Immune stimulation by vaccination e.g. Staphylococcus Toxoid Vaccine, BCG

Long-Term Treatment with a Staphylococcus Toxoid Vaccine in Patients with Fibromyalgia and Chronic Fatigue Syndrome

Carl-Gerhard Gottfries, Ove Häger, Björn Regland, Olof Zachrisson

Abstract
One hundred and sixty patients with fibromyalgia and chronic fatigue syndrome, who were on a continuous treatment with a Staphylococcus vaccine, were followed during one year with repeated consultation visits. The patients had participated in controlled studies and been on continuous treatment with the vaccine for 22±10 months before inclusion into this follow-up study. They were treated with 1 mL of the vaccine subcutaneously every third to fourth week. Adverse events were few.

The adherence to the treatment was very good. Over a period of one year, 8% withdrew, and in only 5%, the withdrawal was due to insufficient clinical effect. Only in two cases where the patients were allergic to the preservative of the vaccine, the side effects caused the withdrawal of the treatment.

Ratings with scales (CPRS-15 and FibroFatigue) showed improvement from start of treatment and also further improvement during the follow-up year. In view of the natural history for these disorders the result is of interest.

Link (Journal of Chronic Fatigue Syndrome) [Paywall]

 

In 2009, there was a full text of what appears to be the same study, but with a differently worded abstract, published in Bulletin of the IACFS/ME:

Snippets from sections:

Background

Methods

Results

Discussion

Limitations

 

How has this not been tested again?

I found this group's results cited as recently as 2018 and 2022, with no mention of newer studies on the vaccine.

Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model, 2018, Blomberg et al

Could the kynurenine pathway be the key missing piece of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) complex puzzle?, 2022, Kavyani et al

Maybe because of adverse events?

Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review, 2006, Chambers et al

36 is the following, which is a previous staph study by the same authors. Mentioned in the study for this thread.

Treatment with staphylococcus toxoid in fibromyalgia/chronic fatigue syndrome--a randomised controlled trial, 2002, Zachrisson et al

This does not seem adverse enough to never try it or anything similar again for 20 years.

 

Because the manufacturer of this particular vaccine stopped making it, supposedly (based on what I've been told by Gottfries' patients years ago).

 

Yeah, they say that in the above paper:

But still, I don't see why similar vaccines aren't tested. I'd be very surprised if that's the only possible vaccine that could provide a benefit. Some people with ME/CFS even report a temporary benefit from the COVID vaccine.

 

I agree with you, @forestglip. I'd love to see this explored and tested properly.

A side note, there's a thread from 2015 on PR about the closing down of the Gottfries' clinic. I don't know the whole story myself, but it's very clear that the BPS lobby was doing everything they could to put Gottfries down, including going after their research and treatments efforts through political means behind the scenes.

 

There's a 5 part series of videos on YouTube, an interview with prof Gottfries from 2014. He talks about his reseach (but I can't remember any details at the moment, it's been so many years since I last watched it).

Interview with Professor Carl-Gerhard Gottfries, Part 1: Background and Vaccine

https://www.youtube.com/watch?v=TCF_RYCnHW4

Interview with Professor Carl-Gerhard Gottfries, Part 2: Experience and The Clinic

https://www.youtube.com/watch?v=cUlXZ8qmNrI

Interview with Professor Carl-Gerhard Gottfries, Part 3: The Clinic and Urgent Needs

https://www.youtube.com/watch?v=q0wUSkK4Z20

Interview with Professor Carl-Gerhard Gottfries, Part 4: Continued Research

https://www.youtube.com/watch?v=Kyyc6U1M7pY

Interview with Professor Carl-Gerhard Gottfries, Part 5: Wishes For The Future

https://www.youtube.com/watch?v=gGq1rhk_yG8

 

Thanks! I'll definitely try to watch those.

 

interesting on starting part 4 already. He says that originally the 3 of them came from psychiatry, but that it became clear it was something immunological ie the illness isn't psychiatric

And just because of the 'which speciality' discussion elsewhere I'll note he then confirms there is now 3 psychiatrists, one gerontologist, one internist and research nurses

 

These interviews were very interesting. I've transcribed the parts I found most interesting. Note that I wasn't 100% accurate with the transcriptions. Reworded some parts to make them clearer or more succinct, and skipped some parts, and may not have put [...] at every part I skipped.

Interview from February 2014

Video 1

Video 2

Video 3

Video 4

Video 5

I wonder what he's doing now. He seems like quite a nice fellow from this interview.

 

I don't know what he's doing now, but I believe he's currently about 96 years old?

And yes, he's been very much appreciated by his patients and the ME community over the years.

 

Wow, well then I hope he's still alive and just relaxing. (Unless he wants to work of course)

 

Really great find @forestglip and great follow up @mango, many thanks.

I watched the first video.
Prof. Gottfries started in 1957, the year I was born.
A 50% of reduction of symptons because of this vaccine, injected once a month, could have been available when I got ME/CFS in 1991.

The BPS-lot stole half my life.

 

Here are the two RCTs they performed:

Effects of staphylococcus toxoid vaccine on pain and fatigue in patients with fibromyalgia/chronic fatigue syndrome, 1998, Andersson et al

Treatment with staphylococcus toxoid in fibromyalgia/chronic fatigue syndrome--a randomised controlled trial, 2002, Zachrisson et al

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Second one does appear to be double blind. (Maybe first one too, I haven't looked yet.)

One thing I was wondering was if these patients had previously been receiving this treatment at the clinic, in which case they might be able to detect presence or absence of certain known side effects. But I think they would have included that in the paper and I don't see that.

Possibly didn't have PEM if they used CDC criteria, but they did have "mild immune activation".

 

Finally, an upside to Brexit? We could start up the old company again with the original manufacturing process.

I think part of the issue was that the vaccine contained mercury-based preservatives and so I’m quite glad these were deemed in need of improvement, but apparently that would also necessitate going through the whole, expensive, regulatory approval process again. Potentially costing 100s of millions of dollars. It’s a real shame; I’d like to see a new improved staph toxoid vaccine approved and tested for ME/CFS. Anyone know any organisations or wealthy individuals willing to fund this project?

 

Looking at this paper, the second RCT by Gottfries:
Treatment with staphylococcus toxoid in fibromyalgia/chronic fatigue syndrome--a randomised controlled trial, 2002, Zachrisson et al

I haven't heard much about pregnancy being a trigger.

Here are all the symptoms tested, with a star next to those that had significant improvement at 26 weeks. The number is the baseline score for the active group.

That it seems to continue to improve more and more with time makes me think that assuming there is viral persistence, it is doing more than keeping the infection at bay. It seems that it is slowly chipping away at it with time, and that maybe a larger dose or more effective vaccine could do so more quickly. Although it did still return to near placebo level after withdrawal.

"Good responders" means "One-third (33%, n = 16) of the 49 patients receiving active treatment were classified as good responders (>50% reduction in scores at end-point)."

Here is one of the secondary outcomes, a different rating scale "Clinical global impression of change (CGI-C)":

Two other secondary outcomes were related to pain, "Visual Analogue Scale (VAS) of Pain", and "Fibromyalgia Impact Questionnaire (FIQ)".

So it doesn't seem pain was much improved.

Concerning blinding:

Side effects:

Susceptibility to infections:

Interesting, considering the opposite observations often made by researchers/clinicians (I think I've heard of researchers saying this) and patients that people with ME/CFS report fewer infections.


Something about nickel allergy and smoking:

Will have to check what that Regland paper is.


Mechanism speculations

Formulation:

Hmm, injecting mercury doesn't sound too great.

One thing we can see is that Dr. Gottfries took this for around 50 years, and in his interview at 85 or 86 years old still seems quite healthy, so no obvious evidence of severe negative health effects in that specific case.

 

The RCT mentioned this paper, where Gottfries is also an author:

--------

Nickel Allergy is Found in a Majority of Women with Chronic Fatigue Syndrome and Muscle Pain—and may be Triggered by Cigarette Smoke and Dietary Nickel Intake, 2001, Regland et al
Bjorn Regland, Olof Zachrisson, Vera Stejskal, Carl Gerhard Gottfries

Abstract
Two hundred and four women with chronic fatigue and muscle pain, with no signs of autoimmune disorder, received immune stimulation injections with a Staphylococcus vaccine at monthly intervals over 6 months. Good response was defined as a decrease by at least 50% of the total score on an observer's rating scale.

Nickel allergy was evaluated as probable if the patient had a positive history of skin hyper-sensitivity from cutaneous exposure to metal objects. The patient's smoking habits were recorded. Fifty-two percent of the patients had a positive history of nickel contact dermatitis.

There were significantly more good responders among the non-allergic non-smokers (39%) than among the allergic smokers (6%). We also present case reports on nickel-allergic patients who apparently improved after cessation of cigarette smoking and reducing their dietary nickel intake.

Our observations indicate that exposure to nickel, by dietary intake or inhalation of cigarette smoke, may trigger systemic nickel allergy and contribute to syndromes of chronic fatigue and muscle pain.

Link | PDF (Journal of Chronic Fatigue Syndrome) [Paywall, but the full text PDF linked is available from a website called MELISA.org]

 

I don't think much of these:

"Here are all the symptoms tested, with a star next to those that had significant improvement at 26 weeks. The number is the baseline score for the active group.

*4.8 Fatiguability
4.8 Aches and pains
*4.0 Reduced sleep
3.4 Muscular tension
*2.9 Failing memory
*2.8 Concentration difficulties
2.5 Autonomic disturbances
*2.2 Hostile feelings
*1.7 Sadness
1.3 Inner tension
1.1 Pessimistic thoughts
1.0 Worrying over trifles
0.8 Suicidal thoughts
0.5 Hypochondriasis
0.4 Phobias"

Many of these are psychiatric symptoms which are not part of ME. And where is possibly the most important symptom - post-exertional malaise (PEM)?

 

Yeah, he was going by Fukuda/CDC criteria in his practice originally. CCC and ICC weren't created until after this paper, and the paper doesn't mention PEM.

 

In regards to BCG, there were an abundance of different trials on different BCG formulations with tens of thousands of participants to see whether there is an impact on acute Covid (I don't think any had a Long-Covid follow-up). At the beginning of the pandemic there was the speculation that certain regions in the world (for instance Africa and Latin America) were doing better with acute Covid and some speculated that this could be due to BCG vaccination status, given the tremenounds amount of funding for acute Covid it was really easy for them to launch trials. It seems the results were a rather mixed bag, with largely negative results.

Similarly there has been a large study on BCG vaccination and MS risk. I'm sure there's hundreds of other studies for different conditions as well.

I know that even today, there are ME/CFS patients groups still experimenting with different formulations of BCG vaccines.