Prevalence in Northern Angola of Cytochrome P450 (CYP) 2C8 Alleles Associated with Amodiaquine Decreased Metabolism

Amodiaquine-artesunate is one of the recommended options by the Angolan National Malaria Control Program for the treatment of uncomplicated malaria and for malaria seasonal chemoprevention. CYP2C8 is a critical enzyme in the metabolism of amodiaquine. The CYP2C8 gene harbors alleles coding for less active enzymes that have been linked to amodiaquine-associated adverse events. In this work, we analyzed the prevalences of the CYP2C8 main alleles in a sample of the Angolan population. We found an expected robust frequency of a very-low-activity allele, CYP2C8*2 (18.2%) but also the unusual presence of alleles CYP2C8*3 (1%) and CYP2C8*4 (0.5%). Together, these alleles were seen in a non-negligible group of Plasmodium falciparum malaria patients and children under amodiaquine-based therapies and prophylactic strategies.