Multiple origins and regional dispersal of resistant dhps in African Plasmodium falciparum malaria.

Hdl Handle:
http://hdl.handle.net/10144/98755
Title:
Multiple origins and regional dispersal of resistant dhps in African Plasmodium falciparum malaria.
Authors:
Pearce, Richard J; Pota, 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
Journal:
PLoS Medicine
Abstract:
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.
Affiliation:
London School of Hygiene & Tropical Medicine, Department of Infectious Tropical Diseases, London, UK.
Issue Date:
14-Apr-2009
URI:
http://hdl.handle.net/10144/98755
DOI:
10.1371/journal.pmed.1000055
PubMed ID:
19365539
Language:
en
ISSN:
1549-1676
Appears in Collections:
Malaria

Full metadata record

DC FieldValue Language
dc.contributor.authorPearce, Richard Jen
dc.contributor.authorPota, Hirvaen
dc.contributor.authorEvehe, Marie-Solange Ben
dc.contributor.authorBâ, El-Hadjen
dc.contributor.authorMombo-Ngoma, Ghyslainen
dc.contributor.authorMalisa, Allen Len
dc.contributor.authorOrd, Rosalynnen
dc.contributor.authorInojosa, Walteren
dc.contributor.authorMatondo, Alexandreen
dc.contributor.authorDiallo, Diadier Aen
dc.contributor.authorMbacham, Wilfreden
dc.contributor.authorvan den Broek, Ingrid Ven
dc.contributor.authorSwarthout, Todd Den
dc.contributor.authorGetachew, Asefawen
dc.contributor.authorDejene, Seyoumen
dc.contributor.authorGrobusch, Martin Pen
dc.contributor.authorNjie, Fantaen
dc.contributor.authorDunyo, Samuelen
dc.contributor.authorKweku, Margareten
dc.contributor.authorOwusu-Agyei, Sethen
dc.contributor.authorChandramohan, Danielen
dc.contributor.authorBonnet, Marylineen
dc.contributor.authorGuthmann, Jean-Paulen
dc.contributor.authorClarke, Sianen
dc.contributor.authorBarnes, Karen Ien
dc.contributor.authorStreat, Elizabethen
dc.contributor.authorKatokele, Stark Ten
dc.contributor.authorUusiku, Petrinaen
dc.contributor.authorAgboghoroma, Chris Oen
dc.contributor.authorElegba, Olufunmilayo Yen
dc.contributor.authorCissé, Badaraen
dc.contributor.authorA-Elbasit, Ishraga Een
dc.contributor.authorGiha, Hayder Aen
dc.contributor.authorKachur, S Patricken
dc.contributor.authorLynch, Carolineen
dc.contributor.authorRwakimari, John Ben
dc.contributor.authorChanda, Pascalinaen
dc.contributor.authorHawela, Moongaen
dc.contributor.authorSharp, Brianen
dc.contributor.authorNaidoo, Inbaranien
dc.contributor.authorRoper, Callyen
dc.date.accessioned2010-05-13T22:22:17Z-
dc.date.available2010-05-13T22:22:17Z-
dc.date.issued2009-04-14-
dc.identifier.citationMultiple origins and regional dispersal of resistant dhps in African Plasmodium falciparum malaria. 2009, 6 (4):e1000055 PLoS Med.en
dc.identifier.issn1549-1676-
dc.identifier.pmid19365539-
dc.identifier.doi10.1371/journal.pmed.1000055-
dc.identifier.urihttp://hdl.handle.net/10144/98755-
dc.description.abstractBACKGROUND: 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.en
dc.language.isoenen
dc.rightsPublished by Public Library of Science, [url]http://medicine.plosjournals.org/[/url] Archived on this site by Open Access permissionen
dc.subject.meshAfricaen
dc.subject.meshAllelesen
dc.subject.meshAnimalsen
dc.subject.meshAntimalarialsen
dc.subject.meshChloroquineen
dc.subject.meshDNA, Protozoanen
dc.subject.meshDihydropteroate Synthaseen
dc.subject.meshDrug Combinationsen
dc.subject.meshDrug Resistanceen
dc.subject.meshHumansen
dc.subject.meshMalaria, Falciparumen
dc.subject.meshMembrane Transport Proteinsen
dc.subject.meshMicrosatellite Repeatsen
dc.subject.meshPhylogenyen
dc.subject.meshPlasmodium falciparumen
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshPopulation Surveillanceen
dc.subject.meshProtozoan Proteinsen
dc.subject.meshPyrimethamineen
dc.subject.meshSelection, Geneticen
dc.subject.meshSulfadoxineen
dc.titleMultiple origins and regional dispersal of resistant dhps in African Plasmodium falciparum malaria.en
dc.contributor.departmentLondon School of Hygiene & Tropical Medicine, Department of Infectious Tropical Diseases, London, UK.en
dc.identifier.journalPLoS Medicineen

Related articles on PubMed

All Items in MSF are protected by copyright, with all rights reserved, unless otherwise indicated.