  We investigate the rates of drug resistance acquisition in a natural
population using molecular epidemiological data from Bolivia. First, we study
the rate of direct acquisition of double resistance from the double sensitive
state within patients and compare it to the rates of evolution to single
resistance. In particular, we address whether or not double resistance can
evolve directly from a double sensitive state within a given host. Second, we
aim to understand whether the differences in mutation rates to rifampicin and
isoniazid resistance translate to the epidemiological scale. Third, we estimate
the proportion of MDR TB cases that are due to the transmission of MDR strains
compared to acquisition of resistance through evolution. To address these
problems we develop a model of TB transmission in which we track the evolution
of resistance to two drugs and the evolution of VNTR loci. However, the
available data is incomplete, in that it is recorded only {for a fraction of
the population and} at a single point in time. The likelihood function induced
by the proposed model is computationally prohibitive to evaluate and
accordingly impractical to work with directly. We therefore approach
statistical inference using approximate Bayesian computation techniques.

Quantitative Methods;Populations and Evolution;Applications