Doctor of Philosophy / Department of Diagnostic Medicine/Pathobiology / Wenjun Ma / Rift Valley fever virus (RVFV) is an enveloped, negative-sense, ssRNA virus with a tripartite genome that causes morbidity and mortality in both livestock and humans. Although RVFV is mainly circulating in mainland Africa, this arthropod-borne virus is a potential threat to the other parts of the world. No fully licensed vaccines for human or animal use in the U.S., and effective antiviral drugs have not been identified. As virulent RVFV strains are only handled in biosafety level (BSL) 3 or higher level facilities in the U.S., few laboratories have access to RVFV which limits antiviral development. However, it is crucial to develop effective antivirals to protect public and animal health. Animal models that reproduce Rift Valley fever are vital to identifying and developing antiviral compounds. The currently available attenuated RVFV strain, MP12, provides a BSL-2 challenge model virus for preliminary investigations of RVFV prior to using the virulent RVFV strains. All strains of RVFV have a highly conserved genome, indicating that antivirals or vaccines effective against any RVFV strain will most likely be effective for all RVFV strains. Therefore, we hypothesize that the MP12 is a suitable model virus that can be used for identification and evaluation of effective RVF antivirals. The first objective of this project was to establish a mouse model susceptible to MP12 infection. Based on the literature, we selected and screened six different strains of mice to test their susceptibilities to MP12. We found the STAT-1 knockout mice are the most susceptible to MP12 infection based on clinical symptoms, mortality, viremia, virus replication, histopathological, and immunochemical analyses. Importantly, these mice displayed acute-onset hepatitis and delayed-onset encephalitis similar to severe cases of human RVFV infection. Our second objective was to identify potential antiviral drugs in vitro. We developed and employed a cell-based assay using the recombinant MP12 virus expressing Renilla luciferase to screen a library of 727 small compounds purchased from National Institutes of Health. Of the compounds, 23 were identified and further tested for their inhibitory activities on the recombinant MP12 virus expressing green fluorescent protein. Further plaque reduction assays confirmed that two compounds inhibited replication of parental RVFV MP12 strain with limited cytotoxic effects. The 50% inhibitory concentrations using an MP12 multiplicity of infection (MOI) of 2 were 211.4 µM and 139.5 µM, respectively. Our third objective was to evaluate these two candidates, 6-azauridine and mitoxantrone, in vivo using our mouse model. After one-hour post MP12 infection via an intranasal route, treatment was given intranasally twice daily. Mice treated with placebo and 6-azauridine displayed severe weight loss and reached the threshold for euthanasia with obvious neurological signs, while mice treated with ribavirin (a known antiviral drug) or mitoxantrone showed delayed onset of disease. This result indicates that the mitoxantrone can improve the outcome of RVFV infection in our mouse model. The underlying mechanism of mitoxantrone to inhibit RVFV replication remains to be investigated. Our studies build the foundation for identification and development of antivirals against RVFV in a BSL-2 environment.

This thesis investigates the development of regional drainage patterns within intra-continental rift basins using remote sensing data, field studies and numerical models. By examining modern-day extensional settings, such as the Basin and Range, USA, and the East African Rift System (EARS), this study elucidates the controls upon regional source-to-sink systems and assesses the findings in relation to existing, conceptual tectono-stratigraphic and drainage models. Rift basins are generally well studied and facies models well established. However, there is a tendency to overlook the regional perspective. Many drainage evolution studies and tectono-stratigraphic models focus upon the development of individual basin-bounding faults and half-grabens, often overlooking the influence of regional-scale drainage evolution upon landscape and stratigraphic development. On a regional scale, extensional basins are segmented into numerous sub-basins, which: (i) exist at different elevations; (ii) subside at different rates; (iii) vary in their degree of fluvial connectivity; and, (iv) may experience significant shifts between erosional and depositional regimes as drainage networks evolve. Through observations of the Basin and Range, and three-dimensional numerical modelling, it is shown how sub-basins with identical tectonic and climatic boundary conditions can exhibit vastly different stratigraphic fills depending on the degree of fluvial connectivity and their relationship to adjacent sub-basins. In addition, drainage integration is recognised as an overlooked, yet important process in the source-to-sink evolution of rift basins. Drainage integration between sub-basins of varying elevations is shown to cause widespread erosion and sediment bypass in the upstream basin, while contemporaneously increasing sediment supply to the downstream basin. A case study of the Tecopa Basin shows drainage integration as a powerful driver of base level fall and landscape transience in the absence of significant tectonic or eustatic controls. The differential gradients created by base level fall cause further upstream drainage rearrangements. To understand the evolution of regional hinterland drainages, two rift segments of varying maturity are compared. The Okavango Rift Zone represents a rift initiation phase segment while the Albertine Rift represents a rift climax phase segment. Through analysis of the contributing drainage patterns a model is proposed where early rift drainage is dominated by antecedent directions, with large, low relief, low slope catchments. As rifts mature catchments increase in relief and slope but reduce in asymmetry as the influence of antecedent drainage direction is reduced via tectonic tilting, drainage reversals and ponding. The thesis concludes that current tectono-stratigraphic models of sub-aerial rift settings commonly overlook the role of inter-basin erosion, under-appreciate the influence of antecedent drainage direction in hinterland input, and over-emphasise the role of axial rivers. Future tectono-stratigraphic models should acknowledge distinctions based upon the degree of fluvial connectivity (isolated or integrated sub-basins) and the regional position relative to adjacent sub-basins (upstream and terminal and sub-basins).

Rift Valley fever (RVF) is a peracute or acute disease of domestic ruminants and humans in sub-Saharan Africa, caused by a mosquito-borne virus. It is a high priority pathogen because of its potential to cause severe economic harm to the livestock industry and to cause life threatening haemorrhagic disease in humans. The disease was first recorded in southern Africa when a large epidemic occurred in the South Africa in 1950, and the first recorded outbreak in Namibia was in 1957. Since then, occasional large epidemics have occurred in southern Africa, with long interepidemic periods. The epidemiology of RVF is complex and many questions regarding the movements of the virus and its survival during the interepidemic period remain unanswered. The aim of this study was to compile a comprehensive description of the history of RVF in Namibia and to describe its epidemiological characteristics. This was accomplished using information available in the scientific literature, annual reports, disease reports and reports to the OIE. The geographical location and temporal occurrence of each outbreak was recorded as accurately as allowed by available records. Also recorded were suspected RVF outbreaks, defined as those outbreaks in which samples were not collected for laboratory analysis or RVF was not confirmed on submitted samples but where the clinical picture was suggestive of the disease. Serological surveys done in humans and animals were also included in the study. The collected data were analysed descriptively, by risk mapping and by cluster analysis. The relatively low number of recorded outbreaks and the poor spatial resolution of much of the data prevented more detailed multivariable analysis. Maps were produced to show the districts affected for the outbreaks with no coordinates and the exact location of the outbreaks which had coordinates. This was then followed by a detailed description of each outbreak showing the species affected and the mortalities caused. Risk mapping was done to identify areas of the country which are at high risk of having outbreaks. A quarter degree square grid was used to show the cumulative number of confirmed outbreaks occurring from 1957 to 2011. The accuracy of this was, however, limited due to the poor spatial resolution of data prior to 1986, which recorded only the district(s) affected. The risk map was visually compared with maps of sheep and cattle density and rainfall. A space-time permutation model, using case-only data, was used to detect space-time clusters with high rates, using SaTScan software on all the confirmed outbreaks with GPS coordinates. The objective was to detect areas of significantly high rates of RVF in Namibia, testing whether the outbreaks were randomly distributed over space and time. Space time permutation requires the use of precise geographic coordinates; therefore the only confirmed outbreaks that could be used for this analysis were those occurring during 2010 and the 2011. A total of six years had outbreaks of RVF in Namibia, the major outbreaks occurring in 1957, 1974, 1984, 2010 and 2011. Rift Valley fever was confirmed in the Karas, Hardap, Khomas, Erongo, Otjozondjupa, Omaheke and Oshikoto regions, with suspected outbreaks occurring in the Kavango and Caprivi regions. SaTScan analysis showed that there were two statistically significant outbreak clusters observed, one in the Hardap region in 2010 and the other in the Oshikoto region in 2011. The south-eastern part of the country was shown to be predisposed to RVF outbreaks; this correlated with sheep population density. The southern part of Namibia receives less rainfall and is hotter than the north, with colder winters, factors which may reduce vector and virus survival and therefore limit continuous viral circulation. This likely renders livestock highly susceptible to infection and if there is an introduction of the virus a severe epidemic may occur. In the Northern Communal Areas and adjacent Etosha National Park the positive serological results in humans and wildlife show that there is continuous or intermittent low level circulation of the virus. This could be leading to high levels of herd immunity and hence no confirmed outbreaks recorded in these areas to date. Nevertheless, all suspected cases should be tested for RVF to avoid misdiagnosis and under-reporting of cases. / Mini-dissertation (MSc)--University of Pretoria, 2015. / tm2016 / Veterinary Tropical Diseases / MSc / Unrestricted

The serodiagnosis of Rift Valley fever (RVF) relies on the use of inactivated whole virus based reagents which present biosafety, financial and operational constraints. There are no vaccines for humans, the availability of animal vaccines is limited and they have several drawbacks. The aim of this study was to evaluate a bacterially expressed recombinant RVF virus (RVFV) nucleocapsid protein (recNP) as a safe immunodiagnostic reagent, and an immunogen in a mouse and host animal model. Several enzyme-linked immunosorbent assays (ELISAs) were developed in this study, enabling sensitive and specific detection of antibodies and RVFV antigen in human and animal specimens. The recNP was combined with different adjuvants and used to immunize mice and sheep subsequently challenged with a virulent wild type RVFV strain. Depending on the recNP/adjuvant combination, protection against disease in mice ranged between 17 and 100%, with sterilizing immunity elicited in some experimental groups, compared to 100% morbidity/mortality and excessive viral replication in adjuvant and PBS control mice. Immunization with recNP combined with Alhydrogel, an adjuvant that biases immunity towards Th2 humoral immunity, that yielded 100% protection, induced an earlier and stronger type I interferon response in mice after challenge, compared to repression of the same gene in adjuvant and PBS control mice. There was massive activation of pro-inflammatory responses and genes with pro-apoptotic effects in the livers of control mice at the acute phase of infection, accompanied by high viral replication, possibly contributing to the pathology of the liver. There was also evidence of activation and repression of several genes involved in activation of B- and T-cell immunity in control mice, some indicating possible immune evasion by the challenge virus. Immunization of sheep with the same recNP/adjuvant combinations were, however, not able to decrease replication of challenge virus. The recNP based ELISAs are an important addition to and improvement of the currently available serodiagnostic tests for RVF. The mechanism by which recNP immunization protects mice from developing severe disease during the acute phase of infection is now better understood, but the mechanism for earlier clearance of the virus needs further investigation.

Composition for orchestra.

L'objectif de ce travail est (1) d'étudier les relations existant entre déformation, érosion et sédimentation et (2) de quantifier les bilans érosion – sédimentation dans un rift continental en domaine tropical : le rift Albert, localisé au nord de la branche ouest du Rift est-africain. Cette étude consiste en une triple analyse de la déformation, du remplissage sédimentaire (biochronostratigraphie, sédimentologie et stratigraphie séquentielle) et des formes du relief (géomorphologie) basée sur l'interprétation de données de subsurface et d'affleurement. Un modèle d'âge des sédiments a été obtenu en combinant données biostratigraphiques, corrélations séquentielles et courbes de variations des paléoprécipitations. L'analyse sédimentologique a permis de caractériser (1) la source des sédiments et (2) le milieu de sédimentation qui consiste en un lac pérenne profond (<100 m) alimenté par des dépôts de crues, sans cônes alluviaux significatifs. Couplée à l'analyse des formes du relief, cette étude sédimentologique permet reconstituer l'évolution du bassin et de sa déformation: (1) 55-45 Ma : formation de latérites correspondant à la Surface africaine; (2) 45-22 Ma : dégradation de la Surface africaine à la faveur d'un début de surrection du dôme est-africain et formation d'une pédiplaine dont le niveau de base est l'Océan atlantique; (3) 17-2.5 Ma : initiation du bassin du Lac Albert aux alentours de 17 Ma et création de niveaux de base locaux auquel s'adaptent trois pédiplaines correspondant chacune aux trois dépocentres (Lacs Albert, George et Edward) – la surrection du dôme est-africain se poursuit; (i) 17 à 6.2 Ma : stade bassin « flexural » (vitesse de subsidence : 150-200 m/Ma ; vitesse de sédimentation : 1,3 km3/Ma entre 17 et 12 Ma et 0,6 km3/Ma entre 12 et 6 Ma) – les dépôcentres (localisés au sud) sont peu contrôlés par des failles; (ii) 6.2 à 2.5 Ma : stade rift 1 (vitesse de subsidence : > 500 m/Ma jusqu'à 600-800 m/Ma; vitesse de sédimentation : 2,4 km3/Ma) – paroxysme d'activité du rift; (4) 2.5-0.4 Ma : surrection de la Ruwenzori et changement de type de système alluvial à l'incision d'un réseau de drainage - stade rift 2 (vitesse de subsidence : 450 à 250 m/Ma; vitesse de sédimentation : 1,5 km3/Ma); (5) 0.4-0 Ma : flexuration initiation de la dépression du Lac Victoria, inversion du réseau de drainage et création de l'escarpement. La mesure du bilan-érosion sédimentation montre des ordres de grandeur identiques, avec, entre 17 et 2,5 Ma, un excès de matériel érodé (22 000 km3) par rapport aux sédiments déposés (19 000 à 18 000 km3). De 16%, cette différence de volume peut s'expliquer par la forte érosion chimique qui prévaut durant cette période, laquelle est péjorée par la différence de nature des argiles entre le bassin versant (kaolinites) et le bassin (smectites dominante), la néoformation de smectites à partir de kaolinites requérant des apports d'éléments disponibles dans les solutions issues de l'altération chimique des roches. / The aim of this work is (1) to study the relationships existing between deformation, erosion and sedimentation and (2) to quantify the erosion-sedimentation budget in a continental rift: the Rift Albert located in Uganda, in the north of the Western Branch of the East African Rifts. This study consists in a triple analysis of the deformation, the sedimentary infilling (biochonostratigraphy, sedimentology and sequence stratigraphy) and the landforms (geomorphology) based on the interpretation of subsurface and surface data. An age model of the sedimentary infilling has been obtained by combination of biotratigraphic data, sequential correlations and paleoprecipitation variation curves. The sedimentological analysis led to the characterization (1) of the sediments source – most of the quartz grains coming from the erosion of a lateritic profile (with low transportation) – and (2) of the depositional environment which consist of perennial deep (<100 m) feeding by flood deposits, without evidences of alluvial fan. This sedimentological study, along with the analysis of landforms allow to reconstitute the evolution of the basin and of its deformation: (1) 55-45 Ma: formation of laterites corresponding to the African Surface during the very humid period of the Lower-Middle Eocene; (2) 45-22 Ma: stripping of the African Surface in response of the beginning of the East-African Dome uplift and formation of a pediplain connected to the Atlantic Ocean; (3) 17-2.5 Ma: Initiation of the Lake Albert Basin around 17 Ma and creation of local base levels (Lake Albert, Edward and George) on which three pediplains tend to adapt; (i) 18—16 to 6.2 Ma: "Flexural" stage (subsidence rate: 150-200 m/Ma; sedimentation rate 1.3 km3/Ma between 17 and 12 Ma and 0.6 km3/Ma from 12 to 6 Ma) – depocenters location poorly controlled by fault; (ii) 6.2 Ma to 2.5 Ma: Rift stage 1 (subsidence rate: > 500m/Ma up to 600-800 m/Ma; sedimentation rate: 2.4 km3/Ma) – Rifting climax; (4) 2.5-0.4 Ma: uplift of the Ruwenzori Mountains and shifting from an alluvial system to a network of bedrock river incision – Rift Stage 2 (subsidence rate: 450 to 250 m/Ma; sedimentation rate: 1.5 km3/Ma); (5) 0.4-0 Ma: long wavelength downwarping, initiation of the Lake Victoria trough, drainage network inversion and uplift of the present-day escarpment.The measurement of the erosion-sedimentation budget show the same order of magnitude with, between 17 and 2.5 Ma, an excess of eroded material (22 000 km3) compared to the sediment volume deposited in the basin (19 000 to 18 000 km3). This difference of volume of 16% can be explained by the high chemical erosion occurring during this period, which one is depreciated by the difference of mineralogy of the clays between the catchment (kaolinites) and the sedimentary basin (dominantly smectites), the neoformation of smectites from kaolinites needing the input of element available in the solution resulting from the chemical weathering of the substratum.

The Adames strain of Punta Toro virus (PTV-A) causes acute hepatic disease in hamsters and mice similar to that seen in natural Rift Valley fever virus (RVFV) infection, while the Balliet strain (PTV-B) is apathogenic. The ability of PTV-A to suppress the interferon (IFN) response has been demonstrated in hamsters and is thought to be a contributing factor to PTV-A's pathogenicity in hamsters. PTV-B is not assumed to exhibit this IFN-antagonistic activity, as it stimulates production of significantly higher IFN-β levels. To elucidate the role of IFN in resistance of mice to PTV-B infection, we utilized mice deficient in a critical IFN signaling protein, STAT-1. We found that these mice were drastically more susceptible to PTV-B, which caused 100% lethality compared to 0% in their wild-type counterparts. STAT-1 deficient mice were also more susceptible to PTV-A, as these mice succumbed to infection significantly earlier than wild-type mice (p=0.0058). We sought to determine whether PTV-A's IFN-antagonistic mechanism is functional in mice by examining expression of IFN-β in primary macrophages infected with either strain. We found that IFN-β protein concentration is higher in samples taken from PTV-B-infected cells. We employed quantitative PCR arrays specific to IFN signaling and response pathways to evaluate changes in gene expression throughout the course of infection with either virus strain. We found several genes with differentially regulated expression between PTV-A- and PTV-B-infected macrophages, including Ifnβ1 and multiple Ifnα subtypes. Also, several genes coding for inflammatory and chemotactic molecules, Cxcl11, Cxcl10, Cxcl9, Vcam1, and Il6, demonstrated increased expression in PTV-B samples compared to PTV-A. Of particular interest, Isg20, a 3'-5' exonuclease with specificity for single-stranded RNA, was stimulated ~2-fold higher by PTV-B, and Iigp1, from the family of GTPases associated with host defense against intracellular pathogens, was stimulated ~2.7-fold higher by PTV-B. The individual functions of each of these genes in mouse resistance to PTV-B could be a focus of future studies to better understand essential host defense mechanisms to phleboviral infection.

From 1930 to 2000 Rift Valley Fever (RVF) was limited to the African continent. It is vector borne disease caused by a virus of the genus Phlebovirus, member of the Bunyaviridae family. The main vectors for transmission are Aedes and Culex. In September 2000 it was reported for the first time out of Africa, affecting Yemen and Saudi Arabia. This epidemic opened a new era in the history of RVF. It proved that the virus had the capaciity to affect new zones, different eco-systems and to spread to any area in the world. The outbreak lifted many hypothesis related to its introduction and to the factors associated with the outbreak. Although difficult to evaluate precisely its socio-economic impact was considered to be the heaviest in the modern history of Yemen animal diseases even when compared to the rinderpest outbreak that the country encountered in the seventies because of its zoonotic characteristic. To answer to these hypotheses it was of great importance to study and investigate all the factors associated with the outbreak. Thus after estimating the socio-economic impact of the disease in the world and more specifically in Yemen we studied the descriptive epidemiology of RVF in the first and most affected zone of the outbreak of 2000-2001 (Tihama Wadi Mawr) and then we analysed the socio-economic and environmental factors associated to the outbreak, to finish with the risk assessment of the re-introduction of RVFV from the Horn of Africa through legal animals trade. The descriptive study showed that at the national level 90% of the RVF cases were in the plain of Tihama coast, Hodiedah, Hajjah and Sadah governorates, the majority of the villages being located around the main canals of Wadi Mawr at an altitude < 300 m. Environmental as well as socio-economic factors likely to play a role in RVF transmission in Yemen were highlighted with the study of the period 1997-2007 in the country. As in previous RVF outbreaks in neighbouring countries in the Horn of Africa, the year 2000 presented above-normal vegetation index values, which reflected important precipitations, for both rainy seasons (the first occurring between March and May; the second between July and October). These environmental conditions favourable to the vectors populations were found concomitant with a late starting date of Eid-al Kabeer celebration (March) in 2000, related to high hosts (cattle, sheep and goats) densities. According to these criteria, 2000 was considered as an atypical year. Yemeni Veterinary Services did not declare any RVF outbreak since 2000. Thus, we assumed Yemen free of the disease when assessing the risk of introduction of RVF into Yemen via the legal trade of small ruminants from the Horn of Africa (Kenya, Somalia, Djibouti, and Ethiopia). After precisely describing the routes and volume of trade from the Horn of Africa to Yemen, the pathway and different scenarios for introduction were developed following the OIE risk assessment method. A matrix of likelihood combinations including four possible levels (very low, low, medium, high) was built and used to combine likelihood of events. The overall probability of introduction was assessed very low to medium depending on the period of the year and most likely to occur via ovine males exported during festival periods that change depending of the year considered. The uncertainty was considered to be low. The socio-economic impact although difficult to estimate was shown to be dramatic as RVF affects all the chain of life in particular of those associated to livestock and animal products trade. Despite the dramatic impact of the outbreak of RVF in 2000 but it had the advantage to draw the attention of decision makers, of international organizations and of local veterinary services on the importance of livestock diseases and their possible effects on human health and national economies. Veterinary education also improved significantly in Yemen. It enhanced the epidemiologists skills, disease surveillance in general and the cooperation between human health care people and veterinary services. A national P3 laboratory should also soon open with the help of the IAEA and the FAO and Al-Mukkah quarantine could be modernized and extended in the near future. Regional collaboration and improvement of knowledge on animal trade but also field studies related to the disease and its entomological features are seen as compulsory to hope improving the prevention and control of RVF.But the best way and strategy for prevention of Rift Valley Fever in Yemen as well as in the world is to develop more efficient surveillance and control tools to implement coordinated regional monitoring and control programmes. - Résumé - De 1930 à 2000, la Fièvre de la Vallée du Rift (RVF) était une maladie essentiellement africaine. Cest une maladie vectorielle causée par un virus du genre Phlebovirus de la famille des Bunyaviridae. Les principaux vecteurs sont les Aedes et les Culex. En Septembre 2000, des cas furent rapportés pour la première fois hors du continent africain touchant le Yémen et lArabie Saoudite. Cette épidémie ouvrit une nouvelle ére dans lhistoire de la RVF. Elle prouva la capacité du virus à infecter des zones nouvelles, des écosystèmes différents et sa capacité à se propager à nimporte quelle région du monde. Plusieurs hypothèses furent avancées concernant son introduction et les facteurs socio-économiques associés aux foyers. Sil est difficile dévaluer précisement son impact socio-economique, il fut considéré comme le plus lourd de lhistoire moderne des maladies animales au Yémen même comparé à celui de la peste bovine dans les années 70 à cause de son caractère zoonotique. Pour répondre à ses hypothèses, il était important détudier et de rechercher tous les facteurs associés aux foyers. Ainsi après avoir estimé limpact soci-èconomique de la maladie dans le monde et plus particulièrement au Yemen, lon sintéréssa à lépidémiologie descriptive de la RVF dans les premières zones touchées mais aussi les plus affectées lors des foyers de 2000-2001 (Tihama Wadi Mawr) Puis lon analysa les facteurs socio-économiques et environmentaux associés aux foyers pour finir avec lévaluation de risque de la réintroduction du RVFV à partir du commerce légal danimaux de la Corne dAfrique. Létude descriptive montre quau niveau national, en 2000-2001 environ 90 % des cas étaient dans la plaine de la côte de Tihama, Hodiedah, Hajjah et Sadah, la plupart des villages étant localisées autour des canaux principaux de Wadi Mawar à une altitude infereure à 300 Mètres (m). Les facteurs environmentaux et socioèconomiques susceptibles davoir un rôle dans la transmission de la RVF au Yémen furent soulignés avec létude de la période 1997-2007 dans le pays. Comme dans les foyers précédents de RVF dans les pays voisins de la Corne de lAfrique, lannée 2000 présentait des valeurs anormalement élevées dindex normal de végétation refletant dimportantes précipitations lors des deux saisons des pluies (la première entre mars et mai, la seconde entre juillet et octobre). Ces conditions environmentales favorables aux populations de vecteurs apparurent concommitantes avec une date tardive de début des festivités de lEid-al Kabeer en (mars) 2000 entraînant à une densité importante de populations hôtes (bovins, moutons, chèvres). Considérant ces facteurs lannée 2000 fut considérée comme une année atypique. Les services vétérinaires yéménites ne déclarèrent pas de foyers de RVF depuis 2000. Ainsi on fit lhypothèse que le Yémen nétait plus infecté pusqon lon sintéressa au risque de ré-introduction de la RVF au Yémen via le commerce légal de petits ruminants depuis la Corne de lAfrique (Kenya, Somalie, Djibouti et Ethiopie). Après avoir précisemment décrit les routes et volumes déchanges depuis la Corne de lAfrique jusquau Yémen, les chemins événementiels et différents scénarios dintroduction furent développé en suivant la méthode de lOIE. Une matrice de combinaison des probabilités incluant quatre niveaux (très bas, bas, modéré, élevé) fut construite et utilisée pour combiner les probabilité de réalisation des évènements. La probabilité globale dintroduction fut trouvée très basse à modérée en fonction de la période de survenue dans lannée et plus probablement via lintroduction dovins males exportés pendant les périodes de fêtes dont loccurrence change en fonction de lannée considérée. Lincertitude fut considérée basse. Si l'impact socio-économique de la RVF est difficile à évaluer, il est pourtant dramatique en atteignant tous les maillons du réseau de ceux dont la vie sorganise autour du bétail et de son commerce ou du commerce de ses produits. Malgré limpact dramatique des foyers de RVF en 2000, ceci a eu lavantage de dattirer l'attention de décideurs, dorganisations internationales et des services vétérinaires locaux sur l'importance des maladies de bétail et leurs effets possibles sur la santé humaine et les économies nationales. L'éducation vétérinaire s'est aussi améliorée de façon significative au Yémen. La qualification des épidémiologistes et la surveillance des maladies en général sen sont trouvées meilleures, ainsi que la coopération entre les services médicaux humains et les services vétérinaires. Un laboratoire national P3 devrait voir le jour prochainement avec laide de lIAEA (International Atomic Energy Agency) et de la FAO (Food and Agriculture Organization). La modernisation et l'extension de la quarantaine Al-Mukkah, est aussi prévue dans un avenir proche. La collaboration régionale, lamélioration de la connaissance du commerce du bétail mais aussi des études de terrain relatives à la maladie et à ses caractéristiques épidémiologiques sont indispensables pour espérer améloirer la prévention et le contrôle de la RVF. Mais la meilleures stragtègie pour la prevèntion de la fièvre de la vallée de Rift au Yemen comme dans le monde est de developper une surveillance plus efficace et controler des outils pour mettre en place un suivi regional coordonnée et des programmes de contrôle.

This thesis examines how the growth, interaction and linkage of normal faults, and the broader structural styles within rift basins, provide first-order controls upon syn-rift sediment routing and the development of coeval syn-rift stratigraphy. To achieve this, this thesis integrates observations from an area of active extension, alongside the stratigraphic record of an ancient rift basin. The former allows greater insight into sediment erosion, transport and preservation processes during rifting, whereas the latter represents the net depositional history, hence permitting a reconstruction of rift tectono-stratigraphic evolution. Recent advances in the understanding of landscape response to active faulting, have focused predominantly on large-scale rift provinces or where fault segments are widely-spaced across-strike (~15-30 km). As such, the neotectonic portion of this study integrates field and digitial terrain analysis to examine the geomorphic response to active faulting across the Perachora Peninsula (Gulf of Corinth, Central Greece), an uplifting, faulted-terrace setting. Here, the across-strike fault-spacing is small (~2-3 km), allowing fault segments to interact across-strike, and landscape evolution to be driven by a complex configuration of perched, intermittent and marine base-levels. These base-levels have a propensity to switch, with implications for sediment-routing and hanging-wall stratigraphic development. The preservation potential of sub-aerial syn-rift landscapes and basin-fill is extremely low in settings such as Perachora, due to the aggressive headward cannibalisation driven by ongoing tectonic uplift and short downstream distances to terminal base level. The subsurface stratigraphic study examines the Triassic-Jurassic syn-rift stratigraphy of the Danish Central Graben, an area displaying lateral variability in the original thickness and mobility of Late Permian Zechstein evaporites along-strike of the bounding Coffee-Soil Fault System. This setting enables a direct comparison between evaporite-influenced and non- evaporite-influenced rifting at a range of scales. By integrating observations of variability in structural style, with a systematic seismic-stratigraphic analysis of the syn-rift interval, the study documents how interactions between normal fault evolution and mobile evaporites influence: i) the variability in rift basin structural style; ii) the development of stratal geometries; and iii) the nature and location of depositional systems. On a basin-wide scale, the evaporite-influenced rift portions display more prominent fault-related and evaporite-related folding, which in turn controls syn-rift deposition, along with variable degrees of decoupling of basement and cover fault and fold systems. Focusing on the evaporite-influenced Coffee-Soil Fault System, variations in the locations and rates of accommodation generated by both load-driven withdrawal of evaporites up the hanging-wall dip-slope, and fault-related subsidence, provide a critical, and hitherto neglected control upon dip- and strike-oriented variability in hanging-wall stratigraphic architecture. Conceptual models for the development of hanging-wall stratigraphy, incorporating the influence of sediment supply rates upon load-induced evaporite mobilisation, provide a framework which may be used in the analysis of evaporite-influenced border fault systems worldwide. Overall, the findings of this thesis have implications for understanding the controls on spatial and temporal variability in structural style, sediment routing and syn-rift stratigraphic evolution in rift basins. In particular, the study highlights that to determine a deeper understanding of the interactions which determine the evolution of syn-rift stratigraphy, it is essential to examine basin processes in both modern and ancient rift settings, as well as at a range of scales.

Syn-rift exposures are a prime source of knowledge on the structure and stratigraphy of rift basins and are vital for the petroleum industry as analogues for subsurface reservoirs. Focusing on superb exposures of the Oligo-Miocene rift initiation Nukhul half-graben in the Suez Rift, Egypt, this study investigates applications of 3D digital survey techniques, particularly terrestrial light detection and ranging (lidar), for (i) the analysis of syn-rift fault and facies architecture, and (ii) the building and testing of outcrop-based reservoir analogue models for early syn-rift settings. Lidar-based digital outcrop mapping of the Nukhul half-graben, combined with conventional fieldwork, facilitated quantification of thickness and facies relationships within syn-rift strata, and variations of throw along normal faults. The results provide new insights into the tectono-sedimentary evolution of the intra-block half-graben. At rift initiation, regional/eustatic sea-level and antecedent drainage are interpreted as the dominant controls on accommodation development and deposition, respectively. However, after just c. 2.5 myr of rifting, the structural template imposed by the propagation and linkage of four initially isolated pre-cursor segments of the Nukhul Fault became the dominant control on accommodation development and basin physiography. Progressive SE-NW back-stepping of facies strike-parallel to the Nukhul Fault suggests hangingwall subsidence was locally sufficient to outpace falls in regional sea-level, resulting in a dynamic transgressive system that progressed from a restricted tidal embayment to shallow marine seaway along fault strike. After c. 4.3 myr of rifting, regional drowning of the tidal system provides evidence for progressive localisation of displacement onto the present-day block-bounding structures and declining activity on the intra-block Nukhul Fault during the transition from rift initiation to rift climax. Development of digital outcrop techniques such as point cloud facies classification, 3D deterministic channel modelling and net-to-gross analysis provided reliable geostatistics on the geometry, distribution and heterogeneity of tide-influenced facies of the syn-rift Nukhul Formation. The high volume, reliability and spatial coverage of data reduced uncertainties related to stochastic facies modelling (in this case sequential indicator simulation and object-based techniques), facilitating building and testing of high-resolution analogue models for the complex facies and sequence architecture of early syn-rift tidal reservoirs. Visual analysis of static reservoir connectivity suggests some of the smallest-scale depositional elements, i.e. thin intercalations of mudstone and sandstone lamina in heterolithic facies, have the biggest impact on both reservoir volume and vertical connectivity in this syn-rift tidal system. Heterogeneities at the sequence stratigraphic scale also have significant impact on vertical reservoir compartmentalisation, whereas tidal channel lag deposits and tidal mud drapes have more localised effects. Use of lidar, when combined with conventional fieldwork, offers a powerful tool for quantitative spatial analysis of fault and facies architecture, tightly constraining 3D structural and stratigraphic interpretations and effectively increasing the statistical significance of outcrop analogues for reservoir characterisation. Future developments in survey technologies alongside geoscience-specific software for the integration and analysis of outcrop datasets will provide more diverse and quantitative information on geological heterogeneity, and promote wider-ranging applications in Earth sciences.