Independent origin of Plasmodium falciparum antifolate super-resistance, Uganda, Tanzania, and Ethiopia

TY - JOUR

T1 - Independent origin of Plasmodium falciparum antifolate super-resistance, Uganda, Tanzania, and Ethiopia

AU - Alifrangis, Michael

AU - Nag, Sidsel

AU - Schousboe, Mette L

AU - Ishengoma, Deus

AU - Lusingu, John

AU - Pota, Hirva

AU - Kavishe, Reginald A

AU - Pearce, Richard

AU - Ord, Rosalynn

AU - Lynch, Caroline

AU - Dejene, Seyoum

AU - Cox, Jonathan

AU - Rwakimari, John

AU - Minja, Daniel T R

AU - Lemnge, Martha M

AU - Roper, Cally

PY - 2014/8

Y1 - 2014/8

N2 - 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.

AB - 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.

U2 - 10.3201/eid2008.131897

DO - 10.3201/eid2008.131897

M3 - Journal article

C2 - 25061906

SN - 1080-6040

VL - 20

SP - 1280

EP - 1286

JO - Emerging Infectious Diseases (Print Edition)

JF - Emerging Infectious Diseases (Print Edition)

IS - 8

ER -