Abstract

BackgroundIn 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.ResultsWe 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.

Highlights

  • In India, despite impressive progress in the scale-up of DOTS (Directly Observed Treatment Short course) coverage by the public sector, tuberculosis (TB) remains a pressing public health problem [1], owing partly to a vast and unorganized private sector [2,3,4,5,6]

  • Public-sector deployment of high-sensitivity diagnostic testing and universal drug susceptibility testing (DST) appropriately linked with treatment could substantially impact multi-drug resistance (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 between 2015 and 2025

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Summary

Introduction

In India, despite impressive progress in the scale-up of DOTS (Directly Observed Treatment Short course) coverage by the public sector, tuberculosis (TB) remains a pressing public health problem [1], owing partly to a vast and unorganized private sector [2,3,4,5,6]. DST is currently prioritized for patients categorized as ‘high-risk’, including those with known HIV co-infection; those with a history of TB treatment; and those not responding to first-line treatment [7]. These technological and resource limitations are amplified by operational challenges. A substantial proportion of persons in risk groups currently eligible for DST are not tested [8,9] Among those diagnosed as drug-resistant and eligible for a regimen for multi-drug resistant TB, treatment success rates are currently reported at less than 50% [8]. We draw from a recent multi-centric demonstration study conducted in India that involved upfront Xpert MTB/RIF testing of all TB suspects

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