Sulphadoxine/pyrimethamine versus amodiaquine for treating uncomplicated childhood malaria in Gabon: a randomized trial to guide national policy

• Published in: Malaria journal Vol. 7; no. 1; p. 31
• Main Authors: Nsimba, Basile, Guiyedi, Vincent, Mabika-Mamfoumbi, Modeste, Mourou-Mbina, Jean Romain, Ngoungou, Edgard, Bouyou-Akotet, Marielle, Loembet, Romaric, Durand, Rémy, Le Bras, Jacques, Kombila, Maryvonne
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 12.02.2008; BioMed Central; BMC
• Subjects: Amodiaquine - therapeutic use; Animals; Antimalarials - therapeutic use; Artemisinins - therapeutic use; Child, Preschool; Dihydropteroate Synthase - genetics; Drug Resistance; Drug Therapy, Combination; Female; Follow-Up Studies; Gabon; Health Policy; Humans; Infant; Infant, Newborn; Malaria, Falciparum - drug therapy; Malaria, Falciparum - parasitology; Male; Mutation; Plasmodium falciparum - enzymology; Plasmodium falciparum - genetics; Plasmodium falciparum - isolation & purification; Polymerase Chain Reaction; Pyrimethamine - therapeutic use; Sesquiterpenes - therapeutic use; Sulfadoxine - therapeutic use; Treatment Outcome; Gabon
• ISSN: 1475-2875; 1475-2875
• DOI: 10.1186/1475-2875-7-31

In Gabon, following the adoption of amodiaquine/artesunate combination (AQ/AS) as first-line treatment of malaria and of sulphadoxine/pyrimethamine (SP) for preventive intermittent treatment of pregnant women, a clinical trial of SP versus AQ was conducted in a sub-urban area. This is the first study carried out in Gabon following the WHO guidelines. A random comparison of the efficacy of AQ (10 mg/kg/day x 3 d) and a single dose of SP (25 mg/kg of sulphadoxine/1.25 mg/kg of pyrimethamine) was performed in children under five years of age, with uncomplicated falciparum malaria, using the 28-day WHO therapeutic efficacy test. In addition, molecular genotyping was performed to distinguish recrudescence from reinfection and to determine the frequency of the dhps K540E mutation, as a molecular marker to predict SP-treatment failure. The day-28 PCR-adjusted treatment failures for SP and AQ were 11.6% (8/69; 95% IC: 5.5-22.1) and 28.2% (20/71; 95% CI: 17.7-38.7), respectively This indicated that SP was significantly superior to AQ (P = 0.019) in the treatment of uncomplicated childhood malaria and for preventing recurrent infections. Both treatments were safe and well-tolerated, with no serious adverse reactions recorded. The dhps K540E mutation was not found among the 76 parasite isolates tested. The level of AQ-resistance observed in the present study may compromise efficacy and duration of use of the AQ/AS combination, the new first-line malaria treatment. Gabonese policy-makers need to plan country-wide and close surveillance of AQ/AS efficacy to determine whether, and for how long, these new recommendations for the treatment of uncomplicated malaria remain valid.