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

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.