Despite significant vector control advancements in the past years, the current malaria trends suggest that new control strategies are urgently required. These new approaches should address the current frontline intervention challenges like increasing insecticide resistance in mosquitoes and residual transmission issues. Insecticide-treated livestock (ITL) is one of the novel potential strategies to overcome the above challenges. ITL involves treating livestock near humans with an insecticide like ivermectin (IVM) to kill zoophagic malaria vectors. However, ivermectin pharmacokinetics data suggests that most IVM-administered drugs remain intact, and more than 90 % of this drug is eliminated in feces. Biological metabolites: 3′′-O-demethylivermectin (3DI) and 24-hydroxymethyl ivermectin (24OHI) are also excreted in feces. Therefore, using manure from treated cattle as fertilizers contaminates the soil, ground, and surface water with IVM or its metabolites through leaching and hydraulic water flow affecting the soil and aquatic ecosystems. Contemplating the contamination impacts, these drugs' environmental fate and effects could be regarded before massive IVM applications. Many researchers have tried to address this subject in temperate regions compared to the tropics, where IVM is urgently needed. Regional discrepancies such as soil types and climate can independently and dependently determine the fate and impact of ivermectin. Our research investigates the environmental fate of IVM and its primary biological metabolites. Laboratory and field studies in Tanzania and Virginia were conducted to simulate the difference between tropical and temperate climates. Soil and soil-manure mixture spiked with IVM were layered into two 5 mm layers in columns exposed to natural sunlight. The remaining IVM and its primary metabolite were quantified using Liquid Chromatography with a tandem mass spectrometry detector (LC-MS/MS. These compounds degraded up to 1.5 times faster in Tanzania than in Virginia, depending on temperature, soil depths and type, organic matter, and soil moisture. When IVM is subcutaneously injected into cattle, drug residues and metabolites: 3DI and 24OHI are excreted in feces following a positive skewed Poisson distribution profile. IVM, 3DI, and 24OH were found to degrade rapidly when cattle pats when exposed to the field. Since we conducted our study in the Summer, no IVM or its metabolites leached into the soil beneath. The obtained half-lives suggest that ivermectin's massive drug administration has little to worry about, primarily when the dung from treated cattle is spread into the field in thin layers in the Summer before farm application. / Doctor of Philosophy / Despite significant vector control advancements in the past years, the current malaria trends suggest that new control strategies are urgently required. These new approaches should address the current frontline intervention challenges like increasing drug resistance in mosquitoes and residual transmission issues. Treating cattle with ivermectin is one of the novel potential strategies to overcome the above challenges. This strategy is effective because the amount of ivermectin (IVM) found in the blood of treated cattle is enough to kill malaria vectors feeding on them. However, the literature suggests that most IVM-administered drugs remain intact, and more than 90 % of this drug is eliminated in feces. Metabolite bioproducts: 3″-O-demethylivermectin (3DI) and 24-hydroxymethyl ivermectin (24OHI) are also excreted in feces. Therefore, using manure from treated cattle as fertilizers contaminates the soil, ground, and surface water with IVM or its metabolites through leaching and hydraulic water flow affecting the soil and aqua ecosystems. Contemplating the contamination impacts, these drugs' environmental fate and effects could be regarded before massive IVM applications. Many researchers have tried to address this subject in temperate regions compared to the tropics, where IVM is more needed. Regional discrepancies such as soil types and climate can independently and dependently determine the fate and impact of ivermectin. Our research investigates the environmental fate of IVM and its primary bioproducts. Laboratory and field studies in Tanzania and Virginia were conducted to simulate the difference between tropical and temperate climates. Soil and soil-manure mixture spiked with IVM were layered into two 5 mm layers in columns exposed to natural sunlight. The remaining IVM and its primary metabolite were quantified on the appropriate instrument. These compounds degraded up to 1.5 times faster in Tanzania than in Virginia, depending on temperature, soil depths and type, organic matter, and soil moisture. When IVM drug is injected into cattle, the intact drug and its bioproducts: 3DI and 24OHI, are eliminated in feces following a favorable skewed normal distribution profile. IVM, 3DI, and 24OH were found to degrade rapidly when cattle pats when exposed to the field. Since we conducted our study in the Summer, no IVM or its bioproducts leached into the soil beneath. The obtained data suggest that ivermectin's massive drug administration has little to worry about, primarily when the dung from treated cattle is spread into the field in thin layers in the Summer before farm application.