Randomized, Controlled Dose-Optimization Studies of Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Multidrug-Resistant Falciparum Malaria in Thailand
Elizabeth A. Ashley, Srivicha Krudsood, Lucy Phaiphun, Siripan Srivilairit, Rose McGready, วัฒนา เลี้ยววัฒนา, Robert Hutagalung, Polrat Wilairatana, Alan Brockman, Sornchai Looareesuwan, Franc¸ois Nosten, Nicholas J. White
Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand (nickw@tropmedres.ac)
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 140% 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.
The Journal of Infectious Diseases ปี 2547, November ปีที่: 190 ฉบับที่ 10 หน้า 1773-1782