Baseline and end-of-treatment host serum biomarkers predict relapse in adults with pulmonary tuberculosis

Hygon Mutavhatsindi; Charles M Manyelo; Candice I Snyders; Ilana Van Rensburg; Martin Kidd; Kim Stanley; Gerard Tromp; Reynaldo Dietze; Bonnie Thiel; Paul D van Helden; John T Belisle; John L Johnson; W Henry Boom; Gerhard Walzl; Novel N Chegou

doi:10.1016/j.jinf.2024.106173

Baseline and end-of-treatment host serum biomarkers predict relapse in adults with pulmonary tuberculosis

J Infect. 2024 May 9;89(1):106173. doi: 10.1016/j.jinf.2024.106173. Online ahead of print.

Authors

Affiliations

¹ Division of Immunology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town 8000, South Africa; South African Medical Research Council Centre for Tuberculosis Research, Cape Town 8000, South Africa; Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg, South Africa. Electronic address: Hygon.mutavhatsindi@mrc.ac.za.
² Division of Immunology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town 8000, South Africa; South African Medical Research Council Centre for Tuberculosis Research, Cape Town 8000, South Africa; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town 8000, South Africa.
³ Centre for Statistical Consultation, Department of Statistics and Actuarial Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa.
⁴ Núcleo de Doenças Infecciosas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Brazil.
⁵ Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, Cleveland, USA.
⁶ Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA.
⁷ Division of Immunology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town 8000, South Africa; South African Medical Research Council Centre for Tuberculosis Research, Cape Town 8000, South Africa; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town 8000, South Africa. Electronic address: novel@sun.ac.za.

PMID: 38734311
DOI: 10.1016/j.jinf.2024.106173

Abstract

Background: There is a need for new tools for monitoring of the response to TB treatment. Such tools may allow for tailored treatment regimens, and stratify patients initiating TB treatment into different risk groups. We evaluated combinations between previously published host biomarkers and new candidates, as tools for monitoring TB treatment response, and prediction of relapse.

Methods: Serum samples were collected at multiple time points, from patients initiating TB treatment at research sites situated in South Africa (ActionTB study), Brazil and Uganda (TBRU study). Using a multiplex immunoassay platform, we evaluated the concentrations of selected host inflammatory biomarkers in sera obtained from clinically cured patients with and without subsequent relapse within 2 years of TB treatment completion.

Results: A total of 130 TB patients, 30 (23%) of whom had confirmed relapse were included in the study. The median time to relapse was 9.7 months in the ActionTB study (n = 12 patients who relapsed), and 5 months (n = 18 patients who relapsed) in the TBRU study. Serum concentrations of several host biomarkers changed during TB treatment with IL-6, IP-10, IL-22 and complement C3 showing potential individually, in predicting relapse. A six-marker signature comprising of TTP, BMI, sICAM-1, IL-22, IL-1β and complement C3, predicted relapse, prior to the onset of TB treatment with 89% sensitivity and 94% specificity. Furthermore, a 3-marker signature (Apo-CIII, IP-10 and sIL-6R) predicted relapse in samples collected at the end of TB treatment with sensitivity of 71% and specificity of 74%. A previously identified baseline relapse prediction signature (TTP, BMI, TNF-β, sIL-6R, IL-12p40 and IP-10) also showed potential in the current study.

Conclusion: Serum host inflammatory biomarkers may be useful in predicting relapse in TB patients prior to the initiation of treatment. Our findings have implications for tailored patient management and require prospective evaluation in larger studies.

Keywords: Biomarkers; Biosignatures; Relapse; Treatment response; Tuberculosis.