Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease

Abstract:

The etiology of myalgic encephalomyelitis also known as chronic fatigue syndrome or ME/CFS has not been established. Controversies exist over whether it is an organic disease or a psychological disorder and even the existence of ME/CFS as a disease entity is sometimes denied. Suggested causal hypotheses have included psychosomatic disorders, infectious agents, immune dysfunctions, autoimmunity, metabolic disturbances, toxins and inherited genetic factors.

Clinical, immunological and epidemiological evidence supports the hypothesis that: ME/CFS is an infectious disease; the causal pathogen persists in patients; the pathogen can be transmitted by casual contact; host factors determine susceptibility to the illness; and there is a population of healthy carriers, who may be able to shed the pathogen.

ME/CFS is endemic globally as sporadic cases and occasional cluster outbreaks (epidemics). Cluster outbreaks imply an infectious agent. An abrupt flu-like onset resembling an infectious illness occurs in outbreak patients and many sporadic patients. Immune responses in sporadic patients resemble immune responses in other infectious diseases.

Contagion is shown by finding secondary cases in outbreaks, and suggested by a higher prevalence of ME/CFS in sporadic patients’ genetically unrelated close contacts (spouses/partners) than the community. Abortive cases, sub-clinical cases, and carrier state individuals were found in outbreaks.

The chronic phase of ME/CFS does not appear to be particularly infective. Some healthy patient-contacts show immune responses similar to patients’ immune responses, suggesting exposure to the same antigen (a pathogen). The chronicity of symptoms and of immune system changes and the occurrence of secondary cases suggest persistence of a causal pathogen.

Risk factors which predispose to developing ME/CFS are: a close family member with ME/CFS; inherited genetic factors; female gender; age; rest/activity; previous exposure to stress or toxins; various infectious diseases preceding the onset of ME/CFS; and occupational exposure of health care professionals. The hypothesis implies that ME/CFS patients should not donate blood or tissue and usual precautions should be taken when handling patients’ blood and tissue. No known pathogen has been shown to cause ME/CFS.

Confirmation of the hypothesis requires identification of a causal pathogen. Research should focus on a search for unknown and known pathogens. Finding a causal pathogen could assist with diagnosis; help find a biomarker; enable the development of anti-microbial treatments; suggest preventive measures; explain pathophysiological findings; and reassure patients about the validity of their symptoms.

 

Source: Underhill RA. Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease. Med Hypotheses. 2015 Dec;85(6):765-73. Epub 2016 Oct 19. https://www.ncbi.nlm.nih.gov/pubmed/26604026

 

Immunity and the pathophysiology of chronic fatigue syndrome

Abstract:

The pathophysiology of chronic fatigue syndrome (CFS) remains unknown. The syndrome often follows a recognized or presumed infection and the disorder may therefore result from a disordered immune response to a precipitating infection or antigenic challenge.

Abnormalities of both humoral and cellular immunity have been demonstrated in a substantial proportion of patients with CFS. The most consistent findings are of impaired lymphocyte responses to mitogen and reduced natural killer cell cytotoxicity. Cutaneous anergy and immunoglobulin G subclass deficiencies have also been found.

Further studies are needed examining cytokine levels in serum and cerebrospinal fluid, and cytokine production in vitro in patients with CFS. Interpretation of the findings of published studies of immunity is limited by probable heterogeneity in the patient groups studied, and by the lack of standardization and reproducibility in the assays used.

The pattern of abnormalities reported in immunological testing in patients with CFS is consistent with the changes seen during the resolving phases of acute viral infection. These data provide circumstantial support for the hypothesis that CFS results from a disordered immune response to an infection. Longitudinal studies of immunity in patients developing CFS after defined infectious illnesses will provide the best means of further examining this hypothesis.

 

Source: Lloyd AR, Wakefield D, Hickie I. Immunity and the pathophysiology of chronic fatigue syndrome. Ciba Found Symp. 1993;173:176-87; discussion 187-92. http://www.ncbi.nlm.nih.gov/pubmed/8491097

 

Follow up of patients presenting with fatigue to an infectious diseases clinic

Abstract:

OBJECTIVES: To determine the symptomatic and functional status during follow up of patients referred to hospital with unexplained fatigue and to identify patient variables associated with persistent functional impairment.

DESIGN: Follow up by postal questionnaire six weeks to four years (median 1 year) after initial clinical assessment of patients referred to hospital during 1984-8.

SETTING: Infectious diseases outpatient clinic in a teaching hospital.

PATIENTS: 200 consecutive patients with fatigue of uncertain cause for at least six weeks; 177 fulfilled the inclusion criteria.

MAIN OUTCOME MEASURES: Findings at initial assessment; current symptoms, beliefs about the cause of illness, coping behaviours emotional disorder, social variables including membership of self help organizations, and degrees of recovery and functional impairment from questionnaire responses.

RESULTS: 144 (81%) patients returned completed questionnaires. Initial assessment did not indicate the cause of fatigue, other than preceding infection. The proportion of patients with functional impairment was significantly smaller with longer follow up (33% (11/33) at two to four years, 73% (29/40) at six weeks to six months; chi 2 for trend = 12.5, df = 1; p less than 0.05). Functional impairment was significantly associated with belief in a viral cause of the illness (odds ratio = 3.9; 95% confidence interval 1.5 to 9.9), limiting exercise (3.2; 1.5 to 6.6), avoiding alcohol (4.5; 1.8 to 11.3), changing or leaving employment (3.1; 1.4 to 6.9), belonging to a self help organization (7.8; 2.5 to 23.9), and current emotional disorder (4.4; 2.0 to 9.3).

CONCLUSIONS: Short term prognosis for recovery of function was poor but improved with time. Most patients had made a functional recovery by two years after initial clinic attendance. Impaired functioning was more likely with certain patient characteristics. Prospective studies are required to clarify whether these associations are the consequences of a more disabling illness or indicate factors contributing to impaired function.

Comment in

Outcome in the chronic fatigue syndrome. [BMJ. 1992]

Outcome in the chronic fatigue syndrome. [BMJ. 1992]

Outcome in the chronic fatigue syndrome. [BMJ. 1992]

 

Source: Sharpe M, Hawton K, Seagroatt V, Pasvol G. Follow up of patients presenting with fatigue to an infectious diseases clinic. BMJ. 1992 Jul 18;305(6846):147-52. http://www.ncbi.nlm.nih.gov/pubmed/1515828

Note: You can read the full article herehttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1883193/