title: Dose-response relationships for environmentally mediated infectious disease transmission models.
abstract: Environmentally mediated infectious disease transmission models provide a mechanistic approach to examining environmental interventions for outbreaks, such as water treatment or surface decontamination. The shift from the classical SIR framework to one incorporating the environment requires codifying the relationship between exposure to environmental pathogens and infection, i.e. the dose-response relationship. Much of the work characterizing the functional forms of dose-response relationships has used statistical fit to experimental data. However, there has been little research examining the consequences of the choice of functional form in the context of transmission dynamics. To this end, we identify four properties of dose-response functions that should be considered when selecting a functional form: low-dose linearity, scalability, concavity, and whether it is a single-hit model. We find that i) middle- and high-dose data do not constrain the low-dose response, and different dose-response forms that are equally plausible given the data can lead to significant differences in simulated outbreak dynamics; ii) the choice of how to aggregate continuous exposure into discrete doses can impact the modeled force of infection; iii) low-dose linear, concave functions allow the basic reproduction number to control global dynamics; and iv) identifiability analysis offers a way to manage multiple sources of uncertainty and leverage environmental monitoring to make inference about infectivity. By applying an environmentally mediated infectious disease model to the 1993 Milwaukee Cryptosporidium outbreak, we demonstrate that environmental monitoring allows for inference regarding the infectivity of the pathogen and thus improves our ability to identify outbreak characteristics such as pathogen strain.
authors.affiliation: Department of Epidemiology, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Andrew F
authors.identifier: 0000-0002-3779-5287
authors.initials: AF
authors.lastname: Brouwer
authors.affiliation: Division of Environmental Health Sciences, The Ohio State University, Columbus, OH, United States of America.
authors.forename: Mark H
authors.identifier: 0000-0002-6995-1037
authors.initials: MH
authors.lastname: Weir
authors.affiliation: Department of Epidemiology, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Marisa C
authors.identifier: 0000-0003-4221-830X
authors.initials: MC
authors.lastname: Eisenberg
authors.affiliation: Department of Epidemiology, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Rafael
authors.identifier: 0000-0002-1076-5037
authors.initials: R
authors.lastname: Meza
authors.affiliation: Department of Epidemiology, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Joseph N S
authors.initials: JNS
authors.lastname: Eisenberg
mesh_terms: D019295:Computational Biology; D003457:Cryptosporidiosis; D003458:Cryptosporidium; D004196:Disease Outbreaks; D018562:Disease Transmission, Infectious; D006801:Humans; D008954:Models, Biological