title: Coxiella burnetii dormancy in a fatal ten-year multisystem dysfunctional illness: case report.
abstract: BACKGROUND
  In a previous study of a Q fever outbreak in Birmingham, our group identified a non-infective complex of Coxiella burnetii (C.b.) antigens able to survive in the host and provoked aberrant humoral and cell-mediated immunity responses. The study led to recognition of a possible pathogenic link between C.b. infection and subsequent long-term post Q fever fatigue syndrome (QFS). This report presents an unusually severe case of C.b. antigen and DNA detection in post-mortem specimens from a patient with QFS.
  
  
  METHODS
  We report a 19-year old female patient who became ill with an acute unexplained febrile encephalitis-like illness, followed by increasingly severe multisystem dysfunction and death 10 years later. During life, extensive clinical and laboratory investigations from different disciplinary stand points failed to deliver a definitive identification of a cause. Given the history of susceptibility to infection from birth, acute fever and the diagnosis of "post viral syndrome", tests for infective agents were done starting with C.b. and Legionella pneumophila. The patient had previously visited farms a number of times. Comprehensive neuropathological assessment at the time of autopsy had not revealed gross or microscopic abnormalities. The aim was to extend detailed studies with the post-mortem samples and identify possible factors driving severe disturbance of homeostasis and organ dysfunction exhibited by the course of the patient's ten-year illness. Immunohistochemistry for C.b. antigen and PCR for DNA were tested on paraffin embedded blocks of autopsy tissues from brain, spleen, liver, lymph nodes (LN), bone marrow (BM), heart and lung. Standard H&E staining of brain sections was unrevealing. Immuno-staining analysis for astrocyte cytoskeleton proteins using glial fibrillary acidic protein (GFAP) antibodies showed a reactive morphology. Coxiella antigens were demonstrated in GFAP immuno-positive grey and white matter astrocytes, spleen, liver, heart, BM and LN. PCR analysis (COM1/IS1111 genes) confirmed the presence of C.b. DNA in heart, lung, spleen, liver & LN, but not in brain or BM.
  
  
  CONCLUSIONS
  The study revealed the persistence of C. b. cell components in various organs, including astrocytes of the brain, in a post-infection QFS. The possible mechanisms and molecular adaptations for this alternative C.b. life style are discussed.
authors.affiliation: Q Fever Research Group (1993-2009), Hanson Institute, Adelaide, South Australia.|School of Health Sciences, Flinders University, Bedford Park, South Australia.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Sukocheva
authors.affiliation: Centre for Neurological Diseases, SA Pathology, Adelaide, South Australia.
authors.forename: Jim
authors.initials: J
authors.lastname: Manavis
authors.affiliation: School of Biological Sciences, University of Adelaide, Adelaide, South Australia. tuckweng.kok@adelaide.edu.au.
authors.forename: Tuck-Weng
authors.initials: TW
authors.lastname: Kok
authors.affiliation: Microbiology and Infectious Diseases Laboratory, SA Pathology, Adelaide, South Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Turra
authors.affiliation: Colorado State University, Colorado, USA.
authors.forename: Angelo
authors.initials: A
authors.lastname: Izzo
authors.affiliation: Centre for Neurological Diseases, SA Pathology, Adelaide, South Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Blumbergs
authors.affiliation: Q Fever Research Group (1993-2009), Hanson Institute, Adelaide, South Australia.|Microbiology and Infectious Diseases Laboratory, SA Pathology, Adelaide, South Australia.
authors.forename: Barrie P
authors.initials: BP
authors.lastname: Marmion
mesh_terms: D000208:Acute Disease; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D001853:Bone Marrow / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016997:Coxiella burnetii / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D016133:Polymerase Chain Reaction; D011778:Q Fever / Q000175:diagnosis* / Q000473:pathology; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D004269:DNA, Bacterial
keywords: Antigen persistence; Chronic fatigue syndrome; Q Fever