The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

Abstract

Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival

“…Our data point to functionally connected genes and pathways involved in innate immunity responses as differentially expressed in the CFS group and might suggest less efficient viral clearance or reactivation of latent viruses such as members of the herpes virus family, in the CFS group [79]. Of note, the herpes virus Epstein-Barr virus (EBV) is a well-known trigger of CFS in adolescents [80].…”

A novel mutation in Slc2a4 as a mouse model of fatigue

“…Mice from two N ‐ethyl‐ N ‐nitrosourea (ENU) lines show abnormal, low amplitude voluntary wheel‐running activity patterns. Circadian activity patterns are double plotted for ease of visualization, with each horizontal line representing 48 hours and successive days plotted along the Y‐axis. Wheel revolutions are depicted as black marks on the horizontal lines.…”

“…Excessive fatigue affects subsections of the population and results in diminished daily functioning and quality of life . Fatigue can be a symptom or side effect of various diseases and disorders (or their treatments) but can also manifest independently from other comorbidities . In order for new treatments of fatigue to be identified and developed, informative animal models of human fatigue are crucial.…”

A Novel Nutriceutical Treatment of Myalgic Encephalitis/Chronic Fatigue Syndrome (ME/CFS): “What it is and what it is not”

“…The examples described herein included hidden focal (bacterial) infection, active viral disease [24], hormone deregulation with severe osteoporosis or with hypoandrogenism, and the burn-out syndrome. These patients should be classified as suffering from "ME/CFSnondisease", and they require a different therapeutic approach.…”