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© 2007 Handel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Handel A, Longini IM Jr, Antia R (2007) Neuraminidase Inhibitor Resistance in Influenza: Assessing the Danger of Its Generation and Spread. PLoS Comput Biol 3(12): e240. doi:10.1371/journal.pcbi.0030240

Abstract

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.

Details

Title
Neuraminidase Inhibitor Resistance in Influenza: Assessing the Danger of Its Generation and Spread
Author
Handel, Andreas; Jr, Ira MLongini; Antia, Rustom
Pages
e240
Section
Research Article
Publication year
2007
Publication date
Dec 2007
Publisher
Public Library of Science
ISSN
1553734X
e-ISSN
15537358
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1312436724
Copyright
© 2007 Handel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Handel A, Longini IM Jr, Antia R (2007) Neuraminidase Inhibitor Resistance in Influenza: Assessing the Danger of Its Generation and Spread. PLoS Comput Biol 3(12): e240. doi:10.1371/journal.pcbi.0030240