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


Alifrangis, M; Nag, S; Schousboe, ML; Ishengoma, D; Lusingu, J; Pota, H; Kavishe, RA; Pearce, R; Ord, R; Lynch, C; Dejene, S; Cox, J; Rwakimari, J; Minja, DTR; Lemnge, MM; Roper, C; (2014) Independent Origin of Plasmodium falciparum Antifolate Super-Resistance, Uganda, Tanzania, and Ethiopia. Emerging infectious diseases, 20 (8). pp. 1280-1286. ISSN 1080-6040 DOI: 10.3201/eid2008.131897

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Abstract

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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Disease Control
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Malaria Centre
Antimicrobial Resistance Centre (AMR)
Maternal Health Group
PubMed ID: 25061906
Web of Science ID: 339864000002
URI: http://researchonline.lshtm.ac.uk/id/eprint/1924565

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