Effects of praziquantel on different developmental stages of Schistosoma mansoni in vitro and in vivo.

To discern whether stage-specific resistance of Schistosoma mansoni to praziquantel occurs in vitro, we determined minimal effective concentrations (MECs) of drug needed to increase motor activity, produce contraction and/or paralysis, and cause tegumental vesiculation of developmental stages from day 0 to day 42 of S. mansoni. Recovery of these stages from exposure to praziquantel in vitro was also evaluated. MECs of praziquantel inducing increased motor activity and muscular contraction or paralysis or both were 0.005-0.01 micrograms/ml, irrespective of the stage examined. However, day-3 lung forms were more resistant than other stages when either drug-induced tegumental vesiculation (MEC, 1 microgram/ml) or recovery from drug exposure was tested. Three-day infections with S. mansoni in CF1 mice were also less responsive to praziquantel treatment than were infections of shorter or longer duration. The concentrations of praziquantel and periods of drug exposure causing gross tegumental damage to S. mansoni in vitro correlated with the peak serum levels and time course of unchanged praziquantel associated with reduction of worm burden in vivo. Thus, stage-specific resistance of S. mansoni to praziquantel does occur in vitro and correlates better with the tegumental than the muscular action of the drug.