Artesunate/Amodiaquine Versus Artemether/Lumefantrine for the Treatment of Uncomplicated Malaria in Uganda: A Randomized Trial.

Abstract

BACKGROUND:

In treating malaria in Uganda, artemether-lumefantrine (AL) has been associated with a lower risk of recurrent parasitemia, compared with artesunate-amodiaquine (AS/AQ), but changing treatment practices may have altered parasite susceptibility.

METHODS:

We enrolled 602 children aged 6-59 months with uncomplicated falciparum malaria from 3 health centers in 2013-2014 and randomly assigned them to receive treatment with AS/AQ or AL. Primary outcomes were risks of recurrent parasitemia within 28 days, with or without adjustment to distinguish recrudescence from new infection. Drug safety and tolerability and Plasmodium falciparum resistance-mediating polymorphisms were assessed.

RESULTS:

Of enrolled patients, 594 (98.7%) completed the 28-day study. Risks of recurrent parasitemia were lower with AS/AQ at all 3 sites (overall, 28.6% vs 44.6%; P < .001). Recrudescences were uncommon, and all occurred after AL treatment (0% vs 2.5%; P = .006). Recovery of the hemoglobin level was greater with AS/AQ (1.73 vs 1.39 g/dL; P = .04). Both regimens were well tolerated; serious adverse events were uncommon (1.7% in the AS/AQ group and 1.0% in the AL group). AS/AQ selected for mutant pfcrt/pfmdr1 polymorphisms and AL for wild-type pfcrt/pfmdr1 polymorphisms associated with altered drug susceptibility.

CONCLUSIONS:

AS/AQ treatment was followed by fewer recurrences than AL treatment, contrasting with older data. Each regimen selected for polymorphisms associated with decreased treatment response. Research should consider multiple or rotating regimens to maintain treatment efficacies.

• Authors: Adoke Yeka, Ruth Kigozi, Melissa D Conrad, Myers Lugemwa, Peter Okui, Charles Katureebe, Kassahun Belay, Bryan K Kapella, Michelle A Chang, Moses R Kamya, Sarah G Staedke, Grant Dorsey, Philip J Rosenthal
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 213 Issue 7 Pg. 1134-42 (Apr 01 2016) ISSN: 1537-6613 [Electronic] United States
• PMID: 26597254 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
• Copyright: © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail [email protected].

Chemical References

• Artemether, Lumefantrine Drug Combination
• Artemisinins
• Drug Combinations
• Ethanolamines
• Fluorenes
• amodiaquine, artesunate drug combination
• Amodiaquine

Topics

• Amodiaquine (therapeutic use)
• Artemether, Lumefantrine Drug Combination
• Artemisinins (therapeutic use)
• Child, Preschool
• Drug Combinations
• Ethanolamines (therapeutic use)
• Female
• Fluorenes (therapeutic use)
• Humans
• Infant
• Malaria, Falciparum (drug therapy, epidemiology)
• Male
• Uganda (epidemiology)