Contents

1 Introduction 4

2 Mathematical model of Hepatitis B virus 6

2.1 Representation of Hepatitis B virus model as ODE system . . . . . . . . . . . . . 6
2.2 Non-negative orthant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2.3 Positivity of solution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
2.4 Boundedness of solution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2.5 Dynamical system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
2.6 Disease free and endemic equilibrium points . . . . . . . . . . . . . . . . . . . . . 10
2.7 Basic reproductive number . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
2.8 Local stability analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
2.9 Global stability analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
2.10 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

3 Numerical solution of the Hepatitis B model 23

3.1 Runge-Kutta method of order 4 for initial value problem . . . . . . . . . . . . . . 23
3.2 RK4 method for Hepatitis B model . . . . . . . . . . . . . . . . . . . . . . . . . . 24
3.3 Graphical representation of solution of Hepatitis B model and discussion . . . . . 25
3.4 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

1
 Abstract
In this project, we consider a Hepatitis B epidemic model [48] that describes the dynamical
aspects of acute and chronic Hepatitis B virus. We discuss the positivity of solution of the
model. We present the disease free and endemic equilibrium points. We calculate the threshold
number R0 and present the local and global stability analysis of the model of Hepatitis B virus.
We use Runga Kutta method of order 4 to calculate the numerical solutions of Hepatitis B
virus. We present the numerical results of di¤erent classes of Hepatitis B model with the help
of graphs.

3
Chapter 1

Introduction

Hepatitis B is an in‡ammation of the liver that is caused by a variety of infectious viruses

and noninfectious agents leading to a range of health problems, some of which can be fatal.
Hepatitis B lead to chronic disease in hundreds of millions of people and together are the most
common cause of liver cancer and viral hepatitis-related deaths. HBV is not cytopathic. It
should be noted that HBV hijacks host machinery and results in cancerous cells. HBV is most
commonly spread from mother to child at birth, or from person to person in early childhood.
It has a worldwide distribution and currently more than2 billion persons have been infected,
with approximately 360 million chronically infected. The outcomes of HBV infection are age-
dependent and persons with chronic HBV infection have a 15 25% risk of dying prematurely
from HBV. More than 90% of people who get hepatitis B as adults ultimately recover from their
symptoms. According to death certi…cates, approximately 1800 persons die from hepatitis B
annually. In Pakistan, there are estimated 7 9 million carriers of hepatitis B virus (HBV)
with a carrier rate of 3 5%.
After entering into the body, HBV infects the hepatocyte cells in the liver. The immune
system, in response to such infection, conduces to irritation of the liver. Most hepatitis infections
are caused by a virus, infection due to bacteria or active exposure to alcohol and drugs. Usually,
HBV infection has two stages: acute and chronic HBV. The former stage referred to the initial
six months of HBV infection after the exposition. During this phase, mostly the immune
system is enough strong that could clear the Hepatitis B virus from the infected body and
as a result, an individual may recover within a fraction of year. For the rest of individuals

4
with weak immunity, the infection spreads gradually and leads to the more severe phase of
hepatitis B: the chronic stage, i.e., a life long illness. In a clinical setting, CHB is identi…ed
when a person is found HBsAg positive for more than 6 months. Mostly, patients who are
su¤ering from chronic HBV have no prior history of the acute phase, however, it may cause
liver scarring. As a result, an individual may face the liver’s failure or cancer may attack
his/her liver [1]. Horizontal transmission of HBV may spread in several ways like by blood
transmission (through toothbrushes, blades or razors etc), vaginal and semen secretion (unsafe
sexual practices) etc [2, 6]. Another major transmission route is called vertical transmission,
which is from infectious mother to her o¤spring during delivery [4]. HBV infection is perhaps
one of the serious, life-threating and major health problems worldwide [7]. World Health
Organization (WHO) reported that between 350 and400 million individuals are chronically
infected worldwide with hepatitis B. In China alone,93 million people are su¤ering from hepatitis
B virus infection [8, 11]. Vaccines for hepatitis B are available, which are very e¤ective and
provide safeness: almost 95 percent of vaccinated individuals take e¤ective antibodies and are
protected from hepatitis B virus [12, 13]. Hepatitis B is an infectious disease caused by the
hepatitis B virus (HBV) that a¤ects the liver; it is a type of viral hepatitis . It can cause both
acute and chronic infection. Many people have no symptoms during the initial infection. Viral
Hepatitis is a systemic infection a¤ecting the liver predominately with primary in‡ammation
of the liver by any one of a heterogeneous group of a hepatotropic viruses. The term hepatitis
describe in‡ammation of the liver Hepatitis B may be caused by alcohols ,drugs autoimmune
diseases , metabolic diseases , and viruses .Viral infections accounts for more than half the cases
of acute Hepatitis. Further, the author investigated the long-term e¤ectiveness of the control
policy. The di¤erent stages of Hepatitis B with both vertical and horizontal spreading plays
a critical role in the transmission of Hepatitis B infection. Especially the chronic carriers are
very signi…cant they don’t have ant symptoms but transmit the disease.
In this project, we review the study of Din [48]. In chapter 2, we discuss the local and
global stability analysis of the model Hepatitis B virus [48]. We calculate the basic reproduction
number and equilibrium points. In chapter 3, we calculate the numerical solution of the model
of Hepatitis B virus [48] with the help of graphs. All the results of this project are taken from
[48].

5
Chapter 2

Mathematical model of Hepatitis B

virus

In this chapter, we considered a mathematical model for the dynamics of Hepatitis B virus [48]
based on some features of the virus transmission. The host population is denoted by T (t) which
is divided into four compartments namely: susceptible individuals S(t) which denotes individu-
als vulnerable to the infection; infected A(t) which stand for acutely infected individuals; B(t)
represent individuals having chronic HBV and R(t) showing people recovered from infection
and having lifetime immunity.
The assumptions of the model are as follows:
1. All of the parameters and states of the model under discussion are nonnegative.
2. The susceptible people move to the recovered individuals after inducing successful vacci-
nation as the vaccine provide him lifetime protection from HBV infection.
3. The in‡ow of newborns with parental infection goes to chronic carrier compartment B(t).
4. The population of recovered individuals has permanent immunity.

2.1 Representation of Hepatitis B virus model as ODE system

The assumption (1-4) leads to the mathematical model given by the following system of four
ordinary di¤erentials equations [48]:

6
 dS(t)
= (1 B(t)) A(t)S(t) S(t)B(t) (v + d0 )S(t);
dt
dA(t)
= S(t)B(t) (d0 + 1 + )A(t); (2.1)
dt
d
B(t) = A(t) (d0 + d1 + 2 )B(t);
dt
d
R(t) = 1 A(t) + 2 B(t) d0 R(t) + vS(t);
dt

with subsidiary conditions

S(0) = S0 > 0; A(0) = A0 0; B(0) = B0 0; R(0) = R0 > 0: (2.2)

The detail of parameters used in model (2.1) with complete descriptions are given in Table 2.1.

Table 2.1. Description of parameters

Parameters Description
Birth rate
Hepatitis B vaccination rate
Proportion of prenatally infected individuals
Reduced transmission rate
d0 Natural death rate
d1 Hepatitis B induced death rate
contact rate of infected and non infected individual

1 Recovery rate of acute population

2 Recovery rate of chronic population

Rate at which acutely infected individuals go to the chronic phase

2.2 Non-negative orthant

In this section, we show the non-negative orthant of the model (2.1).

Proposition [48].
4
The proposed problem (2.1) is invariant in the non negative orthant R+

7
 Proof.
Let Y = (S; A; C; R)T , then model (2.1) will takes the form

dY (t)
= LY + C; (2.3)
dt

where
0 1
( A(t) + B(t) + d0 + v 0 0
B C
B C
B A(t) + B(t) (d0 + + 1) 0 0 C
L=B
B
C;
C
B 0 (d0 + d1 + 2 ) 0 C
@ A
v 1 2 d0

0 1
B C
B C
B 0 C
B
C=B C:
C
B 0 C
@ A
0

clearly,
C 0 and L is a Metzler matrix since all of its o¤ diagonal elements are non negative.
4:
Hence, system (2.1) is positive invariant in R+

2.3 Positivity of solution

In this section, we show the positivity of the solution of the model Hepatitis B virus (2.1).
Proposition [48].
Any solution (S; A; B; R) of the model (2.1) with conditions (2.2) is positive for all t > 0:
Proof.
As, the right hand side (RHS) of model (2.1) is di¤erentiable,therefore, associating it with
Cauchy problem guarantees the existence of a unique maximal solution. The solution of the
…rst equation of system (2.1) can be expressed alternatively as

dS(t)
= (d0 + v + A(t) + B(t))S(t): (2.4)
dt

8
The solution of eq(2.4) is

Z t
S(t) = S0 exp ((d0 + v) t + ( A(x) + B(x))dx + (2.5)
0
Z t
exp ((d0 + v) t + ( A(x) + B(x))dx
0
Z t Z l
exp (d0 + v)y + ( A(u) + B(u))du dy;
0 0

8t > 0: it is to be noted that the RHS of eq (2.5) is non negative i.e. S(t) > 0 for all t > 0:in
the same way , solution of the second equation of model(2.1)is of the form

Z t
A(t) = A0 exp( (d0 + + 1 )t)+exp( (d0 + + 1 )t) (( A(y)+ B(y) exp( (d0 + + 1 ))ydy:
0

which shows that A(t) is nonnegative. It is handy to show that R(t) > 0 and B(t) 0:Thus, a
solution(S; A; B; R) of (2.1)and (2.2) is nonnegative 8t > 0:

2.4 Boundedness of solution

In this section, we show the boundness of the solution of Hepatitis B virus model (2.1).
Proposition [48].
The solution (S; A; B; R) of the model (2.1) and (2.2) is bounded.
Proof.
As

T (t) = S(t) + A(t) + B(t) + R(t): (2.6)

Di¤erentiating relation (2.6) with respect to t yields

dT
+ d0 T = d1 B: (2.7)
dt

Clearly, dT
dt + d0 T :By integrating both sides of the inequality, we obtain

d0 t
0 < T (t) + (T (0) )e : (2.8)
d0 d0

9
By applying the limit t ! 1;relation (2.8) gives 0 < T (S; A; B; R) d0 :

2.5 Dynamical system

In the section, we show the dynamical system of Hepatitis B virus model (2.1).
Proposition [48].
Let T (t) be given as in (2.6). If T (0) d0 :then the initial value problem (2.1)and (2.2) is
a dynamical system that is well de…ned in the biological feasible region.

4
= (S; A; B; R) 2 R+ :0<T ; (2.9)
d0

i.e. every solution of (2.1) with initial condition (2.2) in fort 0:

Proof.
Since all the states are non negative, therefore, the initial value problem (2.1)and (2.2) is
biologically feasible as well as well posed . Assumption T (0) d0 concludes that T (t) d0

for all t using (2.8). thus each solution of model (2.1) with subsidiary condition (2.2) in (2.9)
remain in (2.9).

2.6 Disease free and endemic equilibrium points

In this section, we present the disease free and endemic equilibrium points of Hepatitis B virus
model (2.1).
Let

r1 = d0 + v; (2.10)

r2 = d 0 + + 1;

r3 = d 0 + d 1 + 2 :

Now …nd the disease free equilibrium points by using model(2.1)

10
 Put the value of r1 in equation (2.1)

dS(t)
= (1 B(t)) A(t)S(t) S(t)B(t) r1 S(t):
dt

dS(t)
put dt =0

0 = (1 B(t)) A(t)S(t) S(t)B(t) r1 S(t);

0 = (1 B(t)) ( A(t) + B(t) + r1 )S(t);

(1 B(t)) = ( A(t) + B(t) + r1 )S(t);

(1 B(t))
S(t) = :
( A(t) + B(t) + r1 )

Put A(t) = 0 and B(t) = 0

S1 = :
r1

Now
d
R(t) = 1 A(t) + 2 B(t) d0 R(t) + vS(t):
dt
d
Put dt R(t) = 0; A(t) = 0; B(t) = 0

0 = d0 R(t) + vS(t);

d0 R(t) = vS(t):

Put S(t) = r1

v
d0 R(t) = ;
r1
v
R(t) = :
r1 d 0

11
The disease free equilibrium (DFE) is denoted by E1 and is given by

E1 = (S1 ; 0; 0; R1 ); (2.11)

S1 = ;
r1
v
R1 = :
d 0 r1

This equilibrium is used to compute the threshold number R0 ;which is actually the basic re-
production number and is de…ned as the expected number of secondary infections produced by
an index case i.e. the average number of secondary infections during its entire infectious period
arising from one individual bring in into a totally susceptible population . This number R0 is
then conveniently used to study the endemic steady state as well.
By using equation (2.10) and (2.13) and denoting E2 the endemic equilibrium points are as
follows:

E2 = (S ; A ; B ; R ); (2.12)
1
S = ( (1 B ) + r2A A );
r1
r1 r2 r32 (R0 1)
A = ;
( r3 + ) + r2 r32 + r2 r3
r1 r2 r3 (R0 1)
B = ;
( r3 + ) + r2 r32 + r2 r3
1
R = ( A + 2 B + S ):
d0 1

2.7 Basic reproductive number

In this section, we …nd the basic reproductive number of Hepatitis B virus model (2.1).
To calculate the number R0 for our model , it is preferred to use van den Driessche and
Watmough method [32].For this , let = (A(t); B(t))T :From (2.1), we can write

d
= V + F;
dt

12
whereV and F are de…ned by
2 3
S(t)A(t) + S(t)B(t)
F = 4 5;
0
2 3
r2 A(t)
V = 4 5:
r3 B(t) A(t)

By considering the jacobian of F and V at Disease Free Equilibrium (2.1) we get

2 3
S1 S1
F = 4 5;
0 0
2 3
r2 0
V = 4 5:
r3

it is to be noted that the threshold parameters R0 dominant eigenvalue of K = F V 1 ;Now we

1, 1 1 adjv
…nd F V …rst we …nd V we know that V = jV j

Now …nd , 2 3
r3 0
adjV = 4 5;
r2

Now …nd det(V )

jV j = r2 r3 ;

Now 2 3
1
0
V 1
=4 r2 5;
1
r2 r3 r3

Now …nd F V 1

2 32 3
1
S1 S1 0
FV 1
= 4 54 r2 5;
1
0 0 r2 r3 r3
2 3
S1 S1 S1
FV 1
= 4 r2 r2 r3 r3 5;
0 0

13
Now we …nd F V 1 I
2 3 2 3
S1 S1 S1
0
FV 1
I = 4 r2 r2 r3 r3 5 4 5;
0 0 0
2 3
S1 S1 S1
FV 1
I = 4 r2 r2 r3 r3 5;
0

R0 = R01 + R02 ; where (2.13)

R01 = ;
r1 r2
R02 = :
r1 r2 r3:

2.8 Local stability analysis

In this section, we discuss local stability of disease free equilibrium of Hepatitis B virus model
(2.1).
Theorem 2.1[48]
If we assume that R0 < 1; then model (2.1) is locally stable at the disease free equilibrium
E1 :
Proof.

dS(t)
= (1 B(t)) A(t)S(t) S(t)B(t) (v + d0 )S(t);
dt
dA(t)
= S(t)B(t) (d0 + 1 + )A(t); (2.14)
dt
d
B(t) = A(t) (d0 + d1 + 2 )B(t);
dt
d
R(t) = 1 A(t) + 2 B(t) d0 R(t) + vS(t);
dt

The disease free equilibrium is denoted by E1 and is given by

E1 = (S1 ; 0; 0; R1 );

14
Now we …nd jacobi matrix by taking partial derivatives of the model w.r.t (S; A; B; R)
Taking partial derivative w.r.t S(t) ofE1 (2:11)

S(t) = A B (v + d0 );

S = A B r1 :

According to disease free equilibrium

A(t) = B :

and
B(t) = 0:

and
R(t) = v:

Taking partial derivative w.r.t A(t) of E1 (2:11)

S(t) = 0;

A(t) = 0;

B(t) = 0;

R(t) = 0:

Taking partial derivative w.r.t B (t) of E1 (2:11)

S(t) = 0;

A(t) = 0;

B(t) = 0;

R(t) = 0:

15
Taking partial derivative w.r.t R(t) of E1 (2:11)

S(t) = 0;

A(t) = 0;

B(t) = 0;

R(t) = d0 :

So, jacobi matrix is given as

2 3
A B r1 0 0 0
6 7
6 7
6 B 0 0 0 7
J =6
6
7;
7
6 0 0 0 0 7
4 5
v 0 0 d0

Now, …nd eigen values 2 3

0 0 0
6 7
6 7
6 0 0 0 7
I=6
6
7;
7
6 0 0 0 7
4 5
0 0 0

Now, subtract J I
2 3
A B r1 0 0 0
6 7
6 7
6 B 0 0 7
J I=6
6
7 = 0;
7
6 0 0 0 7
4 5
v 0 0 d0

16
Now we …nd the determinant of jJ Ij. By expending row 1

0 0
jJ Ij = ( A B r1 ) 0 0 = 0;
0 0 d0

0
jJ Ij = ( A B r1 )( ) = 0;
0 d0
jJ Ij = ( A B r1 )( )[( )( d0 )] = 0;

( A B r1 ) = 0;

= A B r1 :

Clearly,
The existence of relation (2.12) depends on the basic reproduction number. Thus, we
describe the following theorem 2.2.
Theorem 2.2.[48]
If we assume that R0 > 1 then the endemic equilibrium (2.12) exist for the model (2.1).
Now to calculate the local dynamics of the proposed model around endemic equilibrium
(2.12), we will state and prove the following result.
Theorem 2.3.[48]
If R0 > 1;then the system (2.1) is locally stable at the endemic equilibrium E2 (2.12).
Otherwise, (2.1) is unstable.
Proof

0 1
r1 A B S S 0
B C
B C
B A + B S r2 S 0 C
J =B
B
C;
C
B 0 r3 0 C
@ A
v 1 2 d0

one eigenvalue of the above matrix J is 1 = 0: To …nd the nature of the remaining eigenvalue

17
, we take the following matrix
0 1
r1 A B S S
B C
B C
J =B A + B S r2 S C;
@ A
0 r3

Using the simple row elementary operation , we express the above matrix takes the following
form.
Where K1 = r1 + A + B and K2 = A + B the eigenvalue of (2.18) are

2 = K1 ; 3 = K1 ( S r2 ) S K2 ; 4 = r3 (K1 ( S r2 )+ S K2 K1 S ( + S )K2 ):
(2.15)
clearly 2; 3 ;and 4 are negative, if the S > r2
and K1 ( S r2 )+ S K2 > K1 S +K2 ( + S ); holds, which proves the conclusion.

2.9 Global stability analysis

Theorem 2.4 [48]

Assume that R0 < 1; then model (2.1) is globally stable at the disease free equilibrium
E1 (2:11):Otherwise model (2.1) is unstable.
Proof.
To show the global behavior of model (2.1) at E1 = (S1 ; 0; 0; R1 ); we have to develop a
suitable Lyapunov function given by

F (t) = c1 (S S1 ) + c2 A(t) + c3 B(t);

hereci > 0; i = 1; 2; 3 to be determine later. By di¤erentiating the function F (t) with respect
to time and using (2.1), we get

dF
= c1 ( (1 B(t)) A(t)S(t) S(t)B(t) r1 S(t)) (2.16)
dt
+c2 ( S(t)A(t) + S(t)B(t) r2 A(t)) + c3 ( A(t) r3 B(t)): (2.17)

18
let us assume that c1 = c2 = r2 ; c3 = r3 and S1 = r1 in eq(2.16) then

dF
= r1 ((r1 S1 S(t)A(t) S(t)B(t) r1 S(t))) + r1 ((r1 S(t)A(t)
dt
+ S(t)B(t) r2 A(t))) + ( A(t) r3 B(t)):
r3

upon simpli…cation and arrangements of term in the above equation, we will obtain

dF
= r12 [S S1 ] (r1 r2 (1 R02 ))A(t) (r1 + )B(t):
dt
2 3
K1 S S
6 7
6 7
J =6 0 K1 ( S r2 ) S K2 K1 S ( + S )K2 7;
4 5
0 0 r3 (K1 ( S r2 ) + S K 2 K1 S S K2
(2.18)
dF dF
Thus when R0 < 1 we have0 < R01 < 1 and0 < R02 < 1, then dt < 0. Also dt = 0 i¤
S(t) = S1 ; A(t) = 0 and B(t) = 0:Hence by the invariance principle due to [33, 34] one can say
that (2.11) is stable.
Theorem 2.5 [48]
Assumption of R0 > 1 guarantees that endemic equilibrium E2 = (S ; A ; B ; R ) of the
model (2.1) is globally asymptotically stable and unstable otherwise.
Proof.
As R(t) = T (t) S(t) A(t) B(t) with T (t)being the solution of (2.7),therefore ,we will
neglect the class R(t)which will reduced the system under consideration to …rst three equations
j2j
describing the dynamics of S(t); A(t) and B(t)only. Thus,letJ2 and J2 be the jacobian matrix
and second additive compound matrix of the system containing only the the …rst three equations
of model (2.1)then 0 1
w11 w12 w13
B C
B C
J2 = B w21 w22 w23 C;
@ A
w31 w32 w33

19
 0 1
(w11 + w22 ) w23 w13
B C
j2j B C
J2 = B w32 (w11 + w33 ) w12 C;
@ A
w31 w21 (w22 + w33)

where
a11 = r1 A(t) B(t); a12 = S ; a13 = + S ; a21 = A + B ;
a22 = S r2 ; a23 = S ; a31 = 0; a32 = ; a33 = r3 :
Next we will take into account the function
S S S 1 (x) A A A
P (x) = diag A; A; A ; thenP = diag S; S; S :
By considering the derivatives Pf (x); we have

S SA S SA S SA
Pf (x) = diag ; ; ;
S A2 S A2 S A2

Thus,
1 S A S A S A
Pf P = diag ; ; ;
S A S A S A
j2j 1 j2j
and P J2 P = J2 taking

1 j2j 1
B = Pf P + P J2 P ;

For the sake of simplicity , we may write B in the form of

0 1
B11 B12
B=@ A;
B21 B22

where

S A
B11 = r1 r2 A(t) B(t) S(t);
S A
B12 = ( S + S);
0 1

B21 = @ A;
0
0 1
S A
r1 r2 A(t) B(t) S(t)
B22 = @ S A A:
S A
A(t) + B(t) S A r2 r3 + S(t)

20
Let us assume that(b1 ; b2 ; b3 ) be a vector inR3 with the normjj:jjde…ned by

jjb1 ; b2 ; b3 jj = maxfjjb1 jj; jjb2 jj; jjb3 jjg;

considering the Lozinski measure `(B)[35; 36] with endowed norm de…ned above

`(B) supfg1 ; g2 g = supf`(B11 ) + jjB12 jj; `(B22 ) + jjB21 jjg;

where gi = jjBij jj + `(Bii )for i; j = 1; 2and i 6= j; which implies that g1 = jjB12 jj + `(B11 ); g2 =
jjB21 jj + `(B22 );
where

AS
`(B11 ) = r1 r2 A(t) B(t) S(t);
AS
S A S A S A
`(B22 ) = maxf r1 r2 ; r1 r2 g = r3 d0 minfv; 1 + g:
S A S A S A

where

jjB12 jj = + S;

and
jjB21 jj = maxf ; 0g = ;

therefore, g1 and g2 becomes

S A
g1 = r1 r2 A B (1 )S + ;
S A
S A
g2 = r3 d0 minfv; 1 + g:
S A

As a result we get

A S
`(B) supfg1 ; g2 g; = 2d0 minfv + + 1 + A+ B + (1 )S; d1
A S
+ 2 + minfv; 1 + g g:

21
 S
Thus `(B) S 2d0 . Integrate the Lozinski measure `(B) with respect to t over the interval
[0; t] and applying thelimt!1 we have

Z 1
1
lim sup `(B)dt 2d0 < 0:
t!1 t 0

we conclude that
Z 1
1
q = lim sup `(B)dt < 0:
t!1 t 0

Hence the subsystem (reduced model )of model (2.1) is globally stable around its interior
equilibrium . thus system (2.1)is globally stable around its interior equilibrium.

2.10 Summary

In this chapter, we have considered a Hepatitis B epidemic model [48]. We have presented the
positivity of solution of the model. We have presented the disease free and endemic equilibrium
points. We have calculated the threshold number R0 and presented the local and global stability
analysis of the model Hepatitis B virus.

22
Chapter 3

Numerical solution of the Hepatitis

B model

In this chapter, we use Runga Kutta method of order 4 to solve the Hepatitis B virus model
(2.1).

3.1 Runge-Kutta method of order 4 for initial value problem

In this section, we discuss the formula of RK4 method for initial value problem.
Considered a …rst order di¤erential equations

d(x)t
= f (x(t); x(t0 ) = x0 : (3.1)
dt

Thus, the approximation of the equation (3.1) with Runge-Kutta method of order 4 is given by
the following formula

1
xm+1 = xm + (k1 + 2k2 + 2k3 + k4 ); m = 0; 1; 2; :::n 1; (3.2)
6

where
tm+1 = tm + h;

k1 = hf (tm ; xm );

23
 h k1
k2 = hf (tm + ; xm + );
2 2
h k2
k3 = hf (tm + ; xm + );
2 2

k4 = hf (tm + h; xm + k3 ):

3.2 RK4 method for Hepatitis B model

In this section, we present the formula of RK4 method for Hepatitis B model (2.1).
Let us considered a system of di¤erential equations given in model (2.1),

dS(t)
= (1 B(t)) A(t)S(t) S(t)B(t) (v + d0 )S(t);
dt
dA(t)
= S(t)B(t) (d0 + 1 + )A(t);
dt
dB(t)
= A(t) (d0 + d1 + 2 )B(t);
dt
dR(t)
= 1 A(t) + 2 B(t) d0 R(t) + vS(t);
dt

The above approximation of the system with RK4 method is given by the following formula.
8
>
> Sm+1 = Sm + 61 (k11 + 2k21 + 2k31 + k41 );
>
>
>
>
< Am+1 = Am + 16 (k12 + 2k22 + 2k32 + k42 );
>
> Bm+1 = Bm + 16 (k13 + 2k23 + 2k33 + k43 );
>
>
>
>
: R = Rm + 16 (k14 + 2k24 + 2k34 + k44 );
m+1

for, m = 0; 1; 2; :::n 1; where,

8
>
> k11 = h ( (1 Bm ) A m Sm Sm Bm (v + d0 )Sm ) ;
>
>
>
>
< k12 = h ( Sm Bm (d0 + 1 + )Am ) ;
>
> k13 = h( Am (d0 + d1 + 2 )Bm );
>
>
>
>
: k14 = h( 1 Am + 2 Bm d0 Rm + vSm );

24
 8
>
> k21 = h( (1 (Bm + K13 K12 K11
>
> 2 ) (Am + 2 )(Sm + 2 )
>
>
>
> (Sm + K11 K13 K11
>
< 2 )(Bm + 2 ) (v + d0 )(Sm + 2 ));
K11 K13 K12
k22 = h( (Sm + 2 )(Bm + 2 ) (d0 + 1 + )(Am + 2 ));
>
>
>
> K12 K13
>
> k23 = h( (Am + 2 ) (d0 + d1 + )(Bm + 2 ));
>
>
2
>
: K12 K13 K14 K11
k24 = h( 1 (Am + 2 ) + 2 (Bm + 2 ) d0 (Rm + 2 ) + v(Sm + 2 ));

8
>
> k31 = h( (1 (Bm + K23 K22 K21
>
> 2 ) (Am + 2 )(Sm + 2 )
>
>
>
> (Sm + K21 K23 K21
>
< 2 )(Bm + 2 ) (v + d0 )(Sm + 2 ));
K21 K23 K22
k32 = h( (Sm + 2 )(Bm + 2 ) (d0 + 1 + )(Am + 2 ));
>
>
>
> K22 K23
>
> k33 = h( (Am + 2 ) (d0 + d1 + )(Bm + 2 ));
>
>
2
>
: K22 K23 K24 K21
k34 = h( 1 (Am + 2 ) + 2 (Bm + 2 ) d0 (Rm + 2 ) + v(Sm + 2 ));

8
>
> k41 = h( (1 (Bm + K33 ) (Am + K32 )(Sm + K31 )
>
>
>
>
>
> (Sm + K31 )(Bm + K33 ) (v + d0 )(Sm + K31 ));
>
<
k42 = h( (Sm + K31 )(Bm + K33 ) (d0 + 1 + )(Am + K32 ));
>
>
>
>
>
> k43 = h( (Am + K32 ) (d0 + d1 + )(Bm + K33 ));
>
>
2
>
: k44 = h( 1 (Am + K32 ) + 2 (Bm + K33 ) d0 (Rm + K34 ) + v(Sm + K31 ));

3.3 Graphical representation of solution of Hepatitis B model

and discussion

In this section, we calculate the numerical solution of Hepatitis B model (2.1) and discussion
using RK4 method.
The following parameter values are used.

= 0:4; = 0:11; = 0:005; = 0:16; = 0:01; d0 = 0:03; (3.3)

d1 = 0:002; 1 = 0:05; 2 = 0:06; v = 0:02: (3.4)

Graph solution between Susceptible Human and time(days), this graph shows that when
time is 0 the value of Susceptible Human is approaches to 100. In the beginning the value

25
of Susceptible Human is maximum. With the Passage of time(days) susceptible human is
decreasing. After 30 days the value of susceptible human between 0 and 1.

100

90

80

70

Susceptible Human S(t)

60

50

40

30

20

10

0
0 50 100 150 200
Time(days)

Figure 3.1. Graph of Susceptible Humans for 200 days

Graph solution between Acute infected Human and time(days), this graph shows that when
time is 0 the value of Acute Human is approaches to 20 and when time is 5 the value of acute
humans approaches to 25. With the Passage time(days) Acute infected human is decreasing.
After 80 days the value of susceptible human remains same.

30

25

20
Acute Infected Human

15

10

0
0 50 100 150 200
Tim e(day s)

Figure 3.2. Graph of Acute infected Human for 200 days

Graph solution between Chronically infected Human and time(days), shows when time is
0 the value of Chronically infected Human is approaches to 10. In the beginning the value of

26
Susceptible Human is maximum. With the Passage time(days) susceptible human is decreasing.
After 150 days the value of Chronically infected human remain same.

10

Chronically Infected Human 6

0
0 50 100 150 200
Time(day s)

Figure 3.3. Graph of Chronically Infected for 200 days

Graph solution between Recovered Human and time(days),this graph shows that when time
is 0 the value of Recovered Human is approaches to 10. In the beginning the value of Recovered
is minimum. With the Passage time(days) Recovered is increasing. After 50 days the value of
Recovered human is decreasing. After 80 days the value of Recovered human is remain same.

35

30

25
Recovered Human

20

15

10

5
0 50 100 150 200
Time(day s)

Figure 3.4. Graph of Recovered Human for 200 days

27
3.4 Summary

In this chapter, we have used Runge-Kutta method of order 4 and presented the numerical
solutions of the Hepatitis B virus model (2.1). We have ploted the graphs to show the solution
of Hepatitis B model. The discussion on the numerical solution was also provided.

28
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