Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
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
_version_ 1782429373074243584
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
work_keys_str_mv AT ewersevanc naturalhistoryofaerosolexposurewithmarburgvirusinrhesusmacaques
AT prattwilliamd naturalhistoryofaerosolexposurewithmarburgvirusinrhesusmacaques
AT twenhafelnancya naturalhistoryofaerosolexposurewithmarburgvirusinrhesusmacaques
AT shamblinjoshua naturalhistoryofaerosolexposurewithmarburgvirusinrhesusmacaques
AT donnellyginger naturalhistoryofaerosolexposurewithmarburgvirusinrhesusmacaques
AT eshamheather naturalhistoryofaerosolexposurewithmarburgvirusinrhesusmacaques
AT wlazlowskicarly naturalhistoryofaerosolexposurewithmarburgvirusinrhesusmacaques
AT johnsonjoshuac naturalhistoryofaerosolexposurewithmarburgvirusinrhesusmacaques
AT bottomiriam naturalhistoryofaerosolexposurewithmarburgvirusinrhesusmacaques
AT hensleylisae naturalhistoryofaerosolexposurewithmarburgvirusinrhesusmacaques
AT goffarthurj naturalhistoryofaerosolexposurewithmarburgvirusinrhesusmacaques