Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine

Abstract:

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated to infections and it has been suggested that vaccination can trigger the disease. However, little is known about the specific association between clinically manifest influenza/influenza vaccine and CFS/ME. As part of a registry surveillance of adverse effects after mass vaccination in Norway during the 2009 influenza A (H1N1) pandemic, we had the opportunity to estimate and contrast the risk of CFS/ME after infection and vaccination.

METHODS: Using the unique personal identification number assigned to everybody who is registered as resident in Norway, we followed the complete Norwegian population as of October 1, 2009, through national registries of vaccination, communicable diseases, primary health, and specialist health care until December 31, 2012. Hazard ratios (HRs) of CFS/ME, as diagnosed in the specialist health care services (diagnostic code G93.3 in the International Classification of Diseases, Version 10), after influenza infection and/or vaccination were estimated using Cox proportional-hazards regression.

RESULTS: The incidence rate of CFS/ME was 2.08 per 100,000 person-months at risk. The adjusted HR of CFS/ME after pandemic vaccination was 0.97 (95% confidence interval [CI]: 0.91-1.04), while it was 2.04 (95% CI: 1.78-2.33) after being diagnosed with influenza infection during the peak pandemic period.

CONCLUSIONS: Pandemic influenza A (H1N1) infection was associated with a more than two-fold increased risk of CFS/ME. We found no indication of increased risk of CFS/ME after vaccination. Our findings are consistent with a model whereby symptomatic infection, rather than antigenic stimulation may trigger CFS/ME.

Copyright © 2015 Elsevier Ltd. All rights reserved.

 

Source: Magnus P, Gunnes N, Tveito K, Bakken IJ, Ghaderi S, Stoltenberg C, Hornig M, Lipkin WI, Trogstad L, Håberg SE. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine. Vaccine. 2015 Nov 17;33(46):6173-7. doi: 10.1016/j.vaccine.2015.10.018. Epub 2015 Oct 17. https://www.ncbi.nlm.nih.gov/pubmed/26475444

 

Humoral and cellular immune responses after influenza vaccination in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a clinical condition characterized by severe and disabling fatigue that is medically unexplained and lasts longer than 6 months. Although it is possible to effectively treat CFS, the nature of the underlying physiology remains unclear. Various studies have sought evidence for an underlying disturbance in immunity. The aim of this study was to compare the humoral and cellular immune responses upon influenza vaccination in CFS patients and healthy controls.

RESULTS: Identical antibody titers were observed in CFS patients and healthy controls. Patients and controls demonstrated similar seroprotection rates against all three virus-strains of the influenza vaccine, both pre- and post-vaccination. Functional T cell reactivity was observed in both CFS patients and healthy controls. CFS patients showed a non-significant, numerically lower cellular proliferation at baseline compared to controls. Vaccination induced a significant increase in cellular proliferation in CFS patients, but not in healthy controls. Cytokine production and the number of regulatory T cells were comparable in patients and controls.

CONCLUSIONS: The humoral and cellular immune responses upon influenza vaccination were comparable in CFS patients and healthy controls. Putative aberrations in immune responses in CFS patients were not evident for immunity towards influenza. Standard seasonal influenza vaccination is thus justified and, when indicated, should be recommended for patients suffering from CFS.

 

Source: Prinsen H, de Vries IJ, Torensma R, Pots JM, Mulder SF, van Herpen CM, Elving LD, Bleijenberg G, Stelma FF, van Laarhoven HW. Humoral and cellular immune responses after influenza vaccination in patients with chronic fatigue syndrome. BMC Immunol. 2012 Dec 17;13:71. doi: 10.1186/1471-2172-13-71. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3534525/ (Full article)

 

Double-blind, randomized study of the effects of influenza vaccination on the specific antibody response and clinical course of patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To determine whether influenza immunization is associated with early side effects, a deleterious impact on the illness course and depressed antibody response in patients with chronic fatigue syndrome (CFS).

DESIGN: Prospective, randomized, double-blind, placebo controlled trial. CFS patients and healthy volunteers filled out a questionnaire on immunization side effects and had hemagglutination-inhibiting (HI) antibody titres measured pre- and three weeks after immunization. CFS patients completed symptom and function questionnaires before and during the six-week, postimmunization period.

SETTING: Ambulatory care.

POPULATION STUDIED: Convenience sample of 40 CFS patients fulfilling the Centers for Disease Control and Prevention criteria and 21 demographically matched healthy volunteers.

INTERVENTIONS: CFS patients were randomly selected to receive commercially available whole virus influenza vaccine (n=19) or an injection of saline placebo (n=21). Healthy volunteers received vaccine only.

MAIN RESULTS: As a group, immunized CFS patients had lower geometric mean HI antibody rises than healthy volunteers (P<0.001). However, there was no difference in the rates of fourfold titre rises, and immunization did achieve a probably protective titre (1:32 or greater) in most CFS patients. No difference could be detected between immunized and placebo CFS patients in immunization side effects, although CFS patients as a group reported four times as many side effects as healthy volunteers. Further, in the six weeks following immunization, placebo and immunized CFS patients did not demonstrate any differences in terms of functioning, symptom severity and sleep disturbance.

CONCLUSIONS: In patients with CFS, influenza immunization is safe, not associated with any excess early reactions, and stimulates an immunizing response comparable with that of healthy volunteers.

 

Source: Sleigh KM, Danforth DG, Hall RT, Fleming JA, Stiver HG. Double-blind, randomized study of the effects of influenza vaccination on the specific antibody response and clinical course of patients with chronic fatigue syndrome. Can J Infect Dis. 2000 Sep;11(5):267-73. https://www.ncbi.nlm.nih.gov/pubmed/18159300