ArticleAntimicrobial agents and chemotherapy2016
Little Polymorphism at the K13 Propeller Locus in Worldwide Plasmodium falciparum Populations Prior to the Introduction of Artemisinin Combination Therapies.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Malaria epidemiological research in the Republic of Congo.Malaria journal · 2016Pooled it
- Screening for K13-Propeller Mutations Associated with Artemisinin Resistance in Plasmodium falciparum in Yambio County (Western Equatoria State, South Sudan).The American journal of tropical medicine and hygiene · 2023Article
- Kelch13 mutations in Plasmodium falciparum and risk of spreading in Amazon basin countries.The Journal of antimicrobial chemotherapy · 2021Article
- Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea.PLoS pathogens · 2020Article
- Evolution of Antimalarial Drug Resistance Markers in the Reservoir of Plasmodium falciparum Infections in the Upper East Region of Ghana.The Journal of infectious diseases · 2020Article
- Molecular surveillance of Pfcrt and k13 propeller polymorphisms of imported Plasmodium falciparum cases to Zhejiang Province, China between 2016 and 2018.Malaria journal · 2020Article
- The Diversity of theAntimicrobial agents and chemotherapy · 2019Article
- Evolution and Genetic Diversity of theAntimicrobial agents and chemotherapy · 2019Article
- Polymorphisms in Plasmodium falciparum Kelch 13 and P. vivax Kelch 12 Genes in Parasites Collected from Three South Pacific Countries Prior to Extensive Exposure to Artemisinin Combination Therapies.Antimicrobial agents and chemotherapy · 2019Article
- Molecular surveillance of putative drug resistance markers of antifolate and artemisinin among importedPathogens and global health · 2019Article
- Artemisinin Resistance Outside of Southeast Asia.The American journal of tropical medicine and hygiene · 2018Article
- Absence ofThe American journal of tropical medicine and hygiene · 2018Article
- No polymorphisms in K13-propeller gene associated with artemisinin resistance in Plasmodium falciparum isolated from Brazzaville, Republic of Congo.BMC infectious diseases · 2018Article
- Resistance screening and trend analysis of imported falciparum malaria in NSW, Australia (2010 to 2016).PloS one · 2018Article
- Limited genetic diversity in the PvK12 Kelch protein in Plasmodium vivax isolates from Southeast Asia.Malaria journal · 2016Article
Corrections and comments
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Authors and funding
21 authors at 10 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The emergence and spread of artemisinin-resistant Plasmodium falciparum is of huge concern for the global effort toward malaria control and elimination. Artemisinin resistance, defined as a delayed time to parasite clearance following administration of artemisinin, is associated with mutations in the Pfkelch13 gene of resistant parasites. To date, as many as 60 nonsynonymous mutations have been identified in this gene, but whether these mutations have been selected by artemisinin usage or merely reflect natural polymorphism independent of selection is currently unknown. To clarify this, we sequenced the Pfkelch13 propeller domain in 581 isolates collected before (420 isolates) and after (161 isolates) the implementation of artemisinin combination therapies (ACTs), from various regions of endemicity worldwide. Nonsynonymous mutations were observed in 1% of parasites isolated prior to the introduction of ACTs. Frequencies of mutant isolates, nucleotide diversity, and haplotype diversity were significantly higher in the parasites isolated from populations exposed to artemisinin than in those from populations that had not been exposed to the drug. In the artemisinin-exposed population, a significant excess of dN compared to dS was observed, suggesting the presence of positive selection. In contrast, pairwise comparison of dN and dS and the McDonald and Kreitman test indicate that purifying selection acts on the Pfkelch13 propeller domain in populations not exposed to ACTs. These population genetic analyses reveal a low baseline of Pfkelch13 polymorphism, probably due to purifying selection in the absence of artemisinin selection. In contrast, various Pfkelch13 mutations have been selected under artemisinin pressure.
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