Kenyan Plasmodium falciparum Field Isolates: Correlation between Pyrimethamine and Chlorcycloguanil Activity In Vitro and Point Mutations in the Dihydrofolate Reductase Domain

作者: A. Nzila-Mounda , E. K. Mberu , C. H. Sibley , C. V. Plowe , P. A. Winstanley

DOI: 10.1128/AAC.42.1.164

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摘要: Sixty-nine Kenyan Plasmodium falciparum field isolates were tested in vitro against pyrimethamine (PM), chlorcycloguanil (CCG), sulfadoxine (SD), and dapsone (DDS), their dihydrofolate reductase (DHFR) genotypes determined. The data show that CCG is more potent than PM DDS SD. DHFR genotype correlated with drug response. Isolates can be classified into three distinct groups based on 50% inhibitory concentrations (IC 50 s) for ( P s of 3.71 ± 6.94 0.24 0.21 nM, respectively. second group includes parasites which all have mutations at codon 108 alone or also codons 51 59 represents one homogeneous 25- 6-fold increases IC s, respectively, are observed. Parasites 108, 51, (triple mutants) form a third nine- eightfold compared to the Surprisingly, there significant decrease

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