Extensions to Bayesian generalized linear mixed effects models for household tuberculosis transmission
McIntosh, Avery Isaac
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Understanding tuberculosis transmission is vital for efforts at interrupting the spread of disease. Household contact studies that follow persons sharing a household with a TB case—so-called household contacts—and test for latent TB infection by tuberculin skin test conversion give investigators vital information about risk factors for TB transmission. In these studies, investigators often assume secondary cases are infected by the primary TB case, despite substantial evidence that infection from a source outside the home is often equally likely, especially in high-prevalence settings. Investigators may discard information on contacts who test positive at study initiation due to uncertainty of the infection source, or assume infected contacts were infected from the index case prior to study initiation. With either assumption, information on transmission dynamics is lost or incomplete, and estimates of household risk factors for transmission will be biased. This dissertation describes an approach to modeling TB transmission that accounts for community-acquired transmission in the estimation of transmission risk factors from household contact study data. The proposed model generates population-specific estimates of the probability a contact of an infectious case will be infected from a source outside the home—a vital statistic for planning effective interventions to halt disease spread—in additional to estimates of household transmission predictors. We first describe the model analytically, and then apply it to synthetic datasets under different risk scenarios. We then fit the model to data taken from three household contact studies in different locations: Brazil, India, and Uganda. Infection predictors such as contact sleeping proximity to the index case and index case disease severity are underestimated in standard models compared to the proposed method, and non-household TB infection risk increases with age stratum, reflecting longer at-risk duration for community-based exposure for older contacts. This analysis will aid public health planners in understanding how best to interrupt TB spread in disparate populations by characterizing where transmission risk is greatest and which risk factors influence household-acquired transmission. Finally, we present an open-source software package in the R environment titled upmfit for modular implementation of the Bayesian Markov Chain Monte Carlo methods used to estimate the model.