Decreased susceptibility of Plasmodium falciparum to both dihydroartemisinin and lumefantrine in northern Uganda
Patrick K. Tumwebaze,
Melissa D. Conrad (melissa.conrad@ucsf.edu),
Martin Okitwi,
Stephen Orena,
Oswald Byaruhanga,
Thomas Katairo,
Jennifer Legac,
Shreeya Garg,
David Giesbrecht,
Sawyer R. Smith,
Frida G. Ceja,
Samuel L. Nsobya,
Jeffrey A. Bailey,
Roland A. Cooper and
Philip J. Rosenthal (philip.rosenthal@ucsf.edu)
Additional contact information
Patrick K. Tumwebaze: Infectious Diseases Research Collaboration
Melissa D. Conrad: University of California
Martin Okitwi: Infectious Diseases Research Collaboration
Stephen Orena: Infectious Diseases Research Collaboration
Oswald Byaruhanga: Infectious Diseases Research Collaboration
Thomas Katairo: Infectious Diseases Research Collaboration
Jennifer Legac: University of California
Shreeya Garg: University of California
David Giesbrecht: Brown University
Sawyer R. Smith: Brown University
Frida G. Ceja: Dominican University of California
Samuel L. Nsobya: Infectious Diseases Research Collaboration
Jeffrey A. Bailey: Brown University
Roland A. Cooper: Dominican University of California
Philip J. Rosenthal: University of California
Nature Communications, 2022, vol. 13, issue 1, 1-12
Abstract:
Abstract Artemisinin partial resistance may facilitate selection of Plasmodium falciparum resistant to combination therapy partner drugs. We evaluated 99 P. falciparum isolates collected in 2021 from northern Uganda, where resistance-associated PfK13 C469Y and A675V mutations have emerged, and eastern Uganda, where these mutations are uncommon. With the ex vivo ring survival assay, isolates with the 469Y mutation (median survival 7.3% for mutant, 2.5% mixed, and 1.4% wild type) and/or mutations in Pfcoronin or falcipain-2a, had significantly greater survival; all isolates with survival >5% had mutations in at least one of these proteins. With ex vivo growth inhibition assays, susceptibility to lumefantrine (median IC50 14.6 vs. 6.9 nM, p 20 nM (p = 0.0002). Targeted sequencing of 819 isolates from 2015–21 identified multiple polymorphisms associated with altered drug susceptibility, notably PfK13 469Y with decreased susceptibility to lumefantrine (p = 6 × 10−8) and PfCRT mutations with chloroquine resistance (p = 1 × 10−20). Our results raise concern regarding activity of artemether-lumefantrine, the first-line antimalarial in Uganda.
Date: 2022
References: Add references at CitEc
Citations: View citations in EconPapers (2)
Downloads: (external link)
https://www.nature.com/articles/s41467-022-33873-x Abstract (text/html)
Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.
Export reference: BibTeX
RIS (EndNote, ProCite, RefMan)
HTML/Text
Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33873-x
Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/
DOI: 10.1038/s41467-022-33873-x
Access Statistics for this article
Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie
More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla (sonal.shukla@springer.com) and Springer Nature Abstracting and Indexing (indexing@springernature.com).