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Background  Babesiosis represents a veterinary and medical threat, with a need for novel drugs. Artemisinin-based combination therapies (ACT) have been successfully implemented for malaria, a human disease caused by related parasites,  Plasmodium  spp. The aim of this study was to investigate whether ACT is active against  Babesia in vitro  and  in vivo .    Methods  Mefloquine, tafenoquine, primaquine, methylene blue and lumefantrine, alone or in combination with artesunate, were tested  in vitro  against  Babesia bovis . Parasite growth was verified using a SYBR green I-based fluorescence assay. Mice infected with  Babesia microti  were treated with mefloquine or tafenoquine, alone or in combination with artesunate, and parasitemia was verified by microscopy and PCR.    Results  All drugs, except lumefantrine, showed  in vitro  activity against  B .  bovis , with methylene blue showing the most potent activity (concentration 0.2 μM). Combination with artesunate led to improved activity, with mefloquine showing a striking 20-fold increase in activity. Tafenoquine (10 mg/kg, base), combined or not with artesunate, but not mefloquine, induced rapid clearance of  B .  microti in vivo  by microscopy, but mice remained PCR-positive. Blood from mice treated with tafenoquine alone, but not with tafenoquine-artesunate, was infective for naive mice upon sub-inoculation.    Conclusions  Tafenoquine, and most likely other 8-aminoquinoline compounds, are promising compounds for the development of ACT for babesiosis.

Activities of artesunate-based combinations and tafenoquine against Babesia bovis in vitro and Babesia microti in vivo