• Melissa D Conrad, Victor Asua, Shreeya Garg, David Giesbrecht, Karamoko Niaré, Sawyer Smith, Jane F Namuganga, Thomas Katairo, Jennifer Legac, Rebecca M Crudale, Patrick K Tumwebaze, Samuel L Nsobya, Roland A Cooper, Moses R Kamya, Grant Dorsey, Jeffrey A Bailey, and Philip J Rosenthal.
• From the University of California, San Francisco, San Francisco (M.D.C., S.G., J.L., G.D., P.J.R.); the Infectious Diseases Research Collaboration (V.A., J.F.N., T.K., P.K.T., S.L.N., M.R.K.) and Makerere University (M.R.K.) - both in Kampala, Uganda; the University of Tübingen, Tübingen, Germany (V.A.); Brown University, Providence, RI (D.G., K.N., S.S., R.M.C., J.A.B.); and Dominican University of California, San Rafael (R.A.C.).
• N. Engl. J. Med. 2023 Aug 24; 389 (8): 722732722-732.

BackgroundPartial resistance of Plasmodium falciparum to the artemisinin component of artemisinin-based combination therapies, the most important malaria drugs, emerged in Southeast Asia and now threatens East Africa. Partial resistance, which manifests as delayed clearance after therapy, is mediated principally by mutations in the kelch protein K13 (PfK13). Limited longitudinal data are available on the emergence and spread of artemisinin resistance in Africa.MethodsWe performed annual surveillance among patients who presented with uncomplicated malaria at 10 to 16 sites across Uganda from 2016 through 2022. We sequenced the gene encoding kelch 13 (pfk13) and analyzed relatedness using molecular methods. We assessed malaria metrics longitudinally in eight Ugandan districts from 2014 through 2021.ResultsBy 2021-2022, the prevalence of parasites with validated or candidate resistance markers reached more than 20% in 11 of the 16 districts where surveillance was conducted. The PfK13 469Y and 675V mutations were seen in far northern Uganda in 2016-2017 and increased and spread thereafter, reaching a combined prevalence of 10 to 54% across much of northern Uganda, with spread to other regions. The 469F mutation reached a prevalence of 38 to 40% in one district in southwestern Uganda in 2021-2022. The 561H mutation, previously described in Rwanda, was first seen in southwestern Uganda in 2021, reaching a prevalence of 23% by 2022. The 441L mutation reached a prevalence of 12 to 23% in three districts in western Uganda in 2022. Genetic analysis indicated local emergence of mutant parasites independent of those in Southeast Asia. The emergence of resistance was observed predominantly in areas where effective malaria control had been discontinued or transmission was unstable.ConclusionsData from Uganda showed the emergence of partial resistance to artemisinins in multiple geographic locations, with increasing prevalence and regional spread over time. (Funded by the National Institutes of Health.).Copyright © 2023 Massachusetts Medical Society.

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