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Using molecular testing and whole-genome sequencing for tuberculosis diagnosis in a low-burden setting: a cost-effectiveness analysis using transmission-dynamic modelling
  1. Tendai Mugwagwa1,2,
  2. Ibrahim Abubakar3,
  3. Peter J White1,2
  1. 1 Modelling and Economics Unit, National Infection Service, Public Health England, London, UK
  2. 2 MRC Centre for Global Infectious Disease Analysis and NIHR Health Protection Research Unit in Modelling and Health Economics, Department of Infectious Disease Epidemiology, Imperial College London, London, UK
  3. 3 Institute for Global Health, University College London, London, UK
  1. Correspondence to Prof Peter J White, Modelling and Economics Unit, National Infection Service, Public Health England, London NW9 5EQ, UK; peter.white{at}, p.white{at}


Background Despite progress in TB control in low-burden countries like England and Wales, there are still diagnostic delays. Molecular testing and/or whole-genome sequencing (WGS) provide more rapid diagnosis but their cost-effectiveness is relatively unexplored in low-burden settings.

Methods An integrated transmission-dynamic health economic model is used to assess the cost-effectiveness of using WGS to replace culture-based drug-sensitivity testing, versus using molecular testing versus combined use of WGS and molecular testing, for routine TB diagnosis. The model accounts for the effects of faster appropriate treatment in reducing transmission, benefiting health and reducing future treatment costs. Cost-effectiveness is assessed using incremental net benefit (INB) over a 10-year horizon with a quality-adjusted life-year valued at £20 000, and discounting at 3.5% per year.

Results WGS shortens the time to drug sensitivity testing and treatment modification where necessary, reducing treatment and hospitalisation costs, with an INB of £7.1 million. Molecular testing shortens the time to TB diagnosis and treatment. Initially, this causes an increase in annual costs of treatment, but averting transmissions and future active TB disease subsequently, resulting in cost savings and health benefits to achieve an INB of £8.6 million (GeneXpert MTB/RIF) or £11.1 million (Xpert-Ultra). Combined use of Xpert-Ultra and WGS is the optimal strategy we consider, with an INB of £16.5 million.

Conclusion Routine use of WGS or molecular testing is cost-effective in a low-burden setting, and combined use is the most cost-effective option. Adoption of these technologies can help low-burden countries meet the WHO End TB Strategy milestones, particularly the UK, which still has relatively high TB rates.

  • tuberculosis
  • diagnosis
  • whole-genome sequencing
  • molecular testing
  • transmission-dynamic modelling
  • cost-effectiveness

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  • Contributors The study was conceived by PJW and TM, who designed the model and obtained and analysed the data. The model was implemented and analysed by TM under the guidance of PJW, with input from IA. All authors contributed to the interpretation of the analysis. PJW and TM wrote the first draft of the paper and all authors contributed to subsequent drafts. All authors approve the work for publication.

  • Funding PJW and TM thank the National Institute for Health Research (NIHR) Health Protection Research Unit in Modelling Methodology at Imperial College London, in partnership with Public Health England (PHE), for funding (HPRU-2012-10080). PJW also thanks the NIHR HPRU in Modelling and Health Economics, a partnership between PHE, Imperial College London and LSHTM, for funding (NIHR200908). PJW acknowledges support from the MRC Centre for Global Infectious Disease Analysis (MR/R015600/1); this award is jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO) under the MRC/FCDO Concordat agreement and is also part of the EDCTP2 programme supported by the EU. PJW and IA received funding from NIHR Health Technology Assessment (NIHR127459). IA was also supported by NIHR through a Senior Research Fellowship (SRF-2011-04-001) and a Senior Investigator Award (NF-SI-0616-10037).

  • Disclaimer This report is independent research and the funders of this study had no role in study design; data collection, analysis or interpretation; or writing of the report. The views expressed are those of the authors and not necessarily those of the Department of Health and Social Care, EU, FCDO, Medical Research Council, National Health Service, National Institute for Health Research or Public Health England.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Ethical approval was not required. The surveillance data analysed were routinely collected by Public Health England under Section 251 of the National Health Service Act 2006. All records were anonymised before analysis.

  • Provenance and peer review Not commissioned; externally peer-reviewed.

  • Data availability statement Data are available from the cited sources.