Comparing Dose-Response for Infection and Illness in Human Challenge Studies of Norwalk Virus Pubblico
Foster, Allison (Spring 2019)
Abstract
Noroviruses are the leading cause of acute viral gastroenteritis among all age groups worldwide. This study used both older and recent Norwalk virus (GI.1 norovirus genotype) to model the dose-response relationship for Norwalk virus infection and illness. By comparing data from all published Norwalk virus human challenge studies (N=17) to studies published in 2008 or later (N=5), we assessed whether the 8fIIa dose-response relation has shifted over time. Data from the 17 published challenge studies were used to establish a Beta Poisson dose-response model that accounts for variation in susceptibility among hosts while also accounting for the different inocula used in these studies (8fIIa, 8fIIb, or pool lot number 42399). We found no evidence to suggest a shift in the dose-response model among recent studies compared to all studies and concluded that the concentration of infectious virus in the 8fIIa inoculum has apparently persisted over time. We estimated that the average probability of infection for a single Norwalk virus particle is approximately 0.04, and our estimate of the ID50 of Norwalk virus is 5.65 X 103 GEC (95% CI: 687-34,231) among susceptible hosts. These results are consistent with other published estimates of Norwalk virus infectivity and pathogenicity. Future research should focus on expanding existing norovirus dose-response models to incorporate data from human challenge studies using other norovirus genotypes and outbreak data.
Table of Contents
Chapter 1: Literature Review.................................................2
Background..........................................................................2
Virus classification and laboratory diagnosis..........................7
Human challenge studies and outbreaks...............................10
Dose-response models.........................................................11
References..........................................................................14
Chapter 2: Manuscript..........................................................26
Abstract..............................................................................26
Background.........................................................................27
Methods..............................................................................30
Results................................................................................34
Discussion...........................................................................35
References...........................................................................40
Figures................................................................................46
Tables.................................................................................50
Chapter 3: Public Health Implications and Future Research....54
References..........................................................................57
Appendix............................................................................60
R Code................................................................................60
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