Public health impact of foodborne exposure to naturally occurring virulence-attenuatedListeria monocytogenes:inference from mouse and mathematical models

Abstract

Listeriosis is a clinically severe foodborne disease caused by Listeria monocytogenes (Lm). However, approximately 45% of Lm isolates in food carry a virulence-attenuating single-nucleotide polymorphism in inlA, which normally facilitates crossing the intestinal barrier during the initial stages of infection. We hypothesized that (i) natural exposure to virulence-attenuated (vA) Lm strains through food can confer protective immunity against listeriosis attributable to fully virulent (fV) strains and (ii) current food safety measures to minimize exposure to both Lm strains may have adverse population-level outcomes. To test these hypotheses, we evaluated the host response to Lm in a mouse infection model and through mathematical modelling in a human population. After oral immunization with a murinized vA Lm strain, we demonstrated the elicitation of a CD8+ T-cell response and protection against subsequent challenge with an fV strain. A two-strain compartmental mathematical model of human exposure to Lm with cross-protective immunity was also developed. If food safety testing strategies preferentially identify and remove food contaminated by vA strains (potentially due to their common occurrence in foods and higher concentration in food compared to fV strains), the model predicted minimal public health benefit to potentially adverse effects. For example, reducing vA exposures by half, while maintaining fV exposures results in an approximately 6% rise in annual incidence.

Multi-scale dynamics of infectious diseases

“…Multiscale approaches are needed to elucidate how immune responses at the individual level influence population-level disease dynamics. Stout et al [42] demonstrate that exposure to virulence-attenuated Listeria monocytogenes strains confers cross-immunity to full virulent strains in a dose-dependent manner. This cross-protection has some counterintuitive population-level implications: control aiming at reducing exposure to L. monocytogenes may decrease population immunity level against L. monocytogenes, increasing the incidence of listeriosis, the clinical manifestation of L. monocytogenes infection.…”

“…This cross-protection has some counterintuitive population-level implications: control aiming at reducing exposure to L. monocytogenes may decrease population immunity level against L. monocytogenes, increasing the incidence of listeriosis, the clinical manifestation of L. monocytogenes infection. By using mechanistic models, Stout et al [42] explore the implications of pathogen-host interactions at the population scale much like Tsao et al [16] and Garira & Chirove [35].…”

“…However, in many other types of biological systems, like those describing hostpathogen interactions or inter-and intra-cellular dynamics, the identification of appropriate model scales may not be obvious and may need to be derived empirically based on some observables of the system. When the effects of scales are not well understood, there is a tendency in all systems to mechanistically model all those scales that may have a role in the system and use data available at those different scales to parametrize theoretical models and explore the implications of assumptions [16,35,42]. To inform these complex models, new methods of data collection and analysis [31,41] are needed to explain how different scales are connected and modelled.…”

“…This allows for replacing the equilibrated portion of royalsocietypublishing.org/journal/rsfs Interface Focus 10: 20190118 the system with its steady state. The examples of application of various versions of quasi-steady-state approximations may be seen in the papers on FMD, vector-borne infections and enteric infections [16,35,42] in this theme issue. These approaches often employ sensitivity analyses to explore the limitations of their steady-state assumptions.…”

A Mathematical Model and Optimal Control for Listeriosis Disease from Ready-to-Eat Food Products

“…Recently, mathematical models have been used to study the transmission dynamics of Listeriosis (see for example Stout et al (2020); Otoo et al (2020); Osman et al (2018); Witbooi etal. (2020); Chukwu and Nyabadza (2020)).…”