Where did this infection come from? Covert infections selected by demographic variability

This week we continued along our current path of pathogen models and looked at a recent paper (Sorrell et al 2009) investigating covert infections, a common and unexplained phenomenon of some pathogens exhibiting long periods of infection where they are silent (or covert in the language of the paper). During this silent/covert stage, the infections are mostly avirulent and non-infectious. These authors extend a previous SI type model that incorporated a covert state (Boots et al 2003) to understand what forces select for this kind of pathogen.

Extending a previous SI model (Boots et al 2003), the authors build a two strain model that includes susceptible hosts and multiple classes of infected hosts. With two strains, there are two broad types of infected hosts. Each of these is split again. The hosts can carry a covert infection or an overt infection. Covert infections are allowed to become overt but not the other way around. There are multiple trade-offs built into this model. A covert infection does not cause an increased host death rate (avirulent), but it does impose a cost to host fecundity where as an overt infection is virulent but does not decrease fecundity. In addition, covert infections are only transmitted vertically (from parent to offspring), while on the other hand overt infections are only transmitted horizontally (among individuals within the population).

Without additional forces, they find no selection for covert infections. However, given the abundance of such pathogens in nature, there must be some forces that are generating the proper conditions. The paper explores three different mechanisms that may be involved in selection for covert infections. The first examines the effect of superinfection (multiple pathogen strains in the same host). They conclude that selection will favor covert infections that are protective, that is they prevent superinfection. The other two mechanisms consider nonequilibrium host dynamics, temporal variation in host density and transmission. When variation is high and the potential to be lost from the population because of a lack of hosts or a lack of transmission events, then covert infections which again are vertically transmitted become more likely.

A question that was brought up during our discussion was: are these results different from a horizontal vertical transmission trade-off? When transmission opportunities are likely (high populations), then horizontally transmitting virulent pathogens are favored. In situations when there are fewer opportunities (e.g. during host population declines), then a pathogen that retains some vertical transmission and will be favored. Favoring a more covert pathogen is really just selecting for these two fixed trade-offs. I think what this paper contributes thought is a more thorough mechanistic explanation for how this trade-off works. They provide many biological examples of pathogens with complex covert behavior and this study certainly provides evidence of how they may have arisen.

This paper was quite interesting to me in that it was the first adaptive dynamics analysis that I've really understood. The authors walk through their methods and explain how to read the pairwise invisibility plots (PIPs) and provide some helpful but uncomplicated simulations too. Recently Dercole and Rinaldi (2008) published an introduction to this modeling/analysis technique that I'm looking forward to reading in the near future.

References

Boots, M., J. Greenman, D. Ross, R. Norman, R. Hails, and S. Sait. 2003. The population dynamical implications of covert infections in host-microparasite interactions. Journal of Animal Ecology 72:1064-1072.

Dercole, F., and S. Rinaldi. 2008. Analysis of Evolutionary Processes: The Adaptive Dynamics Approach and its Applications. Princeton University Press, Princeton.

Sorrell, I., A. White, A. B. Pedersen, R. S. Hails, and M. Boots. 2009. The evolution of covert, silent infection as a parasite strategy. Proceedings of the Royal Society B: Biological Sciences: online early.

Paper read

Sorrell, I., White, A., Pedersen, A., Hails, R., & Boots, M. (2009). The evolution of covert, silent infection as a parasite strategy Proceedings of the Royal Society B: Biological Sciences DOI: 10.1098/rspb.2008.1915

Why doesn’t this pathogen kill me and why is it taking so long to clear?

This week the Coevolvers read a brand new paper by King et al (2009). The authors present a pathogen model that incorporates within host dynamics of pathogen growth as well as multiple forms of transmission among hosts which depend on pathogen load. The authors do motivate the study by telling us about two human disease pathogens, Bordetella pertussis and Bordetella parapertussis (which can cause whooping cough), but model is not meant to be a predictive model of future outbreaks. The main message of the paper is that including within host dynamics in conjunction with SIR models of populations leads to a better understand of disease evolution. Mideo et al (2008) wrote a recent review on including within host dynamics in evolutionary epidemiological models for more general information on this approach.

While the outline of the model was well written, how they combined the multiple different parts was unclear. The model consisted of three components: 1) within host pathogen replication 2) dose dependent transmission and 3) between host/SIR type model. What we found hard to understand was how the model incorporated the variation in pathogen loads among the hosts into the overall transmission rate. It appeared as if the model integrates over a number of classes of hosts (depending on their age of infection), but we felt that this then removed quite a bit of the variation that was being captured by including within host dynamics. A simplifying assumption that the authors made also was that each host was always infected with the same dose of pathogens and that their immune system had to be restarted each time. The authors do state that they have already worked on a stochastic model of this system which hasn't yet been published. We are very interested on the quantitative results from that analysis since some of these problems could be addressed there.

Why not make a population genetics model to address the questions posed by the authors at the beginning of the paper. This was question stimulated by our previous reading of Boots et al (2009) and Day and Gandon (2007) that provide detailed reviews of different modeling approaches as well as addressing specific problems in evolutionary epidemiology. King et al (2009) present their results of how intermediate within host pathogen growth rates can maximize R₀ under some transmission models, but what they don't do is present an analysis where they look at how different pathogens might evolve. Is the intermediate growth rate a stable strategy? Given the model framework, there might be complex interactions between different pathogens mediated through hosts. Higher growth rates of an aggressive pathogen could lead to a tragedy of the commons.

References

Boots, M., A. Best, M. R. Miller, and A. White. 2009. The role of ecological feedbacks in the evolution of host defence: what does theory tell us? Philos. Trans. R. Soc. B-Biol. Sci. 364:27-36.

Day, T and S Gandon. 2007. Applying population-genetic models in theoretical evolutionary epidemiology. Ecology Letters 10 (10), 876–888.

King, A. A., S. Shrestha, E. T. Harvill, and O. N. Bjørnstad. 2009. Evolution of Acute Infections and the Invasion-Persistence Trade-Off. The American Naturalist 173:446-455.

Mideo, N., S. Alizon, and T. Day. 2008. Linking within- and between-host dynamics in the evolutionary epidemiology of infectious diseases. Trends in Ecology and Evolution 23(9): 511-517.

Paper read:

King, A., Shrestha, S., Harvill, E., & Bjørnstad, O. (2009). Evolution of Acute Infections and the Invasion‐Persistence Trade‐Off The American Naturalist, 173 (4), 446-455 DOI: 10.1086/597217