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<p>Despite the prevalence of co-infection with drug-sensitive and drug-resistant <i>Mycobacterium tuberculosis</i> strains within a single host, the implications of such dual infections remain poorly understood. In this study, we develop a comprehensive within-host model that incorporates both bacterial strains, their mutation dynamics, and cross-reactive immune responses. We analyze the basic reproduction number (<InlineEquation ID="IEq1"> <EquationSource Format="TEX">\( \mathcal {R}_0 \)</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi mathvariant="script">R</mi> <mn>0</mn> </msub> </math></EquationSource> </InlineEquation>) and identify its dependence on key parameters, finding that <InlineEquation ID="IEq2"> <EquationSource Format="TEX">\( \mathcal {R}_0 \)</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi mathvariant="script">R</mi> <mn>0</mn> </msub> </math></EquationSource> </InlineEquation> is strongly influenced by the adaptive immune response rate, bacterial fitness cost, and macrophage engulfment rates. Our bifurcation analysis reveals the presence of a backward bifurcation at <InlineEquation ID="IEq3"> <EquationSource Format="TEX">\( \mathcal {R}_0 = 1 \)</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <msub> <mi mathvariant="script">R</mi> <mn>0</mn> </msub> <mo>=</mo> <mn>1</mn> </mrow> </math></EquationSource> </InlineEquation>, indicating complex threshold dynamics. Utilizing optimal control theory, we evaluate treatment strategies and demonstrate that a combination therapy with at least 85% efficacy against both strains can effectively control the infection. These findings deepen our understanding of host-pathogen interactions in tuberculosis and provide valuable insights for the development of more effective anti-tuberculosis therapies.</p>

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Optimizing combination therapy against drug resistance Mycobacterium tuberculosis: a modelling study

  • 期刊论文

  • 发表日期：

    2025年6月6日

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  • Mlyashimbi Helikumi,
  • Salamida Daudi,
  • Eva Lusekelo,
  • Steady Mushayabasa

摘要

Despite the prevalence of co-infection with drug-sensitive and drug-resistant Mycobacterium tuberculosis strains within a single host, the implications of such dual infections remain poorly understood. In this study, we develop a comprehensive within-host model that incorporates both bacterial strains, their mutation dynamics, and cross-reactive immune responses. We analyze the basic reproduction number ( \( \mathcal {R}_0 \) R 0 ) and identify its dependence on key parameters, finding that \( \mathcal {R}_0 \) R 0 is strongly influenced by the adaptive immune response rate, bacterial fitness cost, and macrophage engulfment rates. Our bifurcation analysis reveals the presence of a backward bifurcation at \( \mathcal {R}_0 = 1 \) R 0 = 1 , indicating complex threshold dynamics. Utilizing optimal control theory, we evaluate treatment strategies and demonstrate that a combination therapy with at least 85% efficacy against both strains can effectively control the infection. These findings deepen our understanding of host-pathogen interactions in tuberculosis and provide valuable insights for the development of more effective anti-tuberculosis therapies.