Absence of Putative Artemisinin Resistance Mutations Among Plasmodium falciparum in Sub-Saharan Africa: A Molecular Epidemiologic Study
Graduate School of Biomedical Sciences; Department of Pediatrics; Division of Transfusion Medicine; Program in Bioinformatics and Integrative Biology
Bioinformatics | Computational Biology | Epidemiology | Immunology of Infectious Disease | Infectious Disease | Integrative Biology | International Public Health | Molecular Biology | Parasitic Diseases | Parasitology | Pediatrics
Plasmodium falciparum parasites that are resistant to artemisinins have been detected in Southeast Asia. Resistance is associated with several polymorphisms in the parasite's K13-propeller gene. The molecular epidemiology of these artemisinin resistance genotypes in African parasite populations is unknown. We developed an assay to quantify rare polymorphisms in parasite populations that uses a pooled deep-sequencing approach to score allele frequencies, validated it by evaluating mixtures of laboratory parasite strains, and then used it to screen P. falciparum parasites from >1100 African infections collected since 2002 from 14 sites across sub-Saharan Africa. We found no mutations in African parasite populations that are associated with artemisinin resistance in Southeast Asian parasites. However, we observed 15 coding mutations, including 12 novel mutations, and limited allele sharing between parasite populations, consistent with a large reservoir of naturally occurring K13-propeller variation. Although polymorphisms associated with artemisinin resistance in P. falciparum in Southeast Asia are not prevalent in sub-Saharan Africa, numerous K13-propeller coding polymorphisms circulate in Africa. Although their distributions do not support a widespread selective sweep for an artemisinin-resistant phenotype, the impact of these mutations on artemisinin susceptibility is unknown and will require further characterization. Rapid, scalable molecular surveillance offers a useful adjunct in tracking and containing artemisinin resistance. Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
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Citation: J Infect Dis. 2015 Mar 1;211(5):680-8. doi: 10.1093/infdis/jiu467. Epub 2014 Sep 1. Link to article on publisher's site
Taylor, Steve M.; DeConti, Derrick K.; Moormann, Ann M.; Bailey, Jeffrey A.; and Juliano, Jonathan J., "Absence of Putative Artemisinin Resistance Mutations Among Plasmodium falciparum in Sub-Saharan Africa: A Molecular Epidemiologic Study" (2015). Immunology/Infectious Disease. 75.