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Mechanisms of pathogenesis, infective dose and virulence in human parasites

Helen C Leggett1, Charlie K Cornwallis, Stuart A West

  • 1Department of Zoology, Oxford University, Oxford, United Kingdom. helen.leggett@zoo.ox.ac.uk

Plos Pathogens
|February 24, 2012
PubMed

Insights

Pathogen infective dose varies. While local action pathogens have lower doses, virulence is not reduced. Virulence is negatively linked to infective dose and higher in skin-infecting pathogens.

Area of Science:

  • * Pathogen biology and host-pathogen interactions.
  • * Evolutionary ecology and infectious disease dynamics.

Background:

  • * The infective dose (ID) of a pathogen, the number required to cause infection, varies significantly across species.
  • * Recent predictions suggest ID depends on the mode of action of pathogen molecules (local vs. distant).
  • * Pathogens using distantly acting molecules or immune modulators were predicted to have higher virulence due to larger initial cell numbers.

Purpose of the Study:

  • * To formally test predictions linking pathogen molecular action, infective dose, and virulence.
  • * To investigate the relationship between infective dose, virulence, and infection site using empirical data.

Main Methods:

  • * Comparative analysis of data from 43 diverse human pathogens.
  • * Examination of pathogen traits including infective dose, virulence, mode of action (local/distant), and infection site.

Main Results:

  • * Pathogens utilizing locally acting molecules indeed exhibited lower infective doses.
  • * However, local action did not correlate with reduced virulence compared to distant action.
  • * Virulence was negatively correlated with infective dose and was higher in pathogens infecting wounded skin versus those ingested or inhaled.

Conclusions:

  • * Broad-scale comparative analyses can elucidate variations in pathogen traits like infective dose and virulence.
  • * Mechanistic details, such as the mode of molecular action and infection site, are crucial for understanding pathogen evolution and impact.
  • * Virulence is influenced by factors beyond infective dose, including infection route and pathogen strategy.

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