ArticleThe Journal of infectious diseases2022
Mutant PfCRT Can Mediate Piperaquine Resistance in African Plasmodium falciparum With Reduced Fitness and Increased Susceptibility to Other Antimalarials.
Article in The Journal of infectious diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- A Multidimensional Analysis of the Bimodal Piperaquine Response inbioRxiv : the preprint server for biology · 2026Article
- Changing genetic profiles ofAntimicrobial agents and chemotherapy · 2026Article
- Heme processing in the malaria parasite, Plasmodium falciparum: a time-dependent basal-level analysis.Communications biology · 2025Article
- Plasmodiumfalciparum protein kinase 6 and hemozoin formation are inhibited by a type II human kinase inhibitor exhibiting antimalarial activity.Cell chemical biology · 2025Article
- The plasmepsin-piperaquine paradox persists in Plasmodium falciparum.PLoS pathogens · 2025Article
- Plasmodium falciparum African PfCRT Mutant Isoforms Conducive to Piperaquine Resistance Are Infrequent and Impart a Major Fitness Cost.The Journal of infectious diseases · 2025Article
- Deletion of theAntimicrobial agents and chemotherapy · 2025Article
- Assessing fitness costs in malaria parasites: a comprehensive review and implications for drug resistance management.Malaria journal · 2025Review
- Dihydroartemisinin-Piperaquine Combination in the Treatment of UncomplicatedJournal of clinical medicine · 2024Review
- AmBio · 2024Article
- Emergence, transmission dynamics and mechanisms of artemisinin partial resistance in malaria parasites in Africa.Nature reviews. Microbiology · 2024Review
- Deaggregation of mutant Plasmodium yoelii de-ubiquitinase UBP1 alters MDR1 localization to confer multidrug resistance.Nature communications · 2024Article
- Assessing emergence risk of double-resistant and triple-resistant genotypes of Plasmodium falciparum.Nature communications · 2024Article
- Article
- The landscape of drug resistance in Plasmodium falciparum malaria in the Democratic Republic of Congo: a mapping systematic review.Tropical medicine and health · 2023Review
- Mapping the genomic landscape of multidrug resistance inScience advances · 2023Article
- Preventing antimalarial drug resistance with triple artemisinin-based combination therapies.Nature communications · 2023Article
- Seasonal malaria chemoprevention in Africa and China's upgraded role as a contributor: a scoping review.Infectious diseases of poverty · 2023Article
- Malaria Control by Mass Drug Administration With Artemisinin Plus Piperaquine on Grande Comore Island, Union of Comoros.Open forum infectious diseases · 2023Article
- Prevalence and characterization of piperaquine, mefloquine and artemisinin derivatives triple-resistant Plasmodium falciparum in Cambodia.The Journal of antimicrobial chemotherapy · 2023Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAdditional therapeutic strategies could benefit efforts to reverse the recent increase in malaria cases in sub-Saharan Africa, which mostly affects young children. A primary candidate is dihydroartemisinin + piperaquine (DHA + PPQ), which is effective for uncomplicated malaria treatment, seasonal malaria chemoprevention, and intermittent preventive treatment. In Southeast Asia, Plasmodium falciparum parasites acquired PPQ resistance, mediated primarily by mutations in the P falciparum chloroquine resistance transporter PfCRT. The recent emergence in Africa of DHA-resistant parasites creates an imperative to assess whether PPQ resistance could emerge in African parasites with distinct PfCRT isoforms.
methodsWe edited 2 PfCRT mutations known to mediate high-grade PPQ resistance in Southeast Asia into GB4 parasites from Gabon. Gene-edited clones were profiled in antimalarial concentration-response and fitness assays.
resultsThe PfCRT F145I mutation mediated moderate PPQ resistance in GB4 parasites but with a substantial fitness cost. No resistance was observed with the PfCRT G353V mutant. Both edited clones became significantly more susceptible to amodiaquine, chloroquine, and quinine.
conclusionsA single PfCRT mutation can mediate PPQ resistance in GB4 parasites, but with a growth defect that may preclude its spread without further genetic adaptations. Our findings support regional use of drug combinations that exert opposing selective pressures on PfCRT.
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