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1
Iyer JK, Milhous WK, Cortese JF, Kublin JG, Plowe CV, 2001. Plasmodium falciparum cross-resistance between trimethoprim and pyrimethamine. Lancet 29 :1066–1067.
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2
Jelinek T, Kilian A, Curtis J, Duraisingh M, Kabagambe G, Warhurst DP, 1999. Plasmodium falciparum: selection for Ser 108 of DHFR during treatment of uncomplicated malaria with cotrimoxazole in Ugandan children. Am J Trop Med Hyg 61 :125–130.
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3
World Health Organization, 1996. Assessment of Therapeutic Efficacy of Antimalarial Drugs for Uncomplicated Falciparum Malaria in Areas with Intense Transmission. Geneva: World Health Organization. WHO/MAL/96.1077.
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4
Khalil IF, Alifrangis M, Ronn AM, Gabar HA, Jelinek T, Satti GM, Bygbjerg IC, 2002. Pyrimethamine/sulfadoxine combination in the treatment of uncomplicated falciparum malaria: relation between dihydropteroate synthase/dihydrofolate reductase genotypes, sulfadoxine plasma levels, and treatment outcome. Am J Trop Med Hyg 67 :225–229.
-
5
Snounou G, Beck H, 1998. The use of PCR genotyping in the assessment of recrudescence or re-infection after antimalarial treatment. Parasitol Today 14 :462–467.
-
6
Rønn AM, Mutabingwa T, Kreisby S, Angelo HM, Fuursted K, Bygbjerg IC, 1999. A reversed phase high-pressure liquid chromatography method for the determination of cotrimoxazole (TRM/SMX) in children treated for malaria. Ther Drug Monit 21 :609–614.
-
7
Djimde A, Doumbo OK, Traore O, Guindo AB, Kayentao K, Diourte Y, Niare-Doumbo S, Coulibaly D, Kone AK, Cissoko Y, Tekete M, Fofana B, Dicko A, Diallo DA, Wellems TE, Kwiatkowski D, Plowe CV, 2003. Clearance of drug-resistant parasites as a model for protective immunity in Plasmodium falciparum malaria. Am J Trop Med Hyg 69 :558–563.
-
8
Wang P, Shinn O, Bayoumi R, Djimde A, Doumbo O, Swedbrg G, Daol L, Mshinda H, Hyde JE, 1997. Resistance to the antifolates in Plasmodium falciparum monitored by sequence analysis of dihydropteroate synthase and dihydrofolate reductase alleles in a large number of field samples of diverse origin. Mol Biochem Parasitol 89 :161–177.
-
9
Warhurst D, 2002. Resistance to antifolates in P. falciparum, the causative agent of tropical malaria. Sci Prog 85 :89–111.
-
10
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 Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase and epidemiologic patterns of pyrimethamine-sulfadoxine use and resistance. J Infect Dis 176 :1590–1596.
-
11
Kilian AH, Jelinek T, Prislin I, Kabagambe G, Byamukama W, Mpigika G, Korte R, von Sonnenburg F, 1998. Resistance in vivo of P. falciparum to cotrimoxazole in western Uganda. Trans R Soc Trop Med Hyg 92 :197–200.
-
12
Reeves D, Wilkinson P, 1979. The pharmacokinetics of trimethoprim and trimethoprim/sulphonamide combinations, including penetration into body tissues. Infection 7 (Supp 4):S330–S341.
-
13
Hansford C, Hoyland J, 1982. An evaluation of cotrimoxazole in the treatment of P. falciparum malaria. S Afr Med J 61 :512–514.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 30 | 30 | 10 |
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RESPONSE OF PLASMODIUM FALCIPARUM TO COTRIMOXAZOLE THERAPY: RELATIONSHIP WITH PLASMA DRUG CONCENTRATIONS AND DIHYDROFOLATE REDUCTASE AND DIHYDROPTEROATE SYNTHASE GENOTYPES
INSAF F. KHALIL
INSAF F. KHALIL
Centre for Medical Parasitology, Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; Department of International Health, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark; Department of Biochemistry, Faculty of Medicine, University of Khartoum, Khartoum, Sudan; Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany; Department of Biochemistry, King Faisal University; Dammam, Saudi Arabia
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ANITA M. RØNN
ANITA M. RØNN
Centre for Medical Parasitology, Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; Department of International Health, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark; Department of Biochemistry, Faculty of Medicine, University of Khartoum, Khartoum, Sudan; Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany; Department of Biochemistry, King Faisal University; Dammam, Saudi Arabia
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MICHAEL ALIFRANGIS
MICHAEL ALIFRANGIS
Centre for Medical Parasitology, Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; Department of International Health, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark; Department of Biochemistry, Faculty of Medicine, University of Khartoum, Khartoum, Sudan; Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany; Department of Biochemistry, King Faisal University; Dammam, Saudi Arabia
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HYTHAM A. GABAR
HYTHAM A. GABAR
Centre for Medical Parasitology, Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; Department of International Health, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark; Department of Biochemistry, Faculty of Medicine, University of Khartoum, Khartoum, Sudan; Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany; Department of Biochemistry, King Faisal University; Dammam, Saudi Arabia
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THOMAS JELINEK
THOMAS JELINEK
Centre for Medical Parasitology, Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; Department of International Health, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark; Department of Biochemistry, Faculty of Medicine, University of Khartoum, Khartoum, Sudan; Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany; Department of Biochemistry, King Faisal University; Dammam, Saudi Arabia
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GWIRIA M. H. SATTI
GWIRIA M. H. SATTI
Centre for Medical Parasitology, Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; Department of International Health, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark; Department of Biochemistry, Faculty of Medicine, University of Khartoum, Khartoum, Sudan; Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany; Department of Biochemistry, King Faisal University; Dammam, Saudi Arabia
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IB C. BYGBJERG
IB C. BYGBJERG
Centre for Medical Parasitology, Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; Department of International Health, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark; Department of Biochemistry, Faculty of Medicine, University of Khartoum, Khartoum, Sudan; Department of Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany; Department of Biochemistry, King Faisal University; Dammam, Saudi Arabia
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We assessed the efficacy of trimethoprim/sulfamethoxazole (TRM/SMX) in vivo in relation to the frequency of dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) alleles in 45 Sudanese malaria patients. Plasma levels of TRM, SMX, and acetylsulfamethoxazole (AcSMX) were measured before treatment and at days 3, 7, and 14 or upon recrudescence to ascertain drug absorption. Forty patients (89%) had an adequate clinical response, one patient (2%) had an early treatment failure response, while four patients (8%) showed late treatment failure responses. Genotyping of merozoite surface protein 1, MSP-1, MSP-2, and glutamate-rich protein before treatment and upon recrudescence showed that all recurring parasites were recrudescences. The plasma levels of TRM, AcSMX, and SMX indicated adequate drug absorption in all patients. This suggests parasite resistance as a cause of treatment failure. The presence of dhfr Ile 51 and Asn 108 alone or coupled with dhps Ala-436 among parasites that were cleared after treatment indicates that these alleles alone are insufficient to cause in vivo resistance. However, the presence of the triple mutant dhfr (Ile-51/Arg-59/Asn-108) with the dhps Gly-437 genotype in all recurring infections, suggests the importance of codon 59 and 437 alleles in susceptibility to TRM/SMX. However, the number is too little to make firm conclusions.
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RefWorks
Reference Manager
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-
1
Iyer JK, Milhous WK, Cortese JF, Kublin JG, Plowe CV, 2001. Plasmodium falciparum cross-resistance between trimethoprim and pyrimethamine. Lancet 29 :1066–1067.
-
2
Jelinek T, Kilian A, Curtis J, Duraisingh M, Kabagambe G, Warhurst DP, 1999. Plasmodium falciparum: selection for Ser 108 of DHFR during treatment of uncomplicated malaria with cotrimoxazole in Ugandan children. Am J Trop Med Hyg 61 :125–130.
-
3
World Health Organization, 1996. Assessment of Therapeutic Efficacy of Antimalarial Drugs for Uncomplicated Falciparum Malaria in Areas with Intense Transmission. Geneva: World Health Organization. WHO/MAL/96.1077.
-
4
Khalil IF, Alifrangis M, Ronn AM, Gabar HA, Jelinek T, Satti GM, Bygbjerg IC, 2002. Pyrimethamine/sulfadoxine combination in the treatment of uncomplicated falciparum malaria: relation between dihydropteroate synthase/dihydrofolate reductase genotypes, sulfadoxine plasma levels, and treatment outcome. Am J Trop Med Hyg 67 :225–229.
-
5
Snounou G, Beck H, 1998. The use of PCR genotyping in the assessment of recrudescence or re-infection after antimalarial treatment. Parasitol Today 14 :462–467.
-
6
Rønn AM, Mutabingwa T, Kreisby S, Angelo HM, Fuursted K, Bygbjerg IC, 1999. A reversed phase high-pressure liquid chromatography method for the determination of cotrimoxazole (TRM/SMX) in children treated for malaria. Ther Drug Monit 21 :609–614.
-
7
Djimde A, Doumbo OK, Traore O, Guindo AB, Kayentao K, Diourte Y, Niare-Doumbo S, Coulibaly D, Kone AK, Cissoko Y, Tekete M, Fofana B, Dicko A, Diallo DA, Wellems TE, Kwiatkowski D, Plowe CV, 2003. Clearance of drug-resistant parasites as a model for protective immunity in Plasmodium falciparum malaria. Am J Trop Med Hyg 69 :558–563.
-
8
Wang P, Shinn O, Bayoumi R, Djimde A, Doumbo O, Swedbrg G, Daol L, Mshinda H, Hyde JE, 1997. Resistance to the antifolates in Plasmodium falciparum monitored by sequence analysis of dihydropteroate synthase and dihydrofolate reductase alleles in a large number of field samples of diverse origin. Mol Biochem Parasitol 89 :161–177.
-
9
Warhurst D, 2002. Resistance to antifolates in P. falciparum, the causative agent of tropical malaria. Sci Prog 85 :89–111.
-
10
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 Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase and epidemiologic patterns of pyrimethamine-sulfadoxine use and resistance. J Infect Dis 176 :1590–1596.
-
11
Kilian AH, Jelinek T, Prislin I, Kabagambe G, Byamukama W, Mpigika G, Korte R, von Sonnenburg F, 1998. Resistance in vivo of P. falciparum to cotrimoxazole in western Uganda. Trans R Soc Trop Med Hyg 92 :197–200.
-
12
Reeves D, Wilkinson P, 1979. The pharmacokinetics of trimethoprim and trimethoprim/sulphonamide combinations, including penetration into body tissues. Infection 7 (Supp 4):S330–S341.
-
13
Hansford C, Hoyland J, 1982. An evaluation of cotrimoxazole in the treatment of P. falciparum malaria. S Afr Med J 61 :512–514.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 30 | 30 | 10 |
| Full Text Views | 239 | 98 | 0 |
| PDF Downloads | 43 | 16 | 0 |