Дисертації з теми "Maladie de Farber"

Les amyotrophies spinales sont un groupe de maladies qui se caractérisent par une dégénérescence progressive des motoneurones de la moelle épinière entrainant une faiblesse et atrophie musculaire de sévérité variable. La forme la plus fréquente est liée à des mutations dans le gène SMN1, pour laquelle un produit de thérapie génique a été approuvé et mis sur le marché. Une autre forme d'amyotrophie spinale avec épilepsie myoclonique progressive, nommée SMA-PME, est due à des mutations dans le gène ASAH1 codant une enzyme lysosomale, la céramidase acide (ACDase). L'espérance de vie des patients atteints de SMA-PME ne dépasse pas l'adolescence. Certaines mutations dans ce même gène peuvent causer la maladie de Farber (MF), avec pour les formes les plus sévères un décès des patients avant l'âge de deux ans en raison d'atteintes multi systémiques sévères. La SMA-PME et la MF sont des maladies de surcharge lysosomale ultra-rares. L'ACDase catalyse le céramide, un lipide bioactif, en sphingosine et acide gras. En raison du déficit de l'activité enzymatique, les céramides s'accumulent à l'intérieur des lysosomes, provoquant de graves dysfonctionnements dans plusieurs organes. Une approche thérapeutique basée sur la transplantation de cellules souches hématopoïétiques a déjà été testée chez des patients Farber mais n'a pas empêché la détérioration neurologique au cours du temps. La génération de modèles murins de déficience en ACDase, notamment le modèle Asah1P361R/P361R récapitulant les symptômes de la forme sévère de la maladie Farber, a permis de mieux comprendre la physiopathologie de la déficience en ACDase et d'évaluer différentes approches thérapeutiques. L'enzymothérapie et la thérapie génique utilisant un vecteur lentiviral ont permis de prolonger la survie des animaux de plusieurs semaines mais la correction des atteintes neurologiques était absente. Puisqu'il n'existe aucun traitement curatif pour ces patients, le but principal de mon projet de thèse a été de développer une approche de thérapie génique en administrant un vecteur recombinant adéno-associé (AAV). L'injection intraveineuse d'un vecteur AAV9-ASAH1 chez des souris Asah1P361R/P361R aux stades pré- et symptomatiques de la maladie a été capable de prolonger la durée de vie des animaux et de corriger l'ensemble du phénotype. Cette approche a apporté la preuve de concept qu'une restauration généralisée de l'expression du gène ASAH1 permet d'obtenir un effet thérapeutique dans un modèle murin sévère de déficience en ACDase. Ces résultats nous ont conduit à réaliser une étude de dose chez le modèle murin Asah1P361R/P361R pour déterminer la dose minimale efficace de ce vecteur. Trois doses d'AAV9-ASAH1 ont été administrées par voie intraveineuse chez les souris mutantes à un stade avancé de la maladie et l'effet a été analysé au niveau clinique, moléculaire et histologique pendant une période de 6 mois. Nous avons identifié une dose de vecteur capable de corriger le phénotype et d'éviter l'infiltration des macrophages dans les tissus, y compris dans le système nerveux central (SNC). L'administration du vecteur AAV9-ASAH1 par voie intracérébroventriculaire (ICV) a également été évaluée chez les souris mutantes à la naissance afin d'investiguer le potentiel thérapeutique de cette voie d'administration directe au SNC. Dans le cas du modèle Asah1P361R/P361R, la correction de l'ensemble du phénotype nécessite une injection systémique du vecteur AAV9-ASAH1, mais des résultats préliminaires indiquent qu'une administration ICV du vecteur permet aussi de prévenir l'apparition des atteintes neurologiques présentes chez les souris mutantes. Ce travail de thèse ouvre la perspective d'un développement clinique de cette thérapie génique pour les patients atteints des maladies de Farber et SMA-PME
Spinal muscular atrophies are a heterogeneous group of disorders characterized by spinal cord α-motor neuron degeneration, leading muscle weakness and atrophy. The most common form is associated to mutations in the SMN1 gene, for which a gene therapy product obtained marketing approval. Another form of spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME), is due to mutations in the ASAH1 gene encoding a lysosomal enzyme,the acid ceramidase (ACDase). The life expectancy of patients with SMA-PME does not exceed adolescence. Some mutations in this same gene can cause Farber disease (FD), with the most severe forms causing death of patients before the age of 2 years due to severe multisystemic damage. SMA-PME and FD are ultra-rare lysosomal storage diseases. ACDase catalyzes the bioactive lipid ceramide into sphingosine and fatty acid. Due to the deficiency of enzyme activity, ceramides accumulate inside lysosomes causing serious dysfunctions in several organs. A therapeutic approach based on hematopoietic stem cell transplantation was previously tested in Farber patients but did not prevent neurological deterioration over time. The generation of mouse models of ACDase deficiency, in particular the Asah1P361R/P361R model that recapitulates the signs of Farber disease, has allowed a better understanding of the pathophysiology of acid ceramidase deficiency in tissues and the evaluation of different therapeutic approaches. Enzyme replacement therapy and gene therapy using a lentiviral vector extended the survival of mutant animals by several weeks, but did not correct the neurological signs of the disease. Since there is no curative treatment for patients, the main goal of my thesis project was to develop an efficacious gene therapy approach using an AAV vector. Intravenous administration of an AAV9-ASAH1 vector in Asah1P361R/P361R mice at pre- and symptomatic stages of the disease was able to prolong the lifespan and correct the phenotype. This approach provided proof of concept that generalized restoration of ASAH1 gene expression achieves a therapeutic effect in a severe mouse model of acid ceramidase deficiency. These results prompted us to perform a dose escalation study in Asah1P361R/P361R mice to determine the minimum effective dose of this vector. Three doses of AAV9-ASAH1 were administered intravenously in mutant mice at a late stage of the disease and the effect was analyzed at the clinical, molecular and histological level for a 6-month period. We identified a vector dose able to correct the phenotype and to avoid macrophage infiltrates in tissues, including the central nervous system. Intracerebroventricular administration (ICV) of the AAV9-ASAH1 vector in neonatal mutant mice was also evaluated to investigate the efficacy of this direct route of administration in correcting the neurological signs of the disease. The results show that systemic injection of the AAV9-ASAH1 vector was able to correct the whole-body phenotype of Asah1P361R/P361R mutant mice, whereas preliminary results indicate that ICV administration of the vector is efficacious in preventing mainly the neurological signs of the disease. This thesis work paves the way for clinical translation of this gene therapy in patients with Farber and SMA-PME diseases

Malaria is a problem in Africa. Thus, the aim of this research is to present a reliable measure of the farmers’ Willingness-To-Pay for malaria abatement in Africa. We develop a model that inputs the stochastic frontier model into the household production model. We analyse our model using the Bayesian Markov chain Monte Carlo techniques of Gibbs Sampling and Metropolis-Hastings. In order to arrive at a reliable posterior distribution for our Willingness To Pay, we multiply the individual households’ price for agricultural staples by the corresponding malaria estimates from our analysis together with a constant value. We apply our model to datasets from Nigeria, Ethiopia, and, Tanzania and report the corresponding Willingness To Pay point estimates and posterior distributions. Our results show that on the average, farmers in these three countries are willing to pay less than US$1 for a 100 per cent increase in malaria case per 1000 individual per annum. Policy makers can use these values to introduce minimum prices and gradual repayment schemes for prophylactic measures.

Common beans are one of the most important food and cash crops for most Malawians. The insufficient production of the crop in the country coupled with low yields has made scientists give much interest to the crop so that they can address the constraints to the productivity problems. In this regard, breeders have been engaged in the development and release of improved varieties of common beans which in most cases are disease resistant, high yielding, drought resistant, and fast cooking. Therefore it is the interest of this study to find the reasons why productivity of the crop is still low despite the release of the improved varieties. The study adopted contingent valuation (CV), a method frequently used to assess willingnessto- pay of people for non-market goods or services and this was applied to assess farmer’s willingness-to-pay for the new improved bean seed varieties which are high yielding. Double bounded dichotomous choice with an open ended follow-up format was used to obtain the household’s willingness-to-pay. In addition; the study reviewed the existing dissemination channels of bean seed to make recommendations with regard to seed supply. Descriptive statistics from the 132 households interviewed shows that the structural constraints to seed acquisition are compounded by farmers’ poverty. Otherwise, most farmers are aware of the existence of improved varieties of common bean seed and perceive that with the use of this seed, productivity can improve hence willing to pay for the good. The study is 95% confident that mean price farmers are willing to pay for improved common bean seed is between MK 527.78 and MK 591.92. Three major existing informal dissemination channels of bean seed were discovered in the study areas. Therefore there is a need for government to work in collaboration with NGOs towards ensuring a formal supply system of bean seed characterised by vertically organised production and dissemination of tested and approved seed varieties, and using strict quality control rules, so that farmers can be assured of accessing improved seed varieties. This will increase the nation’s food security.
Dissertation (MSc Agric)--University of Pretoria, 2013.
gm2014
Agricultural Economics, Extension and Rural Development
unrestricted

Agriculture is the single most important sector in Malawi due to its contribution to the economy ranging from employment creation, contribution to GDP growth to source of foreign exchange earnings. These significant contributions have necessitated the Government of Malawi to develop strategies and policies such as the Farm Input Subsidy Programme (FISP), whose main aim is to increase household incomes and reduce food insecurity and ultimately reduce poverty. It is nine years since the introduction of FISP but its results remain mixed. Using the 2009/10 Integrated Household Survey Phase 3 (IHS3) dataset, a logistic regression in a multivariate data analysis approach was used to investigate the impact of FISP on income levels and food security of rural smallholder farmers in Malawi. The analysis showed that about 82 percent of smallholder farmers live in rural areas, about 75 percent of them were males, 71 percent were married, 70 percent did not go to school and 69 percent benefited from FISP. In farming, 68 percent of these smallholder farmers had less than 1 hectare of farms, 70 percent of them had labour force of less than 5 people, 51 percent of them harvest less than 5 bags of 50kgs of maize of which 92 percent sell most of their harvested maize and 89 percent of them receive less than MK5, 000 from sales. In addition, about 99 percent of these smallholder farmers were food insecure as they save less than 1 bag of 50kgs after harvest. Only 1 percent of these smallholder farmers receive remittances and 21 percent had other income generating activities (IGAs). Demographic and socio-economic factors have no impact on these farmers capability to increase income levels and enhance their food security. There is also no statistically significant difference between FISP beneficiaries and non-beneficiaries in terms of capabilities of increasing incomes and enhancing food security. It is, therefore, concluded that FISP had no significant impact on the abilities of these smallholder farmers to increase their incomes and enhancing their food security. Hence, FISP did not prove to be the best food security and poverty alleviation tool in Malawi.

Fish products are essential to the food and economic security for almost a billion people around the world. Parasitic diseases outbreaks are a major concern for aquaculture and fishery industries, and they may represent a major constraint for sectors’ expansion. Fish-borne parasitic zoonoses due to the consumption of fishery products are an increasing phenomenon in European Countries. This work maps the available information on Enterospora nucleophila and Cryptosporidium molnari presence in gilthead sea bream Mediterranean aquaculture. The existing diagnostic techniques for the detection of E. nucleophila and C. molnari were reviewed and a new in situ hybridization assay for the detection of E. nucleophila developmental stages is provided. Data from a survey involving 17 gilthead sea bream facilities showed a wide distribution pattern of E. nucleophila and C. molnari, with their detection in 41% and 47% farms, respectively. Data also showed a non-homogeneous distribution within different production phases and type of facilities. Parasites were mainly detected in post-weaning production phases, with higher detection of E. nucleophila at ongrowing in-land and cage-based rearing systems, and higher positivity percentages of C. molnari at pre-growing and in-land tanks. The absence of positivity at early production stages including eggs led to consider vertical transmission unlikely and to confirm the role of water in transmitting the infection. This work aimed at shedding light on emerging zoonotic parasites in European freshwater fishery products. This work provided consistent information on Eustrongylides excisus epidemiology in Central Italy lakes and confirmed the presence of infective stages in freshwater fish. A molecular assay for the identification of adult and larval stages of E. excisus is reported. A novel multiplex PCR assay for the simultaneous identification of Opisthorchis felineus, Pseudamphistomum truncatum, Metorchis spp., Metagonimus spp. and Apophallus spp., the main zoonotic or potentially zoonotic trematodes described in Europe, is also provided.

The “Unleashing the Power of Cassava in Africa in Response to the Food Price Crisis” (UPoCA) project carried out by the International Institute of Tropical Agriculture from 2008 to 2010 aimed to assist farmers to increase food security and improve livelihoods through promoting cassava cultivation. In this study, 120 beneficiary households of the UPoCA project in Kasungu and Dowa provinces in Malawi were interviewed using a semi-structured questionnaire together with key informant interviews and focus group discussions. The aim was to find out their perceptions of the UPoCA project, food security situation and gendered differences, through which sustainability aspects of the project were discussed. Using the SPSS 19 software, descriptive statistics, chi-square tests and logistic regressions were generated for statistical results. In general, despite issues regarding quality and timeliness of the seed distribution service the majority of the beneficiary households were satisfied with the project stating that it helped improve their food security and livelihoods. However there emerged issues of exclusion of the most vulnerable households and the low participation of female-headed households which were initially targeted by the project. The study also found out the prevalence of seasonal hunger among the studied households and challenges facing the farmers in growing cassava which affect the adoption of the crop and the project’s sustainability. The study suggested that future similar projects should be designed for a longer duration than UPoCA. They should use clear criteria to identify target beneficiaries, exercise thorough monitoring on quality of distributed planting materials and time delivery as well as put more focus on training.

Les éleveurs laitiers-bovins présentent une incidence plus élevée de symptômes respiratoires et de maladies broncho-pulmonaires que la population générale. Un facteur de risque important serait l’exposition professionnelle à divers aéro-contaminants d’origine biologique et chimique. Les déterminants professionnels de ces expositions et les effets biologiques des contaminants inhalés de manière répétée restent cependant mal connus. Dans ce contexte, les travaux réalisés au cours de cette thèse avaient pour objectifs i) de rechercher les déterminants professionnels de l’exposition aux bio-aérosols thoraciques (poussières organiques, endotoxines, bactéries et moisissures), à l’ammoniac et à l’acétaldéhyde, et ii) de caractériser les effets pro-inflammatoires des poussières thoraciques émises lors de la tâche de paillage mécanisé qui est connue pour induire une forte exposition aux bio-aérosols. Pour atteindre ces objectifs, nous avons réalisé une campagne de 112 mesures individuelles répétées dans 29 exploitations laitières d’élevage bovin localisées en Bretagne. Par l’utilisation de modèles multivariés à effets mixtes, nous montrons que l’exposition aux bio-aérosols est majoritairement induite par l’exécution de tâches liées à la distribution de litières et d’aliments (paille, foin, ensilage). L’exposition à l’ammoniac est fortement dépendante du nombre de vaches présentes dans l’exploitation et des temps passés en stabulation et en salle de traite. L’exposition à l’acétaldéhyde est dépendante de la taille de l’exploitation et des tâches liées à la distribution d’ensilage. Nos travaux soulignent également qu’une augmentation de la surface des ouvertures de la stabulation est associée à une réduction significative de l’exposition aux moisissures, à l’ammoniac et à l’acétaldéhyde. Enfin, notre étude montre que les poussières émises lors du paillage mécanisé ont (1) une taille leur permettant de se déposer majoritairement dans les régions trachéo-bronchiques, (2) une composition bactériologique et fongique complexe et (3) in vitro des effets pro-inflammatoires puissants induisant l’expression de TNF-α, d’IL-1β, d’IL-6 et d’IL-8 dans des macrophages humains. Au total, ces travaux de thèse ont permis d’identifier des activités professionnelles et des caractéristiques d’exploitations augmentant significativement les niveaux d’expositions des éleveurs laitiers-bovins à des contaminants chimiques et à des poussières organiques pouvant théoriquement se déposer dans les tissus bronchiques où sont censées se développer différentes maladies broncho-pulmonaires. Les modèles statistiques développés au cours de la thèse permettent dès à présent la reconstitution des expositions des éleveurs et pourront être utilisés dans de futures études épidémiologiques et dans l’élaboration de programmes de prévention
Dairy farmers have an increased risk of lower airway diseases that is likely related to occupational exposures to airborne contaminants. Nevertheless, occupational determinants of dairy farmers’ exposures remain poorly documented and the biological effects of the contaminants chronically inhaled by farmers need to be fully characterized. In this context, the objectives of this PhD thesis were i) to identify the occupational determinants of exposure to thoracic bio-aerosols (organic dusts, endotoxins, bacteria and moulds), ammonia and acetaldehyde, and ii) to characterize the pro-inflammatory effects of thoracic dusts emitted during the mechanical spreading of straw bedding, a task well-known to generate inhalable dusts. To achieve these goals, we carried out a 112-repeated exposure measurement campaign on 29 dairy farms located in Britany. Using multivariate mixed-effect regression models, we have demonstrated that farmers’ exposures to bio-aerosols were mainly induced by tasks related to bedding material distribution and cow feeding (straw, hay, silage). Exposure levels to ammonia were highly dependent on cow numbers and times spent by the farmers in stable and milking parlour. Acetaldehyde exposure was modulated according to the farm size and times spent to distribute silage. Our work also highlighted that an increase of the area of wall opening significantly reduced exposure to mould, acetaldehyde and ammonia. Finally, our study showed that dusts emitted during mechanical straw spreading have (1) a size small enough to allow them to deposit in the tracheobronchial regions, (2) a complex bacterial and fungal composition, and (3) strong in vitro pro-inflammatory effects that induced TNF-α, IL-1β, IL-6 and IL-8 expression in human macrophages. In conclusion, these results have identified different dairy farm characteristics and occupational tasks that significantly increased the exposure levels to chemical contaminants and thoracic organic dusts. Statistical models built during this research project already allow reconstitution of dairy farmers’ exposure that may of use in future epidemiological studies and to develop new preventive measures

Cette thèse porte sur l’analyse des apports des approches participatives épidémiologiques (PE) dans l’amélioration de la surveillance de la fièvre aphteuse (FA), en particulier dans l’implication des éleveurs à l’échelle locale. Le premier objectif était d’évaluer l’efficacité de la surveillance et de la vaccination contre la FA à l’échelle locale en utilisant PE. Le deuxième objectif était d’évaluer la faisabilité d’application des outils de PE pour améliorer l’implication des éleveurs dans la surveillance de la FA au Vietnam. Les méthodes de PE ont compris des entretiens informelles (en groupes ou individuels), des outils de notation (classement par paires, empilement proportionnel, matrice de notation), des outils de visualisation (cartographie, lignes de temps, diagramme d’écoulement) et d’outil sociologique appelée méthode Q. 122 entretiens en groupe, 467 entretiens individuels, 339 questionnaires ont été effectuées en 2014 et 2015. 409 sérums et 152 fluides d’oesophagiens ont été prélevées. Les enquêtes par questionnaire, les tests d’ELISA et de rtRT-PCR et la modélisation de Bayésienne ont été utilisées pour valider la performance de PE dans la surveillance de la FA. La maladie a été considérée comme la problème la plus importante dans la production animale. La FA était la maladie la plus importante pour la production laitière, suivie par la septicémie hémorragique. Pour la production de bovin de viande, elle a été enregistrée dans l'ordre inverse. La maladie la plus importante pour la production porcine était le syndrome reproducteur et respiratoire porcin tandis que la FA était classé en quatrième. Les agriculteurs ont des capacités de diagnostic différentiel des maladies en fonction des symptômes cliniques. La prévalence sérique de la FA a été estimée à 23% pour la population 1 (proche la frontière du Cambodge) et 31% pour la population 2 (loin de la frontière du Cambodge), respectivement. La sensibilité et la spécificité de PE a été estimée à 59% et 81%, respectivement. La valeur prédictive positive et négative a été estimée à 48% et 86% pour la population 1 et 58% et 81% pour la population 2, respectivement. La présence du sérotype A, de la lignée A/Asia/Sea-97 et du sérotype O, lignées O/ME-SA/PanAsia et O/SEA/Mya-98 a soutenu la circulation du virus par des mouvements transfrontalières des animaux. Les fermes laitières ont appliquées la quarantaine, la désinfection et la vaccination comme méthodes de prévention. Les fermes de bovin de viande ont préférées la propreté et les bonnes pratiques de gestion de l'élevage. Les fermes porcines ont considérées que toutes les méthodes de prévention avaient la même importance. Trois discours «Croire», «Confiance», «Défi», représentés les perceptions communes des éleveurs et représentés 57,3% de la variance, ont été identifiés en utilisant méthode Q. Les éleveurs ont pris eux-mêmes les décisions de vaccination et se sont sentis plus en sécurité après la vaccination contre la FA. Cependant, une partie de la population étudiée n'a pas considérée la vaccination comme le premier choix de prévention. L'analyse de sensibilité de rapport de bénéfice-coût de la vaccination de la FA a montré que la vaccination était rentable pour tous les types de production, même si l'augmentation du coût de la vaccination et la diminution du prix de lait et de viande. 18 nouveaux villages sentinelles ont été identifiés comme potentiellement infectés par la FA. 77 animaux soupçonnés ont été confirmés positives avec la FA. La sensibilité et la spécificité de PE a été estimée à 0,75 et 0,65 respectivement. L'efficacité de PE pour détecter une épidémie de FA au Vietnam ont été démontrée. La vaccination a était montré la méthode la plus économique et la plus efficace pour prévenir la FA. Grâce à l'application des outils simples et adaptables qui facilitent la participation directe et active des éleveurs, PE permet d'obtenir une meilleure acceptabilité de la surveillance et des informations qualifiées
This PhD thesis aimed at evaluating the contribution of participatory epidemiology (PE) to improve the foot-and-mouth disease (FMD) surveillance and control activities, especially the involvement of farmers at local level. The first objective aimed at assessing the effectiveness of the FMD surveillance and vaccination strategy at local level by using PE approach. The second objective aimed at assessing the feasibility of applying PE tools to improve the involvement of farmers in the FMD surveillance in Vietnam. PE methods performed in our study included informal interviews (focus group and individual), scoring tools (pairwise ranking, proportional pilling, disease impact matrix scoring and disease signs matrix scoring), visualization tools (mapping, timeline, flow chart) and sociological tools called Q methodology. 122 focus groups, 467 individual interviews, 339 questionnaire surveys were performed during two field studies in 2014 and 2015. 409 sera and 152 probang samples were taken. Conventional questionnaire surveys, Bayesian modelling and laboratory test (ELISA and rtRT-PCR) was used to validate the performance of PE in FMD surveillance. Disease was considered as the most important issues in animal production. FMD was the most important disease for dairy cattle production, followed by haemorrhagic septicaemia. For beef cattle production, it was recorded in reverse order. The most important disease for pig production was porcine reproductive and respiratory syndrome while FMD was ranked fourth. Farmers showed their abilities in differential diagnostic of important diseases based on its clinical symptoms. Sero-prevalence of FMD were estimated at 23% for population 1 (bordering with Cambodia) and 31% for population 2 (locating far from the border), respectively. Sensitivity and Specificity of PE were found to be 59% and 81%, respectively. The positive and negative predictive value were found to be 48% and 86% for population 1 and 58% and 81% for population 2, respectively. The presence of serotype A, lineage A/Asia/Sea-97 and serotype O with two separate lineages, O/ME-SA/PanAsia and O/SEA/Mya-98 supported virus circulation through trans-boundary animal movement activities. Dairy farms frequently applied quarantine, disinfection and vaccination as prevention methods. Beef farms preferred cleanliness and good husbandry management practices. Pig farms considered that all prevention methods had the same importance. Three distinct discourses “Believe”, “Confidence”, “Challenge”, representing common perceptions among farmers and accounting for 57.3 % of the variance, were identified based on Q methodology. Farmers take vaccination decisions themselves without being influenced by other stakeholders and feel more secure after FMD vaccination campaigns. However, part of the studied population did not consider vaccination to be the first choice of prevention strategy. The benefitcost ratio of FMD vaccination for dairy cow production in large-scale and in small-scale and meat cattle production were 37.2, 30.0 and 7.3, respectively. The sensibility analysis showed that FMD vaccination was profitable for all of production types even through the increase of vaccine cost and decrease of market price of milk and slaughter cattle. From the focus groups organized at sentinel villages, 18 new villages were identified as potentially infected by FMD. 77 suspected animals were confirmed positive for FMD, with viral serotypes O and A. Sensitivity and specificity of participatory surveillance were recorded at 0.75 and 0.65, respectively. The effectiveness of PE in FMD surveillance system to detect outbreak in Vietnam was demonstrated. It was demonstrated that vaccination was the most effective and economic method to prevent FMD. Through the application of simple, adaptive tools which facilitate direct and active participation of farmers, PE allowed to reach a better acceptability of surveillance and to obtain qualified information

Le titre de la thèse concernant le succès des nématodes peut sembler extremement vaste. Notre projet était pourtant bien d’avoir une vue d’ensemble de l’ensemble des acteurs, à savoir les nématodes parasites du tube digestif mais également l’hôte et certains aspects de sa réponse, et enfin l’éleveur qui est celui qui décide du mode d’élevage et des traitements antiparasitaires. Nous avons essentiellement travaillé en conditions expérimentales et sur une espèce de ces strongles. En ce qui concerne les traits de vie des nématodes plusieurs grands phénomènes conditionnent leur succès : a) leur capacité assez variable selon les isolats à infester un hôte, b) l’interaction entre résistance aux antiparasitaires et cette capacité à infester, c) enfin leur aptitude à survivre aux stress climatiques au cours de leur phase non-parasitaire
The success of gastrointestinal nematodes in their sheep hosts is so extensive that they present one of the leading threats to ruminant health and production throughout the globe. This thesis research identified three key factors which influence their success including the gastrointestinal nematode biology, the sheep host protective response and the farmers control decisions. Using Haemonchus contortus as a model species, we demonstrated that the success of GIN biology is aided by their capacity to overcome numerous selective pressures that target both parasitic and free-living stages in their life cycle. This was achieved by amplifying life-history traits following challenge to recoup any costs in survival and reproduction. In turn, high levels of fitness were maintained and they remained stable in the face of numerous selective pressures. Sheep have the capacity to exert almost perfect control over GIN success by blocking their life cycle through via protective responses

De nos jours, l'épidémiologie des bactéries multi-résistantes a évolué et ne se limite plus aux milieux hospitaliers. En effet, les animaux sont désormais considérés comme d’importants réservoirs de bactéries multi-résistantes, notamment des Bacilles à Gram négatif sécréteurs de bêta-lactamases et/ou résistant à la colistine. L'émergence de ces bactéries chez les animaux est due principalement à l’utilisation excessive d’antibiotiques en tant que prophylaxie et facteurs de croissance. Le transfert d’organismes multi-résistants aux antibiotiques provenant d’animaux vers les humains est un problème majeur pouvant entrainer de graves infections. La transmission zoonotique se fait par contact direct/indirect mais aussi par voie environnementale. Au Liban, plusieurs études ont été menées dans les hôpitaux et ont montré une prévalence élevée de bactéries multi-résistantes. En revanche, ces études sont rares dans le milieu vétérinaire. Le but de ce travail de thèse est de décrire l'épidémiologie des organismes multi-résistants dans les animaux d’élevage destinés à la consommation au Liban. Le typage des bactéries par MLST et le séquençage du génome entier ont été utilisés pour décrire la prévalence des organismes multi-résistants et les mécanismes de résistance chez les souches isolées. Nous pouvons ainsi conclure que les élevages de poulets et de porcs sont de puissants réservoirs de gènes de résistance BLSE et mcr-1 au Liban. La dissémination de la résistance semble être polyclonale et liée à la propagation de plasmides porteurs de gènes de résistance. Par conséquent, l'utilisation de la colistine en médecine vétérinaire au Liban doit être interdite
Nowadays, the epidemiology of multi-drug resistance has changed and is no more confined to the hospital settings. Food producing animals are increasingly regarded as potent reservoirs of multi-drug resistant organisms i.e. beta lactamase producers and colistin-resistant Gram-negative bacilli. The emergence of multi-drug resistance in animals is thought to be mainly driven by the overuse of antibiotics as growth promoters and prophylaxis. The dissemination of resistant organisms in animals is sparked by the concern of being transferred to humans where they can be candidates for infections with limited therapeutic options. The zoonotic transmission of resistant organisms from animals to humans occurs mainly via direct/indirect contact but also via environmental routes. In Lebanon, several studies were conducted in hospitals and showed a high prevalence of multi-drug resistance; unlikely, these studies are scarce in animals. The aim of this thesis research was thus to describe the epidemiology of multi-drug resistant organisms in Lebanese Livestock Multi-locus sequence typing and whole genome sequencing were used to describe the prevalence of multi-drug resistant organisms and the corresponding mechanisms of resistance in the isolated strains from chicken, pigs, farmers and environment. Chicken and swine farms showed to be potent reservoirs of ESBL and mcr-1 genes in Lebanon. The dissemination of multi-drug resistance appears to be multi-clonal and related to the spread of plasmid carrying resistance genes. Colistin use in veterinary medicine in Lebanon should be banned

Health communication has become recently an essential and powerful tool for public health. Its role has been largely recognized in human medicine, but it has been less considered in veterinary medicine even if this latter field is not less decisive for the human health. The One Health concept unified the two medicines recognizing that human health is inextricably connected to animal health and environment. Within this framework, we design this study to investigate the relationship between health communication and One Health. Particularly, we focused on the role of communication in veterinary medicine and how it has the potential to improve human health. Veterinary medicine competences include a broad spectrum of aspects, which can’t be covered in a single study. Moreover, we were interested in investigate if communication has a role also in the veterinary areas traditionally considered less linked to public health. Therefore, this study was focused on clinical communication, both in companion and in food-producing animals practice. This study confirmed the outcomes from previous surveys and showed the importance of communication in veterinary medicine in improving human health. Communication in veterinary medicine is not less important for human health, and is not different from what is usually considered health communication. Indeed, both of them cover the same issue (zoonoses, food safety etc.) and use the same strategies. Therefore, a “One Communication” approach appear to be the most helpful tool in improving human health in the One World-One Health-One Medicine.

Agriculture contributes about 70 percent of Malawi's Gross Domestic Product and sustains the livelihood of over 85 percent of the rural population. Soil erosion, which has reached alarming proportions, is threatening this resource base. Despite being rated the most serious environmental problem, soil erosion research lags behind in the listing of agricultural research priorities, particularly with regard to factors influencing the implementation of soil conservation policy and legislation. This study aimed to assess the impact of such policy implementation on smallholder farmer soil conservation practices. A postal, self administered, structured questionnaire was used to interview twenty-three farmers and fourteen agricultural extension staff members. The questions were designed to assess the influence of their perceptions of soil erosion as a problem and its causes. They also sought to assess how effectively relevant policy had been implemented before and after independence. Socio-economic information was additionally elicited from the farmers. After preliminary analysis of these questionnaires, ten days was spent in the field verifying data collected. A Spearman's Rank correlation analysis at 95 percent confidence level was carried out between various components of the farmers' socioeconomic profile data and their responses to the perception questions. Perceptions regarding different aspects of soil erosion and conservation were found to be influenced by the sex, age and educational level of respondents. The study revealed that both farmers and extension staff perceived soil erosion as a problem, had a sound knowledge of the mechanics of the process and attributed it to anthropogenic factors. While both farmers and extension staff attributed declining yields and fertility to accelerated soil erosion, they appeared to have difficulty in identifying physical indicators of such activity in the field. The study also revealed that both believed the top-down approach of the pre-independence period and the post-independence to 1990 period, had been partially effective. Since 1990, policy implementation has become more effective as a result of a more democratic governance and increased extension staff awareness of sustainability concepts which stress the need to incorporate the aspirations of farmers in a bottom-up implementation. This awareness led to the formulation of a new soil and water conservation policy in 1996 which ensures the voices of decision makers are taken into account in policy review. Once legislated, this policy bodes well for further improvements in soil conservation efforts in Malawi. However, the study also revealed that effective implementation of this policy will be dependent on the government providing adequate support and skills to both extension staff and farmers.
Thesis (M.Sc.)-University of Natal, Durban, 2003.

This thesis aimed at measuring the economic costs of soil degradation and to determine factors that influence the incidence and extent of adoption of soil conservation technologies by smallholder farmers in Malawi. A dynamic optimisation model was used to derive and analyse the optimal conditions for soil resource extraction and use in Malawi, while a selective tobit model was used to simulate the two-step decision-making process of farmers with respect to adoption of soil conservation technologies. Soil degradation has long-term consequences and static models, which form the bulk of studies that have so far been carried out in Africa on this topic, do not account for the inter-temporal dimension of optimal resource management. To deal with this shortcoming, this thesis used an inter-temporal optimisation framework, which considers soil in a time-dependent resource extraction perspective. This thesis has demonstrated that soil degradation is causing an enormous reduction in the productive value of smallholder land in Malawi. Current user cost of soil quality based on current practices of smallholder farmers, which represents annual loss in productive value of land, was estimated to be US$21 per hectare. Based on this value and land area under smallholder agriculture in Malawi, economic costs of soil degradation among smallholder farmers were estimated to amount to 14 per cent of the agricultural GDP. If left unabated, soil degradation threatens not only the future of smallholder agriculture but also, economic growth prospects of the nation. Although not operating on the SS optimal path in terms of soil resource management, current practices show that smallholder farmers in Malawi still consider, to certain degree, the dynamic costs in soil resource use. Hence, there is no strong evidence to suggest that current trends in land degradation are due to an institution failure (i.e., smallholder farmers have private incentives to conserve their soil resource). A result that suggests presence of other factors, most likely market distortions, behind existing deviations of farmers' practices from dynamic optimum. Government's serious support of the input and output market reforms is important not only to make the markets work but also, to make smallholder agriculture a profitable enterprise. It is only when smallholder agriculture becomes profitable that farmers can seriously invest in the soil resource. Agricultural support programs such as "food for work" if extended to include soil conservation, could lead to substantial curtailment of soil erosion since farmers can invest their labour in their own gardens during the critical times of land preparation. The sensitivity analysis indicated that increasing the discount rate to' 5%, SS solutions were close to current practice solutions. This suggests that one reason smallholder farmers are exploiting the soil resource is because they have a higher time preference. The high levels of poverty, especially among the smallholder subsistence farmers in Malawi, entail that farming households are more concerned with their survival now than their future well being. The study estimated an optimal output of 1.5tonlha and nitrogen fertiliser rate of 49 kg/ha at SS. The fertiliser estimates are based on smallholder farming system that incorporates soil conservation. In one of the most detailed studies on nitrogen use efficiency in Malawi, Itimu (1997) indicated that with the incorporation of manure, nitrogen fertiliser use dropped from 60 to 30 kg/ha to produce about 2.5 tons of maize. Malawi uses area specific recommendations for fertiliser application. However, using "best bet" technologies, at least 35kgN/ha is recommended for smallholder farmers on average. The SS optimum fertiliser estimated in the current study was somehow higher due to the fact that an inter-temporal framework, which considered the dynamic costs of soil nutrient extraction, was used. Results from fertiliser recommendation trials may be reinforced if researchers consider the inter-temporal nature and dynamic costs associated with the use of soil. The selective tobit model results indicate that factors that influence smallholder farmers' decisions to adopt soil conservation technologies may not necessarily be the same factors that influence subsequent decision on levels of adoption. The implication of this finding is that different policy prescriptions on soil conservation should strictly be guided by the goals the government wants to achieve. With fertiliser prices being out of the reach of most smallholder farmers in Malawi, soil conservation is one of the reliable options available to reduce soil degradation. However, any policy aimed at improving adoption of soil conservation technologies among smallholder farmers would succeed only if the various needs of smallholder farmers at the two decision stages are properly identified and addressed.
Thesis (PhD (Agricultural Economics))--University of Pretoria, 2006.
Agricultural Economics, Extension and Rural Development
unrestricted

This case study investigated the impact of irrigation on household food security at Ibu and Kalizinje villages in Chingale, Malawi. The aim of the study was to investigate whether irrigation improved household food security. The study was qualitative in nature. Fifty-eight farmers and three World Vision field staff participated in the study. Group discussions with participatory techniques and in-depth interviews were used to collect data. Data were analysed qualitatively using matrix/logical analysis. Irrigation improved irrigating farmers’ household food security through an increase in production and income levels. Irrigating farmers were better off in terms of crop production and income levels than non-irrigating farmers. Irrigating farmers planted irrigated maize two to three times a year, while non-irrigating farmers planted rain-fed maize only once a year. In terms of income levels, irrigating farmers produced more food than households required, and sold surpluses. Most irrigating farmers began cash cropping after the introduction of irrigation and also earned higher incomes, as irrigation enabled production of crops during lean periods and enabled them to sell surpluses at higher prices. Irrigation did not improve crop diversification. Non-irrigating farmers diversified crops more than irrigating farmers by planting groundnuts and sweet potatoes. Income from irrigating farmers did not increase dietary diversity and the acquisition of assets for irrigating farmers. Few farmers consumed a variety of foods and few acquired assets with the income derived from irrigation. Nevertheless, irrigation has the potential to smooth production cycles and provide food and income during seasons when food and income would be low. In addition, the study revealed the following as problems faced by farmers: constraining size of small diesel pumps, pump breakdown at Kalizinje, floods, pests and diseases, storage problems, lack of market places and poor roads, small land sizes, and expensive farm inputs.
Thesis (M.Sc..)-University of KwaZulu-Natal, Pietermaritzburg, 2008.

Rice (Oryza sativa L.) is the second most important cereal crop in Malawi. Rice productivity in the dominant (85%) rainfed ecosystem is very low, with mean yield of only 1.4 t ha-1. Farmers plant traditional landraces that have low yield potential and are susceptible to various stresses such as drought and diseases. Development and introduction of improved rice varieties, with stress tolerance traits from introduced varieties, such as the New Rice for Africa (NERICAs), could significantly increase productivity. Previous attempts to introduce high yielding irrigated varieties into the dominant rainfed ecosystem in Malawi have not been successful because farmers basically did not adopt the varieties, claiming that the varieties were lacking in grain traits that they preferred but that the traits were present in their landraces. The notable traits mentioned, through previous informal surveys, were long grains, medium to slender shape and aromatic grain with intermediate gelatinization temperature. No formal study has been conducted to ascertain the preferences, and the genetic control of the traits, including yield and yield related traits, have not been studied. The objectives of this study were to: 1) confirm farmers’ preferences for grain traits using participatory rural appraisal; 2) determine amount of genetic variability for yield and yield related traits in Malawi rice landraces, 3) determine the genetic control and correlations of grain length, grain shape and 1000-grain weight, 4) determine the inheritance of aroma and gelatinization temperature and, 5) determine the genetic control, correlations and path coefficients of yield and yield related traits, in F2 generations of Malawi rice landraces and NERICA varieties crosses. To confirm the farmers’ preferences for grain traits, a participatory rural appraisal was conducted in 2006 in two villages that were representative of rainfed rice growing areas in Malawi. The villages were Liundi and Nawanga in Machinga and Salima Districts, respectively. Qualitative and quantitative data were collected through questionnaires and discussions with 190 respondents, as well as through observations. To determine variability among Malawi rice landraces, 19 landraces were planted at Lifuwu in a Randomized Complete Block Design with three replicates in 2006. Data on plant height, days to 50% flowering, number of panicles per hill, panicle length, number of filled grains per panicle, 1000-grain weight, panicle weight, grain length and grain yield were collected and analyzed. Four Malawi rice landraces were crossed to four NERICA varieties in 2006 in a North Carolina Design II mating scheme to determine the genetic control of grain size. F1 plants were raised in 2007 and in 2008, 16 F2 populations together with their parents were planted in a Randomized Complete Block Design with three replicates at Lifuwu. Data on grain length, grain shape and 1000-grain weight were collected and analyzed. To determine the inheritance of aroma and gelatinization temperature, four Malawi rice landraces were crossed to four NERICA varieties in 2006 and F1 plants were raised in 2007. In 2008, 16 F2 populations together with their parents were planted in a Randomized Complete Block Design with three replicates at Lifuwu. Aroma and gelatinization temperature were evaluated. To determine the gene action of yield and yield related traits, four Malawi rice landraces were crossed to four NERICA varieties in 2006 in a North Carolina Design II mating scheme and F1 plants were raised in 2007. In 2008, 16 F2 populations together with their parents were planted in a Randomized Complete Block Design with three replicates at Lifuwu. Data on grain yield, the number of panicles per hill, days to 50% flowering, panicle length, panicle weight and 1000-grain weight were collected and analyzed The participatory rural appraisal confirmed that that long, slender or medium shape grains, with aroma and intermediate gelatinization temperature were the key traits preferred by farmers. Therefore the farmer preferred traits of long, slender grains, with aroma and medium gelatinization temperature, must be selected for in any high yielding varieties to be developed for the rainfed rice ecosystem. Results showed that differences were significant (P=0.05) for all the traits that were studied. Heritability estimates were low to moderate: 18.3% for panicle weight, 40.0% for panicles per hill and 56.3% for days to 50% flowering date. The high genetic variability among the landraces could be used in a breeding programme to develop improved varieties for various morphological traits. The number of panicles per hill and 1000-grain weight combined moderate heritabilities with relatively high genetic advance and therefore could be reliable traits for yield improvement. Genetic analysis of grain size showed that Malawi rice landraces were variable for all three grain size characteristics, namely grain length, grain shape and 1000-grain weight. NERICA varieties were variable for 1000-grain weight. Sixteen F2 progenies were variable for all three characteristics, and the variability was significant (P=0.05). Heritability estimates were high (45.4%) for grain length and low for grain shape (12.3%) and for 1000-grain weight (14.3%) suggesting that early generation selection would be effective for grain length. Predominance of additive gene action for grain length and grain shape suggested that early generation selection would be effective for these traits. Selection for 1000-grain weight would be more effective in later generations because of preponderance of non-additive gene action in the control of this trait. The correlation between grain length and grain shape was positive (r=0.769) and highly significant (P=0.01) suggesting that breeders would choose to select for both traits simultaneously, or they would choose one of the traits to develop varieties with long grains and medium shape. Crosses between aromatic and non-aromatic varieties had non-aromatic F1. The F2 progenies segregated into 3:1 ratio for non-aromatic: aromatic suggesting that, in the Malawi rice landraces, aroma was probably simply inherited through a single recessive gene. F1 progenies, between parents with high and intermediate gelatinization temperatures had intermediate gelatinization temperature. F2 progenies segregated into 1:3 ratios for high; intermediate gelatinization temperature in three out of four crosses suggesting control by one dominant gene. The segregation pattern in one cross was not significantly different from 3:13 ratio for high: intermediate suggesting that two dominant genes, one an inhibitor, were controlling the trait. Breeding and selecting for aroma and intermediate gelatinization temperature could be accomplished relatively easily because the traits are simply inherited. The genetic variability for yield and yield related traits was wide and significant (P=0.05) in the F2 populations of Malawi rice landraces and NERICA varieties crosses indicating that the populations would be valuable sources to develop varieties with improved yield. Panicle weight and the number of panicles per hill were positively correlated with, and had high direct effects on grain yield, therefore they could be used to indirectly select for high yield. Grain yield, the number of panicles per hill and plant height were predominantly controlled by additive gene action suggesting that bulk breeding methods would be adopted for these traits. The days to 50% flowering, panicle weight and 1000-grain weight were predominantly under the control of nonadditive gene action suggesting that hybrid development would be profitable for these traits. Faya Mpata, Faya Zidyana and NERICA 3 could be the best parents for improving yield and yield related traits because they had high general combining abilities for the traits.
Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2010.
Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2010.

Low agricultural productivity and the associated poverty caused by the rapid degradation of soil fertility have negatively affected agricultural based livelihoods in Malawi. As a result, sustainable improved practices (SIPs) such as improved maize and legume seeds and conservation agriculture packages, among others, have been developed and promoted as suitable options to reverse the issue of low food production. Although there have been strong-minded efforts by scientists and agriculture extension staff to improve the adoption of these technologies, questions remain regarding their uptake among smallholder farmers. Furthermore, even in places where the technologies have been in practice, this process has been very slow, with big variations of adoption across all smallholder farmers. This study draws its empirical data from two sources: Firstly, from collaborative work between the International Maize and Wheat Improvement Centre (CIMMYT) and the Department of Agricultural Research Services (DARS)in Malawi. Secondly from the data collected by Western Sydney University in collaboration with assistance of Bunda College of Agriculture under the University of Malawi (now LUARNAR). Data collection was mainly through farmer household surveys and farmer focus group discussions conducted between 2011 and 2013. The research took place in 6 target districts on a total of 1293 (891 and 402) farmers in the north, central and southern Malawi. Therefore, this study sought to address three main objectives by administering and evaluating a structured questionnaire specifically to capture farm household data on: a) the diversity that exist among the smallholder farmers which influences their use of sustainable intensification practices, b) opportunities and constraints for the intensifications of improved maize-legume varieties among smallholder farmers for dietary intensification and ecological intensification, c) the stepwise adoption and factors that influence farmers decision to adopt the individual components of the adapted conservation agriculture package in Malawi. Three standalone empirical chapters are merged to form the core of this thesis which has been integrated and synthesised in the final chapter. Overall, this thesis contributes both to literature and methodology. Overall, this thesis contributes both to literature and methodology. Results from principal component analysis (PCA) and cluster analysis (CA) technics consistently indicated that there is diversity among the smallholder farmers revealing four different farmer classes which influenced their adoption of the improved soil fertility technologies. These farm types were: a) type 1 farms (35.13%) were classed as ‗small subsistence-oriented family farms‘ practiced crop residue retention and crop rotation, b) type 2 (31.43%) were ‗small semi-subsistence family farms‘, type 3 (25.36%) were ‗survivalist‘ (small, independent, semi-specialized family farms whose main objective was family sustenance) and, c) type 4 (7.52%) were ‗production-oriented, small, dependent, semi-specialized family farms‘. Farm typologies indicated that farm types 1 and 2 practiced crop residue retention and crop rotation by intercropping of maize–legumes improved varieties, potentially making them the possible adopters of improved farm technologies among the rest of the farm types. Minimum tillage adoptions remained sparse. Type 3 farms, in addition to being family sustenance-oriented, specialised in a cash crop such as tobacco, cotton, legume which made them party commercial, which had a negative impact on practicing of improved farm technology. Type 4 farms were like type 3 but different high level of specialization as tenants in tobacco growing largely dictated by their landlords, which limited their adoption of improved farm technology. Evaluation of the opportunities and constraints for maize-legume intensification among the smallholder farmers for dietary fortification and ecological intensification was done by comparing results of three random effects regression models using multilevel logistic analysis. Two different methods - first multivariate and second econometric technics were applied to correct for potential bias in estimating the factors that influenced adoption of maize-legume intensification. The results of the models indicated that farmers who had a shorter distance to walk to the farm inputs market and village market, had a higher participation in the intensification of maize-legume by 72 % of the farmers. The thesis indicated that farmers decision to adopt or not to adopt each component combination from the adapted CA package (residue retention, minimum tillage, crop rotation and use of herbicides) was considered to be sequential and incremental. The results also revealed that the households‘ decision to adopt the individual component depended on farmers experience in growing cowpeas, soil depth and the households‘ food availability throughout the year. However, crop residue retention was the highest adopted (85%), followed by minimum tillage ate 70% and use of herbicide at 69%, with crop rotation the least at 30%.