Short-course, high-dose primaquine regimens for treatment of liver-stage vivax malaria in children.

Objectives: To assess the pharmacokinetics, safety, and tolerability of two high-dose short-course PQ regimens compared to standard care in children with Plasmodium vivax infections.

Methods: We performed an open-label paediatric dose-escalation study in Madang, Papua New Guinea (Clinicaltrials.gov NCT02364583). Children aged 5-10 years with confirmed blood-stage vivax malaria and normal G6PD activity were allocated to one of three PQ treatment regimens in a stepwise design (Group A: 0·5 mg/kg once daily for 14-days, Group B: 1 mg/kg once daily for 7-days, and Group C: 1 mg/kg twice daily for 3·5-days). Study assessments were completed at each treatment time-point, and fortnightly for 2-months after PQ administration.

Results: Between August 2013 and May 2018, 707 children were screened and 73 met eligibility criteria (15, 40 and 16 allocated to Groups A, B and C, respectively). All children completed study procedures. The three regimens were safe and generally well tolerated. Pharmacokinetic analysis indicated that additional weight adjustment of conventionally recommended mg/kg PQ doses is not necessary to ensure therapeutic plasma concentrations in paediatric patients.

Conclusions: A novel ultra-short 3·5-day PQ regimen has potential benefits for improving treatment outcomes in children with vivax malaria that warrants further investigation in large-scale clinical trial.