Treatment of uncomplicated multidrug-resistant falciparum malaria with artesunate-atovaquone-proguanil.
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.
van Vugt
Michèle
M
Shoklo Malaria Research Unit, Mae Sot, Thailand.
Leonardi
Elisabetta
E
Phaipun
Lucy
L
Slight
Thra
T
Thway
Kyaw Lay
KL
McGready
Rose
R
Brockman
Alan
A
Villegas
Leopoldo
L
Looareesuwan
Sornchai
S
White
Nicholas J
NJ
Nosten
François
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use; D000077332:Artesunate; D053626:Atovaquone; D002648:Child; D002675:Child, Preschool; D018432:Drug Resistance, Multiple / Q000502:physiology*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009285:Naphthoquinones / Q000009:adverse effects / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects; D002727:Proguanil / Q000009:adverse effects / Q000627:therapeutic use; D012717:Sesquiterpenes / Q000009:adverse effects / Q000627:therapeutic use; D017211:Treatment Failure
D000962:Antimalarials; D037621:Artemisinins; D009285:Naphthoquinones; D012717:Sesquiterpenes; D000077332:Artesunate; D002727:Proguanil; D053626:Atovaquone