Virulence and competitive ability in genetically diverse malaria infections

Abstract

Explaining parasite virulence is a great challenge for evolutionary biology. Intuitively, parasites that depend on their hosts for their survival should be benign to their hosts, yet many parasites cause harm. One explanation for this is that within-host competition favors virulence, with more virulent strains having a competitive advantage in genetically diverse infections. This idea, which is well supported in theory, remains untested empirically. Here we provide evidence that within-host competition does indeed select for high parasite virulence. We examine the rodent malaria Plasmodium chabaudi in laboratory mice, a parasite-host system in which virulence can be easily monitored and competing strains quantified by using strain-specific real-time PCR. As predicted, we found a strong relationship between parasite virulence and competitive ability, so that more virulent strains have a competitive advantage in mixed-strain infections. In transmission experiments, we found that the strain composition of the parasite populations in mosquitoes was directly correlated with the composition of the bloodstage parasite population. Thus, the outcome of within-host competition determined relative transmission success. Our results imply that within-host competition is a major factor driving the evolution of virulence and can explain why many parasites harm their hosts.competition ͉ evolution ͉ parasite ͉ Plasmodium ͉ mixed infection E xplaining virulence is fundamental to understanding the life history of parasites, arguably the most abundant group of creatures on the planet (1). The problem is to explain why parasites, which rely on their hosts for survival and fitness, should cause disease or indeed kill their hosts (2-6). Many explanations of parasite virulence have been put forward (3, 4), but the idea that has received the most attention is that virulence is a consequence of a parasite's efforts to maximize its fitness: parasites require extensive within-host replication to achieve transmission to the next host, but at the same time such replication damages host tissues, increasing the chances of killing the host (2, 3, 7-9). Higher levels of virulence than predicted by this model, however, could arise due to within-host competition between parasite strains (9-14). Many, if not most, parasite infections consist of genetically distinct strains of the same parasite species or contain virulent mutants that have arisen de novo (15). It is generally assumed that parasites that exploit their hosts prudently suffer great fitness losses in hosts simultaneously infected with more aggressive parasites. This is because virulent parasites could kill the host or competitively exclude prudent parasites before the latter have realized transmission. Even though host death also reduces the fitness of virulent parasites, prudent parasites suffer disproportionately and are eliminated by natural selection, a process commonly known as ''the tragedy of the commons'' (16).Several authors (17, 18) have gone so far as to claim that reducing t...

The dynamics of acute malaria infections. I. Effect of the parasite's red blood cell preference

“…day 24 for AS and approx. day 20 for AJ from (de Roode et al 2005a) figure 3 single infections) is the time required for new target cells to appear. This is roughly the sum of the time lag associated with increased RBC production (2.5 days) and the time taken for these newly produced RBCs to enter the susceptible age range (t min ).…”

“…We used data from infections of C57BL /6 mice with two strains of P. chabaudi (De Roode et al 2004, 2005a as shown in figure 2. The two parasite strains reach different maximum densities and cause different levels of anaemia-with strain AJ reaching higher densities and causing greater anaemia than strain AS.…”

Malaria Parasites in the Asymptomatic: Looking for the Hay in the Haystack

“…Moreover, reduced parasite diversity in areas of low transmission may increase the rate of acquisition of immunity, which, combined with fewer opportunities for superinfection, may allow persistence and thus detection of low-density infections for long periods of time [73]. Finally, genetically homogeneous infections in areas of low transmission could reduce within-host competition, eventually selecting for lower levels of virulence [91]. TNF/-producing CD4 + T cells [46], suggesting that production of this inflammatory cytokine may decrease with increasing cumulative malaria exposure, enabling a transition to asymptomatic infection.…”

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“…A series of elegant experiments with mice co-infected with different strains of Plasmodium chabaudi revealed that competition favours strains with higher virulence (de Roode et al 2005, Bell et al 2006, greater gametocyte production and increased transmissibility to mosquitoes (Taylor et al 1997, de Roode et al 2005. Early gametogenesis allows P. vivax transmission to occur before symptoms appear and, thus, before drug treatment is started.…”