The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC.

Antimalarials / pharmacology Chloroquine / pharmacology Democratic Republic of the Congo Drug Combinations Drug Resistance / genetics Genome, Protozoan Genotype Geography Haplotypes Humans Malaria, Falciparum / parasitology Mutation Plasmodium falciparum / drug effects Polymorphism, Single Nucleotide Principal Component Analysis Pyrimethamine / pharmacology Sulfadoxine / pharmacology

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
30 04 2020
Historique:
received: 31 05 2019
accepted: 28 03 2020
entrez: 2 5 2020
pubmed: 2 5 2020
medline: 8 8 2020
Statut: epublish

Résumé

The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequence 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a high-throughput genotyping tool. We identify an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identify highly related parasites over large geographic distances, indicative of gene flow and migration. Our results are consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.

Identifiants

DOI: 10.1038/s41467-020-15779-8 PMID: 32355199 PMC: PMC7192906
pubmed: 32355199
doi: 10.1038/s41467-020-15779-8
pii: 10.1038/s41467-020-15779-8
pmc: PMC7192906
doi:

Substances chimiques

Antimalarials 0
Drug Combinations 0
fanasil, pyrimethamine drug combination 37338-39-9
Sulfadoxine 88463U4SM5
Chloroquine 886U3H6UFF
Pyrimethamine Z3614QOX8W

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2107

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI139520
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI089680
Pays : United States
Organisme : NIAID NIH HHS
ID : K24 AI134990
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI121465
Pays : United States
Organisme : Medical Research Council
ID : MR/R015600/1
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI075045
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI089674
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI107949
Pays : United States
Organisme : FIC NIH HHS
ID : K01 TW010868
Pays : United States
Organisme : NIAID NIH HHS
ID : F30 AI143172
Pays : United States

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Auteurs

Robert Verity (R)

Medical Research Council Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK. r.verity@imperial.ac.uk.
ORCID: 0000-0002-3902-8567

Ozkan Aydemir (O)

Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, USA.
ORCID: 0000-0002-3458-6527

Nicholas F Brazeau (NF)

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, USA.
ORCID: 0000-0003-3976-7965

Oliver J Watson (OJ)

Medical Research Council Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK.
ORCID: 0000-0003-2374-0741

Nicholas J Hathaway (NJ)

Program in Bioinformatics and Integrative Biology, University of Massachusetts, Worcester, MA, USA.

Melchior Kashamuka Mwandagalirwa (MK)

Kinshasa School of Public Health, Hôpital Général Provincial de Référence de Kinshasa, Kinshasa, Democratic, Republic of Congo.

Patrick W Marsh (PW)

Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, USA.

Kyaw Thwai (K)

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, USA.

Travis Fulton (T)

Division of Infectious Diseases, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Madeline Denton (M)

Division of Infectious Diseases, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Andrew P Morgan (AP)

Division of Infectious Diseases, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
ORCID: 0000-0003-1942-4543

Jonathan B Parr (JB)

Division of Infectious Diseases, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Patrick K Tumwebaze (PK)

Infectious Disease Research Collaboration, Kampala, Uganda.

Melissa Conrad (M)

Department of Medicine, University of California- San Francisco, San Francisco, CA, USA.

Philip J Rosenthal (PJ)

Department of Medicine, University of California- San Francisco, San Francisco, CA, USA.

Deus S Ishengoma (DS)

National Institute for Medical Research, Tanga, Tanzania.

Jeremiah Ngondi (J)

RTI International, Dar es Salaam, Tanzania.
ORCID: 0000-0003-4357-4816

Julie Gutman (J)

Malaria Branch, Center for Global Health, Centers for Disease Control, Atlanta, GA, USA.
ORCID: 0000-0001-6769-7322

Modest Mulenga (M)

Tropical Disease Research Centre, Ndola, Zambia.

Douglas E Norris (DE)

Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

William J Moss (WJ)

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Benedicta A Mensah (BA)

Noguchi Memorial Institute of Medical Research, University of Ghana, Accra, Ghana.

James L Myers-Hansen (JL)

Noguchi Memorial Institute of Medical Research, University of Ghana, Accra, Ghana.
ORCID: 0000-0001-7125-1673

Anita Ghansah (A)

Noguchi Memorial Institute of Medical Research, University of Ghana, Accra, Ghana.

Antoinette K Tshefu (AK)

Kinshasa School of Public Health, Hôpital Général Provincial de Référence de Kinshasa, Kinshasa, Democratic, Republic of Congo.

Azra C Ghani (AC)

Medical Research Council Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK.

Steven R Meshnick (SR)

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, USA.

Jeffrey A Bailey (JA)

Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, USA.
ORCID: 0000-0002-6899-8204

Jonathan J Juliano (JJ)

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, USA. jjuliano@med.unc.edu.
Division of Infectious Diseases, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jjuliano@med.unc.edu.
Curriculum in Genetics and Molecular Biology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jjuliano@med.unc.edu.
ORCID: 0000-0002-0591-0850

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiparasitaires › Antiprotozoaires › Antipaludiques › The impact of antimalarial resistance on the...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Quinoléines › Aminoquinoléines › Chloroquine › The impact of antimalarial resistance on the...
questionsmedicales.fr › Régions géographiques › Afrique › Afrique subsaharienne › Afrique centrale › République démocratique du Congo › The impact of antimalarial resistance on the...
questionsmedicales.fr › Préparations pharmaceutiques › Association médicamenteuse › The impact of antimalarial resistance on the...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › The impact of antimalarial resistance on the...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Génome de protozoaire › The impact of antimalarial resistance on the...
questionsmedicales.fr › Phénomènes génétiques › Génotype › The impact of antimalarial resistance on the...
questionsmedicales.fr › Disciplines des sciences naturelles › Sciences de la Terre › Géographie › The impact of antimalarial resistance on the...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Haplotypes › The impact of antimalarial resistance on the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The impact of antimalarial resistance on the...
questionsmedicales.fr › Infection › Maladies vectorielles › Paludisme › Paludisme à Plasmodium falciparum › The impact of antimalarial resistance on the...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › The impact of antimalarial resistance on the...
questionsmedicales.fr › Eucaryotes › Alveolata › Apicomplexa › Haemosporida › Plasmodium › Plasmodium falciparum › The impact of antimalarial resistance on the...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › The impact of antimalarial resistance on the...
questionsmedicales.fr › Techniques d'investigation › Analyse en composantes principales › The impact of antimalarial resistance on the...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyrimidines › Pyriméthamine › The impact of antimalarial resistance on the...
questionsmedicales.fr › Composés chimiques organiques › Composés du soufre › Sulfones › Sulfonamides › Sulfamides › Sulfadoxine › The impact of antimalarial resistance on the...