Q fever, a zoonosis caused by
Coxiella burnetii, has been present all over the world for many years [
1]. Between 2007 and 2010, the south-eastern part of the Netherlands has faced the largest outbreak of Q fever ever reported. To date, more than 4000 people have developed symptomatic disease [
2], and at least up to 44,000 are estimated to have been infected [
3,
4]. In recent years, several studies have described the sequelae of Q fever. Acute Q fever is followed by a chronic infection in 1-5% of cases [
5‐
7]. In addition, following acute Q fever, patients frequently report long-lasting fatigue, which often persists for more than six months [
8‐
10]. After an outbreak of Q fever in the UK, 10 years of follow-up revealed a high percentage of persisting fatigue, with almost 20% of patients fulfilling the Centre for Disease Control (CDC) criteria of chronic fatigue syndrome, compared to 4% in healthy controls [
11]. 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]. A recent study carried out in the Netherlands among 85 patients with acute Q fever found that 59% of patients had persistent symptoms at six months after disease onset, with fatigue being the most prevalent complaint in 52% of patients. Furthermore, 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‐
16]. According to the recently published Dutch algorithm on QFS [
14], the diagnosis of QFS can be made after a uniform diagnostic work-up. There has to be a severe fatigue, which lasts for at least six months and has a reference to an acute Q fever infection. There must be an absence of fatigue before the episode of acute Q fever or a significant increase in fatigue since the acute Q fever infection. Furthermore, it is causing significant disabilities in daily practice. Finally, chronic Q fever and other causes of fatigue, somatic or psychiatric, need to be excluded.
In the Netherlands, QFS resulted in a large incurred loss due to loss of quality of life and health-related absenteeism in the past few years [
17]. Currently, extrapolating the present data, at least 800 patients suffer from QFS in the Netherlands. It is expected that Q fever will remain an endemic disease, leading to a further increase in patients with QFS, stressing the need for further research into treatment regimens for QFS.
Both acute and chronic Q fever have been extensively studied in recent years; however, less attention has been given to QFS. Although QFS is a well documented finding and has already been described in 1996 [
8,
10], at present there is no consensus on the pathogenetic process underlying QFS [
15,
18,
19]. In QFS, as in chronic fatigue syndrome, persistence of live microbes has been suggested [
19]. Furthermore, it is still unclear whether effective treatment for QFS is possible. So far, few studies on the effect of treatment with antibiotics on fatigue after Q fever have been done. The available studies suggest a positive effect of long-term treatment with a tetracycline on performance status [
20‐
22]; however, these studies suffer from several limitations. So far, no controlled trials have been performed and the above long-term treatment is currently not often used in clinical care of patients with QFS. Previously, it has been shown in patients with chronic fatigue syndrome (CFS) that fatigue-related cognitions and behavior can maintain chronic fatigue [
23‐
26]. CBT for chronic fatigue is aimed at these fatigue-related cognitions and behavior thought to perpetuate the symptoms. Several systematic reviews and meta analyses demonstrated that CBT for CFS is able to reduce symptoms and to improve function in patients with CFS [
26‐
28]. To date, the efficacy of CBT has not been studied in patients with QFS. However, our recent clinical experience with this treatment modality in a small cohort of QFS patients shows promising results.
The primary aim of our study is to determine the effect of different treatment modalities which have been suggested to be effective for patients with QFS. In this paper we describe the protocol to assess the efficacy of two treatment strategies for QFS: long-term treatment with either doxycycline or CBT.