ArticleInternational journal for parasitology. Drugs and drug resistance2021
Plasmodium falciparum resistance to ACTs: Emergence, mechanisms, and outlook.
Article in International journal for parasitology. Drugs and drug resistance, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 96 citations in OpenAlex.
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- MalDeepSeq panel: A targeted ultra-deep sequencing approach to trace drug resistance markers in Plasmodium falciparum.Cell reports methods · 2026Article
- Experimental evolution and functional genetics identify KIC1 as a determinant of reduced artemisinin susceptibility in BangladeshibioRxiv : the preprint server for biology · 2026Article
- Hit-To-Lead Optimization of a Pyridylpiperazine Class Against Malaria: Pharmacokinetic Profile and In Vivo Efficacy of Optimized Compounds.ChemMedChem · 2026Article
- Efficacy of artemether-lumefantrine combination for the treatment of uncomplicated Plasmodium falciparum malaria after 16 years of its introduction into Ghana's antimalarial medicines policy.Malaria journal · 2026Article
- Spatial and temporal description of antimalarial drug resistance markers in Ghana using targeted amplicon deep sequencing.Antimicrobial agents and chemotherapy · 2026Article
- The case for exploring innate memory in Plasmodium infection.Current opinion in microbiology · 2026Review
- Synergistic Antimalarial Activity of Alpha-Mangostin Chitosan Alginate Nanoparticles with Chloroquine in Mice Infected withIranian journal of medical sciences · 2026Article
- Russian Dolls of Heme Metabolism in Malaria-Infected Red Blood Cells: Nested Vulnerabilities and Therapeutic Opportunities.Pathogens (Basel, Switzerland) · 2026Review
- Application Strategy and Research Progress of Large-Scale Population Drug Intervention in Malaria Control.Tropical medicine and infectious disease · 2026Review
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- Antimalarial drug resistance inParasitology · 2026Article
- Targeting Infected Host Cell Heme Metabolism to Kill Malaria Parasites.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Replication stress increases de novo CNVs across the malaria parasite genome.Nucleic acids research · 2026Article
- Malaria Public Health Status: Global Context and Update on Gulf Cooperation Council Countries.Advances in experimental medicine and biology · 2026Review
- Fluorescence-based bioassay for the detection of changes in mitochondrial physiology during artemisinin-induced growth arrest of blood-stage Plasmodium falciparum.Scientific reports · 2025Article
- Eschweilenol C and subfractions from Terminalia plants disrupt haemoglobin metabolism, inhibiting Plasmodium falciparum growth at rings and trophozoite stages.Malaria journal · 2025Article
- PfPI3K inhibition reversed artemisinin resistance by increasing ROS and ubiquitinated protein levels in Plasmodium falciparum.Communications biology · 2025Article
- Role of novel mutations in food vacuole transporters beyond K13-mediated artemisinin resistance inAntimicrobial agents and chemotherapy · 2025Article
- Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Emergence and spread of resistance in Plasmodium falciparum to the frontline treatment artemisinin-based combination therapies (ACTs) in the epicenter of multidrug resistance of Southeast Asia threaten global malaria control and elimination. Artemisinin (ART) resistance (or tolerance) is defined clinically as delayed parasite clearance after treatment with an ART drug. The resistance phenotype is restricted to the early ring stage and can be measured in vitro using a ring-stage survival assay. ART resistance is associated with mutations in the propeller domain of the Kelch family protein K13. As a pro-drug, ART is activated primarily by heme, which is mainly derived from hemoglobin digestion in the food vacuole. Activated ARTs can react promiscuously with a wide range of cellular targets, disrupting cellular protein homeostasis. Consistent with this mode of action for ARTs, the molecular mechanisms of K13-mediated ART resistance involve reduced hemoglobin uptake/digestion and increased cellular stress response. Mutations in other genes such as AP-2μ (adaptor protein-2 μ subunit), UBP-1 (ubiquitin-binding protein-1), and Falcipain 2a that interfere with hemoglobin uptake and digestion also increase resistance to ARTs. ART resistance has facilitated the development of resistance to the partner drugs, resulting in rapidly declining ACT efficacies. The molecular markers for resistance to the partner drugs are mostly associated with point mutations in the two food vacuole membrane transporters PfCRT and PfMDR1, and amplification of pfmdr1 and the two aspartic protease genes plasmepsin 2 and 3. It has been observed that mutations in these genes can have opposing effects on sensitivities to different partner drugs, which serve as the principle for designing triple ACTs and drug rotation. Although clinical ACT resistance is restricted to Southeast Asia, surveillance for drug resistance using in vivo clinical efficacy, in vitro assays, and molecular approaches is required to prevent or slow down the spread of resistant parasites.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.