title: Analysis of major genome loci underlying artemisinin resistance and pfmdr1 copy number in pre- and post-ACTs in western Kenya.
abstract: Genetic analysis of molecular markers is critical in tracking the emergence and/or spread of artemisinin resistant parasites. Clinical isolates collected in western Kenya pre- and post- introduction of artemisinin combination therapies (ACTs) were genotyped at SNP positions in regions of strong selection signatures on chromosome 13 and 14, as described in Southeast Asia (SEA). Twenty five SNPs were genotyped using Sequenom MassArray and pfmdr1 gene copy number by real-time PCR. Parasite clearance half-life and in vitro drug sensitivity testing were performed using standard methods. One hundred twenty nine isolates were successfully analyzed. Fifteen SNPs were present in pre-ACTs isolates and six in post-ACTs. None of the SNPs showed association with parasite clearance half-life. Post-ACTs parasites had significantly higher pfmdr1 copy number compared to pre-ACTs. Seven of eight parasites with multiple pfmdr1 were post-ACTs. When in vitro IC50s were compared for parasites with single vs. multiple gene copies, only amodiaquine and piperaquine reached statistical significance. Data showed SNPs on chromosome 13 and 14 had different frequency and trend in western Kenya parasites compared SEA. Increase in pfmdr1 gene copy is consistent with recent studies in African parasites. Data suggests genetic signature of artemisinin resistance in Africa might be different from SEA.
authors: 1] Department of Emerging Infectious Diseases-Global Emerging Infections Surveillance and Response System (DEID-GEIS) Program, United States Army Medical Research Unit-Kenya (USAMRU-K), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, Kisumu, Kenya [2] Institute of Tropical Medicine and Infectious Diseases, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya.
authors: Bidii S
authors: BS
authors: Ngalah
authors: Department of Emerging Infectious Diseases-Global Emerging Infections Surveillance and Response System (DEID-GEIS) Program, United States Army Medical Research Unit-Kenya (USAMRU-K), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, Kisumu, Kenya.
authors: Luiser A
authors: LA
authors: Ingasia
authors: Department of Emerging Infectious Diseases-Global Emerging Infections Surveillance and Response System (DEID-GEIS) Program, United States Army Medical Research Unit-Kenya (USAMRU-K), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, Kisumu, Kenya.
authors: Agnes C
authors: AC
authors: Cheruiyot
authors: 1] Department of Emerging Infectious Diseases-Global Emerging Infections Surveillance and Response System (DEID-GEIS) Program, United States Army Medical Research Unit-Kenya (USAMRU-K), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, Kisumu, Kenya [2] Institute of Tropical Medicine and Infectious Diseases, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya.
authors: Lorna J
authors: LJ
authors: Chebon
authors: Department of Emerging Infectious Diseases-Global Emerging Infections Surveillance and Response System (DEID-GEIS) Program, United States Army Medical Research Unit-Kenya (USAMRU-K), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, Kisumu, Kenya.
authors: Dennis W
authors: DW
authors: Juma
authors: 1] Department of Emerging Infectious Diseases-Global Emerging Infections Surveillance and Response System (DEID-GEIS) Program, United States Army Medical Research Unit-Kenya (USAMRU-K), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, Kisumu, Kenya [2] Institute of Tropical Medicine and Infectious Diseases, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya.
authors: Peninah
authors: P
authors: Muiruri
authors: Department of Emerging Infectious Diseases-Global Emerging Infections Surveillance and Response System (DEID-GEIS) Program, United States Army Medical Research Unit-Kenya (USAMRU-K), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, Kisumu, Kenya.
authors: Irene
authors: I
authors: Onyango
authors: Department of Emerging Infectious Diseases-Global Emerging Infections Surveillance and Response System (DEID-GEIS) Program, United States Army Medical Research Unit-Kenya (USAMRU-K), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, Kisumu, Kenya.
authors: Jack
authors: J
authors: Ogony
authors: Department of Emerging Infectious Diseases-Global Emerging Infections Surveillance and Response System (DEID-GEIS) Program, United States Army Medical Research Unit-Kenya (USAMRU-K), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, Kisumu, Kenya.
authors: Redemptah A
authors: RA
authors: Yeda
authors: 1] Department of Emerging Infectious Diseases-Global Emerging Infections Surveillance and Response System (DEID-GEIS) Program, United States Army Medical Research Unit-Kenya (USAMRU-K), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, Kisumu, Kenya [2] School of Biological/physical sciences, Department of Zoology, Maseno University, Maseno, Kenya.
authors: Jelagat
authors: J
authors: Cheruiyot
authors: Ifakara Health Institute, Bagamoyo, Tanzania.
authors: Emmanuel
authors: E
authors: Mbuba
authors: Ifakara Health Institute, Bagamoyo, Tanzania.
authors: Grace
authors: G
authors: Mwangoka
authors: 1] Department of Emerging Infectious Diseases-Global Emerging Infections Surveillance and Response System (DEID-GEIS) Program, United States Army Medical Research Unit-Kenya (USAMRU-K), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, Kisumu, Kenya [2] School of Biological/physical sciences, Department of Zoology, Maseno University, Maseno, Kenya.
authors: Angela O
authors: AO
authors: Achieng
authors: Institute of Tropical Medicine and Infectious Diseases, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya.
authors: Zipporah
authors: Z
authors: Ng'ang'a
authors: Department of Emerging Infectious Diseases-Global Emerging Infections Surveillance and Response System (DEID-GEIS) Program, United States Army Medical Research Unit-Kenya (USAMRU-K), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, Kisumu, Kenya.
authors: Ben
authors: B
authors: Andagalu
authors: Department of Emerging Infectious Diseases-Global Emerging Infections Surveillance and Response System (DEID-GEIS) Program, United States Army Medical Research Unit-Kenya (USAMRU-K), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, Kisumu, Kenya.
authors: Hoseah M
authors: HM
authors: Akala
authors: Department of Emerging Infectious Diseases-Global Emerging Infections Surveillance and Response System (DEID-GEIS) Program, United States Army Medical Research Unit-Kenya (USAMRU-K), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, Kisumu, Kenya.
authors: Edwin
authors: E
authors: Kamau
mesh_terms: D000483:Alleles; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D037621:Artemisinins / Q000494:pharmacology* / Q000627:therapeutic use; D018628:Gene Dosage; D005787:Gene Frequency; D056426:Genetic Loci; D006801:Humans; D020128:Inhibitory Concentration 50; D007630:Kenya; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C513498:Mdr1 protein, Plasmodium falciparum; C031327:artemisinin
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