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Investigation of the natural history of Equine Encephalitis Viruses with radiofrequency telemetry for detection of subclinical disease patterns

Ma, Henry (2017) Investigation of the natural history of Equine Encephalitis Viruses with radiofrequency telemetry for detection of subclinical disease patterns. Master's Thesis, University of Pittsburgh. (Unpublished)

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Neither licensed vaccines nor antiviral therapeutics with proven efficacy exist to protect against the equine encephalitis viruses (EEVs), specifically Eastern, Western, and Venezuelan Equine Encephalitis Viruses (EEEV, WEEV, and VEEV, respectively). Due to rigorous ethical, regulatory, and scientific considerations, animal models that can faithfully demonstrate aspects of clinical disease must be established for testing of countermeasure candidates. Such models must satisfy the Animal Rule promulgated and enforced by the United States Food and Drug Administration and capture key aspects of equine encephalitis virus presentation in humans, especially with respect to encephalitic disease, whose manifestations include fever and neurological signs.
This study seeks to establish and study a model of human equine encephalitis virus infection via the aerosol route in the nonhuman primate, the cynomolgus macaque (Macaca fascicularis) with a focus on the natural history of disease through examination of radiofrequency electrocardiography data, and evaluates the feasibility of the use of such data to prognosticate severe disease courses which include encephalitis. Twelve nonhuman primate subjects, grouped four per type of equine encephalitis virus, were challenged with aerosol exposures of the alphaviruses in various doses.
The following electrocardiography metrics compose a core set of variables suited to the characterization of disease rendered by EEVs: HR, PCt, P-Width, PR-I, QRS, QRSA, QT-I, R-H, and RR-I. Frequency spectrum analysis conducted on these metrics can be used to distinguish different periods of disease, if not distinguish between diseases, and Poincare plots of heart rate variability data can be used to track the progression of illness.
The public health significance of this work rests in its contributions to disease detection to aid in vaccine and therapeutic development for both the prevention of infectious disease and the mitigation of risk posed by potential biological weapons attacks. Finally, improved clinical disease detection through RF telemetry and other markers will abet the surveillance function of public health.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Ma, Henryhem53@pitt.eduhem53
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee MemberHartman,
Committee MemberKlimstra,
Committee MemberMartinson,
Thesis AdvisorReed,
Date: 2 April 2017
Defense Date: 10 April 2017
Approval Date: 29 June 2017
Submission Date: 3 April 2017
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 151
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Infectious Diseases and Microbiology
Degree: MPH - Master of Public Health
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Alphavirus, Aerosol, Radiofrequency Telemetry, Electrocardiography, ECG, Equine Encephalitis Virus, EEEV, WEEV, VEEV
Date Deposited: 29 Jun 2017 22:34
Last Modified: 29 Jun 2017 22:34


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