title: Within-host competition does not select for virulence in malaria parasites; studies with Plasmodium yoelii.
abstract: In endemic areas with high transmission intensities, malaria infections are very often composed of multiple genetically distinct strains of malaria parasites. It has been hypothesised that this leads to intra-host competition, in which parasite strains compete for resources such as space and nutrients. This competition may have repercussions for the host, the parasite, and the vector in terms of disease severity, vector fitness, and parasite transmission potential and fitness. It has also been argued that within-host competition could lead to selection for more virulent parasites. Here we use the rodent malaria parasite Plasmodium yoelii to assess the consequences of mixed strain infections on disease severity and parasite fitness. Three isogenic strains with dramatically different growth rates (and hence virulence) were maintained in mice in single infections or in mixed strain infections with a genetically distinct strain. We compared the virulence (defined as harm to the mammalian host) of mixed strain infections with that of single infections, and assessed whether competition impacted on parasite fitness, assessed by transmission potential. We found that mixed infections were associated with a higher degree of disease severity and a prolonged infection time. In the mixed infections, the strain with the slower growth rate was often responsible for the competitive exclusion of the faster growing strain, presumably through host immune-mediated mechanisms. Importantly, and in contrast to previous work conducted with Plasmodium chabaudi, we found no correlation between parasite virulence and transmission potential to mosquitoes, suggesting that within-host competition would not drive the evolution of parasite virulence in P. yoelii.
authors: Malaria Unit, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; Laboratory of Molecular Biology of Infectious Agents, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors: Hussein M
authors: HM
authors: Abkallo
authors: Malaria Unit, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; Laboratory of Entomology, Wageningen University, Wageningen, The Netherlands.
authors: Julie-Anne
authors: JA
authors: Tangena
authors: Malaria Unit, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
authors: Jianxia
authors: J
authors: Tang
authors: Laboratory of Molecular Biology of Infectious Agents, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors: Nobuyuki
authors: N
authors: Kobayashi
authors: Malaria Unit, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
authors: Megumi
authors: M
authors: Inoue
authors: Malaria Unit, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
authors: Augustin
authors: A
authors: Zoungrana
authors: Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors: Nick
authors: N
authors: Colegrave
authors: Malaria Unit, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
authors: Richard
authors: R
authors: Culleton
mesh_terms: D000818:Animals; D005260:Female; D006790:Host-Parasite Interactions / Q000502:physiology*; D008288:Malaria / Q000235:genetics / Q000382:microbiology*; D051379:Mice; D008808:Mice, Inbred CBA; D010967:Plasmodium yoelii / Q000235:genetics / Q000472:pathogenicity*; D060888:Real-Time Polymerase Chain Reaction; D014774:Virulence