Frailty as a Framework to Understand Tuberculosis Severity, Recovery, and Sequelae

Authors

• Yoscelina Estrella Martinez-Lopez, University of Texas Health Science Center at Houston
• Benjamin W. Black, University of Texas Health Science Center at Houston
• Jessica Lee, University of Texas Health Science Center at Houston
• Brian J. Buta, The Johns Hopkins University
• Lisa Y. Armitige, University of Texas Health Science Center at Tyler
• William A. Fountain
• Rafael Samper
• Aanand D. Naik
• Joanne Turner
• Blanca I. Restrepo, The University of Texas Rio Grande ValleyFollow

Document Type

Article

Publication Date

8-14-2026

Abstract

Tuberculosis (TB) causes profound systemic illness, and many survivors experience long-term sequelae associated with disability and premature mortality. Current TB severity indicators capture isolated aspects of disease and may not reflect the integrated physiological impact of infection on the host. Frailty, a multidimensional syndrome characterized by reduced physiological reserve and increased vulnerability to stressors, predicts adverse outcomes and guides clinical management in geriatrics. We propose frailty as an integrative framework for understanding the systemic effects of TB across the life course, encompassing disease severity, recovery, and long-term sequelae. We discuss biological mechanisms through which Mycobacterium tuberculosis infection may erode physiological reserve and promote frailty, including inflammation and metabolic and endocrine dysregulation. We further consider how frailty assessment could improve risk stratification and guide individualized supportive care to mitigate post-TB sequelae. Unlike aging-related frailty, TB-associated frailty may provide a unique opportunity to study mechanisms of resilience and recovery following severe infection.

Frailty offers a multidimensional framework for understanding the systemic impact of tuberculosis (TB) beyond conventional disease severity measures, with potential to improve risk stratification, guide individualized supportive care, and evaluate recovery and post-TB sequelae.

Comments

© The Author(s) 2026. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Recommended Citation

Martinez-Lopez, Y. E., Black, B. W., Lee, J., Buta, B. J., Armitige, L. Y., Fountain, W. A., ... & Restrepo, B. I. (2026). Frailty as a framework to understand tuberculosis severity, recovery and sequelae. The Journal of Infectious Diseases, jiag415. https://doi.org/10.1093/infdis/jiag415

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Publication Title

The Journal of Infectious Diseases

DOI

10.1093/infdis/jiag415

Academic Level

faculty