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

Paul W. Blair; Mark G. Kortepeter; Lydia G. Downey; Cristian S. Madar; Isaac L. Downs; Karen A. Martins; Franco Rossi; Janice A. Williams; Annie Madar; Christopher W. Schellhase; Jeremy J. Bearss; Xiankun Zeng; Sina Bavari; Veronica Soloveva; Jay B. Wells; Kelly S. Stuthman; Nicole L. Garza; Sean A. Vantongeren; Ginger C. Donnelly; Jesse Steffens; Jennifer Kalapaca; Perry Wiseman; Joseph Henry; Shannon Marko; Mark Chappell; Luis Lugo-Roman; Elliot Ramos-Rivera; Christian Hofer; Eugene Blue; Joshua Moore; Jimmy Fiallos; Darrel Wetzel; William D. Pratt; Tami Unangst; Adele Miller; James J. Sola; Ronald B. Reisler; Anthony P. Cardile

doi:10.1093/infdis/jiaa781

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

Paul W. Blair, Mark G. Kortepeter, Lydia G. Downey, Cristian S. Madar, Isaac L. Downs, Karen A. Martins, Franco Rossi, Janice A. Williams, Annie Madar, Christopher W. Schellhase, Jeremy J. Bearss, Xiankun Zeng, Sina Bavari, Veronica Soloveva, Jay B. Wells, Kelly S. Stuthman, Nicole L. Garza, Sean A. Vantongeren, Ginger C. Donnelly, Jesse SteffensJennifer Kalapaca, Perry Wiseman, Joseph Henry, Shannon Marko, Mark Chappell, Luis Lugo-Roman, Elliot Ramos-Rivera, Christian Hofer, Eugene Blue, Joshua Moore, Jimmy Fiallos, Darrel Wetzel, William D. Pratt, Tami Unangst, Adele Miller, James J. Sola, Ronald B. Reisler, Anthony P. Cardile^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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.

Original language	English
Pages (from-to)	632-642
Number of pages	11
Journal	Journal of Infectious Diseases
Volume	224
Issue number	4
DOIs	https://doi.org/10.1093/infdis/jiaa781
State	Published - 15 Aug 2021
Externally published	Yes

Keywords

Ebola virus disease
Filoviridae
Mononegavirales
animal
hemorrhagic fevers
intensive care
models
viral

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10.1093/infdis/jiaa781

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Blair, P. W., Kortepeter, M. G., Downey, L. G., Madar, C. S., Downs, I. L., Martins, K. A., Rossi, F., Williams, J. A., Madar, A., Schellhase, C. W., Bearss, J. J., Zeng, X., Bavari, S., Soloveva, V., Wells, J. B., Stuthman, K. S., Garza, N. L., Vantongeren, S. A., Donnelly, G. C., ... Cardile, A. P. (2021). Intensive Care Unit-Like Care of Nonhuman Primates with Ebola Virus Disease. Journal of Infectious Diseases, 224(4), 632-642. https://doi.org/10.1093/infdis/jiaa781

@article{cc5063023f8f4b80ae40ffa0bec16d22,

title = "Intensive Care Unit-Like Care of Nonhuman Primates with Ebola Virus Disease",

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.",

keywords = "Ebola virus disease, Filoviridae, Mononegavirales, animal, hemorrhagic fevers, intensive care, models, viral",

author = "Blair, {Paul W.} and Kortepeter, {Mark G.} and Downey, {Lydia G.} and Madar, {Cristian S.} and Downs, {Isaac L.} and Martins, {Karen A.} and Franco Rossi and Williams, {Janice A.} and Annie Madar and Schellhase, {Christopher W.} and Bearss, {Jeremy J.} and Xiankun Zeng and Sina Bavari and Veronica Soloveva and Wells, {Jay B.} and Stuthman, {Kelly S.} and Garza, {Nicole L.} and Vantongeren, {Sean A.} and Donnelly, {Ginger C.} and Jesse Steffens and Jennifer Kalapaca and Perry Wiseman and Joseph Henry and Shannon Marko and Mark Chappell and Luis Lugo-Roman and Elliot Ramos-Rivera and Christian Hofer and Eugene Blue and Joshua Moore and Jimmy Fiallos and Darrel Wetzel and Pratt, {William D.} and Tami Unangst and Adele Miller and Sola, {James J.} and Reisler, {Ronald B.} and Cardile, {Anthony P.}",

note = "Publisher Copyright: {\textcopyright} 2020 Published by Oxford University Press for the Infectious Diseases Society of America 2020.",

year = "2021",

month = aug,

day = "15",

doi = "10.1093/infdis/jiaa781",

language = "English",

volume = "224",

pages = "632--642",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

number = "4",

}

Blair, PW, Kortepeter, MG, Downey, LG, Madar, CS, Downs, IL, Martins, KA, Rossi, F, Williams, JA, Madar, A, Schellhase, CW, Bearss, JJ, Zeng, X, Bavari, S, Soloveva, V, Wells, JB, Stuthman, KS, Garza, NL, Vantongeren, SA, Donnelly, GC, Steffens, J, Kalapaca, J, Wiseman, P, Henry, J, Marko, S, Chappell, M, Lugo-Roman, L, Ramos-Rivera, E, Hofer, C, Blue, E, Moore, J, Fiallos, J, Wetzel, D, Pratt, WD, Unangst, T, Miller, A, Sola, JJ, Reisler, RB & Cardile, AP 2021, 'Intensive Care Unit-Like Care of Nonhuman Primates with Ebola Virus Disease', Journal of Infectious Diseases, vol. 224, no. 4, pp. 632-642. https://doi.org/10.1093/infdis/jiaa781

TY - JOUR

T1 - Intensive Care Unit-Like Care of Nonhuman Primates with Ebola Virus Disease

AU - Blair, Paul W.

AU - Kortepeter, Mark G.

AU - Downey, Lydia G.

AU - Madar, Cristian S.

AU - Downs, Isaac L.

AU - Martins, Karen A.

AU - Rossi, Franco

AU - Williams, Janice A.

AU - Madar, Annie

AU - Schellhase, Christopher W.

AU - Bearss, Jeremy J.

AU - Zeng, Xiankun

AU - Bavari, Sina

AU - Soloveva, Veronica

AU - Wells, Jay B.

AU - Stuthman, Kelly S.

AU - Garza, Nicole L.

AU - Vantongeren, Sean A.

AU - Donnelly, Ginger C.

AU - Steffens, Jesse

AU - Kalapaca, Jennifer

AU - Wiseman, Perry

AU - Henry, Joseph

AU - Marko, Shannon

AU - Chappell, Mark

AU - Lugo-Roman, Luis

AU - Ramos-Rivera, Elliot

AU - Hofer, Christian

AU - Blue, Eugene

AU - Moore, Joshua

AU - Fiallos, Jimmy

AU - Wetzel, Darrel

AU - Pratt, William D.

AU - Unangst, Tami

AU - Miller, Adele

AU - Sola, James J.

AU - Reisler, Ronald B.

AU - Cardile, Anthony P.

PY - 2021/8/15

Y1 - 2021/8/15

N2 - 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.

AB - 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.

KW - Ebola virus disease

KW - Filoviridae

KW - Mononegavirales

KW - animal

KW - hemorrhagic fevers

KW - intensive care

KW - models

KW - viral

UR - http://www.scopus.com/inward/record.url?scp=85116957966&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiaa781

DO - 10.1093/infdis/jiaa781

M3 - Article

C2 - 33367826

AN - SCOPUS:85116957966

SN - 0022-1899

VL - 224

SP - 632

EP - 642

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 4

ER -

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

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Keywords

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