Quantifying progression and regression across the spectrum of pulmonary tuberculosis: a data synthesis study

Background Prevalence surveys show a substantial burden of subclinical (asymptomatic but infectious) tuberculosis, from which individuals can progress, regress, or even persist in a chronic disease state. We aimed to quantify these pathways across the spectrum of tuberculosis disease.Methods We created a deterministic framework of untreated tuberculosis disease with progression and regression between three states of pulmonary tuberculosis disease: minimal (non-infectious), subclinical (asymptomatic but infectious), and clinical (symptomatic and infectious). We obtained data from a previous systematic review of prospective and retrospective studies that followed and recorded the disease state of individuals with tuberculosis in a cohort without treatment. These data were considered in a Bayesian framework, enabling quantitative estimation of tuberculosis disease pathways with rates of transition between states and 95% uncertainty intervals (UIs).Findings We included 22 studies with data from 5942 individuals in our analysis. Our model showed that after 5 years, 40% (95% UI 31 center dot 3-48 center dot 0) of individuals with prevalent subclinical disease at baseline recover and 18% (13 center dot 3-24 center dot 0) die from tuberculosis, with 14% (9 center dot 9-19 center dot 2) still having infectious disease, and the remainder with minimal disease at risk of re-progression. Over 5 years, 50% (40 center dot 0-59 center dot 1) of individuals with subclinical disease at baseline never develop symptoms. For those with clinical disease at baseline, 46% (38 center dot 3-52 center dot 2) die and 20% (15 center dot 2-25 center dot 8) recover from tuberculosis, with the remainder being in or transitioning between the three disease states after 5 years. We estimated the 10-year mortality of people with untreated prevalent infectious tuberculosis to be 37% (30 center dot 5-45 center dot 4).Interpretation For people with subclinical tuberculosis, classic clinical disease is neither an inevitable nor an irreversible outcome. As such, reliance on symptom-based screening means a large proportion of people with infectious disease might never be detected.Funding TB Modelling and Analysis Consortium and European Research Council.Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.