Abstract
Artemisinin derivative-based combination therapy is expected to suppress the development of Plasmodium falciparum drug resistance in Africa. We have performed an artemether-lumefantrine (Coartem; Novartis) follow-up clinical trial in Zanzibar, in which pfcrt K76T and pfmdr1 N86Y frequencies were determined before drug administration and in all recurrent parasites during a follow-up period of 42 days. A significant increase in pfmdr1 86N was observed after exposure to the drug. This points to 86N as a potential marker of lumefantrine resistance in vivo, while suggesting that Coartem is not robust enough to avoid selection of resistance-associated mutations in some malarial settings.
Publication types
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Clinical Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP-Binding Cassette Transporters / genetics*
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Alleles
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Animals
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Antimalarials / pharmacology*
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Antimalarials / therapeutic use
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Artemether
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Artemisinins / pharmacology*
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Artemisinins / therapeutic use
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Child
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Drug Resistance / genetics
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Drug Therapy, Combination
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Ethanolamines / pharmacology*
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Ethanolamines / therapeutic use
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Fluorenes / pharmacology*
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Fluorenes / therapeutic use
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Genes, MDR
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Humans
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Infant
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Lumefantrine
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Malaria, Falciparum / drug therapy
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Malaria, Falciparum / parasitology
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Plasmodium falciparum / drug effects*
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Plasmodium falciparum / genetics
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Polymorphism, Single Nucleotide
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Protozoan Proteins / genetics*
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Selection, Genetic*
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Sesquiterpenes / pharmacology*
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Sesquiterpenes / therapeutic use
Substances
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ATP-Binding Cassette Transporters
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Antimalarials
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Artemisinins
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Ethanolamines
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Fluorenes
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Protozoan Proteins
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Sesquiterpenes
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mdr gene protein, Plasmodium
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Artemether
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Lumefantrine