In response to growing levels of resistance to currently used antimalarials, there is an urgent need to develop drugs that exhibit novel mechanisms to kill Plasmodium parasites. The objective of this study was to examine the antiparasitic activity of newly synthesized compounds based on imidazolium and triazolium rings. According to our structure/activity relationship studies the key components appear to be their positively charged rings and hydrophobic side groups, and bivalent compounds, which incorporate two positively charged rings, show even greater potency than monovalent compounds. Depending on the concentration used, our compounds appear to primarily inhibit intracellular parasite development or invasion into red blood cells. Selected compounds have been tested in vivo using a P. berghei ANKA murine model. Together, our findings demonstrate that small imidazolium- and triazolium-based compounds display both in vitro and in vivo activity through a novel mechanism of action that may involve inhibition of erythrocyte invasion.

Few empirical studies examine the influence that the maternal parasite environment can have on offspring fitness (maternal effects) in invertebrates. Several recent studies have found that mothers can adjust offspring phenotype to counter the negative effects of parasite infection. In this thesis I subjected the parental generation of the host species, Tenebrio molitor (Insecta: Coleoptera), to a high parasite, high density, or control treatment. Offspring were subsequently subjected to either the same stress, the alternate stress, or to the control, and fitness-related life history traits were measured in both generations. The results from this thesis do not support the hypothesis that T. molitor mothers influence offspring fitness in a positive way. Instead, maternal effects led to a reduction in offspring fitness under both types of stress. At least under some environmental conditions, females invest in their fitness at the expense of their offspring.

Few empirical studies examine the influence that the maternal parasite environment can have on offspring fitness (maternal effects) in invertebrates. Several recent studies have found that mothers can adjust offspring phenotype to counter the negative effects of parasite infection. In this thesis I subjected the parental generation of the host species, Tenebrio molitor (Insecta: Coleoptera), to a high parasite, high density, or control treatment. Offspring were subsequently subjected to either the same stress, the alternate stress, or to the control, and fitness-related life history traits were measured in both generations. The results from this thesis do not support the hypothesis that T. molitor mothers influence offspring fitness in a positive way. Instead, maternal effects led to a reduction in offspring fitness under both types of stress. At least under some environmental conditions, females invest in their fitness at the expense of their offspring.

The increasing prevalence of apicomplexan parasites such as Plasmodium, Toxoplasma, and Cryptosporidium represents a significant global healthcare burden. Treatment options are increasingly limited due to the emergence of new resistant strains. We postulate that parasites have evolved distinct metabolic strategies critical for growth and survival during human infections, and therefore susceptible to drug targeting using a systematic approach. I developed iCS306, a fully characterized metabolic network reconstruction of the model organism Toxoplasma gondii via extensive curation of available genomic and biochemical data. Using available microarray data, metabolic constraints for six different clinical strains of Toxoplasma were modeled. I conducted various in silico experiments using flux balance analysis in order to identify essential metabolic processes, and to illustrate the differences in metabolic behaviour across Toxoplasma strains. The results elucidate probable explanations for the underlying mechanisms which account for the similarities and differences among strains of Toxoplasma, and among species of Apicomplexa.

Master of Public Health / Department of Diagnostic Medicine/Pathobiology / Michael W. Sanderson / A zoonotic disease is any disease or infection that is naturally transmissible from vertebrate animals to humans. Over 200 zoonoses have been described (Zoonoses and the Human-Animal-Ecosystems Interface, 2013). Many zoonotic viruses are arboviruses, viruses transmitted by an infected, blood-sucking, arthropod vector (Hunt, 2010). There are several endemic arboviruses in the United States; some foreign arboviruses, such as Rift Valley fever (RVF) virus, are potential bioterrorism agents (Dar, 2013). Arboviruses, both endemic and foreign, threaten public health (Gubler, 2002) and therefore disease surveillance, vector control and public education are all vital steps in minimizing arboviral disease impact in the United States. Mosquito-borne disease threats, such as West Nile virus and Rift Valley fever, are constant concerns in the United States and globally. Current strategies to prevent and control mosquito-borne diseases utilize vector distribution, seasonal and daylight timing, and variation in population numbers. Climate factors, such as availability of still water for development of immature mosquitoes, shade, and rainfall, are known to influence population dynamics of mosquitoes. Using 1995-2011 mosquito population surveillance data from Fort Riley, Kansas, we compared population numbers of Culex tarsalis (Diptera: Culicidae), a vector of several arboviruses including West Nile virus and potentially Rift Valley fever, to a satellite-derived index of climate, the Normalized Difference Vegetation Index (NDVI) anomaly. No correlation between the population numbers and NDVI anomaly was observed, which contrasts with results from similar analyses in other locations. These findings suggest a need for continued investigation into mosquito population dynamics in additional ecological regions of the United States to better describe the heterogeneity of environment-population relationships within and among mosquito species.

La leishmaniose est une zoonose à transmission vectorielle due au parasite protozoaire Leishmania ; des co-infections avec plusieurs espèces de Leishmania ont également été rapportées. Il a été démontré que les vésicules extracellulaires (VE) de ce parasite jouent un rôle dans l'infection précoce, ainsi que la propagation de la résistance in vitro aux médicaments. Peu de médicaments anti-Leishmania sont disponibles, et la résistance continue de croître chez ce parasite; il est donc impératif de comprendre la propagation de la résistance aux antileishmaniens. Nous avons exploré la capacité des VE xénogéniques de Leishmania à moduler la physiopathologie de l'infection et la sensibilité du parasite aux médicaments après contact in vivo. La co-inoculation de parasites et de VE provenant de souches/espèces de Leishmania présentant divers profils de résistance aux médicaments a été réalisée chez la souris. La physiopathologie et la charge parasitaire ont été suivies, et des tests de sensibilité aux médicaments effectués. Les résultats ont démontré que les VE de Leishmania infantum influencent la physiopathologie de Leishmania major dans le cadre in vivo. Nous avons également constaté que ces VE modulent la sensibilité aux médicaments de L. major après un contact in vivo dans un modèle d'infection précoce, entraînant une diminution significative de la sensibilité à l’antileishmanien antimoine. Nous démontrons ici pour la première fois que les VE des parasites xénogéniques peuvent participer à la propagation de la résistance aux médicaments entre les populations de parasites après un contact in vivo, ce qui pourrait expliquer en partie l'augmentation des taux d'échec des traitements contre Leishmania. / Leishmaniasis is a zoonotic disease caused by the protozoan parasite Leishmania, endemic to 98 countries and territories. There are several manifestations of leishmaniasis, some fatal if left untreated. Furthermore, co-infections with multiple species of Leishmania have also been reported. Extracellular vesicles (EVs) from Leishmania have been demonstrated to play a role in early infection, as well as spread of drug resistance in vitro. Few antileishmanial drugs are available, and drug resistance to those in use continues to grow; as such, there is an urgent need to better understand the spread of Leishmania drug resistance. In this study, the ability of xenogeneic Leishmania EVs to modulate infection pathophysiology and parasite drug sensitivity after in vivo contact was explored. Co-inoculation of parasites and purified EVs from strains/species of Leishmania with contrasting drug resistance profiles was performed in BALB/c mice. Pathophysiology and parasite burden were monitored, and drug-susceptibility testing performed on recovered parasites. Results demonstrated that EVs from Leishmania infantum influence pathophysiology of Leishmania major in in vivo experiments. These EVs were also found to modulate drug sensitivity of L. major after in vivo contact in a 6-hour infection model, leading to a highly significant decrease in susceptibility to antileishmanial antimony. Here it is demonstrated for the first time that EVs from xenogeneic parasites can participate directly in propagating drug resistance between parasite populations after in vivo contact. These findings may help explain current observations of rising rates of Leishmania treatment failure.

No description available.

Au Canada, les pertes de rendement en agriculture attribuées aux nématodes sont généralement associées aux nématodes des lésions du genre Pratylenchus. En 2011, la découverte d’une nouvelle espèce exotique au Canada et qualifiée de rare dans le Nord-Est américain, soit Pratylenchus alleni Ferris, a soulevé de nouvelles inquiétudes. Afin de déterminer si cette espèce représente une menace pour les productions agricoles du Québec, mon projet de maîtrise visait à recueillir des informations sur sa virulence. Dans un premier temps, le spectre d’hôtes de P. alleni a été étudié et les résultats ont montré que ce nématode se développe très bien sur la pomme de terre, mais non sur la luzerne et le trèfle rouge. Ensuite, la reproduction de P. alleni dans un contexte de changements climatiques a été étudiée. L’augmentation prévue des températures et CO2 devrait favoriser le développement de P. alleni puisqu’il possède un meilleur taux de reproduction sur le soya lorsque soumis à un régime de températures de 17/28 ˚C et à une concentration en CO2 de 1200 ppm comparativement à 12/23 ˚C (400 ppm) et 15/26 ˚C (800 ppm). Dans cette même étude, une réduction de 19 à 58 % du poids sec racinaire des plants de soya inoculés avec P. alleni a été observée comparativement aux plants témoins. De plus, une méthode moléculaire de détection et de quantification simultanée de P. alleni et P. penetrans, l’espèce de Pratylenchus la plus répandu dans l’Est canadien, par qPCR a également été développée. Pour chacune des deux espèces, une sonde TaqMan associée avec le fluorophore CY5 pour P. alleni et FAM pour P. penetrans ciblant la région D2/D3 de la grande sous-unité ribosomale (28S) ont été développées et celles-ci se sont avérées spécifiques à chaque espèce. Ces résultats amènent de nouvelles connaissances sur ce ravageur et mettent en lumière sa pathogénicité. / In Canada, yield losses attributed to nematodes are generally associated with root-lesion nematodes from the genus Pratylenchus. In 2011, a new exotic species was detected in Canada and identified as Pratylenchus alleni Ferris. Pratylenchus alleni is rare in the Northeastern U.S. and its discovery has raised new concerns. To determine whether this species is a threat to agricultural production in Québec, my project aims to collect information about its pathogenicity. First, the host range of P. alleni was studied and the results showed that the nematode was developing well on potato, but poorly performed on alfalfa and red clover. The reproduction of P. alleni has also been studied in a context of climate change. The results showed that anticipated temperature and CO2 increases should favor P. alleni since it has a better reproduction rate on soybeans subjected to a night/day temperature regime of 17/28°C and a CO2 concentration of 1200 ppm compared to 12/23˚C (400 ppm) and 15/26°C (800 ppm) regimes. In the same study, a reduction of 19 to 58 % of roots dry weight of soybeans inoculated with P. alleni was observed compared to control plants. A simultaneous molecular detection and quantification method by qPCR of P. alleni and P. penetrans, the most widespread Pratylenchus species in Eastern Canada, was also developed. For each species, a TaqMan probe associated with the CY5 fluorophore for P. alleni and FAM for P. penetrans targeting the D2/D3 expansion segments of the large ribosomal subunit (28S) were developed and proved to be specific to each species. These results bring new insights into this new pest and highlight its pathogenicity.

No description available.

Le parasitisme est omniprésent dans l’environnement et une attention croissante est récemment apportée sur son impact sur les communautés écologiques. En effet, les parasites peuvent affecter la valeur adaptative des animaux sauvages, en altérant leur physiologie et/ou leur comportement. Ainsi, le rôle des parasites dans le maintien ou l’érosion des différences persistantes comportementales et cognitives entre individus est le sujet de nombreux débats et recherches. La relation entre l’infection parasitaire et le comportement de l’hôte est souvent complexe. Le comportement des individus agit sur leur susceptibilité au parasitisme, mais l’infection parasitaire peut aussi modifier le comportement de l’hôte, favorisant parfois la transmission du parasite. En outre, l’inclusion d’un proxy de santé, tel que la condition corporelle est importante à considérer dans des populations naturellement infectées où la santé des individus peut varier. Dans cette étude, nous avons examiné la relation entre un gradient de densité parasitaire, la personnalité (exploration et témérité), la cognition (apprentissage par stimuli aversifs) et la condition corporelle (Indice K de Fulton) chez les crapets-soleil (Lepomis gibbosus) sauvages, naturellement infectés par des endoparasites, comme le trématode responsable de la maladie du point noir (Trematoda : Apophallus sp. et Uvulifer sp.) et le ver solitaire de l’achigan (Cestoda : Proteocephallus ambloplites). Nous avons trouvé que l’exploration, mais pas la témérité, était répétable ce qui suggère que ce trait reflète la personnalité. De plus, l’exploration a diminué avec l’augmentation de la densité de parasites et la diminution de la condition corporelle de l’hôte. Ainsi, étant donné que la relation entre le comportement explorateur et la densité de parasites variait avec la condition corporelle, il est possible que les parasites aient un effet indirect sur le comportement de l’hôte en impactant sa physiologie. L’exploration variait également selon la densité de points noirs et la densité de cestodes, suggérant un potentiel conflit entre ces deux parasites, leurs hôtes finaux étant différents. Les individus avec plus de cestodes ont moins bien exécuté la tâche d’apprentissage, ce qui laisse à penser que ces parasites imposeraient un coût énergétique qui réduit les performances cognitives de l’hôte. Nos résultats contribuent à démontrer que les parasites et la condition corporelle de l’hôte doivent être pris en considération dans les études écologiques, comportementales ou physiologiques afin de mieux comprendre le maintien des variations inter-individuelles au sein des populations sauvages. / Parasites are ubiquitous in nature and increasing attention is given to their impact on ecological communities. Indeed, parasites can affect host fitness through changes in physiology and/or behaviour. Thus, their role in maintaining or eroding persistent inter-individual differences in behaviour (i.e. personality) and cognitive abilities in hosts is the subject of increasing study and debate. The relationship between parasite infection and host behaviour can sometimes be complex. For instance, personality traits may affect an individuals’ susceptibility to parasites. Conversely, parasite infection can itself modify host behaviour, sometimes favouring the parasite’s own transmission. In addition, including a general fitness proxy, such as body condition, is important when studying naturally infected populations, where individual health can vary greatly among individuals. Here, we examine the relationships among host body condition (Fulton’s K index), personality (i.e. exploration, boldness), cognition (aversive learning) and parasite density in wild pumpkinseed sunfish (Lepomis gibbosus), naturally infected with endoparasites, including trematodes causing blackspot disease (Trematoda: Apophallus sp. and Uvulifer sp.) and bass tapeworms (Cestoda: Proteocephallus ambloplites). We found that exploration but not boldness was repeatable, which suggests that this trait reflects personality. Host exploration decreased with both increasing parasite density and decreasing host body condition. Because the relationship between exploration and parasite density varied with body condition, this suggests a possible indirect effect of parasites on host behaviour through effects on host physiology. Exploration varied depending on blackspot and bass tapeworm density suggesting a possible conflict between these two parasites, as their final hosts are different. Inhibitory avoidance learning decreased with increasing cestode density, suggesting that these parasites could impose an energetic cost which decreases host cognitive performances. Our results provide more evidence that including host body condition and parasite density in ecological, behavioural or physiological studies can help better understand the persistence of inter-individual differences in wild populations.