Ultra-short course, high-dose primaquine to prevent Plasmodium vivax infection following uncomplicated pediatric malaria: A randomized, open-label, non-inferiority trial of early versus delayed treatment

Objectives: We aimed to assess safety, tolerability, and Plasmodium vivax relapse rates of ultra-short course (3.5 days) high-dose (1 mg/kg twice daily) primaquine (PQ) for uncomplicated malaria because of any Plasmodium species in children randomized to early-or delayed treatment.Methods: Children aged 0.5 to 12 years with normal glucose-6-phosphate-dehydrogenase (G6PD) activ-ity were enrolled. After artemether-lumefantrine (AL) treatment, children were randomized to receive PQ immediately after (early) or 21 days later (delayed). Primary and secondary endpoints were the appear-ance of any P. vivax parasitemia within 42 or 84 days, respectively. A non-inferiority margin of 15% was applied (ACTRN12620 0 0 0855921).Results: A total of 219 children were recruited, 70% with Plasmodium falciparum and 24% with P. vivax. Abdominal pain (3.7% vs 20.9%, P < 0.0 0 01) and vomiting (0.9% vs 9.1%, P = 0.01) were more common in the early group. At day 42, P. vivax parasitemia was observed in 14 (13.2%) and 8 (7.8%) in the early and delayed groups, respectively (difference, -5.4%; 95% confidence interval -13.7 to 2.8). At day 84 , P. vivax parasitemia was observed in 36 (34.3%) and 17 (17.5%; difference -16.8%, -28.6 to -6.1).Conclusion: Ultra-short high-dose PQ was safe and tolerated without severe adverse events. Early treat-ment was non-inferior to delayed treatment in preventing P. vivax infection at day 42.(c) 2023 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

This study aimed to assess the safety, tolerability, and relapse rates of ultra-short course high-dose primaquine for uncomplicated malaria in children. The results showed that ultra-short high-dose primaquine was safe and well-tolerated, and early treatment was non-inferior to delayed treatment in preventing Plasmodium vivax infection.