Evaluation of mefloquine-praziquantel combination therapy in pre- patent and patent Schistosoma mansoni infection in mice
نویسندگان
چکیده
The reliance on a single drug to treat a population of over 200 million people infected and over 700 million people at risk over three continents seems particularly perilous when considering the threat of drug resistance. An important shortcoming of praziquantel is its relative inactivity against migratory juvenile and subadult worms. Antischistosomal properties of the antimalarial drug, mefloquine were previously noticed and it was found potent against the young developing stages of the parasite. Moreover, the difference in the mechanism of action between the two drugs was encouraging to assess the antischistosomal effect of their combined curative doses (400 mg/kg mefloquine and 500 mg/kg praziquantel) or half-curative doses (200 mg/kg mefloquine and 250 mg/kg praziquantel) in both pre-patent and patent schistosome infections. Therapeutic efficacies of the drugs were assessed using the worm count technique, ova count technique in intestine and liver, oogram pattern, liver function tests and histopatholoical examination of liver sections. With the exception of mild additive reduction of ova count in the liver, mefloquine monotherapy was as potent as the combined full dose regimen. The combined treatment was much potent than praziquantel monotherapy even in its low dose regimen.
منابع مشابه
Mefloquine—An Aminoalcohol with Promising Antischistosomal Properties in Mice
BACKGROUND The treatment and control of schistosomiasis, an often neglected tropical disease that exacerbates poverty, depends on a single drug, praziquantel. The large-scale use of praziquantel might select for drug-resistant parasites, hence there is a need to develop new antischistosomal compounds. Here, we report that the antimalarial drug mefloquine possesses promising antischistosomal pro...
متن کاملInteractions of mefloquine with praziquantel in the Schistosoma mansoni mouse model and in vitro.
OBJECTIVES Mefloquine has interesting antischistosomal properties, hence it might be an attractive partner drug for combination treatment with praziquantel. The aim of this study was to evaluate activities of mefloquine/praziquantel combinations against Schistosoma mansoni in vitro and in vivo. METHODS Dose-response relationships were established following exposure of adult S. mansoni to mefl...
متن کاملSchistogram changes after administration of antischistosomal drugs in mice at the early phase of Schistosoma mansoni infection
Mice infected with Schistosoma mansoni were treated with oxamniquine, praziquantel, artesunate at the pre-patent phase, aiming at observing schistogram alterations. Half of the animals were perfused five days post-treatment for counting and classification of immature worms, based on pre-established morphological criteria (schistogram); the remaining animals were evaluated 42 or 100 days after i...
متن کاملBlockade of Pge2, Pgd2 Receptors Confers Protection against Prepatent Schistosomiasis Mansoni in Mice.
Schistosomiasis is a chronic disease with considerable social impact. Despite the availability of affordable chemotherapy, drug treatment has not significantly reduced the overall number of disease cases. Among other mechanisms, the parasite produces PGE2 and PGD2 to evade host immune defenses. To investigate the role of PGE2 and PGD2 in schistosomiasis, we evaluated the effects of L-161,982, A...
متن کاملPharmacodynamics of mefloquine and praziquantel combination therapy in mice harbouring juvenile and adult Schistosoma mansoni.
Praziquantel (PZQ) is currently the only drug widely used for the treatment of schistosomiasis, but the antimalarial drug mefloquine (Mef) possesses interesting antischistosomal properties. Combination therapy with these two drugs has been suggested as a strategy for transmission control, as PZQ is active against adult worms and Mef is active against schistosomula. To examine the efficacy of co...
متن کامل