Limiting damage during infection: lessons from infection tolerance for novel therapeutics.
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.
Centre for Immunity, Infection, and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom ; Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Pedro F
PF
Vale
Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
Andy
A
Fenton
Centre for Immunity, Infection, and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom ; Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Sam P
SP
Brown
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D001422:Bacterial Adhesion / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005075:Biological Evolution; D015169:Colony Count, Microbial; D015507:Drugs, Investigational / Q000627:therapeutic use*; D054884:Host-Pathogen Interactions / Q000187:drug effects*; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use; D007108:Immune Tolerance / Q000187:drug effects; D015233:Models, Statistical; D053038:Quorum Sensing / Q000187:drug effects / Q000502:physiology; D019562:Viral Load / Q000187:drug effects*; D014774:Virulence / Q000187:drug effects; D037521:Virulence Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014777:Virus Diseases / Q000188:drug therapy* / Q000276:immunology / Q000821:virology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001427:Bacterial Toxins; D015507:Drugs, Investigational; D037521:Virulence Factors; D001241:Aspirin; D007052:Ibuprofen