title: Modelling the effect of short-course multidrug-resistant tuberculosis treatment in Karakalpakstan, Uzbekistan.
abstract: BACKGROUND
  Multidrug-resistant tuberculosis (MDR-TB) is a major threat to global TB control. MDR-TB treatment regimens typically have a high pill burden, last 20 months or more and often lead to unsatisfactory outcomes. A 9-11 month regimen with seven antibiotics has shown high success rates among selected MDR-TB patients in different settings and is conditionally recommended by the World Health Organization.
  
  
  METHODS
  We construct a transmission-dynamic model of TB to estimate the likely impact of a shorter MDR-TB regimen when applied in a low HIV prevalence region of Uzbekistan (Karakalpakstan) with high rates of drug resistance, good access to diagnostics and a well-established community-based MDR-TB treatment programme providing treatment to around 400 patients. The model incorporates acquisition of additional drug resistance and incorrect regimen assignment. It is calibrated to local epidemiology and used to compare the impact of shorter treatment against four alternative programmatic interventions.
  
  
  RESULTS
  Based on empirical outcomes among MDR-TB patients and assuming no improvement in treatment success rates, the shorter regimen reduced MDR-TB incidence from 15.2 to 9.7 cases per 100,000 population per year and MDR-TB mortality from 3.0 to 1.7 deaths per 100,000 per year, achieving comparable or greater gains than the alternative interventions. No significant increase in the burden of higher levels of resistance was predicted. Effects are probably conservative given that the regimen is likely to improve success rates.
  
  
  CONCLUSIONS
  In addition to benefits to individual patients, we find that shorter MDR-TB treatment regimens also have the potential to reduce transmission of resistant strains. These findings are in the epidemiological setting of treatment availability being an important bottleneck due to high numbers of patients being eligible for treatment, and may differ in other contexts. The high proportion of MDR-TB with additional antibiotic resistance simulated was not exacerbated by programmatic responses and greater gains may be possible in contexts where the regimen is more widely applicable.
authors.affiliation: School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. james.trauer@monash.edu.|The Victorian Tuberculosis Program at the Peter Doherty Institute, Melbourne, Australia. james.trauer@monash.edu.
authors.forename: James M
authors.initials: JM
authors.lastname: Trauer
authors.affiliation: Médecins sans Frontières, Manson Unit, London, UK.
authors.forename: Jay
authors.initials: J
authors.lastname: Achar
authors.affiliation: National TB Institute, Ministry of Health, Tashkent, Uzbekistan.
authors.forename: Nargiza
authors.initials: N
authors.lastname: Parpieva
authors.affiliation: Ministry of Health, Nukus, Uzbekistan.
authors.forename: Atadjan
authors.initials: A
authors.lastname: Khamraev
authors.affiliation: The Victorian Tuberculosis Program at the Peter Doherty Institute, Melbourne, Australia.
authors.forename: Justin T
authors.initials: JT
authors.lastname: Denholm
authors.affiliation: Global TB Programme, World Health Organization, Geneva, Switzerland.
authors.forename: Dennis
authors.initials: D
authors.lastname: Falzon
authors.affiliation: Global TB Programme, World Health Organization, Geneva, Switzerland.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Jaramillo
authors.affiliation: Médecins sans Frontières Holland, Amsterdam, The Netherlands.
authors.forename: Anita
authors.initials: A
authors.lastname: Mesic
authors.affiliation: Médecins sans Frontières, Manson Unit, London, UK.
authors.forename: Philipp
authors.initials: P
authors.lastname: du Cros
authors.affiliation: James Cook University, Queensland, Australia.
authors.forename: Emma S
authors.initials: ES
authors.lastname: McBryde
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage*; D023801:Directly Observed Therapy; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D015995:Prevalence; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000453:epidemiology* / Q000635:transmission; D014610:Uzbekistan / Q000453:epidemiology; D014944:World Health Organization
chemical_list: D000995:Antitubercular Agents
keywords: Epidemiology; Extensively drug-resistant tuberculosis; Modelling; Multidrug-resistant tuberculosis; Public health; Treatment; Tuberculosis; Uzbekistan