Efficacy of dihydroartemisinin/piperaquine in patients with noncomplicated Plasmodium falciparum malaria in Yaoundé, Cameroon

Mélissa Mairet-Khedim (1, 2, 3) , Sandrine Nsango (4, 5) , Christelle Ngou (5, 6) , Sandie Menard (2) , Camille Roesch (1) , Nimol Khim (1) , Sreynet Srun (1) , Xavier Iriart (2, 7) , Thomas Lanot (7) , Laure Otam (2, 8) , Francis Abega (9) , Lawrence Ayong (1) , Isabelle Morlais (10) , Peggy Gandia (7, 11) , Benoit Witkowski (1) , Antoine Berry (2, 7)

1 Malaria Molecular Epidemiology
2 Infinity - Institut Toulousain des Maladies Infectieuses et Inflammatoires
3 Microb. Struc. (UMR_3528 / U-Pasteur_5) - Microbiologie structurale - Structural Microbiology
4 Université de Douala
5 Centre Pasteur du Cameroun
6 MIVEGEC - Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle
7 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
8 UN - Université de Ngaoundéré/University of Ngaoundéré [Cameroun]
9 Dispensaire Nkol Eton, , Yaounde, Cameroon
10 MIVEGEC-TRIAD - Transmission-Interactions-Adaptations hôtes/vecteurs/pathogènes
11 InTheRes - Innovations Thérapeutiques et Résistances

Background: Dihydroartemisinin/piperaquine is increasingly used for the treatment of uncomplicated Plasmodium falciparum malaria in Africa. The efficacy of this combination in Cameroon is poorly documented, while resistance to dihydroartemisinin/piperaquine readily spreads in Southeast Asia. Objectives: This study evaluated the clinical efficacy of dihydroartemisinin/piperaquine in Cameroon, as well as the molecular profile and phenotypic susceptibility of collected isolates to dihydroartemisinin and piperaquine. Patients and methods: Dihydroartemisinin/piperaquine efficacy in 42 days was followed-up for 138 patients presenting non-complicated falciparum malaria. Piperaquine concentration was determined at day 7 for 124 patients. kelch13 gene polymorphisms (n = 150) and plasmepsin2 gene amplification (n = 148) were determined as molecular markers of resistance to dihydroartemisinin and piperaquine, respectively. Parasite susceptibility to dihydroartemisinin and piperaquine was determined using validated in vitro survival assays. Results: The efficacy of dihydroartemisinin/piperaquine treatment was 100% after PCR correction. The reinfections were not associated with a variation of piperaquine concentration at day 7. Ninety-six percent (144/150) of the samples presented a WT allele of the kelch13 gene. Two percent (3/150) presented the non-synonymous mutation A578S, which is not associated with resistance to dihydroartemisinin. No duplication of the plasmep-sin2 gene was observed (0/148). All the samples tested in vitro by survival assays (n = 87) were susceptible to dihydroartemisinin and piperaquine. Conclusions: Dihydroartemisinin/piperaquine has demonstrated excellent therapeutic efficacy with no evidence of emerging artemisinin or piperaquine resistance in Yaoundé, Cameroon. This observation suggests that dihydroartemisinin/piperaquine could be a sustainable therapeutic solution for P. falciparum malaria if implemented in areas previously free of artemisinin-and piperaquine-resistant parasites, unlike Southeast Asia.

Domains: Life Sciences [q-bio]; Microbiology and Parasitology; Parasitology

Mélissa Mairet-Khedim, Sandrine Nsango, Christelle Ngou, Sandie Menard, Camille Roesch, et al.. Efficacy of dihydroartemisinin/piperaquine in patients with noncomplicated Plasmodium falciparum malaria in Yaoundé, Cameroon. Journal of Antimicrobial Chemotherapy, 2021, 76 (11), pp.3037-3044. ⟨10.1093/jac/dkab281⟩. ⟨pasteur-03494748⟩