Mefloquine--an aminoalcohol with promising antischistosomal properties in mice

Abstract

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 properties in mice.

Methodology/principal findings: 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.

Conclusions/significance: 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.

Figure 1. Chemical structures of mefloquine, quinine, halofantrine, and lumefantrine.

Figure 2. Stage-specific susceptibility of mefloquine compared to praziquantel in the S. mansoni- and S. japonicum-mouse models.

Red squares: mefloquine 400 mg/kg, blue circles: praziquantel 400 mg/kg. The stage-specific susceptibilities of praziquantel and mefloquine on S. mansoni have been established in the laboratories of the Swiss Tropical Institute (Basel, Switzerland). The efficacy of praziquantel against S. japonicum has been reported by Yue et al. and that of mefloquine has been established at the laboratories of the National Institute of Parasitic Diseases (Shanghai, China).