AbstractThe human whipworm Trichuris trichiura is a parasite that infects around 500 million people globally, with consequences including damage to physical growth and educational performance. Current drugs such as mebendazole have a notable lack of efficacy against whipworm, compared to other soil-transmitted helminths. Mass drug administration programs are therefore unlikely to achieve eradication and new treatments for trichuriasis are desperately needed. All current drug control strategies focus on post-infection eradication, targeting the parasite in vivo. Here we propose developing novel anthelmintics which target the egg stage of the parasite in the soil as an adjunct environmental strategy. As evidence in support of such an approach we describe the actions of a new class of anthelmintic compounds, the 2,4-diaminothieno[3,2-d]pyrimidines (DATPs). This compound class has found broad utility in medicinal chemistry, but has not previously been described as having anthelmintic activity. Importantly, these compounds show efficacy against not only the adult parasite, but also both the embryonated and unembryonated egg stages and thereby may enable a break in the parasite lifecycle.Author SummaryThe human whipworm, Trichuris trichiura, infects around 500 million people globally, impacting on their physical growth and educational performance. There are currently huge mass drug administration (MDA) programs aiming to control whipworm, along with the other major soil transmitted helminths, Ascaris and hookworm. However single doses of albendazole and mebendazole, which are used in MDA, have particularly poor effectiveness against whipworm, with cure rates less than 40%. This means that MDA may not be able to control and eliminate whipworm infection, and risks the spread of resistance to albendazole and mebendazole in the parasite population.We are attempting to develop new treatments for parasitic worm infection, particularly focused on whipworm. We report the identification of a class of compounds, diaminothienopyrimidines (DATPs), which have not previously been described as anthelmintics. These compounds are effective against adult stages of whipworm, and also block the development of the model nematode C. elegans.Our DATP compounds reduce the ability of treated eggs to successfully establish infection in a mouse model of human whipworm. These results support a potential environmental spray to control whipworm by targeting the infectious egg stage in environmental hotspots.
An unexpected new species of Habrophlebia from Algeria (Ephemeroptera, Leptophlebiidae)
