Burden of transmitted multidrug resistance in epidemics of tuberculosis: a transmission modelling analysis

Abstract

BackgroundMultidrug-resistant tuberculosis (MDR-TB) can be acquired through de novo mutation during TB treatment or through transmission from other individuals with active MDR-TB. Understanding the balance between these two mechanisms is essential when allocating resources for MDR-TB.MethodsWe constructed a dynamic transmission model of an MDR-TB epidemic, allowing for both treatment-related acquisition and person-to-person transmission of resistance. We used national TB notification data to inform Bayesian estimates of the fraction of each country’s 2013 MDR-TB incidence that resulted from MDR transmission rather than treatment-related MDR acquisition.FindingsGlobal estimates of 3·5% MDR-TB prevalence among new TB notifications and 20·5% among retreatment notifications translate into an estimate that resistance transmission rather than acquisition accounts for a median 96% (95% UR: 68–100%) of all incident MDR-TB, and 61% (16–95%) of incident MDR-TB in previously-treated individuals. The estimated percentage of MDR-TB resulting from transmission varied substantially with different countries’ notification data; for example, we estimated this percentage at 48% (30–75%) of MDR-TB in Bangladesh, versus 99% (91–100%) in Uzbekistan. Estimates were most sensitive to estimates of the transmissibility of MDR strains, the probability of acquiring MDR during tuberculosis treatment, and the responsiveness of MDR TB to first-line treatment.InterpretationNotifications of MDR prevalence from most high-burden settings are most consistent with the vast majority of incident MDR-TB resulting from transmission rather than new treatment-related acquisition of resistance. Merely improving the treatment of drug-susceptible TB is unlikely to greatly reduce future MDR-TB incidence. Improved diagnosis and treatment of MDR-TB – including new tests and drug regimens – should be highly prioritized.