Choisy and de Roode set out to build a conceptual bridge between the somewhat disjoint empirical and theoretical study of the evolution of virulence in mixed parasitic infections. Theoretical studies at the within host and population level suggest that mixed infections lead to increased virulence. Mixed infections ought to select for higher competitive ability, generally considered to be an increase in parasite densities which in turn increases the virulence of the parasite. Most empirical studies are (quite reasonably) conducted at the individual rather than the population level and simply measure the virulence (in the form of morbidity and mortality) in mixed vs. single infections. Even studies which determine the difference in parasite densities under these two regimes are truly measuring facultative increases in reproduction rather than evolutionary increases in virulence. To explore the implications of this disconnect the authors build a relatively simple compartmental SIS model with 4 classes (Susceptible, Infected with parasite 1, Infected with parasite 2, and Infected with both parasites) and briefly explain and provide differential equations and an R0 formulation for both the single parasite and 2 parasite scenario.
Things begin to heat up when evolutionary dynamics are introduced. Each parasite has a “host exploitation strategy” e which positively affects both transmission (with a saturating function) and parasite induced host mortality(linearly). They introduce three additional parameters to provide biological realism to the model: A is a dimensionless parameter which represents the parasites plasticity in its ability to increase its host exploitation in the presence of a competitor; C scales from 0 to 1 and represents the degree to which the two parasites compete directly for the same resources within the host; and B scales from 0 to 1 and represents the efficiency with which a host recovers from a mixed infection as compared to a single infection. They proceed to solve analytically for the evolutionary stable strategy for an invading mutant of one parasite in one or two parasite system but note that when both parasites are present the ESS of one parasite is dependent on the ESS of the other, motivating a graphical analysis of their Coevolutionary stable strategies (CoESS). This point is simply the intersection of the curve representing the ESS of parasite 1 given parasite 2’s strategy and the curve of the ESS of parasite 2 given parasite 1’s strategy. They proceed to explore a series of scenarios:
- When there is no plasticity or competition the CoESS of both parasites is slightly higher than the ESS alone.
- When there is no plasticity but maximal competition this effect is magnified because each parasite suffers from the increased mortality produced by the other parasite and from the competition for resources within the host, forcing a further increase in exploitation.
- Increases in parasite plasticity decreases the CoESS exploitation level because increased exploitation represents a cost in single infections which can be avoided by using plasticity to compensate for the cost of decreased exploitation in multiple infections.
- As the efficiency of a host’s recovery from mixed infections decreases CoESS exploitation levels also decrease because the cost associated with mixed infections is compensated somewhat by a decreased rate of recovery for either parasite from the coinfected state.
The massive differences between the CoESS and the ESS under many conditions exacerbates the disconnect between empirical and theoretical approaches. Empiricists typically measure the difference in mortality or morbidity between singly infected and mixed infected individuals which realistically represent the ESS of each parasite when it has evolved on its own prior to the single generation infection experiment. This conclusion argues for the development of more (likely very complex and laborious) multi-generation population scale mixed infection experiments. Though this work may not fit even a somewhat less strict definition of a multi-scale model (as it does not explicitly model the within host dynamics but rather provides simple parameters which represent within host processes) but it does propose a number of within host mechanisms for a decrease in virulence evolution that ought to be explored in a more mechanistic multi-scale model.
Choisy, Marc, and Jacobus C. de Roode. “Mixed infections and the evolution of virulence: effects of resource competition, parasite plasticity, and impaired host immunity.” The American Naturalist 175.5 (2010): E105-E118.