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Effects of diethylcarbamazine and ivermectin treatment on Brugia malayi gene expression in infected gerbils (Meriones unguiculatus)

  • Mary J. Maclean (a1) (a2), W. Walter Lorenz (a3), Michael T. Dzimianski (a1), Christopher Anna (a4), Andrew R. Moorhead (a1), Barbara J. Reaves (a1) (a2) and Adrian J. Wolstenholme (a1) (a2)...

Abstract

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 elimination programs for LF rely on mass drug administration of albendazole plus diethylcarbamazine (DEC) or ivermectin. Only the mechanism of action of albendazole is well understood. To gain a better insight into antifilarial drug action in vivo, we treated gerbils harbouring patent Brugia malayi infections with 6 mg kg−1 DEC, 0.15 mg kg−1 ivermectin or 1 mg kg−1 albendazole. Treatments had no effect on the numbers of worms present in the peritoneal cavity of treated animals, so effects on gene expression were a direct result of the drug and not complicated by dying parasites. Adults and microfilariae were collected 1 and 7 days post-treatment and RNA isolated for transcriptomic analysis. The experiment was repeated three times. Ivermectin treatment produced the most differentially expressed genes (DEGs), 113. DEC treatment yielded 61 DEGs. Albendazole treatment resulted in little change in gene expression, with only 6 genes affected. In total, nearly 200 DEGs were identified with little overlap between treatment groups, suggesting that these drugs may interfere in different ways with processes important for parasite survival, development, and reproduction.

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      Effects of diethylcarbamazine and ivermectin treatment on Brugia malayi gene expression in infected gerbils (Meriones unguiculatus)
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Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

Author for correspondence: Adrian J. Wolstenholme, E-mail: adrianw@uga.edu

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Current address: Laboratory of Immunology, National Eye Institute, Bethesda MD 20892, USA.

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Effects of diethylcarbamazine and ivermectin treatment on Brugia malayi gene expression in infected gerbils (Meriones unguiculatus)

  • Mary J. Maclean (a1) (a2), W. Walter Lorenz (a3), Michael T. Dzimianski (a1), Christopher Anna (a4), Andrew R. Moorhead (a1), Barbara J. Reaves (a1) (a2) and Adrian J. Wolstenholme (a1) (a2)...

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