This dissertation is made up of three distinct parts: 1) A comprehensive, structured literature review 2) a mixed-methods descriptive study and 3) an inductive thematic qualitative analysis. The objective of this dissertation is to explore the concepts of compassion fatigue, compassion satisfaction and burnout as they relate to the practices of narrative medicine among expatriate humanitarian aid workers. Data collected for this research focuses on expatriate healthcare workers who provided direct patient care during the 2013-2016 Ebola response in Sierra Leone, Liberia and Guinea. Findings from these studies support the growing body of evidence and discussion regarding psychosocial support of healthcare workers in humanitarian contexts. To the extent that global health is public health (Fried, 2010), results from this dissertation will contribute guidance in the understanding and management of aid workers in contexts beyond the Ebola response.

The continued study of asymptomatic Ebolavirus infection is necessary to develop a more complete understanding of Ebola transmission dynamics. This paper conducts a meta-analysis of eight studies that measure seroprevalence (the number of subjects that test positive for anti-Ebolavirus antibodies in their blood) in subjects with household exposure or known case-contact with Ebola, but that have shown no symptoms. In our two random effects Bayesian hierarchical models, we find estimated seroprevalences of 8.76% and 9.72%, significantly higher than the 3.3% found by a previous meta-analysis of these eight studies. We also produce a variation of this meta-analysis where we exclude two of the eight studies. In this model, we find an estimated seroprevalence of 4.4%, much lower than our first two Bayesian hierarchical models. We believe a random effects model more accurately reflects the heterogeneity between studies and thus asymptomatic Ebola is more seroprevalent than previously believed among subjects with household exposure or known case-contact. However, a strong conclusion cannot be reached on the seriousness of asymptomatic Ebola without an international testing standard and more data collection using this adopted standard.

Increasing global occurrences of highly infectious, easily transmissible diseases unfamiliar to nurses affect the learning environment and the required skill set for professional nurses. The global threat of Ebola Virus Disease and other high-risk diseases requiring biocontainment necessitates competency in the management of complex patient needs, while ensuring safety measures that prevent spread of the potentially fatal disease. Guided by Bandura's social cognitive theory, this quantitative correlational study addressed the relationships between nurses' professional characteristics and their perceived self-efficacy when providing care to highly infectious patients requiring biocontainment. A full census of 92 nurses was used to recruit participants from eligible nurses for this study. Participants anonymously completed a cross-sectional electronic survey consisting of the Nursing Care Self-Efficacy Scale (NCSES) and questions related to the nurses' professional practice characteristics. Data analysis included descriptive statistics, correlations, and multiple linear regression. Results showed that the number of biocontainment drills and a higher level of formal education were significantly correlated with a higher total NCSES score. Years of nursing significantly predicted a higher total NCSES score. Results support the establishment of prerequisites criteria for learner participation in biocontainment training and the inclusion of multiple drill within the education design. Findings from this study may inform positive social change through educational enhancements that support the development of professional self-efficacy and competency in skill performance for nurses who care for patients with highly contagious diseases requiring biocontainment.

Denna undersöknings främsta teoretiska utgångspunkt är att medier på ett eller annat sätt påverkar människors uppfattning av verkligheten. Medierna kan visa oss de dimensioner av verkligheten vi inte själva har möjligheten att uppleva och blir då ofta vår enda källa till information. Därför finns ett intresse att undersöka hur medier framställer sådana situationer och händelser. Undersökningen har begränsats till hur två av Sveriges största dagstidningar, Dagens Nyheter och Svenska Dagbladet, i sina reportage, framställt den ebolasituation som pågått i Västafrika under det senaste året. Detta har undersökts med hjälp av en kvalitativ analys av innehållet, där fokus lagts på att urskilja generella mönster och drag som karaktäriserar framställningen. Under den valda sökperioden har endast åtta reportage publicerats och samtliga av dem inom en tvåmånadersperiod. Värt att notera är det faktum att ebolasituationen enbart framställts utifrån ett av de drabbade länderna i Västafrika, Liberia. Analysen av materialet har påvisat flertalet relevanta mönster, bland annat att situationen framställts gå från allvarlig till kontrollerad trots att ebolaepidemin varit fortsatt pågående månader efter att det sista reportaget publicerats. Det har även konstaterats att majoriteten av personerna i reportagen har kopplingar till Läkare utan gränser, vilket dessutom är den organisation som spelar överlägset störst roll i den sammantagna bild som framställts i reportagen. Med hänsyn till undersökningens resultat har det sedan avslutningsvis getts förslag på eventuell fortsatt forskning, däribland att det skulle kunna vara av intresse att vidare studera hur ebolasituationen framställts i medieinnehåll som inte producerats inom samma kulturella ramar. Detta skulle kunna ge en bredare bild och öppna upp för kulturella jämförelser i framställningen av ebolasituationen.

The development of hybridoma technology nearly forty years ago set the foundation for the use of antibodies in the life sciences. Subsequent advances in recombinant DNA technology have allowed us to adapt antibody genes to various screening systems, greatly increasing the throughput and specialized applications for which these complex biomolecules can be adapted. While selection systems are a powerful tool for discovery and evolution, they can be slow and prone to unintended biases. We see computational approaches as an efficient process for rapid discovery and engineering of antibodies. This is particularly relevant for biodefense and emerging infectious disease applications, for which time is a valuable commodity. In the first chapter of this work, we examine computational protocols for ‘supercharging’ proteins. This process resurfaces the target protein, adding charged moieties to impart specialized functions such as thermoresistance and cell penetration. Current algorithms for resurfacing proteins are static, treating each mutation as an event within a vacuum. The net result is that while several variants can be created, each must be tested experimentally to ensure the resultant protein is functional. In many cases, the designed proteins were severely impaired or incapable of folding. We hypothesize that a more dynamic approach, keeping an eye on energetics and the consequences of mutations will yield a more efficient and robust method for supercharging, successfully adding charges to proteins while minimizing deleterious effects. We continue on this theme applying the successful algorithm to supercharging antibodies for increased function. Utilizing the MS2 model biosensor system, we rationally engineer charges onto the surface of an antibody fragment, increasing thermoresistance, minimizing destabilizing effects, and in some cases actually increasing affinity. Finally, we apply next-generation sequencing approaches to the rapid discovery of antibodies directed against the Zaire Ebolavirus species. We utilize a local immunization strategy to generate a polarized antibody repertoire that is then sequenced to provide a database of antigen-specific variants. This repertoire is probed in silico and individual antibodies selected for analysis, bypassing time- and resource-consuming selection experiments. / text

A method has been developed to track infectious diseases by using data mining of active Twitter accounts and its efficacy was demonstrated during the West African Ebola outbreak of 2014. Using a meme based n-gram semantic usage model to search the Twitter database for indications of illness, flight and death from the spread of Ebola in Africa, principally from Guinea, Sierra Leone and Liberia. Memes of interest relate disease to location and severity and are coupled to the density of Tweets and re-Tweets. The meme spreads through the community of social users in a fashion similar to nonlinear wave propagation- like a shock wave, visualized as a spike in Tweet activity. The spreading was modeled as a system isomorphic to a modified SIR (Susceptible, Infected, Removed disease model) system of three coupled nonlinear differential equations using Twitter variables. The nonlinear terms in this model lead to feedback mechanisms that result in unusual behavior that does not always reduce the spread of the disease. The resulting geographic Tweet densities are coupled to geographic maps of the region. These maps have specific threat levels that are ported to a mobile application (app) and can be used by travelers to assess the relative safety of the region they will be in.

Ebola virus (EBOV) is a zoonotic pathogen which causes a fulminant hemorrhagic fever and results in up to 90% fatality. Despite efforts over the past 38 years, a licensed prophylactic or post-exposure option remains unavailable. Several experimental vaccines have already demonstrated protection from lethal EBOV disease in nonhuman primates (NHPs). However, attempts to translate this research from bench to bedside have been hampered, since the immune responses that correlate with protection against EBOV are not well-defined. Without this information, it is not possible to reliably predict the efficacy of vaccines or treatments in humans without lethal challenge. The goal of this thesis is to determine the immune parameters that are predictive of protection against EBOV. Due to the rapid speed of EBOV pathogenesis, it was originally hypothesized that a rapid and robust CD8+ T-cell response must be crucial for survival. Using a previously-characterized adenovirus-vectored Ebola vaccine (Ad5-optGP), transgenic/knockout C57BL/6J mice with ablation for selected immune responses were vaccinated and challenged 28 days later. Surprisingly, while CD8+ T-cell knockout mice survived infection, B-cell knockout mice did not, indicating that the antibody response played a critical role in protection. Humoral and cell-mediated responses were compared between survivor and moribund guinea pigs and NHPs from previous vaccination and post-exposure therapy experiments, either with Ad5-optGP or a vesicular stomatitis virus (VSV)-vectored vaccine (VSVΔG/EBOVGP). Circulating EBOV glycoprotein (GP)-specific IgG antibody levels were the best correlation for protection independent of vaccine platform or timing of exposure (p<0.0001), strongly supporting the role of antibody responses in the control of EBOV infection. To demonstrate that antibodies are also responsible for protection, three previously-characterized monoclonal antibodies recognizing different GP epitopes were combined into a cocktail (ZMAb). Initiation of ZMAb treatment 1 and 2 days post infection (dpi) with EBOV protected 100% and 50% of NHPs, respectively. These results provide a reliable measure for predicting protection from EBOV in three commonly used animal models, and present a strong case for the use of antibodies as an effective post-exposure treatment. This knowledge will ultimately help in the development and validation of a clinical product against EBOV infection.

Thesis (Ph. D.)--University of Virginia, 2008. / Title from title page. Includes bibliographical references. Also available online through Digital Dissertations.

Thesis (Ph. D.)--McMaster University, 2005. / Advisor: Vic Stzewich. Includes bibliographical references (leaves 267-290). Also available online.

abstract: Ebola hemorrhagic fever (EHF) is a severe and often fatal disease in human and nonhuman primates, caused by the Ebola virus. Approximately 30 years after the first epidemic, there is no vaccine or therapeutic medication approved to counter the Ebola virus. In this dissertation, a geminiviral replicon system was used to produce Ebola immune complex (EIC) in plant leaves and tested it as an Ebola vaccine. The EIC was produced in Nicotiana benthamiana leaves by fusing Ebola virus glycoprotein (GP1) to the C-terminus of heavy chain of 6D8 monoclonal antibody (mAb), which is specific to the 6D8 epitope of GP1, and co-expressing the fusion with the light chain of 6D8 mAb. EIC was purified by ammonium sulfate precipitation and protein A or protein G affinity chromatography. EIC was shown to be immunogenic in mice, but the level of antibody against Ebola virus was not sufficient to protect the mice from lethal the Ebola challenge. Hence, different adjuvants were tested in order to improve the immunogenicity of the EIC. Among several adjuvants that we used, Poly(I:C), which is a synthetic analog of double-stranded ribonucleic acid that can interact with a Toll-like receptor 3, strongly increased the efficacy of our Ebola vaccine. The mice immunized with EIC co-administered with Poly(I:C) produced high levels of neutralizing anti-Ebola IgG, and 80% of the mice were protected from the lethal Ebola virus challenge. Moreover, the EIC induced a predominant T-helper type 1 (Th1) response, whereas Poly(I:C) co-delivered with the EIC stimulated a mixed Th1/Th2 response. This result suggests that the protection against lethal Ebola challenge requires both Th1 and Th2 responses. In conclusion, this study demonstrated that the plant-produced EIC co-delivered with Poly(I:C) induced strong and protective immune responses to the Ebola virus in mice. These results support plant-produced EIC as a good vaccine candidate against the Ebola virus. It should be pursued further in primate studies, and eventually in clinical trials. / Dissertation/Thesis / Ph.D. Plant Biology 2010