Predominance of Wild K13 Propeller Haplotypes in three localities of Côte d'Ivoire one decade after the adoption of Therapeutic Combinations based on Artemisinin Derivatives

Background: The emergence of P. falciparum resistance to artemisinin-based combination therapy (ACT) threatens malaria control in Africa. The monitoring of polymorphisms in molecular markers associated with antimalarial drug resistance is essential for malaria control and elimination efforts. The purpose of this study is to analyze the polymorphism of the pfK13 propeller gene of P. falciparum to artemisinin-based combination therapy (ACT) in three sites in southern Côte d'Ivoire. Methods: After obtaining informed consent, blood samples were collected from patients of any sex and aged over 2 years with uncomplicated P. falciparum malaria in Anonkoua-Kouté, Port-Bouët and Ayamé. P. falciparum genomic DNA was extracted and amplified by Nested-PCR using Pfk13 propeller gene-specific primers. The amplification products were sequenced using the Sanger method at Eurofins Genomics. The key codons (493, 539, 543 and 580), molecular markers of the resistance of P. falciparum to ACTs and the additional codons (476 and 561) were analyzed. Results: A total of 186 DNA extracts from blood samples collected from the three study sites were amplified and sequenced. Of the 93 PCR products sequenced, 84.94% (158/186), 91.39% (170/186), 95.69% (178/186), 100% (186/186), 82.79% (154/186) and 94.62% (178/186) corresponding to codons 493, 539, 543, 580, 476, 561, respectively, were successfully analyzed. Thus, the prevalences of wild-type alleles were 92.40% (Tyr493), 94.11% (Arg539), 94.38% (Ile543), 91.39% (Cys580), 89.61% (Met476) and 88.63% (Arg561) against 1.26% (His493), 3.52% (Thr539) and 1.29% (Ile476) of mutant alleles. The mutant alleles Thr543, Tyr580, and His561 were not observed in all three study sites. The analysis indicated a predominance of the YRICMR allelic form representing a susceptible haplotype (78.49%). No significant difference was observed between the prevalences of the wild-type alleles determined in the three study sites (p>0.05). Conclusion: More than a decade after the adoption of ACTs for the management of uncomplicated malaria, these combinations are still effective in Anonkoua-Kouté, Port-Bouët and Ayamé in the south of Côte d'Ivoire.