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In an open-label trial carried out on the northwest border of Thailand, 1596 patients with uncomplicated multidrug-resistant falciparum malaria were randomly assigned to receive atovaquone-proguanil, atovaquone-proguanil-artesunate, or artesunate-mefloquine and were followed up for 42 days. All 3 regimens were highly effective and well tolerated. Fever duration and parasite clearance times were significantly shorter among patients who received artesunate (P<.001). Polymerase chain reaction genotyping confirmed that recrudescence occurred in 13 patients who received artesunate-mefloquine (2.4%), 5 who received atovaquone-proguanil-artesunate (0.9%), and 15 who received atovaquone-proguanil (2.8%). Adding artesunate to atovaquone-proguanil reduced the risk of failure 3-fold (95% confidence interval [CI], 1.1-8.2) and subsequent gametocyte carriage 21-fold (95% CI, 14-30). Gastrointestinal complaints in the first 48 h after initiation of treatment were more common among artesunate recipients, but after day 2, dizziness, sleep disturbance, nausea, vomiting, and anorexia were more common among mefloquine recipients (P< or =.014). Artesunate-atovaquone-proguanil is a highly effective and well-tolerated treatment for multidrug-resistant falciparum malaria.

Original publication

DOI

10.1086/344901

Type

Journal article

Journal

Clin Infect Dis

Publication Date

15/12/2002

Volume

35

Pages

1498 - 1504

Keywords

Adolescent, Adult, Aged, Animals, Antimalarials, Artemisinins, Artesunate, Atovaquone, Child, Child, Preschool, Drug Resistance, Multiple, Drug Therapy, Combination, Female, Humans, Malaria, Falciparum, Male, Middle Aged, Naphthoquinones, Plasmodium falciparum, Proguanil, Sesquiterpenes, Treatment Failure