Transmission and the Evolution of Virulence

The key to understanding virulence evolution, from the modern, individual-selection perspective, is in terms of the optimization of transmission, on the one hand, and dealing with within-host competition on the other (that is, among parasite individuals). The latter I consider under the heading of "Parasite Expedience versus Economy". Here I emphasize the optimization of transmission. That is, in a 'perfect' world, from the perspective of a parasite, only hard selection would be operating – selection resulting in increases in the average fitness of a population – and soft selection would not exist as a 'distraction' from that 'goal'. Thus, in this section I concentrate on the hard selection effected by the need for transmission between hosts.

As with much of biology, we can view selection acting on parasite transmission along a spectrum as well as in terms of tradeoffs. The spectrum is in terms of the impact of parasite transmission out of a host on the fitness of the current, parasite-infected host, ranging from not at all to extreme. Here transmission is defined broadly to include not just the process of physical movement from host to host but also in terms of other, supporting factors such as the production of the parasite individuals that are responsible for that move. Specifically, if there is a conflict between host fitness and parasite transmission, then there can be a conflict between a parasite's short-term versus longer-term fitness, that is, to the extent that host fitness affects parasite fitness, including in terms of a longer-term ability of parasites to survive, replicate, and also explicitly transmit. In the short term, it therefore can pay for the parasite to exploit the host to effect transmission both sooner and to a greater initial extent. Such host exploitation, however, may reduce the ability of that host to support parasite transmission over the longer term (re: Tragedy of the Commons). This particularly can occur in the extreme: If the parasite needs a living host to transmit while excessive host exploitation can result in host death, then the result of excessive parasite exploitation of its host can be a reduction of parasite fitness to zero, and particularly so if host death occurs prior to parasite transmission. Note again that this is not an issue for predators, who do not require a living victim in order to extract resources from that victim—as a consequence, predators are not affected by the extent that they may reduce the fitness of their prey whereas parasites, which are dependent to some degree of host health, can be affected, often greatly, by the extent that they cause host health to decline.

Given conflicts between parasite transmission, host health, and the potential for a host to support subsequent parasite transmission, a tradeoff therefore can exist between immediate, per-unit-time rates of parasite transmission versus the duration or ongoing quality of that transmission. Of course, these tradeoffs may not exist if there are no costs to the host stemming from parasite transmission. That view might be misleading, however, since it would seem likely that no matter what the current parasite transmission rate might be, it may still be possible to increase near-term rates of transmission out of the host at the expense of host fitness. A parasite therefore might be expected to evolve to the point where host health/fitness is reduced to some optimal amount that coincides with that degree of host damage a parasite population must instill in order to maximize its transmission over the life of an infection. This optimum in turn will serve balance out the parasite's potential to transmit over the short-, medium-, and longer-term time scales of infection.

That is, given the availability of sufficient genetic variation it is always possible for a species to evolve to exploit its environment to a greater extent, to the detriment of that environment's ability to support that species. This potential, however, does not imply that the species will necessarily gain in terms of fitness even over the short term from increasing the degree to which it exploits its environment, but even if gains are made over the short term, those gains nevertheless may not be sustainable over longer time frames. Thus, under almost all circumstances for parasites there will exist a level of virulence that is both optimizes its fitness over longer time spans (e.g., the duration of an infection) and which also is less than maximally harmful to the host organism, versus particularly the impact of predators on prey.

Imagine yourself working at a job that can take a toll on your health. The more you work in this case, the more you earn. You could work very hard, earning relatively large amounts of money in the short term, but this can come at the expense of your ability to earn the same or even otherwise 'normal' amounts in the longer term. This would be, in effect, the hare strategy from the Aesop's fable, "The Tortoise and the Hare", that is, short term gain associated with longer-term reduction in performance (it also potentially is an example of an antagonistic pleiotropy). The tortoise strategy by contrast is slow and steady, here meaning forgoing high transmission rates especially early during infections to achieve transmission over longer time periods. The latter, to the extent that host health is required to sustain transmission rates over those longer time periods, would result in a lower virulence than that displayed by the 'hare' strategy of biasing transmission rates over the maintenance of host health. The major difference with parasite virulence in comparison to the impact of your own work habits on your long-term earning potential is that rather than impacting your own heath directly, the parasite instead impacts its "health" indirectly, that is, by damaging the environment in which its replication takes place. Indeed, it is only because that environment is a body that we describe that impact as virulent and affecting host health. Otherwise we could just as easily view virulence evolution in same light as logistic growth, with the hare strategy the more r selected (emphasizing rapidity over long-term stability) and the tortoise strategy more K like (emphasizing maximization of the equivalent of carrying capacity – that is, long- or at least longer-term maintenance of populations – rather than how rapidly a population reaches carrying capacity densities).

At the other end of the spectrum from no host cost, there can exist extreme declines in host fitness stemming from parasite transmission. That is, the host can die. Here, if host survival is necessary for ongoing transmission, then selection at least might operate on the parasite to not kill the host. On the other hand, host survival is not necessary for the continued transmission of all parasites. Indeed, in many cases host morbidity or even host death can actually have a positive impact on parasite transmission—that is, parasite modification of host phenotype that is costly to the host, in terms of health/fitness, but also serves to aid parasite transmission, e.g., such as diarrhea to effect parasite dissemination. In these latter cases selection may actually favor those parasites that effect a greater negative impact on their host. In a subsequent section I will provide examples to illustrate these points. First, though, I consider two additional factors involved in the optimization of parasite virulence: host availability and intra-host competition among parasites.

Host Availability and Virulence Evolution

There are three components determining the quality as well as quantity of parasite transmission: parasite genotype (i.e., parasite-encoded propensities), host genotype (i.e., host-encoded propensities), and circumstances (i.e., impact of the environment). In short, even a parasite that is best adapted to a specific host's physiology will not necessarily represent the most fit parasite since transmission involves not just movement out of current hosts but also movement into new hosts. The efficacy of various transmission strategies will, in part, therefore be a function of new-host availability.

Host availability can be viewed in terms of the receiving (new) host's suitability to infection (e.g., in terms of host genetics or immunity), the population density of those new hosts, and their behaviors. All three of these factors can be modified as a consequence of parasite infection. That is, less-susceptible host genotypes may be selected for as a consequence of a host population's exposure to a given parasite, immunity may develop following infection by a similar parasite, density of not-yet-infected hosts can decline in absolute terms if parasites are successful at infecting members of a host population, and potential hosts can display behaviors that limit the likelihood of parasite transmission, such as avoiding contact with sick individuals. These host tendencies can place brakes on the evolution of ever increasing parasite virulence. It is not that parasites necessarily have an inherent tendency towards an evolution of reduced virulence, that is, but instead that too-great parasite virulence can reduce the likelihood of parasite transmission. The result can be selection for parasite variants that, for example, emphasize the duration of the period over which they might be transmitted rather than the gap (or latent period) between initial infection and subsequent transmission (often a function of within-host growth rates or expedience) or the number of parasite progeny (yield) available at any given time for transmission.

In other words, there is no reason that parasites will display altruistic behavior, especially between infections (i.e., between parasite "groups"), with parasites restraining their virulence or rates of transmission for the good of the larger parasite population. Instead, one should view virulence evolution in terms of parasites seeking to maximize their fitness by maximizing their transmission rates or likelihood. If a parasite characteristic increases that parasite's potential for transmission, then that property will tend to be adaptive, at least in the short term, regardless of its impact on the infected host. The utility of a specific transmission strategy, and therefore a specific parasite property, however, will be dependent in part on what happens to the parasite after it leaves the host within which it was formed. What happens to that parasite after exit from a host will be dependent on extra-host environmental conditions, the properties of potentially obtainable new hosts, and, to no small degree, the population density (i.e., physical availability) of those new hosts.

In particular, if more virulent parasites possess a shorter interval during which transmission can occur, or otherwise produce fewer transmittable progeny, and new hosts to infect are sufficiently rare that encounter is relatively unlikely, then an optimal parasite strategy in terms of virulence may be to employ different tactics. For example, opportunities for transmission may be extended over longer periods and/or more transmittable progeny may be produced (again over longer periods). To the extent that such strategies are associated with lower virulence towards hosts, then lower opportunities for transmission due to new-host rarity could select for lower parasite virulence. Note the equivalence of these ideas to the idea of enhancement of fitness later during growth at the expense of fitness earlier during growth, such as we considered in terms of optimizing bacterial replication and transmission within a biofilm context (see "Specific Circumstances: Biofilms and Cooperation").

For evolution to favor more commensal strategies, parasites displaying infection restraint must come to predominate over their more virulent brethren. How or why this can occur may be viewed as equivalent to the evolution of a cooperative behavior both in terms of parasite impact on hosts and in terms of parasite interactions within parasite populations infecting a single host. The evolution of more cooperative behaviors between individual parasites infecting the same host in turn is well informed by our previous considerations of the evolution of economy versus expediency.