Polymorphisms in the K13-propeller gene in artemisinin-susceptible Plasmodium falciparum parasites from Bougoula-Hameau and Bandiagara, Mali.
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.
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.
Amed
A
Ouattara
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.
Aminatou
A
Kone
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.
Matthew
M
Adams
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.
Bakary
B
Fofana
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.
Amelia Walling
AW
Maiga
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.
Shay
S
Hampton
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.
Drissa
D
Coulibaly
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.
Mahamadou A
MA
Thera
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.
Nouhoum
N
Diallo
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.
Antoine
A
Dara
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.
Issaka
I
Sagara
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.
Jose Pedro
JP
Gil
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.
Anders
A
Bjorkman
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.
Shannon
S
Takala-Harrison
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.
Ogobara K
OK
Doumbo
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.
Christopher V
CV
Plowe
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 adjimde@icermali.org.
Abdoulaye A
AA
Djimde
D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D001483:Base Sequence; D001742:Blackwater Fever / Q000188:drug therapy / Q000469:parasitology; D004351:Drug Resistance / Q000235:genetics; D017125:Genes, Protozoan / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008302:Mali / Q000453:epidemiology; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016415:Sequence Alignment
D000962:Antimalarials; D037621:Artemisinins; C031327:artemisinin