Are fatigue symptoms and chronic fatigue syndrome following Q fever infection related to psychosocial variables?
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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Explaining the long-term impact of chronic Q fever and Q fever fatigue syndrome on psychosocial functioning: A comparison with diabetes and the general population
2019, Journal of Psychosomatic ResearchCitation Excerpt :This condition is characterized by debilitating fatigue, persisting for >6 months, often with additional complaints, such as muscle and joint aches, night sweats and loss of concentration [4,5]. Previous research examined the health status of Q fever patients two to four years after acute infection and found higher levels of fatigue and an impaired quality of life compared to a healthy reference group [6,7]. However, these studies did not distinguish whether patients suffered from chronic Q fever, QFS or neither.
Post-bacterial infection chronic fatigue syndrome is not a latent infection
2019, Medecine et Maladies InfectieusesCitation Excerpt :Patients presenting with QFS were described as differing in the frequency of HLA-DRB1*11 carriage and the 2/2 genotype of the IFNγ intron 1 microsatellite when compared with controls [17]. In addition, cytokine release pattern of peripheral blood monocyte cells of QFS patients was reported as aberrant with an increased IL-6 release, a decreased level of IL2 release, and an increased INFγ and CXCL10 production [18]. Just like PTLDS, it is unknown whether QFS is a direct consequence of the non-viable or viable bacteria or if its origin is psychological.
A comparison of patients with Q fever fatigue syndrome and patients with chronic fatigue syndrome with a focus on inflammatory markers and possible fatigue perpetuating cognitions and behaviour
2015, Journal of Psychosomatic ResearchCitation Excerpt :One study determined the prevalence of CFS in patients with Q fever compared to a healthy control group. In both groups only one patient met these criteria, although a substantial proportion of the patients with Q fever was chronically fatigued [12]. Little is known about the aetiology of QFS.
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