Independent origin of plasmodium falciparum antifolate super-resistance, Uganda, Tanzania, and Ethiopia.
Super-resistant Plasmodium falciparum threatens the effectiveness of sulfadoxine-pyrimethamine in intermittent preventive treatment for malaria during pregnancy. It is characterized by the A581G Pfdhps mutation on a background of the double-mutant Pfdhps and the triple-mutant Pfdhfr. Using samples collected during 2004-2008, we investigated the evolutionary origin of the A581G mutation by characterizing microsatellite diversity flanking Pfdhps triple-mutant (437G+540E+581G) alleles from 3 locations in eastern Africa and comparing it with double-mutant (437G+540E) alleles from the same area. In Ethiopia, both alleles derived from 1 lineage that was distinct from those in Uganda and Tanzania. Uganda and Tanzania triple mutants derived from the previously characterized southeastern Africa double-mutant lineage. The A581G mutation has occurred multiple times on local Pfdhps double-mutant backgrounds; however, a novel microsatellite allele incorporated into the Tanzania lineage since 2004 illustrates the local expansion of emergent triple-mutant lineages.
['Alifrangis|Michael|M|', 'Nag|Sidsel|S|', 'Schousboe|Mette L|ML|', 'Ishengoma|Deus|D|', 'Lusingu|John|J|', 'Pota|Hirva|H|', 'Kavishe|Reginald A|RA|', 'Pearce|Richard|R|', 'Ord|Rosalynn|R|', 'Lynch|Caroline|C|', 'Dejene|Seyoum|S|', 'Cox|Jonathan|J|', 'Rwakimari|John|J|', 'Minja|Daniel T R|DT|', 'Lemnge|Martha M|MM|', 'Roper|Cally|C|']
D000293:Adolescent D000483:Alleles D002648:Child D002675:Child, Preschool D004094:Dihydropteroate Synthase D004351:Drug Resistance D005002:Ethiopia D005493:Folic Acid Antagonists D005787:Gene Frequency D006239:Haplotypes D006801:Humans D007223:Infant D016778:Malaria, Falciparum D018895:Microsatellite Repeats D009154:Mutation D010963:Plasmodium falciparum D013636:Tanzania D013762:Tetrahydrofolate Dehydrogenase D014454:Uganda D055815:Young Adult
Plasmodium falciparum Uganda Tanzania Ethiopia sulfadoxine-pyrimethamine malaria Pfdhps Pfdhfr microsatellite eastern Africa 581 Dihydrofolate reductase dihydropteroate synthetase intermittent preventive treatment in pregnant women parasites resistance single-nucleotide polymorphism vector-borne infections