Chapter 1

Introduction

“The man who moves a mountain begins by

carrying away small stones.”
– Confucius
1.1 Rationale

Infectious diseases are leading threats and highest risk to human population

globally. Millions of people die as well as forced to live with disability adjusted

life for years. Number of deaths that occurred in year 2012 alone due to different

infectious diseases in different continents and countries per million persons are

shown in figure 1.1. Numbers are too high and lead us to establish all possible

controls and strategies to stop disease spread.

Figure 1.1 Number of deaths from infectious and parasitic diseases in 2012 per

million persons
https://commons.wikimedia.org/wiki/File%3AInfectious_and_parasitic_diseases_world_map-Deaths_per_million_persons-WHO2012.svg

Microscopic size organisms like bacteria, viruses, fungi or parasites passes directly or

indirectly from one host (human or animal) to another and makes individual sick.

Infection transmits from one infected host to susceptible host through two different

routes namely horizontal transmission and vertical transmission. The transmission of

infection by physical contacts or by inhalation or ingestion of contaminated material

refers horizontal transmission, while the direct transfer of a disease from an infective

parent to an unborn or newly born offspring is called vertical transmission of disease.

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1.1.1 Vertical Transmission of Diseases

The vertical transmission of disease is transmission of infection from one

generation to the next generation. HIV, Hepatitis B and Syphilis are few examples of

infectious diseases that can be transmitted vertically. It can occur when the mother

gets an infection as an intercurrent disease during pregnancy. Hence, the transmission

can also be called mother-to-child transmission. A vertically transmitted infection is

an infection caused by bacteria, viruses, or in some rare cases parasites transmitted

directly from the mother to an embryo, foetus, or childbirth. The term congenital

infection can be used if the vertically transmitted infection persists after childbirth. A

vertically transmitted infection can be called a perinatal infection if it is transmitted in

the perinatal period, the period starting at a gestational age of 22 weeks to (with

regional variations in the definition) and ending seven completed days after birth. The

main routes of transmission of vertically transmitted infections are across

the placenta (A temporary organ that joins the mother and foetus, transferring oxygen

and nutrients from the mother to the foetus and permitting the release of carbon

dioxide and waste products from the foetus) and across the female reproductive

tract during childbirth. During birth, babies are exposed to maternal blood and body

fluids, hence they can also be infected by their mothers. Some infectious agents like

blood-borne microorganisms (hepatitis B, HIV), organisms associated with sexually

transmitted disease (e.g., Neisseria gonorrhoea and Chlamydia trachomatis) and

normal fauna of the genitourinary tract (e.g., Candida Albicans) may be transmitted to

the embryo or foetus in the uterus, while passing through the birth canal or even

shortly after birth. Figure 1.2 represents the different paths of vertical transmission of

diseases. Few of the vertically transmitted diseases considered in this research are

described below.

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Congenital transmission of ZIKAV Vertical transmission of gonorrhea

https://www.frontiersin.org/articles/10.3389/fcimb.2017.00486/full http://intranet.tdmu.edu.ua/data/kafedra/internal/infect_desease/classes_stud/en/stom

at/ptn/dermatovenereology/4/05.methods%20of%20examination%20of%20patients%

20with%20std.%20primary%20and%20secondary%20syphilis.html

Figure 1.2 Gateway for Vertical infection

https://biocyclopedia.com/index/medicinal_microbiology/congenital_and_perinatal_infections.php

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 HIV/AIDS

HIV is short name for Human immunodeficiency virus, which causes HIV

infection. Pre-AIDS is pre stage of AIDS. AIDS (acquired immunodeficiency

syndrome) is the advance stage of HIV infection. Infection of HIV gradually destroys

the CD4 cells of the immune system of the infected. HIV spreads through direct

contacts of body fluids like blood, semen, vaginal fluids and breast milk. Hence, HIV

can also transmit vertically. As per global HIV factsheet (2017) by unaids, globally

36.7 people were living with HIV in 2016 out of which 2.1 million children (< 15

years) were suffering from HIV. Our aim is to study HIV transmission vertically with

the effect of sexually mature infected new-borns as a time delay and effect of delay in

treatment and pre-AIDS.

HBV

A viral infection that infects liver through virus Hepatitis B is called

hepatitis (HBV). HBV can spread through blood transmission, sexual contacts, use of

contaminated needles and syringes. As per NCDC newsletter, (January-march 2014)

worldwide 7,80,000 people die each year due to acute HBV.

As vaginal secretions are contaminated it can spread from mother to child. It can be

acute or chronic. Chronic infection of HBV causes liver damage or lead to liver

cancer. The alcoholic habits results in acute or sub- acute liver failure and hence are

categorized under hepatitis infection. The sexual transmission makes population to be

carrier. The carrier female results in to vertical transmission. So, to control spread of

disease, vaccination is advocated at the carrier stage and new-borns. Our aim is to

propose a model of HBV transmission vertically under treatment with the effects of

vaccination to new-borns, vaccination to carrier mother and alcoholic habits in male

on spread of HBV are studied.

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 HIV HBV Coinfection

The individuals who are infected with both diseases HIV and HBV

simultaneously, are said to be HIV-HBV coinfected. These infected individuals have

high risk of liver failure. It is the main cause for serious liver complications like

cirrhosis and liver cancer at younger age. Carrier class results in the vertical

transmission. Our aim is to establish a deterministic model incorporating liquor habit

in men and vaccination to new-borns and carrier mother.

Chagas

Chagas disease is life-threatening illness caused by the protozoan

parasite Trypanosoma cruzi (T. cruzi). It is also known as American trypanosomiasis.

As per WHO fact sheet 2016, worldwide, approximately 6 to 7 million people got

infected with T. cruzi. Buckner et. al. (1998) observed that about one third of the

infected got disability and early death because of disease. Vertical transmission of

disease also plays vital role in spreading disease as it increases infected population.

Spraying insecticide and treatment of infected individuals with benznidazole and

nifurtimox drugs are effective ways to control disease spread. Anti-parasitic

treatment curbs the disease progression but creates side effects amongst pregnant

women or amongst individuals having kidney failure, liver failure, neurological

disorders or psychiatric disorders. As per WHO fact sheet 2016, approximately 30%

of chagas patients suffer from cardiac disorders, while approximately 10% suffer

from digestive or neurological or mixed alterations during chronic phase. To control

vectors, spraying insecticide is the easiest and safest way, but sometimes it is costly

for long period of spraying. Also, for most of the vector-borne diseases treatments

are available, but because of unawareness they spread at high frequency. People may

start to opt the treatment but the side effects or cost of treatment, force them to leave

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treatment in between and that create larger dropouts. As costs are incorporated with

spraying and dropout both, our aim is to minimise the total cost associated by

controlling both, spraying and drop-out in a way that spraying should be maximum

and dropout should be minimum for disease control.

Measles

Measles is an infectious disease spread by Paramyxovirus. As per report of

WHO (2014), measles spreads especially when a person comes in direct contact with

nasal secretions of infected individual. As per WHO report (2016), measles is one of

the leading causes among young children, despite of availability of safe and effective

vaccination. In 2014, 114900 deaths were registered globally because of measles

infection, out of which most of them were children, having age less than 5 years.

Unvaccinated young children and pregnant women are at high risk of measles

infection. Our aim is to study the effect of loss of immunity generated by vaccination

and delay in vaccination on the severity of measles using concept of pulse

vaccination.

ZIKA

Zika is the vector-borne disease which initially spreads by the bite of an

infected Aedes species mosquito (Ae.aegypti and Ae.albopictus) and then it transmits

vertically from a pregnant woman to fetus or from an infected human to their sexual

partners. The congenital transmission of Zika virus (ZIKV) results in new born with

microcephaly and other neurological abnormalities. Pan American Health

Organization noted that the recent outbreak began in April 2015 from Brazil, has

covered many southern, central American countries and the Caribbean with spread of

disease, and more than 140,000 suspected and confirmed cases are reported by the

end of February 2016. The control of infected mosquitos is the best efficient way to

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control spread of ZIKV. Spraying insecticide is the safest and easiest way to control

mosquitos, but sometimes it is costly for long period of spraying. Controlled

prevention from the vector bites can also help to control disease spread. To control

congenital transmission and sexual transmission of ZIKV, preventions should be

taken to reduce/stop pregnancy rate and safe heterosexual transmission among adults.

Also, there is no specific treatment available for Zika disease. Treatment is aimed at

relieving symptoms with rest, fluids and intake medications. The costs are

incorporated with spraying, preventions and treatment, our aim is to minimise the

total cost associated by controlling spraying, preventions and treatment.

Ebola virus disease

The Ebola virus disease (EVD) is one of the deadly diseases amongst

human and non-human primates caused by most virulent pathogens viz Ebola virus.

Socio - economic impacts of Ebola is very high. In 2014, the latest and largest major

outbreak occurred in West African countries Guinea, Sierra Leone, and Liberia. Ebola

virus diseases (EVD), formerly known as Ebola haemorrhagic fever spreads by

infection from virus of the family Filoviridae, genus Ebolavirus. As per WHO Ebola

situation report March 2015, around 10,311 deaths with total 24,872 infection cases of

Ebola were reported from western African countries. In 1976, two simultaneous

outbreaks of Ebola were occurred in South Sudan and Democratic Republic of Congo.

Thereafter, outbreak occurred in a village near river Ebola, and then it was started to

be identified as EVD. As a Zoonotic disease Ebola virus can transmit amongst animal

and human population. During the outbreak, cases were reported about presence of

Ebola virus in semen and breast milk of individuals after recovery which leads to

vertical transmission of disease spread. Our aim is to study effective early diagnosis,

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isolation, awareness campaigns and mass media coverage during disease outbreak

can help to break the chain of infectious cases and control disease spread.

Syphilis

Syphilis is sexually transmitted disease having different signs and

symptoms with four main multiple stages namely primary, secondary, latent, and

tertiary. The subspecies pallidum from the bacterium Treponema pallidum are

responsible for syphilis spread. Congenital (vertical) transmission of syphilis from

infected mother to fetus or neonatal is still a cause of high perinatal morbidity and

mortality. Our aim is to develop a model of transmission of syphilis with controlled

treatment.

1.2 Significance of the Study

The quantitative predictions of the future trends of such infections are required

to control their spread. This leads us to the construction and analysis of suitable

models by considering distinctive aspects of vertical transmission. Control and

preventions of vertical transmissions of such diseases has become a critical

component of national and global responses. Women living with vertically

transmitted diseases have the right to enjoy the benefits of scientific progress and the

health services that enable them to reduce the risk of transmitting diseases to their

children. They also have the right, like all other women, to have their family. A child

taking birth with infection has right to live long healthy life. The economic costs of

these diseases are significant. They disturb routine health care services. The loss of

productivity and high cost of health care directly affect economic and social growth of

the mankind and consequently nation. Organizations such as World Bank, CDC,

WHO and various NGOs are working hard for improving global surveillance and

response system for such diseases. Although advent of new medicines and vaccines

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do a lot to cure such diseases, still there is a need to welcome all possible methods for

fighting these killer infectious diseases whether it is biological, medical,

environmental, social or mathematical.

The outcomes of this study will help the health care and social welfare

departments to establish policies, programmes and optimal plan for control of the

diseases by taking into account the study of vertical transmission of diseases. It will

help the society, in general, to have an understanding on how the disease can be

controlled. Also, it will add more knowledge to the existing literature and help

researchers to do more research on these diseases. Lastly, this study will help

educationalists to develop educational seminars, workshops or training programmes to

educate people in curbing down the disease epidemic.

1.3 Disease Dynamics in Population and Mathematical Modelling

"Knowing is not enough; we must apply. Willing is not enough; we must do."

- Johann Wolfgang von Goethe, German poet (1749‐1832)

“Understanding the transmission dynamics of disease spread will not only

help us to control the disease, but will also make us prepared for the future as it will

make the scenario and intensity of spread clear.” (Gupta Jyoti (2015), Mathematical

Modelling of Infectious Diseases - Dynamics and Control (In Indian Context): a

thesis)

Biological mechanism and behaviour of a parasite or virus involved in disease

spread for their intensity as well as their ability to survive in host and make an

individual infected is too complex to understand. The mathematical modelling is a

tool to measure or understand such mechanism and the relevance of any public health

care strategy. With certain constitutive assumptions, notations and variable

definitions, a mathematical model transforms a biological problem in to mathematical

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equations which describes the actual situation. Using mathematics as language to

interpret the assumptions concerning the biological and population mechanics, one

can make predictions by comparing the actual epidemiological data and verify

validity of same using mathematical tests and results. Age plays an important role in

the dynamics of disease transmission. Age enters as a fundamental parameter in

vertically transmitted diseases and it is always necessary to take age into account in

one way or another in order to produce a valid model. Two reasons, first, the new-

born who are individuals of age zero; second, the pathogenic agent builds up in an

infected female as time goes by, are susceptible to vertical transmission of diseases.

Figure 1.3 Mathematical Approach to disease spread

In particular, mathematical models can be used to visualize the transmission

dynamics and spread of these diseases. These models can help us to understand the

right disease status and predict if the disease is going to be genetic or controlled. Such

applications are highly helpful to the society if utilized wisely.

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 Models under consideration are deterministic models, also known as

compartmental models. Stochastic models depend on chance and provide deeper

insight as it is individual-level modelling but they deal with small population and very

complex in nature. Deterministic models that are described in this study can deal with

the case of large population by dividing and subdividing the total population into

various compartments.

In this research phase, our focus is to understand the disease dynamics in

population.

1.3.1 Mathematical epidemiology and modelling

Daniel Bernoulli (1766) was first to use mathematical epidemiology. He

applied it for the programme of inoculation against smallpox. Somewhere between

1873 and 1894 En’ko had put foundation stone on modern mathematical

epidemiology which was laid by Ross, Hamer, McKendrick and Kermack between

1900 and 1935. They suggested the modern approach of compartmental methods

along with important contributions from a statistical perspective by Brownlee.

Some basic terminologies required for model constitution are:

Susceptible: An individual who is at a risk of catching infection though still not

infected.

Exposed: An individual person who is infected but not capable to transmit

infection.

Infectious: An infected individual capable of transmitting infection.

Recovered: After treatment or due to immunity development, infection heals up

and the individual does not remain infectious.

Epidemic: Disease is said to be in epidemic stage if the number of cases rapidly

increases within a short duration of time for said population.

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 Endemic: Disease is said to be endemic if it persist for long time amongst

population of particular area.

Incubation Period: The duration between an individual receives an infection and

having first apparent symptom of the disease.

For development of model, our concern is with both situations epidemic as well as

endemic. Our goal is to introduce mathematical epidemiology, by developing

mathematical models for the spread of disease and using them as tools for analysis. In

epidemiology, mathematical modelling provides better understanding and control

strategies about mechanisms that influence the disease spread. Here, we first start with

simple models in order to establish broad principles. These simple models are the

building blocks of models that include more detailed structure. Simple model

excludes most details and describes only general qualitative behaviour, while detailed

model describes specific situations including short-term quantitative predictions.

Usefulness of detailed models for theoretical purposes is limited as it is difficult or

impossible to solve them analytically but their strategic value may be high. The list of

different variables and parameters used in explaining basics of these models is

summarized below:

Capital letters such as S  t  , E  t  , I  t  , R  t  etc. are state variables used to represent

various compartments.

S t  : Number of susceptible individuals at time t

E t  : Number of exposed individuals at time t

I t  : Number of infectious individuals at time t

R t  : Number of recovered individuals at time t

N t  : Total human population at time t

B : Recruitment rate
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  : Transmission rate of infection from an infectious individual to a
susceptible one.
 : Natural death rate
 : Disease Induced death rate
 : Rate of progression from exposed class to infectious class
k : Recovery rate
 : Rate of progression from recovered class to susceptible class
again

We start by formulating our descriptions as compartmental models, by

dividing the population under consideration into compartments and incorporating

suitable assumptions about the nature as well as time for rate of transfer from one

compartment to another. Mathematically, this flow of individuals from one to another

compartment will be described using differential equations of compartments with

respect to time.

Starting with the simplest compartmental model consisting of only two classes,

SI Model: This model is formulated by dividing total population in two

compartments namely Susceptible and Infected. An individual from susceptible

compartment comes in contact with an infected individual from infectious

compartment and joins infectious compartment. It is assumed that an individual

enters in infectious compartment will remain in infectious compartment forever.

Here natural birth and natural deaths are not taken in consideration.

SIR Model: In 1927, Kermack and McKendrick had suggested a mathematical

model with three compartments namely susceptible, infected and removed. This

model was introduced with natural birth and natural death. SIR model is an

extension of SI model with one more added compartment recovered. Infectious

individual after getting recovery through natural immunity or by any other

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 sources joins recovered class and remains there forever. Measles, mumps, flu,

rubella are few examples of infectious diseases which follows SIR dynamics.

SIRS Model: It is further extension of SIR model adding one more situation that

a recovered individual loses temporary immunity and re-joins the susceptible

class.

SEIR Model: Many time an infection takes a time gap (may vary from disease to

disease) to make a susceptible individual infectious after catching infection from

an infected individual, called incubation period. During this time period,

susceptible individuals who acquired infection but still not become infectious

joins exposed compartment. SIR model with one more compartment added as

exposed compartment suggests the dynamics of SEIR-model.

Very basic models of mathematical epidemiology are described above. We are going

to formulate more complicated models by adding more compartments and variables

or parameters associated with vertical transmission, isolation, treatment, insect

spraying, mass media effect and many more.

1.3.2 Disease spread in terms of dynamical system and methodology

Dynamical system theory was established by LaSalle (1976), Lakshmikantham

et al. (1989), Holmes and Guckenheimer (2002), while Anderson and May (1992),

Brauer and Castillo-Chavez (2001), and Murray (2002, 2003) worked on its real

world applications. Strategies developed by them with some advancement are

reviewed and applied as follow.

Mathematical modelling of disease spread (using state variables that

completely describe the state of dynamical system) formulates a dynamical system in

the form of non-linear ordinary differential equations as it represents evolution of

disease spread over time with specified rules. By knowing complete description of

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such system (i.e. the value of variables which describes state of system) at particular

time, one can completely describe the set of all possible values of state variables

called state space. If the state space is continuous and finite-dimensional, it is called

the phase space. As we are dealing with continuous dynamical system, the state of the

system flows smoothly through state space. This flow takes a form of curve or

trajectory which decides future trends of system. Assuming, the state as X  t  at time

t , with the evolution rule for disease spread as  , velocity for X  t  that specifies

 i  X  t   , where
dxi
how as point X  t  moves through state space. Thus,
dt

X  t    xi  t   for i  1, 2,3,..., n with initial state as X 0 at time t  0 and movement

of X  t  starting with X 0 through state space represents all future trends of X  t  in

form of trajectory or curve in state space. In case of disease dynamics, one can predict

about disease spread and develop strategies to curb disease spread by analysing this

trajectory or curve using different mathematical results as tools. That said results used

in this research work are described as below.

Equilibrium point: An equilibrium point of the dynamical system is solution of

given dynamical system which does not change with time. It is also called fixed

point of the system. i.e. those X e  t  which satisfies  i  X e  t    0 (with

independent time), for the given system of non-linear ordinary differential

 i  X  t   , where X  t    xi  t   for i  1, 2,3,..., n , are called

dxi
equations
dt

equilibrium points of the system.

Two types of equilibrium points are taken in consideration

(1) Disease free equilibrium point (DFE)

(2) Endemic equilibrium point (EE)

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Stability Analysis: There are three different conceptual analyses available for

stability, namely; stability according to Poisson (1808), stability according to

Lyapunov (1892), and asymptotic stability. Our interest is in the stability of a

trajectory at X e . As per Poisson one can say equilibrium point X e is stable if

after some time, the phase trajectory starting from X e returns to an arbitrarily

small neighbourhood of the X e . This stability is of weaker form as here it is not

possible to predict anything about behaviour of neighbouring trajectories of X e .

Lyapunov and asymptotic stability involves the temporal dynamics of the

perturbation, which gives stronger form of stability. The trajectory at X e is said

to be Lyapunov stable for every   0 ,    0 such that

X  t0   X e  t0     X  t   X e  t    for every t  t0 , and if

X  t   X e  t   0 as t   then trajectory holds more stronger form called

asymptotic stability.

Theorems and results used in this study to analyse stability are

summarised below.

Theorem 1.1 (Jacobian method): For the given system of nonlinear ordinary

 i  X  t   , X  t    xi  t  
dxi
differential equations where and let
dt

   X  
J   i e  for i, j  1,2,3,..., n denotes the Jacobian matrix at each
 x j 

equilibrium point X e , then the equilibrium point X e is stable if all the

eigenvalues have negative real parts, the equilibrium point X e is unstable if at

least one of the eigenvalue has positive real part and the equilibrium X e is

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saddle point if it is possible to find at least one eigenvalue with negative real

part and at least one eigenvalue with positive real part.

Result 1.1: Moreover, Edward et al. (2014), Fred et al. (2014), Liao and Yang

(2013), Mpeshe et al. (2011) proposed that if the Jacobian matrix has a negative

trace and a positive determinant then equilibrium point becomes locally

asymptotically stable.

Theorem 1.2 (Lyapunov’s stability criterion): For the given system of

 i  X  t   , where X (t )   xi  t   ,
dxi
nonlinear ordinary differential equations
dt

i : R n  R n , for i  1, 2,3,..., n and with equilibrium point given as X 0  0 , if

there exists a function V : R n  R such that (i) V ( X )  0 if and only if X 0  0

dV ( X )
(ii) V ( X )  0 if and only if X 0  0 (iii)  0 if and only if X 0  0 , then
dt

dV ( X )
X 0  0 is stable. If condition (iii) is  0 if and only if X 0  0 , then
dt

X 0  0 is asymptotically stable. Asymptotically stable X 0  0 is said to be

globally asymptotically stable if V ( X ) is radially unbounded.

In case of disease spread, stability near equilibrium points gives

idea if the disease will be epidemic or endemic. It also provides the deeper

insight about disease spread and helps to design control strategies to curb

disease spread.

Basic Reproduction Number: Lotka and Ross (1923) are known as pioneer for

focusing on new aspects in control of disease spread. Ross proposed a bunch of

model parameters not involving any state variable, using which a new control

strategy was designed to control malaria and positive results were obtain. Later

on, this bunch with little advancement was declared as basic reproduction
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number R0 . Dublin and Lotka (1923) and Kuczynski (1931) suggested classical

methods for calculation of R0 . Basic reproduction number is a value which

gives the average number of new infections caused by a single typical infected

individual in whole susceptible population. Initially, Diekmann et al. (1990) and

then van den Drichesche and Watmough (2002) introduced a modern approach

in calculation of R0 called next generation matrix method to find R0 . With

simple mathematical calculation, they proposed R0 as dominant eigenvalue of

next generation matrix. To generate next generation matrix K , for

compartmental model of infectious disease the following phenomenon is

undertaken.

Theorem 1.3 (Calculation of R0 ) : Let us given a system of non-linear

ordinary differential equations which represents mechanism of disease spread

by n -equations (dividing total population in n compartments), out of which

(say) m -equations represents mechanism of infected compartments then we can

dxi
represent this situation mathematically as  i  X   vi  X  for
dt

i  1, 2,3,..., n ; where i  X  denotes rate of the new incoming infected

individuals in ith-compartment while vi  X  gives the difference between rate of

incoming and outgoing individuals other than infected from ith -compartment

and X   xi  , for i  1, 2,3,..., n ; and if X 0 is disease free equilibrium, then the

basic reproduction number R0 of the given system is spectral radius of the next

   X      X  
generation matrix K  FV 1 , where F   i 0  and V   i 0  for
 x j   x j 

i, j  1,2,3,..., n are n  n matrices.

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1.4 Objectives

The objectives of this study are

 To design and analyse mathematical models for vertical transmission of

diseases in order to understand the dynamics of diseases (with enforced

conditions) like HIV-AIDS (with delay treatment), Hepatitis B (with liquor

habits), Chagas (with control spraying and dropouts), Measles (with threshold

for vaccination), Zika (with prevention and control of congenital transmission) ,

Ebola (with mass media impacts), Syphilis (with control treatment).

 To suggest effective control strategies using stability of equilibrium points in

terms of basic reproduction number and to determine impact of each embedded

parameter on the disease transmission.

 To validate obtained analytical results and conclusions using software like

Matlab and Maple with sufficient large data and conclude more strategies to

curb the spread of disease.

1.5 Outline of Thesis

Chapter 1 includes introduction and methodology.

Chapter 2 proposes mathematical model of HIV transmission vertically with

delays in treatment and pre-AIDS. This model in terms of the system of non-linear

differential equations includes the effect of sexually mature infected new born as a

time delay and effect of delay in treatment and pre-AIDS are analysed. Total

population is divided in to five compartment viz. Susceptible, Infectious, Treated, pre-

AIDS and AIDS. Basic reproduction number is obtained and stability of the infection

free as well as the endemic equilibrium are analysed. Effect of time delays in

Treatment, Infection and Pre-AIDS has been studied for disease free equilibrium. The

local and global stability of the system is discovered. Sensitivity of the key parameters
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is measured using numerical simulation and observed that it supports the analytical

results.

Chapter 3 suggests mathematical model for HBV transmission vertically

under treatment and alcoholic habits. This model of non-linear differential equations

includes study of the transmission dynamics of HBV with the effects of vaccination to

new-borns, vaccination to carrier mother and alcoholic habits in male on spread of

HBV. The alcoholic habits result in acute or sub- acute liver failure and hence are

categorized under hepatitis infection. The sexual transmission makes population to be

carrier. The carrier female results in to vertical transmission. Vaccination is advocated

at the carrier stage and new-borns to control spread of disease. Total population is

divided in to nineteen compartments viz. Susceptible under-age, Susceptible female,

Susceptible non-alcoholic male, Susceptible alcoholic male, Exposed under-age,

Exposed female, Exposed non-alcoholic male, Exposed alcoholic male ,Infected

under-age, Infected female, Infected non-alcoholic male, Infected alcoholic male,

Carrier under-age, Carrier female, Carrier non-alcoholic male, Carrier alcoholic male,

Vaccinated individuals, Recovered under-aged and recovered adults. The sensitivity

analysis of basic reproduction number R0 indicates that alcoholic habits in adults

should be controlled. It is also observed that awareness programs for vaccination of

under-aged and carrier mother should be conducted to control disease spread.

In Chapter 4, the transmission dynamics of HIV-HBV co-infection is carried

out. The individuals who are infected with both diseases HIV and HBV

simultaneously, are said to be HIV-HBV co-infected. A deterministic model is

considered with liquor habit in men and vaccination to new-borns and carrier mother.

Carrier class results in the vertical transmission. Mathematical model is suggested by

dividing total population in to twenty eight class viz. Susceptible, HBV Vaccinated,

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HBV-infected female, HBV-carrier female, HBV infected alcoholic male, HBV

carrier alcoholic male, HBV infected non-alcoholic male, HBV carrier non-alcoholic

male, HBV recovered class, pre-AIDS female, AIDS female, pre-AIDS-HBV co-

infected female, AIDS-HBV co-infected female, pre-AIDS-HBV carrier female,

AIDS-HBV carrier female, pre-AIDS alcoholic male, AIDS alcoholic male, pre-AIDS

non-alcoholic male, AIDS non-alcoholic male, pre-AIDS-HBV co-infected alcoholic

male, pre-AIDS-HBV co-infected non-alcoholic male, pre-AIDS-HBV carrier

alcoholic male, pre-AIDS-HBV carrier non-alcoholic male, AIDS-HBV co-infected

alcoholic male, AIDS-HBV co-infected non-alcoholic male, AIDS-HBV carrier non-

alcoholic male, HIV infected -HBV recovered classes. The basic reproduction

numbers for HIV, for HBV and for HIV-HBV co-infection along with local and

global stability of HIV-HBV disease free equilibrium is worked out. At last, the

model is validated with the numerical simulation.

Chapter 5 proposes model of measles transmission vertically with vaccination

failure and delay of vaccination. In this model, the effect of infected new borns as a

time delay is analysed. Time delay is considered as loss of maternal immunity

amongst new borns. Total population is divided into four compartments viz.

Susceptible, Infectious, Recovered and Vaccinated. The system of non-linear

differential equations for the proposed problem is established. The next generation

matrix method is used to find the reproduction number, and to obtain the stability of

the infection free as well as the endemic equilibrium. Effect of time delay in

vaccination has been studied for disease free equilibrium. The local and global

stability of the system is analysed. Sensitivity of the key parameters is measured using

numerical simulation and observed that it supports the analytical results.

Chapter 6 suggests the mathematical model for congenital transmission of

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chagas with control dropouts and spraying. Disease dynamics for chagas in ten

compartments namely Susceptible treated human child, Susceptible untreated human

child, Susceptible treated human adult, Susceptible untreated human adult, Infected

treated human child, Infected untreated human child, Infected treated human adult,

Infected untreated human adult, Susceptible vector and infected vector including

vertical transmission of disease is proposed. Also, control function for minimising the

cost of spraying and dropout is calculated. Numerical simulations have been

established to find basic reproduction number, stability and minimising control

function.

In Chapter 7, mathematical analysis to prevent and control congenital

transmission of zika virus is proposed with the help of a mathematical model which is

developed with disease dynamics in nine compartments namely Susceptible human

child, Susceptible human male, Susceptible human female, Infected human child,

Infected human male, Infected human female, Recovered human, Susceptible vector

and Infected vector. Basic reproduction number and stability are calculated.

Numerical simulations have been carried out to optimise controls.

Vertical transmission of Ebola disease spread and its impacts on population

are studied in Chapter 8. The effectiveness of early diagnosis, isolation, awareness

campaigns to break the chain of infectious cases and control the disease spread is

studied. Mathematical model for vertical transmission of Ebola with media effect is

developed using seven compartments namely Susceptible, Exposed, Infectious,

Hospitalised/Isolated, Convalescent, Dead (not properly buried dead bodies of Ebola

victims), and Recovered. Basic reproduction number, disease free equilibrium and

endemic equilibrium are computed. Stability of DFE and EE is established.

Numerical simulations are carried out. It is observed that mass media is one of the

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most effective ways of creating awareness about such type of high mortality

diseases. Informative awareness amongst public may curb the disease spread and

help to control disease in initial stage.

In Chapter 9, a model of transmission of syphilis with three different ways

of transmission namely vertical, heterosexual and homosexual is formulated as a

system of non-linear ordinary differential equations. Treatment is also incorporated

at various stages of infection as it plays a vital role to control disease transmission.

Total population is divided in various classes viz. Susceptible, Exposed, primary and

secondary Infected, early and late Latent, Tertiary. Basic reproduction number,

disease free equilibrium and endemic equilibrium are derived and their stabilities are

established. Numerical simulations are carried out. It is observed that safe sexual

habits, controlled treatment in each stage including pregnancy are effective

parameters to curb disease spread.

Chapter 10 enlightens the research work through analysis and conclusion

with discussion of its benefits to the society. It also provides future directions to

researchers.

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