Sensitivity to antifolates and genetic analysis of Plasmodium vivax isolates from Thailand.
Am J Trop Med Hyg
; 76(6): 1057-65, 2007 Jun.
Article
em En
| MEDLINE
| ID: mdl-17556611
ABSTRACT
We investigated the association between the Plasmodium vivax dihydrofolate reductase (Pvdhfrtas) and the P. vivax dihydropteroate synthase (Pvdhps) genotype and in vitro sensitivity to the antifolates pyrimethamine, WR99210, chlorcycloguanil, sulfadoxine, and dapsone. Drug responses of 32 P. vivax isolates were assessed in two in vitro systems schizont maturation inhibition and a yeast expression system. The geometric mean of 50% inhibition concentration (IC(50)) values for pyrimethamine, chlorcycloguanil, WR99210, sulfadoxine, and dapsone were 85 +/- 88, 784 +/- 662, 95 +/- 87, 2,424 +/- 2,784, and 1,625 +/- 1,801 nM, respectively, for the schizont maturation assay. Five different Pvdhfr alleles and four Pvdhps alleles were observed 26 of 32 quadruple mutant alleles of Pvdhfr (F57I,L/S58R/T61M/S117T), four triple mutants (S58R/T61M/S117T, K49C/S58R/S117N), and two double mutant isolates (S58R/S117N). All isolates carried Pvdhps 585V. Twenty four isolates carried double mutant Pvdhps (A383G/A553G), six an additional mutation, S382A,C/A383G/A553G, and two a single mutation, A383G. Increasing geometric mean IC(50) values were observed with increased number of Pvdhfr mutations from double to quadruple. Results suggest that quadruple mutant alleles confer decreased sensitivity to pyrimethamine but retain sensitivity to WR99210.
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Base de dados:
MEDLINE
Assunto principal:
Plasmodium vivax
/
Tetra-Hidrofolato Desidrogenase
/
Malária Vivax
/
Di-Hidropteroato Sintase
/
Antagonistas do Ácido Fólico
/
Antimaláricos
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
País como assunto:
Asia
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article