Comprendre les rétroactions entre les maladies infectieuses, la structure des écosystèmes et le développement économique est nécessaire pour alléger le fardeau des maladies tropicales négligées. Ce groupe d'infections parasitaires, virales, et bactériennes est étroitement associé à des conditions géographiques, environnementales, sanitaires et économiques particulières aux régions tropicales. A travers l'étude de l'ulcère de Buruli, une maladie émergente et négligée associé à une morbidité et handicap très importants dans des régions tropicales, ce travail de thèse s'intéresse aux interactions complexes entre ces différents composants des systèmes épidémiologiques. Combinant un travail de terrain important pour la collecte des données environnementales avec une approche de recherche multidisciplinaire, cette thèse vise à améliorer notre compréhension des différents aspects de l'écologie et de l'épidémiologie de cette maladie infectieuse. Notamment, la dynamique de son agent pathogène, M. ulcerans, est caractérisée pour un large éventail d'écosystèmes et communautés aquatiques au Cameroun, permettant d'identifier les facteurs environnementaux permettant sa propagation. En outre, nous évaluons la transmission de l'agent pathogène de l'environnement à l'homme et l'impact de la maladie sur le développement économique des populations endémiques. Ainsi, ce travail montre comment les dynamiques écologiques, épidémiologiques, environnementales et économiques interagissent de concert, mettant en évidence de façon criante le besoin d'une telle approche interdisciplinaire dans l'étude des maladies tropicales négligées. / Understanding the feedbacks between infectious diseases, ecosystem structure and economic development is necessary to alleviate the burden of Neglected Tropical Diseases. This group of parasitic, viral, and bacterial infections is closely associated with particular geographical and environmental conditions mainly present in the tropics, thriving under conditions of poverty, inefficient sanitation and malnutrition. This PhD thesis works through the case study of Buruli ulcer, an emerging and neglected infectious disease associated with a great morbidity and disability burden in tropical regions. Relying on an extensive environmental field survey and a multidisciplinary research approach, this PhD attempts to gain a better understanding of different aspects of the ecology and epidemiology of Buruli ulcer. Notably, the dynamics of its pathogen, M. ulcerans are characterized for a wide range of freshwater ecosystems and aquatic communities in Cameroon, and the environmental drivers of M. ulcerans presence are investigated. Furthermore, we assess the transmission of the pathogen from the environment to humans and the impact of the disease on the economic development of endemic populations. Thus, this work shows how the interplay between ecological, epidemiological and economic dynamics interact together and calls for an urgent need to apply such inter-disciplinary approach to decrease the burden of neglected tropical diseases.

Malgré leur importance reconnue pour la santé publique et la conservation, les études sur l’écologie et l’évolution des maladies infectieuses dans les populations sauvages souffrent de contraintes sur la disponibilité de données permettant l’identification des processus impliqués dans les systèmes considérés. Les méthodes sérologiques (i.e., détection d’anticorps dans des échantillons biologiques) permettent de retracer l’exposition à des agents infectieux spécifiques mais leur interprétation est complexe. Par exemple, la prévalence d’individus séropositifs dans une population résulte d’une combinaison de dynamiques épidémiologiques (ex. : l’incidence de la maladie) et démographiques (ex. le taux de renouvellement de la population). Dans ce contexte, l’objectif de cette thèse est de montrer comment les processus sous-jacents à la circulation d’agents infectieux en populations sauvages peuvent être inférés à partir de données sérologiques. Tout d’abord, j’illustre comment les études transversales focalisée sur une espèce sentinelle à l’interface entre populations sauvages et humaines peuvent permettre d’efficacement décrire informer sur les patterns d’exposition à une hiérarchie d’échelles spatiales. Ensuite, je compare les avantages et inconvénients de ce type d’approches transversales à ceux d’approches longitudinales basées sur les suivis d’individus marqués et je propose une solution pour intégrer ensemble ces deux types de données pour quantifier les dynamiques éco-épidémiologiques. Finalement, en utilisant une population menacée d’oiseaux longévifs régulièrement touchée par des épizooties de choléra aviaire comme cas d’étude, j’illustre les bénéfices de combiner la sérologie avec d’autres approches. Ce travail souligne la valeur des études à long-terme de l’exposition d’hôtes à des agents infectieux en milieu naturel, où les processus écologiques et évolutifs sont clés pour comprendre les dynamiques éco-épidémiologiques et peuvent avoir d’importantes implications pour la conservation de la biodiversité. / Despite their increasingly recognized interest for public health and biodiversity conservation, investigations on the ecology and evolution of infectious diseases in wildlife have been hampered by the difficulty of collecting data allowing efficient inference of underlying processes. Serology (i.e., detection of antibodies in biological samples) is a useful tool to detect past exposure to specific infectious agents. Still, interpreting serological data is not straightforward. For instance, the prevalence of seropositive individuals in a population is driven by a combination of epidemiological (e.g., disease incidence) and demographic (e.g., population turnover) dynamics. In this context, the objective of this thesis is to show how processes underlying infectious agent circulation in wild populations can be inferred from serological data. First, I illustrate how cross-sectional studies focusing on a sentinel species at the wildlife-human interface can efficiently inform on patterns at a hierarchy of scales. Then, I compare the pros and cons of such cross-sectional approaches to longitudinal sampling designs involving marked individuals when attempting to quantify the dynamics of infectious agents and I propose a way to integrate those two approaches in future studies. Finally, using avian cholera epizootics in a threatened long-lived seabird on an isolated island as a case study, I illustrate the benefits of combining serology with other approaches. This work notably highlights the value of detailed long-term studies of host exposure to infectious agents in the wild, where ecological and evolutionary processes are likely critical drivers of disease dynamics and can have important implications for biodiversity conservation.

No description available.

Chapter one introduces the concept of disease emergence and factors associated with emergence. The role of wildlife as reservoirs of emerging diseases and specifically the history of bats as reservoirs of zoonotic diseases is previewed. Finally, the aims and structure of the thesis are outlined. In Chapter two, the literature relating to the emergence of Hendra virus, Nipah virus, and Australian bat lyssavirus, the biology of flying foxes, methodologies for investigating wildlife reservoirs of disease, and the modelling of disease in wildlife populations is reviewed. Chapter three describes the search for the origin of Hendra virus and investigations of the ecology of the virus. In a preliminary survey of wildlife, feral and pest species, 6/21 Pteropus alecto and 5/6 P. conspicillatus had neutralizing antibodies to Hendra virus. A subsequent survey found 548/1172 convenience-sampled flying foxes were seropositive. Analysis using logistic regression identified species, age, sample method, sample location and sample year, and the interaction terms age*species and age* sample method as significantly associated with HeV serostatus. Analysis of a subset of the data also identified a significant or near-significant association between time of year of sampling and HeV serostatus. In a retrospective survey, 16/68 flying fox sera collected between 1982 and 1984 were seropositive. Targeted surveillance of non-flying fox wildlife species found no evidence of Hendra virus. The findings indicate that flying foxes are a likely reservoir host of Hendra virus, and that the relationship between host and virus is mature. The transmission and maintenance of Hendra virus in a captive flying fox population is investigated in Chapter four. In study 1, neutralizing antibodies to HeV were found in 9/55 P. poliocephalus and 4/13 P. alecto. Titres ranged from 1:5 to 1:160, with a median of 1:10. In study 2, blood and throat and urogenital swabs from 17 flying foxes from study 1 were collected weekly for 14 weeks. Virus was isolated from the blood of a single aged non-pregnant female on one occasion. In study 3, a convenience sample of 19 seropositive and 35 seronegative flying foxes was serologically monitored monthly for all or part of a two-year period. Three individuals (all pups born during the study) seroconverted, and three individuals that were seropositive on entry became seronegative. Two of the latter were pups born during the study period. Dam serostatus and pup serostatus at second bleed were strongly associated when data from both years were combined (p<0.001; RR=9, 95%CI 1.42 to 57.12). The serial titres of 19 flying foxes monitored for 12 months or longer showed a rising and falling pattern (10), a static pattern (1) or a falling pattern (8). The findings suggest latency and vertical transmission are features of HeV infection in flying foxes. Chapter five describes Australian bat lyssavirus surveillance in flying foxes, insectivorous bats and archived museum bat specimens. In a survey of 1477 flying foxes, 69/1477 were antigen-positive (all opportunistic specimens) and 12/280 were antibody-positive. Species (p<0.001), age (p=0.02), sample method (p<0.001) and sample location (p<0.001) were significantly associated with fluorescent antibody status. There was also a significant association between rapid focus fluorescent inhibition test status and species (p=0.01), sample method (p=0.002) and sample location (p=0.002). There was a near-significant association (p=0.067) between time of year of sampling and fluorescent antibody status. When the analysis was repeated on P. scapulatus alone, the association stronger (p=0.054). A total of 1234 insectivorous bats were surveyed, with 5/1162 antigen–positive (all opportunistic specimens) and 10/390 antibody-positive. A total of 137 archived bats from 10 species were tested for evidence of Australian bat lyssavirus infection by immunohistochemistry (66) or rapid focus fluorescent inhibition test (71). None was positive by either test but 2 (both S. flaviventris) showed round basophilic structures consistent with Negri bodies on histological examination. The findings indicate that Australian bat lyssavirus infection is endemic in Australian bats, that submitted sick and injured bats (opportunistic specimens) pose an increased public health risk, and that Australian bat lyssavirus infection may have been present in Australian bats 15 years prior to its first description. In Chapter six, deterministic state-transition models are developed to examine the dynamics of HeV infection in a hypothetical flying fox population. Model 1 outputs demonstrated that the rate of transmission and the rate of recovery are the key parameters determining the rate of spread of infection, and that population size is positively associated with outbreak size and duration. The Model 2 outputs indicated that that long-term maintenance of infection is inconsistent with lifelong immunity following infection and recovery. Chapter seven discusses alternative hypotheses on the emergence and maintenance of Hendra virus and Australian bat lyssavirus in Australia. The preferred hypothesis is that both Hendra virus and Australian bat lyssavirus are primarily maintained in P. scapulatus populations, and that change in the population dynamics of this species due to ecological changes has precipitated emergence. Future research recommendations include further observational, experimental and/or modeling studies to establish or clarify the route of HeV excretion and the mode of transmission in flying foxes, the roles of vertical transmission and latency in the transmission and maintenance of Hendra virus in flying foxes, and the dynamics of Hendra virus infection in flying foxes.

Chapter one introduces the concept of disease emergence and factors associated with emergence. The role of wildlife as reservoirs of emerging diseases and specifically the history of bats as reservoirs of zoonotic diseases is previewed. Finally, the aims and structure of the thesis are outlined. In Chapter two, the literature relating to the emergence of Hendra virus, Nipah virus, and Australian bat lyssavirus, the biology of flying foxes, methodologies for investigating wildlife reservoirs of disease, and the modelling of disease in wildlife populations is reviewed. Chapter three describes the search for the origin of Hendra virus and investigations of the ecology of the virus. In a preliminary survey of wildlife, feral and pest species, 6/21 Pteropus alecto and 5/6 P. conspicillatus had neutralizing antibodies to Hendra virus. A subsequent survey found 548/1172 convenience-sampled flying foxes were seropositive. Analysis using logistic regression identified species, age, sample method, sample location and sample year, and the interaction terms age*species and age* sample method as significantly associated with HeV serostatus. Analysis of a subset of the data also identified a significant or near-significant association between time of year of sampling and HeV serostatus. In a retrospective survey, 16/68 flying fox sera collected between 1982 and 1984 were seropositive. Targeted surveillance of non-flying fox wildlife species found no evidence of Hendra virus. The findings indicate that flying foxes are a likely reservoir host of Hendra virus, and that the relationship between host and virus is mature. The transmission and maintenance of Hendra virus in a captive flying fox population is investigated in Chapter four. In study 1, neutralizing antibodies to HeV were found in 9/55 P. poliocephalus and 4/13 P. alecto. Titres ranged from 1:5 to 1:160, with a median of 1:10. In study 2, blood and throat and urogenital swabs from 17 flying foxes from study 1 were collected weekly for 14 weeks. Virus was isolated from the blood of a single aged non-pregnant female on one occasion. In study 3, a convenience sample of 19 seropositive and 35 seronegative flying foxes was serologically monitored monthly for all or part of a two-year period. Three individuals (all pups born during the study) seroconverted, and three individuals that were seropositive on entry became seronegative. Two of the latter were pups born during the study period. Dam serostatus and pup serostatus at second bleed were strongly associated when data from both years were combined (p<0.001; RR=9, 95%CI 1.42 to 57.12). The serial titres of 19 flying foxes monitored for 12 months or longer showed a rising and falling pattern (10), a static pattern (1) or a falling pattern (8). The findings suggest latency and vertical transmission are features of HeV infection in flying foxes. Chapter five describes Australian bat lyssavirus surveillance in flying foxes, insectivorous bats and archived museum bat specimens. In a survey of 1477 flying foxes, 69/1477 were antigen-positive (all opportunistic specimens) and 12/280 were antibody-positive. Species (p<0.001), age (p=0.02), sample method (p<0.001) and sample location (p<0.001) were significantly associated with fluorescent antibody status. There was also a significant association between rapid focus fluorescent inhibition test status and species (p=0.01), sample method (p=0.002) and sample location (p=0.002). There was a near-significant association (p=0.067) between time of year of sampling and fluorescent antibody status. When the analysis was repeated on P. scapulatus alone, the association stronger (p=0.054). A total of 1234 insectivorous bats were surveyed, with 5/1162 antigen–positive (all opportunistic specimens) and 10/390 antibody-positive. A total of 137 archived bats from 10 species were tested for evidence of Australian bat lyssavirus infection by immunohistochemistry (66) or rapid focus fluorescent inhibition test (71). None was positive by either test but 2 (both S. flaviventris) showed round basophilic structures consistent with Negri bodies on histological examination. The findings indicate that Australian bat lyssavirus infection is endemic in Australian bats, that submitted sick and injured bats (opportunistic specimens) pose an increased public health risk, and that Australian bat lyssavirus infection may have been present in Australian bats 15 years prior to its first description. In Chapter six, deterministic state-transition models are developed to examine the dynamics of HeV infection in a hypothetical flying fox population. Model 1 outputs demonstrated that the rate of transmission and the rate of recovery are the key parameters determining the rate of spread of infection, and that population size is positively associated with outbreak size and duration. The Model 2 outputs indicated that that long-term maintenance of infection is inconsistent with lifelong immunity following infection and recovery. Chapter seven discusses alternative hypotheses on the emergence and maintenance of Hendra virus and Australian bat lyssavirus in Australia. The preferred hypothesis is that both Hendra virus and Australian bat lyssavirus are primarily maintained in P. scapulatus populations, and that change in the population dynamics of this species due to ecological changes has precipitated emergence. Future research recommendations include further observational, experimental and/or modeling studies to establish or clarify the route of HeV excretion and the mode of transmission in flying foxes, the roles of vertical transmission and latency in the transmission and maintenance of Hendra virus in flying foxes, and the dynamics of Hendra virus infection in flying foxes.

Spatially-explicit information is essential for planning and implementing interventions against vector-borne diseases. This is also true for African trypanosomoses, a group of diseases of both humans and animals caused by protozoa of the Genus Trypanosoma, and transmitted by tsetse flies (Genus Glossina).<p>In this thesis the knowledge gaps and the requirements for an evidence-based decision making in the field of tsetse and trypanosomoses are identified, with a focus on georeferenced data and Geographic Information Systems (GIS). Datasets, tools and analyses are presented that aim to fill some of the identified knowledge gaps.<p>For the human form of the disease, also known as sleeping sickness, case detection and treatment are the mainstay of control, so that accurate knowledge of the geographic distribution of infections is paramount. In this study, an Atlas was developed that provides village-level information on the reported occurrence of sleeping sickness. The geodatabase underpinning the Atlas also includes the results of active screening activities, even when no cases were detected. The Atlas enables epidemiological maps to be generated at a range of scales, from local to global, thus providing evidence for strategic and technical decision making.<p>In the field of animal trypanosomosis control, also known as nagana, much emphasis has recently been placed on the vector. Accurate delineation of tsetse habitat appears as an essential component of ongoing and upcoming interventions against tsetse. The present study focused on land cover datasets and tsetse habitat. The suitability for tsetse of standardized land cover classes was explored at continental, regional and national level, using a combination of inductive and deductive approaches. The land cover classes most suitable for tsetse were identified and described, and tailored datasets were derived.<p>The suite of datasets, methodologies and tools presented in this thesis provides evidence for informed planning and implementation of interventions against African trypanosomoses at a range of spatial scales. / Doctorat en Sciences agronomiques et ingénierie biologique / info:eu-repo/semantics/nonPublished

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No description available.

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Abstract :Bluetongue (BT) is a vector-borne infectious disease primarily transmitted to even- toed ungulates by the bite of several Culicoides species. The global distribution of BT can be attributed to the ubiquity of its vectors and its rapid spread, likely to the enhancement of human activities (intensification of animal production, trans- port, changing habitat). During the last decades, BT established in Southern Europe and more recently emerged in Northern Europe, causing the death of millions of domestic ruminants. On the same time, a Belgian research project has been set up to develop remote-sensing tools to study the EPidemiology and Space-TIme dynamicS of infectious diseases (EPISTIS). In that general framework, this thesis aimed to study the space-time distribution of the main Culicoides vectors occurring in Italy and Belgium, at two different scales. Firstly, we aimed to clarify the role of several eco-climatic factors on the regional-scale distribution of C. imicola in time, based on weekly samplings achieved throughout Italy from 2001 to 2006 and to develop an easy-to-use and reproducible tool, which could be widely validated on the basis of former vector sampling and freely accessible remote-sensing data. Secondly, we aimed to investigate how Culicoides species were distributed in the fine-scale habitat encountered throughout the agro-ecological landscapes of Belgium, while recent studies have suggested that the landscapes configuration could explain the spatial distribution of BT. In the first part, we showed that an autoregressive model where the observed monthly growth rate is predicted by monthly temperature, allowed predicting >70% of the seasonal variability in C. imicola trap catches. The model predicted the seasonality, the altitudinal gradient, and the low populations’ activity taking place during the winter. Incorporating eco-climatic indices such as the Normalized Difference Vegetation Index into the model did not enhance its predictive power. In the second part, we quantified how Culicoides populations are spatially structured in the neighbourhood of farms, and demonstrated the unexpectedly high level of population found in forest. We also showed how four classes of land use could influence the relative abundances of Culicoides species in the agro-ecological landscapes of Belgium. Although in summer, BT vectors were abundant in each of the four classes investigated, their relative abundances varied strongly as a function of sex, species and environmental conditions, and we quantified these variations. Finally, we also presented a new method to quantify the interference between Onderstepoort light traps, and used it to measure their range of attraction for several of the most common BT vectors species in Northern Europe. The model developed on C. imicola in Italy provided enthusiastic perspectives regarding the regional-scale analyses of its distribution in time, although further improvements are nevertheless required in order to assess the broad scale ecology of BT vectors throughout Europe. Mapping the abundances of C. imicola in Sardinia high- lighted an important lack of reliability attributable to the many land use classes that are currently not sampled in the vector surveillance achieved across Europe. Together with the novelties presented in the second part and the recent findings establishing that BT could circulate among wild hosts in both epidemiological systems (i.e. in Southern and Northern Europe), we call for increasing epidemiological and entomo- logical studies at the interface between farms and the surrounding natural habitats. Last, depicting in time the landscape-scale findings for Northern Europe highlighted how dramatic could be the role played by intensive farming practices to maintain BT within the agro-ecological landscapes studied and to facilitate its circulation between them. Quantifying the amplitude of the risk of disease transmission linked to these practices would require a further complex modeling approach accounting simultaneously for the diel activity of hosts, mainly resulting from the farming activities, the diel activities of different vector species and the landscapes configuration found in contrasted agro-ecological systems.<p>Résumé :La fièvre catarrhale ovine (FCO), encore appelée maladie de la langue bleue, est une maladie infectieuse des ruminants transmise par la piqûre d’un vecteur de type moucheron appartenant au genre Culicoides (Diptera :Ceratopogonidae). L’ubiquité de ses vecteurs peut expliquer son succès d’installation à l’échelle globale. Par ailleurs, sa rapide expansion a été grandement facilitée par l’importante activité anthropique (élevage, transport, modification de l’habitat) et peut-être même par les changements climatiques globaux. La FCO a été récemment qualifiée de maladie infectieuse émergente en Europe du fait de (i) son récent établissement dans la région, bien au delà de son aire de répartition traditionnelle, (ii) de sa forte capacité de dispersion affectant chaque jour un nombre plus important d’hôtes et enfin (iii) de sa forte virulence. Après avoir détaillé les caractéristiques majeures des deux principaux foyers de FCO rencontrés en Europe depuis 1998, la présente thèse s’est plus particulièrement intéressée à l’étude de la distribution spatio-temporelle de ses principaux vecteurs dans le sud (partie 1) puis dans le nord (partie 2) de l’Europe, à différentes échelles. Dans la première partie, un modèle discret, spatialement et temporellement explicite, a été développé afin de mesurer l’influence de différents facteurs éco-climatiques sur la distribution de Culicoides imicola, principal vecteur de la FCO dans le Bassin Méditerranéen. Les profils mensuels de distribution rencontrés en Sardaigne durant 6 années consécutives ont ainsi pu être reconstitués, principalement sur base de la température. Une cartographie de l’abondance de C. imicola sur le territoire a permis de mettre à jour le manque d’information sur sa distribution en dehors des exploitations agricoles. Dans la deuxième partie du travail, nous nous sommes penchés sur la distribution spatiale des Culicoides tels qu’on peut les rencontrer au sein de différents paysages agro-écologiques de Belgique. Nous avons ainsi pu décrire la structure adoptée par les populations de Culicoides au voisinage des fermes ainsi que quantifier l’importante population présente dans les forêts avoisinantes. Nous avons par ailleurs montré l’influence de différentes catégories d’utilisation du sol sur l’abondance et la composition en espèces. Enfin, nous avons présenté une méthode permettant de quantifier l’interférence entre des pièges lumineux utilisés dans un même paysage pour échantillonner les populations, et l’avons utilisé afin de mesurer leur rayon d’attractivité sur les espèces vectrices les plus communément rencontrées dans le nord de l’Europe. En guise de conclusion générale et conjointement aux récentes découvertes de cas de FCO au sein de la faune sauvage européenne, nous appelons à réaliser un plus grand nombre d’études éco-épidémiologiques à l’interface entre exploitations agricoles et zones (semi-) naturelles avoisinantes. En outres, les résultats présentés dans la seconde partie ont été mis en relation avec le mode de fonctionnement journalier de nos exploitations agricoles. Nous avons ainsi pu déduire le rôle dramatique joué par les pratiques agricoles intensives dans le maintien du virus de la FCO au sein de nos paysages agro-écologiques, ainsi que dans sa circulation d’un paysage à l’autre. Un cadre de modélisation complexe permettant une analyse simultanée de l’activité nycthémérale des hôtes de la FCO et de ses vecteurs Culicoides en fonction de la configuration des paysages agro-écologiques est néanmoins requis afin de quantifier l’amplitude du risque de transmission de la FCO lié aux pratiques agricoles intensives. / Doctorat en Sciences agronomiques et ingénierie biologique / info:eu-repo/semantics/nonPublished