Improved treatments for helminth infections, new formulations and drug candidates and screening tools.

Schistosomiasis and soil transmitted helminths are two neglected tropical diseases affecting over 1.5 billion people worldwide. Drug treatment for these diseases is available, however, its performance is suboptimal and the diseases remain uncontrolled despite many years of intense work. Within this frame, new and more effective drugs are urgently needed. The objective of this thesis was to boost the discovery and improvement of drugs used to treat schistosomiasis and soil transmitted helminth (STH) infections.
To treat STH, the most used drugs are albendazole and mebendazole. Several studies documented their unsatisfactory efficacy, with alarming cure rates of as low as 16% given in MDA. The first objective of this thesis was to evaluate if the increase of the water solubility of these drugs could improve their efficacy in the treatment of STH infections. Another STH, S. stercoralis, affects 30 – 100 million people and drug resistance against the gold standard drug, Ivermectin, represents an imminent thread. The second objective of this thesis was to evaluate the potential of moxidectin as an alternative treatment for human strongyloidiasis.
For the treatment of schistosomiasis, praziquantel is the only used drug but its application has several drawbacks. The third objective of this thesis was to follow up on the characterization and activity evaluation of three derivatives of oxamniquine, which had showed promising results in the treatment of S. mansoni and S. haematobium. The last objective of this thesis was to set up and validate a simple, fast, reliable and reproducible method for drug screening assays on juvenile S. mansoni worms.