• Cindy S Chu, Aung Pyae Phyo, Khin Maung Lwin, Htun Htun Win, Thida San, Aye Aye Aung, Rattanaporn Raksapraidee, Verena I Carrara, Germana Bancone, James Watson, Kerryn A Moore, Jacher Wiladphaingern, Stéphane Proux, Kanlaya Sriprawat, Markus Winterberg, Phaik Yeong Cheah, Amy L Chue, Joel Tarning, Mallika Imwong, François Nosten, and Nicholas J White.
• Department of Medicine, Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
• Clin. Infect. Dis. 2018 Oct 30; 67 (10): 1543-1549.

BackgroundChloroquine 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.MethodsPatients 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.ResultsBetween 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).ConclusionsVivax malaria relapses are predominantly delayed by chloroquine but prevented by primaquine.Clinical Trials RegistrationNCT01074905.

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