Development of an acute model of inhalational melioidosis in the common marmoset (Callithrix jacchus)
Summary Studies of inhalational melioidosis were undertaken in the common marmoset (Callithrix jacchus). Following exposure to an inhaled challenge with aerosolized Burkholderia pseudomallei, lethal infection was observed in marmosets challenged with doses below 10 cfu; a precise LD50 determination...
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Published in | International journal of experimental pathology Vol. 92; no. 6; pp. 428 - 435 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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Oxford, UK
Blackwell Publishing Ltd
01.12.2011
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Abstract | Summary
Studies of inhalational melioidosis were undertaken in the common marmoset (Callithrix jacchus). Following exposure to an inhaled challenge with aerosolized Burkholderia pseudomallei, lethal infection was observed in marmosets challenged with doses below 10 cfu; a precise LD50 determination was not possible. The model was further characterized using a target challenge dose of approximately 102 cfu. A separate pathogenesis time‐course experiment was also conducted. All animals succumbed, between 27 and 78 h postchallenge. The challenge dose received and the time to the humane endpoint (1 °C below normal body temperature postfever) were correlated. The first indicator of disease was an increased core body temperature (Tc), at 22 h postchallenge. This coincided with bacteraemia and bacterial dissemination. Overt clinical signs were first observed 3–5 h later. A sharp decrease (typically within 3–6 h) in the Tc was observed prior to humanely culling the animals in the lethality study. Pathology was noted in the lung, liver and spleen. Disease progression in the common marmoset appears to be consistent with human infection in terms of bacterial spread, pathology and physiology. The common marmoset can therefore be considered a suitable animal model for further studies of inhalational melioidosis. |
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AbstractList | Studies of inhalational melioidosis were undertaken in the common marmoset (Callithrix jacchus). Following exposure to an inhaled challenge with aerosolized Burkholderia pseudomallei, lethal infection was observed in marmosets challenged with doses below 10 cfu; a precise LD(50) determination was not possible. The model was further characterized using a target challenge dose of approximately 10(2) cfu. A separate pathogenesis time-course experiment was also conducted. All animals succumbed, between 27 and 78 h postchallenge. The challenge dose received and the time to the humane endpoint (1 °C below normal body temperature postfever) were correlated. The first indicator of disease was an increased core body temperature (T(c) ), at 22 h postchallenge. This coincided with bacteraemia and bacterial dissemination. Overt clinical signs were first observed 3-5 h later. A sharp decrease (typically within 3-6 h) in the T(c) was observed prior to humanely culling the animals in the lethality study. Pathology was noted in the lung, liver and spleen. Disease progression in the common marmoset appears to be consistent with human infection in terms of bacterial spread, pathology and physiology. The common marmoset can therefore be considered a suitable animal model for further studies of inhalational melioidosis. Summary Studies of inhalational melioidosis were undertaken in the common marmoset (Callithrix jacchus). Following exposure to an inhaled challenge with aerosolized Burkholderia pseudomallei, lethal infection was observed in marmosets challenged with doses below 10 cfu; a precise LD50 determination was not possible. The model was further characterized using a target challenge dose of approximately 102 cfu. A separate pathogenesis time‐course experiment was also conducted. All animals succumbed, between 27 and 78 h postchallenge. The challenge dose received and the time to the humane endpoint (1 °C below normal body temperature postfever) were correlated. The first indicator of disease was an increased core body temperature (Tc), at 22 h postchallenge. This coincided with bacteraemia and bacterial dissemination. Overt clinical signs were first observed 3–5 h later. A sharp decrease (typically within 3–6 h) in the Tc was observed prior to humanely culling the animals in the lethality study. Pathology was noted in the lung, liver and spleen. Disease progression in the common marmoset appears to be consistent with human infection in terms of bacterial spread, pathology and physiology. The common marmoset can therefore be considered a suitable animal model for further studies of inhalational melioidosis. Studies of inhalational melioidosis were undertaken in the common marmoset (Callithrix jacchus). Following exposure to an inhaled challenge with aerosolized Burkholderia pseudomallei, lethal infection was observed in marmosets challenged with doses below 10cfu; a precise LD50 determination was not possible. The model was further characterized using a target challenge dose of approximately 102cfu. A separate pathogenesis time-course experiment was also conducted. All animals succumbed, between 27 and 78h postchallenge. The challenge dose received and the time to the humane endpoint (1 degree C below normal body temperature postfever) were correlated. The first indicator of disease was an increased core body temperature (Tc), at 22h postchallenge. This coincided with bacteraemia and bacterial dissemination. Overt clinical signs were first observed 3-5h later. A sharp decrease (typically within 3-6h) in the Tc was observed prior to humanely culling the animals in the lethality study. Pathology was noted in the lung, liver and spleen. Disease progression in the common marmoset appears to be consistent with human infection in terms of bacterial spread, pathology and physiology. The common marmoset can therefore be considered a suitable animal model for further studies of inhalational melioidosis. Studies of inhalational melioidosis were undertaken in the common marmoset ( Callithrix jacchus ). Following exposure to an inhaled challenge with aerosolized Burkholderia pseudomallei , lethal infection was observed in marmosets challenged with doses below 10 cfu; a precise LD 50 determination was not possible. The model was further characterized using a target challenge dose of approximately 10 2 cfu. A separate pathogenesis time-course experiment was also conducted. All animals succumbed, between 27 and 78 h postchallenge. The challenge dose received and the time to the humane endpoint (1 °C below normal body temperature postfever) were correlated. The first indicator of disease was an increased core body temperature ( T c ), at 22 h postchallenge. This coincided with bacteraemia and bacterial dissemination. Overt clinical signs were first observed 3–5 h later. A sharp decrease (typically within 3–6 h) in the T c was observed prior to humanely culling the animals in the lethality study. Pathology was noted in the lung, liver and spleen. Disease progression in the common marmoset appears to be consistent with human infection in terms of bacterial spread, pathology and physiology. The common marmoset can therefore be considered a suitable animal model for further studies of inhalational melioidosis. |
Author | Lever, Mark S. Dean, Rachel E. Salguero, Francisco J. Taylor, Christopher Pearce, Peter C. Nelson, Michelle Simpson, Andrew J. H. |
Author_xml | – sequence: 1 givenname: Michelle surname: Nelson fullname: Nelson, Michelle organization: Biomedical Sciences, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, UK – sequence: 2 givenname: Rachel E. surname: Dean fullname: Dean, Rachel E. organization: Biomedical Sciences, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, UK – sequence: 3 givenname: Francisco J. surname: Salguero fullname: Salguero, Francisco J. organization: Veterinary Laboratories Agency, Weybridge, Addlestone, Surrey, UK – sequence: 4 givenname: Christopher surname: Taylor fullname: Taylor, Christopher organization: Biomedical Sciences, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, UK – sequence: 5 givenname: Peter C. surname: Pearce fullname: Pearce, Peter C. organization: Biomedical Sciences, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, UK – sequence: 6 givenname: Andrew J. H. surname: Simpson fullname: Simpson, Andrew J. H. organization: Biomedical Sciences, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, UK – sequence: 7 givenname: Mark S. surname: Lever fullname: Lever, Mark S. organization: Biomedical Sciences, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, UK |
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Studies of inhalational melioidosis were undertaken in the common marmoset (Callithrix jacchus). Following exposure to an inhaled challenge with... Studies of inhalational melioidosis were undertaken in the common marmoset (Callithrix jacchus). Following exposure to an inhaled challenge with aerosolized... Studies of inhalational melioidosis were undertaken in the common marmoset ( Callithrix jacchus ). Following exposure to an inhaled challenge with aerosolized... |
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SubjectTerms | Acute Disease Administration, Inhalation animal model Animal models Animals Bacteremia Body temperature Body Temperature - physiology Burkholderia pseudomallei Burkholderia pseudomallei - isolation & purification Callithrix Callithrix jacchus Culling Disease Models, Animal Disease Progression Female Infection Lethality Liver Liver - microbiology Liver - pathology Lung Lung - microbiology Lung - pathology Male marmoset Melioidosis Melioidosis - microbiology Melioidosis - pathology Melioidosis - physiopathology non-human primate Original pathology Spleen Spleen - microbiology Spleen - pathology Time Factors |
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Title | Development of an acute model of inhalational melioidosis in the common marmoset (Callithrix jacchus) |
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