Treatment of uncomplicated multidrug-resistant falciparum malaria with artesunate-atovaquone-proguanil.

Abstract

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.

• Authors: Michèle van Vugt, Elisabetta Leonardi, Lucy Phaipun, Thra Slight, Kyaw Lay Thway, Rose McGready, Alan Brockman, Leopoldo Villegas, Sornchai Looareesuwan, Nicholas J White, François Nosten
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 35 Issue 12 Pg. 1498-504 (Dec 15 2002) ISSN: 1537-6591 [Electronic] United States
• PMID: 12471569 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Artemisinins
• Naphthoquinones
• Sesquiterpenes
• Artesunate
• Proguanil
• Atovaquone

Topics

• Adolescent
• Adult
• Aged
• Animals
• Antimalarials (adverse effects, therapeutic use)
• Artemisinins (adverse effects, therapeutic use)
• Artesunate
• Atovaquone
• Child
• Child, Preschool
• Drug Resistance, Multiple (physiology)
• Drug Therapy, Combination
• Female
• Humans
• Malaria, Falciparum (drug therapy)
• Male
• Middle Aged
• Naphthoquinones (adverse effects, therapeutic use)
• Plasmodium falciparum (drug effects)
• Proguanil (adverse effects, therapeutic use)
• Sesquiterpenes (adverse effects, therapeutic use)
• Treatment Failure