The Qure study: Q fever fatigue syndrome--response to treatment; a randomized placebo-controlled trial.

Hans Knoop,Tom Sprong,Chantal P Bleeker-Rovers,Corine E Delsing,Gijs Bleijenberg,Stephan P Keijmel,Jos WM van der Meer

doi:10.1186/1471-2334-13-157

Abstract

BackgroundQ fever is a zoonosis that is present in many countries. Q fever fatigue syndrome (QFS) is one of the most frequent sequelae after an acute Q fever infection. QFS is characterized by persistent fatigue following an acute Q fever infection, leading to substantial morbidity and a high socio-economic burden. The occurrence of QFS is well-documented, and has been described in many countries over the past decades. However, a treatment with proven efficacy is not available. Only a few uncontrolled studies have tested the efficacy of treatment with antibiotics on QFS. These studies suggest a positive effect of long-term treatment with a tetracycline on performance state; however, no randomized controlled trials have been performed. Cognitive behavioral therapy (CBT) has been proven to be an effective treatment modality for chronic fatigue in other diseases, but has not yet been tested in QFS. Therefore, we designed a trial to assess the efficacy of long-term treatment with the tetracycline doxycycline and CBT in patients with QFS.Methods/designA randomized placebo-controlled trial will be conducted. One-hundred-eighty adult patients diagnosed with QFS will be recruited and randomized between one of three groups: CBT, long-term doxycycline or placebo. First, participants will be randomized between CBT and medication (ratio 1:2). A second double-blinded randomization between doxycycline and placebo (ratio 1:1) will be performed in the medication condition. Each group will be treated for six months. Outcome measures will be assessed at baseline and post intervention. The primary outcome measure is fatigue severity. Secondary outcome measures are functional impairment, level of psychological distress, and Coxiella burnetii PCR and serology.DiscussionThe Qure study is the first randomized placebo-controlled trial, which evaluates the efficacy of long-term doxycycline and of cognitive behavioral therapy in patients with QFS. The results of this study will provide knowledge about evidence-based treatment options for adult patients with QFS.Trial registrationClinicalTrials.gov: http://NCT01318356, and Netherlands Trial Register: NTR2797

Highlights

Q fever is a zoonosis that is present in many countries
The Qure study is the first randomized placebo-controlled trial, which evaluates the efficacy of longterm doxycycline and of cognitive behavioral therapy in patients with Q fever fatigue syndrome (QFS)
A study among abattoir employees in Australia showed that 28% of patients with proven acute Q fever fulfilled the Centre for Disease Control (CDC) criteria of chronic fatigue syndrome five years after the infection compared to none of the seronegative controls [10]

Summary

Introduction

Q fever is a zoonosis that is present in many countries. Q fever fatigue syndrome (QFS) is one of the most frequent sequelae after an acute Q fever infection. A study among abattoir employees in Australia showed that 28% of patients with proven acute Q fever fulfilled the CDC criteria of chronic fatigue syndrome five years after the infection compared to none of the seronegative controls [10]. Over 25% still had complaints after one year [12] Another recent survey in the Netherlands among 515 patients with Q fever found that 20% had severe fatigue and an impaired health status at 12–26 months of follow-up [13]. This fatigue following acute Q fever, sometimes accompanied by several other complaints, has been designated Q fever fatigue syndrome (QFS) [14,15,16]. Chronic Q fever and other causes of fatigue, somatic or psychiatric, need to be excluded

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