ArticleEmerging infectious diseases2015
Induction of Multidrug Tolerance in Plasmodium falciparum by Extended Artemisinin Pressure.
Article in Emerging infectious diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Hybrid Molecules as Efficient Drugs against Multidrug-Resistant Malaria Parasites.ChemMedChem · 2025Review
- In vitro evaluation of ganaplacide/lumefantrine combination against Plasmodium falciparum in a context of artemisinin resistance.The Journal of antimicrobial chemotherapy · 2024Article
- A kalihinol analog disrupts apicoplast function and vesicular trafficking inScience (New York, N.Y.) · 2024Article
- Novel molecular inhibitor design for Plasmodium falciparum Lactate dehydrogenase enzyme using machine learning generated library of diverse compounds.Molecular diversity · 2024Article
- Characterization of antimalarial activity of artemisinin-based hybrid drugs.Antimicrobial agents and chemotherapy · 2024Article
- tRNA modification reprogramming contributes to artemisinin resistance in Plasmodium falciparum.Nature microbiology · 2024Article
- In vitro delayed response to dihydroartemisinin of malaria parasites infecting sickle cell erythocytes.Malaria journal · 2024Article
- Epidrugs as Promising Tools to EliminatePharmaceutics · 2023Article
- Molecular Mechanisms of Persistence in Protozoan Parasites.Microorganisms · 2023Review
- Article
- Safe drugs with high potential to block malaria transmission revealed by a spleen-mimetic screening.Nature communications · 2023Article
- Assessment of artemisinin tolerance in Plasmodium falciparum clinical isolates in children with uncomplicated malaria in Ghana.Malaria journal · 2023Article
- Synthesis and Antimalarial Activities of New Hybrid Atokel Molecules.ChemistryOpen · 2022Article
- In Vitro and In Silico Antimalarial Evaluation of FM-AZ, a New Artemisinin Derivative.Medicines (Basel, Switzerland) · 2022Article
- A New Thienopyrimidinone Chemotype Shows Multistage Activity against Plasmodium falciparum, Including Artemisinin-Resistant Parasites.Microbiology spectrum · 2021Article
- Protecting future antimalarials from the trap of resistance: Lessons from artemisinin-based combination therapy (ACT) failures.Journal of pharmaceutical analysis · 2021Review
- 2-Phenoxy-3-Trichloromethylquinoxalines Are Antiplasmodial Derivatives with Activity against the Apicoplast ofPharmaceuticals (Basel, Switzerland) · 2021Article
- Daily rhythms of both host and parasite affect antimalarial drug efficacy.Evolution, medicine, and public health · 2021Article
- Genetic Diversity Analysis of Surface-Related Antigen (SRA) inFrontiers in genetics · 2021Article
- Antimalarial Activity ofJournal of pathogens · 2021Article
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasmodium falciparum resistance to artemisinin derivatives in Southeast Asia threatens global malaria control strategies. Whether delayed parasite clearance, which exposes larger parasite numbers to artemisinins for longer times, selects higher-grade resistance remains unexplored. We investigated whether long-lasting artemisinin pressure selects a novel multidrug-tolerance profile. Although 50% inhibitory concentrations for 10 antimalarial drugs tested were unchanged, drug-tolerant parasites showed higher recrudescence rates for endoperoxides, quinolones, and an antifolate, including partner drugs of recommended combination therapies, but remained susceptible to atovaquone. Moreover, the age range of intraerythrocytic stages able to resist artemisinin was extended to older ring forms and trophozoites. Multidrug tolerance results from drug-induced quiescence, which enables parasites to survive exposure to unrelated antimalarial drugs that inhibit a variety of metabolic pathways. This novel resistance pattern should be urgently monitored in the field because this pattern is not detected by current assays and represents a major threat to antimalarial drug policy.
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