Intended for healthcare professionals


Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study

BMJ 2006; 333 doi: (Published 14 September 2006) Cite this as: BMJ 2006;333:575
  1. Ian Hickie, psychiatrist1,
  2. Tracey Davenport, biostatistician1,
  3. Denis Wakefield, immunologist2,
  4. Ute Vollmer-Conna, psychologist3,
  5. Barbara Cameron, research fellow2,
  6. Suzanne D Vernon, molecular virologist4,
  7. William C Reeves, epidemiologist4,
  8. Andrew Lloyd (a.lloyd{at}, infectious diseases physician Dubbo Infection Outcomes Study Group2
  1. 1 Brain and Mind Research Institute, Sydney University, Sydney, NSW 2050, Australia,
  2. 2School of Medical Sciences, University of New South Wales, Sydney, NSW 2052,
  3. 3School of Psychiatry, University of New South Wales,
  4. 4Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, GA 31033, USA
  1. Correspondence to: A Lloyd
  • Accepted 2 August 2006


Objective To delineate the risk factors, symptom patterns, and longitudinal course of prolonged illnesses after a variety of acute infections.

Design Prospective cohort study following patients from the time of acute infection with Epstein-Barr virus (glandular fever), Coxiella burnetii (Q fever), or Ross River virus (epidemic polyarthritis).

Setting The region surrounding the township of Dubbo in rural Australia, encompassing a 200 km geographical radius and 104 400 residents.

Participants 253 patients enrolled and followed at regular intervals over 12 months by self report, structured interview, and clinical assessment.

Outcome measures Detailed medical, psychiatric, and laboratory evaluations at six months to apply diagnostic criteria for chronic fatigue syndrome. Premorbid and intercurrent illness characteristics recorded to define risk factors for chronic fatigue syndrome. Self reported illness phenotypes compared between infective groups.

Results Prolonged illness characterised by disabling fatigue, musculoskeletal pain, neurocognitive difficulties, and mood disturbance was evident in 29 (12%) of 253 participants at six months, of whom 28 (11%) met the diagnostic criteria for chronic fatigue syndrome. This post-infective fatigue syndrome phenotype was stereotyped and occurred at a similar incidence after each infection. The syndrome was predicted largely by the severity of the acute illness rather than by demographic, psychological, or microbiological factors.

Conclusions A relatively uniform post-infective fatigue syndrome persists in a significant minority of patients for six months or more after clinical infection with several different viral and non-viral micro-organisms. Post-infective fatigue syndrome is a valid illness model for investigating one pathophysiological pathway to chronic fatigue syndrome.


  • Embedded ImageOther members of the Dubbo Infection Outcomes Study Group are listed on

    We gratefully acknowledge the support of the general practitioners and the diagnostic pathology services in the Dubbo region and the enduring cooperation of the participants in the research. Other members of the Dubbo Infection Outcomes Study Group are listed on

  • Contributors IH, TD, UV-C, BC, and AL designed and implemented the Dubbo infection outcomes study. SDV and WCR contributed to data analysis and manuscript preparation. All authors commented on and approved the final draft. AL is the guarantor.

  • Funding The Dubbo infection outcomes study is funded by project grants from the National Health and Medical Research Council of Australia (No 157092 and No 157062), by Meat & Livestock, Australia, and by a cooperative research agreement with the Centers for Disease Control and Prevention, USA (No U50/CCU019851-01). The researchers involved in this study were independent of the funding agencies, with the exception of SDV and WCR, who are employees of the Centers for Disease Control, USA.

  • Competing interests None declared.

  • Ethical approval Human research ethics committees of the University of New South Wales and the Orana and Far West Area Health Service.

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