SUMMARY

MATHEMATICAL MODELS FOR THE DYNAMICS OF TUBERCULOSIS DISEASE IN DENSITY DEPENDENT POPULATIONS

CHAPTER I INTRODUCTION

1.1 Background Issues TB is one of the major public health problem in Indonesia (Ministry of Health Republic of Indonesia, 2008). Tuberculosis is an infectious disease directly caused by TB bacteria (Mycobacterium Tuberculosis) is transmitted from person to person through the air rather than by insects, blood transfusion or drinking water. TB infection can be divided into two kinds, namely, latently infected and actively infected. People with latent TB is not spread TB bacteria to people who are vulnerable to TB disease, whereas patients with active TB disease can transmit TB to people who are vulnerable to TB disease. Basic reproduction number represented by is defined as the average

number of secondary infections caused by individuals who are infected during the infectious period (Diekmann and Heesterbeek, 2000). One alternative method for determining the value of is the next generation matrix method. is defined as

the Spectral Radius (the dominant eigenvalue of the next generation matrix) will be discussed in this thesis. Epidemic model in this thesis is formed by combining the parameters for the size of a territory occupied by a population in a period of transmission that can help analyze the density dependence of population dynamics of tuberculosis

disease. It is assumed that there is a homogeneous population mixing in which all people have equal opportunity to become infected by contact with infected individuals. Populations distributed throughout the region with a very small area. Also assumed that all immigrants and births are not infected, so get into the susceptible class.

CHAPTER II BASIC THEORY

In the second chapter we will discuss some definitions and theorems are used to support the discussion of the next chapter. 2.1 Systems Theory Here are presented some basic materials systems theory, namely the nonlinear system, the notion of Jacobian matrix, the equilibrium point and linearization, and stability theorems of nonlinear systems. Given system of nonlinear differential equations:

(2.1) with condition rewritten as (2.2) , i = 1, 2, ..., n and for . With the initial . System of equation (2.1) can be

with conditions

, . Furthermore, the

and initial notation .

declared system solution (2.1) with initial conditions

Solution differential equation of some point can be constant in time, the point which we called as an equilibrium point. Here are the definition of equilibrium point of (2.2) system. Definition 2.1 Given system (2.2). Point (equilibrium point) System (2.2) if f( = 0. is called the equilibrium point

The following definition is given Jacobian matrix. Definition 2.2 Given Matrix the system (2.2) with

Called the Jacobian matrix of f at point x. Next, we use the stability concept to recognize the behaviour system near the equilibrium point. Here are the definition of the stability of equilibrium point for (2.2) system. Definition 2.3 The equilibrium point on system (2.2) said :

1. Stabil local if for every > 0 there is > 0 so that for each solution system (2.2) which satisfy every 2. Unstable if the equilibrium point does not satisfy 1. then the resulting for

3. Stabil local asymptotic if the equilibrium point there are numbers satisfy

local stable and

so that for each solution system (2.2) x(t) which then the result

Below is given the definition of linear and nonlinear systems. Given system (2.2), with (2.2) is said linear if system (2.2) can be written and continuous function on E. System each linearly with . So the

(2.3)

with

is continuous on

Furthermore system (2.3) can be expressed in the form (2.4) with and A matrix size .

Shows that the solution of linear system (2.4) with initial condition given by

is

with The following definition is given eigenvalue of a matrix.

Definition 2.4 A given n x n matrix A nonzero vector in eigenvector of A if Ax scalar multiples of x, he explained Ax = corresponding to .

is called an for any scalar

. A scalar is called eigenvalue of A and x is referred to as an eigenvector of A

Next, (2.2) system is called as nonlinear system if (2.2) system cannot be formed as (2.4) system. Here are the definition of linearization nonlinear diferential equation system. Definition 2.5 linear system (2.2) around the point point . By using the Jacobian matrix equilibrium point , the nature of the stability of the linear system is called the linearization of non with is the Jacobian matrix of f at

of system (2.2) can be determined provided that the point is

hyperbolic. Below is given a definition of the hyperbolic equilibrium point. Definition 2.6 The equilibrium point of system (2.2) if all eigenvalues from is called the equilibrium point hyperbolic has no zero real part.

The following theorem is used to determine the local stability properties of non-linear system (2.2) the terms of the Jacobian matrix eigenvalue Theorem 2.7 Jacobian matrix is given non-linear system (2.2) with eigenvalue , then : a. If all real parts of eigenvalues of the matrix equilibrium point stable. b. If there is at least one eigenvalue of the Real side the equilibrium point of system (2.2) is unstable. positive then is negative then the dari sistem nonlinear (2.2) of

of the non-linear system (2.2) locally asymptotically

Next we discuss the various phase portraits that are possible for the (2.4) linear system when and A is a 2 x 2 matrix. We begin by describing the

phase portraits for the linear system (2.5) Where the matrix . The phase portrait for the (2.4) linear system is

then obtained from the phase portrait for (2.5) under the linear transformation of coordinates Given matrix B as follows. (i) Solution from (2.5) system with initial value is

(ii) Solution from (2.5) system with initial value is

(iii) Solution from (2.5) system with initial value is

We now list the various phase portraits that result from these solutions, grouped according to their topological type. (i) , with

The system (2.5) is said to have a saddle at the origin in this case. Whenever A has two real eigenvalues of opposite sign, the phase portrait for the linear system (2.4) is linearly equivalent to the phase portrait shown in figure 2.1.

Figure 2.1 Phase portrait for case (i)

(ii)

, with

The origin is referred to as a stable node in each of these cases. Whenever A has two real eigenvalues of the same sign, the phase portrait for the linear system (2.4) is linearly equivalent to one of the phase portrait shown in figure 2.2. The stability of the node is determined by the sign of the eigenvalues : stable if and unstable if .

Figure 2.2.a Phase portrait for case (ii)

or

with

The phase portrait shown in figure 2.2.b. as follows

Figure 2.2.b Phase portrait for case (ii) with

(iii)

, with The origin is referred to as a stable focus in this case. Sistem (2.5) fokus stabil pada titik asal. Whenever A has a pair of complex conjugate eigenvalues with non zero real part, the phase portrait for the linear system (2.4) is linearly equivalent to one of the phase portrait shown in figure 2.3.

Figure 2.3 Phase portrait for case (iii) (iv) The system (2.5) is said to have a center at the origin in this case. Whenever A has a pair of pure imaginary complex conjugate eigenvalues, the phase portrait for the linear system (2.4) is linearly equivalent to one of the phase portrait shown in figure 2.4.

Figure 2.4 Phase portrait for case (iv)

Definition 2.8 The linear system (2.4) is said to have a saddle, a node, a focus or a center at the origin if its phase portrait is linearly equivalent to one of the phase portraits in Figures 2.1, 2.2.a, 2.2.b, 2.3 or 2.4 respectively; i.e., if the matrix A is similar to one of the matrices B in case I, II, III or IV respectively. We can determined eigenvalue of a matrix from the determinan and trace signs from the matrix above. This theorem below we use to determine the stability of (2.2) system. Theorem 2.9 Let i. ii. If If stable if iii. If origin; it is stable if iv. If and then (2.2) system has a saddle at the origin. and then (2.2) system has a node at the origin; it is and unstable if and then (2.2) system has a focus at the

and unstable if then (2.2) system has a center at the origin.

2.2 Spektral Radius Diekmann defined as Spectral Radius (eigen dominant value of next

generation matrix). Here's Lemma and the theorem which states about the Spectral Radius. Lemma 2.10 Let H be a real matrix with positive off-diagonal elements (i.e. for s(H) defined by s(H) = sup {Re we have the equivalence is an eigenvalue of H} Then is a positive matrix. Moreover, for the spectral bound

Theorem 2.11 Let T be a positive matrix,

a positive off-diagonal matrix and D is negative. denote the dominant

a positive diagonal matrix. Assume that the spectral bound Let r denote the spectral bound eigenvalue of the positive matrix K = r<0 and let Then

CHAPTER III DISCUSSION

Here below we will explain about the feature and characteristic of Tuberculosis disease also the infection of tuberculosis disease. Next we formed mathematical models that incorporate a parameter for the size of the area occupied by the population in a period of transmission that can help analyze the density dependence of population dynamics of tuberculosis disease. 3.1 Model Formulation Assumptions used in the model are as follows : 1. Population consist of birth and migration. 2. Natural of death occured. 3. Natural of death occur in the class S, L, I and T. 4. The disease is curable. 5. Individu who have recovered can be returned to the latent class. 6. The disease is transmitted through direct contact between latent TBinfected individuals with active tuberculosis-infected individuals. 7. There is a homogeneous mixing of the population where all people are equally likely to be infected by the infectious individuals in case of contact.

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8. The population is distributed over the whole settlement (in the specified area) with a negligibly small area. Here are the mathematical model equation for Tuberculosis disease which depend on density population.

Model above briefly presented in the diagram transfer following

+d

Figure 3.1 Flow Chart of mathematical models for the dynamics of tuberculosis disease is dependent on population density

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Here are the parameters used in mathematical models for the dynamics of tuberculosis disease is dependent on population density. Notation S(t) L(t) I(t) T(t) A Defines The number of susceptible individuals at time t The number of latently infected/exposed individuals at time t The number of infectious individuals at time t The number of recovered/treated individuals at time t The total area of the camp occupied by the population Recruitment rate The per capita natural mortality rate d The tuberculosis-induced moratlity rate The probability that a susceptible individual becomes infected by one infectious individual per contact per unit time The probability that a treated individual becomes infected by one infectious individual per contact per unit time k The rate of progression to active tuberculosis Recovery rate of the latent class Recovery rate of the infectious class C The per capita contact rate Tabel 3.1 The definition of parameters used in the model (All the parameters above are constant and positive) 3.2 The existence of equilibrium point and the stability Equilibrium in the system (3.1) occurs at .

Based on (3.1.a), (3.1.b), (3.1.c) and (3.1.d) equation we can determined the equilibrium point through the following equation :

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We obtain I = 0 or For I = 0, we substitute to (3.2.c) equation so that we have L = 0. The value of I = 0 and L = 0 we substitute to (3.2.a) equation se we have (3.3)

So that

Next we substitute I = 0 and L = 0 to (3.2.d) equation, we have T = 0. I = 0 value means that there is no individu in the infected class. So that we obtain the free disease equilibrium point for (3.2) system is .

Next, we discuss about the transmition disease of the model. We need some parameter to determine the transmission of the disease. We use Basic Reproduction Number parameter denote as (2000) defines matrix). Population is categorized into three classes, namely: X = (S, T), Y = (L) and Z = (I). Class X represents the class of the number of susceptible individuals, individuals who are cured (in treatment) and another class of individuals who are not infected. Y class is the class of individuals who are infected but not infectious, and the Z class is a class of individuals who are infected and have the ability to
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Diekmann dan Heesterbeek

as Spectral Radius (dominant eigenvalue of next generation

transmit disease (eg, infected individuals and individuals who do not enter quarantine). ). With and h(X, 0, 0) = 0 while is a disease-free equilibrium point, with

From (3.1) equation, we formed the new equation, i.e : and

Furthermore, the value of

substituted into equation (3.5) thus obtained

Because

so that

And

Equation (3.7) are substituted into equation (3.6) so as to produce

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Further we define the partial derivative for Z to the matrix in order to get

. Suppose

Equation (3.9) is expressed in the form H = M D. So that

and D = Basic reproductive number eigenvalue) of the matrix is defined as the spectral radius (dominant so that the with M as new . Matrix D as transtition

infection case, we called infection matrix and matrix with D > 0, diagonal matrix.

The density of the susceptibles,

emphasizes the role played by the size

of the area, A occupied by the population.When the area is big enough, the density will be samll thereby reducing on the size of the basic reproductive number. And when the area size A is small, the density will be higher and consequently the basic reproductive number or the number of secondary infections due to a single infectious individual will be higher. 1. When < 1, we have implying that

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2. When

> 1, we have .

implying that

3.3 Stability of Disease free equiliubrium point To determine the stability of free disease equilibrium point we can linearize the nonlinear (3.1) equation. First we determine partial derivatif from x, y, z and w function, with function , and , .

The Jacobian matrix is given by

The Jacobian matrix at disease free equilibrium point

is given by

eigenvalues of the Jacobian matrix for disease-free equilibrium point above is determined by

so obtained

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Because is obtained :

with i state i-th row then by cofactor expansion

Because obtained :

with i state i-th row then by cofactor expansion is

Can be expressed in the form of value and

So that the

From the above equation eigenvalue And from the equation and , with : and Eigenvalue

obtained means generates two eigenvalues, namely

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And eigenvalue

Because the value of whereas , and if if and then if and

, then . So, if .

will always be negative, then

Furthermore, the stability properties are analyzed disease-free equilibrium point of system (3.1). Stability investigated by looking at the eigenvalues of the Jacobian matrix.

From Jacobian matrix of eigenvalues are determined by the sign of the trace Then a matrix obtained from det (A) = and trace (A) =

. The sign of the and the sign of det ( ).

. Because the value of all

parameters are positive then obviously the value of the trace (A) < 0. The diseasefree equilibrium point will be stable if the value of det (A) > 0, so that

Thus, to have a Tuberculosis-free stable population, the characteristic area per unit individual must always be greater than the product of the probability of survival from latent stage into the infectious stage and the number of latent infections produced by a typical infectious individual during his/her mean infectious period.

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3.4 Conditions for the minimization of the disease For the minimization of the disease incidence, we require that the population sizes of the latently infected and the infectious individuals decrease. This is attained when We obtain and < 0.

We substitute (3.11) equation to (3.1.c) equation, when

< 0, we have

Implying that

Therefore, in order to minimize the incidence of tuberculosis in densitydependent populations the area occupied, A must always be greater in magnitude than the product of the probability of survival from latent stage into the infectious stage. and the number of latent infections produced by a typical .

infectious individual during his/her mean infectious period

3.4 Numerical Simulation In this section, numerical simulations of the epidemic are discussed to provide a clearer picture of the model the spread of TB disease depend on population
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density by using the parameters and the initial value specified. Given the values of parameters : and Here's a numerical simulation results are influenced by variations in the size of the occupied area (A). To see the influence of the size of the occupied area (A) the class of the different epidemiology, an area the size of the simulated varied from area (A) = (A) = 20 km2, 200 km2 dan 2000 km2.

Figure 3.2 The effect of a size of the area occupied, on the susceptible population with respect to time

Figure 3.3 The effect of a size of the area occupied, on the exposed population with respect to time

Figure 3.4 The effect of a size of the area occupied, on the infected population with respect to time
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Figure 3.5 The effect of a size of the area occupied, on the recovered population with respect to time

While the following is the numerical simulation results are influenced by variations in the level of recruitment ( ). To see the effect of recruitment rate ( ) the class of the different epidemiological, simulated recruitment rate that varies from the level of recruitment ( ) = 0, 1500 and 5000.

Figure 3.6 The effect of the recruitment ( ), on the susceptible population with respect to time

Figure 3.7 The effect of the recruitment ( ), on the exposed population with respect to time

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Figure 3.8 The effect of the recruitment ( ), on the infected population with respect to time

Figure 3.9 The effect of the recruitment ( ), on the recovered population with respect to time

CHAPTER IV CONCLUSION AND SUGGESTION

Based on the result of the discussion in Chapter III, several conclusions can be drawn as follows. 4.1 Conclusion From the mathematical model for Tuberculosis disease we obtained free disease equilibrium point motality rate. From the analysis with of recruitment rate and the stability, we natural have

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Thus, to have a Tuberculosis-free stable population, the characteristic area per unit individual must always be greater than the product of the probability of survival from latent stage into the infectious stage and the number of latent infections produced by a typical infectious individual during his/her mean infectious period. With next generation . matrix method we defined

a. When

< 1, we have

implying that

b. When

> 1, we have

implying that

The density of susceptibles,

emphasizes the role played by the size of

the area A occupied by the population. When the area is big enough, the density will be small thereby reducing on the size of the basic reproductive number. And when the area size A is small, the density will be higher and consequently the basic reproductive number of secondary infections due to a single infectious individual will be higher.

4.2 Suggestions Through writing and discussion of this thesis needs to be developed for discussion and further research to mathematical models for the dynamics of tuberculosis disease is dependent on population density which analyze the stability of endemic equilibrium point.

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REFERENCES

A. Ssematimba, J.Y.T. Mugisha dan L.S. Luboobi, 2005. Mathematical Models for the Dynamics of Tuberculosis in Density-dependent Populations. Journal of Mathematics and Statistics 1, 3 : 217-224.

Departemen Kesehatan Republik Indonesia, 2008. Pedoman Penanggulangan Tuberkulosis, Departemen Kesehatan Indonesia, Jakarta.

Nasional Republik

Diekmann, O. dan Heesterbeek, J.A.P., 2000. Mathematical Epidemiology of Infectious Diseases : Model Building, Analysis and Interpretation, John Wiley and Sons, Chichester.

Kocak, H dan Hole, J.K., 1991. Dynamic and bifurcation, Springer-Verlag, New York, USA.

Olsder, G. J., 1994. Mathematical System Theory, Delftse Uitgevers Maatschappij, Netherlands.

Perko, S., 1991. Differential Equations and Dynamical Systems. Texts in Applied Mathematics Vol 7, Springer-Verlag, New-York, USA.

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