Tuberculosis outbreak investigation using phylodynamic analysis

Kühnert, Denise and Coscolla, Mireia and Brites, Daniela and Stucki, David and Metcalfe, John and Fenner, Lukas and Gagneux, Sebastien and Stadler, Tanja. (2018) Tuberculosis outbreak investigation using phylodynamic analysis. Epidemics, 25. pp. 47-53.

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The fast evolution of pathogenic viruses has allowed for the development of phylodynamic approaches that extract information about the epidemiological characteristics of viral genomes. Thanks to advances in whole genome sequencing, they can be applied to slowly evolving bacterial pathogens like Mycobacterium tuberculosis. In this study, we investigate and compare the epidemiological dynamics underlying two M. tuberculosis outbreaks using phylodynamic methods. Specifically, we (i) test if the outbreak data sets contain enough genetic variation to estimate short-term evolutionary rates and (ii) reconstruct epidemiological parameters such as the effective reproduction number. The first outbreak occurred in the Swiss city of Bern (1987-2012) and was caused by a drug-susceptible strain belonging to the phylogenetic M. tuberculosis Lineage 4. The second outbreak was caused by a multidrug-resistant (MDR) strain of Lineage 2, imported from the Wat Tham Krabok (WTK) refugee camp in Thailand into California. There is little temporal signal in the Bern data set and moderate temporal signal in the WTK data set. Thanks to its high sampling proportion (90%) the Bern outbreak allows robust estimation of epidemiological parameters despite the poor temporal signal. Conversely, there is much uncertainty in the epidemiological estimates concerning the sparsely sampled (9%) WTK outbreak. Our results suggest that both outbreaks peaked around 1990, although they were only recognized as outbreaks in 1993 (Bern) and 2004 (WTK). Furthermore, individuals were infected for a significantly longer period (around 9 years) in the WTK outbreak than in the Bern outbreak (4-5 years). Our work highlights both the limitations and opportunities of phylodynamic analysis of outbreaks involving slowly evolving pathogens: (i) estimation of the evolutionary rate is difficult on outbreak time scales and (ii) a high sampling proportion allows quantification of the age of the outbreak based on the sampling times, and thus allows for robust estimation of epidemiological parameters.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Research (Gagneux)
UniBasel Contributors:Coscollá Devís, Mireia and Brites, Daniela and Stucki, David and Fenner, Lukas and Gagneux, Sebastien
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:04 Dec 2018 11:25
Deposited On:04 Dec 2018 11:25

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