Multiple origins and regional dispersal of resistant dhps in African Plasmodium falciparum malaria.
Authors
Pearce, Richard JPota, Hirva
Evehe, Marie-Solange B
Bâ, El-Hadj
Mombo-Ngoma, Ghyslain
Malisa, Allen L
Ord, Rosalynn
Inojosa, Walter
Matondo, Alexandre
Diallo, Diadier A
Mbacham, Wilfred
van den Broek, Ingrid V
Swarthout, Todd D
Getachew, Asefaw
Dejene, Seyoum
Grobusch, Martin P
Njie, Fanta
Dunyo, Samuel
Kweku, Margaret
Owusu-Agyei, Seth
Chandramohan, Daniel
Bonnet, Maryline
Guthmann, Jean-Paul
Clarke, Sian
Barnes, Karen I
Streat, Elizabeth
Katokele, Stark T
Uusiku, Petrina
Agboghoroma, Chris O
Elegba, Olufunmilayo Y
Cissé, Badara
A-Elbasit, Ishraga E
Giha, Hayder A
Kachur, S Patrick
Lynch, Caroline
Rwakimari, John B
Chanda, Pascalina
Hawela, Moonga
Sharp, Brian
Naidoo, Inbarani
Roper, Cally
Affiliation
London School of Hygiene & Tropical Medicine, Department of Infectious Tropical Diseases, London, UK.Issue Date
2009-04-14
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PLoS MedicineAbstract
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.PubMed ID
19365539Language
enISSN
1549-1676ae974a485f413a2113503eed53cd6c53
10.1371/journal.pmed.1000055
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