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(Unpublished)
Abstract
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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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| 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 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/31557 |
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