We study a switching heroin epidemic model in this paper, in which the switching of supply of heroin occurs due to the flowering period and fruiting period of opium poppy plants. Precisely, we give three equations to represent the dynamics of the susceptible, the dynamics of the untreated drug addicts and the dynamics of the drug addicts under treatment, respectively, within a local population, and the coefficients of each equation are functions of Markov chains taking values in a finite state space. The first concern is to prove the existence and uniqueness of a global positive solution to the switching model. Then, the survival dynamics including the extinction and persistence of the untreated drug addicts under some moderate conditions are derived. The corresponding numerical simulations reveal that the densities of sample paths depend on regime switching, and larger intensities of the white noises yield earlier times for extinction of the untreated drug addicts. Especially, when the switching model degenerates to the constant model, we show the existence of the positive equilibrium point under moderate conditions, and we give the expression of the probability density function around the positive equilibrium point.
Citation: Hui Jiang, Ling Chen, Fengying Wei, Quanxin Zhu. Survival analysis and probability density function of switching heroin model[J]. Mathematical Biosciences and Engineering, 2023, 20(7): 13222-13249. doi: 10.3934/mbe.2023590
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Abstract
We study a switching heroin epidemic model in this paper, in which the switching of supply of heroin occurs due to the flowering period and fruiting period of opium poppy plants. Precisely, we give three equations to represent the dynamics of the susceptible, the dynamics of the untreated drug addicts and the dynamics of the drug addicts under treatment, respectively, within a local population, and the coefficients of each equation are functions of Markov chains taking values in a finite state space. The first concern is to prove the existence and uniqueness of a global positive solution to the switching model. Then, the survival dynamics including the extinction and persistence of the untreated drug addicts under some moderate conditions are derived. The corresponding numerical simulations reveal that the densities of sample paths depend on regime switching, and larger intensities of the white noises yield earlier times for extinction of the untreated drug addicts. Especially, when the switching model degenerates to the constant model, we show the existence of the positive equilibrium point under moderate conditions, and we give the expression of the probability density function around the positive equilibrium point.
1.
Model establishment
Heroin is a semi-synthetic opioid drug, which is mainly extracted from opium poppy. Heroin was originally developed as a drug to cure morphine addiction, but later it was found to be highly addictive, dependence causing and toxic [1]. Heroin became one of the most popular drugs in the world [2]. White and Comiskey [3] were the first to study the spreading of heroin by using an ordinary differential equation (ODE) compartmental model, and they separated the local population into three compartments based on the states of drug addicts: the susceptible individuals, the untreated drug addicts and drug addicts under treatment. Based on White's model, many scholars developed different mathematical models to discuss the transmission mechanisms of heroin, such as age structure models [4,5,6], distributed delay models [7,8,9] and nonlinear incidence models [10,11,12,13] as well. Within the above-mentioned works, the authors found that the consumption of heroin was transmitted from a drug addict to a non-drug addict, which was similar to the mechanism of the spreading of infectious diseases. They further discussed the basic reproduction number R0 as the threshold, and they determined the stability of the drug-free equilibrium and the endemic equilibrium.
Meanwhile, environmental noises usually affected the dynamics of heroin models in [14,15,16,17,18,19]. More precisely, Liu et al. [14] proposed a stochastic heroin epidemic model, in which they obtained a threshold for the extinction of the drug addicts. Further, [15] studied a stochastic heroin epidemic model with the bilinear incidence within a varying population. Then, Wei et al. [16] analyzed the long-term dynamics of a perturbed heroin epidemic model under non-degenerate noise. Later, Wei et al. [17] established a heroin population model with the standard incidence rates between distinct patches, and by constructing suitable Lyapunov functions, they established the sufficient criteria for the existence of the addict elimination and the existence of an ergodic stationary distribution. The recent contributions in [20,21,22,23,24,25,26,27,28,29,30,31,32,33] governed the continuous-time Markov chains taking values in a finite-state space to describe the regime switchings, in which Markov-chains were memoryless, and the waiting time from one state to another state usually obeyed the exponential distribution. Therefore, in this paper, we consider the following stochastic heroin model with the bilinear incidence rate under regime switching:
where S(t) is the number of the susceptible individuals; U(t) is the number of the untreated drug addicts; and T(t) is the number of the drug addicts under treatment at time t respectively. Moreover, N(t)=S(t)+U(t)+T(t) denotes the total population size at time t; Bi(t)(i=1,2,3) are mutually independent standard Brownian motions defined on a complete probability space (Ω,F,P) with a filtration {Ft}t≥0, which is increasing and right continuous while F0 contains all P-null sets; and σ2i>0(i=1,2,3) denote the intensities of the white noises. Λ is the population density entering the susceptible per unit of time, μ is the natural death rate of the total population, p is the proportion of drug users who are under treatment, β1 is the rate that an individual becomes a drug user, β2 is the rate that drug users under treatment relapsed to the untreated, δ1 is the drug-related death rate, δ2 is the successful cure rate. We assume that all parameters of model (1.1) are non-negative.
Let m(t) be a right-continuous Markov chain on the complete probability space (Ω,F,P) taking values in a finite state space S={1,2,⋯,N} for t≥0 and Δt>0, which is generated by the transition matrix Γ=(pij)N×N, i.e., P{m(t+Δt)=j|m(t)=i}≤pijΔt+o(Δt) if i≠j; otherwise, P{m(t+Δt)=j|m(t)=i}≤1+piiΔt+o(Δt) if i=j, where pij≥0 is the transition rate from state i to state j if i≠j while ∑Nj=1pij=1.
In this paper, we assume that pij>0 for i,j=1,⋯,N with i≠j. In model (1.1), the parameters Λ, p, μ, β1, β2, δ1, δ2, σi(i=1,2,3) are not constants; instead they are generated by a homogeneous continuous-time Markov chain m(t) for t≥0. That is, for each fixed k∈S, Λ(k), p(k), μ(k), β1(k), β2(k), δ1(k), δ2(k) and σi(k)(i=1,2,3) are all positive constants. We assume that the Markov chain m(t) is irreducible, which means that the system can switch from one regime to another regime. It implies that the Markov chain m(t) has a unique stationary distribution π=(π1,π2,⋯,πN) which can be determined by the equation πΓ=0 subject to ∑Nk=1πk=1 and πk>0 for any k∈S. Define Rn+={x∈Rn:xi>0,1≤i≤n}. For any vector g=(g(1),g(2),⋯,g(N)), let ˆg=mink∈S{g(k)} and ˇg=maxk∈S{g(k)}. Next, we will show the existence and uniqueness of a global positive solution. Then, we will discuss the survival dynamics including the extinction and persistence of the untreated drug addicts for the switching model (1.1). Further, we will investigate the probability density function of the degenerated model (2.20) under some sufficient conditions.
2.
Main results
In this section, we give the generalized SDEs
dX(t)=f(X(t),m(t))dt+g(X(t),m(t))dB(t),t≥0,
(2.1)
with the initial values X(0)=X0,m(0)=m, where B(⋅) and m(⋅) are the d-dimensional Brownian motions and the right-continuous Markov chains, respectively. f(⋅,⋅) and g(⋅,⋅) respectively map Rn×S to Rn and Rn×d with g(X,k)gT(X,k)=(gij(X,k))n×n. For each k∈S, let V(⋅,k) be any twice continuously differentiable function, and the operator L can be defined by
We first of all consider the existence and uniqueness of a global positive solution before investigating other long-term properties of model (1.1) in this section.
Theorem 1.For any initial value (S(0),U(0),T(0),m(0))∈R3+×S, there exists a unique solution (S(t),U(t),T(t),m(t)) of model (1.1) on t≥0, and the solution will remain in R3+×S with probability one.
Proof. We write down similar lines as we did in [34,35] and define the stopping time
The rest of the proof is similar to Theorem 1 in [17], so we omit it. The proof is complete.
2.2. Extinction of the untreated drug addicts within local population
For a long time, extinction always refers to the disappearance of infectious diseases in epidemiology. So, the most important concern of the dynamical behaviors for the stochastic heroin model is to control the spreading of heroin and the number of the untreated drug addicts. By the approaches given in [34,35,36,37,38,39], together with constructing several Lyapunov functions, combining generalized Itô's formula and the strong law of large numbers, we derive the moderate conditions for the extinction of the untreated drug addicts to model (1.1). With these conditions, we find that the spreading of heroin ultimately vanishes in the local population, in other words, the number of the untreated drug addicts declines to zero.
Lemma 1.Assume that ˆμ>12(ˇσ21∨ˇσ22∨ˇσ23), and the solution (S(t),U(t),T(t),m(t)) of model (1.1) satisfies
In other words, the leading principal minors of A are all positive, which means that A is a nonsingular M-matrix. For the vector β1∈RN, the linear system (2.7) has a solution c1=(c1(1),c1(2),⋯,c1(N))T. Similarly, we show that the linear system (2.8) has a solution c2=(c2(1),c2(2),⋯,c2(N))T.
Theorem 3. If Rs0>0, then model (1.1) admits a unique ergodic stationary distribution.
here ωk will be determined later. Obviously, there exists a point (x0,y0,z0,k) at which the minimum value W(x0,y0,z0,k) is taken. We define a non-negative C2-Lyapunov function as follows:
We define a vector R0=(R01,R02,⋯,R0N)T, since the generator matrix Γ is irreducible, there exists a solution of the Poisson system ω=(ω1,⋯,ωN)T such that
Γω=(N∑k=1πkR0k)→1−R0,
(2.14)
where →1 is a column vector in which all elements are one, which further implies
R0k+∑l∈Spklω(l)=N∑k=1πkR0k,
and together with (2.6), the expression (2.13) turns into
Then, we investigate the existence of the probability density function of model (2.20). First of all, we consider the existence of the positive equilibrium point to model (2.20).
Theorem 4.If the conditions
g1=0,1+m1m2m1p−β1Λ>0,
(2.21)
or
g1<0,Δ>0,β1Λ−m1p−m1m2>0,
(2.22)
or
g1<0,Δ=0,(β2m1−β1m3)(m2+p)+β2(m1p−β1Λ)>0,
(2.23)
hold, then, model (2.20) admits a positive equilibrium point P∗, where g1,m1,m2,m3 and Δ could be found later.
Proof. Let (z1,z2,z3)T=(lnS,lnU,lnT)T, by using Itô's formula, the following is derived from model (2.20) that
Case 3. When g1>0, if the drug addicts under treatment T(t) has a unique positive root, the value of β1 will be very small, and the drug addicts U(t) and susceptible individuals S(t) are negative, so we omit this case.
Theorem 5.If the conditions of Theorem 4 are satisfied, and
Λβ21−m3β2p>0,
(2.30)
then, model (2.20) possesses a probability density function
Let X=(x1,x2,x3)T,B(t)=(B1(t),B2(t),B3(t))T,M=diag{σ1,σ2,σ3} and
A=(−a11−a120a210a230a32−a33).
Therefore, Eq (2.31) can be equally rewritten as
dX(t)=AX(t)dt+MdB(t).
According to the relative theory in Gardiner [43], there is a unique density function Φ(X) around the positive equilibrium point P∗ which satisfies the following equation (i.e., Fokker-Planck equation):
On the basis of Roozen [44], we can approximate it with a Gaussian distribution
Φ(X)=Φ(x1,x2,x3)=C0e−12(x1,x2,x3)Q(x1,x2,x3)T,
where C0 is a positive constant, which is determined by
∫R3Φ(x1,x2,x3)dx1dx2dx3=1.
Also, the real symmetric inverse matrix Q meets the subsequent algebraic equation
QM2Q+QA+ATQ=0,
such that Σ=Q−1, and then we derive
M2+AΣ+ΣAT=0.
(2.33)
Furthermore, we have C0=(2π)−32|Σ|−12.
According to the finite independent superposition principle, we express Eq (2.33) as the sum of the solutions of the following algebraic sub-equations:
M2k+AΣk+ΣkAT=0,k=1,2,3,
(2.34)
where
M1=diag(σ1,0,0),M2=diag(0,σ2,0),M3=diag(0,0,σ3)
with
Σ=Σ1+Σ2+Σ3,M2=M21+M22+M23.
Obviously, the characteristic polynomial of matrix A is
Furthermore, algebraic Eq (2.38) can be converted to the equivalent
H1M21HT1+B1H1Σ1HT1+H1Σ1HT1BT1=0,
letting
Θ1=ϱ−21H1Σ1HT1,ϱ1=a21a32σ1,
and algebraic Eq (2.38) is converted as
G20+B1Θ1+Θ1BT1=0.
(2.40)
We notice that the real parts of the eigenvalues of A are all negative, so B1 is a Hurwitz matrix. By Lemma 4, Θ1 is positive definite and takes the form
Θ1=12(y1y2−y3)(y20−1010−10y1y3).
Therefore, Σ1=ϱ21H−11Θ1(HT1)−1.
Case 1.2. If a32=0, we choose ˆH1 such that ˆB1=ˆH1AˆH−11 with
ˆH1=(a210a23010001),ˆB1=(−b1−b2−b310000−a33),
where
b1=a11,b2=a12a21,b3=a23a33−a11a23.
One can equivalently transform (2.38) into
ˆH1M21ˆHT1+ˆB1ˆH1Σ1ˆHT1+ˆH1Σ1ˆHT1ˆBT1=0,
letting
ˆΘ1=ˆϱ−21ˆH1Σ1ˆHT1,ˆϱ1=a21σ1.
The algebraic Eq (2.38) becomes
G20+ˆB1ˆΘ1+ˆΘ1ˆBT1=0,
(2.41)
with
ˆΘ1=diag{12b1,12b1b2,0}.
(2.42)
Therefore, Σ1=ˆϱ21ˆH−11ˆΘ1(ˆHT1)−1.
Step 2. Let us consider the following algebraic equation
M22+AΣ2+Σ2AT=0,
(2.43)
we select the corresponding elimination matrix J2 and let A2=J2AJ−12 with
We assume that the Markov chain m(t) takes values in the state space S={1,2} with the generator
Γ=(−0.800.800.20−0.20).
The initial value is (S(0),U(0),T(0))=(0.70,0.50,0.40), and the unique stationary distribution of m(t) is π=(π1,π2)=(0.20,0.80), respectively. We next apply two methods to simulate the sample paths of model (1).
Milstein's higher order method (MHOM). The discretization equations of model (1.1) by MHOM in [46] are written as follows:
vk,i are the Gaussian random variables, which follow the standard normal distribution N(0,1). Next, we use PTEMM to simulate the figures in Examples 1–3.
Example 1 We choose (Ⅰ) and (Ⅱ) of Table 1 to simulate the extinction in Theorem 2. By (Ⅰ), we obtain
Compare the trajectories of solutions under conditions (Ⅰ) and (Ⅱ), and the time spent in Figure 2 under (Ⅱ) is shorter than that in Figure 1 under (Ⅰ) when the intensities of the white noises increase.
Figure 1.
The extinction of the untreated drug addicts to model (1.1) under (Ⅰ) with initial conditions (S(0),U(0),T(0))=(0.70,0.50,0.40) and σ21(1)=0.2,σ21(2)=0.1,σ22(1)=0.45,σ22(2)=0.35,σ23(1)=0.1,σ23(2)=0.05.
Figure 2.
The extinction of the untreated drug addicts to model (1.1) under (Ⅱ) with initial conditions (S(0),U(0),T(0))=(0.70,0.50,0.40) and σ21(1)=0.2,σ21(2)=0.1,σ22(1)=0.49,σ22(2)=0.4,σ23(1)=0.1,σ23(2)=0.05.
Example 2 We choose (Ⅲ) of Table 1 to present the results in Theorem 3. In fact, the following condition is valid:
Rs0=∑k∈SπkR0k=0.707>0.
As shown in Figure 3, the densities of the susceptible, the untreated drug addicts, and the drug addicts under treatment are stationary over time. The related simulations are demonstrated by MHOM in the middle and by PTEMM on the right. Moreover, for 50000 sample paths in total, the distributions of frequency for the solution of model (1.1) are carried out in Figure 4.
Figure 3.
The stationary distributions with same Markov chain (left) under MHOM (middle) and PTEMM (right) respectively.
hold, we derive the equilibrium point P∗=(1.078,0.861,0.407) by Theorem 4. Meanwhile, the stochastic persistence of density function of model (2.20) is demonstrated in Figure 5.
Figure 5.
Persistence and density function of model (2.20) around (1.078, 0.861, 0.407).
Or, we take parameter (Ⅴ) to compute the following conditions
β1Λ−m1p−m1m2=0.105>0,Λβ21−m3β2p=0.106>0
then, the equilibrium point P∗=(0.746,1.670,0.768) is followed. Further, the stochastic persistence of density function of model (2.20) is shown in Figure 6. Or, by selecting parameter (Ⅵ), the following conditions
hold, we obtain the positive equilibrium point P∗=(0.967,0.845,0.679). So, the same dynamical properties appear, and we omit this case hereby.
4.
Conclusions and discussion
Heroin is an addictive drug made from the various opium poppy plants around the world. The price and spreading of heroin depend on the flowering period (usually May–July for a year) and the fruiting period (usually June–August for a year). So, we give an SUT epidemic model with regime switching to describe the flowering period and fruiting period of opium poppy plants in this paper. We are motivated by the switching between flowering period and fruiting period of opium poppy plants in years, and the recent contributions [17,30,31] on epidemic models. We focus on the survival analysis of switching model (1.1) and its probability density function of constant model (2.20) for investigating their long-time dynamical properties.
For the switching SUT epidemic model (1.1), the existence and uniqueness is first derived with probability one in Theorem 1 by contradiction and stochastic analysis. Further, Theorem 2, Figures 1 and 2 verify the extinction of the switching SUT model under moderate conditions in theoretical and numerical aspects. The simulations therein also reveal that the larger intensities of the white noises make the time of extinction earlier. As a consequence of theoretical investigation, we derive the important index Rs0>0 of the existence and uniqueness of the ergodic stationary distribution in Theorem 3. The corresponding sample paths and histogram frequencies are demonstrated in Figures 3 and 4, respectively, in which Milstein's higher order method and partially truncated Euler-Maruyama method both verify well under the same Markovian chain.
For the constant SUT epidemic model (2.20), we aim at the existence of the positive equilibrium point in Theorem 4 and the existence of probability density function in Theorem 5, respectively. One of three types of sufficient conditions is required for determining a positive equilibrium point, and details could be found in Example 3. The sample paths of model (2.20) under distinct positive equilibrium points are demonstrated in Figure 5. Further, the expression of probability density function around the positive equilibrium point is obtained in Theorem 5 after we prove that coefficient matrix A is a Hurwitz matrix and diffusion matrix Σ is positive definite by using the Fokker-Planck equation.
Acknowledgments
The research is supported by the Natural Science Foundation of Fujian Province of China (2021J01621), Special Projects of the Central Government Guiding Local Science and Technology Development (2021L3018) and Education and Research Project for Middle and Young Teachers in Fujian Province (JAT220307).
Conflict of interest
The authors declare there is no conflict of interest.
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Figure 1. The extinction of the untreated drug addicts to model (1.1) under (Ⅰ) with initial conditions (S(0),U(0),T(0))=(0.70,0.50,0.40) and σ21(1)=0.2,σ21(2)=0.1,σ22(1)=0.45,σ22(2)=0.35,σ23(1)=0.1,σ23(2)=0.05
Figure 2. The extinction of the untreated drug addicts to model (1.1) under (Ⅱ) with initial conditions (S(0),U(0),T(0))=(0.70,0.50,0.40) and σ21(1)=0.2,σ21(2)=0.1,σ22(1)=0.49,σ22(2)=0.4,σ23(1)=0.1,σ23(2)=0.05
Figure 3. The stationary distributions with same Markov chain (left) under MHOM (middle) and PTEMM (right) respectively
Figure 4. Histogram of S(t),U(t),T(t) to model (1.1) with 50000 sample paths
Figure 5. Persistence and density function of model (2.20) around (1.078, 0.861, 0.407)
Figure 6. Persistence and density function of model (2.20) around (0.746, 1.670, 0.768)