Artemisinin pressure in field isolates can select highly resistant <i>Plasmodium falciparum</i> parasites with unconventional phenotype and no K13 mutation
Artemisinin resistance, which poses a serious threat to malaria control efforts, is monitored in the field by delayed parasite clearance in patients, elevated parasite survival rate in the ring-stage survival assay, and mutations in the <i>Plasmodium falciparum kelch13</i> gene. However, sporadic cases of artemisinin-resistant malaria do not meet all of these criteria, highlighting that our understanding of artemisinin resistance is still incomplete. Here, we selected for artemisinin resistance <i>in vitro</i> in nine <i>P. falciparum</i> field isolates from Africa, Asia, and South America. Artemisinin pressure selected highly resistant parasites in all lineages, but only one acquired a validated <i>pfkelch13</i> mutation. Phenotypic tests evidenced an unconventional response of selected parasites that can be artemisinin-resistant only at an advanced ring age, making them undetectable by the standard "0-3 h" test used to monitor resistance. These results highlight the need for broader approaches to artemisinin resistance monitoring.
Authors
- Stéphanie Blandin (ORCID: https://orcid.org/0000-0003-4566-1200)
- Françoise Benoit‐Vical (ORCID: https://orcid.org/0000-0002-9468-4823)
- Luana Mathieu (ORCID: https://orcid.org/0000-0002-6021-468X)
- L. Musset (ORCID: https://orcid.org/0000-0003-0215-4110)
- Marion Laurent (ORCID: https://orcid.org/0000-0002-9029-027X)
- Romain Coppée (ORCID: https://orcid.org/0000-0002-3024-5928)
- Jean‐Michel Augereau (ORCID: https://orcid.org/0000-0002-2847-1969)
- Lucie Paloque (ORCID: https://orcid.org/0000-0003-0359-3959)
- Pascal Campagne (ORCID: https://orcid.org/0000-0001-7018-1896)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- Université Paris Cité (FR)
- Institut de Pharmacologie et de Biologie Structurale (FR)
- Institut Pasteur de la Guyane (GF)
- Laboratoire de Chimie de Coordination (FR)
- Université de Rouen Normandie (FR)
- Université de Strasbourg (FR)
Publication Details
- Journal
- Antimicrobial Agents and Chemotherapy
- Published
- 2025-02-04
- DOI
- https://doi.org/10.1128/aac.01541-24
- Citations
- 1
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 1.88
Funders
- International Business Machines Corporation
- Infrastructures en Biologie Santé et Agronomie
- Equipex
- European Commission
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique