title: QMRA for Drinking Water: 1. Revisiting the Mathematical Structure of Single-Hit Dose-Response Models.
abstract: Dose-response models are essential to quantitative microbial risk assessment (QMRA), providing a link between levels of human exposure to pathogens and the probability of negative health outcomes. In drinking water studies, the class of semi-mechanistic models known as single-hit models, such as the exponential and the exact beta-Poisson, has seen widespread use. In this work, an attempt is made to carefully develop the general mathematical single-hit framework while explicitly accounting for variation in (1) host susceptibility and (2) pathogen infectivity. This allows a precise interpretation of the so-called single-hit probability and precise identification of a set of statistical independence assumptions that are sufficient to arrive at single-hit models. Further analysis of the model framework is facilitated by formulating the single-hit models compactly using probability generating and moment generating functions. Among the more practically relevant conclusions drawn are: (1) for any dose distribution, variation in host susceptibility always reduces the single-hit risk compared to a constant host susceptibility (assuming equal mean susceptibilities), (2) the model-consistent representation of complete host immunity is formally demonstrated to be a simple scaling of the response, (3) the model-consistent expression for the total risk from repeated exposures deviates (gives lower risk) from the conventional expression used in applications, and (4) a model-consistent expression for the mean per-exposure dose that produces the correct total risk from repeated exposures is developed.
authors.affiliation: Department of Mathematical Sciences and Technology, Norwegian University of Life Sciences, N-1432 Aas, Norway.
authors.forename: Vegard
authors.initials: V
authors.lastname: Nilsen
authors.affiliation: Department of Mathematical Sciences and Technology, Norwegian University of Life Sciences, N-1432 Aas, Norway.
authors.forename: John
authors.initials: J
authors.lastname: Wyller
mesh_terms: D015169:Colony Count, Microbial; D060766:Drinking Water / Q000382:microbiology / Q000821:virology*; D006801:Humans; D016012:Poisson Distribution; D011336:Probability; D018570:Risk Assessment; D014871:Water Microbiology
chemical_list: D060766:Drinking Water
keywords: Dose response; QMRA; microbial risk; single hit