Document Detail

High prevalence of mutations in the dihydrofolate reductase gene of Plasmodium falciparum in isolates from Tanzania without evidence of an association to clinical sulfadoxine/pyrimethamine resistance.
MedLine Citation:
PMID:  9391510     Owner:  NLM     Status:  MEDLINE    
Recently the efficacy of sulfadoxine/pyrimethamine (S/P) in treatment of uncomplicated falciparum malaria in Tanzania has been seriously compromised by the development of resistance. The occurrence of active site mutations in the Plasmodium falciparum gene sequence coding for dihydrofolate reductase (DHFR) is known to confer resistance to pyrimethamine. This study investigates the occurrence of these mutations in infected blood samples taken from Tanzanian children before treatment with S/P and their relationship to parasite breakthrough by day 7. The results confirm the occurrence of one or more DHFR mutations in all the samples, but no relationship was found with the presence of parasites in the blood at day 7. The results suggest that alterations in the coding region for dihydropteroate synthetase (DHPS), the enzyme target for sulfadoxine, should be studied in order to predict resistance to the S/P combination. It has been proposed earlier that sulfadoxine could itself act on DHFR, because of a false dihydrofolate produced by drug metabolism through DHPS and dihydrofolate synthase. The results of this treatment study suggest that such a possibility is unlikely.
T Jelinek; A M Rønn; J Curtis; M T Duraisingh; M M Lemnge; J Mhina; I C Bygbjerg; D C Warhurst
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Tropical medicine & international health : TM & IH     Volume:  2     ISSN:  1360-2276     ISO Abbreviation:  Trop. Med. Int. Health     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1997-12-18     Completed Date:  1997-12-18     Revised Date:  2010-08-25    
Medline Journal Info:
Nlm Unique ID:  9610576     Medline TA:  Trop Med Int Health     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1075-9     Citation Subset:  IM    
Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, United Kingdom.
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MeSH Terms
Antimalarials / therapeutic use*
Child, Preschool
DNA, Protozoan / analysis
Drug Combinations
Drug Resistance / genetics
Malaria, Falciparum / drug therapy,  parasitology*
Plasmodium falciparum / enzymology*,  genetics*,  isolation & purification
Point Mutation*
Pyrimethamine / therapeutic use*
Sulfadoxine / therapeutic use*
Tetrahydrofolate Dehydrogenase / genetics*
Grant Support
//Wellcome Trust
Reg. No./Substance:
0/Antimalarials; 0/DNA, Protozoan; 0/Drug Combinations; 2447-57-6/Sulfadoxine; 37338-39-9/sulfadoxine-pyrimethamine; 58-14-0/Pyrimethamine; EC Dehydrogenase
Comment In:
Trop Med Int Health. 1998 Mar;3(3):249   [PMID:  9593365 ]

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