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Linking individual natural history to population outcomes in tuberculosis

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dc.contributor.author Salvatore, Phillip P.
dc.contributor.author Proano, Alvaro
dc.contributor.author Kendall, Emily A.
dc.contributor.author Gilman, Robert H.
dc.contributor.author Dowdy, David W.
dc.date.accessioned 2018-12-01T00:04:14Z
dc.date.available 2018-12-01T00:04:14Z
dc.date.issued 2018
dc.identifier.uri http://doi.org/10.1093/infdis/jix555
dc.identifier.uri http://repositorio.upch.edu.pe/handle/upch/4243
dc.description.abstract 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.
dc.language.iso eng
dc.publisher Oxford University Press
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject adult
dc.subject Bayes theorem
dc.subject calibration
dc.subject cohort analysis
dc.subject controlled study
dc.subject disease association
dc.subject disease course
dc.subject disease progression
dc.subject Disease progression
dc.subject disease transition
dc.subject female
dc.subject human
dc.subject immunocompetence
dc.subject intermethod comparison
dc.subject major clinical study
dc.subject male
dc.subject mathematical models
dc.subject Mathematical models
dc.subject medical history
dc.subject natural history
dc.subject Natural history
dc.subject outcome assessment
dc.subject priority journal
dc.subject process development
dc.subject spontaneous remission
dc.subject Spontaneous remission
dc.subject stochastic model
dc.subject tuberculosis
dc.subject Tuberculosis
dc.title Linking individual natural history to population outcomes in tuberculosis
dc.type info:eu-repo/semantics/article
dc.identifier.journal Journal of Infectious Diseases


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