An Open Label, Randomised Trial of Artesunate+Amodiaquine, Artesunate+Chlorproguanil-Dapsone and Artemether-Lumefantrine for the Treatment of Uncomplicated Malaria

Abstract

BackgroundArtesunate+amodiaquine (AS+AQ) and artemether-lumefantrine (AL) are now the most frequently recommended first line treatments for uncomplicated malaria in Africa. Artesunate+chlorproguanil-dapsone (AS+CD) was a potential alternative for treatment of uncomplicated malaria. A comparison of the efficacy and safety of these three drug combinations was necessary to make evidence based drug treatment policies.MethodsFive hundred and thirty-four, glucose-6-phosphate dehydrogenase (G6PD) normal children were randomised in blocks of 15 to the AS+AQ, AL or AS+CD groups. Administration of study drugs was supervised by project staff and the children were followed up at r home on days 1,2,3,7,14 and 28 post treatment. Parasitological and clinical failures and adverse events were compared between the study groups.Main FindingsIn a per-protocol analysis, the parasitological and clinical failure rate at day 28 post treatment (PCF28) was lower in the AS+AQ group compared to the AL or AS+CD groups (corrected for re-infections: 6.6% vs 13.8% and 13.8% respectively, p = 0.08; uncorrected: 14.6% vs 27.6% and 28.1% respectively, p = 0.005). In the intention to treat analysis, the rate of early treatment failure was high in all three groups (AS+AQ 13.3%; AL 15.2%; and AS+CD 9.3%, p = 0.2) primarily due to vomiting. However, the PCF28 corrected for re-infection was lower, though not significantly, in the AS+AQ group compared to the AL or the AS+CD groups (AS+AQ 18.3%; AL 24.2%; AS+CD 20.8%, p = 0.4) The incidence of adverse events was comparable between the groups.ConclusionsAS+AQ is an appropriate first line treatment for uncomplicated malaria in Ghana and possibly in the neighbouring countries in West Africa. The effectiveness of AL in routine programme conditions needs to be studied further in West Africa.Trial RegistrationClinicalTrials.gov NCT00119145

Treatment with Coartem (Artemether-Lumefantrine) in Papua New Guinea

“…Rather low levels of drug efficacy had also been reported from two studies in Ghana 30,31 where PCR corrected cure rates at Day 28 were only 86.2% and 88.3%, respectively. In one of these studies only the first dose was given under supervision, whereas in the other study the administration of all 6 tablets was supervised.…”

Assessment of the efficacy of first-line antimalarial drugs after 5 years of deployment by the National Malaria Control Programme in Côte d'Ivoire

“…Therefore, the data are in line with studies conducted in Ghanaian children showing lower parasitological and clinical failure rates in the ASAQ compared with the AL arm. [37][38][39] In contrast, results from Central and East Africa show higher efficacy of AL than ASAQ, especially a higher potency in preventing reinfections. 14,40 In the present study, both treatments were equivalent regarding parasite and fever clearance rates and gametocyte carriage.…”

Chlorproguanil–Dapsone–Artesunate versus Chlorproguanil–Dapsone: A Randomized, Double-Blind, Phase III Trial in African Children, Adolescents, and Adults with Uncomplicated Plasmodium falciparum Malaria

“…29 A trial in Ghana reported PCR-corrected Day 28 parasitological and clinical cure rates (PP population) of 86.3% (138/160) for CPG-DDS + A, 86.2% (131/152) for AL, and 93.4% (141/151) for amodiaquine + A ( P = 0.08). 30 Neither of these studies has reported pfdhfr mutation frequencies, though the authors of the Rwandan study state that a later analysis is planned. 29 There was no difference in re-infection rates between CDA and CPG-DDS.…”