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Methods of Drug Screening Against Soil-Transmitted Helminthes /

Abstract

Intestinal roundworm parasites infect two billion people in the world. In much of the developing world, children have intestinal worms that make them sick and anemic. Furthermore, physical and cognitive stunting as a result of worm infections directly impacts the children's ability to attend school, keeping them in a cycle of poverty. Studies show that deworming kids is a cost effective way to keep kids in school, yet there is only one drug with adequate efficacy to be used for mass drug administration. As a result drug resistance is a huge problem and discovery of new anthelmintics is of utmost importance. In regards to this problem we ask, can we develop a high- throughput system for screening drug compounds that kill or intoxicate these parasites? To answer this question I optimize a high-throughput drug screening method using 384 -well plates to screen against A. ceylanicum, a zoonotic hookworm. In addition I optimized a medium-throughput drug screening system using 96-well plates to screen on two parasites: A. ceylanicum and Trichuris muris (whipworm) and use it to test an FDA-approved library consisting of drugs that are approved for human use. Finally, experiments were done on different adult stage nematodes with two goals in mind: First to verify the validity of potential drug hits found by this screening system, and secondly to test potential drug candidates on a range of different nematodes. Discovery of a drug that is effective on multiple parasites would be a huge advantage in the fight to cure worm infections

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