Implementing a New Dose-response Model for Estimating Infection Probability of Campylobacter Jejuni based on the Key Events Dose-response Framework

Abstract

Understanding the dose-response relationship between ingested pathogenic bacteria and infection probability is a key factor for appropriate risk assessment of foodborne pathogens. The objectives of this study were to develop and validate a novel mechanistic dose-response model for Campylobacter jejuni and simulate the underlying mechanism of foodborne illness during digestion. Bacterial behavior in the human gastrointestinal environment, including gastric reductions, transition to intestines, and invasion to intestinal tissues, was described using a Bayesian statistical model based on the reported experimental results of each process while considering physical food types (liquid or solid) and host age (young or elderly). Combining the models in each process, the relationship between pathogen intake and the cell invasion probability of C. jejuni was estimated and compared with reported epidemiological dose-response relationships. Taking food types into account, estimations of the cell invasion probability of C. jejuni successfully described the reported dose-response relationships from substantial accidents. The developed calculation framework is thus potentially applicable to other pathogens to quantify the dose-response relationship from experimental data obtained from digestion.

Competitive growth kinetics of Campylobacter jejuni , Escherichia coli O157:H7 and Listeria monocytogenes with enteric microflora in a small‐intestine model

“…There already have been some examples for application of a simple growth prediction in intestines for mechanistic dose-response model (Rahman et al, 2016(Rahman et al, , 2018, although they used simple monocultured behaviour for L. monocytogenes doseresponse model. Recently, reported that the cell-invasion rate of C. jejuni into human intestinal cells depends on the pathogen concentration around intestinal cells, and the prediction of cell-invading behaviour has the potential to estimate dose-response relationship Abe, Takeoka, 2021). Therefore, an accurate estimation of the pathogen concentration in human intestinal tracts will be necessary for estimating the dose-response model for pathogens such as C. jejuni, L. monocytogenes and Salmonella spp., which invade body tissues and cause adverse health effects.…”

“…Recently, Abe, Koyama, et al ( 2021 ) reported that the cell‐invasion rate of C . jejuni into human intestinal cells depends on the pathogen concentration around intestinal cells, and the prediction of cell‐invading behaviour has the potential to estimate dose–response relationship (Abe, Koyama, et al, 2021 ; Abe, Takeoka, 2021 ). Therefore, an accurate estimation of the pathogen concentration in human intestinal tracts will be necessary for estimating the dose–response model for pathogens such as C .…”

“…The key events dose-response framework (KEDRF) has been proposed (Buchanan et al, 2009;Julien et al, 2009) to examine the major events occurring in the body from the entry of a bioactive substance until the first appearance of symptoms; at each step of digestion, factors including dose, pathogen's characteristic and protective host mechanisms are examined. One recent study has indicated the validity of the KEDRF concept based on the epidemic data of C. jejuni (Abe, Takeoka, et al, 2021). The use of the KEDRF fills the gap in our knowledge of digestive phenomena that providing insight into the low-dose-response relationships.…”

“…One recent study has indicated the validity of the KEDRF concept based on the epidemic data of C . jejuni (Abe, Takeoka, et al, 2021 ). The use of the KEDRF fills the gap in our knowledge of digestive phenomena that providing insight into the low‐dose–response relationships.…”