Poster Presentation First Malaria World Congress 2018

Comparison of the cumulative efficacy and safety of chloroquine, artesunate and chloroquine-primaquine in Plasmodium vivax malaria (#258)

Cindy S Chu 1 , Aung Pyae Phyo 1 , Khin Maung Lwin 1 , Htun Htun Win 1 , Thida San 1 , Aye Aye Aung 1 , Rattanaporn Raksapraidee 1 , Verena Carrara 1 , Germana Bancone 1 , James Watson 2 , Kerryn A Moore 3 , Jacher Wiladphaingern 1 , Stéphane Proux 1 , Kanlaya Sriprawat 1 , Markus Winterberg 2 , Joel Tarning 2 , Mallika Imwong 4 , François Nosten 1 , Nicholas J White 2
  1. Shoklo Malaria Research Unit, Mae Sot, TAK, Thailand
  2. Mahidol–Oxford Tropical Medicine Research Unit, Bangkok, Thailand
  3. Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Australia
  4. Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand


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 [3] 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.


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  2. White NJ. Determinants of relapse periodicity in Plasmodium vivax malaria. Malar J 2011; 10:297.
  3. Commons RJ, Thriemer K, Humphreys G, et al. The Vivax Surveyor: Online mapping database for Plasmodium vivax clinical trials. Int J Parasitol Drugs Drug Resist 2017; 7:181–190.
  4. Nelwan EJ, Ekawati LL, Tjahjono B, et al. Randomized trial of primaquine hypnozoitocidal efficacy when administered with artemisinin-combined blood schizontocides for radical cure of Plasmodium vivax in Indonesia. BMC Med 2015; 13:294.
  5. Betuela I, Rosanas-Urgell A, Kiniboro B, et al. Relapses contribute significantly to the risk of Plasmodium vivax infection and disease in Papua New Guinean children 1-5 years of age. J Infect Dis 2012; 206:1771–80.