A proof-of-concept trial to evaluate artesunate-mefloquine as a novel alternative treatment for schistosomiasis in African children

Schistosomiasis is a major Neglected Tropical Disease in sub-Saharan Africa, disproportionally affecting children living in poor rural areas. For decades, both treatment and control of schistosomiasis have relied on a single drug, praziquantel (PZQ). Given its massive use in current mass drug administration campaigns, emergence of praziquantel resistance is a threat, and finding alternative treatments against schistosomiasis is an urgent priority. Artesunate-mefloquine (AM) is a well-established antimalarial treatment of which both component drugs have demonstrated activity on Schistosoma larval and adult worms. We hypothesize that the therapeutic effect in Schistosoma infected children of one course of AM is similar to that of PZQ. This will be investigated in a randomized controlled clinical trial which aims to compare the efficacy and safety of AM versus PZQ as primary endpoints. Secondary endpoints of the trial will include the cumulative parasitological/clinical efficacy and overall safety of additional AM courses, and the reduction of schistosomiasis morbidity and of malaria infection and morbidity. In addition, the value of novel antigen- and DNA-based assays for diagnosis and follow up of antischistosomal treatment response will be determined. Year 1 will focus on trial design and preparation. In year 2, Schistosoma-infected children will be individually randomized to one of the two study arms (AM or PZQ) and followed-up during 48 weeks for infection and morbidity assessment. During years 3 and 4, the laboratory workup will be completed, and the trial results analyzed and disseminated. This project will provide a conclusive answer on the usefulness of AM as an alternative treatment option for schistosomiasis. Moreover, it will provide a thorough evaluation of innovative diagnostic tools for monitoring infection and morbidity after antischistosomal treatment.