Host response biomarkers of tuberculosis recurrence and treatment failure

Bauer, Bernadette; Ahmed, Mohamed I. M.; Baranov, Olga; Bakuli, Abhishek; Lin, Luming; Kisinda, Abisai; Chachage, Mkunde; Ntinginya, Nyanda E.; Khosa, Celso; Hoelscher, Michael; Rassool, Mohammed; Charalambous, Salome; Sutherland, Jayne S.; Held, Kathrin; Rachow, Andrea; Geldmacher, Christof (2026): Host response biomarkers of tuberculosis recurrence and treatment failure. Communications Medicine, 6: 184. ISSN 2730-664X

Abstract

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.

Publication on behalf of the TB sequel consortium

• Dokumententyp: Artikel (Klinikum der LMU)
• Organisationseinheit (Fakultäten): 07 Medizin > Klinikum der LMU München > Institut für Infektions- und Tropenmedizin
• DFG-Fachsystematik der Wissenschaftsbereiche: Lebenswissenschaften
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892