title: Polymorphisms of the Pfatpase 6 and Pfcrt gene and their relationship with the in vitro susceptibility to dihydroartemisinin and chloroquine of Plasmodium falciparum isolates from Abobo, Côte d'Ivoire.
abstract: As a result of widespread resistance to chloroquine (CQ) and sulphadoxine-pyrimethamine (SP), artemisinin-based combination therapy (ACT) has been recommended as a first-line anti-malarial regimen in Côte d'Ivoire since 2005. A thorough understanding of the molecular bases of P. falciparum resistance to existing drugs is therefore needed. The aims of this study were to analyze the in vitro sensitivity of P. falciparum field isolates from Abobo to CQ, pyronaridine (PYR) and dihydroartemisinine (DHA), and to investigate the polymorphisms associated with drug resistance. The standard in vitro drug sensitivity microtechnique recommended by the WHO was used to assess the sensitivity of Plasmodium falciparum isolates collected in December 2006. The Pfcrt haplotype 76 was analysed by PCR-RFLP while Pfatpase 6 amplification products were sequenced. Associations between drug sensitivity and parasite gene polymorphisms were evaluated with Cohen's kappa test. The correlation between the IC50 values for different drugs was assessed by the coefficient of determination (r²). Significance was assumed at p<0.05. Of 128 in vitro tests performed, 112 (87.5%) were successful. Of the isolates, 56.2% were resistant for CQ and 48% for PYR. One isolate (3.6%) demonstrated reduced DHA sensitivity (IC50 higher than 10 nM). The mutant K76T pfcrt codon, present in 90% of DNA fragments analyzed, was associated with CQ-R (ĸ=0.76). The N669Y (16.1%), D734Y (28.6%) and D734H (1.8%) isolates were found to have mutant Pfatpase6, however, these mutations were not associated with diminished DHA sensitivity (k=0.01). These high levels of antimalarial drug resistance in Abobo (Côte d'Ivoire) demand further studies of drug efficacy across the whole country.
authors.forename: Brice K
authors.initials: BK
authors.lastname: Bla
authors.forename: William
authors.initials: W
authors.lastname: Yavo
authors.forename: Jonhson
authors.initials: J
authors.lastname: Trébissou
authors.forename: Rolland G
authors.initials: RG
authors.lastname: Kipré
authors.forename: Félix H
authors.initials: FH
authors.lastname: Yapi
authors.forename: Jean D
authors.initials: JD
authors.lastname: N'guessan
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Djaman
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D037621:Artemisinins / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D007560:Cote d'Ivoire / Q000453:epidemiology; D004351:Drug Resistance; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C039060:artenimol; D002738:Chloroquine; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases