Schistosomiasis is caused by infection with one of several species of parasitic worms and, although not usually fatal, is considered to be the second only to malaria in terms of human impact. Infection with the parasite typically occurs when wading, swimming or washing in water containing fresh water snails, the intermediate host for the parasite.
Although many countries are working to eradicate the disease by drug treatment, snail control, education and improved sanitation, the disease remains endemic in more than 70 countries and is estimated to affect around 200 million people worldwide. Schistosomiasis is readily treated with praziquantel but, despite being the mainstay of treatment for several decades, the mechanism of action of praziquantel is still debated. Writing in the journal PLoS Neglected Tropical Diseases, researchers at University of Minnesota Medical School have now shown how praziquantel kills a species of free-living flatworm that is often used as a model organism. These worms have remarkable regenerative properties and are able to reform a complete body from even a small fragment. Praziquantel was found to cause aberrant regeneration, producing two-headed organisms with duplicated, integrated central nervous systems and organs. The team further showed that voltage-operated calcium channel (VOCC) β subunits are important for the activity of praziquantel, supporting an earlier hypothesis about its mechanism of action.
The authors hope that elucidation of the mechanism of praziquantel toxicity – albeit in a free-living flatworm species – will help in the rational design of new antischistosomal drugs.