Antimalarial activity of artefenomel against asexual parasites and transmissible gametocytes during experimental blood-stage Plasmodium vivax infection.

BACKGROUND

Interventions that effectively target Plasmodium vivax are critical for the future control and elimination of malaria. We conducted a P. vivax volunteer infection study to characterise the antimalarial activity of artefenomel, a new drug candidate.

METHODS

Eight healthy, malaria-naïve participants were intravenously inoculated with blood-stage P. vivax and subsequently received a single oral 200 mg dose of artefenomel. Blood samples were collected to monitor the development and clearance of parasitemia, and plasma artefenomel concentration. Mosquito feeding assays were conducted prior to artefenomel dosing to investigate parasite transmissibility.

RESULTS

Initial parasite clearance occurred in all participants following artefenomel administration (log10 parasite reduction ratio over 48 hours 1.67; parasite clearance half-life 8.67 h). Recrudescence occurred in 7 participants 11-14 days after dosing. A minimum inhibitory concentration of 0.62 ng/mL and minimum parasiticidal concentration that achieves 90% of maximum effect of 0.83 ng/mL was estimated, and a single 300 mg dose was predicted to clear 109 parasites/mL with 95% certainty. Gametocytemia developed in all participants and was cleared 4-8 days after dosing. At peak gametocytemia, 75% of participants were infectious to mosquitoes.

CONCLUSIONS

The in vivo antimalarial activity of artefenomel supports its further clinical development as a treatment for P. vivax malaria.