Transmission-blocking activity of artesunate, chloroquine and methylene blue onPlasmodium vivaxgametocytes

Abstract

ABSTRACTPlasmodium vivaxis now the main cause of malaria outside Africa. The gametocytocidal effects of antimalarial drugs are important to reduce malaria transmissibility, particularly in low transmission settings, but they are not well characterized forP. vivax. The transmission-blocking effects of chloroquine, artesunate and methylene blue onP. vivaxgametocytes were assessed. Blood specimens were collected from patients presenting with vivax malaria, incubated with or without the tested drugs, and then fed to mosquitos from a laboratory-adapted colony ofAnopheles dirus(a major malaria vector in Southeast Asia). The effects on oocyst and sporozoite development were analyzed under a multi-level Bayesian model accounting for assay variability and the heterogeneity of mosquitoPlasmodium-infection. Artesunate and methylene blue, but not chloroquine, exhibited potent transmission-blocking effects. Gametocyte exposures to artesunate and methylene blue reduced the mean oocyst count 469 fold (95%CI: 345 to 650) and 1438 fold (95%CI: 970 to 2064) respectively. The corresponding estimates for the sporozoite stage were a 148 fold reduction (95%CI: 61 to 470) and a 536 fold reduction (95%CI: 246 to 1311) in the mean count, respectively. In contrast, high chloroquine exposures reduced the mean oocyst count by only 1.40 fold (95%CI: 1.20 to 1.64) and the mean sporozoite count 1.34 fold (95%CI: 1.12 to 1.66). This suggests that patients with vivax malaria often remain infectious to anopheline mosquitos after treatment with chloroquine. Immediate initiation of primaquine radical cure or use of artemisinin combination therapies would reduce the transmissibility ofP. vivaxinfections.