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 DIMACS
Series in Discrete Mathematics
and Theoretical Computer Science

Volume 75

Modeling Paradigms
and Analysis of Disease
Transmission Models
Abba B. Gumel
Suzanne Lenhart
Editors

American Mathematical Society

 Modeling Paradigms
and Analysis of Disease
Transmission Models
 https://doi.org/10.1090/dimacs/075

DIMACS
Series in Discrete Mathematics
and Theoretical Computer Science

Volume 75

Modeling Paradigms
and Analysis of Disease
Transmission Models
Abba B. Gumel
Suzanne Lenhart
Editors

Center for Discrete Mathematics

and Theoretical Computer Science
A consortium of Rutgers University, Princeton University,
AT&T Labs–Research, Alcatel-Lucent Bell Laboratories,
Cancer Institute of New Jersey (CINJ), NEC Laboratories America,
and Telcordia Technologies
(with partners at Avaya Labs, HP Labs, IBM Research, Microsoft
Research, Georgia Institute of Technology, Rensselaer Polytechnic
Institute, and Stevens Institute of Technology)

American Mathematical Society

Providence, Rhode Island
 This DIMACS volume presents selected papers from the U.S.–Africa Advanced Study
Institute on Mathematical Modeling of Infectious Diseases in Africa, held at the African
Institute for Mathematical Sciences, Muizenberg, South Africa, from June 11–22, 2007,
and the DIMACS Workshop of the same name, hosted by the South Africa Centre for
Epidemiological Modeling and Analysis, Stellenbosch, South Africa, from June 25–27,
2007.
2000 Mathematics Subject Classification. Primary 34D05, 34D20, 34D23, 92B05, 92–01,
92–02, 92–06, 92D25, 92D30.

Library of Congress Cataloging-in-Publication Data

Modeling paradigms and analysis of disease transmission models / Abba B. Gumel, Suzanne
Lenhart, editors.
p. cm. — (DIMACS series in discrete mathematics and theoretical computer science ; v. 75)
Includes bibliographical references.
ISBN 978-0-8218-4384-0 (alk. paper)
1. Epidemiology—Mathematical models. 2. Communicable diseases—Transmission—
Mathematical models. 3. Public health—Mathematical models. I. Gumel, Abba B., 1966–
II. Lenhart, Suzanne.
RA652.2M3M63 2010
614.4015118—dc22
2010016461

Copying and reprinting. Material in this book may be reproduced by any means for edu-
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c 2010 by the American Mathematical Society. All rights reserved.
The American Mathematical Society retains all rights
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Copyright of individual articles may revert to the public domain 28 years
after publication. Contact the AMS for copyright status of individual articles.
Printed in the United States of America.

∞ The paper used in this book is acid-free and falls within the guidelines
established to ensure permanence and durability.
Visit the AMS home page at http://www.ams.org/
10 9 8 7 6 5 4 3 2 1 15 14 13 12 11 10
 Contents

Foreword vii
Preface
A. B. Gumel and S. Lenhart xi
Prologue
S. Levin xiii
Introduction to Mathematical Modeling of Infectious Diseases
S. Shrestha and J. O. Lloyd-Smith 1
Tools for Mathematical Epidemiology
E. M. Lungu, M. Kgosimore, and F. Nyabadza 47
An Introduction to Optimal Control with an Application in Disease Modeling
R. Miller Neilan and S. Lenhart 67
Introduction to Discrete-time Epidemic Models
A.-A. Yakubu 83
Introduction to Optimal Control for Discrete Time Models with an Application
to Disease Modeling
W. Ding and S. Lenhart 109
Incorporating Stochasticity in Simple Models of Disease Spread
J. Dushoff 121
Using Mathematical Models to Monitor and Evaluate the Impact of Public
Health Interventions on Epidemics: The Case of the TB/HIV Co-pandemic in
Africa
M. S. Sánchez, J. O. Lloyd-Smith, B. G. Williams,
and W. M. Getz 135
Modelling the Epidemiological and Economic Impact of HIV/AIDS with
Particular Reference to Zimbabwe
S. D. Hove-Musekwa, V. Runyowa, and Z. Mukandavire 187
Mathematical Analysis of HIV Treatment Model with Variable Viral Load and
Infection Stages
O. Sharomi and A. B. Gumel 209
Greedy Algorithms in Economic Epidemiology
F. S. Roberts 249

v
 Foreword

In recent years, mathematical modeling of infectious diseases has had an in-

creasing influence on the theory and practice of disease management and control
with such diseases as HIV/AIDS, foot-and-mouth disease, and H1N1 virus, and
this is increasingly the case with diseases of Africa. In order to understand and
prevent the spread of infectious diseases endemic to or emanating from Africa, it
is vitally important to train a cadre of workers who are both knowledgeable about
modeling and about disease contexts and data gathering in Africa. The success of
recent joint US-African modeling studies points to the major advantages of such
collaborations while at the same time pointing to the vital need for more trained
researchers from both sides. To address the issue of training researchers knowl-
edgeable about African diseases and expert in mathematical modeling of disease,
DIMACS, in collaboration with the South African DST/NRF Centre of Excellence
in Epidemiological Modeling and Analysis (SACEMA) and the African Institute for
Mathematical Sciences (AIMS), held a two-week advanced study institute (ASI) on
mathematical modeling and infectious diseases in Africa, culminating in a subse-
quent 3-day “capstone” workshop at which ASI students and researchers from both
the US and Africa interacted and established collaborations. The ASI and work-
shop gave rise to this volume, though it is by no means a proceedings of those two
events and, in fact, is aimed at laying out in an organized way some of the major
themes of infectious disease modeling, with special emphasis on infectious diseases
of Africa.
The ASI, held at AIMS in Cape Town, South Africa, on June 11-22, 2007,
was aimed at training junior US and African participants (graduate students and
postdoctoral fellows) in mathematical epidemiology and the control of emerging
and re-emerging diseases. The capstone workshop, held at Stellenbosch University,
Stellenbosch, South Africa, on June 25-27, 2007, was a culmination of the ASI,
enabling ASI students to participate fully in a workshop involving active US and
African researchers and aimed at furthering research on the modeling of diseases in
Africa. The ASI emphasized basic mathematical techniques used in modeling and
reviewed key diseases of Africa. It then introduced the basic ideas of epidemiological
modeling, including classical epidemic models such as SIR, SIS, and SEIR; struc-
tured modeling; deterministic vs. stochastic models; and uncertainty and sensitivity
analysis. It went on to more advanced topics such as meta-population modeling;
continuous vs. discrete-time stochastic models; models with vertical transmission;
spatial and individual-based models; age structure; and optimal allocation of dis-
ease control resources such as vaccine and antiviral doses.
Speakers at the capstone workshop discussed the design and evaluation of cost-
effective and sustainable strategies for combating disease spread in Africa, with

vii
viii FOREWORD

emphasis on modern statistical tools for surveillance, network methods to elu-

cidate patterns of spread, and evolutionary aspects of endemic African diseases.
Challenges from and opportunities arising from increasing availability of data from
African studies were discussed. A second theme involved the potential consequences
of emerging and re-emerging diseases, in the context of shortage of resources. Speak-
ers addressed drug resistance to tuberculosis, challenges from HIV and malaria, and
alternative interventions for pandemic flu, including vaccination, targeted antiviral
prophylaxis, and quarantines. Finally, a special session introduced the rapidly-
emerging topic of “economic epidemiology,” with its emphasis on health economics
and the economic aspects of disease burden.
These activities were part of the DIMACS Special Focus on Computational and
Mathematical Epidemiology. One specific special focus workshop was instrumental
in leading us to develop this DIMACS activity. This was a workshop on “Evolution-
ary Aspects of Vaccine Use,” organized at DIMACS in June 2005, and stemming
from the work of the DIMACS working group on Methodologies for Comparing Vac-
cination Strategies. The special problems of vaccination strategies in Africa that
arose in this workshop were one of the primary motivations that led Abba Gumel,
one of the editors of this volume, to propose that DIMACS sponsor a workshop that
would directly focus on mathematical modeling of infectious diseases in Africa.
A second activity that led to the DIMACS African activities was the sum-
mer research conference on “Modeling Dynamics of Human Diseases: Emerging
Paradigms and Challenges,” held at Snowbird in Utah July 17-21, 2005. One no-
table feature of the conference was the recognition of the central role of developing
nations in the emergence of novel pathogens, and the need to involve researchers
from these nations in addressing problems of the spread of disease. This recognition
was central in motivating meeting participant Simon Levin, a major leader of the
DIMACS Special Focus, to suggest that we pursue ways to more directly engage
US researchers and students with African researchers and students.
In turn, the DIMACS African activities that led to this volume have led to
a major US-African-Canadian Bio-Mathematics Initiative that includes ASIs and
workshops in Uganda, Kenya, and Madagascar, modeled after those in South Africa.
DIMACS thanks Professors Gumel and Levin for their efforts in promoting the
ASI and workshop on Mathematical Modeling and Infectious Diseases in Africa.
Special thanks go to the Directors of SACEMA and AIMS, John Hargrove and
Fritz Hahne, respectively, for their scientific, administrative, and financial support.
Brenda Latka of DIMACS played a major role in helping to administer the ASI
and workshop and Latka, Wayne Getz, Gumel, Hahne, Hargrove, Levin, Edward
Lungu, and Alex Welte helped to organize it. Others who played an important
role in developing the concept and scope of the ASI and workshop were Dominic
Clemence, Ronald Mickens, Asamoah Nkwanta, and Abdul-Aziz Yakubu. DIMACS
is extremely grateful to all of these people for their involvement and support in its
African initiatives. Finally, DIMACS thanks Gumel and Suzanne Lenhart for their
efforts in putting this volume together.
DIMACS gratefully acknowledges the generous support that makes its pro-
grams possible. Special thanks go to the National Science Foundation, under grant
0629720 to Rutgers University, which made the ASI and workshop that led to this
book possible. Thanks also go to the DIMACS partners at Rutgers, Princeton,
AT&T Labs - Research, Alcatel-Lucent Bell Labs, NEC Laboratories America,
 FOREWORD ix

and Telcordia Technologies, and affiliate partners Avaya Labs, Georgia Institute of
Technology, HP Labs, IBM Research, Microsoft Research, Rensselaer Polytechnic
Institute, and Stevens Institute of Technology.

Fred S. Roberts
DIMACS Director
 Preface

This volume is a product of two activities under the auspices of DIMACS

Special Focus on Computational and Mathematical Epidemiology, namely the U.S.-
Africa Advanced Study Institute (ASI) on Mathematical Modeling of Infectious
Diseases in Africa, which took place at the African Institute for Mathematical
Sciences (AIMS), Muizenberg, South Africa, June 11-22, 2007, and the DIMACS
Workshop on Mathematical Modeling of Infectious Diseases in Africa, hosted by
the South Africa Centre for Epidemiological Modeling and Analysis (SACEMA),
Stellenbosch, South Africa, on June 25-27, 2007. About 50 graduate students,
from across Africa and the USA, attended the ASI, and a total of about 80 people
attended the workshop.
The volume consists of two types of papers: tutorial papers and research papers.
While the tutorial papers introduce the basic and general principles, concepts,
challenges and types of disease modeling, the research papers focus on advanced
topics associated with the mathematical modeling (and analysis) of diseases relevant
to Africa.
The tutorial-type papers cover topics such as basic principles and framework
for modeling diseases, classical (Kermack-McKendrick type) epidemic models, mod-
eling challenges, basic methods of analysis, epidemiological thresholds, uncertainty
and sensitivity analysis and the interpretation of the analytical and simulation re-
sults obtained. In addition to the aforementioned basic topics, the volume also
contains papers on more advanced topics. These include papers on optimal control
techniques in disease modeling, design and analysis of discrete-time models, the role
of stochasticity in disease modeling, economic aspects of disease modeling and con-
trol (including the use of greedy algorithms to obtain optimal solutions) and some
advanced dynamical systems techniques for qualitatively analyzing relatively large
disease transmission models. Some of these papers address the problem of the trans-
mission dynamics and control of some diseases that inflict major socio-economic and
public health burden in Africa, notably HIV and HIV-TB co-infection.
The Editors are very grateful to all those who contributed papers to the vol-
ume (S. Shrestha, J. O. Lloyd-Smith, E. M. Lungu, M. Kgosimore, F. Nyabadza,
R. Miller Neilan, S. Lenhart, A.-A Yakubu, W. Ding, J. Dushoff, M. S. Sánchez,
B. G. Williams, W. Getz, S. D. Hove-Musekwa, V. Runyowa, Z. Mukandavire,
O. Sharomi, A. B. Gumel and F. Roberts). In addition to the great scholarly con-
tributions of the authors, this volume would not have been possible without the
support of the sponsors of the ASI and the workshop in Stellenbosch, namely AIMS,
DIMACS, The U.S. National Science Foundation and SACEMA.
The Editors are immensely grateful to Fred Roberts, who made the whole
U.S.-Africa program possible. We are thankful to the DIMACS staff (notably,

xi
xii PREFACE

Margaret Barry Cozzens, Gene Fiorini, Brenda Latka, Christine Spassione and
Ricardo Collado) and Ms. Christine Thivierge (Editorial Assistant, AMS) for their
support. Finally, we are very grateful to the many anonymous reviewers who helped
in reviewing the contributed papers. The Editors are also very thankful to Simon
Levin for writing the Prologue to this volume.

Abba Gumel and Suzanne Lenhart

January 23, 2010
 Prologue

In recent years, computational biology has become one of the hottest areas in
science, spawning new journals, new scientific societies, new departments, and new
training programs for undergraduates and graduates. The challenges of genomics
and systems biology have attracted leading scientists from other disciplines—in par-
ticular physics, computer science and mathematics—who have been motivated to
bring their skills to bear on some of the most important and fundamental problems
facing humanity. Indeed, the excitement of the advances in genomics, and in certain
branches of systems biology, has to some made these applications synonymous with
the field of “computational biology.” It therefore often comes as a surprise when
people learn that computational biology is a very old field, tracing back more than
a century, and with roots firmly planted in population genetics and in epidemiology.
The mathematical description of the dynamics of infectious diseases is one of
the oldest and most successful branches of quantitative science, tracing back at
least a century to the landmark malaria models of the Nobel Laureate, Sir Ronald
Ross. It has remained a vibrant area of research since Ross, a subdiscipline with
a rigorous theoretical foundation, a highly developed mathematical and statistical
framework, and strong contact with data and with management. The concepts of
theoretical epidemiology have played fundamental roles in understanding disease
dynamics, and in the optimal application of vaccination and other management
strategies. This volume continues that tradition, with papers by some of the leading
researchers of the subject.
Infectious diseases kill millions of people worldwide every year, and sicken bil-
lions of others. Africa has always been a cauldron of devastating diseases, and
malaria remains one of the world’s greatest killers. Despite the heroic efforts of
Ross and others, malaria remains at the top of the world’s public health agenda,
developing resistance to wonder drugs and frustrating public health workers. Char-
itable foundations, like the Gates Foundation, have thus placed the elimination or
control of malaria and other diseases, especially in Africa, at the tops of their agen-
das; but money alone cannot solve the problems. We need new approaches, new
insights, and new methodologies. The quantitative study of infectious diseases has
made remarkable advances in the years since Ross, and powerful new mathematical,
statistical and computational tools are available; but much more needs to be done.
It is thus urgent that quantitative biologists increase their efforts to attack the
problems of infectious diseases in the African subcontinent, and that has led DI-
MACS to sponsor a variety of ongoing efforts to address the scientific challenges
and to train African scientists in the modern methods of the theory of infectious
diseases. This volume is one product of that effort, and will help to strengthen
the foundations and the partnerships that have been initiated. It is a mixture

xiii
xiv PROLOGUE

of pedagogy and research, building from the foundations of the subject to recent
mathematical advances, including especially the application of modern control the-
ory. Most impressively, through a mixture of contributions from U.S., Canadian
and African scientists, it is testimony to the vision of Fred Roberts in sponsoring
these activities, and to the success of his efforts.

Simon Levin
Princeton University
October 14, 2009
 https://doi.org/10.1090/dimacs/075/01

DIMACS Series in Discrete Mathematics

and Theoretical Computer Science
Volume 75, 2010

Introduction to Mathematical Modeling of Infectious

Diseases

Sourya Shrestha1 and James O. Lloyd-Smith2,3

1. Introduction
Despite major advances in science and public health, infectious diseases con-
tinue to cause significant morbidity and mortality in human populations worldwide,
with disproportionate impact in developing countries. A recent survey estimated
that infectious diseases are responsible for more than half of human deaths in sub-
Saharan Africa, and sub-lethal effects of disease impose heavy burdens on quality
of life and economic development (Lopez et al., 2002). Impacts of infectious disease
extend beyond human populations, exacting tolls on domestic animal, wildlife and
plant populations. The combination of complex ecology, rapid evolution in response
to changing circumstances, and the on-going emergence of novel pathogens, ensures
that infectious diseases will continue to pose serious challenges for the foreseeable
future.
Thus there is strong motivation to pursue the scientific study of infectious dis-
eases, and mathematical models make a unique contribution to this endeavor. In-
fectious diseases can exhibit complex nonlinear dynamics, and mathematical models
enable clear and rigorous analysis of the underlying mechanisms. Models provide a
crucial link between individual-level ‘clinical’ knowledge of disease properties and
population-scale patterns of incidence and prevalence, and help to establish the
relative importance of different processes to focus research and management effort.
Models can provide a testing ground to investigate the possible efficacy of alter-
native disease control policies, in settings where direct experimentation is often
ethically or logistically impossible. Finally, the process of formulating and analyz-
ing models has the salutary effect of focusing research questions and forcing clear
enunciation of assumptions and hypotheses.

This chapter is a summary of lectures given by JL-S at the DIMACS Advanced Studies
Institute at AIMS in 2007. We are grateful to Ottar Bjørnstad and Matt Ferrari for sharing
materials that helped with the preparation of these lectures. We are also very grateful to the
students and other instructors at the institute, whose questions and comments helped to improve
the presentation of this material. JL-S was funded by a Center for Infectious Disease Dynamics
Fellowship at Penn State University, and by the RAPIDD program of the Science & Technology
Directorate, US Department of Homeland Security, and the Fogarty International Center, National
Institutes of Health.

0000
c (copyright holder)

2010
c
2 S. SHRESTHA AND J. O. LLOYD-SMITH

In this article we seek to provide a concise introduction to the concepts and

basic methods of infectious disease modelling. We begin by briefly reviewing some
key concepts and terminology for the study of infectious disease dynamics, then
introduce some classical models and broad decisions faced in model design. We dis-
cuss formulation of the transmission term that sits at the heart of infectious disease
models, and approaches to incorporating population heterogeneity and structure.
We conclude with a survey of approaches to parameter estimation, model fitting,
and sensitivity and uncertainty analysis. Our treatment is far from comprehensive
and for details we refer the reader to books by Anderson & May (1991), Diekmann
& Heesterbeek (2000) or Keeling & Rohani (2007).

2. Basic concepts in infectious disease dynamics

2.1. Pathogens. It is conventional among disease modellers to categorize
disease-causing organisms into two broad groups based on their size and life cy-
cle. (i) Microparasites are very small organisms that multiply, often to reach very
large population sizes, within individual hosts. This category includes viruses (such
as influenza or HIV), bacteria (such as Bordetella pertussis that causes whooping
cough and Bacillus anthracis that causes anthrax), protozoa (such as Trypanosoma
species that cause sleeping sickness and Plasmodium species that cause malaria),
and pathogenic fungi (such as Candida species that cause thrush and Tinea pedis
that causes Athlete’s foot). Microparasitic infections range from acute to chronic,
lasting days to years, and cause effects ranging from asymptomatic infection to
rapid death. Host individuals that survive infection often have some degree of im-
munity to re-infection, though the duration of this protection varies greatly among
pathogens. Microparasites have a short generation time relative to their host, and
undergo many generations in the course of a single infection. Hence micropara-
sites can evolve rapidly, with important applied consequences for development of
drug resistance, evasion of host immune responses, and adaptation to changing
environmental circumstances.
(ii) Macroparasites are larger multicellular organisms, which multiply outside
of the host. Macroparasites can be further divided into endoparasites that enter the
host’s body, such as roundworms and flukes, and ectoparasites that dwell on the
surface of the host, such as ticks and mites. Macroparasites typically have longer
generation times than microparasites, and their life cycles tend to be complex often
comprising stages both within and outside the host and specialized infective stages.
Macroparasitic infections are often chronic and sub-lethal, and the host immune
response often serves to contain or limit the infection rather than eliminate it.
From a disease modelling standpoint, there are several important distinctions
between macroparasites and microparasites. Typically, microparasite models clas-
sify hosts according to infection status (e.g. susceptible vs infected), while macropar-
asite models explicitly quantify the parasite burden within each host. The burden
of macroparasites, which accumulates as a result of multiple infection events of the
same host individual, is assumed to affect transmission rates from that host and
morbidity or mortality of the host. In contrast, parasite burden and multiple infec-
tion events are typically assumed to be unimportant for microparasites (i.e. once
infected, further exposures do not matter) – though exceptions exist for models
addressing multi-strain dynamics or other particular questions.
 INTRODUCTION TO MATHEMATICAL MODELING OF INFECTIOUS DISEASES 3

2.2. Host immune response. Immunology is a vast and fast-moving field,

and we certainly do not aim to summarize it here. Instead we present a few deliber-
ately simplified concepts that motivate the formulation of basic disease models. A
more in-depth treatment with a focus on dynamical aspects can be found in Perel-
son & Weisbuch (1997). The host immune response can be broadly divided into
two parts. The innate immune response is an intrinsic, mostly non-specific re-
sponse to any foreign intruder, which provides a first line of defense particularly for
pathogens that the host has not encountered before. The acquired or adaptive
immune response is a pathogen-specific defense based on recognition of char-
acteristic molecular ‘signatures’ of pathogens that have been encountered before.
The acquired immune response is the basis for the practice of vaccination, which
is based on exposing the host to molecules from the parasite to prime the immune
system for subsequent exposures.
A greatly simplified timecourse of the immune response to an acute micropara-
sitic infection is as follows. Following infection with a bacterial pathogen, the innate
immune response is activated immediately as macrophages recognize molecules in
the bacterial wall as foreign particles. Macrophages begin killing the bacteria, and
they also produce chemical signals or chemokines that recruit neutrophils and other
innate effectors to the site of infection to aid in killing the bacteria. The adaptive
part of the immune response begins several days after the beginning of the infection,
stimulated by other chemokines and antigens (molecular motifs from the parasite)
which stimulate antigen-specific B cells. These stimulated B cells multiply to pro-
duce plasma B cells that in turn produce antibodies (large molecules that bind
the corresponding antigen with high affinity). These antibodies bind to the anti-
gens on the bacteria, and cytotoxic T cells recognize the bound antibodies and kill
the bacteria, eventually eliminating the infection. Apart from producing plasma
cells, the stimulated B cells also produce long-lived memory B cells. This helps the
immune system to react swiftly and effectively if the host is later exposed to the
same antigen, so re-infection by the same bacterial strain is less likely. Depending
on the efficacy of the memory response, that host may be said to be ‘immune’ to
that bacterial pathogen. The duration and efficacy of immunity can vary greatly
from one pathogen to another, from essentially no lasting immunity in the case of
gonorrhea to lifelong protective immunity in the case of measles.
Immunology has mostly been a stand-alone field, but recent advances in im-
munology as well as epidemiology and disease ecology have generated both the
need and the interest to study the immune system in conjunction with epidemi-
ological aspects of disease dynamics. The interaction between pathogens and the
host immune system is likely to affect various characteristics of an infection, such as
how much pathogen the host will be carrying during the infection or how long the
infection will last. These characteristics in turn will influence epidemiological prop-
erties of the disease, including transmissibility. These complexities are beyond the
scope of this chapter, so we will direct readers to a sampling of recent papers that
address the interaction between immunology and epidemiology. (Schmid-Hempel,
2008; Antia et al., 2005; Mideo et al., 2008; King et al., 2009)

2.3. Clinical course of disease. Once a pathogen becomes established in a

host, the infection goes through different phases as it runs its course. Understanding
the details of the course of infection is crucial when modelling disease spread. One
is typically concerned about the time it takes for a newly infected host to become
4 S. SHRESTHA AND J. O. LLOYD-SMITH

Table 1. Incubation, latent and infectious periods (in days) for a

variety of viral and bacterial infections. Adapted from Anderson
and May (1991).

Infectious Incubation Latent Infectious

disease period period period
Measles 8 - 13 6-9 6-7
Mumps 12 - 16 12 - 18 4-8
Pertussis 6 - 10 21 - 23 7 - 10
Rubella 14 - 21 7 - 14 11 - 12
Diphtheria 2-5 14 - 21 2-5
Chicken pox 13 - 17 8 - 12 10 - 11
Hepatitis B 30 - 80 13 - 17 19 - 22
Poliomyelitis 7 - 12 1-3 14 - 20
Influenza 1-3 1-3 2-3
Smallpox 10 - 15 8 - 11 2-3
Scarlet fever 2-3 1-2 14 - 21

infectious and begin transmitting, the time it takes for the onset of symptoms,
and the duration of infectiousness. These details correspond to basic parameters in
epidemic models, and their values will determine basic properties of the resulting
epidemic curves, some of which we shall discuss in the later sections. For now we
introduce some of the frequently-used terminologies:
Incubation period: the time from infection to the onset of symptoms.
Latent period: the time from infection to the onset of transmissibility.
This is also called the pre-patent period for macroparasites.
Infectious period: the time during which individual can transmit disease.
Generation time (or serial interval): the time period between infection
of one host and infection of other secondary cases caused by that host.
Table 1 shows the range of values for these periods for some important micropar-
asites. Note that the incubation and latent periods are not always equal, so the
onset of transmission can come before or after the onset of symptoms for some
pathogens. This has important consequences for the ability to control these disease
(Fraser et al., 2004).

2.4. Transmission. Transmission of infection between individuals is the cen-

tral process of infectious disease dynamics – indeed it is the reason why these disease
are ‘infectious’ – so it is essential to consider transmission carefully in designing an
epidemic model. There are many different modes of transmission (see Table 2),
and models must account for the relevant modes and how they affect the disease
spread. Often one has to confront questions such as:
• What is the host contact structure relevant to this mode of transmission?
For example, sexually transmitted diseases (STDs) clearly follow different
contact structures from respiratory pathogens.
• Are there important heterogeneities among hosts that will impact trans-
mission?
• What disease control measures are relevant for this mode of transmission?
 INTRODUCTION TO MATHEMATICAL MODELING OF INFECTIOUS DISEASES 5

The answers to these questions gives us a good platform to develop accurate models
of disease dynamics. We will return to the topic of different transmission models
and their consequences in section 4.1.
2.5. Epidemiological terms and population-level patterns. Infectious
disease epidemiology is the study of the spread of disease at the population level.
Here are a few basic terms that are used in epidemiological descriptions of infectious
diseases:
Incidence: the number of new infections per unit time.
Prevalence: the proportion of population that is infected at a particular
time.
Attack rate: the proportion of susceptible individuals in a given setting
that become infected during a given interval.
Force of infection: the per capita rate of infection per unit time (i.e. the
hazard rate of infection experienced by each susceptible individual).
Seroprevalence: the proportion of population carrying antibodies indicat-
ing past exposure to pathogen.
The population-level patterns of disease spread can be broadly categorized as
follows (see Fig 1 for schematic depictions):
Endemic infections: infections which do not exhibit wide temporal fluc-
tuations in incidence or prevalence in a defined place. For microparasites,
the term ‘endemic’ can also be used to indicate an infection that can
persist locally without the need for reintroduction from outside host com-
munities. Stable endemicity is where the incidence of infection or disease
shows no secular trend for increase or decrease.
Simple epidemic: an outbreak of infection entailing a rapid increase in in-
cidence followed by decline and (possibly temporary) disappearance of the
pathogen. This epidemic pattern is typical of the microparasitic infections
with high transmission rates, short generation times, and long-lasting host
immunity. An epidemic usually begins with an exponential rise in the
number of cases and a subsequent decline as the population of susceptible
hosts is exhausted (or control measures are imposed).
Recurrent epidemics: a population-level pattern in which simple epidemics
occur sporadically due to repeated introduction of the pathogen. Follow-
ing each epidemic there may be a ‘refractory period’ in which the suscepti-
ble population is diminished so that another epidemic cannot occur. After

Table 2. Different modes of transmission

Modes Diseases
Direct (droplet, aerosol, fomite) influenza, measles, SARS
Sexual transmission HIV, gonorrhea, HSV-2, chlamydia
Vector-borne (mosquitoes, malaria, trypanosomiasis,
tsetse flies, sandflies) leishmaniasis
Free-living infectious stages helminths, anthrax
and environmental reservoirs
Waterborne, food-borne, cholera, polio, Salmonella
fecal-oral
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