Multi-scale models for drug resistant tuberculosis

A multi-scale model is proposed to study co-circulation of drug-resistant and - sensitive strains of Mycobacterium tuberculosis. At the population level, strain competition depends first on strains ability to be transmitted among susceptible individuals, represented by the strain specific reproduction numbers, R0s and R0r. When reinfection occurs a new level of competition can be considered. Hence, for mixed infections transmission depends on the competition outcome at the individual level. A between-host model is presented for which mixed infections transmission profile and infectious period are governed by a within-host model. The within-host model describes strain competition for a mixed infection during a disease episode with a fixed treatment schedule, depending on the relative fitness of strains, f. The linkage to the epidemiological model provides a comprehensive relation between pathogen-specific growth rates and general between-host transmission ability. Longterm behaviour of the epidemiological model is driven by both between and within-host traits.