In vitro responses of praziquantel-resistant and -susceptible Schistosoma mansoni to praziquantel

Abstract

The resistance status of five praziquantel-susceptible and five praziquantel-resistant isolates was confirmed by chemotherapy in CD(1) mice with 3 x 200mg/kg micronised praziquantel. Micronised praziquantel had higher efficacy than two other praziquantel formulations (prepared without milling). The five resistant isolates were less responsive to praziquantel than the five susceptible isolates (59-74% reduction in worm burden in resistant isolates compared with 92-100% in susceptible isolates). Observations were made on the in vitro responses of different stages of 10 isolates to praziquantel. There were different in vitro responses to praziquantel at the egg, miracidial, cercarial and adult stages of Schistosoma mansoni between praziquantel-resistant and praziquantel-susceptible isolates. There were differences in the response of resistant and susceptible isolates following exposure of freshly hatched miracidia to 10(-6)M praziquantel for 1 min and observing the percent change in shape. Using this test it should be possible to determine whether failed therapy in patients infected with S. mansoni is due to the presence of praziquantel-resistant worms. Similarly, by exposing freshly shed cercariae to 4 x 10(-7)M praziquantel and observing the percent of tail shedding over 80 min it should be possible to monitor for the presence of praziquantel-resistant worms in snails collected in the field.