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Soil-transmitted helminths are parasitic nematodes that inhabit the human intestine. These parasites, which include two hookworm species,Ancylostomaduodenaleand   Necator americanus  , the whipwormTrichuristrichiura    , and the large roundwormAscarislumbricoides    , infect upwards of two billion people and are a major cause of disease burden in children and pregnant women. The challenge with treating these diseases is that poverty, safety, and inefficient public health policy have marginalized drug development and distribution to control infection in humans. Anthelmintics (anti-worm drugs) have historically been developed and tested for treatment of non-human parasitic nematodes that infect livestock and companion animals. Here we systematically compare the  in vitro  efficacy of all major anthelmintic classes currently used in human therapy (benzimidazoles, nicotinic acetylcholine receptor agonists, macrocyclic lactones, nitazoxanide) against species closely related to human parasitic nematodes-  Ancylostoma ceylanicum  ,Trichurismuris    , andAscarissuum    --- as well as a rodent parasitic nematode used in veterinary drug discovery,Heligmosomoidesbakeri    , and the free-living nematode   Caenorhabditis elegans  . Extensive  in vitro  data is complemented with single-dose  in vivo  data in three rodent models of parasitic diseases. We find that the effects of the drugs  in vitro  and  in vivo  can vary greatly among these nematode species, e.g., the efficacy of albendazole is strong on   A. ceylanicum   but weak onH.  bakeri    . Nonetheless, certain commonalities of the  in vitro  effects of the drugs can be seen, e.g., nitazoxanide consistently shows an all-or-nothing response. Our  in vitro  data suggest that further optimization of the clinical efficacy of some of these anthelmintics could be achieved by altering the treatment routine and/or dosing. Most importantly, our  in vitro  and  in vivo  data indicate that the hookworm   A. ceylanicum   is a particularly sensitive and useful model for anthelmintic studies and should be incorporated early on in drug screens for broad-spectrum human soil-transmitted helminth therapies.

An Extensive Comparison of the Effect of Anthelmintic Classes on Diverse Nematodes