ArticleBMC medicine2018
High-level artemisinin-resistance with quinine co-resistance emerges in P. falciparum malaria under in vivo artesunate pressure.
Article in BMC medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Artemether for severe malaria.The Cochrane database of systematic reviews · 2019Pooled it
- Pharmacokinetics and Toxicity Assessment of Artesunate and Its Metabolite, Dihydroartemisinin, in NOD Scid Gamma Mice.Molecules (Basel, Switzerland) · 2026Article
- Improved Malaria Therapy with Cationic Nanocapsules Demonstrated inPharmaceutics · 2024Article
- Biogenically synthesized green silver nanoparticles exhibit antimalarial activity.Discover nano · 2024Article
- Defining the next generation of severe malaria treatment: a target product profile.Malaria journal · 2024Review
- Article
- Oleuropein mediated autophagy begets antimalarial drug resistance.Frontiers in microbiology · 2024Article
- Predicting Optimal Antimalarial Drug Combinations from a Standardized Plasmodium falciparum Humanized Mouse Model.Antimicrobial agents and chemotherapy · 2023Article
- Optimizing bulk segregant analysis of drug resistance usingiScience · 2022Article
- Fucoxanthin: A Promising Phytochemical on Diverse Pharmacological Targets.Frontiers in pharmacology · 2022Review
- The emergence of chloroquine-sensitive Plasmodium falciparum is influenced by selected communities in some parts of the Central Region of Ghana.Malaria journal · 2021Article
- Role of a Concentration Gradient in Malaria Drug Resistance Evolution: A Combined within- and between-Hosts Modelling Approach.Scientific reports · 2020Article
- Role of GRP78 inhibiting artesunate-induced ferroptosis inDrug design, development and therapy · 2019Article
- Humanized Mice Are Instrumental to the Study ofFrontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHumanity has become largely dependent on artemisinin derivatives for both the treatment and control of malaria, with few alternatives available. A Plasmodium falciparum phenotype with delayed parasite clearance during artemisinin-based combination therapy has established in Southeast Asia, and is emerging elsewhere. Therefore, we must know how fast, and by how much, artemisinin-resistance can strengthen.
methodsP. falciparum was subjected to discontinuous in vivo artemisinin drug pressure by capitalizing on a novel model that allows for long-lasting, high-parasite loads. Intravenous artesunate was administered, using either single flash-doses or a 2-day regimen, to P. falciparum-infected humanized NOD/SCID IL-2Rγ
resultsArtemisinin resistance evolved very rapidly up to extreme, near-lethal doses of artesunate (240 mg/kg), an increase of > 3000-fold in the effective in vivo dose, far above resistance levels reported from the field. Artemisinin resistance selection was reproducible, occurring in 80% and 41% of mice treated with flash-dose and 2-day regimens, respectively, and the resistance phenotype was stable. Measuring in vitro sensitivity proved inappropriate as an early marker of resistance, as IC
conclusionP. falciparum has the potential to evolve extreme artemisinin resistance and more complex patterns of multidrug resistance than anticipated. If resistance in the field continues to advance along this trajectory, we will be left with a limited choice of suboptimal treatments for acute malaria, and no satisfactory option for severe malaria.
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