Independent Origin of Plasmodium falciparum Antifolate Super-Resistance, Uganda, Tanzania, and Ethiopia

The full article is available in Emerging Infectious Diseases

Controlling and reducing malaria requires a combination of vector control measures and administration of antimalarial drugs as prophylaxis or treatment. The widespread use of antimalarial drugs has resulted in the emergence of resistant Plasmodium falciparum, recurrently exposing persons in malaria-endemic regions to an unacceptably high risk for treatment failures.


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.


Michael Alifrangis, Sidsel Nag, Mette L. Schousboe, Deus Ishengoma, John Lusingu, Hirva Pota, Reginald A. Kavishe, Richard Pearce, Rosalynn Ord, Caroline Lynch, Seyoum Dejene, Jonathan Cox, John Rwakimari, Daniel T.R. Minja, Martha M. Lemnge, and Cally Roper