# American Institute of Mathematical Sciences

August  2021, 26(8): 4147-4171. doi: 10.3934/dcdsb.2020278

## Optimal control of an avian influenza model with multiple time delays in state and control variables

 1 School of Mathematics and Statistics, Ningxia University, Yinchuan, 750021, China 2 Xinhua College, Ningxia University, Yinchuan, 750021, China 3 School of Mathematical and Natural Sciences, Arizona State University, AZ, USA

* Corresponding author: Qimin Zhang

Received  December 2019 Revised  August 2020 Published  August 2021 Early access  September 2020

Fund Project: Ting Kang and Qimin Zhang are supported by the Natural Science Foundation of China (11661064), Ningxia Natural Science Foundation Project (2019AAC03069) and the Funds for Improving the International Education Capacity of Ningxia University (030900001921)

In this paper, we consider an optimal control model governed by a class of delay differential equation, which describe the spread of avian influenza virus from the poultry to human. We take three control variables into the optimal control model, namely: slaughtering to the susceptible and infected poultry ($u_{1}(t)$), educational campaign to the susceptible human population ($u_{2}(t)$) and treatment to infected population ($u_{3}(t)$). The model involves two time delays that stand for the incubation periods of avian influenza virus in the infective poultry and human populations. We derive first order necessary conditions for existence of the optimal control and perform several numerical simulations. Numerical results show that different control strategies have different effects on controlling the outbreak of avian influenza. At the same time, we discuss the influence of time delays on objective function and conclude that the spread of avian influenza will slow down as the time delays increase.

Citation: Ting Kang, Qimin Zhang, Haiyan Wang. Optimal control of an avian influenza model with multiple time delays in state and control variables. Discrete and Continuous Dynamical Systems - B, 2021, 26 (8) : 4147-4171. doi: 10.3934/dcdsb.2020278
##### References:
 [1] A. Abta, A. Kaddar and H. T. Alaoui, Global stability for delay SIR and SEIR epidemic models with saturated incidence rates, Electronic Journal of Differential Equations, 2012 (2012), 1-13. [2] C. Bao, L. Cui and M. Zhou et al., Live-animal markets and influenza a (H7N9) virus infection, New England Journal of Medicine, 368 (2013), 2337-2339.  doi: 10.1056/NEJMc1306100. [3] E. B. M. Bashier and K. C. Patidar, Optimal control of an epidemiological model with multiple time delays, Applied Mathematics and Computation, 292 (2017), 47-56.  doi: 10.1016/j.amc.2016.07.009. [4] L. Bourouiba, S. A. Gourley, R. Liu and J. Wu, The interaction of migratory birds and domestic poultry and its role in sustaining avian influenza, SIAM Journal on Applied Mathematics, 71 (2011), 487-516.  doi: 10.1137/100803110. [5] F. Chen and J. Cui, Cross-species epidemic dynamic model of influenza, in 2016 9th International Congress on Image and Signal Processing, BioMedical Engineering and Informatics (CISP-BMEI), IEEE, 2016. doi: 10.1109/CISP-BMEI.2016.7852965. [6] Z. Chen and Z. Xu, A delayed diffusive influenza model with two-strain and two vaccinations, Applied Mathematics and Computation, 349 (2019), 439-453.  doi: 10.1016/j.amc.2018.12.065. [7] N. S. Chong, J. M. Tchuenche and R. J. Smith, A mathematical model of avian influenza with half-saturated incidence, Theory in Biosciences, 133 (2014), 23-38.  doi: 10.1007/s12064-013-0183-6. [8] E. Claas, A. Osterhaus and R. Van-Beek, Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus, The Lancet, 351 (1998), 472-477.  doi: 10.1016/S0140-6736(97)11212-0. [9] C. A. Y. E. Committee, China agriculture yearbook, 2012. [10] W. H. Fleming and R. W. Rishel, Deterministic and stochastic optimal control, Springer Verlag, New York, 1975. [11] H. Gaff and E. Schaefer, Optimal control applied to vaccination and treatment strategies for various epidemiological models, Mathematical Biosciences and Engineering, 6 (2009), 469-492.  doi: 10.3934/mbe.2009.6.469. [12] N. Gao, Z. Lu and B. Cao, Clinical findings in 111 cases of influenza A (H7N9) virus infection, New England Journal of Medicine, 369 (2013), 1869-1869.  doi: 10.1056/NEJMoa1305584. [13] R. Gao, B. Cao and Y. Hu, Human infection with a novel avian-origin influenza A (H7N9) virus, New England Journal of Medicine, 368 (2013), 1888-1897.  doi: 10.1056/NEJMoa1304459. [14] L. Göllmann, D. Kern and H. Maurer, Optimal control problems with delays in state and control variables subject to mixed control-state constraints, Optimal Control Applications and Methods, 30 (2009), 341-365.  doi: 10.1002/oca.843. [15] S. Iwami, Y. Takeuchi, A. Korobeinikov and X. Liu, Prevention of avian influenza epidemic: what policy should we choose?, Journal of Theoretical Biology, 252 (2008), 732-741.  doi: 10.1016/j.jtbi.2008.02.020. [16] S. Iwami, Y. Takeuchi and X. Liu, Avian-human influenza epidemic model, Mathematical Biosciences, 207 (2007), 1-25.  doi: 10.1016/j.mbs.2006.08.001. [17] S. Iwami, Y. Takeuchi and X. Liu, Avian flu pandemic: Can we prevent it?, Journal of Theoretical Biology, 257 (2009), 181-190.  doi: 10.1016/j.jtbi.2008.11.011. [18] S. Iwami, Y. Takeuchi, X. Liu and S. Nakaoka, A geographical spread of vaccine-resistance in avian influenza epidemics, Journal of Theoretical Biology, 259 (2009), 219-228.  doi: 10.1016/j.jtbi.2009.03.040. [19] E. Jung, S. Iwami and Y. Takeuchi, Optimal control strategy for prevention of avian influenza pandemic, Journal of Theoretical Biology, 260 (2009), 220-229.  doi: 10.1016/j.jtbi.2009.05.031. [20] T. Kang, Q. Zhang and L. Rong, A delayed avian influenza model with avian slaughter: Stability analysis and optimal control, Physica A: Statistical Mechanics and its Applications, 529 (2019), 121544. doi: 10.1016/j.physa.2019.121544. [21] M. J. Keeling and P. Rohani, Modeling infectious diseases in humans and animals, Princeton University Press, 2008. [22] A. Lahrouz, H. El Mahjour and A. Settati, Dynamics and optimal control of a non-linear epidemic model with relapse and cure, Physica A: Statistical Mechanics and its Applications, 496 (2018), 299-317.  doi: 10.1016/j.physa.2018.01.007. [23] D. Liu, W. Shi and Y. Shi, Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: Phylogenetic, structural, and coalescent analyses, The Lancet, 381 (2013), 1926-1932.  doi: 10.1016/S0140-6736(13)60938-1. [24] S. Liu, L. Pang, S. Ruan and X. Zhang, Global dynamics of avian influenza epidemic models with psychological effect, Computational and Mathematical Methods in Medicine, 2015, Article ID 913726. doi: 10.1155/2015/913726. [25] S. Liu, S. Ruan and X. Zhang, On avian influenza epidemic models with time delay, Theory in Biosciences, 134 (2015), 75-82.  doi: 10.1007/s12064-015-0212-8. [26] S. Liu, S. Ruan and X. Zhang, Nonlinear dynamics of avian influenza epidemic models, Mathematical Biosciences, 283 (2017), 118-135.  doi: 10.1016/j.mbs.2016.11.014. [27] F. K. Mbabazi, J. Y. T. Mugisha and M. Kimathi, Modeling the within-host co-infection of influenza {A} virus and pneumococcus, Applied Mathematics and Computation, 339 (2018), 488-506.  doi: 10.1016/j.amc.2018.07.031. [28] O. P. Misra and D. K. Mishra, Spread and control of influenza in two groups: A model, Applied Mathematics and Computation, 219 (2013), 7982-7996.  doi: 10.1016/j.amc.2013.02.050. [29] G. P. Samanta, Permanence and extinction for a nonautonomous avian-human influenza epidemic model with distributed time delay, Mathematical and Computer Modelling, 52 (2010), 1794-1811.  doi: 10.1016/j.mcm.2010.07.006. [30] S. Sharma, A. Mondal and A. K. Pal, Stability analysis and optimal control of avian influenza virus A with time delays, International Journal of Dynamics and Control, 6 (2018), 1351-1366.  doi: 10.1007/s40435-017-0379-6. [31] Z. Shi, X. Zhang and D. Jiang, Dynamics of an avian influenza model with half-saturated incidence, Applied Mathematics and Computation, 355 (2019), 399-416.  doi: 10.1016/j.amc.2019.02.070. [32] P. Van den Driessche and J. Watmough, Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission, Mathematical Biosciences, 180 (2002), 29-48.  doi: 10.1016/S0025-5564(02)00108-6. [33] A. Wang and Y. Xiao, A filippov system describing media effects on the spread of infectious diseases, Nonlinear Analysis: Hybrid Systems, 11 (2014), 84-97.  doi: 10.1016/j.nahs.2013.06.005. [34] World Health Organization, WHO risk assessments of human infection with avian influenza A(H7N9) virus, 2017, https://www.who.int/influenza/human_animal_interface/influenza_h7n9/Risk_Assessment/en/. [35] Y. Xiao, X. Sun and S. Tang, Transmission potential of the novel avian influenza A(H7N9) infection in mainland China, Journal of Theoretical Biology, 352 (2014), 1-5.  doi: 10.1016/j.jtbi.2014.02.038. [36] H. Yoko, K. Yoshinari and Y. Takehisa, Potential risk associated with animal culling and disposal during the foot-and-mouth disease epidemic in japan in 2010, Research in Veterinary Science, 102 (2015), 228-230.  doi: 10.1016/j.rvsc.2015.08.017. [37] X. Zhang, Global dynamics of a stochastic avian-human influenza epidemic model with logistic growth for avian population, Nonlinear Dynamics, 90 (2017), 2331-2343.  doi: 10.1007/s11071-017-3806-5. [38] X. Zhang and X. Liu, Backward bifurcation of an epidemic model with saturated treatment function, Journal of Mathematical Analysis and Applications, 348 (2008), 433-443.  doi: 10.1016/j.jmaa.2008.07.042.

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##### References:
 [1] A. Abta, A. Kaddar and H. T. Alaoui, Global stability for delay SIR and SEIR epidemic models with saturated incidence rates, Electronic Journal of Differential Equations, 2012 (2012), 1-13. [2] C. Bao, L. Cui and M. Zhou et al., Live-animal markets and influenza a (H7N9) virus infection, New England Journal of Medicine, 368 (2013), 2337-2339.  doi: 10.1056/NEJMc1306100. [3] E. B. M. Bashier and K. C. Patidar, Optimal control of an epidemiological model with multiple time delays, Applied Mathematics and Computation, 292 (2017), 47-56.  doi: 10.1016/j.amc.2016.07.009. [4] L. Bourouiba, S. A. Gourley, R. Liu and J. Wu, The interaction of migratory birds and domestic poultry and its role in sustaining avian influenza, SIAM Journal on Applied Mathematics, 71 (2011), 487-516.  doi: 10.1137/100803110. [5] F. Chen and J. Cui, Cross-species epidemic dynamic model of influenza, in 2016 9th International Congress on Image and Signal Processing, BioMedical Engineering and Informatics (CISP-BMEI), IEEE, 2016. doi: 10.1109/CISP-BMEI.2016.7852965. [6] Z. Chen and Z. Xu, A delayed diffusive influenza model with two-strain and two vaccinations, Applied Mathematics and Computation, 349 (2019), 439-453.  doi: 10.1016/j.amc.2018.12.065. [7] N. S. Chong, J. M. Tchuenche and R. J. Smith, A mathematical model of avian influenza with half-saturated incidence, Theory in Biosciences, 133 (2014), 23-38.  doi: 10.1007/s12064-013-0183-6. [8] E. Claas, A. Osterhaus and R. Van-Beek, Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus, The Lancet, 351 (1998), 472-477.  doi: 10.1016/S0140-6736(97)11212-0. [9] C. A. Y. E. Committee, China agriculture yearbook, 2012. [10] W. H. Fleming and R. W. Rishel, Deterministic and stochastic optimal control, Springer Verlag, New York, 1975. [11] H. Gaff and E. Schaefer, Optimal control applied to vaccination and treatment strategies for various epidemiological models, Mathematical Biosciences and Engineering, 6 (2009), 469-492.  doi: 10.3934/mbe.2009.6.469. [12] N. Gao, Z. Lu and B. Cao, Clinical findings in 111 cases of influenza A (H7N9) virus infection, New England Journal of Medicine, 369 (2013), 1869-1869.  doi: 10.1056/NEJMoa1305584. [13] R. Gao, B. Cao and Y. Hu, Human infection with a novel avian-origin influenza A (H7N9) virus, New England Journal of Medicine, 368 (2013), 1888-1897.  doi: 10.1056/NEJMoa1304459. [14] L. Göllmann, D. Kern and H. Maurer, Optimal control problems with delays in state and control variables subject to mixed control-state constraints, Optimal Control Applications and Methods, 30 (2009), 341-365.  doi: 10.1002/oca.843. [15] S. Iwami, Y. Takeuchi, A. Korobeinikov and X. Liu, Prevention of avian influenza epidemic: what policy should we choose?, Journal of Theoretical Biology, 252 (2008), 732-741.  doi: 10.1016/j.jtbi.2008.02.020. [16] S. Iwami, Y. Takeuchi and X. Liu, Avian-human influenza epidemic model, Mathematical Biosciences, 207 (2007), 1-25.  doi: 10.1016/j.mbs.2006.08.001. [17] S. Iwami, Y. Takeuchi and X. Liu, Avian flu pandemic: Can we prevent it?, Journal of Theoretical Biology, 257 (2009), 181-190.  doi: 10.1016/j.jtbi.2008.11.011. [18] S. Iwami, Y. Takeuchi, X. Liu and S. Nakaoka, A geographical spread of vaccine-resistance in avian influenza epidemics, Journal of Theoretical Biology, 259 (2009), 219-228.  doi: 10.1016/j.jtbi.2009.03.040. [19] E. Jung, S. Iwami and Y. Takeuchi, Optimal control strategy for prevention of avian influenza pandemic, Journal of Theoretical Biology, 260 (2009), 220-229.  doi: 10.1016/j.jtbi.2009.05.031. [20] T. Kang, Q. Zhang and L. Rong, A delayed avian influenza model with avian slaughter: Stability analysis and optimal control, Physica A: Statistical Mechanics and its Applications, 529 (2019), 121544. doi: 10.1016/j.physa.2019.121544. [21] M. J. Keeling and P. Rohani, Modeling infectious diseases in humans and animals, Princeton University Press, 2008. [22] A. Lahrouz, H. El Mahjour and A. Settati, Dynamics and optimal control of a non-linear epidemic model with relapse and cure, Physica A: Statistical Mechanics and its Applications, 496 (2018), 299-317.  doi: 10.1016/j.physa.2018.01.007. [23] D. Liu, W. Shi and Y. Shi, Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: Phylogenetic, structural, and coalescent analyses, The Lancet, 381 (2013), 1926-1932.  doi: 10.1016/S0140-6736(13)60938-1. [24] S. Liu, L. Pang, S. Ruan and X. Zhang, Global dynamics of avian influenza epidemic models with psychological effect, Computational and Mathematical Methods in Medicine, 2015, Article ID 913726. doi: 10.1155/2015/913726. [25] S. Liu, S. Ruan and X. Zhang, On avian influenza epidemic models with time delay, Theory in Biosciences, 134 (2015), 75-82.  doi: 10.1007/s12064-015-0212-8. [26] S. Liu, S. Ruan and X. Zhang, Nonlinear dynamics of avian influenza epidemic models, Mathematical Biosciences, 283 (2017), 118-135.  doi: 10.1016/j.mbs.2016.11.014. [27] F. K. Mbabazi, J. Y. T. Mugisha and M. Kimathi, Modeling the within-host co-infection of influenza {A} virus and pneumococcus, Applied Mathematics and Computation, 339 (2018), 488-506.  doi: 10.1016/j.amc.2018.07.031. [28] O. P. Misra and D. K. Mishra, Spread and control of influenza in two groups: A model, Applied Mathematics and Computation, 219 (2013), 7982-7996.  doi: 10.1016/j.amc.2013.02.050. [29] G. P. Samanta, Permanence and extinction for a nonautonomous avian-human influenza epidemic model with distributed time delay, Mathematical and Computer Modelling, 52 (2010), 1794-1811.  doi: 10.1016/j.mcm.2010.07.006. [30] S. Sharma, A. Mondal and A. K. Pal, Stability analysis and optimal control of avian influenza virus A with time delays, International Journal of Dynamics and Control, 6 (2018), 1351-1366.  doi: 10.1007/s40435-017-0379-6. [31] Z. Shi, X. Zhang and D. Jiang, Dynamics of an avian influenza model with half-saturated incidence, Applied Mathematics and Computation, 355 (2019), 399-416.  doi: 10.1016/j.amc.2019.02.070. [32] P. Van den Driessche and J. Watmough, Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission, Mathematical Biosciences, 180 (2002), 29-48.  doi: 10.1016/S0025-5564(02)00108-6. [33] A. Wang and Y. Xiao, A filippov system describing media effects on the spread of infectious diseases, Nonlinear Analysis: Hybrid Systems, 11 (2014), 84-97.  doi: 10.1016/j.nahs.2013.06.005. [34] World Health Organization, WHO risk assessments of human infection with avian influenza A(H7N9) virus, 2017, https://www.who.int/influenza/human_animal_interface/influenza_h7n9/Risk_Assessment/en/. [35] Y. Xiao, X. Sun and S. Tang, Transmission potential of the novel avian influenza A(H7N9) infection in mainland China, Journal of Theoretical Biology, 352 (2014), 1-5.  doi: 10.1016/j.jtbi.2014.02.038. [36] H. Yoko, K. Yoshinari and Y. Takehisa, Potential risk associated with animal culling and disposal during the foot-and-mouth disease epidemic in japan in 2010, Research in Veterinary Science, 102 (2015), 228-230.  doi: 10.1016/j.rvsc.2015.08.017. [37] X. Zhang, Global dynamics of a stochastic avian-human influenza epidemic model with logistic growth for avian population, Nonlinear Dynamics, 90 (2017), 2331-2343.  doi: 10.1007/s11071-017-3806-5. [38] X. Zhang and X. Liu, Backward bifurcation of an epidemic model with saturated treatment function, Journal of Mathematical Analysis and Applications, 348 (2008), 433-443.  doi: 10.1016/j.jmaa.2008.07.042.
Schematic diagram of the model with delay
The optimal states of $I_a(t)$ and $I_h(t)$, and optimal controls under all of control
The optimal states of $I_a(t)$ and $I_h(t)$ with one control and without control
The optimal states of $I_a(t)$ and $I_h(t)$ with two controls and without control
Values of objective function under different time delays for model (6)
Effect of $\mathscr{R}_0$
Effect of $\alpha$
Effect of $\alpha_1$
Effect of $\alpha_2$
Effect of $\beta_1$
Effect of $\beta_1$
Algorithm
 Step 1: for $k = -m, -(m-1), ..., 0$ do: $S_a^k = S_a(0); I_a^k = I_a(0); S_h^k = S_h(0); I_h^k = I_h(0); R_h^k = R_h(0)$ end for for $k = n, n+1, ..., n+m$ do: $\lambda_1^k = 0; \lambda_2^k = 0; \lambda_3^k = 0; \lambda_4^k = 0; \lambda_5^k = 0$ end for $m_1 = \lfloor\tau_1/\Delta\rfloor$; $m_2 = \lfloor\tau_2/\Delta\rfloor$ Step 2: for $k = 0, 1, ..., n-1$ do: $S_a^{k+1} = S_a^{k} + \Delta\left[\Lambda_{a} -\frac{\beta_{a} S_{a}^k I_{a}^k}{1 +\alpha_{1} S_{a}^k+\alpha_{2} I_{a}^k}-(\mu_{a} +u_{1}(t)) S_{a}^k \right]$ $I_a^{k+1} = I_a^{k} + \Delta\left[ \frac{\beta_{a} e^{-\mu_{a} \tau_{1}}S_{a}^{k-m_1} I_{a}^{k-m_1}}{1 +\alpha_{1}S_{a}^{k-m_1} +\alpha_{2} I_{a}^{k-m_1}} -(\mu_{a} +\delta_{a} +u_{1}^k) I_{a}^k \right]$ $S_h^{k+1} = S_h^{k} + \Delta\left[ \Lambda_{h} -(1-u_{2}^k) \frac{\beta_{h} S_{h}^k I_{a}^k}{1 +\beta_{1}S_{h}^k +\beta_{2}I_{a}^k} -\mu_{h}S_{h}^k \right]$ $I_h^{k+1} = I_h^{k} + \Delta\Big[ (1-u_{2}^{k-m_2}) \frac{\beta_{h}e^{ -\mu_{h}\tau_{2}} S_{h}^{k-m_2} I_{a}^{k-m_2}}{1 +\beta_{1} S_{h}^{k-m_2} +\beta_{2} I_{a}^{k-m_2}}$ $-(\mu_{h} +\delta_{h} +\gamma) I_{h}^k -\frac{c u_{3}^k I_{h}^k}{1+\alpha I_{h}^k} \Big]$ $R_h^{k+1} = R_h^{k} + \Delta\left[ \gamma I_{h}^k -\mu_{h}R_{h}^k +\frac{c u_{3}^k I_{h}^k}{1 +\alpha I_{h}^k} \right]$ for $j = 1, 2, 3, 4, 5$ do: $\lambda_j^{n-k-1} = \lambda_j^{n-k} - \Delta\times\text{Temp}_j$ end for $D_1^{k+1} = [(\lambda_{1}^{n-k}-B_{1})S_{a}^k +(\lambda_{2}^{n-k} -B_{1})I_{a}^k]/C_{1}$; $D_2^{k+1} = \text{Temp}_6/C_2$ $D_3^{k+1} = \left[(\lambda_{4}^{n-k} -\lambda_{5}^{n-k}) \frac{c I_{h}^k}{1+\alpha I_{h}^k} -B_{3}I_{h}^k \right] /C_3$ $u_1^{k+1} = \min\{\max(0, D_1^{k+1}), 1\}$; $u_2^{k+1} = \min\{\max(0, D_2^{k+1}), 1\}$ $u_3^{k+1} = \min\{\max(0, D_3^{k+1}), 1\}$ end for Step 3: for $k = 1, 2, ..., n$ do: $S_a^*(t_k) = S_a^k; I_a^*(t_k) = I_a^k; S_h^*(t_k) = S_h^k; I_h^*(t_k) = I_h^k; R_h^*(t_k) = R_h^k$ $u_1^*(t_k) = u_1^k; u_2^*(t_k) = u_2^k; u_3^*(t_k) = u_3^k$ end for $\dagger$ The $\text{Temp}_i (1\leq i\leq 6)$ is defined in C.
 Step 1: for $k = -m, -(m-1), ..., 0$ do: $S_a^k = S_a(0); I_a^k = I_a(0); S_h^k = S_h(0); I_h^k = I_h(0); R_h^k = R_h(0)$ end for for $k = n, n+1, ..., n+m$ do: $\lambda_1^k = 0; \lambda_2^k = 0; \lambda_3^k = 0; \lambda_4^k = 0; \lambda_5^k = 0$ end for $m_1 = \lfloor\tau_1/\Delta\rfloor$; $m_2 = \lfloor\tau_2/\Delta\rfloor$ Step 2: for $k = 0, 1, ..., n-1$ do: $S_a^{k+1} = S_a^{k} + \Delta\left[\Lambda_{a} -\frac{\beta_{a} S_{a}^k I_{a}^k}{1 +\alpha_{1} S_{a}^k+\alpha_{2} I_{a}^k}-(\mu_{a} +u_{1}(t)) S_{a}^k \right]$ $I_a^{k+1} = I_a^{k} + \Delta\left[ \frac{\beta_{a} e^{-\mu_{a} \tau_{1}}S_{a}^{k-m_1} I_{a}^{k-m_1}}{1 +\alpha_{1}S_{a}^{k-m_1} +\alpha_{2} I_{a}^{k-m_1}} -(\mu_{a} +\delta_{a} +u_{1}^k) I_{a}^k \right]$ $S_h^{k+1} = S_h^{k} + \Delta\left[ \Lambda_{h} -(1-u_{2}^k) \frac{\beta_{h} S_{h}^k I_{a}^k}{1 +\beta_{1}S_{h}^k +\beta_{2}I_{a}^k} -\mu_{h}S_{h}^k \right]$ $I_h^{k+1} = I_h^{k} + \Delta\Big[ (1-u_{2}^{k-m_2}) \frac{\beta_{h}e^{ -\mu_{h}\tau_{2}} S_{h}^{k-m_2} I_{a}^{k-m_2}}{1 +\beta_{1} S_{h}^{k-m_2} +\beta_{2} I_{a}^{k-m_2}}$ $-(\mu_{h} +\delta_{h} +\gamma) I_{h}^k -\frac{c u_{3}^k I_{h}^k}{1+\alpha I_{h}^k} \Big]$ $R_h^{k+1} = R_h^{k} + \Delta\left[ \gamma I_{h}^k -\mu_{h}R_{h}^k +\frac{c u_{3}^k I_{h}^k}{1 +\alpha I_{h}^k} \right]$ for $j = 1, 2, 3, 4, 5$ do: $\lambda_j^{n-k-1} = \lambda_j^{n-k} - \Delta\times\text{Temp}_j$ end for $D_1^{k+1} = [(\lambda_{1}^{n-k}-B_{1})S_{a}^k +(\lambda_{2}^{n-k} -B_{1})I_{a}^k]/C_{1}$; $D_2^{k+1} = \text{Temp}_6/C_2$ $D_3^{k+1} = \left[(\lambda_{4}^{n-k} -\lambda_{5}^{n-k}) \frac{c I_{h}^k}{1+\alpha I_{h}^k} -B_{3}I_{h}^k \right] /C_3$ $u_1^{k+1} = \min\{\max(0, D_1^{k+1}), 1\}$; $u_2^{k+1} = \min\{\max(0, D_2^{k+1}), 1\}$ $u_3^{k+1} = \min\{\max(0, D_3^{k+1}), 1\}$ end for Step 3: for $k = 1, 2, ..., n$ do: $S_a^*(t_k) = S_a^k; I_a^*(t_k) = I_a^k; S_h^*(t_k) = S_h^k; I_h^*(t_k) = I_h^k; R_h^*(t_k) = R_h^k$ $u_1^*(t_k) = u_1^k; u_2^*(t_k) = u_2^k; u_3^*(t_k) = u_3^k$ end for $\dagger$ The $\text{Temp}_i (1\leq i\leq 6)$ is defined in C.
Parameter values of numerical experiments for model (2)
 Parameter Value Source of data $\Lambda_a$ $1000/245$ per day [5,9] $\beta_a$ $5.1\times10^{-4}$ per day [5], $\mu_a$ $1/245$ per day [5,9] $\delta_a$ $1/400$ per day [5] $\Lambda_h$ $2000/36500$ per day [5] $\beta_h$ $2\times10^{-6}$ per day [5] $\mu_h$ $5.48\times10^{-5}$ per day [26,37] $\delta_h$ 0.001 per day [26,37] $\gamma$ 0.1 per day [26,37] $c$ 0.5 Assumed $\alpha$ 0.1 Assumed $\alpha_1$ 0.01 Assumed $\alpha_2$ 0.03 Assumed $\beta_1$ 0.01 Assumed $\beta_2$ 0.01 Assumed
 Parameter Value Source of data $\Lambda_a$ $1000/245$ per day [5,9] $\beta_a$ $5.1\times10^{-4}$ per day [5], $\mu_a$ $1/245$ per day [5,9] $\delta_a$ $1/400$ per day [5] $\Lambda_h$ $2000/36500$ per day [5] $\beta_h$ $2\times10^{-6}$ per day [5] $\mu_h$ $5.48\times10^{-5}$ per day [26,37] $\delta_h$ 0.001 per day [26,37] $\gamma$ 0.1 per day [26,37] $c$ 0.5 Assumed $\alpha$ 0.1 Assumed $\alpha_1$ 0.01 Assumed $\alpha_2$ 0.03 Assumed $\beta_1$ 0.01 Assumed $\beta_2$ 0.01 Assumed
Values of objective function under different control variables for model (2)
 Value of control $\mathbf{u(t)}$ Value of objective function ($\times10^4$) $u_1(t), u_2(t), u_3(t)\equiv0$ (Without control) $1.4681$ $u_1(t) \neq 0, u_2(t), u_3(t)\equiv0$ $1.2038$ $u_2(t) \neq 0, u_1(t), u_3(t)\equiv0$ $1.4692$ $u_3(t) \neq 0, u_1(t), u_2(t)\equiv0$ $1.4684$ $u_1(t), u_2(t) \neq 0, u_3(t)\equiv0$ $1.2039$ $u_1(t), u_3(t) \neq 0, u_2(t)\equiv0$ $1.2041$ $u_2(t), u_3(t) \neq 0, u_1(t)\equiv0$ $1.4692$ $u_1(t), u_2(t), u_3(t) \neq 0$ (With all of controls) $1.2043$
 Value of control $\mathbf{u(t)}$ Value of objective function ($\times10^4$) $u_1(t), u_2(t), u_3(t)\equiv0$ (Without control) $1.4681$ $u_1(t) \neq 0, u_2(t), u_3(t)\equiv0$ $1.2038$ $u_2(t) \neq 0, u_1(t), u_3(t)\equiv0$ $1.4692$ $u_3(t) \neq 0, u_1(t), u_2(t)\equiv0$ $1.4684$ $u_1(t), u_2(t) \neq 0, u_3(t)\equiv0$ $1.2039$ $u_1(t), u_3(t) \neq 0, u_2(t)\equiv0$ $1.2041$ $u_2(t), u_3(t) \neq 0, u_1(t)\equiv0$ $1.4692$ $u_1(t), u_2(t), u_3(t) \neq 0$ (With all of controls) $1.2043$
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