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Theses

Contribution à l'étude de la résistance
de Plasmodium falciparum à l'atovaquone-proguanil

Abstract : The recurrent emergence and spread of multidrug-resistant Plasmodium falciparum delays the control of malaria. Since 2000, a safe and efficient new combination, atovaquone-proguanil, has rapidly became the first line antimalarial drug in most European infectious diseases wards. This work aimed to better understand falciparum resistance to atovaquone-proguanil. The copy number of the cytochrome b gene, pfcytb, the main atovaquone-proguanil target, was evaluated by real-time PCR at 16 ± 9 copies per parasite. No natural resistance to atovaquone/proguanil was detected by in vitro phenotyping in West African and Indian Ocean isolates although therapeutic failures were observed. The majority of early therapeutic failures were linked to poor drug absorption while late therapeutic failures were associated with day failure parasites highly resistant in vitro and carrying a pfcytb mutation (Y268S or Y268C) without any amplification of pfcytb gene. Mitochondrial genome sequencing associated with microsatellite marker analysis of parasites from before and after parasite recrudescence show that these mutations had appeared independently within each of the six patients experiencing a therapeutic failure. With falciparum resistance being less than 0.1%, atovaquone-proguanil is efficient for treatment of travellers experiencing malaria. As resistance emerged within patient without risk of transmission, resistance spread has not begun. Combination with an antimalarial drug having a different target should be a prerequisite of deployment in endemic areas.
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https://tel.archives-ouvertes.fr/tel-00130030
Contributor : Lise Musset <>
Submitted on : Thursday, February 8, 2007 - 6:27:01 PM
Last modification on : Wednesday, August 19, 2020 - 11:16:38 AM
Long-term archiving on: : Thursday, April 8, 2010 - 2:41:12 PM

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  • HAL Id : tel-00130030, version 1

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Lise Musset. Contribution à l'étude de la résistance
de Plasmodium falciparum à l'atovaquone-proguanil. Médicaments. Université René Descartes - Paris V, 2006. Français. ⟨tel-00130030⟩

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