Understanding Ebola virus disease through a critical care lens: what can we learn from the effect of supportive care on the course of infection in non-human primates?
| dc.contributor.author | Poliquin, Philippe Guillaume | |
| dc.contributor.examiningcommittee | Embree, Joanne (Medical Microbiology and Infectious Diseases) Ghia, Jean-Eric (Immunology) Ball, T. Blake (Medical Microbiology and Infectious Diseases) Basler, Christoper (Icahn School of Medicine at Mount Sinai) | en_US |
| dc.contributor.supervisor | Strong, Jim (Medical Microbiology and Infectious Diseases) | en_US |
| dc.date.accessioned | 2019-08-26T14:57:11Z | |
| dc.date.available | 2019-08-26T14:57:11Z | |
| dc.date.issued | 2018-11-15 | en_US |
| dc.date.submitted | 2019-05-27T21:34:15Z | en |
| dc.date.submitted | 2019-08-21T21:11:33Z | en |
| dc.date.submitted | 2019-08-23T19:55:18Z | en |
| dc.degree.discipline | Medical Microbiology and Infectious Diseases | en_US |
| dc.degree.level | Doctor of Philosophy (Ph.D.) | en_US |
| dc.description.abstract | Background: Ebola Virus Disease is a clinical syndrome caused by infection with one of the ebolaviruses that affect humans. The resulting infection carries a high mortality rate, up to nearly 90% in some outbreaks. Despite significant research and investment in countering this virus, there are no currently licensed treatments or vaccines. This project tested the use of typical intensive care unit interventions on EVD in a non-human primate (NHP) model. The central hypothesis was that providing supportive care to the animals would lengthen survival long enough to allow the endogenous immune response to clear the infection. Methods: NHPs were sedated and ventilated for the duration of the experiments. Following infection with a universally lethal dose of Ebola Virus variant Makona, the animals were monitored continuously and interventions including fluid resuscitation, blood transfusion, vasoactive medications and hydrocortisone were provided in response to clinical need. Biochemical, hematological, immunologic and virological tests were also performed regularly. Results: The first achievement was development of a long-term sedation model for NHPs. This model was then used to test the interventions. These interventions did not lead to survival in the animals, nor did they lengthen survival when compared to historical controls. The data gleaned from the cardiovascular, respiratory and blood sampling was then analysed to gain insight into the pathophysiology of EVD that was not previously available due to limited sampling and monitoring abilities. Immune activation in EVD was different from that observed during other immune triggers, such as ventilator-associated pneumonia, and immune events could be mapped to clinical course with more precision than previous studies. Conclusions: Once EVD becomes established, a rapid progression toward septic shock occurs. A brief window of time was observed to be fluid responsive, followed by a fluid-refractory state. Failure to respond to fluid and vasoactive medications, combined with biochemical observations, suggest that endovascular dysfunction is the primary cause of unresponsive sepsis. These findings shed novel light on EVD pathophysiology support the need for continued development of Ebola-specific therapies. | en_US |
| dc.description.note | October 2019 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/34088 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Ebola | en_US |
| dc.subject | Supportive Care | en_US |
| dc.subject | Fluids | en_US |
| dc.subject | Ebola Virus Disease | en_US |
| dc.subject | Filovirus | en_US |
| dc.subject | Critical Care | en_US |
| dc.subject | Vasoactive medications | en_US |
| dc.subject | Nonhuman primate | en_US |
| dc.title | Understanding Ebola virus disease through a critical care lens: what can we learn from the effect of supportive care on the course of infection in non-human primates? | en_US |
| dc.type | doctoral thesis | en_US |