Consequences of immunopathology for pathogen virulence evolution and public health: malaria as a case study

Grainne H. Long, Andrea L. Graham

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Evolutionary theories explaining virulence-the fitness damage incurred by infected hosts-often focus on parasite strategies for within-host exploitation. However, much virulence can be caused by the host's own immune response: for example, pro-inflammatory cytokines, although essential for killing malaria parasites, also damage host tissue. Here we argue that immune-mediated virulence, or 'immunopathology,' may affect malaria virulence evolution and should be considered in the design of medical interventions. Our argument is based on the ability of immunopathology to disrupt positive virulence-transmission relationships assumed under the trade-off theory of virulence evolution. During rodent malaria infections, experimental reduction of inflammation using reagents approved for field use decreases virulence but increases parasite transmission potential. Importantly, rodent malaria parasites exhibit genetic diversity in the propensity to induce inflammation and invest in transmission-stage parasites in the presence of pro-inflammatory cytokines. If immunopathology positively correlates with malaria parasite density, theory suggests it could select for relatively low malaria virulence. Medical interventions which decrease immunopathology may therefore inadvertently select for increased malaria virulence. The fitness consequences to parasites of variations in immunopathology must be better understood in order to predict trajectories of parasite virulence evolution in heterogeneous host populations and in response to medical interventions.

Original languageEnglish
Pages (from-to)278-291
Number of pages14
JournalEvolutionary Applications
Issue number2
Early online date17 Feb 2011
Publication statusPublished - 31 Mar 2011


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