Natural History of Aerosol-Induced Ebola Virus Disease in Rhesus Macaques

Ebola virus disease (EVD) is a serious global health concern because case fatality rates are approximately 50% due to recent widespread outbreaks in Africa. Well-defined nonhuman primate (NHP) models for different routes of Ebola virus exposure are needed to test the efficacy of candidate countermea...

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Autores principales:	Isaac Downs, Joshua C. Johnson, Franco Rossi, David Dyer, David L. Saunders, Nancy A. Twenhafel, Heather L. Esham, William D. Pratt, John Trefry, Elizabeth Zumbrun, Paul R. Facemire, Sara C. Johnston, Erin L. Tompkins, Nathan K. Jansen, Anna Honko, Anthony P. Cardile
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Ebola Kikwit Zaire virus viral hemorrhagic fever natural history Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2fa118039cb14a46aec8589930dbc3a1
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spelling	oai:doaj.org-article:2fa118039cb14a46aec8589930dbc3a12021-11-25T19:14:18ZNatural History of Aerosol-Induced Ebola Virus Disease in Rhesus Macaques10.3390/v131122971999-4915https://doaj.org/article/2fa118039cb14a46aec8589930dbc3a12021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2297https://doaj.org/toc/1999-4915Ebola virus disease (EVD) is a serious global health concern because case fatality rates are approximately 50% due to recent widespread outbreaks in Africa. Well-defined nonhuman primate (NHP) models for different routes of Ebola virus exposure are needed to test the efficacy of candidate countermeasures. In this natural history study, four rhesus macaques were challenged via aerosol with a target titer of 1000 plaque-forming units per milliliter of Ebola virus. The course of disease was split into the following stages for descriptive purposes: subclinical, clinical, and decompensated. During the subclinical stage, high levels of venous partial pressure of carbon dioxide led to respiratory acidemia in three of four of the NHPs, and all developed lymphopenia. During the clinical stage, all animals had fever, viremia, and respiratory alkalosis. The decompensatory stage involved coagulopathy, cytokine storm, and liver and renal injury. These events were followed by hypotension, elevated lactate, metabolic acidemia, shock and mortality similar to historic intramuscular challenge studies. Viral loads in the lungs of aerosol-exposed animals were not distinctly different compared to previous intramuscularly challenged studies. Differences in the aerosol model, compared to intramuscular model, include an extended subclinical stage, shortened clinical stage, and general decompensated stage. Therefore, the shortened timeframe for clinical detection of the aerosol-induced disease can impair timely therapeutic administration. In summary, this nonhuman primate model of aerosol-induced EVD characterizes early disease markers and additional details to enable countermeasure development.Isaac DownsJoshua C. JohnsonFranco RossiDavid DyerDavid L. SaundersNancy A. TwenhafelHeather L. EshamWilliam D. PrattJohn TrefryElizabeth ZumbrunPaul R. FacemireSara C. JohnstonErin L. TompkinsNathan K. JansenAnna HonkoAnthony P. CardileMDPI AGarticleEbolaKikwitZairevirusviral hemorrhagic fevernatural historyMicrobiologyQR1-502ENViruses, Vol 13, Iss 2297, p 2297 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ebola Kikwit Zaire virus viral hemorrhagic fever natural history Microbiology QR1-502
spellingShingle	Ebola Kikwit Zaire virus viral hemorrhagic fever natural history Microbiology QR1-502 Isaac Downs Joshua C. Johnson Franco Rossi David Dyer David L. Saunders Nancy A. Twenhafel Heather L. Esham William D. Pratt John Trefry Elizabeth Zumbrun Paul R. Facemire Sara C. Johnston Erin L. Tompkins Nathan K. Jansen Anna Honko Anthony P. Cardile Natural History of Aerosol-Induced Ebola Virus Disease in Rhesus Macaques
description	Ebola virus disease (EVD) is a serious global health concern because case fatality rates are approximately 50% due to recent widespread outbreaks in Africa. Well-defined nonhuman primate (NHP) models for different routes of Ebola virus exposure are needed to test the efficacy of candidate countermeasures. In this natural history study, four rhesus macaques were challenged via aerosol with a target titer of 1000 plaque-forming units per milliliter of Ebola virus. The course of disease was split into the following stages for descriptive purposes: subclinical, clinical, and decompensated. During the subclinical stage, high levels of venous partial pressure of carbon dioxide led to respiratory acidemia in three of four of the NHPs, and all developed lymphopenia. During the clinical stage, all animals had fever, viremia, and respiratory alkalosis. The decompensatory stage involved coagulopathy, cytokine storm, and liver and renal injury. These events were followed by hypotension, elevated lactate, metabolic acidemia, shock and mortality similar to historic intramuscular challenge studies. Viral loads in the lungs of aerosol-exposed animals were not distinctly different compared to previous intramuscularly challenged studies. Differences in the aerosol model, compared to intramuscular model, include an extended subclinical stage, shortened clinical stage, and general decompensated stage. Therefore, the shortened timeframe for clinical detection of the aerosol-induced disease can impair timely therapeutic administration. In summary, this nonhuman primate model of aerosol-induced EVD characterizes early disease markers and additional details to enable countermeasure development.
format	article
author	Isaac Downs Joshua C. Johnson Franco Rossi David Dyer David L. Saunders Nancy A. Twenhafel Heather L. Esham William D. Pratt John Trefry Elizabeth Zumbrun Paul R. Facemire Sara C. Johnston Erin L. Tompkins Nathan K. Jansen Anna Honko Anthony P. Cardile
author_facet	Isaac Downs Joshua C. Johnson Franco Rossi David Dyer David L. Saunders Nancy A. Twenhafel Heather L. Esham William D. Pratt John Trefry Elizabeth Zumbrun Paul R. Facemire Sara C. Johnston Erin L. Tompkins Nathan K. Jansen Anna Honko Anthony P. Cardile
author_sort	Isaac Downs
title	Natural History of Aerosol-Induced Ebola Virus Disease in Rhesus Macaques
title_short	Natural History of Aerosol-Induced Ebola Virus Disease in Rhesus Macaques
title_full	Natural History of Aerosol-Induced Ebola Virus Disease in Rhesus Macaques
title_fullStr	Natural History of Aerosol-Induced Ebola Virus Disease in Rhesus Macaques
title_full_unstemmed	Natural History of Aerosol-Induced Ebola Virus Disease in Rhesus Macaques
title_sort	natural history of aerosol-induced ebola virus disease in rhesus macaques
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2fa118039cb14a46aec8589930dbc3a1
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Natural History of Aerosol-Induced Ebola Virus Disease in Rhesus Macaques

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