Elucidating the genetic causes of anthelmintic resistance in nematode-borne neglected tropical diseases

Many neglected tropical diseases (NTD) are caused by parasitic nematodes. NTD carry a disease burden nearly one-quarter that of HIV and half that of malaria. They also indirectly increase susceptibility to HIV, tuberculosis, and malaria, exacerbating health impacts in the developing world. Within the last twenty years, a massive campaign to administer anti-nematode (anthelmintic) drugs was initiated. Unfortunately, there are few anthelmintics and resistance is growing rapidly, prompting an urgent need to identify resistance genes and new drugs. In addition to this impact on human health, nematode-borne diseases of livestock and plants are major agricultural problems, resulting in severe economic losses. Effective future treatments of parasitic infections require knowledge of which genetic variants cause resistance to a particular drug. For these reasons, I propose to identify the genetic basis for how resistance to anthelmintics develops. These discoveries will allow physicians to tailor existing treatments to exploit the weaknesses found in parasites and will enable researchers to identify new drugs that act broadly against multiple species.