BibTex format
@article{Meier-Scherling:2025:10.1016/j.lanmic.2024.101027,
author = {Meier-Scherling, CPG and Watson, OJ and Asua, V and Ghinai, I and Katairo, T and Garg, S and Conrad, MD and Rosenthal, PJ and Okell, LC and Bailey, JA},
doi = {10.1016/j.lanmic.2024.101027},
journal = {The Lancet Microbe},
title = {Selection of Plasmodium falciparum kelch13 mutations in Uganda in comparison with southeast Asia: a modelling study},
url = {http://dx.doi.org/10.1016/j.lanmic.2024.101027},
year = {2025}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - BackgroundArtemisinin partial resistance, mediated by mutations in the Plasmodium falciparum kelch13 gene (k13), rapidly spread in southeast Asia, undermining the antimalarial effectiveness of artemisinin-based combination therapies. k13 mutations have also arisen in Africa, but their rates of increase are not well characterised. We aimed to quantify the selection of k13 mutations in Africa and compare the selection with that in southeast Asia.MethodsIn this modelling study, we investigated k13 mutation allele frequency at 16 sites in Uganda (2016–22) and five sites in southeast Asia (in Cambodia, Thailand, and Viet Nam; 2003–14). The Ugandan data were obtained from annual clinical surveillance studies and the southeast Asian data were obtained from the MalariaGEN Pf7 dataset. We investigated five validated and candidate k13 mutations: Pro441Leu, Cys469Phe, Cys469Tyr, Arg561His, and Ala675Val. We calculated annual selection coefficients using Bayesian mixed-effect linear models. We then tested whether the k13 mutation allele frequency in southeast Asia could have been forecast accurately using up to the first 5 years of available data and forecast future k13 mutation allele frequency in Uganda.FindingsWe used data from 7564 samples from Uganda and 6568 samples from southeast Asia. The annual selection coefficient of evaluable k13 mutations (Pro441Leu, Cys469Phe/Tyr, Arg561His, and Ala675Val) across all sites was estimated at 0·381 (95% credible interval 0·298 to 0·472) per year, a 38% increase in relative allele frequency. Selection coefficients across Uganda were 0·494 (−0·462 to 1·410) for Pro441Leu, 0·324 (−0·629 to 1·150) for Cys469Phe, 0·383 (0·207 to 0·591) for Cys469Tyr, and 0·237 (0·087 to 0·403) for Ala675Val. In southeast Asia, the selection coefficients were 0·627 (−0·088 to 1·312) for Cys580Tyr, 0&mid
AU - Meier-Scherling,CPG
AU - Watson,OJ
AU - Asua,V
AU - Ghinai,I
AU - Katairo,T
AU - Garg,S
AU - Conrad,MD
AU - Rosenthal,PJ
AU - Okell,LC
AU - Bailey,JA
DO - 10.1016/j.lanmic.2024.101027
PY - 2025///
SN - 2666-5247
TI - Selection of Plasmodium falciparum kelch13 mutations in Uganda in comparison with southeast Asia: a modelling study
T2 - The Lancet Microbe
UR - http://dx.doi.org/10.1016/j.lanmic.2024.101027
UR - https://doi.org/10.1016/j.lanmic.2024.101027
ER -