A Doença de Lyme-símile brasileira ou Síndrome Baggio-Yoshinari (SBY) é uma zoonose emergente, transmitida por carrapatos e até o momento, de descrição restrita ao território brasileiro. O agente etiológico da SBY era desconhecido até o presente trabalho. O objetivo principal do estudo foi identificar a etiologia da SBY. Foi selecionado 2 grupos de pacientes: grupo A (n=68) composto por pacientes com suspeita diagnóstica de SBY, a maioria na fase latente da doença; grupo B (n=10), composto por pacientes com diagnóstico de SBY, que apresentaram obrigatoriamente eritema migratório e que encontravam-se sintomáticos no momento da coleta. Foi utilizado também um grupo controle composto por indivíduos saudáveis e com epidemiologia negativa (n=50). Amostras de sangue foram coletadas para a realização de sorologias, culturas, análises microscópicas (óptica e eletrônica) e reação de cadeia da polimerase (PCR) para diferentes micro-organismos (Mycoplasma spp, Chlamydia spp e Borrelia spp). Além disso, foi realizado um estudo preliminar, através da PCR para Borrelia spp em 47 amostras de carrapatos oriundos de áreas de risco do Espírito Santo (sendo 17 Rhipicephalus microplus e 30 Rhipicephalus sanguineus), e amostras de sangue total de 27 bovinos e 26 equinos, animais estes oriundos da Universidade Federal Rural do Rio de Janeiro. Os resultados mostraram que a SBY não se trata de uma zoonose causada por um conjunto de micro-organismos como pensado inicialmente e sim pela Borrelia burgdorferi sensu lato. Descoberta essa que foi possível empregando-se novos primers amplificadores do principal gene envolvido na síntese do gancho flagelar da Borrelia, chamado flgE. A positividade para flgE foi confirmada em 6 pacientes do grupo B, 2 carrapatos, 1 bovino e 1 equino, os quais apresentaram homologia de 99% com o gene da proteína do gancho flagelar da Borrelia burgdorferi (flgE) depositado no GenBank (L43849). Esta importante descoberta, associada às pesquisas anteriores, permitiu definir a SBY como zoonose emergente e própria do país, causada pela bactéria B. burgdorferi na apresentação morfológica atípica, transmitida por carrapatos não pertencentes ao complexo Ixodes ricinus, responsável por manifestações clínicas semelhantes à Doença de Lyme, exceto pela grande frequência de sintomas recorrentes / Brazilian Lyme disease-like illness (BLDL) or Baggio-Yoshinari Syndrome (BYS) is an emerging zoonosis, transmitted by ticks and so far, restricted to the description of the Brazilian territory. The causative agent of BYS was unknown until now. The main objective of this study was to identify the etiology of BYS. We have selected two groups of patients: group A (n = 68) consisting of patients suspected of BYS, mostly in the latent stage of disease; group B (n = 10), composed of patients diagnosed with BYS, who had compulsorily erythema migrans and that were symptomatic at the time of blood collection. We also used a control group composed of healthy individuals with negative epidemiology (n = 50). Blood samples were collected, in which we performed serology, cultures, microscopic analysis (optical and electron) and polymerase chain reaction (PCR) for different microorganisms (Mycoplasma spp, Chlamydia spp and Borrelia spp). In addition, a preliminary study was conducted by PCR for Borrelia spp in 47 samples of ticks from risk areas at Espirito Santo State (being 17 Rhipicephalus microplus and 30 Rhipicephalus sanguineus), 27 cattle and 26 horses, being these animals from the Universidade Federal Rural do Rio de Janeiro. The results showed that BYS is not a zoonosis caused by a set of microorganisms as initially thought, but by Borrelia burgdorferi sensu lato. These findings were possible after employing new primers that are able to amplify portions of the main genes involved in the synthesis of the Borrelia flagellar hook protein, called flgE. We confirmed positivity for the flgE in 6 patients from group B, 2 ticks, a cow, and a horse, which showed 99% homology with the gene of Borrelia burgdorferi flagellar hook protein (flgE) deposited in GenBank (L43849). This important discovery, coupled with previous research, helped to define BYS as an emerging zoonosis particular from Brazil, caused by B. burgdorferi of atypical morphologic presentation, transmitted by ticks outside the Ixodes ricinus complex, responsible for clinical signs similar to Lyme disease, except for the high frequency of relapsing symptoms

Introdução e Objetivo: A doença mixomatosa da valva mitral leva ao comprometimento de sua matriz devido à alteração em sua composição tecidual provocada pelo desequilíbrio na quantidade de ácidos mucopolissacarídeos ou glicosaminoglicanos. Sua etiologia ainda não está totalmente esclarecida, podendo ocorrer em formas familiares com transmissão autossômica dominante de penetrância variável, que pode ser dependente do tempo ou de prováveis fatores ambientais, situações em que a interação de agentes infecciosos necessita de maiores esclarecimentos. O objetivo deste estudo é a análise dos produtos dos patógenos da Chlamydophila pneumoniae, Mycoplasma pneumoniae e Borrelia burgdorferi em segmentos de cúspide retirados da valva mitral com degeneração mixomatosa, comparada ao grupo controle e a relação dos produtos bacterianos com aumento de marcadores inflamatórios (CD20, CD48, CD68) e de metaloproteinase (MMP9) na etiopatogenia da degeneração mixomatosa da valva mitral. Método: Estudo observacional, analítico, tipo caso-controle, que analisou 2 grupos contendo 20 pacientes cada e divididos em grupo 1, composto por fragmentos de tecido valvar mitral com diagnóstico de degeneração mixomatosa extraídos em procedimentos de troca ou plásticas valvares mitrais; e grupo 2, formado por segmentos de valvas mitrais sem valvopatia retirados no serviço de verificação de óbito. Foram realizadas colorações de hematoxilina e eosina e Movat para diagnóstico histológico da degeneração mixomatosa e técnica de imunohistoquímica para detecção de antígenos da Borrelia burgdorferi, Mycoplasma pneumoniae, mediadores inflamatórios (CD20, CD45, CD68) e marcadores de metaloproteinase (MMP9). A presença de antígenos da Chlamydophila pneumonia e foi pesquisada pela técnica de hibridização in situ. A análise quantitativa dos aspectos microscópicos foi realizada com o analisador de imagens Aperio. A pesquisa de elementos bacterianos foi feita através de microscopia eletrônica de transmissão. Resultados: No grupo 1, 14 (70%) pacientes são do gênero masculino e 6 (30%) do gênero feminino. A idade média é de 67,4 anos (51 a 79 anos, dp = 9,2). No grupo 2, 11 (55%) pacientes são do gênero masculino e 9 (45%) do gênero feminino. A idade média é de 67,6 anos (42 a 84 anos, dp= 12,0). Na análise da porcentagem de degeneração mixomatosa pela coloração Movat, houve diferença com significância estatística entre os grupos DM (G1), com média de 54,6 % ± 23,7 e grupo controle (G2) com média de 35,5 % ± 22,5 com valor de p = 0,013. Houve um maior número de células CD20 positivas/mm2 no grupo com DM com mediana igual a 17,8 (6,7 - 27,9) x 4,6 (3,6 - 9,8) com p = 0,007 para a área 1. Houve maior número de células CD45 positivas/mm2 no grupo com DM com mediana igual a 17,3 (3,4 - 92,5) x 2,8 (1,4 - 10,1) com p = 0,008 para a área 1. Houve maior número de células CD68 positivas/mm2 no grupo controle (G2), porém sem significância estatística com mediana igual a 38,7 (26,6 - 81,8) x 70 (42,7 - 120,4) com p = 0,098 para a área 1. Em relação à presença de antígenos de Mycoplasma pneumoniae, houve uma maior área (?m2) de antígenos detectados no grupo 1, quando comparadas com o grupo 2 com diferença estatisticamente significante para as duas áreas. Na área 1, mediana de 180.993 (24.856 - 387.477) x 7.970 (2.736 - 15.992) com p < 0,001 e na área 2, mediana igual a 105.968 (2.503 - 416.585) x 7.190 (3.314 - 17.833) com p = 0,02 A análise da presença de antígenos de Chlamydophila pneumoniae demonstrou que em ambas as áreas, houve uma maior área (?m2) de antígenos detectados no grupo de valvas com degeneração mixomatosa, quando comparadas com o grupo controle, porém sem diferença estatística com mediana para o G1 de 9.905 (4.716 - 16.912) x 5.864 (2.382 - 8.692) com p = 0,2 e para o G2, mediana de 3.199 (1.791 - 10.746) x 2.536 (683 - 6.125) com p = 0,3. Em relação à presença de antígenos de Borrelia burgdorferi, houve uma maior área (um2) de antígenos detectados no grupo 2 em relação ao grupo 1, em ambas as áreas. Na área 1, mediana de 7.596 (3.203 - 13.519) x 10.584 (7.223 - 15.974) com p = 0,14 e na área 2, mediana igual a 5.991 (3.009 - 8.475) x 8.403 (1.626 - 27.887) com p = 0,47. Em relação à presença da metaloproteinase MMP9, observamos maior área (um2) de antígeno marcado de MMP9 no grupo com degeneração mixomatosa tanto na área 1 quanto na área 2, com diferença estatística significante. Na área 1, mediana de 503.894 (202.428 - 938.072) x 269.244 (111.953 - 354.022) com p = 0,03. Na área 2, houve diferença estatística representada pela mediana de 389.844 (214.459 - 679.711) x 144.397 (29.894 - 247.453) com p < 0,001. No grupo DM houve correlação positiva entre Borrelia burgdorferi e porcentagem de DM com R = 0,52 e p = 0,018. Em relação às células inflamatórias, houve correlação positiva entre CD45 e Mycoplasma pneumoniae com R = 0,51 e p = 0,02. A presença de MMP9 se correlacionou positivamente com a presença de Mycoplasma pneumoniae com R = 0,45 e p = 0,04. Estas correlações estiveram ausentes no grupo controle. Conclusões: Houve associação de agentes infecciosos Mycoplasma pneumoniae e Borrelia burgdorferi na etiopatiopatogenia da degeneração mixomatosa da valva mitral. Na análise da relação dos produtos bacterianos com os marcadores inflamatórios e com a metaloproteinase, houve relação positiva entre o marcador inflamatório CD45 e a metaloproteinase (MMP9) apenas com a Mycoplasma pneumoniae, nas valvas com degeneração mixomatosa. O marcador inflamatório CD68 foi encontrado em maior número no grupo controle / Background: The myxomatous mitral valve disease leads to impairment due to changes in their tissue composition caused by the imbalance in the amount of acid mucopolysaccharides or glycosaminoglycans. Its etiology is not yet fully understood and may occur in familial forms of autosomal dominant trait with variable penetrance that can be time-dependent or probable environmental factors, where the interaction of infectious agents requires further elucidation. The purpose of this study is the analysis of the pathogens products of Chlamydophila pneumoniae, Mycoplasma pneumoniae and Borrelia burgdorferi in removed cusp segments of the mitral valve with myxoid degeneration, compared to the control group and the ratio of bacterial products with increased inflammatory markers (CD20, CD48, CD68) and metalloproteinase (MMP9) in the pathogenesis of myxomatous degeneration of the mitral valve. Method: Observational, analytical, case-control study which analyzed 2 groups of 20 patients each and divided in group 1, consisting of fragments of mitral valve tissue with diagnosis of myxomatous degeneration extracted in replacement procedures or mitral valve repair; group 2, formed by segments of mitral valves without valvolpaty clinial disease removed in the coroner service. Hematoxylin and eosin and Movat stains were done for histological diagnosis of myxoid degeneration and immunohistochemical technique for the detection of Borrelia burgdorferi, Mycoplasma pneumonia antigens, inflammatory mediators (CD20, CD45, CD68) and markers of metalloproteinase (MMP9). The presence of Chlamydophila pneumonia antigens was verified through an in situ hybridization technique. The quantitative analysis of the microscopic aspects was performed with the Aperio image analyzer. The research of bacterial elements was performed by a transmission electron microscopy. Results: In group 1, 14 (70%) patients were male and 6 (30%) were female. The mean age was (51 to 79 years, sd = 9.2). In group 2, 11 (55%) patients were male gender and 9 (45%) were female. The mean age was 67,6 years (42 to 84 years, sd= 12). In the analysis percentage of myxomatous tissue by Movat staining, there was a significant difference between the DM (G1) groups, with a media of 54.6 % ± 23,7 and control group (G2) with a media of 35.5 % ± 22.5 with p = 0.013. There was an increased number of CD20 cells/mm2 in myxomatous degeneration group (G1) with a median of 17.8 (6.7 - 27.9) x 4.6 (3.6 - 9.8) with p = 0.007 for the area 1. There was a higher number of CD45 cells/mm2 in myxomatous degeneration group (G1) with a median of 17.3 (3.4 - 92.5) x 2.8 (1.4 - 10.1) with p = 0.008 for the area 1. There was a higher number of CD68 cells/mm2 in control group (G2) without a statistically significant difference, with a median of 38.7 (26.6 - 81.8) x 70 (42.7 - 120.4) with p = 0,098 for the area 1. In quantifying Mycoplasma pneumoniae we observed a higher area (um2) antigen marked by, there was a higher amount of antigen detected in myxomatous degeneration group. In area 1, a median of 180,993 (24,856 - 387,477) x 7,970 (2,736 - 15,992) with p < 0.001 and in area 2, a median of 105,968 (2,503 - 416,585) x 7,190 (3,314 - 17,833) with p = 0.02. The analysis of the presence of Chlamydophila pneumoniae antigens showed that in both area, there was a larger area (?m2) antigens detected in the group of valves with MD when compared with the control group, but without significant differences with median for the G1 of 9,905 (4,716 - 16,912) x 5,864 (2,382 - 8,692), with p = 0.2 and the G2, median 3,199 (1,791 - 10,746) x 2,536 (683 - 6,125) with p = 0.3. Regarding the presence of Borrelia burgdorferi antigens, there was a greater area (?m2) antigens detected in group 2 than in group 1, in both areas. In one area, median 7,596 (3,203 - 13,519) x 10,584 (7,223 - 15,974), with p = 0.14 and in area 2, a median of 5,991 (3,009 - 8,475) x 8,403 (1,626 - 27,887) with p = 0.47. Regarding the presence of metalloproteinase MMP9, we observed a higher area (um2) antigen marked by MMP9 in the group with MD both in area 1and area 2, with statistically significant difference. In area 1, median of 503,894 (202,428 - 938,072) x 269,244 (111,953 - 354,022), p = 0.03. In area 2, median 389,844 (214,459 - 679,711) x 144,397 (29,894 - 247,453) with p < 0.001. In the DM group there was a positive correlation between Borrelia burgdorferi and the percentage of MD with R = 0.52 and p = 0.018. Regarding inflammatory cells, there was a positive correlation between CD45 and Mycoplasma pneumoniae with R = 0.51 and p = 0.02. The presence of MMP9 was positively correlated with the presence of Mycoplasma pneumoniae with R = 0.45 and p = 0.04. These correlations were absent in the control group. Conclusions: There was an association of infectious agents Mycoplasma pneumoniae and Borrelia burgdorferi in etiopathogeny of myxoid degeneration of the mitral valve. In the analysis of the relationship of bacterial products with the inflammatory markers and the metalloproteinase, there was a positive relationship between the inflammatory marker CD45 and metalloproteinase (MMP9) only with Mycoplasma pneumoniae. The inflammatory marker CD68 was found in greater numbers in the control group

A Doença de Lyme-símile brasileira ou Síndrome Baggio-Yoshinari (SBY) é uma zoonose emergente, transmitida por carrapatos e até o momento, de descrição restrita ao território brasileiro. O agente etiológico da SBY era desconhecido até o presente trabalho. O objetivo principal do estudo foi identificar a etiologia da SBY. Foi selecionado 2 grupos de pacientes: grupo A (n=68) composto por pacientes com suspeita diagnóstica de SBY, a maioria na fase latente da doença; grupo B (n=10), composto por pacientes com diagnóstico de SBY, que apresentaram obrigatoriamente eritema migratório e que encontravam-se sintomáticos no momento da coleta. Foi utilizado também um grupo controle composto por indivíduos saudáveis e com epidemiologia negativa (n=50). Amostras de sangue foram coletadas para a realização de sorologias, culturas, análises microscópicas (óptica e eletrônica) e reação de cadeia da polimerase (PCR) para diferentes micro-organismos (Mycoplasma spp, Chlamydia spp e Borrelia spp). Além disso, foi realizado um estudo preliminar, através da PCR para Borrelia spp em 47 amostras de carrapatos oriundos de áreas de risco do Espírito Santo (sendo 17 Rhipicephalus microplus e 30 Rhipicephalus sanguineus), e amostras de sangue total de 27 bovinos e 26 equinos, animais estes oriundos da Universidade Federal Rural do Rio de Janeiro. Os resultados mostraram que a SBY não se trata de uma zoonose causada por um conjunto de micro-organismos como pensado inicialmente e sim pela Borrelia burgdorferi sensu lato. Descoberta essa que foi possível empregando-se novos primers amplificadores do principal gene envolvido na síntese do gancho flagelar da Borrelia, chamado flgE. A positividade para flgE foi confirmada em 6 pacientes do grupo B, 2 carrapatos, 1 bovino e 1 equino, os quais apresentaram homologia de 99% com o gene da proteína do gancho flagelar da Borrelia burgdorferi (flgE) depositado no GenBank (L43849). Esta importante descoberta, associada às pesquisas anteriores, permitiu definir a SBY como zoonose emergente e própria do país, causada pela bactéria B. burgdorferi na apresentação morfológica atípica, transmitida por carrapatos não pertencentes ao complexo Ixodes ricinus, responsável por manifestações clínicas semelhantes à Doença de Lyme, exceto pela grande frequência de sintomas recorrentes / Brazilian Lyme disease-like illness (BLDL) or Baggio-Yoshinari Syndrome (BYS) is an emerging zoonosis, transmitted by ticks and so far, restricted to the description of the Brazilian territory. The causative agent of BYS was unknown until now. The main objective of this study was to identify the etiology of BYS. We have selected two groups of patients: group A (n = 68) consisting of patients suspected of BYS, mostly in the latent stage of disease; group B (n = 10), composed of patients diagnosed with BYS, who had compulsorily erythema migrans and that were symptomatic at the time of blood collection. We also used a control group composed of healthy individuals with negative epidemiology (n = 50). Blood samples were collected, in which we performed serology, cultures, microscopic analysis (optical and electron) and polymerase chain reaction (PCR) for different microorganisms (Mycoplasma spp, Chlamydia spp and Borrelia spp). In addition, a preliminary study was conducted by PCR for Borrelia spp in 47 samples of ticks from risk areas at Espirito Santo State (being 17 Rhipicephalus microplus and 30 Rhipicephalus sanguineus), 27 cattle and 26 horses, being these animals from the Universidade Federal Rural do Rio de Janeiro. The results showed that BYS is not a zoonosis caused by a set of microorganisms as initially thought, but by Borrelia burgdorferi sensu lato. These findings were possible after employing new primers that are able to amplify portions of the main genes involved in the synthesis of the Borrelia flagellar hook protein, called flgE. We confirmed positivity for the flgE in 6 patients from group B, 2 ticks, a cow, and a horse, which showed 99% homology with the gene of Borrelia burgdorferi flagellar hook protein (flgE) deposited in GenBank (L43849). This important discovery, coupled with previous research, helped to define BYS as an emerging zoonosis particular from Brazil, caused by B. burgdorferi of atypical morphologic presentation, transmitted by ticks outside the Ixodes ricinus complex, responsible for clinical signs similar to Lyme disease, except for the high frequency of relapsing symptoms

Les acyl stéryl glycosides (ASGs) appartiennent à une famille de glycolipides qui possèdent un caractère amphiphile particulier dû à la présence de deux parties hydrophobes, un stéroïde et une chaine grasse. Dans le cadre de nos études des propriétés d’auto-organisation des glycoamphiphiles, ce travail est dédié à l’étude de deux ASGs, α-CAG et BbGL 1, composés naturels présents respectivement dans les membranes des bactéries Helicobacter pylori et Borrelia burgdorferi., présentant des structures similaires mais des activités biologiques différentes. Notre travail a consisté à déterminer les paramètres structuraux qui gouvernent leurs propriétés d’auto-assemblage. Deux séries de 6-O-acyl cholestéryl glycosides (glucosides et galactosides) variant dans leur configuration anomérique et la longueur et le niveau d’insaturation de leur chaine grasse ont été synthétisées et leur capacité à former des cristaux liquides et à promouvoir une ségrégation lipidique dans des monocouches de Langmuir modèles de membrane ont été étudiées. Les relations structure-propriétés établies montrent que la longueur de la chaine grasse est le paramètre le plus discriminant dans le comportement d’auto-assemblage dans les deux types d’expériences. Pour les cristaux liquides thermotropes, l’autre facteur discriminant est la configuration anomérique, deux phases colonnaires successives rectangulaires puis hexagonales étant observées pour les séries α alors qu’une seule a été observée en séries β Changer de sucre n’induit pas de différence significative dans le comportement LC. Concernant la formation de domaines lipidiques, les modifications de la configuration (α/β) et du sucre influencent significativement leur temps d’apparition, apportant pour la première fois une définition claire des paramètres structuraux et physicochimiques qui gouvernent le comportement de l’α-CAG et ses analogues, en lien avec les données commues sur l’augmentation de pathogénicité d’Helicobacter pylori. Ce travail de thèse donne une illustration de l’importance de la structure des carbohydrates dans les processus biologiques et du concept de glycoamphiphilie. / Acyl steryl glycosides (ASGs) are a family of glycolipids which exhibit a peculiar amphiphilic character based on the presence of two hydrophobic appendages, one steroid moiety and one fatty alkyl chain, attached on a polar carbohydrate backbone. In the frame of our studies on the self-organisation properties of carbohydrate-based amphiphiles, this thesis is an investigation of the behavior of ASGs, in particular α-CAG and BbGL 1, two natural compounds found in bacterial membranes, Helicobacter pylori, Borrelia burgdorferi repectively, who exhibit close structures but different bioactivity. Our work has aimed at determining the key structural parameters governing their self-organization behavior. Two series of acyl cholesteryl glycosides (glucosides or galactosides) have been synthesized, with variations in the anomeric configuration, the 6-O-acyl chain length and level of unsaturation, and investigated with respect to their ability to form liquid crystalline mesophases, and to drive lipid domain segregation in Langmuir monolayers as model membranes. Structure-properties relationships have been established, indicating that the fatty chain length showed the most remarkable influence on the self-organization behavior, in LC and model membrane experiments. For the LC mesophases, the other important parameter is the anomeric configuration, two successive columnar phases, rectangular then hexagonal, being observed for the α-anomers, whereas only one was found for the β-anomers. No significant changes were observed when comparing glucosides and galactosides. With respect the formation of domains, configuration modifications at both C-1 (α or β) and C-4 (gluco or galacto) influenced significantly the domains appearance time, giving the first, clear physicochemical proof of the structural influential factors in the behavior of α-CAG and analogues, in the context of the known increased pathogenicity of Helicobacter pylori. Overall, this thesis provides a nice illustration of the subtlety and the importance of carbohydrate structure in biological processes, and of the concept of glycoamphiphilicity.

No description available.

Lyme disease is an emerging tick-borne illness in Canada, with human case numbers increasing 15- to 20-fold since Lyme disease became nationally notifiable in 2009 until the present. In Ontario, Canada's largest province by population, average Lyme disease incidence across the province is similar to that of national estimates. However, in eastern Ontario, which is near tick endemic regions in the northeastern Unites States, Lyme disease incidence is disproportionately higher compared to the rest of the province. The objectives of this thesis are to identify environmental Lyme disease risk areas in Ontario, to explore spatiotemporal trends in Lyme disease emergence, and to identify neighbourhood-level socioecological risk factors for Lyme disease. In addition, this thesis also aims to assess the risk of other tick-borne illnesses that are transmitted by the blacklegged tick, Ixodes scapularis, which is also the main vector for Lyme disease in Canada. Using maximum entropy species distribution modelling to correlate blacklegged tick occurrence data with environmental variables, predictive risk models for I. scapularis and the Lyme disease pathogen, Borrelia burgdorferi, were developed. The model prediction was used to classify low and high environment risk areas and, using a case-control epidemiological study, we assessed that residence in risk areas was a strong predictor of Lyme disease. However, this relationship was modulated by socioecological factors linked to higher overall rurality of the locality of home residence. Spatial cluster analyses further revealed that human Lyme disease cases clustered in regions with the high numbers of reported B. burgdorferi-infected ticks in the environment. Many individuals residing in large metropolitan regions, like the City of Ottawa, reported tick exposures outside their public health unit of residence; however, local clusters of Lyme disease were also detected in suburban regions near conservation areas, trails, and urban woodlands. The prevalence of other tick-borne pathogens was low, although several pathogens of public health significance including Borrelia miyamotoi and Anaplasma phagocytophilum were detected at multiple sites surveyed for ticks between 2017-2021. Overall, this thesis identify patterns in Lyme disease emergence (and potentially other tick-borne illnesses), defines environmental risk areas for Lyme disease in Ontario, and highlights important socioecological risk factors for Lyme disease in eastern Ontario.

Indiana University-Purdue University Indianapolis (IUPUI) / Borrelia burgdorferi, a bacterium which causes Lyme disease, is maintained in nature through a cycle involving two distinct hosts: a tick vector and a mammalian host. To adapt to these two diverse environments, B. burgdorferi undergoes dramatic alterations in its surface lipoprotein. Two essential lipoproteins, outer surface protein A (OspA) and outer surface protein C (OspC), are reciprocally regulated throughout the B. burgdorferi lifecycle. Very little is known about the regulation of OspA. These studies elucidate the regulatory mechanisms controlling the expression of OspA. Various truncations of the ospA promoter were created and then studied in our novel in vitro model of ospA repression or grown within the host-adapted model. A T-Rich region of the ospA promoter was determined to be a cis-element essential for both the full expression and full repression of ospA.

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Infectious diseases such as malaria and relapsing fever borreliosis (RF), cause severe human mortality and morbidity in developing countries. Malaria, caused by Plasmodium spp. parasites, is estimated by the World Health Organization to cause 1.5-2.7 million deaths annually. RF, caused by Borrelia spirochetes, has the highest prevalence described for any bacterial disease in Africa, with infection outcomes ranging from asymptomatic to fatal. RF borreliosis manifests in humans as a recurring fever and with other symptoms very similar to those of malaria. RF borreliosis has been regarded as a transient infection of the blood. However, B. duttonii exploits the brain as an immunoprivileged site escaping the host immune response while spirochetes in the blood are cleared. To investigate whether residual bacteria are dormant or actively dividing, mice with residual brain infection were administered ceftriaxone, a β-lactam antibiotic interfering with cell wall synthesis. Hence, it only affects actively dividing bacteria. Ceftriaxone eradicated brain RF infection in all treated mice, demonstrating that the bacteria are actively multiplying rather than in a dormant state. The findings support the therapeutic use of ceftriaxone for RF neuroborreliosis since penetration into cerebrospinal fluid is greater for ceftriaxone than for the often recommended doxycycline. The clinical features of malaria and RF are similar and diagnosis is further complicated by the frequently occurring concomitant malaria-RF infections. Therefore, we established a mouse model to study the pathogenesis and immunological response to Plasmodium/Borrelia mixed infection. Interestingly, malaria was suppressed in the co-infected animals whereas spirochete numbers were elevated 21-fold. The immune response in the concomitantly infected mice was polarized towards malaria leaving the spirochetes unharmed. Mice with co-infections also exhibited severe anemia and internal damages, probably attributed to escalating spirochete numbers. A secondary malaria infection reactivated the residual brain RF infection in 60% of the mice. This highlights the importance of co-infections as diagnostic pitfalls as well as the need for novel treatment strategies. Currently there is no commercial malaria vaccine and increasing drug resistance presents an urgent need for new malaria chemotherapeutics. Blood-stage malaria parasites are rapidly growing with high metabolic and biosynthetic activity, making them highly sensitive to limitations in polyamine supply. Disrupting polyamine synthesis in vivo with trans-4-methylcyclohexylamine (4MCHA) eradicated the malaria infection gradually, resulting in protective immunity. This leads the way for further biochemical and pharmacological development of the polyamine inhibitor 4MCHA and similar compounds as antimalarial drugs

Die vorliegende epidemiologische Studie umfaßte 153 Hunde aus der Nähe von Athen, Griechenland. Um die Prävalenz arthropogener Infektionen abschätzen zu können, wurden Serumproben auf Antikörper gegen Leishmania infantum, Ehrlichia canis und Borrelia burgdorferi sowie auf Antigene von Dirofilaria immitis überprüft. Blutausstriche wurden auf das Vorkommen von Babesia canis und Hepatozoon canis untersucht. Außerdem wurden von den Hunden abgesammelte Zecken bestimmt. Bei 126 Hunden erfolgte eine klinische Allgemeinuntersuchung. Des weiteren wurden die serologischen Testverfahren ELISA und IFAT für den Nachweis von Antikörpern gegen Borrelia burgdorferi miteinander verglichen. Insgesamt waren 94 (61,4 %) der 153 untersuchten Hunde infiziert, 63 (41,2 %) Hunde wiesen Antikörper gegen Ehrlichia canis auf. Infektionen mit Borrelia burgdorferi wurden im ELISA insgesamt bei 43 (28,1 %), im IFAT bei 35 (22,9 %) Tieren nachgewiesen. Außerdem konnte bei 28 (18,3 %) Tieren eine Infektion mit Leishmania infantum und bei 20 (13,1 %) mit Dirofilaria immitis gefunden werden. Ein Nachweis von Babesia canis im Blutausstrich gelang bei vier (2,6 %) Hunden, von Hepatozoon canis nur bei einem (0,7 %) Hund. Für keinen der untersuchten Infektionserreger konnten signifikante Alters-, Geschlechts- oder Rasseprädispositionen festgestellt werden. Die Infektionsraten mit Leishmanien, Babesien, Dirofilarien und Borrelien waren bei den im Tierheim lebenden Hunden geringer als bei den Streunern. Vierundvierzig (28,8 %) der 153 getesteten Hunde waren gleichzeitig mit zwei, drei oder vier durch Arthropoden übertragene Erregerarten infiziert. Zweifachinfektionen kamen bei 29 (19,0 %), Dreifachinfektionen bei sieben (4,6 %) und Vierfachinfektionen bei acht (5,2 %) Tieren vor. In der Regel war das Risiko für Hunde, einen Erreger zu beherbergen, höher, wenn bereits eine Infektion mit einem anderen Erreger vorhanden war. Insgesamt waren 28 (18,3 %) Streuner und 15 (9,8 %) Tierheimhunde von Mehrfachinfektionen betroffen. Von den 94 mit mindestens einem der berücksichtigten Erreger infizierten Hunden wurden 75 (79,8 %) einer klinischen Untersuchung unterzogen. Dreiunddreißig (44,0 %) dieser Tiere zeigten Krankheitserscheinungen. Bei 21 (67,7 %) der 31 klinisch untersuchten und mit mehreren Erregern gleichzeitig infizierten Hunde konnten Krankheitssymptome diagnostiziert werden. Von 44 klinisch untersuchten Tieren, die nur mit einem Erreger infiziert waren, zeigten 12 (27,3 %) klinische Symptome. Die diagnostizierten Symptome waren bei allen untersuchten Erregern von einer starken Variabilität geprägt. Die Übereinstimmung der Testsysteme IFAT und ELISA für den Nachweis von Antikörpern gegen Borrelia burgdorferi lag bei 92,2 %. Die Testverfahren sind damit als nahezu gleichwertig anzusehen, wobei der ELISA etwas sensitiver zu sein scheint. Eine Infektionsgefahr besteht demnach in Griechenland vor allem für Ehrlichia canis, Borrelia burgdorferi und Leishmania infantum, aber auch für Infektionen mit Dirofilaria immitis besteht ein Risiko. Infektionen mit Babesia canis kommen in dieser Region seltener vor, es muss jedoch insbesondere bei geschwächten oder in Deutschland geborenen und somit hochempfänglichen Tieren mit Erkrankungen gerechnet werden. Hepatozoon canis ist nach den vorliegenden Ergebnissen in der Umgebung von Athen von geringer Verbreitung. Ein Rückschluß vom klinischen Bild auf das Vorliegen einer Infektion mit einem bestimmten Erreger kann aufgrund der Variabilität der Symptome in Verbindung mit häufig auftretenden Mehrfachinfektionen nicht gezogen werden. Die Möglichkeit von gleichzeitig vorliegenden Infektionen sollte in der Diagnostik und Therapie unbedingt berücksichtigt werden. Gute Haltungsbedingungen und eine tierärztliche Überwachung und Prophylaxe reduzieren offensichtlich die Inzidenz von Infektionen mit arthropodenübertragenen Erregern. Die überwiegende Anzahl (449 von 457 Exemplaren) der bestimmten Zecken gehörte der Art Rhipicephalus sanguineus an. Es wurden sechs Nymphen und 443 adulte Tiere gefunden. Die adulten Tiere verteilten sich auf 243 männliche und 200 weibliche Zecken. Bei acht Zecken handelte es sich um weibliche Ixodes ricinus. Bei aus Griechenland stammenden Hunden wie auch bei Tieren, die sich reisebegleitend dort aufgehalten haben, muss mit einer starken Infestation mit Rhipicephalus sanguineus gerechnet werden. Da Rhipicephalus sanguineus der Vektor für Ehrlichia canis, Babesia canis vogeli und Hepatozoon canis ist, sollten Prophylaxemaßnahmen eine geeignete Zeckenbekämpfung einbeziehen. / 153 dogs from the environs of Athens, Greece, were surveyed for tick infestation and arthropod borne infections. Serology was performed for Leishmania infantum, Dirofilaria immitis, Ehrlichia canis and Borrelia burgdorferi and bloodfilms were microscopically examined for Babesia canis and Hepatozoon canis. Ticks collected from the dogs were differentiated. 126 dogs underwent clinical examination. Suitability of an indirect immunofluorescent antibody assay (IFAT) and an enzyme-linked immunosorbent assay (ELISA) for the diagnosis of antibodies to Borrelia burgdorferi was compared. Altogether 94 (61.4 %) dogs were infected with an arthropod borne pathogen, 63 (41.2 %) produced antibodies to Ehrlicha canis. ELISA detected Borrelia burgdorferi infection in 43 (28.1 %) dogs while IFAT was positive in 35 (22.9 %). 28 (18.3 %) dogs were infected with Leishmania infantum and 20 (13.1 %) with Dirofilaria immitis. Babesia canis was found in blood smears of four (2.6 %) dogs, Hepatozoon canis was detected only in one case (0,7 %). No association was found between the breed, age or sex of the dogs and any of the tested pathogens. The rate of infection with Leishmania, Babesia, Dirofilaria or Borrelia was lower in dogs living in the animal shelter than in those living as strays. 44 (28.8 %) of the 153 dogs examined were infected concurrently with two (n = 29, 19,0 %), three (n = 7, 4,6 %) or four (n = 8, 5,2 %) arthropod borne pathogens. In general the risk of infection was higher in dogs that were already infected with another pathogen. Altogether 28 (18.3 %) of the strays and 15 (9.8 %) of the dogs living in the animal shelter had a multiple infection. 75 of the 94 dogs infected with at least one of the tested pathogens were examined clinically. 33 (44.0 %) showed clinical symptoms. In 21 (67,7 %) of the 31 clinically examined dogs with multiple infection symptoms of disease were diagnosed. Twelve (27.3 %) of the 44 clinically examined dogs that were only infected with one pathogen had symptoms of some kind. Clinical symptoms varied considerably irrespective of the causative agent. The concordance of the IFAT and the ELISA for the diagnosis of Borrelia burgdorferi was 92.2 %. The serologic diagnosis of Borrelia burgdorferi with IFAT or ELISA can be regarded similarly suitable although ELISA seems to be somewhat more sensitive. In conclusion the risk of infection in Greece is particularly high for Ehrlichia canis, Borrelia burgdorferi and Leishmania infantum and Dirofilaria immitis as well. Babesia canis is obviously transmitted less. However dogs in poor condition or born in non endemic areas may acquire babesiosis in Greece. According to the results of this study Hepatozoon canis seems to be of negligible relevance in Greece. Due to the variability of the clinical symptoms and the frequent occurrence of multiple infections diagnosis based on the clinical picture only is not possible. Multiple infections should also be considered with respect to treatment. Infections with arthropod borne pathogens seem to occur less often in prophylactically treated dogs living under good conditions. Most of the examined ticks were identified as Rhipicephalus sanguineus (449 out of 457 specimens). Six nymphs and 419 adults were found. Of the adult Rhipicephalus sanguineus ticks 243 were males and 200 were females. Eight of the ticks were female Ixodes ricinus. In dogs originating from Greece as well as in dogs having accompanied tourists into Greece infestation with Rhipicephalus sanguineus is probable. As Rhipicephalus sanguineus is known to transmit Ehrlicha canis, Babesia canis vogeli and Hepatozoon canis prophylactic measures should include a suitable tick-control.