Study of the Relationship between the Presence of the Pfcrt 76T Mutation and the Therapeutic Efficacy of the Artesunate-Amodiaquine Combination in the Treatment of Uncomplicated Plasmodium falciparum Malaria in Burkina Faso

Abstract

The emergence and development of resistance of Plasmodium falciparum to antimalariques commonly used (chloroquine, sulfadoxine-pyrimethamine) led to the adoption of combinations based on artemisinin including artesunate amodiaquine, which has shown a good therapeutic efficacy in areas where amodiaquine monotherapy remains effective. The genetic mutation Pfcrt 76T has been validated as a marker that confers resistance to chloroquine. So far, there is no known marker associated with resistance to artesunate. Because of the structural similarity of amodiaquine with chloroquine, it is interesting to investigate the existence of an association between the presence of point mutation Pfcrt 76T and effectiveness of the association for artesunate amodiaquine, better monitoring of the development of resistance to ACT (Artemisinin-based Combination Therapies). We conducted a randomized clinical trial opened in two rural sites in Burkina Faso (Dande and Gourcy) during which we assessed the therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine in patients with uncomplicated malaria and monitored them for 28 days. The study of polymorphism parasitic PCR has helped distinguish new infections from recrudescences (Real failures). In total, 47 patients were treated with artesunate and amodiaquine and included in this study. The cumulative treatment failure (clinical and parasitological) was 14.89% (7/47). The study of parasitic polymorphism showed 12.77% (6/47) cases of recrudescence (real failure). A total 48.94% of patients were carriers of the mutation Pfcrt 76T before treatment and 66.67% among recrudescences. In Burkina Faso, artesunate-amodiaquine is still effective; there was no association of the point mutation Pfcrt 76T with clinical outcomes of the patients treated with artesunate-amodiaquine. Other point mutations may be investigated to help with these drugs’ failure prediction.