Evaluation of ivermectin as an antimalarial therapy against P. falciparum liver stage

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Project Summary/Abstract Ivermectin mass drug administration (MDA) is proposed as a novel malaria transmission control tool to kill the mosquito vectors. Where Ivermectin MDA has been examined and found to be effective against the transmission of Plasmodium berghei, it unclear if this translates to human malaria. The objective of this study is to determine if Ivermectin MDA, when combined with other antimalarial drug treatments, could be effective in eliminating P. falciparum transmission, aiding in the malaria eradication initiative. Ivermectin metabolites will be identified using metabolically-active primary human hepatocytes in the liver stage development assay. Leveraging these data as the baseline, pharmacokinetic drug-drug interactions will be evaluated between ivermectin and artemisinin-based combination therapies to be analyzed in future clinical trials. These methods will also utilize the primary human hepatocyte liver stage assay as a way to obtain metabolites and further examine them via LC-MS.