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  • Title: Molecular surveillance of mutations in the cytochrome b gene of Plasmodium falciparum in Gabon and Ethiopia.
    Author: Gebru T, Hailu A, Kremsner PG, Kun JF, Grobusch MP.
    Journal: Malar J; 2006 Nov 21; 5():112. PubMed ID: 17118179.
    Abstract:
    BACKGROUND: Atovaquone is part of the antimalarial drug combination atovaquone-proguanil (Malarone) and inhibits the cytochrome bc1 complex of the electron transport chain in Plasmodium spp. Molecular modelling showed that amino acid mutations are clustered around a putative atovaquone-binding site resulting in a reduced binding affinity of atovaquone for plasmodial cytochrome b, thus resulting in drug resistance. METHODS: The prevalence of cytochrome b point mutations possibly conferring atovaquone resistance in Plasmodium falciparum isolates in atovaquone treatment-naïve patient cohorts from Lambaréné, Gabon and from South Western Ethiopia was assessed. RESULTS: Four/40 (10%) mutant types (four different single polymorphisms, one leading to an amino acid change from M to I in a single case) in Gabonese isolates, but all 141/141 isolates were wild type in Ethiopia were found. CONCLUSION: In the absence of drug pressure, spontaneous and possibly resistance-conferring mutations are rare.
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