Sulfadoxine-pyrimethamine efficacy and selection of Plasmodium falciparum DHFR mutations in Burkina Faso before its introduction as intermittent preventive treatment for pregnant women.
Sulfadoxine-pyrimethamine efficacy was determined with a 28-day follow-up in 97 children between 6 months and 15 years of age. The polymerase chain reaction (PCR)-corrected treatment failure was 8.2% and the uncorrected was 21.6%. The presence of the dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) mutations linked to sulfadoxine-pyrimethamine resistance before and after treatment was determined by PCR-restriction fragment length polymorphism (RFLP) and by a fluorogenic PCR assay. Before treatment, the prevalence of the triple DHFR mutations was higher among the patients having had a recurrent parasitemia (either recrudescence or new infection; 28.6% versus 9.3%), although the difference was not significant (P = 0.1). The double mutation Ala-436/Gly-437 was observed in 67% of samples, whereas no Glu-540 mutation was found. After treatment, the triple DHFR mutation was found in 76.2% of patients with recurrent parasitemia, recrudescence, and new infection alike. Such high prevalence of mutant parasites indicates that sulfadoxine-pyrimethamine should not be used as monotherapy.
Tinto
Halidou
H
Centre Muraz, Bobo Dioulasso, Burkina Faso.
Ouédraogo
Jean Bosco
JB
Zongo
Issaka
I
van Overmeir
Chantal
C
van Marck
Eric
E
Guiguemdé
Tinga Robert
TR
D'Alessandro
Umberto
U
D000293:Adolescent; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002050:Burkina Faso / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000517:prevention & control*; D008297:Male; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000517:prevention & control; D011739:Pyrimethamine / Q000008:administration & dosage* / Q000494:pharmacology*; D012641:Selection, Genetic; D013413:Sulfadoxine / Q000008:administration & dosage* / Q000494:pharmacology*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D013762:Tetrahydrofolate Dehydrogenase; D011739:Pyrimethamine