RESUMEN
We conducted a randomized single-blinded trial comparing the efficacy and safety of artesunate (AS) + amodiaquine (AQ, 3 days) versus AS (3 days) + sulfadoxine-pyrimethamine (SP, single dose) versus AS monotherapy (5 days) in Southern Mali. Uncomplicated malaria cases were followed for 28 days. Molecular markers of drug resistance were determined. After identification of recrudescences by genotyping, both artemisinin-based combination therapies (ACTs) reached nearly 100% efficacy at Day 14 and Day 28 versus 98.3% and 96.5% for AS, respectively (P > 0.05). AS + SP significantly selected DHFR and DHPS mutations associated with sulfadoxine and pyrimethamine resistance (P < 0.001), and AS + AQ equally selected PfCRT and PfMDR1 point mutations associated with chloroquine and AQ resistance (P < 0.001). No significant adverse event attributable to any of the study drugs was found. The ACTs were efficacious and safe, but the selection of markers for resistance to the partner drugs raises concerns over their lifespan in areas of intense malaria transmission.
Asunto(s)
Amodiaquina/uso terapéutico , Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Resistencia a Medicamentos , Malaria Falciparum/tratamiento farmacológico , Pirimetamina/uso terapéutico , Sesquiterpenos/uso terapéutico , Sulfadoxina/uso terapéutico , Amodiaquina/administración & dosificación , Amodiaquina/efectos adversos , Animales , Artemisininas/administración & dosificación , Artemisininas/efectos adversos , Artesunato , Biomarcadores/análisis , Combinación de Medicamentos , Quimioterapia Combinada , Humanos , Malaria Falciparum/epidemiología , Malí/epidemiología , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/genética , Pirimetamina/administración & dosificación , Pirimetamina/efectos adversos , Sesquiterpenos/administración & dosificación , Sesquiterpenos/efectos adversos , Sulfadoxina/administración & dosificación , Sulfadoxina/efectos adversos , Factores de Tiempo , Vómitos/inducido químicamenteRESUMEN
The choice of artemisinin-based combination that is being adopted for malaria treatment in sub-Saharan Africa may depend on several factors, including cost, efficacy, side effects, and simplicity of administration. We tested the hypothesis that artesunate-sulfamethoxypyrazine-pyrimethamine is as efficacious as the four-dose regimen of artemether-lumefantrine for treatment of Plasmodium falciparum malaria. The study was carried out during two transmission seasons (2003 and 2004) in Sotuba, Mali. Participants at least 6 months of age with uncomplicated P. falciparum malaria were randomly assigned to receive artesunate-sulfamethoxypyrazine-pyrimethamine or artemether-lumefantrine. Treatment efficacy was assessed using the World Health Organization 28-day protocol. A total of 606 (303 in each arm) patients were enrolled. The cure rate was higher for artesunate-sulfamethoxypyrazine-pyrimethamine than for artemether-lumefantrine (98.7% versus 89.6%; P < 0.0001). After correction for cases of re-infection, the cure rates were 100% and 99.0%, respectively (P = 0.08). No serious adverse events occurred. Artesunate-sulfamethoxypyrazine-pyrimethamine is well-tolerated and effective against P. falciparum malaria. It showed an additional benefit of preventing new infections.