The burden of Plasmodium vivax relapse has long been recognised. In South East Asia and Oceania P. vivax relapses early and frequently [1,2]. Chloroquine is the standard schizonticidal treatment against P. vivax, but resistance is increasing. High-grade resistance appears still confined to Oceania and Indonesia  where dihydroartemisinin-piperaquine is now the standard treatment. The benefit of using a long acting partner drug that provides post treatment prophylaxis against recurrence is unclear. Prevention of relapse requires radical treatment with an 8-aminoquinoline (primaquine) but carries the risk of haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient persons. As G6PD testing is seldom available, primaquine is commonly not given despite being widely recommended. Preventing relapses with primaquine could reduce the total number of relapses substantially [4,5]. To compare the cumulative benefits of using slowly eliminated (chloroquine) versus rapidly eliminated (artesunate) antimalarials in P. vivax malaria, to determine whether chloroquine prevents or delays relapses, and to characterise the risks and benefits of radical cure (primaquine), a three way randomised comparison was conducted on the Thailand-Myanmar border.
From May 2010 to October 2012, 644 patients were enrolled. Parasite clearance was faster with artesunate compared to chloroquine. Recurrence rates by day 28 were: artesunate (50%, 112/224), chloroquine (8%, 18/222; p<0.001) and chloroquine-primaquine (0.5%, 1/198; p<0.001). The median (IQR) days to a first recurrence were: artesunate 28 (21 – 42), chloroquine 49 (35 – 74) and chloroquine-primaquine 195 (82 – 281). The addition of primaquine reduced the recurrence rate by 94% compared to chloroquine. Recurrence rates over one year were: artesunate 4.51 (95% CI 4.19 to 4.85)/person year, chloroquine 3.45 (95% CI 3.18 – 3.75); p=0.002 and chloroquine-primaquine 0.26 (95% CI 0.19 – 0.36); p<0.001.
Chloroquine retains clinical efficacy in this population. Chloroquine delays rather than prevents relapse. Radical cure with primaquine eliminates most recurrences.