Helminths are parasitic worms and flukes that can cause disease in humans. The most common mode of transmission to humans is through ingesting or coming into contact with contaminated food, water, or soil. Helminth infections transmitted in this manner include ancylostomiasis and necatoriasis (hookworm), ascariasis (roundworm), trichuriasis (whipworm) and strongyloidiasis (intestinal roundworms) – collectively referred to as soil-transmitted helminths – as well as taeniasis/cysticercosis (tapeworm) and schistosomiasis (bilharziasis, also known as snail fever). Other helminth infections are transmitted by bites of blood-sucking arthropods: these include lymphatic filariasis, which is transmitted by mosquitoes, and river blindness (onchocerciasis), which is transmitted by the black fly.
Adult worms can reside in the intestines and other organs, causing malnutrition and impaired cognitive development (hookworms), or progressive damage to the bladder, ureter and kidneys (schistosomiasis). Onchocerciasis is a major cause of blindness in many African and some Latin American countries, while lymphatic filariasis can cause painful, disfiguring swelling of the scrotum (hydrocele) and limbs (elephantiasis).
Preventive chemotherapy in the form of mass drug administration or targeting specific groups such as preschool and school-aged children is the only medical countermeasure available for the control and elimination of helminthic diseases. Only one vaccine candidate, rSh28GST/Alhydrogel, targeting schistosomiasis, has ever reached an efficacy trial. Current vaccine development efforts are concentrated on hookworm, onchocerciasis and schistosomiasis, with most candidates either in pre-clinical development or human safety studies. The heavy reliance on preventive therapeutic agents, often as a monotherapy, has the potential to cause drug resistance. New therapies are urgently needed to counteract the future threat of resistance and overcome the shortcomings of current therapies, including child-friendly formulations and macrofilaricidal agents for onchocerciasis. The current therapeutic pipeline includes emodepside and oxfendazole for onchocerciasis, oxantel pamoate for trichuriasis, tribendimidine for hookworm and TylAMac for filariasis. Diagnosis remains reliant on stool/urine microscopy, underlining the need for rapid, point-of-care, molecular diagnostic tests which can detect resistance.
The Pediatric Praziquantel Consortium program completed clinical development of arpraziquantel – a new pediatric treatment for schistosomiasis – with the positive results from the pivotal clinical Phase III trial leading to a positive scientific opinion from the EMA in December 2023. Emodepside is an anti-filarial agent long approved for treating veterinary helminthic infections now being developed by a consortium including DNDi as a potential treatment for onchocerciasis. It succeeded in a Phase I human clinical trial and is now in Phase II; as of December 2022, the trial has reached 50% recruitment, with no safety signal observed. Sm-TSP-2 has been successfully investigated as a schistosomiasis vaccine in Phase I clinical trials in Brazil and Texas, and has been shown to be safe, well-tolerated and to induce a strong immune response in healthy adults. A Phase II trial of its efficacy is ongoing in Uganda, with estimated completion in November 2025.