Research

Molecular surveillance of mutations in the cytochrome b gene of Plasmodium falciparum in Gabon and Ethiopia

Tamirat Gebru^1,2 , Asrat Hailu³ , Peter G Kremsner^2,4 , Jürgen FJ Kun⁴ and Martin P Grobusch^2,5

¹Department of Medical Laboratory Technology, Faculty of Health Sciences, Haramaya University, Haramaya, Ethiopia

²Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon

³Department of Microbiology, Immunology and Parasitology, Faculty of Medicine, Addis Ababa University, Addis Ababa, Ethiopia

⁴Department of Parasitology, Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany

⁵Infectious 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

author email corresponding author email

Malaria Journal 2006, 5:112doi:10.1186/1475-2875-5-112

Published:	21 November 2006

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.