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Reference Manager
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-
1
Plowe C, Cortese J, Djimde A, Nwanyanwu O, Watkins W, Winstanley P, Estrada-Franco J, Mollinedo R, Avila J, Cespedes J, Carter D, Doumbo O, 1997. Mutations in P. falciparum dihydrofolate reductase and dihydropteroate synthase genes and epidemiologic patterns of pyrimethamine/sulfadoxine use and resistance. J Infect Dis 176 :1590–1596.
-
2
WHO, 1992. The overlap in the clinical presentation and treatment of malaria and pneumonia in children. Report No. 12, Geneva: World Health Organization.
-
3
Lyer JK, Milhous WK, Cortese JF, Kublin JG, Plowe CV, 2001. P. falciparum cross-resistance between trimethoprim and pyrimethamine. Lancet 358 :1–4.
-
4
Peterson D, Walliker D, Wellems T, 1988. Evidence that a point mutation in dihydrofolate reductase thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. Proc Natl Acad Sci U S A 85 :9114–9118.
-
5
Zolg J, Plitt J, Chen G, Palmer S, 1989. Point mutations in the dihydrofolate reductase thymidylate synthase as molecular basis for pyrimethamine resistance in P. falciparum. Mol Biochem Parasitol 36 :253–262.
-
6
Brooks D, Wang P, Read M, Watkins W, Sims P, Hyde J, 1994. Sequence variation of the hydroxymethyldihydropterin pyrophosphokinase: DHPS gene in line of human malaria parasite P. falciparum with differing resistance to sulfadoxine. Eur J Biochem 224 :397–405.
-
7
Wang P, Read M, Sims P, Hyde J, 1997. Sulfadoxine resistance in human malaria parasite P. falciparum is determined by mutations in the dihydropteroate synthase gene and an additional factor associated with folate utilisation. Mol Microbiol 23 :979–986.
-
8
Foote S, Galatis D, Cowman A, 1990. Amino acids in the dihydrofolate reductase thymidylate synthase gene of P. falciparum involved in pyrimethamine resistance. Proc Natl Acad Sci U S A 87 :3014–3017.
-
9
Peterson D, Milhous W, Wellems T, 1990. Molecular basis of differential resistance to cycloguanil and pyrimethamine in P. falciparum malaria. Proc Natl Acad Sci U S A 87 :3018–3022.
-
10
Martin P, Arnold J, 1986. Treatment of acute falciparum malaria with sulfalene and trimethoprim. JAMA 203 :134–138.
-
11
Schapira A, Bygbjerg IC, Jepsen S, Flachs H, Bentzon A, 1986. The susceptibility of P. falciparum to sulfadoxine and pyrimethamine: correlation of in vivo and in vitro studies. Am J Trop Med Hyg 35 :239–245.
-
12
Petersen E, 1987. In vitro susceptibility of P. falciparum to pyrimethamine, sulfadoxine, trimethoprim and sulfamethoxazole singly and in combination. Trans R Soc Trop Med Hyg 81 :238–241.
-
13
Jensen JB, Trager W, 1977. Plasmodium falciparum in culture: use of outdated erythrocytes and description of the candle jar method. J Parasitol 63 :883–886.
-
14
Ausubel F, Brent R, Kingston R, Moore D, Seidman J, Smith, J, Struhl K, 1997. Short protocols in molecular biology. 3rd ed. New York: Welly & Sons.
-
15
Taylor A, 1997. Titration of heparinase for the removal of the PCR inhibitory effect of heparin in DNA samples. Mol Ecol 6 :383–385.
-
16
Jelinek T, Kilian A, Curtis J, Duraisingh M, Kabagambe G, Warhurst D, 1999. P. falciparum: selection of serine 108 of dhfr during treatment uncomplicated malaria with cotrimoxazole in Ugandan children. Am J Trop Med Hyg 61 :125–130.
-
17
Peterson D, Santi M, Povoa V, Scalvosa V, Rosario D, Wellems T, 1991. Prevalence of dihydrofolate reductase Asp-108 mutation as basis for pyrimethamine resistant falciparum malaria in the Brazilian Amazon. Am J Trop Med Hyg 45 :492–497.
-
18
Basco L, Eldin P, Wilson CJ, Le Brase J, Mazabrand A, 1995. Point mutations in the dihydrofolate reductasethymidylate synthase gene and pyrimethamine and cycloguanil resistance in P. falciparum. Mol Biochem Parasitol 69 :135–138.
-
19
Nzila-Mounda A, Mberu E, Sibley C, Plowe C, Winstanley P, Watkins W, 1998. Kenyan P. falciparum isolates: correlation between pyrimethamine and cycloguanil activity in vitro and point mutations in the dihydrofolate reductase domain. Antimicrob Agent Chemother 44 :164–169.
-
20
Khalil IF, 2000. Cotrimoxazole and Fansidar in the treatment of acute uncomplicated falciparum malaria: efficacy, safety and molecular characterization of resistance. PhD thesis. Faculty of Health Sciences, University of Copenhagen, Denmark.
-
21
Magesa SM, Mdira KY, Farnert A, Simonsen PE, Bygbjerg IC, Jakobsen PH, 2001. Distinguishing P. falciparum treatment failures from re-infections by using polymerase chain reaction genotyping in a holoendemic area in Northeastern Tanzania. Am J Trop Med Hyg 65 :477–483.
-
22
Milhous W, Weatherly N, Bowdre J, Desjardins R, 1985. In vitro activities and mechanisms of resistance to antifolate drugs. Antimicrob Agents Chemother 27 :525–530.
-
23
Chulay JD, Watkins WM, Sixsmith DG, 1984. Synergistic antimalarial activity of pyrimethamine and sulfadoxine against P. falciparum in vitro. Am J Trop Med Hyg 33 :325–330.
-
24
Watkins W, Sixsmith D, Chulay J, Spencer H, 1985. Antagonism of sulfadoxine and pyrimethamine antimalarial activity in vitro by para-aminobenzoic acid, para-aminobenzoylglutamic acid and folic acid. Mol Biochem Parasitol 14 :55–61.
-
25
Wang P, Sims P, Hyde J, 1997. Modified in vitro susceptibility assay for P. falciparum suitable for investigating sulfadoxine resistance. Parasitology 115 :223–230.
-
26
Ndounga M, Basco LK, Ringwald P, 2001. Evaluation of a new SDX sensitivity assay in vitro for field isolates of P. falciparum. Trans R Soc Trop Med Hyg 95 :55–57.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 585 | 515 | 26 |
| Full Text Views | 521 | 9 | 0 |
| PDF Downloads | 148 | 9 | 0 |
DIHYDROFOLATE REDUCTASE AND DIHYDROPTEROATE SYNTHASE GENOTYPES ASSOCIATED WITH IN VITRO RESISTANCE OF PLASMODIUM FALCIPARUM TO PYRIMETHAMINE, TRIMETHOPRIM, SULFADOXINE, AND SULFAMETHOXAZOLE
INSAF KHALIL
INSAF KHALIL
Center for Medical Parasitology, Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark; Department of Biochemistry, Faculty of Medicine, University of Khartoum, Sudan; Department of Clinical Pharmacology, Copenhagen University Hospital, Denmark; Department of Biochemistry, King Faisal University, Dammam, Saudi Arabia; Department of International Health, Institute of Public Health, University of Copenhagen, Denmark
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ANITA M. RØNN
ANITA M. RØNN
Center for Medical Parasitology, Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark; Department of Biochemistry, Faculty of Medicine, University of Khartoum, Sudan; Department of Clinical Pharmacology, Copenhagen University Hospital, Denmark; Department of Biochemistry, King Faisal University, Dammam, Saudi Arabia; Department of International Health, Institute of Public Health, University of Copenhagen, Denmark
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MICHAEL ALIFRANGIS
MICHAEL ALIFRANGIS
Center for Medical Parasitology, Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark; Department of Biochemistry, Faculty of Medicine, University of Khartoum, Sudan; Department of Clinical Pharmacology, Copenhagen University Hospital, Denmark; Department of Biochemistry, King Faisal University, Dammam, Saudi Arabia; Department of International Health, Institute of Public Health, University of Copenhagen, Denmark
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HAYTHAM A. GABAR
HAYTHAM A. GABAR
Center for Medical Parasitology, Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark; Department of Biochemistry, Faculty of Medicine, University of Khartoum, Sudan; Department of Clinical Pharmacology, Copenhagen University Hospital, Denmark; Department of Biochemistry, King Faisal University, Dammam, Saudi Arabia; Department of International Health, Institute of Public Health, University of Copenhagen, Denmark
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GWIRIA M. H. SATTI
GWIRIA M. H. SATTI
Center for Medical Parasitology, Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark; Department of Biochemistry, Faculty of Medicine, University of Khartoum, Sudan; Department of Clinical Pharmacology, Copenhagen University Hospital, Denmark; Department of Biochemistry, King Faisal University, Dammam, Saudi Arabia; Department of International Health, Institute of Public Health, University of Copenhagen, Denmark
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IB C. BYGBJERG
IB C. BYGBJERG
Center for Medical Parasitology, Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark; Department of Biochemistry, Faculty of Medicine, University of Khartoum, Sudan; Department of Clinical Pharmacology, Copenhagen University Hospital, Denmark; Department of Biochemistry, King Faisal University, Dammam, Saudi Arabia; Department of International Health, Institute of Public Health, University of Copenhagen, Denmark
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A total of 70 Plasmodium falciparum isolates were tested in vitro against pyrimethamine (PYR), tri-methoprim (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 μg/100 μl 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 μg/100 μl (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.
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ProCite
RefWorks
Reference Manager
BibTeX
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-
1
Plowe C, Cortese J, Djimde A, Nwanyanwu O, Watkins W, Winstanley P, Estrada-Franco J, Mollinedo R, Avila J, Cespedes J, Carter D, Doumbo O, 1997. Mutations in P. falciparum dihydrofolate reductase and dihydropteroate synthase genes and epidemiologic patterns of pyrimethamine/sulfadoxine use and resistance. J Infect Dis 176 :1590–1596.
-
2
WHO, 1992. The overlap in the clinical presentation and treatment of malaria and pneumonia in children. Report No. 12, Geneva: World Health Organization.
-
3
Lyer JK, Milhous WK, Cortese JF, Kublin JG, Plowe CV, 2001. P. falciparum cross-resistance between trimethoprim and pyrimethamine. Lancet 358 :1–4.
-
4
Peterson D, Walliker D, Wellems T, 1988. Evidence that a point mutation in dihydrofolate reductase thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. Proc Natl Acad Sci U S A 85 :9114–9118.
-
5
Zolg J, Plitt J, Chen G, Palmer S, 1989. Point mutations in the dihydrofolate reductase thymidylate synthase as molecular basis for pyrimethamine resistance in P. falciparum. Mol Biochem Parasitol 36 :253–262.
-
6
Brooks D, Wang P, Read M, Watkins W, Sims P, Hyde J, 1994. Sequence variation of the hydroxymethyldihydropterin pyrophosphokinase: DHPS gene in line of human malaria parasite P. falciparum with differing resistance to sulfadoxine. Eur J Biochem 224 :397–405.
-
7
Wang P, Read M, Sims P, Hyde J, 1997. Sulfadoxine resistance in human malaria parasite P. falciparum is determined by mutations in the dihydropteroate synthase gene and an additional factor associated with folate utilisation. Mol Microbiol 23 :979–986.
-
8
Foote S, Galatis D, Cowman A, 1990. Amino acids in the dihydrofolate reductase thymidylate synthase gene of P. falciparum involved in pyrimethamine resistance. Proc Natl Acad Sci U S A 87 :3014–3017.
-
9
Peterson D, Milhous W, Wellems T, 1990. Molecular basis of differential resistance to cycloguanil and pyrimethamine in P. falciparum malaria. Proc Natl Acad Sci U S A 87 :3018–3022.
-
10
Martin P, Arnold J, 1986. Treatment of acute falciparum malaria with sulfalene and trimethoprim. JAMA 203 :134–138.
-
11
Schapira A, Bygbjerg IC, Jepsen S, Flachs H, Bentzon A, 1986. The susceptibility of P. falciparum to sulfadoxine and pyrimethamine: correlation of in vivo and in vitro studies. Am J Trop Med Hyg 35 :239–245.
-
12
Petersen E, 1987. In vitro susceptibility of P. falciparum to pyrimethamine, sulfadoxine, trimethoprim and sulfamethoxazole singly and in combination. Trans R Soc Trop Med Hyg 81 :238–241.
-
13
Jensen JB, Trager W, 1977. Plasmodium falciparum in culture: use of outdated erythrocytes and description of the candle jar method. J Parasitol 63 :883–886.
-
14
Ausubel F, Brent R, Kingston R, Moore D, Seidman J, Smith, J, Struhl K, 1997. Short protocols in molecular biology. 3rd ed. New York: Welly & Sons.
-
15
Taylor A, 1997. Titration of heparinase for the removal of the PCR inhibitory effect of heparin in DNA samples. Mol Ecol 6 :383–385.
-
16
Jelinek T, Kilian A, Curtis J, Duraisingh M, Kabagambe G, Warhurst D, 1999. P. falciparum: selection of serine 108 of dhfr during treatment uncomplicated malaria with cotrimoxazole in Ugandan children. Am J Trop Med Hyg 61 :125–130.
-
17
Peterson D, Santi M, Povoa V, Scalvosa V, Rosario D, Wellems T, 1991. Prevalence of dihydrofolate reductase Asp-108 mutation as basis for pyrimethamine resistant falciparum malaria in the Brazilian Amazon. Am J Trop Med Hyg 45 :492–497.
-
18
Basco L, Eldin P, Wilson CJ, Le Brase J, Mazabrand A, 1995. Point mutations in the dihydrofolate reductasethymidylate synthase gene and pyrimethamine and cycloguanil resistance in P. falciparum. Mol Biochem Parasitol 69 :135–138.
-
19
Nzila-Mounda A, Mberu E, Sibley C, Plowe C, Winstanley P, Watkins W, 1998. Kenyan P. falciparum isolates: correlation between pyrimethamine and cycloguanil activity in vitro and point mutations in the dihydrofolate reductase domain. Antimicrob Agent Chemother 44 :164–169.
-
20
Khalil IF, 2000. Cotrimoxazole and Fansidar in the treatment of acute uncomplicated falciparum malaria: efficacy, safety and molecular characterization of resistance. PhD thesis. Faculty of Health Sciences, University of Copenhagen, Denmark.
-
21
Magesa SM, Mdira KY, Farnert A, Simonsen PE, Bygbjerg IC, Jakobsen PH, 2001. Distinguishing P. falciparum treatment failures from re-infections by using polymerase chain reaction genotyping in a holoendemic area in Northeastern Tanzania. Am J Trop Med Hyg 65 :477–483.
-
22
Milhous W, Weatherly N, Bowdre J, Desjardins R, 1985. In vitro activities and mechanisms of resistance to antifolate drugs. Antimicrob Agents Chemother 27 :525–530.
-
23
Chulay JD, Watkins WM, Sixsmith DG, 1984. Synergistic antimalarial activity of pyrimethamine and sulfadoxine against P. falciparum in vitro. Am J Trop Med Hyg 33 :325–330.
-
24
Watkins W, Sixsmith D, Chulay J, Spencer H, 1985. Antagonism of sulfadoxine and pyrimethamine antimalarial activity in vitro by para-aminobenzoic acid, para-aminobenzoylglutamic acid and folic acid. Mol Biochem Parasitol 14 :55–61.
-
25
Wang P, Sims P, Hyde J, 1997. Modified in vitro susceptibility assay for P. falciparum suitable for investigating sulfadoxine resistance. Parasitology 115 :223–230.
-
26
Ndounga M, Basco LK, Ringwald P, 2001. Evaluation of a new SDX sensitivity assay in vitro for field isolates of P. falciparum. Trans R Soc Trop Med Hyg 95 :55–57.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 585 | 515 | 26 |
| Full Text Views | 521 | 9 | 0 |
| PDF Downloads | 148 | 9 | 0 |