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DAINO, GIANLUCA. "Characterization of Ebola virus VP35-dsRNA binding for drug development against Ebola virus disease." Doctoral thesis, Università degli Studi di Cagliari, 2017. http://hdl.handle.net/11584/248693.
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The Ebola virus (EBOV) VP35 protein plays an important role in the inhibition of the initial innate immune responses to EBOV infection leading to Ebola virus disease development. In fact, VP35 interaction with the RIG-I like receptors (RLR) cascade components inhibits the interferon (IFN) production, impeding proper host immune response. Hence, it has been shown that VP35 is a validate drug target. Full-length His-tagged recombinant VP35 (rVP35) has been previously expressed in prokaryotic system and used to validate a biochemical pull-down assay for the screening of small molecules targeted to the VP35-double strand (ds)-RNA interactions. However, low rVP35 amount of purified protein and the use of radioactive substrate for binding evaluation, strongly limited the screening system. In the present study, a new method for high-yield rVP35 expression and purification, based on denaturation and subsequent protein refolding was established. Subsequently, a novel assay based on the use of Nickel-coated plates using a fluorescent labeled 30mer dsRNA was validated, showing a VP35 Kd value for dsRNA binding around 4 nM, comparable to the one previously reported, and a Z'-factor equal to 0.69, that indicate a good assay.
The use of this biochemical assay to screen the ability of plant extracts and derived compounds to inhibit the rVP35 binding to dsRNA allowed to identified a few small molecules able to inhibit the VP35-dsRNA binding with IC50 values in the low micromolar range. Active plant extracts and derived compounds were also tested in a cellular assay to evaluate their ability to counteract the inhibitory activity of VP35 on the IFN response. We identified a number of compounds able to inhibit the VP35 function in biochemical assay but ineffective in the cellular system. Conversely, some other compound, unable to inhibit rVP35 binding to dsRNA in biochemical assay, subverted VP35 inhibition of IFN production in cellular assay. These results suggested that the VP35 binding to dsRNA may not be the driving force of the VP35 inhibition of the IFN cascade and that an alternative mechanisms of action could be hypothesized for those compounds not able to inhibit VP35-dsRNA binding but effective against the VP35 IFN inhibitory effect. An interesting compound showed activity in both biochemical and cellular assays, suggesting the possibility that some small molecules interact with VP35 in such way to disrupt its interaction with multiple targets.
In order to understand the relative role of VP35-dsRNA binding in inhibiting the RLR cascade, we studied the effects of the lack of VP35 dimerization, considered essential for VP35 binding to dsRNA. For this purpose, three single point mutations, proposed to be essential for VP35 dimerization, were introduced into the coiled-coil VP35 domain. We confirmed by in silico studies that introduction of these three mutations disrupted coiled-coil dimerization. The importance of VP35 dimerization for VP35-dsRNA binding was confirmed by biochemical assay studies, where the mutant rVP35 showed a reduce ability to bind dsRNA. However, the mutant VP35 expressed in a cellular system showed a limited reduction of the ability of IFN production inhibition compared to the wild-type VP35. These results seem to confirm the hypothesis that VP35 binding to dsRNA is not the main interaction needed for VP35 inhibition of the IFN production and suggested that the VP35 interactions with cellular components do not require VP35 dimerization.
In conclusion, we demonstrated that small molecules interacting with VP35 can subvert its inhibition of the IFN production, possibly inhibiting its interactions with cellular components of RLR pathway and suggested that VP35 binding to dsRNA is not the driving for VP35 inhibition RLR cascade activation.
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Dia, Emilia. ""Ebola har nu nått Europa" : En kritisk diskursanalys av nyhetsrapporteringen om ebola i svenska medier." Thesis, Stockholms universitet, JMK, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-120325.
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Genom kritiska diskursanalyser ämnar studien att undersöka nyhetsrapporteringen av ebola i de svenska tidningarna Dagens Nyheter och Aftonbladet. Delvis för att få förståelse för hur mediepanik skapas, men även hur relationen mellan nyhetsläsaren och den lidande konstrueras. Undersökningsperioden för studien är oktober 2014. Den tidigare forskningen som belyses i denna undersökning är studier om nyhetsrapporteringar kring svininfluensan, SARS-smittan och salmonellabakterien. Dessa visar på att de intensiva perioderna i nyhetsrapporteringen ofta innefattar användningen av visuella och lingvistiska medel som bidrar till att skapa en mediepanik. De teoretiska ramarna som denna uppsats utgår ifrån är Simon Cottles teorier om hur medier konstruerar mediepaniker i rapporterandet om globala kriser, Roger Fowlers teorier om nyheternas språk vid rapporteringar om kriser och Lilie Chouliarakis teorier om lidandets spektakel. Resultatet visar således att nyhetsmedierna talar om ebolan som hot mot Europa och USA, om regional spridning, katastrofhjälp, geopolitik och sjukvård. De röster som främst får en talan i dessa artiklar är Världshälsoorganisationen, myndigheter, politiker och experter som uttalar sig om olika situationer. Patienter är de som inte får komma till tals även om de nämns i artiklarna. Resultatet av de ingående analyserna i denna studie visar att avståndet till nyhetshändelserna påverkar hur nyheter om ebola skildras i medierapporteringen. I artiklar som behandlade nyhetshändelser om ebola i Afrika, betonades det att ebolasmittan fanns på en avlägsen plats. Samtidigt upptäcktes det att innehållet såsom språket blev intensivare när medierapporteringen skildrade nyheter om ebola i Europa. Därmed skapades även en känsla av kris och risk.
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Miller, Michele. "Development and Validation of Virus and Ebola Misconceptions Assessment (VirEMiA): Ebola Virus Misconceptions in College Students." Wright State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=wright1459333659.
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LaTouche, Alina S. "East Harlem seniors' knowledge about ebola." Thesis, Icahn School of Medicine at Mount Sinai, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10107190.
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Older adults’ knowledge and perceptions about Ebola have not been previously explored in the literature. A survey, administered during the Ebola outbreak in 2014, was performed to capture East Harlem senior residents’ knowledge about Ebola and identify their major sources of information, their self-reported levels of trust in city officials, and whether or not they would follow officials’ directions. Results using frequency testing showed that senior respondents were not knowledgeable about disease transmission. The major trusted sources of information identified were television and newspapers. Overall, respondents trusted city officials and were very likely to follow city instructions. This study is important because it elucidates the need for better information to be more efficiently disseminated through media during a health emergency.
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Seiler, Nina. "Inkubationszeit und Übertragungsparameter der Ebola-Viruskrankheit." [S.l. : s.n.], 2008.
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Lennemann, Nicholas Joseph. "Biochemical characterization of Ebola virus GP." Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/3127.
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Filoviruses cause sporadic outbreaks of highly lethal hemorrhagic fever throughout central Africa. Virus entry is mediated by the sole viral glycoprotein, GP. Furthermore, GP is the main target for neutralizing antibodies. Thus, a better understanding of GP and its functions is critical for the development of antivirals and vaccines.
GP contains a high number of N- and O-linked glycans, which shield the majority of the protein. These glycans are required for cell surface interactions with C-type lectins that mediate internalization of the virus. We found that GP1, but not GP2, N-linked glycans were required for efficient entry into cells expressing the C-type lectins: L-SIGN, DC-SIGN, and LSECtin expressing cells, but O-linked glycans were sufficient for ASGPRI- and hMGL-dependent entry. However, filoviruses also utilize phosphatidylserine (PS) receptors, which bind PS in the viral membrane, to mediate entry into host cells. We found that all N-linked glycosylation sites in GP1 could be mutated without significant impact on expression. Furthermore, removal of all N-linked glycans increased entry into a PS receptor-dependent cell line and primary murine macrophages. These results correlated with an increase in sensitivity to proteolysis, which is required within the late endosome/lysosome to expose the receptor-binding domain. Surprisingly, removal of N-linked glycans that directly shield the receptor-binding domain did not allow for binding to the intracellular receptor, NPC1. Thus, proteolytic removal of heavily glycosylated domains within the late endosome/lysosome exposes critical receptor-binding residues that are masked by polypeptides and not N-linked glycans. Furthermore, removal of the conserved N-linked glycan on the heptad repeat 1 region in GP2 led to an increase in entry. Conversely, removal of the conserved N-linked glycan on the heptad repeat 2 region decreased entry. Removal of either glycan resulted in a decrease in entry mediated by protease-treated GP. Together, these results suggest N-linked glycans on GP2 are involved in controlling fusion. Interestingly, removal of N-linked glycans masking conserved regions of GP led to a significant increase in convalescent antibody-mediated neutralization. Overall, these results indicate that there is an evolutionary trade-off that results in a decrease in entry efficiency in order to protect virus from the immune system.
Analysis of entry mediated by multiple species of ebolavirus indicated that the residue occupying position 95 is a critical determinant of entry. For Ebola virus (EBOV) GP, Sudan virus (SUDV) GP, and Bundibugyo (BDBV) GP, a lysine at position 95 imparts dependence on the cysteine protease cathepsin B. However, a glutamine at this position alleviates this dependence and is found in some early isolates of SUDV. Furthermore, cathepsin B dependence inversely correlated with an increase in sensitivity to protease-mediated degradation of GP. Mutation of K95 to a glutamine in EBOV GP and BDBV GP led to decreased sensitivity to NPC1 and voltage-operated calcium channel inhibitors. Conversely, mutation of the Q95 to a lysine in SUDV GP decreased sensitivity to NPC1 inhibitors and had no impact on voltage-operated calcium channel inhibitors. However, all proteins regardless of the residue at position 95 required NPC1 for entry. Together these results indicate that a single amino acid polymorphism in GP of ebolaviruses has dramatic impacts on entry factor dependence, suggesting potential differences in entry pathways.
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Dapiaggi, F. "MOLECULAR MODELING OF EBOLA VIRUS INHIBITORS." Doctoral thesis, Università degli Studi di Milano, 2018. http://hdl.handle.net/2434/545872.
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In this PhD thesis computational methods have been employed in order to study different biologically relevant systems. In the first part of the thesis two Ebola virus proteins were studied, namely Viral Protein 24 (VP24) and Viral Protein 35 (VP35), responsible for the inhibition of the immune response .
After a brief theoretical introduction to the main computational methods employed in the thesis, a study of VP35 in complex with small organic molecules is presented. These
compounds are able to inhibit the interaction between VP35 and viral nucleoprotein. This study confirms the experimental findings highlighting new important key interactions
between the protein the inhibitors. Moreover, an Essential Dynamics analysis points out an interesting collective motion of the apo-form that is hindered by the presence of the
ligands.
Afterwards, the protein-protein interaction VP24-Karyopherin (KPNA) is studied. An atomistic analysis of the interactions at the interface leads to the design of a
nonapeptide with VP24 binding capability. The peptide is derived from a KPNA subsequence and could potentially inhibit the VP24-KPNA interaction.
Subsequently an analysis on the pockets present on VP24 surface in different solvents is performed. Once the most promising pocket has been located, a virtual screening on a
subset of ZINC database is carried out, leading to the identification of few classes of molecules potentially able to bind VP24.
Finally the effect of the osmolytes on VP24 protein structure is studied, pointing out how osmoprotectants and urea have opposite effects on the protein, the former stabilizing
the folded state and the latter shifting the equilibrium to the denatured state.
In the second part of the manuscript the study of the interaction of an antimicrobial peptide with a lipid membrane is presented. This work was carried out in the
University of Groningen under the supervision of Prof. Siewert Jan Marrink in order to deepen the Coarse Grain method.
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Elmberg, Emma, and Mathilda Nordahl. "”Världen förlorar kampen mot ebola” : En kvantitativ innehållsanalys om hur ebola gestaltades i svensk storstadspress hösten 2014." Thesis, Linnéuniversitetet, Institutionen för medier och journalistik (MJ), 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-45042.
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Mbala-Kingebeni, Placide. "Virus Ebola à l’interface homme – faune sauvage et réservoir animal des virus Ebola en République Démocratique du Congo." Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTT035.
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Chaque épidémie de la maladie à virus Ebola résulte très probablement d'événements zoonotiques indépendants. Plus de quatre décennies après la première identification du virus Ebola, son réservoir demeure encore inconnu. Nous avons montré dans ce travail que la prévalence du virus Ebola dans la faune sauvage était très faible avec une présence d’anticorps anti-virus Ebola (Zaïre et/ou Sudan) chez moins de 1% des chauves-souris testées de la RDC, Guinée et Cameroun ; et de 0% chez les primates non humains de la RDC, Cote d’Ivoire et Cameroun, en période inter-épidémique. Aucun anticorps n’a été détecté dans les échantillons prélevés en période épidémique en RDC. La recherche de l’ARN du virus Ebola, au cours de ces études, était négative. Néanmoins, nous avons confirmé et caractérisé chez l’homme, les nouveaux variants du virus Ebola responsables des récentes épidémies de 2018 en RDC. Le séquençage génomique précoce et continu a permis d'orienter les interventions en matière de santé publique.Ainsi, malgré la présence d'anticorps du virus Ebola, le rôle des chauves-souris en tant qu'espèce réservoir reste flou, car la détection de l'ARN viral est encore rare. Les anticorps anti-virus Ebola sont très rares chez les primates non humains, ce qui confirme que les PNH ne sont pas des espèces réservoirs. Les efforts pour retrouver le réservoir de ce virus doivent continuer car c’est le seul moyen qui nous permettra de prévenir efficacement les prochaines épidémiesEvery Ebola outbreak is most likely the result of independent zoonotic events. More than four decades after the first identification of the Ebola virus, its reservoir remains unknown. We have shown in this work that the prevalence of Ebola virus in wildlife was very low with antibodies against Ebola virus (Zaire and / or Sudan) detected in less than 1% of bats tested in the DRC, Guinea and Cameroon; and 0% in non-human primates from the DRC, Cote d'Ivoire and Cameroon, during inter-epidemic period. No antibodies were detected in samples collected during the epidemic period in the DRC, and the search for Ebola RNA in these studies was negative. Nevertheless, we have confirmed and characterized in humans, new variants of the Ebola virus which caused the recent outbreaks of 2018 in the DRC. Early and ongoing genomic sequencing has been used to guide public health interventions.Thus, despite the presence of antibodies to the Ebola virus, the role of bats as a reservoir species remains unclear, as the detection of viral RNA is still rare. Ebola virus antibodies are very rare in non-human primates, confirming that PNH are not reservoir species. Efforts to recover the reservoir of this virus must continue because it is the only way that will allow us to effectively prevent future outbreaks
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Victoriano, Analisa Machado. "Ébola: uma revisão bibliográfica." Bachelor's thesis, [s.n.], 2020. http://hdl.handle.net/10284/9282.
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Projeto de Graduação apresentado à Universidade Fernando Pessoa para obtenção do grau de Licenciada em EnfermagemO vírus Ébola é um agente patogénico causador de uma doença sistémica, grave e com alta taxa de mortalidade em humanos e primatas não-humanos. Foi descoberto pela primeira vez em 1976 na República Democrática do Congo. Existem cinco espécies conhecidas do vírus, das quais quatro foram identificadas na África Equatorial. Uma vez que entra na população humana a transmissão ocorre principalmente pelo contato com fluídos corporais contaminados. O vírus causa uma supressão do sistema imunitário, bem como uma resposta inflamatória acentuada e grande perda de fluídos e eletrólitos. Embora existam vacinas e tratamentos em desenvolvimento, a gestão dos casos baseia-se na sintomatologia e manutenção e reposição de fluídos e eletrólitos, para prevenção e controlo da falência de órgãos. Em 2014 a Organização Mundial da Saúde classificou a epidemia causada pelo vírus Ébola como um problema da saúde pública em África e que preocupa o mundo. O Centro de Controlo e Prevenção de Doenças dos Estados Unidos listou o vírus Ébola como um agente de bioterrorismo de categoria A.
The Ebola virus is a pathogen causing a systemic, severe disease with a high mortality rate in humans and non-human primates. It was first discovered in 1976 in the Democratic Republic of congo. There are five known species of the virus, four of which have been identified in Equatorial Africa. Once it enters the human population transmission occurs mainly by contact with infected body fluids. The virus causes a suppression of the immune system, as well as a marked inflammatory response and large loss of fluids and electrolytes. Although vaccines and treatments are in development, case management is based on symptomatology and maintenance and replacement of fluids and electrolytes, for prevention and control of organ failure. In 2014, the World Health Organization classified the Ebola virus epidemic as a public health problem in Africa that worries the world. The U.S. Centers for Disease Control and Prevention has listed the Ebola virus as a Category A bioterrorism agent.
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Gasquet, Clélia. "Une géographie de la fièvre hémorragique à virus Ebola : représentations et réalités d'une maladie émergente au Gabon et en République du Congo." Paris 10, 2010. http://www.theses.fr/2010PA100131.
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La fièvre hémorragique à virus Ebola est une maladie qui constitue une menace pour les populations d'Afrique Centrale, notamment en milieu rural forestier. Au Gabon et en République du Congo, où 7 épidémies ont sévit entre 1994 et 2005, elle y est devenue un problème de santé publique. Cette zoonose émerge chez l'homme lors d'un contact direct avec un animal contaminé, une carcasse ou un vecteur du virus. L'émergence est directement liée aux pratiques ancestrales des lieux (chasse, cueillette, etc. ). La contamination inter humaine a lieu lors d'un contact direct avec les fluides corporels d'un malade. Elle s'effectue en premier lieu au sein des familles des victimes, lors des soins prodigués aux malades et ceux donnés aux morts lors des cérémonies funéraires. Nous tentons dans les premiers temps de cette étude de comprendre, en nous appuyant sur le concept de pathocénose, en quels termes l'émergence virale éclaire sur les liens existants entre les hommes et les virus. Lors de telles épidémies la médecine d'urgence « s'associe » au système de santé national dont l'emprunte territoriale est localement faible. Plusieurs types d'offres de soins antérieurs (traditionnels) ou postérieurs (clinique religieuses) se surimpose au modèle de santé biomédical représenté par les cases de santé et centres médicaux. Les médicaments manquent, les personnels de santé ne se rendent pas toujours sur les lieux de leur affectation. Au quotidien, les recours aux soins des populations apparaît pluriel. Lors d'une épidémie d'Ebola, en raison de son taux de mortalité (jusqu'à 80%) et de sa contagiosité élevés, la logique des malades sembles plus liée à une errance thérapeutique, conditionnée par la recherche des soins et de la causalité du malheur. La multiplicité des acteurs présents lors de la crise exacerbe l'anomie créée par la maladie et met en exergue un rapport de force, de violence, qui n'est parfois que l'expression de la contestation des plus démunisThe Ebola hemorrhagic viral fever is a disease which constitutes a threat for the populations of Central Africa, in particular in rural forester areas. In the Gabon and Republic of Congo (7 epidemics between 1994 and 2005) it became a problem of public health? This zoonos appears at the man's during a direct contact with a contaminated animal, a carcass or a vector of the Ebola virus. The emergence is directly connected, in these enclosed villages, to the ancestral practices of places (hunting, picking, etc. ). The contamination takes place during a direct contact with the physical fluids of a patient. It's made first of all within the families of the victims, during the care lavished on the patients and during those given to the deaths during ceremonies funeral. Firstly, with pathocenosis' concept help, we try in this study to understand in which terms the viral emergence lights us on existing links between people and virus. The amplified rôle of hospital's care confirms the inmportance of the risk in this structure and th panic perception of the world opinion. The North carries a particular interest there. There is no epidemic of Ebola which is accompanied with the procession of international institution. This procession « joins » to the national health system of which takes it territorial is low locally. Several types of care's offers exist with the biomedical model of health represented by « house of health » and health centers. During an epidemic of Ebola, because of his high mortality rate (ut to 80%) and of its contagiousness, the logic of the patient seems more connected to a therapeutic wandering, conditioned by the search for the care and for the causality of the misfortune. In the absence of vaccine, the treatment against Eobla remains symptomatic. The multiplicity of the present actors during the crisis aggravates the anomie created by the disease and highlights a balance of powers, violence, wich is sometimes only the expression of the contesting of the most deprived
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Schneider, Brian J. (Brian Joseph) 1973. "Protein dissection of the Ebola virus glycoprotein." Thesis, Massachusetts Institute of Technology, 1998. http://hdl.handle.net/1721.1/88820.
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Lindström, Jöran. "Covid-19 i Afrika: Beredskap efter ebola." Thesis, Högskolan i Skövde, Institutionen för hälsovetenskaper, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-20045.
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Introduktion Afrika har haft flera utbrott av ebola (EVD). Det Västafrikanska EVD-utbrottet 2014-2016 var det mestförödande med mer än 28 000 fall och mer än 11 000 dödsfall. Utbrottet började i Guinea och spredsöver gränsen till Sierra Leone och Liberia. 2018-2020 var det ett utbrott av EVD i DemokratiskaRepubliken Kongo (DRC) som spreds till Uganda. På grund av utbrotten av EVD har de drabbadeländerna byggt upp kapacitet att hantera epidemier. Syfte Syftet med studien är att beskriva den kapacitet som byggts upp i respons till EVD-utbrott, och hurkapaciteten har varit till nytta för staterna under deras första sex månaders respons till covid-19 iLiberia, Guinea, Sierra Leone, Uganda, samt DRC. Metod Studien är en systematisk litteraturstudie. Resultat De tre Västafrikanska länderna var hårt drabbade av EVD på grund av svaga hälsosystem, en historiaav interna konflikter, porösa gränser och det faktum att EVD kunde spridas till fler områden innan detupptäcktes. De Västafrikanska staterna kunde med internationell hjälp bygga upp kapacitet för atthantera epidemier, vilken har använts i arbetet mot covid-19. EVD-utbrottet i DRC hade en snabbarerespons eftersom det hade byggts upp kapacitet både på en afrikansk- och internationell nivå sedandet Västafrikanska utbrottet. Slutsats De Afrikanska länderna i denna studie har kunnat använda sig av kapacitet som de byggt upp för atthantera EVD i sin hantering av covid-19. Detta trots att de fortfarande har fortfarande svagahälsosystem och saknar resurser.Introduction Africa has had several outbreaks of Ebola (EVD). The West African EVD outbreak 2014-2016 was themost devastating with more than 28 000 cases and more than 11 000 deaths. It started in Guinea andspilled over the border to Sierra Leone and Liberia. In 2018–2020, there was an outbreak of EVD inDemocratic Republic of Congo (DRC), which spilled over the border to Uganda. Due to the outbreaksof EVD, the affected countries have built capacity to respond to epidemics.AimThe aim of the study is to describe the capacity that was built-up to respond to EVD outbreaks andhow the capacity has aided the countries in their first six months of response to COVID-19 in Liberia,Guinea, Sierra Leone, Uganda and DRC. Methods The study is a systematic literature study. Results The three West African countries were severely affected by EVD because of weak health systems, ahistory of civil conflicts, porous borders and the fact that the EVD could spread to several locationsbefore it was discovered. The West African countries have with international help built up capacityagainst epidemics that has been used in response to COVID-19. The EVD outbreak in DRC had a moreswift response since there has been capacity building on an African and International level since theWest African outbreak. Conclusion The African countries in this study have been able to use capacity that was built-up to respond to EVDin their response to COVID-19, despite of the fact that they still have weak health systems with lack ofresources.
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Nilsson, Marina. "Utvecklingen av nya vacciner mot ebolafeber : Erfarenheter efter senaste utbrottet i Kongo 2018." Thesis, Linnéuniversitetet, Institutionen för kemi och biomedicin (KOB), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-93287.
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Introduction: Since the first outbreaks of Ebola virus disease 1976 in the Democratic Republic of the Congo (DRC) and Sudan there has been recurrent epidemics. The biggest outbreak so far hit West Africa between 2013-2016 when at least 28 600 people were estimated to have been infected and approximately 11 300 died in the most severely affected countries Guinea, Sierra Leone and Liberia. Ebola hemorrhagic fever (EHF) or Ebola virus disease (EVD) is caused by a virus that together with the Marburg virus belongs to the Filovirus family. The Ebola virus can cause hemorrhagic bleeding, has a rapid disease progression rate and a high mortality (25-90%). The symptoms are initially headache, fever, sore throat and muscle pain but during the latter part of the disease the characteristic bleedings from all bodily orifices occurs. Many internal organs do damage and survivors often have persistent sequels and long convalescense. EVD is a zoonosis and might infect antelopes, monkeys, porcupines among others. The natural reservoir is believed to be different species of bats. In august 2018, another outbreak of Ebola was reported in DRC. This was the tenth time the disease hit the country. However, for the first time there was candidate vaccine in clinical trial that could be used during an emergency. Experts within the WHO recommended that vaccination was initiated using Merck`s Ebolavaccine rVSV-∆G-ZEBOV-GP that was ready for a phase III clinical trial. This vaccine had already been used during the West African outbreak and had been known to provide a good safety profile as well as immunogenicity. The second vaccine to be used was a two-dose heterologous prime-boost vaccine regimen called Ad26.ZEBOV/MVA-BN-Filo which was marketed by Johnson&Johnson. Ad26.ZEBOV was given as a first dose to prime the immune system and then MVA-BN-Filo was administered as a second dose approximately 8 weeks later as a booster. This vaccine regimen had also been showing promising results in phase I and II clinical trials. Objective: This degree project was made in attempt to answer the issue: How effective and safe are the new Ebola vaccines against EVD? Methods: To answer this question, a literature study was conducted. The outbreak in DRC was ongoing by the time of this degree project and there were no phase III trials conducted for the Ad26.ZEBOV/MVA-BN-Filo vaccine regimen. A lot of information was therefore retrieved from WHO, Doctors without borders, and so on. Merck`s vaccine had been prequalified and received the generic name Ervebo in the fall of 2018. Randomised clinical trials (RCT) and clinical trials regarding Ervebo was downloaded from the internet using the search engine PubMed that`s accessing different databases. Results: Both Ervebo and the 2-dose vaccine regimen Ad26.ZEBOV/MVA-BN-Filo initiated an immune response against ebolavirus that was almost 100%. The most frequent solicited local and systemic adverse events were injection site pain and headache, myalgia and fever. All adverse events were reported to be mild and resolved in a short period of time. No severe adverse events were reported. Discussion: The biggest challenge in the future will concern how to initiate vaccination strategies in countries with a lack of financial resources and infrastructure as well as ongoing armed conflicts (mainly DRC). Conclusion: The new vaccines against Ebola virus infection are all effective with a good safety profile.Bakgrund: Sedan de första utbrotten av ebolafeber 1976 i Demokratiska republiken Kongo (DRK) och Sudan har epidemier blossat upp med jämna mellanrum. Det hittills största utbrottet drabbade Västafrika 2013-2016 då minst 28 600 beräknades ha smittats och minst 11 300 avled i de hårdast drabbade länderna Guinea, Sierra Leone och Liberia. Ebolafeber, eller ebola hemorragisk feber, orsakas av ett virus som tillsammans med Marburgviruset hör till familjen Filovirus. Ebolaviruset kan orsaka hemorragiska blödningar, har snabbt sjukdomsförlopp och hög dödlighet (25-90%). Symptomen är inledningsvis influensaliknande men under den senare delen av sjukdomsförloppet förekommer de karaktäristiska blödningarna från alla kroppsöppningar. Många inre organ tar skada och överlevare har ofta bestående men och lång konvalescens. Ebolafeber är en zoonos och kan drabba antiloper, olika sorters apor m fl. Den naturliga reservoaren tros vara olika arter av fladdermöss. I augusti 2018 rapporterades om ännu ett utbrott av ebolafeber i DRK, det 10:e i ordningen. En avgörande skillnad vid detta utbrott var att det nu fanns kandidatvaccin i kliniska studier att tillgå. En expertgrupp inom WHO rekommenderade att vaccination inledddes med rVSV-∆G-ZEBOV, ett ebolavaccin tillverkat av Merck redo för kliniska studier fas III. Detta vaccin hade använts redan under utbrottet i Västafrika och visat goda resultat vad gällde immunogenicitet och säkerhet. Det andra vaccinet att sättas in var Ad26.ZEBOV/MVA-BN-Filo, tillhandahållet av Johnson&Johnson. Detta bestod av två olika doser som gavs med ca 8 veckors mellanrum, ofta kallat ”prime/boost”-vaccin. Även för Ad26.ZEBOV/MVA-BN-Filo fanns dokumenterade positiva resultat. Syfte: Detta examensarbetet gjordes med syftet att svara på frågeställningen: Hur effektiva och säkra är de nya vaccinen mot ebolafeber? Metod: För att svara på frågan gjordes en litteraturstudie. När detta examensarbete författades pågick fortfarande utbrottet i DRK och fas III studierna för Ad26.ZEBOV/MVA-BN-Filo var inte avslutade. Mycket information fick hämtas från olika hemsidor, bl a WHO och Läkare utan gränser. Mercks vaccin prekvalificerades hösten 2019 och gavs handelsnamnet Ervebo. För detta vaccin fanns fler RCT-studier tillgängliga, vilka uteslutande valdes m h a sökmotorn PubMed som är länkad till olika databaser. Resultat: Både singeldosvaccinet Ervebo och dubbeldosvaccinen Ad26.ZEBOV/MVA-BN-Filo konstaterades ge ett nästan 100%-igt immunsvar mot ebolavirus. I den mån biverkningar förekom var de milda och övergående. Den mest rapporterade lokala biverkningen var ömhet vid injektionsstället och de vanligaste systemiska biverkningarna var huvudvärk, myalgi och feber. Diskussion: Den största utmaningen i framtiden blir att inleda vaccinationsprogram i länder med bristande finansiella resurser och infrastruktur samt pågående väpnade konflikter (främst DRK). Slutsatsen blev att de nya vaccinen mot ebolafeber är effektiva och säkra vid behandling mot ebolavirusinfektion.
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Karlsson, Johanna. "Kunskapsläget om ebola bland Örebros läkarstudenter ht 2014." Thesis, Örebro universitet, Institutionen för läkarutbildning, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-42968.
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Foster, Felicity Laurel. "Contagion and Violence | "No Ebola in West Point!"." Thesis, The American University of Paris (France), 2019. http://pqdtopen.proquest.com/#viewpdf?dispub=13871614.
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Ahmadi, Fard Ala. "Ebola hemorrhagic fever: outbreaks, modeling, and vaccine development." Kansas State University, 2016. http://hdl.handle.net/2097/32649.
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Master of ScienceDepartment of Biological & Agricultural Engineering
Caterina M. Scoglio
Lisa R. Wilken
Between the years 2014 and 2015, the world experienced a catastrophic outbreak of Ebola virus, which killed over 26,000 people. Several authorities and organizations actively participated in fighting the epidemic. Infectious disease modelers proved to be invaluable towards this goal. This report provides a background on the Ebola epidemic in West Africa and reviews the biological features of the Ebola virus. Moreover, this report applies a new model for Ebola propagation using data collected by the World Health Organization during the span of the outbreak. The model estimates the reproduction number and assesses the role of mitigation strategies in slowing down the progress of the disease. The report also concludes a review of recent advancements in vaccine production against Ebola.
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Lin, Kaisen. "Aerosolization of Ebola Virus Surrogates in Wastewater Systems." Thesis, Virginia Tech, 2016. http://hdl.handle.net/10919/73043.
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Recent studies have shown that Ebola virus can persist in wastewater, and the potential for the virus to be aerosolized and pose a risk of inhalation exposure has not been evaluated. We considered this risk for three wastewater systems: toilets, a lab-scale model of an aeration basin, and a lab-scale model of converging sewer pipes. We measured the aerosol size distribution generated by each system, spiked Ebola virus surrogates into each system, and determined the emission rate of viruses into the air. While the number of aerosols released ranged from 105 to 107 per flush from the toilets or per minute from the lab-scale models, the total volume of aerosols generated by these systems was ~10-8 to 10-7 mL per flush or per minute in all cases. The Ebola virus surrogates MS2 and Phi6, spiked into toilets at an initial concentration of 107 PFU mL-1, were not detected in air after flushing. Airborne concentrations of MS2 and Phi6 were ~20 PFU L-1 and ~0.1 PFU L-1, respectively, associated with the aeration basin and sewer models. This corresponds to emission rates of 547 PFU min-1 and 3.8 PFU min-1 of MS2 and Phi6, respectively, for the aeration basin and 79 PFU min-1 and 0.3 PFU min-1 for the sewer model. Since information on the aerosolization of Ebola virus is quite limited, these emission rates can greatly help inform risk assessment of inhalation exposure to Ebola virus.Master of Science
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Leroy, Éric. "Infection asymptomatique de l'homme par le virus ebola." Paris 6, 2000. http://www.theses.fr/2000PA066292.
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La fievre hemorragique ebola, due a un virus enveloppe a simple brin d'arn non segmente de polarite negative, est une maladie d'evolution aigue qui tue environ 70% des malades. Les desordres physiopathologiques et immunitaires qu'elle entraine sont essentiellement lies a l'infection des monocytes et des cellules endotheliales. Durant les trois epidemies survenues au gabon entre 1995 et 1997, nous avons identifie sept personnes qui n'ont jamais developpe de symptomes malgre des contacts physiques avec certains liquides biologiques infectieux. L'infection par le virus ebola fut d'abord suspectee grace a la detection d'igm et d'igg anti-np, et -vp40 et -vp35. La mise en evidence d'arn viral () pendant pres de trois semaines ainsi que celle d'arn (+) dans les cellules sanguines prouvent que le virus s'est transitoirement replique, et confirment l'existence de personnes asymptomatiquement infectees par le virus ebola. Le sequencage des genes codant pour quatre proteines qui jouent un role majeur dans les interactions hote/virus (np, gp, vp24, vp40) revele une identite des sequences nucleotidiques entre asymptomatiques, convalescents et decedes, suggerant que le statut asymptomatique ne resulte pas de mutations virales. Une forte reponse inflammatoire, caracterisee par des taux eleves en il-i, tnf, il-6, mcp-1, mip-1 et mip-1, est mise en evidence, chez les asymptomatiques, au septieme jour suivant le premier contact infectieux. La presence quasi concomitante de mediateurs anti-inflammatoires (stnfri/ii, il-ira, il-io, cortisol) est probablement en partie responsable de l'extinction de la reponse inflammatoire au 9 i e m e jour apres l'infection. La disparition simultanee des mediateurs inflammatoires et de l'arn (+) evoque l'hypothese
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Lee, Christopher T. "Critical Heat Stress Evaluation In Two Ebola Ensembles." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6299.
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Ebola, a type of filovirus that causes hemorrhagic fevers, dominated global headlines in 2014 when the largest Ebola epidemic in history took place in West Africa. Healthcare practitioners were at particular risk of contracting Ebola while taking care of patients with the disease because they were easily exposed to bodily fluids such as blood, urine, saliva, and feces, quite often in the intensive care unit (ICU). While personal protective equipment (PPE) protects the healthcare practitioner by providing an effective barrier against the virus, users were also at risk for heat stress because of the type of protective clothing. In this study, coveralls made of monolithic barriers, which prevent water vapor from escaping the suit, were compared to coveralls made of micro- porous material, which allows evaporated sweat to escape the suit. The Microgard® 2000 TS Plus, made of micro-porous barrier material and the monolithic barrier Microgard® 2300 Plus were compared against a control ensemble of work clothes consisting of a long-sleeve shirt and trouser.
A progressive heat stress protocol was used to determine the critical environment at the upper limit of compensable heat stress. The critical condition was the point at which the heat gain caused by wearing the protective ensemble as well as dry heat exchange was balanced by the maximum heat loss due to evaporative cooling. Wet bulb globe temperature at the critical condition (WBGTcrit ) ,total evaporative resistance (Re,T,a), and clothing adjustable factor (CAF) were calculated for each ensemble based on data at the critical point. Also at the critical condition, participant rectal temperature vi (Tre) , heart rate (HR), skin temperature (Tsk), and physiological strain index (PSI) were noted and compared for each ensemble.
A two-way ANOVA (ensemble x participant) for WBGTcrit and Re,T,a as dependent variables was used to determine whether or not there were differences among ensembles. Tukey’s honest significance test was used to determine where significant differences occurred. WBGTcrit was 33.8, 26.3, and 22.9 °C-WBGT for Work Clothes, M2000, and M2300 respectively. Re,T,a was 0.012, 0.031, and 0.054 kPa m2 W-1 for WC, M2000, and M2300 respectively. The higher the WBGTcrit for an ensemble, the more it can support evaporative cooling and hence the better it is at ameliorating heat stress. Based on this trial, the micro-porous ensemble Microgard® 2000 TS Plus has better heat stress performance than vapor-barrier Microgard® 2300 Plus. As expected, there were no differences for any of the physiological metrics at the critical conditions.
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Brody-Moore, Peter. "Bayesian Hierarchical Meta-Analysis of Asymptomatic Ebola Seroprevalence." Scholarship @ Claremont, 2019. https://scholarship.claremont.edu/cmc_theses/2228.
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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.
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Leigh, Laurasona. "Behavioral and Environmental Attributes of Ebola Epidemic in West Africa and United States Emergency Nurses’ Motivation to Protect Themselves against Ebola Infection." University of Toledo / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1470411786.
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Weik, Michael. "Untersuchung cis-aktiver Elemente im Genom des Ebola-Virus." [S.l.] : [s.n.], 2001. http://archiv.ub.uni-marburg.de/diss/z2002/0194/.
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Änäkkälä, Nicola. "Seroprevalence study on Ebola Virus in patients in Uganda." Thesis, Örebro universitet, Institutionen för hälsovetenskap och medicin, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-44931.
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Gjyljeta, Fifa. "Ebola Virus (EVD) through the lenses of news articles." Thesis, Linnéuniversitetet, Institutionen för statsvetenskap (ST), 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-39539.
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Media in modern society uses their influence and power to frame social phenomenon in society from political elections, health crisis, war to terrorism etc. The aim of this study is on a global level to observe how selected newspapers have portrayed Ebola virus (EVD). The conceptual framework presented will be a mixture of concepts based in Peace and Development studies and Media studies with an emphasis on the first as this thesis is iwhitn Peace and Development Studies. This study will be a qualitative study, where selected articles are observed and analyzed with the help of a content analysis (textual analysis). The selected newspapers are The Salone Monitor (Sierra Leone), The Daily News (US), Dagens Nyheter (Sweden) and The Guineeconakry (Guinea). The selection of each newspaper is influenced by the research questions in terms of using two African newspapers located geographically in countries effected by Ebola virus (EVD) and two Western newspapers with geographical distance, to observe similarities and differences in how Ebola virus (EVD) has been portrayed in correlation to geographical placement. The conclusion drawn from this research indicates similarities and differences in how Ebola virus (EVD) has been portrayed in respect to the conceptual framework used which relates to the risk and crisis communication, power, securitization and “Them and us” concepts. Indicating similarities concerning limitations in reporting about care communication in terms of raising awareness by communicating knowledge about transmission and protection strategies for respective audience. In addition, Ebola virus (EVD) is greatly securitized through the lenses of each newspaper using their (newspapers) influence (form of power) to create fear between readers at the same time showing differences in the process of how Ebola virus (EVD) becomes a global threat. Additionally, also reporting risk and crisis communications greatly by communicating information about dangers EVD possesses. Processes of “them and us” are established characterizing Ebola virus (EVD) as a threat for Africa until confirmed cases occur outside Africa. Therefore changing how Ebola virus (EVD) becomes shaped and identified as a global security threat after outbreaks in US and Spain. Keywords: Securitization, “Them and us”, power, risk and crisis communication, Ebola virus (EVD), newspaper, global health news, articles
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Montazeri, Shahtori Narges. "Quantifying the impact of contact tracing on ebola spreading." Thesis, Kansas State University, 2016. http://hdl.handle.net/2097/34540.
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Master of ScienceDepartment of Electrical and Computer Engineering
Faryad Darabi Sahneh
Recent experience of Ebola outbreak of 2014 highlighted the importance of immediate response to impede Ebola transmission at its very early stage. To this aim, efficient and effective allocation of limited resources is crucial. Among standard interventions is the practice of following up with physical contacts of individuals diagnosed with Ebola virus disease -- known as contact tracing. In an effort to objectively understand the effect of possible contact tracing protocols, we explicitly develop a model of Ebola transmission incorporating contact tracing. Our modeling framework has several features to suit early–stage Ebola transmission: 1) the network model is patient–centric because when number of infected cases are small only the myopic networks of infected individuals matter and the rest of possible social contacts are irrelevant, 2) the Ebola disease model is individual–based and stochastic because at the early stages of spread, random fluctuations are significant and must be captured appropriately, 3) the contact tracing model is parameterizable to analyze the impact of critical aspects of contact tracing protocols. Notably, we propose an activity driven network approach to contact tracing, and develop a Monte-Carlo method to compute the basic reproductive number of the disease spread in different scenarios. Exhaustive simulation experiments suggest that while contact tracing is important in stopping the Ebola spread, it does not need to be done too urgently. This result is due to rather long incubation period of Ebola disease infection. However, immediate hospitalization of infected cases is crucial and requires the most attention and resource allocation. Moreover, to investigate the impact of mitigation strategies in the 2014 Ebola outbreak, we consider reported data in Guinea, one the three West Africa countries that had experienced the Ebola virus disease outbreak. We formulate a multivariate sequential Monte Carlo filter that utilizes mechanistic models for Ebola virus propagation to simultaneously estimate the disease progression states and the model parameters according to reported incidence data streams. This method has the advantage of performing the inference online as the new data becomes available and estimating the evolution of the basic reproductive ratio R₀(t) throughout the Ebola outbreak. Our analysis identifies a peak in the basic reproductive ratio close to the time of Ebola cases reports in Europe and the USA.
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Hanson, Jessi, Patrick Seeco Faley, and Megan Quinn. "Analysis of the Liberian Ebola Survivors Support System (ESSS)." Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/6786.
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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.
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Hanson, Jessi, Alexis Decosimo, and Megan Quinn. "Diminished Quality of Life among Women affected by Ebola." Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/6867.
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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.
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Scully, William. "A Critical Analysis of the Ebola and Marburg Viruses." Miami University Honors Theses / OhioLINK, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=muhonors1111685379.
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Gopalakrishnan, Arjun. "Probabilistic Analysis of Contracting Ebola Virus Using Contextual Intelligence." Thesis, University of North Texas, 2017. https://digital.library.unt.edu/ark:/67531/metadc984182/.
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The outbreak of the Ebola virus was declared a Public Health Emergency of International Concern by the World Health Organisation (WHO). Due to the complex nature of the outbreak, the Centers for Disease Control and Prevention (CDC) had created interim guidance for monitoring people potentially exposed to Ebola and for evaluating their intended travel and restricting the movements of carriers when needed. Tools to evaluate the risk of individuals and groups of individuals contracting the disease could mitigate the growing anxiety and fear. The goal is to understand and analyze the nature of risk an individual would face when he/she comes in contact with a carrier. This thesis presents a tool that makes use of contextual data intelligence to predict the risk factor of individuals who come in contact with the carrier.
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Escudero, Pérez Beatriz. "The role of shed GP in Ebola virus pathogenicity." Thesis, Lyon, École normale supérieure, 2014. http://www.theses.fr/2014ENSL0933/document.
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Au cours de l’infection par le virus Ebola (EBOV), plusieurs glycoprotéines solubles sont massivement libérées à partir de cellules infectées mais le rôle précis de ces protéines virales n’a pas encore été identifié. Nous émettons l'hypothèse que l'altération de l’hémostase et du système et vasculaires observée au cours de l'infection à virus Ebola pourrait être, au moins en partie causée par ces glycoprotéines solubles. Ainsi pour la première fois, nous avons identifié les cibles cellulaires de la protéine soluble « shed GP » d’Ebola et nous avons démontré que sa partie glycosylé peut activer les cellules dendritiques et les macrophages non infectés, induisant, par le récepteur TLR4, la sécrétion de cytokines pro-inflammatoires. Nous démontrons aussi que l'activité de la shed GP est neutralisé lors de l'addition de la MBL, une protéine connue pour interagir avec certains motifs glycosylés présents à la surface de différents micro-organismes. Nous avons également montré que la shed GP active la perméabilité des HUVEC de façon directe et indirecte, via la libération de cytokines. En conclusion, cette étude suggère que la shed GP peut être l'un des principaux facteurs responsables de la stimulation précoce des cellules immunitaires qui produisent alors de grandes quantités de cytokines pro-inflammatoires, des éléments qui, combinés avec la réplication massive du virus et les dommages cellulaires induits par le virus, peuvent conduire à un syndrome de type choc septique et une mortalité élevéeDuring Ebola virus (EBOV) infection several soluble glycoproteins are released in high amounts from infected cells but as yet still no clear role has been identified for these viral proteins. We hypothesized that the impairment of coagulation and vascular systems observed during EBOV infection could be, at least in part, due to these soluble glycoproteins.Here, for the first time we identify the cellular targets of EBOV soluble protein shed GP and provide evidence that through its glycosylation, shed GP can activate non-infected dendritic cells and macrophages, inducing, through TLR4, the secretion of pro-inflammatory cytokines. We also demonstrate that shed GP activity is negated upon addition of Mannose-Binding sera Lectin (MBL), a molecule known to interact with sugar arrays present on the surface of different microorganisms. We have also revealed that shed GP activates permeability of HUVECs both directly and indirectly through cytokine release. Overall, this study suggests that shed GP may be one of the principal factors responsible for the early stimulation of immune cells that then produce high amounts of proinflammatory cytokines that, combined with massive virus replication and virus-induced cell damage, can lead to a septic shock-like syndrome and high mortality
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Fuhrmann, Didier. "Les fièvres hémorragiques africaines : les virus Lassa - Ebola - Marbourg." Strasbourg 1, 1988. http://www.theses.fr/1988STR15028.
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Martin, Baptiste. "Méthyltransférases des filovirus et autres mononégavirus : caractérisation, originalités et drug design." Thesis, Aix-Marseille, 2017. http://www.theses.fr/2017AIXM0258.
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Les virus appartenant à l’ordre des Mononegavirales possèdent une « large » protéine L, responsable du cycle réplication/transcription et de maturation des ARNs. Six domaines conservés portent les différentes activités de cette protéine dont le site catalytique d’une activité méthyltransférase (MTase) de la coiffe. La coiffe est une structure chimique constituée d’une guanosine méthylée en position N7 reliée à l’extrémité 5’ des ARNm par une liaison 5’-5’ triphosphate. Une seconde méthylation est également présente en position 2’O du ribose du premier nucléotide de l’extrémité 5’ de l’ARNm. Ces méthylations ont un rôle critique chez les virus car elles permettent la traduction efficace des ARNm mais permettent également aux ARNs viraux d’échapper à leur détection par l’immunité innée de l’hôte. Ainsi, la caractérisation de ce domaine chez le virus Ebola serait un point clé pour une meilleure compréhension de la réplication des filovirus et un pas vers l’élaboration d’une nouvelle stratégie thérapeutique. Nous avons donc produit le domaine MTase du virus Soudan (SUDV) afin de caractériser son activité. Il a été démontré que le domaine C-terminal de la protéine L joue un rôle dans le recrutement de l’ARN, crucial pour l’activité MTase. Nous avons pu identifier une activité A-2’O MTase interne originale. Le domaine MTase de SUDV est également capable de méthyler les positions N7 et 2’O de la coiffe mais une caractérisation plus approfondie est nécessaire. Enfin, nous avons identifié des molécules inhibant l’activité MTase des filovirus. Une analyse biochimique plus poussée permettra d’initier le développement d’une nouvelle stratégie antivirale contre le virus EbolaIn the Mononegavirales order, viruses encode a large protein (L), which is responsible for replication/transcription and RNA modifications. This protein harbours six conserved domains accountable of these different activities. Among these domains, the conserved region VI (CRVI) has been predicted to support cap-methyltransferase (MTase) activity. The cap consists in a N7-methylated guanosine linked to the first nucleotide at the mRNA 5'-end by a 5'-5' triphosphate bond. This structure can also be methylated at the 2'O position of N1 ribose. These methylations play a critical role in virus life cycle as N7 methylation triggers efficient viral RNA translation and 2'O methylation hampers the detection of viral RNA by the host innate immunity. Thus, the characterization of this domain in Ebola virus is a key point to understand replication of mononegaviruses and design new antiviral strategies. We produced the MTase domain of Sudan ebolavirus (SUDV) to characterize its MTase activity. We demonstrated that the protruding C-terminal domain is essential for MTase activity as this domain is a key for the RNA recognition. Using synthetic short RNAs holding different cap structures, we discovered that SUDV MTase harbours an unconventional A-2’O MTase activity. Besides this, the MTase domain is able to methylate the cap structure at N7 and 2'O positions but further characterization would be necessary to fully understand the cap synthesis. Finally, we identified compounds limiting the Ebola virus MTase activity. Further biochemistry and compounds characterization results will thus pave the way towards the development of an innovative antiviral strategy
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Sandersfeld, Lindsay Marie Maury Wendy J. "Identification of ebola glycoprotein mutants that exhibit increased transduction efficiency." [Iowa City, Iowa] : University of Iowa, 2009. http://ir.uiowa.edu/etd/428.
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Modrof, Jens. "Strukturelle Charakteristika des Ebola-Virus-VP30 und deren funktionelle Bedeutung." [S.l.] : [s.n.], 2002. http://archiv.ub.uni-marburg.de/diss/z2002/0078/.
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Mehedi, Masfique. "Ebola virus RNA editing:Characterization of the mechanism and gene products." American Society of Microbiology, 2011. http://hdl.handle.net/1993/11465.
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Ebola virus (EBOV) is an enveloped, negative-sense single-stranded RNA virus that causes severe hemorrhagic fever in humans and nonhuman primates. The EBOV glycoprotein (GP) gene encodes multiple transcripts due to RNA editing at a conserved editing site (ES) (a hepta-uridine stretche). The majority of GP gene transcript is unedited and encodes for a soluble glycoprotein (sGP); a defined function has not been assigned for sGP. In contrast, the transmembrane glycoprotein (GP1,2) dictates viral tropism and is expressed through RNA editing by insertion of a nontemplate adenosine (A) residue. Hypothetically, the insertion/deletion of a different number of A residues through RNA editing would result in another yet unidentified GP gene product, the small soluble glycoprotein (ssGP). I have shown that ssGP specific transcripts were indeed produced during EBOV infection. Detection of ssGP during infection was challenging due to the abundance of sGP over ssGP and the absence of distinguishing antibodies for ssGP. Optimized two- dimensional (2-D) gel electrophoresis verified the expression of ssGP during infection. Biophysical characterization revealed ssGP is a disulfide-linked homodimer that is exclusively N-glycosylated. Although ssGP appears to share similar structural properties with sGP, it does not have the same anti-inflammatory function. Using a new rapid transcript quantification assay (RTQA), I was able to demonstrate that RNA editing is an inherent feature of the genus Ebolavirus and all species of EBOV produce multiple GP gene products. A newly developed dual-reporter minigenome system was utilized to characterize EBOV RNA editing and determined the conserved ES sequence and cis-acting sequences as primary and secondary requirements for RNA editing, respectively. Viral protein (VP) 30, a transcription activator, was identified as a contributing factor of RNA editing— a proposed novel function for this largely uncharacterized viral protein. Finally, I could show that EBOV RNA editing is GP gene-specific because a similar sequence located in L gene did not serve as an ES, most likely due to the lack of the necessary cis-acting sequences. In conclusion, I identified a novel soluble protein of EBOV whose function needs further characterization. I also shed light into the mechanism of EBOV RNA editing, a potential novel target for intervention.
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Rodríguez, Morales Alfonso J., Daniel E. Henao, Tulio B. Franco, Percy Mayta-Tristan, Toloza Patricio Alfaro, and Mondolfi Alberto E. Paniz. "Ebola: A latent threat to Latin America. Are we ready?" Elsevier B.V, 2014. http://hdl.handle.net/10757/334794.
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Garcia-Dorival, G. I. "Investigation of the interaction between Ebola virus and the host." Thesis, University of Liverpool, 2016. http://livrepository.liverpool.ac.uk/3002887/.
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Ebola viruses cause viral haemorrhagic fever in humans and non human primates. Due to the severity of their symptoms, the lack of an approved treatment or vaccine, and the mechanism of transmission, these viruses have been classified as containment level 4 (CL4) pathogens. In December 2013, an Ebola virus outbreak initiated in West Africa, which lasted more than two years, and has been considered the worst outbreak in the history of the Ebola viruses. More than twenty-seven thousand people had a positive diagnosis of infection with more than eleven thousand confirmed dead. This outbreak highlights not only the urgent necessity for new treatments and vaccines against this virus but also that there is still a large knowledge gap for Ebola viruses compared to other pathogens. This thesis focuses on using high resolution approaches to characterise the interaction between the Zaire ebolavirus species (EBOV) and the host. The work focuses on using high resolution sequencing to characterise the evolution of EBOV throughout the outbreak in West Africa and also in adapting to grow in a novel host. The work also focuses on two viral proteins that are critical to the virus life cycle. The VP24 protein that is an interferon antagonist and the nucleoprotein (NP) which encapsidates the viral genome. Quantitative proteomics was used to identify host cell proteins that interacted with these viral proteins and inhibitors were used to ablate cellular protein function and monitor the effect on viral biology. The thesis is written in the style of ‘by publication’ and the publications associated with this work are reproduced in the Appendix.
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Sandersfeld, Lindsay Marie. "Identification of ebola glycoprotein mutants that exhibit increased transduction efficiency." Thesis, University of Iowa, 2009. https://ir.uiowa.edu/etd/428.
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Gene delivery via lentiviruses can yield long term expression of transgenes. Specificity of host cell targeting by viral vectors occurs primarily through viral glycoprotein (GP)/cellular receptor interactions. Ebola virus (EBOV) GP has broad tropism for a variety of cell types making this viral GP a potentially useful reagent for delivery of gene therapy. However, titers of EBOV GP pseudotyped lentiviruses are insufficient for practical use in clinical applications. Enhancement of EBOV-GP pseudotyped titers by as little as half a log might yield clinically applicable titers.
In an alanine scanning study, we identified 19 residues in EBOV-GP1 that increased transduction efficiency two to three fold. When mapped onto the crystal structure of EBOV GP, these residues were primarily located at the interface of GP1/GP2 suggesting these residue substitutions may confer conformational changes in the protein structure thereby enhancing transduction efficiency. To determine if combinations of these alanine substitutions might further enhance transduction, we have introduced the changes into EBOV GP in a stepwise manner. To date, introduction of some combinations of alanine substitutions resulted in as much as an eight-fold increase in transduction over WT GP, this being our super mutant combination, whereas other combinations eliminated transduction.
Identification of 5 additional mutations via 3D modeling of the glycoprotein uncovered an additional mutation in GP2, located at the GP1/GP2 interface, which also enhances EBOV GP transduction. Transduction of cell lines important for gene therapy including hepatocytes and porcine airway cells confirmed an enhancement in transduction as well. Other cell populations, specifically fibroblasts and renal cells, were also transduced but enhanced transduction was not observed indicating this phenomenon may be cell type specific. The in vivo studies were inconclusive because no expression was detected from any of the EBOV GP pseudovirions. Even expression of the positive control, GP64 particles, waned after 3 weeks post inoculation indicating insufficient quantities or poor quality pseudovirions were used. These EBOV GPs should prove useful for future gene therapy studies by providing an alternate glycoprotein that is as effective as GP64 at producing high titer lentiviral vectors.
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Rhein, Bethany Ann. "Ebola virus: entry, pathogenesis and identification of host antiviral activities." Diss., University of Iowa, 2015. https://ir.uiowa.edu/etd/6629.
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Ebola virus (EBOV) is a member of the Filoviridae family of highly pathogenic viruses that cause severe hemorrhagic fever and is the causative agent of the 2014 West Africa outbreak. Currently, there are no approved filovirus vaccines or treatments to combat these sporadic and deadly epidemics. One target for EBOV antiviral therapy is to block viral entry into host cells. Recently, phosphatidylserine (PtdSer) receptors, primarily known for their involvement in the clearance of dying cells, were shown to mediate entry of enveloped viruses including filoviruses. The PtdSer receptors, T-cell immunoglobulin mucin domain-1 (TIM-1) and family member TIM-4, serve as filovirus receptors, significantly enhancing EBOV entry. TIM-dependent virus uptake occurs via apoptotic mimicry by binding to PtdSer on the surface of virions through a conserved PtdSer binding pocket within the amino terminal IgV domain. TIM-4 is expressed on antigen presenting cells (APCs), including macrophages and dendritic cells (DCs), which are critical in early EBOV infection. My studies are the first to define the molecular details of virion/TIM-4 interactions and establish the importance of TIM-4 for EBOV infection of murine resident peritoneal macrophages. In addition, previous work has utilized only in vitro models to establish the importance of the TIM proteins in EBOV entry. My studies are the first to demonstrate the importance of TIM-1 and TIM-4 for in vivo EBOV pathogenesis and to confirm them as relevant targets of future filovirus therapeutics.
Macrophage phenotypes can vary greatly depending upon chemokine and cytokine signals from their microenvironment. Historically, macrophages have been classified into two major subgroups: classically activated macrophages (M1) and alternatively activated macrophages (M2). Macrophages are a critical early target of EBOV infection and my work primarily focused on interferon gamma-stimulated (M1) macrophages since this treatment profoundly inhibited EBOV infection of human and murine macrophages. Interferon gamma treatment blocked EBOV replication in macrophages, reducing viral RNA levels in a manner similar to that observed when cultures were treated with the protein synthesis inhibitor, cycloheximide. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited EBOV infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit infection of negative strand RNA viruses including EBOV. In addition and most exciting, using MA-EBOV, we found that murine interferon gamma, when administered either 24 hours before or after infection, protects lethally challenged mice and significantly reduces morbidity. Our findings suggest that interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option.
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Danet, Nicolas. "Molecular characterisation of the recombinant Vesicular Stomatitis Virus- ZEBOV-GP virus, prototype vaccine against Ebola virus." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSE1009/document.
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Ebolavirus (EBOV) est un filovirus responsable de fièvres hémorragiques virales sévères chez l’humain, qui peuvent être létales dans 90% des cas. L’actuelle épidémie en République Démocratique du Congo et l’ampleur démesurée de l'épidémie de 2014-2016 en Afrique de l’Ouest, qui a causé la mort de plus de 11 000 personnes, ont poussé les agences sanitaires internationales à tester plusieurs approches thérapeutiques afin d’essayer d’endiguer rapidement la propagation virale et de limiter la mortalité liée au virus lors de futures épidémies. Parmi toutes les stratégies testées, le virus recombinant réplicatif rVSV-ZEBOV qui exprime la glycoprotéine de surface d’EBOV, semble offrir la meilleur protection, aussi bien en modèle animaliers que sur le terrain. Avant d’être testé chez l’humain, de nombreuses études ont permis de mettre en évidence l’efficacité et l’innocuité de ce vaccin prototype. Pourtant et malgré le fait que de nombreuses études ont démontré l’importance et le rôle de la glycoprotéine GP dans l’efficacité des vaccins contre ce virus, aucune étude n’a encore été réalisé sur la nature des glycoprotéines virales synthétisées par le gène GP d’EBOV inséré dans le génome du virus VSV. Ainsi, les caractérisations moléculaires des protéines virales produites lors de l’infection par le virus rVSV-GP décrites dans ces travaux de thèse offrent de nouvelles perspectives pour comprendre le succès de ce vaccin mais aussi l’origine virales dans les effets secondaires sévères observés lors de la vaccination, et pourront aider à développer un vaccin plus sûr, qui n’est actuellement pas utilisable chez les personnes immunodépriméesThe filovirus Ebolavirus (EBOV) is the causative agent of severe viral hemorrhagic fevers in humans that can be lethal in 90% of cases. The current outbreak in the Democratic Republic of Congo and the extraordinary scale of the 2014-2016 outbreak in West Africa, that caused the death of more than 11 000 disease victims, lead the international public health agencies to test several therapeutic approach to limit viral spreading and mortality. Amongst those, the recombinant replication-competent rVSV-ZEBOV virus, that expressed EBOV GP glycoprotein, appears to offer the best protection in animal models and outbreak settings. While its effectiveness and safety have been widely investigated before human trials and despite numerous studies that showed the importance the nature of the glycoproteins which are produced during the infection from the EBOV GP gene that has been inserted in VSV genome are unknown. In this respect, the molecular characterisations of the viral glycoproteins synthesised during rVSV-GP presented in this thesis, offer new insights with which to understand the success of the rVSV-GP vaccine but also the potential viral origins of the severe adverse side effects observed during vaccination and could help in developing a safer vaccine, which currently cannot be used in an immunocompromised population
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Magro, Laura. "Microfluidique papier : de la physique des écoulements au diagnostic du virus Ebola en Guinée." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066281/document.
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Les propriétés du papier - pompe capillaire, prix et disponibilité - lui permettent de répondre à tout type de contraintes logistiques et économiques d'un diagnostic médical de terrain. En amont de l'application, nous avons étudié les écoulements dans des géométries confinées par des barrières de cire. Une focalisation hydrodynamique associée à l'évaporation, crée un effet de concentrateur atteignant un facteur d'amplification de 1000. La continuité du diagnostic depuis le terrain jusqu'au laboratoire est assurée par des dispositifs hybrides papier-microsystèmes. Dans cette thèse, l'élution d'échantillons séchés dans le papier est quantifiée et sa compatibilité avec différentes fonctions microfluidiques démontrée. Nous nous sommes intéressés à deux applications de diagnostic : la détection d'un biomarqueur cardiaque par immunoessai et celle du virus Ebola par amplification d'acides nucléiques (RT-RPA). Avec un dispositif papier simple et une révélation colorimétrique, la troponine a été détectée jusqu'à une concentration de 1 ng/mL. Le diagnostic précoce de maladies infectieuses est rendu possible par la biologie moléculaire sur papier. Après des développements en laboratoires sur ARN synthétiques, des expériences réalisées en Guinée, sur des échantillons cliniques, à partir de papiers prêts à l'emploi, avec une instrumentation transportable ont atteint une sensibilité à 85.3%. Le multiplexage du diagnostic est obtenu dans des géométries multicouches par la réalisation simultanée de tests et contrôles. Enfin, l'application à d'autres pathogènes comme HIV et la Dengue, a montré les limites du papier et de son environnement biochimique non contrôléPaper properties – such as capillary pump, affordability and availability – made it suitable for medical diagnostics in logistic and economic field constraints. Upstream of application, we studied liquid flows in wax-confined geometries. Hydrodynamic focus coupled to evaporation creates a concentrator effect reaching an amplification factor of 1000. Diagnosis continuity from the point of care to testing laboratory is insured thanks to hybrid paper-microsystem devices. In this thesis, the elution of dried samples in paper is quantified and its compatibility with various microfluidic functions demonstrated. We were interested in two diagnostics application: detection of a cardiac biomarker by immunoassay and of Ebola virus by nucleic acids amplification (RT-RPA). With simple paper devices and a colorimetric signal, Troponin has been detected until a concentration of 1 ng/mL. Early diagnostics of infectious diseases is made possible with molecular biology on paper. After laboratory preliminary developments on synthetic RNA strains, experiments performed in Guinea with clinical samples, from ready to use papers, with carry-on equipments achieved a sensitivity of 85.3%. Multiplexed diagnostics is obtained in multilayered geometries enabling simultaneous tests and controls. Finally, application to other pathogens, like HIV and Dengue, showed paper limits from its uncontrolled bio-chemical environment
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DANFÁ, Lassana. "Alteridade, racismo e representações sociais: o caso do ebola no Brasil." Universidade Federal de Pernambuco, 2015. https://repositorio.ufpe.br/handle/123456789/17791.
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CAPEs
O presente trabalho objetivou estudar a construção social do ebola na mídia impressa brasileira à luz da Teoria das Representações Sociais, articulando conceitos de alteridade, do risco, problema social, mídia e racismo. Trata-se de uma pesquisa qualitativa feita por intermédio da análise do conteúdo clássica e do tratamento automático com ajuda do IRAMUTEQ. Foram feitos dois estudos, uma na revista Veja (5 matérias publicadas no último surto) e outro no jornal Folha de São Paulo (291 matérias publicadas desde 1976 até março de 2015). Os resultados do estudo na revista Veja, através da análise de conteúdo com foco no eixo semântico (sentidos) e sintático (forma) apontam para 4 eixos de construção de sentidos: uso da metáfora da companhia militar para demonstrar o combate do homem contra um vírus potencialmente destrutivo; a alteridade radical, colocando o outro africano como “estranho e “poluente”, neste caso, com qualidades essencialmente negativas; o distanciamento, em que o vírus ebola é colocado como problema inerentemente africano e África como lugar que oferece condições propícias para disseminação da doença; a ideia da infra-humanização, colocando as qualidades do africano e respectivas crenças ou traços culturais como sub-humanas. O estudo do jornal Folha de São Paulo foi realizado com ajuda de tratamento automático de texto pelo software IRAMUTEQ, proporcionado a Classificação Hierárquica Descendente e análise fatorial de correspondência. Os resultados mostram mundos léxicos organizados em função, de um lado, do discurso do especialista, e de outro, do discurso do não especialista. O discurso dos especialistas traduz as hipóteses científicas explicativas em torno do vírus do ebola focalizadas no macaco como principal responsável pela passagem em humanos e o caráter destrutivo do ebola. O segundo eixo, dos não especialistas, aponta para a dicotomia ocidente versus África, representada através das oposições: ordem/caos, controle/descontrole, longínquo/próximo, “civilidade”/“incivilidade”, “superior”/“inferior”. Os resultados da Análise Fatorial de Correspondência nos permitiram constatar a emergência de dois polos. No polo horizontal vimos na classe 5 o discurso de especialista se opondo aos discursos das outras classes, que agrupam os discursos de não especialistas: a transnacionalização e pânico global (classe 3); mobilização mundial versus distanciamento (classe 1); olhar exótico e ambiente caótico (classe 4); histórico, prognóstico e dados epidemiológicos (classe 2). No polo vertical vimos as classes 1 (mobilização mundial versus distanciamento) e 2 (histórico, prognóstico e dados epidemiológicos) se opondo às classes 3 (transnacionalização e pânico global) e 4 (olhar exótico e ambientes caóticos). Apesar dos dois estudos serem feitos em períodos e veículos midiáticos diferentes, as representações sobre ebola não mudaram com o tempo. Percebem-se uma atitude ambivalente da mídia na construção do risco (aproxima e afasta); alteridade radical que relega ao africano e sua cultura o caráter essencialmente negativo e infra-humanização do africano. Por meio destes dois veículos de comunicação os sentidos atribuídos sobre ebola se organizam nas seguintes oposições: pureza /impureza, sujeira/limpeza, civilidade/incivilidade, caos/ordem. Os nossos achados demonstraram que a crise do ebola reatualiza a thêmata do reconhecimento social pela sua negativa. Vimos o olhar valorativo do outro africano pelo viés negativo, ligado à sujeira, impureza, incivilidade, descontrole.
This work aimed to study the social construction of Ebola in Brazilian's media using TRS, articulating concepts of alterity, risk, social problem, media and racism. It is a qualitative research done through the classical content analisys and automatic data processing with the help of IRAMUTEQ. Two studies, one in Veja magazine (5 articles published in the latest outbreak) and one in the newspaper Folha de São Paulo (291 articles published from 1976 to March 2015), were made. The results of the study in Veja magazine, through content analysis focused on the semantic axis (mean) and syntactic (build) point to 4 axis of construction: use metaphor of military company to demonstrate man's fight against a virus potentially destructive; the radical alterity, setting other African as "strange and pollutant", in this case, with essentially negative qualities; the distance, where the virus is Ebola placed as inherently African problem and Africa as a place that offers favorable conditions for spread of the disease; the idea of infrahumanization, setting the qualities of African and their beliefs or cultural traits as subhuman. The study of the newspaper Folha de São Paulo was accomplished out automated processing of help text by IRAMUTEQ software, provided a Descending Hierarchical Classification and correspondence factor analisys. The results show lexical worlds organized in function, on the one hand, the specialist speech and, in another speech, the non-specialist speech. Speaking of experts translate the explanatory scientific hypotheses around the Ebola virus in monkeys as focused primarily responsible for the passage in humans and the destructive character of Ebola. The second axis, the non-specialist, points to the dichotomy versus West Africa, represented by the oppositions: order/chaos, control/lack, far/close, "civility"/"incivility", "superior"/"inferior". The results of the AFC allowed us to note the emergence of two poles. The horizontal pole we saw, in class 5, specialist speech opposing the speeches of other classes, the speeches of non-specialists that talking about the transnationalization and global panic (Class 3); global mobilization versus distance (Class 1); exotic look and chaotic environment (class 4); history, prognosis and epidemiological data (class 2). The vertical pole we saw class 1 (global mobilization versus distance) and 2 (history, prognosis and epidemiological data) opposing Classes 3 (transnationalization and global panic) and 4 (exotic look and chaotic environments). Although the two studies were made in different periods and newspapers, the representations of Ebola have not changed over time. Realize up an ambivalent attitude of the media to building risk (approach and move way); radical alterity that relegates to the african and his culture an essentially negative character and infrahumanization of Africa. The Brazilian's media organizes the meanings attributed to Ebola around the following oppositions: purity/impurity, dirt/cleanliness, civility/incivility, chaos/order. Our findings demonstrate that ebola crisis renews the themata social for its negative. We saw the valuative gaze of the other African by the negative bias on the dirt, uncleanness, incivility, lack.
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Rijal, Pramila. "A study of human monoclonal antibodies to Influenza and Ebola viruses." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:ce156cca-cc96-407a-8a3f-779e5c25f445.
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This thesis describes an analysis of the B cell repertoire in humans in response to infection or vaccination with Influenza or Ebola. We isolated monoclonal antibodies (mAbs) from individuals using single B cell cloning and PCR technology, and defined their epitopes, binding characteristics and neutralisation properties. As summarised by Thomas Francis in 1960, we found that the secondary B cell response to Influenza is largely determined by the primary response to the virus that the donor was exposed to in childhood. In some individuals this can lead to focusing of the polyclonal antibody response to a single site on the influenza haemagglutinin. Monoclonal antibodies isolated from such focused responses selected escape mutations in vitro that matched actual antigenic drift observed in circulating viruses. Recapitulation of antigenic drift in vitro with human mAbs, in parallel with standard analysis with ferret anti-sera, may contribute to improved selection of vaccine strains by the WHO. A second consequence of preferential selection of B cell responses from memory cells laid down early in life, is the expansion of broadly cross-reactive clones during exposures to viruses that are only distantly related to the original stimulus. We have isolated many protective antibodies to conserved epitopes on both haemagglutinin and neuraminidase from individuals with appropriate exposure histories. One novel antibody binds to the conserved active site of neuraminidase. Antibodies of this type may have therapeutic potential to complement antibodies to the conserved stem of Haemagglutinin. In contrast to Influenza, the antibody response to the Ebola glycoprotein (GP) in vaccinated humans was essentially primary. The elicited antibodies were closer in sequence to germline than those to Influenza, and contained fewer somatic mutations. The response was more diverse, employing a wide selection of VH/L genes, and was directed at multiple epitopes in at least three distinct regions on the GP. Despite these features, half of the antibodies neutralised an Ebola surrogate virus in vitro, and many were therapeutic in a murine infection model. We developed a cocktail of antibodies to three non-overlapping sites for testing as a therapy in a stringent model of Ebola infection in the guinea pig. Taken together our results fit with a Darwinian model of selection of the fittest B cells in the germinal centre reaction, where memory cells have a selective advantage over naïve B cells.
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Kane, Michaela Lynn. "Covering an Epidemic: The Ebola Virus and AIDS in the News." Thesis, The University of Arizona, 2015. http://hdl.handle.net/10150/579331.
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This paper aims to investigate media coverage of disease outbreaks and epidemics by focusing on the 2014 Ebola outbreak and the AIDS epidemic as specific examples. Using news articles and scientific reports, this paper investigates the biology and history of both diseases to provide context and analyze how news coverage changes. A study of articles published by news organizations such as The New York Times, The Economist, TIME, Associated Press, and The Los Angeles Times reveals that media coverage of disease outbreaks and epidemics follows three different "waves": early scientific reporting, analysis of the political and social ramifications of an outbreak, and finally in-depth and investigative reporting of an epidemic.
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Sumo, Augustine M. "Coping With the Threat of Ebola in Monrovia: A Case Study." ScholarWorks, 2017. https://scholarworks.waldenu.edu/dissertations/4817.
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In early 2014, 3 West African states of Guinea, Liberia, and Sierra Leone made news headlines when Ebola virus disease (EVD) ravaged the sub-region. The Liberian government was ill-equipped to efficiently contain EVD outbreak due to inadequate training for hospitals and healthcare workers. The government's mandatory cremation policies and the banning of public gatherings significantly contributed to the spread of EVD. EVD infected 10,666 and 4,808 died from the disease in the first 6 months of the epidemic. Using Bandura's Social Cognitive Theory (SCT) as the theoretical framework, the purpose of this case study research was to examine the social, economic, and policy factors that contributed to the spread of EVD in the city of Monrovia, Liberia. Utilizing snowball sampling to identify participants, data were collected through in-depth interviews with 30 participants that included 10 EVD survivors, 10 family caregivers, 2 government officials, 4 nongovernmental organization staff, 2 academicians, and 2 members of the media. All data were inductively coded and analyzed using Braun and Clarke's thematic analysis procedure. Two key themes were identified through data analysis. First, participants noted that a better understanding of cultural traditions may have created opportunities for intervention that prevented unnecessary exposure to the virus. Second, survivors and caregivers experienced a 'hope for the best, but expect the worst' mentality throughout the experience that guided faith. The positive social change implications stemming include recommendations to the government of Monrovia to implement culturally sensitive policies related to pandemic containment, including training of healthcare workers and the public in the event of disease outbreak.
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Kamara, Kandeh. "Predictors and Risk Factors of Ebola Virus Disease in Sierra Leone." ScholarWorks, 2019. https://scholarworks.waldenu.edu/dissertations/7677.
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Sierra Leone had the highest number of cases of Ebola virus disease in history during the 2014 Ebola epidemic. The purpose of this quantitative, cross-sectional study was to examine the relationship between sociocultural and behavioral risk factors and Ebola status among women and men ages 15 to 49 years in Sierra Leone. The ecological model served as the theoretical framework. Secondary data were collected from the Sierra Leone Ebola Disease Survey. Results of chi-square tests revealed that attending a funeral (p = .001), touching a dead body at a funeral (p = .023), contact with a sick person (p = .001), touching bodily fluids (p = 0.001), gender (p = .035), traditional healer occupation (p = .001), and housewife/care taker occupation (p = .001) were significantly associated with Ebola infection status among the study population. Age, seeking traditional healer care, and preparation and consumption of primate meat were not associated with Ebola virus infection. Results of stepwise backward elimination logistic regression indicated the only significant predictor of Ebola infection was attending a funeral (adjusted R2 = .013 or 1.3%, p = .031). Findings may be used to promote awareness of funeral-related Ebola infection risk and avoiding traditional and religious practices that elevate infection risk during burial of the dead, which may be used to reduce or prevent future Ebola outbreaks in Sierra Leone.
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Cederblad, Anna, and Henrik Hägg. "Nurses educating patients and relatives about viral hemorrhagic fever diseases : A qualitative study in Uganda." Thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-253503.
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Introduction: Recent Ebola epidemic in West Africa have put viral hemorrhagic fever diseases in the spotlight. Uganda has had several outbreaks throughout the years, which have successfully been managed. Nurses’ patient education plays an important role in the work to increase public awareness about viral hemorrhagic fever diseases. Objectives: To assess how nurses at the emergency department educate the patients and relatives about the viral hemorrhagic fever diseases. Methods: An explorative and descriptive qualitative study with qualitative approach have been used. In-depth interviews with 18 open-ended questions have been conducted with nurses in the emergency department. Data was analyzed by qualitative content analysis and analyzed with Peplau’s theory of interpersonal relationship. Results: Through data analysis four categories were developed; Wide variety of educational techniques, Experienced obstacles, How to attain wider audience and Preferable characteristics as an educating nurse. Nurses used many different approaches when educating about viral hemorrhagic fever diseases, often uniquely combined. Lack of time and too unstable patients in the emergency department were seen as the main obstacles to educate. Methods to reach the community and employing a special education-nurse on the ward were suggestions to improve the preventive work against viral hemorrhagic fever diseases. Conclusion: Nurses are aware of the importance of patient education and use the educational methods they believe to be the most effective. However, patients in the emergency department often come in too late and priority should be on preventive measures. Training the nurses in educational techniques and patient education could be a key in decreasing the risk of coming outbreaks.Bakgrund: Den senaste ebolaepidemin i västafrika har gjort att blödarsjukdomar hamnat i rampljuset. Uganda har genom åren drabbats av flera utbrott som framgångrikt hanterats. Sjuksköterskors patientutbildning spelar en viktig roll i arbetet för att öka allmänhetens medvetenhet om blödarsjudkomar. Syfte: Att undersöka hur sjuksköterskor på akutmottagningen utbildar patienter och anhöriga om blödarsjukdomar. Metod: En explorativoch deskriptiv kvalitativ studie med kvalitativ ansats användes. Sjuksköterskor som arbetar på akutmottagningen har djupintervjuats med 18 öppna frågor. Data har analyserats med en kvalitativ innehållsanalys och analyserats utifrån Peplaus ”interpersonal relationship theory”. Resultat: Genom dataanalysen utvecklades fyra kategorier; Stor variation på utbildningstekniker, Upplevda hinder, Hur man ska nå en bredare publik och Önskvärda egenskaper som utbildande sjuksköterska. Sjuksköterskorna använder många olika metoder för utbilda patienter och anhöriga om blödarsjukdomar, ofta i unika kombinationer. Tidsbrist och alltför instabila patienter på akutmottagningen sågs som de största hindren för att utbilda. Metoder för att nå allmänheten och att anställa en speciell utbildningssjuksköterska på avdelningen var några av förslagen för att förbättra det förebyggande arbetet mot blödarsjukdomar. Slutsats: Sjuksköterskorna är medvetna om vikten av patientutbildning och använder de pedagogiska metoder de anser vara mest effektiva. Då patienterna kommer till akutmottagningen är det dock ofta för sent och preventiva åtgärder borde prioriteras. Att öka sjuksköterskornas kunskap i utbildningstekniker och patientutbildning kan vara en viktig del i det preventiva arbetet för att minska risken för kommande utbrott.
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Christiansson, Camilla, and Ellen Ferm. "DEN FRUKTADE BLÖDARFEBERN : En studie om två svenska dagstidningars framställning av ebola." Thesis, Högskolan i Halmstad, Akademin för hälsa och välfärd, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:hh:diva-27699.
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Syfte och frågeställning: Att undersöka hur två svenska nyhetstidningar valt att skildra en nyhet under vald period. Detta görs genom att besvara följande frågeställning: På vilket sätt skildrar Dagens Nyheter och Svenska Dagbladet ebolaviruset i sina tidningsartiklar från 1 maj 2014 till och med den 31 oktober 2014? Metod och material: Kvantitativ innehållsanalys på samtliga artiklar publicerade i DN och SvD under perioden 1 maj 2014 till och med 31 oktober 2014 samt diskursanalys på sex artiklar. Huvudresultat: I studien framkom det en tydlig förändring i artiklarna under hela undersökningsperioden. Det förändrades från att vara diskussioner om en kris till att sedan diskuteras om olika åtgärder för att minska oroligheten bland invånarna.
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Hohnstein, Nicole M. "Determining the Reservoir Species of Zaire Ebola Virus: A Proposed Epidemiological Survey." Scholarship @ Claremont, 2016. http://scholarship.claremont.edu/cmc_theses/1394.
Full textAbstract:
Ebola virus (EBOV) is a re-emerging zoonotic virus (it is transmitted between animals and humans) that causes acute hemorrhagic fever and a high fatality rate in humans. First reported in 1976 in the Democratic Republic of the Congo (formerly Zaire), the virus is transmitted between humans through direct contact with body fluids of an infected person, causing fever, weakness, diarrhea, abdominal pain, cramping, nausea and vomiting in those affected. There is neither a licensed vaccine nor an approved treatment for Ebola virus in human patients. The reservoir species for Ebola virus is similarly unknown, as many studies have attempted yet failed to isolate living virus from potential candidates. The widely accepted and circulated hypothesis based on preliminary findings of outbreaks past is that bat species, specifically the fruit bat species Hypsignathus monstrosus, Epomops franqueti and Myonycteris torquata are potential reservoirs. Recent reports, especially concerning findings from the 2014 Ebola outbreak, have determined that insectivorous bats could similarly be reservoir species. Successful isolation of a live virus from a bat species found through a widened sampling of a variety of bat species would confirm the hypothesis that bats, either fruit or insectivorous, are the reservoir species for Ebola virus.