LAUSR

Due to resistance to chloroquine and sulfadoxine-pyrimethamine, treatment for uncomplicated Plasmodium falciparum malaria switched to artemisinin-based combination therapy (ACT) in 2006 in Senegal. Several mutations in the gene coding the kelch13 helix (pfk13-propeller) were identified to be associated with in vitro and in vivo artemisinin resistance in Southeast Asia. Additionally, three mutations in the pfcoronin gene (G50E, R100K and E107V) have been identified in two culture-adapted Senegalese field isolates which became resistant in vitro to artemisinin after 4 years of intermittent selection with dihydroartemisinin. The aims of this study were first to assess the prevalence of pfcoronin and pfk13 mutations in Senegalese field isolates from Dakar and then to investigate their association with artemisinin derivatives clinical failures. A total of 348 samples of P. falciparum from 327 patients, collected from 2015 to 2019 in the Hôpital Principal de Dakar, were successfully analyzed. All sequences had wild-type pfk13 allele. The three mutations (G50E, R100K and E107V), previously identified in reduced susceptibility parasites to artemisinin, were not found in the present study but a new mutation P76S was detected (mean prevalence 16.2%). The P76S mutation was identified in 5 of the 16 isolates (31.3%) collected from patients still parasitaemic on Day 3 after ACT treatment and in 31 samples among the 203 patients considered as successfully cured (15.3%). There was no significant association between in vivo reduced efficacy to artemisinin derivatives and the P76S mutation (p = 0.151; Fisher's exact test). The present data suggest that polymorphisms on pfk13 and pfcoronin are not the best predictive markers for artemisinin resistance in Senegal.