Mechanistic within-host mathematical model of inhalational anthrax

Area of Science:

• Mathematical modeling
• Infectious disease dynamics
• Microbiology

Background:

• Bacillus anthracis causes inhalational anthrax, a severe disease.
• Understanding early infection dynamics and dose-response relationships is crucial for risk assessment.

Purpose of the Study:

• To develop a mathematical model simulating Bacillus anthracis infection dynamics in hosts.
• To analyze the probabilities of infection clearance and symptom onset based on inhaled spore dose.
• To explain dose-response data for inhalational anthrax.

Main Methods:

• A stochastic mathematical model incorporating bacterial and protective antigen dynamics.
• Bayesian calibration using in vivo data from rabbit and guinea pig studies.
• Validation with human incubation-period data from the 1979 Sverdlovsk anthrax outbreak.

Main Results:

• The model provides a mechanistic description of early inhalational anthrax infection.
• Estimated within-host parameters using Bayesian inference.
• Demonstrated accurate prediction of human time-to-symptoms data.

Conclusions:

• The model accurately describes early inhalational anthrax dynamics and predicts human response.
• It can explain dose-response relationships and estimate infection clearance probabilities.
• A formula for symptom onset probability was derived for Poisson-distributed spore inhalation.