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Multiple Origins and Regional Dispersal of Resistant dhps in African Plasmodium falciparum Malaria

2009; Public Library of Science; Volume: 6; Issue: 4 Linguagem: Inglês

10.1371/journal.pmed.1000055

1549-1676

Richard Pearce, Hirva Pota, Marie-Solange B. Evehe, El-Hadj Bâ, Ghyslain Mombo‐Ngoma, Allen L Malisa, Rosalynn Ord, Walter O Inojosa, Alexandre Matondo, Diadier Diallo, Wilfred Fon Mbacham, Ingrid V. van den Broek, Todd D. Swarthout, Asefaw Getachew, Seyoum Dejene, Martin P. Grobusch, Fanta Njie, Samuel Dunyo, Margaret Kweku, Seth Owusu‐Agyei, Daniel Chandramohan, Maryline Bonnet, Jean‐Paul Guthmann, Siân E. Clarke, Karen I. Barnes, Elizabeth Streat, Stark Katokele, Petrina Uusiku, Chris O Agboghoroma, Olufunmilayo Y. Elegba, Badara Cissé, Ishraga E. A‐Elbasit, Hayder A. Giha, S. Patrick Kachur, Caroline A. Lynch, John Bosco Rwakimari, Pascalina Chanda‐Kapata, Moonga Hawela, Brian Sharp, Inbarani Naidoo, Cally Roper,

Research on Leishmaniasis Studies

Background Although the molecular basis of resistance to a number of common antimalarial drugs is well known, a geographic description of the emergence and dispersal of resistance mutations across Africa has not been attempted. To that end we have characterised the evolutionary origins of antifolate resistance mutations in the dihydropteroate synthase (dhps) gene and mapped their contemporary distribution. Methods and Findings We used microsatellite polymorphism flanking the dhps gene to determine which resistance alleles shared common ancestry and found five major lineages each of which had a unique geographical distribution. The extent to which allelic lineages were shared among 20 African Plasmodium falciparum populations revealed five major geographical groupings. Resistance lineages were common to all sites within these regions. The most marked differentiation was between east and west African P. falciparum, in which resistance alleles were not only of different ancestry but also carried different resistance mutations. Conclusions Resistant dhps has emerged independently in multiple sites in Africa during the past 10–20 years. Our data show the molecular basis of resistance differs between east and west Africa, which is likely to translate into differing antifolate sensitivity. We have also demonstrated that the dispersal patterns of resistance lineages give unique insights into recent parasite migration patterns.