Mapping therapeutic alternatives: a systematic review of preclinical drug repurposing for schistosomiasis.

Schistosomiasis is an acute and chronic illness caused by parasites of the genus Schistosoma. It is present in 79 countries worldwide and primarily affects socioeconomically vulnerable populations due to exposure to infested water during daily activities. Praziquantel is the primary drug used in international schistosomiasis treatment. However, adverse effects and parasite resistance mechanisms have been reported, ranging from experimentally induced resistance to naturally occurring resistance in real-world populations. New therapeutic targets have been identified to address these issues. Consequently, drug repurposing is often considered a faster alternative that may offer lower development risks and potentially fewer adverse outcomes than newly synthesized drugs. Building on this potential, this study aimed to identify drug repurposing candidates as alternatives for schistosomiasis treatment through a systematic review. Two databases (ScienceDirect and PubMed) were searched. The selection of studies and writing of this systematic review followed the PRISMA guidelines. Of the 313 articles identified, 28 were selected after applying the exclusion criteria. The best results observed were celecoxib (over 90% for egg burden and parasite load), mefenamic acid (92% for parasite load and 82% for egg burden), and chlorambucil (75% parasite load and 85% egg burden). This review highlights the data supporting this strategy as a viable alternative for developing new therapies for schistosomiasis. As these compounds have been used clinically for a long time, substantial preclinical, biosafety, and pharmacovigilance data are already available. Their adverse effects and toxicities are well characterized, which may contribute to a reduction in overall costs and development timelines, although robust clinical validation remains a prerequisite for their use.