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.

To determine whether artemether, a derivative of the antimalarial agent qinghaosu, is therapeutically active against Schistosoma mansoni, we determined the in vitro, in vivo, and histopathologic effects of the drug on S. mansoni worms. In vitro, toxic effects of artemether on S. mansoni were not seen at concentrations of less than 100 ,ug/ml. However, in vivo, 30 Qinghaosu (artemisinin) is a new antimalarial drug derived from a traditional Chinese herbal remedy, qinghao or Artemisia annua L. (7). To enhance the antimalarial activity and solubility of qinghaosu (Fig. 1A), a series of chemical derivatives of qinghaosu, e.g., artemether and artesunate, have been synthesized and studied in laboratory and clinical trials (8, 13). As a result of these studies, qinghaosu, artemether (Fig. 1B), and artesunate were found to be active against malarial parasites as well as effective in the treatment of Schistosoma japonicum infections (9, 10). Thus, qinghaosu (2) and its derivatives appear to have antischistosomal as well as antimalarial chemotherapeutic potential. Recently, it was suggested (3) that resistance might be developing to praziquantel, the current drug of choice for the treatment of all species of human schistosomiasis (5). Thus, continued identification and evaluation of new antischistosomal agents are important in the event that clinical resistance to praziquantel therapy develops. Using Schistosoma mansoni-infected mice as a model of infection as well as for a source of parasites for in vitro studies, we investigated the potential usefulness of artemether in the treatment of S. mansoni infections.(An abstract of this work was published as part of the proceedings of the Southern Regional Meeting of the Amer-

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Long-term treatment with doxycycline did not improve outcomes of GWVIs at 1 year.