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Atovaquone-proguanil for treating uncomplicated Plasmodium falciparum malaria.

ABSTRACT:

SUBMITTER: Blanshard A

PROVIDER: S-EPMC8094970 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Atovaquone-proguanil for treating uncomplicated Plasmodium falciparum malaria.

Blanshard Andrew A Hine Paul P

The Cochrane database of systematic reviews 20210115

<h4>Background</h4>The World Health Organization (WHO) in 2015 stated atovaquone-proguanil can be used in travellers, and is an option in malaria-endemic areas in combination with artesunate, as an alternative treatment where first-line artemisinin-based combination therapy (ACT) is not available or effective. This review is an update of a Cochrane Review undertaken in 2005.<h4>Objectives</h4>To assess the efficacy and safety of atovaquone-proguanil (alone and in combination with artemisinin dru ...[more]

PMID: 33459345

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Project description:BackgroundAtovaquone/proguanil, registered as Malarone®, is a fixed-dose combination recommended for first-line treatment of uncomplicated Plasmodium falciparum malaria in non-endemic countries and its prevention in travellers. Mutations in the cytochrome bc1 complex are causally associated with atovaquone resistance.MethodsThis systematic review assesses the clinical efficacy of atovaquone/proguanil treatment of uncomplicated malaria and examines the extent to which codon 268 mutation in cytochrome b influences treatment failure and recrudescence based on published information.ResultsData suggest that atovaquone/proguanil treatment efficacy is 89%-98% for P. falciparum malaria (from 27 studies including between 18 and 253 patients in each case) and 20%-26% for Plasmodium vivax malaria (from 1 study including 25 patients). The in vitro P. falciparum phenotype of atovaquone resistance is an IC50 value >28 nM. Case report analyses predict that recrudescence in a patient presenting with parasites carrying cytochrome b codon 268 mutation will occur on average at day 29 (95% CI: 22, 35), 19 (95% CI: 7, 30) days longer than if the mutation is absent.ConclusionsEvidence suggests atovaquone/proguanil treatment for P. falciparum malaria is effective. Late treatment failure is likely to be associated with a codon 268 mutation in cytochrome b, though recent evidence from animal models suggests these mutations may not spread within the population. However, early treatment failure is likely to arise through alternative mechanisms, requiring further investigation.

| S-EPMC5890752 | biostudies-literature

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