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dc.contributor.authorCadosch, Dominique
dc.contributor.authorAbel zur Wiesch, Pia
dc.contributor.authorKouyos, Roger
dc.contributor.authorBonhoeffer, Sebastian
dc.date.accessioned2017-03-15T14:05:08Z
dc.date.available2017-03-15T14:05:08Z
dc.date.issued2016
dc.description.abstractTreatment 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.en_US
dc.description.sponsorshipThis work was supported by the department of the authors, the Swiss National Science Foundation grant PBEZP3_140163 and the German Academic Exchange Service grant D/11/ 45747 to PAzW, the Swiss National Science Foundation grant PZ00P3-142411 to RK and the European Research Council under the 7th Framework Programme of the European Commission (PBDR: Grant Agreement Number 268540) to SB.en_US
dc.descriptionPublished version. Source at <a href=http://doi.org/10.1371/journal.pcbi.1004749>http://doi.org/10.1371/journal.pcbi.1004749</a>. License <a href=https://creativecommons.org/licenses/by/4.0/>CC BY 4.0</a>.en_US
dc.identifier.citationCadosch, Abel zur Wiesch P, Kouyos R, Bonhoeffer. The Role of Adherence and Retreatment in De Novo Emergence of MDR-TB. PloS Computational Biology. 2016;12(3)en_US
dc.identifier.cristinIDFRIDAID 1381706
dc.identifier.doi10.1371/journal.pcbi.1004749
dc.identifier.issn1553-734X
dc.identifier.issn1553-7358
dc.identifier.urihttps://hdl.handle.net/10037/10713
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.journalPloS Computational Biology
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/268540/EU//PBDR/en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Lung diseases: 777en_US
dc.titleThe Role of Adherence and Retreatment in De Novo Emergence of MDR-TBen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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