Q fever: persistence of antigenic non-viable cell residues of Coxiella burnetii in the host--implications for post Q fever infection fatigue syndrome and other chronic sequelae

Abstract

All specimens, including a recently excised heart valve from a Birmingham patient with late developing endocarditis, were infection negative in SCID mice. Dilutions of SCID mouse spleen and liver homogenates titrated in PCR assays were negative at dilutions attained by control mice inoculated with an endpoint dilution of a viable prototype strain of C. burnetii. Sections of the spleens from all specimens showed a complex of coxiella antigen-LPS by IFA. DISCUSSION/REVIEW: We advance a concept of long-term persistence of a non-infective, non-biodegraded complex of coxiella cell components with its antigens and specific LPS [so called Immunomodulatory complex (IMC)] associated with traces of genomic DNA that signalled its presence in our earlier studies. The IMC's survival in patients for at least 12 years, and in one patient for 70 years implies a capacity for serial passage in macrophages with effective down-regulation of their biodegrading functions. The review assesses the compatibility of the IMC concept in relation to cogent literature on C. burnetii interactions with macrophage and cell-mediated immunity. Some remaining gaps in our knowledge of the organ sites and duration of carriage of viable coxiellas after initial infection are also identified.

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

“…Several hypotheses regarding the etiology of QFS exist, varying from a biopsychological etiology with C. burnetii acting as trigger for fatigue development [6] and the determination of symptoms by host and genetic factors [36], to cytokine dysregulation, supported by low levels of C. burnetii DNA found in bone marrow aspirates, thin-needle liver biopsies, and blood mononuclear cells [37][38][39]. In addition, it should be noted that prevalence of chronic fatigue differs between studies in different countries [40].…”

Role of Infection and Neurologic Dysfunction in Chronic Fatigue Syndrome

“…185 A condition very similar to CFS has been described following Q fever, and is associated with the persistence of bacterial antigen. 186,187 Cytokine dysregulation has been reported in these patients and could explain the symptoms. 188 …”

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

“…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.…”