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High-dose Primaquine Regimens against Relapse of Plasmodium vivax Malaria

Srivicha Krudsood^*, Noppadon Tangpukdee, Polrat Wilairatana, Nantaporn Phophak, J. Kevin Baird, Gary M. Brittenham, AND Sornchai Looareesuwan

Plasmodium vivax causes debilitating but usually non-lethal malaria in most of Asia and South America. Prevention of relapse after otherwise effective therapy for the acute attack requires a standard daily dose of primaquine administered over 14 days. This regimen has < 90% efficacy in Thailand, and is widely regarded as ineffective because of poor compliance over the relatively long duration of dosing. We evaluated the efficacy, safety, and tolerability of alternative primaquine dosing regimens combined with artesunate among 399 Thai patients with acute, symptomatic P. vivax malaria. Patients were randomly assigned to one of six treatment groups: all patients received artesunate, 100 mg once a day for 5 days. Groups 1–5 then received primaquine, 30 mg a day for 5, 7, 9, 11, and 14 days, respectively. Group 6 received primaquine, 30 mg twice a day for 7 days. The 28-day cure rates were 85%, 89%, 94%, 100%, and 96%, respectively. Treatment of P. vivax malaria with artesunate for 5 days followed by high-dose primaquine, 30 mg twice a day for 7 days, was highly effective, well-tolerated, and equivalent or superior to the standard regimen of primaquine therapy.

Received July 6, 2007. Accepted for publication January 26, 2008.

Acknowledgments: We thank the patients for participating in the study and the nurses and laboratory technicians of Bangkok Hospital for Tropical Diseases (Faculty of Tropical Medicine, Mahidol University) for help.

Financial support: The study was supported by the World Health Organization Regional Office for South-East Asia Region and a grant from Mahidol University.

Disclosure: The authors have no conflict of interest with respect to this study.

^* Address correspondence to Srivicha Krudsood, Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand. E-mail: tmsks{at}mahidol.ac.th

Deceased

Authors’ addresses: Srivicha Krudsood, Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand. Noppadon Tangpukdee, Polrat Wilairatana, and Nantaporn Phophak, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. J. Kevin Baird, ALERTAsia Foundation, Jakarta, Indonesia. Gary M. Brittenham, Department of Pediatrics and Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032. Sornchai Looareesuwan (deceased).