Mathematical modeling and optimization of monocyte-driven immune dynamics and treatment strategies in within-host Mycobacterium tuberculosis
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Date
2026-03-23
Authors
Helikumi , Mlyashimbi
Mushayabasa, Steady
Journal Title
Journal ISSN
Volume Title
Publisher
MATHEMATICS IN MEDICAL AND LIFE SCIENCES
Abstract
Tuberculosis (TB) remains a major global health challenge, driven by complex within-host interactions between Mycobacterium tuberculosis (Mtb) and the host immune system. To better understand these dynamics, we develop a mathematical model that incorporates monocytes, macrophages, and T lymphocytes. Analytical results show that the basic repro- duction number, R0, depends on key infection and immune-response parameters and can exceed unity under biologically plausible conditions, leading to persistent infection. Bifur- cation analysis reveals the occurrence of a backward bifurcation at R0 = 1, indicating that reducing R0 below unity may not be sufficient for disease eradication, as stable endemic equilibria can coexist with the disease-free equilibrium when R0 < 1. Numerical simu- lations under baseline parameter values demonstrate that enhancing immune response parameters substantially lowers bacterial burden, reducing bacterial populations by up to 70% within 60 days, whereas increased infection rates accelerate disease progression, doubling bacterial populations in approximately half the time. Furthermore, an optimal control analysis suggests that, under representative treatment scenarios, intensified drug treatment can reduce bacterial loads by more than 90% within 30 days; however, com- plete bacterial clearance may remain unattainable because of the backward bifurcation phenomenon. These findings underscore the importance of integrating immune enhance- ment with optimized treatment strategies and highlight that achieving R0 < 1 alone may not guarantee eradication of TB infection.
Description
This journal was published by department of Mathematics and Statistics, College of Science and Technical Education, Mbeya University of Science and Technology, Mbeya, Tanzania; department of Mathematics and Computational Sciences, University of Zimbabwe, Harare, Zimbabwe
Keywords
uberculosis, mathematical model, monocytes, drug combination, optimal control