Can breeders prevent pathogen adaptation when selecting for increased resistance to infectious diseases?

Recent research shows that genetic selection has high potential to reduce the prevalence of infectious diseases in livestock. However, like all interventions that target infectious diseases, genetic selection of livestock can exert selection pressure on pathogen populations. Such selection on the pathogen may lead to escape strategies and reduce the effect of selection of livestock for disease resistance. Thus, to successfully breed livestock for lower disease prevalence, it is essential to develop strategies that prevent the invasion of pathogen mutants that escape host resistance. Here we investigate the conditions under which such "escape mutants" can replace wild-type pathogens in a closed livestock population using a mathematical model of disease transmission.

Assuming a single gene that confers sufficient resistance, results show that genetic selection for resistance in livestock typically leads to an "invasion window" within which an escape mutant of the pathogen can invade. The bounds of the invasion window are determined by the frequency of resistant hosts in the population. The lower bound occurs when the escape mutant has an advantage over the wild-type pathogen in the population. The upper bound occurs when local eradication of the pathogen is expected. The invasion window is smallest when host resistance is strong and when infection with the wild-type pathogen provides cross immunity to infection with the escape mutant.

To minimise opportunities for pathogens to adapt, under the assumptions of our model, the aim of disease control through genetic selection should be to achieve herd-level eradication of the infection faster than the rate of emergence of escape mutants of the pathogen. Especially for microparasitic infections, this could be achieved by placing animals into herds according to their genetic resistance, such that these herds stay completely out of the invasion window. In contrast to classical breeding theory, our model suggests that multi-trait selection with gradual improvement of each trait of the breeding goal might not be the best strategy when resistance to infectious disease is part of the breeding goal. Temporally, combining genetic selection with other interventions helps to make the invasion window smaller, and thereby reduces the risk of invasion of escape mutants.