferons as mediators of psychiatric morbidity. Lancet, ii, 1175-1178

 

I thought the Oxford criteria required 6 months of unexplained fatigue?

If interferon therapy is already known to cause lasting fatigue how is that unexplained?

"IFN-alpha, which is used in the treatment of chronic Hepatitis C Virus (HCV) infection, induces a persistent fatigue in some individuals, which does not abate post-treatment, that is, once there is no longer immune activation."

To me it only emphasises the inaccuracy of the Oxford criteria for CFS.

(If they had said they wanted to find out why the drug therapy causes long lasting fatigue that's one thing, to equate it to ME/CFS is quite another).

 

Think there is some confusion here. The paper never claims the patients with persistent fatigue after interferon alpha had cfs, they simply compared them to a sample of cfs patients selected by the Oxford criteria. The comparison showed that the persistent fatigue patients had much less fatigue on the chalder scale than the cfs sample.

 

I was meaning if this was investigated systematically.

Somebody could ask Pariante to reinvestigate. I am afraid he would have to be convinced of the relevance of PEM/ the CCC to ME first.

"Happy" sounds odd in this context to my non-native-speaker's ears.

 

If that is the case then it proves nothing and it is not the message that is being disseminated.

eta:
Interesting that it is in
Chapter 16. Psychopathology: Biological Basis of Behavior Disorders
https://www.biopsychology.com/news/index.php?descType=always&id=16&type=bpchapter&page=0

 

We'll be lucky if it's just that. The other possibility is that it's the prelude to something very unpleasant.

Thanks, I'll quote that next time someone thinks they're helping by telling me to have a "mind like water".

 

I assumed the authors intended the readers to make that inference given in the introduction they refer to the suggestion that the persistent fatigue following interferon has associated cognitive problems. Unfortunately they do not follow up on this or even demonstrate they understand the difference between the symptom of chronic fatigue and chronic fatigue syndrome.

Because they only look at fatigue and use the Oxford criteria, we have no idea what other symptoms were present in the HepC adverse drug reaction group or whether their 'CFS group' would meet more strenuous ME/CFS criteria.

In all they make it hard to take anything useful or meaningful from their findings in terms of a model for ME/CFS. Also the suggestion of a single event triggering a persistent symptamotologgy seems to imply the resultant condition should be stable or improving. They do not discuss this in relation to their HepC patients, and would presumably have to come up with some form of additional explaination for ongoing deterioration or relapsing remitting forms of ME/CFS.

Why is it that some many researchers associated with the British BPS school of thought feel free to pontificate on ME/CFS on the basis of selected, incomplete or inaccurate information?

 

Just want to throw in that criticism of the study is not about downplaying the severity of interferon alpha induced fatigue.

PWME, their allies and ME interested scientists with high scientific standards apply similarly sharp criticism to any other research as well, in particular when it claims to be research into ME.

 

The BPSers have used the days before Christmas to publicise things before. I can't remember details, but I do remember feeling upset and angry.

This research is just another superficial study done by people with no understanding of ME and is just being used as a hook to get a specific message out into the media. It is not being trumpeted because they believe there has been a massive breakthough in ME or even fatigue studies but for a reason we can't see yet. That is the only thing which explains the disconnect between the actual results and the claims. The biopsychosocial group could give Trump pointers on political manoeuvring and have always used underhand tactics which rely on the scientific world being naive and taking things at face value. Pariente may not even be in the know.

We are cynical as a community as this has happened over and over. At the very least it will be used to stop our complaints about the makeup of the NICE committee as Partiente is now firmly in the biophysical group. Anything we say will be dismissed as patient whining.

 

I just want to dissect some of what Carmine Pariante said on the Radio Wales programme yesterday:

As far as I understand it, they were looking at a group who had a high risk of developing chronic (or persisting) fatigue - not CFS per se. These patients had already had a very strong viral infection (HCV), which is why they were being treated with IFN-alfa at all, so to claim that they were looking at what happens early on in the infection is not true. These were patients with a known persistent viral infection who were undergoing therapeutic immune challenge.

Not sure this is true. It might show that those who mount a strong immune response to their persistent infection without clearing it are more at risk, but did it show "hyperactivity"?

Or is it more an indicator of the severity of the infection?

Is IFN-alfa /ribavirin therapy a good proxy for viral infection though?

Early stage of the illness? The paper doesn't tell us how long these patients had had chronic HCV - just that they were recruited from outpatient clinics across London.

I'd be interested to know what an HCV immunologist/clinician would say about this study, because it seems to run contrary to what others have found, eg: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477271/