A mathematical model to study resistance and tolerance to infection at the animal and population levels: application to E. coli mastitis

Abstract

A mathematical model is proposed that describes the colonization of host tissues by a contagious pathogen and the early nonspecific immune response, the impact of the infection on the performances of the host, and the spread of the infection in the population. The model obeys specific biological characteristics: Susceptible hosts are infected after contact with an infected one. The number of pathogenic units that invade a susceptible host is dependent on the infectious dose provided by the infected host and on the ability of the susceptible host to resist the invasion. After entry in host, pathogenic changes over time are expressed as the difference between the intrinsic logistic growth rate and the Holling type II kill rate provided by the immune response cells. Hosts have different ability to restrict reproduction of the pathogen units. The number of response cells actively recruited to the site of infection depends on the number of the pathogenic units. Response cells are removed after having killed a fixed number of pathogenic units. The effects of the number of pathogenic units on the performances of the host depend upon its levels of tolerance to the deleterious effects of both pathogenic and response cells. Pre-infection costs are associated to tolerance and resistance levels. Estimates of most biological parameters of the model are based on published experimental studies while resistance/tolerance parameters are varied across their allowable ranges. The model reproduces qualitatively realistic outcomes in response to infection: healthy response, recurrent infection, persistent infectious and non-infectious inflammation, and severe immunodeficiency. Evolution across time at the animal and population levels is presented. Effects on animal performances are discussed with respect to changes in resistance/tolerance parameters and selection strategies are suggested.

Structural equation models to estimate risk of infection and tolerance to bovine mastitis

“…Resistance traits are ‘direct’ when they reduce pathogen transmission by contact (resistance to infection) and ‘indirect’ when they reduce pathogen growth rate once infection has occurred, through the establishment of an immune response (resistance to disease). Tolerance traits are direct when they aim at reducing damage inflicted by the pathogen and indirect when the damage is caused by the immune response [4]. The distinction between these traits is important when determining selection objectives because they are predicted to have different evolutionary effects on pathogens and hosts [3,4] and they have been found to be negatively genetically correlated in plants and mice [2].…”

“…Tolerance traits are direct when they aim at reducing damage inflicted by the pathogen and indirect when the damage is caused by the immune response [4]. The distinction between these traits is important when determining selection objectives because they are predicted to have different evolutionary effects on pathogens and hosts [3,4] and they have been found to be negatively genetically correlated in plants and mice [2]. One way to test whether mechanisms are direct or indirect is to use structural equation models (SEM).…”

Should we aim for genetic improvement in host resistance or tolerance to infectious disease?

“…Rather, tolerance mechanisms work on host repair and damage control. Although the immunological mechanisms underlying tolerance are largely unknown, it has been suggested that tolerance can be related to tissue damage caused by the pathogen (direct tolerance) or by the host immune response (indirect tolerance) which can be achieved through tissue protection and repair [6,10].…”

Mutations in CD14 gene causes mastitis in different breeds of buffalo as confirmed by in silico studies and experimental validation

“…Economic losses due to mastitis may reach upto 35 million dollars per year world wide ( Giraudo et al,1997;Pereira et al2011). Subclinical mastitis is of greater concern than clinical mastitis, since incidences were 15 to 40 times more than that of clinical mastitis and it forms the basis of herd outbreaks (Boichard et al 2003;Detilleux et al, 2012). As no gross abnormality in milk and udder is noticed, subclinical mastitis goes unnoticed to the farmers.…”