Discussion
malaria, deaths
MALARIA, ADVERSE EVENT
This is the first study to evaluate the efficacy and safety of a single 300-mg dose of tafenoquine co-administered with an artemisinin-based combination therapy for the radical cure of The reasons for the lack of clinically relevant efficacy with tafenoquine plus dihydroartemisinin–piperaquine are unknown. Although no pharmacokinetic data are yet available, a pharmacokinetic interaction is considered unlikely given that there was no clinically significant pharmacokinetic interaction between tafenoquine and dihydroartemisinin–piperaquine in a previous healthy volunteer study.Previous studies of primaquine plus chloroquine indicate that diminished primaquine efficacy might be associated with impaired CYP2D6 activity.The soldiers' battalion had a significant effect on estimates of efficacy, whereas other covariates (weight and baseline parasite counts) exerted no significant influence on the primary endpoint. Although these observations did not change the overall interpretation of the study (treatment differences were in the same direction in both battalions), there was a notably higher relapse rate across all treatment groups in the second battalion compared with the first battalion, which could not be explained by differences in study conduct or drug supplies. Despite both battalions having similar baseline characteristics and being deployed to the same region of Indonesian Papua for similar durations, sharp differences in transmission intensity within that region are believed to have occurred. Battalion 1 had been working in a sparsely populated and forested sector, whereas battalion 2 had been operating in a relatively settled (cleared forest) and populated area—conditions conducive to relatively light and heavy malaria transmission, respectively—on the basis of the dominant anopheline vectors in New Guinea, which prefer open sunlight to shady forests.Consideration has been given to whether the 300-mg dose of tafenoquine used in this study might be suboptimal.Patients in this study were infected with The adverse event profile for tafenoquine plus dihydroartemisinin–piperaquine was consistent with the known adverse event profiles for the individual drugs and there were no new safety signals. There were no deaths, and no patients withdrew from the study. Two patients had a serious adverse event, which the investigator considered related to study treatment, but neither received tafenoquine. QTc prolongation is a known risk with dihydroartemisinin–piperaquine.The current study has several limitations. It was only done in patients who had been infected with The study design in which patients were infected in a highly malarious region and returned to an area free of malaria transmission meant that In conclusion, the results of this study do not support co-administration of single 300-mg dose tafenoquine with dihydroartemisinin–piperaquine for the radical cure of 

