A nested model for tuberculosis: Combining within-host and between-host processes in a single framework

Tuberculosis (TB) is among the 10 top causes of deaths worldwide, and one-quarter of the world population hosts latent TB pathogens. Therefore, avoiding the emergence of drug-resistant strains has become a central issue in TB control. In this work, we propose a nested model for TB transmission and control, wherein both within-host and between-host dynamics are modeled. We use the model to compare the effects of three types of antibiotic treatment protocols and combinations thereof in an in silico population. For a fixed value of antibiotics clearance rate and relative efficacy against resistant strains, the oscillating intermittent protocol, pure or combined, is the most effective against the sensitive strains. However, this protocol also creates a selective advantage for the resistant strains, returning the worst result in comparison to the other protocols. We suggest that nested models should be further developed, since they might be able to inform decision-makers regarding the optimal TB control protocols to be applied under the specific parameters and other epidemiological factors in different populations.