Full text

Turn on search term navigation

© 2016 Public Library of Science. 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: Emergence of MDR-TB. PLoS Comput Biol 12(3): e1004749. doi:10.1371/journal.pcbi.1004749

Abstract

Treatment failure after therapy of pulmonary tuberculosis (TB) infections is an important challenge, especially when it coincides with de novo emergence of multi-drug-resistant TB (MDR-TB). We seek to explore possible causes why MDR-TB has been found to occur much more often in patients with a history of previous treatment. We develop a mathematical model of the replication of Mycobacterium tuberculosis within a patient reflecting the compartments of macrophages, granulomas, and open cavities as well as parameterizing the effects of drugs on the pathogen dynamics in these compartments. We use this model to study the influence of patient adherence to therapy and of common retreatment regimens on treatment outcome. As expected, the simulations show that treatment success increases with increasing adherence. However, treatment occasionally fails even under perfect adherence due to interpatient variability in pharmacological parameters. The risk of generating MDR de novo is highest between 40% and 80% adherence. Importantly, our simulations highlight the double-edged effect of retreatment: On the one hand, the recommended retreatment regimen increases the overall success rate compared to re-treating with the initial regimen. On the other hand, it increases the probability to accumulate more resistant genotypes. We conclude that treatment adherence is a key factor for a positive outcome, and that screening for resistant strains is advisable after treatment failure or relapse.

Details

Title
The Role of Adherence and Retreatment in De Novo Emergence of MDR-TB
Author
Cadosch, Dominique; Wiesch, Pia Abelzur; Kouyos, Roger; Bonhoeffer, Sebastian
Section
Research Article
Publication year
2016
Publication date
Mar 2016
Publisher
Public Library of Science
ISSN
1553734X
e-ISSN
15537358
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1783063953
Copyright
© 2016 Public Library of Science. 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: Emergence of MDR-TB. PLoS Comput Biol 12(3): e1004749. doi:10.1371/journal.pcbi.1004749