Combination treatments for uncomplicated falciparum malaria in Kampala, Uganda: randomised clinical trial.
BACKGROUND: Plasmodium falciparum resistance has rendered chloroquine monotherapy ineffective in much of Africa, but data on alternative regimens are limited. We compared chloroquine+sulfadoxine-pyrimethamine, amodiaquine+sulfadoxine-pyrimethamine, and amodiaquine+artesunate for treatment of uncomplicated malaria in Kampala, Uganda. METHODS: Of 1017 consecutive patients aged 6 months to 10 years with uncomplicated malaria who were screened, 418 were randomised to receive: chloroquine (25 mg/kg over 3 days) and sulfadoxine-pyrimethamine (25 mg/kg sulfadoxine, 1.25 mg/kg pyrimethamine, single dose); amodiaquine (25 mg/kg over 3 days) and sulfadoxine-pyrimethamine; or amodiaquine and artesunate (4 mg/kg daily for 3 days). Primary efficacy outcomes were 28-day clinical failure risks, adjusted and unadjusted by genotyping to distinguish new infection and recrudescence. The primary safety endpoint was incidence of serious adverse events during follow-up. Analysis was intention to treat and per protocol. FINDINGS: 18 patients were excluded before enrollment. Of those enrolled, 384 of 400 (96%) were assigned an efficacy outcome and 396 (99%) were assessed for safety. Risk of 28-day clinical treatment failure was significantly higher with chloroquine+sulfadoxine-pyrimethamine (44/125 [35%]) than with amodiaquine+sulfadoxine-pyrimethamine (12/129 [9%]; risk difference 26% [95% CI 16-36]; p<0.0001) or amodiaquine+artesunate (3/130 [2%]; 33% [24-42]; p<0.0001). The greater risk of clinical treatment failure with amodiaquine+sulfadoxine-pyrimethamine was balanced by a lower risk of new infection, resulting in a similar need for retreatment over 28 days for amodiaquine+sulfadoxine-pyrimethamine (17/129 [13%]) and amodiaquine+artesunate (16/130 [12%]; p=0.854). Serious adverse events were uncommon with all regimens. INTERPRETATION: Risk of treatment failure with chloroquine+sulfadoxine-pyrimethamine was unacceptably high. Combinations of amodiaquine and sulfadoxine-pyrimethamine or artesunate were significantly more efficacious, and each regimen could be an appropriate alternative for treatment of uncomplicated malaria in Africa.
Item Type | Article |
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Keywords | Amodiaquine/administration & dosage/adverse effects, Antimalarials/*administration & dosage/adverse effects, Artemisinins/administration & dosage/adverse effects, Child, Child, Preschool, Chloroquine/administration & dosage/adverse effects, Drug Combinations, Drug Therapy, Combination, Female, Humans, Infant, Malaria, Falciparum/*drug therapy, Male, Pyrimethamine/administration & dosage/adverse effects, Sesquiterpenes/administration & dosage/adverse effects, Sulfadoxine/administration & dosage/adverse effects, Treatment Failure, Uganda, Amodiaquine, administration & dosage, adverse effects, Antimalarials, administration & dosage, adverse effects, Artemisinins, administration & dosage, adverse effects, Child, Child, Preschool, Chloroquine, administration & dosage, adverse effects, Drug Combinations, Drug Therapy, Combination, Female, Humans, Infant, Malaria, Falciparum, drug therapy, Male, Pyrimethamine, administration & dosage, adverse effects, Sesquiterpenes, administration & dosage, adverse effects, Sulfadoxine, administration & dosage, adverse effects, Treatment Failure, Uganda |
ISI | 225327000033 |