Effects of immunological targeting of two mosquito antigens and oral ingestion of anthelmintic drugs on the yellow fever mosquito, Aedes aegypti (Diptera: culicidae)

Deus, Kelsey Marie, author
Foy, Brian D., advisor
Avery, Anne, committee member
Black, William C., IV, committee member
Bowen, Richard A., committee member
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Aedes aegypti is one of the most important mosquito vectors of human arboviruses, including dengue viruses, chikungunya virus, and yellow fever virus. Human infection with these viruses constitutes an enormous global disease burden. Current control methods rely heavily on the use of insecticides, which are rapidly losing their utility due to the spread of insecticide resistance. Anti-vector vaccines and anthelmintic drugs with insecticidal properties have been proposed as novel means to decrease pathogen transmission by reducing the daily probability of mosquito survival. The aims of this dissertation research were to: evaluate the Ae. Aegypti mosquito lysosomal aspartic protease and the glutamate-gated chloride anion channel as potential mosquitocidal antigens, evaluate drugs frequently used in mass drug administration campaigns for their ability to induce a mosquitocidal effect when imbibed in a blood meal, to assess the variation in susceptibility of Ae. Aegypti strains to orally imbibed ivermectin, and finally to determine if resistance to ivermectin could be selected for in a genetically diverse laboratory strain of Ae. Aegypti . Despite the utilization of several immunization regimens, a specific mosquitocidal immune response against the Ae. Aegypti mosquito lysosomal aspartic protease could not be verified. In vitro experiments in which high titer glutamate-gated chloride anion channel serum was fed to mosquitoes failed to elicit a mosquitocidal response, suggesting that it is an unlikely mosquitocidal antigen. In vitro blood feeding experiments with several anthelmintic drugs revealed that high concentrations of macrocyclic lactones (including ivermectin, selamectin and moxidectin) were effective in reducing adult mosquito survival and that sublethal concentrations resulted in reduced fecundity and egg hatch rate. When imbibed in a blood meal, diethylcarbamazine, albendazole-sulfoxide and pyrantel pamoate, which are all currently used in human mass drug administration campaigns for controlling parasitic pathogens in humans, had no effect on adult mosquito survival. Significant differences in susceptibility to ivermectin, according to mosquito strain, were observed, with three permethrin-resistant strains of Ae. Aegypti being the most refractory to ivermectin, suggesting a possible permethrin-induced cross resistance mechanism to ivermectin. After subjecting a genetically diverse laboratory strain of Ae. Aegypti to three successive rounds of selection with orally imbibed ivermectin, no resistance to the drug was apparent. Although mass drug administration is unlikely to have any impact on the transmission of Ae. Aegypti vectored pathogens, Ae. Aegypti may prove to be a useful model for studying the effects of ivermectin in the mosquito, including studying potential resistance and cross-resistance mechanisms to anthelmintic drugs.
2011 Fall.
Includes bibliographical references.
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Aedes aegypti
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