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

Abstract

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.

Fig 1

Survival curves of post-infective fatigue syndrome by infective agent after onset of acute infection. Kaplan-Meier analyses of proportion of participants within each infective subcohort who remained as cases. Test of equality across groups: χ²=3.45, df=3, P>0.05

Fig 2

Pattern of change in individual symptom factors in participants with and without post-infective fatigue syndrome. Median (horizontal bar) and 25th/75th centiles (box extremities) of normalised factor scores for six symptom domains in confirmed cases of post-infective fatigue syndrome cases (orange boxes; n=28) and those who recovered more promptly (white boxes; n=225)

Fig 3

Differential rates of resolution of individual symptom factors after acute infection. Scores on each of six symptom factors for each participant (n=229) over 12 months in three divided time periods, calculated from factor analysis. Mean symptom scores standardised (to ensure comparability) by dividing the mean at each time point for each factor by its mean at baseline. Each bar represents gradient of resolution of factor scores between each time point of assessment. ^*Period of non-resolution of individual symptom domain between two time points of assessment (that is, gradient=0)