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Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2020 Sep 8;102(1):489–509. doi: 10.1007/s11071-020-05929-4

Global dynamics of a multi-strain SEIR epidemic model with general incidence rates: application to COVID-19 pandemic

Omar Khyar 1,, Karam Allali 1
PMCID: PMC7478444  PMID: 32921921

Abstract

This paper investigates the global stability analysis of two-strain epidemic model with two general incidence rates. The problem is modelled by a system of six nonlinear ordinary differential equations describing the evolution of susceptible, exposed, infected and removed individuals. The wellposedness of the suggested model is established in terms of existence, positivity and boundedness of solutions. Four equilibrium points are given, namely the disease-free equilibrium, the endemic equilibrium with respect to strain 1, the endemic equilibrium with respect to strain 2, and the last endemic equilibrium with respect to both strains. By constructing suitable Lyapunov functional, the global stability of the disease-free equilibrium is proved depending on the basic reproduction number R0. Furthermore, using other appropriate Lyapunov functionals, the global stability results of the endemic equilibria are established depending on the strain 1 reproduction number R01 and the strain 2 reproduction number R02. Numerical simulations are performed in order to confirm the different theoretical results. It was observed that the model with a generalized incidence functions encompasses a large number of models with classical incidence functions and it gives a significant wide view about the equilibria stability. Numerical comparison between the model results and COVID-19 clinical data was conducted. Good fit of the model to the real clinical data was remarked. The impact of the quarantine strategy on controlling the infection spread is discussed. The generalization of the problem to a more complex compartmental model is illustrated at the end of this paper.

Keywords: Global stability analysis, SEIR, General incidence function, Multi-strain epidemic model, Basic reproduction number, COVID-19

Introduction

Nowadays, several infectious diseases are still targeting huge populations. They are considered amongst the principal causes of mortality, especially in many developing countries. Accordingly, mathematical modelling in epidemiology occupies more and more an increasingly preponderant place in public health research. This research discipline contributes indeed to well understand the studied epidemiological phenomenon and apprehend the different factors that can lead to a severe epidemic or even to a dangerous pandemic worldwide. The classical susceptible-infected-recovered (SIR) epidemic model was first introduced in [1]. Nevertheless, in many cases, the infection incubation period may take a long time interval. In this period, an incubated individual remains latent but not yet infectious. Therefore, another class of exposed individuals should be added to SIR and the new epidemic model will have SEIR abbreviation. Furthermore, epidemiological studies have revealed that the phenomenon of mutation causes more and more resistant viruses giving appearance of many new harmful epidemics or even new dangerous pandemics. Indeed, H1N1 flu virus is considered as mutation of the seasonal influenza [2, 3]. Also, the late coronavirus disease COVID-19 caused by the severe acute respiratory syndrome-related coronavirus SARS-Cov-2 is classified as a strain of SARS-CoV-1 [4]. Other processes of mutation were observed in many infections such as tuberculosis, human immunodeficiency virus and dengue fever [57]. For this reason, the multi-strain SEIR epidemic models present an important tool to study several infectious diseases that include a long incubation period and also various infection strains. The relevance of studying multi-strain models is to find out the different conditions permitting the coexistence of all acting strains. The global dynamics of one-strain SEIR model have been the subject of many investigations by considering either bilinear or nonlinear incidence rates [810]. The global stability of two-strain SEIR model have been tackled in [11], the authors include to the studied model two incidence functions, the first one is bilinear, while the second function is non-monotonic. Recently, the same problem was studied in [12] by assuming that the two incidence functions are non-monotonic. It is worthy to mention that the incidence rate gives more information of the disease transmission. Hence, the general incidence function has as goal to represent a large set of infection incidence rates. Accordingly, the purpose of this work is to generalize the previous models by taking into account a multi-strain SEIR model with two general incidence rates. Hence, our study will be carried out on the following two- strain generalized epidemic model:

dSdt=Λ-f(S,I1)I1-g(S,I2)I2-δS,dE1dt=f(S,I1)I1-(γ1+δ)E1,dE2dt=g(S,I2)I2-(γ2+δ)E2,dI1dt=γ1E1-(μ1+δ)I1,dI2dt=γ2E2-(μ2+δ)I2,dRdt=μ1I1+μ2I2-δR, 1.1

with

S(0)0,E1(0)0,E2(0)0,I1(0)0,I2(0)0,R(0)0.

where (S) is the number of susceptible individuals, (E1) and (E2) are, respectively, the numbers of each latent individuals class, (I1) and (I2) are, respectively, the numbers of each infectious individuals class and (R) is the number of removed individuals. The parameter Λ is the recruitment rate, δ is the death rate of the population, γ1 and γ2 are, respectively, the latency rates of strain 1 and strain 2, μ1 and μ2 are, respectively, the two-strain transfer rates from infected to recovered. The general incidence functions f(S,I1) and g(S,I2) stand for the infection transmission rates for strain 1 and strain 2, respectively. The incidence functions f(S,I1) and g(S,I2) are assumed to be continuously differentiable in the interior of R+2 and satisfy the same properties as in [13, 14]:

graphic file with name 11071_2020_5929_Equ109_HTML.gif

The properties (H1), (H2) and (H3), for the both functions f and g, are easily verified by several classical biological incidence rates such as the bilinear incidence function βS  [1, 15, 16], the saturated incidence function βS1+α1S or βS1+α2I [17, 18], Beddington–DeAngelis incidence function βS1+α1S+α2I [1921], Crowley–Martin incidence function βS1+α1S+α2I+α1α2SI [2224], the specific nonlinear incidence function βS1+α1S+α2I+α3SI [2529] and non-monotone incidence function βS1+αI2 [3034]. The flowchart of the two-strain epidemiological SEIR model is illustrated in Fig. 1. Our main contribution centres around the global stability of multi-strain SEIR epidemic model with general incidence rates. In addition, a numerical comparison between our two-strain epidemic model results and COVID-19 clinical data will be conducted. It will be worthy to notice that the dynamics of SEIR COVID-19 epidemic model with two bilinear incidence functions was tackled in [35], and the authors introduce seasonality and stochasticity in order to describe the infection rate parameters. Taking into account non-monotone incidence function, the technique of sliding mode control was used to study an SEIR epidemic model describing COVID-19 disease [36]. The COVID-19 SEIR epidemiological model with Crowley–Martin incidence rate was studied [37], and the authors study the effect of different parameters on the disease spread. In our numerical comparison with COVID-19 clinical data, we will take into account the three latter incidence functions along with Beddington–DeAngelis incidence rate. A brief analysis to a more complex compartmental epidemic model will be established in Appendix of this paper.

Fig. 1.

Fig. 1

Flowchart of two-strain SEIR model

The rest of this paper is outlined as follows. In the next section, we will establish the wellposedness of the suggested model by proving the existence, positivity and boundedness of solutions. In Sect. 3, we present an analysis of the model, we calculate the basic reproduction number of our epidemic model and we prove the global stability of the equilibria. Numerical simulations are given in Sect. 4 by using different specific incidence functions, and the comparison between the numerical results and COVID-19 clinical data is conducted in the same section. The generalization of the problem to a more complex compartmental model as well as concluding remarks is given at the end of this paper.

The problem wellposedness and steady states

Positivity and boundedness of solutions

For the problems dealing with population dynamics, all the variables must be positive and bounded. We will assume first that all the model parameters are positive.

Proposition 1

For all non-negative initial data, the solutions of the problem (1.1) exist, remain bounded and non-negative.

Moreover, we have N(t)Λδ+N(0).

Proof

By the fundamental theory of differential equations functional framework (see for instance [38] and the references therein), we confirm that there exists a unique local solution to the problem (1.1).

In order to prove the positivity result, we will show that any solution starting from non-negative orthant R+6={(S,E1,E2,I1,I2,R)R6:S0,E10,E20,I10,I20,R0} remains there forever.

First, let

T=sup{τ0|t[0,τ]such thatS(t)0,E1(t)0,E2(t)0,I1(t)0,I2(t)0,R(t)0} 2.1

Let us now prove that T=+. Suppose that T is finite; by continuity of solutions, we have

S(T)=0orE1(T)=0orE2(T)=0orI1(T)=0orI2(T)=0orR(T)=0.

If S(T)=0 before the other variables E1, E2, I1, I2, R, become zero. Therefore,

dS(T)dt=limtT-S(T)-S(t)T-t=limtT--S(t)T-t0. 2.2

From the first equation of system (1.1), we have

S˙(T)=Λ-f(S(T),I1(T))I1(T)-g(S(T),I2(T))I2(T)-δS(T), 2.3

then,

S˙(T)=Λ-f(0,I1(T))I1(T)-g(0,I2(T))I2(T), 2.4

However, from (H1) we have

S˙(T)=Λ>0 2.5

which presents a contradiction.

If E1(T)=0 before S, E2, I1, I2 and R. Then,

dE1(T)dt=limtT-E1(T)-E1(t)T-t=limtT--E1(t)T-t0. 2.6

Again, from the second equation of the system (1.1) with the fact E1(T)=0, we will have

dE1(T)dt=f(S,I1)I1. 2.7

However, from (H1) and (H2), f(S,I1)I1 is positive, then we will have

dE1(T)dt>0. 2.8

Also, if I1=0 before S, E1, E2, I2, R become zero then

dI1(T)dt=limtT-I1(T)-I1(t)T-t=limtT--I1(t)T-t0. 2.9

But from the fourth equation of the system (1.1) with I1(T)=0, we will have

dI1(T)dt=γ1E1. 2.10

Since γ1>0, we have

dI1(T)dt=γ1E1>0. 2.11

This leads to contradiction.

Similar proofs for E2(t), I2(t) and R(t).

We conclude that T could not be finite, which implies that S(t)0,E1(t)0,E2(t)0,I1(t)0,I2(t)0,R(t)0 for all positive times. This proves the positivity of solutions.

About boundedness, let the total population

N(t)=S(t)+E1(t)+E2(t)+I1(t)+I2(t)+R(t). 2.12

From the system (1.1), we have

dN(t)dt=Λ-δN(t), 2.13

and therefore,

N(t)=Λδ+Ke-δt, 2.14

at t=0, we have

N(0)=Λδ+K, 2.15

then

N(t)=Λδ+(N(0)-Λδ)e-δt, 2.16

consequently

N(t)Λδ+N(0)e-δt, 2.17

since 0<e-δt1, for all t0, we conclude that

N(t)Λδ+N(0). 2.18

This implies that N(t) is bounded, and so are S(t),E1(t),E2(t),I1(t),I2(t)andR(t). Thus, the local solution can be prolonged to any positive time, which means that the unique solution exists globally.

The steady states

In this subsection, we show that there exist a disease-free equilibrium and three endemic equilibria. First, since the first five equations of the system (1.1) are independent of R and knowing that the number of the total population verifies the Eq. (2.14), so we can omit the sixth equation of the system (1.1). Therefore, the problem can be reduced to:

dSdt=Λ-f(S,I1)I1-g(S,I2)I2-δS,dE1dt=f(S,I1)I1-(γ1+δ)E1,dE2dt=g(S,I2)I2-(γ2+δ)E2,dI1dt=γ1E1-(μ1+δ)I1,dI2dt=γ2E2-(μ2+δ)I2, 2.19

with

R=N-S-E1-E2-I1-I2. 2.20

As usual, the basic reproduction number can be defined as the average number of new cases of an infection caused by one infected individual when all the population individuals are susceptibles. We will use the next generation matrix FV-1 to calculate the basic reproduction number R0. The formula that gives us the basic reproduction number is: R0=ρ(FV-1), where ρ stands for the spectral radius, F is the non-negative matrix of new infection cases and V is the matrix of the transition of infections associated with the model (2.19). We have

F=00f(Λδ,0)0000g(Λδ,0)00000000,V=γ1+δ0000γ2+δ00-γ10μ1+δ00-γ20μ2+δ.

So,

FV-1=f(Λδ,0)γ1(γ1+δ)(μ1+δ)0f(Λδ,0)(μ1+δ)00g(Λδ,0)γ2(γ2+δ)(μ2+δ)0g(Λδ,0)(μ1+δ)00000000.

The basic reproduction number is the spectral radius of the matrix FV-1. This fact implies that

R0=max{R01,R02}, 2.21

with

R01=f(Λδ,0)γ1(γ1+δ)(μ1+δ) 2.22

and

R02=g(Λδ,0)γ2(γ2+δ)(μ2+δ). 2.23

We denote

a=γ1+δ,b=γ2+δ,c=μ1+δ,e=μ2+δ,

then

R01=f(Λδ,0)γ1ac 2.24

and

R02=g(Λδ,0)γ2be. 2.25

We call R01 the strain 1 reproduction number and R02 the strain 2 reproduction number.

Theorem 1

The problem (2.19) have the disease-free equilibrium Ef and three endemic equilibria Es1, Es2 and Est. Moreover, we have

  • The strain 1 endemic equilibrium Es1 exists when R01>1.

  • The strain 2 endemic equilibrium Es2 exists when R02>1.

  • The third endemic equilibrium Est exists when R01>1 and R01>1.

Proof

In order to find the steady states of the system (2.19), we solve the following equations

Λ-f(S,I1)I1-g(S,I2)I2-δS=0, 2.26
f(S,I1)I1-(γ1+δ)E1=0, 2.27
g(S,I2)I2-(γ2+δ)E2=0, 2.28
γ1E1-(μ1+δ)I1=0, 2.29
γ2E2-(μ2+δ)I2=0. 2.30

From where, we obtain

  • When I1=0andI2=0, we find the disease-free equilibrium
    Ef=Λδ,0,0,0,0.
  • When I10andI2=0, we find the strain 1 endemic equilibrium defined as follows
    Es1=S1,1a(Λ-δS1),0,γ1ac(Λ-δS1),0,whereS10,Λδ.
    Define now a function Ψon[0,+[ as follows
    Ψ(S)=f(S,γ1ac(Λ-δS))-acγ1. 2.31
    We have
    Ψ(S)S=f(S,I1)S+f(S,I1)I1-δγ1ac, 2.32
    using the conditions (H2) and (H3), we deduce that
    Ψ(S)S0. 2.33
    However, Ψ(0)=f(0,I1,s1)-acγ1=-acγ1<0. Therefore, for R01>1, we he have
    ΨΛδ=fΛδ,0-acγ1=acγ1(R01-1)>0. 2.34
    Hence, there exists a unique strain 1 endemic equilibrium
    Es1=S1,E1,s1,E2,s1,I1,s1,I2,s1, 2.35
    with S1]0,Λδ[, E1,s1>0, I1,s1>0 and E2,s1=I2,s1=0.
  • When I20andI1=0, we find the strain 2 endemic equilibrium defined as follows
    Es2=S2,0,1b(Λ-δS2),0,γ2be(Λ-δS2),whereS20,Λδ.
    Define also a function Φon[0,+[ as follows
    Φ(S)=g(S,γ2be(Λ-δS))-beγ2. 2.36
    We have
    Φ(S)S=g(S,I2)S+g(S,I2)I2-δγ2be, 2.37
    using the conditions (H2) and (H3), we conclude that
    Φ(S)S0. 2.38
    However, Φ(0)=g(0,I2,s2)-beγ2=-beγ2<0. So, for R02>1, we have
    ΦΛδ=gΛδ,0-beγ2=beγ2(R02-1)>0. 2.39
    Hence, there exists a unique strain 2 endemic equilibrium
    Es2=S2,E1,s2,E2,s2,I1,s2,I2,s2, 2.40
    with S20,Λδ, E2,s2>0, I2,s2>0 and E1,s2=I1,s2=0.
  • When I10andI20, we find the third endemic equilibrium defined as follows
    Et=St,E1,t,E2,t,I1,t,I2,t, 2.41
    where
    E1,t=cγ1I1,t,E2,t=eγ2I2,t, 2.42
    St=1δΛ-f(Λδ,0)R01I1,t-g(Λδ,0)R02I2,t, 2.43
    with Λf(Λδ,0)R01I1,t+g(Λδ,0)R02I2,t, R01>1 and R02>1.

Global stability of equilibria

Global stability of disease-free equilibrium

Theorem 2

If R01, then the disease-free equilibrium Ef is globally asymptotically stable.

Proof

First, we consider the following Lyapunov function in R+5:

Lf(S,E1,E2,I1,I2)=S-S0-S0Sf(S0,0)f(X,0)dX+E1+E2+aγ1I1+bγ2I2. 3.1

The time derivative is given by

L˙f(S,E1,E2,I1,I2)=S˙-f(S0,0)f(S,0)S˙+E1˙+E2˙+aγ1I1˙+bγ2I2˙,=δS01-SS01-f(S0,0)f(S,0)+acγ1I1f(S,I1)f(S,0)R01-1 3.2
+beγ2I2f(S0,0)f(S,0)g(S,I2)g(S0,0)R02-1 3.3
δS01-SS01-f(S0,0)f(S,0)+acγ1I1R01-1+beγ2I2f(S0,0)f(S,0)g(S,I2)g(S0,0)R02-1 3.4

We will discuss two cases:

  • If SS0, using (H2), we will have g(S,I2)g(S0,0)1, then,
    L˙f(S,E1,E2,I1,I2)δS01-SS01-f(S0,0)f(S,0)+acγ1I1R01-1+beγ2I2f(S0,0)f(S,0)R02-1. 3.5
    Since R02f(S,0)f(S0,0)1, we obtain
    f(S0,0)f(S,0)R02-10. 3.6
    Otherwise, 1-f(S0,0)f(S,0)0, therefore
    δS01-SS01-f(S0,0)f(S,0)0. 3.7
  • If S0<S, using (H2), we will have g(S,I2)g(S0,0)>1 and f(S0,0)f(S,0)<1 then,
    L˙f(S,E1,E2,I1,I2)δS01-SS01-f(S0,0)f(S,0)+acγ1I1R01-1+beγ2I2g(S,I2)g(S0,0)R02-1. 3.8
    Since R02<g(S0,0)g(S,I2)<1, we obtain
    g(S,I2)g(S0,0)R02-1<0. 3.9
    From f(S0,0)f(S,0)<1, we have
    δS01-SS01-f(S0,0)f(S,0)0. 3.10

By the above discussion, we deduce that, if R021 and R011 (which means that R01), then

L˙f(S,E1,E2,I1,I2)0. 3.11

Thus, the disease-free equilibrium point Ef is globally asymptotically stable when R01.

Global stability of strain 1 endemic equilibrium

For the global stability of Es1, we assume that the function f satisfies the following condition:

1-f(S,I1)f(S,I1,s1)f(S,I1,s1)f(S,I1)-I1I1,s10,S,I1>0. 3.12

Theorem 3

The strain 1 endemic equilibrium Es1 is globally asymptotically stable when R021<R01.

Proof

First, we consider the Lyapunov function L1 defined by:

L1(S,E1,E2,I1,I2)=S-S1-S1Sf(S1,I1,s1)f(X,I1,s1)dX+E1E1E1,s1-lnE1E1,s1-1+E2+aγ1I1,s1I1I1,s1-lnI1I1,s1-1+bγ2I2. 3.13

The time derivative is given by

L˙1(S,E1,E2,I1,I2)=Λ-f(S,I1)I1-g(S,I2)I2-δS1-f(S1,I1,s1)f(S,I1,s1)+f(S,I1)I1-aE11-E1,s1E1+g(S,I2)I2-bE2+aγ1γ1E1-cI11-I1,s1I1+bγ2γ2E2-eI2. 3.14

We have

Λ=δS1+f(S1,I1,s1)I1,s1,f(S1,I1,s1)I1,s1=acγ1I1,s1=aE1,s1,E1,s1I1,s1=cγ1. 3.15

Therefore,

L˙1(S,E1,E2,I1,I2)=δS11-f(S1,I1,s1)f(S,I1,s1)-δS1-f(S1,I1,s1)f(S,I1,s1)+f(S1,I1,s1)I1,s1-f(S1,I1,s1)I1,s1f(S1,I1,s1)f(S,I1,s1)+f(S1,I1,s1)f(S,I1,s1)f(S,I1)I1-f(S,I1)I1E1,s1E1+aE1,s1-acγ1I1-aI1,s1I1E1+acγ1I1,s1+f(S1,I1,s1)f(S,I1,s1)g(S,I2)I2-beγ2I2. 3.16

Then,

L˙1(S,E1,E2,I1,I2)=aE1,s14-aE1,s1f(S,I1,s1)I1,s1-f(S,I1)I1aE1-I1,s1E1I1E1,s1-f(S,I1,s1)f(S,I1)+aE1,s1f(S,I1,s1)f(S,I1)+f(S,I1)f(S,I1,s1)I1I1,s1-I1I1,s1-1+f(S1,I1,s1)f(S,I1,s1)g(S,I2)I2-beγ2I2 3.17
L˙1(S,E1,E2,I1,I2)=aE1,s14-aE1,s1f(S,I1,s1)I1,s1-f(S,I1)I1aE1-I1,s1E1I1E1,s1-f(S,I1,s1)f(S,I1)+aE1,s1f(S,I1,s1)f(S,I1)+f(S,I1)f(S,I1,s1)I1I1,s1-I1I1,s1-1+beγ2I2f(S1,I1,s1)f(S,I1,s1)g(S,I2)g(S0,0)R02-1. 3.18

From (H2) and (H3), we have g(S,I2)g(S0,0)1, then,

L˙1(S,E1,E2,I1,I2)aE1,s14-aE1,s1f(S,I1,s1)I1,s1-f(S,I1)I1aE1-I1,s1E1I1E1,s1-f(S,I1,s1)f(S,I1)+aE1,s1f(S,I1,s1)f(S,I1)+f(S,I1)f(S,I1,s1)I1I1,s1-I1I1,s1-1+beγ2I2f(S1,I1,s1)f(S,I1,s1)R02-1, 3.19

From (3.12), we have

f(S,I1,s1)f(S,I1)+f(S,I1)f(S,I1,s1)I1I1,s1-I1I1,s1-1=1-f(S,I1)f(S,I1,s1)f(S,I1,s1)f(S,I1)-I1I1,s10, 3.20

by the relation between arithmetic and geometric means, we have

4-aE1,s1f(S,I1,s1)I1,s1-f(S,I1)I1aE1-I1,s1E1I1E1,s1-f(S,I1,s1)f(S,I1)0, 3.21

We discuss two cases:

  • If S1S, from (H2), we will have f(S1,I1,s1)f(S,I1,s1)1, since f(S1,I1,s1)f(S,I1,s1)R02-10, we obtain, for R021, the following L˙10.

  • If SS1, from (H2), we will have f(S1,I1,s1)f(S,I1,s1)1, since R02f(S,I1,s1)f(S1,I1,s1)1, we obtain f(S1,I1,s1)f(S,I1,s1)R02-10, which implies, L˙10. By the above discussion, we deduce that if R021, we will have L˙10.

We conclude that the steady state Es1 is globally asymptotically stable when R021 and 1<R01.

Global stability of strain 2 endemic equilibrium

For the global stability of Es2, we assume that the function g satisfies the following condition:

1-g(S,I2)g(S,I2,s2)g(S,I2,s2)g(S,I2)-I2I2,s20,S,I2>0. 3.22

Theorem 4

The strain 2 endemic equilibrium point Es2 is globally asymptotically stable when R011<R02.

Proof

First, we consider the Lyapunov function L2 defined by:

L2(S,E1,E2,I1,I2)=S-S2-S2Sg(S2,I2,s2)g(X,I2,s2)dX+E2,s2E2E2,s2-lnE2E2,s2-1+E1+aγ1I1+bγ2I2,s2I2I2,s2-lnI2I2,s2-1. 3.23

The time derivative is given by

L˙2(S,E1,E2,I1,I2)=Λ-f(S,I1)I1-g(S,I2)I2-δS1-g(S2,I2,s2)g(S,I2,s2)+g(S,I2)I2-bE21-E2,s2E2+f(S,I1)I1-aE1+bγ2γ2E2-eI21-I2,s2I2+aγ1γ1E1-cI1. 3.24

We have

Λ=δS2+g(S2,I2,s2)I2,s2,g(S2,I2,s2)I2,s2=beγ2I2,s2=bE2,s2,E2,s2I2,s2=eγ2. 3.25

Therefore,

L˙2(S,E1,E2,I1,I2)=δS21-g(S2,I2,s2)g(S,I2,s2)-δS1-g(S2,I2,s2)g(S,I2,s2)+g(S2,I2,s2)I2,s2-g(S2,I2,s2)I2,s2g(S2,I2,s2)g(S,I2,s2)+g(S2,I2,s2)g(S,I2,s2)g(S,I2)I2-g(S,I2)I2E2,s2E2+bE2,s2-beγ2I2-bI2,s2I2E2+beγ2I2,s2+g(S2,I2,s2)g(S,I2,s2)f(S,I1)I1-acγ1I1, 3.26

then

L˙2(S,E1,E2,I1,I2)=bE2,s24-bE2,s2g(S,I2,s2)I2,s2-g(S,I2)I2bE2-I2,s2E2I2E2,s2-g(S,I2,s2)g(S,I2)+bE2,s2g(S,I2,s2)g(S,I2)+g(S,I2)g(S,I2,s2)I2I2,s2-I2I2,s2-1+g(S2,I2,s2)g(S,I12,s2)f(S,I1)I1-acγ1I1 3.27
L˙2(S,E1,E2,I1,I2)=bE2,s24-bE2,s2g(S,I2,s2)I2,s2-g(S,I2)I2bE2-I2,s2E2I2E2,s2-g(S,I2,s2)g(S,I2)+bE2,s2g(S,I2,s2)g(S,I2)+g(S,I2)g(S,I2,s2)I2I2,s2-I2I2,s2-1+acγ1I1g(S2,I2,s2)g(S,I2,s2)f(S,I1)f(S0,0)R01-1. 3.28

From (H2) and (H3), we have f(S,I1)f(S0,0)1, then,

L˙2(S,E1,E2,I1,I2)bE2,s24-bE2,s2g(S,I2,s2)I2,s2-g(S,I2)I2bE2-I2,s2E2I2E2,s2-g(S,I2,s2)g(S,I2)+bE2,s2g(S,I2,s2)g(S,I2)+g(S,I2)g(S,I2,s2)I2I2,s2-I2I2,s2-1+acγ1I1g(S2,I2,s2)g(S,I2,s2)R01-1, 3.29

From (3.22), we have

g(S,I2,s2)g(S,I2)+g(S,I2)g(S,I2,s2)I2I2,s2-I2I2,s2-1=1-g(S,I2)g(S,I2,s2)g(S,I2,s2)g(S,I2)-I2I2,s20. 3.30

By the relation between arithmetic and geometric means, we have

4-bE2,s2g(S,I2,s2)I2,s2-g(S,I2)I2bE2-I2,s2E2I2E2,s2-g(S,I2,s2)g(S,I2)0 3.31

We discuss two cases:

  • If S2S, then from (H2), we will have g(S2,I2,s2)g(S,I2,s2)1, since g(S2,I2,s2)g(S,I2,s2)R01-10, from R011, we will have L˙20.

  • If SS2, then from (H2) we will obtain g(S2,I2,s2)g(S,I2,s2)1, from R01g(S,I2,s2)g(S2,I2,s2)1, we will get g(S2,I2,s2)g(S,I2,s2)R01-10, which implies, L˙20. By the above discussion, we deduce that if R011, then L˙20.

We conclude that the steady state Es2 is globally asymptotically stable when R011 and 1<R02.

Global stability of the third endemic equilibrium

For the global stability of Et, we assume that the functions f and g satisfy the following condition:

1-g(S,I2)g(St,I2,t)f(St,I1,t)f(S,I1,t)g(St,I2,t)g(S,I2)f(S,I1,t)f(St,I1,t)-I2I2,s20,S,I1,I2>0. 3.32

Theorem 5

The endemic equilibrium Est is globally asymptotically stable when R01>1 and R02>1.

Proof

We consider the Lyapunov function L3 defined by:

L3(S,E1,E2,I1,I2)=S-St-StSf(St,I1,t)f(X,I1,t)dX+E1,tE1E1,t-lnE1E1,t-1+E2,tE2E2,t-lnE2E2,t-1+aγ1I1,tI1I1,t-lnI1I1,t-1+bγ2I2,tI2I2,t-lnI2I2,t-1, 3.33

then

L˙3(S,E1,E2,I1,I2)=1-f(St,I1,t)f(S,I1,t)S˙+1-E1,tE1E1˙+1-E2,tE2E2˙+aγ11-I1,tI1I1˙+bγ21-I2,tI2I2˙. 3.34

It is easy to verify that

Λ=δSt+f(St,I1,t)I1,t+g(St,I2,t)I2,t,f(St,I1,t)I1,t=aE1,t,g(St,I2,t)I2,t=bE2,t,E1,tI1,t=cγ1,E2,tI2,t=eγ2. 3.35

As a result,

L˙3(S,E1,E2,I1,I2)=δSt1-SSt1-f(St,I1,t)f(S,I1,t)+aE1,t4-aE1,tf(S,I1,t)I1,t-f(S,I1)I1aE1-I1,tE1I1E1,t-f(S,I1,t)f(S,I1)+bE2,t4-f(St,I1,t)f(S,I1,t)-g(S,I2)I2bE2-I2,tE2I2E2,t-bE2,tf(S,I1,t)g(S,I2)f(St,I1,t)I2,t+aE1,tf(S,I1,t)f(S,I1)+f(S,I1)f(S,I1,t)I1I1,t-I1I1,t-1+bE2,s2g(St,I2,t)g(S,I2)f(S,I1,t)f(St,I1,t)+g(S,I2)g(St,I2,t)f(St,I1,t)f(S,I1,t)I2I2,t-I2I2,t-1. 3.36

Using the following trivial inequalities

1-f(St,I1,t)f(S,I1,t)0forSSt 3.37
1-f(St,I1,t)f(S,I1,t)<0forS<St, 3.38

then

1-SSt1-f(St,I1,t)f(S,I1,t)0, 3.39

by the relation between arithmetic and geometric means, we have

4-aE1,tf(S,I1,t)I1,t-f(S,I1)I1aE1-I1,tE1I1E1,t-f(S,I1,t)f(S,I1)0 3.40
4-f(St,I1,t)f(S,I1,t)-g(S,I2)I2bE2-I2,tE2I2E2,t-bE2,tf(S,I1,t)g(S,I2)f(St,I1,t)I2,t0, 3.41

from (3.12) we have

f(S,I1,t)f(S,I1)+f(S,I1)f(S,I1,t)I1I1,t-I1I1,t-1=1-f(S,I1)f(S,I1,t)f(S,I1,t)f(S,I1)-I1I1,t0, 3.42

also from (3.32) we have

g(St,I2,t)g(S,I2)f(S,I1,t)f(St,I1,t)+g(S,I2)g(St,I2,t)f(St,I1,t)f(S,I1,t)I2I2,t-1-I2I2,t=1-Γ1Γ-I2I2,t0, 3.43

with Γ=g(S,I2)g(St,I2,t)f(St,I1,t)f(S,I1,t)

We conclude that the steady state Et is globally asymptotically stable when 1<R01 and 1<R02.

Numerical simulations

In this section, we will perform some numerical simulations in order to examine numerically the SEIR infection dynamics under various incidence functions and also validating our theoretical results. Indeed, we will restrict ourselves to four cases, the first one is to consider the model (1.1) along with the simplest two bilinear incidence functions f(S,I1)=αS and g(S,I2)=βS, the second case deals with two Beddington–DeAngelis incidence functions, f(S,I1)=αS1+ω1S+ω2I1 and g(S,I2)=βS1+ω3S+ω4I2, while the third case is devoted to check the impact of choosing both incidence functions under Crowley–Martin incidence form, f(S,I1)=αS1+χ1S+χ2I1+χ1χ2SI1 and g(S,I2)=βS1+χ3S+χ4I2+χ3χ4SI2. The last case consists of incorporating into the model two non-monotonic incidence functions f(S,I1)=αS1+α1I12 and g(S,I2)=βS1+α2I22.

The stability of the disease-free equilibrium

The disease-free equilibrium is characterized by the extinction of the infection, and the disease cannot invade the population. In this subsection, attention will be focused to the numerical stability of such disease-free equilibrium. Indeed, Theorem 2 points out that we can expect the stability of disease-free equilibrium when the basic reproduction number is less than unity. This permits us to look for the right model parameters in order to check numerically the stability of the first steady sate.

Figure 2 shows the behaviour of the infection for the following parameter values: Λ=1, α=0.17, β=0.15, γ1=0.3, γ2=0.4, μ1=0.65, μ2=0.75, δ=0.2, ω1=0.4, ω2=0.6, ω3=4.5, ω4=5.8, χ1=2.5, χ2=3, χ3=6.5, χ4=5, α1=2.5 and α2=3. We clearly see that the solutions of the system, under the various suggested incidence functions (bilinear, Beddington–DeAngelis, Crowley–Martin and non-monotonic functions), converge towards the same disease-free equilibrium point Ef=(5,0,0,0,0,0). In this situation, the nature of the incidence function has no effect on the steady-state value. Consequently, it was remarked that the disease-free equilibrium first nonzero component depends only on the birth and death rates of the susceptible individuals and does not depend, in any way, on the incidence functions parameters. Here, the disease dies out, the susceptible reaches their maximum value, and the other variables vanish. With the chosen parameters, we can easily calculate the two- strain basic reproduction numbers; in our case, we will have R01=0.6 and R02=0.5263 for the bilinear incidence functions case; we will have also R01=0.1 and R02=0.6579 for the Beddington–DeAngelis incidences case; R01=0.1154 and R02=0.1645 are calculated for Crowley–Martin incidence functions case, and finally, we have R01=0.6 and R02=0.5263 for the non-monotonic incidence functions case. In all these cases, we have the basic reproduction number R0 is less than unity which is consistent with the theoretical result concerning the stability of the disease-free equilibrium Ef.

Fig. 2.

Fig. 2

Time evolution of susceptible (top left), the strain 1 latent individuals (top middle), the strain 2 latent individuals (top right), the recovered (bottom left), the strain 1 infectious individuals (bottom middle) and the strain 2 infectious individuals (bottom right) illustrating the stability of the disease-free equilibrium Ef. The bilinear incidence functions (dotted red), Beddington–DeAngelis incidence functions (yellow), Crowley–Martin incidence functions (green) and the non-monotone incidence functions (blue). (Color figure online)

The stability of the endemic equilibria

The dynamics behaviour concerning the stability of the strain 1 endemic equilibrium Es1 is shown in Fig. 3. Indeed, we have chosen the following parameter values: Λ=1, α=0.5, β=0.12, γ1=0.4, γ2=0.3, μ1=0.4, μ2=0.75, δ=0.2, ω1=0.4, ω2=0.85, ω3=1.5, ω4=0.05, χ1=4, χ2=3.5, χ3=0.3, χ4=0.05, α1=2 and α2=1.5. For the bilinear incidence functions case, the solution converges towards the strain 1 endemic equilibrium (1.8, 1.0667, 0, 0.7111, 0, 1.4222) and with the chosen parameters we have R01=2.7778 and R02=0.3789. For the model with Beddington–DeAngelis, we observe the convergence towards (3.1788,0.6071,0,0.4047,0,0.8094) and we have R01=11.1111 and R02=0.3609; for the third case, Crowley–Martin incidence type, we observe the convergence towards the equilibrium (2.3664, 0.8779, 0, 0.5852, 0, 1.1705) and we have R01=11.1111 and R02=0.1024. For the last non-monotonic incidence functions case, we see in the figure the convergence towards the steady state (2.7223, 0.7592, 0, 0.5062, 0, 1.0123) and we have R01=2.7778 and R02=0.3789. We remark that, for the all four cases, the strain 1 basic reproduction number R01 is greater than unity while the other strain 2 basic reproduction number R02 is less than one which confirms our theoretical findings concerning the stability of the strain 1 endemic equilibrium Es1. This endemic equilibrium is characterized by the vanishing the strain 2 latent and infectious individuals.

Fig. 3.

Fig. 3

Time evolution of susceptible (top left), the strain 1 latent individuals (top middle), the strain 2 latent individuals (top right), the recovered (bottom left), the strain 1 infectious individuals (bottom middle) and the strain 2 infectious individuals (bottom right) illustrating the stability of the strain 1 endemic equilibrium Es1. The bilinear incidence functions (dotted red), Beddington–DeAngelis incidence functions (yellow), Crowley–Martin incidence functions (green) and the non-monotone incidence functions (blue). (Color figure online)

The strain 2 endemic equilibrium Es2 stability is illustrated in Fig. 4. In this figure, the following parameters are chosen: Λ=1, α=0.2, β=0.4, γ1=0.4, γ2=0.3, μ1=1, μ2=0.5, δ=0.2, ω1=0.4, ω2=0.85, ω3=1.5, ω4=0.05, χ1=4, χ2=3.5, χ3=0.3, χ4=0.05, α1=2 and α2=1.5. We observe the convergence of the solution towards the steady state (2.9167, 0, 0.8333, 0, 0.3571, 0.8928) for the bilinear incidence functions case and with the adopted parameters we have R01=0.5556 and R02=1.7143. For the model with Beddington–DeAngelis, we observe the convergence towards (4.1559,0,0.3376,0,0.1447,0.3617) and we have R01=0.5291 and R02=6.8571; for the third case, Crowley–Martin incidence type, we observe the convergence towards the equilibrium (3.6876, 0, 0.5250, 0, 0.2250, 0.5624) and we have R01=0.1502 and R02=6.8571. For the last non-monotonic incidence functions case, we see in the figure the convergence towards the steady state (3.2918, 0, 0.6833, 0, 0.2928, 0.7321) and we have R01=0.5556 and R02=1.7143. We remark that, for all the four cases, the strain 1 basic reproduction number R01 is less than unity while the other strain 2 basic reproduction number R02 is greater than one which is in good agreement with our theoretical findings concerning the stability of the strain 2 endemic equilibrium Es2. From the components of this endemic equilibrium, we remark the clearance of the strain 1 latent and infectious individuals.

Fig. 4.

Fig. 4

Time evolution of susceptible (top left), the strain 1 latent individuals (top middle), the strain 2 latent individuals (top right), the recovered (bottom left), the strain 1 infectious individuals (bottom middle) and the strain 2 infectious individuals (bottom right) illustrating the stability of the strain 2 endemic equilibrium Es2. The bilinear incidence functions (dotted red), Beddington–DeAngelis incidence functions (yellow), Crowley–Martin incidence functions (green) and the non-monotone incidence functions (blue). (Color figure online)

The last endemic equilibrium Et stability behaviour is depicted in Fig. 5 for Λ=1, α=0.6, β=0.6, γ1=0.5, γ2=0.5, μ1=0.15, μ2=0.15, δ=0.2, ω1=1.2, ω2=0.06, ω3=1.2, ω4=0.06, χ1=0.4, χ2=0.05, χ3=0.4, χ4=0.05, α1=0.14 and α2=0.145. As the previous figures, the dynamics for the different suggested incidence functions are illustrated. For the first one, the bilinear incidence function, we observe the convergence towards (0.8167, 0.5196, 0.6757, 0.7422, 0.9652, 1.2806) and with the adopted parameters we have R01=6.1224 and R02=6.1224. For Beddington–DeAngelis case, we observe the convergence towards (1.5783,0.4888,0.4888,0.6983,0.6983,1.0474) and we have R01=23.5479 and R02=23.5479, for the third case, Crowley–Martin incidence type, we observe the convergence towards the equilibrium (1.1353,0.5519,0.5523,0.7884,0.7890,1.1831) and we have R01=24.4898 and R02=24.4898. About the last non-monotonic incidence functions case, we see the convergence towards the steady state (0.8982,0.5904,0.5815,0.8433,0.8309,1.2557) and we have R01=6.1224 and R02=6.1224. We remark that both the two-strain basic reproduction numbers R01 and R02 are greater than unity which confirms our theoretical findings concerning the stability of the last endemic equilibrium Et. This last endemic equilibrium is characterized by the persistence of all strains latent and infectious individuals. The numerical simulations confirm that the model with general incidence functions encompasses a large number of classical well-known incidence functions. Therefore, the generalized mathematical model can give a wide view about the stability of the different problem equilibria.

Fig. 5.

Fig. 5

Time evolution of susceptible (top left), the strain 1 latent individuals (top middle), the strain 2 latent individuals (top right), the recovered (bottom left), the strain 1 infectious individuals (bottom middle) and the strain 2 infectious individuals (bottom right) illustrating the stability of the endemic equilibrium Et. The bilinear incidence functions (dotted red), Beddington–DeAngelis incidence functions (yellow), Crowley–Martin incidence functions (green) and the non-monotone incidence functions (blue). (Color figure online)

Comparison with COVID-19 clinical data

As we have mentioned in the introduction, the recent pandemic COVID-19 is a multi-strain infection. Therefore, the main interest of this subsection is to compare the numerical simulations resulting from our multi-strain epidemic model with COVID-19 clinical data. We have chosen to make our comparison the Moroccan clinical data during the year 2020 in the period between March 31 and June 20 [39, 40].

Figure 6 shows the time evolution of infected cases for the following parameter values: Λ=1.5, α=1.67, β=0.88, δ=0.2, γ1=1.05, γ2=6.8, μ1=0.005, μ2=0.087, ω1=0.3, ω2=0.5, ω3=0.1, ω4=0.3, χ1=0.01, χ2=0.01, χ3=2.5, χ4=2.8, α1=0.0005 and α2=0.007. We observe that a significant relationship exists between the curve representing the COVID-19 clinical data and the numerical simulations resulting from our mathematical model for the different incidence functions. Indeed, a good fit between the infected cases given by the mathematical model and the clinical data is observed. Each numerical result with the incidence function (bilinear, Beddington–DeAngelis, Crowley–Martin or non-monotonic function) fits well the clinical data, especially for a certain period of observation. Hence, the multi-strain mathematical model with generalized incidence functions is more appropriate to represent the studied disease.

Fig. 6.

Fig. 6

Time evolution of infected cases with the bilinear incidence functions (dotted red), Beddington–DeAngelis incidence functions (yellow), Crowley–Martin incidence functions (green) and the non-monotone incidence functions (blue). The clinical infected cases are illustrated by magenta circles. (Color figure online)

Figure 7 (left-hand side) shows the time evolution of infected cases for the following parameter values: Λ=2, α=0.01, β=0.01, γ1=0.3, γ2=0.4, μ1=0.07, μ2=0.5, δ=0.2, ω1=0.5, ω2=0.6, ω3=0.1, ω4=0.3, χ1=1.5, χ2=2, χ3=0.7, χ4=3.7, α1=2 and α2=1.5. We see that the solution of our model, under the various suggested incidence functions, converges towards the same disease-free equilibrium point Ef. In this situation, the disease dies out, the susceptible reaches their maximum value and the other variables vanish. Within the chosen parameters, we can easily calculate the basic reproduction number; in our case we will have R0=0.23 for the bilinear incidence functions case; we will have also R0=0.28 for the Beddington–DeAngelis incidences case; R0=0.2 are calculated for Crowley–Martin incidence functions case, and finally, we have R0=0.23 for the non-monotonic incidence functions case.

Fig. 7.

Fig. 7

Time evolution of infected cases with the bilinear incidence functions (dotted red), Beddington–DeAngelis incidence functions (yellow), Crowley–Martin incidence functions (green) and the non-monotone incidence functions (blue). The clinical infected cases are illustrated by magenta circles. (Color figure online)

The COVID-19 disease persistence case is illustrated in Fig. 7 (right-hand side). In this figure, the following parameters are chosen: Λ=1.2, α=0.1, β=0.52, γ1=0.4, γ2=0.1, μ1=0.23, μ2=0.2, δ=0.03, ω1=0.5, ω2=0.6, ω3=0.1, ω4=0.3, χ1=1.5, χ2=4.5, χ3=0.7, χ4=0.12, α1=2 and α2=1.5. We remark the convergence of the solution towards the endemic equilibrium for all the taken incidence functions. Indeed, for the case with bilinear incidence functions, we have the basic reproduction number is greater than unity R0=14.31. For other cases, the basic reproduction number is also greater than one; indeed for Beddington–DeAngelis case, we have R0=36.6956; for the third case, Crowley–Martin incidence type, we have R0=14.3113. For the last non-monotonic incidence functions case, we have R0=14.3113 which means that the disease persists. We can conclude that the numerical simulations fit well COVID-19 clinical data. Our numerical simulations reveal two scenarios of evolution for this pandemic, and within the first scenario the disease will die out. The other scenario happens when the basic reproduction number is greater than unity; in this case the disease will persist. In this situation, it will be important to eventually undertake some strategies like quarantine, isolation, wearing of masks, disinfection and if it will be possible vaccination.

The effect of quarantine strategy

In this subsection, we will study the effect of quarantine strategy in controlling the infection spread. To illustrate this effect and for simplicity, we will restrict ourselves to the case of the bilinear incidence function. More precisely, we will take the following incidence forms:

f(S,I1)=α(1-u1)Sandg(S,I2)=β(1-u2)S, 4.1

where u1 stands for the efficiency of the quarantine strategy concerning the first strain infection rate, while u2 represents the efficacy of the quarantine measures concerning the second-strain infection rate. Our numerical simulations will be performed in order to check the impact of the quarantine strategy for the case of the last endemic equilibrium.

Figure 8 shows the time evolution of the susceptible, the two- strain latent individuals, two-strain infected individuals and the recovered for the following parameter values: Λ=1, α=0.6, β=0.6, γ1=0.5, γ2=0.5, μ1=0.15, μ2=0.15, δ=0.2 and for different values of the strategy controls u1 and u2. When no strategy is applied, we find the same result as in Fig. 5. By increasing the efficiency of the quarantine measures, we observe an interesting result. Indeed, the number of the susceptible individuals increases when u1 and u2 increase. For higher values of these two control parameters, the number of two-strain latent and infected individuals is reduced considerably, which means that the quarantine strategy can reduce the infection in efficient manner.

Fig. 8.

Fig. 8

Effect of quarantine strategy on the SEIR model dynamics

Conclusion

In this paper, we have studied the global stability of two-strain epidemic model with two general incidence functions. The model included six compartments, namely the susceptible, two categories of the exposed, two categories of the infected and the removed individuals, this kind of model takes the abbreviation SEIR. We have established the existence, positivity and boundedness of solutions results which guarantee the wellposedness of our SEIR model. The disease-free equilibrium, the endemic equilibrium with respect to strain 1, the endemic equilibrium with respect to strain 2 and the endemic equilibrium with respect to both strains are given. By using an appropriate Lyapunov functionals, the global stability of the equilibria is established depending on the basic reproduction number R0, the strain 1 reproduction number R01 and the strain 2 reproduction number R02. Numerical simulations are performed in order to confirm our different theoretical results. It was observed that the model with a generalized incidence function encompasses a large number of classical incidence functions and it can give more clear view about the equilibria stability. In addition, a numerical comparison between our model results and COVID-19 clinical data is conducted. We have observed a good fit between our numerical simulations and the clinical data which indicates that our multi-strain mathematical model can fit and predict the evolution of the infection. We have observed that strict quarantine measures can reduce significantly the infection spread. It is worthy to notice that a generalization form of this problem to a more complex compartmental model is proposed in Appendix of this paper. For this complex model, we have given its basic reproduction number and each strain reproduction number. Furthermore, the forms of the Lyapunov functionals for this complex compartmental model are also formulated.

Appendix

Multi-strain compartmental epidemiological model

The generalization of the problem to a more complex compartmental model with general incidence rates is formulated as follows

(P)dSdt=Λ-i=1i=nfi(S,Ii)Ii-δS,dEidt=fi(S,Ii)Ii-(γi+δ)Ei,i=1,2,,ndIidt=γiEi-(μi+δ)Ii,i=1,2,,ndRdt=i=1i=nμiIi-δR, A.1

with

S(0)0,Ei(0)0,Ii(0)0,R(0)0,i{1,2,,n}.

This model contains 2n+2 variables (nN) that are: the susceptible individuals S, removed individuals R, n categories of latent individuals E1,E2,En and n categories of infectious individuals I1,I2,,In. The parameter 1δ represents the average life expectancy of the population, 1μi represents the average infection period of strain i, 1γi represents the average latency period of strain i. Finally, fi(S,Ii) represents the general incidence rate for the strain i and verifies the follows conditions:

fi(0,Ii)=0,Ii0,i=1,2,,nfi(S,Ii)S>0,S>0,Ii0,i=1,2,,nfi(S,Ii)Ii0,S0,Ii0,i=1,2,,n.

Main steps of the global analysis

The model is well defined, all solutions with non-negative initial conditions exist, remain non-negative and bounded. Let N(t) be the total population, we have

N(t)=S(t)+i=1i=nEi(t)+i=1i=nIi(t)+R(t). A.2

By adding all equations of the problem (P), we will have

dN(t)dt=Λ-δN(t), A.3

then,

N(t)=Λδ+(N(0)-Λδ)e-δt, A.4

and consequently,

limt+N(t)=Λδ. A.5

This means that the biological feasible region is given by

H={(S,E1,E2,,En,I1,I2,,In,R)R+2n+2such thatS+i=1i=nEi+i=1i=nIi+RΛδ} A.6

is positively invariant.

The basic reproduction number is given by

R0=maxi{1,2,,n}fi(Λδ,0)γi(γi+δ)(μi+δ). A.7

and the strain i reproduction number is given by

R0i=fi(Λδ,0)γi(γi+δ)(μi+δ),i=1,2,,n. A.8

By simple reasoning, we can easily prove that this problem has 2n steady states.

It is clear that the disease-free equilibrium point Ef(Λδ,0,,0) is globally asymptotically stable if R01.

In order to study the global stability for each equilibrium point Esi (i{1,2,,n}), it appears that the Lyapunov functional can take the following form

Li(S,E1,E2,,En,I1,I2,,In)=S-Ssi-SsiSf(Ssi,Ii,si)f(X,Ii,si)dX+i=1i=nEi,siEiEi,si-lnEiEi,si-1+i=1i=nγi+δγiIi,siIiIi,si-lnIiIi,si-1. A.9

The functions fi are assumed to verify the following condition:

1-Γ1Γ-IiIi,si0,S,Ii>0i=1,2,,n,

with Γ=i=1i=nfi(S,Ii,si)fi(Ssi,Ii,si)fj(Ssi,Ij,sj)fj(S,Ij,sj) such that Ii,si0, Ij,sj0,i{1,2,,n},j{1,2,,n}andij.

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The authors declare that they have no conflict of interest.

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