Schistosomiasis—a century searching for chemotherapeutic drugs

Abstract

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.

Schistosomes—proteomics studies for potential novel vaccines and drug targets

“…Despite the testing of drugs from different classes over the past decades [2], Praziquantel remains the strategic cornerstone for the treatment of schistosomiasis worldwide, which heavily relies on massive chemotherapy [3]. Praziquantel is effective against all Schistosoma species infecting humans, has been extensively tested, does not display severe side effects and is currently inexpensive and available [4,5].…”

Isothermal Microcalorimetry To Study Drugs against Schistosoma mansoni

“…The extensive use and reliance on one single agent have raised concerns about the emergence of praziquantel resistance (3,8), and indeed, schistosome strains with increased drug tolerance have already been isolated from patients as well as selected in the laboratory (9, 26). Therefore, there is growing consensus that novel antischistosomal drugs should be discovered and developed (8,15,33).Antischistosomal drug discovery at many academic institutions (e.g., the Special Programme for Research and Training in Tropical Diseases; screening centers in London, United Kingdom, and Cairo, Egypt; the University of California, San Francisco, Sandler Center in San Francisco, CA; and the Swiss Tropical and Public Health Institute [Swiss TPH] in Basel, Switzerland) is based on in vitro whole-organism drug screening assays followed by in vivo tests in infected mice (15, 31). Stages used for in vitro assays are 1-to 7-day-old schistosomula (newly transformed schistosomula [NTS]) and juvenile and adult schistosomes.…”

“…The extensive use and reliance on one single agent have raised concerns about the emergence of praziquantel resistance (3,8), and indeed, schistosome strains with increased drug tolerance have already been isolated from patients as well as selected in the laboratory (9, 26). Therefore, there is growing consensus that novel antischistosomal drugs should be discovered and developed (8,15,33).…”

In Vitro Activities of Trioxaquines against Schistosoma mansoni

“…However, the prospect of having a single drug available for a disease affecting 200 million people is quite alarming, especially if both laboratory and field observations leave little room for doubt that resistance to praziquantel has emerged or will soon emerge (1,6). Consequently, the development of new drugs is ongoing (8,13,15).…”