Convergent evolution of artemisinin and chloroquine resistance in Ethiopian Plasmodium falciparum parasites

Letebo, A, Vanheer, LNORCID logo, Engdaw, M, Alemayehu, DH, Deressa, JD, Adnew, B, Ayele, A, Keffale, M, Demisse, M, Seyoum, T, Shiferaw, M, Sime, H, Gebreegziabxier, A, Shimelash, A, Tafa, EB, Chali, W, Alemayehu, L, Kassa, FA, Zeleke, AJ, Hamza, TA, Tamirat, AB, Misganaw, T, Bogale, A, Abriham, ZY, Nasir, Y, Jebessa, G, Ejigu, LA, Yohannes, M, Kebede, BA, Ayele, MK, Abdo, M, Habtamu, G, Gizat, A, Phelan, JORCID logo, Matlock, B, Fidock, DA, Campino, SORCID logo, Assefa, A, Koepfli, C, Massebo, F and Tadesse, FGORCID logo (2025). Convergent evolution of artemisinin and chloroquine resistance in Ethiopian Plasmodium falciparum parasites. [Dataset]. Dryad. https://doi.org/10.5061/dryad.1vhhmgr6c
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The emergence of antimalarial drug resistance has threatened the control and elimination of malaria in Africa. Ethiopia, once a success story in case reduction, is now facing resurgence. This study examined the key drug resistance genes (Pfmdr1, Pfcrt, Pfk13, Pfdhfr, and Pfdhps) and mitochondrial genomes of 605 Plasmodium falciparum isolates from 15 districts across Ethiopia, varying in transmission intensity and P. vivax co-endemicity. A dominant PfMDR1 NFSND haplotype, associated with reduced lumefantrine susceptibility, was identified alongside near-fixation of the PfCRT CVIET chloroquine-resistant haplotype in specific areas. Concerningly, PfK13 variants associated with partial artemisinin resistance – R622I (10%), A675V (1.7%), and P441L (1.1%) – were expanding. Drug resistance markers were primarily found in settings with low transmission of P. falciparum and high levels of P. vivax coendemicity. Along with a distinct parasite lineage and limited gene flow, these findings suggest that local evolutionary and therapeutic pressures shape resistance. This underscores the urgent need for targeted genomic surveillance to guide tailored interventions and contain the spread of multidrug-resistant P. falciparum.

Keywords

Antimicrobial resistance, Genomics, Malaria, Biological sciences

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