Intensive Care Unit–Like Care of Nonhuman Primates with Ebola Virus Disease

Author:

Blair Paul W12,Kortepeter Mark G3,Downey Lydia G4,Madar Cristian S5,Downs Isaac L4,Martins Karen A4,Rossi Franco4,Williams Janice A4,Madar Annie5,Schellhase Christopher W4,Bearss Jeremy J4,Zeng Xiankun4,Bavari Sina6,Soloveva Veronica4,Wells Jay B4,Stuthman Kelly S4,Garza Nicole L4,Vantongeren Sean A4,Donnelly Ginger C4,Steffens Jesse4,Kalapaca Jennifer4,Wiseman Perry4,Henry Joseph4,Marko Shannon4,Chappell Mark4,Lugo-Roman Luis4,Ramos-Rivera Elliot4,Hofer Christian4,Blue Eugene4,Moore Joshua4,Fiallos Jimmy4,Wetzel Darrel4,Pratt William D4,Unangst Tami4,Miller Adele4,Sola James J4,Reisler Ronald B4,Cardile Anthony P4

Affiliation:

1. Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

2. Austere Environments Consortium for Enhanced Sepsis Outcomes, Henry M. Jackson Foundation, Bethesda, Maryland, USA

3. University of Nebraska Medical Center, Omaha, Nebraska, USA

4. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA

5. Tripler Army Medical Center, Honolulu, Hawaii, USA

6. Edge BioInnovation Consulting and Management, Frederick, Maryland, USA

Abstract

Abstract Background Ebola virus disease (EVD) supportive care strategies are largely guided by retrospective observational research. This study investigated the effect of EVD supportive care algorithms on duration of survival in a controlled nonhuman primate (NHP) model. Methods Fourteen rhesus macaques were challenged intramuscularly with a target dose of Ebola virus (1000 plaque-forming units; Kikwit). NHPs were allocated to intensive care unit (ICU)–like algorithms (n = 7), intravenous fluids plus levofloxacin (n = 2), or a control group (n = 5). The primary outcome measure was duration of survival, and secondary outcomes included changes in clinical laboratory values. Results Duration of survival was not significantly different between the pooled ICU-like algorithm and control groups (8.2 vs 6.9 days of survival; hazard ratio; 0.50; P = .25). Norepinephrine was effective in transiently maintaining baseline blood pressure. NHPs treated with ICU-like algorithms had delayed onset of liver and kidney injury. Conclusions While an obvious survival difference was not observed with ICU-like care, clinical observations from this model may aid in EVD supportive care NHP model refinement.

Funder

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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