Natural History of Aerosol-Induced Ebola Virus Disease in Rhesus Macaques
| Autor: | John Trefry, Nathan K Jansen, Sara C. Johnston, Anna N. Honko, David L. Saunders, Anthony P. Cardile, William D. Pratt, Erin L Tompkins, Elizabeth E. Zumbrun, Nancy A. Twenhafel, David W. Dyer, Heather L. Esham, Joshua C. Johnson, Paul Facemire, Franco Rossi, Isaac L Downs |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Macaca mulatta aerosol Viremia virus medicine.disease_cause Microbiology Article Virus Viral hemorrhagic fever Kikwit Virology medicine Animals respiratory alkalosis viral hemorrhagic fever Zaire Subclinical infection Aerosols Ebola virus biology business.industry telemetry Hemorrhagic Fever Ebola Viral Load Ebolavirus biology.organism_classification medicine.disease QR1-502 Disease Models Animal Rhesus macaque Infectious Diseases natural history Ebola cytokine storm Immunology RNA Viral Female Cytokine storm business Viral load rhesus macaque |
| Zdroj: | Viruses Volume 13 Issue 11 Viruses, Vol 13, Iss 2297, p 2297 (2021) |
| ISSN: | 1999-4915 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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