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Abstract
Filarial infections caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori threatens nearly one billion people worldwide with lymphatic filariasis, and millions of dogs are at risk for contracting heartworm (Dirofilaria immitis). Control of these infections relies on very few drugs; ivermectin, albendazole, and diethylcarbamazine are distributed in mass drug administration programs to prevent lymphatic filariasis, and heartworm is controlled by macrocyclic lactone drugs, which include ivermectin. The mode of action of diethylcarbamazine and ivermectin in filarial nematodes is unclear, with in vitro assays using the Worminator system confirming that treated parasites are alive at drug concentrations much greater than those that kill them in vivo. These findings suggest that the clearance of microfilariae from the blood of infected people and dogs is a complex process that might involve host factors. Aiming to gain further insight into this possibility, we carried out a transcriptomic analysis of Brugia malayi males, females, and microfilariae treated with ivermectin, diethylcarbamazine, or albendazole in vivo. Ivermectin treatment produced the majority of differentially expressed genes, with a total of 113 transcripts in males and microfilariae at 24 hours, and in females and males at 7 days post-treatment. Diethylcarbamazine treatment yielded 61 total differentially expressed transcripts in males at 24 hours and in females and microfilariae at 7 days post-treatment. In total, nearly two hundred differentially expressed genes were identified with little overlap between treatment groups, suggesting that these drugs may interfere with processes important for parasite survival, development, and reproduction.