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Articles

Analysis of latent CHIKV dynamics models with general incidence rate and time delays

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Pages 700-730 | Received 14 Sep 2017, Accepted 17 Jul 2018, Published online: 01 Aug 2018

ABSTRACT

In this paper, we study the stability analysis of latent Chikungunya virus (CHIKV) dynamics models. The incidence rate between the CHIKV and the uninfected monocytes is modelled by a general nonlinear function which satisfies a set of conditions. The model is incorporated by intracellular discrete or distributed time delays. Using the method of Lyapunov function, we established the global stability of the steady states of the models. The theoretical results are confirmed by numerical simulations.

1. Introduction

Chikungunya virus (CHIKV) is an alphavirus and is transmitted to humans by Aedes aegypti and Aedes albopictus mosquitos. The CHIKV attacks the monocytes and causes Chikungunya fever. The humoral response is important to limit the CHIKV progression [Citation33]. In the literature of CHIKV infection, most of the mathematical models have been presented to describe the disease transmission in mosquito and human populations (see e.g. [Citation3–5,Citation31,Citation35,Citation37,Citation38,Citation48]). In a very recent work, Wang and Liu [Citation43] have presented a mathematical model for in host CHIKV infection as (1) S˙=μaSbSV,(1) (2) I˙=bSVϵI,(2) (3) V˙=mIrVqBV,(3) (4) B˙=η+cBVδB,(4) where S, I, V, and B are the concentrations of uninfected monocytes, infected monocytes, CHIKV particles and B cells, respectively. The uninfected monocytes are created at rate μ and die at rate aS. The uninfected monocytes are attacked by the CHIKV at rate bSV, where b is rate constant of the CHIKV-target incidence. The infected monocytes and free CHIKV particles die are rates ϵI and rV, respectively. An actively infected monocytes produces an average number m of CHIKV particles. The CHIKV particles are attacked by the B cells at rate qBV. The B cells are created at rate η, proliferated at rate cBV and die at rate δB.

In recent years, stability analysis of virus dynamics models has become one of the hot topics in virology (see e.g. [Citation1,Citation2,Citation6,Citation24,Citation26,Citation30,Citation32,Citation36,Citation39,Citation42,Citation44,Citation47]). Studying the stability analysis of the models is important for developing antiviral drugs, understanding the virus-host interaction and for predicting the disease progression. Stability of model (Equation1)–(Equation4) has been studied by Wang and Liu [Citation43].

In system (Equation1)–(Equation4) it is assumed that the incidence rate between the CHIKV and uninfected monocytes is given by bilinear form. However, such bilinear form is imperfect to depict the dynamical behaviour of the viral infection in detail [Citation27]. Moreover, it is assumed that when the CHIKV contacts the uninfected monocytes it becomes infected and viral producer in the same time. In [Citation34], the authors have described the CHIKV replication cycle as (see Figure ):

Figure 1. CHIKV replication cycle [Citation34].

Figure 1. CHIKV replication cycle [Citation34].

The virus enters susceptible cells through endocytosis, mediated by an unknown receptor. As the endosome is acidic, conformational changes occur resulting in the fusion of the viral and host cell membranes, causing the release of the nucleocapsid into the cytoplasm, The RNA genome is first translated into the 4nsPs, which together will form the replication complex and assist in several downstream processes (depicted by dashed arrowed line in Figure ). Subsequently, the genome is replicated to its negative-sense strand, which in turn will be used as a template for the synthesis of the 49S viral RNA and 26S subgenomic mRNA. The 26S subgenomic mRNA will be translated to give the structural proteins (C–pE2–6K–E1). After a round of processing by serine proteases, the capsid is released into the cytoplasm. The remaining structural proteins are further modified post-translationally in the endoplasmic reticulum and subsequently in the Golgi apparatus. E1 and E2 associate as a dimer and are transported to the host plasma membrane, where they will ultimately be incorporated onto the virion surface as trimeric spikes. Capsid protein will form the icosahedral nucleocapsid that will contain the replicated 49S genomic RNA before being assembled into a mature virion ready for budding. During budding the virions will acquire a membrane bilayer from part of the host cell membrane.

Therefore, this process may take time period which can be incroporated into the CHIKV model by considering the time delay and latently infeced cells.

The objective of this paper is to propose a CHIKV infection model which improves the model presented in [Citation43] by taking into account (i) two types of infected monocytes, latently infected monocytes and actively infected monocytes, (ii) two types of discrete or distributed time delays (iii) the incidence rate between the CHIKV and the uninfected monocytes is given by a general nonlinear function Ψ(S,V), where the function Ψ is supposed to satisfy a set of conditions. We investigate the nonnegativity and boundedness of the solutions of the CHIKV dynamics model. We show that the CHIKV dynamics is governed by one bifurcation parameter (the basic reproduction numbers R0). We use Lyapunov direct method to establish the global stability of the model's steady states.

2. CHIKV model with discrete time delays

We propose the following latent CHIKV dynamics model with general incidence rate taking into account two discrete time delays: (5) S˙(t)=μaS(t)Ψ(S(t),V(t)),(5) (6) L˙(t)=(1ρ)eδ1τ1Ψ(S(tτ1),V(tτ1))(θ+λ)L(t),(6) (7) I˙(t)=ρeδ2τ2Ψ(S(tτ2),V(tτ2))+λL(t)ϵI(t),(7) (8) V˙(t)=mI(t)rV(t)qB(t)V(t),(8) (9) B˙(t)=η+cB(t)V(t)δB(t),(9) where L and I are the concentrations of latently infected monocytes and actively infected monocytes, respectively. The parameter λ is the latent to active transmission rate constant. A fraction (1ρ) of infected cells is assumed to be latently infected monocytes and the remaining ρ becomes actively infected monocytes, where 0<ρ<1. Here, τ1 is the time between CHIKV entry an uninfected monocyte to become latently infected monocyte (such monocyte contains the CHIKV but is not producing it), and τ2 is the time between CHIKV entry an uninfected monocyte to become actively infected monocyte (such monocyte produces the CHIKV particles). The probability of latently and actively infected monocytes surviving to the age of τ1 and τ2 are represented by eδ1τ1 and eδ2τ2, respectively, where δ1>0 and δ2>0 are constants. The incidence of new infections of uninfected monocytes occurs at a rate Ψ(S,V), which includes the rate of contacts between CHIKV and uninfected monocytes as well as the probability of cell entry per contact [Citation42].

We consider the following initial conditions: (10) S(ϑ)=ϕ1(ϑ),L(ϑ)=ϕ2(ϑ),I(ϑ)=ϕ3(ϑ),V(ϑ)=ϕ4(ϑ),B(ϑ)=ϕ5(ϑ),ϕi(ϑ)0,ϑϱ,0andϕiCϱ,0,R0,i=1,2,,5,(10) where ϱ=max{τ1,τ2} and C is the Banach space of continuous functions mapping the interval [ϱ,0] into R0 with norm ϕj=supϱϑ0|ϕj(ϑ)|. Then the uniqueness of the solution for t>0 is guaranteed [Citation25].

The function Ψ is assumed to satisfy the following:

Assumption 2.1

  1. Ψ is continuously differentiable, Ψ(S,V)>0,Ψ(0,V)=Ψ(S,0)=0 for all S>0,V>0,

  2. ∂Ψ(S,V)/S>0,∂Ψ(S,V)/V>0,∂Ψ(S,0)/V>0 for all S>0,V>0.

  3. (d/dS)(∂Ψ(S,0)/V)>0 for all S>0.

Assumption 2.2

Ψ(S,V)/V is a decreasing function of V for all S>0,V>0,

Remark 2.1

Assumption 2.1(iii) implies that (11) 1∂Ψ(S0,0)/V∂Ψ(S,0)/V1SS00.(11) From 2.2 we get (12) Ψ(S,V)VlimV0+Ψ(S,V)V=∂Ψ(S,0)V.(12) From 2.1(ii) and 2.2 we obtain Ψ(S,V)VΨ(S,V1)V1Ψ(S,V)Ψ(S,V1)0, which yields (13) Ψ(S,V)Ψ(S,V1)VV11Ψ(S,V1)Ψ(S,V)0.(13)

2.1. Preliminaries

In this subsection we investigate the nonnegativity and boundedness of the solutions of model (Equation5)–(Equation9).

Lemma 2.1

The solutions of system (Equation5)–(Equation9) with the initial states (Equation10) are nonnegative and ultimately bounded.

Proof.

From Equations (Equation5) and (Equation9) we have S˙|S=0=μ>0 and B˙|B=0=η>0. Thus, S(t)>0 and B(t)>0 for all t0. Moreover, for t[0,τ] we have L(t)=ϕ2(0)e(θ+λ)t+(1ρ)eδ1τ1×0tΨ(S(ωτ1),V(ωτ1))e(θ+λ)(tω)dω0,I(t)=ϕ3(0)eϵt+ρeδ2τ20tΨ(S(ωτ2),V(ωτ2))+λL(ω)eϵ(tω)dω0,V(t)=ϕ4(0)e0t(r+qB(z))dz+0tmI(ω)eωt(r+qB(z))dzdω0. By recursive argument, we get L(t)0,I(t)0 and V(t)0 for all t0.

Next, we establish the boundedness of the model's solutions. Let M1=μ/σ1 where σ1=min{a,θ,ϵ}. The nonnegativity of the model's solution implies that dS(t)/dtμaS(t), which yields limtsupS(t)μ/aM1. Let us define T1(t)=(1ρ)eδ1τ1S(tτ1)+ρeδ2τ2S(tτ2)+L(t)+I(t) then T˙1(t)=(1ρ)eδ1τ1μaS(tτ1)Ψ(S(tτ1),V(tτ1))+(1ρ)eδ1τ1Ψ(S(tτ1),V(tτ1))(θ+λ)L(t)+ρeδ2τ2μaS(tτ2)Ψ(S(tτ2),V(tτ2))+ρeδ2τ2Ψ(S(tτ2),V(tτ2))+λL(t)ϵI(t)=μ(1ρ)eδ1τ1+ρeδ2τ2a(1ρ)eδ1τ1S(tτ1)+ρeδ2τ2S(tτ2)θL(t)ϵI(t). Since (1ρ)eδ1τ1+ρeδ2τ2<1, then T˙1(t)μσ1(1ρ)eδ1τ1S(tτ1)+ρeδ2τ2S(tτ2)+L(t)+I(t)=μσ1T1(t), It follows that limtsupT1(t)M1, limtsupL(t)M1, limtsupI(t)M1. Let us define T2(t)=V(t)+qcB(t). Then T˙2(t)=mI(t)rV(t)qV(t)B(t)+qcη+cB(t)V(t)δB(t)=qηc+mI(t)rV(t)qδcB(t)qηc+mM1rV(t)qδcB(t)qηc+mM1σ2V(t)+qcB(t)=qηc+mM1σ2T2(t),σ2=min{r,δ}, limtsupV(t)M2, and limtsupB(t)M3, M2=qη/cσ2+mM1/σ2 and M3=(c/q)M2. Therefore, S(t),L(t),I(t),V(t) and B(t) are ultimately bounded.

Lemma 2.1 reveal that the following positively invariant set contains omega limit sets of system (Equation5)–(Equation8): Ω=(S,L,I,V,B)C5:SM1,LM1,IM1,VM2,BM3.

2.2. The existence of steady states

The basic reproduction number of system (Equation5)–(Equation9) is given by R0=mγϵ(θ+λ)(r+qB0)∂Ψ(S0,0)V, where S0=μ/a, B0=η/δ and γ=λ(1ρ)eδ1τ1+ρeδ2τ2(θ+λ).

Lemma 2.2

For system (Equation5)–(Equation9), assume that Assumptions 2.1–2.2 are satisfied, then there exists a threshold parameter R0>0 such that if R01, then the CHIKV-free steady state Q0 is the only steady state for the system. If R0>1, then the system has a unique endemic steady state Q1.

Proof.

Let Q(S,L,I,V,B) be any steady state of the system (Equation5)–(Equation9) satisfying the following equations: (14) 0=μaSΨ(S,V),(14) (15) 0=(1ρ)eδ1τ1Ψ(S,V)(θ+λ)L,(15) (16) 0=ρeδ2τ2Ψ(S,V)+λLϵI,(16) (17) 0=mIrVqBV,(17) (18) 0=η+cBVδB.(18) From Equations (Equation14)–(Equation18) we obtain (19) L=(1ρ)eδ1τ1Ψ(S,V)θ+λ,I=γΨ(S,V)ϵ(θ+λ).(19) Substituting Equation (Equation19) into Equation (Equation17) we have (20) mγΨ(S,V)ϵ(θ+λ)rVqBV=0.(20) Applying Assumption A1, we have V =0 is one of the solutions of Equation (Equation20), which gives a CHIKV-free steady state Q0=(S0,L0,I0,V0,B0). If V0, then from Equations (Equation14) and (Equation20) we have V=mγΨ(S,V)ϵ(θ+λ)(r+qB)=mγ(μaS)ϵ(θ+λ)(r+qB), which implies S=S0ϵ(θ+λ)(r+qB)amγV. Then, from Equation (Equation18) we have B=η/(δcV). We define a function Φ1 as Φ1(V)=mγϵ(θ+λ)ΨS0ϵ(θ+λ)(r(δcV)+qη)amγ(δcV)V,V(r(δcV)+qη)δcVV=0. Now we get a value of V such that (21) S0ϵ(θ+λ)(r(δcV)+qη)amγ(δcV)V=0,Vδc.(21) Let α1=ϵ(θ+λ)/amγ, then Equation (Equation21) becomes crα1V2(cS0+α1rδ+qη)V+δS0=0. Let K1(V)=crα1V2(cS0+α1rδ+qη)V+δS0=0, we have K1(0)=δS0>0, K1(δ/c)=qηα1δ/c<0 and K1(0)=(cS0+α1(rδ+qη))<0. Then K1(V)=0 gives a unique V=V~(0,δ/c). It follows that B~=η/(δcV~)>0. Clearly, Φ1(0)=0,Φ1(V~)=mγϵ(θ+λ)Ψ(0,V~)(r+qB~)V~=(r+qB~)V~<0,Φ1(0)=mγϵ(θ+λ)ϵ(θ+λ)(r+qB0)amγ∂Ψ(S0,0)S+∂Ψ(S0,0)V(r+qB0). From Assumption 2.1, ∂Ψ(S0,0)/S=0, then Φ1(0)=mγϵ(θ+λ)∂Ψ(S0,0)V(r+qB0)=(r+qB0)R01. Therefore, if R0>1, then Φ1(0)>0 and there exists a V1(0,V~) such that Φ1(V1)=0. From Equations (Equation17) and (Equation18) we obtain B1=ηδcV1>0,I1=(r+qB1)mV1>0. Let V=V1 in Equation (Equation14) and define a function Φ2 as Φ2(S)=μaSΨ(S,V1)=0. By Assumption 2.1, we have Φ2(0)=μ>0 and Φ2(S0)=Ψ(S0,V1)<0. Since Φ2 is a strictly decreasing function of S, then there exists a unique S1(0,S0) such that Φ2(S1)=0. Thus an endemic steady state Q1=(S1,L1,I1,V1,B1) exists when R0>1.

2.3. Global stability

The following theorems investegate the global stability of the CHIKV-free and endemic steady states of system (Equation5)–(Equation8) by constructing suitable Lyapunov functionals. We define H(x)=xlnx1. Clearly, H(1)=0 and H(x)0 for x>0. Denote (S,L,I,V,B)=(S(t),L(t),I(t),V(t),B(t)).

Theorem 2.1

Suppose that R01 and 2.1–2.2 are satisfied, then Q0 is GAS.

Proof.

Define W0(S,L,I,V,B)=γθ+λSS0S0SlimV0+Ψ(S0,V)Ψ(ϑ,V)dϑ+λθ+λL+I+ϵmV+ϵqmcB0HBB0+λ(1ρ)eδ1τ1θ+λ0τ1Ψ(S(tϑ),V(tϑ))dϑ+ρeδ2τ20τ2Ψ(S(tϑ),V(tϑ))dϑ. Note that, W0(S,L,I,V,B)>0 for all S,L,I,V,B>0 and W0(S0,0,0,0,B0)=0. Calculating dW0/dt along the trajectories of (Equation5)–(Equation9) we get (22) dW0dt=γθ+λ1limV0+Ψ(S0,V)Ψ(S,V)μaSΨ(S,V)+λθ+λ(1ρ)eδ1τ1Ψ(S(tτ1),V(tτ1))(θ+λ)L+ρeδ2τ2Ψ(S(tτ2),V(tτ2))+λLϵI+ϵmmIrVqBV+ϵqmc1B0Bη+cBVδB+λ(1ρ)eδ1τ1θ+λΨ(S,V)Ψ(S(tτ1),V(tτ1)+ρeδ2τ2Ψ(S,V)Ψ(S(tτ2),V(tτ2)).(22) Simplifying Equation (Equation22) we get dW0dt=γθ+λ1limV0+Ψ(S0,V)Ψ(S,V)(μaS)+γθ+λΨ(S,V)limV0+Ψ(S0,V)Ψ(S,V)ϵmrVϵqmB0V+ϵqmc1B0BηδB=γθ+λ1∂Ψ(S0,0)/V∂Ψ(S,0)/V(μaS)+γθ+λΨ(S,V)∂Ψ(S0,0)/V∂Ψ(S,0)/VϵmrVϵqmB0V+ϵqmc1B0BηδB. Using a=μ/S0, η=δB0 and inequality (Equation12) we get (23) dW0dtμγθ+λ1∂Ψ(S0,0)/V∂Ψ(S,0)/V1SS0+γθ+λV∂Ψ(S0,0)VϵmrVϵqmB0V+ϵqmc1B0BδB0δB=μγθ+λ1∂Ψ(S0,0)/V∂Ψ(S,0)/V1SS0+ϵ(r+qB0)m×mγϵ(θ+λ)(r+qB0)∂Ψ(S0,0)V1Vϵqδmc(BB0)2B=μγθ+λ1∂Ψ(S0,0)/V∂Ψ(S,0)/V1SS0+ϵ(r+qB0)mR01Vϵqδmc(BB0)2B.(23) From Assumption 2.1 we have, if R01, then dW0/dt0 for all S,V,B>0. Also, dW0/dt=0 if and only if S=S0, B=B0 and V=0. Let Γ0={(S,L,I,V,B):dW0/dt=0} and Γ0 be the largest invariant subset of Γ0. The solutions of system (Equation5)–(Equation9) converge to Γ0 [Citation25]. Each element in Γ0 satisfies V(t)=V˙(t)=0. Then from Equations (Equation7)–(Equation8) we have L(t)=I(t)=0. By the LaSalle's invariance principle, Q0 is GAS.

Theorem 2.2

Suppose that R0>1 and 2.1–2.2 are satisfied, then Q1 is GAS.

Proof.

W1(S,L,I,V,B)=γθ+λSS1S1SΨ(S1,V1)Ψ(ϑ,V1)dϑ+λθ+λL1HLL1+I1HII1+ϵmV1HVV1+ϵqmcB1HBB1+λ(1ρ)eδ1τ1θ+λΨ(S1,V1)×0τ1HΨ(S(tϑ),V(tϑ))Ψ(S1,V1)dϑ+ρeδ2τ2Ψ(S1,V1)0τ2HΨ(S(tϑ),V(tϑ))Ψ(S1,V1)dϑ. We have W1(S,L,I,V,B)>0 for all S,L,I,V,B>0 and W1(S1,L1,I1,V1,B1)=0. Calculating dW1/dt along the trajectories of (Equation5)–(Equation9) we get (24) dW1dt=γθ+λ1Ψ(S1,V1)Ψ(S,V1)μaSΨ(S,V)+λθ+λ1L1L(1ρ)eδ1τ1Ψ(S(tτ1),V(tτ1))(θ+λ)L+1I1Iρeδ2τ2Ψ(S(tτ2),V(tτ2))+λLϵI+ϵm1V1VmIrVqBV+ϵqmc1B1Bη+cBVδB+λ(1ρ)eδ1τ1θ+λΨ(S,V)Ψ(S(tτ1),V(tτ1)+λ(1ρ)eδ1τ1θ+λΨ(S1,V1)lnΨ(S(tτ1),V(tτ1))Ψ(S,V)+ρeδ2τ2Ψ(S,V)Ψ(S(tτ2),V(tτ2))+ρeδ2τ2Ψ(S1,V1)lnΨ(S(tτ2),V(tτ2))Ψ(S,V).(24) Simplifying Equation (Equation24) we get dW1dt=γθ+λ1Ψ(S1,V1)Ψ(S,V1)μaS+γθ+λΨ(S,V)Ψ(S1,V1)Ψ(S,V1)λ(1ρ)eδ1τ1θ+λΨ(S(tτ1),V(tτ1))L1L+λL1ρeδ2τ2Ψ(S(tτ2),V(tτ2))I1IλLI1I+ϵI1ϵV1IVϵmrV+ϵmrV1+ϵqmBV1ϵqmB1V+ϵqmc1B1BηδB+λ(1ρ)eδ1τ1θ+λΨ(S1,V1)lnΨ(S(tτ1),V(tτ1))Ψ(S,V)+ρeδ2τ2Ψ(S1,V1)lnΨ(S(tτ2),V(tτ2))Ψ(S,V). Applying μ=aS1+Ψ(S1,V1),η=δB1cB1V1, we obtain dW1dt=γθ+λ1Ψ(S1,V1)Ψ(S,V1)aS1aS+γθ+λΨ(S1,V1)1Ψ(S1,V1)Ψ(S,V1)+γθ+λΨ(S,V)Ψ(S1,V1)Ψ(S,V1)λ(1ρ)eδ1τ1θ+λΨ(S(tτ1),V(tτ1))L1L+λL1ρeδ2τ2Ψ(S(tτ2),V(tτ2))I1IλLI1I+ϵI1ϵV1IVϵmrV+ϵmrV1+ϵqmBV1ϵqmB1V1+ϵqmB1V1B1BϵqmB1V+ϵqmc1B1BδB1δB+λ(1ρ)eδ1τ1θ+λΨ(S1,V1)lnΨ(S(tτ1),V(tτ1))Ψ(S,V)+ρeδ2τ2Ψ(S1,V1)lnΨ(S(tτ2),V(tτ2))Ψ(S,V). From Lemma 2.2 we have (1ρ)eδ1τ1Ψ(S1,V1)=(θ+λ)L1,ρeδ2τ2Ψ(S1,V1)+λL1=ϵI1,mI1=rV1+qB1V1, then ϵmrV1=γθ+λΨ(S1,V1)ϵqmB1V1, and (25) dW1dt=aS1γθ+λ1Ψ(S1,V1)Ψ(S,V1)1SS1+γθ+λΨ(S1,V1)Ψ(S,V)Ψ(S,V1)VV1+γθ+λΨ(S1,V1)1Ψ(S1,V1)Ψ(S,V1)λ(1ρ)eδ1τ1θ+λΨ(S1,V1)×Ψ(S(tτ1),V(tτ1))L1Ψ(S1,V1)L+λ(1ρ)eδ1τ1θ+λΨ(S1,V1)ρeδ2τ2Ψ(S1,V1)Ψ(S(tτ2),V(tτ2))Ψ(S1,V1)I1Iγθ+λΨ(S1,V1)IV1I1Vλ(1ρ)eδ1τ1θ+λΨ(S1,V1)LI1L1I+λ(1ρ)eδ1τ1θ+λΨ(S1,V1)+ρeδ2τ2Ψ(S1,V1)+λ(1ρ)eδ1τ1θ+λΨ(S1,V1)+ρeδ2τ2Ψ(S1,V1)2ϵqmB1V1+ϵqmBV1+ϵqmB1V1B1Bϵqδmc(BB1)2B+λ(1ρ)eδ1τ1θ+λΨ(S1,V1)lnΨ(S(tτ1),V(tτ1))Ψ(S,V)+ρeδ2τ2Ψ(S1,V1)lnΨ(S(tτ2),V(tτ2))Ψ(S,V).(25) Using the following equalities: lnΨ(S(tτ1),V(tτ1))Ψ(S,V)=lnΨ(S1,V1)Ψ(S,V1)+lnIV1I1V+lnLI1L1I+lnVΨ(S,V1)V1Ψ(S,V)+lnL1Ψ(S(tτ1),V(tτ1))LΨ(S1,V1),lnΨ(S(tτ2),V(tτ2))Ψ(S,V)=lnΨ(S1,V1)Ψ(S,V1)+lnIV1I1V+lnVΨ(S,V1)V1Ψ(S,V)+lnI1Ψ(S(tτ2),V(tτ2))IΨ(S1,V1), we get dW1dt=aS1γθ+λ1Ψ(S1,V1)Ψ(S,V1)1SS1+γθ+λΨ(S1,V1)×1+Ψ(S,V)Ψ(S,V1)VV1+VΨ(S,V1)V1Ψ(S,V)+λ(1ρ)eδ1τ1θ+λΨ(S1,V1)1Ψ(S1,V1)Ψ(S,V1)+lnΨ(S1,V1)Ψ(S,V1)+λ(1ρ)eδ1τ1θ+λΨ(S1,V1)1IV1I1V+lnIV1I1V+λ(1ρ)eδ1τ1θ+λΨ(S1,V1)1LI1L1I+lnLI1L1I+λ(1ρ)eδ1τ1θ+λΨ(S1,V1)1VΨ(S,V1)V1Ψ(S,V)+lnVΨ(S,V1)V1Ψ(S,V)+λ(1ρ)eδ1τ1θ+λΨ(S1,V1)1L1Ψ(S(tτ1),V(tτ1))LΨ(S1,V1)+lnL1Ψ(S(tτ1),V(tτ1))LΨ(S1,V1)+ρeδ2τ2Ψ(S1,V1)1Ψ(S1,V1)Ψ(S,V1)+lnΨ(S1,V1)Ψ(S,V1)+ρeδ2τ2Ψ(S1,V1)×1IV1I1V+lnIV1I1V+ρeδ2τ2Ψ(S1,V1)1I1Ψ(S(tτ2),V(tτ2))IΨ(S1,V1)+lnI1Ψ(S(tτ2),V(tτ2))IΨ(S1,V1)+ρeδ2τ2Ψ(S1,V1)1VΨ(S,V1)V1Ψ(S,V)+lnVΨ(S,V1)V1Ψ(S,V)ϵqδmc(BB1)2BϵqB1V1m2BB1B1B (26) =aS1γθ+λ1Ψ(S1,V1)Ψ(S,V1)1SS1+γθ+λΨ(S1,V1)×Ψ(S,V)Ψ(S,V1)VV11Ψ(S,V1)Ψ(S,V)ϵqηmcB1(BB1)2Bλ(1ρ)eδ1τ1θ+λΨ(S1,V1)×HΨ(S1,V1)Ψ(S,V1)+HIV1I1V+HLI1L1I+HVΨ(S,V1)V1Ψ(S,V)+HL1Ψ(S(tτ1),V(tτ1))LΨ(S1,V1)ρeδ2τ2Ψ(S1,V1)HΨ(S1,V1)Ψ(S,V1)+HIV1I1V+HVΨ(S,V1)V1Ψ(S,V)+HI1Ψ(S(tτ2),V(tτ2))IΨ(S1,V1).(26) Using Assumption 2.1(ii) and inequality (Equation13), we get dW1/dt0. Let Γ1={(S,L,I,V,B):dW1/dt=0} and Γ1 be the largest invariant subset of Γ1. It can be verified that dW1/dt=0 if and only if S=S1, B=B1, and (27) LL1=II1=VV1=Ψ(S1,V)Ψ(S1,V1).(27) For each element of Γ1 we have B=B1, then B˙(t)=0=η+cB1V(t)δB1, which gives V(t)=V1. From Equation (Equation27) we get L=L1, I=I1. Then Γ1 contains a single point that is {Q1}. It follows from LaSalle's invariance principle, Q1 is GAS.

3. CHIKV model with delay-distributed

We consider the following latent CHIKV dynamics model with distributed delays: (28) S˙(t)=μaS(t)Ψ(S(t),V(t)),(28) (29) L˙(t)=(1ρ)0κ1g1(τ)eδ1τΨ(S(tτ),V(tτ))dτ(θ+λ)L(t),(29) (30) I˙(t)=ρ0κ2g2(τ)eδ2τΨ(S(tτ),V(tτ))dτ+λL(t)ϵI(t),(30) (31) V˙(t)=mI(t)rV(t)qV(t)B(t),(31) (32) B˙(t)=η+cB(t)V(t)δB(t).(32) Here, g1(τ)eδ1τ is probability that uninfected monocyte contacted by CHIKV at time tτ survived τ time units and becomes latently infected monocyte at time t, where κ1 is limit superior of this delay, and g2(τ)eδ2τ is probability that uninfected monocyte contacted by the CHIKV at time tτ survived τ time units and becomes actively infected monocyte at time t, where κ2 is limit superior of this delay. The probability distribution functions g1(τ) and g2(τ) are assumed to satisfy (33) gi(τ)>0,0κigi(τ)dτ=1,0κigi(u)eιudu<,i=1,2.(33) where, ι is a positive number. Let Gi=0κigi(τ)eδiτdτ,i=1,2, Then, 0<Gi1, i=1,2.

The initial conditions for system (Equation28)–(Equation32) is the same as given by (Equation10) where ϱ=max{κ1,κ2}.

3.1. Preliminaries

Lemma 3.1

The solutions (S(t),L(t),I(t),V(t),B(t)) of system (Equation28)–(Equation32) with the initial conditions (Equation10) are nonnegative and ultimately bounded.

Proof.

From Lemma 2.1 we have S(t)>0 and B(t)>0 for all t0. Moreover, one can show that for t0 L(t)=e(θ+λ)tψ2(0)+(1ρ)0te(θ+λ)(tu)0κ1eδ1τg1(τ)Ψ(S(uτ),V(uτ))dτdu0,I(t)=eϵtψ3(0)+ρ0teϵ(tu)0κ2eδ2τg2(τ)Ψ(S(uτ),V(uτ))dτ+λL(u)du0,V(t)=e0t(r+qB(z))dzψ4(0)+0tmI(u)eut(r+qB(z))dzdu0. From Equation (Equation28), we have limtsupS(t)M1. Let T2(t)=(1ρ)0κ1g1(τ)eδ1τS(tτ)dτ+ρ0κ2g2(τ)eδ2τS(tτ)dτ+L(t)+I(t)+ϵ2mV(t)+ϵq2mcB(t) then T˙2(t)=(1ρ)0κ1g1(τ)eδ1τμaS(tτ)Ψ(S(tτ),V(tτ))dτ+(1ρ)0κ1g1(τ)eδ1τΨ(S(tτ),V(tτ))dτ(θ+λ)L(t)+ρ0κ2g2(τ)eδ2τμaS(tτ)Ψ(S(tτ),V(tτ))dτ+ρ0κ2g2(τ)eδ2τΨ(S(tτ),V(tτ))dτ+λL(t)ϵI(t)+ϵ2mmI(t)rV(t)qV(t)B(t)+ϵq2mcη+cB(t)V(t)δB(t)=μ(1ρ)0κ1g1(τ)eδ1τdτ+ρ0κ2g2(τ)eδ2τdτa(1ρ)0κ1g1(τ)eδ1τS(tτ)dτ+ρ0κ2g2(τ)eδ2τS(tτ)dτθL(t)ϵ2I(t)+ϵqη2mcϵr2mV(t)ϵqδ2mcB(t)μ+ϵqη2mcσ1(1ρ)0κ1g1(τ)eδ1τS(tτ)dτ+ρ0κ2g2(τ)eδ2τS(tτ)dτ+L(t)+I(t)+ϵ2mV(t)+ϵq2mcB(t)=μ+ϵqη2mcσ1T2(t). It follows that limtsupT2(t)M1, limtsupL(t)M1, limtsupI(t)M1, limtsupV(t)M2, and limtsupB(t)M3, where M1, M2 and M3 are defined previously. This shows the ultimate boundedness of S(t),L(t),I(t),V(t) and B(t).

3.2. The existence of steady states

Lemma 3.2

For system (Equation28)–(Equation32), assume that Assumptions 2.1–2.2 are satisfied, then there exists a threshold parameter R0D>0 such that if R0D1, then the CHIKV-free steady state Q0D is the only steady state for the system. If R0D>1, then the system has a unique endemic steady state Q1D.

Proof.

Let Q(S,L,I,V,B) be any steady state of the system (Equation28)–(Equation32) satisfying the following equations: (34) 0=μaSΨ(S,V),(34) (35) 0=(1ρ)G1Ψ(S,V)(θ+λ)L,(35) (36) 0=ρG2Ψ(S,V)+λLϵI,(36) (37) 0=mIrVqBV,(37) (38) 0=η+cBVδB.(38) The proof can be completed in the same line as the proof in Lemma 2.2. The basic reproduction number is defined as R0D=mβϵ(θ+λ)(r+qB0)∂Ψ(S0,0)V, where β=G1λ(1ρ)+G2ρ(θ+λ).

3.3. Global Stability

Theorem 3.1

Suppose that R0D1 and Assumtions 2.1–2.2 is satisfied then Q0D is GAS.

Proof.

Let W0D(S,L,I,V,B)=βθ+λSS0S0SlimV0+Ψ(S0,V)Ψ(ϑ,V)dϑ+λθ+λL+I+ϵmV+ϵqmcB0HBB0+λ(1ρ)θ+λ0κ1g1(τ)eδ1τ×0τΨ(S(tϑ),V(tϑ))dϑdτ+ρ0κ2g2(τ)eδ2τ0τΨ(S(tϑ),V(tϑ))dϑdτ. Calculating dW0Ddt along the trajectories of (Equation28)–(Equation32) we get dW0Ddt=βθ+λ1limV0+Ψ(S0,V)Ψ(S,V)μaSΨ(S,V)+λθ+λ(1ρ)0κ1g1(τ)eδ1τΨ(S(tτ),V(tτ))dτ(θ+λ)L+ρ0κ2g2(τ)eδ2τΨ(S(tτ),V(tτ))dτ+λLϵI+ϵmmIrVqBV+ϵqmc1B0Bη+cBVδB+λ(1ρ)θ+λ0κ1g1(τ)eδ1τΨ(S,V)Ψ(S(tτ),V(tτ))dτ+ρ0κ2g2(τ)eδ2τΨ(S,V)Ψ(S(tτ),V(tτ))dτ. Then, we have (39) dW0Ddtμβθ+λ1∂Ψ(S0,0)/V∂Ψ(S,0)/V1SS0+βθ+λV∂Ψ(S0,0)VϵmrVϵqmB0V+ϵqmc1B0BδB0δB=μβθ+λ1∂Ψ(S0,0)/V∂Ψ(S,0)/V1SS0+ϵ(r+qB0)mmβϵ(θ+λ)(r+qB0)∂Ψ(S0,0)V1Vϵqδmc(BB0)2B=μβθ+λ1∂Ψ(S0,0)/V∂Ψ(S,0)/V1SS0+ϵ(r+qB0)mR01Vϵqδmc(BB0)2B.(39) From Remark 2.1 we have, if R0D1, then dW0D/dt0 for all S,V,B>0. Also, dW0D/dt=0 if and only if S=S0, B=B0, V=0. Then Q0D is GAS.

Theorem 3.2

Suppose that R0D>1 and 2.1–2.2 are satisfied, then Q1D is GAS.

Proof.

Define a Lyapunov functional as W1D(S,L,I,V,B)=βθ+λSS1S1SΨ(S1,V1)Ψ(ϑ,V1)dϑ+λθ+λL1HLL1+I1HII1+ϵmV1HVV1+ϵqmcB1HBB1+λ(1ρ)θ+λΨ(S1,V1)0κ1g1(τ)eδ1τ×0τHΨ(S(tϑ),V(tϑ))Ψ(S1,V1)dϑdτ+ρΨ(S1,V1)0κ2g2(τ)eδ2τ×0τHΨ(S(tϑ),V(tϑ))Ψ(S1,V1)dϑdτ. Calculating dW1D/dt along the trajectories of (Equation28)–(Equation32) we get dW1Ddt=βθ+λ1Ψ(S1,V1)Ψ(S,V1)μaSΨ(S,V)+λθ+λ1L1L(1ρ)0κ1g1(τ)eδ1τΨ(S(tτ),V(tτ))dτ(θ+λ)L+1I1Iρ0κ2g2(τ)eδ2τΨ(S(tτ),V(tτ))dτ+λLϵI+ϵm1V1VmIrVqBV+ϵqmc1B1Bη+cBVδB+λ(1ρ)θ+λ0κ1g1(τ)eδ1τΨ(S,V)Ψ(S(tτ),V(tτ))dτ+λ(1ρ)θ+λΨ(S1,V1)0κ1g1(τ)eδ1τlnΨ(S(tτ),V(tτ))Ψ(S,V)dτ+ρ0κ2g2(τ)eδ2τΨ(S,V)Ψ(S(tτ),V(tτ))dτ+ρΨ(S1,V1)0κ2g2(τ)eδ2τlnΨ(S(tτ),V(tτ))Ψ(S,V)dτ. Applying μ=aS1+Ψ(S1,V1),η=δB1cB1V1, we obtain dW1Ddt=βθ+λ1Ψ(S1,V1)Ψ(S,V1)aS1aS+βθ+λΨ(S1,V1)1Ψ(S1,V1)Ψ(S,V1)+βθ+λΨ(S,V)Ψ(S1,V1)Ψ(S,V1)λ(1ρ)θ+λ×0κ1g1(τ)eδ1τL1Ψ(S(tτ),V(tτ))Ldτ+λL1ρ0κ2g2(τ)eδ2τI1Ψ(S(tτ),V(tτ))IdτλLI1I+ϵI1ϵV1IVϵmrV+ϵmrV1+ϵqmBV1ϵqmB1V1+ϵqmB1V1B1BϵqmB1V+ϵqmc1B1BδB1δB+λ(1ρ)θ+λΨ(S1,V1)0κ1g1(τ)eδ1τlnΨ(S(tτ),V(tτ))Ψ(S,V)dτ+ρΨ(S1,V1)0κ2g2(τ)eδ2τlnΨ(S(tτ),V(tτ))Ψ(S,V)dτ. Using the steady state conditions for Q1D: (1ρ)G1Ψ(S1,V1)=(θ+λ)L1,ρG2Ψ(S1,V1)+λL1=ϵI1,mI1=rV1+qB1V1, then ϵmrV1=βθ+λΨ(S1,V1)ϵqmB1V1, and (40) dW1Ddt=aS1βθ+λ1Ψ(S1,V1)Ψ(S,V1)1SS1+βθ+λΨ(S1,V1)Ψ(S,V)Ψ(S,V1)VV1+βθ+λΨ(S1,V1)1Ψ(S1,V1)Ψ(S,V1)λ(1ρ)θ+λΨ(S1,V1)0κ1g1(τ)eδ1τL1Ψ(S(tτ),V(tτ))LΨ(S1,V1)dτ+G1λ(1ρ)θ+λΨ(S1,V1)ρΨ(S1,V1)×0κ2g2(τ)eδ2τI1Ψ(S(tτ),V(tτ))IΨ(S1,V1)dτG1λ(1ρ)θ+λΨ(S1,V1)LI1L1I+G1λ(1ρ)θ+λΨ(S1,V1)+G2ρΨ(S1,V1)βθ+λΨ(S1,V1)IV1I1V+G1λ(1ρ)θ+λΨ(S1,V1)+G2ρΨ(S1,V1)2ϵqmB1V1+ϵqmBV1+ϵqmB1V1B1Bϵqδmc(BB1)2B+λ(1ρ)θ+λΨ(S1,V1)0κ1g1(τ)eδ1τlnΨ(S(tτ),V(tτ))Ψ(S,V)dτ+ρΨ(S1,V1)0κ2g2(τ)eδ2τlnΨ(S(tτ),V(tτ))Ψ(S,V)dτ.(40) Applying the following equalities: lnΨ(S(tτ),V(tτ))Ψ(S,V)=lnΨ(S1,V1)Ψ(S,V1)+lnIV1I1V+lnLI1L1I+lnVΨ(S,V1)V1Ψ(S,V)+lnL1Ψ(S(tτ),V(tτ))LΨ(S1,V1),lnΨ(S(tτ),V(tτ))Ψ(S,V)=lnΨ(S1,V1)Ψ(S,V1)+lnIV1I1V+lnVΨ(S,V1)V1Ψ(S,V)+lnI1Ψ(S(tτ),V(tτ))IΨ(S1,V1), we get dW1Ddt=aS1βθ+λ1Ψ(S1,V1)Ψ(S,V1)1SS1+βθ+λΨ(S1,V1)×1+Ψ(S,V)Ψ(S,V1)VV1+VΨ(S,V1)V1Ψ(S,V)+G1λ(1ρ)θ+λΨ(S1,V1)1Ψ(S1,V1)Ψ(S,V1)+lnΨ(S1,V1)Ψ(S,V1)+G1λ(1ρ)θ+λΨ(S1,V1)1IV1I1V+lnIV1I1V+G1λ(1ρ)θ+λΨ(S1,V1)1LI1L1I+lnLI1L1I+G1λ(1ρ)θ+λΨ(S1,V1)1VΨ(S,V1)V1Ψ(S,V)+lnVΨ(S,V1)V1Ψ(S,V)+λ(1ρ)θ+λΨ(S1,V1)0κ1g1(τ)eδ1τ1L1Ψ(S(tτ),V(tτ))LΨ(S1,V1)+lnL1Ψ(S(tτ),V(tτ))LΨ(S1,V1)dτ+G2ρΨ(S1,V1)1Ψ(S1,V1)Ψ(S,V1)+lnΨ(S1,V1)Ψ(S,V1)+G2ρΨ(S1,V1)×1IV1I1V+lnIV1I1V+ρΨ(S1,V1)0κ2g2(τ)eδ2τ1I1Ψ(S(tτ),V(tτ))IΨ(S1,V1)+lnI1Ψ(S(tτ),V(tτ))IΨ(S1,V1)dτ+G2ρΨ(S1,V1)1VΨ(S,V1)V1Ψ(S,V)+lnVΨ(S,V1)V1Ψ(S,V)ϵqδmc(BB1)2BϵqB1V1m2BB1B1B (41) =aS1βθ+λ1Ψ(S1,V1)Ψ(S,V1)1SS1+βθ+λΨ(S1,V1)Ψ(S,V)Ψ(S,V1)VV1×1Ψ(S,V1)Ψ(S,V)ϵqηmcB1(BB1)2BG1λ(1ρ)θ+λΨ(S1,V1)HΨ(S1,V1)Ψ(S,V1)+HIV1I1V+HLI1L1I+HVΨ(S,V1)V1Ψ(S,V)+1G10κ1g1(τ)eδ1τHL1Ψ(S(tτ),V(tτ))LΨ(S1,V1)dτG2ρΨ(S1,V1)HΨ(S1,V1)Ψ(S,V1)+HIV1I1V+HVΨ(S,V1)V1Ψ(S,V)+1G20κ2g2(τ)eδ2τHI1Ψ(S(tτ),V(tτ))IΨ(S1,V1)dτ.(41) Clearly, dW1D/dt0, and similar to the proof of Theorem 2.2 it can be easily show that dW1D/dt=0 occurs at Q1D. It follows from LaSalle's invariance principle, Q1D is GAS.

4. Numerical simulations

In order to confirm our theoretical results, we carry out some numerical simulations for systems (Equation5)– (Equation8).

We choose the function Ψ as Ψ(S,V)=βShVα1+Sh1α2+Vn. Then we have (42) S˙(t)=μaS(t)βSh(t)V(t)α1+Sh1(t)α2+Vn(t),(42) (43) L˙(t)=(1ρ)eδ1τ1βSh(tτ1)V(tτ1)α1+Sh1(tτ1)α2+Vn(tτ1)(θ+λ)L(t),(43) (44) I˙(t)=ρeδ2τ2βSh(tτ2)V(tτ2)α1+Sh1(tτ2)α2+Vn(tτ2)+λL(t)ϵI(t),(44) (45) V˙(t)=mI(t)rV(t)qB(t)V(t),(45) (46) B˙(t)=η+cB(t)V(t)δB(t),(46) where b,α1,α2,h1,n,h>0. Assume that 0<h1h,0<n1. Now, we have to verify Assumptions A1–A2. Clearly, Ψ(S,V)>0,Ψ(0,V)=Ψ(S,0)=0 for all S,V>0. Moreover, for S>0 and V >0 we have ∂Ψ(S,V)S=bα1h+hh1Sh1Sh1Vα1+Sh12α2+Vn,∂Ψ(S,V)V=bα2+1nVnShα1+Sh1α2+Vn2,∂Ψ(S,0)V=bShα2α1+Sh1,ddS∂Ψ(S,0)V=bα1hSh1+(hh1)Sh+h11α2α1+Sh12>0. Since 0<h1h,0<n1, then ∂Ψ(S,V)/S>0,∂Ψ(S,V)/V>0 and ∂Ψ(S,0)/V>0 for all S,V>0. Thus, Assumption 2.1 holds true. We have Ψ(S,V)V=bShα1+Sh11α2+Vn,VΨ(S,V)V=bShα1+Sh1nVn1α2+Vn2<0, for all S>0, which shows that Assumption 2.2 also holds true. Thus, the global stability results shown in Theorems 2.1–2.2 are guaranteed for model (Equation42)–(Equation46). The parameter R0 for model (Equation42)–(Equation46) is given by R0=mλ(1ρ)eδ1τ1+ρeδ2τ2(θ+λ)ϵ(θ+λ)(r+qB0)∂Ψ(S0,0)V=mγbS0hα2ϵ(θ+λ)(r+qB0)α1+S0h1. From the above analysis, we perform the numerical results for system (Equation42)–(Equation46) with parameters values given in Table . All computations are executed by MATLAB.

Table 1. The data of system (Equation42)–(Equation46).

Firstly, the effect of parameter b on the qualitative behaviour of the system will be discussed below. We assume τe=τ1=τ2=0.5. We consider three different initial conditions as

  • IC1: ϕ1(ϑ)=2.0,ϕ2(ϑ)=0.2,ϕ3(ϑ)=0.4,ϕ4(ϑ)=0.4 and ϕ5(ϑ)=1.0,

  • IC2: ϕ1(ϑ)=1.7,ϕ2(ϑ)=0.4,ϕ3(ϑ)=0.6,ϕ4(ϑ)=0.6 and ϕ5(ϑ)=1.6,

  • IC3: ϕ1(ϑ)=1.4,ϕ2(ϑ)=0.6,ϕ3(ϑ)=0.8,ϕ4(ϑ)=0.8 and ϕ5(ϑ)=2.4. ϑ[τe,0].

We use two sets of values of parameter b to get the following:

Set (I): We choose b=0.5. Using these data, we compute R0=0.4941<1. From Figures , we can see that, the concentration of uninfected monocytes are increasing and tends to its normal value (the case when there is no CHIKV) S0=2.2885, while the concentrations of latently infected monocytes, actively infected monocytes and the CHIKV paticles are decreasing and tend to zero. As a result the proliferation rate of the B cells i.e. cBV will tend to zero and then the concentration of the B cells tends to its normal value (the case when there is no CHIKV) B0=1.1207. Thus, the solutions of the system eventually lead to the CHIKV-free steady state Q0 for all the three initial conditions IC1–1C3. This result is consistent with the result of Theorem 2.1 that Q0 is GAS. In this case, the CHIKV will be eliminated from the body.

Figure 2. The concentration of uninfected monocytes.

Figure 2. The concentration of uninfected monocytes.

Figure 3. The concentration of latently infected monocytes.

Figure 3. The concentration of latently infected monocytes.

Figure 4. The concentration of actively infected monocytes.

Figure 4. The concentration of actively infected monocytes.

Figure 5. The concentration of free CHIKV particles.

Figure 5. The concentration of free CHIKV particles.

Figure 6. The concentration of B cells.

Figure 6. The concentration of B cells.

Set (II): We take b=3.5. Then, we compute R0=3.4584>1. It means that, the system has two positive steady states Q0 and Q1, where Q1 is GAS. Figures  show that the concentration of uninfected monocytes are decreasing, while the concentrations of latently infected monocytes, actively infected monocytes and the CHIKV paticles are increasing. The increasing of the CHIKV paticles will increase the proliferation rate of the B cells and then the concentration of the B cells are also increased. The states of the system converge to the steady state Q1=(1.6217,0.3453,0.5443,0.5689,2.4994) for all the three initial conditions IC1–IC3. This confirms the result of Theorem 2.2.

Next, we investigate the effect of time delays on the stability of the steady states. We vary the parameter τe, and fix b=2.5. The following initial conditions are used: ϕ1(ϑ)=2.0,ϕ2(ϑ)=0.2,ϕ3(ϑ)=0.3,ϕ4(ϑ)=0.3,ϕ5(ϑ)=1.7,ϑτe,0. In Figures , we show the evolution of the states of system S, L, I, V and B with respect to the time. We can see that, for lower values of τe e.g. τe=0.0, 0.5, 1.0 and 1.5, the corresponding values of R0 satisfy R0>1, and the trajectory of the system tends to the steady states Q1. This confirms the results of Theorem 2.2 that Q1 is GAS. On the other hand, when τe becomes higher e.g. τe=3.5 and 5.0, then R0<1, and the system has one positive steady state Q0 which confirms the results of Theorem 2.1 that Q0 is GAS. In this case, the CHIKV particles are cleared from the body.

Figure 7. The concentration of uninfected monocytes.

Figure 7. The concentration of uninfected monocytes.

Figure 8. The concentration of latently infected monocytes.

Figure 8. The concentration of latently infected monocytes.

Figure 9. The concentration of actively infected monocytes.

Figure 9. The concentration of actively infected monocytes.

Figure 10. The concentration of free CHIKV particles.

Figure 10. The concentration of free CHIKV particles.

Figure 11. The concentration of B cells.

Figure 11. The concentration of B cells.

Let τcr be the critical value of the parameter τe, such that R0=mλ(1ρ)eδ1τcr+ρeδ2τcr(θ+λ)bS0hα2ϵ(θ+λ)(r+qB0)α1+S0h1=1. From Table  we obtain τcr=2.3086. The value of R0 for different values of τe are listed in Table . We can observed that as τe is increased then R0 is decreased. Moreover, we have the following cases:

  1. if 0τe<2.3086, then Q1 exists and it is GAS,

  2. if τe2.3086, then Q0 is GAS. It is clearly seen that, an increasing in time delay will stabilize the system around Q0. In terms of biology, the time delay has a similar effect as the antiviral treatment which can be used to eliminate the CHIKV. We observe that, sufficiently large periods of delay reduce CHIKV replication and also clear the virus.

Table 2. The values of steady states, R0 for model (Equation42)–(Equation46) with different values of τe.

5. Conclusion and discussion

In this paper, we have studied two within-host CHIKV dynamics models with antibody immune response. The incidence rate between the CHIKV and the uninfected monocytes has been modelled by a general nonlinear function Ψ. We have incorporated intracellular discrete or distributed time delays into the model. We have considered two types of infected monocytes, latently infected monocytes (such monocytes contain the CHIKV but are not producing it) and the actively infected monocytes (such monocytes are producing the CHIKV). We have shown that, the solutions of each model are nonnegative and ultimate bounded which ensure the well-posedness of the model. We have derived the basic reproduction number R0 for the model. Sufficient conditions on Ψ and R0 are established which guarantee the existence and global stability of the two steady states, CHIKV-free steady state Q0 and endemic steady state Q1. We have investigated the global stability of the steady states of the model by using Lyapunov method and LaSalle's invariance principle. We have conducted numerical simulations with a specific choice of the function Ψ and have shown that both the theoretical and numerical results are consistent.

The results show that, for the CHIKV infection model, the time delay has a significant effect on both global asymptotic properties of Q0 and global asymptotic properties of Q1. This is due to the dependence of the parameter R0 on the time delay. For model (Equation42)–(Equation46) R0 is given by R0(τ1,τ2)=mλ(1ρ)eδ1τ1+ρeδ2τ2(θ+λ)bS0hα2ϵ(θ+λ)(r+qB0)α1+S0h1, which is a decreasing function in both τ1 and τ2. It has a clear meaning that, if the length of the delay is large, infected monocytes may die before it spreads CHIKV due to the small survival probability in the delay period between the infection phase and the CHIKV-producing phase. Clearly, R0(τ1,τ2)<R0(0,0), where R0(0,0) is the basic reproduction number of system (Equation42)–(Equation46) without delay. It follows that, the system with delay is more stabilizable abound Q0 than that without delay.

Acknowledgments

This article was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah. The authors, therefore, acknowledge with thanks DSR for technical and financial support.

Disclosure statement

No potential conflict of interest was reported by the authors.

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