M. Yu. Khristichenko’s research while affiliated with Russian Academy of Sciences and other places

Optimal disturbances of the periodic solution of the hepatitis B dynamics model corresponding to the chronic recurrent form of the disease are found. The dependence of the optimal disturbance on the phase of periodic solution is analyzed. Four phases of the solution are considered, they correspond to clinically different periods of development of the immune response and severity of the disease, namely, activation of antiviral immune reactions, attenuation of reactions, peak and minimum viral load. The possibility of using optimal disturbances to exit the domain of attraction of the considered periodic solution using minimal impact is studied. The components of disturbances that may underlie the phenomenon of spontaneous recovery from chronic hepatitis B observed in clinical practice are identified.

This work is devoted to the technology developed by the authors that allows one for fixed values of parameters and tracing by parameters to calculate stationary solutions of systems with delay and analyze their stability. We discuss the results of applying this technology to the Marchuk–Petrov antiviral immune response model with parameter values corresponding to hepatitis B infection. The presence of bistability and hysteresis properties in this model is shown for the first time.

Optimal disturbances of a number of typical stationary solutions of the hepatitis B virus infection dynamics model have been found. Specifically optimal disturbances have been found for stationary solutions corresponding to various forms of the chronic course of the disease, including those corresponding to the regime of low-level virus persistence. The influence of small optimal disturbances of individual groups of variables on the stationary solution is studied. The possibility of transition from stable stationary solutions corresponding to chronic forms of hepatitis B to stable stationary solutions corresponding to the state of functional recovery or a healthy organism using optimal disturbances is studied. Optimal disturbances in this study were constructed on the basis of generalized therapeutic drugs characterized by one-compartment and two-compartment pharmacokinetics.

The paper is focused on the dependence of optimal disturbances of stable periodic solutions of time-delay systems on phases of such solutions. The results of numerical experiments with the well-known model of the dynamics of infection caused by lymphocytic choriomeningitis virus are presented and discussed. A new more efficient method for computing the optimal disturbances of periodic solutions is proposed and used.

This work is devoted to the technology developed by the authors that allows one for fixed values of parameters and tracing by parameters to calculate stationary solutions of systems with delay and analyze their stability. We discuss the results of applying this technology to Marchuk-Petrov's antiviral immune response model with parameter values corresponding to hepatitis B infection. The presence of bistability and hysteresis properties in this model is shown for the first time.

A concept of optimal disturbances of periodic solutions for a system of time-delay differential equations is defined. An algorithm for computing the optimal disturbances is proposed and justified. This algorithm is tested on the known system of four nonlinear time-delay differential equations modelling the dynamics of the experimental infection caused by the lymphocytic choriomeningitis virus. The results of numerical experiments are discussed.

Systems of time-delay differential equations are widely used to study the dynamics of infectious diseases and immune responses. The Marchuk-Petrov model is one of them. Stable non-trivial steady states and stable periodic solutions to this model can be interpreted as chronic viral diseases. In this work we briefly describe our technology developed for computing steady and periodic solutions of time-delay systems and present and discuss the results of computing periodic solutions for the Marchuk-Petrov model with parameter values corresponding to the hepatitis B infection.

The paper is focused on computation of stable periodic solutions to systems of delay differential equations modelling the dynamics of infectious diseases and immune response. The method proposed here is described by an example of the well-known model of dynamics of experimental infection caused by lymphocytic choriomeningitis viruses. It includes the relaxation method for forming an approximate periodic solution, a method for estimating the approximate period of this solution based on the Fourier series expansion, and a Newton-type method for refining the approximate period and periodic solution. The results of numerical experiments are presented and discussed. The proposed method is compared to known ones.

In this paper, we apply optimal perturbations to control mathematical models of infectious diseases expressed as systems of nonlinear differential equations with delayed independent variables. We develop the method for calculation of perturbations of the initial state of a dynamical system with delayed independent variable producing maximal amplification in the given local norm taking into account weights of perturbation components. For the model of experimental virus infection, we construct optimal perturbation for two types of stationary states, with low or high viral load, corresponding to different variants of chronic virus infection flow.

Novel fast algorithms for computing the maximum amplification of the norm of solution and optimal disturbances for delay systems are proposed and justified. The proposed algorithms are tested on a system of four nonlinear delay differential equations providing a model for the experimental infection caused by the lymphocytic choriomeningitis virus (LCMV). Numerical results are discussed.