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Epithelial Cell Infection Analyses with Shigella
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The Shigella human challenge model.

C K Porter1, N Thura1, R T Ranallo2

  • 1Enteric Diseases Department, Naval Medical Research Center, Silver Spring, MS, USA.

Epidemiology and Infection
|August 22, 2012
PubMed
Summary
This summary is machine-generated.

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The Shigella human challenge model, used for decades, requires more dose-ranging studies. Expanding strain diversity is crucial for understanding Shigella infection variability and vaccine development.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Clinical Trials

Background:

  • Shigella causes global infectious diarrhea.
  • The Shigella human challenge model aids pathogenesis, immune response, and vaccine efficacy studies.
  • This model has been utilized since 1946.

Purpose of the Study:

  • To systematically review the literature on experimental shigellosis in human subjects.
  • To analyze summative estimates of Shigella infection by strain and dose.
  • To identify limitations and suggest future directions for the human challenge model.

Main Methods:

  • A systematic literature review was conducted.
  • Studies involving experimental Shigella infection in humans were identified.
  • Summative estimates were calculated based on strain and administered dose.

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Main Results:

  • 19 studies evaluating nine Shigella strains at doses from 10 to 1 × 10^10 CFU were identified.
  • S. sonnei strain 53G and S. flexneri strain 2457T were most frequently used.
  • Diarrhea attack rates plateaued around 75-80% and dysentery rates remained constant, irrespective of dose variations.

Conclusions:

  • Existing Shigella human challenge models show consistent attack and dysentery rates, indicating a need for further dose-ranging studies.
  • Variability in inoculum preparation methods was noted.
  • Expanding the model to include diverse serotypes and strains is recommended to understand outcome variability.