title: Independent lineages of highly sulfadoxine-resistant Plasmodium falciparum haplotypes, eastern Africa.
abstract: Sulfadoxine-resistant Plasmodium falciparum undermines malaria prevention with sulfadoxine/pyrimethamine. Parasites with a highly resistant mutant dihydropteroate synthase (dhps) haplotype have recently emerged in eastern Africa; they negated preventive benefits of sulfadoxine/pyrimethamine, and might exacerbate placental malaria. We explored emerging lineages of dhps mutant haplotypes in Malawi, the Democratic Republic of the Congo, and Tanzania by using analyses of genetic microsatellites flanking the dhps locus. In Malawi, a triple-mutant dhps SGEG (mutant amino acids are underlined) haplotype emerged in 2010 that was closely related to pre-existing double-mutant SGEA haplotypes, suggesting local origination in Malawi. When we compared mutant strains with parasites from the Democratic Republic of the Congo and Tanzania by multiple independent analyses, we found that SGEG parasites were partitioned into separate lineages by country. These findings support a model of local origination of SGEG dhps haplotypes, rather than geographic diffusion, and have implications for investigations of emergence and effects of parasite drug resistance.
authors: Steve M
authors: SM
authors: Taylor
authors: Alejandro L
authors: AL
authors: Antonia
authors: Whitney E
authors: WE
authors: Harrington
authors: Morgan M
authors: MM
authors: Goheen
authors: Victor
authors: V
authors: Mwapasa
authors: Ebbie
authors: E
authors: Chaluluka
authors: Michal
authors: M
authors: Fried
authors: Edward
authors: E
authors: Kabyemela
authors: Mwayi
authors: M
authors: Madanitsa
authors: Carole
authors: C
authors: Khairallah
authors: Linda
authors: L
authors: Kalilani-Phiri
authors: Antoinette K
authors: AK
authors: Tshefu
authors: Stephen J
authors: SJ
authors: Rogerson
authors: Feiko O
authors: FO
authors: Ter Kuile
authors: Patrick E
authors: PE
authors: Duffy
authors: Steven R
authors: SR
authors: Meshnick
mesh_terms: D000351:Africa, Eastern; D000962:Antimalarials / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D004094:Dihydropteroate Synthase / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D008295:Malawi; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D011247:Pregnancy; D013413:Sulfadoxine / Q000627:therapeutic use*
chemical_list: D000962:Antimalarials; D013413:Sulfadoxine; D004094:Dihydropteroate Synthase
keywords: Plasmodium falciparum; drug resistance; eastern Africa; genetics; haplotypes; lineages; malaria; parasites; population; sulfadoxine