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Coxiella burnetii dormancy in a fatal ten-year multisystem dysfunctional illness: case report.

Sukocheva OA, Manavis J, Kok TW, Turra M, Izzo A, Blumbergs P, Marmion BP - BMC Infect. Dis. (2016)

Bottom Line: During life, extensive clinical and laboratory investigations from different disciplinary stand points failed to deliver a definitive identification of a cause.PCR analysis (COM1/IS1111 genes) confirmed the presence of C.b.The possible mechanisms and molecular adaptations for this alternative C.b. life style are discussed.

View Article: PubMed Central - PubMed

Affiliation: Q Fever Research Group (1993-2009), Hanson Institute, Adelaide, South Australia.

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.

Case presentation: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

a Immuno-peroxidase staining of myocardium - close to mitral valve - with specific monoclonal antibodies for presence of C.b. antigens X400. b Negative control
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Fig4: a Immuno-peroxidase staining of myocardium - close to mitral valve - with specific monoclonal antibodies for presence of C.b. antigens X400. b Negative control

Mentions: Tissue samples from several lymphoid organs and those previously determined as targets for C.b. were further stained using specific antisera. Figures 3 and 4 show C.b. Phase 1 LPS antigens detected in the macrophages of the patient’s bone marrow (Fig. 3a), liver (Fig. 3b), lymph node (Fig. 3c), spleen (Fig. 3d) and heart (Fig. 4). Strong staining with the monoclonal antibody to C.b. Phase 1 LPS antigen was detected in both immuno-peroxidase (see Fig. 4) and IFA reactions (data not shown). However, the pattern was markedly different to that commonly described in Q fever endocarditis (early or late stage) where the valve lesions show fibrosis and calcification in the late stage [15]. The paucity of inflammatory cells including monocyte/macrophage lineage and the rapid decline of infective coxiella leaving antigen LPS complex has frequently been remarked, as are low levels of genomic DNA [16].Fig. 3


Coxiella burnetii dormancy in a fatal ten-year multisystem dysfunctional illness: case report.

Sukocheva OA, Manavis J, Kok TW, Turra M, Izzo A, Blumbergs P, Marmion BP - BMC Infect. Dis. (2016)

a Immuno-peroxidase staining of myocardium - close to mitral valve - with specific monoclonal antibodies for presence of C.b. antigens X400. b Negative control
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835832&req=5

Fig4: a Immuno-peroxidase staining of myocardium - close to mitral valve - with specific monoclonal antibodies for presence of C.b. antigens X400. b Negative control
Mentions: Tissue samples from several lymphoid organs and those previously determined as targets for C.b. were further stained using specific antisera. Figures 3 and 4 show C.b. Phase 1 LPS antigens detected in the macrophages of the patient’s bone marrow (Fig. 3a), liver (Fig. 3b), lymph node (Fig. 3c), spleen (Fig. 3d) and heart (Fig. 4). Strong staining with the monoclonal antibody to C.b. Phase 1 LPS antigen was detected in both immuno-peroxidase (see Fig. 4) and IFA reactions (data not shown). However, the pattern was markedly different to that commonly described in Q fever endocarditis (early or late stage) where the valve lesions show fibrosis and calcification in the late stage [15]. The paucity of inflammatory cells including monocyte/macrophage lineage and the rapid decline of infective coxiella leaving antigen LPS complex has frequently been remarked, as are low levels of genomic DNA [16].Fig. 3

Bottom Line: During life, extensive clinical and laboratory investigations from different disciplinary stand points failed to deliver a definitive identification of a cause.PCR analysis (COM1/IS1111 genes) confirmed the presence of C.b.The possible mechanisms and molecular adaptations for this alternative C.b. life style are discussed.

View Article: PubMed Central - PubMed

Affiliation: Q Fever Research Group (1993-2009), Hanson Institute, Adelaide, South Australia.

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.

Case presentation: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus