Plasmodium falciparum:: Selection of serine 108 of dihydrofolate reductase during treatment of uncomplicated malaria with co-trimoxazole in Ugandan children

被引：37

作者：

Jelinek, T

Kilian, AHD

Curtis, J

Duraisingh, MT

Kabagambe, G

von Sonnenburg, F

Warhurst, DC

机构：

[1] Univ London London Sch Hyg & Trop Med, Dept Med Parasitol, London WC1E 7HT, England

[2] Univ Munich, Dept Trop Med & Infect Dis, D-80802 Munich, Germany

[3] German Soc Tech Cooperat, Basic Hlth Serv, Ft Portal, Uganda

[4] Dist Hlth Serv, Kabarole, Uganda

来源：

AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE | 1999年 / 61卷 / 01期

基金：

英国惠康基金;

关键词：

D O I：

10.4269/ajtmh.1999.61.125

中图分类号：

R1 [预防医学、卫生学];

学科分类号：

1004 ; 120402 ;

摘要：

In vivo testing for resistance of Plasmodium falciparum to co-trimoxazole (trimethoprim/sulfamethoxazole) was performed in Uganda in 41 children with uncomplicated malaria, and blood samples were screened before and after treatment for polymorphisms in the antifolate target genes for dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). Selection towards a specific genotype at some codons of the DHFR and DHPS genes was observed in samples collected after exposure to co-trimoxazole drug pressure. The alleles 51-isoleucine, 59-arginine, and 108-serine of DHFR were significantly associated with clinical resistance, as was allele 581-alanine of DHPS. Resistance against antifolate combinations probably requires resistance-related polymorphisms in both the DHFR and the DHPS genes. In addition, it appears that the trimethoprim-resistant DHFR genotype differs from that for pyrimethamine at residue 108.

引用

收藏

页码：125 / 130

页数：6

相关论文

共 30 条

[1] COTRIMOXAZOLE FOR CHILDHOOD FEBRILE ILLNESS IN MALARIA-ENDEMIC REGIONS [J].

BLOLAND, PB ;

REDD, SC ;

KAZEMBE, P ;

TEMBENU, R ;

WIRIMA, JJ ;

CAMPBELL, CC .

LANCET, 1991, 337 (8740) :518-520

[2] SEQUENCE VARIATION OF THE HYDROXYMETHYLDIHYDROPTERIN PYROPHOSPHOKINASE - DIHYDROPTEROATE SYNTHASE GENE IN-LINE SO THE HUMAN MALARIA PARASITE, PLASMODIUM-FALCIPARUM, WITH DIFFERING RESISTANCE TO SULFADOXINE [J].

BROOKS, DR ;

WANG, P ;

READ, M ;

WATKINS, WM ;

SIMS, PFG ;

HYDE, JE .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1994, 224 (02) :397-405

[3] AMINO-ACID CHANGES LINKED TO PYRIMETHAMINE RESISTANCE IN THE DIHYDROFOLATE-REDUCTASE THYMIDYLATE SYNTHASE GENE OF PLASMODIUM-FALCIPARUM [J].

COWMAN, AF ;

MORRY, MJ ;

BIGGS, BA ;

CROSS, GAM ;

FOOTE, SJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (23) :9109-9113

[4] Direct evidence that asparagine at position 108 of the Plasmodium falciparum dihydrofolate reductase is involved in resistance to antifolate drugs in Tanzania [J].

Curtis, J ;

Duraisingh, MT ;

Trigg, JK ;

Mbwana, H ;

Warhurst, DC ;

Curtis, CF .

TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 1996, 90 (06) :678-680

[5] SENSITIVITY OF PLASMODIUM-FALCIPARUM IN THE-GAMBIA TO COTRIMOXAZOLE [J].

DARAMOLA, OO ;

ALONSO, PL ;

ODEMPSEY, TJD ;

TWUMASI, P ;

MCARDLE, TF ;

GREENWOOD, BM .

TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 1991, 85 (03) :345-348

[6] PLASMODIUM-FALCIPARUM - DETECTION OF ANTIFOLATE RESISTANCE BY MUTATION-SPECIFIC RESTRICTION ENZYME DIGESTION [J].

DEPECOULAS, PE ;

BASCO, LK ;

ABDALLAH, B ;

DJE, MK ;

LEBRAS, J ;

MAZABRAUD, A .

EXPERIMENTAL PARASITOLOGY, 1995, 80 (03) :483-487

[7] Plasmodium falciparum:: Detection of polymorphisms in the Dihydrofolate reductase and Dihydropteroate synthetase genes by PCR and restriction digestion [J].

Duraisingh, MT ;

Curtis, J ;

Warhurst, DC .

EXPERIMENTAL PARASITOLOGY, 1998, 89 (01) :1-8

[8] SEVERAL ALLELES OF THE MULTIDRUG-RESISTANCE GENE ARE CLOSELY LINKED TO CHLOROQUINE RESISTANCE IN PLASMODIUM-FALCIPARUM [J].

FOOTE, SJ ;

KYLE, DE ;

MARTIN, RK ;

ODUOLA, AMJ ;

FORSYTH, K ;

KEMP, DJ ;

COWMAN, AF .

NATURE, 1990, 345 (6272) :255-258

[9] AMINO-ACIDS IN THE DIHYDROFOLATE REDUCTASE-THYMIDYLATE SYNTHASE GENE OF PLASMODIUM-FALCIPARUM INVOLVED IN CYCLOGUANIL RESISTANCE DIFFER FROM THOSE INVOLVED IN PYRIMETHAMINE RESISTANCE [J].

FOOTE, SJ ;

GALATIS, D ;

COWMAN, AF .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (08) :3014-3017

[10] Geographic differences in the sensitivity of a polymerase chain reaction for the detection of Plasmodium falciparum infection [J].

Jelinek, T ;

Proll, S ;

Hess, F ;

Kabagambe, G ;

VonSonnenburg, F ;

Loscher, T ;

Kilian, AHD .

AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1996, 55 (06) :647-651