The objectives of this study were to determine the distribution of Borrelia burgdorferi (Bb), the bacterium that causes Lyme disease, and its tick vector (Ixodes scapularis) in the Thousand Islands in Ontario, and to assess the effects of various factors, including host populations, temperature, and vegetation, on the distribution of Bb and ticks in this new endemic region. Data were collected via drag sampling and small mammal trapping at 12 sites and multimodel inference was used to evaluate variables. There was inter-island variation in the abundance of ticks and prevalence of Bb in ticks. Important predictors of tick numbers and infection prevalence included deer abundance, distance to the United States, temperature, species richness, and relative mouse abundance. These results will contribute to management strategies to reduce Lyme disease risk in the Thousand Islands and to our understanding of the effects of biodiversity on disease risk. / Canadian Cooperative Wildlife Health Centre; Ontario Ministry of Natural Resources; Parks Canada; Public Health Agency of Canada; Ontario Graduate Scholarship

Access to abstract permanently restricted to Ball State community only / Access to thesis permanently restricted to Ball State community only / Department of Physiology and Health Science

Thesis (M.S.)--Michigan State University. Dept. of Fisheries and Wildlife, 2008. / Title from PDF t.p. (viewed on July 30, 2009) Includes bibliographical references (p. 176-183). Also issued in print.

Made available in DSpace on 2014-12-17T14:13:44Z (GMT). No. of bitstreams: 1 ArlineteSM_Dissert.pdf: 1812083 bytes, checksum: 376b552fc90bb11b8b551d6db7f2d45f (MD5) Previous issue date: 2009-08-26 / Desenvolvido no Parque das Dunas, segunda reserva ambiental urbana do Brasil, ocupando uma ?rea de 1.172,80 hectares, com caracter?stica de mata atl?ntica de dunas, situada numa faixa litor?nea na regi?o urbana do munic?pio de Natal (05? 46 S, 35? 12 W), o presente estudo, realizado durante os anos de 2004 a 2006, teve como objetivo identificar as esp?cies de culic?deos existentes no Parque das Dunas, capazes de transmitir arbov?rus, tendo em vista que em 2004 houve uma epizootia de saguis (Callitrix jacchus), que causou grande mortandade, sem defini??o do agente etiol?gico. No ano de 2004, foram pesquisados sete pontos no interior da mata, com instala??o de 20 armadilhas de ovitrampas e 20 de bambu para coleta dos imaturos. Para os adultos, durante quatro vezes por semana, foram usadas as armadilhas de Sannhon. Foram coletados 5.691 imaturos, sendo 839 Ae. aegypti, 3.184 Ae. albopictus e 1.668 Hg. leucocelaenus. A coleta dos adultos foi realizada de 2004 a 2006, etapa em que se recolheu 17.506 culic?deos adultos, sendo 17.244 Wy. bourrouli, 255 Ae. aegypti, 593 Ae. albopictus, 1.275 Hg. leucocelaenus, 294 Oc. scapularis, 05 Oc. taeniorynchus, 02 Oc. serratus e 3 Li. durhami. Para os imaturos houve correla??o significativa entre Ae. aegypti e umidade relativa do ar p = 0, 049 e pluviometria p = 0,00, Ae. albopictus apresentou correla??o significativa positiva com a pluviometria, enquanto Hg. leucocelaenus n?o apresentou nenhuma das vari?veis clim?ticas. Para os adultos, a an?lise de s?rie temporal aponta flutua??o sazonal significativa para Ae. aegypti (p = 0,003); Ae. albopictus (p = 0,04); Oc. scapularis (p = 0,008 ) e Hg. leucocelaenus (p = 0,003). Uma correla??o significativa negativa foi observada entre o n?mero de Ae. albopictus coletado e a temperatura (Corr= - 0,50, p = 0,01); isto ?, para cada 1?C a mais h? diminui??o de 7 esp?cimes. Este estudo teve a participa??o de uma equipe multidisciplinar: bi?logos, entomologistas, para confirma??o das esp?cies; t?cnicos de laborat?rio, para acompanhamento di?rio das larvas eclodidas das armadilhas de ovitrampas. Teve a importante colabora??o de profissionais da Funda??o Oswaldo Cruz FIOCRUZ/Rio de Janeiro, da Universidade de S?o Paulo USP para identifica??o do grupo Wyeomyia.

A presente tese compreende 2 capítulos, dedicados à investigação de complexo de espécie e polimorfismo em Aedes scapularis. No Capítulo 1 foi desenvolvido um resumo técnico dos procedimentos utilizados na análise e montagem dos genes do DNA mitocondrial de 19 indivíduos da espécie Aedes scapularis e de como foi realizada a filtragem do DNA de alguns mosquitos em relação ao DNA amplificado do animal picado. No Capítulo 2 realizamos as análises de complexo de espécies e polimorfismo molecular em Aedes scapularis, com espécimes da Mata Atlântica, Caatinga e Mata Amazônica utilizando os marcadores: Morfometria Geométrica, gene Citocromo Oxidase Subunidade I e análise do DNA mitocondrial completo. Encontramos alto polimorfismo evidenciados por todos os marcadores populacionais nos mosquitos dos diferentes biomas estudados e alta estruturação populacional na análise filogenética dos genes mitocondriais codificadores de proteínas. Obtivemos duas conclusões majoritárias em nosso trabalho: 1) a espécie Aedes scapularis é genética e morfologicamente polimórfica em todos os ambientes estudados 2) Não encontramos evidência de complexo de espécies neste mosquito e então acreditamos que este mosquito trate-se de uma única entidade taxonômica. / The present thesis comprises 2 chapters, dedicated to the investigation of species complex and polymorphism in Aedes scapularis. In Chapter 1 a technical summary of procedures used in the analysis and assembly of mitochondrial DNA genes of 19 individuals of the species Aedes scapularis and how the \"filtering\" of the DNA of some mosquitoes was performed in relation to the amplified DNA of the animal bitten. In Chapter 2 we performed the analyzes of species complex and molecular polymorphism in Aedes scapularis, with Atlantic Forest, Caatinga (Xerophytic sparse tropical scrub) and Amazon Forest specimens using the markers: geometric morphometrics, Cytochrome Oxidase Subunit I gene Whole mitochondrial DNA analysis. We found high polymorphism evidenced for every markers in the mosquitoes of different biomes studied and high population structure in the phylogenetic analysis of the protein-coding mitochondrial genes. We obtained two principal conclusions in our work: 1) the species Aedes scapularis is genetic and morphologically polymorphic in all studied environments 2) We did not find evidence of species complex in this mosquito and therefore we believe that this mosquito is a single taxonomic entity.

Submitted by (edna.saturno@ufrpe.br) on 2016-07-19T14:48:33Z No. of bitstreams: 1 Cristiane Maia da Silva.pdf: 1998511 bytes, checksum: 58b33e4aff3f932a9eed5c8296403044 (MD5) / Made available in DSpace on 2016-07-19T14:48:33Z (GMT). No. of bitstreams: 1 Cristiane Maia da Silva.pdf: 1998511 bytes, checksum: 58b33e4aff3f932a9eed5c8296403044 (MD5) Previous issue date: 2014-02-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The insects from culicidae family are present in different habitats since homes until places of habitation of domestics animals. The State of Pernambuco is considered endemic for various diseases transmitted by Culicidae. This is the first survey about culicids in the Municipality of Cabo de Santo Agostinho. The aim of this study was to evaluate the occurrence of different species of Culicidae in the Cabo de Santo Agostinho county located in Rainforest Zone of Pernambuco, Brazil. For this purpose, the larvae of culicidae from 3rd and 4th instars were collected weekly during the period from October 2012 to September 2013. Twenty-three artificial traps were distributed and installed in domiciliary environments, peridomiciliary and within the forest, 20 meters away between them. The larvae were collected and transported in plastic containers containing water. When the larvae arrived in the laboratory were identified. A total of 12,718 culicids larvae (average of 1059.83 specimens / month) were collected during study period. The largest number of specimens was detected in September 2013 (n = 4,084) and lowest in December 2012 (n = 86). Notably, 2,441 (19.2%), 7,098 (55.9%) and 3,179 (24.9%) larvae were collected in domiciliary, peridomiciliary environments and at forest, respectively. In relation to the placement of traps (peridomicile and forest) 8,585 (67.5%) specimens were collected on the floor and 1,692 (13.3%) in the treetop. Ten different species of Culicidae were identified, the more often was Aedes albopictus (46.45%; 5,908/12,718), Culex maxi (35.56%; 4,523/12,718) and Limatus durhami (12.58%; 1,600/12,718). Interestingly, Ae. albopictus was the only species detected throughout all the study period (average of 492 specimens / month). In distributed traps in domicile environments Ae. albopictus was responsible for 95.58% (2,333/2,441) of the samples, while the predominance in around peridomicile (floor) traps were Cx maxi (73.22%; 4,523/6,177) species and (treetop) Ae. albopictus (97.94%, 902/921). The presence of Oc. scapularis was exclusively observed in the peridomicile floor traps, demonstrating the preference of this species in this local. This is very worrying, because this specie is epidemiologically important as vector in filariasis and arboviruses transmission. Thus, there is a need of evaluate the vector competence of the Oc. scapularis population of Cabo de Santo Agostinho, Pernambuco for D. immitis, W. bancrofti and arboviruses, considering epidemiologics aspects and public health importance. Although Ae. albopictus, the most common specie in the studied area, has presented two population peaks from February to April and from June to September, it is also possible to conclude that the human and animal populations who live in studied area are exposed to culicids and pathogenics agents, especially, after the rains. Therefore, control and prevention measures of culicids should be adopted in the studied area in order to reduce the health impact of endemic species here reported. / Os culicídeos estão presentes em diferentes habitats frequentando domicílios humanos e locais de permanência de animais domésticos. O Estado de Pernambuco é considerado endêmico para diversas doenças transmitidas por culicídeos. Trata-se do primeiro levantamento de culicideos realizado na região do Cabo de Santo Agostinho, PE. O objetivo do presente estudo foi avaliar a ocorrência de diferentes espécies de culicídeos no município do Cabo de Santo Agostinho, na zona da Mata do estado de Pernambuco. Para tanto, larvas de culicídeos de 3º e 4º estádios foram coletadas, semanalmente, em criadouros artificiais no período de outubro de 2012 a setembro de 2013. Foram instaladas 23 armadilhas artificiais do tipo larvitrampa distribuídas em ambientes domiciliar, peridomiciliar e dentro da mata distando 20 metros entre elas. As larvas coletadas foram transportadas em recipientes plásticos contendo água e no laboratório foram identificadas. Um total de 12.718 larvas de culicídeos (média de 1.059,83 espécimes/mês) foi coletado durante o período de estudo. O maior número de espécimes foi detectado em Setembro de 2013 (n = 4.084) e o menor em Dezembro de 2012 (n = 86). Particularmente, 2.441 (19,2%), 7.098 (55,9%) e 3.179 (24,9%) larvas foram coletados nos ambientes domiciliar, peridomiciliar e de mata, respectivamente. Em relação ao posicionamento das armadilhas (peridomicílio e mata) 8.585 (67,5%) espécimes foram coletados no solo e 1.692 (13,3%) na copa. Dez diferentes espécies de culicídeos foram identificadas sendo Aedes albopictus (46,45%; 5.908/12.718), Culex maxi (35,56%; 4.523/12.718) e Limatus durhami (12,58%; 1.600/12.718) as mais frequentes. Curiosamente Ae. albopictus foi a única espécie detectada durante todo o período de estudo (média 492 espécimes/mês). Nas armadilhas distribuídas nos ambientes domiciliares houve predominância da espécie Ae. albopictus (95,58%; 2.333/2.441) enquanto nas posicionadas no peridomicílio (solo) predominou a espécie Cx. (Cx.) maxi (73,22%; 4.523/6.177) e (copa) Ae. albopictus (97,94%; 902/921). Nas armadilhas localizadas na mata várias espécies foram encontradas sendo Li. durhami (50,33%; 1.212/2.408) predominante no solo e Ae. albopictus no solo (38,12%; 918/2.408) e copa (55,71%; 430/771). Foi observada também a presença de Oc. scapularis, com frequência nas armadilhas instaladas no solo do peridomicílio demonstrando a domiciliação dessa espécie na área estudada, o que é muito preocupante, uma vez que essa espécie tem importância epidemiológica, pois possui competência vetorial para a transmissão de diversas arboviroses e filarioses. Conclui-se que há a necessidade, então, de avaliar o potencial vetorial da população de Oc. scapularis do Cabo de Santo Agostinho, PE para D. immitis, W. bancrofti e arboviroses considerando os aspectos epidemiológicos e a importância para saúde pública. Embora Ae. albopictus, a espécie mais frequente na área estudada, tenha apresentando dois picos populacionais, de Fevereiro a Abril e de Junho a Setembro, é possível concluir também que a população humana e animal residente na área de estudo está exposta aos culicídeos e aos agentes por eles veículados durante todo o ano, sobretudo após o período de chuvas. Portanto, medidas de controle e prevenção dos culicídeos devem ser adotadas na área estudada visando a redução do impacto sanitário causado pela endemicidade das espécies aqui reportadas.

Ticks are hematophagous ectoparasites capable of transmitting various pathogens, including bacteria, protozoa, and viruses, to vertebrates. In the United States, tick-borne pathogens are responsible for around 95% of arthropod-borne diseases. Lyme disease is the most common tick-borne illness. However, emerging tick-borne viruses such as Bourbon virus (BRBV), Powassan virus (POWV), and Heartland virus (HRTV) can cause more severe health problems, including death and neurological abnormalities. The reports of molecular detection of viral RNA in field-collected ticks and serological evidence in a pilot study of wildlife species suggest the presence of these emerging viruses in Virginia. The presence poses a serious health threat, but the extent of their presence or circulation in Virginia is unknown. The objectives of the research are (1) to determine the evidence of circulation of POWV, HRTV, and BRBV in Virginia through serological assessment of domestic and wild animals in Virginia and (2) estimate transmission parameters and the basic reproduction number underlying tick-borne virus distribution and prevalence via a mathematical model. Here, we discuss the known literature relevant to tick-borne virus emergence; we assessed the presence of specific neutralizing antibodies against POWV, HRTV, and BRBV in wildlife and livestock sera collected from different health planning regions in Virginia. We used a susceptible-infected-susceptible (SIS) ordinary differential equation model to estimate transmission parameters that best describe the disease dynamics of emerging tick-borne viruses in Virginia. In our study, wildlife sera were seropositive against POWV (18%), BRBV (8%), and HRTV (5%). A wide range of different wildlife species were shown to be exposed to each virus examined. Livestock are also exposed to tick-borne viruses, with seroprevalences of 1%, 1.2%, and 8% detected in cattle for POWV, BRBV, and HRTV, respectively. We estimated the transmission rate and basic reproduction number to be 1.57 and 0.645, respectively. In conclusion, there is a widespread circulation of tick-borne viruses in western and northern Virginia within diverse species of animal populations. / Master of Science in Life Sciences / Ticks are blood-sucking ectoparasites that can transmit various pathogens, including bacteria, protozoa, and viruses, to humans and other vertebrates. In the United States, tick-borne pathogens are responsible for about 95% of all arthropod-borne disease cases. Lyme disease is the most common tick-borne illness. However, emerging tick-borne viruses such as Bourbon virus (BRBV), Powassan virus (POWV), and Heartland virus (HRTV), can cause more severe health problems, including potentially death or neurological abnormalities. The reports of molecular detection of viral RNA in field-collected ticks and serological evidence in a pilot study of wildlife species suggest the presence of these emerging viruses in Virginia. However, there is a lack of knowledge on the extent of their circulation. Firstly, this study aims to determine the evidence of circulation of POWV, HRTV, and BRBV in Virginia through serological assessment of domestic and wild animals. Secondly, this study aims to estimate transmission parameters and calculate the basic reproduction number of emerging tick-borne viruses. Evidence of prior infection against all three tick-borne viruses was detected in both wild and domestic animal species from the five Virginia health planning regions, with most samples in the study coming from southwestern and northwestern regions. In conclusion, there is a circulation of tick-borne viruses in Virginia, which is a potential threat to the public health.

Lyme disease, the most common tick borne disease in United States, is caused by the bacterial pathogen Borrelia burgdorferi. In nature, B. burgdorferi exists in an enzootic infectious cycle between an arthropod vector and mammalian hosts. Identification and characterization of the genes essential for B. burgdorferi survival throughout its infectious cycle is an important step toward understanding the molecular mechanisms involved in B. burgdorferi pathogenesis. B. burgdorferi contains a small genome, which lacks the genes encoding for the enzymes required for de novo synthesis of amino acids, fatty acids and nucleic acid precursors. Therefore, the spirochete is dependent upon the host environment for the uptake of these essential nutrients. Purines are required for the synthesis of nucleotides for the biosynthesis of DNA and RNA. Due to the lack of de novo purine synthesis, the ability of B. burgdorferi to salvage purines from its host environments is essential to its survival. While the enzymes critical for the B. burgdorferi purine salvage pathway are known, the transporters involved in the uptake of purines from the host environments are not. The work in this thesis is focused on identification of the genes encoding purine permeases in B. burgdorferi and genetic and biochemical characterization of their functions in the infectious cycle of B. burgdorferi. Here, we demonstrate that homologous genes bbb22 and bbb23 present on circular plasmid 26 encode for purine permeases, which are important for transport of hypoxanthine, adenine and guanine. Furthermore, genes bbb22-23 together were essential for B. burgdorferi infection in mice. BBB22 and BBB23 share 78% amino acid identify. And although, individually both BBB22 and BBB23 were found to be capable of purine transport, BBB22 has higher affinity for hypoxanthine and adenine compared to BBB23. Moreover, the bbb22 gene alone was sufficient to restore mouse infectivity to spirochetes lacking both bbb22 and bbb23, whereas, bbb23 was not. Nonetheless, the spirochete loads in the tissues of mice infected with B. burgdorferi carrying bbb22 alone were significantly reduced compared to B. burgdorferi carrying both bbb22 and bbb23, demonstrating the importance of the two genes together for the spirochetes to achieve wild type levels of infection. In ticks, genes bbb22 and bbb23 were dispensable for spirochete survival but contributed to spirochete replication in fed larvae. The replication of spirochetes lacking bbb22-23 in larval ticks was restored to wild type levels by the reintroduction of the low affinity purine transporter encoded by bbb23 alone. Overall, we have identified a purine transport system in B. burgdorferi, which is essential for spirochete survival in the mammalian host and contributes to spirochete replication in the tick vector. As B. burgdorferi lacks typical virulence factors and toxins, these studies highlight the critical role of physiological functions in the virulence of this pathogen. Moreover, the BBB22-23 in vivo essential transport system may represent a novel therapeutic target to deliver antimicrobial drugs to treat Lyme disease.

The thesis focuses on the investigation of the role of tick salivary components in the course of Lyme disease in mice. It includes studies on the saliva-facilitated transmission of Borrelia burgdorferi in vivo and the effect of tick cysteine protease inhibitors (cystatins) both on murine immune cells and the transmission of B. burgdorferi spirochetes in mice. The thesis also reveals practical applications of salivary cystatins for the development of anti-tick vaccine and the application of the pharmacological action of a tick salivary cystatin for the therapy of the disease symptoms in a mouse model of experimental asthma.

Les réservoirs de Borrelia burgdorferi jouent un rôle clé pour assurer sa transmission dans l’environnement. Récemment, de nouveaux acaricides, comme le fluralaner, présentant une efficacité élevée contre les tiques et une longue durée d’action, ont été commercialisés sur le marché des médicaments vétérinaires. Cibler les réservoirs de B. burgdorferi, comme les souris du genre Peromyscus, avec le fluralaner permettrait : d’abord, d’en altérer le cycle endémique; ensuite, de réduire la densité de tiques infectées dans l’environnement ; et, ultimement, de réduire le risque de transmission de la maladie de Lyme (ML). En premier lieu, l’efficacité du fluralaner à tuer des larves de l’espèce Ixodes scapularis infestant des souris du genre Peromyscus a été démontrée en laboratoire. Lors d’infestations expérimentales, des doses de 12,5 et 50 mg/kg ont tué > 90 % des larves d’I. scapularis dans les 4 jours suivant l’administration du traitement. Cependant, cette efficacité a été réduite à moins de 5 % dans les 30 premiers jours. En second lieu, dans le cadre d’une étude controllée non randomisée, des appâts de fluralaner ont été administrés répétitivement à une population de micromammifères sauvages à des densités de 2,1 ou 4,4 appâts/1000 m2 pendant 3 à 4 ans. L’efficacité du traitement à réduire l’infestation des micromammifères a, au préalable, été évaluée. Les densités de 2,1 et 4,4 ont respectivement réduit de 68 % et 86 % le nombre de larves infestant les souris du genre Peromyscus. Seule la densité de 4,4 a réduit significativement le nombre de nymphes de 72 %. Après quoi, l’effet des deux densités d’appâts sur le cycle endémique de B. burgdorferi a été évalué par le biais de 3 paramètres : 1- la prévalence de Peromyscus spp. infectées (PIM), 2- la densité de nymphes en quête (DON), 3- la prévalence de nymphes infectées par B. burgdorferi (NIP). La prévalence d’infection des souris par B. burgdorferi a chuté de 60 à 37 % après deux années de déploiements du traitement. Le traitement a provoqué une réduction de la DON de 45 à 63 % dans les zones traitées. Aucun effet n’a été observé sur le dernier paramètre. En troisième lieu, la pharmacologie du fluralaner a été caractérisée chez des souris du genre Peromycus dans une étude réalisée en laboratoire. Les données recueillies ont été utilisées pour simuler et interpréter différents scénarios de traitement de souris Peromyscus spp. pour une durée équivalente aux pics d’activités des larves et des nymphes d’I. scapularis. Les simulations ont permis d’identifier un jeu de scénarios qui conféreraient une protection contre les tiques pendant toute la saison d’activité des stades immatures d’I. scapularis. L’étude de la pharmacologie des acaricides chez les espèces ciblées et la modélisation de la pharmacocinétique représentent des étapes cruciales pour développer ce type d’intervention. Cette thèse a permis d’entreprendre le développement d’une approche ciblant les réservoirs de B. burgdorferi en utilisant une molécule de la famille des isoxazolines. L’approche décrite a montré le potentiel d’altérer le cycle endémique de B. burgdorferi et de réduire la densité de nymphes infectées dans l’environnement. Plus généralement, en intégrant des études sur la pharmacologie du fluralaner en laboratoire et des études terrains, elle permet d’initier la réflexion quant à l’importance d’avoir un cadre de développement commun pour structurer la recherche autour de ce type d’approches. / Reservoirs of Borrelia burgdorferi play a key role in ensuring its transmission in the environment. Recently, new acaricides, such as fluralaner, with high efficacy against ticks and a long duration of action have been commercialized in the veterinary drug market. Targeting B. burgdorferi reservoirs, such as Peromyscus spp. mice, with fluralaner would yield the following benefits: first, alter its transmission in the environment; second, reduce the density of B. burgdorferi-infected ticks in the environment; and, ultimately, reduce the risk of Lyme disease (LD). Firstly, the efficacy of fluralaner for killing Ixodes scapularis larvae infesting Peromyscus mice was demonstrated in a laboratory setting. Doses of 12.5 and 50 mg/kg showed > 90% efficacy at killing I. scapularis larvae infesting Peromyscus spp. mice within 4 days of treatment during experimental infestations. However, efficacy was reduced to less than 5% beyond 30 days. Secondly, in a non-randomized controlled study, fluralaner baits were repeatedly administered to a wild population of small mammals at densities of 2.1 or 4.4 baits/1000m2 over a period of 3 to 4 years. First, the treatment's efficacy at reducing small mammal infestation was evaluated. Densities of 2.1 and 4.4 baits/1000m2 reduced the number of larvae infesting Peromyscus mice by 68% and 86% respectively. Only the density of 4.4 baits/1000m2 significantly reduced the number of nymphs by 72%. Next, the effect of the both bait densities on the B. burgdorferi endemic cycle was evaluated through 3 parameters: i- the prevalence of B. burgdorferi-infected Peromyscus spp. mice (PIM), ii- the density of questing nymphs (DON), and iii- the prevalence of B. burgdorferi in questing nymphs (NIP). Mouse infection by B. burgdorferi decreased from 60 to 37% following two years of treatment deployment. The treatment reduced the DON by 45-63% in the treated areas but no effect was observed on B. burgdorferi prevalence in the NIP. Thirdly, fluralaner pharmacology was characterized in Peromycus mice in a laboratory setting. The data collected were used to simulate and interpret different treatment scenarios for Peromyscus mice over a period corresponding to the peak activities of I. scapularis larvae and nymphs. The simulations identified a set of treatment scenarios that confer protection against ticks for an entire season of I. scapularis activity. The results indicate that investigation of acaricide pharmacology in target species and pharmacokinetic modeling are critical steps in the development of this type of intervention. This thesis initiated the development of an approach targeting B. burgdorferi reservoirs using a molecule of the isoxazoline family. This approach showed potential for disrupting the endemic cycle of B. burgdorferi and reducing the density of B. burgdorferi-infected nymphs in the environment. More broadly, by integrating studies on fluralaner pharmacology in laboratory and field settings, this work has initiated a reflection on the importance of establishing a general development framework to structure research around this type of approach.