The risk of global epidemic replacement with drug resistant M. tuberculosis strains

Objectives. Multi-drug resistant tuberculosis (MDR-TB) is a threat to TB control. To guide TB control, it is essential to understand the extent to which and the circumstances in which MDR-TB will replace drug-susceptible TB (DS-TB) as the dominant phenotype. We examined the issue by presenting evidence from genomics, pharmacokinetics and epidemiology studies. We then synthesised this evidence into a mathematical model. Methods. Our model consider two TB strains, one with and one without MDR phenotype. We allowed that intrinsic transmissibility may be different between the two strains, as may the control response including detection rate, treatment failure and default rates. We explored the outcomes in terms of incidence of MDR-TB and time until MDR-TB surpasses DS-TB as the dominant strain. 3 Results and conclusions. The ability of MDR-TB to dominate DS-TB was highly sensitive to the relative transmissibility of the resistant strain; however, MDR-TB could dominate even when its transmissibility was modestly reduced (to between 50% and 100% as transmissible as DS-TB strain). Our model suggest that it may take decades or more for strain replacement to occur. We also found that while amplification of resistance is the early cause of MDR-TB, this will rapidly give way to person-to-person transmission.