title: The Potential Impact of Up-Front Drug Sensitivity Testing on India's Epidemic of Multi-Drug Resistant Tuberculosis.
abstract: BACKGROUND
  In India as elsewhere, multi-drug resistance (MDR) poses a serious challenge in the control of tuberculosis (TB). The End TB strategy, recently approved by the world health assembly, aims to reduce TB deaths by 95% and new cases by 90% between 2015 and 2035. A key pillar of this approach is early diagnosis of tuberculosis, including use of higher-sensitivity diagnostic testing and universal rapid drug susceptibility testing (DST). Despite limitations of current laboratory assays, universal access to rapid DST could become more feasible with the advent of new and emerging technologies. Here we use a mathematical model of TB transmission, calibrated to the TB epidemic in India, to explore the potential impact of a major national scale-up of rapid DST. To inform key parameters in a clinical setting, we take GeneXpert as an example of a technology that could enable such scale-up. We draw from a recent multi-centric demonstration study conducted in India that involved upfront Xpert MTB/RIF testing of all TB suspects.
  
  
  RESULTS
  We find that widespread, public-sector deployment of high-sensitivity diagnostic testing and universal DST appropriately linked with treatment could substantially impact MDR-TB in India. Achieving 75% access over 3 years amongst all cases being diagnosed for TB in the public sector alone could avert over 180,000 cases of MDR-TB (95% CI 44187 - 317077 cases) between 2015 and 2025. Sufficiently wide deployment of Xpert could, moreover, turn an increasing MDR epidemic into a diminishing one. Synergistic effects were observed with assumptions of simultaneously improving MDR-TB treatment outcomes. Our results illustrate the potential impact of new and emerging technologies that enable widespread, timely DST, and the important effect that universal rapid DST in the public sector can have on the MDR-TB epidemic in India.
authors.affiliation: Central TB Division, Government of India, New Delhi, India.
authors.forename: Kuldeep Singh
authors.initials: KS
authors.lastname: Sachdeva
authors.affiliation: Foundation for Innovative New Diagnostics, New Delhi, India.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Raizada
authors.affiliation: Central TB Division, Government of India, New Delhi, India.
authors.forename: Radhey Shyam
authors.initials: RS
authors.lastname: Gupta
authors.affiliation: World Health Organization, India Country Office, New Delhi, India.
authors.forename: Sreenivas Achuthan
authors.initials: SA
authors.lastname: Nair
authors.affiliation: Foundation for Innovative New Diagnostics, New Delhi, India.
authors.forename: Claudia
authors.initials: C
authors.lastname: Denkinger
authors.affiliation: Foundation for Innovative New Diagnostics, New Delhi, India.
authors.forename: Chinnambedu Nainarappan
authors.initials: CN
authors.lastname: Paramasivan
authors.affiliation: Foundation for Innovative New Diagnostics, New Delhi, India.
authors.forename: Shubhangi
authors.initials: S
authors.lastname: Kulsange
authors.affiliation: Foundation for Innovative New Diagnostics, New Delhi, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Thakur
authors.affiliation: Bill and Melinda Gates Foundation, New Delhi, India.
authors.forename: Puneet
authors.initials: P
authors.lastname: Dewan
authors.affiliation: Foundation for Innovative New Diagnostics, New Delhi, India.
authors.forename: Catharina
authors.initials: C
authors.lastname: Boehme
authors.affiliation: Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Nimalan
authors.initials: N
authors.lastname: Arinaminpathy
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use; D058872:Epidemics / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D007194:India / Q000453:epidemiology; D008826:Microbial Sensitivity Tests; D008962:Models, Theoretical; D015995:Prevalence; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology / Q000517:prevention & control* / Q000635:transmission
chemical_list: D000995:Antitubercular Agents