Dessalegn Geleta, Bokretsion G Brhane, Adugna Abera, Mahlet Belachew, Heven Sime, Atsbeha Gebreegziaxher, Melak Getu, Abraham Ali, Neamin Tesfay, Medhanye Habtetsion, Belayneh Kokobe, Mandefro Kebede, Zemene Worku, Geremew Tasew, Gemechu Tadesse, Getachew Tollera, Abebe A Fola, Jeffrey A Bailey, Jonathan J Juliano, Jonathan B Parr, Melkamu Abte, Ashenafi Assefa
The current study documents cases of recurrent parasitemia caused by P. falciparum with K13 P441L during the malaria resurgence in Gelana district of the Oromia region, Ethiopia. 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.
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 are threatened by the emergence of artemisinin partial resistance (ART-R), which is associated with mutations in the P. falciparum kelch13 (k13) gene, that could undermine treatment efficacy and accelerate transmission.
METHODS AND MATERIAL: The study was conducted as part of country wide resurgence response. 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 two 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 pfk13, pfcrt, pfmdr1, pfdhfr, and pfdhps using PfSMARRTer multiplex amplicon sequencing in Addis Ababa, Ethiopia. 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 nearly 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 Gelana district of the Oromia region, Ethiopia. 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.