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

• Main Authors: Michael Alifrangis, Sidsel Nag, Mette L. Schousboe, Deus S. 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, Cally Roper
• Format: Article
• Language: English
• Published: Centers for Disease Control and Prevention 2014-08-01
• Series: Emerging Infectious Diseases
• Subjects: Dihydrofolate reductase; Pfdhfr; dihydropteroate synthetase; Pfdhps; 581; eastern Africa
• Online Access: https://wwwnc.cdc.gov/eid/article/20/8/13-1897_article

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.