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Please use this identifier to cite or link to this item: https://doi.org/10.21256/zhaw-22585
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dc.contributor.authorPecerska, Julija-
dc.contributor.authorKühnert, Denise-
dc.contributor.authorMeehan, Conor J.-
dc.contributor.authorCoscollá, Mireia-
dc.contributor.authorde Jong, Bouke C.-
dc.contributor.authorGagneux, Sebastien-
dc.contributor.authorStadler, Tanja-
dc.date.accessioned2021-06-03T14:02:46Z-
dc.date.available2021-06-03T14:02:46Z-
dc.date.issued2021-
dc.identifier.issn1755-4365de_CH
dc.identifier.issn1878-0067de_CH
dc.identifier.urihttps://digitalcollection.zhaw.ch/handle/11475/22585-
dc.description.abstractAs multi-drug resistant tuberculosis (MDR-TB) continues to spread, investigating the transmission potential of different drug-resistant strains becomes an ever more pressing topic in public health. While phylogenetic and transmission tree inferences provide valuable insight into possible transmission chains, phylodynamic inference combines evolutionary and epidemiological analyses to estimate the parameters of the underlying epidemiological processes, allowing us to describe the overall dynamics of disease spread in the population. In this study, we introduce an approach to Mycobacterium tuberculosis (M. tuberculosis) phylodynamic analysis employing an existing computationally efficient model to quantify the transmission fitness costs of drug resistance with respect to drug-sensitive strains. To determine the accuracy and precision of our approach, we first perform a simulation study, mimicking the simultaneous spread of drug-sensitive and drug-resistant tuberculosis (TB) strains. We analyse the simulated transmission trees using the phylodynamic multi-type birth-death model (MTBD, (Kühnert et al., 2016)) within the BEAST2 framework and show that this model can estimate the parameters of the epidemic well, despite the simplifying assumptions that MTBD makes compared to the complex TB transmission dynamics used for simulation. We then apply the MTBD model to an M. tuberculosis lineage 4 dataset that primarily consists of MDR sequences. Some of the MDR strains additionally exhibit resistance to pyrazinamide – an important first-line anti-tuberculosis drug. Our results support the previously proposed hypothesis that pyrazinamide resistance confers a transmission fitness cost to the bacterium, which we quantify for the given dataset. Importantly, our sensitivity analyses show that the estimates are robust to different prior distributions on the resistance acquisition rate, but are affected by the size of the dataset – i.e. we estimate a higher fitness cost when using fewer sequences for analysis. Overall, we propose that MTBD can be used to quantify the transmission fitness cost for a wide range of pathogens where the strains can be appropriately divided into two or more categories with distinct properties.de_CH
dc.language.isoende_CH
dc.publisherElsevierde_CH
dc.relation.ispartofEpidemicsde_CH
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/4.0/de_CH
dc.subjectAntibiotic resistancede_CH
dc.subjectWhole genome M. tuberculosisde_CH
dc.subjectMulti-type birth-death modelde_CH
dc.subjectPhylodynamicsde_CH
dc.subject.ddc614: Public Health und Gesundheitsförderungde_CH
dc.titleQuantifying transmission fitness costs of multi-drug resistant tuberculosisde_CH
dc.typeBeitrag in wissenschaftlicher Zeitschriftde_CH
dcterms.typeTextde_CH
zhaw.departementLife Sciences und Facility Managementde_CH
zhaw.organisationalunitInstitut für Computational Life Sciences (ICLS)de_CH
dc.identifier.doi10.1016/j.epidem.2021.100471de_CH
dc.identifier.doi10.21256/zhaw-22585-
zhaw.funding.euNode_CH
zhaw.issue100471de_CH
zhaw.originated.zhawYesde_CH
zhaw.publication.statuspublishedVersionde_CH
zhaw.volume36de_CH
zhaw.publication.reviewPeer review (Publikation)de_CH
zhaw.webfeedBiomedical String Analysisde_CH
zhaw.author.additionalNode_CH
zhaw.display.portraitYesde_CH
Appears in collections:Publikationen Life Sciences und Facility Management

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Pecerska, J., Kühnert, D., Meehan, C. J., Coscollá, M., de Jong, B. C., Gagneux, S., & Stadler, T. (2021). Quantifying transmission fitness costs of multi-drug resistant tuberculosis. Epidemics, 36(100471). https://doi.org/10.1016/j.epidem.2021.100471
Pecerska, J. et al. (2021) ‘Quantifying transmission fitness costs of multi-drug resistant tuberculosis’, Epidemics, 36(100471). Available at: https://doi.org/10.1016/j.epidem.2021.100471.
J. Pecerska et al., “Quantifying transmission fitness costs of multi-drug resistant tuberculosis,” Epidemics, vol. 36, no. 100471, 2021, doi: 10.1016/j.epidem.2021.100471.
PECERSKA, Julija, Denise KÜHNERT, Conor J. MEEHAN, Mireia COSCOLLÁ, Bouke C. DE JONG, Sebastien GAGNEUX und Tanja STADLER, 2021. Quantifying transmission fitness costs of multi-drug resistant tuberculosis. Epidemics. 2021. Bd. 36, Nr. 100471. DOI 10.1016/j.epidem.2021.100471
Pecerska, Julija, Denise Kühnert, Conor J. Meehan, Mireia Coscollá, Bouke C. de Jong, Sebastien Gagneux, and Tanja Stadler. 2021. “Quantifying Transmission Fitness Costs of Multi-Drug Resistant Tuberculosis.” Epidemics 36 (100471). https://doi.org/10.1016/j.epidem.2021.100471.
Pecerska, Julija, et al. “Quantifying Transmission Fitness Costs of Multi-Drug Resistant Tuberculosis.” Epidemics, vol. 36, no. 100471, 2021, https://doi.org/10.1016/j.epidem.2021.100471.


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