The risk of global epidemic replacement with drug-resistant Mycobacterium tuberculosis strains

OBJECTIVES: Multidrug-resistant tuberculosis (MDR-TB) is a threat to tuberculosis (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. The issue was examined by assessing evidence from genomics, pharmacokinetics, and epidemiology studies. This evidence was then synthesized into a mathematical model. METHODS: This model considers two TB strains, one with and one without an MDR phenotype. It was considered that intrinsic transmissibility may be different between the two strains, as may the control response including the detection, treatment failure, and default rates. The outcomes were explored in terms of the incidence of MDR-TB and time until MDR-TB surpasses DS-TB as the dominant strain. 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 the DS-TB strain). This model suggests that it may take decades or more for strain replacement to occur. It was also found that while the amplification of resistance is the early cause of MDR-TB, this will rapidly give way to person-to-person transmission.