Combining genomics and epidemiology to analyse bi-directional transmission of Mycobacterium bovis in a multi-host system

Abstract

Quantifying pathogen transmission in multi-host systems is difficult, as exemplified in bovine tuberculosis (bTB) systems, but is crucial for control. The agent of bTB, Mycobacterium bovis, persists in cattle populations worldwide, often where potential wildlife reservoirs exist. However, the relative contribution of different host species to bTB persistence is generally unknown. In Britain, the role of badgers in infection persistence in cattle is highly contentious, despite decades of research and control efforts. We applied Bayesian phylogenetic and machine-learning approaches to bacterial genome data to quantify the roles of badgers and cattle in M. bovis infection dynamics in the presence of data biases. Our results suggest that transmission occurs more frequently from badgers to cattle than vice versa (10.4x in the most likely model) and that within-species transmission occurs at higher rates than between-species transmission for both. If representative, our results suggest that control operations should target both cattle and badgers.

eLife digest

Disease-causing microbes that infect more than one type of animal can be difficult to control. This is especially true when they infect wildlife. For example, Mycobacterium bovis is a bacterium that causes tuberculosis in tens of thousands of cattle in Britain every year and also infects badgers and other wildlife. Controlling the infections in cattle is essential, as it helps prevent the bacteria from infecting humans, improves cattle welfare and reduces the substantial costs to the livestock industry.

Analysing the relatedness of M. bovis genomes from infected cattle and badgers may help scientists work out how often badgers infect cattle and vice versa. Scientists have collected data and M. bovis samples from infected badgers in Woodchester Park, in England, for over three decades. Using these data and additional information about M. bovis infecting nearby cattle may help scientists learn how the bacteria spreads and how to stop it.

Now, Crispell et al. show that complex patterns of contact between cattle and badgers likely drive the persistence of tuberculosis in cattle, also known as bovine tuberculosis. In three separate analyses, Crispell et al. compared the genomes of M. bovis found in cattle and badgers, the animals' locations, when they were infected, and whether they could have been in contact. The analyses found that M. bovis was likely to have been transmitted more frequently from badgers to cattle rather than from cattle to badgers. They also showed that transmission within each species happened more often than transmission between species.

If these results are confirmed by other studies, they may help scientists develop better strategies for controlling tuberculosis in British cattle. In particular, controversial control strategies – such as badger culls – could be more targeted to better combat tuberculosis in cattle but have less of an impact on badgers. These insights might also aid control efforts in other countries where bovine tuberculosis is a problem and an important source of human tuberculosis.