Schistosomiasis--a century searching for chemotherapeutic drugs

Schistosomiasis affects 200 million individuals in underdeveloped and developing regions and is a growing concern for travelers worldwide. There has been evidence of resistance to the praziquantel-based therapy and reports of acute-disease manifestation; therefore, other drugs affecting different stages of the schistosome parasites life cycle and alternative therapeutic regimens should be developed and become accessible. The present review results from a comprehensive search in the scientific literature for substances and compounds tested in the past centennial for schistosomiasis therapy. We gathered over 40 drugs providing information on therapeutic action in humans or animal model, toxicity, susceptible Schistosoma stages, species, etc. The drugs were grouped according to their known metabolic effects on the parasite, whether they are on membrane structure and function, carbohydrate metabolism, protein synthesis and function, or on nucleic acid metabolism. We discuss the current knowledge of drug-target interactions, their mechanism of action and possible therapy combinations. Furthermore, based in the literature and in our own experience with large-scale Schistosoma mansoni genome and transcriptome analyses, we put forward several recently described gene products that are promising target candidates for existing or new drugs.