Research
Molecular surveillance of mutations in the cytochrome b gene of Plasmodium falciparum in Gabon and Ethiopia
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* Corresponding author: Martin P Grobusch martin.grobusch@wits.ac.za
1 Department of Medical Laboratory Technology, Faculty of Health Sciences, Haramaya University, Haramaya, Ethiopia
2 Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon
3 Department of Microbiology, Immunology and Parasitology, Faculty of Medicine, Addis Ababa University, Addis Ababa, Ethiopia
4 Department of Parasitology, Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany
5 Infectious Diseases Unit, Division of Clinical Microbiology and Infectious Diseases, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
Malaria Journal 2006, 5:112 doi:10.1186/1475-2875-5-112
Published: 21 November 2006Abstract
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.