Limiting damage during infection: lessons from infection tolerance for novel therapeutics

Pedro F Vale, Andy Fenton, Sam P Brown

Research output: Contribution to journalArticlepeer-review


The distinction between pathogen elimination and damage limitation during infection is beginning to change perspectives on infectious disease control, and has recently led to the development of novel therapies that focus on reducing the illness caused by pathogens (‘‘damage limitation’’)rather than reducing pathogen burdens directly (‘‘pathogen elimination’’). While beneficial at the individual host level, the population consequences of these interventions remain unclear. To address this issue,we present a simple conceptual framework for damage limitation during infection that distinguishes between therapies that are either host-centric (pro-tolerance) or pathogen-centric (anti-virulence). We then draw on recent developments from the evolutionary ecology of disease tolerance to highlight some potential epidemiological and evolutionary responses of pathogens to medical interventions that target the symptoms of infection. Just as pathogens are known to evolve in response to antimicrobial and vaccination therapies, we caution that claims of ‘‘evolution-proof’’ anti-virulence interventions may be premature, and further, that in infections where virulence and transmission are linked, reducing illness without reducing pathogen burden could have non-trivial epidemiological and evolutionary consequences that require careful examination.

Original languageEnglish
Pages (from-to)e1001769
JournalPLoS Biology
Issue number1
Publication statusPublished - Jan 2014


  • Anti-Inflammatory Agents, Non-Steroidal
  • Aspirin
  • Bacterial Adhesion
  • Bacterial Infections
  • Bacterial Toxins
  • Biological Evolution
  • Colony Count, Microbial
  • Drugs, Investigational
  • Host-Pathogen Interactions
  • Humans
  • Ibuprofen
  • Immune Tolerance
  • Models, Statistical
  • Quorum Sensing
  • Viral Load
  • Virulence
  • Virulence Factors
  • Virus Diseases


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