Model formulation and oscillatory patterns in immune-pathogen dynamics during Brucellosis infection.

Area of Science:

• Immunology
• Mathematical Biology
• Infectious Diseases

Background:

• Brucellosis is a global zoonotic disease causing significant health and economic impacts.
• Clinical manifestations include recurrent undulant fever, attributed to Brucella's intracellular persistence in macrophages.

Purpose of the Study:

• To develop a mathematical model explaining the immune-pathogen dynamics behind brucellosis-induced fever periodicity.
• To identify key thresholds and mechanisms driving recurrent febrile episodes in brucellosis.

Main Methods:

• A novel mathematical model integrating macrophage self-renewal, logistic growth, and intracellular Brucella replication was developed.
• Stability and bifurcation analyses, including supercritical Hopf bifurcation, were employed to study system dynamics.

Main Results:

• Two critical thresholds were identified: one for infection persistence (R₀>1) and another for undulant fever emergence.
• Recurrent fevers arise from a dynamic imbalance between macrophage regeneration and bacterial proliferation, explained by stable limit cycles post-Hopf bifurcation.
• Excessive macrophage renewal or carrying capacity can paradoxically destabilize the system, worsening febrile cycles.

Conclusions:

• The model provides a mechanistic explanation for recurrent febrile episodes in brucellosis.
• Interventions targeting both immune resource depletion and intracellular bacterial survival may suppress pathological oscillations.
• Findings offer novel perspectives for managing chronic brucellosis by addressing underlying immune-pathogen dynamics.