How mycobacterium tuberculosis infection could lead to the increasing risks of CFS and the potential immunological effects (...), 2022, Yang et al

[Wyva]

Full title: How mycobacterium tuberculosis infection could lead to the increasing risks of chronic fatigue syndrome and the potential immunological effects: a population-based retrospective cohort study

Abstract

Background
Chronic fatigue syndrome (CFS) has been shown to be associated with infections. Tuberculosis (TB) is a highly prevalent infectious disease. Patients with chronic fatigue syndrome and post-tuberculosis experience similar symptoms. Furthermore, chronic fatigue syndrome and tuberculosis share similar plasma immunosignatures. This study aimed to clarify the risk of chronic fatigue syndrome following the diagnosis of Mycobacterium tuberculosis infection (MTI), by analyzing the National Health Insurance Research Database of Taiwan.

Methods
7666 patients aged 20 years or older with newly diagnosed Mycobacterium tuberculosis infection during 2000–2011 and 30,663 participants without Mycobacterium tuberculosis infection were identified. Both groups were followed up until the diagnoses of chronic fatigue syndrome were made at the end of 2011.

Results
The relationship between Mycobacterium tuberculosis infection and the subsequent risk of chronic fatigue syndrome was estimated through Cox proportional hazards regression analysis, with the incidence density rates being 3.04 and 3.69 per 1000 person‐years among the non‐Mycobacterium tuberculosis infection and Mycobacterium tuberculosis infection populations, respectively (adjusted hazard ratio

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 = 1.23, with 95% confidence interval [CI] 1.03–1.47). In the stratified analysis, the Mycobacterium tuberculosis infection group were consistently associated with a higher risk of chronic fatigue syndrome in the male sex (HR = 1.27, 95% CI 1.02–1.58) and age group of ≥ 65 years old (HR = 2.50, 95% CI 1.86–3.38).

Conclusions
The data from this population‐based retrospective cohort study revealed that Mycobacterium tuberculosis infection is associated with an elevated risk of subsequent chronic fatigue syndrome.

Open access: https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03301-1

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[Andy]

The definition of disease in NHIRD is based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM).

Which would mean that the definition of CFS would be a clinical one, probably this, http://www.icd9data.com/2015/Volume1/780-799/780-789/780/780.71.htm

 

[CRG]

Higher risk in 65+ year old males ! I think there has to be some doubt as whether the authors are identifying CFS - or chronic fatigue that is part of some post infection syndrome. Even if using ICD10-CM as the disease definition, following infection specific cases may have difficulty separating a disease specific condition from what appears to be the far more ubiquitous ME/CFS.

 

[Hutan]

Yeah, tuberculosis destroys lung tissue and one reference I saw said that 50% of patients had permanent pulmonary dysfunction. So, not breathing well due to lung damage, maybe coupled with years of smoking and old age - it's going to look pretty much like a vaguely defined chronic fatigue syndrome in a lot of cases.

That said, I think it's quite possible that some people who get tuberculosis do get ME/CFS as a result. If they don't it would be good to know why they don't.

This is the bit about 'similar plasma signatures' - a description that oversells the limited observation I think:

Abnormal cytokine profiles such as increased production of interferon (IFN) γ were observed in patients with CFS [14] and latent MTI [15].

 

[Hutan]

Having got to the Discussion now, I see that there is more about possible similarities between CFS and people with TB on terms of 'plasma signatures' there. e.g.

Immunoinflammatory pathway activation is one of the most researched topics related to CFS [14, 16]. Immune activation markers in CFS include increased levels of proinflammatory cytokines such as TNF-α, IL-6, and IL-1β [27, 28]. In patients with TB, the interaction of M. tuberculosis ligands with Toll-like receptors eventually results in immune activation, including activated nuclear factor (NF) κB and TNF-α, IL-1, and IL-12 production through myeloid differentiation primary response protein 88-dependent or -independent pathways [29, 30]. Increased production of NF-κB, a major upstream molecule regulating immunoinflammatory response, is associated with fatigue and a subjective feeling of infection [31].

TNF-α, which is secreted by macrophages, dendritic cells, and T cells, plays a major protective role against MTI and transmits signals regulating immune cell migration to the infection sites [32] and the formation of microbicidal granulomas [33]. IL-1 and TNF-α levels are significantly positively correlated with fatigue, autonomic symptoms, and flu-like symptoms [34]. TNF-α inhibitors, a type of immunomodulator, has also been reported to alleviate fatigue symptoms in some autoimmune diseases [35, 36] and attenuate CFS risk in patients with psoriasis [37].

I want to come back and read more, but just thought I should acknowledge the detail in the Discussion. There may be some consistent findings of higher TNF-a in ME/CFS?

 

[Jonathan Edwards]

Immunoinflammatory pathway activation is one of the most researched topics related to CFS [14, 16]. Immune activation markers in CFS include increased levels of proinflammatory cytokines such as TNF-α, IL-6, and IL-1β [27, 28].

Three out of four citations are to Maes including the dreaded Morris & Maes review.
This is just plain wrong. A bot could do better having scanned the literature.