Need for developing case definitions and guidelines for fatigue as an adverse event following immunization:

Fatiguing illnesses, including chronic fatigue syndrome (CFS), following infection are well-documented [1], [2], [3], [4], [5]. Fatigue and related symptoms following immunization have also been described, and the role of immunization as a causative factor in CFS has been hypothesized [6], [7], [8], [9], [10]. Similar to the post-infection setting, post-immunization fatigue is not likely to be limited to the syndrome designated as CFS, as short-lived fatigue states are far more common and transiently disabling. The term “acute fatigue” as defined by Fukuda et al. in 1994 refers to the symptom when it has been present for less than 1 week, “transient fatigue” when it has been present for 1 week to less than 1 month, “prolonged fatigue” if present for 1 month to less than 6 months, and chronic fatigue if present for 6 or more consecutive months [11]. Although standardized case definitions for the study of CFS have been developed previously [11], [12], [13], the Brighton Collaboration identified the need for a case definition which covers the broad range of fatigue states applicable to immunization safety, because: (a) fatigue itself (which may or may not fulfill all of the diagnostic criteria for CFS which are rarely available in vaccine safety surveillance or trials), has not been previously defined in a standardized way; (b) previous criteria did not accommodate the varied availability of data in different study settings; and (c) guidelines for the standardized collection, analysis, and presentation of data on fatigue following immunization have not previously been developed to improve comparability of such data.

This paper lists, in Sections 2 Case definition of fatigue, 3 Guidelines for data collection, analysis, and presentation of fatigue, respectively, the case definition and guidelines for data collection, analysis, and presentation that the Working Group has developed for the standardized collection and assessment of fatigue with applicability in study settings with different availability of resources and access to health care. Widespread use of this definition with its guidelines in studies focussing on fatigue as an AEFI will enable data comparability and lead to a better understanding of this event in the context of immunization.

1.2. Methods for the development of the case definition and guidelines for fatigue as an adverse event following immunization
Following the process described in the overview paper in this volume [14], a Brighton Collaboration Fatigue Working Group was formed in June 2003 with 16 members from clinical, public health, and professional organizations. This working group benefited from participation of many of the same scientists who were instrumental in developing previously standardized case definitions for CFS [11], [12], [13]. The member composition and results of the web-based survey completed by the reference group with subsequent discussions in the working group can be viewed at: http://brightoncollaboration.org/internet/en/index/working_groups.html.

To guide decision-making for the case definition and guidelines, a systematic literature search was conducted for the Brighton Collaboration by a professional search person from the Cochrane Collaboration (http://www.cochrane.org/) to identify English and non-English citations addressing fatigue following immunization. Sources included the Cochrane Library (Issue 3, 2003), MEDLINE (OvidWeb 1966-August week 1 2003) and EMBASE (OvidWeb 1980–2003 Week 33). Search terms used for fatigue were: muscle fatigue, mental fatigue, lethargy, weary or weariness, tired, exhausted, lassitude, lack energy. Search terms for CFS were: fatigue syndrome, chronic, neurasthenia, neurocirculatory asthenia, chronic fatigue immune dysfunction, myalgic encephalomyelitis, post viral fatigue or postviral fatigue or post-viral fatigue, infectious mononucleosis, infectious mononucleosis like, glandular fever, whiplash syndrome, whiplash, royal free disease, Iceland disease, chronic Epstein Barr or chronic Epstein-Barr, Epstein-Barr viruses, Yuppie flu or yuppy flu, ME and chronic, CFIDS or CFS, neuromyasthenia. Search terms for immunization included: vaccine, vaccination, and inoculation. The literature search for fatigue and immunization resulted in 678 articles, of which 100 were selected for further review, and in 753 articles for chronic fatigue syndrome and immunizations, of which 37 were selected. Articles were selected based on a review of the title and abstract to include information on defining fatigue or chronic fatigue in humans. Each article was summarized to include information on demographics of the vaccinee, accompanying signs or symptoms of the fatigue, and which case definition criteria were used, if any, from previously published CFS definitions.

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