Neuraminidase inhibitor resistance in influenza: assessing the danger of its generation and spread.

Neuraminidase Inhibitors (NI) are currently the most effective drugs against influenza. Recent cases of NI resistance are a cause for concern. To assess the danger of NI resistance, a number of studies have reported the fraction of treated patients from which resistant strains could be isolated. Unf...

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Autores principales:	Andreas Handel, Ira M Longini, Rustom Antia
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2007
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0655c695faec40d2a1420a1aec7845cc
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spelling	oai:doaj.org-article:0655c695faec40d2a1420a1aec7845cc2021-11-25T05:41:29ZNeuraminidase inhibitor resistance in influenza: assessing the danger of its generation and spread.1553-734X1553-735810.1371/journal.pcbi.0030240https://doaj.org/article/0655c695faec40d2a1420a1aec7845cc2007-12-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.0030240https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Neuraminidase Inhibitors (NI) are currently the most effective drugs against influenza. Recent cases of NI resistance are a cause for concern. To assess the danger of NI resistance, a number of studies have reported the fraction of treated patients from which resistant strains could be isolated. Unfortunately, those results strongly depend on the details of the experimental protocol. Additionally, knowing the fraction of patients harboring resistance is not too useful by itself. Instead, we want to know how likely it is that an infected patient can generate a resistant infection in a secondary host, and how likely it is that the resistant strain subsequently spreads. While estimates for these parameters can often be obtained from epidemiological data, such data is lacking for NI resistance in influenza. Here, we use an approach that does not rely on epidemiological data. Instead, we combine data from influenza infections of human volunteers with a mathematical framework that allows estimation of the parameters that govern the initial generation and subsequent spread of resistance. We show how these parameters are influenced by changes in drug efficacy, timing of treatment, fitness of the resistant strain, and details of virus and immune system dynamics. Our study provides estimates for parameters that can be directly used in mathematical and computational models to study how NI usage might lead to the emergence and spread of resistance in the population. We find that the initial generation of resistant cases is most likely lower than the fraction of resistant cases reported. However, we also show that the results depend strongly on the details of the within-host dynamics of influenza infections, and most importantly, the role the immune system plays. Better knowledge of the quantitative dynamics of the immune response during influenza infections will be crucial to further improve the results.Andreas HandelIra M LonginiRustom AntiaPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 3, Iss 12, p e240 (2007)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Andreas Handel Ira M Longini Rustom Antia Neuraminidase inhibitor resistance in influenza: assessing the danger of its generation and spread.
description	Neuraminidase Inhibitors (NI) are currently the most effective drugs against influenza. Recent cases of NI resistance are a cause for concern. To assess the danger of NI resistance, a number of studies have reported the fraction of treated patients from which resistant strains could be isolated. Unfortunately, those results strongly depend on the details of the experimental protocol. Additionally, knowing the fraction of patients harboring resistance is not too useful by itself. Instead, we want to know how likely it is that an infected patient can generate a resistant infection in a secondary host, and how likely it is that the resistant strain subsequently spreads. While estimates for these parameters can often be obtained from epidemiological data, such data is lacking for NI resistance in influenza. Here, we use an approach that does not rely on epidemiological data. Instead, we combine data from influenza infections of human volunteers with a mathematical framework that allows estimation of the parameters that govern the initial generation and subsequent spread of resistance. We show how these parameters are influenced by changes in drug efficacy, timing of treatment, fitness of the resistant strain, and details of virus and immune system dynamics. Our study provides estimates for parameters that can be directly used in mathematical and computational models to study how NI usage might lead to the emergence and spread of resistance in the population. We find that the initial generation of resistant cases is most likely lower than the fraction of resistant cases reported. However, we also show that the results depend strongly on the details of the within-host dynamics of influenza infections, and most importantly, the role the immune system plays. Better knowledge of the quantitative dynamics of the immune response during influenza infections will be crucial to further improve the results.
format	article
author	Andreas Handel Ira M Longini Rustom Antia
author_facet	Andreas Handel Ira M Longini Rustom Antia
author_sort	Andreas Handel
title	Neuraminidase inhibitor resistance in influenza: assessing the danger of its generation and spread.
title_short	Neuraminidase inhibitor resistance in influenza: assessing the danger of its generation and spread.
title_full	Neuraminidase inhibitor resistance in influenza: assessing the danger of its generation and spread.
title_fullStr	Neuraminidase inhibitor resistance in influenza: assessing the danger of its generation and spread.
title_full_unstemmed	Neuraminidase inhibitor resistance in influenza: assessing the danger of its generation and spread.
title_sort	neuraminidase inhibitor resistance in influenza: assessing the danger of its generation and spread.
publisher	Public Library of Science (PLoS)
publishDate	2007
url	https://doaj.org/article/0655c695faec40d2a1420a1aec7845cc
work_keys_str_mv	AT andreashandel neuraminidaseinhibitorresistanceininfluenzaassessingthedangerofitsgenerationandspread AT iramlongini neuraminidaseinhibitorresistanceininfluenzaassessingthedangerofitsgenerationandspread AT rustomantia neuraminidaseinhibitorresistanceininfluenzaassessingthedangerofitsgenerationandspread
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Neuraminidase inhibitor resistance in influenza: assessing the danger of its generation and spread.

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