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Emerging infectious diseases continue to threaten human health and healthcare resources across the world, and with the sustained emergence of some like Lyme disease, this trend is only expected to get worse. Even though some research has examined the spread of Lyme disease in different parts of the United States, focusing on its origin, spread, surveillance, and reporting, there has been minimal research on the recent spread of Lyme disease into and within Central and Southern Appalachia. This is an important gap, considering that this region is at the edge of the disease's expanding incidence and range. Considering this factor and the consequences that this disease may have on the residents of Appalachia who already face an array of underlying problems like chronic conditions, decreased access to health care, and exposure through outdoor work like resource extraction, addressing this gap will be important in understanding the current and future spatial range and impacts of the continued emergence of Lyme disease in Appalachia. This study thus sought to examine the extent of the emergence of Lyme disease in Appalachia between 2000 and 2019 using spatial scan statistic. This type of analysis uses spatiotemporal information to quantify disease emergence and diffusion using retrospective case and location data within a GIS environment; hence it helped quantify the spatial distribution and diffusion of Lyme disease into and within Appalachia and identify additional areas that can be targeted with public health prevention measures. We found five statistically significant clusters of Lyme disease across the contiguous US, indicating that the disease expanded spatially over the study period. Lyme disease has more than tripled across the US, with the number of counties with RR>1 increasing from 130 in 2000 to 453 by 2019. Lyme disease also increased more than eightfold in Appalachia, with spread southwards into and within Appalachia. The number of Appalachian counties with RR>1 increased from 16 in 2000 to 127 in 2019. These findings are important in understanding the current and future spatial range and the impacts of the continued emergence of Lyme disease in Appalachia. With this understanding, we can minimize the misdiagnosis of Lyme disease and inform public health action to reduce public vulnerability. / Master of Science / Emerging infectious diseases are diseases that have not been present, the persistence of diseases that were previously unknown, or those diseases that are rapidly increasing in a given location. These diseases continue to threaten human health and healthcare resources across the world, and with the sustained emergence of some like Lyme disease, this trend is only expected to get worse. Even though some research has investigated the spread of Lyme disease in different parts of the United States, focusing on its origin, spread, monitoring, and reporting, there has been minimal research on the recent spread of Lyme disease in Central and Southern Appalachia. This is an important gap, considering that this region is next to areas where the disease has recently spread, thereby making it vulnerable to continued spread. Considering this factor and the consequences that this disease may have on the residents of Appalachia who already face many underlying problems like long-term conditions, decreased access to health care, and exposure through outdoor work like resource extraction, addressing this gap will be important in understanding the current and future geographic occurrence and impacts of the continued spread of Lyme disease in Appalachia. This study thus sought to investigate the extent of the spread of Lyme disease in Appalachia between 2000 and 2019 using statistics and identification of places with a higher than expected number of cases. This type of analysis uses location information to quantify disease occurrence and spread using past case and location data using GIS software; hence it helped identify the distribution and spread of Lyme disease into and within Appalachia and identify additional areas that can be targeted with public health prevention measures. We found five areas with higher than expected number of Lyme disease cases across the contiguous US, indicating that the disease increased over the study period. Lyme disease has more than tripled across the US, with the number of counties with higher cases than expected increasing from 130 in 2000 to 453 by 2019. Lyme disease also increased more than eightfold in Appalachia, with spread southwards into and within Appalachia. The number of Appalachian counties with higher than expected Lyme disease cases increased from 16 in 2000 to 127 in 2019. These findings are important in understanding the current and future spread and the impacts of this continued spread of Lyme disease in Appalachia. With this understanding, we can properly detect Lyme disease and inform public health action to reduce public vulnerability.

Lyme disease has been a growing problem in the United States over the last few decades, and is currently the most common vector-borne disease in the country. This research evaluates the land cover within specified counties of northern Virginia to determine if a correlation exists between forest fragmentation, suburbanization, and cases of human Lyme disease as has been demonstrated in other Lyme endemic regions in the United States. Few studies have focused specifically on northern Virginia when considering the impacts of land cover change on Lyme disease. Discovered through the use of geospatial and statistical analysis, the cluster of Lyme disease cases in northern Virginia are associated with forest fragmentation within the study region, which creates an ideal habitat for black-legged ticks and the white-footed mouse, allowing for an increase in Lyme disease transfer from vector to humans. The goal is for the research findings to be applicable to other regions with similar land cover types. Regions with similar characteristics would then be able to recognize the potential risk of human Lyme disease and implement ways to reduce the Lyme disease risk associated with suburban development. The purpose of this study is to answer the following research questions: 1) How has the spatial distribution of Lyme disease in Northern Virginia changed since 2005 with respect to land cover? 2) Which suburban communities are more at risk for Lyme disease when considering their land cover types and the increasing spatial distribution of Lyme disease? / Master of Science / Lyme disease has been a growing problem in the United States over the last few decades, and is currently the most common vector-borne disease in the country. This research evaluates the land cover within specified counties of northern Virginia to determine if a correlation exists between forest fragmentation, suburbanization, and cases of human Lyme disease as has been demonstrated in other Lyme endemic regions in the United States. Few studies have focused specifically on northern Virginia when considering the impacts of land cover change on Lyme disease. Discovered through the use of geospatial and statistical analysis, the cluster of Lyme disease cases in northern Virginia are associated with forest fragmentation within the study region, which creates an ideal habitat for black-legged ticks and the white-footed mouse, allowing for an increase in Lyme disease transfer from vector to humans. The goal is for the research findings to be applicable to other regions with similar land cover types. Regions with similar characteristics would then be able to recognize the potential risk of human Lyme disease and implement ways to reduce the Lyme disease risk associated with suburban development. The purpose of this study is to answer the following research questions: 1) How has the spatial distribution of Lyme disease in Northern Virginia changed since 2005 with respect to land cover? 2) Which suburban communities are more at risk for Lyme disease when considering their land cover types and the increasing spatial distribution of Lyme disease?

Le mode de collecte web gagne de plus en plus de popularité depuis sa création, ceci notamment en raison des avantages qu’il apporte en termes de coût et de temps. Cependant, les tendances nonprobabilistes des échantillons web font souvent douter de leur capacité à fournir des résultats aussi représentatifs que ceux d’un mode traditionnel typique tel que le téléphone. Le but de ce mémoire est de comparer les modes non-probabiliste web et probabiliste téléphone souvent suggérés par les firmes de sondage au Québec. Nous analysons principalement les éventuelles différences entre les échantillons web et téléphone du point de vue de l’adaptation à la maladie de Lyme. Plus spécifiquement, les trois objectifs de l’étude sont de : (1) comparer la représentativité des deux échantillons avec les données du recensement en termes de caractéristiques sociodémographiques, (2) comparer ces modes d’enquête en ce qui concerne l’estimation des taux d’adoption de comportements préventifs à l’égard de la maladie de Lyme tel que rapportés par les répondants aux deux sondages, et (3) tester l’invariance de la mesure des comportements préventifs des échantillons non probabiliste (panel Web) et probabiliste (téléphone). Les données proviennent d’une étude sur les comportements d’adaptation à la maladie de Lyme. Les échantillons panel Web (n=956) et téléphone (n=1003) sont constitués de résidents québécois de 18 ans et plus habitant les régions de risques faible à significatif. Les résultats montrent premièrement qu’aucun des échantillons n’est représentatif de la population cible au regard des caractéristiques sociodémographiquestelles que rapportées dans le recensement canadien de 2016. Deuxièmement, nos résultats indiquent que le taux de non-réponse aux comportements préventifs d’adaptation à la maladie et autres variables associées est significativement plus élevé dans l’échantillon web. Cependant, la magnitude de cette différence est nulle pour 19 items sur 30, et faible pour les 11 autres. De plus, aucune différence importante n’a été relevée lors de la comparaison des deux échantillons du point de vue de l’estimation de la prévalence desdits comportements et leurs déterminants. Enfin, les analyses d’invariance de l’indice d’adaptation ou de prévention à l’égard de la maladie de Lyme révèle que la structure de l’indice est la même pour les deux échantillons. On en conclut que malgré certaines différences observées entre les modes web et téléphone, les répondants des deux échantillons ont tendance à adopter des comportements similaires d’adaptation à la maladie de Lyme. / The web data collection mode has been increasing in popularity since its creation, primarily due to its cost and time effective benefits. However, its non-probabilistic tendencies often bring doubts concerning the representativity of its results in comparison to a typical mode such as the telephone. This master’s thesis compares the non-probability web and probability telephone modes, often suggested by polling firms in the province of Quebec. It principally analyzes the eventual differences between both samples on their adaptation to the Lyme disease. More specifically, the three main goals of this study are: (1) to compare the representativeness of both samples with the census data in terms of their socio-demographic characteristics, (2) to compare those two survey modes regarding their respondents’ preventive behaviour estimates against the Lyme disease, and (3) to test the measurement invariance of the nonprobability (Web panel) and probability (telephone) samples’ preventive behaviour. The data comes from a study on the adaptation of prevention behaviors against Lyme disease. The web (n=956) and telephone samples (n=1003) are made of individuals, 18 years old and above, from low and significant risk regions. Results firstly reveal that neither survey is representative of the Canadian census of 2016. Secondly, results show that the non-response rate for Lyme disease prevention adaptive behaviors and other associated variables is higher in the web survey. However, the magnitude of this significance is nil for 19 out of 30 the items, and small for the other 11. Moreover, no important dissimilarities were found in comparing both samples’ estimates in terms of the behaviours’ prevalence and their determinants. Finally, the measurement invariance analyses on the index of adaptation to the Lyme disease show a similar structure of the index for both samples. In conclusion, although the web and telephone samples are different in some respects, their respondents tend to have similar behaviors of adaptation to the disease.

Mon étude vise à évaluer la propagation d’une zoonose en émergence au Québec, la maladie de Lyme, en conséquence du réchauffement climatique. Le pathogène responsable de cette infection, Borrelia burgdorferi, est transmis par l’intermédiaire d’une tique parasite, Ixodes scapularis, de plus en plus commune au Québec en raison de l’augmentation de la température moyenne du climat depuis les dernières décennies. Puisque la tique a une capacité de déplacement très restreinte, on s'attend à ce que sa dispersion soit liée à celle de son hôte primaire, soit la souris à pattes blanches (Peromyscus leucopus). Je décrirai donc d’abord les espèces impliquées, leur écologie et leur rôle dans ce système à trois niveaux (hôte/pathogène/vecteur). Puis, à l’aide de séquences d’ADN mitochondrial, je comparerai la phylogéographie des deux principales espèces de souris au Québec, la souris à pattes blanches et la souris sylvestre (P. maniculatus). Des analyses d’arbres et de réseaux d’haplotypes ont révélé des différences significatives dans la structure génétique et ainsi montré que les populations de P. leucopus seraient en expansion dans le sud du Québec. Cette étude nous a finalement permis d’émettre des hypothèses sur le patron d’établissement de la maladie de Lyme au Québec. / My study aims to assess the spread of an emerging zoonosis in Québec, Lyme disease, as a consequence of global warming. The pathogen responsible for this infection, Borrelia burgdorferi, is transmitted through a tick parasite, Ixodes scapularis, increasingly common in Québec due to the elevation of the average temperature of the atmosphere over the past decades. Since the tick has a very limited dispersal capacity, it is expected that its dispersion is linked to that of its primary host, the white-footed mouse (Peromyscus leucopus). I first described the species involved, their ecology and role in this three-level system (host / pathogen / vector). Then, using mitochondrial DNA sequences, I compared the phylogeography of the two main mouse species in Québec, the white-footed mouse and the deer mouse (P. maniculatus). Analyses of trees and haplotype networks revealed significant differences in the genetic structure, and thus showed that populations of P. leucopus are expanding in southern Québec. This study finally allowed making assumptions on the pattern of establishment of Lyme disease in Québec.

Klinische, epidemiologische und experimentelle Daten deuten darauf hin, dass Autoimmunkrankheiten wie z.B. rheumatoide Arthritis, multiple Sklerose oder Typ I Diabetes durch Infektionen ausgelöst oder verschlimmert werden können. Bis heute ist jedoch nicht bekannt, welche molekularen und zellulären Mechanismen den Zusammenhang zwischen Infektion und Autoimmunität vermitteln. Eine Hypothese, die diesen Zusammenhang zu erklären versucht, ist die Hypothese der molekularen Mimikry. Dieser Hypothese zufolge sind kreuzreaktive Lymphozyten, die sowohl Selbst- als auch Fremdantigene erkennen, für die Induktion von Autoimmunität verantwortlich. Die Hypothese der molekularen Mimikry erklärt die Kreuzreaktivität von Lymphozyten durch Sequenzhomologie oder Identität von Selbst- und Fremdantigenen. Wir haben diese Hypothese an zwei Modellen, der chronischen Lyme Arthritis und einem Maus Modell der multiplen Sklerose, getestet und dabei festgestellt, dass Kreuzreaktivität von Lymphozyten weitaus häufiger ist als bis vor kurzem noch vermutet wurde. Wir konnten weiterhin zeigen, dass nicht die Primärstruktur sondern definierbare strukturelle Motive die Ursache für die Kreuzerkennung von Selbst- und Fremdpeptiden sind, und das Kreuzreaktivität in den seltensten Fällen von pathogenetischer Relevanz ist. Die Vorstellung, immunologische Kreuzreaktivität zwischen einem definierten mikrobiellen Antigen und einem definierten Selbstantigen sei für die Pathogenese von Autoimmunkrankheiten verantwortlich, ist also zu einfach. Der zweite Schwerpunkt dieser Arbeit ist die immunologische Analyse eines von uns charakterisierten Th2-spezifisch exprimierten Moleküls, T1/ST2. Wir konnten zeigen, dass T1/ST2 auf Th2, nicht jedoch Th1-Zellen exprimiert wird; dass die Expression von T1/ST2 ex vivo die Lokalisation aktueller Th2-Antworten widerspiegelt; und dass T1/ST2 von funktioneller Bedeutung für die Th2 Zellen ist: Kreuzvernetzung des T1/ST2 Moleküls durch einen T1/ST2-spezifischen monoklonalen Antikörper induziert Proliferation und die Produktion von Typ 2 Zytokinen. In vivo läßt sich durch Applikation des löslichen Antikörpers gegen T1/ST2 die pathogene Th2-Immunantwort im Mausmodell von Asthma modulieren. T1/ST2 ist also ein Kandidat für die gezielte immunmodulatorische Therapie Th2-dominierter Erkrankungen wie Asthma und Allergie. / Clinical, epidemiological, and experimental data suggest that infections can sometimes trigger or exacerbate autoimmune diseases such as multiple sclerosis, type I diabetes, or rheumatoid arthritis. To date, the molecular and cellular mechanisms leading from infection to autoimmunity have not been defined. The molecular mimicry hypothesis proposes that crossreactive lymphocytes that recognize both self- and microbial antigens are key factors in the pathogenesis of autoimmunity. According to the molecular mimicry hypothesis, sequence identity or marked sequence similarity between self- and microbial antigens is the cause of such crossreactivity. We have examined the molecular mimicry hypothesis systematically in two different models: treatment-resistant Lyme arthritis and experimental autoimmune encephalitis (EAE). The major findings were: i) crossreactivity at the level of peptide recognition by T cells is far more frequent than previously expected; ii) structural criteria rather than sequence similarity determine cross-recognition; iii) immunoregulatory mechanisms normally prevent pathogenic effects mediated by crossreactive lymphocytes. Thus, the idea that crossrecognition of a defined microbial peptide and a particular self-peptide would explain autoimmunity is most likely too simple. The other major topic of this work was the immunological analysis of T1/ST2, a Th2-specific molecule that we characterized. Here, we could show that T1/ST2 is expressed on Th2 but not Th1 cells. Furthermore, T1/ST2 expression can be used to identify sites of ongoing Th2 reactions directly ex vivo. Most importantly, T1/ST2 is important for Th2 effector functions: crosslinking of T1/ST2 via a T1/ST2-specific monoclonal antibody induces proliferation and type 2-cytokine production. In vivo, administration of the soluble antibody against T1/ST2 ameliorates the immunological parameters of bronchial hyperreactivity in a murine model of asthma. Thus, T1/ST2 is a candidate target for therapeutic immunomodulation of diseases such as allergy and asthma.

La maladie de Lyme est la maladie à transmission vectorielle la plus répandue de l’hémisphère Nord. La peau est un organe clef dans cette maladie, car c’est à cet endroit qu’interagissent les cellules de l’hôte, le pathogène, le microbiote cutané et le vecteur. Nous avons développé un modèle murin d’infection disséminée de borréliose de Lyme, qui nous a permis de développer une méthode spécifique de détection de protéines de Borreliella dans le tissu cutané murin par SRM-MS, pouvant aboutir à une méthode de diagnostic chez l’homme. Dans un deuxième temps, nous nous sommes intéressés aux relations entre le microbiote cutané, les cellules résidentes de la peau, kératinocytes et fibroblastes, avec Borreliella. Les sécrétomes de trois bactéries commensales, S. epidermidis, P. acnes et C. striatum possèdent un effet synergique sur l’expression de gènes inflammatoires par les kératinocytes et les fibroblastes. Les sécrétomes de P. acnes et de C. striatum se sont également montrés capables d’inhiber une partie de la réponse inflammatoire des kératinocytes, pouvant aider le pathogène lors de la transmission/dissémination précoce. / Lyme disease is the most common vector-borne disease in the Northern Hemisphere. Skin is a key organ in the disease, since it is the key interface where host cells, pathogen, skin microbiota and vector interact early during pathogen transmission. We developed a late lyme borreliosis model on mice. This model allowed us to develop a specific detection method of Borreliella proteins in the mouse skin by SRM-MS that might be used to develop a human diagnosis of disseminated Lyme disease. In a second part, we analysed the relationship between skin microbiota, resident skin cells (keratinocytes and fibroblasts), in the presence or absence of Borreliella. The secretome of three commensals bacteria, S. epidermidis, P. acnes and C. striatum was shown to have a synergistic activity with Borreliella in pro-inflammatory gene expressions by keratinocytes and fibroblasts. P. acnes and C. striatum secretomes were also able to inhibit partially the inflammatory response of keratinocytes that might help the transmission/dissemination of the pathogen.

Depuis les années 90, les études réalisées au Canada ont permis d’identifier de nouvelles zones endémiques de l’agent de la maladie de Lyme, Borrelia burgdorferi, ou de sa tique vectrice, Ixodes scapularis. Ces régions représentent des zones privilégiées pour étudier le cycle de transmission dans son contexte environnemental. L’objectif principal de ce projet est d’étudier les relations spirochètes – tiques - hôtes et les facteurs environnementaux impliqués dans le cycle de transmission à partir des données du vecteur et de l’agent pathogène recueilli dans le Sud-Ouest du Québec de 2007 à 2008. Tout d’abord sera décrite la saisonnalité des tiques et des associations entre le vecteur et les hôtes rongeurs capturés. En effet, l’identification de la saisonnalité spécifique à chaque stade de la tique I. scapularis permet d’établir quels seront les mois propices pour effectuer les futures collectes de tiques. La saisonnalité synchrone des tiques immatures en quête peut également être un indicateur de la nature ou des souches de B. burgdorferi retrouvées. L’association des tiques immatures à différentes espèces ou à différentes classes d’hôtes (c.-à-d. âge, sexe, statut reproductif) a également été explorée. Nos résultats montrent que les souris du genre Peromyscus, principalement les mâles adultes, contribuent significativement à la survie et au développement du complexe I. scapularis - B. burgdorferi. Les tamias et les écureuils contribuent aussi à la survie et au développement des populations de la tique I. scapularis. Ensuite les associations entre le vecteur et les hôtes cervidés ont été examinées en tenant compte des facteurs environnementaux associés à leur niveau d’infestation. Ceci a permis d’évaluer l’utilisation des cerfs à titre de sentinelles pour le vecteur et les agents pathogènes. D’après nos résultats, bien qu’ils soient des sentinelles efficaces pour détecter Anaplasma phagocytophilum, les cerfs semblent des sentinelles inefficaces pour détecter les zones d’établissement du complexe I. scapularis-B. burgdorferi. Enfin, une analyse de l’impact de la diversité des hôtes et de l’habitat sur l’abondance de la tique I. scapularis et la prévalence de B. burgdorferi a été effectuée et ce, en tenant compte d’autres facteurs environnementaux. Ces analyses ont permis de déterminer les facteurs critiques pour l’établissement du complexe I. scapularis – B. burgdorferi et d’explorer la contribution relative de diverses espèces d’hôtes. D’après nos études, la diversité de la communauté d’hôte et la diversité de l’habitat influencent le complexe I. scapularis - B. burgdorferi. De plus, le climat (la température et les précipitations) joue un rôle significatif dans l’établissement, la survie et le développement des populations d’I. scapularis. Ce projet de recherche a permis d’explorer et d’identifier divers facteurs environnementaux biotiques et abiotiques influençant l’établissement du complexe I. scapularis - B. burgdorferi dans le Sud-Ouest du Québec. Ceux-ci pourraient être utilisés à titre d’indicateurs environnementaux du risque de la maladie de Lyme au Québec et possiblement ailleurs au Canada. / Since the 90s in Canada, studies have identified new endemic areas for the agent of Lyme disease, Borrelia burgdorferi and the tick vector, Ixodes scapularis. These newly endemic areas for complex I. scapularis - B. burgdorferi are prime areas to study the transmission cycle in its environmental context. The main objective of this project is to study the spirochete-tick-host relationships and environmental factors involved in the transmission cycle from the data of the vector and the pathogen collected in southwestern Quebec, 2007 to 2008. First, a description of the seasonality of ticks and associations between the vector and captured rodent hosts was performed. The identification of specific seasonality at each stage of the tick I. scapularis establishes months conducive to make the future collections of ticks. Synchronous seasonality of questing immature ticks may also be an indicator of the nature or strain of B. burgdorferi found. In addition, the association of immature ticks in different species or different classes of hosts (i.e. age, sex, reproductive status) was explored. The Peromyscus mice and adult males in particular contributed significantly to the survival and development of complex I. scapularis-B. burgdorferi. Chipmunks and squirrels also contributed to the survival and development of I. scapularis populations. Second, the associations between vector and examined deer was described taking into account the environmental factors associated with the level of infestation and the use of deer as sentinels for the vector and the pathogen was evaluated. According to our results, the deer are effective sentinels to detect Anaplasma phagocytophilum, but seem ineffective or imprecise to detect endemic areas for complex I. scapularis-B. burgdorferi. Finally, an analysis of the impact of the host diversity and habitat on the abundance of I. scapularis and prevalence of B. burgdorferi considering other environmental factors was performed. These analyzes were used to determine the critical factors in the establishment of complex I. scapularis-B. burgorferi and explore the relative contribution of various host species. According to our studies, the diversity of the host community and habitat influences the complex I. scapularis-B. burgdorferi. On the other hand, the climate (temperature and precipitation) plays a significant role in the establishment, survival and development of the I. scapularis populations. This study allowed us to explore and identify various biotic and abiotic environmental factors influencing the establishment of complex I. scapularis-B. burgdorferi in southwestern Quebec. These environmental factors could be used as environmental indicators of the risk of Lyme disease in Quebec and possibly elsewhere in Canada.

No description available.

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