Randomized, Double-Blind, Placebo-Controlled Trial of Monthly versus Bimonthly Dihydroartemisinin-Piperaquine Chemoprevention in Adults at High Risk of Malaria
- 1 March 2012
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 56 (3), 1571-1577
- https://doi.org/10.1128/aac.05877-11
Abstract
Intermittent preventive treatment (IPT) is increasingly used to reduce malaria morbidity and mortality in children and pregnant women. The efficacy of IPT depends on the pharmacokinetic and pharmacodynamic properties of the antimalarial drugs used. Healthy adult male volunteers whose occupation put them at high risk of malaria on the Northwest border of Thailand were randomized to receive a 3-day-treatment dose of dihydroartemisinin-piperaquine monthly (DPm) or every 2 months (DPalt) or an identical placebo with or without fat (6.4g/dose) over a 9-month period. All volunteers were monitored weekly. One thousand adults were recruited. Dihydroartemisinin-piperaquine was well tolerated. There were 114 episodes of malaria (49 Plasmodium falciparum, 63 P. vivax, and 2 P. ovale). The protective efficacy against all malaria at 36 weeks was 98% (95% confidence interval [CI], 96% to 99%) in the DPm group and 86% (95% CI, 81% to 90%) in the DPalt group (for both, P < 0.0001 compared to the placebo group). As a result, the placebo group also had lower hematocrits during the study (P < 0.0001). Trough plasma piperaquine concentrations were the main determinant of efficacy; no malaria occurred in participants with a trough concentration above 31 ng/ml. Neither plasma piperaquine concentration nor efficacy was influenced by the coadministration of fat. DPm is safe to use and is effective in the prevention of malaria in adult males living in an area where P. vivax and multidrug-resistant P. falciparum malaria are endemic.Keywords
This publication has 17 references indexed in Scilit:
- Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trialThe Lancet Infectious Diseases, 2010
- Long-Lasting Insecticidal Hammocks for Controlling Forest Malaria: A Community-Based Trial in a Rural Area of Central VietnamPLOS ONE, 2009
- Safety and Efficacy of Dihydroartemisinin-Piperaquine in Falciparum Malaria: A Prospective Multi-Centre Individual Patient Data AnalysisPLOS ONE, 2009
- Changes in the Treatment Responses to Artesunate-Mefloquine on the Northwestern Border of Thailand during 13 Years of Continuous DeploymentPLOS ONE, 2009
- Population Pharmacokinetics of Piperaquine after Two Different Treatment Regimens with Dihydroartemisinin-Piperaquine in Patients with Plasmodium falciparum Malaria in ThailandAntimicrobial Agents and Chemotherapy, 2008
- Development and validation of a liquid chromatographic-tandem mass spectrometric method for determination of piperaquine in plasma: Stable isotope labeled internal standard does not always compensate for matrix effectsJournal of Chromatography B, 2008
- Randomized Comparison of Amodiaquine plus Sulfadoxine-Pyrimethamine, Artemether-Lumefantrine, and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Burkina FasoClinical Infectious Diseases, 2007
- Effects of a High-Fat Meal on the Relative Oral Bioavailability of PiperaquineAntimicrobial Agents and Chemotherapy, 2005
- Intermittent Presumptive Treatment for MalariaPLoS Medicine, 2005
- Population pharmacokinetics of piperaquine in adults and children with uncomplicated falciparum or vivax malariaBritish Journal of Clinical Pharmacology, 2004