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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

Assessment of Patient BI and control astrocyte GFAP immune-staining in occipital cortex and occipital subcortical white matter using peroxidase staining technique and anti-GFAP antibodies as described in Methods. a Peroxidase staining with GFAP in samples from BI occipital cortex showing a reactive astrocyte with numerous “beaded” processes (400X). b Peroxidase staining with GFAP in BI samples from occipital subcortical white matter showing increased GFAP immune-staining and a reactive phenotype. Representative photographs are shown
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Fig1: Assessment of Patient BI and control astrocyte GFAP immune-staining in occipital cortex and occipital subcortical white matter using peroxidase staining technique and anti-GFAP antibodies as described in Methods. a Peroxidase staining with GFAP in samples from BI occipital cortex showing a reactive astrocyte with numerous “beaded” processes (400X). b Peroxidase staining with GFAP in BI samples from occipital subcortical white matter showing increased GFAP immune-staining and a reactive phenotype. Representative photographs are shown

Mentions: Given the history of susceptibility to infection from birth, the acute fever in 1986 and the diagnosis of “post (viral) infection syndrome”, tests for infective agents were done starting with C.b. and Legionella pneumophila (L.p.). Patient BI had previously visited farms a number of times. Previous comprehensive neuropathological assessment at the time of autopsy in 1986 had not revealed gross or microscopic (H & E staining) abnormalities. The H&E examination was repeated on fresh sections of brain from the patient and an unrelated control brain but no abnormalities were detected (data not shown). Immuno-peroxidase staining for glial fibrillary acidic protein (GFAP) showed prominent immune-staining of astrocytes and “beading” of the fibrillary processes compared with control brain sections which did not show such striking changes (Fig. 1a and b). Increased GFAP immuno-staining may be seen in many conditions that may be a non-specific reactive response of the astrocytes [9, 10].Fig. 1


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)

Assessment of Patient BI and control astrocyte GFAP immune-staining in occipital cortex and occipital subcortical white matter using peroxidase staining technique and anti-GFAP antibodies as described in Methods. a Peroxidase staining with GFAP in samples from BI occipital cortex showing a reactive astrocyte with numerous “beaded” processes (400X). b Peroxidase staining with GFAP in BI samples from occipital subcortical white matter showing increased GFAP immune-staining and a reactive phenotype. Representative photographs are shown
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Assessment of Patient BI and control astrocyte GFAP immune-staining in occipital cortex and occipital subcortical white matter using peroxidase staining technique and anti-GFAP antibodies as described in Methods. a Peroxidase staining with GFAP in samples from BI occipital cortex showing a reactive astrocyte with numerous “beaded” processes (400X). b Peroxidase staining with GFAP in BI samples from occipital subcortical white matter showing increased GFAP immune-staining and a reactive phenotype. Representative photographs are shown
Mentions: Given the history of susceptibility to infection from birth, the acute fever in 1986 and the diagnosis of “post (viral) infection syndrome”, tests for infective agents were done starting with C.b. and Legionella pneumophila (L.p.). Patient BI had previously visited farms a number of times. Previous comprehensive neuropathological assessment at the time of autopsy in 1986 had not revealed gross or microscopic (H & E staining) abnormalities. The H&E examination was repeated on fresh sections of brain from the patient and an unrelated control brain but no abnormalities were detected (data not shown). Immuno-peroxidase staining for glial fibrillary acidic protein (GFAP) showed prominent immune-staining of astrocytes and “beading” of the fibrillary processes compared with control brain sections which did not show such striking changes (Fig. 1a and b). Increased GFAP immuno-staining may be seen in many conditions that may be a non-specific reactive response of the astrocytes [9, 10].Fig. 1

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