Affiliation:
1. Department of Biology, Emory University, Atlanta, GA, USA
Abstract
Theoretical models suggest that mixed-strain infections, or co-infections, are an important driver of pathogen evolution. However, the within-host dynamics of co-infections vary enormously, which complicates efforts to develop a general understanding of how co-infections affect evolution. Here, we develop a general framework which condenses the within-host dynamics of co-infections into a few key outcomes, the most important of which is the overall
R
0
of the co-infection. Similar to how fitness is determined by two different alleles in a heterozygote, the
R
0
of a co-infection is a product of the
R
0
values of the co-infecting strains, shaped by the interaction of those strains at the within-host level. Extending the analogy, we propose that the overall
R
0
reflects the
dominance
of the co-infecting strains, and that the ability of a mutant strain to invade a population is a function of its dominance in co-infections. To illustrate the utility of these concepts, we use a within-host model to show how dominance arises from the within-host dynamics of a co-infection, and then use an epidemiological model to demonstrate that dominance is a robust predictor of the ability of a mutant strain to save a maladapted wild-type strain from extinction (evolutionary emergence).
Funder
National Heart, Lung, and Blood Institute
National Institute of General Medical Sciences
National Institute of Allergy and Infectious Diseases
Subject
Biomedical Engineering,Biochemistry,Biomaterials,Bioengineering,Biophysics,Biotechnology
Cited by
8 articles.
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