Mycobacteria in ME?

[Just found this sitting long forgotten in my 'thought experiments needing more thought' draft file. Brain not volunteering many sharp thoughts atm but I think the draft is coherent enough to serve as discussion starter. Seems topical in context of Nath's interpretation of intramural study findings as caused by some (unidentified) persistent antigen]

Was reading about mycobacteria for unrelated reasons but idly googled, as you do, to see if anyone had looked at them in the context of ME.

Appears not, apart from a couple of studies suggesting a slightly increased risk of CFS, or possibly just CF, after infection with mycobacterium tuberculosis, same as after many other infections.

Lack of interest a bit surprising given the recurring fashions for persistent antigen hypotheses, some obscure mycobacterium would look to be a good candidate in many ways.

Apart from the well-known TB and leprosy mycobacteria there are nearly 200 others, a few linked to other diseases (see links below) but most are considered harmless. But that could just be due to little being known about them. If one of them had the right combination of features known to occur in mycobacteria, that would make a credible candidate for a persistent antigen which has managed to evade detection, features like:

• very difficult to test for and treat so unlikely to be found by accident
• not or poorly transmissible but ubiquitous in the environment
• only problematic in genetically susceptible people
• can infect tissues like bones or lymphoid and not show in blood
• can be latent for years or decades
• can become active following some other immune system disturbance

So, not inconceivable that a sneaky "harmless" mycobacterium could have gone unsuspected and undetected, smoldering away in some difficult to access tissue with just enough activity to annoy the immune system of genetically predisposed people.

Testing the hypothesis wouldn't be easy though. Individually testing approx 200 difficult to test for bacteria in heaven knows how many difficult to access tissue types seems a tad tricky. Plus, apparently mycobacteria are notorious for creating false positive results due to lab contamination issues, something we really don't need a repeat of

There are plenty of other unanswered questions with the persistent antigen idea in general, like how to link the antigen to something somewhere that fluctuates with levels of exertion. Etc etc etc. Still, why is it that the proponents of the persistent antigen hypothesis seem to have ignored the possibility of non-tuberculous mycobacteria in pwME, what am I missing?

Reviews of non-tuberculous mycobacterial disease:

Approach to the diagnosis and treatment of non-tuberculous mycobacterial disease (2021) Pennington et al

Epidemiology, diagnosis & treatment of non-tuberculous mycobacterial diseases (2020) Sharma & Upadhyay