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Journal of Advanced Research logoLink to Journal of Advanced Research
. 2015 Jun 27;7(2):271–283. doi: 10.1016/j.jare.2015.06.004

Numerical study for multi-strain tuberculosis (TB) model of variable-order fractional derivatives

Nasser H Sweilam a,, Seham M AL-Mekhlafi b
PMCID: PMC4767813  PMID: 26966568

Abstract

In this paper, we presented a novel multi-strain TB model of variable-order fractional derivatives, which incorporates three strains: drug-sensitive, emerging multi-drug resistant (MDR) and extensively drug-resistant (XDR), as an extension for multi-strain TB model of nonlinear ordinary differential equations which developed in 2014 by Arino and Soliman [1]. Numerical simulations for this variable-order fractional model are the main aim of this work, where the variable-order fractional derivative is defined in the sense of Grünwald–Letnikov definition. Two numerical methods are presented for this model, the standard finite difference method (SFDM) and nonstandard finite difference method (NSFDM). Numerical comparison between SFDM and NSFDM is presented. It is concluded that, NSFDM preserves the positivity of the solutions and numerically stable in large regions than SFDM.

Keywords: Nonstandard finite difference, Epidemic model, Tuberculosis, M/XDR-TB, Variable-order fractional, Grünwald–Letnikov definition

Introduction

Variable-order fractional calculus (i.e., the fractional differentiation and integration of variable order) is the generalization of classical calculus and fractional calculus, which were invented by Newton and Leibnitz hundreds of years ago. Now the study on it becomes a hot pot in recent ten years [2], [3], [4], [5], [6], [7]. It has turned out that many problems in physics, biology, engineering, and finance can be described excellently by models using mathematical tools from variable-order fractional calculus, such as mechanical applications [2], diffusion process [5], multifractional Gaussian noise [8], and FIR filters [9]. For more details, see [7], [10] and references therein. Understanding the transmission characteristics of infectious diseases in communities, regions and countries can lead to better approaches to decrease the transmission of these diseases [11]. Variable-order fractional derivative is good at depicting the memory property which changes with time or spatial location [3], [5].

TB is growing more resistant to treatment worldwide according to study released in August 2012 in the journal Lancet, a finding that suggests the potentially fatal disease is becoming more difficult and costly to treat [12]. In this article we focused our attention in Egypt.

We consider in this work a model developed by Arino and Soliman for TB [1]. The model incorporates three strains, drug-sensitive, MDR and XDR. Several papers considered modeling TB such as [13], [14], but the model we consider here includes several factors of spreading TB such as the fast infection, the exogenous reinfection and secondary infection along with the resistance factor. The main aim of this paper was to study numerically the multi-strain TB model of variable-order fractional derivatives which incorporates three strains: drug-sensitive, MDR and XDR. We develop a special class of numerical method, known as NSFDM for solving this model. This technique, developed by Mickens (1980) [15], [16], [17], [18], [19], [20], [21], [22], [23] has brought a creation of new numerical schemes preserving the physical properties, especially the stability properties of equilibria, of the approximated system. Numerical comparison between NSFDM and SFDM is presented. When the secondary infection generated by an infected individual exceeds the unity, there are no analytical results proved for the model, such as the existence and stability of the endemic equilibrium (EE). In this case we use the developed NSFD numerical scheme to approximate the endemic solution numerically and investigate its stability. Furthermore, with the help of the NSFDM, we answer the following question: Given the data provided by the World Health Organization (2012) on the current parameters corresponding to the propagation of the TB in Egypt, what would be the required rate of treatment to achieve in order to control the disease? The proposed method showed its superiority in preserving the positivity (compared to the numerical standard method considered in this work) of the state variables of the systems under study. This is an essential requirement when simulating systems especially those arising in biology. This paper is organized as follows: In Section ‘Mathematical model’, Mathematical model is presented. Preliminaries and notations on variable-order fractional differential equations are given, in Section ‘Preliminaries and notations’. Equilibrium points and their asymptotic stability are presented in Section ‘Variable-order fractional derivatives for multi-strain TB model’. Variable-order fractional derivatives for the multi-strain TB model are presented; moreover, the construction of the proposed nonstandard numerical scheme is carried out in Section ‘Equilibrium points and their asymptotic stability’. In Section ‘Numerical results and simulations’, Numerical results and simulation are discussed. Finally, in Section ‘Conclusions’ we presented the conclusions.

Mathematical model

The multistrain TB-model given in [1] can be formulated as follows:

S=b-dS-βsSIsN-βmSImN-βxSIxN, (1)
Ls=λsβsSIsN+σsλsβsRIsN+γsIs-αssβsLsIsN-αsmβmLsImN-αsxβxLsIxN-(d+εs+t1s)Ls, (2)
Lm=λmβmSImN+σmλmβmRImN+γmIm+αsmβmλmLsImN+(1-P1)t1sLs+(1-P2)t2sIs-αmmβmLmImN-αmxβxLmIxN-(d+εm)Lm, (3)
Lx=λxβxSIxN+σxλxβxRIxN+γxIx+αsxβxλxLsIxN+αmxβxλxLmIxN+(1-P3)t2mIm-αxxβxLxIxN-(d+εx)Lx, (4)
Is=αssβsLsIsN+(1-λs)βsSIsN+σsRIsN+εsLs-(d+δs+t2s+γs)Is, (5)
Im=αmmβmLmImN+(1-λm)βmSImN+σmRImN+αsmLsImN+εmLm-(d+δm+t2m+γm)Im, (6)
Ix=αxxβxLxIxN+(1-λx)βxSIxN+σxRIxN+αsxLsIxN+αmxLmIxN+εxLx-(d+δx+t2x+γx)Ix, (7)
R=P1t1sLs+P2t2sIs+P3t2mIm+t2xIx-σsβsRIsN-σmβmRImN-σxβxRIxN-dR. (8)

All variables in above system and their definition are in Table 1. Also, all parameters and their interpretation are in Table 2.

Table 1.

All variables of the system (1), (2), (3), (4), (5), (6), (7), (8) and their interpretation.

Variable Definition
S(t) The susceptible population individuals who have never encountered TB
Ls(t) The individuals infected with the drug-sensitive TB strain but who are in a latent stage, i.e., who are neither showing symptoms nor infecting others
Lm(t) Individuals latently infected with MDR-TB
Lx(t) Individuals latently infected with XDR-TB
Is(t) Individuals infected with the drug-sensitive TB strain who are infectious to others (and most likely, showing symptoms as well)
Im(t) Those individuals who are infectious with the MDR-TB strain
Ix(t) Individuals who infectious with the XDR-TB strain
R(t) Those individuals for whom treatment was successful
N(t) The total population
N=S+Ls+Lm+Lx+Is+Im+Ix+R

Table 2.

All parameters of the system (1), (2), (3), (4), (5), (6), (7), (8) and their interpretation.

Parameter Interpretation
b Birth/recruitment rate
d Per capita natural death rate
Disease dynamics
βr Transmission coefficient for strain r
λr Proportion of newly infected individuals developing LTBI with strain r
1-λr Proportion of newly infected individuals progressing to active TB with strain r due to fast infection
εr Per capita rate of endogenous reactivation of Lr
αr1,αr2 Proportion of exogenous reinfection of Lr1 due to contact with Ir2
γr Per capita rate of natural recovery to the latent stage Lr
δr Per capita rate of death due to TB of strain r
Treatment related
t1s Per capita rate of treatment for Ls
t2r Per capita rate of treatment for Ir. Note that t2x is the rate of successful treatment of Ix,r{x,m,s}
1-σr Efficiency of treatment in preventing infection with strain r
P1 Probability of treatment success for Ls
1-P1 Proportion of treated Ls moved to Lm due to incomplete treatment or lack of strict compliance in the use of drugs
P2 Probability of treatment success for Is
1-P2 Proportion of treated Is moved to Lm due to incomplete treatment or lack of strict compliance in the use of drugs
P3 Probability of treatment success for Im
1-P3 Proportion of treated Im moved to Lx due to incomplete treatment or lack of strict compliance in the use of drugs

The basic reproduction number R0

The basic reproduction number R0 for system (1), (2), (3), (4), (5), (6), (7), (8) is given by [1]

R0=max(R0s,R0m,R0x), (9)

where

R0s=βs(εs+(1-λs)(d+t1s))(εs+d+t1s)(t2s+δs+d)+γs(t1s+d),
R0m=βm(εm+(1-λm)d)(εm+d)(t2m+δm+d)+dγm,
R0x=βx(εx+(1-λx)d)(εx+d)(t2x+δx+d)+dγx.

Theorem [1] assumes that

0αss(1-λs), (10)
0αmm(1-λm), (11)
0αxx(1-λx). (12)

Then the disease free equilibrium is globally asymptotically stable when R0<1 and endemic equilibria are locally asymptotically stable when R0>1.

Preliminaries and notations

In this section, some basic definitions and properties in the theory of the variable-order fractional calculus are presented.

Grünwald–Letnikov approximation

We will begin with the signal variable-order fractional differential

Dtα(t)y(t)=f(t,y(t)),Tt0,and,y(t0)=0, (13)

where α(t)>0, and Dtα(t) denotes the variable fractional order derivative, defined by

Dtα(t)y(t)=Jn-α(t)Dtα(t)y(t), (14)

where n-1<α(t)n, nN and Jn is the nth-order Riemann–Liouville integral operator defined as

Jny(t)=1Γ(t)t0(t-τ)n-1y(τ)dτ,witht>0, (15)

where Γ(·) is the gamma function.

To apply Miken’s scheme, we have chosen this Grünwald–Letnikov approximation variable-order fractional derivative as follows [15]:

Dtα(t)y(t)=limh0h-α(t)j=0[th](-1)jα(t)jy(t-jh), (16)

where [t] denotes the integer part of t and h is the step size; therefore, Eq. (16) is discretized as

j=0[th]ωjα(tn)y(tn-j)=f(tn,y(tn))n=1,2,3,. (17)

where tn=nh, and ωjα(tn), are the Grünwald–Letnikov coefficients defined as

ωjα(tn)=1-1+α(tn)jωj-1α(tn)andω0α(tn)=h-α(tn),j=1,2,3,.

.

Variable-order fractional derivatives for multi-strain TB model

In the following, we introduce the multi-strain TB model of variable-order fractional derivatives which is the integer order given in system (1), (2), (3), (4), (5), (6), (7), (8), and the new system is described by variable-order fractional differential equations as follows:

Dtα(t)S=b-dS-βsSIsN-βmSImN-βxSIxN, (18)
Dtα(t)Ls=λsβsSIsN+σsλsβsRIsN+γsIs-αssβsLsIsN-αsmβmLsImN-αsxβxLsIxN-(d+εs+t1s)Ls, (19)
Dtα(t)Lm=λmβmSImN+σmλmβmRImN+γmIm+αsmβmλmLsImN+(1-P1)t1sLs+(1-P2)t2sIs-αmmβmLmImN-αmxβxLmIxN-(d+εm)Lm, (20)
Dtα(t)Lx=λxβxSIxN+σxλxβxRIxN+γxIx+αsxβxλxLsIxN+αmxβxλxLmIxN+(1-P3)t2mIm-αxxβxLxIxN-(d+εx)Lx, (21)
Dtα(t)Is=αssβsLsIsN+(1-λs)βsSIsN+σsRIsN+εsLs-(d+δs+t2s+γs)Is, (22)
Dtα(t)Im=αmmβmLmImN+(1-λm)βmSImN+σmRImN+αsmLsImN+εmLm-(d+δm+t2m+γm)Im, (23)
Dtα(t)Ix=αxxβxLxIxN+(1-λx)βxSIxN+σxRIxN+αsxLsIxN+αmxLmIxN+εxLx-(d+δx+t2x+γx)Ix, (24)
Dtα(t)R=P1t1sLs+P2t2sIs+P3t2mIm+t2xIx-σsβsRIsN-σmβmRImN-σxβxRIxN-dR, (25)

where Dtα(t) is the Caputo variable fractional order derivative. Because model (18), (19), (20), (21), (22), (23), (24), (25) monitors the dynamics of human populations, all the parameters are assumed to be nonnegative.

Equilibrium points and their asymptotic stability

Let α(t)(0,1] and consider the system (18), (19), (20), (21), (22), (23), (24), (25)

Dtα(t)S(t)=f1(S,Ls,Lm,Lx,Is,Im,Ix,R),Dtα(t)Ls(t)=f2(S,Ls,Lm,Lx,Is,Im,Ix,R),Dtα(t)Lm(t)=f3(S,Ls,Lm,Lx,Is,Im,Ix,R),Dtα(t)Lx(t)=f4(S,Ls,Lm,Lx,Is,Im,Ix,R),Dtα(t)Is(t)=f5(S,Ls,Lm,Lx,Is,Im,Ix,R),Dtα(t)Im(t)=f6(S,Ls,Lm,Lx,Is,Im,Ix,R),Dtα(t)Ix(t)=f7(S,Ls,Lm,Lx,Is,Im,Ix,R),Dtα(t)R(t)=f8(S,Ls,Lm,Lx,Is,Im,Ix,R).

With the initial values (S(0),Ls(0),Lm(0),Lx(0),Is(0),Im(0),Ix(0),R(0)).

To evaluate the equilibrium points let

Dtα(t)S=Dtα(t)Ls=Dtα(t)Lm=Dtα(t)Lx=Dtα(t)Is=Dtα(t)Im=Dtα(t)Ix=Dtα(t)R=0fi(Seq,Lseq,Lmeq,Lxeq,Iseq,Imeq,Ixeq,Req)=0,i=1,2,3,,8.

From which we can get the equilibrium points (Seq,Lseq,Lmeq,Lxeq,Iseq,Imeq,Ixeq,Req).

To evaluate the asymptotic stability let

S(t)=Seq+ε1(t),Ls(t)=Lseq(t)+ε2(t),Lm(t)=Lmeq(t)+ε3(t),Lx(t)=Lxeq(t)+ε4(t),Is(t)=Iseq(t)+ε5(t),Im(t)=Imeq(t)+ε6(t),Ix(t)=Ixeq(t)+ε7(t),R(t)=Req+ε8(t).

So the equilibrium point (Seq,Lseq,Lmeq,Lxeq,Iseq,Imeq,Ixeq,Req) is locally asymptotically stable if all eigenvalues of Jacobian evaluated at the equilibrium point satisfy [16]

|argλi|>α(t)π2,α(t)(0,1],t0wherei=1,2,,8. (26)

To evaluate the equilibrium points, let

Dtα(t)S=Dtα(t)Ls=Dtα(t)Lm=Dtα(t)Lx=Dtα(t)Is=Dtα(t)Im=Dtα(t)Ix=Dtα(t)R=0fi(Seq,Lseq,Lmeq,Lxeq,Iseq,Imeq,Ixeq,Req)=0,i=1,2,3,,8.

Now, if Is=Im=Ix=0Ls=Lm=Lx=0, R=0 and S=bd.

Then the disease free equilibrium (DFE) is E0=bd,0,0,0,0,0,0,0.

We calculate the Jacobian matrix of the system (18), (19), (20), (21), (22), (23), (24), (25) at the disease free equilibrium point as follows:

J(E0)=a000bcd00e00f0000gh0pq00000r0st00u00v00000w00x00000y00z00m00njka,

where a=-d,b=-βs,c=-βm,d=-βx,e=-(d+εs+t1s),f=γs+λsβs, v=-(d+δs+t2s+γs),g=(1-P1)t1s,h=-(d+εm),p=(1-P2)t2s,q=γm+λmβm,r=-(d+εx), s=(1-P3)t2m,t=γx+λxβx,u=εs,x=-(d+δm+t2m+γm),w=εm.

y=εx,z=-(d+δx+t2x+γx),m=P1t1s,n=P2t2s,j=P3t2m,k=t2x.

The characteristic equation associated with above matrix is |J(E0)-λI|=0(a-λ)2(λ2-(r+z)λ-yt+zr)(-λ2+(h+x)λ-xh+wq)(-λ2+(e+v)λ+uf-ve)=0. Then the eigenvalues of Jacobian matrix are λ1,2=-d, λ3,4=r+z±(r2+2zr+z2+4yt)2,λ5,6=x+h±(x2-2xh+h2+4wq)2,λ7,8=v+e±(v2+2ve+e2+4uf)2, by using Theorem (Routh Hurwitz criteria) [17], these roots are negative or have negative real parts and DFE is locally asymptotically stable if all eigenvalues of the Jacobian matrix satisfies |argλi|=|-π|>α(t)π2, α(t)(0,1], t0. For simplicity, we will determine the stability of the DFE numerically by using Table 3 and put βs=βm=βx=0.1. Then eigenvalues are λ1=-0.3800, λ2=-0.3800, λ3=-0.3675, λ4=-0.3675, λ5=-1.2215, λ6=-1.2215, λ7=-2.0882, λ8=-1.2268. So, if R0<1, the DFE is locally asymptotically stable since |argλi|=|-π|>α(t)π2, α(t)(0,1], t0.

Table 3.

All parameters in the system (18), (19), (20), (21), (22), (23), (24), (25) and the reference of the parameters.

Parameter Value Reference
b 3190 Assumed
d 0.38 [26]
βs=βm=βx 14 [26]
λs=λm=λx 0.5 Assumed
εs=εm=εx 0.5 Assumed
αr1,r2 0.05 Assumed
γs=γm=γx 0.3 Assumed
t1s 0.88 [26]
t2r:r(s,m,x) t2s=0.88; t2m=t2x=0.034 [26]
σr 0.25 [26]
Pr 0.88 [26]
δr 0.045 [26]

If at least one of the infected variables is non-zero, then the solutions for model (18), (19), (20), (21), (22), (23), (24), (25) are the endemic equilibrium [1]. This system is highly nonlinear in Is, Im and Ix, and hence explicit solutions are not obtainable. So we solved the system (18), (19), (20), (21), (22), (23), (24), (25) numerically to obtain endemic fixed point using NSFDM.

SFD discretization

SFD methods are simple numerical methods for approximating the solutions of differential equations using finite differences to approximate the derivatives.

The forward Euler method is one of these methods, in this method the derivative term dydt is replaced by y(t+h)-y(t)h, where h is the step size, for more details see [18].

NSFD discretization

The nonstandard finite difference schemes were introduced by Mickens in the 1980s as a powerful numerical method that preserves significant properties of exact solutions of the involved differential equation [19]. The concept of the nonstandard finite difference method is discussed in [20].

Definition 1

A numerical scheme is called NSFD discretization if at least one of the following conditions is satisfied [18]:

  • 1.

    Nonlocal approximation is used.

  • 2.

    The discretization of derivative is not traditional and uses a nonnegative function [19], [20].

To describe the main aspects of NSFD schemes, we consider an ODE in the form

dydt=f(t,y,λ), (27)

where λ is a possibly vector, parameter. Given a mesh-grid tn=t0+hn that just for simplicity we assume to be equispaced with step-size h> 0, NSFD schemes are constructed by the following two main steps: 1- the derivative at the left-hand side of (27) is replaced by a discrete representation in the form

dydt=yn+1-ynφ(λ,h),

where yn+1 is an approximation of y(tn), 2-the nonlinear term in (27) is replaced by a nonlocal discrete representation F(t,yn+1,yn,,λ) depending on some of the previous approximations.

For example, if there are nonlinear terms such as y(t)x(t)N(t) in the differential equation, these are replaced by y(t+h)x(t)N(t) or x(t+h)y(t)N(t).

Let us denote by Sn, Lsn, Lmn, Lxn, Isn, Imn, Ixn and Rn the values of the approximations of S(nh), Ls(nh), Lm(nh), Lx(nh), Is(nh), Im(nh), Ix(nh) and R(nh) respectively, for n=0,1,2, and h is the timestep of the scheme. The sequences Sn, Lsn, Lmn, Lxn, Isn, Imn, Ixn and Rn should be nonnegative in order to be consistent with the biological nature of the model [21].

NSFDM has many advantages than SFDM, for more details see [20], [21], [22], [23], [24]. Generally speaking, we can say that NSFDM is more efficient and accurate than SFDM [15], [25].

NSFD for variable-order fractional derivatives system

The system (18), (19), (20), (21), (22), (23), (24), (25) can be discretized as follows:

j=0n+1ωjα(tn)Sn+1-j=b-dSn+1-βsSn+1IsnNn-βmSn+1ImnNn-βxSn+1IxnNn, (28)
j=0n+1ωjα(tn)Lsn+1-j=λsβsSn+1IsnNn+σsλsβsRn+1IsnNn+γsIsn-αssβsLsn+1IsnNn-αsxβxLsn+1IxnNn-(d+εs+t1s)Lsn-αsmβmLsn+1ImnNn, (29)
j=0n+1ωjα(tn)Lmn+1-j=λmβmSn+1ImnNn+σmλmβmRn+1ImnNn+λmαsmβmLsn+1ImnNn+γmImn+t1sLsn+1-P1t1sLsn+1+t2sIsn-P2t2sIsn-αmmβmLmn+1ImnNn-αmxβxLmn+1IxnNn-(d+εm)Lmn+1, (30)
j=0n+1ωjα(tn)Lxn+1-j=λxβxSn+1IxnNn+σxλxβxRn+1IxnNn+λxαsxβxLsn+1IxnNn+γxIxn+λxαmxβxLmn+1IxnNn+t2mImn-P3t2mImn-αxxβxLxn+1IxnNn-(d+εx)Lxn+1, (31)
j=0n+1ωjα(tn)Isn+1-j=αssβsLsn+1IsnNn+(1-λs)βsSn+1IsnNn+σsRn+1IsnNn+εsLsn+1-(d+δs)Isn+1-(γs+t2s)Isn, (32)
j=0n+1ωjα(tn)Imn+1-j=αmmβmLmn+1ImnNn+(1-λm)βmSn+1ImnNn+σmRn+1ImnNn+αsmLsn+1ImnNn+εmLmn+1-(d+δm)Imn+1-(γm+t2m)Imn, (33)
j=0n+1ωjα(tn)Ixn+1-j=αxxβxLxn+1IxnNn+(1-λx)βmSn+1IxnNn+σxRn+1IxnNn+αmxLxn+1ImnNn+εxLxn+1-(d+δx)Ixn+1-(γx+t2x)Ixn, (34)
j=0n+1ωjα(tn)Rn+1-j=P1t1sLsn+1+P2t2sIsn+P3t2mImn+t2xIxn-dRn+1-σsβsRn+1IsnNn-σmβmRn+1ImnNn-σxβxRn+1IxnNn. (35)

where the discretization for N(t) is given as

Nn=Sn+Lsn+Lmn+Lxn+Isn+Imn+Ixn+Rn.

And ω0α(tn)=(φi(h))-α(tn), i=1,2,,8 where the nonlocal approximations are used for the nonlinear terms and the following denominator functions are used:

φ1(h)=edh-1d,φ2(h)=e(d+εs+t1s)h-1(d+εs+t1s),φ3(h)=e(d+εm)h-1(d+εm),φ4(h)=e(d+εx)h-1(d+εx),φ5(h)=1-e-(d+δs)h(γs+t2s),φ6(h)=1-e-(d+δm)h(γm+t2m),φ7(h)=1-e-(d+δx)h(γx+t2x),φ8(h)=edh-1d.

We obtain,

Sn+1=b-j=1n+1ωjα(tn)Sn+1-j(φ1(h))-α(tn)+d+βsIsn+βmImn+βxIxnNn, (36)
Lsn+1=βsIsnNnλs(Sn+1+σsRn+1)+γsIsn-j=1n+1ωjα(tn)Lsn+1-j(φ2(h))-α(tn)+(d+t1s+εs)+1Nn(αssβsIsn+αsmβmImn+αsxβxIx), (37)
Lmn+1=βmλmImnNn(Sn+1+σmRn+1+αsmLsn+1)+γmImn+t1sLsn+1(1-P1)(φ3(h))-α(tn)+(d+εm)+1Nn(αmmβmImn+αmxβxIxn)+t2sIsn(1-P2)-j=1n+1ωjα(tn)Lmn+1-j(φ3(h))-α(tn)+(d+εm)+1Nn(αmmβmImn+αmxβxIxn), (38)
Lxn+1=βxλxIxnNn(Sn+1+σxRn+1+αsxLsn+1+αmxLmn+1)+t2sImn(1-P3)(φ4(h))-α(tn)+(d+εx)+1Nn(αxxβxIxn)+γxIxn-j=1n+1ωjα(tn)Lxn+1-j(φ4(h))-α(tn)+(d+εx)+1Nn(αxxβxIxn), (39)
Isn+1=φ5(h)βsIsnNn(αssLsn+1+(1-λs)(Sn+1+σsRn+1))(φ5(h))-α(tn)+(d+δs)+(γs-(t2s))Isn+εsLsn+1-j=1n+1ωjα(tn)Isn+1-j(φ5(h))-α(tn)+(d+δs), (40)
Imn+1=βmImnNn(αmmLmn+1+(1-λm)(Sn+1+σmRn+1+αsmLsn+1))(φ6(h))-α(tn)+(d+δm)+(γm-(t2m))Imn+εmLmn+1-j=1n+1ωjα(tn)Imn+1-j(φ6(h))-α(tn)+(d+δm), (41)
Ixn+1=βxIxnNn(αxxLxn+1+(1-λx)(Sn+1+σxRn+1+αsxLsn+1+αmxLmn+1))(φ7(h))-α(tn)+(d+δx)+(γx-(t2x))Ixn+εxLxn+1-j=1n+1ωjα(tn)Ixn+1-j(φ7(h))-α(tn)+(d+δx), (42)
Rn+1=t1sP1Lsn+1+P2t2sIsn+t2mP3Imn+t2xIxn-j=1n+1ωjα(tn)Rn+1-j(φ8(h))-α(tn)+d+1Nn(σsβsIsn+σmβmImn+σxβxIxn). (43)

Numerical results and simulations

Since most of the variable-order fractional differential equations do not have exact analytic solutions, so approximation and numerical techniques must be used. Several analytical and numerical methods have been proposed to solve variable-order fractional differential equations. For numerical solutions of the system (18), (19), (20), (21), (22), (23), (24), (25) one can use NSFDM, the approximate solution S(t), Ls(t), Lm(t), Lx(t), Is(t), Im(t), Ix(t), R(t) is displayed in Fig. 1, when R0<1 and in Fig. 2, when R0>1, in each figures, and three different values of α(t)=1, α(t)=0.95-0.01/100t, α(t)=0.85-0.01/100t are considered. The approximate solutions are displayed in Fig. 2 that, the equilibrium point (S,0,0,Lx,0,0,Ix,R) of NSFDM is locally asymptotically stable when α(t)=0.95-0.01/100t, t[0,20], where the eigenvalues are given as λ1=-9.8100, λ2=-0.4098,λ3=-0.3688, λ4=-2.7660, λ5=-2.4591, λ6=-1.2392, λ7=-1.6005, λ8=-1.4465. By applying the relationship (26) we obtained that, |argλi|=|-π|>α(t)π2, α(t)(0,1]. When α(t)=1, system (18), (19), (20), (21), (22), (23), (24), (25) is the classical integer-order system. Moreover, we observed that, the integer order derivative can be used to characterize the short memory of systems, and the variable-order fractional derivative can be employed to depict the variable memory of systems. In Fig. 3, we presented the result obtained by NSFDM and SFDM and ode45 schemes with step size h=0.02 and α(t)=1, and we observed that, all numerical methods converge almost to the equilibrium point when R0>1. In Table 4, we reported the convergence behavior of numerical methods to the disease free equilibrium, and in Table 5, we reported the convergence behavior of numerical methods to the equilibrium point (S,0,0,Lx,0,0,Ix,R).

Fig. 1.

Fig. 1

Profiles obtained by using NSFDM for solving variable-order fraction model with different α(t),h=0.5, βs=βm=βx=0.1, an R0<1.

Fig. 2.

Fig. 2

Profiles obtained by using NSFDM for solving variable-order fraction model with different α(t),h=0.2, βs=βm=βx=14, and R0>1.

Fig. 3.

Fig. 3

Profiles obtained by using different methods with α(t)=1, h=0.02, βs=βm=βx=14, and R0>1.

Table 4.

Result obtained by SFDM and NSFDM for Bs=Bm=Bx=0.1, R0<1,α(t)=0.98-0.01/100t, t[0,100] and initial conditions as (5000,50,50,50,30,30,30,60) with different time step size.

h SFDM NSFDM
0.01 Convergent Convergent
0.1 Convergent Convergent
1 Convergent Convergent
20 Divergent Convergent
100 Divergent Convergent

Table 5.

Result obtained by SFDM and NSFDM for Bs=Bm=Bx=14, R0>1,α(t)=0.98-0.01/100t, t[0,100] and initial conditions as (5000,50,50,50,30,30,30,60) with different time step size.

h SFDM NSFDM
0.01 Convergent Convergent
0.1 Convergent Convergent
1 Divergent Convergent
20 Divergent Convergent
100 Divergent Convergent

From Table 4, we can conclude that NSFDM unconditionally converges to the correct disease free equilibria for large h, while the SFDM converges only when h is small.

From Table 5, we can conclude that NSFD scheme unconditionally converges to the equilibrium point (S,0,0,Lx,0,0,Ix,R) for large h, while the SFD scheme converges only when h is small. Moreover, the system (28), (29), (30), (31), (32), (33), (34), (35) is unconditionally locally asymptotically stable.

Previous Fig. 4(a)–(d), illustrates propagation of TB along the time when α(t)=0.98-0.03/100t as follows:

Fig. 4.

Fig. 4

Illustrate propagation of multi-strain TB along the time α(t)=0.98-0.03/100t, h=3, βs=βm=βx=14, and R0>1, by using NSFDM.

In Fig. 4(a), the relationship between R(t) and Is(t) illustrates that, there are individuals succeeded treatment with them and may exposed to infection again by contagious members Is(t) of the first strain. At the beginning of the period of the time the number of Is(t) members increases and the number of R(t) members decreases, then after time steps the curves intersect again, Is(t) will be responsible to treatment and their numbers will be decreased.

In Fig. 4(b), the relationship between S(t) and Ix(t), describes the spread of infection from the members of the third strain to healthy people, then the number of infectious people increases and the number of healthy people decreases with proper time.

In Fig. 4(c), the relationship between S(t) and Im(t), describes the spread of contagious from the members Im(t) of the second strain to healthy people, then the number of infectious people increases and the number of healthy people decreases with proper time.

In Fig. 4(d), the relationship between Ls(t) and Is(t), describes the spread of contagious from the members Is(t) of the first strain to individuals who carry the disease latent of the first strain Ls(t), after time steps the curves intersect again then Is(t) will be responsible to treatment and the number of them decreases.

In Fig. 5, we presented the result obtained by NSFDM and SFDM schemes with step size h=0.1 and α(t)=0.98-0.01/100t, t[0,100]. We can clearly see, all schemes converge to correct equilibrium point when R0>1.

Fig. 5.

Fig. 5

Profiles obtained by using NSFDM and SFDM with α(t)=0.98-0.01/100t, h=0.2, βs=βm=βx=14, and R0>1.

In Fig. 6, we presented the results obtained by NSFD and SFD schemes with step size h=1 and α(t)=0.98-0.01/100t. As we can clearly see, the SFD scheme is unstable and the solutions are divergent, so we cannot use this scheme to solve the system when step size is large.

Fig. 6.

Fig. 6

Profiles obtained by using NSFDM and SFDM with α(t)=0.98-0.01/100t, h=1, βs=βm=βx=14, and R0>1.

From these numerical results obtained in this work we can control the disease and turn the endemic point to the disease free point as follows:

Let us consider:

R0s<1-t2s2+5.3950t2s+8.6060t2s2+1.6050t2s+1.050<0,wheret1s=t2s. (44)
R0m<19.1720-0.8800t2m0.8800t2m+0.4880<0, (45)
R0x<19.1720-0.8800t2x0.8800t2x+0.4880<0. (46)

Then,

t1s=t2s6.6828,t2m10.4227,t2x10.4227. (47)
T=max{t2s,t2m,t2x}T=t2m=t2x10.4227. (48)

So, we derive the rate of treatment required for achieving control of the disease.

For example, if we choose the following elements which belong to such as t2s=t2m=t2x=17, Bs=Bm=Bx=14, h=1 and α(t)=0.85-0.02/100t, we obtained the disease free point (see Fig. 7).

Fig. 7.

Fig. 7

Profiles obtained by using NSFDM for h=1, α(t)=0.85-0.02/100t, βs=βm=βx=14, and t2s=t2m=t2x=17, R0>1.

Conclusions

In this article, a novel multi-strain TB model of variable-order fractional derivatives which incorporates three strains: drug-sensitive, MDR and XDR, is studied. It can be concluded from the numerical results presented in this paper, that the variable-order fractional TB model given here is a general model than the integer and fractional order models. Furthermore, the integer order model can be used to characterize the short memory of systems, and the variable-order fractional model can be employed to depict the variable memory of systems. Moreover, we can conclude that NSFDM is more efficient for solving variable-order fractional mathematical model for multi-strain TB, than the SFDM, because it preserves the positivity of the solution and the stability regions using it are bigger than the SFDM stability regions. All results in this paper are obtained using MATLAB (R2013a), on a computer machine with intel (R) core i3-3110M @ 2.40 GHz and 4 GB RAM.

Conflict of Interest

The authors have declared no conflict of interest.

Compliance with Ethics Requirements

This article does not contain any studies with human or animal subjects.

Footnotes

Peer review under responsibility of Cairo University.

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