Cindy S. ChuAung Pyae PhyoKhin Maung LwinHtun Htun WinThida SanAye Aye AungRattanaporn RaksapraideeVerena I. CarraraGermana BanconeJames WatsonKerryn A. MooreJacher WiladphaingernStéphane ProuxKanlaya SriprawatMarkus WinterbergPhaik Yeong CheahAmy L. ChueJoel TarningMallika ImwongFrançois NostenNicholas J. WhiteMelbourne School of Population and Global HealthMacfarlane Burnet Institute for Medical ResearchMahidol UniversityNuffield Department of Clinical MedicineMahidol-Oxford Tropical Medicine Research Unit2019-08-232019-08-232018-10-30Clinical Infectious Diseases. Vol.67, No.10 (2018), 1543-154915376591105848382-s2.0-85052723930https://repository.li.mahidol.ac.th/handle/20.500.14594/46241© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. 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.Mahidol UniversityMedicineArticleSCOPUS10.1093/cid/ciy319