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Title: Randomized, controlled dose-optimization studies of dihydroartemisinin- piperaquine for the treatment of uncomplicated multidrug-resistant falciparum malaria in Thailand
Authors: Elizabeth A. Ashley
Srivicha Krudsood
Lucy Phaiphun
Siripan Srivilairit
Rose McGready
Wattana Leowattana
Robert Hutagalung
Polrat Wilairatana
Alan Brockman
Sornchai Looareesuwan
François Nosten
Nicholas J. White
Shoklo Malaria Research Unit
Mahidol University
Churchill Hospital
Menzies School of Health Research
Keywords: Medicine
Issue Date: 15-Nov-2004
Citation: Journal of Infectious Diseases. Vol.190, No.10 (2004), 1773-1782
Abstract: Background. Dihydroartemisinin-piperaquine (DP) is a new and relatively inexpensive artemisinin-containing fixed-combination antimalarial treatment. An adult treatment course contained 6.4 mg/kg dihydroartemisinin (DHA), which is >40% lower than the level in most artemisinin-containing combinations. This raised the possibility that the efficacy of the current coformulation may not be optimal in the treatment of multidrug-resistant falciparum malaria. Methods. In 2 large randomized, controlled studies in Thailand, the recommended dose of DP was compared with a regimen with additional artemisinin derivative (12 mg/kg; DP+) and with mefloquine plus artesunate (MAS3). Results. A total of 731 patients were included: 201 in a hospital-based study and 530 in a community study. Day-28 cure rates in the hospital-based study were 100% (95% confidence interval [CI], 93.9%-100%) in the MAS3 and DP+ groups and 98.3% (95% CI, 91%-99.7%) in the DP group, with a single recrudescence on day 21. In the community study, polymerase chain reaction genotyping-adjusted cure rates on day 63 were 96.1% (95% CI, 92.6%-99.7%) in the DP group, 98.3% (95% CI, 96.1%-100%) in the DP+ group, and 94.9% (95% CI, 91.2%-98.6%) in the MAS3 group (P = .2). Adverse events were few, with an excess of mild abdominal pain in the DP group. Conclusions. The current dosage of DP (6.4 mg/kg DHA and 51.2 mg/kg piperaquine phosphate) given over the course of 48 h is highly effective, safe, and well tolerated for the treatment of multidrug-resistant falciparum malaria, and its efficacy is not improved by the addition of more DHA.
ISSN: 00221899
Appears in Collections:Scopus 2001-2005

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