Unit | Helminth Drug Development

Soil-transmitted helminth infections are caused by different species of parasitic worms, including whipworms, hookworms and roundworms. Worldwide, more than 1.5 billion people are infected with at least one soil-transmitted helminth, with most of the infected population living in sub-Saharan Africa. Safe drugs are available to treat soil-transmitted helminth infections, but the efficacy varies widely. The current treatments recommended by WHO are albendazole and mebendazole. However, in the case of the whipworm Trichuris trichiura, a single dose of these drugs can cure only a handful of infected people. And with drug resistance on the rise, new alternative treatments are urgently needed. Emodepside is an anthelmintic treatment used to date in veterinary medicine. To fill the anthelmintic drug pipeline, Swiss TPH researchers have tested emodepside for the first time in humans infected with soil-transmitted helminths in Phase II trials (see publications in New England Journal of Medicine 2023 and The Lancet 2024). Swiss TPH is working with life sciences company Bayer to develop the drug further, with Phase III trials due to start in 2025. We are also conducting laboratory studies to assess drug combinations with emodepside.

Pharmacomicrobiomic interactions between the human gut microbiota and non-antibiotic drugs have attracted significant research interest due to their proven potential to disrupt treatment outcomes. Despite this, there is a substantial knowledge gap regarding pharmacomicrobiomic interactions of anthelmintic drugs. Our group recently demonstrated a strong association between gut microbiota composition and anthelmintic efficacy against Trichuris trichiura (Nature Communications, 2022). In addition, we described the antibiotic properties of critical anthelmintic drugs against a wide range of bacterial species and their potential to induce cross-resistance to other antibiotics following anthelmintic exposure (Communications Biology, 2024). Our current research is systematically investigating these interactions to understand their contribution to treatment failure and their impact on gut microbial taxonomic and functional diversity. By gaining mechanistic insights into these interactions, we aim to unravel their role in shaping treatment outcomes and improve therapeutic strategies.

Schistosomiasis, caused by Schistosoma mansoni, S. haematobium and S. japonicum, continues to affect the health and quality of life of millions of people worldwide. Yet, we still rely on praziquantel as the sole treatment. Drug repurposing (or repositioning) is the development of new indications from existing, failed or abandoned drugs. Particular attention has been paid to antimalarials, as Plasmodium and Schistosoma spp. both utilise hemin as a common food source. The aim of this project is to investigate the antischistosomal properties of the artemisinins in vitro and in vivo, including pharmacokinetic studies. Read more

Challenges occur on “the last mile” towards schistosomiasis elimination, including the persistence of transmission hotspots, recrudescence of infection in areas where the prevalence has been successfully reduced, and diagnostics that are not sensitive and specific enough to detect light intensity infections. In the SchistoBreak study, we explore the application of new point-of care diagnostic tools and adaptive intervention strategies that are tailored to the micro-epidemiology of schistosomiasis in the North of Pemba island, Zanzibar, United Republic of Tanzania. Read more