Independent lineages of highly sulfadoxine-resistant Plasmodium falciparum haplotypes, eastern Africa

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 mig...

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Published in:Emerging infectious diseases 2014-07, Vol.20 (7), p.1140-1148
Main Authors: Taylor, Steve M, Antonia, Alejandro L, Harrington, Whitney E, Goheen, Morgan M, Mwapasa, Victor, Chaluluka, Ebbie, Fried, Michal, Kabyemela, Edward, Madanitsa, Mwayi, Khairallah, Carole, Kalilani-Phiri, Linda, Tshefu, Antoinette K, Rogerson, Stephen J, Ter Kuile, Feiko O, Duffy, Patrick E, Meshnick, Steven R
Format: Article
Language:English
Subjects:
Africa, Eastern
Analysis
Antimalarials
Antimalarials - therapeutic use
Cross-Sectional Studies
Dihydropteroate Synthase - genetics
Drug resistance
Drug Resistance - genetics
Female
Haplotypes - genetics
Humans
lineages
Malaria
Malaria, Falciparum - drug therapy
Malaria, Falciparum - parasitology
Malawi
Microsatellite Repeats - genetics
Mutation - genetics
parasites
Plasmodium falciparum
Plasmodium falciparum - drug effects
Plasmodium falciparum - genetics
Pregnancy
sulfadoxine
Sulfadoxine - therapeutic use
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Summary: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.
ISSN:1080-6040
1080-6059
DOI:10.3201/eid2007.131720