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


CONCLUSIONS
In the absence of drug pressure, spontaneous and possibly resistance-conferring mutations are rare.
Gebru
Tamirat
T
Department of Medical Laboratory Technology, Faculty of Health Sciences, Haramaya University, Haramaya, Ethiopia. tamiratgw2002@yahoo.com <tamiratgw2002@yahoo.com>
Hailu
Asrat
A
Kremsner
Peter G
PG
Kun
Jürgen F J
JF
Grobusch
Martin P
MP
D000818:Animals; D053626:Atovaquone / Q000494:pharmacology; D003062:Codon; D045303:Cytochromes b / Q000235:genetics*; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D002727:Proguanil / Q000494:pharmacology
D003062:Codon; D004338:Drug Combinations; C109496:atovaquone, proguanil drug combination; D045303:Cytochromes b; D002727:Proguanil; D053626:Atovaquone