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Artikel: Selection of artemisinin partial resistance Kelch13 mutations in Uganda in 2016-22 was at a rate comparable to that seen previously in South-East Asia.

Meier-Scherling, Cecile P G / Watson, Oliver J / Asua, Victor / Ghinai, Isaac / Katairo, Thomas / Garg, Shreeya / Conrad, Melissa / Rosenthal, Philip J / Okell, Lucy C / Bailey, Jeffrey A

medRxiv : the preprint server for health sciences

2024  

Abstract: Background: Artemisinin partial resistance, mediated by mutations in the : Methods: We investigated K13 mutation prevalence at 16 sites in Uganda (2016-2022, 6586 samples), and five sites in SEA (2003-2018, 5465 samples) by calculating selection ... ...

Abstract Background: Artemisinin partial resistance, mediated by mutations in the
Methods: We investigated K13 mutation prevalence at 16 sites in Uganda (2016-2022, 6586 samples), and five sites in SEA (2003-2018, 5465 samples) by calculating selection coefficients using Bayesian mixed-effect linear models. We then tested whether SEA K13 mutation prevalence could have been forecast accurately using up to the first five years of available data and forecast future K13 mutation prevalence in Uganda.
Findings: The selection coefficient for the prevalence of relevant K13 mutations (441L, 469F/Y, 561H, 675V) was estimated at s=0·383 (95% CrI: 0·247 - 0·528) per year, a 38% relative prevalence increase. Selection coefficients across Uganda were s=0·968 (0·463 - 1·569) for 441L, s=0·153 (-0·445 - 0·727) for 469F, s=0·222 (-0·011 - 0·398) for 469Y, and s=0·152 (-0·023 - 0·312) for 675V. In SEA, the selection coefficient was s=-0·005 (-0·852 - 0·814) for 539T, s=0·574 (-0·092 - 1·201) for 580Y, and s=0·308 (0·089 - 0·536) for all validated K13 mutations. Forecast prevalences for Uganda assuming constant selection neared fixation (>95% prevalence) within a decade (2028-2033) for combined K13 mutations.
Interpretation: The selection of K13 mutations in Uganda was at a comparable rate to that observed in SEA, suggesting K13 mutations may continue to increase quickly in Uganda.
Funding: NIH R01AI156267, R01AI075045, and R01AI089674.
Sprache Englisch
Erscheinungsdatum 2024-02-04
Erscheinungsland United States
Dokumenttyp Preprint
DOI 10.1101/2024.02.03.24302209
Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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