Addis Abeba — A nationwide genomic surveillance study has identified widespread antimalarial drug-resistance markers in Ethiopia, including mutations associated with partial artemisinin resistance, raising concerns over the continued effectiveness of artemether-lumefantrine, the country's first-line treatment for Plasmodium falciparum malaria.
Although malaria outbreaks have risen sharply in many parts across Ethiopia since late 2022 and throughout 2023, the country experienced a further surge in cases from the beginning of 2024. Between January and August, more than 4.7 million new cases were reported, resulting in 918 deaths.
Published in Nature Microbiology on 5 August, the study analyzed 605 P. falciparum samples collected between 2019 and 2023 from 15 districts representing different malaria transmission settings and levels of Plasmodium vivax co-endemicity. Following quality control, 584 samples were retained for genetic analysis, covering five major drug-resistance genes: Pfcrt, Pfmdr1, Pfk13, Pfdhfr and Pfdhps.
Ethiopian election coverage The researchers said Ethiopia, which made significant progress in reducing malaria after adopting artemether-lumefantrine in 2004, is now experiencing a resurgence of the disease. The study identified the emergence and spread of PfK13 mutations associated with partial artemisinin resistance alongside persistent resistance markers for older antimalarial drugs.
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Discover moreAfricans & DiasporaBusiness news insightsForeign policy news "The emergence of antimalarial drug resistance threatens malaria control and elimination efforts in Africa," the study said.
Ethiopia travel guide The findings come amid a sharp recent malaria burden. UNICEF reported 1,439,158 malaria cases and 51 related deaths in Ethiopia between 1 September and 31 October 2025. Oromia accounted for 27.4% of cases, followed by Amhara at 24.3%, Southern Ethiopia at 13.1%, Central Ethiopia at 8.4% and Southwestern Ethiopia at 8.2%.
At least one malaria case was reported in 913 woredas, with 92.3% of cases laboratory confirmed. P. falciparum accounted for 60.8% of confirmed infections.
Among the study's most concerning findings was the PfK13 R622I mutation, a validated marker associated with partial artemisinin resistance. It was detected in 10% of the 572 isolates analyzed for PfK13, while another validated marker, A675V, was found in 1.7%. The candidate resistance marker P441L occurred in 1.1% of isolates.
R622I showed marked geographic variation, reaching 48.6% among samples from Gondar. A675V was more prominent in western Ethiopia, reaching 16.3% in Gambella Zuria, while P441L was mainly detected in Batu, where it occurred in 12.5% of samples.
The study also found persistent resistance markers for chloroquine and sulfadoxine-pyrimethamine (SP), despite the withdrawal of SP from malaria treatment in Ethiopia more than two decades ago. The chloroquine-resistance-associated PfCRT CVIET haplotype was detected in 61.2% of isolates, while PfMDR1 NFSND occurred in 93%.
Ethiopian election coverage Researchers linked the persistence of chloroquine-resistance markers partly to Ethiopia's malaria ecology, where P. vivax and P. falciparum circulate together. Chloroquine remains the first-line treatment for P. vivax, potentially maintaining drug pressure on P. falciparum in co-endemic areas.
Across the 15 surveillance sites, the annual parasite index between 2020 and 2022 ranged from 1.0 in Fedis to 124.0 in Salamago, while the proportion of P. vivax infections ranged from 2.4% in Gambella Zuria to 54% in Batu.
The researchers also found substantial co-occurrence of resistance markers. PfCRT N326S occurred with PfK13 R622I in 45 isolates, while PfCRT CVIET and R622I were found together in 40 isolates. They cautioned that the associations do not establish that chloroquine resistance directly causes artemisinin resistance.
"Although CVIET itself does not confer ART-R, it may create a permissive genetic background for Pfk13 mutations," the researchers wrote, adding that the patterns "probably reflect overlapping drug pressures from lumefantrine and chloroquine rather than true epistasis."
The study further identified persistent antifolate-resistance mutations. The PfDHFR triple-mutant AIRNI haplotype was found in half of 490 isolates, while the double-mutant AICNI accounted for 39.6%. In PfDHPS, the double-mutant ISGEAA was detected in 65.7% of 502 isolates, while the combined PfDHFR-PfDHPS quintuple haplotype associated with high-level SP resistance occurred in 42.8% of 453 samples.
Researchers said the persistence of SP-resistance mutations may be linked to continued selective pressure from trimethoprim-sulfamethoxazole, widely used in HIV care, as well as the continued availability of SP and chloroquine in the private sector.
The study identified climate variability, human and environmental factors, insecticide resistance, invasive mosquito species, deletions affecting malaria rapid diagnostic tests and partial artemisinin resistance among factors potentially contributing to the resurgence.
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It warned that further spread of artemisinin resistance could undermine artemether-lumefantrine, given the country's reliance on lumefantrine-based therapies.
"If ART-R spreads further, AL efficacy could be compromised," the study said.
The authors called for region-specific malaria control strategies supported by integrated genomic surveillance of both P. falciparum and P. vivax, alongside diversification of the antimalarial arsenal.
"Sustaining ACT effectiveness will require region-specific control measures guided by integrated surveillance, and proactive diversification of the antimalarial arsenal to stay ahead of evolving resistance," the researchers concluded.
They said whole-genome sequencing and longitudinal surveillance linked to clinical outcomes will be needed to track the evolution of resistance and guide treatment policies, while noting that the current analysis focused on known resistance markers in a limited number of genes and may not capture other resistance mechanisms.
