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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 bc(1 )complex of the electron transport chain in Plasmodium spp. Molecular modelling showed that amino acid mutations are clustered around a putative atovaquone-binding...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1679811/ https://www.ncbi.nlm.nih.gov/pubmed/17118179 http://dx.doi.org/10.1186/1475-2875-5-112 |
Sumario: | BACKGROUND: Atovaquone is part of the antimalarial drug combination atovaquone-proguanil (Malarone(®)) and inhibits the cytochrome bc(1 )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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