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            <title xml:lang="en">Artemisinin pressure in field isolates can select highly resistant Plasmodium falciparum parasites with unconventional phenotype and no K13 mutation</title>
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            <funder>Institut National de la Santé et de la Recherche Médicale (INSERM)</funder>
            <funder>French Ministry for Research</funder>
            <funder>European Commission Grant (Regional Fund for Development, Synergie GY0012082)</funder>
            <funder>Santé Publique France as National Reference Center for Malaria</funder>
            <funder>Investissement d’Avenir grant / Agence Nationale de la Recherche (CEBA, ANR-10-LABX25-01).</funder>
            <funder>This study was supported by the “Centre National de la Recherche Scientifique” (CNRS), the “Institut National de la Santé et de la Recherche Médicale” (INSERM), the Agence Nationale de la Recherche (ANR-21-CE35-0002-01), the French Ministry for Research, the European Commission Grant (Regional Fund for Development, Synergie GY0012082), and Santé Publique France as National Reference Center for Malaria and Investissement d’Avenir grant managed by Agence Nationale de la Recherche (CEBA, ANR-10-LABX25-01).</funder>
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                <title xml:lang="en">Artemisinin pressure in field isolates can select highly resistant Plasmodium falciparum parasites with unconventional phenotype and no K13 mutation</title>
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                <title level="j">Antimicrobial Agents and Chemotherapy</title>
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                <term xml:lang="en">Malaria</term>
                <term xml:lang="en">in vitro selection</term>
                <term xml:lang="en">Artemisinin resistance</term>
                <term xml:lang="en">Non-K13 polymorphism</term>
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              <p>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 Plasmodium falciparum kelch13 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 in vitro in nine P. falciparum field isolates from Africa, Asia, and South America. Artemisinin pressure selected highly resistant parasites in all lineages, but only one acquired a validated pfkelch13 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.</p>
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