Les crises sanitaires touchent tous les pays du monde, mais l’impact est plus grand sur les États fragiles (Flahault, 2009) en raison de l’inefficacité des institutions, d’un manque de résilience ou encore des économies précaires (OCDE, 2016). Le cas d'Ebola en Guinée, est un exemple des lacunes dans les préalables de la résilience ayant mené à des difficultés dans la gestion de la crise (Boozary et al.,2014 ; Kekulé, 2015; Kruk et al.,2015). Depuis que la crise est terminée, des acteurs du terrain ont affirmé qu’il importe qu’un État fragile, comme la Guinée, puisse renforcer la gestion des crises et clarifier le rôle de tous les acteurs et partenaires impliqués afin de mieux coordonner la réponse (Diakité, 2016). La recherche qualitative s’appuie sur un cas empirique pour proposer un modèle de gestion résiliente des crises sanitaires pour les États fragiles. L’étude de cas cible les acteurs internationaux, nationaux et locaux, ayant participé à la gestion d’Ebola en Guinée, et analyse leurs méthodes d’intervention par rapport aux variables de la résilience sanitaire (conscience, diversité, auto-régulation, intégration et adaptabilité) proposées par Kruk et al. (2015). L’analyse triangulée des données a été réalisée grâce à 41 entretiens semi-dirigés réalisés, 36 événements observés, et une analyse documentaire approfondie. Depuis l’épidémie d’Ebola en Guinée, les acteurs sont conscients des insuffisances et des besoins à combler en vue d’avoir un système résilient. Avant l’épidémie, il y avait des faiblesses dans toutes les dimensions de la gestion des crises en Guinée. Depuis, l’État a mis en place divers mécanismes de renforcement du système de santé et du système de gestion des crises. Étant donné les déficiences en termes de résilience avant Ebola, il faut s’attendre à ce que la Guinée prenne encore beaucoup de temps avant de mettre en place un système résilient. Elle est encore trop dépendante des partenaires techniques et financiers. Par contre, il est possible de dire qu’elle dispose désormais de certains mécanismes, qu’on peut lier aux variables de la résilience sanitaire, qui permettraient de mieux organiser la réponse face aux crises. Grâce à l’étude empirique de la façon dont la Guinée a géré Ebola entre 2014 et 2016, nous avons développé un modèle théorique de gestion résiliente des crises sanitaires adapté aux États fragiles qui prend en compte la complexité inhérente aux contextes.

INTRODUCTION: Ebola virus (EBOV) is a highly infectious and often lethal filovirus that causes hemorrhagic fever, with a reported case fatality rate of 40-90%. There are currently no Food and Drug Administration (FDA) approved medical countermeasures (MCMs) for EBOV. Non-human primates (NHPs) remain the gold standard animal model for EBOV research as they most accurately recapitulate human disease. OBJECTIVE: This study aimed to characterize the temporal viral pathogenesis of EBOV in the liver of infected rhesus macaques using routine histopathology, multiplex immunohistochemistry (mIHC) and multiplex fluorescent In Situ Hybridization (mFISH), refined by digital pathology (DP) and image analysis (DIA). METHODS: 21 FFPE liver sections from EBOV-infected rhesus macaques were examined microscopically (Uninfected controls n=3; 3 DPE n=3; 4 DPE n=3; 5 DPE n=3; 6 DPE n=3; Terminal n=6). Tissues were stained with H&E and PTAH for histopathological scoring. Three serial sections were fluorescently immunolabeled or hybridized under three independent conditions (1.EBOV VP35, Tissue Factor, CD68; 2.EBOV VP35, Heppar, Myeloperoxidase (MPO); 3.EBOV VP35, IL-6, ISG-15). Slides were digitized by a Vectra PolarisTM fluorescent whole slide scanner and DIA was conducted using HaloTM image analysis software. Statistical analysis was conducted using GraphPad PrismTM 8.0. RESULTS: Comparing peracute (3-4 DPE) to acute (5-6 DPE) and terminal (6-8 DPE) EBOV infection, there is a statistically significant (p < 0.05) increase in hepatic inflammation and fibrin thrombi, correlating with an absolute increase in macrophages (CD68), neutrophils (MPO), and total % of Tissue Factor in the liver. There is also a significant increase in the severity of necrosis, which correlates with a decrease in Heppar. While there was significant colocalization of VP35 and CD68 starting at 4 DPE, there was only rare colocalization of VP35 with Heppar, even in terminal animals. Similar to mIHC, progressive and statistically significant differences were observed in gene expression when comparing peracute to acute and terminal EBOV infection. IL-6 predominated within periportal fibrovascular compartments, but also colocalized within cells concurrently expressing EBOV VP35. EBOV VP35 expression was observed within histiocytes, endothelial cells, and less commonly hepatocytes. ISG-15 expression was observed in periportal regions and in proximity to cells expressing EBOV VP35, but colocalization within EBOV VP35 expressing cells was an extremely rare event. CONCLUSION: Qualitative tools are well suited for confirming virulence and viral tissue tropism, but do little to build on our current understanding of disease. Using DIA in partnership with mIHC and mFISH, this study quantified statistically significant temporal changes in the immunoreactivity and hybridization of host and viral biomarkers that have previously been linked to the pathogenesis of EBOV. Taken together, these tools have enabled us to characterize minute changes that reflect magnitudes of biological variability simply not feasible to detect with the human eye. Furthermore, spatial context has refined our current understanding of differential gene expression of EBOV, which has the potential to aid in development of host-directed therapies. The establishment of these benchmarks will serve as a guide for the validation of cross-institutional EBOV animal models.

A systems theoretical analysis to capture the evolution and transition of the network systems supporting Ebola survivors and their affected communities, during the 2014-15 Ebola outbreak and recovery phases. The qualitative analysis includes a literature review, archival review, and interviews with representatives of key actors operating in strategic action fields. This paper uses a series of Diagrams that visually illustrate the various complex phases and their network changes that occurred and were established during the outbreak. This case analysis provides crucial phase information that both captures the historical events that informed the systems changes, including the development of the Ebola Survivors’ Support System (ESSS). Secondly, this analysis acts as, a model of understanding how disease support networks first emerge and can be better supported in other outbreaks.

This article analyzes data collected from Liberian women afflicted by the Ebola virus disease, survivors of the virus and noninfected persons living in Ebola-affected homes. This research is one of the first statistical analyses examining factors diminishing quality of life: negative experiences, stigma, and psychosocial symptoms among females affected by the virus after the outbreak. The research presents a thorough literature review, including research related to other infectious diseases like HIV/AIDS, to inform the gap in studies on Ebola’s effects on quality of life. Women who are Ebola virus disease survivors demonstrate significant differences in stigma and psychosocial stress when compared to their female peers. This article attempts to broaden understanding of the conditions and mental health of women affected by Ebola.

The 2014 Ebola outbreak, mostly affecting Liberia, Sierra Leone, and Guinea, is the largest ever recorded. The Ebola response encountered resistance in some affected communities, where some residents accused relief agencies from the Global North of denigrating local cultures. This thesis examines mainstream Western media and health experts’ representation of culture in the Ebola-affected region and employed Foucauldian analysis of discursive power to discuss the impact of such a representation on the concerned communities. Through a content analysis of selected journal and news articles by Western scholars and media and official reports by some relief agencies involved with the Ebola response, the study discovers evidence of culture bias. There was a use of significantly negative words in describing aspects of culture in the Ebola-affected region. Western media and health experts also largely associated the epidemic with African “backwardness.”

I. BACKGROUND: Following a review of donor funding priorities and concepts of health system strengthening (HSS) and resilience, this dissertation documents health system resilience factors existing in the Liberian health system in late 2014/early 2015 as the Ebola epidemic flared. The effectiveness of the WHO health system building blocks framework in addressing resilience was assessed, and specific factors that can promote health system resilience for Liberia going forward were identified. II. METHODS: Methods applied as part of this intrinsic case study include document and literature review, analysis of health facility and population-level statistics, and key informant and group interviews at the county and national levels. The methodology allowed for an in-depth assessment of how HSS (using the WHO health system building blocks) and resilience factors (using the WHO-defined key aspects of emergency preparedness) exist (or could exist) within the Liberian institutional and cultural context, and for tentative conclusions to be drawn about the importance of system factors to building specific health system capacities and overall health system resilience. III. FINDINGS: While dealing with myriad other public health priorities, public health preparedness went largely unaddressed in pre-Ebola Liberia where effectively none of the 16 key components or their 51 essential attributes listed in the WHO table of emergency preparedness were in place. The lack of integration of public health preparedness into HSS interventions left the country vulnerable to public health emergencies. There are two limitations to the government’s Ebola recovery and investment plan: (1) lack of a holistic approach to addressing emergency preparedness; and (2) not integrating emergency preparedness needs and corresponding activities into the existing national HSS framework. IV. CONCLUSION: By integrating emergency preparedness and response initiatives into HSS activities, health systems in Liberia and elsewhere can be strengthened to be more resilient, and thus better able to anticipate and adapt to challenges, and ultimately improve the system to be able to anticipate new future challenges. However, strengthening health systems so that they are resilient takes resources, including sector-wide, HSS resources that can be used to build functioning, integrated systems and skilled, networked individuals and groups across sectors.

<p>This study examines the media coverage of the widely-publicized non-Ebola event in Hamilton during 2001, and its impact on members of the local Hamilton Black community. The study argues that the problemalizalion of the non-Ebola event by both local and national print media stems from the anxiety of Canadians over the growing presence of racial minorities in Canada. The discursive construction of the event as a problem of immigration taps into the experiential consciousness of the public who draws on its racial capacity to make sense of the uncertainty and ambiguity of late modernity.</p> <p>~ism is expressed in the media coverage, but through non-race discourse. The study finds that immigration is problematized through its articulation with future health risks for Canadian. By the same token, racial diversity is dis-articulated from its socioeconomic benefits to Canadian society. Evidently, the discourse of immigration becomes a substitution for the discourse of anti-racial diversity. Findings show that members of the Black community are skeptical of medical and media systems, not necessarily because these systems are fallible, but largely because of their broader experience as a 'racial Other' in Canadian society. As a response to what members of the Black community have interpreted as exclusionary actions of these institutions, and punitive actions of the 'dominant racial group', 'race' is found to be inverted by Blacks, who gloss over within-group differences, out of resistance.</p> <p>The significance of the study lies in the links it draws between moral panic and risk discourses in perpetuating a late modem strain of racialization in the media.</p> / Doctor of Philosophy (PhD)

This study articulates the phenomenon of living under a constant threat of Ebola haemorrhagic fever, including what people’s reactions towards individuals and families affected by the illness symbolizes as well as the meanings ascribed to Ebola. The study was conducted in Kibale district in Midwestern Uganda to aid understanding of the human aspects of Ebola which has continued to result in widespread fear and anxiety, thereby creating challenges for affected individuals, families and health care professionals. A phenomenological inquiry was undertaken using Wertz’s (1983, 2005, 2011) empirical psychological reflection approach for data analysis, after utilizing purposive, convenience and criterion sampling techniques to select twelve (12) adult survivors and caregivers who anticipated, experienced and survived the outbreak and were in good health and also willing to take part in the study. Data were generated using in-depth qualitative interviews and the interviews continued until data redundancy was reached. The interview proceedings were digitally audio-recorded in addition to taking field notes and these were transcribed verbatim. Data analysis occurred at idiographic and nomothetic levels according to the principles of Wertz’s empirical psychological reflection. Thematic analysis of the research data revealed seven (7) themes, namely:  Living under constant threat of Ebola  Nature of Ebola experience: unique and general meanings  Surviving Ebola: physical, psychological, social, spiritual and economic implications on survivors  Caring for Ebola patients: social and psychological implications  Public reaction toward persons affected by Ebola  Social-cultural beliefs and practices related to Ebola  Coping with and living in the aftermath of Ebola outbreaks Adaptation emerged as the single most encompassing and accommodating concept that united the various themes, categories and sub-categories. It further grounded survivors’, caregivers’ and community’s experience of anticipating, experiencing and coping with challenges associated with Ebola. The findings add substantial knowledge about how survivors and caregivers experience Ebola outbreaks. Important recommendations are made and guidelines that may be used to increase survivors’, caregivers’ as well as the community’s resilience to challenges of future Ebola outbreaks are suggested. / Health Studies / D. Lit. et Phil. (Health Science)

This study articulates the phenomenon of living under a constant threat of Ebola haemorrhagic fever, including what people’s reactions towards individuals and families affected by the illness symbolizes as well as the meanings ascribed to Ebola. The study was conducted in Kibale district in Midwestern Uganda to aid understanding of the human aspects of Ebola which has continued to result in widespread fear and anxiety, thereby creating challenges for affected individuals, families and health care professionals. A phenomenological inquiry was undertaken using Wertz’s (1983, 2005, 2011) empirical psychological reflection approach for data analysis, after utilizing purposive, convenience and criterion sampling techniques to select twelve (12) adult survivors and caregivers who anticipated, experienced and survived the outbreak and were in good health and also willing to take part in the study. Data were generated using in-depth qualitative interviews and the interviews continued until data redundancy was reached. The interview proceedings were digitally audio-recorded in addition to taking field notes and these were transcribed verbatim. Data analysis occurred at idiographic and nomothetic levels according to the principles of Wertz’s empirical psychological reflection. Thematic analysis of the research data revealed seven (7) themes, namely:  Living under constant threat of Ebola  Nature of Ebola experience: unique and general meanings  Surviving Ebola: physical, psychological, social, spiritual and economic implications on survivors  Caring for Ebola patients: social and psychological implications  Public reaction toward persons affected by Ebola  Social-cultural beliefs and practices related to Ebola  Coping with and living in the aftermath of Ebola outbreaks Adaptation emerged as the single most encompassing and accommodating concept that united the various themes, categories and sub-categories. It further grounded survivors’, caregivers’ and community’s experience of anticipating, experiencing and coping with challenges associated with Ebola. The findings add substantial knowledge about how survivors and caregivers experience Ebola outbreaks. Important recommendations are made and guidelines that may be used to increase survivors’, caregivers’ as well as the community’s resilience to challenges of future Ebola outbreaks are suggested. / Health Studies / D. Litt. et Phil. (Health Science)

Le virus Ebola, responsable d'une fièvre hémorragique virale létale et le virus de la variole, agent étiologique de la variole, sont des armes biologiques potentielles. Il n'existe pas de traitement ou de prophylaxie autorisés contre le virus Ebola, quelques candidats vaccins étant en cours de développement. Concernant la variole, des vaccins dits de première génération (virus de la vaccine) ont permis l'éradication de la maladie cependant ils sont à l'origine de complications post-vaccinales parfois sévères alors que des vaccins plus récents dits de troisième génération, non-réplicatifs, ont été développés pour leur innocuité mais restent faiblement immunogènes. Nous avons récemment développé plusieurs vecteurs viraux de type virus de la vaccine (VACV) par délétion d'un certain nombre de facteurs de virulence. Nous avons évalué leur innocuité, leur immunogénicité et leur efficacité en tant que candidats vaccins antivarioliques chez la souris puis utilisé l'un de ces vecteurs pour développer un candidat vaccin bivalent antivariolique et anti-virus Ebola. Ces virus de la vaccine délétés sont réplicatifs mais fortement atténués. Ils induisent une réponse en anticorps neutralisants spécifiques anti-vaccine similaire à celle induite par le vaccin antivariolique de première génération et induisent des réponses immunitaires cellulaires CD4+ et CD8+ spécifiques suffisantes pour protéger l'animal d'un challenge létal de cowpoxvirus en intranasal, simulant une infection par le virus de la variole. Le virus délété le plus immunogène et le plus sûr, nommé MVL, a été utilisé pour construire un vecteur viral codant pour la glycoprotéine du virus Ebola (EGP). Le gène entier d'EGP ou une forme chimérique d'EGP (fusion entre l'ectodomaine d'EGP et le domaine transmembranaire de la glycoprotéine B5 du VACV) ont été clonés dans le génome du vecteur viral. Ces deux vecteurs produisent des virus ayant incorporé EGP dans leur enveloppe. Ces deux candidats vaccins recombinants induisent de fortes réponses humorales spécifiques anti-EGP et anti-vaccine chez la souris immunocompétente. En conclusion, nous avons développé plusieurs candidats vaccins antivarioliques aussi immunogènes et efficaces que le vaccin historique et avec une atténuation similaire aux vaccins de troisième génération. L'un de ces candidats (MVL) a été utilisé comme vecteur viral pour exprimer la glycoprotéine hétérologue EGP, contre laquelle il induit une réponse immunitaire humorale forte / Ebola virus, causing a lethal haemorrhagic fever and variola virus, the agent of smallpox are potential biological weapons. There is no treatment and no prophylaxis authorised against Ebola, although some vaccine viral vectors were developed these last years. Concerning smallpox, several types of vaccines exist against smallpox (based on vaccinia virus), first generation that allowed the disease eradication but responsible of some post-vaccination complications and some non-replicative 3rd generation vaccines which are safe but not very immunogenic. We have recently developed several vaccinia virus (VACV) vectors by deletion of some virulence genes, and we have evaluated their safety, immunogenicity and efficacy as smallpox vaccine in mice and used one of them as a bivalent vaccine against Ebola and smallpox. These viral vectors are higly attenuated and replicative competent. They induce a neutralizing specific-VACV antibodies response similar to that of the historical vaccine and induce VACV-specific CD8+ and CD4+ immune responses efficient to protect immunocompetent mouse model intranasally infected by cowpox virus, simulating variola virus infection.The most safety and immunogenic vaccinia virus vector, named MVL, has been used to construct a vector encoding the Ebola glycoprotein (EGP) for immunization against Ebola. The native EGP gene or a chimeric EGP gene (a fusion between the EGP ectodomain and the transmembrane domain of the VACV B5 glycoprotein) have been cloned into the viral vector genome. These two recombinant vaccine candidates induce specific humoral immune responses against Ebola and vaccinia virus in immunocompetent mice. In conclusion, we have developed several vaccine candidates against smallpox as immunogenic and protective as the historical vaccine and as safe as 3rd generation vaccines. One of these candidates, MVL, has been used as a viral vector to express the heterologous glycoprotein EGP, against which it induce a strong humoral immune response.