E1. Epidemiology

LECTURE NOTE FOR EPIDEMIOLOGY
FOR HEALTH OFFICER STUDENTS
November, 2012
Lecture note of epidemiology for health officer students
Contents
CHAPTER ONE: INTRODUCTION TO EPIDEMIOLOGY 4
1.1. 41.2.
51.3.
51.4.
61.5.
61.6.
6CHAPTER TWO: COMMUNICABLE DISEASE EPIDEMIOLOGY
10
2.1. Introduction: 10
A. 11B.
14C.
14D.
16E.
29F.
30G.
32H.
33CHAPTER THREE: BASIC MEASURMENTS IN EPIDEMIOLOGY
31
3.1. 353.2. 37A.
37B. 403.3.
433.4. 453.5.
Standardization of rates 41
3.6. 491. Censuses:
44
2. 493.
50CHAPTER FOUR: EPIDEMIOLOGICL STUDY DESIGNS
45
4.1. 514.2.
511.
512.
56Case-Control
57
4.3. Measures of association and impact 63
4.4. Analysis of cause effect relationship 66
A. 74B.
78CHAPTER FIVE: SCREENING IN DISEASE CONTROL
By Shimeles Dagne (MPH)Page 2

72
5.1. Definition: 72
5.2. Purposes of screening: 73
5.3. Types of screening 73
5.4. Screening tests and evaluation of screening tests 74
A. 82B.
855.5. Criteria for establishing screening program
77
CHAPTER SIX: INVESTIGATION OF EPIDEMICS 79
6.1. Levels of Disease Occurrence 79
6.2. Types of epidemics 80
6.3. Investigation and control of an epidemic 82
A. 91B. 91C.
92D. 926.4.
Management of epidemics 91
6.5. Challenges of investigating out brakes 93
CHAPTER SEVEN: EPIDEMIOLOGIC SURVILLANCE 94
7.1. Introduction 94
7.2. Objectives of surveillance 94
7.3. Attributes, activities of a surveillance system and sources of data 95
7.4. Types of Surveillance 96
7.5. Criteria for selection of disease for surveillance: 97
7.6. Integrated Disease Surveillance and Response (IDSR): Concept and Experience in Ethiopia 99
CHAPTER ONE: INTRODUCTION TO EPIDEMIOLOGY

1.1. Definition
⇒ The term epidemiology is derived from the Greek words
✓ Epi, which means “on or upon;”
✓ Demos, which means “the common people;” and
✓ Logy, which means “study.
⇒ Putting these pieces together yields the following definition of epidemiology: “the study of that which falls
upon the common people.”

⇒ Epidemiology can also be defined as the “branch of medical science which treats epidemics.” The latter
definition was developed by the London Epidemiological Society, which was formed in 1850 to determine the
causes of cholera and other epidemic diseases and methods of preventing them.
⇒ Epidemiology is the study of the frequency, distribution, and determinants of health and health-related states
or events in specified population, and the application of this knowledge for the promotion of health, prevention
and control of diseases /health problems.
⇒ Key words in the definition are:
1. Distribution: Who? Where? And when? of occurrence of health and health related events
2. Determinants: factor which may be event, characteristic or any definable entity that brings about
change in health and health related conditions. It refers to “why diseases occur in certain places? In
a certain period? Or in a certain population groups?”
3. Health, and health related events:
✓ Epidemiology is concerned not only with disease but events like birth, death, migration, e.t.c.
✓ The central concern of epidemiology is promotion and maintenance of health through the
prevention of diseases.
4. Human population:
✓ The definition emphasizes that epidemiologists are concerned with the collective health of the
people in communities; unlike the clinicians who are concerned with the health of the
individual.
✓ Though epidemiology is concerned with population, there is strong interrelation with clinical
medicine.
5. Application:
✓ Epidemiology is an applied science.
✓ The ultimate purpose of all epidemiological studies is the prevention and control of health
problems.
1.2. History of epidemiology

⇒ Although epidemiologic thinking has been traced to the time of Hippocrates, the discipline did not flourish
until the 1940s. Some key dates and contributions to the development of epidemiologic thinking and methods
include:
✓ 1662- John Graunt published Natural and Political Observations on the Bills of Mortality. He was the
first to quantify patterns of birth, death and disease occurrence, noting male- female disparities, high
infant mortality, urban-rural differences, and seasonal variations.
✓ 1747- Lind used an “experimental” approach to prove the cause of scurvy by showing it could be
treated effectively with fresh fruit.
✓ 1839- William Farr took responsibility for medical statistics in the Office of the registrar General for
England and Wales. He extended the epidemiologic analysis of morbidity and mortality data, looking at
effects of marital status, occupation, and altitude.

✓ 1854 – John Snow demonstrated that the risk of mortality due to cholera was related to the drinking
water provided by a particular supplier in London. He used a “natural experiment” to test his
hypothesis. In another study conducted by Snow in 1854, he linked an epidemic of cholera to a specific
pump, the “Broad Street Pump”. According to literatures, Snow removed the handle of that pump and
aborted the cholera epidemic.
⇒ Originally epidemiology was concerned with epidemics of communicable disease.
⇒ Lately, epidemiology was extended to endemic communicable diseases and non-communicable infectious
diseases.
⇒ More recently, epidemiologic methods have been applied to chronic diseases, injuries, birth defects, maternal
and child health, occupational health, and environmental health.
⇒ Now, even health behaviours, such as care-seeking, safety practices, violence, and hygienic practices are valid
subjects for epidemiologic investigation.
1.3. Application/uses of epidemiology

⇒ Epidemiology has been used in several ways in the planning and evaluation of health intervention in an effort
to improving the health status of the population. Four uses are mentioned here:
● Elucidation of the natural history of disease
● Description of the health status of the population
● Establishing causation of disease
● Evaluation of intervention (Evaluating efficaciousness and effectiveness of interventions)
● Supply information for decision:
✓ Individual: behavioral changes… smoking, contraception, sexual
✓ Public health : Planning interventions, priority setting, resource allocation, evaluating effectiveness
of intervention (evaluation)
1.4. Basic assumptions of epidemiology

1) Human disease does not occur at random.
2) Human disease has causal and preventive factors that can be identified through systematic investigation
of different populations or subgroups of individuals within a population in different places or at
different time
1.5. Branches of epidemiology
1) Descriptive Epidemiology – Defines the amount and distribution of health problems. It answers the
questions: Who, what and where.
2) Analytic Epidemiology – Analyses the causes or determinants of health and disease. Answers the questions
why and how.
1.6. Theories and principles of disease causation

● Cause of disease: is an event, condition, characteristic or a combination of these factors which produces the
disease event and without which the disease event either would not occur at all or would not occur until some
later time.
● There are different principles of disease causation:

1) Supernatural theory:
✓ In the early past, disease was thought mainly due to the curse of God or the devil force of
demons.
✓ 30% of developing and 10% of developed countries population is under this thought and
become obstacle for control of some diseases.
2) Hippocratic theory:
✓ Hippocrates is the first physician to reject the supernatural theory. He separated the
discipline of medicine from religion.
✓ Believing and arguing that disease was not a punishment inflicted from God/gods but rather
the product of :
o Environmental factors
o Diet and
o Living habits.
3) The single germ theory:
✓ Sometimes called pure determinism
✓ A theory which says that a germ causes a disease (𝐺𝑒𝑟𝑚 ↔ 𝑑𝑖𝑠𝑒𝑎𝑠𝑒 𝑖𝑛 𝑡ℎ𝑒 ℎ𝑜𝑠𝑡 ).
✓ It is the older theory.
o Each disease will be caused by a germ
o Without the germ the disease will not be caused
o By introducing the germ that disease can be caused in animals experimentally
o That germ can be isolated from that sick animal experimentally
4) Classic epidemiological theory:
✓ Disease occur only when the host and environmental factors make the agent sufficient enough to
cause the disease
5) Ecological disease causation theory:
✓ In the ecology there are more than one factors exist with certain degree of interaction.
✓ Therefore, for a disease to occur there has to be more than one factor.
✓ This theory/concept is known as multiple causation or web causation of disease.

✓ 𝐹𝑎𝑐𝑡𝑜𝑟 𝐴 + 𝐹𝑎𝑐𝑡𝑜𝑟 𝐵 + 𝐹𝑎𝑐𝑡𝑜𝑟 𝐶 + ⋯ → 𝐷𝑖𝑠𝑒𝑎𝑠𝑒

6. Multifactorial disease causation theory
✓ Several factors acting jointly, cumulatively, complementally, or in unexplained manner can lead
to disease.
✓ The causes of disease can be classified in to two:
a) Primary causes – these are the factors which are necessary (in whose absence the disease
will not occur) but not sufficient causes for a disease to occur. The term “etiologic agent”
can be used instead of primary cause for Infectious causes of diseases. For example
“Mycobacterium tuberculosis” is the primary cause (etiologic agent) of pulmonary
tuberculosis.
b) Risk factors (contributing, predisposing, or aggravating factors).
✓ These are not the necessary causes of disease but they are important for a disease to
occur.
✓ A factor associated with an increased occurrence of a disease is risk factor for the
exposed group; and a factor associated with a decreased occurrence of a disease is a
risk factor for the non exposed group.
✓ Risk factors could be related to the agent, the host and the environment and include:
✓ The etiology of a disease is the sum total of all the factors (primary causes and risk factors)
which contribute to the occurrence of the disease.
✓ It is the interaction of the agent, the host, and the environment which determines whether or not
a disease develops, and this can be illustrated using the epidemiologic triangle.
● There are also different models which illustrate concept of disease causation.
✓ Model: is a schematic description of a system or phenomenon which accounts for its known and
inferred properties.
✓ The followings are some of the models of disease causation:
a. Epidemiological triangle/triad model
● The epidemiologic triad or triangle is the traditional model of infectious disease causation. It has
three components: an external agent, a susceptible host, and an environment that brings the host and
agent together, as shown in the two diagrams:
● Infectious diseases result from the interaction of infectious agent, susceptible host/reservoir and
environment that brings the host and the agent together.

o Agent: refers to an Infectious microorganism virus, bacteria, parasite, or other microbe.
o Host: host factors influence individual's exposure, susceptibility or response to a causative
agent. For example- age, sex, race, socio-economic status, and behaviours (smoking, drug
abuse, lifestyle, sexual practices and contraception, eating habits) affect exposure.
o Environment: environmental factors are extrinsic factors, which affect the agent and the
opportunity for exposure.
✓ Physical factors: such as geology, climate, and physical surrounding (home, hospital);
✓ Biologic factors such as insects that transmit the agent; and
✓ Socio-economic factors such as crowding, sanitation, and the availability of health
services
Figure 1.1: The ecological triangle/triad of disease causation

● The model implies that each must be analysed and understood for comprehension and predictions of
patterns of a disease.
● A change in any of the components will alter an existing equilibrium to increase or decrease the
frequency of the disease.
b. The web causation model
● The essence of the concept is that effects (diseases) never depend on single isolated causes, but
rather develop as a result of chains of inter-related causes.
● The large number of inter-related causes creates a condition that may appropriately be
conceptualized as a “web”, which in its complexity and origins lies quite beyond our
understandings.
● This model is most important for chronic diseases
c. The Wheel Model
● The wheel consists of the hub/center, the host or human which has genetic makeup as its core.
● The relative size of the different components of the wheel depend on the specific disease under
consideration
● For hereditary diseases, the genetic core would be larger

Figure 1.2: The wheel model of disease causation

d. The causal pie model
● Causal pie model is one of the models, which takes into account multiple factors which are important in
causation of disease. In the causal pie model, the factors are represented by pieces of the pie called
component causes:
● The Rothmans’s causal pie model illustrates the factors that act to cause disease as pie. The whole pie
making up the sufficient cause for the disease.
● All factors (component causes) together form the sufficient cause while component cause A constitutes
the necessary cause.
Figure 1.3: Rothman's Causal Pies: Conceptual Scheme for Disease Causation
● Component, sufficient and necessary causes.
o This has come for multi-factorial nature of causation in many diseases.
✓ Sufficient Cause:
o As it is in the figure, the whole components of a pie make the sufficient cause for a disease.
o A disease may have more than one sufficient cause; each sufficient cause is composed of
several component causes.
✓ Component Cause:
o Each factor (pieces in the pie) that contributes to causation of a disease is called component
causes.
✓ Necessary Cause:
o A factor that is necessary (or without which) the disease doesn’t exist or occur is a necessary
cause
● Not all associations between exposure and disease are causal. A cause of a disease can be defined as a
factor (characteristic, behaviour, event, etc.) that influences the occurrence of disease.
o If disease does not develop without the factor being present, then we term the causative factor
"necessary".
o If the disease always results from the factor, then we term the causative factor "sufficient".

CHAPTER TWO: COMMUNICABLE DISEASE EPIDEMIOLOGY

2.1. Introduction:
● Communicable disease: is an illness due to a specific infectious agent or its toxic products that arises
through transmission of that agent or its products from an infected person, animal or reservoir to a
susceptible host, either directly or indirectly through an intermediate plant or animal host, vector or
inanimate environment.
● Communicable disease epidemiology: is the study of circumstances under which both infection and disease
occur in a population and the factors which influence their frequency, spread and distribution of infectious
diseases.
● Despite the great scientific advances that have reduced morbidity and mortality from communicable
diseases over the past decades, communicable diseases:
⇒ Continue to account for a major proportion of acute illness, even in technologically advanced
countries, though the types of diseases vary from place to place.
⇒ Occur in epidemic forms
⇒ The problem is exacerbated by:
✓ Poor socio-economic status
✓ Poor personal and environmental hygiene
✓ Inadequate health service coverage, etc.
● Some important aspects of infectious diseases are discussed below.
A. Natural History of Diseases

♦ The “natural history of disease” refers to the progression of disease process in an individual over time, in the
absence of intervention.
✓ The process begins with exposure to the causative agent capable of causing disease.
✓ Without medical intervention, the process ends with recovery, disability, or death.
✓ Most diseases have a characteristic natural history, although the time frame and specific
manifestations of disease may vary from individual to individual.
✓ The usual course of a disease may be halted at any point in the progression by preventive and

therapeutic measures, host factors, and other influences.
✓ There are four stages in the natural history of a disease. These are:
✓ Stage of susceptibility
✓ Stage of pre-symptomatic (sub-clinical) disease
✓ Stage of clinical disease
✓ Stage of disability or death
Figu
re 2.1: The natural history of infectious diseases
1. Stage of susceptibility:
✓ In this stage, disease has not yet developed, but the groundwork has been laid by the presence of
factors that favor its occurrence.
✓ Example: unvaccinated child is susceptible to measles.
✓ Here a contact refers to an association between a susceptible host and a reservoir of infection,
which creates an opportunity for the infectious agents to enter the host.
✓ In the stage of exposure, the susceptible host has come into close contact with the infectious
agent, but it has not yet entered the host’s body cells. Examples of an exposed host include:
o a person who shakes hands with someone suffering from a common cold
o a child living in the same room as an adult with tuberculosis
o a person eating contaminated food or drinking contaminated water
2. Stage of Pre-symptomatic (sub-clinical) disease:
✓ In this stage there are no manifestations of the disease but pathologic changes (damages) have
started to occur in the body.
✓ The disease can only be detected through special tests since the signs and symptoms of the
disease are not present. Examples:
♦ Detection of antibodies against HIV in an apparently healthy person.
♦ Ova of intestinal parasite in the stool of apparently healthy children.
✓ The pre-symptomatic (sub-clinical) stage may lead to the clinical stage, or may sometimes end
in recovery without development of any signs or symptoms.
3. The Clinical stage
✓ At this stage the person has developed signs and symptoms of the disease.
✓ The clinical stage of different diseases differs in duration, severity and outcome.
✓ The outcomes of this stage may be recovery, disability or death. Examples:

♦ Common cold has a short and mild clinical stage and almost everyone recovers quickly
♦ Polio has a severe clinical stage and many patients develop paralysis becoming disabled
for the rest of their lives.
♦ Rabies has a relatively short but severe clinical stage and almost always results in death.
♦ Diabetes Mellitus has a relatively longer clinical stage and eventually results in death if
the patient is not properly treated.
4. Stage of outcome
✓ Some diseases run their course and then resolve completely either spontaneously or by
treatment.
✓ In others the disease may result in a residual defect, leaving the person disabled for a short or
longer duration.
✓ Still, other diseases will end in death.
✓ Disability is limitation of a person's activities including his role as a parent, wage earner, etc

Examples:
♦ Trachoma may cause blindness
♦ Meningitis may result in blindness or deafness.
♦ Meningitis may also result in death.
B. Components of Infectious Disease Process
⇒ Infectious diseases result from the interaction of infectious agent, susceptible host/reservoir and environment
that brings the host and the agent together.
o Agent: refers to an Infectious microorganism virus, bacteria, parasite, or other microbe.
o Host: host factors influence individual's exposure, susceptibility or response to a causative agent. For
example- age, sex, race, socio-economic status, and behaviours (smoking, drug abuse, lifestyle, sexual
practices and contraception, eating habits) affect exposure.
o Environment: environmental factors are extrinsic factors, which affect the agent and the opportunity
for exposure. Physical factors such as geology, climate, and physical surrounding (e.g., maternal
waiting home, hospital); biologic factors such as insects that transmit the agent; and socio-economic
factors such as crowding, sanitation, and the availability of health services.
C. Levels of Prevention
⇒ Disease prevention means to interrupt or slow the progression of disease. Therefore, the aim is to push back the
level of detection and intervention to the precursors and risk factors of disease. Hence, epidemiology plays a
central role in disease prevention by identifying those modifiable causes.
⇒ The different points in the progression of a disease at which one can intervene can be classified according to
three levels of prevention: primary, secondary, and tertiary.
1) Primary prevention: The objectives here are to promote health, prevent exposure, and prevent disease.
✓ Health promotion:
♦ This consists of general non-specific interventions that enhance health and the body’s ability
to resist disease, such as measures aimed at the improvement of socio-economic status
through the provision of adequately- paid jobs, education and vocational training, affordable
and adequate housing, clothing, and food, old-age pension benefits; emotional and social
support, relief of stress, etc.
♦ In short it is any intervention that promotes a healthier and happier life.
✓ Prevention of exposure:

♦ This includes actions such as the provision of safe and adequate water, proper excreta
disposal, vector control, safe environment at home (e.g., proper storage of insecticides and
medicines, out of children’s reach), at school and at work (e.g., proper ventilation, monitoring
of harmful substances in factories), and on the streets (e.g., driver licensing laws).
✓ Prevention of infection or disease:
♦ This occurs during the latency period between exposure and the biological onset of disease.
♦ An example for this is immunization.
● Immunization against an infectious organism does not prevent it from invading the
immunized host, but prevents it from establishing an infection.
● Active immunization means exposing the host to a specific antigen against which it will
manufacture its own protective antibodies after an interval of about three weeks (during
which the immunized person remains susceptible to the disease).
● Passive immunization means providing the host with the antibodies necessary to fight
against disease.
● Both forms of immunization act after exposure. However,
➢ For active immunization to be protective, the timing of its administration must be at
least three weeks prior to exposure.
➢ Passive immunization, on the other hand, is commonly given after exposure has
occurred (as in the case of exposure to rabies or tetanus), or shortly before an
exposure is expected, as in the administration of immune globulin to prevent viral
hepatitis A).
✓ Breastfeeding is an example of an intervention that acts at all three levels of primary prevention:
● Health promotion: by providing optimal nutrition for a young child, either as the sole diet
up to four months of age, or as a supplement in later months.
● Prevention of exposure: by reducing exposure of the child to contaminated milk.
● Prevention of disease after exposure: by the provision of anti-infective factors, including
antibodies, white blood cells, and others.
2) Secondary prevention: After the biological onset of disease, but before permanent damage sets in, we
speak of secondary prevention.
✓ The objective here is to stop or slow the progression of disease so as to prevent or limit permanent
damage, through the early detection and treatment of disease.
✓ Examples:

● Breast cancer (prevention of the invasive stage of the disease)

● Trachoma (prevention of blindness)
● Syphilis (prevention of tertiary or congenital syphilis)
3) Tertiary prevention: After permanent damage has set in,
✓ The objective of tertiary prevention is to limit the impact of that damage. The impact can be
physical, psychological, social (social stigma or avoidance by others), and financial.
✓ Strategy at this stage in general is rehabilitative
✓ Rehabilitation refers to the retraining of remaining functions for maximum effectiveness and should
be seen in a very broad sense, not simply limited to the physical aspect.
✓ Thus the provision of special disability pensions would be a form of tertiary prevention.
D. Chain of disease transmission

⇒ Transmission is a process in which several events happen one after the other in the form of a chain. Hence, this
process is known as a chain of transmission.
⇒ Chain of disease transmission:
✓ This refers to a logical sequence of factors or links of a chain that are essential to the development of
the infectious agent and propagation of disease.
✓ Infection implies that the agent has achieved entry and begun to develop or multiply, whether or not the
process leads to disease. This why chain of disease transmission is sometimes called the chain of
infection, or transmission cycle
✓ The six factors (components) involved in the chain of disease transmission are:
1) Infectious agent (etiologic or causative agent)
2) Reservoir host
3) Portal of exit
4) Mode of transmission
5) Portal of entry
6) Susceptible host

Figure 2.2: Factors involved in the chain of communicable disease transmission.

1. Infectious agent:
⇒ An organism that is capable of producing infection or infectious disease. On the basis of their size, etiological
agents are generally classified into:
a. Metazoa (multicellular organisms). (E.g. Helminthes).
b. Protozoa (Unicellular organisms) (e.g. Amoebae)
c. Bacteria (e.g. Treponema palladium, Mycobacterium tuberculosis, etc.)
d. Fungus (e.g. Candida albicans)
e. Virus (e.g. Chickenpox, polio, etc.)
2. Reservoirs of infectious agents
⇒ The place where the infectious agent is normally present before infecting a new human is called a reservoir.
⇒ This component of an infectious process is defined as an organism or habitat, in which an infectious agent
normally lives, transforms, develops and/or multiplies. Thus, reservoirs of infection include human beings,
animals, and environmental sources (plants, soil, water, etc).
⇒ Without reservoirs, infectious agents could not survive and hence could not be transmitted to other people.
⇒ Many infectious diseases have more than one reservoir.
⇒ Humans and animals which serve as reservoirs for infectious agents are known as infected hosts and non living
things which serve as reservoirs for infectious agents are called vehicles (not infected hosts) because they are
not alive.

⇒ The reservoir may or may not be the source from which an agent is transferred to a host. For example, the
reservoir of Clostridium botulinum is soil, but the source of most botulism infections is improperly canned food
containing C. botulinum spores.
⇒ Types of reservoirs of infectious agent:
1. Humans as reservoir of infectious agents.

✓ There are a number of important pathogens that are specifically adapted to man, such as: measles,
smallpox, typhoid, meningococcal meningitis, gonorrhea and syphilis. The cycle of transmission is
from human to human.
✓ Man can be reservoir for infectious agents in two forms:
a. Clinical cases
● Persons with symptomatic illnesses
● This people are already sick and are able to transmit the agent. But they are less likely to
transmit infection widely because of their symptoms increases their likelihood of getting
diagnosis and treatment.
b. Carriers
● A carrier is a person without apparent disease, but who are able to transmit an agent of a disease.
● The importance of carriers in the transmission of disease depends on their:
♦ Number,
♦ Detectability,
♦ Mobility and
♦ Chronicity.
● Carriers may be:
1. Healthy or asymptomatic carriers
✓ These are persons whose infection remains unapparent.
✓ They transmitting infection without ever showing signs of the disease
✓ For example, in poliovirus, meningococcal and hepatitis virus infections, there is a
high carrier rate.
2. Incubatory or precocious carriers
✓ These are individuals or persons who excrete the pathogen during the incubation

period (i.e. before the onset of symptoms or before the characteristic features of the
disease are manifested).
✓ They transmit infection by shedding the agent before the onset of clinical
manifestations
✓ E.g. Measles, mumps, chickenpox and hepatitis.
3. Convalescent carriers
✓ These are those who continue to harbor the infective agent after recovering from the
illness.
✓ They transmit infection after the time of recovery from the disease /after symptoms
disappear)
✓ E.g. Diphtheria, Hepatitis B virus.
4. Chronic carriers
✓ The carrier state persists for a long period of time.
✓ After they are cured, they harbour an agent they shed the agent for a long period of
time, or even indefinitely
✓ E.g. Typhoid fever, Hepatitis B virus infection
● Carriers transmit a disease at a higher rate because:
✓ Carriers commonly transmit disease because they do not realize they are infected, and
consequently take no special precautions to prevent transmission.
✓ Symptomatic persons who are aware of their illness, on the other hand, may be less likely
to transmit infection because they are either too sick to be out and about, take precautions
to reduce transmission, or receive treatment that limits the disease.

Figure 2.3: Time course of a disease in relation to its clinical expression and communicability
⇒ Time course of a disease in relation to its clinical expression and communicability includes:
● Pre-patent Period: The time interval between biological onset and the time of first shedding of the agent.
● Incubation Period: Interval between infection (biological onset) and the first clinical manifestations of
disease (clinical onset).
● Communicable Period: The time interval during which the agent is shed by the host.
● Latent Period: The interval between recovery and the occurrence of relapse or recrudescence in clinical
disease.
✓ Examples of diseases in which a latent period can occur include malaria and epidemic typhus.
✓ The term “latent period” is sometimes used instead to refer to the incubation period.
● Generation time: The time interval between biological onset and the maximum communicability.
2. Animals as reservoir of infectious agents
● Some infective agents that affect man have their reservoir in animals.
● The term “zoonosis” is applied to disease transmission from animals to man under natural
conditions. Infectious diseases such as rabies, where the infectious agents can be transmitted from
animal hosts to susceptible humans, are called zoonoses (singular, zoonosis).
● For example:
➢ Bovine tuberculosis - cow to man

➢ Brucellosis - Cows, pigs and goats to man

➢ Anthrax - Cattle, sheep, goats, horses to man
➢ Rabies - Dogs, foxes and other wild animals to man
➢ Man is not an essential part (usual reservoir) of the life cycle of the agent.
Animal …….. Animal…………Animal

↓
Human
3. Non-living things (Environment )as reservoir:
● Non-living things like water, food and soil in the environment can also be reservoirs for infectious
agents, but they are called vehicles (not infected hosts) because they are not alive.
● Many fungal agents, including parasitic infestations grow and complete their growth in soil and
water.
● Many of the agents are basically saprophytes living in soil and fully adapted to live freely in nature.
Biologically, they are usually equipped to withstand marked environmental changes in temperature
and humidity. E.g.
o Clostridium botulinum etiologic agent of Botulism
o Clostridium tetani etiologic agent of Tetanus
o Clostridium welchi etiologic agent of gas gangrene
o Hookworm, Ascaries, Schistosomiasis
3. Portal of exit
⇒ Before an infectious agent can be transmitted to other people, it must first get out of the infected host. The site
on the infected host through which the infectious agent gets out is called the portal of exit.
⇒ The portal of exit usually corresponds to the site where the pathogen is localized. For example,
● Influenza viruses and Mycobacterium tuberculosis exit the respiratory tract,
● Schistosomes through urine,
● Cholera vibrios in feces,
● Sarcoptes scabiei in scabies skin lesions, and enterovirus 70, a cause of hemorrhagic conjunctivitis, in
conjunctival secretions.
● Some blood borne agents can exit by crossing the placenta from mother to fetus (rubella, syphilis,
toxoplasmosis), while others exit through cuts or needles in the skin (hepatitis B) or blood-sucking
arthropods (malaria).
⇒ The common routes of exit are described below.
a. Respiratory tract
i. The routes of exit from the respiratory tract are the nose and the mouth.
ii. Some infectious agents get out of the infected host in droplets expelled during coughing,
sneezing, spitting or talking, and then get transmitted to others.
iii. For example, people with tuberculosis in their lungs usually have a persistent cough;
Mycobacterium tuberculosis uses this as its route of exit.
b. Gastrointestinal tract
i. The anus is the route of exit from the gastrointestinal tract (or gut).
ii. Some infectious agents leave the human body in the stool or faeces.
iii. For example, the infectious agents of shigellosis, a disease which can cause bloody diarrhoea,
use this route of exit.
c. Genito-urinary tract:
i. Some types of infectious agents can exit the body through openings of genito-urinary tract.
ii. Example, infectious agents of HIV/AIDS, STDs
d. Skin and mucus membrane
i. Some types of infectious agents can exit the body through breaks in the skin.
ii. For example, this route of exit is used by Plasmodium protozoa, which are present in the blood
and get out of the human body when a mosquito bites through the skin to suck blood.
e. Trans-placenta:
i. Some types of infectious agents can exit the body through placenta.
ii. Example, infectious agents of HIV/AIDS, syphilis
4. Modes of transmission
⇒ Once an infectious agent leaves a reservoir, it must get transmitted to a new host if it is to multiply and cause
disease. The route by which an infectious agent is transmitted from a reservoir to another host is called the
mode of transmission.
● It refers to the mechanisms by which an infectious agent is transferred from one person to another or
from a reservoir to a new host.
● It is important for you to identify different modes of transmission, because prevention and control
measures differ depending on the type.
● Transmission may be direct or indirect.
● Various direct and indirect modes of transmission are summarized in Table 2.1 and discussed below it.
Table 2.1: Summary of different modes of transmission
Mode of transmission Sub-types of transmission
✓ Touching
✓ Sexual intercourse
Direct ✓ Biting
✓ Direct projection of droplets
✓ Across the placenta
✓ Airborne
Indirect ✓ Vehicle-borne
✓ Vector-borne
a. Direct modes of transmission
⇒ Refers to the transfer of an infectious agent from an infected host to a new host, without the need for
intermediates such as air, food, water or other animals.
⇒ Consists of essentially immediate transfer of infectious agents from an infected host or reservoir to an
appropriate portal of entry.
⇒ Direct modes of transmission can occur in two main ways:
1) Direct horizontal
● The infectious agent is spread/transmitted by
✓ Direct contact between people through touching, biting, kissing, sexual intercourse or
✓ Direct projection or spread of respiratory droplets onto the conjunctiva or onto mucus
membrane of eye, nose or mouth during sneezing coughing, spitting or talking. Usually limited
to a distance of about one meter or less.
2) Direct Vertical
● This refers to the transmission of an infectious agent from a pregnant woman to her fetus through the
placenta. Such as:
✓ Transplacental transmission of syphilis,

✓ Mother-to-child transmission (MTCT) of HIV
b. Indirect modes of transmission
⇒ Indirect transmission is when infectious agents are transmitted to new hosts through intermediates.
⇒ An agent is carried from reservoir to a susceptible host by suspended air particles or by animate (vector-mosquitoes,
fleas, ticks...) or inanimate (vehicle-food, water, biologic products, fomites) intermediaries. That is:
✓ Airborne: dust, droplets
✓ Vector-borne: insect animals...
✓ Vehicle-born: food, water, towels...

1) Airborne transmission:
● The infectious agent may be transmitted in dried secretions from the respiratory tract, which can
remain suspended in the air for some time.
● For example, the infectious agent causing tuberculosis can enter a new host through airborne
transmission.
2) Vector-borne transmission:
● A vector is an organism, usually an arthropod, which transmits an infectious agent to a new host.
Arthropods which act as vectors include houseflies, mosquitoes, lice and ticks.
● Vector-borne transmission has two forms:
✓ Mechanical transmission: is a way of transmission in which the vector transmits the pathogens
without any change either in number or form of the disease pathogen. The arthropod transports
the agent by soiling its feet or proboscis, in which case multiplication of the agent in the vector
does not occur. Eg. Trachoma transmission by CHF.
✓ Biological transmission: This is when the agent develops and/or multiplies in the arthropod
before it is transmitted, such as the transmission of malaria by mosquito.
3) Vehicle-borne transmission:
● A vehicle is any non-living substance or object that can be contaminated by an infectious agent,
which then transmits it to a new host. Contamination refers to the presence of an infectious agent in
or on the vehicle.
● Vehicle borne transmission is indirect transmission through contaminated inanimate objects like:

✓ Bedding, toys, handkerchiefs, soiled clothes, cooking or eating utensils, syringes, needles
surgical instruments and other sharp instruments.
✓ Contaminated food and water
✓ Biological products like blood, serum, plasma or IV-fluids or any substance serving as
intermediate means by which an infectious agent is transported and introduced into a
susceptible host through a suitable portal of entry.
● The agent may or may not multiply or develop in the vehicle before it is introduced into man.
● Examples:
✓ The infectious agent of cholera can be transmitted to a person who eats food or drinks water
contaminated with faeces containing the organism.
✓ Sharp instruments contaminated with HIV-infected blood can transmit HIV if they penetrate
the skin of another person.
✓ Soil is a vehicle for some bacteria. For example, a person can be infected with bacteria that
cause tetanus if contaminated soil gets in through broken skin.
5. Portal of entry
⇒ Successful transmission of the infectious agent requires it to enter the host through a specific part of the body
before it can cause disease. The site in which the infectious agent enters to the susceptible host is called the
route of entry.
⇒ The routes of entry are:
a. The respiratory tract: some infectious agents enter the body in air breathed into the lungs. Example:
Mycobacterium tuberculosis.
b. The gastrointestinal tract: some infectious agents enter through the mouth. Example: the infectious
agents causing diarrhoeal diseases enter through the mouth in contaminated food, water or on unclean
hands.
c. The skin or mucus membrane: some can enter through breaks in the skin. Example: malaria parasites
(Plasmodium species) get into the body when an infected mosquito bites through the skin to suck blood.
6. Susceptible host:
⇒ The final link in the chain of infection is a susceptible host. After an infectious agent gets inside the body it has
to multiply in order to cause the disease. In some hosts, infection leads to the disease developing, but in others

it does not.
⇒ Individuals who are likely to develop a communicable disease after exposure to the infectious agents are called
susceptible hosts.
⇒ Different individuals are not equally susceptible to infection, for a variety of reasons. Susceptibility of a host
depends on:
● Genetic or legitimate factors
● Specific immunity and
● Nonspecific factors that affect an individual’s ability to resist infection or to limit pathogenicity
⇒ An individual’s genetic makeup may either increase or decrease susceptibility. For example, persons with
sickle cell trait seem to be at least partially protected from a particular type of malaria.
⇒ Specific immunity refers to protective antibodies that are directed against a specific agent. Such antibodies may
● Develop in response to infection, vaccine, or toxoid (toxin that has been deactivated but retains its
capacity to stimulate production of toxin antibodies) or
● Acquired by transplacental transfer from mother to fetus or by injection of antitoxin or immune

globulin
⇒ Nonspecific factors that defend against infection include
● Skin and mucus membrane
● Mucus, tears, gastric acid secretion
● Cilia in the respiratory tract
● Reflex responses such as coughing and sneezing
⇒ Factors that increase the susceptibility of a host to the development of a communicable disease are called risk
factors.
● Some risk factors arise from outside the individual – for example, poor personal hygiene, or poor
control of reservoirs of infection in the environment.
✓ Factors such as these increase the exposure of susceptible hosts to infectious agents, which
makes the disease more likely to develop.
● Additionally, some people in a community are more likely to develop the disease than others, even
though they all have the same exposure to infectious agents.
✓ This is due to a low level of immunity within the more susceptible individuals. Immunity refers
to the resistance of an individual to communicable diseases, because their white blood cells and
antibodies (defensive proteins) are able to fight the infectious agents successfully.
✓ Low levels of immunity could be due to:
● Disease (like HIV/AIDS) or therapy that suppress immunity/impairs the nonspecific

immune response
● poorly developed or immature immunity, as in very young children
● not being vaccinated
● poor nutritional status (e.g. malnourished children)
● pregnancy
⇒ Finally, we can now summarize the chain of transmission as follows:
● The infectious agent gets out of the reservoir through a route of exit
● It gets transmitted to a susceptible host by a direct or indirect mode of transmission and it gets into the
susceptible host through a route of entry
● If it multiplies sufficiently in the susceptible host it will cause a communicable disease.
● A person or animal lacking sufficient resistance to a particular pathogenic agent to prevent disease if or
when exposed. Occurrence of infection and its outcome are in part determined by host factors. The term
“immunity” is used to describe the ability of the host to resist infection.
⇒ Implications of chain of disease transmission for public health
● Knowledge of the portals of exit and entry and modes of transmission provides a basis for determining
appropriate control measures. In general, control measures are usually directed against the segment in
the infection chain that is most susceptible to intervention, unless practical issues dictate otherwise.
● Interventions are directed at:
✓ Controlling or eliminating agent at source of transmission
✓ Protecting portals of entry

✓ Increasing host’s defences
● Some interventions are directed at the mode of transmission.
✓ Interruption of direct transmission may be accomplished by isolation of someone with infection,

or counseling persons to avoid the specific type of contact associated with transmission.
✓ Vehicle borne transmission may be interrupted by elimination or decontamination of the

vehicle.
✓ For airborne diseases, strategies may be directed at modifying ventilation or air pressure, and
filtering or treating the air.
✓ To interrupt vector borne transmission, measures may be directed toward controlling the vector
population, such as spraying to reduce the mosquito population.
● Some strategies that protect portals of entry are simple and effective. For example,
✓ Bed nets are used to protect sleeping persons from being bitten by mosquitoes that may transmit
malaria.
✓ A dentist’s mask and gloves are intended to protect the dentist from a patient’s blood,
secretions, and droplets, as well to protect the patient from the dentist.
● Some interventions aim to increase a host’s defenses.
✓ Vaccinations promote development of specific antibodies that protect against infection.
✓ On the other hand, prophylactic use of anti-malarial drugs, recommended for visitors to malaria-
endemic areas, does not prevent exposure through mosquito bites, but does prevent infection
from taking root.
● Finally, some interventions attempt to prevent a pathogen from encountering a susceptible host.
✓ The concept of herd immunity suggests that if a high enough proportion of individuals in a
population are resistant to an agent, then those few who are susceptible will be protected by the
resistant majority, since the pathogen will be unlikely to “find” those few susceptible
individuals.
✓ The degree of herd immunity necessary to prevent or interrupt an outbreak varies by disease. In
theory, herd immunity means that not everyone in a community needs to be resistant (immune)
to prevent disease spread and occurrence of an outbreak. In practice, herd immunity has not
prevented outbreaks of measles and rubella in populations with immunization levels as high as
85% to 90%.
✓ One problem is that, in highly immunized populations, the relatively few susceptible persons are
often clustered in subgroups defined by socioeconomic or cultural factors. If the pathogen is
introduced into one of these subgroups, an outbreak may occur.
E. Time line of infection and disease of an infectious disease

⇒ The time lines of infection begin with the successful infection of the susceptible host by infectious agent. The
time line of infectiousness includes the latent period (the time interval from infection to development of
infectiousness) and the period of infectiousness of the host, during which time the host could infect another
susceptible host. The host becomes non-infectious either by recover from the infection or by death. The host
can also become non-infectious while still alive and still harboring the parasite.
⇒ The time line of disease within the host includes the incubation period (the time from infection to development
of symptoms of the disease), and the symptomatic period. The probability of developing symptoms or disease
after becoming infected is referred as pathogenicity. The host eventually becomes asymptomatic either by
recovering from the symptoms or by death. Carrier state develops when the person become asymptomatic but
remains infectious. An inapparent or silent infection is a successful infection that does not develop detected
symptoms, they can be infectious.
Figure 2.4: Time line of infection and disease

⇒ Time line of infection and disease includes:
● Dynamics of infection: susceptible, latent period, infectious period and non infectious (removed, dead,
recovered).

✓ Time line for infection is important for the agent and public health
● Dynamics of disease: susceptible, incubation period, symptomatic period, non diseased (dead, removed,
immune, carrier).
✓ Time line for disease is important to infected person and physician/health worker
F. Spectrum of infectious disease
⇒ Exposure to an infectious agent does not necessarily lead to infection, and an infection does not necessarily
lead to disease. Infection:
✓ May remain asymptomatic or sub-clinical, or
✓ May lead to overt clinical disease
⇒ The impact of disease agents on human host populations is also a bit complex. If a large number of individuals
are equally exposed to an infectious agent, they do not all respond in the same manner. In fact, there may be a
broad range of responses:
✓ Some do not become infected at all
✓ Some become infected but develop no symptoms
✓ Some become infected and develop mild or moderate symptoms
✓ Some become infected and develop severe symptoms
✓ Some become infected and die as a result of their infection
● Thus, the infectious process has a wide spectrum of clinical effects. Effect depends on the nature of the
infectious agent and host susceptibility.
⇒ Spectrum of diseases is the sequence of events that occur in human from the time of exposure to etiological
agent to death.
⇒ In infectious diseases, this spectrum is known as gradient of infection- which reflects the sequence of
manifestations of illness in the host reflecting his response to the infectious agent.
● Spectrum of infectious disease or gradient of infection: different types of host response to an infection
includes:
● In apparent or sub clinical infection
● Mild illness
● Moderate illness
● Severe illness
● Recovery/ death
Figure 2.5: The Spectrum of Illness from Communicable Disease

⇒ The progress of an infectious agent and disease outcome can be quantified as follows:
a) From exposure to infection
● Infectivity: the proportion of exposed susceptible hosts who become infected and measured by
infection rate, as:
𝑡𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑖𝑛𝑓𝑒𝑐𝑡𝑒𝑑 𝑝𝑒𝑟𝑠𝑜𝑛𝑠
𝐼𝑛𝑓𝑒𝑐𝑡𝑖𝑜𝑛 𝑟𝑎𝑡𝑒 = × 100
𝑡𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑠𝑢𝑠𝑢𝑝𝑡𝑖𝑏𝑙𝑒 𝑎𝑛𝑑 𝑒𝑥𝑝𝑜𝑠𝑒𝑑 𝑝𝑒𝑟𝑠𝑜𝑛𝑠
b) From infection to disease

● Pathogenicity: the proportion of infected people who develop clinical disease, and measured by the
clinical-to subclinical ratio, as:
Pathogenicity = 𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑐𝑙𝑖𝑛𝑖𝑐𝑎𝑙 𝑐𝑎𝑠𝑒𝑠 : 𝑡𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑠𝑢𝑏𝑐𝑙𝑖𝑛𝑖𝑐𝑎𝑙 𝑐𝑎𝑠𝑒𝑠
𝑡𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑐𝑙𝑖𝑛𝑖𝑐𝑎𝑙 𝑐𝑎𝑠𝑒𝑠
𝑃𝑎𝑡ℎ𝑜𝑔𝑒𝑛𝑖𝑐𝑖𝑡𝑦 = × 100
𝑡𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑠𝑢𝑏𝑐𝑙𝑖𝑛𝑖𝑐𝑎𝑙 𝑐𝑎𝑠𝑒𝑠
c) From disease to disease outcome

● Virulence: the proportion of persons with clinical disease who become severely ill or die, and measured
by: case fatality rate and hospitalization rate
1. Case-fatality-rate
✓ Case fatality rate is the ratio of the number of deaths caused by a specified disease to the
number of diagnosed cases of that disease.
𝑡𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑑𝑒𝑎𝑡ℎ𝑠 𝑐𝑎𝑢𝑠𝑒𝑑 𝑏𝑦 𝑎 𝑑𝑖𝑠𝑒𝑎𝑠𝑒
𝐶𝑎𝑠𝑒 𝑓𝑎𝑡𝑎𝑙𝑖𝑡𝑦 𝑟𝑎𝑡𝑒 = × 100
𝑡𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑑𝑖𝑎𝑔𝑛𝑜𝑠𝑒𝑑 𝑐𝑎𝑠𝑒𝑠 𝑜𝑓 𝑡ℎ𝑎𝑡 𝑑𝑖𝑠𝑒𝑎𝑠𝑒
✓ For example: Assume 9 deaths among 100 people in a community all diagnosed with the same
disease. This means that among the 100 people formally diagnosed with the disease, 9 died and
91 recovered, or have not died yet. The CFR, therefore, would be 9%.
2. Hospitalization rate

Figure 2.6: Measures of infection and disease outcomes

G. Levels of disease occurrence
⇒ Diseases occur in a community at different levels at a particular point in time. Some diseases are usually
present in a community at a certain predictable level, this is called the expected level, but at times disease may
occur in excess of what is expected.
1) Expected levels
1. Endemic: a persistent level of low to moderate occurrence
2. Hyper endemic: a persistently high level of occurrence
3. Sporadic: occasional cases occurring at irregular intervals
2) Excess of what is expected
1. Epidemic: occurrence of disease in excess of what is expected in a limited period.
2. Outbreak: same as epidemic, often used by public health officials because it is less provocative to the
public.
3. Pandemic: an epidemic spread over several countries or continents, affecting a large number of
people.

Figure 2.7: Levels of disease occurence

H. Spread of Disease through Person-to-Person transmission
⇒ Person to person transmission of an infectious agent is one of the main methods of disease spread in a
community and is dependent on:
● Generation time,
● Herd immunity, and
● Secondary attack rates
1. Generation time: This refers to the period between exposure/infection and the maximum
communicability of the exposed host regardless of whether the disease is apparent or inapparent. In
case of apparent infections generation time may be equivalent to incubation period.
2. Herd immunity: This refers to a community resistance to spread of an infectious agent as a result of
immunity gained by high proportion of individual members of the community. Though it may not be
important to achieve 100% immunity, successful breakage of the chain of infection can be achieved if
the immunity is close to 100%.
✓ Conditions under which herd immunity best functions
a) Single reservoir (the human host): If there is other source of infection it can transmit the
infection to susceptible hosts.
b) Direct transmission (direct contact or direct projection): Herd immunity is less effective
for diseases with efficient airborne transmission.
c) Total immunity: Partially immune hosts may continue to shed the agent, and hence
increase the likelihood of bringing the infection to susceptible hosts.
d) No shedding of agents by immune hosts (no carrier state).
e) Uniform distribution of immunes: Unfortunately, susceptibles usually happen to live in
clusters or pockets because of socioeconomic, religious, or geographic factors.
f) No overcrowding: Overcrowding also increases the likelihood of contact between
reservoirs and susceptible hosts.
✓ However, these conditions for the operation of herd immunity are seldom fulfilled.
3. Secondary attack rate: This is an important measure of spread of disease among contacts of an
index case. It has great use in epidemic situations.
𝑁𝑒𝑤 𝑐𝑎𝑠𝑒𝑠 𝑎𝑚𝑜𝑛𝑔 𝑐𝑜𝑛𝑡𝑎𝑐𝑡𝑠 𝑜𝑓 𝑖𝑛𝑑𝑒𝑥 𝑐𝑎𝑠𝑒𝑠 𝑑𝑢𝑟𝑖𝑛𝑔 𝑡ℎ𝑒 𝑝𝑒𝑟𝑖𝑜𝑑
𝑆𝑒𝑐𝑜𝑛𝑑𝑎𝑟𝑦 𝑎𝑡𝑡𝑎𝑐𝑘 𝑟𝑎𝑡𝑒 = ×
𝑇𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑐𝑜𝑛𝑡𝑎𝑐𝑡𝑠 𝑤𝑖𝑡ℎ 𝑡ℎ𝑒 𝑖𝑛𝑑𝑒𝑥 𝑐𝑎𝑠𝑒𝑠

100
✓ The index cases are excluded from both numerator and denominator.
✓ Index case: The case that brings a household or any other group (community) to the
attention of the public health personnel.

CHAPTER THREE: BASIC MEASURMENTS IN EPIDEMIOLOGY

3.1. Number, ratio, proportion and rate
⇒ Epidemiology is mainly a quantitative discipline, so we should quantify health and health related events. Its
measured quantities and descriptive terms are used to describe groups of persons
⇒ A prerequisite for any epidemiologic investigation is the ability to quantify the occurrence of health and health
related events.
⇒ To quantify health and occurrence of disease, death and other health related conditions in a population we have
to measure them using standard measuring scale and units. Some of the measures include:
✓ absolute or raw number,
✓ ratios,
✓ proportions and
✓ rates
1. Raw Numbers (counts)
⇒ The number of persons in the group studied who have a particular disease or a particular characteristic.
✓ The simplest and most frequently performed quantitative measurement in Epidemiology.
✓ Common descriptive measure
✓ First step in calculating rates
⇒ Example: 10 people in a college dormitory developed infectious hepatitis or 16 stomach cancer patients were
found among foreign born patients etc.
⇒ Use:
✓ Useful for monitoring the occurrence of important infectious diseases, especially outbreaks
✓ Used in drawing an epidemic curve of the new cases of the disease over time
✓ Useful in planning
2. Ratio
⇒ A ratio quantifies the magnitude of one occurrence or condition in relation to another. Compares the relative
frequency of the occurrence of some event to the other event,
⇒ Examples:
✓ The ratio of cases among males to cases among females.
● If there are 15 male cases and 5 female cases of malaria, the ratio of male to female of malaria
is = (15/5 : 5/5)= (15/5 : 1) = 3:1
✓ Sex Ratio (SR): Sex ratio is defined as the total number of male population per 100 female population,
✓ Child-Woman-Ratio (CWR): It is defined as the ratio of the number of children under 5 years of age
to the number of women in the childbearing age group (usually 15-49).
✓ Dependency Ratio (DR): The dependency ratio describes the relation between the potentially self-
supporting portion of the population and the dependent portions at the extremes of age. It is useful in
economic studies.
⇒ Ratio can compare related Categories of Same Variable
In Country X, what is the ratio of males to females in the age group 45-49?
● M/f = 64, 055 males = 0.94: 1
67,795 females
⇒ Ratio also compare different Variables
✓ A city of 4 million people has 400 clinics. Calculate the ratio of clinics per person.
● Ratio = 400 / 4,000,000 = 0.0001 clinics / person
● Multiply by 104 , Ratio = 0.0001 x 104 = 1 clinic / 10,000 persons
3. Proportion
⇒ Proportion is a type of ratio which quantifies occurrences in relation to the population in which these
occurrences take place.
⇒ That is, the numerator is also included in the denominator and the resultant is expressed as percentages, per
1000, 100,000 etc. Percentage is one of the most common ways of expressing proportions
⇒ In order for a count to be descriptive of a group it must be seen in proportion to it, i.e. it must be divided by
the total number in the group.
⇒ Example:
✓ Out of 200 cases of malaria seen at Health Station X last year, 60 were children. The proportion of
children is, (60/200) x 100 = 30%.
✓ The 10 hepatitis cases would have quite a different significance for the dormitory if the dormitory
housed 500 students than if it housed 20. In the 1st case the proportion would be 10/500 or 0.02 or 2
percent - in the second case proportion would be 10/20 or .50
⇒ The use of denominator to convert counts in to proportions seems almost too simple to mention, however,
proportion is one of the basic ways to describe a group.
⇒ One of the central concerns of epidemiology is to find and enumerate appropriate denominators in order to
describe and to compare groups in a meaningful and useful way.
4. Rate:
⇒ Measures the relative frequency of cases per unit of population per unit of time. It can be seen as a proportion
with a time dimension. It measures the occurrence of deaths (mortality), births (natality) and disease
(morbidity).
⇒ A rate is a proportion with a time element, i.e., in which occurrences are quantified over a period of time.
⇒ The term rate appropriately refers to the ratio of cases of event to the population at risk in a specified period.
Where:
✓ K is a constant mainly a multiple of 10 (100, 1000, 10000, etc.).
✓ Population at risk: This could be the mid-year population (population at the first of July 1),
population at the beginning of the year or a more complex definition.
✓ Period for a rate is usually a year.
⇒ Notice three important aspects of this formula:
✓ The persons in the denominator must reflect the population from which the cases in the numerator arose.
✓ The counts in the numerator and denominator should cover the same time period.
✓ In theory, the persons in the denominator must be “at risk” for the event, that is, it should have been
possible for them to experience the event.

⇒ Differences between ratio, proportion and rates
✓ When we call a measure a ratio, we usually mean a non-proportional ratio;
✓ When we call a measure a proportion, we usually mean a proportional ratio that doesn’t measure an event
over time, and
✓ When we use the term rate, we frequently refer to a proportional ratio that does measure an event in a
population over time.
3.2. Measures of occurrence of disease
⇒ Measures of occurrence of disease are measures that quantify the occurrence of disease in a specified
population in a specified time. The frequency of health related events are measured by risk, prevalence and
incidence rate.
A. Incidence rate
⇒ Incidence: The number of new cases or events occurring in a defined population within a given period of time,
commonly one year. Incidence describes the continuing occurrence of new cases of a disease
⇒ It is the basic measure of frequency and is the best indicator of whether a condition is decreasing, increasing or
remaining static.
⇒ Incidence Rate: It is a rate, which measures the occurrence of new cases of disease in the defined population
during a specified period of time.
✓ Not everyone in a study population is at risk for developing a disease. Eg. Some diseases are lifelong
in duration. If once you have, you cannot develop it again. Persons with such a disease are usually
removed from the denominator population at risk.
⇒ Incidence measures the rapidity with which newly diagnosed patients develop over time. Most common way of
measuring and comparing the frequency of disease in populations.
⇒ Incidence can be:
✓ Cumulative incidence
✓ Incidence Density/person-time rate
a) Cumulative incidence
● The ﬁrst measure of incidence is called cumulative incidence, or risk, since it refers to the occurrence of
risk events (disease, injury or death) in a group of people studied over time.
● It is calculated in much the same way as prevalence, but rather than existing cases, only new cases are
counted over the speciﬁed time interval.
● The likelihood that an individual will contract a disease
● Used for infectious diseases and those of short duration
● Measures the risk (the likelihood, probability) that an individual will contract the disease during a
certain time period or before a given age
● Cumulative incidence relates occurrences of new cases to the population at the beginning of the
study period.
● Cumulative Incidence (CI): is the proportion of people who become diseased during a specified period

of time and is calculated as:

𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑛𝑒𝑤 𝑐𝑎𝑠𝑒𝑠 𝑑𝑢𝑟𝑖𝑛𝑔 𝑎 𝑠𝑝𝑒𝑐𝑖𝑓𝑖𝑒𝑑 𝑝𝑒𝑟𝑖𝑜𝑑 𝑜𝑓 𝑡𝑖𝑚𝑒
𝐶𝐼 =
𝑇𝑜𝑡𝑎𝑙 𝑃𝑜𝑝𝑢𝑙𝑎𝑡𝑖𝑜𝑛 𝑎𝑡 𝑟𝑖𝑠𝑘 𝑖𝑛 𝑡ℎ𝑒 𝑠𝑝𝑒𝑐𝑖𝑓𝑖𝑒𝑑 𝑝𝑒𝑟𝑖𝑜𝑑 𝑜𝑓 𝑡𝑖𝑚𝑒
Figure 3.1: Cumulative incidence

b) Incidence Density/person-time rate
● Measures the rate at which new cases of disease occur in the population at risk during a defined period
● Incidence density represents rate at which new cases are occurring.
● Does not indicate the risk for any individual in a population.
● The population at risk is dynamic and each person in the population contributes the amount of time that
they remained under observation and free from disease (person-time)
𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑛𝑒𝑤 𝑐𝑎𝑠𝑒𝑠 𝑜𝑓 𝑑𝑖𝑠𝑒𝑎𝑠𝑒 𝑖𝑛 𝑠𝑝𝑒𝑐𝑖𝑓𝑖𝑒𝑑 𝑝𝑒𝑟𝑖𝑜𝑑
𝐼𝐷 = × 10𝑛
𝑇𝑜𝑡𝑎𝑙 𝑝𝑒𝑟𝑠𝑜𝑛 − 𝑡𝑖𝑚𝑒 𝑜𝑓 𝑜𝑏𝑠𝑒𝑟𝑣𝑎𝑡𝑖𝑜𝑛
● The numerator is still the number of new cases, but the denominator is the sum of the time each person
is observed, totalled for all persons.
● Person-time rates are often used in cohort (follow-up) studies of diseases with long incubation or
latency periods, such as occupationally related diseases, AIDS, and chronic diseases.
● Total person-time for the denominator is computed by either…
1. Summing the amount of person-time contributed by each person in the population during the
study period, or
2. Multiplying the average size of the population at the mid-point of the study period times the
number of years representing the total study period
Figure 3.2: Incidence density
● Example
✓ Investigators enrolled 2,100 men in a study and followed them over 4 years to determine the rate
of heart disease.
✓ We assume that persons diagnosed with disease and those lost to follow-up were disease-free
for half of the year, and thus contribute ½ year to the denominator.
✓ Initial enrolment: 2,100 men free of disease
● After 1 year: 2,000 disease-free, 0 with disease, 100 lost to follow-up
● After 2 years: 1,900 disease-free, 1 with disease, 99 lost to follow-up
● After 3 years: 1,100 disease-free, 7 with disease, 793 lost to follow-up
● After 4 years: 700 disease-free, 8 with disease, 392 lost to follow-up
a. Identify x: x = cases diagnosed = 1 + 7 + 8 = 16
b. Calculate y, the person-years of observation:
● A second way to calculate the person-years of observation is to turn the data around to reflect
how many people were followed for how many years, as follows:
❖ 700 men x 4.0 years = 2,800 person-years
❖ 8 + 392 = 400 menx3.5 years = 1,400 person-years
❖ 7 + 793 = 800 menx2.5 years = 2,000 person-years
❖ 1 + 99 = 100 menx1.5 years = 150 person-years
❖ 0 + 100 = 100 menx0.5 years = 50 person-years
⇒ Total = 6,400 person-years of observation. This is exactly equal to the average
population at risk (1,600) times duration of follow-up (4 years).
c. Calculate Incidence Density/person-time rate:
⇒ Attack rate
● An attack rate is a variant of an incidence rate, applied to a narrowly defined population observed for a
limited time, such as during an epidemic.
● The attack rate is usually expressed as a percent.
● Example: Of 75 persons who attended a church picnic, 46 subsequently developed gastroenteritis.

Calculate the attack rate of gastroenteritis.
● The attack rate is
⇒ Secondary Attack Rate

● A secondary attack rate is a measure of the frequency of new cases of a disease among the contacts of
known cases.
B. Prevalence rate
⇒ Prevalence, sometimes referred to as prevalence rate, is the proportion of persons in a population who have a
particular disease or attribute at a specified point in time or over a specified period of time.
● Prevalence: It is the total number of newly occurring plus pre-existing cases in a given population within a
specified period of time.
● Prevalence Rate: It is a rate that measures the number of existing cases, new and old, in defined
population during specified period (Period prevalence) or at one point in time (Point prevalence).
a) Point prevalence
● Point prevalence is the amount of disease present in a population at a single point in time.
● Point Prevalence rate: Measures the proportion of a population with a certain condition at a given point in time.
✓ Numerator is number of existing cases
✓ Denominator is total population of interest
● The formula for presence of disease is:
𝑎𝑙𝑙 𝑡ℎ𝑒 𝑐𝑎𝑠𝑒𝑠 (𝑜𝑙𝑑 & 𝑛𝑒𝑤) 𝑜𝑓 𝑓𝑎𝑐𝑡𝑜𝑟 𝑜𝑓 𝑖𝑛𝑡𝑒𝑟𝑒𝑠𝑡 𝑎𝑡 𝑎 𝑔𝑖𝑣𝑒𝑛 𝑝𝑜𝑖𝑛𝑡 𝑖𝑛 𝑡𝑖𝑚𝑒
𝑃𝑜𝑖𝑛𝑡 𝑝𝑟𝑒𝑣𝑎𝑙𝑒𝑛𝑐𝑒 = = 10𝑛
𝑝𝑜𝑝𝑢𝑙𝑎𝑡𝑖𝑜𝑛 𝑑𝑢𝑟𝑖𝑛𝑔 𝑡ℎ𝑒 𝑠𝑎𝑚𝑒 𝑝𝑒𝑟𝑖𝑜𝑑
b) Period prevalence.
● Period Prevalence rate: Measures the proportion of a population that is affected with a certain disease during a
specified period of time.
● The numerator in period prevalence is the number of persons who had a particular disease or attribute at
any time during a particular interval (week, month, year, decade, or any other specified time period).
𝑎𝑙𝑙 𝑡ℎ𝑒 𝑐𝑎𝑠𝑒𝑠 (𝑜𝑙𝑑 & 𝑛𝑒𝑤) 𝑜𝑓 𝑓𝑎𝑐𝑡𝑜𝑟 𝑜𝑓 𝑖𝑛𝑡𝑒𝑟𝑒𝑠𝑡 𝑑𝑢𝑟𝑖𝑛𝑔 𝑎 𝑔𝑖𝑣𝑒𝑛 𝑝𝑒𝑟𝑖𝑜𝑑 𝑜𝑓 𝑡𝑖𝑚𝑒
𝑃𝑒𝑟𝑖𝑜𝑑 𝑝𝑟𝑒𝑣𝑎𝑙𝑒𝑛𝑐𝑒 = = 10𝑛
𝑝𝑜𝑝𝑢𝑙𝑎𝑡𝑖𝑜𝑛 𝑑𝑢𝑟𝑖𝑛𝑔 𝑡ℎ𝑒 𝑠𝑎𝑚𝑒 𝑝𝑒𝑟𝑖𝑜𝑑
● Example:
o Period prevalence rate of a disease in 1995 turns out to be the prevalence at the beginning of 1995 plus
the annual incidence during 1995
o Two surveys were done in the same community 12 months apart. Of 5,000 people surveyed the first
time, 25 had antibodies to histoplasmosis. Twelve months later, 35 had antibodies, including the
original 25. Calculate the prevalence at the second survey, and compare the prevalence with the 1-year
incidence.
1. Prevalence at the second survey:
✓ x = antibody positive at second survey = 35
✓ y = population = 5,000
⇒ x/y X10n = 35/5,000 x 1,000 = 7 per 1,000
2. Incidence during the 12-month period:
✓ x = number of new positives during the 12-month period = 35 - 25 = 10
✓ y = population at risk = 5,000 - 25 = 4,975
⇒ x/y x10n = 10/4,975 x1,000 = 2 per 1,000
o In January, 3 new cases of trachoma were detected in a village. There were already 10 people in the
village who had the disease, but two successfully completed a course of therapy during the month and
were considered cured. The population of the village was 2600. In this case:
✓ The incidence rate is (3/2600) x 1000 or 1.2 per 1000 or 0.1%7
✓ The period prevalence rate is (3+10)/2600) x 1000 or 5 per 1000 or 0.5%
✓ The point prevalence rate as of 31 January is ((3+10-2)/2600) x 1000 or 4.2 per 1000 or 0.4%.
⇒ Characteristics of Prevalence
✓ Cause and effect measured simultaneously
o Impossible to infer causation
✓ Useful for planning (e.g. beds, clinics, workforce needs)
✓ High prevalence  high risk
o could reflect increased survival(improved care, behavior change - long duration)
✓ Low prevalence  could reflect rapid fatal or cure process - short duration)
✓ Easy to obtain need only 1

measurement

Figure 3.3: Relationship between prevalence and incidence

⇒ Relationship between prevalence and incidence
● Prevalence is based on both incidence (risk) and duration of disease. High prevalence of a disease
within a population may reflect high risk, or it may reflect prolonged survival without cure.
● Conversely, low prevalence may indicate low incidence or a rapidly fatal process, or rapid recovery
● Thus, prevalence rate is directly proportional to both incidence rate and to the average duration of the
disease and thus expressed as
P ~ IR x D
✓ Assumptions of equation:
1. “Steady state” i.e. the population size is constant for a long period of time
2. Incidence is constant
3. Distribution of durations is constant
4. Prevalence of disease is low (<.10)
● Example: Figuring duration from prevalence and incidence
✓ Lung cancer incidence = 45.9/100,000 PY
✓ Prevalence of lung cancer = 23/100,000 P
✓ Average D = P/I = 23/100,000 P
45.9/100,000 PY
= 0.5 years
✓ Conclusion: individuals with lung cancer survived, on average, 6 months from diagnosis till
death
⇒ Factors influencing observed prevalence rate
● Prevalence rate is increased by
✓ Longer duration of the disease
✓ Prolongation of life of patients without cure
✓ Increase in new cases
✓ Immigration of cases
✓ Out migration of healthy people
✓ In-migration of susceptible people
✓ Improved diagnostic facility
● Prevalence rate is decreased by

✓ Shorter duration of disease

✓ High case-fatality rate from disease
✓ Decreases in new cases (decrease in incidence)
✓ In-migration of healthy people
✓ Out migration of cases
✓ Improved cure rate of cases
⇒ Uses of Prevalence, Incidence
● Prediction of future illness
✓ Incidence - Need to assess causation
● Clinical decision making
✓ Prevalence useful in guiding diagnostic and treatment decisions
● Comparisons of health states
✓ Compare proportion of population with one disease vs. another (prevalence)
✓ Compare rate of disease amongst risk groups (incidence)
● E.g., rates of lung cancer in smokers vs. non-smokers
● Prevalence may be more useful when
✓ Onset of health state not clear
✓ Population at risk difficult/impossible to ascertain
✓ Planning for health resources and facilities
✓ We often use prevalence rather than incidence to measure the occurrence of chronic diseases
such as osteoarthritis which have long duration and dates of onset which are difficult to
pinpoint.
3.3. Mortality Measures

⇒ A mortality rate is a measure of the frequency of occurrence of death in a defined population during a specified
interval. For a defined population, over a specified period of time,
⇒ When mortality rates are based on vital statistics, the denominator most commonly used is the size of the
population at the middle of the time period. Values of 1,000 and 100,000 are both used for 10 n for most types
of mortality rates.
⇒ The following are the formulas of frequently used mortality measures.
1. Crude Death Rate (CDR): is defined as total number of deaths due to all causes occurring in a defined area
during a defined period per 1000 mid-year population in the same area during the same period.

⇒ CDR measures the rate at which deaths are taking place from all causes in a given population during a specified year.
2. Age-Specific Death Rate (ASDR): is defined as total number of deaths occurring in a specified age group of the
population of a defined area during a specified period per 1000 mid-year population of the same age group of the
same area during the same period.
3. Causes Specific Death Ratio: A cause specific death ratio (proportionate mortality ratio) represents the percent
of all deaths due to a particular cause or group of causes.
Where
✓ Dc - is total deaths from cause c and
✓ Dt - is total deaths from all causes in a specified time period
4. Causes Specific Death Rate (CSDR): Cause Specific Death Rate is the number of deaths form cause c during a
year per 1000 of the mid-year population,
5. Infant Mortality Rate (IMR): measures the risk of dying during infancy (the first age of life), and is defined as:
⇒ Infant Mortality rate: the probability of dying between birth and age one year per 1000 live births.
6. Neonatal Mortality Rate (NMR): measures the risk of dying within 28 days of birth. It is defined as
7. Post - Neonatal Mortality Rate (PNMR): Measures the risk of dying during infancy after the first 4 weeks of
life, and is defined as:
8. Child Death Rate (ChDR): measures the mortality condition among children between 1 to 4 years of age, and is
defined as:
9. Maternal Mortality Rate (MMR): is defined as the number of deaths of mothers (Dm) due to maternal causes,
i.e. complications of pregnancy, child birth, and puerperium, per 100,000 live births during a year,
✓ MMR measures the risk of dying of mothers from maternal causes. Ideally the denominator should include
all deliveries and abortions.
10. Under five-mortality rate: the probability of dying between birth and age five years per 1000 live births.
11. Child Mortality Rate: the probability of dying between age one and five year per 1000 children on age one
year.
3.4. Crude versus specific and adjusted (standardized) rates

⇒ Rate could be crude or specific or standardized:
✓ It is considered as crude when it shows the frequency of a class of events throughout the entire
population without regarding to any of the smaller groupings. Crude rates apply to the total population
of a given area. Crude rates are highly sensitive to the structure (age) of the population and are not
directly used for comparison purposes.
✓ Whereas specific rate implies the events in a particular category of age, sex, race, particular disease, or
other classification variables are used. Specific rates apply to specific subgroups in the population (such
as by age, sex, or occupation) or specific diseases.
✓ Adjusted rates are often used to permit comparison of morbidity or mortality rates in populations which
differ in age structure. Rates computed with adjustment techniques are called adjusted or standardized
rates.
⇒ A principal role in epidemiology is to compare the incidence of disease or mortality between two or more
populations. However, the comparison of crude mortality or morbidity rates is often misleading because the
populations being compared may differ significantly with respect to certain underlying characteristics, such as
age or sex that will affect the overall rate of morbidity or mortality.
✓ For example, age is an important determinant of mortality. An older population will have a higher
overall mortality rate than a younger population. As a result, variations in age will complicate any
comparison between two or more populations that have different age structures.
✓ To understand how a comparison of crude rates can be affected by differing population distributions, it
should be recognized that a crude overall rate is simply a weighted average of the individual category
specific rates, with the weights being the proportion of the population in each category.
✓ One method of overcoming the effects of confounding variables such as age is to simply present and
compare the age specific rates. While this allows for a more comprehensive comparison of mortality or
morbidity rates between two or more populations, as the number of stratum specific rates being
compared increases, the volume of data being examined may become unmanageable.

✓ It is, therefore, more useful to combine category specific rates into a single summary rate that has been
adjusted to take into account its age structure or other confounding factor. This is achieved by using the
methods of standardization.
3.5. Standardization of rates

⇒ Standardization is a process permitting comparisons among sets that show different compositions for
confounding factors (e.g. age and sex).
⇒ For instance, an age standardized rate is used to eliminate the effect of age differences in the populations
compared. An age-sex standardization rate is used to eliminate the effect of differences in the age and sex
distribution.
⇒ For example, do the following three populations with different levels of exposure have equal prevalence rates?
Table: Prevalence of Outcome by level of exposure
⇒ There are two methods of standardization commonly used in epidemiological studies, and these are
characterized by whether the standard used is a population distribution or a set of specific rates. Both direct and
indirect standardization involves the calculation of numbers of expected events (e.g. deaths), which are
compared to the number of observed events.
a) Direct standardization
● The standard used is population distribution.
✓ Would the overall prevalence be different if the population distribution was the same?
● In the direct method of standardization, adjusted rates are derived by applying the category specific
rates of each population to a single standard population. This produces age standardized rates that these
populations would have if they had the same age distribution as the standard population.
● Note that the 'standard population' used may be the distribution of one of the populations being
compared or may be an outside standard population such as the 'European' or 'World' standard
population.
Table: Direct standardization

Table: Summary of Direct standardization
● Comparisons are performed using the low exposure group population as standard.
✓ SRR (%) = Adjusted prevalence/Observed prevalence x 100
b) Indirect standardization
● Would the overall prevalence be different if the populations had the same age-specific rates?
● The indirect method of standardization is commonly used when age-specific rates are unavailable. For
example if we did not know the age specific mortality rates for country medium or high exposure
population.
● In this method, instead of taking one population structure as standard and applying sets of rates to it to
estimate expected events, a set of rates from a standard population (low exposure population) is applied
to each of the populations being compared to calculate standardized morbidity/mortality ratios.
Table: Indirect standardization

Table: Summary of indirect standardization
● Comparisons are performed using the low exposure group prevalence (rate) as standard.
✓ SMR= Observed cases/Expected Cases x 100
⇒ Note.
● Standardization may be used to adjust for the effects of a variety of confounding factors including age,
sex, race or socio-economic status.
● Standardized rates are used for the comparison of two or more populations; they represent a weighted
average of the age specific rates taken from a 'standard population' and are not actual rates.
✓ The direct method of standardization requires that the age-specific rates for all populations
being studied are available and that a standard population is defined.
✓ The indirect method of standardization requires the total number of cases
✓ The ratio of two directly standardized rates is called the Comparative Incidence Ratio or
Comparative Mortality Ratio.
✓ The ratio of two indirectly standardized rates is called the Standardized Incidence Ratio or the
Standardized Mortality Ratio.
✓ Indirect standardization is more appropriate for use in studies with small numbers or when the
rates are unstable.
✓ As the choice of a standard population will affect the comparison between populations, it should
always be stated clearly which standard population has been applied.

3.6. Sources of epidemiologic data

⇒ Population statistics and basic demographic data are essential to the epidemiologist. When describing and
comparing the rates of disease between populations, we need to know the size of the local population to
provide a denominator for estimates of prevalence and incidence. Even though all of them may not found in
every country, the following are key sources of epidemiologic data:
● Census data
● Vital records
● Data from health institutions
✓ Mortality reports (birth and death certificates, autopsy reports)
✓ Morbidity reports (notifiable disease reports)
✓ Hospital data (discharge diagnoses, surgical logs, hospital infection reports)
✓ Absenteeism records (school, workplace, compensation claims)
✓ Epidemic reports
✓ Laboratory test utilization and result reports
✓ Drug utilization records
✓ Adverse drug reaction reports
● Special surveys (e.g. serologic surveys, disease survey, general public health status survey)
● Others
✓ Police records (especially for injury, alcohol-related crime)
✓ Information on animal reservoirs and vectors (e.g., for rabies, plague, Lyme disease)
✓ Environmental data (hazard surveillance, water and food testing)
✓ Special surveillance systems (e.g., for injury and occupational illness)
1. Censuses:
⇒ In modern usage, the term “census” refers to a nation-wide counting of population. It is obtained by a direct
canvass of each person or household, which is a large and complicated undertaking.
⇒ A population census is taken to:
✓ Determine the size of the population of a country at a given date and
✓ Obtain statistical information on various demographic, economic and social characteristics of every
individual in the population.
⇒ Information to be collected
✓ Sex, age, marital status, educational characteristics, economic characteristics, place of birth,
language, fertility mortality , citizenship ( nationality), living conditions (e.g. house-ownership, type
of housing and the like), religion, etc..
2. Survey:
⇒ A survey is a technique based on sampling methods by means of which we try to obtain specific
information from part of the population liable to be considered as representative of the whole.
⇒ Surveys are made at a given moment, in a specific territory; sporadically and without periodicity for the
deep study of a problem.
⇒ A sample survey is a lighter operation than a census, needing less time, less hand and fewer funds.
⇒ Smaller size than census allows collection of more in-depth information that can then be generalized
⇒ From data obtained from a part of the population (the sample), a sample survey infers information valid for
the whole population.

3. Vital events registration:

⇒ It is an ongoing (a continuous) recording of vital events (birth, death, marriage, divorce, etc) as they
become available.
⇒ The registration of vital events (births, deaths, marriages, etc) is a system by which all births, deaths, etc.
occurring nationwide are registered, reported to a control body and compiled centrally.
⇒ The taking of a census is merely a snapshot of an event while the counting of births and deaths (vital
records) is a continuous process.

CHAPTER FOUR: EPIDEMIOLOGICL STUDY DESIGNS

4.1. Introduction
⇒ Epidemiology is primarily concerned with the distribution and determinants of disease in human populations.
This concern is achieved through conducting epidemiological studies which have different design.
⇒ Study design is the arrangement of conditions for collection & analysis of data (overall structure of the study).
According to their focus of investigation, epidemiological studies categorized into two basic categories:
o Descriptive epidemiological study
▪ Focus on the distribution of disease
▪ Based on the study unit, it include the following sub-types
● Population as study subject
o Correlational /ecological studies
● Individual as study subjects
o Case report / Case series
o Cross-sectional surveys
o Analytic epidemiological study
▪ Focus in elucidating the determinants of disease.
▪ Include the following sub-types
● Observational studies
o Case-control study
o Cohort study
● Experimental / intervention studies
o Randomized
o Non-randomized
4.2. Types of epidemiological studies

1. Descriptive studies
⇒ As described in chapter one, epidemiology is defined as the study of the distribution and determinants of
disease frequency in human populations and the application of this study to control health problems.
⇒ The portion of the definition pertaining to the distribution of disease is the domain of descriptive
epidemiology, which involves the analysis of disease patterns according to the characteristics of person, place,
and time.
o Person
▪ Personal characteristics that are usually available for descriptive epidemiology include age, sex,
race and ethnic group, socioeconomic status, occupation, religion, and marital status.
▪ These attributes can be associated with major variations in disease occurrence.
o Place
▪ Place can be defined in terms of geopolitical units such as countries or states or in terms of natural
geographic features such as mountains or rivers.
▪ The characteristics of place encompass numerous aspects of the environment including
● The physical environment (such as climate, water, and air),
● Biological environment (such as flora and fauna), and

● Social environment (such as cultural traditions).
▪ For example, malaria occurs in parts of the world where all these facets of the environment are
conducive to the life cycle of the Anopheles mosquito.
● Physical conditions that are necessary for the development and survival of the mosquito
include a favorable temperature (20° to 30° C is optimal), adequate humidity, moderate
rainfall and the presence of standing or gently flowing water.
● Biological factors beneficial to the mosquito include plants that can collect small pools of
water.
● Social factors that encourage transmission of the disease include the proximity of homes to
mosquito breeding sites, housing construction that facilitates mosquito entry, and certain
occupations that increase a person’s exposure to mosquito such as those involving outdoor
work at night.
o Time
▪ Analysis of the changes in disease and death rates over calendar time provides epidemiologists
with useful information for causal research and public health planning and evaluation.
▪ The scale of time that is examined depends on the disease and can range from decades or years to
months, weeks, days, or hour
● For example, the death rate from lung cancer has increased dramatically among women
over the 53-year period from 1950 through the 2003.
● Over the same period, there has been a dramatic decline in deaths from cerebrovascular
diseases.
o Both of these are examples of long-term or secular trends.
● Short-term trends are commonly examined for infectious diseases.
● Other types of temporal changes include periodic or regular fluctuations occurring on an
annual, weekly, or even daily basis.
o Seasonal variations in disease frequency are the most common type of periodic
fluctuations.
⇒ Variations in disease occurrence by these three characteristics provide useful information for:
● Understanding the health status of a population;
● Formulation hypotheses about the causes of disease; and
● Planning, implementing, and evaluating public health programs to control and prevent adverse health
events.
⇒ Some of the important features described below show the commonness and usefulness of descriptive studies in
improving health services and promoting health research. Descriptive study:
● Describes the general characteristics of the distribution of a disease in relation to person, place and
time. (Who? Where? When? ). It usually answers:
✓ Who gets a disease and who doesn’t (Person)
✓ Where rates are highest and lowest (Place)
✓ Temporal patterns of disease (Time)

o Seasonality
o Secular trends
● It provides valuable information for health managers
✓ To allocate resources efficiently and
✓ To plan effective prevention or education programs.
● Useful to generate epidemiological hypothesis, an important first step in the search for disease
determinants or risk factors.
● Can use information collected routinely which are readily available in many places.
✓ So generally descriptive studies are less expensive and less time-consuming than analytic
studies.
● It is the most common type of epidemiological design strategy in medical literature.
● There are three main types:
a) Correlational
b) Case report or case series
c) Cross-sectional
A. Correlational or Ecological study

⇒ Uses data from entire population to compare disease frequencies - between different groups during the same
period of time, or in the same population at different points in time.
● Measures that represent characteristics of entire population are used to describe disease in relation to
some factor of interest
✓ Does not provide individual data, rather presents average exposure level in the community.
✓ The units of analysis are populations or groups of people rather than individuals
✓ Cause could not be ascertained.
● Compare populations in different countries at the same time or the same population on one country at
different times
● Correlation coefficient (r) is the measure of association in correlational studies. It is important to note
that positive association does not necessarily imply a valid statistical association.
● Example:
✓ To describe patterns of mortality from CHD in 1960, death rates from 44 states were correlated
with per capita cigarette sales. Death rates were highest in states with the most cigarette sales.
➢ This contributed to the formulation of the hypothesis that cigarette smoking causes fatal
CHD
➢ This has been substantiated in a large number of subsequent analytic epidemiologic studies.
✓ Hypertension rates and average per capita salt consumption compared between two communities.
✓ Average per capita fat consumption and breast cancer rates compared between two communities.
✓ Comparing incidence of dental cares in relation to fluoride content of the water among towns in the

rift valley.
● Strength:
✓ Can be done quickly and inexpensively, often using available data.
● Limitation:
✓ Inability to link exposure with disease in particular individuals. Data on exposure and outcome are
not linked at the individual level.
● For example, in a society with high fat intake, perhaps it is the individual women with
low intake that get breast cancer. Again in the association with the reduced mortality
from cervical cancer and Pap smear screening, it is difficult to know whether the
reduction is really in those women who were screened by smear or otherwise.
✓ Since the unit of analysis is a population or group, the individual link between exposure and effect
cannot be made
✓ Lack of ability to control for effects of potential confounding factors. There may be other things
that are the true cause.
● For example, often people with high fat consumption also have high meat consumption.
Perhaps it is the meat that is actually responsible for the breast cancer - or may be
because of reduced vegetable intake or merely a reflection of socio-economic status.
✓ Correlational data represent average exposure levels rather than actual individual values. The result
can be sometimes misleading. Remember that the average can be affected by the extreme values
✓ It may mask a non-linear relationship between exposure and disease. For example alcohol
consumption and mortality from CHD have a non-linear relationship (the curve is "J" shaped), but
this type of relationship is impossible to demonstrate in correlational studies.
B. Case Report and Case Series

⇒ Describes the experience of a single or a group of patients with similar diagnosis.
⇒ Useful for:
● The recognition of new diseases,
● Constructing of the natural history of a disease, and
● The formulation of hypothesis and detection of epidemics
● Case report:
● It is the study of health profile of a single individual using a careful and detailed report by one or more
clinicians.
● It is made using a history, physical examination and lab investigation.
● Report is usually documented if there is unusual medical occurrence, thus it may be first clue for
identification of a new disease.
● It is useful in constructing a natural history of individual disease.
● Example: It was a single case report that formulated the hypothesis of OC use increases venous
thrombo-embolism.
● Case series:
● Individual case report can be expanded to a case series, which describes characteristics of a number of
patients with a similar disease.
● It is often used to detect the emergence of new disease or an epidemic.
● Has limited value, but occasionally revolutionary.
⇒ Example:
● 5 young homosexual men with PCP seen between Oct. 1980 and May 1981 in Los Angeles arose
concern among physicians. Later, with further follow-up and thorough investigation of the strange
occurrence of the disease the diagnosis of AIDS was established for the first time.
● One case of pulmonary embolism observed 5 weeks after oral contraceptive usage was the first clue to
the association, later established, between oral contraception and increased risk of venous
thromboembolism.
⇒ Both case report and case series are able to formulate a hypothesis but are not able to test for presence of valid
association.
⇒ Strength:
● Very useful for hypothesis generation.
⇒ Limitations:
● Fundamental limitation of case report is presence of a risk factor could be simply coincidental.
● You are not able to test for association because there is no relevant comparison group
C. Cross Sectional Studies (Survey)

⇒ Is generally called prevalent study
⇒ Is conducted in a population, to find prevalence of a disease or health related conditions and exposure.
● Exposure and disease status are assessed simultaneously among individuals in a well-defined
population. Since exposure and disease status is assessed at a single point in time, it is not possible to
determine whether the exposure preceded or resulted from the disease.
● Information about the status of an individual with respect to the presence or absence of exposure and
disease is assessed at the same point in time. Easy to do - many surveys are like this.
⇒ Provide information about the frequency and characteristics of a disease by furnishing a “snapshot” of the
health experience of the population at a specified time (provide information on the prevalence of disease or
other health outcomes)
⇒ Has great value to public health administrators in assessing the health status and health care needs of a
population
⇒ Useful for raising the question of the presence of an association rather than for testing a hypothesis.
⇒ Cross sectional studies can reveal valid association only when the current values of the exposure variables are
unalterable over time. Such variables include factors present at birth, such as sex, race, eye color or blood
group.
⇒ Cross sectional studies either
● Compare prevalence rate of the outcome in exposed Vs non-exposed, or
● Compare prevalence rate of the exposure in those with and without the outcome
⇒ Timing of the subdivision of the study population into comparison groups distinguishes cross sectional studies
from other observational analytic studies

● In cohort and case control studies, this takes place prior to the data collection process
● In a cross sectional study, this takes place after the information has been collected
⇒ Limitation:
● "Chicken or egg" dilemma - difficult to know which occurred first, the determinant/exposure or the
outcome. Therefore, difficult to distinguish whether the exposure preceded the development of the
disease or whether presence of the disease affected the individual's level of exposure
o E.g. In the study of knowledge of modern contraceptive, and use of contraception, you may
show that women who know about modern contraception are more likely to use it. So you may
want to educate women about it, believing that this will lead to higher rate of use. The problem
is, did the women know about it and then start to use it, or did they learn about it because they
were using it?
● It may not show strong cause-effect relationships if sample size is small.
2. Analytic studies
⇒ Focuses on the determinants of a disease by testing the hypothesis formulated from descriptive studies, with the
ultimate goal of judging whether a particular exposure causes or prevents disease.
⇒ Broadly classified into two:
✓ Observational and
✓ Interventional studies.
● Both types use "controls".
● The use of controls is the main distinguishing feature of analytic studies.
A. Observational studies
⇒ Information is obtained by observation of events.
⇒ No intervention is done.
⇒ Cohort and case-control are in this category.
a) Case Control study
⇒ It is an epidemiologic research method in which the two study groups are selected on their disease status.
✓ Subjects are selected with respect to presence or absence of disease, or outcome of interest, and then
inquiries are made about past exposure to the factor(s) of interest.
✓ Example:
● Take people with and without TB, ask them if they ever had BCG vaccination.
⇒ This is a design strategy developed in response to the difficulty of studying diseases with very long latency
period. The design is capable of evaluating the association of a disease to exposure many years after the actual
exposure.
⇒ Because of this and its efficiency in time and cost case-control studies have became the most common analytic
design encountered in medical literature.
⇒ Design and conduct of case-control studies:
✓ In the design of the study always seek for the comparability between cases and controls; this is the

basis for valid conclusion.

✓ Defining Cases:
● Establish a clear operational definition or use standard definition of disease (outcome) of
interest in order to have a clear understanding of exposure-disease association.
✓ Selection of Cases:
● Do not always go for random representation of cases, rather it is better to restrict yourself to
cases on which you can get complete and reliable information.
● Incident Vs Prevalent cases:
➢ Prevalent cases:
o Increase sample size available for rare disease.
o Difficult to establish temporal sequence between exposure and outcome. E.g. Coffee
consumption and peptic ulcer disease.
o Use is unavoidable in certain situations, like in studying congenital malformations
which are rare to find.
➢ Incident cases:
o Helpful to establish temporal relationship between exposure and outcome. So, it is
better to limit cases to those newly diagnosed within a specified period of time if the
aim is also to establish temporal relationship.
o Records are easily obtainable and recall is not a serious problem.
● Sources of cases
a. Hospital or medical care facility
➢ Referred as Hospital-based case control study
➢ Easy and inexpensive to conduct
➢ But it is prone for selection bias.
b. General population
➢ Referred as population-based case control study
➢ Involves locating and obtaining data from all affected individuals or a random sample from a
defined population
➢ Avoids selection bias (It avoids bias arising from whatever selection factors lead affected
individual to utilize a particular health care facility or physician)
o Allows the description of a disease in the entire population and the direct computation
of rates of disease in exposed and non-exposed persons.
✓ Selection of controls:
➢ Involves consideration of a number of issues including :
o The characteristics and source of the cases
o The need to obtain comparable information from cases and controls
o Practical and economic considerations.
➢ Controls should be selected from the same study base (target population) as cases
➢ Should be selected independently of their exposure status!!

➢ Comparable information should be obtained from controls as it is from cases
➢ Controls should be as similar as cases except for the disease (outcome) in question.
➢ The control subjects should be selected to be comparable to the cases
➢ There is no control group that is optimal for all situations.
➢ Select controls which are comparable to the cases entered into the study; do not try to represent
the entire non-diseased population rather try to achieve comparability between the cases and
controls.
➢ The control series is intended to provide an estimate of the exposure rate that would be expected
to occur in the cases if there were no association between the study disease and exposure.
● Sources of controls:
a. Hospital Controls
✓ Advantages:
1) Easily identified and readily available in sufficient number with reduced cost than population
controls.
2) More likely than healthy individuals to be aware of antecedent exposures or events
 Minimize recall bias.
3) Controls are also likely to have been subject to the same intangible selection factors that influence
cases to come to this particular physician or hospital
 Minimize selection bias
4) More likely to be cooperative because they anticipate benefit from their involvement or might
think that its related with their illness
 Reduce bias due to non-response.
✓ Disadvantages:
1) Because they are ill they are different from healthy individuals in many ways.
⇒ Thus, the experience of these other patients may not accurately represent the exposure
distribution in the population from which the cases derived
2) There is danger of altering the direction of association or masking a true association between
exposure and outcome of interest.
⇒ Patients with diseases known to be associated either positively or negatively, with the
exposure of interest, should be excluded from the control series. For example, in studying
the association of cigarette smoking and lung Cancer, individuals with other respiratory
illnesses could not be taken as controls, since smoking is also known to have some
association with other respiratory illnesses.
b. General population controls
✓ Advantages:
1) Generalizability is possible
2) Good when cases are selected to represent affected individuals in a defined population. For
example, if cases to that particular hospital are coming from a geographically defined area
selection of controls from the entire population could be possible.
✓ Disadvantages:
1) Costly and time-consuming

2) Population lists are not always available
3) it is difficult to contact healthy people with busy work and leisure activity schedules
4) May not recall exposures with the same level of accuracy as those who have developed the disease
 Recall bias.
5) Tend to be less motivated to participate
 Increase non-response rate
6) People might be less motivated to participate for the same reason given above
⇒ Selection bias
c. Special controls
✓ Special controls are individuals, which are related to the cases in some way. These are friends,
household members (siblings...), neighbors...
✓ Advantages:
1) They are healthy.
2) More likely to be cooperative than members of the general population, because of their interest
in the cases.
3) Offer a degree of control over some confounding factors, such as ethnicity, socio-economic
status, or environment.
✓ Disadvantage:
● If the study factor is likely to be similar to the cases, an underestimate of the true effect of the
exposure of interest may result. E.g. if the study factor is diet, it will be similar for both cases and
controls, if controls are siblings.
● Number of control groups and case-control ratio
✓ When the number of available cases and controls is large and the cost of obtaining information from
both groups is comparable, the optimal control-to-case ratio is 1:1.
✓ When the sample size of cases is limited, or when the cost of obtaining information is greater for cases
or controls, the control-to-case ratio can be altered to achieve the desired sample size.
✓ Conditions for multiple controls:
● Add more control groups only:
o When you are not confident with the control group (When the control is not considered
appropriate) or
o When the selected group has a specific deficiency that could be overcome by inclusion of
another control group
✓ Control-case ratio
● As the number of controls per case increases, the power of the study also increases.
o The optimal control-case ratio is 4:1.
o But, beyond 4:1, there is only a small increase in statistical power, which cannot justify
the expenditure of additional resources.
● Ascertainment of disease and exposure status
✓ Potential source of information must be carefully considered in terms of its ability to provide

accurate as well as comparable information for all study groups.

✓ Procedures used to obtain information must be similar for cases and controls:
o Place and circumstances of interview must be the same.
o Blind interviewers or record reviewers, if possible.
o Data collectors should be unaware of the specific hypotheses being tested
 To reduce observation bias
o The ability to obtain exposure information from records completed before the occurrence of
outcome events is especially valuable. E.g. record of X-ray during pregnancy in studying its
effect on the child (congenital malformation).
o Ascertainment of exposure should involve defining the part of a person's exposure history
that could be relevant to the aetiology of the disease under study
● E.g. Smoking & lung Ca - duration of smoking is important than the amount currently
smoked. Smoking & Myocardial Infarction - current smoking is most important.
✓ Collect information in such a way that it allow you to identify the most appropriate time window for
the evaluation of the possible harmful effects of an exposure - try to avoid collecting information
over too wide a period, such as "ever use" in order to avoid the inclusion of some period in time that
cannot be causally related to the disease.
✓ Sources of information for disease status:
o Review of death certificates, case registries that maintain ongoing surveillance
o Office records of physicians
o Hospital admission or discharge records
o Pathology department log books
✓ Sources of information about the exposure:
o From study subjects themselves, by either interview or mail questionnaire
o From a surrogate, such as spouses of participants or mothers of children
o From information recorded in medical records.
● Issues in analysis
✓ Compare between cases and controls with respect to the frequency of an exposure
✓ This comparison is made primarily by estimating the RR as computed by the OR.
o If the case control study is population based, or if estimates of disease incidence are available
from an outside source, rates of disease for those exposed and non-exposed can be computed
and compared directly
✓ Evaluate the role of chance by testing the significance of this measure of association and calculating
confidence intervals.
✓ Cases and controls must also be compared to ensure similarity with respect to other baseline
differences that could be associated with the risk of developing the outcome under study.
b) Cohort study
⇒ A design in which the two groups are defined according to their exposure status to a suspected risk factor for a
disease. The two groups should be free of the study outcome.

⇒ Subjects are selected by exposure, or determinants of interest, and followed to see if they develop the disease
or outcome of interest.
⇒ Example:
✓ Take woredas with trained manager and untrained managers and follow them to see which group will do
better to increase coverage.
✓ Follow 100 children who received BCG vaccination and another 100 who didn't get BCG vaccination
and see how many of them get tuberculosis.
⇒ Types:
✓ There are two types of cohort studies, prospective and retrospective, depending on the temporal
relationship between the initiation of the study and the occurrence of the disease.
1) Prospective:
✓ At the beginning of the study the outcome has not yet occurred.
✓ Regarded as more reliable than the retrospective, if the sample size is large and follow-up
complete.
2) Retrospective:
✓ Both exposure and outcome status have occurred before the beginning of the study.
✓ Efficient in cost and time.
✓ Often uses of data collected for other purposes, so information obtained might be
incomplete and non-comparable for all subjects.
⇒ Design and conduct of cohort studies:
● Selection of exposed group
✓ Selection of exposed group should consider scientific and feasibility issues which include:
a. The frequency of the exposure of interest in the study population.
b. The need to obtain complete and accurate exposure and outcome information on all study
subjects.
c. The ability of obtaining sufficient exposed individuals in a reasonable period of time:
identify high risk population (special group) to the exposure of interest.
● Selection of high-risk group also allows the evaluation of a rare disease. Although
cohort studies are in general not optimal for the evaluation of rare diseases, if the
outcome of interest is relatively common among those exposed; i.e., if the attributable
risk percent is high the design can be used efficiently.
d. The ease to collect relevant information and to follow-up.
● Selection of controls
✓ Always attempt to select a control group, which is comparable to the characteristics of the exposed
population.
✓ There is no single optimal control group that can be used for any circumstance.
● Source of data

✓ The major consideration should be the availability of accurate and complete information on
exposure and outcome of interest in the study groups in a way that is comparable to both.
● Exposure ascertainment:
1. Using Pre-existing records: from hospital, employer’s record.
o Advantages:
● Can make available information for high proportion of cohort.
● Relatively inexpensive to obtain.
● Allow objective and unbiased classification of exposure status.
o Disadvantages:
● Information on exposure level may be insufficient.
● May not contain adequate information on potential confounders.
2. By conducting Interview and filling questionnaire
o Advantages:
● Enables to record exposure information that is not routinely recorded, particularly
lifestyle factors.
o Disadvantages:
● Potential for information bias, particularly recall. In such situations, where objective
sources cannot be used, it is important that information is obtained in a comparable
manner for all participants.
● Outcome ascertainment:
✓ With adequate consideration to the resources available for the study, the aim is to obtain complete,
comparable and unbiased information on the subsequent health experience of every study subject.
✓ One or a combination of the following sources could be used:
o Routine surveillance,
o Death certificate,
o Periodic health examination,
o Autopsy records,
o Hospital records, etc.
✓ Always try to have a firm outcome criteria and standard diagnostic procedure which are equally
applied for exposed and non-exposed individuals.
o Do not do any diagnostic examination only for one group, because the difference, which
might be observed, could be just due to the greater opportunity offered to be diagnosed.
● Follow-up
✓ This the major challenge in cohort studies, as well as the major cost in terms of time.
o Unless complete or nearly complete information could be obtained the results might be un-
interpretable.
o If the loss to follow-up is not comparable between the two groups, this will also be a source
for bias.
✓ Therefore, if there is a need for long follow-up period, the mechanism to achieve complete follow-
up should be thought carefully in the planning of the study.

● Analysis
✓ The basic analysis in cohort studies are:
o Comparison of the two groups with baseline characteristic to ensure similarity.
o Calculation and comparison of rates of the incidence of the outcome for exposed and non-
exposed.
o Control of confounding
● Issues in interpretation of cohort studies
✓ Role of bias:
➢ Misclassification bias to some extent might be unavoidable.
o So, always attempt must be done to avoid the introduction of any systematic
misclassification.
o Random misclassification or error unrelated to the outcomes of interest may not affect
comparability, rather it dilute or underestimate any true association that may exist
between the exposure and outcome. As a result, the observed RR estimate will always
be biased towards the null value of 1. On the other hand differential misclassification
can result in a biased risk estimate that is either an underestimate, an over estimate, or,
by chance, the same as the true measure of association
✓ Effects of losses to follow-up:
o If the probability of loss is related to exposure, outcome or to both, or if the proportion is
large the estimate of exposure-disease association may be biased.
o Because of the difficulty to know which factors are related to loss, the best way to eliminate
bias is by reducing loss to follow-up to an absolute minimum.
o For losses:
● Try to obtain information from other sources
● Examine previously collected data to determine whether there are systematic
differences between the losses and follow-ups.
● Indirectly calculate exposure-disease association, assuming the two extreme outcomes.
● One assuming all those who were lost to follow-up developed the outcome of
interest and
● The other assuming that none developed the outcome - this provides a range
within which the true association will lie.
● If losses to follow-up are large, the observed range will be so wide as to provide
little useful information.
✓ Effect of non-participation
o This does not affect validity unless non-response is related to both the exposure and other
risk factors for the outcome under study. The effect of the difference is mainly on
generalizability of the study results.
o The possible effect of non-response on either generalizability or validity can be assessed by
comparing basic social and demographic characteristics of those who do and do not
participate in a study.
Table 4.2: Advantages and limitations of cohort and case-control study designs
Case-Control Cohort
Advantages
a. Optimal for the evaluation of rare diseases a. Valuable when the exposure is rare
b. Can examine multiple etiologic factors for a b. Can examine multiple effects of a single exposure
single disease
c. Quick and inexpensive c. Can elucidate temporal relationship
d. Relatively simple to carry out d. Allows direct measurement of risk
e. Guarantee the number of persons with cases e. Minimize bias in ascertainment of exposure
Limitations
a) Inefficient for the evaluation of rare exposure a. Inefficient in evaluation of rare diseases
b) Can not directly compute risk b. Expensive
c) Difficult to establish temporal relationship c. Time consuming
d) Determining exposure will often relay on d. Loss to follow-up create problem

memory
e) Persons who die as a result of disease caused
by the determinant may not be known to the
study
B. Interventional / Experimental
⇒ This is an epidemiologic design that closely resembles the controlled experiment used in basic science
researches, and can produce high quality data if done properly.
⇒ The researcher does something about the disease or exposure and observes the changes.
✓ Investigator has control over who gets exposure and who don't. The key is that the investigator assign
into either group, whether it is done randomly or not.
✓ Always prospective.
✓ Example:
▪ Assign children randomly to get chloroquine or not, and see how many develop symptomatic
malaria.
⇒ Classification
1. Based on population
a. Clinical trial: usually performed in clinical setting and the subjects are patients.
b. Field trial: used in testing medicine for preventive purpose and the subjects are healthy people.
E.g. vaccine trial

c. Community trial: unit of the study is group of people/community. E.g. fluoridation of water to
prevent dental caries.
2. Based on design
a. Uncontrolled trial: no control group. Control will be past experience (history).
b. Non-randomized controlled: there is control group but allocation into either group is not
randomized.
c. Randomized controlled: there is control group and allocation into either group is randomized.
3. Based on objective
a. Phase I: trail on small subjects to test a new drug with small dosage to determine the toxic effect.
b. Phase II: trial on small group to determine the therapeutic effect.
c. Phase III: study on large population to test effectiveness- usually a randomized control trial.
● Issues in the design and conduct of clinical trials
● Intervention studies to represent the "gold standard" for epidemiologic research should consider the
following:
1. Selection of a study population
✓ Reference population: The general group to whom investigators expect the results of the
particular trial to be applicable. Represents the scope of the public health impact of the
intervention. And, it is related to the issue of generalizability.
✓ Experimental population: The actual group in which the trial is conducted. It is preferable
that if this group is not different from the reference population for the sake of
generalizability, but this should not be a concern.
✓ Considerations in choosing the experimental group:
a) Check whether the proposed experimental population is sufficiently large to achieve
the required sample size for the trial.
b) Choose population that will experience a sufficient number of endpoints to permit
meaningful comparison.
c) Likelihood of obtaining complete and accurate follow-up information for the period
of trial.
2. Allocation of study groups
● Allocation into either group must be done after determining eligibility and getting consent. It
is always advantageous to do the allocation at random.
● Randomization: can be done using random-number table or using small computers, which are
capable of generating random numbers. If the sampling frame is small a lottery method can be
applied.
● Advantages:
a. Treatment groups will not be known by the researcher.
b. "On average" the study group will be comparable; i.e., known and unknown potential
confounders will be equally distributed between the two groups.
c. Randomization can provide a degree of assurance about the comparability of the study
groups that is simply not possible in any observational design.

d. The impression it poses on the readers (consumers) - less proof is needed to show that
the observed result is due to a selection bias or confounder effects.
3. Maintenance and assessment of compliance
✓ Subjects may decline from the treatment protocol for various reasons after randomization, and this
related to the length of time that subjects are expected to adhere to the intervention, as well as to
the complexity of the study protocol. It is always important to obtain as complete follow-up
information as possible since they will be included in the primary analysis.
✓ Methods to enhance compliance:
a) Select population who are both interested and reliable.
b) Arrange frequent contacts with individuals
c) Use incentives, such as providing medical information
✓ Assessment of compliance:
❖ Non-compliance will decrease the statistical power of a trial to detect any true effect of the
study intervention. Therefore, to see its effect compliance levels in any study must be
measured. Measuring compliance is not easy, and all the measures available have inherent
limitations. Some of the measures are:
1) Self-report the simplest and the only way to assess behavioural modification and
exercise programs.
2) Pills count: ask participants to bring unused pills to each clinic visit, this may
eliminate inaccuracies due to poor memory; it assumes that all the unreturned pills
have been ingested.
3) Biochemical tests
● Used to validate self-report
● Objective but expensive and logistically difficult
4. Ascertainment of outcome
✓ Use uniform ascertainment of outcome for complete follow-up period for all study subjects. To
eliminate a possible bias, maintain a high level of follow-up and reduce the proportion of
outcomes that are not ascertained to the minimum and comparable between the two groups.
Follow-up is short in assessing the effect of acute disease and long in assessment of chronic
disease outcomes. The difficulty in maintaining complete ascertainment of outcome increases
with increasing length of follow-up.
✓ The quality of "gold standard" in intervention studies can be achieved through:
1. Randomization
2. Use of placebo
3. Double Blinding
✓ Potential for observation bias in ascertainment of outcome can exist in an intervention study in
that knowledge of a participant's treatment status might, consciously or not, influence the
identification or reporting of relevant events. This can be overcome by the use of placebo and
blinding.
✓ Placebo: an inert agent indistinguishable from the active treatment. Use of placebo
minimizes bias in the ascertainment of both subjective disease outcomes and side
effects.
✓ Placebo effect: tendency for individuals to report favourable response to any therapy
regardless of the physiologic efficacy of what they received.
✓ The use of placebo ensures that all aspects of the intervention offered to participants are identical
except for the actual experimental treatment. With no placebo, it is impossible to tell whether
subjective outcomes are due to the actual trial treatments, to the extra attention participants
receive, or merely to their belief that the treatment will help.
✓ The primary strength of a double -blind design is to eliminate the potential for observation bias.
Of course, a concomitant limitation is that such trials are usually more complex and difficult to
conduct. Circumstances in which double-blinding is not possible are evaluation of programs
involving substantial changes in life-style, such as exercise, cigarette smoking or diet, surgical
procedures, or drugs with characteristics side effects.
✓ Problems associated with un blinded trails:
2) Subjects who are not on the new or experimental program may become dissatisfied and
dropout of the trial, thus resulting in differential compliance or loss to follow-up.
3) Knowledge of the intervention to which group the participant has been assigned might raise
the potential for observation bias in the reporting of side effects or assessment of outcome.
5. Stopping Rules: Decision for early termination of a trial
✓ To assure the welfare of the participants is protected, interim results should be monitored by a
group that is independent of the investigators conducting the trial.
✓ Consider termination if the interim results indicate a clear and extreme benefit on the primary end
point due to intervention, or if one treatment is clearly harmful.
✓ It would also be unethical to stop a trial prematurely based solely on emerging trends from a small
number of patients - the aim must be to achieve an equitable balance between, on the one hand,
protection of randomized participants against real harm and, on the other, minimizing the risk of
mistakenly modifying or stopping the trial prematurely.
6. Requirements for modification or termination of an ongoing trial:
✓ First, observation of a sustained statistical association that is so extreme, and, therefore, so
highly significant, that it is virtually impossible to arise by chance alone.
✓ Second, consider the observed association in the context of totality of evidence:
a. Are there known or postulated biologic mechanisms that might explain the observed effect?
b. Is it in-line with other randomized trials, or those from observational studies?
c. How does the observed association (effect) affect the risk-to-benefit ratio of the
intervention?
⇒ Problems Related to Intervention Studies

1. Ethical considerations prevent evaluation of many treatments or procedures using an intervention

design strategy. Some of the ethical issues are:
✓ Practices or substances already known to be harmful should not be used in this study.
✓ Therapies known to be beneficial should not be withheld from any affected individuals in the
study population.
✓ Investigators have to have a complete knowledge of the subject under study.
✓ The researcher must have at least informed consent from each study participant and subjects
should be left free to withdraw from the study at anytime.
✓ A written research protocol is a must.
2. Feasibility/ practical issues
✓ Subject recruitment, getting adequate individuals to enroll into a study is not easy.
✓ Conducting trial on a widespread practice poses difficulty in getting sufficiently large
population who are willing to undergo through a new treatment or practice believed to be
more beneficial than the old treatment or practice for the duration of the entire study period;
i.e., it is difficult to achieve satisfactory compliance from all study subjects for a long time,
particularly if study period is quite long. Getting an appropriate control group is also difficult
sometimes.
✓ For example, if you want to see the association of chat chewing and dental caries and the
prevalence of chat chewing is 70%, it will be difficult for you get an adequate control.
3. Cost - experimental studies are very expensive.
⇒ Power of the study
● The statistical power of a trial to detect a postulated difference between treatment groups, if one truly
exists, is dependent on:
1. Sample Size
➢ Trials with inadequate sample size might have a great potential for scientific harm - could
be as a result of misinterpretation. Always its advisable to take sample large enough to
detect small to moderate (10-20%) benefit or differences that resulted from the
intervention.
2. Accumulation of adequate end points
➢ There are at least two major strategies to obtain adequate numbers of end points:
a. Selection of a high-risk population
✓ The collection of baseline data can be planned to allow the identification of
particular subgroups who might experience the effects of an intervention more
than others; i.e., those at a higher risk of developing the outcome of
intervention.
b. Length of follow-up period
✓ It is always better to consider that the actual rate of occurrence of end points
will be less than the projected level, which could be due to the low incidence
of the outcome of interest in the volunteer study population, this is referred as

"healthy volunteer effect"- the only way to compensate for this deficit is to
extend the length of follow-up to get more events.
✓ Secular changes in disease rates during the course of the trial might be
sometimes as great as that due to the intervention. E.g. During the decade in
which MRFIT trail was conducted, the entire U.S population including all
MRFIT participants, experienced a marked 25 to 30% decline in Coronary
Heart Disease (CHD) mortality. As a result, the expected numbers of deaths in
the trial was less by two-third, so the follow-up was extended to increase the
number of end-points (the outcome).
✓ Consider the postulated mechanism by which the study agent (the exposure)
exerts its effect in deciding the length of follow-up period. That is, how long
will it take for the study agent to exert its effect on the end result.
✓ Every effort should be made to incorporate an adequate length of follow-up
during the planning phase of the trial. IF, for any reason, there is a need to
alter the follow-up period, the decision should be made as early in the trail as
possible to maintain the scientific credibility of the study and avoid the
implication that the change in study design was based on last-minute efforts to
achieve statistical significance.
3. Effect of Compliance
➢ Compliance must be assessed in all study participants, regardless of their particular
treatment assignment. The effect of non-compliance in any participant is to make the
intervention and comparison groups more alike, as a result decreases the ability of the trial
to detect any true differences between the groups.
➢ One strategy to increase compliance is to use "Run-in or Wash out" period prior to the
actual randomization- all participants receive either the active treatment or the placebo for a
number of weeks or months before formal randomization to a treatment group. The only
limitation to this strategy is the limitation to generalize study into reference or general
population, but the primary goal of a trial must be to attain a valid result.
⇒ Issues in Analysis and Interpretation of Intervention Studies
● Basically the same with analysis of cohort studies. The fundamental comparison to estimate the true
benefit of the intervention program should be obtained through analysing the data by intention to treat -
"once randomized, always analyzed"- so always maintain high level of compliance, keep losses to
follow-up at a minimum, and collect information on all randomized subjects.
● Reasons:
1. Non-compliance may be related to factors that also affect the risk of the outcome under the
study, and failure to analyze data on all randomized participants could introduce bias. In most
studies, perfect compliers represent only a fraction of the total study population.
2. Analysis of compliers data does not address the actual research question posed in an
intervention study.
✓ First, it is only the entire groups allocated by randomization that are truly comparable -
so preserve the power of randomization by analysing the entire population.
✓ Secondly, if a particular regimen is so difficult and uncomfortable that it is likely to be
accepted and used by only a small proportion of the reference population, it may not be
practical to recommend its use, no matter how effective the actual treatment may be.
3. Rule out other possible alternative explanations for the observed findings. Alternative
explanations for the observed result in any analytic epidemiological study include:
3.1. Chance
1) Obtaining adequate sample size for the study could reduce the likelihood of chance as
a possible explanation.
2) Statistically significant finding leave little room for chance.
3.2.Bias
a. Selection bias is best eliminated by randomization
b. Information bias can be eliminated by:
a. Using blinding procedures
b. Using standard and comparable exposure and outcome ascertainment in
both groups.
3.3.Confounding
● Ways to control for confounding include:
a) Use appropriate analytic tools to control known confounding factors -
multivariate analysis
b) Control for known and unknown confounders can be best achieved by
randomization
c) Matching if properly applied, is another method used for control of known
confounders
d) Compare basic socio-demographic characteristics to assure that balance was
achieved.
4.3. Measures of association and impact

⇒ An important application of epidemiology is to estimate how much disease is caused by a certain modifiable
risk factor. The data on the impact of risk factors or interventions are essential to assess the effectiveness and
cost-effectiveness of interventions.
⇒ Now, you will learn about epidemiological measures used to quantify the association between a risk (or
protective) factor and an outcome, and the measures used to assess the impact of a risk factor or interventions
in the population. The following table, two by two table, (contingency table) is used to simplify the calculation
of these measures.
Table 4.3: Two by two table (contingency table)
Disease
Cases Controls Total
Exposed a b 𝑎+𝑏
Exposure Non exposed c d 𝑐+𝑑
Total 𝑎+𝑐 𝑏+𝑑 𝑎+𝑏+𝑐+𝑑
A. Measures of Association
⇒ Summarize the frequency measures of two variables into a single summary parameter that estimates the degree
of association. Requires comparing two groups:
● With outcome Vs Without Outcome
● Exposed Vs Unexposed
⇒ These are relative measures which answer the questions:
● Is there a relationship between the exposure and outcome of interest?
● How strong is the association?
⇒ Relative measures
● Relative measures estimate the size of an association between exposure and disease, and indicate how
much more likely people in an exposed group are to develop the disease than those in an unexposed
● There are three relative measures that can be used to calculate association between disease and exposure:
✓ Risk ratio,
✓ Rate ratio and
✓ Odds ratio
1) Risk ratio
✓ The risk ratio, also commonly referred to as relative risk is calculated as the ratio between the cumulative
incidence in the exposed group and the cumulative incidence in the unexposed group.
✓ Risk ratio is defined as:
𝑅𝑖𝑠𝑘 (𝑐𝑢𝑚𝑢𝑙𝑎𝑡𝑖𝑣𝑒 𝑖𝑛𝑐𝑖𝑑𝑒𝑛𝑐𝑒) 𝑖𝑛 𝑒𝑥𝑝𝑜𝑠𝑒𝑑
𝑅𝑖𝑠𝑘 𝑟𝑎𝑡𝑖𝑜 (𝑅𝑅) =
𝑅𝑖𝑠𝑘 (𝑐𝑢𝑚𝑢𝑙𝑎𝑡𝑖𝑣𝑒 𝑖𝑛𝑐𝑖𝑑𝑒𝑛𝑐𝑒) 𝑖𝑛 𝑢𝑛𝑒𝑥𝑝𝑜𝑠𝑒𝑑
✓ Relative measure of risk estimating the magnitude of association between an exposure and disease (or
other outcome)
✓ Indicates the likelihood of developing the disease in the exposed group relative to those who are not
exposed.
● By referring table 4.3, the incidence of disease in the entire population is (a + c) / (a + b + c + d)
per a given time.
● Since the incidence of disease in the exposed group is a/(a + b) and in the unexposed group is c/(c
+ d), the risk ratio can be calculated as:
𝑎
(𝑎 + 𝑏)
𝑅𝑖𝑠𝑘 𝑟𝑎𝑡𝑖𝑜 (𝑅𝑅) = 𝑐
(𝑐 + 𝑑)
✓ The risk ratio is used as a measure of aetiological strength (i.e. the strength of association between risk
factor and outcome).
● A value of RR equal to 1.0

● Will be obtained if the incidence of disease in the exposed and unexposed groups is
identical, and therefore indicates that there is no observed association between the exposure
and the disease, according to the given data.
● A value of RR greater than 1.0
● Indicates a positive association or an increased risk among those exposed to the factor.
● A value of RR less than 1.0
● Means that there is an inverse association or a decreased risk among those exposed, or in
other words, the exposure is protective.
2) Rate ratio
✓ The rate ratio is calculated in the same way as the risk ratio, except that the incidence rates in the
exposed and unexposed groups are used:
𝐼𝑛𝑐𝑖𝑑𝑒𝑛𝑐𝑒 𝑟𝑎𝑡𝑒 𝑖𝑛 𝑒𝑥𝑝𝑜𝑠𝑒𝑑
𝑅𝑎𝑡𝑒 𝑟𝑎𝑡𝑖𝑜 =
𝐼𝑛𝑐𝑖𝑑𝑒𝑛𝑐𝑒 𝑟𝑎𝑡𝑒 𝑖𝑛 𝑢𝑛𝑒𝑥𝑝𝑜𝑠𝑒𝑑
✓ The rate ratio takes into account the amount of time that each person contributes to the study, and is
therefore preferred in analytical studies in which the outcome is common, and in which large numbers of
people are entering and leaving the study population or have changing levels of exposure.
3) Odds Ratio (OR)

✓ The odds ratio is calculated in a similar way to the risk ratio and the rate ratio, in that the odds in the
exposed group are compared with the odds in the unexposed group:
● Indicates the likelihood of having been exposed among cases relative to controls
● A ratio that measures the odds of exposure for cases compared to controls
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑒𝑥𝑝𝑜𝑠𝑒𝑑
𝑂𝑑𝑑𝑠 𝑜𝑓 𝑒𝑥𝑝𝑜𝑠𝑢𝑟𝑒 =
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑢𝑛𝑒𝑥𝑝𝑜𝑠𝑒𝑑
𝑂𝑑𝑑𝑠 𝑜𝑓 𝑒𝑥𝑝𝑜𝑠𝑢𝑟𝑒 𝑎𝑚𝑜𝑛𝑔 𝑐𝑎𝑠𝑒𝑠

𝑂𝑑𝑑𝑠 𝑟𝑎𝑡𝑖𝑜 (𝑂𝑅) =
𝑂𝑑𝑑𝑠 𝑜𝑓 𝑒𝑥𝑝𝑜𝑠𝑢𝑟𝑒 𝑎𝑚𝑜𝑛𝑔 𝑐𝑜𝑛𝑡𝑟𝑜𝑙𝑠
✓ If we use the information from Table 4.3,

(𝑎+𝑐)
o The odds of disease of the population is calculated as: (𝑏+𝑑)
𝑎 𝑏
o The odds of exposure in cases are 𝑐 and in the non diseased group are 𝑑 , therefore the odds ratio is:
𝑎
𝑎𝑑
𝑂𝑑𝑑𝑠 𝑟𝑎𝑡𝑖𝑜 = 𝑐 =
𝑏 𝑏𝑐
𝑑
✓ Odds ratios are usually used in studies where the incidence of the disease of interest is not known or if
the study participants are selected on the basis of their disease status rather than because of their
exposure status. In this case, rather than calculating the odds of disease in the exposed and unexposed
groups, the odds of exposure are calculated in those with and without disease.
B. Measures of impact
⇒ These are absolute or attributable measures which answer the questions:
● What is the excess risk among exposed individuals?
● What is the excess risk among the general population that is due to exposure of interest?
⇒ Relative measures are useful when we want to know how strongly an exposure is associated with a particular
disease, but they do not give us any indication of the impact of that exposure on the incidence of disease in that
population. This has important implications for any public health prevention measures we may want to take.
⇒ Absolute measures are therefore used to indicate exactly what impact a particular disease or condition will
have on a population, in terms of the numbers or percentage of that population affected by their being exposed.
The following are the common absolute measures:
1. Attributable (absolute) risk
● The attributable or absolute risk can give information on how much greater the frequency of a disease is in
the exposed group than in the unexposed group, assuming the association between the exposure and disease
is causal.
● Answers, what is the excess risk among exposed individuals?
● Attributable risk measures the difference in frequency of a disease between two groups, not the magnitude
of association between the risk factor and the outcome (as in a relative risk). It is the risk of disease in the
exposed group that is attributable to the risk factor, after taking into account the underlying level of disease
in the population (from other causes).
● Attributable risk is also known as risk difference or excess risk. Defined as:
𝐴𝑡𝑡𝑟𝑖𝑏𝑢𝑡𝑎𝑏𝑙𝑒 𝑟𝑖𝑠𝑘 (𝐴𝑅) = 𝑅𝑖𝑠𝑘 𝑖𝑛 𝑒𝑥𝑝𝑜𝑠𝑒𝑑 − 𝑅𝑖𝑠𝑘 𝑖𝑛 𝑢𝑛𝑒𝑥𝑝𝑜𝑠𝑒𝑑
✓ Measures public health impact

✓ Quantify the excess risk in the exposed that can be attributable to the exposure by removing the risk of
disease that could have occurred anyway due to other causes.
✓ Indicates the number of cases of the disease among the exposed that can be attributed to the exposure
itself.
2. Attributable risk percent (AR %)
✓ Attributable risk can be expressed as the proportion of disease in the exposed group attributable to the
exposure (the proportion of additional cases), this is known as the attributable risk percent of the
aetiologic fraction.
✓ Answers, what proportion of cases is attributed to the actual exposure among exposed people?
✓ Measures public health impact of an exposure
✓ Estimate the proportion of cases among the exposed that is attributable to the exposure, or the
proportion of the disease that could be prevented by eliminating the exposure among the exposed.
𝑅𝑖𝑠𝑘 𝑖𝑛 𝑒𝑥𝑝𝑜𝑠𝑒𝑑 − 𝑅𝑖𝑠𝑘 𝑖𝑛 𝑢𝑛𝑒𝑥𝑝𝑜𝑠𝑒𝑑
𝐴𝑡𝑡𝑟𝑖𝑏𝑢𝑡𝑎𝑏𝑙𝑒 𝑟𝑖𝑠𝑘 𝑝𝑒𝑟𝑐𝑒𝑛𝑡 (𝐴𝑅 %) = × 100
𝑅𝑖𝑠𝑘 𝑖𝑛 𝑒𝑥𝑝𝑜𝑠𝑒𝑑
3. Population attributable (absolute) risk (PAR)

● The same concept can be applied to the population as a whole. It is of benefit to public health if we can
estimate the excess disease present in a population that is due to a particular risk factor, or estimate the relative

importance of different risk factors.

𝑃𝐴𝑅 = 𝑅𝑖𝑠𝑘 𝑖𝑛 𝑝𝑜𝑝𝑢𝑙𝑎𝑡𝑖𝑜𝑛 − 𝑅𝑖𝑠𝑘 𝑖𝑛 𝑢𝑛𝑒𝑥𝑝𝑜𝑠𝑒𝑑
= 𝐴𝑅 × 𝑝𝑟𝑜𝑝𝑜𝑟𝑡𝑖𝑜𝑛 𝑜𝑓 𝑒𝑥𝑝𝑜𝑠𝑒𝑑 𝑖𝑛 𝑡ℎ𝑒 𝑝𝑜𝑝𝑢𝑙𝑎𝑡𝑖𝑜𝑛

✓ Estimate the excess rate of disease in the total study population that is attributable to the exposure.
✓ Indicates the number of cases of the disease in the total population that can be attributed to the exposure
itself.
4. Population Attributable Risk Percent (PAR %)
✓ What proportion of cases is attributed to the actual exposure among the general population?
𝑅𝑖𝑠𝑘 𝑖𝑛 𝑝𝑜𝑝𝑢𝑙𝑎𝑡𝑖𝑜𝑛 − 𝑅𝑖𝑠𝑘 𝑖𝑛 𝑢𝑛𝑒𝑥𝑝𝑜𝑠𝑒𝑑
𝑃𝐴𝑅 % = × 100
𝑅𝑖𝑠𝑘 𝑖𝑛 𝑝𝑜𝑝𝑢𝑙𝑎𝑡𝑖𝑜𝑛

✓ Estimate the proportion of disease in the study population that is attributable to the exposure and
thus could be eliminated if the exposure were eliminated.
4.4. Analysis of cause effect relationship

A. Accuracy of Measurement
⇒ 𝐴𝑐𝑐𝑢𝑟𝑎𝑐𝑦 = 𝑉𝑎𝑙𝑖𝑑𝑖𝑡𝑦 + 𝑃𝑟𝑒𝑐𝑖𝑠𝑖𝑜𝑛
⇒ Validity is the extent to which data collected actually reflect the truth.
● The concepts of sensitivity (ability to detect true positive) and specificity (ability to detect true negatives)
can be used to characterize the validity of a measure ("measurement validity").
● Study results are also described as "valid" when there is no systematic misrepresentation of effect or
"bias" ("validity in the estimation of effect").
⇒ Precision, on the other hand, describes the extent to which random error (i.e., sampling variation and the
statistical characteristics of the estimator) alters the measurement of effects.
⇒ Misclassification may result in problems with either
● validity (due to systematic misclassification bias attributable to methodological aspects of study design
or analysis) or
● precision (due to random misclassification error attributable to sampling variation). Random
misclassification errors always bias measures of relative risk toward one. Systematic misclassification
bias can either increase or decrease the strength of the measured association.
1. Bias
⇒ Bias may be defined as any systematic error in an epidemiologic study that results in an incorrect estimate of
the association between exposure and risk of disease.
⇒ Bias may result from systematic error (or difference between exposed and unexposed populations or between
cases and controls) in the collection, recording, analysis, or interpretation of data. Evaluating the role of bias as
an alternative explanation for an observed association is a necessary step in interpreting any study result.
Unlike chance (including lack of precision) and confounding, which can be evaluated quantitatively, the effects
of bias are far more difficult to evaluate and may even be impossible to take into account in the analysis. For

this reason, it is important to design and conduct studies in such a way that every possibility for introducing
bias has been taken into account and to take steps to minimize chances of bias. In evaluation of study results, it
is important to estimate the magnitude and direction of any suspected bias.
⇒ Types of bias may be grouped into two categories:
a. Selection bias:
✓ Refers to any error that arises in the process of identifying the study populations.
✓ Selection bias can occur whenever the identification of individual subjects for inclusion in the study
on the basis of either exposure (cohort) or disease (case-control) status depends in some way on the
other axis of interest.
✓ Examples of selection bias include:
1) Berkson's bias - Case-control studies carried out exclusively in hospital settings are subject to
selection bias attributable to the fact that risks of hospitalization can combine in patients who
have more than one condition.
2) Ascertainment bias - Differential surveillance or diagnosis of individuals make those
exposed or those diseased systematically more or less likely to be enrolled in a study.
3) Non-response bias - Rates of response to surveys and questionnaires in many studies may
also be related to exposure status, so that bias is a reasonable alternative explanation for an
observed association between exposure and disease.
4) Loss to follow-up - This is a major source of bias in cohort studies. Persons lost to follow-
up may differ from with respect to both exposure and outcome, biasing any observed
association.
5) Volunteer/Compliance bias - In studies comparing disease outcome in persons who volunteer
or comply with medical treatment to those who do not, better results might be expected among
those persons who volunteer or comply than among those who do not.
6) Cohort bias - Refers to the biased view of the natural history of disease presented in survival
cohorts, since only the prevalent cases (those with less lethal disease) are available for study in
the latter part of the period of observation.
b. Observation or information bias
✓ Includes any systematic error in the measurement of information on exposure or outcome.
✓ Examples of Information bias include:
1. Interviewer bias - This can occur if the interviewer or examiner is aware of the disease status (in a case-
control study) or the exposure status (in cohort and experimental studies). This kind of bias may affect
every kind of epidemiologic study.
2. Recall bias - May result because affected persons may be more (or less) likely to recall an exposure that
healthy subjects, or exposed persons more (or less) likely to report disease. This source of bias is more
problematic in retrospective cohort or case-control studies.
3. Social desirability bias - Occurs because subjects are systematically more likely to provide a socially
acceptable response.
4. Hawthorn effect - Refers to the changes in the dependent variable, which may be due to the process of
measurement or observation itself.

5. Placebo effect - In experimental studies, which are not placebo-controlled, observed changes may be
ascribed to the positive effect of the subject's belief that the intervention will be beneficial.
6. Regression to the mean - Refers to the statistical phenomenon that extreme values will tend to
"regress" to more average values. Thus a change from a very high or very low values in the dependent
variable may be attributable to simple random variation, rather than to changes in the independent
variable.
7. Healthy worker bias - Refers to the bias in occupational health studies, which tends to underestimate
the risk associated with an occupation due to the fact that employed people tend to be healthier than the
general population.
8. Lead-time bias - Results in overestimation of the effectiveness of a screening program for a condition,
which is actually caused by the early detection of a condition. It is more exaggerated in conditions with
a long "lead-time" (such as cervical carcinoma). The detection of a condition before the person shows
clinical signs and symptoms (the "lead time") is the cause of the measurement of prolonged survival in
persons who participate in screening programs rather than a real prolongation of a real survival. Those
individual who are diagnosed early may actually gained more "disease time".
9. Length/time bias - Occurs in studies of screening tests for cancer. This occurs due to the fact that
screening tests for cancer tend to detect more slow-growing tumours with a better prognosis (since
faster growing tumours are more often detected because they cause symptoms). As a result, the
mortality rate of cancers found on screening will appear better than that of tumours not found on
screening (though the effect is not due to the screening itself).
✓ Some recommendations to minimize bias at the time of study design are:
a. Choose study design carefully. If ethical and feasible, a randomized double blind trial has
the least potential for bias. If loss to follow-up will not be substantial, a prospective
cohort study may have less bias than a case-control study. Controls for case-control
studies should be maximally comparable to cases except for the variable under study.
b. Choose "hard" (i.e., objective) rather than subjective outcomes.
c. "Blind" interviewers or examiners wherever possible.
d. Use well-defined criteria for identifying a "case" and use closed-ended questions
whenever possible.
e. Collect data on variables you do not expect to differ between the two groups. If such a
"dummy" variable regarding exposure, for example, in a case-control study shows an
unexpected difference, it may alert you to recall bias.
2. Confounding
⇒ Confounding refers to the mixing of the effect of an extraneous variable with the effects of the exposure and
disease of interest.
⇒ Confounding arises when some cause other than the exposure under study is more, or less, prevalent in the
exposed group than in the unexposed. Such variable is defined as an extraneous (third) variable, which is
associated with the exposure and, independent of that exposure, be a risk factor for the disease.

⇒ Characteristic of a confounding variable

1) Associated with the disease of interest in the absence of exposure
1. Risk factor for the study outcome among exposed group
2. Risk factor for the study outcome among non-exposed
2) Associated with the study exposure but not as a consequence of the exposure.
⇒ Effect of Confounding
● Without prior knowledge of the effect of the variable on the outcome and exposure it is very difficult to
predict the direction of effect of a suspected confounding variable.
● However, the effect could be categorized into three:
1) Totally or partially accounts for the apparent effect
2) Mask an underlying true association
3) Reverse the actual direction of the association
⇒ Control for Confounding Variables
● The list of potential confounders in a study is limited to established risk factors for the disease of interest,
though still some other variables may play a confounding role in the association it might be difficult to
identify them and explain their effects.
● In the design confounding could be minimized by:
a) Randomization
b) Restriction
c) Matching
● Evaluation of confounding in the analysis by:
a) Standardization
b) Stratification/pooling
c) Multivariate analysis
3. Chance
⇒ One of the alternative explanations to the observed association between an exposure and a disease is chance.
⇒ Since the general aim of epidemiological studies is to make generalization about a larger group of individuals
on the basis of a sample population it is always important to evaluate the role of chance or sampling variability
in any study, which tries to elucidate association.
⇒ Evaluation of the role of chance is mainly the domain of statistics and it involves:
1. Hypothesis Testing (Test of Statistical Significance)
✓ Test of statistical significance quantifies the degree to which sampling variability may account for
the observed results.
✓ The "P value" is used to indicate the probability or likelihood of obtaining a result at least as
extreme as that observed in a study by chance alone, assuming that there is truly no association
between exposure and outcome under consideration (i.e., H0 is true).
✓ For medical research, the P value < 0.05 is set conventionally to indicate statistical significant.
2. Estimation of Confidence Interval
✓ The confidence interval represents the range within which the true magnitude of effect lies within

a certain degree of assurance.

✓ It is more informative than just P value because it reflects on both the size of the sample and the
magnitude of the effect.
B. Establishing a Causal Association
⇒ Sequence in establishing a causal association between an exposure and outcome
1) Incidental observation of possible causal association between an exposure and outcome.
2) Descriptive epidemiologic analysis establishing the association on a population level.
3) Analytic epidemiologic studies establishing the association on an individual level.
4) Experimental reproduction of the outcome by the exposure and/or looking for biologic explanation.
5) Observation that removal of the exposure (or modification of the host response to it) decreases the
occurrence of the outcome.
⇒ Our primary objective in epidemiology is to judge whether an association between exposure and disease is, in
fact, causal.
⇒ Scientific proof of a cause-effect relationship is often difficult to obtain, since experimental studies may be
either not feasible or not ethical.
⇒ Since associations documented by other kinds of epidemiologic studies do not constitute proof of causation,
one must assess the validity of individual studies and examine the totality of evidence from all available studies
and make a judgement about the likelihood of a cause-effect relationship.
⇒ Judgements of causality must first consider whether, for any individual study, the observed association is valid
(i.e., Whether the findings reflect the true relationship between exposure and disease or may be explained by
chance, bias, or confounding) and, second, whether the accumulated evidence supports a cause-effect
relationship. The validity of an observed association is established by eliminating alternative explanations of
that association. Associations can be:
1) Artifactual (spurious) associations, which may be:
a. The result of chance variation (i.e., type 1 error). Statistical tests and confidence intervals
can help to evaluate the likelihood of this as an explanation for an association.
b. The result of bias, or systematic error in the design or conduct of the study. Examples of
how bias can lead to artifactual (i.e., not real) associations are presented below.
2) Noncausal (indirect) associations, which may occur when:
1.The associated factor is itself an effect, rather than a cause (reverse causation), or both a
cause and an effect (reciprocal causation). For example, in the association between
vitamin A deficiency and diarrhoea, vitamin A deficiency could be a cause or an effect of
diarrhoea, or both. Vitamin A deficiency results in abnormalities in epithelial surfaces and,
thus could impair resistance to the infectious agents of diarrhoea. On the other hand,
diarrhoea leads to reduced food intake through loss of appetite and to impaired absorption
of nutrients, both of which could result in vitamin A deficiency after repeated episodes of
diarrhoea.
2.The association is due to a confounding effect by a third variable. A confounding
variable is one independently associated with both the exposure and the disease. To
confound, a variable must fulfil each of the following two criteria: 1) it must be related to
both the frequency of disease exposure and the frequency of disease recognition, and 2) it
must occur with differing frequencies in groups being compared (cohorts or cases and
controls). For example, the association between anaemia and illiteracy is likely non-causal,

due rather to the confounding effect of socio-economic status, which is independently

related to both anaemia (because of poor diet) and illiteracy (because of reduced access to
educational opportunities).
3) Causal associations, which can be established only when other potential explanations of the association
can be ruled out.
⇒ In observational studies, there are many potential confounders and sources of bias, some of which may remain
undetected. The results of one observational study rarely provide adequate support for concluding that there is
a cause-and-effect relationship between an exposure and a disease. Properly conducted experimental trials do
provide direct proof of causality, yet are often impossible because of ethical considerations.
⇒ In the absence of experimental evidence, the following criteria (called the Bradford-Hill criteria) are used to
assess the strength of evidence for a cause-and-effect relationship. The criteria are listed in descending order of
importance:
a. Strength of the Association - The stronger the association, the more likely that it is causal.
b. Consistency of the Relationship - The same association should be demonstrable in studies with
different methods, conducted by different investigators, and in different populations.
c. Specificity of the Association - The association is more likely causal if a single exposure is linked to a
single disease.
d. Temporal Relationship - The exposure to the factor must precede the onset of the disease.
e. Dose-response Relationship - The risk of disease often increases with increasing exposure to a causal
agent.
f. Biological Plausibility - The hypothesis for causation should be coherent with what is known about
the biology and the descriptive epidemiology of the disease.

CHAPTER FIVE: SCREENING IN DISEASE CONTROL

5.1. Definition:
⇒ Screening:
● The presumptive identification of unrecognized disease or defect by the application of tests, examination or
other procedures which can be applied rapidly
✓ Is the application of a relatively simple, inexpensive test, examinations or other procedures to people
who are asymptomatic, for the purpose of classifying them with respect to their likelihood of having a
particular disease
✓ Is applying tests, examinations or other procedures to apparently healthy people for early detection of
disease.
● It sorts out apparently well persons who probably have a disease from those probably do not.
● It is a means of identifying persons at increased risk for the presence of disease, who warrant
further evaluation
✓ Example: ANC, well baby clinics
Population (or targeted group)
Screening test
Re-screen
Re-screen
Negative Positive
Diagnostic test
Positive Negative
Treatment
Figure: The screening process
● Screening differs from diagnostic tests:

✓ Screening tests are applied to apparently healthy people for early detection of disease. Whereas, in
case of clinical diagnosis tests are applied to sick people to diagnose their illness.
✓ A screening test is not intended to be diagnostic. Screening is an initial examination only, and positive
responders require a second, diagnostic examination
● Screening is generally done among individuals who are not suspected of having disease.
● Diagnosis involves confirmation of presence or absence of disease in someone suspected of
or at risk for disease

✓ Screening tests are after sub-clinical disease changes have occurred, but before symptoms are
manifest whereas diagnostic tests are after symptoms manifested. Look the following figure.
Figure: The natural history of disease and time for screening and diagnostic tests
● Note: Screening tests can also often be used as diagnostic tests
5.2. Purposes of screening:

● The main aim of screening is: to reduce mortality and/or morbidity by early detection and treatment.
✓ To reverse, halt, or slow the progression of disease more effectively than would probably normally
happen.
✓ To alter the natural course of disease for a better outcome for individuals affected.
● In general, screening has the following purposes:
✓ As part of an epidemiologic survey to determine the frequency or natural history of a condition. E.g.
Framingham study of coronary heart disease
✓ Control of communicable diseases and protection of the public's health (Protect society from
contagious disease) E.g. mass X-rays to detect pulmonary TB, screening trachoma
✓ To identify individuals at higher risk for developing the disease in the future.
✓ Rational allocation of resources
✓ Selection of healthy individuals: employment, military…
✓ Research; study on natural history of disease…
5.3. Types of screening

⇒ There are different types of screening, each with specific aims
1) Selective Vs mass screening
a) Selective screening: screening of people with selective exposure. It is targeted screening of groups with
specific exposures and is often used in environmental and occupational health
b) Mass screening: screening of people without reference to specific exposure. It involves screening of a whole
population
2) Single Vs Multiple
a) Single screening: involves a single screening test for occasion.
b) Multiple or multiphase screening:
● Involves a variety of screening tests on the same occasion.
● Can be classified as multiple-parallel Vs series
1. Parallel testing: applying two screening tests and a positive result on either test is
sufficient to be labeled as positive E.g. – Breast ca screening
2. Series testing: applying two screening tests and both must be positive in order to prompt
action. Example: HIV testing, Syphilis
3) Case-finding or opportunistic screening: is restricted to patients who consult a health practitioner for
some other purpose
5.4. Screening tests and evaluation of screening tests

⇒ For a screening to be successful a suitable screening test must be available.
● Screening tests are tests used for screening and can be: questions, clinical examinations, laboratory tests, x-
ray, genetic tests, etc….
● A screening test should ideally be inexpensive, easy to administer, and impose minimal discomfort on the
patients.
● The following are characteristics of good screening tests:
● Simple: the screening test should be easy to learn and perform.
● Rapid: the test should not take long time to administer, and the results should be available soon
● Inexpensive: the lower the cost of a test, the more likely it is that the overall program will be cost
beneficial.
● Safe and acceptable: the screening should impose minimal discomfort on the population and also
be acceptable, feasible.
● Valid and reliable: Results of the screening test must be valid and reliable.
✓ A test is reliable if it provides consistent results
✓ A test is valid if it correctly categorizes people into groups with and without disease.
● Therefore, a screening test to be considered as good it has to be evaluated with the above characteristics.
The following are the main measures to evaluate the validity and reliability of a screening test:
A. Validity
⇒ The ability of screening test to differentiate accurately those who have the condition from those who
don’t have, or specifically it is the ability to differentiate accurately between those who have and those
who don't have the disease.
⇒ Answers the question, does the test truly measure what it sets out to measure?
● Such assessments of what is “true” or “false” depend on the selection of a “gold standard”.
Although the truth or falsehood of measures by the “gold standard” method may, themselves, be
questioned, these are usually the best available information, which is the basis for evaluation of
the performance of a second test which is usually cheaper, easier, or safer.

⇒ Validity has two components: sensitivity and specificity and the following are key measures to be
calculated:
o Sensitivity
o Specificity
o Predictive Value
o Yield
⇒ In order to simplify the calculation of these validity measures of a screening test the following contingency
(two by two) table is important.
Table: Two-by-Two Table for Screening test evaluation
Definitive Diagnosis (Gold standard) disease status

Positive Negative Total
Pred.V+ve
S Positive Sens True Positive TP (a) Spec
False Positive FP (b) TP+FP(a + b)
c itivit ificit
Pred.V-ve
r Negative y False Negative FN (c) y True Negative TN (d) FN+TN(c + d)
e
e
n
i
n
g TP+FP+TN+FN
Total TP+FN (a +c ) TN+FP (b + d)
(a + b + c+ d)
T
e
s
t
a) Sensitivity
➢ Is defined as the proportion of cases with a positive screening test among all individuals with pre-clinical
disease (the proportion of people with a disease who have a positive test result
𝑃𝑒𝑜𝑝𝑙𝑒 𝑤𝑖𝑡ℎ 𝑡ℎ𝑒 𝑑𝑖𝑠𝑒𝑎𝑠𝑒 𝑎𝑛𝑑 𝑎 𝑝𝑜𝑠𝑖𝑡𝑖𝑣𝑒 𝑡𝑒𝑠𝑡 𝑇𝑃 𝑎
𝑆𝑒𝑛𝑠𝑖𝑡𝑖𝑣𝑖𝑡𝑦 = = = × 100
𝑇𝑜𝑡𝑎𝑙 𝑝𝑒𝑜𝑝𝑙𝑒 𝑤𝑖𝑡ℎ 𝑡ℎ𝑒 𝑑𝑖𝑠𝑒𝑎𝑠𝑒 𝑇𝑃 + 𝐹𝑁 𝑎 + 𝑐
➢ Is the ability of a test to identify correctly those who have the disease
o A test with high sensitivity will have few false negatives
o Want a highly sensitive test in order to identify as many cases as possible…… but there’s a trade
off with specificity.
➢ A sensitive test is preferable:
✓ When there is an important penalty for failing to detect a disease (e.g., when trying to detect a
dangerous but treatable condition, for rare but potentially severe communicable diseases).
✓ When the probability of disease is relatively low and the purpose of the test is to discover possible
cases.
b) Specificity
➢ Is defined as the proportion of individuals with a negative screening test result among all individuals with
no pre-clinical disease (the proportion of people without a disease who have a negative test
𝑃𝑒𝑜𝑝𝑙𝑒 𝑤𝑖𝑡ℎ𝑜𝑢𝑡 𝑡ℎ𝑒 𝑑𝑖𝑠𝑒𝑎𝑠𝑒 𝑎𝑛𝑑 𝑎 𝑛𝑒𝑔𝑎𝑡𝑖𝑣𝑒 𝑡𝑒𝑠𝑡 𝑇𝑁 𝑑
𝑆𝑝𝑒𝑐𝑖𝑣𝑖𝑡𝑦 = = =
𝑇𝑜𝑡𝑎𝑙 𝑝𝑒𝑜𝑝𝑙𝑒 𝑤𝑖𝑡ℎ𝑜𝑢𝑡 𝑡ℎ𝑒 𝑑𝑖𝑠𝑒𝑎𝑠𝑒 𝑇𝑁 + 𝐹𝑃 𝑏 + 𝑑
➢ Is the ability of a test to identify correctly those without the disease

o A test that has high specificity will have few false positives
➢ A specific test is preferable:
✓ When the test result is positive, and is often used to confirm a diagnosis, which has been suggested
by other data.
✓ When false positive results might have negative (physical, emotional, or financial) consequences.
⇒ Note: Sensitivity and specificity of a test are usually inversely related.
c) Predictive value
➢ It is the ability of the test results to predict the presence or absence of disease
● Measures whether or not an individual actually has the disease, given the results of a screening test
● The predictive value of a test is depend on (determined by):
✓ Specificity
✓ Sensitivity
✓ Prevalence of preclinical disease
𝑎+𝑐
𝑃𝑟𝑒𝑣𝑎𝑙𝑒𝑛𝑐𝑒 =
𝑎+𝑏+𝑐+𝑑
● The higher the prevalence, the more likely it is that a positive test is predictive of the diseases i.e.
PVPT will be high.
● The more sensitive a test, the less likely it is that an individual with a negative test will have the
disease (FN) and thus the greater the predictive value negative.
● The more specific the test, the less likely an individual with a positive test will be free from the
disease (FP) and the greater the predictive value positive.
● For rare disease, however, the major determinant of the predictive value positive is the prevalence
of the preclinical disease in the screened population.
● No matter how specific the test, if the population is at low risk of having the disease, results that are
positive will mostly be false positives.

● Predictive value of a test has two components

a) Predictive value of positive test:
● Is the proportion of individuals with the condition among those who have positive results
● Is the proportion of screening test positives who are truly positive
● It is the probability of disease in a person with a positive (abnormal) test result
𝑃𝑒𝑜𝑝𝑙𝑒 𝑤𝑖𝑡ℎ 𝑡ℎ𝑒 𝑑𝑖𝑠𝑒𝑎𝑠𝑒 𝑎𝑛𝑑 𝑎 𝑝𝑜𝑠𝑖𝑡𝑖𝑣𝑒 𝑡𝑒𝑠𝑡 𝑇𝑃 𝑎
𝑃𝑟𝑒𝑑𝑖𝑐𝑡𝑖𝑣𝑒 𝑣𝑎𝑙𝑢 𝑝𝑜𝑠𝑖𝑡𝑖𝑣𝑒 = = =
𝑇𝑜𝑡𝑎𝑙 𝑝𝑒𝑜𝑝𝑙𝑒 𝑤𝑖𝑡ℎ 𝑎 𝑝𝑜𝑠𝑖𝑡𝑖𝑣𝑒 𝑡𝑒𝑠𝑡 𝑇𝑃 + 𝐹𝑃 𝑎 + 𝑏
b) Predictive value of a negative test:

● It is the proportion of those who don’t have the condition among those have negative results
● It is the proportion of screening test negatives who are truly negative
● It is the probability of not having the disease when the test result is negative (normal)
𝑃𝑒𝑜𝑝𝑙𝑒 𝑤𝑖𝑡ℎ𝑜𝑢𝑡 𝑡ℎ𝑒 𝑑𝑖𝑠𝑒𝑎𝑠𝑒 𝑎𝑛𝑑 𝑎 𝑛𝑒𝑔𝑎𝑡𝑖𝑣𝑒 𝑡𝑒𝑠𝑡 𝑇𝑁 𝑑
𝑃𝑟𝑒𝑑𝑖𝑐𝑡𝑖𝑣𝑒 𝑣𝑎𝑙𝑢 𝑛𝑒𝑔𝑎𝑡𝑖𝑣𝑒 = = =
𝑇𝑜𝑡𝑎𝑙 𝑝𝑒𝑜𝑝𝑙𝑒 𝑤𝑖𝑡ℎ 𝑎 𝑛𝑒𝑔𝑎𝑡𝑖𝑣𝑒 𝑡𝑒𝑠𝑡 𝑇𝑁 + 𝐹𝑁 𝑐 + 𝑑
c) The yield of a screening test:

➢ The number of cases of the condition detected by screening test in relation to the total number of persons
screened (number of cases detected by the screening program)
𝑝𝑒𝑟𝑠𝑜𝑛𝑠 𝑤𝑖𝑡ℎ 𝑡ℎ𝑒 𝑑𝑖𝑠𝑒𝑎𝑠𝑒 𝑑𝑒𝑡𝑒𝑐𝑡𝑒𝑑 𝑏𝑦 𝑡ℎ𝑒 𝑡𝑒𝑠𝑡 𝑇𝑃
𝑌𝑖𝑒𝑙𝑑 = = × 100
𝑇𝑜𝑡𝑎𝑙 𝑠𝑐𝑟𝑒𝑒𝑛𝑒𝑑 𝑇𝑃 + 𝑇𝑁 + 𝐹𝑃 + 𝐹𝑁
➢ Affected by sensitivity, prevalence of unrecognized cases, number of tests employed, frequency of

screening and participation of people in screening and follow-up
B. Reliability (Precision)
❖ Reliability refers to the consistency of results when repeat examinations are performed on the same
persons under the same condition.
❖ The ability of a test to give consistent results when it is performed more than once on the same individual
under the similar conditions
❖ Does the test give the same measurement each time?
❖ Affected by variation in the method, observer and the characteristic to be measured
⇒ There are 4 sources of variability that can affect the reproducibility of results of screening test:
1) Biological variation
● inherent in the actual manifestation being measured such as BP
● which varies considerably for a given individual with time and other circumstances
2) Variation due to the test method or measurement
● Which relates to the reliability of the instrument itself, such as standard mercury
sphygmomanometer for BP
3) Intra observer variability

● Which refers to differences in repeated measurements by the same screener
4) Inter observer variation
● Which refers to inconsistencies attributable to differences in the way different screeners apply or
interpret test results
⇒ These variations can usually be reduced by:
1) Careful standardization of procedures
2) An intensive training period for all observers (or interviewers)
3) Periodic checks on their work
4) The use of two or more observers making independent observations.
5.5. Criteria for establishing screening program

⇒ The criteria for a successful screening program were first summarized in a WHO publication in 1968. They
can be broadened to screening for problems other than human disease:
1) The problem to be detected should be important enough to be worth detecting.
2) There should be an acceptable intervention, which is effective.
3) The intervention should be feasible and available.
4) There should be a recognizable latent or early “asymptomatic” stage.
5) There should be a suitable test.
6) The test should be acceptable to the population to be tested.
7) The natural history of the condition should be adequately understood.
8) There should be an agreed policy regarding when the intervention is appropriate.
9) The cost of detecting the problem and its remedy should be reasonable.
10) The screening program should be ongoing, and not a “one-time” effort.

CHAPTER SIX: INVESTIGATION OF EPIDEMICS

6.1. Levels of Disease Occurrence
⇒ Diseases occur in a community at different levels at a particular point in time.
✓ Expected levels
● Endemic: Presence of a disease at more or less stable level. The following are classification of
endemicity
o Hypoendemicity: little transmission and the disease has little effect on the population.
o Mesoendemicity: varying intensity of transmission; typically found in the small, rural communities
of the sub-tropics.
o Hyperendemicity: Persistently high level of disease occurrence. Intense but seasonal transmission;
immunity is insufficient to prevent the effects of malaria on all age groups.
o Holoendemicity: Intense transmission occurs throughout the year. As people are continuously
exposed to malaria parasites, they gradually develop immunity to the disease. In these areas, severe
malaria is mainly a disease of children from the first few months of life to age 5 years. Pregnant
women are also highly susceptible because the natural immune defence mechanisms are impaired
during pregnancy.
Table 1: Classification of endemicity of malaria
Type Spleen rates Parasite rates Description
<= 10% of children aged Areas where there is a little
<= 10% of children aged 2-9 years but may be transmission and the effects, during the
Hypoendemicity
2-9 years higher for part of the average year, upon the general
year population are unimportant
Typically found among rural
11-50% of children aged 11-50% of children aged communities in subtropical zones
Mesoendemicity
2-9 years 2-9 years where wide geographical variations in
transmission risk exist
Constantly > 50% in
Areas where transmission is intense
Hyperendemicit children aged 2-9 years; Constantly > 50%
but seasonal; immunity is insufficient
y also high in adults among children aged 2-9
in all age groups
(>25%)
Constantly > 75% in Constantly > 75% Intense transmission resulting in a
Holoendemicity children aged 2-9 years, among infants aged 0-11 considerable degree of immunity
but low in adults months outside early childhood
✓ Excess of what is expected

● There is no general rule about the number of cases that must exist for a disease to be considered an
epidemic.
● If the number of cases exceeds the expected level on the basis of the past experience of the particular
population, then it is an epidemic.
o Epidemic: is the occurrence a specific disease more than the expected number in a given area or
among a specific group of people over a specified period of time.
▪ Outbreak: Epidemics of shorter duration covering a more limited area.

▪ Pandemic: An epidemic involving several countries or continents affecting a large number of
people. When epidemics occur at several continents – global epidemic
▪ Epidemics can have the following patterns
● Sporadic: irregular interval E.g. – Plague
● Periodic/Cyclic: regular intervals E.g. –malaria, measles, diarrhea, meningitis
● Secular: slow changes over time E.g. – lung ca
⇒ Note:
o Epidemic lasting long may remain endemic
o Endemic disease can turn out to be epidemic due to increase in susceptibles, ecological changes,
increase in no of carriers, appearance of new strains
Figure 1: Expected Vs Excess Cases

● Cluster is an aggregation of cases in a given area over a particular period without regard to whether the
number of cases is more than expected.
o Disease Clustering
▪ Clustering is commonly due to an aggregation of relatively rare events or diseases in time
and/or place.
▪ Clustering should not be used in the context of common diseases.
▪ Clustering could be a mini-epidemic of a rare event in which occurrence of the disease is
clearly in excess of that expected.
▪ Clusters provide useful clues to public health action.
6.2. Types of epidemics
⇒ Epidemics (outbreaks) can be classified according to the method of spread or propagation, nature and length
of exposure to the infectious agent, and duration:
o Common source epidemics,
o Propagated /progressive epidemics. and
o Mixed epidemics
a. Common source epidemics
✓ Common source epidemics are caused by exposure of a group of susceptible persons to a common source of
a noxious influence, such as an infectious agent or a toxin, often at the same time or within a brief time

period.
✓ Depending on duration of exposure:
o Point source Vs Common source with prolonged (continued or intermittent) exposure
● Point source epidemics
o When the exposure is simultaneous, the resulting cases develop within one incubation
period and this is called a point source epidemic.
o The epidemic curve in a point source epidemic will commonly show a sharp rise and fall.
o E.g. Food borne epidemic following an event where the food was served to many people.
● Common source epidemic with continuous or intermittent exposure

✓ If the source of an outbreak remains for a longer time; days, weeks or longer either continuously or
intermittently, there will be multiple exposures with variable incubation period.
● Exposure continues over a period of time
● Lasts for more than one incubation period
o Continuous common source: makes wide peak in the epidemic curve, because of the
range of exposures and range of incubation periods.
o Intermittent common source: results in an irregular pattern of the epidemic curve
that reflects the intermittent nature of the exposure.
● Examples
o Outbreak of hepatitis A from exposure to food contaminated by infected food
handler intermittently or continuously
o A waterborne outbreak that is spread through a contaminated community water
supply

b. Propagated/Progressive epidemics
✓ Occur as a result of transmission from one person to another
o Infectious agent is transferred from one host to another.
o It can occur through direct and indirect transmissions.
✓ Lasts for more than one incubation period E.g. – Measles, Malaria, Shigellosis
✓ Epidemic curve-initial slow rise, succession of several peaks
✓ In the propagated epidemics there will be successive generations of cases.

c. Mixed
✓ The epidemic begins with a single, common source of an infectious agent with subsequent propagative
spread.
✓ Point source epidemic may be followed by propagated epidemic
✓ Many food borne pathogens result in mixed epidemics.
✓ E.g. Shigelloses epidemic from exposure to common contaminated food supply followed by person-to-
person spread
6.3. Investigation and control of an epidemic
⇒ Investigating disease outbreaks is a form of active surveillance.
⇒ The purpose is to determine the specific cause or causes of the outbreak at the earliest time and to take
appropriate measure and prevent future occurrence.
A. Reasons investigate possible outbreaks
1. To institute control and prevention measures: identify cause of an outbreak, eliminate the source, and
provide post exposure prophylaxis
2. Opportunity for program evaluation: improve public health regulations and recommendations for
disease prevention
3. Opportunity for research:
✓ Outbreak investigation uncover:
o New infectious agents and diseases (Legionnellosis, toxic shock syndrome, Ebola…),
o Spread of agent/disease to new geographic areas (West Nilelike virus encephalitis),
o New means of disease transmission (E. Coli from swimming pools)
4. Training opportunity
5. Public, political, or legal concerns
B. Uncovering (detecting) outbreaks
⇒ In order to investigate and control an epidemic, uncovering of it is essential step.
⇒ Outbreaks are detected in one of the following ways:
1. Through timely analysis of routine surveillance data, this may reveal an increase in reported cases or
unusual clustering of cases.
2. Report from clinician.
3. Report from the community, either from the affected group or concerned citizen.
C. Basic Principles of Outbreak Investigation
1. Conduct multiple activities simultaneously; run a dynamic process.
2. Maintain communication with officials, stakeholder and the public.
3. Apply epidemiological and statistical principles regarding study design and analysis appropriately.
4. Record all steps taken in the investigation and all information gathered.
5. Careful and critical review of the literature should be undertaken.
⇒ Investigators must maintain open but critical mind to uncovered new pathogens/transmission means
D. Steps in epidemic investigation
⇒ There is no hard and fast rule but verification of the diagnosis and establishment of the existence of an
epidemic always deserves early attention
1. Prepare for field work
2. Verify the diagnosis
3. Verify the existence of an epidemic
4. Describe the epidemic with respect to person, place and time
5. Formulate and test hypothesis
6. Search for additional cases
7. Evaluate the hypothesis
8. Refine hypotheses and carry out additional studies
9. Analyze the data
10. Make a decision on the hypothesis tested
11. Intervention and follow up
12. Report of the investigation
1. Prepare for fieldwork.
● Before leaving for the field an investigator must be well prepared to undertake the investigation.
● Preparations can be categorized into three:
a. Investigation related:
✓ Investigator must have the appropriate scientific knowledge, supplies, and equipment to carry out
the investigation.
✓ Discuss the situation with knowledgeable people, review applicable literature, and collect sample
questionnaire.
b. Administration related: includes arrangement of transportation and organizing personnel matters.
c. Consultation related:
✓ Clarify your and your team role in the field.
✓ Identify local contacts at the site where the outbreak is reported and arrange where and when to
meet them.
2. Verify the existence of an epidemic.
✓ Rule- “When you receive a report of epidemic, it is always epidemic unless disproved.”
✓ Before you decide whether an outbreak exists, you must first determine the expected or usual number of
cases for the given area and time. This initial determination is often made on the basis of preliminary data.
✓ Background rates of most conditions show random variation. How can we measure if there is an increase in
incidence is significant?
o Compare the number of cases with the past levels to identify whether the present occurrence is in
excess of its usual frequency.
o Excess cases may be actual/real or artifactual
1. Actual:
a) Change in incidence
b) Change in age composition
c) Catastrophes
d) Duration of illness
2. Artifactual
a) Change in diagnostic methods
b) Change in case detection
c) Change in reporting
d) Change in disease classification/ death
e) Change in population count
o Data Sources:
1. Health department surveillance records for a notifiable disease
● Public Health Surveillance: The ongoing and systematic collection, analysis, and
interpretation of outcome-specific data for use in the planning, implementation, and
evaluation of public health practice.
● Notifiable Disease: Disease for which regular, frequent, and timely information regarding
individual cases is considered necessary for the prevention and control of disease
2. Sources such as hospital discharge records, mortality records and cancer or birth defect registries
for other diseases and conditions
3. If local data is not available, make estimates using data from neighboring states or national data
o Whether or not an outbreak is investigated or control measures are implemented is not strictly tied to
verifying that an epidemic exists…
o Other factors may come into play, including:
➢ Severity of the illness
➢ Potential for spread
➢ Political considerations
➢ Public concern and pressure from community
➢ Availability of resources
3. Verify the diagnosis (Confirm the diagnosis)
✓ Two goals in verifying a diagnosis:
1. Ensure that the problem has been properly diagnosed -- the outbreak really is what it has been
reported to be
● Review clinical findings and laboratory results for affected people
● Visit or talk to several of the people who became ill

2. For outbreaks involving infectious or toxic chemical agents, be certain that the increase in
diagnosed cases is not the result of a mistake in the laboratory.
✓ Carry out clinical and laboratory studies to confirm the diagnosis.
✓ It is necessary to establish criteria for labeling persons as “cases.”
✓ Review clinical and laboratory findings to establish diagnosis.
● Establish case definition
● Identifying and counting cases (Surveillance)
a) Case definition
o Case definition is a standard set of criteria for deciding whether an individual should be classified
as having the health condition of interest.
● Includes clinical criteria, particularly in an outbreak investigation, restricted by time, place,
and person as necessary.
o Application of case definition:
● Set simple and objective measures, and apply them consistently and without bias to all persons
under investigation.
● Do not include an exposure or risk factor, which is going to be tested in the case definition.
● Use "loose" case definition early in the investigation to identify the extent of the problem and
the population affected.
o Classification of Case definition
● Definite: laboratory confirmed case
● Probable: cases with objective signs and symptoms consistent with the case definition
● Possible: cases with subjective signs and symptoms consistent with the case definition
b) Identifying and counting cases (Surveillance)
o The first cases to be recognized are usually only a small proportion of the total number
o To identify other cases, use as many sources possible
● Stimulated or enhanced passive surveillance: Relies on routine notifications by healthcare
personnel (recall Notifiable Diseases)
● Active Surveillance: Involves regular outreach to potential reporters to stimulate reporting
of specific conditions; investigators are sent to the afflicted area to collect more information
✓ Contact physician offices, hospitals, schools to find persons with similar symptoms
or illnesses
✓ Send out a letter, telephone or visit the facilities to collect information
o The following information about person, place and time on every case should be collected from
every affected person in an outbreak:
a) Identifying information - name, address, phone
b) Demographic information - e.g., age, sex, race, occupation
c) Risk factor information
d) Reporter information
e) Clinical information
● Verify the case definition has been met for every case
● Date of onset of clinical symptoms to create an epidemic curve

o Pseudo-Outbreak: false verification
● Could be due to:
➢ Incorrect diagnosis
➢ Failure to separate colonization from infection
➢ Chance clustering
➢ Contamination during specimen collection, transportation, or processing
(contaminated media, solutions, or equipment)
➢ Error in laboratory methods
4. Describe the data in terms of time, place and person (descriptive epidemiology).
✓ Each case must be defined according to standard epidemiologic parameters:
➢ The date of onset of the illness,
➢ The place where the person lives or became ill, and
➢ The socio-demographic characteristics (age, sex, education level, occupation).
✓ Characterizing an outbreak by time, place and person is called descriptive epidemiology. Descriptive
epidemiology is important because:
o You can learn what information is reliable and informative (e.g., similar exposures)
o And what may not be as reliable (e.g., many missing responses to a particular question)
o Provides a comprehensive description of an outbreak by showing its trend over time, its geographic
extent (place) and the populations (people) affected by the disease
✓ The tools to be used when characterizing the epidemic are epidemic curve, spot map and attack rates.
➢ Epidemic curve: the distribution of cases is plotted over time, usually in the form of histogram, with
the date of onset of each case on the horizontal axis, and the number of cases corresponding to each
date of onset on the vertical axis.
➢ Spot map: is a map of locality where the outbreak has occurred, on which the location of cases is
plotted.
o Spot map is often helpful in detecting the source of an outbreak.
o Mapping disease can be done at all levels, on a local, district, regional, countrywide, or
international basis, depending on the purpose, which can be not only to investigate epidemics
or disease etiology, but also to plan the allocation of resources on a geographic basis.
o One limitation of spot map is that it does not take into account underlying geographic
differences in population density.
o Thus the spot map needs to be supplemented by calculation of place specific attack rates
➢ Attack rates: The tool that is important for the analysis of disease outbreaks by personal
characteristics is person specific attack rates i.e. attack rates by age, sex, occupation, income,
religion etc.
✓ Describe and orient the data in terms of time, place and person.
a) Describe and orient the data in terms of time
● The time course of an epidemic is shown by the distribution of the times of onset of the disease,
called the Epidemic curve.

o Graph of the number of cases of the health event by their date of onset
o Provides a simple visual display of the magnitude and time trend of the outbreak
o May stratify epidemic curves by place (residence, work, school, etc.) or by personal traits
(age, gender, race, etc.) to assess whether time of onset varies in relation to place or person
characteristics
b) Describe and orient the data in terms of place
● Assessment of the outbreak by place provides:
o Information on the geographic extent of the problem
o A “spot map” indicating place of occurrence of cases may show clusters or patterns that
provide clues to the nature and source of the outbreak
o Patterns reflecting water supply, wind currents, or proximity to a restaurant, swimming pool,
school room or workplace
o If the size of overall population varies between comparison areas, a “spot map” of the area
may be misleading because it only shows number of cases
c) Describe and orient the data in terms of person
● Examine risks in subgroups of the affected population according to personal characteristics, as well
as interaction between characteristics
● Age, sex, occupation, SES, marital status, religion, ethnicity etc (beware of reverse causality)
● Characterizing an outbreak by person helps to determine which subgroups of the population are at
risk
✓ Studying the PPT distribution or agent host environment relationship, possible source, causative agent,
mode of spread and environmental factors related to epidemic can be delineated.
✓ Epidemic investigation also involves evaluation of ecological factors like sanitary status of hotels, water
and milk supply, breakdown in water supply system, population mobility, atmospheric

5. Formulate and test hypothesis.

✓ This step involves the assessment of the data collected to date and the generation of hypotheses that may
explain the outbreak.
✓ The goal is to explain the specific exposure (s) that caused the outbreak.
✓ Though we generate hypotheses from the beginning of the outbreak, at this point, the hypotheses are
sharpened and more accurately focused.
✓ Use existing knowledge (if any) on the disease, or find analogies to diseases of known etiology
✓ The hypothesis should address:
o Source of agent,
o Mode of transmission and
o Exposure that caused the disease.
o Changes such as temperature, humidity, and air pollution, bionomics of insects and animal reservoirs.
✓ The hypothesis should be proposed in a way that can be tested
✓ The analytic technique utilizes the cohort and the case-control approach to identify possible source of an
outbreak.

6. Search for additional cases.

✓ Locate unrecognized or unreported cases:
✓ Use a case definition.
7. Evaluate the hypothesis
✓ Generally, after a hypothesis is formulated, one should be able to show that:
o all additional cases, lab data, and epidemiologic evidence are consistent with the initial hypothesis; and
o no other hypothesis fits the data as well
o Observations that add weight to validity:
● The greater the degree of exposure (or higher dosage of the pathogen), the higher the
incidence of disease
● Higher incidence of disease in the presence of one risk factor relative to another factor

✓ Attack Rates
o An attack rate is the proportion of a well-defined population that develops illness over a limited period
of time, such as during an epidemic or outbreak
● Useful for comparing the risk of disease in groups with different exposures
● Similar to a cumulative incidence
● Often expressed as a percent
o Identifying the source of an outbreak
● Look for an item with:
➢ A high attack rate among those exposed and
➢ A low attack rate among those not exposed (so the ratio of attack rates for the two groups is
high)
➢ Ideally, most of the people who became ill should have been exposed to the proposed agent
so that the exposure could explain most, if not all, of the cases.
8. Refine hypotheses and carry out additional studies
✓ Additional epidemiologic studies
o What questions remain unanswered about the disease?
o What kind of study used in a particular setting would answer these questions?
o When analytic studies do not confirm the hypotheses
● reconsider the original hypotheses
● look for new vehicles or modes of transmission
✓ Laboratory and environmental studies
o Investigate environmental conditions such as food sanitation, suspected breading sites, animal
reservoirs, according to the type of disease outbreak being investigated
● Epidemiologic studies can
● Implicate the source of infection, and
● Guide appropriate public health action
● But sometimes laboratory evidence can “clinch” the findings
● Environmental studies often help explain why an outbreak occurred and may be very
important in certain settings
9. Analyze the data.
✓ Assemble all the results.
✓ Analyze and interpret findings.
10. Make a decision on the hypothesis tested.
11. Intervention (Implementing control and prevention measures) and follow-up
⇒ The practical objectives of an epidemic investigation are to:
1) Stop the current epidemic, and
● Intervention (preliminary control measures)
✓ Must start as soon as possible depending on the specific circumstances.

✓ Aim control measures at the weak link or links in the chain of infection.
✓ Might aim control measures at the specific agent, source, or reservoir. These measures
have been discussed in the following topic (management of epidemics).
● Follow-up
✓ Evaluation of control measures
✓ Continued surveillance
✓ Sharing experience
2) Establish measures that would prevent similar outbreaks in the future.
12. Report of the investigation.

✓ At the end prepare a comprehensive report and submit to the appropriate/concerned agency (or agencies).
✓ The report should follow the usual scientific format:
➢ Introduction,
➢ Background,
➢ Methods,
➢ Results,
➢ Discussion, and
➢ Recommendations.
✓ The report should discuss in detail:
➢ Factors leading to the epidemic.

➢ Evaluation of measures used for the control of the epidemic.

➢ Recommendations for the prevention of similar episodes in the future.
➢ Management of the outbreak/epidemics
✓ The written report:
➢ Will serve as a record of performance and document for potential legal issues
➢ Will be used as reference by health department for future outbreaks
➢ Will contribute to knowledge base of epidemiology and public health
6.4. Management of epidemics

✓ Management of epidemics requires an urgent and intelligent use of appropriate measures against the spread
of the disease.
✓ Action to be taken is dependent on the type of the disease as well as the source of the outbreak.
✓ Action can be generally categorized as presented below to facilitate easy understanding of the strategies:
A. Measures directed against the reservoir
B. Measures that interrupt the transmission of organisms
C. Measures that reduce host susceptibility
A. Measures Directed Against the Reservoir
● Understand the nature of the reservoir
● Examples of control measures against disease with various reservoirs:
● Domestic animals as reservoir:
o Immunization
o Testing of herds
o Destruction of infected animals. Example: brucellosis and bovine tuberculosis.
● Wild animals as reservoir:
o post-exposure prophylaxis
o Example: rabies
● Humans as reservoir
o Removal of the focus of infection- e.g. cholecystectomy for Typhoid fever.
o Isolation of infected persons.
▪ This is separation of infected persons from non-infected for the period of communicability.
▪ Not suitable in the control of diseases in which a large proportion are inapparent infection or in
which maximal infectivity precedes overt illness.
o Treatment to make them noninfectious- e.g., tuberculosis.
o Disinfection of contaminated objects.
o Quarantine-
▪ Is the limitation of freedom of movement of apparently healthy persons or animals who have
been exposed to a case of infectious disease.
▪ Usually imposed for the duration of the usual maximal incubation period of the disease.
▪ Cholera, Plague, and yellow fever are the three internationally quarantinable diseases by
international agreement.
▪ Now quarantine is replaced in some countries by active surveillance of the individuals;
maintaining close supervision over possible contacts of ill persons to detect infection or illness
promptly
B. Measures that interrupt the transmission of organisms
● Action to prevent transmission of disease by ingestion:
o Purification of water
o Pasteurization of milk
o Inspection procedures designed to ensure safe food supply.
o Improve housing conditions.
o Their freedom of movement is not restricted.
o Attempts to reduce transmission of respiratory infections are made through:
▪ Chemical disinfection of air and use of ultraviolet light.
▪ Work on ventilation patterns, like unidirectional ("laminar") air flow to reduce the transmission
of organisms is used in hospitals.
o In the case of diseases that involve an intermediate host for transmission, for example
schistosomiasis, clearing irrigation farms from snails is an appropriate measure.
C. Measures that reduce host susceptibility
a. Active immunization
b. Passive immunization
c. Chemoprophylaxis
6.5. Challenges of investigating out brakes
✓ Urgency to find the source and prevent additional cases.
✓ Substantial pressure from the public/decision makers to conclude investigation quickly.
✓ Inadequate statistical power of the investigation due to limited number of cases.
✓ Early media reports concerning the outbreak may bias responses of persons subsequently identified and
interviewed for the investigation.
✓ Useful clinical and environmental samples may be very difficult or impossible to obtain if investigation is
not started promptly.

CHAPTER SEVEN: EPIDEMIOLOGIC SURVILLANCE

7.1. Introduction
⇒ Epidemiologic surveillance is an on-going systematic collection, analysis, interpretation and dissemination of
health-related data essential to the planning, implementation, and evaluation of public health practice.
⇒ It is a system of close observation of all aspects of the occurrence and distribution of a given disease through
systematic collection, tabulation, analysis, and dissemination of all relevant data pertaining to that disease.
o Provides "information for action" which can be used to investigate, prevent, and control disease in
communities.
o Provide a factual basis for setting priorities, planning programs, and taking action to promote and protect
community health.
o Essential characteristics surveillance
● Dynamic/continuous
● The continuous nature of surveillance will enable to establish baseline information
regarding the normal pattern of disease so that unusual occurrences e.g. epidemic,
seasonal, cyclic or secular trends could be identified.
● Current/timely
● Public health surveillance main function is to serve as an “early warning system”:
providing timely information needed for action(rapid reporting, confirmation, decision
making and response)
● Purposeful/orientation to action
● Provides "information for action" which can be used to investigate, prevent, and control
disease in communities.
● Provide a factual basis for setting priorities, planning programs, and taking action to
promote and protect community health.
o Can be conducted globally (as in the AIDS surveillance system managed by WHO), regional (as in the
polio surveillance in Latin America), national, or institutional (as in the surveillance for hospital acquired
or nosocomial infections).
7.2. Objectives of surveillance

⇒ Surveillance has the following objectives
1. Monitoring health trends:
o Detection of an increase in adverse health events can alert for further investigation
o Information on the demographic characteristics of individuals with health problems permits identification
of groups at higher risk of disease
o Information on specific exposures or behaviors provides insight into etiology or modes of spread of the
disease.
2. Link to services:
o Surveillance provides aggregated data for health planners and serves to initiate individual preventive
actions.
o By describing where most cases of disease occur or where disease rates are higher surveillance provides
another means for targeting public health interventions.
3. Links to research:
o Surveillance can provide an important bridge to researchers by providing clues for further investigation
and by identifying individuals who may be subjects in specific research projects.
4. Evaluation of interventions:
o Surveillance may provide a comparatively inexpensive and sufficient assessment of the impact of
intervention efforts.
5. Projections:
o Observed trends in disease pattern combined with other information about the population at risk can be
used to estimate future trends.
6. Education and policy:
o Because surveillance data are essential, they are widely and effectively disseminated to those who :
✓ Participated in their collection…
✓ Use them (the public, media, political leaders)
o This information educates those who directly responsible for providing health care, control or influence
the allocation of health resources.
⇒ Principal purposes of surveillance are to:

o Identify diseases, injuries, hazards and other health related factors as early as possible, i.e. prediction
and early detection of outbreaks.
● Enable early recognition, investigation and control of outbreaks.
o Provide scientific baseline data and information for priority setting, planning, implementing and
evaluating disease control programs for both communicable and non-communicable health problems.
o Define the magnitude and distribution of diseases by time, person and place dimension
● Provide information for understanding the distribution of disease by time, place and person and
provide clues for the investigation of disease aetiology and ease effective control
⇒ Generally we undertake surveillance to:
o Estimate magnitude of the problem
o Determine geographic distribution of illness
o Portray( depict or explain or describe) the natural history of a disease
o Detect epidemics/define a problem
o Generate hypotheses, stimulate research
o Evaluate control measures
o Monitor changes in infectious agents
o Detect changes in health practices
o Facilitate planning
⇒ We monitor health events for the following purposes:
o To detect sudden changes in disease occurrence and distribution (determines the need for epidemic
investigation and control) and to ensure that effective action to control the disease is being done.
o To follow secular (long-term) trends and patterns of disease (alerts decision makers of the need to
reallocate resources or shift policy)
o To identify changes in agents and host factors (helps to assess the potential for future disease
occurrence)
o To detect changes in health care practices (points up the need for changes in preventive measures)

7.3. Attributes, activities of a surveillance system and sources of data

⇒ Attributes of a good surveillance system
1. Simple
2. Flexible
3. Acceptable
4. Sensitive; able to detect the problem
5. Good predictive value positive; good yield
6. Representative
7. Timely
8. Cost effective
⇒ Sources of data for surveillance
o The following are some key sources of surveillance data, not all of which are available in every country:
✓ Census data
✓ Mortality reports (birth and death certificates, autopsy reports)
✓ Morbidity reports (notifiable disease reports)
✓ Hospital data (discharge diagnoses, surgical logs, hospital infection reports)
✓ Absenteeism records (school, workplace, compensation claims)
✓ Epidemic reports
✓ Laboratory test utilization and result reports
✓ Drug utilization records
✓ Adverse drug reaction reports
✓ Special surveys (e.g., research data, serologic surveys)
✓ Police records (especially for injury, alcohol-related crime)
✓ Information on animal reservoirs and vectors (e.g., for rabies, plague, Lyme disease)
✓ Environmental data (hazard surveillance, water and food testing)
✓ Special surveillance systems (e.g., for injury and occupational illness)
⇒ Activities in surveillance are:
1) Data collection and recording
2) Reporting and notification
3) Compilation, data analysis and interpretation
4) Dissemination of the findings for appropriate action
o Disease prevention and control
o Health planning and resource allocation
o Research and teaching
7.4. Types of Surveillance

1) Active surveillance:
o Surveillance that in which public health officials contact providers to solicit reports of events or
diseases.

o Surveillance where public health officers seek reports from participants in the surveillance system on a
regular basis, rather than waiting for the reports.
● Such active surveillance is usually limited to specific diseases over a limited period of time,
such as after a community exposure or during an epidemic.
o Conditions in which active surveillance is appropriate:
● For periodic evaluation of ongoing programs. E.g. HIV/AIDS, EPI...
● For programs which have time limit of operation. E.g. Small pox
● With the occurrence of unusual situations:
✓ When a new disease/event discovered
✓ When investigating a new mode of transmission
✓ When a high-risk period is recognized
✓ When a disease appears in a new geographic area or found to affect a new subgroup of
the population
✓ When previously eradicated disease reappear or low incidence disease occur at a higher
level of endemicity
2) Passive surveillance:
o Surveillance that in which health care providers send reports based on a known set of rules and
regulations
o Surveillance where reports are awaited and no attempts are made to seek reports actively from the
participants in the system.
● Incomplete reporting, especially in passive surveillance systems, is very common.
3) Sentinel surveillance
o Surveillance that uses a pre-arranged sample of reporting sources to report all cases of one or more
conditions.
● Usually the sample sources are selected to be those most likely to see cases.
● Particularly in developing countries, sentinel surveillance provides a practical alternative to
population-based surveillance.
● Under this strategy, health officials define homogenous population subgroups and the regions to
be sampled.
● They then identify institutions that serve the population subgroups of interest, and that can and
will obtain data regarding the condition of interest.
● Main Purposes of Sentinel Surveillance
✓ To detect changes
✓ To direct and focus control efforts
✓ To develop intervention strategies
✓ To promote further investigations
✓ Provide the basis for evaluating preventive strategies and activities
➢ Note:

o Enhanced surveillance: The collection of additional data about cases reported under routine surveillance.
o Intensified surveillance:: The upgrading from a passive to an active surveillance system for a specified
reason and for a limited period (usually because of an outbreak)
7.5. Criteria for selection of disease for surveillance:

⇒ Factors related with the selection of disease for surveillance include:
o Magnitude of the disease
● Frequency
● Incidence
● Prevalence
● Mortality
● Severity
● Case fatality ratio
● Hospitalization rate
● Disability rate
● Years of potential life lost
● Quality adjusted life years lost
o Communicability (Potential for spread)
o Preventability
o Feasibility of control measures
o Need for monitoring and evaluating the performance of a control program
o Cost
o Public Interest
⇒ Analysis of surveillance data
o Descriptive analysis: distribution by time, place and person
● Frequency of events
● Calculate rates- need proper denominator
o Observe trends: comparison current data with expected value, identify differences, and assess the
relevance of the difference
● Draw graphs to show long term (secular) trends
⇒ Dissemination of surveillance data
o Disseminate surveillance data to all stakeholders
● Those who provide the reports (health providers)
● The community – affected/potentially affected
● Decision makers
o Disseminate report locally, nationally or globally; as deemed necessary
o Disseminate report timely and regularly
o Disseminate through appropriate media: newsletter or bulletin (paper or electronic)
⇒ Features of good surveillance system
o Uses a combination of passive and active mechanisms to collect data.
o Emphasize the collection of minimum data in a simplest possible way.

o To assure quality and enhance compliance make sure that the data collected is useful for the
workers who collect the data.
o Timely reporting.
o Timely and comprehensive action.
o Action must be targeted towards both case detection and treatment and as well as to the control of
the disease.
o Strong laboratory services for accurate diagnosis.
⇒ Limitations of surveillance systems
o Surveillance systems are never perfect. Understanding the limitations of surveillance data is important
to ensure correct interpretation. The most common limitations of surveillance systems include:
1) Under reporting (such as due to lack of knowledge of reporting requirements, negative attitudes
toward reporting)
2) Lack of representativeness of reported cases (such as due to a bias toward reporting severe
cases, or increased likelihood of reporting after publicity)
3) Lack of timeliness
4) Inconsistency of case-definitions
⇒ These limitations suggest specific steps which may be taken to improve a surveillance system. Most
commonly, surveillance systems are strengthened by improving awareness of practitioners, simplification of
the process of reporting, frequent feedback to those reporting, widening the "net" (for example, obtaining
reports from laboratories or schools, rather than relying on physicians), and using active (rather than passive)
surveillance.
7.6. Integrated Disease Surveillance and Response (IDSR): Concept and Experience in Ethiopia
⇒ Integrated disease surveillance and response (IDSR) is an approach adapted to strengthen national disease
surveillance systems by coordinating and streamlining all surveillance activities and ensuring timely provision
of surveillance data to all disease prevention and control programmes in order to initiate timely response
(intervention).
⇒ IDSR initiative was launched by the WHO-AFRO (Africa regional office for WHO) in the second half of the
1990’s. Since then the initiative has been adapted by many African countries including Ethiopia.
o Improving communicable disease surveillance and response through integrated disease surveillance
(IDSR) linking community, health facility, woreda and national levels in the country promotes rational
use of resources.
o The use un-integrated disease surveillance systems involving using the same constrained structures,
processes and personnel puts a lot of unnecessary pressure on the system and cannot produce results as
needed and effectively. Thus, integration of the surveillance and response activities offers a lot of
advantages.
⇒ Integrated disease surveillance and response:
o Focuses at the woreda level, as this is the lowest level in the health system with full-time staff dedicated
to all aspects of public health.
o Coordinates and streamline all surveillance activities combining available resources (human, material,
financial…) from a single focal point at woreda level.
o Facilitate collaboration between surveillance focal points at the woreda, regional and national levels
and epidemic response committees at each level in taking appropriate and timely public health
responses and actively seek opportunities for combining resources.
o The overall objective of the IDSR is to improve the ability of health workers to detect and respond to
priority communicable diseases at the woreda level.
o Effective and timely decision-making based on good evidence increases efficient utilization of available
resources for preventing and controlling communicable diseases and improving the health status of the
population.
⇒ IDSR in order to achieve its objectives seeks to:
o Strengthen the capacity of woredas to conduct effective surveillance activities
o Integrate multiple surveillance systems so that forms, personnel and resources can be used more
efficiently and effectively
o Improve the use of information for decision making
o Improve the flow of surveillance information between and within levels of the health system
o Improve laboratory capacity in identification of pathogens and monitoring of drug sensitivity
o Increase the involvement of health workers in the surveillance system.
o Emphasize community participation in detection and response to public health problems
o Strengthen the involvement of laboratory personnel in epidemiological surveillance.

E1. Epidemiology

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E1. Epidemiology

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LECTURE NOTE FOR EPIDEMIOLOGY

FOR HEALTH OFFICER STUDENTS

By Shimeles Dagne (MPH)Page 2

CHAPTER ONE: INTRODUCTION TO EPIDEMIOLOGY

By Shimeles Dagne (MPH)Page 3

1.2. History of epidemiology

By Shimeles Dagne (MPH)Page 4

1.3. Application/uses of epidemiology

1.4. Basic assumptions of epidemiology

1.6. Theories and principles of disease causation

● There are different principles of disease causation:

By Shimeles Dagne (MPH)Page 6

✓ 𝐹𝑎𝑐𝑡𝑜𝑟 𝐴 + 𝐹𝑎𝑐𝑡𝑜𝑟 𝐵 + 𝐹𝑎𝑐𝑡𝑜𝑟 𝐶 + ⋯ → 𝐷𝑖𝑠𝑒𝑎𝑠𝑒

environment that brings the host and the agent together.

Figure 1.1: The ecological triangle/triad of disease causation

By Shimeles Dagne (MPH)Page 8

Figure 1.2: The wheel model of disease causation

By Shimeles Dagne (MPH)Page 9

CHAPTER TWO: COMMUNICABLE DISEASE EPIDEMIOLOGY

diseases over the past decades, communicable diseases:

A. Natural History of Diseases

By Shimeles Dagne (MPH)Page 10

therapeutic measures, host factors, and other influences.

✓ Stage of pre-symptomatic (sub-clinical) disease

✓ Stage of clinical disease

✓ Stage of disability or death

3. The Clinical stage

✓ The outcomes of this stage may be recovery, disability or death. Examples:

✓ Still, other diseases will end in death.

By Shimeles Dagne (MPH)Page 12

By Shimeles Dagne (MPH)Page 13

By Shimeles Dagne (MPH)Page 14

● Breast cancer (prevention of the invasive stage of the disease)

D. Chain of disease transmission

By Shimeles Dagne (MPH)Page 15

Figure 2.2: Factors involved in the chain of communicable disease transmission.

⇒ Many infectious diseases have more than one reservoir.

By Shimeles Dagne (MPH)Page 16

⇒ Types of reservoirs of infectious agent:

1. Humans as reservoir of infectious agents.

By Shimeles Dagne (MPH)Page 17

By Shimeles Dagne (MPH)Page 18

By Shimeles Dagne (MPH)Page 19

➢ Brucellosis - Cows, pigs and goats to man

Animal …….. Animal…………Animal

ii. Example, infectious agents of HIV/AIDS, STDs

d. Skin and mucus membrane

ii. Example, infectious agents of HIV/AIDS, syphilis

✓ Transplacental transmission of syphilis,

✓ Airborne: dust, droplets

✓ Vector-borne: insect animals...

✓ Vehicle-born: food, water, towels...

By Shimeles Dagne (MPH)Page 23

By Shimeles Dagne (MPH)Page 24

● Acquired by transplacental transfer from mother to fetus or by injection of antitoxin or immune

⇒ Nonspecific factors that defend against infection include

● Skin and mucus membrane

● Mucus, tears, gastric acid secretion

● Cilia in the respiratory tract

● Reflex responses such as coughing and sneezing

though they all have the same exposure to infectious agents.

✓ Low levels of immunity could be due to:

● Disease (like HIV/AIDS) or therapy that suppress immunity/impairs the nonspecific

● poorly developed or immature immunity, as in very young children