The effect on anthelmintic drugs on Brugia malayi gene expression in vivo

Lymphatic filariasis (LF) threatens nearly 20% of the world's population and has handicapped one-third of the 120 million people currently infected. Current control and eventual elimination of LF rely on mass drug administration (MDA) programs with three drugs: ivermectin (IVM), albendazole (ALB), and diethylcarbamazine (DEC). Only the mechanism of action of albendazole is well-understood. . To gain a better insight into antifilarial drug action, we treated gerbils with patent B. malayi infections with 6 mg/kg DEC, 1 mg/kg ALB, or 0.15 mg/kg IVM to mirror the doses used in human MDA programs. These treatments had no effect on the numbers of worms present in the peritoneal cavity of infected animals. Adults and Mf were collected 1 and 7 days post-treatment and RNA was isolated for transcriptomic analysis. The experiment was repeated three times. Preliminary analysis of the effects of IVM, ALB, and DEC on adult males and females revealed treatment-specific changes in transcripts related to collagen expression, reproduction, embryogenesis, larval development, and lifespan determination. Similar data are currently being collected for the microfilariae. Overall design: Three biological replicates were performed. For each replicate, B. malayi-infected gerbils were treated with either albendazole, DEC or ivermectin, or left untreated. One and seven days post-treatment, parasites were isolated from the peritoneal cavity. Males, females and microfilariae were separated and RNA isolated from each sample.

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Reaves BJ, Wallis C, McCoy CJ, Lorenz WW, Rada B, Wolstenholme AJ