Within-Host Competition in Genetically Diverse Malaria Infections: Parasite Virulence and Competitive Success

Abstract

Abstract. Humans and animals often become coinfected with pathogen strains that differ in virulence. The ensuing interaction between these strains can, in theory, be a major determinant of the direction of selection on virulence genes in pathogen populations. Many mathematical analyses of this assume that virulent pathogen lineages have a competitive advantage within coinfected hosts and thus predict that pathogens will evolve to become more virulent where genetically diverse infections are common. Although the implications of these studies are relevant to both fundamental biology and medical science, direct empirical tests for relationships between virulence and competitive ability are lacking. Here we use newly developed strain-specific real-time quantitative polymerase chain reaction protocols to determine the pairwise competitiveness of genetically divergent Plasmodium chabaudi clones that represent a wide range of innate virulences in their rodent host. We found that even against their background of widely varying genotypic and antigenic properties, virulent clones had a competitive advantage in the acute phase of mixed infections. The more virulent a clone was relative to its competitor, the less it suffered from competition. This result confirms our earlier work with parasite lines derived from a single clonal lineage by serial passage and supports the virulencecompetitive ability assumption of many theoretical models. To the extent that our rodent model captures the essence of the natural history of malaria parasites, public health interventions which reduce the incidence of mixed malaria infections should have beneficial consequences by reducing the selection for high virulence.

Diet quality determines interspecific parasite interactions in host populations

“…Similarly, results of earlier studies on within-host competition showed fitness disadvantages for lesser virulent parasites (Gower and Webster 2005; Bell et al. 2006). The disadvantage is explained by competition favouring increased host exploitation and thus increased virulence (Choisy and de Roode 2010).…”

The Effect of Immunodeficiency on the Evolution of Virulence: An Experimental Test with the Rodent MalariaPlasmodium chabaudi

“…This competition is for resources or enemy-free space (Read and Taylor 2001;Råberg et al 2006;. Competitive ability in this experimental system is correlated with virulence (de Roode et al 2005a(de Roode et al , 2005bBell et al 2006). In CD4 ϩ T cell-depleted mice, competition between rodent malaria parasites is enhanced ), in part due to resource limitation (Hellriegel 1992;Hetzel and Anderson 1996;Haydon et al 2003;Mideo et al 2008).…”

The contribution of Plasmodium chabaudi to our understanding of malaria

“…One of the most useful attributes of P. chabaudi is the variety of well-characterized cloned lines (Box 1) [3]. These lines are all synchronous (unlike P. berghei ANKA or P. yoelii [4]) and exhibit a spectrum of disease severity [5], different levels of sequestration [6] and transmissibility to mosquitoes [7]. The most commonly used line is P. chabaudi chabaudi (AS), which is generally non-lethal, similar to malaria caused by both P. vivax and P. falciparum in humans (less than 0.5% lethality), but sequesters (adheres) on vascular endothelium, induces a chronic infection [8], and can be relatively easily transmitted through Anopheles stephensi mosquitoes.…”