Persisting Rickettsia typhi Causes Fatal Central Nervous System Inflammation, 2016, Osterloh et al

https://journals.asm.org/doi/10.1128/iai.00034-16

ABSTRACT
Rickettsioses are emerging febrile diseases caused by obligate intracellular bacteria belonging to the family Rickettsiaceae. Rickettsia typhi belongs to the typhus group (TG) of this family and is the causative agent of endemic typhus, a disease that can be fatal.

In the present study, we analyzed the course of R. typhi infection in C57BL/6 RAG1−/− mice. Although these mice lack adaptive immunity, they developed only mild and temporary symptoms of disease and survived R. typhi infection for a long period of time. To our surprise, 3 to 4 months after infection, C57BL/6 RAG1−/− mice suddenly developed lethal neurological disorders. Analysis of these mice at the time of death revealed high bacterial loads, predominantly in the brain. This was accompanied by a massive expansion of microglia and by neuronal cell death. Furthermore, high numbers of infiltrating CD11b+macrophages were detectable in the brain. In contrast to the microglia, these cells harbored R. typhi and showed an inflammatory phenotype, as indicated by inducible nitric oxide synthase (iNOS) expression, which was not observed in the periphery.

Having shown that R. typhi persists in immunocompromised mice, we finally asked whether the bacteria are also able to persist in resistant C57BL/6 and BALB/c wild-type mice. Indeed, R. typhi could be recultivated from lung, spleen, and brain tissues from both strains even up to 1 year after infection. This is the first report demonstrating persistence and reappearance of R. typhi, mainly restricted to the central nervous system in immunocompromised mice.

 

This is a 2016 paper but I thought it was relevant to the pathogen persistence and reactivation hypothesis.

A study in Australia found rickettsias in a large proportion of people with ME/CFS, and I also have tested positive to them. Brill-Zinsser disease is when a Rickettsia species stays latent in the body and then reactivates, years to decades after the primary infection. This 2016 Osterloh study found that another Rickettsia species can do this in mice and that it can cause CNS damage.

 

Here's the link to the thread about the Australian study in people with fatiguing illness:
Markers of exposure to spotted fever rickettsiae in patients with chronic illness, including fatigue..., 2008, Unsworth et al

On that thread, I mention the lab run by one of the authors of the Australian study: