Ex vivo RSA and pfkelch13 targeted-amplicon deep sequencing reveal parasites susceptibility to artemisinin in Senegal, 2017

• Published in: Malaria Journal
• Main Authors: Mamadou Samb Yade, Baba Dièye, Romain Coppée, Aminata Mbaye, Mamadou Alpha Diallo, Khadim Diongue, Justine Bailly, Atikatou Mama, Awa Fall, Alphonse Birane Thiaw, Ibrahima Mbaye Ndiaye, Tolla Ndiaye, Amy Gaye, Abdoulaye Tine, Younouss Diédhiou, Amadou Mactar Mbaye, Cécile Doderer-Lang, Mamane Nassirou Garba, Amy Kristine Bei, Didier Ménard, Daouda Ndiaye
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2023
• Subjects: Malaria; Plasmodium falciparum; Artemisinin partial resistance; Ring-stage Survival Assay; Pfkelch13 genotype; Targeted-amplicon deep sequencing; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-023-04588-1; https://doaj.org/article/e410a711431e4fd0be8c703234366640

Abstract Background Malaria control is highly dependent on the effectiveness of artemisinin-based combination therapy (ACT), the current frontline malaria curative treatment. Unfortunately, the emergence and spread of parasites resistant to artemisinin (ART) derivatives in Southeast Asia and South America, and more recently in Rwanda and Uganda (East Africa), compromise their long-term use in sub-Saharan Africa, where most malaria deaths occur. Methods Here, ex vivo susceptibility to dihydroartemisinin (DHA) was evaluated from 38 Plasmodium falciparum isolates collected in 2017 in Thiès (Senegal) expressed in the Ring-stage Survival Assay (RSA). Both major and minor variants were explored in the three conserved-encoding domains of the pfkelch13 gene, the main determinant of ART resistance using a targeted-amplicon deep sequencing (TADS) approach. Results All samples tested in the ex vivo RSA were found to be susceptible to DHA (parasite survival rate < 1%). The non-synonymous mutations K189T and K248R in pfkelch13 were observed each in one isolate, as major (99%) or minor (5%) variants, respectively. Conclusion The results suggest that ART is still fully effective in the Thiès region of Senegal in 2017. Investigations combining ex vivo RSA and TADS are a useful approach for monitoring ART resistance in Africa.