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

Richard J. Pearce; Hirva Pota; Marie-Solange B. Evehe; El-Hadj Ba; 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 Cisse; 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

doi:10.1371/journal.pmed.1000055

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

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

Richard J. Pearce, Hirva Pota, Marie-Solange B. Evehe, El-Hadj Ba, Ghyslain Mombo-Ngoma, Allen L. Malisa, Rosalynn Ord, Walter Inojosa, Alexandre Matondo, Diadier A. Diallo, …

PLoS medicine, Vol.6(4), p.e1000055

14/04/2009

DOI: https://doi.org/10.1371/journal.pmed.1000055

PMID: 19365539

Résumé

General & Internal Medicine

Life Sciences & Biomedicine

Medicine, General & Internal

Science & Technology

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.

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Titre: Multiple Origins and Regional Dispersal of Resistant dhps in African Plasmodium falciparum Malaria
Créateurs - sans rôle: Richard J. Pearce - Univ London London Sch Hyg & Trop Med, Dept Infect Trop Dis, London WC1E 7HT, England
Hirva Pota - Univ London London Sch Hyg & Trop Med, Dept Infect Trop Dis, London WC1E 7HT, England
Marie-Solange B. Evehe - Univ Yaounde I, Ctr Biotechnol, Yaounde, Cameroon
El-Hadj Ba - Inst Rech Dev, Dakar, Senegal
Ghyslain Mombo-Ngoma - Albert Schweitzer Hosp, Med Res Unit, Lambarene, Gabon
Allen L. Malisa - IHRDC, Ifakara, Tanzania
Rosalynn Ord - Univ London London Sch Hyg & Trop Med, Dept Infect Trop Dis, London WC1E 7HT, England
Walter Inojosa - Doctors Africa CUAMM Angola, Luanda, Angola
Alexandre Matondo - Uige Prov Hosp, Uige, Angola
Diadier A. Diallo - CNRFP, Ouagadougou, Burkina Faso
Wilfred Mbacham - Univ Yaounde I, Ctr Biotechnol, Yaounde, Cameroon
Ingrid V. van den Broek - Med Sans Frontieres, Manson Unit, London, England
Todd D. Swarthout - Med Sans Frontieres, Manson Unit, London, England
Asefaw Getachew - Tigray Bur Hlth, Malaria Dept, Tigray, Ethiopia
Seyoum Dejene - Med Sans Frontieres Ethiopia, Addis Ababa, Ethiopia
Martin P. Grobusch - Albert Schweitzer Hosp, Med Res Unit, Lambarene, Gabon
Fanta Njie
Samuel Dunyo
Margaret Kweku - Univ London London Sch Hyg & Trop Med, Dept Infect Trop Dis, London WC1E 7HT, England
Seth Owusu-Agyei - Univ London London Sch Hyg & Trop Med, Dept Infect Trop Dis, London WC1E 7HT, England
Daniel Chandramohan - University of London
Maryline Bonnet - Epictr, Paris, France
Jean-Paul Guthmann - Epictr, Paris, France
Sian Clarke - Univ London London Sch Hyg & Trop Med, Dept Infect Trop Dis, London WC1E 7HT, England
Karen I. Barnes - Univ Cape Town, Dept Med, Div Clin Pharmacol, ZA-7925 Cape Town, South Africa
Elizabeth Streat - Minist Hlth, Matola, Maputo Province, Mozambique
Stark T. Katokele - Old State Hosp Grounds, Minist Hlth & Social Serv, Natl Malaria Control Programme, Windhoek, Namibia
Petrina Uusiku - Old State Hosp Grounds, Minist Hlth & Social Serv, Natl Malaria Control Programme, Windhoek, Namibia
Chris O. Agboghoroma - Natl Hosp Abuja, Garki Abuja, Nigeria
Olufunmilayo Y. Elegba - Natl Hosp Abuja, Garki Abuja, Nigeria
Badara Cisse - Univ Cheikh Anta Diop Dakar, Dakar, Senegal
Ishraga E. A-Elbasit - Univ Khartoum, Dept Biochem, Malaria Res Ctr, Khartoum, Sudan
Hayder A. Giha - Univ Khartoum, Dept Biochem, Malaria Res Ctr, Khartoum, Sudan
S. Patrick Kachur - CDC, Malaria Branch, Div Parasit Dis, Natl Ctr Zoonot Vector Borne & Enter Dis, Atlanta, GA 30333 USA
Caroline Lynch - Univ London London Sch Hyg & Trop Med, Dept Infect Trop Dis, London WC1E 7HT, England
John B. Rwakimari - Minist Hlth Uganda, Natl Malaria Control Programme, Kampala, Uganda
Pascalina Chanda - Natl Malaria Control Ctr, Lusaka, Zambia
Moonga Hawela - Natl Malaria Control Ctr, Lusaka, Zambia
Brian Sharp - MRC, Malaria Res Lead Programme, Durban, South Africa
Inbarani Naidoo - MRC, Malaria Res Lead Programme, Durban, South Africa
Cally Roper - Univ London London Sch Hyg & Trop Med, Dept Infect Trop Dis, London WC1E 7HT, England
Détails de publication: PLoS medicine, Vol.6(4), p.e1000055
Éditeur: Public Library Science
Nombre de pages: 15
Note de subvention: Gates Malaria Partnership (GMP)
Identifiants: 99158549509311
Unité académique: Recherches translationnelles sur le VIH et les Maladies Infect. Endém. émerg. - TransVIHMI
Langue: English
Type de ressource: Journal article