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Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques
Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine ca...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848582/ https://www.ncbi.nlm.nih.gov/pubmed/27043611 http://dx.doi.org/10.3390/v8040087 |
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author | Ewers, Evan C. Pratt, William D. Twenhafel, Nancy A. Shamblin, Joshua Donnelly, Ginger Esham, Heather Wlazlowski, Carly Johnson, Joshua C. Botto, Miriam Hensley, Lisa E. Goff, Arthur J. |
author_facet | Ewers, Evan C. Pratt, William D. Twenhafel, Nancy A. Shamblin, Joshua Donnelly, Ginger Esham, Heather Wlazlowski, Carly Johnson, Joshua C. Botto, Miriam Hensley, Lisa E. Goff, Arthur J. |
author_sort | Ewers, Evan C. |
collection | PubMed |
description | Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine candidates can only be approved through the FDA animal rule—a mechanism requiring well-characterized animal models in which efficacy would be evaluated. Here, we describe a natural history study where rhesus macaques were surgically implanted with telemetry devices and central venous catheters prior to aerosol exposure with Marburg-Angola virus, enabling continuous physiologic monitoring and blood sampling without anesthesia. After a three to four day incubation period, all animals developed fever, viremia, and lymphopenia before developing tachycardia, tachypnea, elevated liver enzymes, decreased liver function, azotemia, elevated D-dimer levels and elevated pro-inflammatory cytokines suggesting a systemic inflammatory response with organ failure. The final, terminal period began with the onset of sustained hypotension, dehydration progressed with signs of major organ hypoperfusion (hyperlactatemia, acute kidney injury, hypothermia), and ended with euthanasia or death. The most significant pathologic findings were marked infection of the respiratory lymphoid tissue with destruction of the tracheobronchial and mediastinal lymph nodes, and severe diffuse infection in the liver, and splenitis. |
format | Online Article Text |
id | pubmed-4848582 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-48485822016-05-04 Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques Ewers, Evan C. Pratt, William D. Twenhafel, Nancy A. Shamblin, Joshua Donnelly, Ginger Esham, Heather Wlazlowski, Carly Johnson, Joshua C. Botto, Miriam Hensley, Lisa E. Goff, Arthur J. Viruses Article Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine candidates can only be approved through the FDA animal rule—a mechanism requiring well-characterized animal models in which efficacy would be evaluated. Here, we describe a natural history study where rhesus macaques were surgically implanted with telemetry devices and central venous catheters prior to aerosol exposure with Marburg-Angola virus, enabling continuous physiologic monitoring and blood sampling without anesthesia. After a three to four day incubation period, all animals developed fever, viremia, and lymphopenia before developing tachycardia, tachypnea, elevated liver enzymes, decreased liver function, azotemia, elevated D-dimer levels and elevated pro-inflammatory cytokines suggesting a systemic inflammatory response with organ failure. The final, terminal period began with the onset of sustained hypotension, dehydration progressed with signs of major organ hypoperfusion (hyperlactatemia, acute kidney injury, hypothermia), and ended with euthanasia or death. The most significant pathologic findings were marked infection of the respiratory lymphoid tissue with destruction of the tracheobronchial and mediastinal lymph nodes, and severe diffuse infection in the liver, and splenitis. MDPI 2016-03-30 /pmc/articles/PMC4848582/ /pubmed/27043611 http://dx.doi.org/10.3390/v8040087 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ewers, Evan C. Pratt, William D. Twenhafel, Nancy A. Shamblin, Joshua Donnelly, Ginger Esham, Heather Wlazlowski, Carly Johnson, Joshua C. Botto, Miriam Hensley, Lisa E. Goff, Arthur J. Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques |
title | Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques |
title_full | Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques |
title_fullStr | Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques |
title_full_unstemmed | Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques |
title_short | Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques |
title_sort | natural history of aerosol exposure with marburg virus in rhesus macaques |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848582/ https://www.ncbi.nlm.nih.gov/pubmed/27043611 http://dx.doi.org/10.3390/v8040087 |
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