A Worldwide Map of<i>Plasmodium falciparum</i>K13-Propeller Polymorphisms
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Machine scores (provisional)
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- Teacher spread
- 0.255 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
BACKGROUND: Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale. METHODS: We analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained from patients who were treated at sentinel sites used for nationwide surveillance of antimalarial resistance. We evaluated the emergence and dissemination of mutations by haplotyping neighboring loci. RESULTS: We identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were distributed within two areas--one in Cambodia, Vietnam, and Laos and the other in western Thailand, Myanmar, and China--with no overlap. In Africa, we observed a broad array of rare nonsynonymous mutations that were not associated with delayed parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which expresses the most frequently observed African allele, was found to be susceptible to artemisinin in vitro on a ring-stage survival assay. CONCLUSIONS: No evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisinin, and many African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others.).
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The record
- Venue
- New England Journal of Medicine
- Topic
- Malaria Research and Control
- Field
- Medicine
- Canadian institutions
- —
- Funders
- European and Developing Countries Clinical Trials PartnershipPresident's Malaria InitiativeNational Institutes of HealthDrugs for Neglected Diseases initiativeInternational Centre for Diarrhoeal Disease Research, BangladeshFundação Oswaldo CruzVlaamse Interuniversitaire RaadScience and Technology Research Partnership for Sustainable DevelopmentThammasat UniversityDélégation Générale pour l'ArmementUnited States Agency for International DevelopmentInstitut de Recherche pour le DéveloppementMinistère de la SantéNatural Science Foundation of Jiangsu ProvinceMedicines for Malaria VentureFundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de JaneiroCalgary Laboratory ServicesJapan International Cooperation AgencyFogarty International CenterFundação de Amparo à Pesquisa do Estado do AmazonasFonds Wetenschappelijk OnderzoekFP7 Research Potential of Convergence RegionsPublic Health EnglandConselho Nacional de Desenvolvimento Científico e TecnológicoNational Natural Science Foundation of ChinaPasteur Institute of IranU.S. Department of DefenseWorld Health OrganizationEuropean CommissionNational Research Council of ThailandNational Institute of Allergy and Infectious DiseasesJiangsu Science and Technology DepartmentAgence Nationale de la RechercheCentre International de Recherches Médicales de FrancevilleGovernment of Jiangsu ProvinceGlobal Fund to Fight AIDS, Tuberculosis and Malaria
- Keywords
- Nonsynonymous substitutionPlasmodium falciparumArtemisininBiologyMalariaGeneticsAlleleDihydroartemisininMutationGeneImmunologyGenome
- Has abstract in OpenAlex
- yes