title: Expected effects of adopting a 9 month regimen for multidrug-resistant tuberculosis: a population modelling analysis.
abstract: In May, 2016, WHO endorsed a 9 month regimen for multidrug-resistant tuberculosis that is cheaper and potentially more effective than the conventional, longer (20-24 month) therapy. We aimed to investigate the population-level implications of scaling up this new regimen.
  
  
  
  In this population modelling analysis, we developed a dynamic transmission model to simulate the introduction of this short-course regimen as an instantaneous switch in 2016. We projected the corresponding percentage reduction in the incidence of multidrug-resistant tuberculosis by 2024 compared with continued use of longer therapy. In the primary analysis in a representative southeast Asian setting, we assumed that the short-course regimen would double treatment access (through savings in resources or capacity) and achieve long-term efficacy at levels seen in preliminary cohort studies. We then did extensive sensitivity analyses to explore a range of alternative scenarios.
  
  
  
  Under the optimistic assumptions in the primary analysis, the incidence of multidrug-resistant tuberculosis in 2024 would be 3·3 (95% uncertainty range 2·2-5·6) per 100 000 population with the short-course regimen and 4·3 (2·9-7·6) per 100 000 population with continued use of longer therapy-ie, the short-course regimen could reduce incidence by 23% (10-38). Incidence would be reduced by 14% (4-28) if the new regimen affected only treatment effectiveness and by 11% (3-24) if it affected only treatment availability. Under more pessimistic assumptions, the short-course regimen would have minimal effect and even potential for harm-eg, when 30% of patients are ineligible for the new regimen because of second-line drug resistance, we projected a change in incidence of -2% (-20 to +28). The new regimen's effect was greater in settings with more ongoing transmission of multidrug-resistant tuberculosis, but results were otherwise similar across settings with different levels of tuberculosis incidence and prevalence of multidrug resistance.
  
  
  
  The short-course regimen has potential to substantially lessen the multidrug-resistant tuberculosis epidemic, but this effect depends on its long-term efficacy, its ability to expand treatment access, and the role of second-line drug resistance.
  
  
  
  US National Institutes of Health and Bill & Melinda Gates Foundation.
authors.affiliation: Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: ekendal2@jhmi.edu.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Kendall
authors.affiliation: Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Fojo
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: D000995:Antitubercular Agents / Q000008:administration & dosage*; D001210:Asia, Southeastern / Q000453:epidemiology; D002985:Clinical Protocols; D004334:Drug Administration Schedule; D005544:Forecasting / Q000379:methods*; D006801:Humans; D015994:Incidence; D008962:Models, Theoretical; D013997:Time Factors; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000453:epidemiology / Q000635:transmission
chemical_list: D000995:Antitubercular Agents