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

Date Published: April 14, 2009

Publisher: Public Library of Science

Author(s): Richard J. Pearce, Hirva Pota, Marie-Solange B. Evehe, El-Hadj Bâ, Ghyslain Mombo-Ngoma, Allen L. Malisa, Rosalynn Ord, Walter Inojosa, Alexandre Matondo, Diadier A. Diallo, Wilfred 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, Sian Clarke, Karen I. Barnes, Elizabeth Streat, Stark T. Katokele, Petrina Uusiku, Chris O. Agboghoroma, Olufunmilayo Y. Elegba, Badara Cissé, Ishraga E. A-Elbasit, Hayder A. Giha, S. Patrick Kachur, Caroline Lynch, John B. Rwakimari, Pascalina Chanda, Moonga Hawela, Brian Sharp, Inbarani Naidoo, Cally Roper, Lorenz von Seidlein

Abstract: Cally Roper and colleagues analyze the distribution of sulfadoxine resistance mutations and flanking microsatellite loci to trace the emergence and dispersal of drug-resistant Plasmodium falciparum malaria in Africa.

Partial Text: Chloroquine (CQ) and the antifolate combination of sulphadoxine–pyrimethamine (SP) were, until recently, the mainstay of malaria treatment in Africa. Resistance to both drugs is now widespread. In both cases the importation of resistance mutations to Africa from Asia played a decisive role in the establishment of resistance [1]–[3], but details of where, when, or how resistance genes were introduced in Africa are unknown.

We examined the contemporary distribution of dhps resistance mutations and found that single, codon 437–mutant (AGK/SGK) alleles were predominant in west and central Africa while the double, codon 437– and 540–mutant (SGE) alleles prevailed throughout east Africa. Flanking sequence analysis showed multiple origins of both single- and double-mutant alleles: three major AGK/SGK lineages and two major SGE lineages. All had been subject to recent selection and each had a highly distinctive regional geographic distribution. In southeast Africa SGE 1 was predominant, while in Northeast Africa SGE 2 prevailed. The three AGK/SGK lineages predominated in different regions: AGK/SGK1 in the southwest, AGK/SGK2 in west Africa, and AGK/SGK3 in central Africa (Cameroon).



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