On the cause and consequences of coinfection: A general mechanistic framework of within-host parasite competition

Coinfections pose serious threats to health and exacerbate parasite burden. If coinfection is detrimental, then what within-host factors facilitate it? Equally importantly, what hinders it, say via exclusion or priority effects? Such interactions ought to stem from their within-host environment (‘niche’), i.e., resources that parasites steal from hosts and immune cells that kill them. Yet, despite two decades of empirical focus on within-host infection dynamics, we lack a mechanistic framework to understand why coinfection arises and the diverse range of its’ consequences. Hence, we construct a trait-based niche framework, one that illustrates general principles that govern parasite competition for a resource and apparent competition for immune cells. We show that coinfection requires a competition-resistance tradeoff and that each parasite most impacts the niche factor to which it is most sensitive. These predictions then provide mechanistic interpretation for infection outcomes seen in a variety of extant experiments: Why does nutrient supplementation shift relative frequencies of coinfecting parasites? When and how does sequence of parasite invasion allow only early invading parasites to win? How does intrinsic variation in immune response shape coinfection burden? Together, this mechanistic framework of parasite competition offers new perspectives to better predict within-host infection dynamics and improve individual health.