12/18/2012

Randomized, Open Label Trial of Primaquine Against Vivax Malaria Relapse in Indonesia (Antimicrob Agents Chemother., abstract, edited)

[Source: Antimicrobial Agents and Chemotherapy, full text: (LINK). Abstract, edited.]

Randomized, Open Label Trial of Primaquine Against Vivax Malaria Relapse in Indonesia

Inge Sutanto 1, Bagus Tjahjono 2, Hasan Basri 3, W. Robert Taylor 3, Fauziah A. Putri 3, Rizka A. Meilia 3, Rianto Setiabudy 1, Siti Nurleila 3, Lenny L. Ekawati 3, Iqbal Elyazar 3, Jeremy Farrar 4,5, Herawati Sudoyo 6 and J. Kevin Baird 3,5↴

Author Affiliations: 1Faculty of Medicine, University of Indonesia, Jakarta, Indonesia; 2Health Service, Army of the Republic of Indonesia, Jakarta, Indonesia; 3Eijkman-Oxford Clinical Research Unit, Jakarta, Indonesia; 4Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; 5Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom; 6 Eijkman Institute for Molecular Biology, Jakarta, Indonesia

 

ABSTRACT

Background

Radical cure of Plasmodium vivax applies blood schizontocidal therapy against the acute attack and hypnozoitocidal therapy against later relapse. Chloroquine and primaquine have been used for 60 years in this manner. Resistance to chloroquine by the parasite now requires partnering other blood schizontocides with primaquine. However, the safety and efficacy of primaquine against relapse when combined with other drugs has not been demonstrated.

Methods

This randomized, open-label, and relapse-controlled trial estimated the efficacy of primaquine against relapse when administered with quinine or dihydroartemisinin-piperaquine for treatment of the acute infection. Among 650 soldiers returned to their malaria-free base in Java after 12 months in malarious Papua, 143 with acute P. vivax malaria were eligible for study. 116 enrolled subjects were randomized to these treatments: artesunate (200mg dose followed by 100mg/d×6days); quinine (1.8g/day×7days) plus concurrent primaquine (30mg/day×14days); or dihydroartemisinin (120mg) plus piperaquine (960mg) daily for 3 days followed 25 days later by primaquine (30mg/day×14days). Follow up was 12 months. 113 subjects were analyzable.

Findings

Relapse occurred in 32 of 41 (78%) subjects administered artesunate alone (2.71 attacks/person-year); 7 of 36 (19%) administered quinine plus primaquine (0.23 attacks/person-year); and 2 of 36 (6%) administered dihydroartemisinin-piperaquine plus primaquine (0.06 attacks/person-year). The efficacy of primaquine against relapse was 92% (95%CI=81%-96%) for quinine plus primaquine, and 98% (95%CI=91%-99%) for dihydroartemisinin-piperaquine plus primaquine.

Conclusions

Anti-relapse therapy with primaquine begun a month after treatment of the acute attack with dihydroartemisinin-piperaquine proved safe and highly efficacious against relapse by P. vivax acquired in Papua, Indonesia.

 

FOOTNOTES

Corresponding Author: Dr. J. K. Baird, Eijkman-Oxford Clinical Research Unit, Jalan Diponegoro No.69, Jakarta 10430 Indonesia, or at kbaird@eocru.org.

Copyright © 2012, American Society for Microbiology. All Rights Reserved.

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