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

Background: 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. Methods: 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. Results: 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. Conclusion: 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.