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Articles

Epidemic models with heterogeneous mixing and indirect transmission

Pages 375-399 | Received 21 Jul 2017, Accepted 13 Apr 2018, Published online: 05 May 2018

ABSTRACT

We develop an age of infection model with heterogeneous mixing in which indirect pathogen transmission is considered as a good way to describe contact that is usually considered as direct and we also incorporate virus shedding as a function of age of infection. The simplest form of SIRP epidemic model is introduced and it serves as a basis for the age of infection model and a 2-patch SIRP model where the risk of infection is solely dependent on the residence times and other environmental factors. The computation of the basic reproduction number R0, the initial exponential growth rate and the final size relation is done and by mathematical analysis, we study the impact of patches connection and use the final size relation to analyse the ability of disease to invade over a short period of time.

1. Introduction

Epidemic model of infectious diseases had been extensively investigated by proposing and investigating mathematical models ([Citation4–6, Citation10, Citation19, Citation22] and references therein). Diseases such as cholera and some airborne infections are pathogenic microorganism diseases that are usually transmitted directly via host to host [Citation19] and/or indirectly by virus transferred through objects such as contaminated hands or objects such as shelves and lump and environments [Citation1, Citation4, Citation8, Citation20]. Pathogen sheds by infected individuals may stay outside of human hosts for a long period of time. However, alternative transmission pathways as a result of the behaviour of host may constitute to the spread of infection, such as drinking contaminated water, touching handles that have been exposed to a virus, eating contaminated food and so on [Citation19]. Brauer [Citation4] proposed an SIVR epidemic model with homogeneous mixing, which is an extension of the SIR model by the addition of a pathogen compartment V to describe the indirect transmission pathway (host–source–host). The basic reproduction number and the final size relation was derived and investigated to determine the impact of indirect transmission pathway on disease spread. Similarly, Derdei Bichara et al. [Citation10] proposed an SIR epidemic model in two patches with residence times which describes patches with residents who spent a proportion of their time in different patches to analyse the direct transmission pathway ( host–host). They derived the basic reproduction number, final size relation and investigated how residence times influence them. Tien and Earn [Citation21] developed an SIWR disease model which extended the SIR model by the addition of a compartment W that describes direct and indirect transmission pathway.

We have based most mathematical results in this paper on the final size relation of epidemic models in an heterogeneous environment. This relation had been extensively discussed in [Citation2–4, Citation10, Citation13] using different models to predict how worst an epidemic could be during a disease outbreak. For example, consider a simple compartmental model, which comes with simple assumptions on rates of flow between different classes of individuals in the population (the special case of the proposed model by Kermack and McKendrick [Citation15–17]) given as (1) S˙=βIS,I˙=βISρI,R˙=ρI.(1) The final size relation to the simple model in Equation (Equation1) is (2) logS0S=β0I(t)dt,=βNρ1SN,=R01SN,(2) where S0 denotes the initial size of the susceptible class, N the size of the entire population, β effective contact rate, ρ removed rate, and R0=(βN/ρ) the basic reproduction number. The first infectious individual is expected to infect R0=(βN/ρ) individuals and this determines if an epidemic will occur at all. The infection dies out whenever R0<1, and an epidemic occur whenever R0>1. Equation (Equation2) which is known as the final size relation gives an estimate of the total number of infections over the course of the epidemic from the parameter in the model [Citation3, Citation4], and can similarly show the relationship between the basic reproduction number and the size of the epidemic. The final size (NS) is usually described in terms of the attack rate/ratio (1S/N). Note that the final size relation in Equation (Equation2) can be generalized to epidemic model with more complex compartments than the simple model in Equation (Equation1). Papers [Citation2–4, Citation10, Citation13] extensively discussed details of age of infection models and their final size relations, and we will use these techniques to derive the final size relations throughout the paper.

We intend in this work to incorporate an epidemic model with age of infection and indirect transmission pathway in which pathogen is shed by infected individuals into the environment, acquired by susceptible individuals from the environment, and transmitted in an heterogeneous mixing environment. We will further investigate the nature of the epidemic when variable virus shedding rate and residence time are taken into consideration. A Lagrangian method is used to monitor the place of residence of each population at all times [Citation6, Citation9–11]. We propose that this may be an alternative way to study disease epidemic in an heterogeneous mixing environment. The rest of the paper is structured as follows. In Section 2, we introduce the age of infection model in an heterogeneous mixing settings and analyse the model succinctly. The analysis of the age of infection model follows similar steps from the simpler version analysed in Section 2.1. We describe in Section 3 how variable pathogen shedding rates are incorporated. In Section 4, we formulate a 2-patch model with residence time and determine the nature of the epidemic when populations in one patch spend some of their time in another patch. We analyse the patchy model for different scenarios numerically in the last part of Section 4 and devote Section 5 to a summarized conclusion. Note that the same analytic approach, a standard way to analyse disease transmission models will be used in each section.

2. A two-group age of infection model with heterogeneous mixing

We consider two subpopulations of sizes N1, N2, each divided into susceptibles S1 and S2 and infectives I1 and I2 with a pathogen class P. We assume that Susceptible individuals become infected only through contact with the pathogen sheds by infectives. Pathogen P is shed by infected individuals I1 and I2 at a rate r1 and r2, respectively, as in [Citation14, Citation19]. The model assumes that epidemic occurs within a short period of time.

Considering the age of infection, we define ϕ1(t) and ϕ2(t) as total infectivity in classes I1 and I2 at time t, respectively, ϕ10(t) and ϕ20(t) represent the total infectivity at time t of all individuals already infected at time t=0, A1(τ) and A2(τ) are the mean infectivity of individuals in classes I1 and I2 at age of infection τ and Γ(τ) the fraction of pathogen remaining τ time units after having been shed by an infectious individual. This is an extension of [Citation4] from homogeneous mixing to heterogeneous mixing, and we therefore have the equation as in [Citation13] as (3) S1(t)=β1S1(t)P(t),ϕ1(t)=ϕ10(t)+0[S1(tτ)]A1(τ)dτ,S2(t)=β2S2(t)P(t),ϕ2(t)=ϕ20(t)+0[S2(tτ)]A2(τ)dτ,P(t)=0r1ϕ1(tτ)+r2ϕ2(tτ)Γ(τ)dτ.(3) We can replace Equation (Equation3) by the limit equation (4) S1(t)=β1S1(t)P(t),ϕ1(t)=0[S1(tτ)]A1(τ)dτ,S2(t)=β2S2(t)P(t),ϕ2(t)=0[S2(tτ)]A2(τ)dτ,P(t)=0r1ϕ1(tτ)+r2ϕ2(tτ)Γ(τ)dτ,(4) with a choice of initial function ϕ10(t) and ϕ20(t) to find the equilibria. Asymptotic theory of integral equations in [Citation18] assures that the asymptotic behaviour of (Equation3) is synonymous to that of the limit equation (Equation4) for every initial function with limtϕ10(t)=limtϕ20(t)=0 [Citation13, Citation18]. We assume that 0Γ(τ)dτ<, where the function Γ is monotone non-increasing with Γ(0)=1, and that 0A(τ)dτ<, where A is not necessarily non-increasing.

In order to evaluate the basic reproduction number, the initial exponential growth rate, and the final size relation in terms of the model parameters, it makes sense to start with the simplest form of the limit equation (Equation4) as was done in [Citation2, Citation12, Citation13] by considering a special case in Section 2.1. For this special case, we assume that there is no age of infection, so that we approximate the model (Equation4) by a compartmental model in (Equation5)

2.1. A special case: heterogeneous mixing and indirect transmission for simple SIRP epidemic model

The age-of-infection model includes models with multiple infective. For example, consider the standard SIRP epidemic model with pathogen P being shed by infected individuals I1 and I2 at a rate r1 and r2, respectively, and these pathogen decay at rate δ. Pathogen shed outside of the host organism can persist and reproduce but the decay rate δ is bigger than the reproduction rate [Citation14, Citation19]. Infected populations are removed at rate α. The indirect transmission model is therefore written as (5) S1=β1S1P,I1=β1S1PαI1,R1=αI1,S2=β2S2P,I2=β2S2PαI2,R2=αI2,P=r1I1+r2I2δP,(5) with initial conditions S1(0)=S10,S2(0)=S20,I1(0)=I10,I2(0)=I20,P(0)=P0,R1(0)=R2(0)=0, in a population of constant total size N=N1+N2 where N1=S1+I1+R1=S10+I10andN2=S2+I2+R2=S20+I20. Again, model (Equation5) is an extension of [Citation4] from homogeneous mixing to heterogeneous mixing in the population (Table ).

Table 1. Model variables, parameters and their descriptions.

Model (Equation5) will be analysed using the method of Kermack–McKendrick epidemic model [Citation4, Citation5].

Lemma 2.1

Let f(t) be a non-negative monotone non-increasing continuously differentiable function such that as t, f(t)f0, f0.

Summation of equations S1 and I1 in Equation (Equation5) gives (S1+I1)=αI10. We can see that (S1+I1) decreases to a limit, and by Lemma 2.1 we could show that its derivative approaches zero, from which we can infer that I1=limtI1(t)=0.

Integrate this equation to have α0I1(t)dt=S1(0)+I1(0)S1()=N1(0)S1(), (6) 0I1(t)dt=N1(0)S1()α,(6) which implies that 0I1(t)dt<.

Similarly, sum S2 and I2 in Equation (Equation5) as (S2+I2)=αI20, and by Lemma 2.1 and integrating, we have (7) 0I2(t)dt=N2(0)S2()α,(7) which implies that 0I2(t)dt<.

2.1.1. Reproduction number R0

Here, we use the next generation matrix approach [Citation22] to find the basic reproduction number. Note that we have three infectious classes I1,I2,P, and the jacobian matrix of Fi=(F1,F2,F3), evaluated at the disease-free equilibrium point

DFE=(S10,0,0,S20,0,0,0)=(N1(0),0,0,N2(0),0,0,0) is given by F=Fixji,j=00β1N1(0)00β2N2(0)000, where xj=I1,I2,P for j=1,2,3 and i=1,2,3.

The jacobian matrix of Vi=(V1,V2,V3), evaluated at the disease-free equilibrium point DFE is V=Vixji,j=α000α0r1r2δ,FV1=β1N1(0)r1αδβ1N1(0)r2αδβ1N1(0)δβ2N2(0)r1αδβ2N2(0)r2αδβ2N2(0)δ000.

Remark 2.1

Since we can not calculate the basic reproduction number for our two-group model (Equation5) by knowing secondary infections, we therefore use the method of next generation matrix in [Citation22] to find the basic reproduction number as the dominant eigenvalues of FV1 (the spectral radius of the matrix FV1). And it is given as R0=r1β1N1αδ+r2β2N2αδ. R0 can be written as R0=β1R1+β2R2, where R1=r1N1/α1δ and R2=r2N2/α2δ.

The first term in this expression represents secondary infections caused indirectly through the pathogen since a single infective I1 sheds a quantity r1 of the pathogen per unit time for a time period 1/α and this pathogen infects β1N1 susceptible individuals per unit time for a time period 1/δ, while the second term represents secondary infections caused indirectly through the pathogen since a single infective I2 sheds a quantity r2 of the pathogen per unit time for a time period 1/α and this pathogen infects β2N2 susceptible individuals per unit time for a time period 1/δ. The following easily proved Theorem will be used to summarize the benefit of the basic reproduction number R0.

Theorem 2.2

For system (Equation5), the infection dies out whenever R0<1 and epidemic occur whenever R0>1.

2.1.2. The initial exponential growth rate

The initial exponential growth rate is a quantity that can be compared with experimental data [Citation7, Citation12]. We can linearize the model (Equation5) about the disease-free equilibrium S1=N1,I1=R1=0,S2=N2,I2=R2=P=0 by letting u1=N1S1, u2=N2S2 to obtain the linearization (8) u1=β1N1P,I1=β1N1PαI1,R1=αI1,u2=β2N2P,I2=β2N2PαI2,R2=αI2,P=r1I1+r2I2δP.(8) The equivalent characteristic equation is given by detλ00000β1N1(0)0αλ0000β1N1(0)0αλ0000000λ00β2N2(0)0000αλ0β2N2(0)0000αλ00r100r20δλ=0. This equation can be reduced to a product of four factors and a third degree polynomial equation (λ4)detαλ0β1N1(0)0αλβ2N2(0)r1r2δλ=0. The initial exponential growth rate is the largest root of this third degree equation and it reduces to (9) G(λ)=(α+λ)2(δ+λ)(α+λ)β1r1N1+β2r2N2,(9) (10) G(λ)=(α+λ)2(δ+λ)(α+λ)αδR0=0.(10) We can measure the initial exponential growth rate, and if the measured value is ξ, then from Equation (Equation10) we obtain (11) (α+ξ)2(δ+ξ)(α+ξ)αδR0=0,(11) and we have (12) R0=(α+ξ)(δ+ξ)αδ.(12) Equation (Equation12) gives a way to estimate the basic reproduction number from known quantities, and ξ=0 in Equation (Equation12) corresponds to R0=1, which confirms the proper threshold behaviour for the calculated R0. We can obviously see that λ>0 in Equation (Equation10) is equivalent to R0>1. Estimating the final epidemic size after an epidemic has passed is possible, and this also makes it feasible to choose values of α and β1β2 that satisfy Equation (Equation11) such that the simulations of the model (Equation5) give the observed final size. In summary, we have the following Theorem;

Theorem 2.3

For eigenvalue λ>0 in Equation (Equation10), we have R0>1 denoting epidemic occurrence, and ξ=0 in Equation (Equation12) which corresponds to R0=1 also confirms the proper threshold behaviour for R0.

2.1.3. The final size relation

The final epidemic size is achieved from the solutions of the final size relationship which gives an estimate of the total number of infections and the epidemic size for the period of the epidemic from the parameters in the model [Citation2, Citation10]. The approach in [Citation2–4] is used to find the final size relation in order to evaluate the number of disease cases and disease deaths in terms of the model parameters. It is assumed that the total population sizes N1,N2 of both groups are constant.

Integrate the equation for S1 and S2 in Equation (Equation5); (13) logSi0Si=βi0P(t)dti=1,2.(13) Integrate the linear equation for P in Equation (Equation5) to have (14) P(t)=P0eδt+r10teδ(ts)I1(s)ds+r20teδ(ts)I2(s)ds.(14) Next, we need to show that (15) limt0teδ(ts)Ii(s)ds=limt0teδsIi(s)dseδt=0i=1,2.(15) If the integral in the numerator of (Equation15) is bounded, this is obvious; and if unbounded, l'Hospital's rule shows that limtIi(t)/δ=0 [Citation4], and Equation (Equation14) implies that P=limtP(t)=0. Integrate Equation (Equation14), and interchange the order of integration, then use Equations (Equation6) and (Equation7) to have (16) 0P(t)dt=r1δ0I1(t)dt+r2δ0I2(t)dt,(16) which implies that 0P(t)dt<.

Substitute Equation (Equation16) into Equation (Equation13) to have logSi0Si=βir1δ0I1(t)dt+r2δ0I2(t)dt+2P0δ, i=1,2, and now the final size relation logSi0Si=βir1N1α1δ1S1()N1+r2N2α2δ1S2()N2+2P0δ,=βiR11S1()N1+R21S2()N2+2P0δ, i=1,2, is from the substitution of Equations (Equation6) and (Equation7) which implies Si>0. If the outbreak begins with no contact with pathogen, P0=0, and then the final size relation is written as logSi0Si=βiR11S1()N1+R21S2()N2 i=1,2. Note that the total number of infected populations over the period of the epidemic in patch 1 and 2 are, respectively, N1S1 and N2S2 which are always described in terms of the attack rate (1S1/N1) and (1S2/N2) as in [Citation3].

Following the steps used in Section 2.1, we can compute the reproduction number, the exponential growth rate and the final size relation from Equation (Equation4) as;

2.2. Reproduction number R0

We have 3 infected classes ϕ1, ϕ2, P and following the approach of van den Driessche and Watmough [Citation22], the next generation matrix is 00β1N10A1(τ)dτ00β2N20A2(τ)dτr10Γ(τ)dτr20Γ(τ)dτ0, and R0 is the largest root of (17) detλ0β1N10A1(τ)dτ0λβ2N20A2(τ)dτr10Γ(τ)dτr20Γ(τ)dτλ=0.(17) The basic reproduction number for the model (Equation4), which is the number of secondary infections caused by a single infective in a totally susceptible population is given by (18) R0=r1β1N10A1(τ)dτ0Γ(τ)dτ+r2β2N20A2(τ)dτ0Γ(τ)dτ,(18) which can be written as β1R1+β2R2, where R1=r1N10A1(τ)dτ0Γ(τ)dτ, represent secondary infections caused by an infectious individual in I1 indirectly by the pathogen shed and R2=r2N20A2(τ)dτ0Γ(τ)dτ, represent secondary infections caused by an infectious individual in I2 indirectly by the pathogen shed. We summarize the analysis and impacts of R1 and R2 in the following Theorem.

Theorem 2.4

Disease dies out whenever R0<1 (i.e. R1<1 and R2<1) and epidemic occur whenever R0>1 (i.e. R1>1 and R2>1).

2.3. The initial exponential growth rate

In order to avoid the difficulties caused by the fact that there is a three-dimensional subspace of equilibria ϕ1=ϕ2=P=0 and following the approach of Fred [Citation12], we include small birth rates in the equations for S1 and S2, and equivalent proportional natural death rates in each of the compartment to give the system (19) S1(t)=μN1μS1β1S1(t)P(t),ϕ1(t)=0[S1(tτ)]eμτA1(τ)dτ,S2(t)=μN2μS2β2S2(t)P(t),ϕ2(t)=0[S2(tτ)]eμτA2(τ)dτ,P(t)=0[r1ϕ1(tτ)+r2ϕ2(tτ)]eμτΓ(τ)dτ.(19) We then linearize Equation (Equation19) about the disease-free equilibrium S1=N1, ϕ1=0, S2=N2, ϕ2=0, P=0 by letting u1=N1S1, u2=N2S2 to obtain the linearization (20) u1(t)=β1N1Pμu1,v1(t)=0β1N1P(tτ)eμτA1(τ)dτ,u2(t)=β2N2Pμu2,v2(t)=0β2N2P(tτ)eμτA2(τ)dτ,P(t)=0[r1v1(tτ)+r2v2(tτ)]eμτΓ(τ)dτ,(20) and form the characteristic equation, which is the condition on λ that the linearization have a solution u1=u10eλt, v1=v10eλt, u2=u20eλt, v2=v20eλt, P=u0eλt, det(λ+μ)000β1N10100β1N100(λ+μ)0β2N20001β2N20r10e(λ+μ)τΓ(τ)dτ0r20e(λ+μ)τΓ(τ)dτ1=0, where =0e(λ+μ)τA1(τ)dτ and =0e(λ+μ)τA2(τ)dτ.

We have a double root λ=μ<0, and the remaining roots of the characteristic equation are the roots of det10β1N10e(λ+μ)τA1(τ)dτ01β2N20e(λ+μ)τA2(τ)dτr10e(λ+μ)τΓ(τ)dτr20e(λ+μ)τΓ(τ)dτ1=0. Since this is true for all sufficiently small μ>0, we may let μ0 and conclude that in a scenario where there is an epidemic, equivalent to an unstable equilibrium of the model, then the positive root of the characteristic equation (21) det10β1N10eλτA1(τ)dτ01β2N20eλτA2(τ)dτr10eλτΓ(τ)dτr20eλτΓ(τ)dτ1=0,(21) is the initial exponential growth rate and this is (22) r1β1N10eλτA1(τ)dτ0eλτΓ(τ)dτ+r2β2N20eλτA2(τ)dτ0eλτΓ(τ)dτ=1.(22) We can obviously see from Equations (Equation18) and (Equation22) that epidemic occurs only if λ>0 which is equivalent to R0>1. In summary, we have a simple Theorem as;

Theorem 2.5

Epidemic occur if and only if λ>0, which is equivalent to R0>1.

2.4. The final size relation

Integrate the equations for S1 and S2 in Equation (Equation4) to have (23) logSi0Si=βi0P(t)dt i=1,2.(23) Interchanging the order of integration, using S1(u) and S2(u) for u<0, and by Lemma 2.1 to have 0ϕi(t)dt=[NiSi]0Ai(τ)dτ i=1,2, 0P(t)dt=r10ϕ1(τ)0Γ(τ)dτ+r20ϕ2(τ)0Γ(τ)dτ=r1[N1S1]0A1(τ)dτ0Γ(τ)dτ+r2[N2S2]0A2(τ)dτ0Γ(τ)dτ. Substitute into Equation (Equation23) to have (24) logSi0Si=βir1[N1S1]0A1(τ)dτ0Γ(τ)dτ+r2[N2S2]0A2(τ)dτ0Γ(τ)dτ,logSi0Si=βiR11S1N1+R21S2N2 i=1,2.(24) Note that the final size of the epidemic, the total number of members of the population infected over the course of the epidemic in patch 1 and 2 are, respectively, N1S1 and N2S2 and are often described in terms of the attack rates (1S1/N1) and (1S2/N2), respectively.

3. Variable pathogen shedding rates

We describe a more realistic model that allows the pathogen shedding rates r1 and r2 depend on age of infection of the shedding individual. We need a more complex model that allows the shedding rates decrease to zero. We therefore let Q1(w) and Q2(w) be rates at which virus is being shed for infectives with age of infection w, and Γ(c) be the proportion of infectivity remaining for virus already shed c time units earlier.

We can reasonably assume that infectivities (Q1(τ) and Q2(τ)) which are functions of infection age, are effective viruses at time t shed by infectives I1 and I2 with age of infection τ at time t.

Then, it therefore makes sense to make changes of A1(τ)=Q1(τ) and A2(τ)=Q2(τ) in the equation for ϕ1 and ϕ2 in Equation (Equation4).

A more general equation for P need to be developed while equations for S1 and S2 from Equation (Equation4) remain unchanged and the idea follows from [Citation4].

Let the number of individuals with age of infection w at time t be i(t,w), which may include individuals with zero infectivity who do not infect any more.

Therefore i(t,w)=i(tw,0)=Si(tw).

Consider infectives that are infected at time tc, 0c with infection age v, 0vc and contribution of their virus at time t.

At time tc+v, we have i(tc+v,v)=i(tc,0)=Si(tc). Their shedding rates are Q1(v) and Q2(v), and the viruses remaining at time t are Q1(v)Γ(cv) and Q2(v)Γ(cv). We therefore have P(t)=00c[S1(tc)]Q1(v)Γ(cv)dvdc+00c[S2(tc)]Q2(v)Γ(cv)dvdc=0v[S1(tc)]Γ(cv)dcQ1(v)dv+0v[S2(tc)]Γ(cv)dcQ2(v)dv=00[S1(tzv)]Γ(z)dzQ1(v)dv+00[S2(tzv)]Γ(z)dzQ2(v)dv. The general model becomes (25) S1(t)=β1S1(t)P(t),ϕ1(t)=0[S1(tτ)]Q1(τ)dτ,S2(t)=β2S2(t)P(t),ϕ2(t)=0[S2(tτ)]Q2(τ)dτ,P(t)=00[S1(tzv)]Γ(z)dzQ1(v)dv+00[S2(tzv)]Γ(z)dzQ2(v)dv.(25) The equation for P can be substituted into equations for S1 and S2 in the model (Equation25) to have two single equations for S1 and S2 as S1(t)=β1S1(t)00[S1(tzv)]Γ(z)dzQ1(v)dv+00[S2(tzv)]Γ(z)dzQ2(v)dv, and S2(t)=β2S2(t)00[S1(tzv)]Γ(z)dzQ1(v)dv+00[S2(tzv)]Γ(z)dzQ2(v)dv.

3.1. Reproduction number R0

We will find the basic reproduction number for Equation (Equation25) by beginning with new infectives and calculating the virus shed over the period of the infection. The effective viruses at time t are given as 0tQi(w)Γ(tw)ds=0tQi(tc)Γ(c)dc i=1,2, and total infectivities over the period of the infection are 00tQi(tc)Γ(c)dcdt=0cQi(tc)dtΓ(c)dc=00Qi(v)dvΓ(c)dc=0Qi(v)dv0Γ(c)dc i=1,2. The basic reproduction number can therefore be written as (26) R0=β1N10Q1(v)dv0Γ(c)dc+β2N20Q2(v)dv0Γ(c)dc,(26) and we have R0=β1R1+β2R2, where R1=N10Q1(v)dv0Γ(c)dcandR2=N20Q2(v)dv0Γ(c)dc, and follows from Theorem 2.4.

3.2. The initial exponential growth rate

The linearization of Equation (Equation25) at the equilibrium S1=N1, S2=N2, ϕ1=ϕ2=0, P=0, are S1(t)=β1N100[S1(tzv)]Γ(z)dzQ1(v)dv+00[S2(tzv)]Γ(z)dzQ2(v)dv, and S2(t)=β2N200[S1(tzv)]Γ(z)dzQ1(v)dv+00[S2(tzv)]Γ(z)dzQ2(v)dv. The characteristic equation is a situation where by the linearization have solutions S1(t)=S10eλt and S2(t)=S20eλt, which are (27a) β1N10eλvQ1(v)dv0eλcΓ(c)dc+0eλvQ2(v)dv0eλcΓ(c)dc=1,(27a) (27b) β2N20eλvQ1(v)dv0eλcΓ(c)dc+0eλvQ2(v)dv0eλcΓ(c)dc=1.(27b)

Theorem 3.1

The disease dies out and there is no epidemic when λ<0 (i.e. when R0<1) in Equation (Equation27), but disease persists when λ>0 (i.e. when R0>1) which corresponds to an epidemic.

Combining Equations (Equation26) and (Equation27) we have R0=0Q1(v)dv0Γ(c)dc+0Q2(v)dv0Γ(c)dc0eλvQ1(v)dv0eλcΓ(c)dc+0eλvQ2(v)dv0eλcΓ(c)dc.

3.3. The final size relation

Integrate the equations for S1 and S2 in Equation (Equation25) to obtain the final size relation, (28) logSi0Si=βi0P(t)dt.(28) But we know that 0P(t)dt=000[S1(tzv)]Γ(z)dzQ1(v)dvdt+000[S2(tzv)]Γ(z)dzQ2(v)dvdt. Interchange the order of integration, integrate with respect to t to obtain (29) 0P(t)dt=000[S1(tzv)dtΓ(z)dzQ1(v)dv+000[S2(tzv)dtΓ(z)dzQ2(v)dv=00[S1(zv)S1]Γ(z)dzQ1(v)dv+00[S2(zv)S2]Γ(z)dzQ2(v)dv=00[N1S1]Γ(z)dzQ1(v)dv+00[N2S2]Γ(z)dzQ2(v)dv=[N1S1]0Γ(z)dz0Q1(v)dv+[N2S2]0Γ(z)dz0Q2(v)dv=R11S1N1+R21S2N2.(29) Using Equation (Equation29) in Equation (Equation28) and by Lemma (2.1), we obtain, (30) logS10S1=β1R11S1N1+R21S2N2,logS20S2=β2R11S1N1+R21S2N2.(30)

4. Heterogeneous mixing and indirect transmission with residence time

Here we examined SIRP two patch model which included an explicit travel rates between patches. We divide the environment into two patches and population in each patch is divided into Susceptible, Infective and Removed with different pathogens in each patches. This model considers patches with residents who spend some of their time in another patch or different environment more probable to allow disease transmission.

The model is considered for a short period of time and therefore assumes no recruitment, birth or natural death. We assume that the rate of travel of individuals between the two patches depends on the status of the disease, and individuals do not change disease status during travel. The disease is assumed to be transmitted by horizontal incidence βiSiPi(i=1,2) with the same removed rate and infectivity loss rate for infected individuals in both patches. We assume that one of the patches has a larger contact rate β2>β1, with short term travel between the two patches and that each patch has a constant total population with p11+p12=1, p21+p22=1, where pij(i,j=1,2) is the fraction of contact made by patch i residents in patch j [Citation2, Citation10].

A Lagrangian perspective is followed to keep track of individual's place of residence at all times. This model with direct transmission of infection is the starting point of [Citation6, Citation10].

2-Patch SIRP model with residence time (31) S1=β1p11S1(p11P1+p21P2)β2p12S1(p12P1+p22P2),I1=β1p11S1(p11P1+p21P2)+β2p12S1(p12P1+p22P2)αI1,R1=αI1,P1=r1I1δP1,S2=β1p21S2(p11P1+p21P2)β2p22S2(p12P1+p22P2),I2=β1p21S2(p11P1+p21P2)+β2p22S2(p12P1+p22P2)αI2,R2=αI2,P2=r2I2δP2,(31) with initial conditions S1(0)=S10,S2(0)=S20,I1(0)=I10,I2(0)=I20,P1(0)=P10,P2(0)=P20,R1(0)=R2(0)=0, in a population of constant total size N=N1+N2 where N1=S1+I1+R1=S10+I10andN2=S2+I2+R2=S20+I20. Since this is an indirect transmission model, each of the p11S1 susceptibles from Group 1 present in patch 1 can be infected by pathogens shed by members of Group 1 and Group 2 present in patch 1. Similarly, each of the p12S1 susceptibles from Group 1 present in patch 2 can be infected by pathogens shed by members of Group 1 and Group 2 present in patch 2 (Table ). The infective proportion in patch 1 is given by p11P1(t)+p21P2(t)and in patch 2 isp12P1(t)+p22P2(t). Therefore, the rate of new infections of members of patch 1 in patch 1 is β1p11S1(p11P1+p21P2). The rate of new infections of members of patch 1 in patch 2 is β2p12S1(p12P1+p22P2). Similarly, the rate of new infections of members of patch 2 in patch 1 is β1p21S2(p11P1+p21P2). The rate of new infections of members of patch 2 in patch 2 is β2p22S2(p12P1+p22P2). From the sum of the equations for S1, S2, I1 and I2 in Equation (Equation31), we have (S1+I1)=αI10. We can see that (S1+I1) decreases to a limit, and by Lemma 2.1 we could show that its derivative approaches zero, from which can be deduced that I1=limtI1(t)=0. Integrate this equation to give (32) α0I1(t)dt=S1(0)+I1(0)S1()=N1(0)S1(),0I1(t)dt=N1(0)S1()α,(32) implying that 0I1(t)dt<. Similarly, (S2+I2)=αI2 and we have (33) 0I2(t)dt=N2(0)S2()α,(33) implying that 0I2(t)dt<.

Table 2. Model variables, parameters and their descriptions.

4.1. Reproduction number R0

Note that we have four infectious classes I1,P1,I2,P2, and the Jacobian matrix of Fi=(F1,F2,F3), evaluated at the disease-free equilibrium point,

DFE=(S10,0,0,0,S20,0,0,0)=(N1(0),0,0,0,N2(0),0,0,0) is given by F=Fixji,j=0(β1p112+β2p122)N1(0)0(β1p11p21+β2p12p22)N1(0)00000(β1p11p21+β2p12p22)N2(0)0(β1p212+β2p222)N2(0)0000, where xj=I1,P1,I2,P2 for j=1,,4 and i=1,,4.

The jacobian matrix of Vi=(V1,V2,V3), evaluated at the disease-free equilibrium point DFE is V=Vixji,j=α000r1δ0000α000r2δ. The dominant eigenvalues of FV1 which is the spectral of the matrix FV1 gives the basic reproduction number for Epidemic from the model (Equation31) as; (34) R0=+±(+)24β1β2(p11p22p12p21)2N1(0)N2(0)r1r22αδ,(34) where =(β1p112+β2p122)N1(0)r1, and =(β1p212+β2p222)N2(0)r2. Note that in the special case of proportionate mixing where we have p11=p21 and p12=p22, so that p12p21=p11p22, the simplified basic reproduction number from Equation (Equation34) is given as (35) R0=(β1p112+β2p222)N1(0)r1+(β1p112+β2p222)N2(0)r2αδ.(35) Similarly for the case of no movement between patches, we have: p11=p22=1,p12=p21=0, so that the simplified basic reproduction number from Equation (Equation34) is given as (36) R0=ρ(FV1)=maxr1β1N1αδ, r2β2N2αδ.(36) R0 in Equation (Equation36) can be written as R0=max(R1,R2), where R1=r1β1N1/αδ (the reproduction number for patch 1) and R2=r2β2N2/αδ(the reproduction number for patch 2). Theorem 2.4 gives the summary of this analysis.

4.2. The initial exponential growth rate

The initial exponential growth rate is a quantity that can be compared with experimental data [Citation7, Citation12]. We can linearize the model (Equation31) about the disease-free equilibrium S1=N1,I1=R1=P1=0,S2=N2,I2=R2=P2=0 by letting u1=N1S1, u2=N2S2 to obtain the linearization (37) u1=β1p11N1(p11P1+p21P2)+β2p12N1(p12P1+p22P2),I1=β1p11N1(p11P1+p21P2)+β2p12N1(p12P1+p22P2)αI1,R1=αI1,P1=r1I1δP1,u2=β1p21N2(p11P1+p21P2)+β2p22N2(p12P1+p22P2),I2=β1p21N2(p11P1+p21P2)+β2p22N2(p12P1+p22P2)αI2,R2=αI2,P2=r2I2δP2.(37) The equivalent characteristic equation be reduced to a product of four factors and a fourth degree polynomial equation λ4detαλ(β1p112+β2p122)N10(β1p11p21+β2p12p22)N1r1δλ000(β1p11p21+β2p12p22)N2αλ(β1p212+β2p222)N200r2δλ=0. The initial exponential growth rate is the largest root of this fourth degree equation and it reduces to G(λ)=(α+λ)2(δ+λ)2(α+λ)(δ+λ)((β1p112+β2p122)r1N1+(β1p212+β2p222)r2N2)+β1β2r1r2N1N2(p11p22p12p21)2. We can write the initial exponential growth rate in a simplified form using Equation (Equation35) as (38) G(λ)=(α+λ)2(δ+λ)2(α+λ)(δ+λ)αδR0=0.(38) Measuring the initial exponential growth rate is possible, and if the measured value is ξ, then from Equation (Equation38) we obtain (39) (α+ξ)2(δ+ξ)2(α+ξ)(δ+ξ)αδR0=0,(39) and we have (40) R0=(α+ξ)(δ+ξ)αδ.(40) Equation (Equation40) gives a way to estimate the basic reproduction number from known quantities, and ξ=0 in Equation (Equation40) corresponds to R0=1, which confirms the proper threshold behaviour for the calculated R0. Estimating the final epidemic size after an epidemic has passed is possible, and this makes it feasible to choose values of α and β1β2 that satisfy Equation (Equation39) such that the simulations of the model (Equation31) give the observed final size.

In the case of no movement, the initial exponential growth rate is given as G(λ)=(α+λ)2(δ+λ)2(α+λ)(δ+λ)β1r1N1+β2r2N2+β1β2r1r2N1N2, and simplified using Equation (Equation36) as (41) G(λ)=(α+λ)2(δ+λ)2(αδ)(α+λ)(δ+λ)R1+R2=0.(41) Measuring the initial exponential growth rate is also possible, and if the measured value is ξ, then from Equation (Equation41) we obtain (42) (α+ξ)2(δ+ξ)2(αδ)(α+ξ)(δ+ξ)R1+R2=0,(42) and we have (43) R1+R2=(α+ξ)(δ+ξ)αδ.(43) On the one hand, if R1>R2, it means disease is more effectively spread in patch 1 and infection in patch 2 is therefore driven to extinction. Then the basic reproduction number from Equation (Equation43) becomes (44) R0=R1=(α+ξ)(δ+ξ)αδ.(44) On the other hand, if R2>R2, it means disease is more effectively spread in patch 2 and infection in patch 1 is therefore driven to extinction. Then the basic reproduction number from Equation (Equation43) becomes (45) R0=R2=(α+ξ)(δ+ξ)αδ.(45) Equations (Equation44) and (Equation45) give a way to estimate the basic reproduction number from known quantities, and by Theorem 2.3 and ξ=0 in either of these equations corresponds to R0=1, which confirms the proper threshold behaviour for the calculated R0. Estimating the final epidemic size after an epidemic has passed is also possible, and this makes it feasible to choose values of α and β1β2 that satisfy Equation (Equation42) such that the simulations of the model (Equation31) give the observed final size when there is no movement between patches.

4.3. The final size relation

Integrate the equation for S1 and S2 in Equation (Equation31); (46) logS10S1=β1p1120P1(t)dt+β1p11p210P2(t)dt+β2p1220P1(t)dt+β2p12p220P2(t)dt,logS20S2=β1p11p210P1(t)dt+β1p2120P2(t)dt+β2p12p220P1(t)dt+β2p2220P2(t)dt.(46) Integrate the linear equation for P1 and P2 in Equation (Equation31) to have (47) P1(t)=P10eδt+r10teδ(ts)I1(s)ds,P2(t)=P20eδt+r20teδ(ts)I2(s)ds.(47) Next, we need to show that (48) limt0teδ(ts)Ii(s)ds=limt0teδsIi(s)dseδt=0 i=1,2.(48) This is clear if the integral in the numerator of (Equation48) is bounded, and if unbounded, l'Hospital's rule shows that the limit is limtIi(t)/δ=0 [Citation4]. And Equation (Equation47) implies that Pi=limtPi(t)=0. But integrate Equation (Equation47), interchange the order of integration, and use Equations (Equation32) and (Equation33) to have (49) 0P1(t)dt=r1δ0I1(t)dt,0P2(t)dt=r2δ0I2(t)dt.(49) implying that 0Vi(t)dt<.

Substitute Equation (Equation49) into Equation (Equation46) to have (50) logS10S1=β1p112r1δ0I1(t)dt+β1p11p21r2δ0I2(t)dt+β2p122r1δ0I1(t)dt+β2p12p22r2δ0I2(t)dt,logS20S2=β1p11p21r1δ0I1(t)dt+β1p212r2δ0I2(t)dt+β2p12p22r1δ0I1(t)dt+β2p222r2δ0I2(t)dt.(50) and now substituting Equations (Equation32) and (Equation33) into Equation (Equation50) and using Lemma 2.1, gives the final size relation (51) logS10S1=(β1p112+β2p122)r1N1αδ1S1()N1+(β1p11p21+β2p12p22)r2N2αδ1S2()N2,logS20S2=(β1p11p21+β2p12p22)r1N1αδ1S1()N1+(β1p212+β2p222)r2N2αδ1S2()N2,(51) which implies Si>0.

Equation (Equation51) can as well be written as (52) logS10S1logS20S2=M11M12M21M221S1()N11S2()N2,(52) where M=(β1p112+β2p122)r1N1αδ(β1p11p21+β2p12p22)r2N2αδ(β1p11p21+β2p12p22)r1N1αδ(β1p212+β2p222)r2N2αδ. In a situation where we have no movement between patches, the final size relation can be written as (53) logS10S1=β1r1N1αδ1S1()N1,logS20S2=β2r2N2αδ1S2()N2,(53) which implies Si>0.

Equation (Equation53) can as well be written as (54) logS10S1logS20S2=M11M12M21M221S1()N11S2()N2,(54) where M=β1r1N1αδ00β2r2N2αδ. Note that the eigenvalues of FV1 (the next generation matrix) is the same as the eigenvalues of the matrices M (the final epidemic size) and M (the final epidemic size for no movement between patches). In a special case where the epidemiological system cannot be controlled, we have the dominant eigenvalue to be R0.

4.4. Numerical simulations

We run simulations to gain deeper understanding of the role of residence time on disease dynamics.

We simulate for Susceptible populations S1(0)=199 in patch 1 with one infective and similarly for S2(0)=298 in patch 2 with two infective. We assume that patch 2 has higher risk with β2=1.2 and patch 1 has lower risk with β1=0.3. We have the parameter values and their sources in Table .

Table 3. Parameter values and their sources.

From our simulations in Figure , we observe that:

Figure 1. Dynamics of I1 and I2 when we vary p11,p12,p21, p22 and have no movement (p11=p22=1, p12=p21=0), half populations moving (p11=p22=p12=p21=0.5), and all populations moving (p11=p22=0, p12=p21=1). The figure on the left panel shows that the prevalence in patch 1 reaches its highest when in extreme mobility case (blue line) and is lowest when there is no mobility between patches (red line). The figure on the right panel show the opposite of this scenario in patch 2 (high risk). (a) The plot of Infected individuals (I1) in patch 1 and (b) The plot of Infected individuals (I2) in patch 2.

Figure 1. Dynamics of I1 and I2 when we vary p11,p12,p21, p22 and have no movement (p11=p22=1, p12=p21=0), half populations moving (p11=p22=p12=p21=0.5), and all populations moving (p11=p22=0, p12=p21=1). The figure on the left panel shows that the prevalence in patch 1 reaches its highest when in extreme mobility case (blue line) and is lowest when there is no mobility between patches (red line). The figure on the right panel show the opposite of this scenario in patch 2 (high risk). (a) The plot of Infected individuals (I1) in patch 1 and (b) The plot of Infected individuals (I2) in patch 2.
  1. For the case of no movement between patches (no mobility), that is, p11=p22=1 and p12=p21=0, the system behaves as two separated patches where we have the disease prevalence to be at its highest in patch 2.

  2. For the symmetric case in which p11=p12=p21=p22=0.5, the system has the same level of disease prevalence in both patches.

  3. The case where everyone move from their patch to the other patch (high mobility), that is p11=p22=1 and p12=p21=0, the system has the highest disease prevalence in patch 1.

Our numerical results is similar to [Citation10] where direct transmission pathway is considered as a form of disease spread. Our results show that considering indirect transmission pathway is of great importance and disease spread may be difficult to control (the case of cholera) if otherwise, as in Figure .

5. Conclusion

In this paper, we proposed and studied an epidemic model in which infection is transmitted when viruses are shed and acquired through host (population)-source (environment)-host (population) in heterogeneous environments. For the three models developed, we calculated the reproduction number, estimated the initial exponential growth rate and obtained the reproduction number in terms of parameters that can be estimated. The final size relation was also analysed to find the number of disease cases and disease deaths in terms of the model parameters.

We examined an SIVR model with residence times and develop a 2-patch model where infection risk is as a result of the residence time and other environmental factors. With this approach, we studied the disease prevalence in heterogeneous environment through indirect transmission pathways without needing to measure contact rates and our analysis was also buttressed by numerical results.

Our primary result shows that the number of populations being infected through indirect transmission medium which had been omitted in some other previous works is worth taking into account. The result of our numerical simulation is similar to one of the results in [Citation10] in which only direct transmission pathway was considered. We were able to show how worst the prevalence of a disease could be when the disease transmission is indirect.

We considered indirect transmission of viruses in heterogeneous mixing population, but considering direct and indirect pathways (the case of Ebola), may give a different/better insight into the disease prevalence and how accurate treatment will be apportioned.

Despite these limitations, our models can be used to compare disease spread between two populations with different contact rates, such as cities against villages, rich against poor populations and so on. The derivation of the age of infection model could be extended to include direct transmission pathways. It is also possible to extend the model with the residence times to incorporate treatment strategies which may reduce the contact rates and then lower the reproduction number. In addition, it may be more realistic to extend the model to incorporate multiple class of hosts and sources in order to compare the disease spread among different populations and with different viruses.

Acknowledgments

This work was first communicated by Professor Fred Brauer. I sincerely appreciate Fred for weekly discussions, contributions and supports from the beginning and throughout the period of compiling the work. Special thanks to two anonymous reviewers for their valuable comments which have improve the paper significantly.

Disclosure statement

No potential conflict of interest was reported by the author.

Additional information

Funding

This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) under Grant RGPIN-2016-03706.

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