Emerging infectious diseases of wildlife have threatened host populations of diverse taxa in recent history, which is largely attributable to anthropogenic global change. In three data chapters, this dissertation examines the drivers of individual- to population-level variation in how host populations respond to novel and emerging pathogens. Each chapter explores these processes in bat populations of North America, predominantly the Northeast and Midwest regions of the United States, impacted by the emerging fungal pathogen that causes white-nose syndrome, Pseudogymnoascus destructans. In Chapter 2, I disentangle the effects of adaptive host traits and environmental influences in driving host population stabilization of the little brown bat (Myotis lucifugus), finding that host-pathogen coexistence in this system is the product of their complex interaction. In Chapter 3, I characterize the range-wide variation in white-nose syndrome impacts on a federally endangered and poorly studied species, the Indiana bat (Myotis sodalis), as well as environmental and demographic determinants of its declines over epidemic time. In Chapter 4, I explore the role of individual variation in roosting microclimate selection of little brown bats in driving their infection severity, yielding important insights into the pathophysiology and environmental dependence of white-nose syndrome. Ultimately, this dissertation characterizes complex drivers of variation in host responses to emerging and invading pathogens, yielding insights essential to the successful mitigation of their impacts. / Doctor of Philosophy / In the same way that Covid-19 swept through our global human population in the year 2020, novel infectious diseases have threatened wildlife populations, sometimes to the point of extinction. Often, however, the processes driving the impacts of novel infectious diseases in wildlife are unknown, despite being important information to protect susceptible populations. In this dissertation, I explore how North American bat populations have been impacted by a recently emerged disease, white-nose syndrome, and what processes cause variation in how individual bats and bat colonies have responded to the disease. In Chapter 2, I explore how the little brown bat (Myotis lucifugus) has evolved to co-exist with its new pathogen and how this coexistence is affected by environmental conditions like temperature and humidity. In Chapter 3, I characterize variation in how populations of the Indiana bat (Myotis sodalis) have responded to white-nose syndrome and how environmental and demographic conditions have affected declines since the disease first emerged. In Chapter 4, I explore how the temperatures used by little brown bats during hibernation affect the severity of their infection, giving us important information on how bats survive with white-nose syndrome and the role of temperature. Altogether, the research in this dissertation describes complex interactions between hosts, pathogens, and their environment in driving the patterns we observe after the emergence of novel infectious diseases.

Public health professionals strive to understand how viruses are distributed in the environment, the factors that facilitate viral transmission, and the diversity of viral agents capable of infecting humans to characterize disease burdens and design effective disease intervention strategies. The public health discipline of conservation medicine supports this endeavor by encouraging researchers to identify previously unknown etiologic agents in wildlife and analyze the ecologic of basis of disease. Within this framework, this research reports the first examination of the prevalence in Southeast Asia of the orthoreovirus Nelson Bay virus in humans and in the Pteropus bat reservoir of the virus. Contact with Pteropus species bats places humans at risk for Nipah virus transmission, an important emerging infectious disease. This research furthermore explores the environmental determinants of Nelson Bay and Nipah viral prevalence in Pteropus bats and reports the characterization of two novel orthoreoviruses isolated from bat tissues collected in Bangladesh.

The thesis traces the successive urban responses made by the Hong Kong government from 1997 to 2014, in an attempt to achieve “imagined immunity” for the city. The urban responses being analysed are efforts to regulate the ways in which “live poultry” (especially live chickens) is metabolized and circulating in the city. The efforts are made to re-order the human-birds-microbes relationships in Hong Kong - a process conceptualized as “re-urbanization of nature.” The consequence of these re-urbanization of nature processes, led to changes in the specific practice of consuming “live poultry” in the city. Four periods of re-urbanization of nature are identified in the analysis, and it is argued that in each wave of restructuring there were markedly different frames constructed to generate distinctive meanings of the “contagion condition,” imagined urban immunity, and practices of re-urbanization of nature. Their meanings and resultant practices were products of negotiations, within an entangled web of human and nonhuman features in particular periods. The context of these interventions and the biopolitical contestations are analyzed in the thesis. It is then argued that such contingencies and context-sensitive processes, call for further studies of post-epidemic urban changes. The thesis also explores the possibility of developing a theoretical framework of “urban biopolitical immunology” to accomplish the inquiry. By so doing, it seeks to contribute to studies of the politics of contemporary epidemics, and to research on the production of urban nature.

Viruses in the Flavivirus genus (e.g., Zika, yellow fever, dengue, West Nile, and Japanese encephalitis viruses) are arthropod-borne, globally distributed, and can cause a range of neurological or hemorrhagic diseases. The ongoing epidemics of flaviviral disease consistently demonstrate the need for new vaccines capable of outbreak control. However, safe, effective, and easy-to-produce vaccines remain relatively elusive due to limitations of conventional vaccine development that make it difficult to balance safety and efficacy. Insect-specific flaviviruses (ISFVs) are emerging as a novel method to overcome this challenge. Herein, we develop a new flavivirus vaccine platform based on the novel insect-specific flavivirus called Aripo virus, which we used to create a preclinical Zika virus (ZIKV) vaccine named Aripo/Zika virus (ARPV/ZIKV). ARPV/ZIKV is a live recombinant virus consisting of the ZIKV pre-membrane and envelope protein genes expressed on an Aripo virus backbone. In this work, we quantify the safety and efficacy of ARPV/ZIKV in multiple murine models, and begin to elucidate the mechanisms of humoral and cell-mediated immune induction for this new platform. Overall, the vaccine showed no evidence of pathogenicity in immunocompromised or suckling mice, and demonstrated a complete inability to replicate in various vertebrate cell lines. Despite this lack of replication, a single dose of live, unadjuvanted ARPV/ZIKV completely prevented ZIKV disease in mice and prevented in utero ZIKV transmission in gravid mice. Direct protection post-ZIKV challenge appears to be primarily mediated by neutralizing antibodies based on passive transfer, adoptive transfer, and T-cell depletion studies. However, vaccination studies in Rag1 KO, Tcra KO, and muMt- mice demonstrate the critical role of T-cell responses in developing immunity post-vaccination. In summary, ARPV/ZIKV is a promising vaccine candidate that induces robust adaptive immune responses, and this success is a positive indication of ARPV's potential as a new resource for flavivirus vaccine development. This body of work contributes to the rapidly expanding field of insect-specific virus-based vaccines and generates new insights into their optimization. Ultimately, this work may help protect the health of millions of people worldwide that are currently at risk of flavivirus infection. / MPH / Arthropod-borne viruses (especially flaviviruses such as Zika virus (ZIKV), yellow fever virus, West Nile virus) represent a major global health threat and a significant burden on human life. Vaccination is a critical tool for controlling the often unpredictable outbreaks of flavivirus diseases. However, licensed flavivirus vaccines remain relatively elusive. This is, in part, because the same characteristics of traditional live-attenuated vaccines that make them highly effective can also reduce their safety. Insect-specific flaviviruses (ISFVs) are emerging as a novel method to overcome this challenge. ISFVs only replicate in insects and thus are safe in humans. They do not cause disease in vertebrates, eliminating the need for the chemical or physical inactivation methods required by traditional whole inactivated vaccines and which can result in reduced efficacy. Herein, we develop a new flavivirus vaccine platform based on a novel ISFV called Aripo virus (ARPV). As proof of concept, we used ARPV to create a preclinical ZIKV vaccine named Aripo/Zika virus (ARPV/ZIKV). ARPV/ZIKV expresses immune system-stimulating ZIKV structural proteins on its virus particle. However, it remains highly safe because the genetic material from ARPV makes it incompatible for replication in human cells. Here, we demonstrate the safety and protective ability of ARPV/ZIKV, and begin to elucidate its mechanisms of protection. Overall, ARPV/ZIKV shows promise as a ZIKV vaccine candidate, which supports the potential of ARPV as a platform for new flavivirus vaccines and the potential to protect the health of the millions of people currently at risk of flavivirus infection.

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L'ulcère de Buruli est une maladie émergente tropicale négligée. Il provoque une défiguration et une incapacité permanente pour les victimes. L'agent causal est Mycobacterium ulcerans. Cependant, le réservoir environnemental et le mode de transmission de cette bactérie ne sont pas connus. Les tentatives visant à gérer la maladie ont été freinées par le manque de connaissances concernant le mode de transmission ainsi que le réservoir environnemental de M. ulcerans. Certains écosystèmes et habitats ont été associés au risque de contracter cette mycobactérie, notamment les milieux aquatiques d'eau douce stagnants et perturbés par les activités humaines des régions tropicales. S'il n'existe pas de vecteur bien identifié, des insectes aquatiques Hémiptères sont fortement suspectés d'intervenir dans la vectorisation de cet agent infectieux à l'humain. Une compréhension complète de la distribution et du mode de transmission de la bactérie aiderait ainsi à la gestion de la maladie. Dans cette thèse, nous utilisons les outils issus de la modélisation de la niche écologique pour décrire la distribution de M. ulcerans. Suite à la construction d'un modèle au Cameroun, en Afrique Centrale, et testé avec une seconde base de données en Guyane Française (Amérique du Sud), nous trouvons que l'agent pathogène montre des variations saisonnières notables dans la répartition de nos sites d'étude, au Cameroun. Pendant la saison humide, M. ulcerans est plus fréquente dans les grands bassins versants et en absence de marécages, tandis que durant la saison sèche, la bactérie est plus présente dans les petits bassins versants où peuvent être présents dans les zones marécageuses. Notre étude a permis de générer des cartes de répartition de l'agent pathogène dans la région d'étude, qui pourront être utilisées dans des études ultérieures contribuant à mieux gérer le risque infectieux pour cette maladie. De plus, nous avons développé une modélisation des niches écologiques des insectes aquatiques soupçonnés d'être des vecteurs de l'agent pathogène. Basé sur un protocole d'échantillonnage d'insectes aquatiques qui couvre l'ensemble du Cameroun, nous avons construit un modèle suivant la méthode de l'entropie maximale. Ceci nous a permis d'interpoler notre modèle sur toute l'Afrique de l'Ouest. Nous avons ensuite testé une corrélation entre la répartition prévue des insectes potentiellement vecteurs, et la prévalence de l'ulcère de Buruli. Nous mettons en évidence une corrélation positive significative entre la répartition des insectes et la répartition de la maladie, et trouvons que cette corrélation varie significativement dans l'espace et le temps. Ceci est cohérent avec la possibilité d'une transmission multi-hôte pour cet agent pathogène.Enfin, en collaboration avec d'autres auteurs, nous avons pu explorer différents facteurs influençant la distribution de M. ulcerans, tels que les réseaux et la structure de la communauté biotique, ou encore l'impact de l'occupation du sol sur la distribution de l'ulcère de Buruli dans notre région d'étude d'Akonolinga au Cameroun. Et enfin nous avons testé le changement de distribution de la maladie à une plus grande échelle, entre le Bénin et le Nigeria. Cette thèse contribue à une meilleure compréhension de la distribution de Mycobacterium ulcerans et de l'ulcère de Buruli, fournissant des éléments de preuve d'une transmission multi-hôtes de la mycobactérie, ainsi que les premières cartes de répartition de l'agent pathogène pour la région d'Akonolinga au Cameroun. / The Buruli ulcer is an emerging environmentally acquired infectious neglected tropical disease. It causes permanent disability and disfigurement in victims. The causative agent is Mycobacterium ulcerans; however the environmental reservoir and mode of transmission of this bacterium are not known. Attempts to manage the disease have been hampered by lack of knowledge of the mode of transmission and the environmental reservoir of M. ulcerans. Certain environments have been associated with the disease, notably disturbed aquatic environments composed of small bodies of stagnant water. There is no known vector, though aquatic insects have been implicated as possible vectors. A full understanding of the distribution and mode of transmission of the bacterium would help in management of the disease.In this thesis, we use the tools developed in ecological niche modelling to describe the distribution of M. ulcerans. Following the construction of a model in Cameroon, Central Africa, and tested against a second database in French Guiana (South America), the pathogen is found to have notable seasonal changes in its distribution in our study sites in Cameroon. In the wet season, M. ulcerans is more common in large watersheds, while in the dry season the bacterium is more common in small watersheds. This enabled the generation of hazard maps of the pathogen distribution in the study region, which will be used in future studies and management of the disease. Following this we undertook ecological niche modelling to describe the distribution of the aquatic insects suspected to be vectors of M. ulcerans. Based on a sampling protocol that spanned the country of Cameroon, we undertake maximum entropy modelling, which enabled us to interpolate our model across all of West Africa. With these maps we explore the correlation between the predicted distribution of the insects to the prevalence of the Buruli ulcer. We find a significant positive correlation between the distribution of the insects and the distribution of the disease, and find that this correlation undergoes significant changes in space and time, consistent with the model of multi-vectorial transmission of the disease.Finally, in collaboration with other authors, we have assisted in exploring how the distribution of M. ulcerans changes according to community structure networks, how the distribution of the Buruli ulcer disease changes in our study region of Akonolinga, Cameroon, and how the distribution of the disease changes at a larger scale, between Benin and Nigeria. This thesis contributes to our understanding of the distribution and drivers of Mycobacterium ulcerans and the Buruli ulcer, providing evidence of multi-vectorial transmission of the disease, and the first hazard maps of the pathogen for Akonolinga, Cameroon.

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