Dihydrofolate reductase and dihydropteroate synthase genotypes associated with in vitro resistance of Plasmodium falciparum to pyrimethamine, trimethoprim, sulfadoxine, and sulfamethoxazole

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Dihydrofolate reductase and dihydropteroate synthase genotypes associated with in vitro resistance of Plasmodium falciparum to pyrimethamine, trimethoprim, sulfadoxine, and sulfamethoxazole. / Khalil, Insaf; Rønn, Anita M; Alifrangis, Michael; Gabar, Haytham A; Satti, Gwiria M H; Bygbjerg, Ib C.

In: American Journal of Tropical Medicine and Hygiene, Vol. 68, No. 5, 2003, p. 586-9.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Khalil, I, Rønn, AM, Alifrangis, M, Gabar, HA, Satti, GMH & Bygbjerg, IC 2003, 'Dihydrofolate reductase and dihydropteroate synthase genotypes associated with in vitro resistance of Plasmodium falciparum to pyrimethamine, trimethoprim, sulfadoxine, and sulfamethoxazole', American Journal of Tropical Medicine and Hygiene, vol. 68, no. 5, pp. 586-9.

APA

Khalil, I., Rønn, A. M., Alifrangis, M., Gabar, H. A., Satti, G. M. H., & Bygbjerg, I. C. (2003). Dihydrofolate reductase and dihydropteroate synthase genotypes associated with in vitro resistance of Plasmodium falciparum to pyrimethamine, trimethoprim, sulfadoxine, and sulfamethoxazole. American Journal of Tropical Medicine and Hygiene, 68(5), 586-9.

Vancouver

Khalil I, Rønn AM, Alifrangis M, Gabar HA, Satti GMH, Bygbjerg IC. Dihydrofolate reductase and dihydropteroate synthase genotypes associated with in vitro resistance of Plasmodium falciparum to pyrimethamine, trimethoprim, sulfadoxine, and sulfamethoxazole. American Journal of Tropical Medicine and Hygiene. 2003;68(5):586-9.

Author

Khalil, Insaf ; Rønn, Anita M ; Alifrangis, Michael ; Gabar, Haytham A ; Satti, Gwiria M H ; Bygbjerg, Ib C. / Dihydrofolate reductase and dihydropteroate synthase genotypes associated with in vitro resistance of Plasmodium falciparum to pyrimethamine, trimethoprim, sulfadoxine, and sulfamethoxazole. In: American Journal of Tropical Medicine and Hygiene. 2003 ; Vol. 68, No. 5. pp. 586-9.

Bibtex

@article{654f5aa0a99a11ddb5e9000ea68e967b,
title = "Dihydrofolate reductase and dihydropteroate synthase genotypes associated with in vitro resistance of Plasmodium falciparum to pyrimethamine, trimethoprim, sulfadoxine, and sulfamethoxazole",
abstract = "A total of 70 Plasmodium falciparum isolates were tested in vitro against pyrimethamine (PYR), trimethoprim (TRM), sulfadoxine (SDX), and sulfamethoxazole (SMX), and their dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genotypes were determined. dhfr genotypes correlated with PYR and TRM drug responses (r = 0.93 and 0.85). Isolates with wild-type alleles showed mean half inhibitory concentrations (IC50 +/- SD) of 0.10 +/- 0.10 and 0.15 +/- 0.06 microg/100 microl for PYR and TRM. Parasites with mutations at codons 108 and 51 alone or combined with codon 59 have IC50 of 11.46 +/- 0.86 (PYR) and 2.90 +/- 0.59 microg/100 microl (TRM). For both drugs, the differences in the mean IC50 between wild and mutant parasites were statistically significant (P < 0.001). Isolates with mixed wild and mutant alleles showed an intermediate level of susceptibility. Our data show partial cross-resistance between PYR/TRM and SDX/SMX (r = 0.85 and 0.65). Correlation was not observed between different dhps genotypes and the in vitro outcome to SDX and SMX (r = 0.30 and 0.34). The lack of correlation could be due to folates and para-aminobenzoic acid in the RPMI medium and the serum used to supplement the cultures.",
author = "Insaf Khalil and R{\o}nn, {Anita M} and Michael Alifrangis and Gabar, {Haytham A} and Satti, {Gwiria M H} and Bygbjerg, {Ib C}",
note = "Keywords: Adolescent; Adult; Aged; Animals; Antimalarials; Child; Dihydropteroate Synthase; Drug Resistance; Genotype; Humans; Malaria, Falciparum; Middle Aged; Parasitic Sensitivity Tests; Plasmodium falciparum; Point Mutation; Pyrimethamine; Reproducibility of Results; Sulfadoxine; Sulfamethoxazole; Tetrahydrofolate Dehydrogenase; Trimethoprim; Trimethoprim Resistance",
year = "2003",
language = "English",
volume = "68",
pages = "586--9",
journal = "Journal. National Malaria Society",
issn = "0002-9637",
publisher = "American Society of Tropical Medicine and Hygiene",
number = "5",

}

RIS

TY - JOUR

T1 - Dihydrofolate reductase and dihydropteroate synthase genotypes associated with in vitro resistance of Plasmodium falciparum to pyrimethamine, trimethoprim, sulfadoxine, and sulfamethoxazole

AU - Khalil, Insaf

AU - Rønn, Anita M

AU - Alifrangis, Michael

AU - Gabar, Haytham A

AU - Satti, Gwiria M H

AU - Bygbjerg, Ib C

N1 - Keywords: Adolescent; Adult; Aged; Animals; Antimalarials; Child; Dihydropteroate Synthase; Drug Resistance; Genotype; Humans; Malaria, Falciparum; Middle Aged; Parasitic Sensitivity Tests; Plasmodium falciparum; Point Mutation; Pyrimethamine; Reproducibility of Results; Sulfadoxine; Sulfamethoxazole; Tetrahydrofolate Dehydrogenase; Trimethoprim; Trimethoprim Resistance

PY - 2003

Y1 - 2003

N2 - A total of 70 Plasmodium falciparum isolates were tested in vitro against pyrimethamine (PYR), trimethoprim (TRM), sulfadoxine (SDX), and sulfamethoxazole (SMX), and their dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genotypes were determined. dhfr genotypes correlated with PYR and TRM drug responses (r = 0.93 and 0.85). Isolates with wild-type alleles showed mean half inhibitory concentrations (IC50 +/- SD) of 0.10 +/- 0.10 and 0.15 +/- 0.06 microg/100 microl for PYR and TRM. Parasites with mutations at codons 108 and 51 alone or combined with codon 59 have IC50 of 11.46 +/- 0.86 (PYR) and 2.90 +/- 0.59 microg/100 microl (TRM). For both drugs, the differences in the mean IC50 between wild and mutant parasites were statistically significant (P < 0.001). Isolates with mixed wild and mutant alleles showed an intermediate level of susceptibility. Our data show partial cross-resistance between PYR/TRM and SDX/SMX (r = 0.85 and 0.65). Correlation was not observed between different dhps genotypes and the in vitro outcome to SDX and SMX (r = 0.30 and 0.34). The lack of correlation could be due to folates and para-aminobenzoic acid in the RPMI medium and the serum used to supplement the cultures.

AB - A total of 70 Plasmodium falciparum isolates were tested in vitro against pyrimethamine (PYR), trimethoprim (TRM), sulfadoxine (SDX), and sulfamethoxazole (SMX), and their dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genotypes were determined. dhfr genotypes correlated with PYR and TRM drug responses (r = 0.93 and 0.85). Isolates with wild-type alleles showed mean half inhibitory concentrations (IC50 +/- SD) of 0.10 +/- 0.10 and 0.15 +/- 0.06 microg/100 microl for PYR and TRM. Parasites with mutations at codons 108 and 51 alone or combined with codon 59 have IC50 of 11.46 +/- 0.86 (PYR) and 2.90 +/- 0.59 microg/100 microl (TRM). For both drugs, the differences in the mean IC50 between wild and mutant parasites were statistically significant (P < 0.001). Isolates with mixed wild and mutant alleles showed an intermediate level of susceptibility. Our data show partial cross-resistance between PYR/TRM and SDX/SMX (r = 0.85 and 0.65). Correlation was not observed between different dhps genotypes and the in vitro outcome to SDX and SMX (r = 0.30 and 0.34). The lack of correlation could be due to folates and para-aminobenzoic acid in the RPMI medium and the serum used to supplement the cultures.

M3 - Journal article

C2 - 12812351

VL - 68

SP - 586

EP - 589

JO - Journal. National Malaria Society

JF - Journal. National Malaria Society

SN - 0002-9637

IS - 5

ER -

ID: 8377980