Chapter three

Infectious Disease
Epidemiology

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

o List the major components of the infectious disease cycle

o Describe natural history and time course of an infectious
disease
o Identify factors that affect person-to-person infectious disease
transmission
o Describe the type of carriers and roles in the infectious disease
transmission

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What are infectious diseases?

 An infectious disease is def ined 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
di s ea s e wi l l depen ds o n i t s ba s i c
biological characteristics like
─I n fec ti v i ty
─Path ogen ec i ty
─I mmu n ogen i c i ty
─Vi ru l en 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%

o HIV and Rabies viruses are highly virulent with

a fatality rate of 100%

o Poliomyelitis are less virulent with fatality rate

2-10%
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 Immunogenicity
 The infection’s ability to produce specific immunity

 It is def ined 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

Exposur Disease
Infection Disease outcome
e
Infectiousness Pathogenecity Virulence
(Infection Rate) (clinical : subclinical) (CFR, HR)

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  Factors that inf lu ence 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 f irst
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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 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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I. Direct transmission

a) Transmission by direct contact
b) Transmission by direct projection
c) Trans-placental transmission
d) Blood transfusion
e) Organ transplantation

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a) Transmission by direct contact

Occurs through skin-to-skin contact, kissing, and sexual intercourse.

Direct contact also refers to contact with soil or vegetation
harboring infectious organisms:
 Touching:
o Trachoma (eye-hand-eye)
o Common cold (nose-hand-eye)
o Shigellosis (feces-hand-mouth)
o Viral hepatitis and HIV (through breaks in skin)
 Sexual intercourse: HIV/AIDS
 kissing : mononucleosis
 Passing through birth canal: Gonorrhea

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b) Transmission by direct projection

 Transmission by direct projection of saliva droplets created by

breathing, coughing, sneezing, spitting, talking, singing etc…

Example: common cold

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c) Trans-placental transmission

 Tra ns- p l a c e nt a l t ra nsm i ssi o n o f i nf e c t i o us a g e nt i s

transmission from mother to fetus via the placental membrane
Examples:
o HIV/AIDS
o Syphilis
o Toxoplasmosis
o Malaria etc...

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II. Indirect transmission

Refers to the transfer of an infectious agent from a
reservoir to a host by suspended air particles,
inanimate objects (vehicles), or animate
intermediaries (vectors)

Reservoir ----------------------------------susceptible host

a) Airborne transmission
b) Vehicle borne transmission
c) Vector borne transmission
d) Non vector intermediate host

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a) Airborne transmission
— I t is the transm ission of infec tious agents by either
suspended dust or droplet nuclei suspended in air for
relatively long period of time

Examples:
 Measles, for example, has occurred in children who came into
a physician’s office after a child with measles had left,
because the measles virus remained suspended in the air

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 b) Vehicle borne transmission
 It is the transmission of infectious agents by a vehicle
 A vehicle may passively carry a pathogen — as food or water
may carry hepatitis A virus.
 Alternatively, the vehicle may provide an environment in which
the agent grows, multiplies, or produces toxin — as improperly
canned foods provide an environment that supports production
of botulinum toxin by Clostridium botulinum.

Examples: Food, milk, water, soil, biological products, fomites

(cooking utensils, towels, bed sheets, clothing, syringe, beddings,
etc…)

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 c) Vector borne transmission
 It is the transmission of infectious agents by a vector
Vector: is an organism usually an arthropod, such as insect, tick, mite,
which transports an infectious agent to a susceptible human host or
to a suitable vehicle
A vector can be
— Biological vector: When the agent multiplies in the vector
before transmission
— salivarian transmission (malaria by mosquito)
— guinea worm

— Mechanical vector: the agent is carried by the leg or proboscis

— trachoma by common fly
— plague by fleas carrying yersina pestis in their gut

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 d) A non-vector intermediate host

— These are hosts which are important for development of the

infectious agent but don’t play an active role in transporting
the agent to the susceptible human host

Example: Aquatic snail for schistosomiasis

Note
- A disease may often have several modes of transmissions

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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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Portal of entry includes:

─ Conjunctiva (trachoma, common cold)

─ Nasal or upper respiratory tract (common cold, diphtheria)
─ Lower respiratory tract (TB)
─ Percutaneous (tetanus, hookworm)
─ GIT (typhoid fever)
─ Viganal (STDs/HIV/AIDS)
─ Anal (STDs/HIV/AIDS) etc…

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 6. Susceptible Human Host
 The susceptible human host is the f inal link in the infectious
disease transmission process
 Host factors inf luence 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 ef fic ient 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 f irst
shedding of the agent by the human host

 For some diseases the time when the agent can f ir st be

detected and the time of the f irst 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 f irst 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 f irst 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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 Chapter-4

Measures of Morbidity and Mortality

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 Measures of Morbidity

Lea r ning 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
The numerators and denominators of a ratio can be related
or unrelated
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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Propor tion


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 male in this class

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 ra 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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 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. Incidence


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 Thus, if we are calculating

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52
 • 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 propor tion/cumulative

2. Incidence rate/incidence density

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 1.I nc id e nc e pro po r tio n/c umulative inc id e nc e

 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 specif ie d 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 attendees of a corporate

picnic, 99 persons ate potato salad,30 of whom developed gastroenteritis.
 Calculate the risk of illness among persons who ate potato salad.
Numerator = 30 persons who ate potato salad and developed
gastroenteritis
Denominator = 99 persons who ate potato salad

• Risk = “Food-specific attack rate” = (30 / 99) x 100 = 0.303 x 100 =

= 30.3%
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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

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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 ref le ct 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…
 Definition of incidence rate contains
three components:

o New cases
o Period of time – time under follow up
o Population at risk

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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

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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 9 Person-Years (PY)
------------------x
Subject 2 10 PY
------------------x 20 PY
Subject 3
39 PY
------------------------------------

X = outcome of interest, thus the incident rate is 2/39 PY

Ex 3. Cohort study of the risk of breast cancer
among women with hyperthyroidism

 Followed 1,762 women ---> 30,324 py

 Average of 17 years of follow-up per woman

 Ascertained 61 cases of breast cancer

 Incidence rate = 61/30,324 py = .00201/py

= 201/100,000 person-years or
persons/y ear


II. Prevalence

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. P o i n t p r e v a l e n c e : number of cases that exist in a
population at a given point in time

2 . P e r i o d p r e v a l e n c e : number of cases that exist in a

population at given period of time

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6/22/2024 Epedimiology course 72
 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 2000, 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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 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..

De c re ase d b y:
I nc re ase d b y:
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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 Measures of Mor tality

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 Mor tality rates

o A m o r tal i ty rate i s a m e asure o f the f re q ue nc y o f

occurrence of death in a def in ed 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 = X10n
size of the population among the death occurred

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

- Control for homogeneous sub

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

Adjusted/ - Provide summary figure - Fictional rates

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

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Measures of mortality
1. Specific mortality rate
2. Age specific mortality rate
3. Sex specific mortality rate
4. Perinatal mortality rate
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…

1. Neonatal mortality rate

2. Post neonatal mortality rate
3. Infant mortality rate
4. Child mortality rate
5. Under five mortality rate
6. Maternal mortality ratio/rate
7. Cause specific mortality rate

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Sources of epidemiological data

1. Introduction
2. Vital statistics registration
3. Census
4. Health service records
5. Health service indicators
6. Mortality and morbidity survey
7. Reportable infectious diseases

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Principles of controlling infectious
diseases:

o d i se ase p re v e nt i o n
o d i se ase c o nt ro l
o d i se ase e l i m i nat i o n
o Di se ase e rad i c at i o n
o Di se ase e x t i nc t i o n

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 Chapter-5

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 c al d e si g n st rat e g i e s

o E p i d e m i o l o g y i s p ri m ari l y c o nc e rne d wi th 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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6/22/2024 Epedimiology course 90
 Epidemiologic approaches
1. DESCRIPTIVE
Used to describe health and disease in the community
by….What? Who? When? Where?
What are the How many Over what Where do the
health problems people period of time? affected people
of the community? are affected? 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
What factors affect outcome mechanism
?
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Descriptive studies


o Descriptive study is one of the basic types of
e p i d e m i o l o g y d e sc ri b i ng t he f re q ue nc y a nd
distribution of diseases by time, place and person

o Analytic studies focus in elucidating the determinants

of disease

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 Wh at?

Cases
Person Time
25

Place 20

15

10

1 2 3 4 5 6 7 8 9 10

Who? Where?
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When? Epedimiology course 93
 Appl i c ati on of des c ri pti v e s tu di es

o Useful for health managers to allocate resource and to plan

effective prevention programs

o To generate hypothesis, an important f irst 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 descriptive 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 prof il e 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 f irst clue for identif ication 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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 Application of case repor t /
series

Useful for the recognition of new disease

Useful for constructing of the natural history of a

disease

Use to f orm ulate hyp othesis and to detec t an

epidemic occurrence of a disease

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 Exerc i s e 1: i s i t c as e repor t or s eri es

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 T hi s unusual c i rc um stanc e sug g e ste d that the se

individuals were actually suffering with a previously
unknown disease, subsequently it was called AIDS
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 Exerc i s e 2: i s i t c as e repor t or
s eri es
A 4 0 - ye ar ol d p re - m e nop ausal wom an d ev e l op e d
pulmonary embolism 5 weeks after beginning to use an
oral contraceptive preparation to treat endometriosis.

What is unusual in this report? Pulmonary embolism is

c o m m o n i n o l d e r, p o s t m e n o p a u s a l w o m e n . T h e
investigator postulated that the drug may have been
responsible for this rare occurrence

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 A d v an t ag e s of c ase re p or t s an d se rie s

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 isad v an t ag e s of c ase re p or t s an d se rie 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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 Ecologica l s tudies

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 TRANDE)

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 ?

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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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 Charac t e ri st i c o f e c o l o g i c al st ud y
o Measures of association in ecological study is correlation coefficient (r)

o Correlation coef fic ient quantif ie s 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 It mostly uses secondary data or report from survey data

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 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?

Suc h quest ions only sensib ly ad d ressed at p op ulat ion (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 (this
is referred as 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 f ind 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
c ollec tion proc ess c an take d ays, weeks, months, years but the
measurement is takes place only once
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 C ross-se c t ion al st u d ie 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 polio induced disability in kebele 8 of Gondar town is 2.3%
- 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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 Cro ss- se c t i o nal st ud 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
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OR = ad/bc
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 Cros s -s ectiona l s tudies ...
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
example- lung cancer Vs cigarette smoking = which comes first
Miss diseases still in latent period -
Recall of previous exposure may be difficult -

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 Chapter-6

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

 I t i s t he use o f c o m pa r i so n gro up t ha t a l l o w s t e st i ng o f
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
identif ied, 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 specif ic
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
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o In cooperative 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
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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

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o Re-call bias increasesEpedimiology
(because course
they are healthy) 138
 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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 Sampl 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.
Odds is defined as the probability that an event will occur divided by
the probability that it will not occur.
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
Ca se s Co n t r o l s To t a l
Ex p o se d a b a +b
U n e x p o se d c d c+d
To t a l a +c b +d a +b +c+d

O d d s o f e xp o su r e in ca se s = a /c
O d d s o f e xp o su r e in co n t r o ls = b /d

O d d s R at io = a/ c = ad
b/d bc
Epedimiology course 143
 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

Ca se s Co n t r o l s To t a l
E v e r sm o k e d 120 100 220
N e v e r sm o k e d 80 300 380
To t a l 200 400 600

O d d s R at io = (1 2 0 x 3 0 0 )/ (8 0 x 1 0 0 )=4 .5

• Odds ratio of 4.5 means that smokers were 4.5 times more likely to
develop stroke compared to non smokers
Epedimiology course 144
 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
s ame in cas es and controls – No as s ociation
between exposure and outcome
Epedimiology course 145
 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
- the probability of selecting a real case and control

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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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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
classif ied 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 resulted in
fetal abnormality/outcome
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 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 features 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 classif ie d 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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6/22/2024 Epedimiology course 154
 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

oBoth exposure and outcome status have occurred at the

beginning of the study

oStudies only prior outcomes and not future ones

oA historical cohort study depends upon the availability of

data or records th at allow recon stru ction of th e
exposure of cohorts to a suspected risk factor and

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follow-up of their mortality or morbidity over time
Epedimiology course 156
 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 f ir st identif ie d, s/he reconstructs exposed and non-
exposed populations from records, and then proceeds as though s/he
had been present throughout the study

o What is the difference b/n case control and retrospective cohort

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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

oThe follow-up is the most critical and demanding part

of a cohort study

oLost to follow-up should be kept to an absolute

minimum (< 10-15%)

oChanges 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 f inding cases, whether deaths, illness episodes, or
people with a characteristic, is as complete as possible
• Must have a f irm 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 (-)

b a +
. .

Yes (+) a
RR = a+b
b
c d
..

.. c .. No (-)
c +d 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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 Interventional studies
• Experimental
• Quasi-experimental

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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 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. M a i n t e n a n c e a n d a s s e s s m e n t o f
compliance

4. Ascertainment of outcomes
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5. Analysis & conclusion of experimental
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 1. Selection of study population
Re fe re nc e p o p ul ati o n: T he g e ne ral g ro up to who m
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 ref lect 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 specif ic diseases are enrolled in
therapeutic trials.
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Additional inclusion and exclusion criteria are used to 175
Epedimiology course
 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 suf fic ient 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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 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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 Consent Process
o All eligible and willing individuals must give consent to participate in an
experimental study

o The process of gaining their agreement is known as informed consent

o During the process, an investigator describes the nature and objectives

of the study, the tasks required of the participants, and the benef its and
risks etc…

o The process also includes obtaining the participant’s oral or written

consent

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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. Lev el s of bl i n di n g
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?
o Only 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

o Follow-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)

o If 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 benef it 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. Ef ficacy analysis – the analysis base only on participant take the whole
treatment coarse or comply
- It answers the question of treatment ef fic acy – 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 benef its 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 T he researc h questi ons c annot b e 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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 Chapter-7

Causation

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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 suf fic ient

condition for causation

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 Accuracy
=
Validity + precision

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 Validity of epidemiological studies

oValidity is the extent to which a measured value actually

reflects truth

oNext step of evaluation of study results is validation of

the findings

oAn 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
oC a u s e o f a d i s e a s e i s a n e v e n t , a c o n d i t i o n ,
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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 A l t e r n a t i v e e x p l a n a t i o n s f o r t h e o b s e r v e d

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” def iciency 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
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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

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1. Test of statistical significance

 P-value quantif ies 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 signif ic ance for medical

researcሀ

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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

 Conf idence 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 ref lects 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 Could it be due
association to Bias?
RR- No
OR- Could it be due to
Confounding?
No
Could it be
Cause?

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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
6/22/2024 4. Loss to follow-up bias
[email protected] 213
Information/observation/bias
 Any syste m ati c e rror i n the m e asure m e nt 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 of placebo in experimental study
5. Use close ended questions whenever possible
6. Train data collectors
7. Pre test, pilot the consistency, completeness and clarity of
your data collection tools
6/22/2024 8. Care full entry, compilation and analysis of your data
[email protected] 215
 Establishing a Causal Association…
Could it be due to
Chance?

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

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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 C an overestimate the true assoc iation (PO STI VE

confounding)

o C an und erestimate the true asso c iatio n (NE GATI VE

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
Epedimiology course 221
 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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 Chapter-8

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

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Purpose of surveillance
i) To be able 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 scientif ic baseline data and information for priority setting,
planning, implementing and evaluating disease control program for
both communicable and non-communicable health problems.

iii) To def ine 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 of ficials def ine homogenous population and
regions to be sampled
o The advantages of sentinel surveillance data are that they can be less
expensive to obtain than those gained through active surveillance of the
total population, and the data can be of higher quality than those
collected through passive systems.

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

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 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
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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

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 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

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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

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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 N e w l a bo ra t o r y t e st o r i m pro v e m e nt i n d i a gno st i c
procedures

o Sudden changes in population size

o Increased health-seeking behavior of the community

o Laboratory error
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 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
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 Dissemination…
Message

Audience

Channel
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 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

6/22/2024 o Cost effectiveness Epedimiology course 247

  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

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Case definition

 Case definition is a set of criteria for deciding whether an

individual should be classif ie d 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

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 Standard case definition

 If th e u se of case def in ition is agreed by

everyone in the country or across boundaries or
continents it is standard case definition

oSu rveillance u sing less specif ic criteria is

sometimes referred as syndromic surveillance

E.g: Polio (AFP)

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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

6/22/2024 disease without laboratory confirmation
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 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

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 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, f loods, 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

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Emergency management phases

Recovery Mitigation

Response Preparedness
Mitigation
 Pre-event planning and actions which are intended to
lessen the impact of a potential disaster

E.g: Risk identification / assessment and reduction

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 Preparedness

 Actions taken before an emergency to prepare for

response
o Develop emergency management plan

o Develop communication plan

 The identif ication of a public health threat by closely and

frequently identif ied monitoring indicators and predicting
the risk it poses on the health of the public and the health
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system (early warning phase)
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 Response

 Activities to address immediate and short-term

effects of a disaster

• Implement emergency management plan

o Save lives

o Meet basic human needs

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 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

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 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

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

Outbreak Investigation & Control

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 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

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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.

• H y per en demic: Persisten tly h igh level of disea se

occurrence.

• Sporadic: Occasional or irregular occurrence of a disease

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 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 without regard to whether the number of cases is more than

expected.

• Pandemic: An epidemic involving several countries or continents

affecting a large number of people.

6/22/2024 example : HIV/AIDS is a pandemic.

Epedimiology course 265
 What is outbreak occurrence?

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 What does outbreak investigation & control?

 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

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 Source of an outbreak information

 Routine surveillance

 Health professionals

 Affected community members

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 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

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 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

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 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 scientif ic
concerns
o The public are more concerned in cluster of disease and
potentials of getting medication
o It is write 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 notif ie s 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

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 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
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 Step 1: Prepare for field work
 Before leaving for the f ield, 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)

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 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

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 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
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 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
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== we will do line listingEpedimiology
by taking the above information
course 277


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

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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

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 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
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 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

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E.g. Food borne outbreak in a wedding feast

Typical Point source epidemics

Peak of
Outbreak

Minimum
incubatio
n period

A single sharp peak of sudden onset

282
 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

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 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

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 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
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Typical Propagated Epidemic
Curve

No sharp peak
286


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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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

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 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 inf luence susceptibility to disease and opportunities for

exposure to risk factors

o We use attack rates to identify high risk groups

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 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

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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 %.)
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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

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 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

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 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 295

 Step 10: Communicating findings of
investigation


 The f in al 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 scientif ic reporting format which
includes:
o introduction
o methods
o results
o discussion
o conclusion, and
6/22/2024 o Recommendations Epedimiology course 296
Summary of the investigation and control of an epidemic
considering procedure

297
 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
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 Chapter-10

Screening & Diagnostic Test s

6/22/2024 Epedimiology course 299

 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

6/22/2024 Epedimiology course 300

 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

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 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
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 Screening tests
o May 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
electro-cardiograph etc…
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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 Clinical disease disability or death
disease
Time of
Screening
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 Screening procedures

6/22/2024 Epedimiology course 305

 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

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 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

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 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.

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 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

oA test should be unbiased, precise, and be able to

determine the disease status of an individual without

error

oAccuracy is the ability of the test to correctly classify

individuals according to their disease status

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 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

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 Reliability versus validity of a test

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 Two-by-two contingency table
Result from Gold standard
Screening Diseased Non-diseased Total
Test
True positive False positive
Positive (a) (b) a+b

False True negative

Negative negative (d) c+d
(c)
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 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

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 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

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 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

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 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

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 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

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 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 inf luenced by test specif icity

and TRUE prevalence of the disease

o Negative predictive value is inf luenced by test sensitivity

and TRUE prevalence of the disease
6/22/2024 Epedimiology course 319
 Prevalence of disease versus predictive
values
oP r e d i c t i v e v a l u e
p o s i t i v e i s d i re c t l y PV (+)
related to the
prevalence of a disease
in a community Prevalenc
e

oP r e d i c t i v e v a l u e
negative is inversely
PV (-)
related to the
prevalence of a disease
in a community Prevalenc
6/22/2024 NB: If sensitivity and specificity
e
Epedimiology course are constant 320
 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

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 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

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 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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6/22/2024 Epedimiology course 324
 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
6/22/2024
comparable groups regarding to their time course
Epedimiology course 325
 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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6/22/2024 Epedimiology course 327
 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
6/22/2024 Epedimiology course 328
 List of References
1) Principles of epidemiology, 2nd
and 3rdedition
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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Thank you!!!