The utilization of advance telemetry to investigate critical physiological parameters including electroencephalography in cynomolgus macaques following aerosol challenge with eastern equine encephalitis virus.

Most alphaviruses are mosquito-borne and can cause severe disease in humans and domesticated animals. In North America, eastern equine encephalitis virus (EEEV) is an important human pathogen with case fatality rates of 30-90%. Currently, there are no therapeutics or vaccines to treat and/or prevent...

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Autores principales:	John C Trefry, Franco D Rossi, Michael V Accardi, Brandi L Dorsey, Thomas R Sprague, Suzanne E Wollen-Roberts, Joshua D Shamblin, Adrienne E Kimmel, Pamela J Glass, Lynn J Miller, Crystal W Burke, Anthony P Cardile, Darci R Smith, Sina Bavari, Simon Authier, William D Pratt, Margaret L Pitt, Farooq Nasar
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/c6d1539e38da43f78f4e7ec443930c9c
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spelling	oai:doaj.org-article:c6d1539e38da43f78f4e7ec443930c9c2021-11-25T06:31:46ZThe utilization of advance telemetry to investigate critical physiological parameters including electroencephalography in cynomolgus macaques following aerosol challenge with eastern equine encephalitis virus.1935-27271935-273510.1371/journal.pntd.0009424https://doaj.org/article/c6d1539e38da43f78f4e7ec443930c9c2021-06-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009424https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735Most alphaviruses are mosquito-borne and can cause severe disease in humans and domesticated animals. In North America, eastern equine encephalitis virus (EEEV) is an important human pathogen with case fatality rates of 30-90%. Currently, there are no therapeutics or vaccines to treat and/or prevent human infection. One critical impediment in countermeasure development is the lack of insight into clinically relevant parameters in a susceptible animal model. This study examined the disease course of EEEV in a cynomolgus macaque model utilizing advanced telemetry technology to continuously and simultaneously measure temperature, respiration, activity, heart rate, blood pressure, electrocardiogram (ECG), and electroencephalography (EEG) following an aerosol challenge at 7.0 log10 PFU. Following challenge, all parameters were rapidly and substantially altered with peak alterations from baseline ranged as follows: temperature (+3.0-4.2°C), respiration rate (+56-128%), activity (-15-76% daytime and +5-22% nighttime), heart rate (+67-190%), systolic (+44-67%) and diastolic blood pressure (+45-80%). Cardiac abnormalities comprised of alterations in QRS and PR duration, QTc Bazett, T wave morphology, amplitude of the QRS complex, and sinoatrial arrest. An unexpected finding of the study was the first documented evidence of a critical cardiac event as an immediate cause of euthanasia in one NHP. All brain waves were rapidly (~12-24 hpi) and profoundly altered with increases of up to 6,800% and severe diffuse slowing of all waves with decreases of ~99%. Lastly, all NHPs exhibited disruption of the circadian rhythm, sleep, and food/fluid intake. Accordingly, all NHPs met the euthanasia criteria by ~106-140 hpi. This is the first of its kind study utilizing state of the art telemetry to investigate multiple clinical parameters relevant to human EEEV infection in a susceptible cynomolgus macaque model. The study provides critical insights into EEEV pathogenesis and the parameters identified will improve animal model development to facilitate rapid evaluation of vaccines and therapeutics.John C TrefryFranco D RossiMichael V AccardiBrandi L DorseyThomas R SpragueSuzanne E Wollen-RobertsJoshua D ShamblinAdrienne E KimmelPamela J GlassLynn J MillerCrystal W BurkeAnthony P CardileDarci R SmithSina BavariSimon AuthierWilliam D PrattMargaret L PittFarooq NasarPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 6, p e0009424 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 John C Trefry Franco D Rossi Michael V Accardi Brandi L Dorsey Thomas R Sprague Suzanne E Wollen-Roberts Joshua D Shamblin Adrienne E Kimmel Pamela J Glass Lynn J Miller Crystal W Burke Anthony P Cardile Darci R Smith Sina Bavari Simon Authier William D Pratt Margaret L Pitt Farooq Nasar The utilization of advance telemetry to investigate critical physiological parameters including electroencephalography in cynomolgus macaques following aerosol challenge with eastern equine encephalitis virus.
description	Most alphaviruses are mosquito-borne and can cause severe disease in humans and domesticated animals. In North America, eastern equine encephalitis virus (EEEV) is an important human pathogen with case fatality rates of 30-90%. Currently, there are no therapeutics or vaccines to treat and/or prevent human infection. One critical impediment in countermeasure development is the lack of insight into clinically relevant parameters in a susceptible animal model. This study examined the disease course of EEEV in a cynomolgus macaque model utilizing advanced telemetry technology to continuously and simultaneously measure temperature, respiration, activity, heart rate, blood pressure, electrocardiogram (ECG), and electroencephalography (EEG) following an aerosol challenge at 7.0 log10 PFU. Following challenge, all parameters were rapidly and substantially altered with peak alterations from baseline ranged as follows: temperature (+3.0-4.2°C), respiration rate (+56-128%), activity (-15-76% daytime and +5-22% nighttime), heart rate (+67-190%), systolic (+44-67%) and diastolic blood pressure (+45-80%). Cardiac abnormalities comprised of alterations in QRS and PR duration, QTc Bazett, T wave morphology, amplitude of the QRS complex, and sinoatrial arrest. An unexpected finding of the study was the first documented evidence of a critical cardiac event as an immediate cause of euthanasia in one NHP. All brain waves were rapidly (~12-24 hpi) and profoundly altered with increases of up to 6,800% and severe diffuse slowing of all waves with decreases of ~99%. Lastly, all NHPs exhibited disruption of the circadian rhythm, sleep, and food/fluid intake. Accordingly, all NHPs met the euthanasia criteria by ~106-140 hpi. This is the first of its kind study utilizing state of the art telemetry to investigate multiple clinical parameters relevant to human EEEV infection in a susceptible cynomolgus macaque model. The study provides critical insights into EEEV pathogenesis and the parameters identified will improve animal model development to facilitate rapid evaluation of vaccines and therapeutics.
format	article
author	John C Trefry Franco D Rossi Michael V Accardi Brandi L Dorsey Thomas R Sprague Suzanne E Wollen-Roberts Joshua D Shamblin Adrienne E Kimmel Pamela J Glass Lynn J Miller Crystal W Burke Anthony P Cardile Darci R Smith Sina Bavari Simon Authier William D Pratt Margaret L Pitt Farooq Nasar
author_facet	John C Trefry Franco D Rossi Michael V Accardi Brandi L Dorsey Thomas R Sprague Suzanne E Wollen-Roberts Joshua D Shamblin Adrienne E Kimmel Pamela J Glass Lynn J Miller Crystal W Burke Anthony P Cardile Darci R Smith Sina Bavari Simon Authier William D Pratt Margaret L Pitt Farooq Nasar
author_sort	John C Trefry
title	The utilization of advance telemetry to investigate critical physiological parameters including electroencephalography in cynomolgus macaques following aerosol challenge with eastern equine encephalitis virus.
title_short	The utilization of advance telemetry to investigate critical physiological parameters including electroencephalography in cynomolgus macaques following aerosol challenge with eastern equine encephalitis virus.
title_full	The utilization of advance telemetry to investigate critical physiological parameters including electroencephalography in cynomolgus macaques following aerosol challenge with eastern equine encephalitis virus.
title_fullStr	The utilization of advance telemetry to investigate critical physiological parameters including electroencephalography in cynomolgus macaques following aerosol challenge with eastern equine encephalitis virus.
title_full_unstemmed	The utilization of advance telemetry to investigate critical physiological parameters including electroencephalography in cynomolgus macaques following aerosol challenge with eastern equine encephalitis virus.
title_sort	utilization of advance telemetry to investigate critical physiological parameters including electroencephalography in cynomolgus macaques following aerosol challenge with eastern equine encephalitis virus.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/c6d1539e38da43f78f4e7ec443930c9c
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The utilization of advance telemetry to investigate critical physiological parameters including electroencephalography in cynomolgus macaques following aerosol challenge with eastern equine encephalitis virus.

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