title: MDR-TB treatment as prevention: The projected population-level impact of expanded treatment for multidrug-resistant tuberculosis.
abstract: BACKGROUND
  In 2013, approximately 480,000 people developed active multidrug-resistant tuberculosis (MDR-TB), while only 97,000 started MDR-TB treatment. We sought to estimate the impact of improving access to MDR-TB diagnosis and treatment, under multiple diagnostic algorithm and treatment regimen scenarios, on ten-year projections of MDR-TB incidence and mortality.
  
  
  METHODS
  We constructed a dynamic transmission model of an MDR-TB epidemic in an illustrative East/Southeast Asian setting. Using approximate Bayesian computation, we investigated a wide array of potential epidemic trajectories consistent with current notification data and known TB epidemiology.
  
  
  RESULTS
  Despite an overall projected decline in TB incidence, data-consistent simulations suggested that MDR-TB incidence is likely to rise between 2015 and 2025 under continued 2013 treatment practices, although with considerable uncertainty (median 17% increase, 95% Uncertainty Range [UR] -38% to +137%). But if, by 2017, all identified active TB patients with previously-treated TB could be tested for drug susceptibility, and 85% of those with MDR-TB could initiate MDR-appropriate treatment, then MDR-TB incidence in 2025 could be reduced by 26% (95% UR 4-52%) relative to projections under continued current practice. Also expanding this drug-susceptibility testing and appropriate MDR-TB treatment to treatment-naïve as well as previously-treated TB cases, by 2020, could reduce MDR-TB incidence in 2025 by 29% (95% UR 6-55%) compared to continued current practice. If this diagnosis and treatment of all MDR-TB in known active TB cases by 2020 could be implemented via a novel second-line regimen with similar effectiveness and tolerability as current first-line therapy, a 54% (95% UR 20-74%) reduction in MDR-TB incidence compared to current-practice projections could be achieved by 2025.
  
  
  CONCLUSIONS
  Expansion of diagnosis and treatment of MDR-TB, even using current sub-optimal second-line regimens, is expected to significantly decrease MDR-TB incidence at the population level. Focusing MDR diagnostic efforts on previously-treated cases is an efficient first-step approach.
authors.affiliation: Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Emily A
authors.identifier: http://orcid.org/0000-0002-0083-422X
authors.initials: EA
authors.lastname: Kendall
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Azman
authors.affiliation: Amsterdam Institute for Global Health and Development, Academic Medical Centre, Amsterdam, Netherlands.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Cobelens
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: David W
authors.initials: DW
authors.lastname: Dowdy
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D001499:Bayes Theorem; D006801:Humans; D015994:Incidence; D009169:Mycobacterium tuberculosis; D011314:Preventive Health Services / Q000379:methods; D011322:Primary Prevention; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control* / Q000635:transmission
chemical_list: D000995:Antitubercular Agents