1. Introduction
Compartmental models for infectious diseases separates a population into various classes according to the stages of infection. The reflected rates of transition between compartments are stated by time derivatives of the population sizes in each compartment, and so such type models are formulated by means of differential equations. Mathematical models, in which the rates of transfer between compartments depend on the sizes of compartments in the past or at the moment of transfer, especially require working with differential, integral or integro-differential equations.
The early studies related to the compartmental models in mathematical epidemiology are based on Kermack and McKendrick, [
1]. In 1927 they introduced a compartmental epidemic model based on basic transfers between divided groups in a population. To explain the compartments, they divided the population into three groups referred as
I and
denotes the number of individuals who are susceptible against the disease at time
t, in other words, who are not yet infected and have not any immunity.
represents the number of infectious, that is, members of
are able to spread the disease to susceptibles with effective contact.
shows the number of recovered individuals, who have immunity against the pathogen and so no there exists any probability of spread of infection via these individuals.
After the model given by Kermack and McKendrick, mathematical epidemiology has been developed with numerous studies providing various contributions to the literature in this field. [
2,
3,
4,
5] are just a few of the studies in this area.
Vaccination of susceptibles against the infection is one of the effective control measures in the process related to the struggle with diseases. So far, a lot of studies explaining the effects of vaccination upon the spread of the diseases has been introduced, see [
6,
7,
8,
9] and references therein.
In recent years, some fractional-order differential equation models of infectious disease dynamics have been introduced with the Caputo derivation. Some authors have extended classical epidemic models to fractional-order epidemic systems and discussed the stability of equilibrias, [
10,
11,
12].
In this study, it will be followed by the terminology of the model to explain a new model related to disease that confers immunity against reinfection, by adding the vaccinated class, too. This paper reveals and analyzes an epidemic model, considering vaccination effect in the spread of any disease. For analysis of the model, firstly disease-free and endemic equilibrium points have been determined. Then the basic reproduction number related to the model has been obtained by using the next generation matrix method. Also, it is shown that the disease-free and the endemic equilibria are locally and globally asymptotically stable for and , respectively.
Local stabilities of equilibrium points have been researched with the way of analyzing the corresponding characteristic equation. To prove global stabilities of equilibria it have been used LaSalle Invariance Principle associated with Lyapunov function and Dulac Criteria, respectively.
2. Some Basic Mathematical Properties and Model Structure
The definitions of the fractional integral and Caputo fractional derivative are defined as follows, [
13].
Definition 1.
Suppose that and x be an integrable function. Then the fractional integral of x of order α is defined as
The Caputo fractional derivative of
x of order
is defined as
where
. When
is an integer number,
is usual derivative of order
of
If
x is a function of class
its fractional derivative is represented by
Especially we write
instead of
It is obvious that the Caputo fractional derivative of order
of
x
for
On the other hand let us recall some properties of Laplace transforms. Laplace transform of the Caputo fractional derivative ([
10]) is given by
Also Laplace transform of Mittag–Leffler function defined by the power series
hold the following equality, [
10]
Theorem 1.
Let be an equilibrium point for and Ω be a domain containing Let be a continuously differentiable function such that
hold for all and where functions are continuous positive definite functions on Then the equilibrium point of system is uniformly asymptotically stable, [11,12].
2.1. Model Structure
We introduce a new fractional
mathematical compartmental model expressed by the system of the following nonlinear fractional integro-differential equations with all parameters being positive:
where and functions and represent the numbers of the susceptible, vaccinated, infectious and recovered individuals at time t, respectively. The total population size is and for all . Also all these functions are nonnegative.
In the model, all newborn individuals get involved in the population by entering to S with a constant rate denotes the effective contact rate between infectious and susceptible or vaccinated individuals. is the natural death rate in each compartment and is the death rate welded from the outbreak. The rate of vaccinated individuals within susceptibles is represented by q. Also denotes the transition rate from infectious compartment to compartment R.
Vaccination may not be always completely effective for individuals. Therefore, in this model, we suppose that the vaccine provides temporary immunity effect or permanent effect for some individuals. In this context, we use the distribution parameter for meaning the protection period caused by vaccination. Essentially, the term designates the protection efficacy of the vaccine. That is, means that the vaccine is completely ineffective. Also, means that the vaccinated individuals have only partial protection. Otherwise it means that the vaccine is wholly effective against the pathogen.
On the other hand, we assume that the protection provided by the vaccination may vary according to individual. So, we use a distribution function f to reflect this fact to the model. f is a distribution function and is the ratio of the individuals whose protection period provided by the vaccine is Classically, it is supposed that is non-negative for each and f is continuous on , also f satisfies . The term represents the number of surviving individuals at time t who have been vaccinated at time and have protection period .
Of course, since it is thought that the vaccine may not provide full protection, some of vaccinated individuals may still be susceptible to infection. Therefore, as a result of a sufficiently effective contact with infectious individuals, a vaccinated individual who no longer has any protection enters to the infectious compartment. To reflect this transition to the compartment I, the expression has been used in the model.
3. Analysis of the Model
In this part, for the model, the convenient and positive invariant region, equilibrium points and basic reproduction number have been determined.
3.0.1. Feasible Region
Theorem 2.
For the system (3), the set
is positively invariant region in which the solutions of the model is bounded.
Proof. (Following [
10]) Adding the four equations in (
3), we write
Then we can get
from (
1) and other properties of Laplace transform. If we take
and consider the inequality (
6), we get
and
Applying the inverse Laplace transform to (
7) and considering the boundedness of Mittag–Leffler function
for all
, we can write
where
C is a constant such that
hold for all
So, if
we get
for all
as
from (
8). Also, if
then solution of (
5) comes with the solution of differential equation
If the integrating factor method is processed, it is obtained that
and so
is obtained for the initial condition
Standard Comparison Theorem [
14] says that the right side of (
9) is the maximal solution of Equation (
5). Thus it is reached to the inequality
for all
Hence, when
we obtain
for all
and
. This means that
is positively invariant for the system (
3 ). □
Because the populations
and
do not feature in remainder equations of system (
3), it will be enough to consider with the reduced system (
10)
3.0.2. Existence of Solutions of the System
In this section, we focus on the existence of solution of the problem
Where
represents the initial functions of system (
10) and
Also let us take
and
. If we choose the function
h as
such that
and
then we can say that the finding the solution of the problem (
11) is equivalent to solving the system (
10) or equivalently the following problem.
Also we can say that the Equation (
11) has a unique solution if
h is Lipschitz continuous in every compact subset
. Indeed this result depends on Schauder fixed point theorem, [
15].
In this study, the fact that the set
is a Banach space with the norm
is also taken into consideration.
Theorem 3. There exists a unique solution of the system (13), or equivalently, of the Equation (11) with , defined by (12).
Proof. The proof depends on the result in [
15]. So it is sufficient to show that
h is Lipschitz continuous in every compact subset
Let
, and
. Then considering
and
for
we can write from the description of
h
and so we conclude
Thus if we take
then the inequality
holds in every compact subset
As a result, it is concluded that there is only one solution of system (
13) since
h satisfies the Lipschitz inequality in every compact
M subset of
. □
3.0.3. Disease-Free Equilibria, Basic Reproduction Number
Since the equilibria of the proposed model are the solutions of the system (
10) then disease-free equilibrium point which we will show with
provides the equations in the system.
Therefore, system (
10) always has a disease-free equilibria
Now we will determine the threshold value
referred as basic reproduction number is the number of secondary infections caused by one infectious individual. This parameter allows us to have an idea about the dynamics of the epidemic and to make predictions. For this reason it is a very important value in epidemiology. Using the next generation matrix method, the value of
related to the model (
10) is calculated by following terminology below, [
16,
17].
First of all, let us specify that for the value of the integral briefly will be used notation F, throughout the remainder of the text.
Let
. Then we can write the system (
10) in the form
that is
The values at
of the derivatives of
and
with respect to
respectively, come in sight with the following Jacobian matrices:
Thus we can obtain
and
So by using the characteristic polynomial of
we get the spectral radius as
Taking into account that
, the basic reproduction number of the system (
10) is calculated in the form of
In the following part, the results about stability dynamics belonging to the epidemic model (
10) have been discussed under the titles "Disease-free case" and "Endemic case", respectively.
3.0.4. Disease-Free Case
Under this title, we consider local and global stabilities of
for the system (
10).
Theorem 4. is locally asymptotically stable for
Proof. The Jacobian matrix at
of system (
10) is
For the point
the characteristic equation for this matrix is
Using the notations
and
for the roots of Eq. (
15) then
and
When
two roots of Equation (
15) are negative. If
then one of roots of Eq.(15) is zero. On the other hand, for
one of roots of Equation (
15) has positive real parts. So
is locally asymptotically stable for
is stable for
and is unstable for
□
Theorem 5. is uniformly asymptotically stable for
Proof. Consider the nonnegative function
L defined as
Computing the time derivative of
we obtain
When
we say that
and
for
By Theorem 1, the disease free equilibrium
is uniformly asymptotically stable in the interior of
, when
. □
3.0.5. Endemic Case
In this part, firstly the existence and uniqueness of the endemic equilibrium point of the model has been shown. Then, in addition to the course of the disease when the local and global stability of this equilibrium point has been investigated.
3.0.6. Existence of the Endemic Equilibria
Since
the endemic equilibria denoted by
satisfies the algebraic equations with
From the second equation of (
16) we write
Since
, it must be
Then the endemic equilibrium point comes with
By the way, we say that
can be expressed as
in terms of
Also it is seen clearly that the system (
10) has a unique endemic equilibria iff
3.0.7. Course of the Disease for
Now, we will focus on how the disease will progress (whether it will disappear or not) in the population when . For this, we will assume the infectious population at the beginning exists, and we will try to see course of the infectious population as time progresses for .
To do this, let us suppose
and
Then, for any given
there exists a
such that
holds for
Specially, we can choose an
such that
and
holds for all
.
Then
Therefore we say that
for
This requires
If we take into account the basic properties of limit inferior and remember the choosing (
17) then we say that there exists a
such that
for all
. Thus
hold for all
. If
T is chosen as
then
for
. This result contradicts with
. Moreover, the fact
for
means that
is increasing, [
18]. But, when
it is not possible that
with the initial assumption
. All these imply that the disease will not disappear in the population when
This case is what should be happen for a consistent model and a meaningful threshold
Now let’s analyze the behavior of function I which do not converge to zero when and of the function S.
3.0.8. Local and Global Asymptotic Stability of the Endemic
Equilibrium Point
Theorem 6. is locally asymptotically stable in Ω for and
Proof. The Jacobian matrix of system (
10) at
is
Herefrom, the characteristic equation of the matrix
forms with the determinant
After the rearrangements, this equation is written as
Let two roots of Equation (
18) be
and
Then
and
So we say that
and
for
. In that case, two roots of Eq. (18) are negative. Since all eigenvalues of the Jacobian matrix of system (
10) at
have negative real parts,
is locally asymptotically stable. □
Now, we will prove that is globally stable for special case by using Dulac criterion and the Poincaré-Bendixson theorem.
Theorem 7. is globally asymptotically stable for .
Proof. We will show that (
10) does not have any periodic solutions in the positive quadrant of the
plane. Let us establish a continuous function
defined by
for system (
10). Setting
G and
H as
we obtain
for all
. We see the last expression is clearly negative. Since it has the same sign almost everywhere in the positive quadrant of the
plane for appropriate Dulac function
. According to the Bendixson-Dulac theorem [
19], we can see that system (
10) has no periodic orbits in the interior of the first quadrant. Thus, all solutions of system (
10) tend to one of the equilibria. Here, this point is the endemic equilibrium point that only exists when
. Hence
is globally asymptotically stable in the interior of the first quadrant.
Consequently, while
system (
10) has a unique endemic equilibrium
, which is globally asymptotically stable. □
4. Sensitivity Analysis
It is difficult to completely eradicate an epidemic in a population in a short period of time. Considering that lots of negative situations brought about by the disease, seeking and attempts to reduce the spread of the disease have great importance. In this context, with various control measures to be implemented; lowering the value is one of the important goals. Therefore, it has a great importance to examine the effect of parameters on the change of and to apply control measures in this direction.
Now we will focus on the sensitivity analysis of
. Sensitivity analysis clarifies us about what direction effective each parameter is to disease transmission. To observe whether the parameters that affect the basic reproduction number have a positive or negative effect, we will explore the normalized forward sensitivity index of
The normalized forward sensitivity index of the variable
with respect to the parameter
is defined as
by using partial derivatives. Where
represents the basic parameters constituting
.
With increasing of values of the parameters that have positive indices , increases and so the spread of the disease progresses in the population. On the other hand, the parameters in which its sensitivity indices are negative cause decreasing of . That is, the average number of secondary infections cases decreases while these parameters increase and so the spread of the disease starts to decrease.
5. Conclusion
Stability is one of the substantial problems in the design and analysis of control systems. Since an unstable control system is considered useless and potentially dangerous, the most basic matter related to the examined control systems is whether it is stable or not.
Nowadays, with the advancement of science, the desires and efforts of individuals have been increased to solve more complex problems. The dynamics of these complex problems often requires nonlinear equations. Furthermore, although there are many methods to investigate the stability of linear systems, examining the stability of nonlinear systems is an important problem. Because nonlinear systems can exhibit different types of behavior which are not visible in linear systems.
Additionally, the existence of delay in a system may lead to being much more complex of analysis and control of the system. Besides, it may cause instability and poor performance in the system. Therefore, the stability analysis of the systems with delay (especially distributed delay) has crucial important theoretically. However, let us immediately state that determining the stability of time-delayed systems is not as easy as non-delayed systems.
In mathematical epidemic models, the course of the disease in population depends on whether is greater than 1 or not. If spread of the disease increasingly goes on. If there is a decrease in outbreak speed and disease dies out gradually. Also if , the outbreak speed is stable. Therefore, determines how much the outbreak will be severe in a population, and it can tell us whether the population is at risk in the face of disease. Moreover, it is very important to calculate the value because the size of allows to determine the amount of required effort to prevent an outbreak or to eliminate an infection from a population.
On the other hand, vaccination is one of the most important mechanisms in the struggle against epidemics. Especially in cases where immunity obtained by vaccination may not be permanent, it should also be taken into account that the duration of immunization of vaccinated individuals may not be the same. Even if they were vaccinated at the same time, while immunity of some of the individuals may continue, the others may lose their immunity and become susceptible to the epidemic.
In this study, prepared by taking all these facts into consideration, a mathematical epidemic model reflecting that the protection period provided by the vaccine effect which may vary from person to person, is presented. This new fractional epidemic model is formed by aid of a system of distributed delay nonlinear fractional integro-differential equations.
Firstly, equilibrium points of formed system are found and the basic reproduction number of the model are determined as
Then it is proved that system (
10) has a unique disease-free equilibrium point
and a unique endemic equilibrium
, which are locally asymptotically stable when
and
respectively. Moreover, it has been shown that in a population with infectious individuals, the disease will never disappear when
. Thus, it has been reinforced that the introduced model is consistent and
is meaningful.
Also, the global behavior of the system (
10) is examined. Firstly, it is proved that all solutions of the system tend to
by constituting the appropriate Lyapunov function for
Then, when
, the proof of global stability of
has been presented by means of the Dulac’s criterion and the Poincaré-Bendixson theorem, which are commonly used in two-dimensional population models.
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