Horton, KC;
Richards, AS;
Emery, JC;
Esmail, H;
Houben, RMGJ;
(2023)
Reevaluating progression and pathways following Mycobacterium tuberculosis infection within the spectrum of tuberculosis.
Proceedings of the National Academy of Sciences of the United States of America
, 120
(47)
, Article e2221186120. 10.1073/pnas.2221186120.
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Abstract
Traditional understanding of the risk of progression from Mycobacterium tuberculosis (Mtb) infection to tuberculosis (TB) overlooks diverse presentations across a spectrum of disease. We developed a deterministic model of Mtb infection and minimal (pathological damage but not infectious), subclinical (infectious but no reported symptoms), and clinical (infectious and symptomatic) TB, informed by a rigorous evaluation of data from a systematic review of TB natural history. Using a Bayesian approach, we calibrated the model to data from historical cohorts that followed tuberculin-negative individuals to tuberculin conversion and TB, as well as data from cohorts that followed progression and regression between disease states, disease state prevalence ratios, disease duration, and mortality. We estimated incidence, pathways, and 10-y outcomes following Mtb infection for a simulated cohort. Then, 92.0% (95% uncertainty interval, UI, 91.4 to 92.5) of individuals self-cleared within 10 y of infection, while 7.9% (95% UI 7.4 to 8.5) progressed to TB. Of those, 68.6% (95% UI 65.4 to 72.0) developed infectious disease, and 33.2% (95% UI 29.9 to 36.4) progressed to clinical disease. While 98% of progression to minimal disease occurred within 2 y of infection, only 71% and 44% of subclinical and clinical disease, respectively, occurred within this period. Multiple progression pathways from infection were necessary to calibrate the model and 49.5% (95% UI 45.6 to 53.7) of those who developed infectious disease undulated between disease states. We identified heterogeneous pathways across disease states after Mtb infection, highlighting the need for clearly defined disease thresholds to inform more effective prevention and treatment efforts to end TB.
| Type: | Article |
|---|---|
| Title: | Reevaluating progression and pathways following Mycobacterium tuberculosis infection within the spectrum of tuberculosis |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1073/pnas.2221186120 |
| Publisher version: | https://doi.org/10.1073/pnas.2221186120 |
| Language: | English |
| Additional information: | Copyright © 2023 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) |
| Keywords: | disease, incidence, infection, progression, tuberculosis, Humans, Tuberculin, Bayes Theorem, Tuberculosis, Mycobacterium tuberculosis, Communicable Diseases |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10182524 |
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