Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2026 Feb 14.
doi: 10.1038/s43856-026-01424-w. Online ahead of print.

Host response biomarkers of tuberculosis recurrence and treatment failure

Bernadette Bauer  1 , Mohamed I M Ahmed  2   3 , Olga Baranov  2   3   4 , Abhishek Bakuli  2   3 , Luming Lin  2   3 , Abisai Kisinda  5 , Mkunde Chachage  2   5   6 , Nyanda E Ntinginya  5 , Celso Khosa  7 , Michael Hoelscher  2   3   4   8 , Mohammed Rassool  9 , Salome Charalambous  10   11 , Jayne S Sutherland  12 , Kathrin Held #  2   3   4   8 , Andrea Rachow #  2   3   8 , Christof Geldmacher #  2   3   4 ; TB sequel consortium
Collaborators, Affiliations
Free article

Host response biomarkers of tuberculosis recurrence and treatment failure

Bernadette Bauer et al. Commun Med (Lond). .
Free article

Abstract

Background: Accurate detection of tuberculosis (TB) treatment failure and recurrence can improve disease control, but current sputum-based monitoring tools pose significant limitations. This study aimed to identify sputum-independent biomarkers for detecting and predicting TB treatment failure and recurrence.

Methods: Within the Pan-African TB Sequel study, we conducted a matched case-control study with 40 participants who had recurrent TB or treatment failure and 37 successfully treated controls matched by sex, age, and HIV status. Cases were classified as (a) non-converters with persistently positive sputum Mycobacterium tuberculosis (MTB) results during treatment, (b) reverters at the end of treatment (EOT), or (c) recurrence after EOT. Peripheral blood was collected at baseline, months 2, 4, 6, 9, and 12, and at suspected recurrence. MTB-specific T-cell activation markers (CD38, CD27, HLA-DR, Ki67) and transcriptomic signatures (Sweeney3, Risk6, MAMS6) were assessed and compared to the reference standard MTB culture and smear results.

Results: Here, we show that both MTB-specific T-cell activation and transcriptomic signatures detected non-conversion and TB recurrence at month 9 or 12 after treatment initiation. CD38 expression demonstrates 100% sensitive (95% CI: 56.6-100%) and 78% specific (95% CI: 56.5-99.4%) for detecting TB recurrence, with an AUC of 0.98 (95% CI: 91-100%). Among transcriptomic signatures, MAMS6, RISK6, and Sweeney3 achieve 75% sensitivity (95% CI: 50-100%) and 87-93% specificity (95% CI: MAMS6 0-100%, RISK6 0-93%, Sweeney3 0-100%), with comparable AUCs (0.78-0.83). Neither marker detected TB reversion at EOT.

Conclusion: These sputum-independent biomarkers effectively identify TB disease, non-conversion and recurrence TB after EOT, whereas their utility in detecting TB reversion during treatment remains limited.

Plain language summary

Tuberculosis (TB) is a serious infectious disease that can be fatal if untreated. While most patients recover with treatment, some do not respond well or develop TB again after completing therapy. Monitoring how well patients respond to TB treatment currently relies on tests using sputum samples, which can be slow and may be less reliable during treatment. This study aimed to identify alternative host-based markers in blood that could help detect patients with poor treatment response or TB recurrence. We found that specific blood markers can reliably identify patients with TB and detect poor treatment response during therapy, as well as TB recurrence after treatment completion. These findings may help improve early detection, guide treatment decisions, and reduce TB transmission.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors (M.A., O.B., M.H., K.H., C.G.) have submitted a European patent application related to the MAMS_6 transcriptomic signature presented in the manuscript. The application is currently unpublished and pending. Otherwise, the authors have no competing interests.

References

    1. Global Tuberculosis Report 2024. 1st ed. [cited 1 Mar 2025]. Available from: https://ebookcentral.proquest.com/lib/kxp/detail.action?docID=31850656 (World Health Organization, 2024).
    1. Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. Available from: https://permalink.obvsg.at/ (World Health Organization, 2014).
    1. Vega, V., Rodríguez, S., van der Stuyft, P., Seas, C. & Otero, L. Recurrent TB: a systematic review and meta-analysis of the incidence rates and the proportions of relapses and reinfections. Thorax 76, 494–502 (2021).
    1. van der Werf, M. J., Langendam, M. W., Huitric, E. & Manissero, D. Multidrug resistance after inappropriate tuberculosis treatment: a meta-analysis. Eur. Respir. J. 39, 1511–1519 (2012).
    1. Espinal, M. A. et al. Determinants of drug-resistant tuberculosis: analysis of 11 countries. Int J. Tuberc. Lung Dis. 5, 887–893 (2001).

LinkOut - more resources