A within-host birth-death and time-dose-response model for Legionnaires' disease

Area of Science:

• Microbiology
• Epidemiology
• Mathematical Biology

Background:

• Dose-response (DR) relationships are vital for infectious disease risk assessment.
• Understanding within-host pathogenesis is key to modeling DR dynamics.
• Existing DR models lack flexibility and specific application to Legionnaires' disease.

Purpose of the Study:

• To develop a novel mathematical model for Legionnaires' disease within-host dynamics.
• To incorporate cellular and population heterogeneity into the DR model.
• To create a flexible DR model accommodating different illness hypotheses and time-dependent incubation periods.

Main Methods:

• Derivation of a new within-host mathematical model for Legionnaires' disease.
• Development of a flexible DR model incorporating single-hit or threshold hypotheses.
• Extension of the DR model to include a dose-dependent incubation period based on biological mechanisms.

Main Results:

• The developed within-host models provide an ID50 between 8-9 Legionella bacteria.
• Median incubation periods are predicted to be approximately 4 days.
• Model predictions align with existing data from animal experiments and human outbreaks.

Conclusions:

• The new model offers a flexible approach to understanding Legionnaires' disease DR dynamics.
• It successfully incorporates within-host heterogeneity and time-dependent factors.
• The findings support quantitative microbial risk assessment for Legionnaires' disease.