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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
41

Seroprevalence of Rift Valley fever and lumpy skin disease in African buffalo (Syncerus caffer) in the Kruger National and Hluhluwe-iMfolozi Parks, South Africa

Fagbo, Shamsudeen 09 October 2012 (has links)
Lumpy skin disease (LSD) and Rift Valley fever (RVF) are transboundary viral diseases occurring in Africa and the Middle East (e.g. Israel, Saudi Arabia and Yemen) with increasing potential for global spread. Although the role of wildlife in the epidemiology of these diseases is still not clearly understood, the African buffalo (Syncerus caffer) is thought to play a role in the epidemiology of these diseases. This study sought to expand our understanding of the role of buffalo in the maintenance of RVF and LSD by determining seroprevalence to these viral diseases in buffalo during the inter-epidemic period. Lumpy skin disease is endemic in Africa, and has spread to the Middle East (e.g. Israel); consequently there is a high risk of lumpy skin disease virus (LSDV) expanding its geographical distribution to other areas and due to its economic importance it is included in the list of Notifiable Diseases of the World Organization of Animal Health (OIE). The African buffalo is also suspected to play a role in the epidemiology of RVF. Like LSD, RVF was, until recently, only endemic in Africa. However, it spread to the Arabian Peninsula (Saudi Arabia and Yemen) in 2000 exacerbating concerns that it will extend to other regions of the world. Studies have already established that competent mosquito vectors for RVFV exist in North America and other parts of the world. A total of 248 buffalo sera was tested for antibodies to capripoxviruses and neutralising antibodies against LSDV and RVFV using an indirect enzyme-linked immunosorbent assay (I-ELISA) as well as the serum neutralisation test (SNT). The samples were obtained from the Kruger National Park (KNP) and Hluhluwe-iMfolozi Park (HiP) in South Africa. The prevalence of antibodies to LSDV and RVFV in the sera tested was 70/248 (28.2%) and 15/248 (6.1%), respectively using an I-ELISA. The LSDV I-ELISA, using a sheeppox virus as antigen, has not been validated for use in African buffalo. The high percentage of LSDV positive antibody results obtained in this study is however a concern. Results obtained is in contrast with other published results as well as results obtained with the SNT for antibodies against LSDV. The SNT is currently the gold standard for LSDV antibody testing. Using this test for LSDV in this study, 5/66 (7.6 %) samples tested positive. The results of the RVF I-ELISA, which had previously been validated for use in the African buffalo, correlated with the SNT results. From 12 SNT RVFV-positive sera, 3 (25%) had very high SNT titres of 1:640. Neutralising antibody titres of more than 1:80 were found in 80% of the positive sera tested. Eleven buffaloes (4.4% of the total samples) also showed evidence of antibodies to both LSDV and RVFV. The results obtained in this study complement other reports indicating the role of African buffalo in the epidemiology of these diseases during inter-epidemic periods. / Dissertation (MSc)--University of Pretoria, 2012. / Veterinary Tropical Diseases / unrestricted
42

Impulsive Differential Equations with Applications to Infectious Diseases

Miron, Rachelle January 2014 (has links)
Impulsive differential equations are useful for modelling certain biological events. We present three biological applications showing the use of impulsive differential equations in real-world problems. We also look at the effects of stability on a reduced two-dimensional impulsive HIV system. The first application is a system describing HIV induction-maintenance therapy, which shows how the solution to an impulsive system is used in order to find biological results (adherence, etc). A second application is an HIV system describing the interaction between T-cells, virus and drugs. Stability of the system is determined for a fixed drug level in three specific regions: low, intermediate and high drug levels. Numerical simulations show the effects of varying drug levels on the stability of a system by including an impulse. We reduce these two models to a two-dimensional impulsive model. We show analytically the existence and uniqueness of T-periodic solutions, and show how stability changes when varying the immune response rate, the impulses and a certain nonlinear infection term. The third application shows how seasonal changes can be incorporated into an impulsive differential system of Rift Valley Fever, and looks at how stability may differ when impulses are included. The analysis of impulsive differential systems is crucial in developing more realistic mathematical models for infectious diseases.
43

An investigation of an outbreak of Rift Valley fever on a cattle farm in Bela-Bela, South Africa in 2008

Mapaco, Lourenco Paulo 24 May 2012 (has links)
During March 2008 a suspected outbreak of Rift Valley fever was reported on a farm in the Bela-Bela area, Limpopo Province of South Africa. The affected dairy farm, where no vaccination programme against RVF were practiced, applies an intensive farming system with 300 Holstein Friesland cattle (calves included) as well as 200 Pedi sheep on the farm. Seven calves died on this farm but no apparent clinical disease was reported in cattle as well as in sheep. During the outbreak blood samples from cattle and sheep were taken and the animals were re-sampled 8 weeks later. A set of sera was also collected from cattle on a neighbouring farm. The aim of the study was to determine the extent of the outbreak by evaluating if the virus had also infected other animals on the affected farm as well as on a neighbouring farm. During the first blood collection 233 samples were taken from cattle and 73 from sheep on the affected farm; 55 blood samples were taken from cattle on a neighbouring farm. A second blood collection was only done on the affected farm and 234 cattle and 85 sheep were bled. All the sera collected were tested by an IgM-capture ELISA and by an indirect IgG ELISA. Selected IgM positive (n=14), IgG positive (n=23) and samples negative for both IgM and IgG (n=19) were then tested by the serum neutralization test (SNT). Sera from IgM positive (14) and negative (20) animals were also tested by a TaqMan PCR. Results from the affected farm showed that 7% (16/233) of cattle samples were IgMpositive and 13.7% (32/233) IgG positive at the first collection of samples, and 2% were IgM-positive at the second sample collection. The number of cattle positive for RVF virus-specific IgG antibodies increased by 20.3% when compared to the first bled. Only 1.4% of sheep were both positive for anti-RVF virus IgM and IgG antibodies at the first collection; IgM-positive cases decreased to 1.2%, while IgG-positive cases increased to 2.4% at the second bled. Although no IgM-positive cattle could be found on the neighbouring farm, 5.5% of cattle were IgG-positive. The SNT confirmed most of the ELISA results. Three samples that tested positive for anti-RVF virus IgM and one anti-RVF virus IgG positive sample using ELISA tested negative using the SNT. Two samples that tested negative for both IgM and IgG antibodies using ELISA, tested low positive (1:10 and 1:20) using the SNT. All samples tested using a TaqMan PCR were negative. On the affected farm, apart from the seven calves that died, cattle were also infected. There was evidence of virus circulation on the neighbouring farm but the negative PCR results indicate that at the time the animals were sampled they were not viraemic. How the virus was introduced onto the farm is not clear. The possibility of low level virus circulation in animals and the reactivation of virus from endemic foci by the breeding of vector competent mosquitoes on the low-lying area on the farm in Bela-Bela may have led to ideal circumstances for an outbreak to occur. The fact that mostly cattle seroconverted suggests a higher host preference of the local population of mosquitoes for cattle rather than sheep. Copyright / Dissertation (MSc)--University of Pretoria, 2011. / Veterinary Tropical Diseases / unrestricted
44

MAVS is Essential for Regulation of Innate Immune Signaling during Rift Valley Fever Virus Infection

Ermler, Megan Elizabeth 21 February 2014 (has links)
No description available.
45

Contribution au développement d’un modèle vaccinal recombinant pour le contrôle des trois infections virales majeures des ruminants, la variole, la PPR et la RVF, adapté à la situation épidémiologique des pays du Maghreb. / Contribution to the development of a model recombinant vaccine for the control of the three major viral infections of ruminants, small pox, PPR and RVF, adapted to the epidemiological situation of the Maghreb countries.

Ayari-Fakhfakh, Saïda Emna 20 May 2011 (has links)
L'objectif de cette thèse est le développement d'un vaccin recombinant capripoxvirus protégeant contre la variole des ruminants, la Fièvre de la Vallée du Rift (FVR) et la Peste des Petits Ruminants (PPR) comme modèle vaccinal destiné aux pays atteints par ces infections. Une première partie de ce travail a consisté en une enquête sérologique en Tunisie pour évaluer les prévalences PPR et FVR. L'enquête menée a montré une séroprévalence PPR de 7,6% et l'absence de FVR. Le risque lié à une infection par le virus de la fièvre de la vallée du Rift n'est pas nul en raison de l'identification des vecteurs compétents Culex theileri et Culex pipiens dans les zones échantillonnées. L'élaboration du vaccin capripoxvirus FVR-PPR porte sur l'expression des gènes NSmGN-FVR et H-PPR où chacune des valences est insérée dans le site de la thymidine kinase et le site d'un analogue du récepteur à l'interleukine 8 respectivement. Le vecteur choisi pour la souche vaccinale Kenya Sheeppox-1. Bien que nos travaux aient conduit à l'obtention du capripoxvirus double recombinant, ce dernier n'a pu être purifié. L'alternative a donc été d'évaluer l'effet protecteur et l'immunogénicité induits par le simple recombinant capripoxvirus- NSmGN-FVR, qui est un produit de l'étape intermédiaire dans l'élaboration du double recombinant FVR-PPR. L'effet protecteur de notre construction a été validé par deux expérimentations chez des souris Mus m. musculus MBT/Pas, avec épreuve infectieuse. Le nombre de doses administrées, les voies d'administration ont été déterminants dans cette protection justifiée par l'obtention d'anticorps neutralisants anti-FVR. L'étude de l'immunogénicité a été réalisée sur un modèle caprin sans épreuve infectieuse, une séroconversion FVR a été observée. La lymphoprolifération et le typage des sous populations lymphocytaires ont été analysés. / The aim of this thesis was to develop a capripoxvirus based recombinant vaccine against ruminant pox, Rift Valley fever (RVF) and peste des petits ruminants (PPR) considered as a vaccine model for countries affected by these infections. The first part of the work consisted in a serological survey conducted in Tunisia to detect the PPR and RVF presence. A PPR seroprevalence of 7.6% has been found and no antibodies against RVF were detected. However, the risk of infection with rift valley fever virus persists since competent vectors such as Culex pipiens and Culex theileri has been identified in the sampled areas. The development of the RVF-PPR vaccine candidate is based on the NSmGN-FVR and H-PPR gene expression - where each of the genes is inserted into the thymidine kinase and the Interleukin 8 receptor analogue genes, respectively. The vector chosen is the vaccine strain Sheeppox Kenya-1. Although the double recombinant RVF-PPR has been produced, it could not be purified. The alternative was to evaluate the protection and the immunogenicity of the single recombinant capripoxvirus NSmGN-FVR, which is a product of an intermediate step of the process of the double recombinant preparation. The protection of our vaccine candidate has been performed by two mice experiments in Mus m. musculus MBT/Pas, with challenge. The number of doses, the route of administration played a key role in the protection confirmed by the presence of neutralizing anti-RVF antibodies. The study of the immunogenicity of the vaccine candidate was conducted in goats without challenge, RVF seroconversion has been shown. Lymphoproliferation studies and lymphocytes subpopulations typing have been analysed.
46

Examining Culex tarsalis (Diptera: Culicidae) population changes with satellite vegetation index data

Bradford, Jessica January 1900 (has links)
Master of Public Health / Department of Diagnostic Medicine/Pathobiology / Michael W. Sanderson / A zoonotic disease is any disease or infection that is naturally transmissible from vertebrate animals to humans. Over 200 zoonoses have been described (Zoonoses and the Human-Animal-Ecosystems Interface, 2013). Many zoonotic viruses are arboviruses, viruses transmitted by an infected, blood-sucking, arthropod vector (Hunt, 2010). There are several endemic arboviruses in the United States; some foreign arboviruses, such as Rift Valley fever (RVF) virus, are potential bioterrorism agents (Dar, 2013). Arboviruses, both endemic and foreign, threaten public health (Gubler, 2002) and therefore disease surveillance, vector control and public education are all vital steps in minimizing arboviral disease impact in the United States. Mosquito-borne disease threats, such as West Nile virus and Rift Valley fever, are constant concerns in the United States and globally. Current strategies to prevent and control mosquito-borne diseases utilize vector distribution, seasonal and daylight timing, and variation in population numbers. Climate factors, such as availability of still water for development of immature mosquitoes, shade, and rainfall, are known to influence population dynamics of mosquitoes. Using 1995-2011 mosquito population surveillance data from Fort Riley, Kansas, we compared population numbers of Culex tarsalis (Diptera: Culicidae), a vector of several arboviruses including West Nile virus and potentially Rift Valley fever, to a satellite-derived index of climate, the Normalized Difference Vegetation Index (NDVI) anomaly. No correlation between the population numbers and NDVI anomaly was observed, which contrasts with results from similar analyses in other locations. These findings suggest a need for continued investigation into mosquito population dynamics in additional ecological regions of the United States to better describe the heterogeneity of environment-population relationships within and among mosquito species.
47

Mécanismes de transmission du virus de la Fièvre de la Vallée du Rift à Madagascar / Transmission mechanisms of Rift Valley Fever virus in Madagascar

Olive, Marie-Marie 16 December 2016 (has links)
La Fièvre de la Vallée du Rift (VFVR) est une arbovirose zoonotique affectant principalement les ruminants et les humains. Son éco-épidémiologie complexe implique de nombreuses espèces de vecteurs, d'hôtes et de voies de transmission. Ainsi, différents mécanismes de transmission et d'émergence sont impliqués dans la circulation du virus de la FVR (VFVR) et ceux-ci dans des écosystèmes contrastés d'Afrique, de la Péninsule Arabique et des îles du sud-ouest de l'Océan Indien, dont l'île de Madagascar.Par sa superficie, sa grande diversité éco-climatique et sa faune et flore endémique, Madagascar est considérée comme une île continent. On y retrouve, en effet, des écosystèmes variés plus ou moins favorables aux moustiques : semi-arides dans le sud-ouest, humides et froids sur les hautes terres centrales, per-humide dans l'est et humides et chaud dans le nord-ouest. Madagascar a été affectée par deux épidémies de FVR en 1990-91 puis 2008-09. Une étude menée lors de la dernière épidémie a montré que le virus avait largement diffusé dans l'île de façon hétérogène.Compte tenu de la complexité des mécanismes de transmission de la FVR et de la diversité des écosystèmes de Madagascar, nous avons supposé que cette hétérogénéité spatiale était due à des mécanismes de transmission et d'émergence qui variaient en fonction des écosystèmes de l'île. Ainsi, le premier objectif de ce travail de thèse étaient de déterminer les mécanismes et les dynamiques de transmission de la FVR inhérents aux différents écosystèmes de Madagascar. Le second objectif a été d'identifier les mécanismes d'émergence de la FVR à Madagascar et de déterminer s'il sera possible, et nécessaire, de prédire cette émergence à l'échelle des écosystèmes.Dans le cadre de ce travail de thèse deux enquêtes sérologiques nationales, l'une bovine (2008) et l'autre humaine (2011-13) ont, premièrement, été analysées par un modèle linéaire mixte généralisé afin d'identifier les facteurs environnementaux et comportementaux favorables à la circulation du virus chez les bovins et les humains. Deuxièmement, deux enquêtes sérologiques bovines, l'une réalisée en 2008 et l'autre en 2014, ont été analysées pour reconstruire la dynamique de transmission de la FVR dans les différents écosystèmes de l'île. Cette reconstruction a été réalisée à partir de données de séroprévalence et d'âge inclues dans un modèle Bayésien hiérarchique pour estimer la force d'infection annuelle de 1992 à 2014. Enfin, afin de faire le lien biologique avec les résultats des travaux menés à une échelle nationale et de décrire les mécanismes de transmission à une échelle fine, des enquêtes longitudinales entomologiques et sérologiques ont été réalisées entre 2015 et 2016 dans un écosystème à risque. Et ceci, afin de décrire la transmission saisonnière du VFVR chez les ruminants associée à la dynamique de transmission des vecteurs potentiels.Nos résultats ont montré que la région du nord-ouest de l'île est une région à risque de transmission. D'une part, elle est constituée d'environnements associant une forte densité de bovins à des zones humides, inondables et irriguées, favorables aux espèces d'Anopheles et Culex. D'autre part, le VFVR semble avoir circulé de façon relativement intense lors de la période inter-épizootique de 1992 à 2007, puis sa transmission a soudainement augmenté en 2007-2008, ce qui est concomitant avec l'apparition des foyers de FVR en 2008. Pour finir, 6 ans après l'épidémie de FVR à Madagascar, le virus semble toujours circuler à bas bruit dans la région. Cette circulation étant probablement due à une transmission vectorielle favorisée par l'abondance de vecteurs potentiels dans la région.Les résultats de ces différents travaux nous ont permis de présenter des hypothèses de transmission dans les différents écosystèmes de l'île et ainsi de proposer des stratégies de surveillance, de prévention et de lutte contre la FVR adaptées au contexte de Madagascar. / Rift Valley fever (RVF) is a zoonotic vector-borne disease affecting ruminants and humans. Its complex eco-epidemiology involves several species of vectors, hosts and transmission routes. These particularities allowed the circulation of RVF virus (RVFV) in a variety of ecosystems involving different transmission and emergence mechanisms. Indeed, the RVFV has affected contrasted eco-regions in Africa, Arabian Peninsula and South-West Indian Ocean islands, including Madagascar.Madagascar is considered as a continent island due to its ecological diversity and its endemicity level of the flora and the fauna. In particular, the variation of the Malagasy ecosystems (semi-arid in the south, humid and cold in the highlands, humid and warm in the north-west and per-humid in the east) has an impact in their presence and /or the relative abundance of some mosquito species. Madagascar was heavily affected by RVF in 1990-91 and 2008-2009, with evidence of a large and heterogeneous spread of the disease.Thus considering the diversity of RVF eco-epidemiological cycles and the variety of Malagasy ecosystems, we hypothesized that, in Madagascar, the mechanisms of transmission would be different according to these ecosystems. Therefore, the first objective of this thesis was to understand the mechanisms and the dynamics of transmission of RVFV in the different ecosystems. The second objective was to determine the mechanisms of emergence of RVFV and if it would be necessary and possible to predict the emergence of RVFV outbreaks according to the ecosystems.Firstly, we analyzed both cattle and human serological data performed at the national level using generalized linear mixed models to identify the environmental and behavioral factors associated with RVF transmission in both cattle and human. Secondly, we reconstructed the dynamic of transmission of RVF in the different Malagasy ecosystems. Seroprevalence data of cattle of known age were fitted using Bayesian hierarchical models to estimate the annual force of infection from 1992 to 2014. Thirdly, to understand the biological process link to the mechanisms of transmission at the national scale, we investigated the fine scale mechanisms of transmission of RVFV in pilot area of an at-risk region. We, thus, performed both longitudinal entomological and serological surveys between 2015 and 2016, in order to describe the seasonal transmission of RVFV among ruminants and its association with the dynamics of RVFV potential vectors.Our results showed that the northwestern part of Madagascar is an at-risk region for RVFV transmission. On one hand, it is characterized by high cattle densities associated with humid, floodplain and irrigated areas suitable for RVFV potential vector like Anopheles and Culex species. On the other hand, RVFV had probably circulated intensively in the region during the 1992-2007 inter-epizootic period and its transmission increased suddenly in 2007-08, almost concomitantly with the first outbreaks recorded in 2008. Finally, RVFV was still circulated in the northwestern region at low level, 6 years after the last epidemic. This circulation is likely due to vectorial transmission favoring by the abundance of several potential vectors of RVFV in this pilot region.Finally, our better understanding of the mechanisms of transmission of RVFV throughout Madagascar allowed us to propose hypothesis of transmission in different ecosystems of Madagascar and consequently refine strategies for RVF surveillance and prevention.
48

Assessment of U.S. Agriculture Sector and Human Vulnerability to a Rift Valley Fever Outbreak

Hughes, Randi Catherine 2011 May 1900 (has links)
Foreign animal disease outbreaks can cause substantial economic losses. Policy makers need information on both the vulnerability of the food supply to disease epidemics and the impacts of alternative protection actions. This research focused on the assessment of the U.S. agricultural sector and human vulnerability to a Rift Valley Fever (RVF) outbreak and the value of a select set of alternative disease control strategies. RVF is a vector-borne, zoonotic disease that affects both livestock and humans; thus both animal and human consequences of an outbreak were examined. This research was conducted in two parts. Livestock impact assessment used an integrated epidemic/economic model to examine the extent of RVF spread in the animal population and its consequences plus the outcome of implementing two different control strategies: emergency vaccination and larvicide vector control. The number of infected, aborted, and dead animals is best controlled by coupling vaccination along with larvicide, but results in the second highest median national welfare loss. Therefore, careful decisions must be made as to what actions should be taken. Total national producer welfare is reduced with each scenario, and is more severe than the total national welfare loss (producer, consumer, and processor together). Consumer welfare is increased with each scenario due to a drop in prices of some commodities, and in some instances, an increase in supply as well. The majority of the national welfare loss can be attributed to the producers' and processors' loss in welfare. The highest damages are seen in the regions of the outbreak such as the South Central (SC). Other regions such as the Corn Belt, Lake States, and South East regions also see high damages due to price changes. The outbreak did not have substantial price effect on dairy products, but did have noticeable price changes for live cattle such as heifer calves, stocked yearling, and dairy calves. Prices for substitutes such as pork, chicken, and turkey experienced a price reduction, which can also be a factor resulting in consumer welfare gains. Human impact assessment utilized an inferential procedure for estimating the human consequences which comprise of a cost of illness calculation to assess the dollar cost of human illnesses and deaths, as well as a Disability Adjusted Life Year calculation to give an estimate of the burden of disease on public health as a whole. With potential costs above $2 billion for human illness, and with this number not accounting for loss or damages to other sectors of the economy, it can be highly probable that investing in a human vaccination campaign can be cost-effective and possibly cost-reducing. This cost along with the economic loss of the agriculture sector suggests substantial potential losses to the U.S. if this hypothetical situation were to become reality. Combining total loss estimates from the cost of illness and ASM models, potential damage of a RVF outbreak could range from 121 million to 2.3 billion US 2010$. The results of this study show the economic damages of an outbreak in the livestock population being much greater relative to the outbreak in the human population (roughly 16 times greater). It should be pointed out that both cost estimates are most likely under estimated. The animal outbreak is not incorporating all susceptible livestock (e.g. hogs and goats), and the human illness is not incorporating other damages to society (e.g. damages due to loss of tourism). By providing estimates on the potential economic outcomes, policy makers can better choose where, when, and how to invest their resources.
49

Persistance de la fièvre de la Vallée du Rift à Mayotte : surveillance, modélisation et perceptions / Persistence of Rift Valley fever in Mayotte : surveillance, modelling and perceptions

Cavalerie, Lisa 02 November 2017 (has links)
La fièvre de la Vallée du Rift (FVR) est une zoonose due à un virus transmissible par une large variété de vecteurs. Au cours des quinze dernières années, elle a rendu malades des dizaines de milliers de personnes, entrainé des centaines de décès humains et provoqué la mort de plus de 100 000 ruminants domestiques en Afrique et dans la péninsule arabique. Suite à la découverte de la présence du virus à Mayotte, les autorités sanitaires, le Cirad (Centre de coopération internationale en recherche agronomique pour le développement) et les éleveurs ont créé en 2009 un système de surveillance en santé animale, le SESAM. L‘objectif de cette thèse était de faire un état des lieux de la situation épidémiologique de la FVR chez les ruminants à Mayotte en 2012-2013, d’évaluer les perspectives de persistance de la maladie et d’étudier les perceptions et les priorités des éleveurs vis-à-vis de cette maladie. En 2012, le fonctionnement du dispositif de surveillance de la FVR a été révisé avec un renouvellement partiel du groupe d’éleveurs sentinelles et un renforcement de la surveillance événementielle basée sur la recherche systématique de la FVR en cas d’avortement ou de mortalité anormale. Une baisse continue de la séroprévalence de 2010 à 2013 a été observée. En 2012-2013, le taux d’incidence est resté stable avec environ deux séroconversions pour 100 animaux-ans. Ce taux est très inférieur au taux d’incidence de 18% observé en 2011. Le virus de la FVR n’a été détecté dans aucun des prélèvements réalisés dans le cadre de la déclaration officielle des avortements chez les ruminants (n=41). Des critères d’évaluation de la performance du dispositif de surveillance ont été proposés et ont mis en évidence une amélioration de la qualité des données entre 2010 et 2013. Un modèle dynamique de type SIR a permis d’estimer le niveau de transmission hôte-vecteur attendu qui expliquerait au mieux la séroprévalence observée de 2008 à 2013 à Mayotte. La probabilité de transmission hôte-vecteur estimée par ce modèle est cinq fois plus faible qu’attendue. Dans ces conditions, la probabilité de persistance de la FVR, en l’absence de nouvelle introduction d’animaux virémiques reste inférieure à 10%, cinq ans après l’arrivée du virus. Enfin, la priorisation des problèmes sanitaires à Mayotte par une démarche d’épidémiologie participative et des réunions d’éleveurs a mis en évidence que les cinq problèmes spontanément rapportés comme les plus importants chez les bovins sont dans l’ordre le charbon symptomatique, les tiques, le syndrome « bavite-fièvre-grippe», le syndrome « dermatophilose-boutons » et la diarrhée. La FVR est absente de ce classement mais les avortements arrivent en 9ème position et à la première selon le critère de « risque ». La surveillance, et les approches interdisciplinaires de modélisation et de sciences humaines doivent être poursuivies pour évaluer plus précisément le risque de réémergence de la FVR à Mayotte et anticiper les réponses à y apporter. La surveillance doit aussi s’adapter aux attentes des éleveurs et développer l’approche syndromique ainsi que s’intégrer pleinement aux dispositifs régionaux et nationaux. / Rift Valley fever (RVF) is a vector-borne zoonosis, with a wide variety of potential competent vectors. During the last fifteen years, RVF caused tens of thousands of human cases, hundreds of human deaths and more than 100,000 domestic ruminant deaths in Africa and in the Arabic peninsula. After the first detection of RVF in Mayotte, an animal health surveillance network has been created in 2009, namely the SESAM. The aim of this PhD was to assess the epidemiological situation of Mayotte toward RVF in 2012-2013, to assess the persistence probability of RVF in the territory and to document farmers’ perceptions and health priorities. In 2012, RVF surveillance has been revised in order to partially renew the pool of the sentinel herds. The passive surveillance with systematic RVF detection assay on abortion and abnormal mortality was enforced. A continuous decrease in the seroprevalence was observed based on 2010-2013 data. During 2012-2013, a steady incidence rate of about 2 seroconversions per 100 animal-year was observed. This rate is much lower than the previous assessment of 18% during 2011. RVF virus was not detected in any of the 41 declared abortion cases. Surveillance performance criteria were discussed and assessed showing mainly an increase in data quality between 2010 and 2013. A SIR dynamic model was built based on vector knowledge and observed seroprevalence in Mayotte from 2008 to 2013. Estimated host-vector transmission rate was fivefold lower than expected according to current literature. Persistence probability, without reintroduction of viremic animals, was predicted to be 10% five years after virus introduction. Finally, health problem prioritization in Mayotte was studied through focus groups, gathering 164 farmers. The five main issues stated were: blackleg, ticks, a respiratory « fever/flu-like» syndrome, a dermatologic syndrome and diarrhoea. RVF was absent from the priority problems list in which abortions were ranked 9th. However abortions came first when « risk » criteria was taken into account, raising issues of cultural risk perceptions. Further surveillance and research using transdisciplinary approaches that mix mathematical modelling and the humanities should be continued with the view to assess more precisely reemergence probability in Mayotte and anticipate mitigating measures. Surveillance and research should also align with farmers’ expectations. The development of syndromic surveillance (abortion, death, etc.) requires strengthening surveillance network and identification data quality. Mayotte surveillance components should also be fully integrated within the regional and national schemes.
50

Structural studies of bunyavirus interferon antagonist proteins

Barski, Michał S. January 2016 (has links)
Bunyaviridae is one of the biggest known viral families, and includes many viruses of clinical and economic importance. The major virulence factor of most bunyaviruses is the non-structural protein (NSs). NSs is expressed early in infection and inhibits the innate immune response of the host by blocking several steps in the interferon induction and signalling pathways. Hence, NSs significantly contributes to the establishment of a successful viral infection and replication, persistent infection and the zoonotic capacity of bunyaviruses. Although functions and structures of many viral interferon antagonists are known, no structure of a bunyavirus NSs protein has been solved to date. This strongly limits our understanding of the role and the mechanism of interferon antagonism in this large virus family. In this work the first structure for a bunyavirus interferon antagonist, the core domain crystal structure of NSs from the Rift Valley fever virus (RVFV) is presented. RVFV is one of the most clinically significant members of the Bunyaviridae family, causing recurrent epidemics in Africa and Arabia, often featuring high-mortality haemorrhagic fevers. The structure shows a novel all-helical fold. The unique molecular packing of NSs in the crystal creates stable fibrillar networks, which could correspond to the characteristic fibrillation of NSs observed in vivo in the nuclei of RVFV infected cells. This first NSs structure might be a useful template for future structure-aided design of drugs that target the RVFV interferon antagonism. Attempts at characterising other bunyavirus NSs proteins of other genera were made, but were hampered by problems with obtaining sufficient amounts of soluble and folded protein. The approaches that proved unsuccessful for the solubilisation of these NSs proteins, however, should inform future experiments aimed at obtaining recombinant NSs for structural studies.

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