Stability and reproductive fitness of Schistosoma mansoni isolates with decreased sensitivity to praziquantel

These studies are focused on schistosomes derived from human infections not cured by three successive doses of praziquantel that also produced infecti ons in mice that were significantly more difficult to cure than infections with control worms. Half (three of six) of these isolates retained their de creased response to praziquantel after multiple passages through the life-c ycle in the absence of therapeutic pressure. Two of the isolates, including the one initially least sensitive to praziquantel reverted, to a sensitivi ty not significantly different from controls. For example, the EE6 isolate initially required 680 mg/ka praziquantel to affect a 50% reduction in worm load in murine infections, but after only six passages through the life cy cle over 5 years this was reduced to 113 mg/kg, not different from control infections. The stability of sonic of the isolates and the reversion of oth ers indicates that the biological or genetic factors conferring decreased p raziquantel response varies among the isolates. The three isolates that ret ained decreased sensitivity to praziquantel all showed compromises in repro ductive fitness in the laboratory, expressed most frequently as a decreased cercarial production from snails infected with those isolates compared to controls. For example, the total cercarial production of snails infected wi th the EE10 isolate was only 57% that of controls. The reversion of some of the isolates to a praziquantel sensitive state and the decreased reproduct ive fitness of those that did not revert suggest that there is sonic biolog ical cost associated with the relative praziquantel insensitivity of these worms, which could help limit the impact of such isolates in the field. Inf ections with the less sensitive isolates also produced significantly less c irculating schistosomal antigen in mice, suggesting that a decrease in the host immune response elicited by these worms could be one of the factors co ntributing to the diminished praziquantel efficacy. (C) 2001 Australian Soc iety for Parasitology Inc. Published by Elsevier Science Ltd. All rights re served.