title: In Vitro and Molecular Surveillance for Antimalarial Drug Resistance in Plasmodium falciparum Parasites in Western Kenya Reveals Sustained Artemisinin Sensitivity and Increased Chloroquine Sensitivity.
abstract: Malaria control is hindered by the evolution and spread of resistance to antimalarials, necessitating multiple changes to drug policies over time. A comprehensive antimalarial drug resistance surveillance program is vital for detecting the potential emergence of resistance to antimalarials, including current artemisinin-based combination therapies. An antimalarial drug resistance surveillance study involving 203 Plasmodium falciparum malaria-positive children was conducted in western Kenya between 2010 and 2013. Specimens from enrolled children were analyzed in vitro for sensitivity to chloroquine (CQ), amodiaquine (AQ), mefloquine (MQ), lumefantrine, and artemisinin derivatives (artesunate and dihydroartemisinin) and for drug resistance allele polymorphisms in P. falciparum crt (Pfcrt), Pfmdr-1, and the K13 propeller domain (K13). We observed a significant increase in the proportion of samples with the Pfcrt wild-type (CVMNK) genotype, from 61.2% in 2010 to 93.0% in 2013 (P < 0.0001), and higher proportions of parasites with elevated sensitivity to CQ in vitro. The majority of isolates harbored the wild-type N allele in Pfmdr-1 codon 86 (93.5%), with only 7 (3.50%) samples with the N86Y mutant allele (the mutant nucleotide is underlined). Likewise, most isolates harbored the wild-type Pfmdr-1 D1246 allele (79.8%), with only 12 (6.38%) specimens with the D1246Y mutant allele and 26 (13.8%) with mixed alleles. All the samples had a single copy of the Pfmdr-1 gene (mean of 0.907 ± 0.141 copies). None of the sequenced parasites had mutations in K13. Our results suggest that artemisinin is likely to remain highly efficacious and that CQ sensitivity appears to be on the rise in western Kenya.
authors.affiliation: Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA NLucchi@cdc.gov.
authors.forename: Naomi W
authors.initials: NW
authors.lastname: Lucchi
authors.affiliation: Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya.
authors.forename: Franklin
authors.initials: F
authors.lastname: Komino
authors.affiliation: Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA Atlanta Research and Education Foundation, Atlanta, Georgia, USA.
authors.forename: Sheila Akinyi
authors.initials: SA
authors.lastname: Okoth
authors.affiliation: Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Goldman
authors.affiliation: Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya.
authors.forename: Philip
authors.initials: P
authors.lastname: Onyona
authors.affiliation: Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Wiegand
authors.affiliation: Centre for Clinical Research, Kenya Medical Research Institute/Division of Malaria Control, Ministry of Health, Nairobi, Kenya.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Juma
authors.affiliation: Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Ya Ping
authors.initials: YP
authors.lastname: Shi
authors.affiliation: Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Barnwell
authors.affiliation: Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA Atlanta Research and Education Foundation, Atlanta, Georgia, USA.
authors.forename: Venkatachalam
authors.initials: V
authors.lastname: Udhayakumar
authors.affiliation: Kenya Medical Research Institute/Centre for Global Health Research, Kisumu, Kenya.
authors.forename: Simon
authors.initials: S
authors.lastname: Kariuki
mesh_terms: D000483:Alleles; D000655:Amodiaquine / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics*; D062665:Epidemiological Monitoring; D004983:Ethanolamines / Q000627:therapeutic use; D005449:Fluorenes / Q000627:therapeutic use; D018628:Gene Dosage; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D007630:Kenya / Q000453:epidemiology; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D015767:Mefloquine / Q000627:therapeutic use; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000655:Amodiaquine; D000962:Antimalarials; D037621:Artemisinins; D002738:Chloroquine; D004983:Ethanolamines; D005449:Fluorenes; D000078102:Lumefantrine; D015767:Mefloquine; 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