Quasi-neutral Dynamics in a Coinfection System with N Strains and Asymmetries along Multiple Traits

TL;DR

This paper develops an analytical framework for understanding the dynamics of multiple co-infecting strains with trait asymmetries, using singular perturbation theory to reduce complex models to a replicator equation that captures strain frequency evolution.

Contribution

It introduces a novel application of singular perturbation theory to multi-trait co-infection models, deriving explicit dynamics and invasion fitnesses in a quasi-neutral setting.

Findings

The model reduces to a replicator equation governing strain frequencies.

Invasion fitnesses are explicit weighted sums of trait asymmetries.

The neutral system parameters determine the weights in the fitness calculations.

Abstract

Understanding the interplay of different traits in a co-infection system with multiple strains has many applications in ecology and epidemiology. Because of high dimensionality and complex feedbacks between traits manifested in infection and co-infection, the study of such systems remains a challenge. In the case where strains are similar (quasi-neutrality assumption), we can model trait variation as perturbations in parameters, which simplifies analysis. Here, we apply singular perturbation theory to many strain parameters simultaneously, and advance analytically to obtain their explicit collective dynamics. We consider and study such a quasi-neutral model of susceptible-infected-susceptible (SIS) dynamics among N strains which vary in 5 fitness dimensions: transmissibility, clearance rate of single-and co-infection, transmission probability from mixed coinfection, and co-colonization vulnerability factors encompassing cooperation and competition. This quasi-neutral system is analyzed with a singular perturbation method through an appropriate slow-fast decomposition. The fast dynamics correspond to the embedded neutral system, while the slow dynamics are governed by an N-dimensional replicator equation, describing the time evolution of strain frequencies. The coefficients of this replicator system are pairwise invasion fitnesses between strains, which, in our model, are an explicit weighted sum of pairwise asymmetries along all trait dimensions. Remarkably these weights depend only on the parameters of the neutral system. Such model reduction highlights the centrality of the neutral system for dynamics at the edge of neutrality, and exposes critical features for maintenance of diversity.