Do mutations in Plasmodium falciparum dihydropteroate synthase and dihydrofolate reductase confer resistance to sulfadoxine-pyrimethamine in Iran?
The key codons of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) genes implicated in sulfadoxine-pyrimethamine (SP) resistance were determined by allele-specific polymerase chain reaction in Plasmodium falciparum isolates collected in 1999 from 35 Iranian patients treated with SP. Seven isolates had Glu-540 dhps allele but 5 of these isolates were characterized to possess wild-type dhfr alleles. Seven additional isolates were polyclonal with mixed Lys- and Glu-540. The key dhfr mutation associated with pyrimethamine resistance, Asn-108, was found in 4 isolates. In one patient the presence of Lys- and Glu-540 in dhps and Asn-108 and Arg-59 in dhfr was associated with treatment failure. However, more studies are needed to determine whether clinical response to SP and mutations in these genes are correlated in Iran.
Eskandarian
Abbas-Ali
AA
Department of Medical Parasitology and Mycology, School of Health, Institute for Health Researches, University of Medical Sciences of Tehran, Tehran, Iran.
Keshavarz
Hossein
H
Basco
Leonardo K
LK
Mahboudi
Fereidoun
F
D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002648:Child; D004094:Dihydropteroate Synthase / Q000235:genetics*; D004338:Drug Combinations; D018432:Drug Resistance, Multiple / Q000235:genetics; D005260:Female; D006801:Humans; D007492:Iran; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010963:Plasmodium falciparum / Q000201:enzymology / Q000235:genetics*; D011739:Pyrimethamine / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine