Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis.

Praziquantel (PZQ) is the only drug being used to treat human schistosomiasis on a large scale. This review focuses on current knowledge about the mechanisms of action of PZQ, prospects for PZQ resistance, possible future alternative drugs and on exhortations that control of schistosomiasis and other so-called neglected tropical diseases becomes more integrated. Schistosome calcium ion (Ca2+) channels are the only moiety so far identified as the molecular target of PZQ, but the evidence remains indirect. In the presence of cytochalasin D worms survive high concentrations of PZQ and experiments with cytochalasin D also indicated that PZQ induced worm death and Ca2+ influx are not correlated. Despite PZQ being widely used, there is no clinically relevant evidence for resistance to date, but worryingly low-cure rates have been recorded in some studies in Africa. Artemisinins and the related 1,2,4-trioxolanes are new promising antischistosomal compounds, as are inhibitors of a schistosome-specific bifunctional enzyme, thioredoxin-glutathione reductase. Use of PZQ will increase in the foreseeable future, whether given alone or coadministered with other anthelminthics in integrated control programmes. PZQ resistance remains a threat and its prevention requires adequate monitoring of current mass drug administration programmes and development of new schistosomicides.