College of Medicine & Health Sciences

Institute of Public Health

Department of Epidemiology & Biostatistics

Epidemiology
By
Mehari W/Mariam (BSc, MPH)
mehariho19@gmail.com

May 2021

Gondar, Ethiopia

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 Course profile

Course Title: Epidemiology

Credit Hours: 3
For Medical Laboratory students

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 Course expectation
• Take out a paper and put some of your
expectations of the course
 Course objective

- After completion of this course, the students will be able

to
 Describe principles of epidemiology,
 Major modes of transmission and preventive methods of
disease
 Distinguish descriptive and analytical epidemiology
 Be able to take part in surveillance disease control and
epidemiological research for prevention of diseases of
public health importance
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 Course Chapters
1)Introduction to epidemiology
2)Natural history of disease & level of prevention
3)Infectious disease epidemiology
4)Measures of morbidity & mortality
5)Sources of epidemiological data
6)Descriptive epidemiology
7)Analytic epidemiology
8)Measures of association
9)Establishing causation
10)Public health surveillance
11)Outbreak investigation & control
12)Screening & diagnostic tests
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 Teaching methods
o Interactive lecturing
o Pair work/Discussion
o Class exercise
o Assignment
o Further reading
o Seminar presentation etc…

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 Teaching materials
o Furnished lecture hall with electricity
o Lap top/desk top
o LCD projector
o White board and non-permanent marker
o Printing materials like handouts
o Library with epidemiology books
o Exercise books and pens etc…

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 Assessment methods
1) Continuous assessment=50%
o Attendance
o Class activities
o Quiz
o Test
o Assignment project
o Seminar presentation
2) Summative assessment=50%
o Final written examination from all chapters of the
course
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 Attendance criteria

o Students are expected to participate in all the classes for

achievement of the required knowledge unless there are
complaining reasons for absence which is valid

o Absence results in reduction of marks

o Attendance is 100% (minimum 80%) and beyond that

will result in repeating of the course with incomplete
grade
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 Reading materials
1) Kiflie et’al Epidemiology for health sciences students,
lecture note series
2) M. Fletcher principles and practice of epidemiology
3) Heineken's CH. Epidemiology in medicine 1st edition
4) Berhane Y, et’al Epidemiology and ecology of health
and disease in Ethiopia 1st edition
5) MoH. Guideline on integrated disease surveillance and
response in Ethiopia

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 Chapter- One

Introduction to Epidemiology

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 Learning objectives

After the end of this session, students will be expected

to:

o Define epidemiology
o Explain concept of disease causation theory
o Describe the scope, application, assumption and approach
of epidemiology

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 Public health Definition
o Epidemiology is the
- study of
- frequency,
- distribution and
- determinants of disease and other health related
conditions in human population

and
- The application of this study to the promotion of health
and to the prevention and control of health problems
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 Components of definition

Study:
o Epidemiology involves collection, analysis and
interpretation of health related data

Epidemiology is a science
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Frequency:

o The magnitude of the occurrence of disease and health

related states or events

o Health related problems and conditions are measured by

frequencies like morbidity and mortality rates

SO
o Epidemiology is quantitative science

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Distribution:

o Distribution of diseases by place, person and time;

o And seeks an explanation for the variation

o Named epidemiological variables

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 Epidemiological variables
o Time characteristics include annual occurrence, seasonal
occurrence, and daily or even hourly occurrence during an
epidemic
o Place characteristics include geographic variation, urban-
rural, topographic differences, and location of worksites
etc…

o Personal characteristics include demographic factors such

as age, race, sex, marital status, and socioeconomic status,
as well as behaviors and environmental exposures

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Determinants:

o It refers to sum of causal factors of a disease or health

related conditions

o These are factors which determine whether or not a

person will get a disease

o Epidemiology looks for primary causes and risk factors

of disease and targets them for prevention and control of a
disease

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 What are determinants of health states or
events?
o The determinants of health states or events are definable
factors that influences the occurrence of health-related
events
o Determinants are also known as risk factors(-) or
protective factors(+)

o Health-related events refer to health outcomes (e.g.

death, illness and disability) and positive health states
(e.g. survival and reduced risk of stroke), and the means
to improve health
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Human population:

o The focus of epidemiology is mainly on the population than

individual

o Epidemiology is a population medicine and studies humans

in aggregates or in groups

o No epidemiological study can be done in a single individual

o However, the size of the population can be as small as a

single family members or as large as the world population

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 Scope of Epidemiology
o Originally, epidemiology was concerned with epidemic of
communicable diseases and epidemic investigations

o Lately, it was extended to endemic communicable

diseases and non communicable diseases

o Epidemiological methods and tools can be applied to all

disease conditions and other health related states, events
and health outcomes

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 Assumptions of Epidemiology

 There are two basic assumptions

1. Human diseases do not occur at random
2. Human diseases have causal and preventive factors

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1. Human diseases do not occur at random

o It believes that human diseases are always

outcomes of underlying conditions or causes

o Epidemiology does not leave a room for chance

of a disease occurrence

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2. Human diseases have causal & preventive
factors

o The causes of human diseases can be identified through

systematic investigation of different population or
subgroups of individuals within a population in different
places at different times

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 Concepts of disease causation
 A cause of a disease can be defined as a factor
(characteristic, behavior, event, etc…) that influences the
occurrence of disease
o An increase in the factor leads to an increase in disease
o Reduction in the factor leads to a reduction in disease

 knowing the causes of a disease is a key knowledge in

preventing and treating the disease

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 Causes of disease can be classified as:

o Primary cause
o Secondary causes (risk factors)

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 Primary cause
o It is a factor which is necessary for a disease to occur and
without which the disease can’t occur

o If disease does not develop without the factor being

present, then the causative factor is necessary cause
o In case of infectious diseases, the primary cause is also
known as the etiologic agent
E. g: Clostridium tetanus is necessary cause of Tetanus
o But, many of the non infectious chronic diseases don’t
have primary cause
E. g: Hypertension
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omany factors may be necessary but not sufficient for
the disease occurrence

E.g 1. Mycobacterium tubercle is a necessary cause of tuberculosis

but it is by no means sufficient to develop tuberculosis

o This leads us to think about other factors whose presence will

make the tubercle bacilli sufficient to cause tuberculosis

oThese factors are called secondary causes (risk factors)

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 Secondary causes (risk factors)
o Risk factors are predisposing, aggravating or contributing factors
for a disease occurrence
o If the disease always results from the factor, then the causative
factor is sufficient cause
o It includes both the primary cause and all the risk factors

o When we say All risk factors – there are more than one factors
collectively can cause the outcome
o A single risk factor from totality is called component factor.

o Component factor/risk factor A + Component factor/risk factor B +

Component factor/risk factor C = sufficient cause

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 Quiz- 1

1. For each of the following risk factors and health

outcomes, identify whether they are necessary
causes ,component and sufficient causes

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 Chapter -Two

Principles of Disease Causation and Models

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 Session objectives

 At the end of this chapter the student is expected to:

Discuss the concept of disease causation

Describe the principles and models of causation

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 HOW THE DISEASE IS CAUSED?

 20th century theories

1. Supernatural theory of disease

2. Ecological theory

3. Germ theory

4. Multifactorial causation theory

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 1. SUPERNATURAL THEORY OF DISEASE
• At least 10% of the people in developed countries and
30% in developing countries still believe in supernatural
origin
• Most of the literates view that disease is the result of
microbes

• Most of the uneducated people (90%) believe that

disease is due to bad physical environment

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 2. ECOLOGICAL THEORY

• Around 463 BC, hippocrates advised to search the environment for

the cause of the disease.

• Mckeown has pointed out, improved health owes less to advances

in medical science than to the operation of natural ecological laws

• He rightly advised to search air, water and places for the cause of a
disease

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 3. GERM THEORY
Germ theory: Microbes (germs)
were found to be the cause for
many known diseases.
Pasteur, Henle and Koch were the
strong proponents of microbial
theory after they discovered the
micro-organisms in the patients’
ROBERT KOCH
secretions or excretions.
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 HENLE-KOCH POSTULATES
 Koch's Postulate states that:

1. The organism must be present in every case.

2. The organism must be isolated and grown in culture.
3. The organism must, when inoculated into a
susceptible animal, cause the specific disease.
4. The organism must then be recovered from the
animal.

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The requirement that more than one factor be present for
disease to develop is referred to as multiple causation or
multifactorial etiology
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 Further reading topics
Disease causation models
1. Epidemiological triangle
2. Web of causation
3. Wheel model

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 Chapter-3

Natural History of Disease

&
Level of Prevention

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 Learning objectives

By the end of this session, students will be expected to:

o Define natural history of a disease

o Discuss the stages of natural history of a disease
o Discuss levels of prevention
o Apply the levels of prevention to diseases of public health
importance

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 Natural History of Disease

It refers to the progression of a disease process in an individual

over time, in the absence of intervention

Knowledge of the natural history of a disease helps to understand

the

- Effects and mechanism of actions,

- Potential interventions, and the

- Different levels of the prevention of disease

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 Stages in the natural history of disease
1. Stage of susceptibility
2. Stage of sub-clinical disease
3. Stage of clinical disease
4. Stage of outcome of disease

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 1. Stage of susceptibility

 The disease has not developed but the groundwork has been laid
by the presence of factors that favor its occurrence

Examples:
 Exposure for TB
- Close contact with pulmonary TB positive patient
- lack of ventilation

o Unsafe sexual exercise to HIV/AIDS

o Sedentary life style to chronic diseases
o Unvaccinated child to vaccine preventable disease
E.g Did you get vaccinated for COVID-19?
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 2.Stage of asymptomatic/sub-clinical
disease

o In this stage, pathologic changes of disease have started but

there is no manifestation
o This stage may or may not be followed by the clinical disease

Example:
o 30% of all exposed individuals will develop TB infection

o seropositivity for HIV infection

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 3.Stage of clinical disease
 There is signs and symptoms of the disease
 The clinical stage can be followed by any of the outcomes
like:
o Recovery from the disease- common cold
o Disability - polio
o Death – Rabies, HIV/AIDS

5% of 30% who develop infection will be clinically

apparent/develop sign and symptom of TB
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 4.Stages of outcome of the disease

 The last stage in the natural history of disease is the stage of

the outcome
Outcome of a disease may be recovery, disability or death

Examples:

- Trachoma may cause blindness

- Meningitis may result in blindness or deafness or death.

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A schematic diagram of the natural history of diseases and expected outcome

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 Level of disease prevention

o Disease prevention means interrupting or slowing the

progression of disease through appropriate intervention

o Epidemiology plays a central role in disease prevention

by identifying modifiable causes of disease or risk
factors

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 There are three levels of prevention

o Primary prevention
o Secondary prevention
o Tertiary prevention

What is primordial prevention?

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 1.Primary prevention

 It includes all interventions before the biologic onset of a disease

 The causative agent exists but the aim is to prevent the

development of the disease
 Primary prevention is mainly done through:
o Health promotion
o Prevention of exposure
o Prevention of disease - Immunization

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 Health promotion

 It is a general non-specific intervention that enhances

health and body’s ability to resist disease and promote
healthier and happier life

Examples:
o Balanced diet
o Health education

o Physical exercise
o Emotional and social supports etc …
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 Prevention of exposure
 Prevention of exposure includes specific means designed or
advocated to avoid exposure to certain risk factors
 It acts before exposure of the risk factors

Examples:
– Use of bed nets for prevention of malaria
– Consistent and correct use of condom for prevention of
HIV/AIDS
– Proper ventilation to control acute respiratory tract infection
– Driving license law for prevention of accidents

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 Prevention of disease
 It includes interventions done after exposure to a certain factor but
before development of the disease (before biologic onset)
 This is when the intervention aims to prevent initiation of disease

Examples:
 INH prophylaxis for prevention of tuberculosis in HIV positive
people
 Prophylaxis after exposure to needle injection

 Immunization

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 2. Secondary prevention

 It includes preventive measures which take place after biologic

onset but before permanent damage
 The objective is to prevent or limit permanent damage and halt
further spread of the disease to others
 Strategy at this stage is through early detection and treatment of
disease
Example:
- Treatment of active trachoma to prevent blindness
- Screening and treatment of HIV cases
- Early detection and treatment of breast cancer to prevent
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its progression to the invasive stage
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 3. Tertiary prevention
Is targeted towards people with chronic diseases and disabilities that
cannot be cured
It has two objectives:
 Treatment to prevent further disability or death and
 To limit the physical, psychological, social, and financial impact
of disability, thereby improving the quality of life
It is primarily done through disability limitation and rehabilitation
activities

Example ; The goal of tertiary prevention in diabetics is to control the level

of their blood sugar using drugs and/ or diet, and to treat complications
promptly in order to improve the quality of life, prevent permanent
damages such as blindness, and prevent early death

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 Disability limitation

 It refers to limiting the continuation of loss of

function or limiting the impact of the damage

Examples:
o Foot care for diabetic patients to prevent injuries

o Passive joint movement for polio to prevent deformity

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Rehabilitation activities

 It refers to the retraining of remaining functions for maximal

effectiveness

 Rehabilitative activities include:

- plastic surgery for burn patients

- kidney transplantation
- wheel chairs
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summary
Primary
Exposure
Prevention

Stage of susceptibility

Biologic Onset

Stage of sub-clinical
illness
Clinical Onset Secondary
Prevention

Stage of clinical illness

Permanent damage
Tertiary
Stage of outcome Prevention
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 Group work Assignment (5 students/group)
Levels of Prevention
Types of Disease
Primary Secondary Tertiary

Tuberculosis

Malaria

HIV/AIDS

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 Infectious Disease Epidemiology

What are infectious diseases?

 An infectious disease is defined as a disease caused
by an infectious agent or its toxic products
- AIDS – HIV - virus
- TB- mycobacterium tuberculosis - bacteria
- Malaria – plasmodium species - protozoa
- Botulism – by toxic product
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 Infectious disease cycle
 Is refers to the process by which infectious diseases are
transmitted from

infectious host ------------- susceptible host

 It is also called transmission cycle or chain of infection

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 Components of Chain of disease transmission

Each element must be presented and lie in sequential order for

infection occurrence
Intervention can be targeted at any of those six elements of the
chain of infection to prevent disease occurrence
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 Reading Assignment
• What intervention activities should be
targeted to the
- Agent
- Reservoir
- Portal of exit
- Mode of transmission
- Portal of entry
- Susceptible host
 To break transmission cycle
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 1. Infectious agent
 The infectious agent is virus, bacteria, parasite or other
microbes
 The agent to causes infection and disease will depends
on its basic biological characteristics like
─I nfe c ti v i t y
─Pat h o g e n e c i t y
─I m m u n o ge n i c i t y
─V i r u l e n c e

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 Infectiousness (infectivity)

 The ability of an agent to invade and multiply in a host,

i.e. the ability to produce infection

 Infectivity is measured by Infection Rate (IR):

Number of inf ectedPerso ns

IR  100
Number of Susceptibl e & exp sedPersons

If all of students in this class equally exposed for TB how

many of them will develop Tb infection????

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 Pathogenicity
─ The ability of an infectious agent to cause clinical disease among infected
human hosts

─ It is measured by clinical to sub-clinical ratio or proportion of clinical cases

among infected human hosts
Examples:
o High Pathogenicity: HIV, Rabies, Measles… etc.
o Moderate Pathogenicity: Mumps virus and Rhino virus
o Highly infectious but less pathogenic: Poliovirus

How many of students who develop Tb infection will be clinically

apparent
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 Virulence
It is the ability of an infectious agent to cause severe clinical disease or death
among clinical cases
Virulence of the infectious agent can be measured by:
o Case fatality Rate (CFR)
o Hospitalization Rate (HR)

Number of Fatal Cases

CFR   100
Total Number of Cases
Number of Hospitaliz ed Cases
HR   100
Total Number of Cases

How many of clinically apparent Tb cases will be hospitalized or

died of Tb
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 Example
Disease type Pathogenecity Virulence
(Clinical: subclinical) (CFR)
Poliomyelitis 1:99 2-10%

Rabies 100:0 100%

AIDS 100:0 100%

oHIV and Rabies viruses are highly virulent with a

fatality rate of 100%

oPoliomyelitis are less virulent with fatality rate 2-10%

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 Immunogenicity
 The infection’s ability to produce specific immunity

 It is defined as the ability of a pathogen to induce an

immune response after an infection respectively

 It may lead to protection against re-infection or re-

activation with the same or similar pathogen in the
future
 Poliomyelitis(permanent),measles (permanent),influenza
 How many of infected Tb cases develop immunity for Tb

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 Disease progression

Disease
Exposure Infection Disease outcome

Infectiousness Pathogenecity Virulence

(Infection Rate) (clinical : subclinical) (CFR, HR)

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Factors that influence disease development other
than infectivity, Pathogenicity, immunogenicity
and virulence of the agent are:
o Strain of agent
o Dose of agent
o Route of infection
o Influence of human host age
o Influence of human host nutritional status
o Influence of human host immune response
o Influence of treatment
o Influence of seasonal variation, etc…
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 2. Reservoir of infection
 Reservoir is the habitat in which an infectious agent lives,
grows, transforms and/or multiplies itself
Examples:
o Human beings: Measles, Mumps, Pertusis, Poliomyelitis
etc…
o Animals: This are a cause for zoonotic disease like
Rabies (dogs), anthrax(sheep), brucelloses(cows and pigs), etc
o Environment (plant, soil, water):
 Many fungal agents, such as those that cause histoplasmosis, live
and multiply in the soil
 Tetanus etc…
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• All infected humans, whether showing signs and symptoms of the
disease or not, are potential sources of infection to others.
• A person who does not have apparent clinical disease, but is a
potential source of infection to other people is called a Carrier.
 Carriers may be classified as

1. Incubatory carriers: Transmitting the disease during incubation

period, i.e. from first shedding of the agent until the clinical onset.

Example: Measles, mumps

2. Convalescent carriers: Transmitting the disease during convalescence

period i.e. from the time of recovery to when shedding stops.
Example: Typhoid fever
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3. Asymptomatic carriers: Transmitting the disease without ever
showing sign and symptom of the disease.

Example: Polio, Amoebiasis

4. Chronic carriers: persons who appear to have recovered from
their clinical illness but remain infectious

Example: Viral Hepatitis, Typhoid fever.

 Carriers are the challenges of public health Professional in that

they are more tapher in spreading disease more than the
clinically apparent ones

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 Ice-berg /hippopotamus/ effect of carriers
• .
Cases

Carriers

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 3. Portal of Exit
The portal of exit is the route by which the infectious agent leaves
the infectious hosts or reservoirs

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 4. Modes of Transmission

 Mode of transmission is the mechanism by which the

infectious agent escapes from a reservoir and enters into
a susceptible human host

 There are two major mechanisms of transmission:

I. Direct transmission
II. Indirect Transmission

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 5. Portal of Entry
Portal of entry is the route through which a microorganism enters
into the susceptible human host

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 6. Susceptible Human Host
 The susceptible human host is the final link in the
infectious disease transmission process
Host factors influence individual's exposure, susceptibility
or response to infectious agent
Host susceptibility can be seen at the individual level and
at the community level
At the individual level -
o Genetic factors (including sex, blood group, ethnicity,…)
o Immunity due past infection or immunization
At community level - Host resistance at the community
(population) level is called herd immunity

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• Herd immunity can be defined as the resistance of a
community (group) to invasion and spread of an infectious
agent, based on the immunity of a high proportion of
individuals in the community
 Conditions under which herd immunity best functions

1. Single reservoir (the human host): If there is other source of

infection it can transmit the infection to susceptible hosts.

2. Direct transmission (direct contact or direct projection): Herd

immunity is less effective for diseases with efficient airborne

transmission.
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3. Total immunity: Partially immune hosts may continue to
shed the agent, and hence increase the likelihood of
bringing the infection to susceptible hosts.
4. No shedding of agents by immune hosts (no carrier state).
5. Uniform distribution of immunes: Unfortunately,
susceptible usually happen to live in clusters or pockets
because of socioeconomic, religious, or geographic
factors.
6. No overcrowding: Overcrowding also increases the
likelihood of contact between reservoirs and susceptible
hosts

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 Time course of a disease
• The time lines of infection begin with the
successful infection of the susceptible host by
infectious agent
─Pre-patent period
─ Incubation period
─ Communicable period
─ Latent period

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 Crucial steps in the natural history of infectious
disease includes:

o Exposure to infectious agent

o Infection
o Agent starts shedding
o Clinical symptoms
o Recovery from symptoms
o Agent stops shedding
o Relapse of symptoms

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 Pre-patent period
 It is the time interval between infection and the time of
first shedding of the agent by the human host

 For some diseases the time when the agent can first be
detected and the time of the first shedding do have
difference- i.e. the detection might not be possible at the
beginning of the shedding of infectious agents

E.g. Window period of HIV/AIDS

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 Incubation period
 It is the time interval between infection and the first clinical
manifestation of disease

The time interval between biological onset and clinical onset

This period may be as brief as seconds for hypersensitivity and
toxic reactions to as long as decades for certain chronic diseases
like leukemia(2-12yrs).
Even for a single disease, the characteristic incubation period has
a range.
For example, the typical incubation period for hepatitis A is as
long as 7 weeks
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 Communicable period

 It extends from the point of the first shedding up to the

last shedding of the infectious agent by the infectious
host

 It is the period during which an infected host can

transmit the infection to other host

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 Latent period

 It is the time interval between recovery and the

occurrence of a relapse in clinical disease

Example: Typhus and malaria have latent period

because they relapse after some time

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 Time course of disease progression

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 Quiz -2
1. Write all elements of chain of disease transmission
2. The ability of an agent to invade and multiply in a host
-----------------------
3. The ability of an infectious agent to cause clinical disease to
susceptible host is called --------------------

4. A person who does not have apparent clinical disease, but is a

potential source of infection to other people is called -------------------
5. Define herd immunity

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 Chapter-5

Measures of Morbidity and

Mortality

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 Measures of Morbidity

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 Learning objectives
After the end of this session, students will be expected to:

Calculate and interpret the following epidemiologic

measures:
– Count
– Ratio
– Proportion
– Rate
– Incidence proportion
– Incidence rate
– Point prevalence
– Period prevalence
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 Frequency measures

The number of cases with the population size can be

determined by calculating ratios, proportions,
and rates

Fertility, morbidity, and mortality rates are three

frequency measures that are used to characterize
the occurrence of health events

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Number (count)

o Common descriptive measure

o It is a base for calculating any frequency measures
o Essential for service delivery and planning
o It is important in planning and outbreak occurrences
o It is more important for health managers and administers than
researchers

o Often hard to interpret if populations being compared differ in

size – hence counts are sometimes termed “numerator data”
Example - Number of malaria/AWD/ cases

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 Ratio

A ratio is the relative magnitude of two

quantities or a comparison of any two values

Shows the relationship between two events

Numerator and denominator can be related

or unrelated
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• In epidemiology, ratios are used as both descriptive measures and
as analytic tools.
• As a descriptive measure, ratios can describe the male-to-female
ratio of participants in a study, or the ratio of controls to cases
(e.g., two controls per case).
• As an analytic tool, ratios can be calculated for occurrence of
illness, injury, or death between two groups.
• These ratio measures, including risk ratio (relative risk), rate ratio,
and odds ratio, are described later in this lesson.

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 Proportion
o A proportion is the comparison of a part to the whole
o It is a type of ratio in which the numerator is included in the
denominator
o Proportion may be expressed as a decimal, a fraction, or a
percentage
o It’s result ranges between 0 and 1 or (0–100%)
o Example ; the proportion of all births that was male

o Proportion of death due to malaria in kebele X

o Proportion of vaccinated children in district X

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 Rate
o Rate is a special form of proportion, with an added time dimension

N u m e r a t o r - Number of events observed in a given time

D e n o m i n a t o r - Population in which the events occur i.e.

(population at risk)
 Measures occurrence of an event in a population over time
Examples:
o Fertility rates
o Morbidity rates
o Mortality rates

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 Type of rates
Crude rate
– total population (e.g. crude birth/death rate)
Specific rate
– Targeted to population subgroups (e.g. age
specific / sex specific/occupation specific
death rate)
Standardized/Adjusted rate
– rates after adjusting for a specific confounding
variables like age
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 Individual assignmnet-1
For each of the fractions shown below, indicate whether it is a ratio, a
proportion, a rate, or none of the three

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 Measures of morbidity
o Morbidity encompasses disease, illness, injury,
disability or any disorder in public health practice

o Morbidity rates are rates that quantify disease

occurrences (frequencies)

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 Measures of morbidity

o Incidence
o Prevalence

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 I. I n c i d e n c e

o Incidence rates are the most common way of measuring and

comparing the frequency of disease occurrence in population

o It refers to the occurrence of new cases of disease in a population

over a specified period of time

o The appropriate denominator for incidence rate is population at risk.

o For incidence to be meaningful, any individual who is included in the
denominator must have the potential to become part of the group
that is counted in the numerator.

o E.g. if we are calculating incidence for endometrial cancer, the

denominator must include only women
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 Incidence…

• Another important issue in regard to the denominator is

the issue of time.
• For incidence to be a measure of risk

- we must specify a period of time and

- we must know that all of the individuals in the group
represented by the denominator have been
followed up for that entire period

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 Types of incidence

1. Incidence proporti on/cumulati ve

2. Incidence rate/incidence density

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 1.Incidence proportion/cumulative
incidence


Incidence proportion is the proportion of an initially disease-free

population that develops disease, becomes injured, or dies after follow

up for specified period of time


The cumulative incidence assumes that the entire population at risk at

the beginning of the study period has been followed for the specified

time interval for the development of the outcome under investigation


It provides an estimate of the probability, or risk, that an individual will

develop a disease during a specified period of time

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 Cumulative incidence (CI)

 The number of new cases of a disease occurred in a

population at risk for the disease during a specified
period of time

 The assumption is static population at risk

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Example A: In the study of diabetics, 100 of the 189 diabetic
men died during the 13-year follow-up period.
 Calculate the risk of death for these men.
Numerator = 100 deaths among the diabetic men
Denominator = 189 diabetic men

Risk = (100 / 189) x 100 = 52.9%

Example B: In an outbreak of gastroenteritis among 200

attendees of a corporate picnic, 99 persons ate potato salad
of whom 30 developed gastroenteritis.
 Calculate the risk of illness among persons who ate potato
salad.

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 Cumulative incidence – example C

Incidence proportion (IP). During a 2-year period, 3 out

of 5 subjects developed the disease; IP = 3/5 = 0.6
 Properties of incidence proportion

o It is a measure of the risk of disease or the probability of

developing the disease during the specified time
o As a measure of incidence, it includes only new cases of
disease in the numerator
o The denominator is the number of persons in the
population at risk at the start of the observation time
o Applicable for only static population of cohort
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 2. Incidence rate/Density
o An incidence rate whose denominator is calculated using person-
time units
o It is for dynamic population under follow up

o The numerator of an incidence rate should reflect new cases of

disease which occurred or were diagnosed during the specified
period
o The denominator, however, is the sum of each individual’s time at
risk or the sum of the time that each person remained under
observation, i.e., person – time denominator
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 Incidence density (ID)

 Often used in cohort studies of diseases with long

incubation or latency period

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Person-time

It is sum of length of time period passed free of illness

(at risk) by each individual member of study

It accounts for the amount of exposure time of members

Dynamic cohort is a cohort of people leaving and

entering a study at different time of period

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 Dynamic cohort study

Birth In-migrants

Death Out-migrants

E. g: Dabat research center at UoG

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 Incidence rate…
 The incidence rate indicates how quickly people become ill
measured in people per year

 Incidence rate is a measure of incidence that incorporates time

directly into the denominator
 Typically, each person is observed from an established starting
time until one of four “end points” is reached:
o onset of disease
o death
o lost to follow-up
o end of the study
E.g. Graduation rate
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Example 1 : The diabetes follow-up study included 218 diabetic women and 3,823
non diabetic women. By the end of the study, 72 of the diabetic women and 511
of the non diabetic women had died. The diabetic women were observed for a
total of 1,862 person-years; the non diabetic women were observed for a total
of 36,653 person-years.
 Calculate the incidence rates of death for the diabetic and non-diabetic women.
- For diabetic women, numerator = 72 and denominator = 1,862 Person-time
= 72 / 1,862
= 0.0386 deaths per person-year
IR = 38.6 deaths per 1,000 person-years
 For non diabetic women, numerator = 511 and denominator = 36,653 Person-
time
= 511 / 36,653 = 0.0139 deaths per person-year
IR= 13.9 deaths per 1,000 person-years

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 Person-Time – example 2
Jan Jan Jan
1980 1989 1999

Subject 1 ------------------x 9 Person-Years (PY)

Subject 2 10 PY
------------------x
Subject 3 19PY
------------------------------------ 38 PY

X = outcome of interest, thus the incident rate is 2/38 PY

 II. P r e v a l e n c e

o It 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

o Prevalence differs from incidence in that prevalence includes both

new and pre-existing cases in the population at the specified time

o It measures disease status (disease burden)

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 The formula for prevalence (p)

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 Types of prevalence

1. Point prevalence: number of cases that exist

in a population at a given point in time

2. Period prevalence: number of cases that

exist in a population at given period of time

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06/26/2021 Epedimiology course 124
1. Point prevalence
o It refers to the prevalence measured at a particular point in time
o It is proportion of a population that is affected by disease at a given
point in time
o May not be useful for assessment of diseases with short generation
period

o This is not a true rate rather it is a simple proportion

All persons with a specific condition at

one point in time x 100
Point prevalence rate =
Total population in that point
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2. Period prevalence
o It refers to prevalence measured over an interval of time
o It is the proportion of persons with a particular disease
or attribute at any time during the interval time period

No of people with the condition

during specific period of time x 100
Period prevalence rate =
Average/total population in the period

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 Example
In a survey of 1,150 women who gave birth in Gondar town in
2020, a total of 468 reported taking a multivitamin at least 4
times a week during the month before becoming pregnant.

 Is it a period or a point prevalence?

 Calculate the prevalence of frequent multivitamin use in this group.

• Numerator = 468 multivitamin users in the year

• Denominator = 1,150 women gave birth in the year

• Période Prévalence = (468 / 1,150) x 100 = 0.407 x 100 = 40.7%

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 Class room Exercise
 On January 1, 2000 there were 20 medical students with Influenza A and
there were a total of 600 students in the class. These 20 students were
immune from contracting Influenza A again during the next nine months.
 From January 2, 2000 through April 2, 2000, 30 more students developed
Influenza A and the class size remained at 600.

A. What was the cumulative incidence of Influenza A from January 2,

2000 through April 2, 2000?

B. What was the prevalence of Influenza A on January 1, 2000?

C. What was the period prevalence of influenza A?

- From Jan 1 to April 2,2000

- From Jan 2 to April 2,2000

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Special Types of Incidence: Attack Rate

o It is a type of cumulative incidence in

Narrowly defined population
Observed for a limited time (e.g. epidemic).
o Usually expressed as a percent.

Attack rate = Number of new cases among the

population during the period x 100
Population at risk at the
beginning of the period
 Attack Rate: Example
 Of 75 persons who attended a church dinner, 46
subsequently developed gastroenteritis.
a) Calculate the attack rate of gastroenteritis :
x = Cases of gastroenteritis occurring within the
incubation period for gastroenteritis among
persons who attended the picnic = 46
y = Number of persons at the picnic = 75
AR= 46/75 x 100%
 Special Types of Incidence:
Secondary Attack Rate
o A measure of the frequency of new cases of a disease among
the contacts of known cases.
o How we can know the case is from secondary contact
o The formula is as follows:
Number of persons exposed(have contact)

SAR = with known cases) who developed disease x100

Total number of contacts

To calculate the total number of household contacts,

Subtract the number of primary cases from the
total number of people residing in those households.
 Secondary Attack Rate: Example

 Seven cases of hepatitis A occurred among 70 children

attending a child care center. Each infected child came from a
different family. The total number of persons in the 7 affected
families was 32. One incubation period later, 5 family members
of the 7 infected children also developed hepatitis A.
– Calculate the primary attack rate in the child care center and the
secondary attack rate among family contacts of those cases.
 Incidence versus prevalence rates

o The prevalence rate (PR) is directly related to the

incidence rate (IR)
Prevalence rate ~ IR x D

o The prevalence rate is inversely related to the

death and cure rates

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 Prevalence will be..

Decreased by:
Increased by:
Shorter duration of disease
 Longer duration of the disease High case-fatality rate from disease
Prolongation of life of patients Decrease in new cases(decrease in
without cure e.g. HIV/AIDS incidence)
Increase in new cases (increase In-migration of healthy people
incidence) Out-migration of cases
In-migration of cases Improved cure rate of cases etc.
Out-migration of healthy people
In-migration of susceptible people
Improved diagnostic facilities
(better reporting system), etc.
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 Comparison

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Relationship of Incidence and Prevalence

Incidence

Death
Prevalence
Cure
Lost to follow-up
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 Individual assignment two
Assume in January 1st 1990, 1000 men aged 30 to 59 years, not having
previously received the BCG vaccine against TB, were examined for the
disease. Of these, 50 were found to have the tuberculosis. One year later, in
January 1st 1991, the same group of men was examined. Ten of the 50 men
with tuberculosis had died, 10 were cured and 20 new cases were found.

Based on the above information, calculate measures of morbidity:

1.The point prevalence of tuberculosis in January 1st , 1990
2.The incidence proportion of tuberculosis in January 1st 1991 , using as
denominator the population at risk at the beginning of the year
3.The period prevalence of tuberculosis in January 1st 1991, using as
denominator the average total population
4.The point prevalence of tuberculosis on January 1st 1991
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 Measures of Mortality

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 Learning objectives

After the end of this session, students will be expected to:

o Explain what mortality mean

o State why and how standardized rates are used
o Calculate a direct and indirect standardized rate

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 Mortality rates

o A mortality rate is a measure of the frequency of

occurrence of death in a defined population during a
specified time interval

o For a defined population, over a specified period of time

death occurring during given time period

Mortality rate = X 10n
size of the population among the death occurred

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 Types of rate

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 Comparison of rates

Advantage Disadvantage
crude - Actual summary rates - Difficult to interpret because of differences
- Easley computable in population structure

- Control for homogeneous

Specific sub groups - Cumbersome if there are many subgroups
rates - Can provide detailed - No summary figure
information

Adjusted/ - Provide summary figure - Fictional rates

standardized - Controls confounder - Magnitude depends on population
- Permit group comparison standard
- Hides sub group difference

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 Standardized rates
Often times, we wish to compare mortality rates between population, or

at different time periods in one population

However, the population groups may differ with respect to underlying

characteristics (e.g. age, sex …) that may affect the overall mortality rate

(hence – not a “fair” comparison)

so…….
 Adjustment for variables that make variation is taken to be mandatory to

make effective comparison

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 Why do we calculate age-adjusted rates ?
1. Many causes of death vary with age.
2. The age structure of populations differs both between areas and
across time.

3. Failing to account for differences in population age structure can

result in inaccurate comparisons of death rates between
populations or within a population across time.
4. The solution is to adjust rates to a standard (or 'reference')
population, producing 'age-adjusted' rates.

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 Types of standardization

Direct method – Population structure come from the standard population

and specific rates come from the study population

Indirect method – Specific rates come from the standard population and

population structure from the study population

 Standard population – agreed population used as a base for both groups

 Study population – actual population under study

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 Summary:
 One type of rate is not necessarily more important than another. Which
you choose depends on the information sought.

 Crude rates are often used to estimate the burden of disease and to
plan health services.

 To compare rates among subpopulations or for various causes, specific

rates are preferred.

 To compare the health of entire populations, adjusted rates are

preferred because they allow for comparison of populations with
different demographic structures.
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 Group assignment-1

Seminar presentation topics

Form eight groups

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 Measures of mortality
Group-1
1.Specific mortality rate
2.Age specific mortality rate
3.Sex specific mortality rate
4.Perinatal mortality rate
Group-2
5.Fetal mortality rate
6.Early neonatal mortality rate
7.Proportionate mortality ratio/rate
8.Case fatality rate
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 Measures of mortality…

Group-3
1. Neonatal mortality rate
2. Post neonatal mortality rate
3. Infant mortality rate
4. Child mortality rate
Group-4
5. Under five mortality rate
6. Maternal mortality ratio/rate
7. Cause specific mortality rate
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 Sources of epidemiological data
Group-5
1. Vital statistics registration
2. Census
3. Health service records
Group-6
4. Health service indicators
5. Mortality and morbidity survey
6. Reportable infectious diseases

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 Group assignment

Group -7
Principles of controlling infecti ous
diseases:
o disease p re ve nti o n
o disease c o nt ro l
o disease e l i m i n ati o n
o Disease e ra d i cati o n
o Disease ex ti n c ti o n

Group -8 Screening and diagnostic tests

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 Chapter-6

Descriptive Epidemiology

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 Learning objectives
After the end of this session, students will be expected to:

o Discuss the difference between descriptive and analytical

studies
o Describe the purpose of descriptive studies
o List type of descriptive studies
o State strength and limitation of descriptive studies

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 E p i d e m i o l o g i ca l d e s i g n st rate g i e s

o Epidemiology is primarily concerned with the distribution

and determinants of disease in human populations

o The basic design strategies in epidemiologic research are

categorized into two according to their focus of
investigation

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06/26/2021 Epedimiology course 156
 Epidemiologic approaches
1. DESCRIPTIVE
Used to describe health and disease in the community by….
What? Who? When? Where?
What are the How many people Over what Where do the
health problems are affected? period of time? affected people
of the community? live, work or
spend leisure
time?
2. ANALYTIC
Used to identify etiology, prognosis and for program evaluation
Why? How?
What are the causal agents? By what mechanism
What factors affect outcome? do they operate?
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 Descripti ve studies
o Descriptive study is one of the basic types of
epidemiology describing the frequency and distribution
of diseases by time, place and person

o Analytic studies focus in elucidating the determinants of

disease

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 What?

Cases
Person Time
25

Place 20

15

10

0
1 2 3 4 5 6 7 8 9 10

Who? Where? When?

06/26/2021 Epedimiology course 159
 Applicati on of descripti ve studies

o Useful for health managers to allocate resource and to

plan effective prevention programs

o To generate hypothesis, an important first step in the

search for disease determinants or risk factors of disease

o It is less expensive and less time-consuming

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 Category of descripti ve studies

 If population as study subjects

o Correlational /ecological studies

 If individual as study subjects

o Case report
o Case series
o Cross-sectional survey

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 Case report
o It is the study of health profile of a single
individual using a careful and detail report by
one or more clinicians
o Report is usually documented if there is
unusual medical occurrence, thus it may be
first clue for identification of a new disease
occurrences
o It is useful in constructing a natural history of
individual disease
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 Case series
o Individual case report can be expanded to a case
series, which describes characteristics of a number
of patients with the same diagnosis

o Similar to case report, it is usually made on cases

having new or unusual disease (giving interest to
clinicians)

o It is often used to detect the emergence of new

disease or an epidemic occurrences
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Exercise 1: is it case report or series?

o Five young, previously healthy homosexual men were

diagnosed as having Pneumocystis carinii pneumonia at
Los Angeles hospital during a six month period from
1980 to 1981
o This form of pneumonia had been seen almost
exclusively among older men and women whose
immune systems were suppressed
o This unusual circumstance suggested that these
individuals were actually suffering with a previously
unknown disease, subsequently it was called AIDS

06/26/2021 Epedimiology course 164

 Exercise 2: is it case report or series

A 40-year old pre-menopausal woman

developed pulmonary embolism 5 weeks after
beginning to use an oral contraceptive
preparation to treat endometriosis.

What is unusual in this report? Pulmonary

embolism is common in older, postmenopausal
women. The investigator postulated that the
drug may have been responsible for this rare
occurrence
06/26/2021 Epedimiology course 165
 Advantages of case reports and series

Used as bridge between clinical medicine and public

health
First clues in the identification of new disease or adverse
effect of exposure /drug
To identify outbreak occurrence or emergency of new
disease
Both case report and case series are able to formulate a
epidemiologic hypothesis

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 D is a d va nta ge s o f ca s e re p o r t s a n d s e r i e s

Unable to test for statistical association between

exposure and outcome variables because of lack of
comparison group
Fundamental limitation of case report is inability to
avoid a roll of chance
Rates can not be calculated since the population
corresponding to the source of cases can not be well
defined
They are prone to atomistic fallacy (cannot be inferred
to the population)
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 Eco l o g i ca l st u d i e s

o 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 (time trend)

o Unit of data source and unit of analysis is population

== > Population level exposure Vs population level outcome

o They use aggregate data and do not measure outcomes and risk
factors at individual level

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 Time-trend ecological study

o Comparisons can be made over time within the same population to

show how incidence of disease changes over time and to identify

patterns of change –

o Time trend studies can investigate whether changes in disease incidence

correlates with changes in risk factors for a disease

o To evaluate a specific intervention program effectiveness

HEP graduated HH Vs diarrheal disease morbidity

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Fig: Factious data to show correlation between salt
sold and mean diastolic BP (positive r ~ 0.67) – is it
time trend or different group in point time ?
110
Mean diastolic BP

90

District
70 Linear (District)

50
5 6 7 8 9 10
salt sold (100gms/person/year)

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o Circumcision and HIV in Ethiopia – cross-sectional

– HIV prevalence of districts in Ethiopia

Vs
– Proportion of male circumcision in the same districts

o Fluoride content of water and dental caries - longitudinal

– Proportion of people with dental caries in a village over
time
Vs
– Fluoride content of water supply in the village over time

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 Characteristi c of ecological study
o Measures of association in ecological study is correlation
coefficient (r)
o Correlation coefficient quantifies the extent to which there is a
linear correlation between exposure and outcome variables (-
1<r<1)
o What does mean when r
o -1 < r <0 ==
o r = 0 = =
o 0 < r < 1 = =

Source of data
o 06/26/2021
It mostly uses secondary data or report from survey data
Epedimiology course 172
 Strength
Can be done quickly and inexpensively, often using available data.

May be best design to study health effects of environmental

exposures, eg
- Do heat waves increase death rate?

- Does soft drinks increase heart disease?

- Do economic recessions increase suicide rate?

Such questions only sensibly addressed at population (or

community) level
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 Limitation

1. Inability to link exposure with disease.

- Data on exposure and outcome are not linked at the individual
level;
- Correlation found with aggregate data may not apply to
individuals (ecological fallacy)
2. Lack of ability to control for effects of potential confounding
factors
- A correlation found between the high per capita color TV and
mortality from CHD, again here it is obvious that color TV
owning is not a good reason for increased mortality from CHD
3. It may mask a non-linear relationship between exposure and
disease while it is exist
4. Inability to test hypothesis
5. Roll of chance can not be avoided
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 Cross-sectional studies
It is also called prevalence study (survey study)

It is the major type of descriptive study designs

Survey is conducted in a population, to find prevalence of a disease
and risk factor at a point in time
Exposure and disease status are assessed simultaneously among
individuals at a point in time
Point in time does not indicates the speed of data collection i.e.
Data collection process can take days, weeks, months, years but
the measurement is takes place only once
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 C ro s s -s e c ti o n al st u d i e s . . .

It helps administrators in assessing the health status and health care

needs of a population
Used to assess prevalence of acute and chronic diseases, disabilities and
utilization of health care resources
- prevalence of common cold in kebele 8 of Gondar town is 23%
- Prevalence of DM in kebele 8 of Gondar town is 10.45%
- prevalence of OPD attendants in health facilities of Gondar town is
18.5%
The purpose is for effective health care planning, priority setting,
resource allocation and administration
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 C ro s s - s e c ti o n a l st u d i e s . . .

o Cross-sectional survey could provide information about the

frequency of health conditions by providing a ‘snapshot’ at a
specified time

o Sample without knowledge of Exposure or Disease – then

classify after result is obtained

o In this study, measure of association is made using odds ratio (OR)

i.e. Prevalence ratio

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 Design of Cross-sectional Studies

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 Design and Analysis

Odds of disease among exposed = odds of exposure among diseased

Odds of disease among non-exposed 0dds of exposure among non-diseased
OR = ad/bc
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 Cros s -s e cti onal studi es ...
It may be used first step in longitudinal or case-control studies
It can be considered as analytic study, if it assesses presence of
statistical association between exposure and outcome
It can provide a good evidence in disease causation i.e. test
hypothesis
===== For factors that remain unaltered over-time such as sex, race,
blood group etc...
------ Prevalence of malaria by blood group --- blood group as exposure
does not change over time.
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Example of cross-sectional study undertaken in
Ethiopia

• Census – house hold level

• Ethiopian demographic and health survey(EDHS)

– house hold level
• National immunization survey

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Advantages
Good design for hypothesis generation

Can estimate overall and specific disease prevalence

Can estimate exposure proportions in the population – proportion of

cigarette smokers in Gondar town, latrine utilization proportion

Can study multiple exposures or multiple outcomes or diseases- malaria and

diarrhea morbidity Vs proportion of latrine and ITN utilization

Relatively easy, quick and inexpensive

Best suited to studying unchanged factors overtime (eye color, sex, blood-
type) – prevalence of malaria by blood type
Often good first step to employ analytical study designs

Highly generalizable
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 Disadvantage

Impractical for rare diseases and rare exposure – because we

need to take very large sample size

Not a useful type of study for establishing causal

relationships – chicken and egg dilemma

Miss diseases still in latent period

Recall of previous exposure may be difficult -

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 Exercise
A researcher wants to assess the effect of chat chewing on academic
performance among Gondar university students. He takes a sample of
400 students and collect data. From the sample, he has found a total of
130 chat chewer and 100 non chewers with good academic
performance and 87 non chewers with bad academic performance.
1. What type of study was conducted
2. Create two-by-two table
3. What is appropriate measure of association
4. Calculate the measure of association
5. Interpret the result

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 Chapter-7

Analytical Epidemiology

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 Learning objectives

After the end of this session, students will be expected

to:

o Describe purpose of analytical studies

o Differentiate observational and interventional studies

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 Introduction to analytic studies
Application:
 To search for cause - effect relationship and mechanism
o Why?
o How?

 It focuses on determinants of disease by testing hypothesis

regarding exposure and outcome of interest
o Proof versus sufficient evidence?

 To quantify the association between exposure and outcome of

interest
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 Analytic studies...
Basic features:
 Key feature of analytic epidemiology is comparison group
 Appropriate comparison group needed:
o Exposed versus non-exposed
o Case versus control
o Experimental versus non-experimental

 It is the use of comparison group that allows testing of

epidemiologic hypotheses

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 Analytic studies...

Two types of analytic studies:

o Observational studies
o Interventional studies

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 Analytic studies...
Observational studies
o An investigator observes the natural course of an event
o An investigator measures but does not intervene

Interventional studies
o An investigator assigns study subjects to exposed and non-
exposed and follows to measure for disease occurrence
o An investigator manipulates the intervention

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 Observational analytic studies

Two basic observational analytic studies:

o Cohort studies
o Case-control studies
o Cross-sectional studies?

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 Case-Control Studies

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 Definition of case-control studies

 A case control study is one in which persons with a

condition (“cases”) and suitable comparison subjects
(“controls”) are identified, and then the two groups are
compared with respect to prior exposure to risk factors

– Subjects are sampled by their outcome status

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 Definition of case-control studies…

o The investigator looks back in time to measure exposure of the study

subjects to the risk factors

o The exposure to the risk factors is then compared among cases and
controls

o To determine if the exposure to the risk factors could account for the
health condition of the cases
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 Steps of case-control studies
1. Define cases and controls
2. Identify group of cases
3. Identify group of controls
4. Asses both groups for previous history of exposure to risk factors
under study
5. Measure frequency of exposure to risk factors occurrence in
both groups
6. Compare frequency of exposure to risk factors between cases
and controls
7. Conclude that previous history of exposure to risk factors
contributed for the cases more than controls or not
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 What is case?
o It is the outcome of interest under study
o It can be:
– A disease
E.g. HIV status, malaria status
– A behavior
E.g. Alcohol drinking habit(yes/no), cigarette
smoking(yes/no)
- Event – traffic accident

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 Selection of case

o Define ‘disease’ and how it will be measured

o Selecting the source population for cases (homogeneous cases)

o Sources of cases are commonly:

– Population based - All persons with the disease in a population during a

specific time of period

– Hospital based - All persons with the disease seen at a particular facility
(e.g. a hospital) in a specific time period

– Incidents cases

– Chronic/prevalent cases
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 Sources of cases

Hospital-based:
o Easy and in-expensive to conduct
o It is prone for selection bias
o Minimize recall bias
o More cooperative
Population-based:
o Avoids selection bias
o Allows the description of a disease in the entire population and the
direct computation of rates of disease in exposed and non-exposed
groups
o High generalizability
o High recall bias
o Incooperative environment
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 What is control?
o It is the comparison group (referent)

o It should be free of the disease (outcome of interest under study)

o It should be as similar as the cases in all aspects except for the

disease of interest under study

o Controls must have the same opportunity of getting exposure to

risk factors as cases and should be subjected to the same

inclusion and exclusion criteria
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 Selection of controls
o Controls should be selected from the same study base (target
population) as cases

o Should be selected independently of their exposure status to the

primary risk factors in question

o If they had developed illness, they should be excluded or should be

considered as cases

o Comparable information should be obtained from controls as it is

from cases
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 Sources of controls

1. Population-based controls

2. Hospital-based (health institution) controls

3. Specials controls: neighbourhood, friends, spouses or

relatives (siblings) – when?

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 Population-based controls

Advantages:
o Generalizability will be improved (representativeness)

o Direct calculation of risk rate is possible

Disadvantages:
o Costly and time-consuming

o Sampling frame is not available

o Less cooperative

o Risk of selection bias

o Re-call bias increases (because they are healthy)

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 Hospital-based controls
Advantages:
o Minimize re-call bias

o Minimize selection bias

o Convenient

o Cooperative non-case patients (minimize non-response bias)

o Preferable if they come from same catchment area as cases

Disadvantages:
o Control disease may be linked to exposure of interest

o Hospitalized controls differ from general population

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 S a m p l i n g in case-control studies

o In case-control study, the limiting factors is usually the number of

available cases

o So, we can increase the number of controls up to fourfold

o Going from one to two controls per case vastly increases the
power, however increase above a ratio of 4 to 1, the gain becomes
very small

o There is a trade-off between the need for higher study power, and
the cost of finding more cases and controls
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 Measuring exposure of interest

o Exposure status could be ascertained by interview (patient,

relative), hospital records, laboratory analysis etc…

o May include analysis of pre-diagnostic biological specimens

(nested case-control approach)

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 Analysis of case-control studies
Comparison is made primarily by estimating the relative risk as
computed by the odds ratio.
In a case–control study, we typically calculate the odds of exposure
in cases (a/b) compared to the odds of exposure in non-cases(c/d).
Two possible outcomes for an exposed person: case or not
Odds=a/b
Two possible outcomes for an unexposed person: case or not
Odds=c/d

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 Analysis 2X2
Cases Controls Total
Exposed a b a+b
Unexposed c d c+d
Total a+c b+d a+b+c+d

Odds of exposure in cases = a/c

Odds of exposure in controls = b/d

Odds Ratio = a/c = ad

b/d bc
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Example; A case control study conducted to identify weather
smoking is a risk factor for occurrence of stroke – calculate ,
interpret the result and test a hypothesis that there is no
association between smoking and stroke
Cases Controls Total
Ever smoked 120 100 220
Never smoked 80 300 380
Total 200 400 600

Odds Ratio = (120x300)/(80x100)=4.5

• Odds ratio of 4.5 means that smokers were 4.5 times more
likely to develop stroke compared to non smokers
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 Interpretation of results

• Odds ratio of > 1 means odds of exposure for cases

is higher than for controls – exposure is a risk factor

• Odds ratio of < 1 means odds of exposure for cases

is lower than for controls – exposure is preventive

• Odds ratio =1 means the odds of exposure is the

same in cases and controls – No association
between exposure and outcome
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 Common bias in case-control studies

o Information bias

- recall bias

- non-response bias
o Selection bias

- using different criteria to select cases and

controls
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 Strengths of case-control studies

o To investigate rare disease (less than 10%)

o Suitable for the evaluation of diseases with long latency period
o Quick with time and in-expensive

o Relatively efficient with small sample size comparing with cohort

studies
o No problem with attrition of study subjects
o Can examine multiple etiologic exposures for single outcome
o No ethical problems
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 Limitation of case-control studies

o In-efficient for rare exposures

o In some situations, the temporal relationship between
exposure and disease may be difficult to establish

o Prone to selection and information bias

o Selection of controls difficult some times

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 Cohort Studies

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 Learning objectives

After the end of this session, students will be expected to:

o Define cohort and cohort studies

o Describe purpose of cohort studies
o Define exposure and outcome of interest
o List type of cohort studies
o State strengths and limitations of cohort studies

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 What is cohort?

 Any designated group of persons who are followed or traced over

a period of time
Examples of cohort:
o Birth cohort
o Marriage cohort
o Immigration cohort
o Treatment cohort
o Exposure cohort
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 Definition of cohort studies
 A cohort study is an observational research design which begins
when a cohort initially free of disease (outcome of interest) are
classified according to a given exposure and then followed (traced)
over time

 The investigator compares whether the sub-sequent development

of a new cases of disease (other outcome of interest) differs
between the exposed and non-exposed cohorts
 For example if a researcher want to investigate weather drinking
more than five cup of coffee/exposure per day in pregnancy
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resulted in fetal abnormality/outcome
 Design of cohort studies
= == > If we want to know weather exposure to drinking coffee during
pregnancy will result in abnormal birth
Diseased
Exposed Give abnormal
Drink more baby
than five cup of
Coffee per day Not diseased
People
without Give normal baby
Population
at risk the Diseased
outcome Not Exposed Give abnormal
Pregnant baby
Not drink
mothers any coffee
Not diseased
Give normal baby
Time
Direction of enquiry
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Basic futures of cohort studies
“Disease free” or “without outcome” population at entry

Selected by exposure status rather than outcome status

Exposure example – deriving after drinking alcohol

- sleeping without using bed net

- feeding kids without washing our hands

- not using glove during injection

Follow up is needed to determine the incidence of the outcome

Compares incidence rates among exposed against non-exposed

groups
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 Types of cohort studies

 Cohort studies can be classified depending on the

temporal relationship between the initiation of the
study and the occurrence of the outcome of interest

– Prospective cohort studies

– Retrospective cohort studies

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 Types of cohort study design

Classical (prospective)

1. measure exposure 2. measure outcome

Historical (retrospective)

1. Record of exposure 2. measure outcome

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 1. Prospective cohort studies
o Study participants are grouped on the basis of past or

current exposure status

o Both groups are followed into the future in order to observe
the outcome of interest
o At the beginning of the study the outcome has not yet
occurred
o Regarded as more reliable than the retrospective, if the
sample size is large and follow-up is complete
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 2. Retrospective cohort studies

o Both exposure and outcome status have occurred at the

beginning of the study

o Studies only prior outcomes and not future ones

o A historical cohort study depends upon the availability of

data or records that allow reconstruction of the exposure of

cohorts to a suspected risk factor and follow-up of their
mortality or morbidity over
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time
Epedimiology course 224
 Retrospective cohort studies…

o Suitable for studies of rare exposures, or where the latent period

between exposure and disease is long

o In other words, although the investigator was not present when

the exposure was first identified, s/he reconstructs exposed and
non-exposed populations from records, and then proceeds as
though s/he had been present throughout the study

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Which type of cohort studies should be used?

 The decision to conduct a retrospective or prospective study

depends on:

o The research question – If very valid outcome is required

o Nature of the outcome of interest – long/short latent period

o Practical constraints such as time and money- if yes/no…..

o Availability of suitable study population and records – if yes….

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Data to be collected in cohort studies

o Data on the exposure of interest to the study hypotheses –

o Exposure is any risk factor that can associated with the occurrence of

that disease

Example - chat chewing habit, alcohol drinking habit

o Data on the outcome of interest to the study hypotheses –

- Development of the disease of interest specific to the exposure

Example- depression, poor academic performance

o Characteristics of the cohort that might confound the association
under study
o Other socio demographic variables like age, sex, income----
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Sources of exposure and outcome information

o Pre-existing records- hospital records

o Information supplied by the study subjects- interview

o Direct physical examination or screening tests

o Death certificate

o Laboratory sample analysis

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Follow up period of cohort studies

o The follow-up is the most critical and demanding part of a cohort

study

o Lost to follow-up should be kept to an absolute minimum (< 10-15%)

o Changes in the level of exposure to key risk factors, after the initial

survey and during the follow-up period, are a potentially important

source of random bias

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 Ascertainment of outcome of interest

• The aim of good case ascertainment is to ensure that the process of

finding cases, whether deaths, illness episodes, or people with a
characteristic, is as complete as possible

• Must have a firm outcome criteria and standard diagnostic

procedure which are equally applied for exposed and non-exposed
individuals

o Any outcome measurement should be done equally both to the

exposed and non-exposed groups
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 Analysis of cohort studies

o The primary objective of the analysis of cohort study data is to

compare disease occurrence in the exposed and unexposed
groups
o It is a direct measurement of a risk to develop the outcome of
interest
o Calculation and comparison of rates of the incidence of the
outcome for exposed and non-exposed subjects using relative risk
(RR) as measure of association

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 Relative Risk…

RR = incidence of a disease among exposed (a/(a+b))

incidence of a disease among non-exposed (c/(c+d))
Disease
. a .
Exposure Yes (+) No (-)
Yes (+) a b a+ b
RR = a+b
.
No (-) c d c+d
. c .

c +d

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Strength of cohort studies:

o Particularly efficient when exposure is rare

o Can examine multiple effects of a single exposure

o Minimize bias in outcome measurement if prospective

o Allows direct measurement of incidence (risk)

o Can elucidate temporal relationship between exposure

and outcome of interest (if prospective )
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 Limitation of cohort studies:
o Costly and time consuming if disease is rare and/or long latency

period (if prospective)

o Validity of the results can be seriously affected by loss to follow up

(if prospective)
o Relatively statistically inefficient unless disease is common (need

large sample size)

o If retrospective, requires availability of adequate records

o Exposure status may change during the course of study

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 Exercise
• The investigator wants to know weather doing exercise prevents the
occurrence of depression in students. He selects 100 students who
under take regular exercise and 100 students who fail to undertake
exercise and follow them for a period of one year for occurrence of
depression. Finally he found 30 students doing exercise and 80
students who did not doing exercise depressed.

1. What type of study was conducted

2. Create two-by-two table
3. What is the appropriate measure of association
4. Calculate and interpret the result
5. Test a hypothesis which depicts there is no association between
regular exercise and depression

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 Interventional Studies

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 Learning objectives

After the end of this session, students will be expected to:

o Define interventional studies

o Describe purpose of interventional studies
o Describe treatment and comparison groups
o Discuss steps of interventional studies
o List types of interventional studies
o State strengths and limitations of interventional studies

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 Definition of interventional studies

o ”An epidemiological experiment in which subjects in a population are

randomly allocated into groups, usually called study and control groups to
receive and not receive an experimental preventive or therapetuic procedure,
or interventition”
o Investigators must formulate a hypothesis before launching an experimental

study

- Ho: New drug “A” can not threat vivax malaria

- Ha : New drug “A” can threat vivax malaria
Or
- Ho: New vaccine “A” can not prevent pneumonia
- Ha : New vaccine “A” can prevent pneumonia
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 Interventional studies…

An experimental design is a study design that gives the

most reliable proof for causation

Investigator assigns subjects to exposure and non-

exposure and makes follow up to measure for the
occurrence of outcome of interest

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 Study groups in interventional studies

 The comparison groups in intervention study are known

as the intervention group and the control group

o The intervention group receives the test drug (the preventive

activity such as health education, diet and physical exercise etc…)

o The control group shall be offered the best known alternative or

placebo activity with no known effect on the outcome variable
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 Study groups in interventional studies…

o It is very important that the two groups gain equal of

attention in the study

o Ideally, the intervention and the control populations are at

the same stage of the natural history of the disease and are
similar in the characteristics that affect disease outcomes,
differing only in the exposure of interest to the intervention
study
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 Classification

1. Based on population
A. clinical trial - usually performed in clinical setting and the
subjects are patients.
B. Community trial-unit of the study is group of
people/community.
E.g. Fluoridation of water to prevent dental caries.
2. Based on purpose
A. Preventive - investigate a measure that prevents disease
occurrence (known as a preventive or prophylactic trial)
B. Therapeutic - measure that treats an existing condition
3. Based on design
A. Uncontrolled trial - no control group and 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
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into either group is randomized.
4. Based on objective
A. Phase I - trail on small healthy subjects to test a new drug with small
dosage to determine the toxic effect to assure drug safety.

B. Phase II - trial on relatively large number of patients to determine the

therapeutic effect.

C. Phase III- study on large population - usually a randomized control

trial

- To determine treatment effectiveness

- It gather information on a drug’s indications of use,
recommended doses, and side effects
- When a phase 3 trial is complete, the drug manufacturer can
request to market the drug for the indication
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D. Phase IV: Post Market Surveillance

- The purpose of this trial is to re-assess the effectiveness, safety,

acceptability and continued use of the drugs

- Post marketing surveillance may be conducted to determine

long- term safety and efficacy of the drug

- Needed because rare and slowly developing adverse events may

not become evident during the typical 3-year phase 3 trial

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 Steps of interventional studies

1. Selection of study population

2. Allocation of treatment regimen

3. Maintenance and assessment of compliance

4. Ascertainment of outcomes
5. Analysis & conclusion of experimental studies
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1. Selection of study population
Reference population: The general group to whom investigators
expect the results of the particular trial to be applicable.
- Related to the issue of generalizability
Experimental population: The actual group selected in which the
trial is conducted based on different eligibility criteria
Eligibility criteria should reflect the purpose of the trial, as well as
scientific, safety, and practical considerations.
– For example
– Healthy or high-risk individuals are enrolled in prevention trials,
– Individuals with specific diseases are enrolled in therapeutic
trials.
– Additional inclusion and exclusion criteria are used to restrict
the study population by factors such as gender and age.
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 Preferable if this group is not different from the reference population

(generalizability)

 Considerations in choosing the experimental group:

Must include an adequate number of individuals (required sample

size for the trial).

Choose population that will experience a sufficient number of

endpoints/outcome to permit meaningful comparison.

Likelihood of obtaining complete and accurate follow-up information

for the period of trial

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06/26/2021 Epedimiology course 248
o Those who are willing to participate and who are eligible are the actual
‘study subjects’

o Selection of study population on their willingness has its own

disadvantage (losing external validity)

 These willing/ voluntarily may be different from those non-voluntary groups

o Knowledge of difference or similarity in baseline variables between

participants and non-participants is necessary to assess for
generalizability
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 2. Allocation of treatment regimen
o Randomization of study subjects
o There is a need of assignment of study population into the two or
more groups by randomization

o To help assure that groups are similar, subjects are randomly

assigned to experimental or control groups

o Randomization is performed to increase the likelihood that groups

would be similar in baseline characteristics
o Randomization is supposed to have the effect of distributing
confounders (both known and unknown equally) between the
intervention and control groups if we use large sample size
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3. Maintenance and assessment of compliance
o An intervention study requires the active participation and cooperation of the study

subjects
o Study subjects may be able to deviate from the study for many reasons:

– Side effects

– Desire to seek other therapies

– Forgetting to take their medication

– Simple withdrawal of their consent

– disease progression and death etc…

o Monitoring compliance is important because non-compliance will decrease the

statistical power of the study

o A very serious threat to the clinical trial is the attrition of patients if it is more than 10-

15 %
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 4. Ascertainment of outcomes

o One should specify explicitly what outcomes are expected, and what

criteria are to be applied to determine occurrence of outcomes

o The outcomes may include prevention of a condition, cure of a

condition, improvement in the condition, alleviation of pain,

improved physical or mental health, etc…

o It should be aimed at ensuring the results not to be biased by

complete and accurate measurement of the outcome

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 Ascertainment of outcomes…
o Presence of knowledge of allocation of study subjects could result in a
bias called “Information bias”

o Even after randomization, it is possible that experimental subjects may be

treated differently than controls

o To avoid this information bias, we can use two mechanisms

1. Blinding - un aware subject ,data collector and data

analyzer about the assignment to treatment or

control group
2. Use of placebo
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 1. Levels of blinding
Non-blinded/open - All know which intervention a patient is
receiving (common in community trials)

Single blinded - The study subjects were not aware of treatment at

which they were assigned

Double blinded - the staff carrying out the treatments and patient
care were unaware of treatment assignment

Triple blinded - Data collectors, analyzers and the other two above
were not aware of treatment assignment

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 2. Use of placebo

o A placebo is a biologically inactive substance given to the control

group so that they think they are being treated equally as
treatment group

o The purpose of placebo is to match as closely as possible the

experience of the comparison group with that of the treatment
group

o The placebo should be similar to the drug being tested in respect

to appearance (size, texture, odor, color and taste)
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 Follow up time

How long must investigators follow subjects to ascertain the outcomes

under study?

oOnly a few months may be needed for a short-term study of drug side effects

but a decade may be necessary for examining slowly developing outcomes

oFollow-up is adversely affected when participants either withdraw from the

study (drop outs) or cannot be located or contacted by the investigator (lost

to follow-up)

oIf attrition is related with outcome , it will be serious effect

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 Decision of terminating a trial
o There is a need of a guideline for deciding when to terminate a
study trial

– Criteria for terminating the trial should be clearly specified

– Criteria for observing and recording side-effects should also be

formulated prior to the study

o In experimental study, there is a need of an independent group
that monitors and keeps the welfare of study subjects
o Data safety and monitoring board
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 Stopping rules
 Many intervention studies now include early stopping rules:

– If side-effects would endanger the health of a patient, he/she should be

excluded from the study and treated appropriately

– Statistical analysis at pre-determined point (interim analysis) to look for

clear benefit or harm which would mandate stopping the trial earlier

This is mainly focused

– To protect participants from harm

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 5. Analysis of experimental studies
o Two types
1. Intent to treat/ones randomized then analyzed/treatment
assignment analysis – All participants randomized will be
considered for analysis weather or not they take full treatment
coarse.
- It answers treatment effectiveness – how many of the
participant assigned to treatment group or placebo group
develop the outcome of interest to the study

2. Efficacy analysis – the analysis base only on participant take the

whole treatment coarse or comply
- It answers the question of treatment efficacy – how many of the
participants who take full dose of treatment was cured/develop
the outcome under study
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 What is the advantage of an intent-to-treat analysis
over efficacy analysis?

o First, it preserves the benefits of randomization (it preserves baseline

comparability of the groups for known and unknown confounders)

o Second, it maintains the statistical power of the original study

population

o Third, because good and poor compliers differ from one another on

important prognostic factors, it helps ensure that the study results are

unbiased
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 The quality of "gold standard" in intervention studies
can be achieved through :

1. Randomization

2. Use of placebo
3. Double Blinding

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 When an experimental studies warranted ?

o Generally reserved for relatively mature research

questions

o The research questions cannot be answered by

observational studies

o Existing knowledge is not sufficient to determine clinical

or public health practices and policies

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Strengths of interventional studies:

Randomization minimizes selection bias and confounding factors

Blinding and use of placebo to minimizes information bias

The best type (gold standard)

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Limitations of interventional studies:

o Ethical issues in question

o Feasibility issues
o Cost implications

o Compliance issue

o Loss to follow up and drop outs issue

o External validity in question – small sample size

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 Example

• Investigator wants to know the effectiveness of new drug “A”

therapeutic effect in treating p. falciparum over the previous
coartem. He randomly allocate 80 malaria patients to treatment
group and 80 malaria patients to control/coartem/ group. Finally
he found good prognosis in 40 patients who took new drug ”A”
and in 10 patents who took previous coartem.
1. What type of study was conducted
2. Create two-by-two table
3. What is the appropriate measure of association
4. Calculate and interpret the result
5. Test a hypothesis which depicts there is no prognosis difference
between drug “A” and the coartem
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 Chapter-8

Association

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 Learning objectives
After the end of this session, students will be expected to:
o List common measures of association and measures of
public health impact
o Calculate and interpret relative risk and odds ratio and
describe their use
o Calculate and interpret attributable risk percent and
preventive fraction
o Calculate and interpret population attributable risk
percent
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 Association

Occurrence of statistical relationship between the disease and the risk

factor
Exposure / risk factor Outcome

The occurrence of disease in a group of people exposed to a risk factor

is compared

To --------

Those un exposed to a risk factor

----- > in order to establish association between risk factor and disease

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 ASSOCIATION….
o Risk factors and disease can be related or unrelated to one
another

o If related, risk factors can be:

– positively or negatively affect the occurrence of disease

– strongly or weakly affect the occurrence of the disease

– significantly or not significantly related

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 Exposure and outcome variables
o The hypothesis to be tested in a study usually defines which
variable is assumed to be cause (i.e. risk factor) and which variable
is considered to be the effect (outcome)

o The definition of a variable therefore depends on the study

hypothesis:

o A variable may be exposure in one hypothesis, a confounder in

another, and outcome in a third hypothesis

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271
 Measuring an association
 The occurrence of association between the exposure and outcome
should be determined
o The common measure of association are;
o Relative risk,

o Odds ratio

=== For measure of exposure public health importance after

the causal path way between exposure and outcome is assured
o Attributable risk/ Preventive fraction and
o Population attributable risk and their percents

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 1. Relative Risk (RR)
Risk: The probability of an event occurring over time
Risk Ratio: The ratio of two risks or relative risk
Relative risk estimates the magnitude of the association
between exposure and disease

It indicates the likelihood of developing the disease in

the exposed group relative to those who are not
exposed for certain factor
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 Relative Risk…

RR incidence of a disease among exposed (a/(a+b))

= incidence of a disease among non-exposed (c/(c+d))

Disease
K
a Exposure Yes (+) No (-)
. . n
Yes (+) a b a+ b
RR = a+b o
.
.
No (-) c d c+d w
.
.
c .
.
n
c +d

– It is a direct measurement of a risk to develop the outcome of

interest
– It is usually used in cohort and experimental studies
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 Example
Table 1: Data from a cohort study of oral contraceptive (OC)
use and bacteruria among women aged 16-49 years

Bacteruria
Yes No Total

Current OC use
Yes 27 455 482
No 77 1831 1908
Total 104 2286 2390
 Example cont…
RR = a/(a+b) =27/482 =1.4
c/(c+d) 77/1908

 Interpretation – OC users had 1.4 times the risk

or were 40 percent (i.e 1.4 minus the null value
of 1.0) more likely to develop bacteruria than
nonusers
 Example cont…

Table 2: Data from a cohort study of postmenopausal hormone

use and coronary heart disease among female nurses

Coronary heart disease

Yes No Person-years

Postmenopausal
hormone use
Yes 30 - 54,308.7
No 60 - 51,477.5
Total 90 105,786.2
 Example cont…
RR = Ie =IDe = a/PY1 = 30/54,308.7 = 0.5
Io IDo c/PYo 60/51,477.5

Interpretation: women who used

postmenopausal hormones had 0.5 times/ 50%
less likely/, or only half, the risk of developing
coronary heart disease compared with nonusers.
 Odds Ratio (OR)

o Odds: The ratio of the probability of an event's

occurring to the probability of its not occurring

o Odds Ratio: The ratio of two odds

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 Odds Ratio…
o OR is the chance of being exposed (or diseased) as opposed to not
being exposed (or diseased)
o It is possible to calculate either exposure or disease odds ratio,
which are exactly the same
o ……… exposure OR = disease OR
odds of exposure in diseased = odds of disease in exposed
Odds of exposure in non diseased odds of disease in non-exposed

o The epidemiological thinking behind odds ratio is that if a disease is

casually associated with an exposure, then -
o The odds of exposure in the diseased group will be higher than the
corresponding odds in the non-diseased group
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 Odds Ratio…
It is an indirect measure of a risk in a disease of rare
occurrence

It is usually used in a case-control and cross-sectional

studies

Cases and controls are predetermined and we are

calculating to determine whether cases or controls are
more exposed to a postulated risk factors
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 Odds Ratio…

OR Odds
= of exposed among cases (a/c)
Odds of exposed among controls (b/d)

Disease
Yes (+) No (-)
a/c Exposure
OR = b/d Yes (+) a b
No (-) c d
a+c b+d
KNOWN
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 Odds Ratio…
Dead Alive
Diabetic 100 89
Non diabetic 811 2340

OR = ad / bc

OR = ad = 100 x 2340 = 3.2

bc 89 x 811

What does OR=3.2 mean?

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Odds ratio could be used as a valid estimate
of the relative risk, when:

– The outcome is rare event

– Study subjects selected as cases are incident

cases
– The cases and controls were drown from
representative population
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 3. Absolute Measures of Risk
o Absolute risk/attributable risk/risk difference: a measure of
association indicating ;
o Absolute difference of diseases in exposed group than unexposed
group
=== assuming the association between the exposure and
disease is causal

o Is also called as excess risk of developing diseases among exposed

groups
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 I. Attributable Risk (AR)
o Risk difference (RD) indicates how much of the risk is due to
( attributable to) the exposure alone

o Quantify the excess risk in the exposed that can be attributable to

the exposure

=== Is the difference between the disease rate in exposed groups

and the disease rate in non-exposed groups

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 Attributable Risk…

Incidence
Incidence

I Exposed – I Unexposed

Exposed Unexposed
Exposed Unexposed

I = Incidence
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 II. Attributable Risk Percent (AR %)
o The attributable proportion, also known as the attributable risk
percent, is a measure of the public health impact of a causative
factors
o It is the proportion of additional cases observed because of the
exposure
o It represents the expected reduction in disease if the exposure
could be eliminated

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 Attributable Risk Percent…
oAR % is an attributable risk expressed as a percentage of risk in exposed

groups

oWhat is the proportion of disease among the exposed groups which can be

attributed to the exposure to risk factor?

oSynonyms:

– Attributable proportion

– Attributable fraction

– Etiologic fraction (EF) in the exposed group

– Preventable fraction in the exposed group?

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 Attributable Risk Percent…
Incidence

Iexposed - Iunexposed
%
Iexposed

Exposed Unexposed

I = Incidence
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 Notes about attributable risk
 Estimation of attributable risk has public health relevance when:

o The exposure of interest is cause of the outcome

o The exposure/risk factor/ should be amenable to intervention

o If the exposure is protective

===== we will calculate preventable fraction

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 Preventable Fraction (PF)

If the exposure is preventive, and the incidence in the exposed

group is less than in the unexposed group, then the AR would be
negative

This is rather meaningless (a negative rate), and in this situation

an analogous measure which is preventive fraction will be used
If exposures is negatively associated with outcome variable it has a

relative risk below the unity (1)

If relative risk is < 1, the exposure is a protective

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 Preventable Fraction (PF)…
I Unexposed – I Exposed
PF = I Unexposed

= 1 - RR

Unexposed Exposed
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 Example: Vaccine efficacy
Vaccine Population Cases Cases/1000 RR
Vaccinated 301,545 150 0.49 0.28
Unvaccinated 298,655 515 1.72
Total 600,200 665 1.11

I Unexposed – I Exposed 1.72 - 0.49

PF = PF = = 72 %
I Unexposed 1.72
= 1 – 0.28 =72%

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 III. Population attributable risk(PAR)

o Excess risk of disease in total population

attributable to exposure to risk factors

o Reduction in risk factors achieved if total

population was entirely unexposed

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 Population attributable risk…

Risk

I population – I unexposed

Population Unexposed

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 IV. Population Attributable Risk Percent (PAR %)

PAR% estimates the proportion of disease in the study population

that is attributable to the exposure and thus could be eliminated if
the exposure were eliminated

Population attributable risk percent is the proportion of the risk in

the population that is related to the exposure to the postulated risk
factor

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 Population Attributable Risk Percent…

 Proportion of cases in the population attributable to the

exposure to the risk factor
 PAR expressed as a percentage of total risk in population

I population – I unexposed
PAR% = X 100
I population

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 Example

Table 1: data from a cohort study of oral contraceptive (OC) use and
bacteruria among women aged 16-49 years

Bacteruria
Yes No Total

Current OC use
Yes 27 455 482
No 77 1831 1908
Total 104 2286 2390

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 Calculate
 AR
- AR = Ie - Io
- AR=27/482 – 77/1908 = 0.01566 = 1566/105
- Thus, the excess occurrence of bacteruria among OC users
attributable to their OC use is 1566 per 100,000.
 AR%
-  AR% = AR x 100 = (Ie – Io) x 100
Ie Ie
- AR% = 1566/105 x 1OO = 27.96%
27/482
- If OC use does cause bacteruria, about 28% of bacteruria among women who
use OCs can be attributable to their OC use and could therefore be
eliminated if they did not use OCs
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3. The PAR of bacteruria associated with OC use (Table 1) is:
PAR = IT - Io = 104/2390 – 77/1908 = 316/105/year

-Thus, if OC use were stopped, the excess annual incidence rate

of bacteruria that could be eliminated among women in this
study is 316 per 100,000.

4. PAR% = PAR x 100

IT
= 316 x 100 = 7.3%
4351.5
- Thus, if OC use causes bacteruria, about 7 percent of all the
bacteruria in the study population could be prevented if OC use
were eliminated.
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 Interpretation of measure of association
RR/ OR:
1. RR/ OR > 1, the exposure is risk
2. RR/ OR = 1, there is no association

3. RR/ OR < 1, the exposure is preventive

4. If confidence interval of RR/ OR includes the null (1),
then there is no statistical significant association
5. If confidence interval of RR/ OR is far from the null (1),
it is a sign of presence of statistical significant
association between exposure and outcome
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 Interpretation…
AR/ PAR:
1. AR/ PAR > 0, the exposure is attributing/risk
2. AR/ PAR = 0, there is no attribution
3. AR/ PAR < 0, the exposure is preventive

In general the strength of association can be considered:

High - if the RR/OR is 3.0 or more

Moderate – if the RR/OR is from 1.5 to 2.9
Weak – if the RR/OR is from 1.2 to 1.4

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 Self-Exercise
Suppose that a cohort study of 400 smokers and 600 non-
smokers documented the incidence of hypertension over a
period of 10 years.
The following table summarizes the data at the end of the
study period:

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Based on the above information, calculate and
interpret the following measures of association:

1. Relative risk (RR)

2. Attributable risk (AR) and/or preventive fraction (PF)
3. Attributable risk percent (AR%)
4. Population attributable risk (PAR)
5. Population attributable risk percent (PAR%)

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 Precaution!

“The attributable risk should be estimated

only when there is reasonable certainty that
the association is causal”

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 Chapter-9

Causation

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 Learning objectives
After the end of this session, students will be expected to:

o Discuss the difference between association and

causation
o Identify the role of chance, confounding factors and bias
in establishing cause-effect relationship
o Discuss on how to control the role of chance,
confounding factors and bias
o Apply Bradford Hill Criteria to establish cause-effect
relationship between exposure and outcome of interest
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 Brain storming

If exposure X is associated with outcome

Y…..then how do we decide if X is a cause
of Y or not?

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 Association Vs Causation

 The existence of an association doesn’t itself

constitute a proof of causation

 An observed association could be a fact or an

artifact

 Hence, an association is a necessary but not a

sufficient condition for causation

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 Accuracy
=
Validity + precision

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Validity of epidemiological studies

o Validity is the extent to which a measured value

actually reflects truth
o Next step of evaluation of study results is validation
of the findings
o An observed association is validated for bias, chance
and confounding factors
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 Types of validity

Internal validity:

=Is the degree to which a measured value is true within

the sample

External validity:

= Is the extent to which a measured value apply beyond

the sample (source population)

- This is related to generalizability

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 Precision
 Precision is the extent to which random error alters the
measurement of effects
 Threats to validity of study:

- Random error (chance): is sampling error

- how we can avoid random error?

- Systematic error (bias): is error in the conduct of the

study
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 Concept of cause
o Cause of a disease is an event, a condition,
characteristics/behavior/ or a combination of these factors
which plays a role of producing a particular disease

– Sufficient versus necessary causes

– A sufficient cause is not usually a single factor
– A necessary cause, is a factor that is necessary (or with out which
the disease doesn’t occur)
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 Judgment of causality
 Judgment of causality is a process by which we assure weather
the observed association is causal or not for that outcome

= Judgment of causality has two steps

1. Check whether the observed association between exposure and

disease is Valid (Rule out chance, bias and confounding)

2. Check whether the observed association is causal (Bradford hill

criteria)

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Alternative explanations for the observed
association other than cause-effect relationships:

o The association may be the result of chance

o The association may be the result of bias
o The association may be the result of a confounding effect
o Associated factor by it self can be an outcome, rather than a
cause (reverse causation)
o The associated factor can be both a cause and effect (reciprocal
causation)
E.g: Vitamin “A” deficiency can cause diarrhea or diarrhea can cause
vitamin “A” deficiency
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 Establishing a Causal Association
Observed association Could it be due to
RR- Chance?
OR- No
Could it be due to
Confounding?
No
Could it be due
to Bias?
No
Could it be
Cause?

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Apply Judgment of causality
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 Role of chance
we can draw inferences about the experience of an entire population
based on an evaluation of only a sample.
Chance may always affect the results observed simply because of
random variation from sample to sample.
Sample size is one of the major determinants of chance.
Evaluation of the role of chance is mainly the domain of statistics and
involves

1. Test of statistical significance

2. Estimation of confidence interval
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 1. Test of statistical significance

 P-value quantifies the degree to which chance accounts for

observed association

 P-value is the probability of obtaining a result at least as

extreme as the observed by chance alone

 P<0.05 indicates statistical significance for medical research

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 Test of statistical…

 A very small difference may be significant if you have large sample

 A large difference may not achieve statistical significance if you

have small sample
SO ----------- >
 One can’t make a definite decision based on p-value only

SO ------------ ?

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 2. Estimation of confidence interval

 Confidence interval represents the range within which true

magnitude of effect lies within a certain degree of assurance

 It is more informative than p-value because it reflects on both

the size of the sample and the magnitude of the effect

= wide interval = inadequate sample

= Narrow interval = adequate sample

- CI(3.12,5.61) = high magnitude/strong association

- CI(1.23,1.56)= very low magnitude/weak association

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=== So to rule-out the roll of chance from our association:

1. Designing phase
 Increase the sample size (increase the power of the study)

2. Analysis phase
 Hypothesis testing, P-value’s role using test statistics like Z-
test, t-test, chi-square test
 Confidence interval determination for the point estimator

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 Establishing a Causal Association…
Could it be due to
Chance?

No
Observed association Could it be due
RR- to Bias?
OR- No
Could it be due to
Confounding?
No
Could it be
Cause?

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Apply Judgment of causality
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 Role of bias
Bias is any systematic error in the design, conduct or
analysis of an epidemiologic study that results in

An incorrect estimate of association between exposure

and disease

Unlike chance bias can’t be statistically evaluated

There are two major types of bias

- Selection bias

- Information bias
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 Selection bias

Any systematic error that arises in the process of identifying the

study population

It affects the representativeness of the study

It occurs when there is a difference between sample and population

with respect to the study variable

Examples of selection bias:

1. Diagnostic bias –ascertainment of outcome

2. Volunteer bias

3. Non-response bias
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4. Loss to follow-up bias
 Information/observation/bias

 Any systematic error in the measurement of

information on exposure or disease
 Examples of information bias:

1. Interviewer bias/observer bias

2. Recall bias
3. Social desirability bias
4. Placebo effect
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 Ways to minimize bias

1. Choose study design carefully -

2. Choose objective rather than subjective outcomes
ascertainment

3. Blind interviewers, subjects and analyzers of data whenever

possible
4. Use close ended questions whenever possible
5. Train data collectors
6. Pre test, pilot the consistency, completeness and clarity of
your data collection tools
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Care full entry, compilation and analysis of your data 328
 Establishing a Causal Association…
Could it be due to
Chance?

No
Could it be due
to Bias?
No
Observed association Could it be due to
RR Confounding?
OR No
Could it be
Cause?

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Apply Judgment of causality
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 Role of confounding factors

Confounding refers to the mixing of the effect of an extraneous variable

with the effect of the exposure and disease of interest

Confounder is a variable that can cause or prevent the outcome of interest,

is not an intermediate variable, and is associated with the factor under
investigation

ITN distribution ------------------ > Malaria

lack of proper Utilization

of ITN
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 Criteria for Confounding Factors
o Must be an independent predictor of disease with or without
exposure

o Must be associated (correlated) with exposure but not caused by

the exposure

o Must not be an intermediate link in a causal pathway between

exposure and outcome
Salt intake ---------- > Hypertension --------- > heart disease

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 Confounding Effect

o Can overestimate the true association (POSTIVE confounding)

o Can underestimate the true association (NEGATIVE confounding)

o Can change the direction of the association between exposure

and outcome (PROTECTIVE Versus AGRAVATIVE)

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 Generally we can use the following technique to alleviate the
problem of confounding:
 During design phase

o Randomization
o Restriction
o Matching

 During analysis phase

o Stratification analysis
o Standardization
o Matched analysis
o Multivariate analysis

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Establishing a Causal Association…
Could it be due to
Chance?

No
Could it be due to
Confounding?
No
Could it be due
to Bias?
No
Observed association Could it be
RR- causal?
OR-
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Apply Judgment of causality
Epedimiology course 334
 Is the association causal?
==Stage I : If the association is not due to:

– Bias?

– Confounding?
– Chance?

==Stage II: If the association is unlikely to be due to bias,

confounding or chance…

===== we apply ‘guidelines’ for causal inference

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 The Bradford Hill Criteria
o It is the statement of epidemiological criteria of a causal
association formulated in 1965 by Sir Austin Bradford Hill
1. Strength of association
2. Consistency of findings with other studies

3. Temporality
4. Biologic gradient
5. Biologic plausibility
6. Specificity of the association
7. Experimental evidence
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 Bradford……….

1. Strength of the Association - The stronger the association,

the more likely that it is causal.

2. Consistency of the Relationship - The same association should

be demonstrable in studies with different methods, conducted by
different investigators, and in different populations.

3. Specificity of the Association - The association is more likely

causal if a single exposure is linked to a single disease.

4. Temporal Relationship - The exposure to the factor must

precede the onset of the disease.
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 Bradford…….

5. Dose-response Relationship - The risk of disease often increases

with increasing exposure to a causal agent

6. Experimental confirmation- Confirmation that the risk of

disease often increases with increasing exposure to a causal agent
by manipulating exposure level.

7. Biological Plausibility - The hypothesis for causation should be

coherent with what is known about the biology and the descriptive
epidemiology of the disease

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 Which Hill’s criteria are essential?
There are no completely reliable criteria for determining whether
an association is causal or not
In judging the different aspects of causation; not all criteria must
be fulfilled to establish scientific causation
The correct temporal relationship is more essential

risk factor/cause --------------------- outcome/effect

=== Once this has been found, weight should be given to:
– Strength of the association
– Biologic plausibility
– Consistency
– Dose-response relationship
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Thank you!
 Chapter-10

Public Health Surveillance

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 Learning objectives
After this session, students will be expected to:

o Define public health surveillance

o List types of case definitions

o Discus purpose of public health surveillance

o Describe the types of surveillance

o List criteria to select a disease for surveillance system

o Discus public health emergency and management

o List priority reportable diseases in Ethiopia

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 Brain Storming

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 What is surveillance?
Systematic, ongoing…
– Collection Health action
– Analysis  investigation
– Interpretation  control
– Dissemination  prevention
…of health outcome data

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 Surveillance system

 A network of peoples and activities that maintain this process and may

function at a range of levels from local to international

 The components of surveillance and resulting public health action are depicted

in the following diagram

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 Components of surveillance and public health action

Public Health Action

Component of Surveillance Priority setting
o Collection Planning,
implementing and
o Analysis
o Interpretation evaluating disease occurrence

o Dissemination in that community

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 Purpose of surveillance
i) To identify diseases, injuries, hazards and other health related

factors as early as possible, i.e. prediction and early detection of

outbreaks.

ii) To provide scientific baseline data and information for priority

setting, planning, implementing and evaluating disease control

program for both communicable and non-communicable health

problems.

iii) To define the magnitude and distribution of diseases by time,

person and place dimension

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 Types of surveillance

o Active surveillance
o Passive surveillance
o Sentinel surveillance

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 Active surveillance

o It is based on active case detection

o Active case detection - is an active search for cases by

special surveys, house to house visits or other methods

outside of the routine health service activities

o It is not routine activities because it is expensive

o However, it is more accurate and better representative as

community based data

E.g: Outbreak investigation and control

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 Active surveillance...

Health Authority

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The advantages of active surveillance
The collected data is complete and accurate
Information collected is timely.
Disadvantages
It requires good organization,
It is expensive
Requires skilled human power
It is for short period of time(not a continuous
process)
It is directed towards specific disease/conditions
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 Passive surveillance

o Based on passive case detection, and routine recording and

reporting activities

Passive case detection

o Cases detected in the course of the normal operation of the health
services, through the self reporting of patients to health institutions

o The data is usually unreliable, incomplete, inaccurate,

unrepresentative and reported untimely

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 Passive Surveillance…

Health Authority

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Advantages of passive surveillance
Covers a wide range of problems
Does not require special arrangement
It is relatively cheap
Covers a wider area
Disadvantages

The information generated is to a large extent unreliable, incomplete

and inaccurate
Most of the time, data from passive surveillance is not available on
time
Most of the time, you may not get the kind of information you desire
It lacks representativeness as it is mainly from health institutions
There is no feed back system
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 Sentinel Surveillance

o Sentinel surveillance involves the collection of case data from only

part of the total population (from a sample of providers) to learn
something about the larger population, such as trends in disease
o Under this strategy, health officials define homogenous population
and regions to be sampled
o The advantages of sentinel surveillance data are that they can be
less expensive to obtain, and the data can be of higher quality
o In developing countries, sentinel surveillance provides a practical
alternative to population-based surveillance

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 Main purposes of sentinel surveillance

o To detect changes

o To direct and focus control efforts

o To develop intervention strategies

o To promote further investigations

o To provide the basis for evaluating preventive

strategies
06/26/2021 Epedimiology course 356
Advantages of sentinel surveillance

Relatively inexpensive

Provides a practical alternative to population-based surveillance

Can make productive use of data collected for other purposes

Disadvantages:

The selected population may not be representative of the whole

population

Use of secondary data may lead to data of lesser quality and

timeliness
06/26/2021 Epedimiology course 357
 Process of public health surveillance

o Data collection and recording

o Reporting and notification

o Data compilation
o Data analysis

o Data interpretation

o Data dissemination

o Link to public health action

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 1. Data collection and recording

o Data for the surveillance system can be obtained from the community
(active surveillance) and health facility (passive surveillance)

o A responsible person (data clerk) must visit the OPD and wards daily to
tally the cases and deaths for each diagnosis

o Daily totals are compiled into weekly or monthly summaries, and

reported to the next higher level

06/26/2021 Epedimiology course 359

 2. Reporting and notification

 A single (case-based report) form is usually used to

report data about the priority diseases
 Depending on their importance diseases can be
classified as:
o Immediately reportable in cases of suspected epidemics

o Weekly reportable for those epidemic-prone diseases

o Monthly reportable for those under routine surveillance
o Quarterly reportable diseases
06/26/2021 Epedimiology course 360
 3. Data compilation, analysis and interpretation

o Data should be compiled at each level of the health system

o Each level of the health care system should also analyze and utilize
for decision making

o Analysis of data includes describing distribution of diseases by

place, person and time

o Calculation of rates and ratios using appropriate denominators and

comparing with expected levels
06/26/2021 Epedimiology course 361
 Excess cases may be due to the following conditions:

o Changes in local reporting procedures or policies

o Changes in case definition

o Increased interest because of local or national awareness

o New laboratory test or improvement in diagnostic procedures

o Sudden changes in population size

o Increased health-seeking behavior of the community

o Laboratory error
o Duplicate reporting etc…

06/26/2021 Epedimiology course 362

 4. Dissemination of findings and feedback

== It is the dispatching of reports to those who are in position to

take action in terms of:

o Prevention and control disease

o Health planning and resource allocation
o Research and teaching activities

==Surveillance findings should be disseminated to all stakeholders

– The community
– Health care providers
– Decision makers
– Stakeholders
06/26/2021 Epedimiology course 363
 Dissemination…
Message

Audience

Channel
06/26/2021 Epedimiology course 364
 Features of good surveillance system

o Uses a combination of passive and active mechanisms to collect data

o Requires timely notification and reporting of the event

o Use strong laboratory services for accurate diagnosis

o Provide complete feed back

o Initiate for action

== Action must be targeted towards case detection, treatment and control of
the disease
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 Attributes of a good surveillance system

o Simplicity
o Flexibility

o Acceptability
o Accuracy and completeness
o Sensitivity
o Good predictive value positive and yield

o Representativeness
o Timeliness
o Cost effectiveness
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 Criteria for selecting and prioritizing health conditions for
surveillance system includes:

o Public health importance of the problem

o If disease has epidemic potential

o If required internationally

o Have available effective control and prevention programs

o Can easily be identified using simple case definitions

06/26/2021 Epedimiology course 367
 Case definition

 Case definition is a set of criteria for deciding whether

an individual should be classified as having the health
condition of interest or if the case can be considered for
reporting and investigation
 Case definition for cholera

- Acute watery diarrhea

06/26/2021 Epedimiology course 368
 Standard case definition

 If the use of case definition is agreed by everyone in the

country or across boundaries or continents it is standard
case definition

o Surveillance using less specific criteria is sometimes

referred as syndromic surveillance
E.g: Polio (AFP)
06/26/2021 Epedimiology course 369
 Types of case definition

Confirmed case
o A case with laboratory verification

Probable case
o A case with typical clinical features of the disease without
laboratory confirmation

Suspected case
o A case presented with fewer of the typical clinical features of the
disease without laboratory confirmation
06/26/2021 Epedimiology course 370
 Advantages of case definition

o Facilitate early detection and prompt management even if diagnosis is not

confirmed by laboratory

o Laboratory test is expensive, difficult to obtain

o Observation of trends

o Comparison from one area to another

06/26/2021 Epedimiology course 371

 Public Health Emergency Management (PHEM)

 Public health emergencies are events or disasters that threaten the

health of communities at large

Some examples are disease outbreaks (emerging and reemerging) and

pandemics, natural disasters such as earthquakes, floods, droughts,
volcanoes; biological terrorist attacks such as an anthrax release

PHEM is the process of anticipating, preventing, preparing for,

detecting, responding to, controlling and recovering from
consequences of public health threats in order that health and
economic impacts are minimized
06/26/2021 Epedimiology course 372
Emergency management phases
Mitigatio
n
Recovery

Prepared
ness

Response
 Mitigation

 Pre-event planning and actions which are

intended to lessen the impact of a potential
disaster

E.g: Risk identification / assessment and reduction

06/26/2021 Epedimiology course 374

 Preparedness

 Actions taken before an emergency to prepare for response

o Develop emergency management plan

o Develop communication plan

The identification of a public health threat by closely and

frequently identified monitoring indicators and predicting the risk
it poses on the health of the public and the health system (early
warning phase)
06/26/2021 Epedimiology course 375
 Response

 Activities to address immediate and short-term effects of a

disaster

– Implement emergency management plan

o Save lives

o Meet basic human needs

06/26/2021 Epedimiology course 376

 Recovery

 Restore essential functions and normal operation

– Assess damage / impact of disaster

– Address psychological needs of patients and community

– Produce after action debriefing and report

06/26/2021 Epedimiology course 377

 Limitations of surveillance system in Ethiopia

o Under reporting

o Lack of representativeness

o Lack of timeliness

o Inconsistency of case definitions

o Shortage of qualified staff

o Lack of motivation

06/26/2021 Epedimiology course 378

 List of priority reportable diseases in Ethiopia
Diseases targeted for eradication
Epidemic-prone diseases
12. Acute flaccid paralysis (Polio)
1. Cholera
2. Diarrhea with blood 13. Dracunculiasis (Guinea worm)
(Shigellosis) 14. Leprosy
3. Measles 15. Neonatal tetanus
4. Meningitis Diseases of public health importance
5. Plague 16. Pneumonia in children
6. Viral hemorrhagic fever 17. Diarrhea in children
7. Yellow fever 18. New AIDS cases
8. Typhoid fever 19. Onchocerciasis
9. Relapsing fever 20. Sexually transmitted diseases
10. Epidemic typhus 21. Tuberculosis
11. Malaria 22. Rabies
23. Emerging unknown liver disease?

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06/26/2021 Epedimiology course 380
 Quiz 5%
Consider Tuberculosis diseases and write its;
1. Confirmed,
2. Probable, and
3. suspected, case definition
 Chapter–11

Outbreak Investigation & Control

06/26/2021 Epedimiology course 382

 Learning objectives
After the end of this session, students will be able to:

o State different level of disease occurrences

o List the rationale to investigate outbreak occurrence
o Discuss steps in the investigation of an outbreak
occurrence
o Describe types of outbreak occurrence
o Discuss the outbreak controlling strategies

06/26/2021 Epedimiology course 383

 Epidemiology in Action

 Outbreak Investigations

 Public Health Surveillance

 Community Screening Programs

 Level of disease occurrences

• Diseases occur in a community at different levels at a

particular point in time.
Occurrence at expected levels
• Endemic: Presence of a disease at more or less stable level.
--==Malaria is endemic in the lowland areas of Ethiopia.
• Hyper endemic: Persistently high level of disease occurrence.

• Sporadic: Occasional or irregular occurrence of a disease

06/26/2021 Epedimiology course 385

Excess of what is expected

• Epidemic: The occurrence of health related condition/disease in

excess of the usual frequency

• Outbreak: Epidemics of shorter duration covering a more limited

area.

• Cluster: is an aggregation of cases in a given area over a particular

period.

• Pandemic: An epidemic involving several countries or continents

affecting a large number of people.

example : COVID-19 is a pandemic.

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 What is outbreak occurrence?

06/26/2021 Epedimiology course 387

 What does outbreak investigation & control
Includes?

It is the process of identifying:

o The cause of the epidemic
o The source of the epidemic
o The mode of transmission and
o Taking preventive and control measures

06/26/2021 Epedimiology course 388

 Source of an outbreak information

 surveillance

 Health professionals

 Affected community members

06/26/2021 Epedimiology course 389

 What are the objectives for outbreak investigation?
1) To initiate control & prevention measures

 The most important public health reasons for investigating an

outbreak are to help guide disease prevention and control
strategies.

 These disease control efforts depend on several factors, including

knowledge of the agent,
The natural course of the outbreak,
The usual transmission mechanism of the disease, and
Available control measures

06/26/2021 Epedimiology course 390

 2) Research and training opportunity

o Each outbreak should be viewed as an experiment waiting to be

analyzed
o It presents a unique opportunity to study the natural history of
the disease
o It could be a good opportunity to gain additional knowledge on

– The impact of prevention and control measures

– The usefulness of new epidemiology and laboratory techniques

06/26/2021 Epedimiology course 391

 3) Public, political and legal obligations

o Politicians and leaders are usually concerned with control of the

epidemic
o Politicians and leaders may sometimes override scientific concerns

o The public are more concerned in cluster of disease and potentials

of getting medication
o It is the right of the community to get treatment/service and it is
government and our duty to protect the community

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 4) Program considerations

o Occurrence of an outbreak notifies the presence of a program

weakness
o This could help program directors to change or strengthen the
program’s effort in the future to prevent potential episodes of
outbreak occurrence

06/26/2021 Epedimiology course 393

 Steps of outbreak investigation and control
1. Prepare to field work
2. Establish the existence of outbreak
3. Verifying the diagnosis
4. Case definition and case finding
5. Perform descriptive epidemiology
6. Formulate hypotheses
7. Testing hypotheses
8. Refine hypothesis and additional studies
9. Implementing prevention and control activities
10. Communicate findings
 In practice, however, several steps may be done at the same
time, or
 The circumstances of the outbreak may dictate that a different
order be followed
06/26/2021 Epedimiology course 394
 Step 1: Prepare for field work
 Before leaving for the field, an investigator must be well
prepared to under take the investigation:

o Investigation (Knowledge in epidemiology and the disease of

concern is important)
o Administrative (Logistics, administrative procedures, travel
arrangements)
o Consultation (Health workers should know their role, and should
participate in the planning phase)
06/26/2021 Epedimiology course 395
Step 2: Establish the existence of outbreak
o An outbreak is the occurrence of more cases of disease than
expected level
o The investigator has to compare previous case load with the
current to assure the existence of the outbreak
o But be careful, excess cases may not always indicate an outbreak
occurrence rather it may be because:
 Change in population size
 Change in case definition
 Change in reporting procedure
 ………..
06/26/2021 Epedimiology course 396
 Step 3: Verifying the diagnosis

o The initial report may be spurious and arise from

misinterpretation of the clinical features
o Review clinical and laboratory findings to establish diagnosis
o Goals in verifying the diagnosis includes:
 To ensure that the problem has been properly diagnosed

 To rule out laboratory error as a basis for the increase in

diagnosed cases
 To ensure the diagnosed disease is possibly epidemic
06/26/2021 Epedimiology course 397
 Step 4: Case definition and case finding
Prepare “case definition” before starting identification of cases
It’s aim is to count all cases of the illness
It is clinical criteria restricted by time, place and person
Use sensitive or "loose case definition” early in the investigation
and use "tight or strict case definition” for testing hypothesis

-=== We can find additional cases in

- health facilities
- home visit in epidemic area( kebele or gote level )
=Information required include personal Identifier(name, tell, address),
demographic(age, sex, occupation), exposure history, clinical
information(date of onset, outcome, sign and symptom),who report?
Information
== we will do line listing by taking the above information
06/26/2021 Epedimiology course 398
06/26/2021 Epedimiology course 399
Step 5: Performing Descriptive Epidemiology

o Once data is collected, it should be analyzed by time, place and person

o The tools to be used when characterizing the epidemic are epidemic

curve, spot map and attack rate

o The characterization often provides clues about etiology, source and

modes of transmission that can be turned into testable epidemiologic
hypothesis

06/26/2021 Epedimiology course 400

 1. Analysis of epidemic by time

 We use epidemic curve to analyze by time taking

- The X- axis; indicating time of onset
-The y-axis; indicating the number of cases appearing
 Epidemic curve can tell as
- nature of epidemic
- hint to etiologies – etiologic agent
- hint about source of exposure

 There are three principal types of epidemic

1. Common source – based on source of exposure

2. Propagative - touches mode of transmission
3. Mixed epidemic – share characteristics of both type
06/26/2021 Epedimiology course 401
 1. Common source epidemic
 It occurs as a result of the exposure of a group of population
to a common source (etiological agent)

o It can result from a single source/ exposure of the population to

the agent
E.g: contaminated water supply, or food in a certain restaurant
 Three types

1. Point common source

2. Continuous common source
3. Intermittent common source
06/26/2021 Epedimiology course 402
 A) Point common source epidemic
o Single/ones/limited time exposure to the source
o All exposed hosts will develop disease within one incubation
period
o The epidemic usually decline after a few generations, either
because the number of susceptible hosts fall below some
critical level, or because intervention measures become
effective
o A rapid rise and gradual fall of an epidemic curve suggests a
point source epidemic
06/26/2021 Epedimiology course 403
 E.g. Food borne outbreak in a wedding feast

Typical Point source epidemics

Peak of
Outbreak

Minimum
incubation
period

A single sharp peak of sudden onset

404
 B) Continuous common source epidemic
 If exposure to a common source continues over time for days,
weeks
 The epidemic curve has a plateau (multimodal epi curve)/ long
peak
 Range of exposures and range of incubation periods is different

06/26/2021 Epedimiology course 405

 C) Intermittent common source epidemic
 Results in an irregular pattern of the epidemic curve that
reflects the intermittent nature of the exposure
E.g. waterborne outbreak
 Often the graph is atypical

Several sharp peaks

06/26/2021 Epedimiology course 406
 2. Propagative /progressive epidemic
o It occurs as a result of transmission of an infectious agent
from one person to another directly or indirectly
o There is a successive generations of cases

o The epidemic curve in a progressive epidemic is usually

presence of successive several peaks, a prolonged duration,
and usually a sharp fall
o Can show geographic spread of the case

Example; Malaria outbreak and different vector born

disease
06/26/2021 Epedimiology course 407
Typical Propagated Epidemic Curve

No sharp peak
408
 3. Mixed Epidemic
o It shows the features of both types of epidemics

o It begins with a common source of infectious agent with

subsequent propagated spread because of person – to-
person transmission of the etiologic agent

E.g. Majority of food borne outbreaks

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06/26/2021 Epedimiology course 410
 2. Analysis of epidemic by place

– A spot map is a simple and useful technique for

illustrating where cases live, work or may have been
exposed
– Area map if large area is affected
– It is important to indicate source of outbreak

06/26/2021 Epedimiology course 411

 3. Analysis of epidemic by person
o Characterizing an outbreak occurrence by person is how we
determine what populations are at risk for the disease
o Host characteristics: age, race, sex, or medical status and
exposures-occupation, leisure activities, use of medications,
tobacco and drug use etc…
o These influence susceptibility to disease and opportunities for
exposure to risk factors
o We use attack rates to identify high risk groups
06/26/2021 Epedimiology course 412
Step 6: Formulating hypothesis
 Depending on the outbreak, the hypothesis may address
o The exposures that caused the disease
o The mode of transmission
 Using :
1. Subject-matter knowledge
2. Descriptive epidemiology
3. Talking with patients
4. Talking with local officials
 The hypotheses should be testable

06/26/2021 Epedimiology course 413

 Step 7: Testing the hypothesis
 Here doing analytic studies may be useful.

 Association between the postulated exposure factor and the disease is

tested using analytic design

1. Case control 2. Retrospective Cohort

 Appropriate measure of association should be made
for case control, odds ratio

for cohort design, relative risk

 Significance of statistics should be done,

(Chi-square is the appropriate test, and P-value

is estimated at 5 %.)
06/26/2021 Epedimiology course 414
Step 8: Refining hypotheses and additional studies

o Search for additional cases: Locate unrecognised or unreported

cases

o Environmental studies are equally important in some settings

06/26/2021 Epedimiology course 415

Step 9: Implementing control and prevention
In outbreak investigation, the primary goal is to control and
prevent the outbreak.
Implementing control measure should be done as soon as possible

It should go in parallel to investigating the outbreak

Source/ Mode of Transmission

Causative
Agent

06/26/2021 Epedimiology course 416

 Control measures (do early)
1. Measures Directed Against the Reservoir:
– Reduce contact rate
– Reduce infectious sources- destruction of infected animal /isolation
– Reduce infectiousness- early treatment

2. Measures that interrupt the transmission of organisms

– Purification of water
– Pasteurization of milk
– Inspection procedures designed to ensure safe food supply.
– Improve housing conditions

3. Measures that reduce host susceptibility and Increase herd immunity

- Immunization

- Chemoprophylaxis - Use of antibiotics for known contacts of cases

417
Step 10: Communicating findings of investigation
 The final responsibility of the investigative team is to prepare a
written report to document the investigations, findings and the
recommendations
The written report should follow the scientific reporting format which
includes:
o introduction
o methods
o results
o discussion
o conclusion, and
o06/26/2021
Recommendations
Epedimiology course 418
Summary of the investigation and control of an epidemic considering
procedure

419
 Post-Epidemic Surveillance
o The efficacy of control measures should be assessed day

by day during the outbreak, a final assessment being

made after it has ended
o This will provide a logical basis for post-epidemic

surveillance, and preventive measures aimed at avoiding

similar outbreaks in the future
o Develop long term early warning system
o Monitor environmental risk factors
06/26/2021 Epedimiology course 420
Thank you
 Chapter-12

Screening & Diagnostic Tests

(Reading assignment)

06/26/2021 Epedimiology course 422

 Learning objectives
After the end of this session, students will be expected to:
– Define screening and diagnostic tests
– List different types of screening program
– List the criteria for establishing a screening program
– Discus measures of accuracy of screening tests
– Discuss ethical issues in screening tests
– Evaluate and minimize bias in screening tests

06/26/2021 Epedimiology course 423

 screening test
o Is “the search for unrecognized disease or defect
by means of rapidly applied tests, examinations or
other procedures in apparently healthy individuals”

o The aim is
- early detection and treatment
- To prevent transmission
- To prevent further disease and complexity
06/26/2021 Epedimiology course 424
 Screening and diagnostic tests
o Diagnostic test – performed in a person with specific sign and

symptom
o Screening Test – is performed in apparently healthy individual

For example,

- A blood sugar test in someone that is healthy would

be a screening test.

- The same test in someone with symptoms of diabetes

would be diagnostic test

06/26/2021 Epedimiology course 425
 Screening tests
oMay be based on:

Standardized interviews(standard questioners)

Example:
- Reporting Questionnaire for Children (RQC) – mental health
problem screening tool for children
- Michigan Alcohol Screening Test (MAST) - is a set of questions
that used to identify individuals at risk of alcoholism.

Physical examinations(checking blood pressure)

Laboratory tests – For malaria
More sophisticated measurements
 radiography
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Natural history of disease and time of screening

Usual Time Late diagnosis

of diagnosis

Exposure Pathologic Onset of

changes symptoms

Stage of Stage of Stage of Stage of recovery,

Susceptibility sub-clinical disease Clinical disease disability or death

Time of Screening
06/26/2021 Epedimiology course 427
 Screening procedures

06/26/2021 Epedimiology course 428

 Aim of screening program
To reduce morbidity and mortality through early detection
and treatment

To alter the natural course of disease for a better outcome

To reverse, halt, or slow the progression of a disease to its

severe form and to improve quality of life
o Research: study on natural history of disease
o Selection of healthy individuals usually for employment

E. g: Military and driving license …

o For fair allocation of resource
06/26/2021 Epedimiology course 429
 Types of screening program
1. Mass/population screening
– It is offered to all, irrespective of the particular risk factors
2. Multiple/multi-phase screening
– The purpose of two or more screening tests in combination to a
large number of people at one time
– Parallel and series test(VCT)
3. Case finding/opportunistic screening
– It is restricted to patients who consult a health professional for
some other purposes – ex STD screening in OPD
4. Targeted screening
– High risk or selective screening- nutritional screening for
children and pregnant mother
06/26/2021 Epedimiology course 430
Criteria for establishing screening program by
WHO
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 available and feasible.

4. There should be a recognizable latent or early "asymptomatic“

stage which is long
5. There should be a suitable test.

6. The test should be acceptable to the population to be tested.

06/26/2021 Epedimiology course 431

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.

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 Accuracy of screening test

o A test should be unbiased, precise, and be able to

determine the disease status of an individual without

error

o Accuracy is the ability of the test to correctly classify

individuals according to their disease status

06/26/2021 Epedimiology course 433
 Measures of accuracy of screening tests
==Validity:
o The application of a screening test is to identify correctly
individuals who do and do not have preclinical disease
o Those who have preclinical disease should test positive,
and those who do not have it should test negative
o It is expressed by its sensitivity and specificity

== Reliability
o Is the ability of a test to come up with similar values
upon repeated measurements in similar occasions

06/26/2021 Epedimiology course 434

 Reliability versus validity of a test

06/26/2021 Epedimiology course 435

 Two-by-two contingency table
Result from Gold standard
Screening Test Total
Diseased Non-diseased

True positive False positive

Positive a+b
(a) (b)

False negative True negative

Negative c+d
(c) (d)

Total a+c b+d n

06/26/2021 Epedimiology course 436
 Two-by-two contingency table…
True positive(TP)
o The number of individuals for whom the screening test is positive
and the individual actually has the disease
False positive(FP)
o The number for whom the screening test is positive but the
individual does not have the disease
True negative(TN)
o The number for whom the screening test is negative and the
individual does not have the disease
False negative(FN)
o The number for whom the screening test is negative but the
individual does have the disease
06/26/2021 Epedimiology course 437
 Measures of validity of a test
1. Sensitivity of test:
o The ability of the test to recognize people with disease
o It describes its ability to correctly identify people who
have the characteristic that is being measured

Sensitivity = TP x 100
TP + FN

06/26/2021 Epedimiology course 438

 Measures of validity of a test …
Specificity of test:
o The ability of the test to recognize people without disease

o The proportion of people who do not have the condition who

are correctly classified as non cases
Specificity = TN x 100
TN + FP

06/26/2021 Epedimiology course 439

 Positive predictive value
o The probability of a person having the preclinical disease
when the test is positive
o It is defined as the proportion of people with the condition
among all those who received a positive test result

Predictive value positive = TP x 100

TP + FP

06/26/2021 Epedimiology course 440

 Negative predictive value
o The probability of a person not having the preclinical
disease when the test is negative
o It is the proportion of people without the condition
among all those who received a negative test result

Predictive value Negative = TN x 100

TN + FN

06/26/2021 Epedimiology course 441

 Predictive values of screening test
• Depends on
– Sensitivity of the test
– Specificity of the test
– Prevalence of the disease in that community

o Positive predictive value is influenced by test

specificity and TRUE prevalence of the disease
o Negative predictive value is influenced by test
sensitivity and TRUE prevalence of the disease
06/26/2021 Epedimiology course 442
 Prevalence of disease versus predictive values

o Predictive value positive

is directly related to the PV (+)

prevalence of a disease in
a community
Prevalence

o Predictive value negative

is inversely related to the
prevalence of a disease in PV (-)

a community
Prevalence
NB: If sensitivity and specificity
06/26/2021 are constant
Epedimiology course 443
 Cost of a screening program

- What is the anticipated outcome in relation to resources

expended? i.e. how many people with the disease of interest
are detected by the program out of all screened?

- This measure of cost effectiveness of a screening program is

known as YIELD.

YEALD = TP X 100

TP + TN + FP + FN
06/26/2021 Epedimiology course 444
 Strategies to increase yield of a test

o Select disease with high prevalence of preclinical

stage

o Target high risk group for screening program

o Select a test with high validity

06/26/2021 Epedimiology course 445

Potential source of bias in screening program

o Self-selection (volunteer) bias

o Lead-time bias (early detection of disease)
o Length bias (chronicity and slow progression
nature of a disease)

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06/26/2021 Epedimiology course 447
 Length bias

Group A
- Includes sample of cases having long entire disease course
- Biological onset – at age 45
- Clinical onset – at age 65
- Death at age 80 years
Group B
• Includes sample of cases having short entire disease course
- Biological onset – at age 45
- Clinical onset – at age 50
- Death at age - at age 55
= Introduce Screening for both groups and report that screening test is
effective in improving survival of group A --- is length bias
== Because disease having long entire disease course will get high
benefit of screening when compared to those having short course
== So in order to avoid length bias in screening we have to take
comparable groups regardingEpedimiology
06/26/2021
to theircourse
time course 448
 Ethical issues in screening program
o Issues of informed consent in screening
o Screening test accuracy(validity + reliability) to
minimize false positive and false negative

Because

o A false positive test may cause unnecessary anxiety and

o A false negative test may result a potential loss of life

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06/26/2021 Epedimiology course 450
 Self Exercise

Screening test of cancer ,Comparison with the gold standard of

biopsy provided the following results

1. What is the prevalence of cancer in this example?

2. Calculate and interpret the specificity and sensitivity.
3. Calculate and comment on the positive and negative predictive
values
4. Calculate and comment on yield of the screening test
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 List of References
1)Principles of epidemiology, 2 nd and 3rd edition
2)Fletcher principles and practice of epidemiology
3)Kiflie et’al Epidemiology for health sciences students
4)Heineken's C. Epidemiology in medicine
5)Berhane Y., Principles of epidemiology lecture notes
6)Modern epidemiology, 2nd and 3rd edition
7)Fundamentals of epidemiology
8)Essentials of epidemiology
9)Beyond the basics epidemiology by Moyses S. et’tal
10)
WHO: Designing and Conducting Health Systems Research Projects-
Volume 1 and 2
11)
WHO: Health Research Methodology
12)
Quantitative Methods for Health Research by Nigel B. et’tal
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06/26/2021 Epedimiology course 453