info:eu-repo/semantics/article
Linking individual natural history to population outcomes in tuberculosis
Fecha
2018Institución
Resumen
Background. Substantial individual heterogeneity exists in the clinical manifestations and duration of active tuberculosis. We sought to link the individual-level characteristics of tuberculosis disease to observed population-level outcomes. Methods. We developed an individual-based, stochastic model of tuberculosis disease in a hypothetical cohort of patients with smear-positive tuberculosis. We conceptualized the disease process as consisting of 2 states-progression and recovery-including transitions between the 2. We then used a Bayesian process to calibrate the model to clinical data from the prechemotherapy era, thus identifying the rates of progression and recovery (and probabilities of transition) consistent with observed population-level clinical outcomes. Results. Observed outcomes are consistent with slow rates of disease progression (median doubling time: 84 days, 95% uncertainty range 62-104) and a low, but nonzero, probability of transition from disease progression to recovery (median 16% per year, 95% uncertainty range 11%-21%). Other individual-level dynamics were less influential in determining observed outcomes. Conclusions. This simplified model identifies individual-level dynamics-including a long doubling time and low probability of immune recovery-that recapitulate population-level clinical outcomes of untreated tuberculosis patients. This framework may facilitate better understanding of the population-level impact of interventions acting at the individual host level.
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