Review Designing studies for post-treatment Lyme disease and other infection-associated chronic illnesses, 2026, Arnaboldi et al

Nightsong

Nightsong

Senior Member (Voting Rights)

Abstract​

Infection-associated chronic illnesses (IACIs) encompass a spectrum of poorly understood syndromes often marked by significant neurologic and multisystem symptoms following an infectious event.

This review focuses on several diseases representative of the IACI spectrum. These are post-treatment Lyme disease syndrome (PTLDS), long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS). Their clinical and biological complexity, combined with a lack of clear diagnostic criteria and objective available laboratory biomarkers, makes them difficult to distinguish from conditions with overlapping features. This presents challenges for research studies, as well as diagnosis and clinical management. This diagnostic ambiguity, coupled with heterogeneous patient presentations, has led to challenges in research, including misclassification of study participants and inconsistent or irreproducible findings. Some PTLDS research exemplifies these issues, which also extend to other IACIs.

To advance the field, we highlight key methodological refinements and approaches for studying IACIs, including rigorous participant selection, standardized sample collection protocols, and the use of appropriate control groups, including those with microbiologic proof of the initial infection when known and technologically feasible. We also address broader influences on research quality, such as stigma, historical neglect, and the urgency to find treatments, which have contributed to the proliferation of poorly controlled studies and questionable practices. Drawing lessons from past challenges, we propose a path forward grounded in fit-for-purpose methodological rigour to improve scientific understanding and support evidence-based therapeutic development for IACIs.

Link | PDF (Brain, May 2026, open access)
 
Some heavy hitters from the Lyme field (Patricia Coyle, Maria Gomes-Solecki; some of you will recall Steven Schutzer when he compared Lyme with CFS several years back).

Why anyone would lead a research-methodological guideline with Lyme - arguably one of the most politically contentious and polarizing diseases, at least within the US - is beyond me. Forget about diagnostics or treatments - definitions alone can be a quagmire.

Within two paragraphs following the abstract, they earn my distrust, although I did read the entire thing as it also invokes ME/CFS and Long Covid, with people like Avindra Nath and Jonas Bergquist listed as contributing authors.
 
dave30th said:
I've just scanned the opening, but it seems like they're discussing post-treatment Lyme disease, which is pretty well-documented and is a different thing than chronic Lyme disease, in which there might be no evidence of initial Lyme infection.
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See? Definitions. :)

There absolutely can be evidence of initial Lyme infection in chronic Lyme, certainly when it comes to formal research. I was enrolled in an NIH chronic Lyme study about 15 years ago, and you had to have documented evidence of a Lyme infection in order to participate.

Some folks played with the definition. Just as they did with PTLDS, which used to be post-Lyme disease syndrome, but PLDS became too much of a hot potato because of the backlash. I would suggest there are plenty of people diagnosed with PTLDS that never had antibody proof since that can be abrogated if treatment is rendered early.

ETA: I was in that chronic Lyme NIH study for three or four years, and I tested 2T positive through NIH researchers something like 10 out of 11 times.
 
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This should not be about the chronic Lyme label, but they introduced it into their screed. So I just want to point out how frequently chronic Lyme was discussed and researched and acknowledged prior to the 1990's - when vaccines started to come into play.

We can thank the Bayh-Dole Act for much of what happened.

Eh. These authors are correct when they say we need better research methodology and practices, I will give them that.
 
One last observation about definitions:

In 1980's in the US, if you had documented Lyme, and were treated, and symptoms persisted, you were categorized as having chronic Lyme. Period. Definition back then of chronic Lyme: Lyme disease that cannot be resolved with "suggested" treatment protocol. You had a Bb case that would not resolve, most likely because treatment had been delayed ( this is similar to syphilis, a sister spirochetal disease). You had Lyme that would persist, even in the face of what some thought was an adequate treatment protocol for acute cases, but not so much for late stage disseminated. In other words, Lyme that went chronic.

There is an argument that the allure of vaccine $'s changed all that. A stubborn and intractable infection, in theory, would make getting a vaccine vetted and approved virtually impossible.

So the definition of Lyme had to change. Hello acute Lyme, and simply by virtue of a nagging patient community, PTLDS. Bye-bye chronic Lyme. You can add to the chaos TBD tandems, which complicated everything, i,e., is Lyme Lyme, or Lyme +?

To refine the definitions, you really needed better diagnostics, and that's where the Bayh-Dole wall slammed on the breaks: patent dollars were involved, and this was big money. Moreover, vaccine revenue was within a decade of the Bayh-Dole act creating a whole new frenzy into the mix, and incenting a different breed of inventive defintions.
 
This looks like someone interested in Lyme wanting to get some oxygen of publicity borrowed from the Long Covid 'IACD' bandwagon.

The introduction uses lay ideas of 'disease' or 'distinct condition' that get you nowhere if you are wanting to do real medical research. The group of diagnostic categories chosen to include makes no great sense - MS has nothing much to do with the others.

The relevant definitions are a mess, more because they should never be proposed as 'distinct conditions' than anything.

And you will never get that number of people to agree to anything cutting edge.

The proverbial camel, I think.
 
In LymeWorld. the Rat Fink factor wields a lot of influence.

It's like Clavell's King Rat: Money rules.

Medicine has been breached, and the Marginot line is/was Lyme and babs and rickettsia. And yes, ME/CFS.
 
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By my sloppy math, at least one third of these Lyme authors has a vested or historic interest in Lyme vaccines.

When money matters in medicine, we should watch.

BTW: What happened to all those Lyme diagnoses in the late 1980's that got undone by 1995? Many, by virtue of Lyme leaders at that time, became, specifically, CFS patients.

If you think it's different in the UK, who do you think dictated terms?
 
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