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Clinical implications of Plasmodium resistance to atovaquone/proguanil: a systematic review and meta-analysis.

Staines, HM; Burrow, R; Teo, BH-Y; Chis Ster, I; Kremsner, PG; Krishna, S (2018) Clinical implications of Plasmodium resistance to atovaquone/proguanil: a systematic review and meta-analysis. J Antimicrob Chemother, 73 (3). pp. 581-595. ISSN 1460-2091 https://doi.org/10.1093/jac/dkx431
SGUL Authors: Staines, Henry Michael

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Abstract

Background: Atovaquone/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. Methods: This 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. Results: Data 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. Conclusions: Evidence 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.

Item Type: Article
Additional Information: © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Microbiology, 1115 Pharmacology And Pharmaceutical Sciences, 0605 Microbiology, 1108 Medical Microbiology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: J Antimicrob Chemother
ISSN: 1460-2091
Language: eng
Dates:
DateEvent
1 March 2018Published
11 December 2017Published Online
23 October 2017Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
304948Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
204809/Z/16/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
PubMed ID: 29237012
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109390
Publisher's version: https://doi.org/10.1093/jac/dkx431

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