The relative fitness of drug-resistant <i>Mycobacterium tuberculosis</i>: a modelling study of household transmission in Peru

The relative fitness of drug-resistant versus susceptible bacteria in an environment dictates resistance prevalence. Estimates for the relative fitness of resistant Mycobacterium tuberculosis ( Mtb ) strains are highly heterogeneous and mostly derived from in vitro experiments. Measuring fitness in the field allows us to determine how the environment influences the spread of resistance. We designed a household structured, stochastic mathematical model to estimate the fitness costs associated with multidrug resistance (MDR) carriage in Mtb in Lima, Peru during 2010-2013. By fitting the model to data from a large prospective cohort study of TB disease in household contacts, we estimated the fitness, relative to susceptible strains with a fitness of 1, of MDR- Mtb to be 0.32 (95% credible interval: 0.15-0.62) or 0.38 (0.24-0.61), if only transmission or progression to disease, respectively, was affected. The relative fitness of MDR- Mtb increased to 0.56 (0.42-0.72) when the fitness cost influenced both transmission and progression to disease equally. We found the average relative fitness of MDR- Mtb circulating within households in Lima, Peru during 2010-2013 to be significantly lower than concurrent susceptible Mtb If these fitness levels do not change, then existing TB control programmes are likely to keep MDR-TB prevalence at current levels in Lima, Peru.