Journal Article

Comparison of the Cumulative Efficacy and Safety of Chloroquine, Artesunate, and Chloroquine-Primaquine in Plasmodium vivax Malaria

San, Thida, Proux, Stéphane, Aung, Aye Aye, Bancone, Germana, Winterberg, Markus, Chu, Cindy S, Raksapraidee, Rattanaporn, Carrara, Verena I, Lwin, Khin Maung, Imwong, Mallika, Chue, Amy L, White, Nicholas J, Moore, Kerryn A, Watson, James, Win, Htun Htun, Cheah, Phaik Yeong, Wiladphaingern, Jacher, Tarning, Joel, Phyo, Aung Pyae, Sriprawat, Kanlaya, Nosten, François

2018

Overview

Vivax malaria relapses frequently even in low-transmission settings. Chloroquine delays but does not prevent recurrences. Adding primaquine to a slowly eliminated schizonticide significantly reduces recurrences and improves hematocrit, but this advantage is offset by hemolysis in G6PD-deficient females. Abstract Background Chloroquine has been recommended for Plasmodium vivax infections for >60 years, but resistance is increasing. To guide future therapies, the cumulative benefits of using slowly eliminated (chloroquine) vs rapidly eliminated (artesunate) antimalarials, and the risks and benefits of adding radical cure (primaquine) were assessed in a 3-way randomized comparison conducted on the Thailand-Myanmar border. Methods Patients with uncomplicated P. vivax malaria were given artesunate (2 mg/kg/day for 5 days), chloroquine (25 mg base/kg over 3 days), or chloroquine-primaquine (0.5 mg/kg/day for 14 days) and were followed for 1 year. Recurrence rates and their effects on anemia were compared. Results Between May 2010 and October 2012, 644 patients were enrolled. Artesunate cleared parasitemia significantly faster than chloroquine. Day 28 recurrence rates were 50% with artesunate (112/224), 8% with chloroquine (18/222; P < .001), and 0.5% with chloroquine-primaquine (1/198; P < .001). Median times to first recurrence were 28 days (interquartile range [IQR], 21-42) with artesunate, 49 days (IQR, 35-74) with chloroquine, and 195 days (IQR, 82-281) with chloroquine-primaquine. Recurrence by day 28, was associated with a mean absolute reduction in hematocrit of 1% (95% confidence interval [CI], .3%-2.0%; P = .009). Primaquine radical cure reduced the total recurrences by 92.4%. One-year recurrence rates were 4.51 (95% CI, 4.19-4.85) per person-year with artesunate, 3.45 (95% CI, 3.18-3.75) with chloroquine (P = .002), and 0.26 (95% CI, .19-.36) with chloroquine-primaquine (P < .001). Conclusions Vivax malaria relapses are predominantly delayed by chloroquine but prevented by primaquine. Clinical Trials Registration NCT01074905.

• Publisher: Oxford University Press
• Subject: Adolescent / Adult / and Commentaries / Antimalarials - therapeutic use / Artesunate - therapeutic use / Child / Child, Preschool / Chloroquine - therapeutic use / Drug Therapy, Combination / Female / Humans / Infant / Malaria, Vivax - drug therapy / Male / Middle Aged / Myanmar / Parasitemia - drug therapy / Plasmodium vivax - drug effects / Primaquine - therapeutic use / Recurrence / Thailand / Treatment Outcome / Young Adult