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Z. Rahmah, B. Subartini, E. Djauhari, N. Anggriani, and A. K. Supriatna

View online: http://dx.doi.org/10.1063/1.4978989

View Table of Contents: http://aip.scitation.org/toc/apc/1825/1

Published by the American Institute of Physics

An Application of Forward-Backward Difference

Approximation Method on the Optimal Control Problem in

the Transmission of Tuberculosis Model

Z. Rahmaha), B. Subartini, E. Djauhari, N. Anggriani, and A.K Supriatna

Jl. Raya Bandung-Sumedang km 21, Jatinangor 45363 Indonesia

a)

zainarahmah@gmail.com

Abstract.Tuberculosis (TB) is a disease that is infected by the bacteria Mycobacterium tuberculosis. The World Health

Organization (WHO) recommends to implement the Baccilus Calmete Guerin (BCG) vaccine in toddler aged two to

three months to be protected from the infection. This research explores the numerical simulation of forward-backward

difference approximation method on the model of TB transmission considering this vaccination program. The model

considers five compartments of sub-populations, i.e. susceptible, vaccinated, exposed, infected, and recovered human

sub-populations. We consider here the vaccination as a control variable. The results of the simulation showed that

vaccination can indeed reduce the number of infected human population.

INTRODUCTION

Tuberculosis has spread both into the human and animal populations. In the record of the World Health

Organization (WHO), about a third of the world's population has been exposed to infection by Mtb (MOH, 2011).

Indonesia is among the five countries with the highest TB burden in the world. The number of TB deaths estimated

61,000 deaths annually (Setiawan, 2012). Direct transmission of active patients to uninfected individuals initially

only leads to the spread of Mtb bacteria to the targeted individuals and it is not directly followed by the symptoms of

the disease. The infected individuals are becoming latent and in fact most of people infected with TB are in the

latent phase, which means not show TB symptoms. The TB disease prevention recommended by the WHO is the

Baccilus Calmete Guerin (BCG) vaccine given to infants aged two to three months. The results of the BCG vaccine

to the population are it can protect to approximately 70% -80% of TB infections (Crofton, 2007). The previous

research of Nainggolan et al. (2012) discusses the TB disease spread model by considering the compartment of the

population that having vaccination. The optimal control discussed in their work was shown to be able to decrease the

number of infected individuals while minimizing the cost of the disease and the treatment. Their model is solved

numerically by forward-backward sweep method using C # program. The results of the numerical solution shows

that the decline in the number of individuals latent and growing number of people cured from TB. In this research

we discuss the same model with the same optimal control problem, but it solved numerically using forward

backward difference approximation method which is implemented in MATLAB program. This numerical method

shows a faster convergence of the infected population. The initial value of parameters used in this paper is obtained

from Nainggolan et al. (2013) and Hattaf (2009).

Here we rewrite the mathematical model of nainggolan et al. (2012) with the following symbols and notations:

S = Susceptible compartment (population of individuals who are susceptible to TB)

V = Vacination compartment (population of individuals who were given the vaccine)

AIP Conf. Proc. 1825, 020020-1–020020-7; doi: 10.1063/1.4978989

Published by AIP Publishing. 978-0-7354-1493-8/$30.00

020020-1

E = Exposed compartment (populations of individuals infected but not yet infectious)

I = Infected compartment (populations of individuals infected and can transmit the disease)

R = Recovered compartment (population of individuals who recovered and can be reinfected by the disease)

ᖴ= Recruitment rate (the number of susceptible individuals born)

ߠ = Rate of vaccination of S

ߤ= Natural mortality rate

c = Contact between S and I

ߪ= Effectiveness of vaccination

d = Number of deaths from the I

ߚ= Chances of contracting

p = Natural healing rate of I

k = Natural active development rate of TB

ߜଵ = The rate of transition of individuals from E(who are in contact with I) to I

ߜଶ = Passive infected individual opportunities of R

f = The rate of transition of individuals from S to E

݂ଵ = The rate of transition of individuals from R to E

The population of individuals is divided into five compartments:

x The population of people who prone to illnessܵሺݐሻ

x The population of people who infected with but still passive (non-infectious)ܧሺݐሻ

x Populations of individuals infected and can transmit the diseaseܫሺݐሻ

x The population of individuals who recovered and can be reinfected by the diseaseܴሺݐሻ

x The population of individuals who were given the vaccineܸሺݐሻ

The model also assumed the following:

x There is a constant birthrate or recruitment rate to enter the S compartment

x There isa proportionate rate of vaccination giving to the S compartment

x There is a recovery rate from E to R and from I to R compartments

x Taking into consideration the rate of re-infected from R toE and from R to I

x There is a proportionate deathrate caused by the disease

x The state variableS,V,E,I,R Ͳand are bounded

x All the parameterᖴǡ ߠǡ ߪǡ ݂ǡ ݂ଵ ǡ ߚǡ ܿǡ ߜଵ ǡ ߜଶ ǡ ݇ǡ ݀ǡ ݎǡ ݎଵ ǡ ߤ Ͳ

From the above assumptions, a schematic diagram of dissemination of TB can be expressed as follows:

020020-2

Based on the schematic diagram and the assumptions, the mathematical model is given by

݀ܵ

ൌ ᖴ െ ߣܵ െ ሺߤ ߠሻܵ

݀ݐ

ܸ݀

ൌ ߠܵ െ ሺͳ െ ߪሻߣܸ െ ሺߤ ݎሻܸ

݀ݐ

݀ܧ

ൌ ݂ߣܵ ሺͳ െ ߪሻߣܸ െ ߜଵ ߣ ܧെ ሺߤ ݇ሻ ܧ ݂ଵ ߜଶ ߣܴ

݀ݐ

݀ܫ

ൌ ሺͳ െ ݂ሻߣܵ ߜଵ ߣ ܧ ݇ ܧെ ሺߤ ݀ ሻ ܫ ሺͳ െ ݂ଵ ሻߣߜଶ ܴ

݀ݐ

ܴ݀

ൌ ܸݎ ܫെ ߤܴ െ ߣߜଶ ܴ

݀ݐ

(1)

ఉூ

where ߣ ൌ .

ே

As in Nainggolan et al. (2013), to minimize the infected population, we formulate an optimal control problem.

Here we seek an optimal effort to decrease the amount of infected people and maintaining treatment costs as low as

possible. As suggested by Nainggolan et al (2013), the mathematical model becomes

݀ܵ

ൌ ᖴ െ ߣܵ െ ሺߤ ߠሻܵ

݀ݐ

ܸ݀

ൌ ߠܵ െ ሺͳ െ ߪሻߣܸ െ ሺߤ ݎሻܸ

݀ݐ

݀ܧ

ൌ ݂ߣܵ ሺͳ െ ߪሻߣܸ െ ߜଵ ߣ ܧെ ሺߤ ݇ሻ ܧ ݂ଵ ߜଶ ߣܴ

݀ݐ

݀ܫ

ൌ ሺͳ െ ݂ሻߣܵ ߜଵ ߣ ܧ ݇ ܧെ ሺߤ ݎଵ ሺͳ ݑሻ ݀ ሻ ܫ ሺͳ െ ݂ଵ ሻߣߜଶ ܴ

݀ݐ

ܴ݀

ൌ ܸݎ ሺݎଵ ሺͳ ݑሻ ሻ ܫെ ߤܴ െ ߣߜଶ ܴ

݀ݐ

(2)

The variable u(t) is the control variable of the treatment. In the case of u=1 means the treatment amounted for

vaccination effort is twice of the default administration, while if u=0 means the default treatment (ݎଵ ) alone is

sufficient to control the TB. Furthermore, the objective function is formulated as the weighted-combined numbers of

the individual of active TB and treatment costs. Therefore, the purpose is to minimizing the population of active TB

and costs incurred by the implementation of the treatment.The costs incurred to implement the control (u(t))is a

quadratic functions. Based on the above assumption, ݑܥଶ ሺݐሻis the cost function with C is a weighted coefficient of

the cost function. If B is the weighted coefficient of the number of individuals in the infected compartment, then

the objective function is given by

்

ܬሺݑሻ ൌ න ሾܫܤሺݐሻ ݑܥଶ ሺݐሻሿ݀ݐ

(3)

The mathematical problem is now minimizing (3) with the respect to the dynamics in (2). It could be done by

using optimal control theory which the control variable is uand the state variables is

ݔሶ ሺݐሻ ൌ ሺܵሶሺݐሻǡ ܸሶ ሺݐሻǡ ܧሶ ሺݐሻǡ ܫሶሺݐሻǡ ܴሶሺݐሻith boundary conditions :

Ͳ ݑሺݐሻ ͳǡ א ݐሾͲǡ ܶሿǡ ܵ ሺͲሻ ൌ ܵ Ͳǡ ܸ ሺͲሻ ൌ ܸ Ͳǡ ܧሺͲሻ ൌ ܧ Ͳǡ ܫሺͲሻ ൌ ܫ Ͳǡ ܴ ሺͲሻ ൌ ܴ Ͳ

The things that need to do is to define the Hamiltonian function

݀ܵ ሺݐሻ ܸ݀ ሺݐሻ ݀ ܧሺݐሻ ݀ ܫሺݐሻ ܴ݀ ሺݐሻ

ܪൌ ܫܤሺݐሻ ݑܥଶ ሺݐሻ ߣଵ ߣଶ ߣଷ ߣସ ߣହ

݀ݐ ݀ݐ ݀ݐ ݀ݐ ݀ݐ

020020-3

where ߣଵ ǡ ߣଶ ǡ ߣଷ ǡ ߣସ ǡ ߣହ are the co-state variables or the Lagrangian multiplier. Based on the Pontryagin

Maximum Principle, there should be a sate equations and co-state equations systems satisfying:

State equation

݀ܪ

ܵሶ ൌ ൌ ᖴ െ ߣܵ െ ሺߤ ߠሻܵ

݀ߣଵ

݀ܪ

ܸሶ ൌ ൌ ߠܵ െ ሺͳ െ ߪሻߣܸ െ ሺߤ ݎሻܸ

݀ߣଶ

݀ܪ

ܧሶ ൌ ൌ ݂ߣܵ ሺͳ െ ߪሻߣܸ െ ߜଵ ߣ ܧെ ሺߤ ݇ሻ ܧ ݂ଵ ߜଶ ߣܴ

݀ߣଷ

݀ܪ

ܫሶ ൌ ൌ ሺͳ െ ݂ሻߣܵ ߜଵ ߣ ܧ ݇ ܧെ ሺߤ ݎଵ ሺͳ ݑሻ ݀ ሻ ܫ ሺͳ െ ݂ଵ ሻߜଶ ܴ

݀ߣସ

݀ܪ

ܴሶ ൌ ൌ ܸݎ ሺݎଵ ሺͳ ݑሻ ሻ ܫെ ߤܴ െ ߣߜଶ ܴ

݀ߣହ

ܵ ሺͲሻ ൌ ܵ Ͳǡ ܸ ሺͲሻ ൌ ܸ Ͳǡ ܧሺͲሻ ൌ ܧ Ͳǡ ܫሺͲሻ ൌ ܫ Ͳǡ ܴ ሺͲሻ ൌ ܴ Ͳ

Co-state equation

݀ܪ ߚܿܫ

ߣଵ ൌ െ ൌ ሺߣ െ ݂ߣଷ െ ሺͳ െ ݂ሻߣସ ሻ ሺߣଵ െ ߣଶ ሻߠ ߣଵ ߤ

݀ܵሺݐሻ ܰ ଵ

݀ܪ ߚܿܫ

ߣଶ ൌ െ ൌ ሺͳ െ ߪ ሻ ሺ ߣ െ ߣଷ ሻ ሺ ߣ ଶ െ ߣହ ሻ ݎ ߣଶ ߤ

ܸ݀ ሺݐሻ ܰ ଶ

݀ܪ ߜଵ ߚܿܫ

ߣଷ ൌ െ ൌ൬ ݇൰ ሺߣଷ െ ߣସ ሻ ߣଷ ߤ

݀ ܧሺݐሻ ܰ

݀ܪ

ߣସ ൌ െ

݀ܫሺݐሻ

ߚܿܵ ߚܸܿ ߜ ߚܿܧ

ൌ െ ܤ ሺߣଵ െ ݂ߣଷ െ ሺͳ െ ݂ሻߣସ ሻ ሺͳ െ ߪሻ ሺ ߣଶ െ ߣ ଷ ሻ ଵ ሺ ߣଷ െ ߣ ସ ሻ

ܰ ܰ ܰ

ߜଶ ߚܴܿ

ሺߣହ െ ݂ଵ ߣଷ െ ሺͳ െ ݂ଵ ሻߣସ ሻ ൫ ݎଵ ሺͳ ݑሻ൯ሺߣସ െ ߣହ ሻ ߣସ ሺߤ ݀ሻ

ܰ

݀ܪ ߜଶ ߚܿܫ

ߣହ ൌ െ ൌ ሺߣହ െ ݂ଵ ߣଷ െ ሺͳ െ ݂ଵ ሻߣସ ሻ ߣହ ߤ

ሺ

ܴ݀ ݐ ሻ ܰ

Stationary equation

݀ܪ

ൌͲ

݀ݑሺݐሻ

భ ூሺఒర ିఒఱ ሻ

Which results in ݑൌ , and since Ͳ ݑ ͳ, it is equivalent to

ଶ

భ ூሺఒర ିఒఱ ሻ

ݑሺݐሻ ൌ ݉݅݊ ቄͳǡ ቂ ቃ ǡ Ͳቅ as the optimal solution to the control problem. To ensure the

ଶ

ௗమ ு

minimum condition, the second derivative of u must satisfies ൌ ʹ ܥ Ͳ.

ௗ௨మ

A nnumerical scheme used is the forward backward difference approximation method. Stages of the numerical

algorithm refer to the work of Elhia (2012). By the discretizeation of the intervalൣݐ ǡ ݐ ൧ with ݐ ൌ ݐ ݄݅ǡ ሺ݅ ൌ

Ͳǡͳǡ ǥ ǡ ݊ሻwhere h is the step size up to ݐ ൌ ݐ , we have the following version of the state and co-state equations:

ܵାଵ െ ܵ ߚܿܫ

ൌ ᖴ െ ܵ െ ሺߤ ߠሻܵାଵ

݄ ܰ ାଵ

020020-4

ܸାଵ െ ܸ ߚܿܫ

ൌ ߠܵାଵ െ ሺͳ െ ߪሻ ܸ െ ሺߤ ݎሻܸାଵ

݄ ܰ ାଵ

ܧାଵ െ ܧ ߚܿܫ ߚܿܫ ߚܿܫ ߚܿܫ

ൌ݂ ܵ ሺͳ െ ߪሻ ܸ െ ߜଵ ܧെ ሺߤ ݇ሻܧାଵ ݂ଵ ߜଶ ܴ

݄ ܰ ାଵ ܰ ାଵ ܰ ାଵ ܰ

ܫାଵ െ ܫ ߚܿܫାଵ ߚܿܫାଵ ߚܿܫାଵ

ൌ ሺͳ െ ݂ሻ ܵାଵ ߜଵ ܧାଵ ݇ܧାଵ െ ሺߤ ݎଵ ሺͳ ݑ ሻ ݀ሻܫାଵ ሺͳ െ ݂ଵ ሻ ߜଶ ܴ

݄ ܰ ܰ ܰ

ܴାଵ െ ܴ ߚܿܫାଵ

ൌ ܸݎାଵ ሺݎଵ ሺͳ ݑ ሻ ሻܫାଵ െ ߤܴାଵ െ ߜଶ ܴାଵ

݄ ܰ

ି ିିଵ

ߣଵ െ ߣଵ ߚܿܫାଵ

ൌ ൫ߣଵ ିିଵ െ ݂ߣଷ ି െ ሺͳ െ ݂ሻߣସ ି ൯ ൫ߣଵ ିିଵ െ ߣଶ ି ൯ߠ ߣଵ ିିଵ ߤ

݄ ܰ

ߣଶ ି െ ߣଶ ିିଵ ߚܿܫାଵ

ൌ ሺͳ െ ߪሻ ൫ߣଶ ିିଵ െ ߣଷ ି ൯ ൫ߣଶ ିିଵ െ ߣହ ି ൯ ݎ ߣଶ ߤ

݄ ܰ

ߣଷ ି െ ߣଷ ିିଵ ߜଵ ߚܿܫାଵ

ൌ ൬ ݇൰ ൫ߣଷ ିିଵ െ ߣସ ି ൯ ߣଷ ିିଵ ߤ

݄ ܰ

ߣସ ି െ ߣସ ିିଵ ߚܿܵାଵ ߚܸܿାଵ

ൌ െ ܤ ൫ߣଵ ିିଵ െ ݂ߣଷ ିିଵ െ ሺͳ െ ݂ሻߣସ ିିଵ ൯ ሺͳ െ ߪሻ ൫ߣଶ ିିଵ െ ߣଷ ିିଵ ൯

݄ ܰ ܰ

ߜଵ ߚܿܧାଵ ߜଶ ߚܴܿାଵ

൫ߣଷ ିିଵ െ ߣସ ିିଵ ൯ ൫ߣହ ି െ ݂ଵ ߣଷ ିିଵ െ ሺͳ െ ݂ଵ ሻߣସ ିିଵ ൯

ܰ ܰ

൫ ݎଵ ሺͳ ݑ ሻ൯൫ߣସ ିିଵ െ ߣହ ି ൯ ߣସ ିିଵ ሺߤ ݀ሻ

ൌ ൫ߣହ ିିଵ െ ݂ଵ ߣଷ ିିଵ െ ሺͳ െ ݂ଵ ሻߣସ ିିଵ ൯ ߣହ ିିଵ ߤ

݄ ܰ

Step 1

Inserting initial value

ܵ ሺͲሻ ൌ ܵ ǡ ܸ ሺͲሻ ൌ ܸ ǡ ܧሺͲሻ ൌ ܧ ǡ ܫሺͲሻ ൌ ܫ ǡ ܴሺͲሻ ൌ ܴ ǡ ߣ ൫ݐ ൯ ൌ Ͳሺ݅ ൌ ͳǡ ǥ ǡ ͷሻǡ ݑሺͲሻ ൌ ͲǤ

Step 2

To݅ ൌ Ͳǡ ǥ ǡ ݊ െ ͳǡcalculate :

Ȧ݄ ܵ

ܵାଵ ൌ ఉூ

ͳ ݄ሺ ߤ ߠሻ

ே

Ʌ݄ܵାଵ ܸ

ܸାଵ ൌ ఉூ

ͳ ݄ሺሺͳ െ ߪሻ ߤ ݎሻ

ே

ఉூ ఉூ ఉூ

݂ ݄ܵାଵ ሺͳ െ ߪሻ݄ ܸ ݂ଵ ߜଶ ݄ ܴ ܧ

ே ே ାଵ ே

ܧାଵ ൌ ఉூ

ͳ ݄ሺ ߜଵ ߤ ݇ሻ

ே

݄݇ܧାଵ ܫ

ܫାଵ ൌ ఉ ఉ ఉ

ͳ ݄ ቀߤ ݎଵ ሺͳ ݑ ሻ ݀ െ ሺͳ െ ݂ሻ ܵାଵ െ ߜଵ ܧାଵ ቁ െ ሺͳ െ ݂ଵ ሻ ߜ ܴ

ே ே ே ଶ

ܸ݄ݎାଵ ݄ሺݎଵ ሺͳ ݑ ሻ ሻܫାଵ ܴ

ܴାଵ ൌ ఉூ

ͳ ݄ሺߤ శభ ߜଶ ሻ

ே

ఉூశభ

ିିଵ

ߣଵ ି ݄൫ሺߣଷ ି ݂ ሺͳ െ ݂ሻߣସ ି ൯ ߣଶ ି ߠሻ

ே

ߣଵ ൌ ఉூశభ

ߠ ߤሻ

ͳ ݄ሺ

ே

ି ఉூశభ ି

ߣଶ ݄ ൬ሺͳ െ ߪሻ ߣଷ ߣହ ି ݎ൰

ିିଵ ே

ߣଶ ൌ ఉூ

ͳ ݄ሺሺͳ െ ߪሻ శభ ݎ ߤሻ

ே

ఉூ

ߣଷ ି ݄ ቀ శభ ߜଵ ߣସ ି ݇ቁ

ߣଷ ିିଵ ൌ ఉூ

ே

ͳ ݄ ቀ శభ ߜଵ ݇ ߤቁ

ே

020020-5

ఉௌశభ ఉశభ

ି

ܤ ൫݂ߣଷ ିିଵ െ ߣଵ ିିଵ ൯ ሺͳ െ ߪሻ ൫ߣଷ ିିଵ െ ߣଶ ିିଵ ൯

ே ே

ߣସ ݄ ቌ ఋ ఉா ఋ ఉோ

ቍ

െ భ శభ ߣଷ ିିଵ మ శభ ൫݂ଵ ߣଷ ିିଵ െ ߣହ ି ൯ ൫ ݎଵ ሺͳ ݑ ሻ൯ߣହ ି

ିିଵ ே ே

ߣସ ൌ

ఉௌశభ ఋభ ఉாశభ ఋమ ఉோశభ

ͳ ݄ ൬ሺ ݎଵ ሺͳ ݑ ሻ ߤ ݀ െ ሺͳ െ ݂ሻ െ െ ሺͳ െ ݂ଵ ሻ൰

ே ே ே

ఉூ

ି

ߣହ ݄ ൬ శభ ߜଶ ൫݂ଵ ߣଷ ିିଵ ሺͳ െ ݂ଵ ሻߣସ ିିଵ ൯൰

ିିଵ ே

ߣହ ൌ ఉூ

ͳ ݄ ቀ శభ ߜଶ ߤቁ

ே

൫ߣସ ିିଵ െ ߣହ ିିଵ ൯ݎଵ ܫାଵ

ܶାଵ ൌ

ʹܥ

ݑାଵ ൌ ݉݅݊൫ͳǡ ݉ܽݔሺͲǡ ܶାଵ ሻ൯

Step 3

To ݅ ൌ Ͳǡ ǥ ǡ ݊displayܵሺݐ ሻ ൌ ܵ ǡ ܸሺݐ ሻ ൌ ܸ ǡ ܧሺݐ ሻ ൌ ܧ ǡ ܫሺݐ ሻ ൌ ܫ ǡ ܴሺݐ ሻ ൌ ܴ ǡ ݑሺݐ ሻ ൌ ݑ .The algorithm is complete.

95703 35703 13670 2000 0 0.6 ͳ͵ିͲͳݔହ

ࢾ ࢾ ܥ ࣆ

0.35 0.2 0.15 0.9 0.7 400 0.01

ࣂ ࢼ

3500 0.2 21 0.8 0.05 0.17 0.015

The initial value of parameters used were obtained from Naiggolan et al. (2013) and (Hattaf, 2009). Numerical

simulations were performed by varying the numbers of iterations and the period in years. The results are shown in

Fig. 2 The figure shows that the infected TB population will increase if no treatment, but with the presence of

treatment the infected population will reduce towards zero in the 5thyear. In the case of no treatment, the initial

infected population (2,000 individual) grows to reach 6,000 individuals. However, if there is an optimal treatment

the number decrease towards zero.The profile of the optimal treatment is given in Fig. 3

020020-6

FIGURE 3. Graph of u.

CONCLUSION

In this paper we have solved an optimal control problem in TB transmission using the method of forward-

backward finite difference method. The simulation shows that by giving the optimal treatment (with optimal

control), the population of the infected individuals experienced a greater decline compared with no treatment or the

default treatment with no control. This result is consistent which the convergent is faster with the previous one

discussed in Nainggolan et al. (2013).

ACKNOWLEDGMENTS

This paper assisted in part by the Indonesian Government through PenelitianUnggulanPerguruanTinggi 2016

Unpad Number: 431/UN6.3.1/PL/2016.

REFERENCES

1. Chapra, S.C.1985.Numerical Methods for Engineers.McGraw Hill Book Company.

2. El hia, M., Balatif, O., Bouyaghroumni, J., Labriji, E., and Rachik, M., 2012. Optimal Control Applied to the

Spread of Influenza A(H1N1). Applied Mathematical Sciences, 82: 4057-4065.

3. Hattaf, K., Rachik, M., Saadi, S., Tabit, Y., danYousfi, N.2008.Optimal Control of Tuberculosis with

Exogenous Reinfection. Applied Mathematical Sciences, 5: 231-240.

4. Kamien, M. I dan Schwarz, N. L .1991. Dynamic Optimization: the calculus of variations and optimal control

in economics and management. North-Holland. Amsterdam.

5. Meyer,W. J., 1984. Concept of Mathematical Modeling, McGraw Hill Book Company.

6. Naidu, D. S. 2002. Optimal Control Systems. USA : CRC Presses LCC.

7. Nainggolan, J. 2013. Optimal Control Solution of A Tuberculosis Transmission Model with Reccurent Infection

and Vaccination Using C# Programming, America Scientific Publishers, 4 : 400-407

8. Pontryagin, L.S ,Boltyanskii, V. G, Gamkrelidze, R. V , and Mishchenko, E.F. 1962. The Mathematical Theory

Of Optimal Processe. Wiley, New York.

9. Setiawan. 2012. Kontrol Optimal PenyebaranTuberkulosisdengan Exogenous Reinfection. Publish thesis on.

Depok : Program Pasca-Sarjana UI.

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