Evolution of Partial Resistance to Artemisinins in Malaria Parasites in Uganda.

Authors

Melissa D. Conrad, University of California, San FranciscoFollow
Victor Asua, University of California, San Francisco
Shreeya Garg, University of California, San Francisco
David Giesbrecht, University of California, San Francisco
Karamoko Niaré, University of California, San Francisco
Sawyer Smith, University of California, San Francisco
Jane F Namuganga, University of California, San Francisco
Thomas Katairo, University of California, San FranciscoFollow
Jennifer Legac, University of California, San FranciscoFollow
Rebecca M. Crudale, University of California, San Francisco
Patrick K. Tumwebaze, University of California, San Francisco
Samuel L. Nsobya, University of California, San FranciscoFollow
Roland A. Cooper, University of California, San FranciscoFollow
Moses R. Kamya, University of California, San FranciscoFollow
Grant Dorsey, University of California, San FranciscoFollow
Jeffrey A. Bailey, University of California, San Francisco
Philip J. Rosenthal, University of California, San FranciscoFollow

Department

Natural Sciences and Mathematics

Document Type

Article

Source

New England Journal of Medicine

Publication Date

8-24-2023

ISSN

1533-4406

Volume

389

Issue

8

First Page

722

Last Page

732

Abstract

BACKGROUND: Partial 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.

METHODS: We 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 (

RESULTS: By 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.

CONCLUSIONS: Data 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.).

PubMed ID

37611122

Rights

Copyright © 2023 Massachusetts Medical Society.