title: Changing Antimalarial Drug Resistance Patterns Identified by Surveillance at Three Sites in Uganda.
abstract: We assessed Plasmodium falciparum drug resistance markers in parasites collected in 2012, 2013, and 2015 at 3 sites in Uganda. The prevalence and frequency of parasites with mutations in putative transporters previously associated with resistance to aminoquinolines, but increased sensitivity to lumefantrine (pfcrt 76T; pfmdr1 86Y and 1246Y), decreased markedly at all sites. Antifolate resistance mutations were common, with apparent emergence of mutations (pfdhfr 164L; pfdhps 581G) associated with high-level resistance. K13 mutations linked to artemisinin resistance were uncommon and did not increase over time. Changing malaria treatment practices have been accompanied by profound changes in markers of resistance.
authors.affiliation: Infectious Diseases Research Collaboration, Kampala, Uganda.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tumwebaze
authors.affiliation: Infectious Diseases Research Collaboration, Kampala, Uganda.
authors.forename: Stephen
authors.initials: S
authors.lastname: Tukwasibwe
authors.affiliation: Center for Communicable Disease Dynamics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Aimee
authors.initials: A
authors.lastname: Taylor
authors.affiliation: Department of Medicine, University of California, San Francisco, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Conrad
authors.affiliation: Infectious Diseases Research Collaboration, Kampala, Uganda.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Ruhamyankaka
authors.affiliation: Infectious Diseases Research Collaboration, Kampala, Uganda.
authors.forename: Victor
authors.initials: V
authors.lastname: Asua
authors.affiliation: Infectious Diseases Research Collaboration, Kampala, Uganda.
authors.forename: Andrew
authors.initials: A
authors.lastname: Walakira
authors.affiliation: Infectious Diseases Research Collaboration, Kampala, Uganda.
authors.forename: Joaniter
authors.initials: J
authors.lastname: Nankabirwa
authors.affiliation: Makerere University School of Public Health, College of Health Sciences, Kampala, Uganda.
authors.forename: Adoke
authors.initials: A
authors.lastname: Yeka
authors.affiliation: London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Staedke
authors.affiliation: Department of Medicine, University of California, San Francisco, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Greenhouse
authors.affiliation: Infectious Diseases Research Collaboration, Kampala, Uganda.
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Nsobya
authors.affiliation: Infectious Diseases Research Collaboration, Kampala, Uganda.|Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.affiliation: Department of Medicine, University of California, San Francisco, USA.
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
authors.affiliation: Department of Medicine, University of California, San Francisco, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
mesh_terms: D000293:Adolescent; D000634:Aminoquinolines / Q000494:pharmacology; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology; D003430:Cross-Sectional Studies; D016054:DNA, Protozoan / Q000302:isolation & purification; D004351:Drug Resistance / Q000235:genetics*; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D005449:Fluorenes / Q000494:pharmacology; D005493:Folic Acid Antagonists / Q000494:pharmacology; D017125:Genes, Protozoan; D006801:Humans; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000188:drug therapy; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014454:Uganda
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D037621:Artemisinins; D016054:DNA, Protozoan; D004983:Ethanolamines; D005449:Fluorenes; D005493:Folic Acid Antagonists; D000078102:Lumefantrine; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum; C031327:artemisinin
keywords: K13; Malaria; Plasmodium falciparum; amodiaquine; artemether; artemisinin; artesunate; chloroquine; dihydroartemisinin; drug resistance; lumefantrine; pfcrt; pfmdr1; piperaquine