Date of Award

2022

Degree Name

Biomedical Sciences

College

Joan C. Edwards School of Medicine

Type of Degree

Ph.D.

Document Type

Dissertation

First Advisor

Hongwei Yu, PhD, Committee Chairperson

Second Advisor

Vincent Munster, PhD, Advisor

Third Advisor

James Denvir, PhD

Fourth Advisor

Richard Egleton, PhD

Fifth Advisor

Philippe Georgel, PhD

Sixth Advisor

Heinz Feldmann, MD, PhD

Abstract

The outbreak of Ebola virus disease (EVD) centered in the West African countries of Guinea, Liberia, and Sierra Leone from 2013-2016 was the longest and largest such outbreak on record. At least 30,000 cases were reported, and the outbreak lasted nearly two-and-a-half years. Despite the progress made during and since that time, many questions remain unanswered. The studies here utilize a large set of nearly 750 whole blood samples from patients that were triaged and treated at the ELWA-3 Ebola treatment unit in Monrovia, Liberia in 2014 and 2015. Viral load, as approximated by qRT-PCR diagnostic assays in the field, has been shown to correlate with outcome, with higher viral loads increasing the risk of death. Here, viral load has been more accurately estimated by droplet digital PCR and shown to likely provide improved prognostic. These reanalyzed viral load data furthermore suggest that earlier initiation of supportive care, prior to peak viremia, did not improve outcomes in EVD patients at ELWA-3. Concern has also arisen regarding the possibility of bacteremia developing secondary to EVD. The samples here were analyzed using both a classic diagnostic microbiological approach and a targeting deep sequencing approach to evaluate this hypothesis, and bacteremia was found to be rare in EVD patients, with no increase in prevalence upon comparison to an EVD-negative cohort. Virological studies were also undertaken that involved isolating Ebola virus (EBOV) from the clinical samples, evaluating the isolation sensitivity of cell lines for these purposes, and analyzing the sequences obtained from EBOV isolates in comparison with sequences directly from the blood. Together, these data should further our understanding of both EVD and EBOV and possibly inform improvements in patient care.

Subject(s)

Ebola virus disease – Liberia – Monrovia – Case studies.

Ebola virus disease – Treatment.

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