Increase of Plasmodium falciparum parasites carrying lumefantrine-tolerance molecular markers and lack of South East Asian pfk13 artemisinin-resistance mutations in samples collected from 2013 to 2016 in Côte d’Ivoire

Abstract

AbstractOne of the major obstacles to malaria elimination in the world is the resistance in Plasmodium falciparum to most antimalarial drugs. This study aimed to estimate the prevalence of molecular markers of antimalarial drugs resistance in Côte d’Ivoire. Samples were collected from 2013 to 2016 from asymptomatic and symptomatic subjects in Abengourou, Abidjan, Grand Bassam, and San Pedro. A total of 704 participants aged between 1 year and 65 years (Mean age: 9 years ± 7.7) were enrolled. All the dried filter paper blood spots were genotyped by sequencing. Plasmodium falciparum kelch propeller domain 13 (pfk13) gene were analyzed for all the samples, while 344 samples were examined for Plasmodium falciparum multi-drug resistance 1 (pfmdr1). Overall, the success rate of molecular tests was 98.8% (340/344), 99.1% (341/344), and 94.3% (664/704) for pfmdr1 N86Y, pfmdr1 Y184F, and pfk13 genes respectively. Molecular analysis revealed twenty (5.9%; 20/340) and 219 (64.2%; 219/341) mutant alleles for pfmdr1 86Y and pfmdr1 184 F, respectively. Twenty-nine mutations in pfk13 gene (4.4%; 29/664) with 2.7% (18/664) of non-synonymous mutations was found. None of the mutations previously described in South East Asia (SEA) involved in P. falciparum resistance to artemisinin derivatives were observed in this study. According to year of collection, a decrease of the prevalence of pfk13 mutation (from 3.6 to 1.8%) and pfmdr1 N86Y mutation (from 8.5 to 4.5%) and an increase of mutant allele of pfmdr1 Y184F proportion (from 39.8 to 66.4%) were found. Comparing to previous studies in the country, this study showed an increase in lumefantrine tolerance of P. falciparum strains. This demonstrates the importance of establishing a strong system for molecular surveillance of malaria in Côte d’Ivoire.