Recurrent parasitemias with artemisinin partial resistance mutations during the 2024 Ethiopia malaria resurgence: a case series

Abstract Background Ethiopia experienced a marked resurgence of malaria in 2024. Artemisinin-based combination therapies (ACTs) are first-line treatment for uncomplicated Plasmodium falciparum malaria and threatened by the emergence of artemisinin partial resistance (ART-R), associated with mutations in the P. falciparum kelch13 ( k13 ) gene, that could undermine treatment efficacy and accelerate transmission. Methods and material: We used the national Public Health Emergency Management (PHEM) surveillance system to characterize malaria resurgence and further investigate antimalarial drug resistance markers among cases of recurrent clinical malaria in three selected resurgence sites in central Ethiopia. Results Parasite isolates from 15 patients with confirmed clinical recurrent P. falciparum malaria were genotyped for molecular markers associated with drug resistance, including mutations in k13, pfcrt , pfmdr1 , pfdhfr , and pfdhps using PfSMARRTer multiplex amplicon sequencing in Addis Ababa. Clinical presentation and treatment history were reviewed alongside genotyping results. Three patients (3/15, 20%) with confirmed recurrence were infected by parasites carrying the WHO-candidate ART-R molecular marker K13 P441L. Markers of resistance to other antimalarial drugs were largely fixed in the population. These cases occurred in the context of increasing malaria incidence, with evidence of clonal expansion or dominance of a related lineage. The findings indicate the presence of ACT resistance-associated markers within genetically heterogeneous parasite populations. Conclusion The current study documents cases of recurrent parasitemia caused by P. falciparum with K13 P441L during the malaria resurgence in the Oromia region. The detection of multiple independent resistance markers suggests ongoing drug pressure on first-line treatments. These findings underscore the need for strengthened molecular surveillance integrated with routine case monitoring to inform treatment policy and support malaria control and elimination efforts in Ethiopia.