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The Natural History of Aerosolized Francisella tularensis Infection in Cynomolgus Macaques
Tularemia is a severe, zoonotic infection caused by the Gram-negative bacterium Francisella tularensis. Inhalation results in a rapid, severe bacterial pneumonia and sepsis, which can be lethal. Because the cynomolgus macaque is the accepted nonhuman primate model for tularemia, we conducted a natur...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153158/ https://www.ncbi.nlm.nih.gov/pubmed/34068262 http://dx.doi.org/10.3390/pathogens10050597 |
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author | Frick, Ondraya M. Livingston, Virginia A. Whitehouse, Chris A. Norris, Sarah L. Alves, Derron A. Facemire, Paul R. Reed, Douglas S. Nalca, Aysegul |
author_facet | Frick, Ondraya M. Livingston, Virginia A. Whitehouse, Chris A. Norris, Sarah L. Alves, Derron A. Facemire, Paul R. Reed, Douglas S. Nalca, Aysegul |
author_sort | Frick, Ondraya M. |
collection | PubMed |
description | Tularemia is a severe, zoonotic infection caused by the Gram-negative bacterium Francisella tularensis. Inhalation results in a rapid, severe bacterial pneumonia and sepsis, which can be lethal. Because the cynomolgus macaque is the accepted nonhuman primate model for tularemia, we conducted a natural history study of pneumonic tularemia by exposing macaques to target inhaled doses of 50, 500, or 5000 colony forming units (CFU) of F. tularensis subsp. tularensis SCHU S4. Two animals within the 50 CFU group (calculated doses of 10 and 11 CFU) survived the challenge, while the remainder succumbed to infection. Exposure of cynomolgus macaques to aerosolized SCHU S4 resulted in fever, anorexia, increased white blood cell counts, lymphopenia, thrombocytopenia, increased liver enzymes, alterations in electrocardiogram (ECG), and pathological changes typical of infection with F. tularensis, regardless of the challenge dose. Blood pressure dropped during the febrile phase, particularly as temperature began to drop and macaques succumbed to the disease. ECG analysis indicated that in 33% of the macaques, heart rate was not elevated during the febrile phase (Faget’s sign; pulse-temperature disassociation), which has been reported in a similar percentage of human cases. These results indicated that infection of cynomolgus macaques with aerosolized F. tularensis results in similar disease progression and outcome as seen in humans, and that cynomolgus macaques are a reliable animal model to test medical countermeasures against aerosolized F. tularensis. |
format | Online Article Text |
id | pubmed-8153158 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81531582021-05-27 The Natural History of Aerosolized Francisella tularensis Infection in Cynomolgus Macaques Frick, Ondraya M. Livingston, Virginia A. Whitehouse, Chris A. Norris, Sarah L. Alves, Derron A. Facemire, Paul R. Reed, Douglas S. Nalca, Aysegul Pathogens Article Tularemia is a severe, zoonotic infection caused by the Gram-negative bacterium Francisella tularensis. Inhalation results in a rapid, severe bacterial pneumonia and sepsis, which can be lethal. Because the cynomolgus macaque is the accepted nonhuman primate model for tularemia, we conducted a natural history study of pneumonic tularemia by exposing macaques to target inhaled doses of 50, 500, or 5000 colony forming units (CFU) of F. tularensis subsp. tularensis SCHU S4. Two animals within the 50 CFU group (calculated doses of 10 and 11 CFU) survived the challenge, while the remainder succumbed to infection. Exposure of cynomolgus macaques to aerosolized SCHU S4 resulted in fever, anorexia, increased white blood cell counts, lymphopenia, thrombocytopenia, increased liver enzymes, alterations in electrocardiogram (ECG), and pathological changes typical of infection with F. tularensis, regardless of the challenge dose. Blood pressure dropped during the febrile phase, particularly as temperature began to drop and macaques succumbed to the disease. ECG analysis indicated that in 33% of the macaques, heart rate was not elevated during the febrile phase (Faget’s sign; pulse-temperature disassociation), which has been reported in a similar percentage of human cases. These results indicated that infection of cynomolgus macaques with aerosolized F. tularensis results in similar disease progression and outcome as seen in humans, and that cynomolgus macaques are a reliable animal model to test medical countermeasures against aerosolized F. tularensis. MDPI 2021-05-13 /pmc/articles/PMC8153158/ /pubmed/34068262 http://dx.doi.org/10.3390/pathogens10050597 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Frick, Ondraya M. Livingston, Virginia A. Whitehouse, Chris A. Norris, Sarah L. Alves, Derron A. Facemire, Paul R. Reed, Douglas S. Nalca, Aysegul The Natural History of Aerosolized Francisella tularensis Infection in Cynomolgus Macaques |
title | The Natural History of Aerosolized Francisella tularensis Infection in Cynomolgus Macaques |
title_full | The Natural History of Aerosolized Francisella tularensis Infection in Cynomolgus Macaques |
title_fullStr | The Natural History of Aerosolized Francisella tularensis Infection in Cynomolgus Macaques |
title_full_unstemmed | The Natural History of Aerosolized Francisella tularensis Infection in Cynomolgus Macaques |
title_short | The Natural History of Aerosolized Francisella tularensis Infection in Cynomolgus Macaques |
title_sort | natural history of aerosolized francisella tularensis infection in cynomolgus macaques |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153158/ https://www.ncbi.nlm.nih.gov/pubmed/34068262 http://dx.doi.org/10.3390/pathogens10050597 |
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