Cargando…

Assessing the impact of imperfect adherence to artemether-lumefantrine on malaria treatment outcomes using within-host modelling

Artemether-lumefantrine (AL) is the most widely-recommended treatment for uncomplicated Plasmodium falciparum malaria worldwide. Its safety and efficacy have been extensively demonstrated in clinical trials; however, its performance in routine health care settings, where adherence to drug treatment...

Descripción completa

Detalles Bibliográficos
Autores principales: Challenger, Joseph D., Bruxvoort, Katia, Ghani, Azra C., Okell, Lucy C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680187/
https://www.ncbi.nlm.nih.gov/pubmed/29123086
http://dx.doi.org/10.1038/s41467-017-01352-3
_version_ 1783277706307174400
author Challenger, Joseph D.
Bruxvoort, Katia
Ghani, Azra C.
Okell, Lucy C.
author_facet Challenger, Joseph D.
Bruxvoort, Katia
Ghani, Azra C.
Okell, Lucy C.
author_sort Challenger, Joseph D.
collection PubMed
description Artemether-lumefantrine (AL) is the most widely-recommended treatment for uncomplicated Plasmodium falciparum malaria worldwide. Its safety and efficacy have been extensively demonstrated in clinical trials; however, its performance in routine health care settings, where adherence to drug treatment is unsupervised and therefore may be suboptimal, is less well characterised. Here we develop a within-host modelling framework for estimating the effects of sub-optimal adherence to AL treatment on clinical outcomes in malaria patients. Our model incorporates the data on the human immune response to the parasite, and AL’s pharmacokinetic and pharmacodynamic properties. Utilising individual-level data of adherence to AL in 482 Tanzanian patients as input for our model predicted higher rates of treatment failure than were obtained when adherence was optimal (9% compared to 4%). Our model estimates that the impact of imperfect adherence was worst in children, highlighting the importance of advice to caregivers.
format Online
Article
Text
id pubmed-5680187
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-56801872017-11-15 Assessing the impact of imperfect adherence to artemether-lumefantrine on malaria treatment outcomes using within-host modelling Challenger, Joseph D. Bruxvoort, Katia Ghani, Azra C. Okell, Lucy C. Nat Commun Article Artemether-lumefantrine (AL) is the most widely-recommended treatment for uncomplicated Plasmodium falciparum malaria worldwide. Its safety and efficacy have been extensively demonstrated in clinical trials; however, its performance in routine health care settings, where adherence to drug treatment is unsupervised and therefore may be suboptimal, is less well characterised. Here we develop a within-host modelling framework for estimating the effects of sub-optimal adherence to AL treatment on clinical outcomes in malaria patients. Our model incorporates the data on the human immune response to the parasite, and AL’s pharmacokinetic and pharmacodynamic properties. Utilising individual-level data of adherence to AL in 482 Tanzanian patients as input for our model predicted higher rates of treatment failure than were obtained when adherence was optimal (9% compared to 4%). Our model estimates that the impact of imperfect adherence was worst in children, highlighting the importance of advice to caregivers. Nature Publishing Group UK 2017-11-09 /pmc/articles/PMC5680187/ /pubmed/29123086 http://dx.doi.org/10.1038/s41467-017-01352-3 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Challenger, Joseph D.
Bruxvoort, Katia
Ghani, Azra C.
Okell, Lucy C.
Assessing the impact of imperfect adherence to artemether-lumefantrine on malaria treatment outcomes using within-host modelling
title Assessing the impact of imperfect adherence to artemether-lumefantrine on malaria treatment outcomes using within-host modelling
title_full Assessing the impact of imperfect adherence to artemether-lumefantrine on malaria treatment outcomes using within-host modelling
title_fullStr Assessing the impact of imperfect adherence to artemether-lumefantrine on malaria treatment outcomes using within-host modelling
title_full_unstemmed Assessing the impact of imperfect adherence to artemether-lumefantrine on malaria treatment outcomes using within-host modelling
title_short Assessing the impact of imperfect adherence to artemether-lumefantrine on malaria treatment outcomes using within-host modelling
title_sort assessing the impact of imperfect adherence to artemether-lumefantrine on malaria treatment outcomes using within-host modelling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680187/
https://www.ncbi.nlm.nih.gov/pubmed/29123086
http://dx.doi.org/10.1038/s41467-017-01352-3
work_keys_str_mv AT challengerjosephd assessingtheimpactofimperfectadherencetoartemetherlumefantrineonmalariatreatmentoutcomesusingwithinhostmodelling
AT bruxvoortkatia assessingtheimpactofimperfectadherencetoartemetherlumefantrineonmalariatreatmentoutcomesusingwithinhostmodelling
AT ghaniazrac assessingtheimpactofimperfectadherencetoartemetherlumefantrineonmalariatreatmentoutcomesusingwithinhostmodelling
AT okelllucyc assessingtheimpactofimperfectadherencetoartemetherlumefantrineonmalariatreatmentoutcomesusingwithinhostmodelling