title: Burden of transmitted multidrug resistance in epidemics of tuberculosis: a transmission modelling analysis.
abstract: BACKGROUND
  Multidrug-resistant (MDR) tuberculosis can be acquired through de-novo mutation during tuberculosis treatment or through transmission from other individuals with active MDR tuberculosis. Understanding the balance between these two mechanisms is essential when allocating resources for MDR tuberculosis. We aimed to create a dynamic transmission model of an MDR tuberculosis epidemic to estimate the contributions of treatment-related acquisition and person-to-person transmission of resistance to incident MDR tuberculosis cases.
  
  
  METHODS
  In this modelling analysis, we constructed a dynamic transmission model of an MDR tuberculosis epidemic, allowing for both treatment-related acquisition and person-to-person transmission of resistance. We used national tuberculosis notification data to inform Bayesian estimates of the proportion of each country's 2013 MDR tuberculosis incidence that resulted from MDR transmission rather than treatment-related MDR acquisition.
  
  
  RESULTS
  Global estimates of 3·5% MDR tuberculosis prevalence among new tuberculosis notifications and 20·5% among re-treatment notifications translate into an estimate that resistance transmission rather than acquisition accounts for a median 95·9% (95% uncertainty range [UR] 68·0-99·6) of all incident MDR tuberculosis, and 61·3% (16·5-95·2) of incident MDR tuberculosis in previously treated individuals. The estimated proportion of MDR tuberculosis resulting from transmission varied substantially with different countries' notification data-ranging from 48% (95% UR 30-75) in Bangladesh to 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 tuberculosis to first-line treatment.
  
  
  CONCLUSIONS
  Notifications of MDR prevalence from most high-burden settings are consistent with most incident MDR tuberculosis resulting from transmission rather than new treatment-related acquisition of resistance. Merely improving the treatment of drug-susceptible tuberculosis is unlikely to greatly reduce future MDR tuberculosis incidence. Improved diagnosis and treatment of MDR tuberculosis-including new tests and drug regimens-should be highly prioritised.
  
  
  BACKGROUND
  National Institutes of Health and the Bill & Melinda Gates Foundation.
authors.affiliation: Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: ekendal2@jhmi.edu.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Kendall
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Mariam O
authors.initials: MO
authors.lastname: Fofana
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Dowdy
mesh_terms: D058872:Epidemics; D006801:Humans; D015233:Models, Statistical; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology* / Q000635:transmission*; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology* / Q000635:transmission*