Using molecular testing and whole-genome sequencing for tuberculosis diagnosis in a low-burden setting: A cost-effectiveness analysis using transmission-dynamic modelling

Tendai Mugwagwa, Ibrahim Abubakar, Peter White*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)281-291
Number of pages11
Issue number3
Publication statusPublished - 1 Mar 2021

Bibliographical note

Funding Information:
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).

Publisher Copyright:

Copyright 2021 Elsevier B.V., All rights reserved.


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


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