Mechanistic modeling to determine demographic, behavioral, and environmental factors that facilitate or prevent influenza transmission in households

Project Summary – Project 3 Despite decades of influenza research into host- and virus-based drivers of infectivity and susceptibility, there remains a considerable gap in our understanding of how the community and household environmental contexts surrounding transmission perpetuate seasonal outbreaks. Individual and household factors such as behavioral patterns, degree of exposure to the community, the household built environment, and indoor air characteristics contribute to infection risk in ways that transcend elements of immunity and virology. The long-term goal of this research is to achieve a mechanistic understanding of human influenza transmission through the modeling of rich datasets collected from household studies. The core objectives of this project are to examine demographic, behavioral, and environmental factors that facilitate or prevent influenza transmission in households, using combined data from multiple household studies. For our proposed study, we will leverage a modern body of observational studies based at the University of Michigan since 2010 that were inspired by the Tecumseh studies, benefitting from improved laboratory assays and innovative sampling methodologies. Specifically, we will take advantage of existing and newly collected data from two prospective household cohort studies and a case- ascertained study. We will use state-of-the-art techniques including data augmentation and stochastic household transmission models to estimate key transmission parameters. We will address key knowledge gaps in human influenza transmission in three specific aims: (Aim 1) Determine the relative contributions of community-to- household and within-household transmission to influenza and other respiratory virus infections. We will use advanced data augmentation approaches to impute the daily infectious status of household members and apply a household transmission model to estimate transmission parameters for influenza and other respiratory viruses. (Aim 2) Determine individual drivers (demographic, behavioral, and infection/vaccination history) of influenza transmission, both from the infected individual and to the exposed individual. Building on the approach developed in Aim 1, we will augment our model with parameters for individual characteristics of both those who are infected and those who are susceptible to build a better understanding of who is driving influenza in the household, and how. (Aim 3) Determine shared household environmental drivers of influenza transmission. We will modify our household transmission model to account for characteristics of the household environment. This project is innovative because it will apply state-of-the-art transmission models to a large and rich dataset of influenza viruses in households. By advancing our understanding of the individual and household factors that contribute to human-to-human influenza transmission in real-world environments, this work will help to design meaningful and efficient mitigation strategies, thereby enhancing public health preparedness efforts.