Effectiveness of Long-term Doxycycline Treatment and Cognitive-Behavioral Therapy on Fatigue Severity in Patients with Q Fever Fatigue Syndrome (Qure Study): A Randomized Controlled Trial

Clin Infect Dis. 2017 Apr 15;64(8):998-1005. doi: 10.1093/cid/cix013.


Background: Approximately 20% of patients with acute Q fever will develop chronic fatigue, referred to as Q fever fatigue syndrome (QFS). The objective of this randomized controlled clinical trial was to assess the efficacy of either long-term treatment with doxycycline or cognitive-behavioral therapy (CBT) in reducing fatigue severity in patients with QFS.

Methods: Adult patients were included who met the QFS criteria according to the Dutch guideline: a new onset of severe fatigue lasting ≥6 months with significant disabilities, related to an acute Q fever infection, without other somatic or psychiatric comorbidity explaining the fatigue. Using block randomization, patients were randomized between oral study medication and CBT (2:1) for 24 weeks. Second, a double-blind randomization between doxycycline (200 mg/day, once daily) and placebo was performed in the medication group. Primary outcome was fatigue severity at end of treatment (EOT; week 26), assessed with the Checklist Individual Strength subscale Fatigue Severity.

Results: Of 155 patients randomized, 154 were included in the intention-to-treat analysis (doxycycline, 52; placebo, 52; CBT, 50). At EOT, fatigue severity was similar between doxycycline (40.8 [95% confidence interval {CI}, 37.3-44.3]) and placebo (37.8 [95% CI, 34.3-41.2]; difference, doxycycline vs placebo, -3.0 [97.5% CI, -8.7 to 2.6]; P = .45). Fatigue severity was significantly lower after CBT (31.6 [95% CI, 28.0-35.1]) than after placebo (difference, CBT vs placebo, 6.2 [97.5% CI, .5-11.9]; P = .03).

Conclusions: CBT is effective in reducing fatigue severity in QFS patients. Long-term treatment with doxycycline does not reduce fatigue severity in QFS patients compared to placebo.

Clinical trials registration: NCT01318356.

Keywords: Coxiella burnetii; Q fever fatigue syndrome.; cognitive-behavioral therapy; doxycycline; placebo.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / therapeutic use*
  • Cognitive Behavioral Therapy / methods*
  • Double-Blind Method
  • Doxycycline / therapeutic use*
  • Fatigue Syndrome, Chronic / therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Netherlands
  • Placebos / administration & dosage
  • Q Fever / complications*
  • Treatment Outcome
  • Young Adult


  • Anti-Bacterial Agents
  • Placebos
  • Doxycycline

Associated data

  • ClinicalTrials.gov/NCT01318356