Re-evaluating progression and pathways followingMycobacteria tuberculosisinfection within the spectrum of tuberculosis disease

Abstract

Background: Traditional understanding of the risk of progression fromMycobacterium tuberculosis(Mtb) infection to tuberculosis (TB) disease overlooks nuance across a spectrum of disease. Methods: We developed a deterministic model ofMtbinfection and minimal (pathological damage but not infectious), subclinical (infectious but no reported symptoms), and clinical (infectious and symptomatic) TB disease, 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 disease, 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 ten-year outcomes followingMtbinfection for a simulated cohort. Results: 90.8% (95% uncertainty interval, UI, 90.2-91.3) of individuals self-cleared within 10 years of infection, while 9.3% (95% UI 8.4-10.0) progressed to TB disease. Of those, 68.1% (95% UI 65.1-71.1) developed infectious disease, and 32.7% (95% UI 29.7-35.7) progressed to clinical disease. While 93% of progression to minimal disease occurred within two years of infection, only 63% and 38% of subclinical and clinical disease, respectively, occurred within this period. Multiple progression pathways from infection were necessary to calibrate the model, and 48.8% (95% UI 45.0-52.6) of those who developed infectious disease undulated between disease states. Conclusions: We identified highly heterogeneous pathways across disease states afterMtbinfection, highlighting the need for clearly defined disease thresholds to inform more effective prevention and treatment efforts to end TB.

Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise

“…[ 27 ] A minority of those infected (currently only inferred by conversion to positive immunoreactivity following exposure) will develop disease. [ 28 , 29 ] While Mtb infection was assumed to be lifelong in the classic framework, evidence now suggests that a substantial proportion of individuals self-clear infection. [ 30 , 31 ] Existing estimates for the proportion of people with Mtb infection are based on immunoreactivity, [ 32 ] likely leading to an overestimate.…”

Latent tuberculosis infection and incident cardiovascular and non-cardiovascular death

“…LTBI is an otherwise asymptomatic condition. Whenever it has been in the crosshairs of clinical or population health research and practice, it has mainly been in relation to its potential progression to active TB, and the resultant individual morbidity and population transmission of M.tb (1), (2), (3), (40). Here we showed that LTBI is independently associated with worse overall survival.…”

“…Infection with Mycobacterium tuberculosis (M.tb) is characterized by an immunopathological spectrum (1), (2), (3), (4), (5). Clinically overt or active TB disease is often associated with a prolonged systemic inflammatory response with symptomatic tissue destruction and remodeling (6).…”

Recent Travel and Tuberculosis in Migrants: Data From a Low-Incidence Country

“…This is evident when using the time since recent travel as the starting point for assessing disease progression, rather than the original time of migration into a low-incidence country. If the high TB rate among migrants is indeed driven by recent exposure, incidence curves using recent travel as follow-up start should better reflect estimated rates of disease onset post-exposure, as demonstrated here [ 9 ].…”