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Polymorphisms in the K13-Propeller Gene in Artemisinin-Susceptible Plasmodium falciparum Parasites from Bougoula-Hameau and Bandiagara, Mali

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  • Department of Epidemiology of Parasitic Diseases, University of Science, Techniques and Technologies of Bamako, Bamako, Mali; Vanderbilt University Medical Center, Nashville, Tennessee; Howard Hughes Medical Institute, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Department of Physiology and Pharmacology, Karolinska University Hospital/Karolinska Institutet, Stockholm, Sweden; Drug Resistance and Pharmacogenetics, Center for Biodiversity, Functional and Integrative Genomics, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal; The Harpur College of Arts and Sciences, Binghamton University, The State University of New York, Binghamton, New York

Artemisinin-resistant Plasmodium falciparum malaria has been documented in southeast Asia and may already be spreading in that region. Molecular markers are important tools for monitoring the spread of antimalarial drug resistance. Recently, single-nucleotide polymorphisms (SNPs) in the PF3D7_1343700 kelch propeller (K13-propeller) domain were shown to be associated with artemisinin resistance in vivo and in vitro. The prevalence and role of K13-propeller mutations are poorly known in sub-Saharan Africa. K13-propeller mutations were genotyped by direct sequencing of nested polymerase chain reaction (PCR) amplicons from dried blood spots of pre-treatment falciparum malaria infections collected before and after the use of artemisinin-based combination therapy (ACT) as first-line therapy in Mali. Although K13-propeller mutations previously associated with delayed parasite clearance in Cambodia were not identified, 26 K13-propeller mutations were identified in both recent samples and pre-ACT infections. Parasite clearance time was comparable between infections with non-synonymous K13-propeller mutations and infections with the reference allele. These findings suggest that K13-propeller mutations are present in artemisinin-sensitive parasites and that they preceded the wide use of ACTs in Mali.

Author Notes

* Address correspondence to Abdoulaye A. Djimde, Department of Epidemiology of Parasitic Diseases, University of Science, Techniques and Technologies of Bamako, BP 1805, Bamako, Mali. E-mail: adjimde@icermali.org

Financial support: This work was supported by European and Developing Countries Clinical Trials Partnership EDCTP IP_07_31060_002, the West African Network for Clinical Trials of Antimalarial Drugs (WANECAM), and the Howard Hughes Medical Institute (sequencing and genetic analysis). S.T.-H. is supported by National Institutes of Health Grant R01AI101713.

Authors' addresses: Amed Ouattara, Department of Epidemiology of Parasitic Diseases, University of Science, Techniques and Technologies of Bamako, Bamako, Mali, and Howard Hughes Medical Institute, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, E-mail: aouattara@medicine.umaryland.edu. Aminatou Kone, Bakary Fofana, Drissa Coulibaly, Mahamadou A. Thera, Nouhoum Diallo, Antoine Dara, Issaka Sagara, Ogobara K. Doumbo, and Abdoulaye A. Djimde, Department of Epidemiology of Parasitic Diseases, University of Science, Techniques and Technologies of Bamako, Bamako, Mali, E-mails: aouattara@medicine.umaryland.edu, amina@icermali.org, bfofana@icermali.org, coulibalyd@icermali.org, mthera@icermali.org, nouhoumd@icermali.org, tonydara@icermali.org, isagara@icermali.org, okd@icermali.org, and adjimde@icermali.org. Matthew Adams, Shay Hampton, Shannon Takala-Harrison, and Christopher V. Plowe, Howard Hughes Medical Institute, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, E-mails: madams@medicine.umaryland.edu, shampton@medicine.umaryland.edu, stakala@medicine.umaryland.edu, and cplowe@medicine.umaryland.edu. Amelia Walling Maiga, Vanderbilt University Medical Center, Nashville, TN, E-mail: kadia.ongoiba@gmail.com. Jose Pedro Gil, Department of Physiology and Pharmacology, Karolinska University Hospital/Karolinska Institutet, Stockholm, Sweden, Drug Resistance and Pharmacogenetics, Center for Biodiversity, Functional and Integrative Genomics, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal, and The Harpur College of Arts and Sciences, Binghamton University, The State University of New York, Binghamton, NY, E-mail: jose.pedro.gil@ki.se. Anders Bjorkman, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden, E-mail: anders.bjorkman@karolinska.se.

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