Are fatigue symptoms and chronic fatigue syndrome following Q fever infection related to psychosocial variables?

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Abstract

Objective

Fatigue is known as one of the most common long-term sequelae of Q fever infections. The study aimed to determine the prevalence of fatigue symptoms, chronic fatigue, and chronic fatigue syndrome (CFS) in a sample of patients who were exposed to Q fever (Coxiella burnetii) infection compared to controls, and to contrast Q fever patients with and without fatigue symptoms related to somatoform symptoms, hypochondriacal worries and beliefs, psychosocial complaints, and social support.

Methods

Cross-sectional study of 84 Q fever exposed patients from a specific region in Jena (Germany) and 85 matched controls using standardized questionnaires (MFI, SF-12, CDC-SI, SOMS, Whiteley Index, OQ-45 and F-Sozu). Diagnostic interviews were performed to validate questionnaire results in a smaller subsample.

Results

Patients who were exposed to a Q fever infection in the past indicated more fatigue symptoms and chronic fatigue than controls (54.8 vs. 20%, 32.1 vs. 4.7%) but did not show more criteria for a CFS (1 patient in each group). Q fever patients showing fatigue symptoms revealed significantly higher scores in the SOMS, the Whiteley-Index, and higher psychosocial complaints measured with the OQ-45. Their health related Quality of Life was reduced, no differences were found related to perceived social support.

Conclusion

Although in our sample fatigue symptoms were common among Q fever patients, we found no increased prevalence of CFS in contrast to several other studies. The combination of fatigue symptoms with other psychosocial symptoms/problems support the view of a biopsychosocial etiology of fatigue symptoms.

Introduction

Fatigue, especially chronic fatigue and the Chronic Fatigue Syndrome (CFS), are highly relevant conditions in psychosomatic medicine both, from a clinical as well as from a research perspective. Until today, the etiology of the CFS and of fatigue syndromes is insufficiently explained [1]. Different origins of the CFS have been discussed during the last 30 years: Immunological dysfunctions, neuroendocrine disturbances, dysfunctions of the CNS and infections (among them EBV, Parvo-virus B19, and since 2009, retrovirus XMRV) were hypothesized [2]. No physical cause has been established to date. Currently, the lack of a somatic cause for the fatigue is the most crucial criterion for the diagnosis of the CFS [3].

Nevertheless, CFS has been linked with a variety of other organic diseases in the past (e.g. [[4], [5]]), amongst them Q (query) fever. Q fever, initially described in 1937 by Edward Derrick [6], is a zoonosis with many manifestations, among them influenza-like illness with pneumonia and hepatitis. The intracellular organism C. burnetii is necessary for the diagnosis of Q fever infections. Q fever outbreaks were commonly observed when individuals were exposed to cattle, sheep or goats. Most Q fever infections result from inhalation of infectious aerosol particles from parturient animals [7].

Meanwhile, a large number of studies from different countries (e.g. Australia, England, Japan, Croatia, Canada) were published indicating an increased amount of fatigue symptoms and/or CFS following Q fever infections [8], [9], [10], [11]. Besides cardiovascular disease [12], post Q fever fatigue syndrome is seen as the most important long-term sequelae of the infection, causing considerable emotional and socioeconomic effects.

In a recent review of the situation in The Netherlands, where at least 4000 Q fever cases have already been registered, patients diagnosed 1 year after their initial infection showed a rate of 50% patients suffering from severe fatigue symptoms (compared to 26% of the control group, [13]). Other studies report prevalence rates of CFS following Q fever of 19.2% compared to 4% in control groups 10 years after the exposure (in the UK [14]). Australian studies indicated an average frequency of CFS of 28% after 5 years [5]. In the study of Wildman et al. [14], investigators differentiated between fatigue symptoms, idiopathic chronic fatigue (ICF) and CFS. They reported prevalence rates of 64.9% for fatigue, 32.5% for ICF and 19.2% CFS, reflecting the need for differential assessment.

Several studies indicated that a considerable proportion of Q fever patients treated with antibiotics still suffered from CFS which contradicts the assumption of a direct relationship between C. burnetii and CFS [e.g. 15]. In general, the association between Q fever infection and fatigue symptoms is incompletely explained. Some authors assume that a dysregulation of cytokines (increased IL-6 release, e.g. [7]) or impaired immune functions in general might be associated with CFS [16], [17], [18], while others think that the persistence of C. burnetii organisms (antigenic non-viable cell residues) in the host's bone-marrow [19], [20], changes of immunogenetics [21], [22], or concurrent cardiovascular problems might account for post Q fever fatigue.

Interestingly, although many studies indicate fatigue and CFS, only a few studies included psychosocial variables into the assessment of Q fever patients. Some registered accompanying psychological symptoms, such as anxiety and depression (e.g. [23]) that have been shown to improve faster than fatigue. Other studies assessed the quality of life (QoL) of Q fever patients indicating impaired QoL in a large amount of patients (e.g. 44.9% in a recent Dutch study [24]).

Although no somatic cause has been established for CFS, it has been repeatedly shown that psychological processes play a role in the persistence of fatigue symptoms in CFS. These psychological processes involve persistent low levels of physical activity or low levels of activity alternated with bursts of activity, the attribution of symptoms to a physical cause, low self-efficacy, and focusing on bodily symptoms [25].

Based upon the high prevalence of fatigue symptoms and syndromes related to Q fever infections, this clinical picture has a specific potential to investigate interactions between biological and psychosocial processes that might be related to chronic (post infection) fatigue. Considering the fact that the formal criteria for CFS state that no somatic cause for the fatigue may be present, the diagnosis CFS by definition cannot be established in patients with prolonged fatigue following a documented Q fever infection. On the other hand, some authors criticize the restrictive criteria of the current CFS definition. Because of the wide variety of pathogenetic mechanisms, the discrimination of subgroups of CFS (e.g. post infection fatigue syndrome, chronic fatigue syndrome, immuno-stimulation syndrome) is reasonable. Under the assumption that CFS is dynamically related to fatigue and chronic fatigue it also seemed reasonable to investigate if Q fever patients with prolonged fatigue can be classified as cases of chronic fatigue or idiopathic chronic fatigue.

Within this study, we wanted to investigate if fatigue symptoms and/or chronic fatigue (syndromes) can be more frequently assessed in a subsample of a population who was infected during an outbreak of Q fever in a determined region compared to a non-infected control group. In addition, Q fever patients with fatigue should be contrasted to patients without symptoms with respect to a variety of psychosocial measures such as somatoform symptoms, health related quality of life, hypochondriacal worries and beliefs, psychosocial complaints, and social support.

The study was related to a sample of Q fever patients in a district of the city of Jena (Winzerla) in Germany, all living less than 400 m away from a sheep run, where a flock of 500 sheep gazed and 35 lambs were born. It is assumed that inadequate disposal of birth products have caused Q fever infections in about 75% of the persons living within a radius of less than 400 m from the sheep. The outbreak can be considered as one of the largest ever in Germany (cf. [26]).

Section snippets

Sample

From 331 registered patients with Q fever, 221 could be contacted via their GPs (a total of 5) approximately 2 years after the outbreak. A complete list of all 331 patients was not accessible due to data protection rules. 84 patients (38%) could be motivated to participate in the study which was approved by the Ethics Committee of the University Hospital Jena. A similar amount of participating patients was reached by Hatchette et al. [27] who interviewed Q fever patients both, 3 and 27 months

Fatigue, chronic fatigue and CFS

To determine the prevalence of fatigue, chronic fatigue and CFS we used the MFI-20 and some additional questions, the SF12 as well as the CDC-SI measure. Patients in both groups were classified as indicating relevant fatigue symptoms if their MFI-20 scores were over the 75th percentile of a German norm population for the subscales “general fatigue” and/or “reduced activity”. In addition, either the score on the physical and/or the mental component summary of the SF-12 had to lie below the 25th

Discussion

A large number of studies from different countries have shown increased rates of fatigue symptoms and CFS as long-term sequelae of Q fever infections. The reported rates of CFS [8], [9], [10], [11], [12], [13] are considerably higher than those in a normal population which are estimated to range between 0.2 and 2.5% [38]. The reported study is the first investigating a group of patients 2 years after Q fever infection in Germany and probably the first that systematically included psychosocial

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