Parasites bearing a single copy of the multi-drug resistance gene (pfmdr-1) with wild-type SNPs predominate amongst Plasmodium falciparum isolates from Malawi

Standwell Nkhoma, Shalini Nair, Mavuto Mukaka, Malcolm E. Molyneux, Stephen A. Ward, Timothy J.C. Anderson

    Research output: Contribution to journalArticlepeer-review

    18 Scopus citations

    Abstract

    We genotyped 160 P. falciparum infections from Malawi for pfmdr-1 copy number changes and SNPs associated with in vivo tolerance and poor in vitro sensitivity to the component drugs of Coartem. We also measured in vitro susceptibility of 49 of these isolates to a variety of drugs in clinical use or with a potential for use in Africa. All 160 infections carried a single copy of pfmdr-1 but 34% exhibited sequence variation at 4 of the 5 polymorphic sites in pfmdr-1. Isolates carrying 86-Asn and 184-Tyr pfmdr-1 alleles were significantly less sensitive (p < 0.001) to mefloquine, lumefantrine, artemether and dihydroartemisinin compared with those bearing 86-Tyr and 184-Phe polymorphisms. This study provides baseline measures prior to policy change: continued surveillance for changes in baseline drug susceptibility, pfmdr-1 copy number and SNPs, and other putative Coartem resistance loci will be necessary to provide an early warning of emerging Coartem resistance in this setting.

    Original languageEnglish (US)
    Pages (from-to)78-81
    Number of pages4
    JournalActa Tropica
    Volume111
    Issue number1
    DOIs
    StatePublished - Jul 1 2009

    Keywords

    • Antimalarial resistance
    • Artemisinin combination therapy (ACT)
    • Coartem
    • Copy number
    • Malawi
    • Multi-drug resistance gene (pfmdr-1)
    • Plasmodium falciparum
    • Single nucleotide polymorphisms (SNPs)

    ASJC Scopus subject areas

    • Parasitology
    • veterinary (miscalleneous)
    • Insect Science
    • Infectious Diseases

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