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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
Summary
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.
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.
