Efficacy and safety of antimalarial combinations for treatment of uncomplicated malaria in children in Bangui, Central African Republic

Abstract

The aim of this study was to evaluate the efficacy and safety of three anti-malarial combinations--artemether-lumefantrine (A-L), amodiaquine-sulfadoxine-pyrimethamine (AQ-SP), and artesunate-amodiaquine (AQ-AS)--in the treatment of uncomplicated malaria in children younger than 5 years in Bangui, Central African Republic. This study included 186 children aged 6-59 months with uncomplicated falciparum malaria who were treated at the Bédé Combattant Hospital from July through October 2010: 63 randomized to receive A-L, 63 AQ-SP, and 60 AQ-AS. Clinical outcome was classified according to WHO criteria as early treatment failure (ETF), late clinical failure (LCF), late parasitological failure (LPF), or adequate clinical and parasitological response (ACPR). The occurrence of mutations in the pfcrt, pfmdr-1, dhfr and dhps genes was studied by PCR-RFLP. After PCR correction, ACPR at D28 was 100% for A-L, 96.55% for AQ-SP, and 100% for AQ-AS, with no significant difference between the three combinations (p = 0.36). The 2 cases of treatment failure for AQ-SP were associated with mutations at the following resistance markers: Pfcrt 76T, PfmdrI 86Y, Dhfr 108N, and Dhps A437. There was no significant difference in the reduction of anemia, fever (p = 0.87), or parasitemia (p = 0.63) between the three combinations. This study demonstrates that artemisinin-based combinations are still effective and tolerated in the treatment of uncomplicated malaria in children younger than 5 years in Bangui. Treatment failures were due to new infections and mutations in resistance markers.