Mefloquine—An Aminoalcohol with Promising Antischistosomal Properties in Mice

Abstract

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 properties in mice. A single dose of mefloquine (200 or 400 mg/kg) administered orally to mice infected with adult Schistosoma mansoni or adult S. japonicum resulted in high or complete total and female worm burden reductions (72.3%–100%). Importantly, high worm burden reductions were also observed for young developing stages of S. mansoni and S. japonicum harbored in the mouse. Both mefloquine erythro-enantiomers resulted in high and comparable total and female worm burden reductions when given to mice with either a sub-patent or patent S. mansoni infection. Our findings hold promise for the development of a novel antischistosomal drug based on an aminoalcohol functionality. Further in vitro and in vivo studies have been launched to elucidate the possible mechanism of action and to study the effect of mefloquine on S. haematobium and other trematodes. It will be interesting to investigate whether mefloquine, which is widely and effectively used for the treatment of malaria, has an impact on schistosomiasis in areas where both malaria and schistosomiasis co-exist. Schistosomiasis is a chronic and debilitating disease that occurs in tropical and subtropical areas. The disease is caused by an infection with a parasitic worm and affects over 200 million people. The treatment and control of schistosomiasis relies on a single drug, praziquantel. This drug is increasingly used, and hence there is mounting concern about the development of resistance to praziquantel. Here we report that mefloquine, a marketed drug for prophylaxis and treatment of malaria, shows promising antischistosomal properties in laboratory studies with mice. When mefloquine was orally administered at a single dose of 200 or 400 mg/kg to mice infected with young or adult stages of the parasitic worm Schistosoma mansoni or S. japonicum, we found very high worm burden reductions. We also found high worm burden reductions when mefloquine enantiomers were given to mice infected with adult S. mansoni. Further studies are needed because our results might be of public health relevance. Indeed, mefloquine is widely used for prophylaxis and treatment of malaria, often in areas where both malaria and schistosomiasis co-exist. In such areas, it might be possible that the use of mefloquine against malaria reduces the burden of schistosomiasis.