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Epidemiologic Study Deigns

Study Design
A study design is a specific plan or protocol for
conducting the study, which allows the investigator
to translate the conceptual hypothesis into an
operational one.

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Epidemiologic study designs
Epidemiological Study designs can be classified in
two ways:
1. According to the power of the investigator to control the
factors to be assigned to the study groups
1. Experimental studies
2. Observational studies
2. According to the intention in carrying out the
epidemiological investigation:
1. Descriptive Studied
2. Analytic Studies

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3
Study Designs

Analytical

Descriptive
Experimental Observational

- Case Report
Clinical Trials - Cohort Study

- Case Series Community - Case-Control


Trials Study

- Cross-Sectional
Cross-Sectional

- Ecological
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Design Selection depends on
Scientific Knowledge
New
Adding
Redoing / Confirming

Hypothesis
Generating
Testing

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Design Selection depends on
Epidemiologic / Statistical
Disease (rare vs rampant)
Exposure
Sample Size

Resources (Usually limiting factor)


Cost
Time

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Types of epidemiologic study
designs
Descriptive (person, place, and time)
Purpose is = Hypothesis generating

Analytic (causal)
Purpose = Hypothesis testing

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Descriptive Study Designs
Purpose and characteristics
mainly concerned with distribution of diseases
useful for managers to allocate resources.
used for hypothesis generation.
less time consuming and less expensive (use routinely
collected information).

Most common study designs used by epidemiologists.

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Descriptive Study Designs
Used to describe disease patterns and generate hypotheses

No attempt to test causal hypotheses

Often the first step in learning about disease etiology, patient


outcomes

Relatively easy, rapid, and inexpensive

Use diverse, often existing, sources of data

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Types of Descriptive study designs
1. Correlational (ecological) studies
Use data from entire population to compare disease
frequencies b/n /or d/t groups during the same period of time,
or in the same population at d/t points in time. (unit of
analysis is population)
Example:
Examination of state data on tobacco sales and mortality from
CHD.
First step in examination of a disease exposure relationship.

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Correlation studies
Strength
Quick and inexpensive, can be used as first step.
It is useful in giving a fruitful start for more detailed
epidemiological studies.

Limitation
Doesnt link specific persons exposure with specific
outcome
Risk of ecological fallacy
Cant control for potential confounding factors

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Descriptive study Designs
Case Reports and Case Series
Describes single patient or group of patients experience
Most common form of study published in medical journals.
Presents an unusual disease or unusual presentation of a
disease.

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Case Report/Series studies
Strengths
May lead to formulation of new hypotheses
Important link between clinical medicine and
epidemiology

Limitation
Cannot be used to test hypotheses

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Case report/series studies:
Examples
E.g. Case report: A 40-year old pre-menopausal woman
developed pulmonary embolism 5 weeks after beginning to
use an oral contraceptive preparation to treat endometriosis.

E.g. Case series: Five young, previously healthy homosexual


men were diagnosed as having pneumocystis carinii
pneumonia at 3 Los Angeles hospitals during a 6 month period
in 1980 to 1981.

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Descriptive studies
Cross-Sectional (or prevalence) Studies (Survey)
Both Exposure and disease status are simultaneously
assessed in a population at a point in time.

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Cross-sectional studies
Strengths
Provides information about the frequency and
characteristics of a disease.
Decision making and priority setting
prevalence of disease or other health outcome in special
groups (e.g. occupations)
investigates exposures that are fixed characteristics of
individuals, ( ethnicity, socio-economic status and blood
groups).

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Cross-sectional studies
Limitation
Cant determine whether exposure preceded or occurred
as a result of the disease (Chicken and egg dilemma!!)

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Analytic studies: Purpose and
Characteristics
focus on the determinants (causes) of diseases.

used to test hypothesis.

use control groups.

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Types of Analytic studies
Observational - Natural course of events assessed.
Case-control,

Cohort and

Cross-sectional

Intervention - investigator allocates exposure and follows


subjects

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Observational studies
Case-Control
Cases: persons with disease
Controls (Comparison group): persons without the disease

Cohort
Subjects classified on basis of exposure of a factor
Follow-up to determine presence of disease
Prospective vs. retrospective

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Intervention studies
Experimental Studies - Clinical Trials
Provides most reliable evidence
Gold standard study design
Randomization
Controls for known risk factors
Controls for unknown risk factors
Useful for studying small to moderate effects
Ethical considerations are main constraints.
Human rights review
Data monitoring

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Case-Control Studies
Properties
the most frequently undertaken analytical studies
the only practical approach for identifying risk factors for
rare diseases
best suited to the study of diseases for which medical
care is sought, such as cancers or hip fracture

Design
At baseline:
Selection of cases and controls based on disease status
Exposure status is unknown
Retrospective design lacks temporality!

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Case control design
Direction of inquiry
Exposed Start with:
Cases (people with disease)

Not exposed

Not exposed
Controls (people with out
disease)
Exposed

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Steps in conducting case-control
studies
1. Define cases
- is establishment of strict diagnostic criteria and definition of
the disease or outcome of interest.

Step 2. Select cases


The investigator should select cases on which he/she can get
complete and reliable information.

- ensures that cases selected for a study represent a


homogenous entity.
- individuals with this condition can be selected from a number
of sources.
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Steps
Places where we can get cases:

1. Hospitals (health institutions)


easy & inexpensive
selection bias is one of the major problems

2. Population (community)
expensive
avoids selection bias

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Steps
3. Select controls
consider comparability, practicability and economic impact.

controls should be similar with the cases except the disease or


other outcome of interest.

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Steps
Sources of controls

1. Hospital controls
Advantages:
easily identified & readily available in sufficient number
less costly
more likely than healthy individuals to be aware of antecedent
exposures or events.
this decreases recall bias
they are more likely to be cooperative

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Hospital controls
Disadvantages:
They are different from healthy individuals in many ways

Patients with diseases known to be associated with the


exposure of interest (either positively or negatively), will pose
danger of altering the direction of association / masking a true
association between the exposure and outcome.
(patients with diseases known to be associated with the
exposure of interest should be excluded from the control
group).

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Sources of controls
2. General population controls
If cases are selected from the population, it is good to select
controls from the population too.

Advantages:
Generalization is possible

Disadvantages:
Costly & time consuming
recall bias (may not be concerned about past exposure since
they are healthy)
people might be less motivated to participate

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Steps
4. Check the exposure status
Information regarding the exposure status can be obtained by
interview or from different records.

5. Analysis
Prepare 2X2 table
calculate Odds Ratio (OR)
Perform statistical tests to check whether there is significant
association.

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Case-Control Analysis
D+ D- Total
Exposed a b a+b
Non-Exposed c d c+d
Total a+c b+d

Odds Ratio (OR) = The ratio of two odds


ad
OR
bc
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Example: this table shows data from case control study of oral
contraceptive (OC) use & myocardial infarction in pre
menopausal female nurses .
Current OC use

Yes No Total

Yes 23 304 327

No 133 2816 2949

Total 156 3120 3276


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Calculate and interpret the OR from the above table

OR = ad/bc= 23*28163
133*304
= 1.6

Interpretation:
Women who were current OC users had 1.6 times higher risk
of developing myocardial infarction when compared to non-
users of OC

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Case- Control studies
Advantages
Uniquely suited to diseases with long incubation periods
More efficient in terms of time and money
Good for study of rare disease
Can look at multiple exposures for a single disease
Disadvantages
Inefficient for evaluation of rare exposures
Cannot directly compute incidence rates of disease
Temporal relationship between E and D may be hard to
establish
Particularly prone to bias (selection and recall in particular)

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Cohort studies
Are those designs in which we start with exposure and look for
the outcome to develop.

The challenge is the loss to follow up in cohort studies

Two terms are used to describe the timing of events:


- prospective,
- retrospective
-

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What to look for in cohort studies?
Who is at risk?

All participants (both exposed and unexposed) in a cohort


study must be at risk of developing the outcome

Who is exposed?

Cohort studies need a clear, unambiguous definition of the


exposure at the outset.

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Types of cohort studies
Classification is based on the temporal relationship between
the initiation of the study and the occurrence of the disease.

1. Prospective cohort study


the outcome has not yet occurred at the beginning.

is the commonest type.


- unless specified cohort study refers to the prospective type of
cohort

more reliable than the retrospective cohort

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Cohort studies -Prospective

Direction of inquiry

Start with: Disease

Exposed
No disease

Disease

Non-Exposed
No disease

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Types of cohort studies
2. Retrospective cohort
Both the exposures and outcomes have already occurred when
the study begins

Studies prior outcomes and not future ones

Less costly and less time consuming

Often uses data collected for other purposes, hence


information obtained might be incomplete and non-
comparable for all subjects
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Cohort design - Retrospective
Direction of inquiry
Disease Start with:
Exposed

Not Disease

Not Disease
Not Exposed

Disease

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Steps in conducting cohort study
Step 1: Define exposure

Step 2: Select exposed groups


During selection consider:
the frequency of the exposure in the population

the need to obtain accurate information (exposure/outcome)

the ease to obtain relevant information and to follow up

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Steps
Step 3: Select controls (non-exposed)
control groups should be comparable to the exposed group

Step 4: Identify sources of data for exposure and outcome


Possible sources of exposure data:
pre-existing records
conducting interview
Possible sources of outcome data:
routine surveillance
death certificate
periodic health examination
hospital records etc.
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Steps
Step 5: Collect data

Step 6: Analyze data


prepare 2X2 table
calculate Relative Risk (RR)
perform statistical tests to check whether there is statistically
significant association

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Relative Risk (RR)
Relative Risk (RR) or Risk Ratio shows the magnitude of
association between exposure & disease.

Indicates the likelihood of developing the disease in exposed


relative to those who are not exposed

RR can also be used to compare risks of death, injury, and


other possible outcomes of the exposure

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Relative Risk (RR) . . .
Incidence among exposed (Ie)
RR = ____________________________
Incidence among non-exposed (Io)
a
= (a + b)
c
(c+d)
= risk of disease among exposed
________________________
risk of disease among exposed

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Example
This table shows data from a cohort study of oral contraceptive
(OC) use and bacteruria among women aged 16-49 years
Bacteruria

OP Use Yes No Total

57 455 512
Yes
No 77 1831 1908
Total 134 2286 2420

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Example . . .
RR = Ie = 57/512
Io 77/1908
= 2.8
Interpretation: women who used oral contraceptive had 2.8
times higher risk of developing bacteruria when compared to
non-users.

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Example . . .
In general the strength of association can be considered:
High - if the RR is 3.0 or more
Moderate if the RR is from 1.5 to 2.9
Weak if the RR is from 1.2 to 1.4

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Cohort Study
Advantages
Can measure incidence and thus risk
No recall bias
Exposure precedes disease
Can study several diseases
Can be very efficient for rare exposures

(can sample on exposure status)

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Cohort Studies
Disadvantages
Large number of subjects/participants
Inefficient for rare diseases
Long follow-up period
Subjects may change health behaviors during course of
study
Possible changes over time in ascertainment of disease
Very costly

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Advantages and limitations of cohort and case control study
Case Control Cohort
Advantages: valuable when exposure is rare
optimal for evaluation of rare disease can examine multiple effects
can examine multiple factors of a single exposure
for a single disease temporal relationship is known
Quick & inexpensive allows direct measurement of risk
relatively simple to carry out minimize bias in ascertainment of
guarantee the number of exposure
persons with a disease

Limitations: inefficient in evaluation of


inefficient in evaluation of rare rare diseases
exposure expensive
can not directly compute risk time consuming
difficult to establish temporal loss to follow up create problem
relationship
determining exposure will
often rely on memory
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Interventional studies
The investigator deliberately gives the drugs/vaccines

There is randomization, control groups, placebo and blinding


in the ideal experiment

Randomization = random allocation of subjects to either


group
Placebo - an inert agent indistinguishable from the active
treatment.
Control groups are those who do not take the treatment.

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Blinding

Single blind: the patients do not know which treatment they


receive

Double blind: The patient and the observer do not know

Triple blind: the patient, the observer and the analyst do not
know

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Experimental design . . .
Experiment design flow sheet

Disease

Healthy Received
Intervention No diseased
Individuals

Diseased

Not Received
Intervention No diseased

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Experimental design . . .
Produces high quality data if done properly.

It has essentially the same design as prospective cohort study


with one very key difference, i.e.
- exposure status of the study population deliberately changed
by the investigator to observe how this alters the incidence of
disease or other features of the natural history

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Experimental design . . .
Intervention studies can generally be considered either
therapeutic or preventive.

Therapeutic (or secondary prevention) trials are conducted


among patients with a particular disease to determine the
ability of an agent or procedure to diminish symptoms, prevent
recurrence, or decrease risk of death from that disease.

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Experimental design . . .
A preventive (or primary prevention) trial involves the
evaluation of whether an agent or procedure reduces the risk of
developing disease among those free from that condition at
enrollment.

While therapeutic trials are conducted among individuals,


primary prevention measures can be studied among either
individuals (e.g. vaccine trial), or entire population
(Community trial).

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Experimental design . . .
A. Uncontrolled trial - no control group. control will be past
experience (history).

B. Non-randomized controlled- there is control group but


allocation into either group is not randomized.

C. Randomized controlled - there is control group and


allocation into either group is randomized.

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Steps in conducting experimental
studies
Step 1. Identify new drug/intervention/prevention

Step 2. Identify comparison - e.g. standard treatment or placebo

Step 3. Define eligible population/ exclusions

Step 4. Define the outcomes and how to assess them

Step 5. Write the protocol

Step 6. Obtain research ethics committee approval


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Steps in experimental studies
Step 7. Recruit and consent required sample of patients/subjects

Step 8. Allocate individuals into:

A. Experimental (study) group


group that will receive a drug, vaccine or other procedure

B. Control group
group that will receive no treatment, a placebo, or standard
form of therapy

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Steps in experimental studies
Step 9. Collect data
Collect all relevant information including the outcome

Step 10. Analyze the results


Analysis is similar to cohort study

Step 11. Publish/ disseminate findings

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Experimental design . . .
Advantages of randomization:
It eliminates selection bias
On average the study groups will be comparable (confounders
will be equally distributed controls confounding effect )

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Problems Related to Intervention
Studies
1. Ethical considerations prevent evaluation of many
treatments or procedures using an intervention design
strategy.

2. Cost

3. Feasibility / practical issues


subject recruitment, getting adequate individuals to enroll
into the study is not easy; difficult to achieve satisfactory
compliance

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Experimental design . . .
Ideally
All subjects adhere to treatment regimens;
do not seek additional treatment;
do not drop out, die, move or have to be withdrawn from
study;
attend follow-up sessions and provide outcome data

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Experimental design . . .
The quality of "gold standard" in experimental studies can
be achieved through :
Randomization

Use of placebo

Double Blinding

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Measures of Association
Exposure Outcome

Is there a relationship between the exposure and outcome


of interest?

Requires comparing two groups:


Exposed Vs Unexposed
With outcome Vs Without Outcome

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Measures of Association . . .
Statistical tests like Chi-square show mainly the presence or
absence of association.

The strength of association is assessed by calculating Relative


Risk (RR), Odds Ratio (OR) or other measures of association.

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Two-by-Two (Contingency) Table

Yes No Total

Yes a b a +b

No c d c+d

Total a+c b+d a +b +c + d


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2x2 table is used for calculating
Risk in Exposed,
Risk in Unexposed,
Odds of exposure,
Odds of outcome
RR,
OR,
AR,
PAR
PAR%

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How strong is the association?
Relative Risk (RR) - indicates the likelihood of developing
the disease in the exposed group relative to those who are not
exposed.

Odds Ratio (OR) - indicates the likelihood of having been


exposed among cases relative to controls

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Example: this table shows data from case control study of oral
contraceptive (OC) use & myocardial infarction in pre
menopausal female nurses .
Current OC use

Yes No Total

Yes 23 304 327

No 133 2816 2949

Total 156 3120 3276


71
Calculate and interpret the OR from the above table

OR = ad/bc= 23*2816
133*304
= 1.6
Interpretation:
Women who were current OC users had 1.6 times higher risk
of developing myocardial infarction when compared to non-
users of OC

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Attributable Risk (AR) / Risk
Difference(RD)
AR is a measure of association that provides information
about the absolute effect of the exposure or the excess risk of
disease in those exposed compared with those who are not
exposed.

AR= Risk in exposed - Risk in unexposed


= Ie -Io

Measures public health impact

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AR . . .
Quantify the excess risk in the exposed that can be attributable
to the exposure by removing the risk of disease that could have
occurred anyway due to other causes.

Indicates the number of cases of the disease among the


exposed that can be attributed to the exposure itself.

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Example
Refer OC use and Bacteruria example and calculate AR

This table shows data from a cohort study of oral contraceptive


(OC) use and bacteruria among women aged 16-49 years
Bacteruria

OP Use Yes No Total

57 455 512
Yes
No 77 1831 1908
Total 134 2286 2420

75
Refer OC use and Bacteruria
example and calculate AR
AR = Risk among exposed (Ie) Risk among non exposed (Io)
= 57/512 - 77/1908
= 0.1113281-0.040356
= 0.0709721 = 709721per 10,000,000 OC users
Interpretation: The excess occurrence of bacteruria among OC
users attributable to their OC use is 709721 per 10,000,000 OC
users.
In a population of 10,000,000 OC users, 709721 would be
expected to develop bacteruria, 1566 of those who developed
bacteruria being related to OC use & the remainder, 4036, to
other factors
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Attributable Risk Percent (AR %)
AR% = Ie-Io
Ie

Estimates the proportion of the disease among the exposed that


is attributable to the exposure, or
the proportion of the disease in the exposed group that could
be prevented by eliminating the exposure

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Refer OC use and Bacteruria example
and calculate AR%
AR % = 27/482 - 77/1908
27/482 X 100
= 27.96%

Interpretation: If OC use causes bacteruria, about 28 % of


bacteruria among women who use OC can be attributed to
their OC use and can be eliminated if they did not use oral
contraceptives.

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Population Attributable Risk
(PAR)

Public health planners want to be able to anticipate the effect


of eliminating the exposure on the population as a whole,
rather than just on the exposed part of the population

PAR = AR X prevalence rate of the exposure

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For the following data calculate
PAR
Given : AR = 89 per 100,000 per year
Prevalence rate of cigarette smoking = 20 %

PAR = 89 per 100,000 per year X 20 %


= 17.8 per 100,000 per year

Interpretation:-In a general population of 100,000 with a


prevalence rate of cigarette smoking of 20 %, about 18 deaths
from lung cancer per year would be prevented by eliminating
cigarette smoking.

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Population Attributable Risk
Percent (PAR %)
PAR % = PAR X 100
Incidence rate in total population

Example: PAR = 17.8 per 100,000 per year


Mortality rate in non-smokers = 7 per 105
Mortality rate in the total population = 24.8 per 105 per year

Calculate PAR %

PAR % = 17.8 per 105 per year X100 =71.8%


24.8 per 105 per year

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PAR% . . .
Interpretation: 72% of deaths from lung cancer occurring in
the general population could be prevented by eliminating
cigarette smoking.

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Where we have been?
Measuring disease occurrence,

Designing studies, and

Estimating strength of associations

83
Where we are heading?
to discuss the various threats we face to getting the right
answer, in other words, the threats to validity.

Anyone can get an answer to the research question or problem

The challenge is to tell if it is correct (Valid)

84
OTHER
POPULATIONS

Disease
+ -

+
Exposure
-

REFERENCE/
TARGET/
Two types of
SOURCE
inferences POPULATION
aka
STUDY BASE STUDY SAMPLE
85
20 to 65 year
>65 years old olds, in Europe
in Ethiopia.

Disease
+ -

+
Exposure
-

20 to 65 year
olds, in Ethiopia, Region 3, 20
outside of to 65 years old
Region 3

SAMPLE of Region 3,
20 to 65 yrs old 86
Attempts in study design to
Most enhance the second inference
important are often in conflict with goal
inference is of making a sound first
the first one inference
Disease
Without an + -
accurate first +
inference, Exposure
-
there is little
point
REFERENCE/
considering TARGET/
the second SOURCE
inference POPULATION
aka
STUDY BASE STUDY SAMPLE
87
Goal of any study
The goal of any study is make an accurate (true) inference, i.e.:
measure of disease occurrence in a descriptive study
measure of association between exposure and disease in an
analytic study

88
Errors
Ways of getting the wrong answer/or missing the truth:
systematic error; also called bias
any systematic process in the conduct of a study that causes
a distortion from the truth in a predictable direction
captured in the validity of the inference

random error; aka chance or sampling error


occurs because we cannot study everyone (we must sample)
direction is random and not predictable
captured in the precision of the inference (e.g., SE and CI)

89
Validity and Precision:
Each Shot at Target Represents a Study Sample of a Given Sample
Size

Good Validity Poor Validity


Good Precision Poor Precision

90
Validity and Precision

Poor Validity Good Validity


Good Precision Poor Precision

91
Validity and Precision Random
error
Random (chance)
error
(chance)

No Systematic
Systematic error
error (bias)
Poor Validity Good Validity
Good Precision Poor Precision

92
Performing an Actual Study:
You Only Have One Shot
Only judgment
can tell you
about
Field of systematic error
statistics can (validity)
tell you the
random error
(precision) with
formulae for
confidence
intervals Judgment
requires
substantive and
methodological
knowledge

93
Validity of epidemiological studies
Validity = The degree of closeness b/n a measured value and
the true value of what is being measured.

Two types of validity, internal and external.

A. Internal validity - is the degree to which the results of the


study are correct for the particular group of people studied

B. External validity (generalizability) - is the extent to which


the results of the study apply to people not in it.

94
OTHER ? EXTERNAL
POPULATIONS
VALIDITY
(generalizability)

Disease
+ -

+
Exposure ?
-
INTERNAL
REFERENC VALIDITY
E/
Two Types of TARGET/
Inferences SOURCE
POPULATIO
Correspond to Two N STUDY SAMPLE
Types of Validity 95
Possible outcomes in studying the
relationship between disease and
exposure
1. No association between exposure and disease, AR=0, RR=1

2. Positive association between exposure and disease (more


exposure, more disease), AR>0, RR>1

3. Negative association between exposure and disease (more


exposure, less disease), AR<0 (negative), RR <1(fraction)

96
Alternative explanations for the
observed association other than
cause and effect relationships.
A) The association may be the result of chance

B) The association may be the result of bias

C) The association can be the result of a confounding effect.

97
Alternative explanations. . .
D) An apparent cause can be an effect, rather than a cause
(reverse causation)

E) The cause can be both a cause and effect (reciprocal causation)


E.g. Vitamin A deficiency can cause diarrhea or diarrhea can
cause Vitamin A deficiency

Rule out these possibilities

98
The role of chance
It is important to quantify the degree to which chance
variability may account for the results observed in any
individual study.

This is done by performing an appropriate test of statistical


significance.

A measure that is often reported from all tests of statistical


significance is the P value.

99
The role of chance . . .
The key question in the statistical analysis is whether an
observed association in a sample is large enough to be
evidence of a true association in the population from which the
sample was drawn.

There are two standard methods of answering this question.

1. Confidence interval and


2. p value

100
The role of chance . . .
Confidence interval gives a plausible range of values that
should contain the true association in the population.

If the 95% confidence interval includes the point of one then,


by convention, any value in the sample cannot be generalized
to the population.

101
The role of chance . . .
P- value
is the probability that an effect at least as extreme as that
observed in a particular study could have occurred by chance
alone, given that there is truly no relationship between the
exposure and disease

Conventionally, if the P value < 0.05, then the association


between the exposure and disease is considered statistically
significant.

102
The role of bias
Bias is any systematic error in the design, conduct, or analysis
of a study that results in a distorted estimate of what the study
is attempting to measure.

Two major types of bias:


1. Selection bias

2. Information/or measurement bias

103
The role of bias
Selection bias affects the representativeness of the study subjects,
either as a result of sample selection, or as a result of non-response
or loss to follow-up.

Several types of selection bias


Diagnostic bias

Self selection/ Volunteer bias/ Compliance

Non-response bias

Loss to follow up

104
Ways of minimizing selection bias
Population based studies are preferred

Avoid volunteered people in the study

Select several different control groups in case-control study

In hospital-based case control study, controls are usually


selected among patients with diseases other than the disease
studied.
Make sure that these other diseases are not related to the
exposure & the disease of interest.

105
minimizing selection bias
In longitudinal studies (cohorts/RCTs):
Screen for occult disease/precursors at baseline
Avoid losses to follow-up
Consider approaches to tracking down the lost

106
Information (Observation) bias
Results from systematic differences in the way data on
exposure or outcome are obtained from the various study
groups

Examples of information bias:-


Investigator bias/ Interviewer bias/ Observer bias
Recall bias
Social desirability bias
Placebo effect

107
Ways of minimizing information
bias
1. Blinding

2. Use same standard procedures, instruments, questionnaires,


interviewing techniques, etc. for data collection in both
comparison groups

3. Use the most objective & accurate methods available for


classification of study subjects as to their outcome & exposure
status.

4. When exposure status is determined by interview, assist all


study subjects to make a thorough attempt at recall, similarly.
108
The role of confounding
An observed association (or lack of association) can be due to
mixing of effects between the exposure, the disease, and a
third factor that is associated with the exposure &
independently affects development of the disease.

This is referred to as confounding, and the extraneous factor


which showed that wrong association is called a confounding
variable.

109
Criteria to be a confounder
1. The variable (confounder) must be associated with the
exposure and, independent of that exposure, be a risk factor
for the disease.

2. The distribution (frequency) of the confounding variable


should vary between the groups that are compared

110
How to control confounding
Randomization

Matching

Restriction

Stratified analysis

Multivariate analysis

111
Epidemiological Surveillance

112
Surveillance
the continuous (ongoing) scrutiny of the factors that
determine the occurrence and distribution of diseases and
other health related events through a systematic collection of
data. (WHO)

Surveillance is the ongoing systematic collection, analysis and


interpretation of data; and the dissemination of information
essential to the planning, implementation, and evaluation of
public health practice.

Information for action


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Surveillance and survey
Surveillance Survey
It is relatively cheap (for It is costly, needs to use by
health department), can hiring a trained once.
often use existing systems Represents only single point
and health personnel in time
Allows monitoring of trends Tells little if anything about
of disease over time change in time (single point
Ongoing collection allows in time).
to use enough cases for Recall bias can be
study introduced (retrospective
data)

114
Surveillance and survey
Surveillance Survey
Quality control may be the More in-depth data could be
major problem collected
May not provide More accurate assessment of
representative data true incidence and
prevalence
Can identify those which
dont warrant medical care

115
Surveillance: purposes and uses
Prediction and early detection of outbreaks, diseases,
injuries, hazards, etc.

To provide scientific baseline data and information for


priority setting, planning, implementing and evaluating
disease control program.

To define the magnitude and distribution of diseases by


time, person and place.

116
Purposes and Uses of Surveillance
Monitoring trends and estimate magnitude of health problem
Epidemic (outbreak) detection and prediction
Monitor progress towards a control objective
Monitor programme performance
Estimate future disease impact
Evaluating an intervention
Understand characteristics of health events
Distribution and spread
Natural history
Facilitate planning

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Surveillance activities and
resulting public health action
Surveillance Activities Public Health Actions
Data collection and Priority Setting
recording
Planning, implementing and
Data compilation, analysis evaluating disease
and interpretation - Investigation
- Control
Reporting and notification - Prevention

Dissemination of
information
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Selection Criteria of disease for
surveillance
The importance of a health event to be included in surveillance
system, it should be assessed by:

1. Magnitude of the disease


Having high Incidence/ prevalence
Mortality (overall and age specific rates)
Morbidity (Hospitalization, disability) (top morbidity )
Severity (case fatality rate)
Health care costs
e.g. Malaria, Pneumonia, Diarrheal dis., TB, HIV/AIDS

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Selection Criteria of disease for
surveillance
2. Feasibility of control measures

3. Need for monitoring and evaluating the performance of a


control program

4. Resource availability

120
Elements of Surveillance System
1. Case definition of diseases included in the surveillance.

2. Determine the population under surveillance

3. Time period of data collection (immediate, weekly, and


monthly)

4. Source of data, who would report, etc.

5. How data are handled (confidentiality)

6. Incentives to participation
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1. Case Definition
A case definition is a set of criteria used to decide a person has
a particular disease.
It includes:
- Criteria: Signs and symptoms with or without a laboratory test
- Restriction by time, place and person can be done depending
on the nature of the disease
Classification of case definition
1. Confirmed: a case definition by appropriate laboratory test
2. Probable: a case with typical clinical features of the disease
without laboratory confirmation
3. Possible/ Suspect: a case with few of the typical clinical
features.
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Advantages of case definition
Facilitates early detection and prompt management of cases

Useful in areas where there is no laboratory

Facilitates observation of trends within specified geographic


areas

Facilitate comparison more accurately from area to area.

123
2. Population under surveillance
target population can:
- < 5 year children,
- women of child bearing age,
- people livining refugee etc
(prepare detail demographic data)

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3. Time period of data collection
It is useful to identify problems and solve timely
There are three periods of reporting:
1. Immediate reporting:
A. For diseases that include presence of a suspect consider as
epidemic.
E.g. Cholera,
B. a suspected epidemic when threshold is crossed
2. On weekly basis: for epidemic prone diseases.
E.g. Malaria, meningitis
3. On monthly basis: for routine surveillance
E.g. Tuberculosis, Leprosy, AIDS cases
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4. Sources of data, who would
report, etc.
Mortality registration
Morbidity registration
Epidemic reporting
Reports of laboratory utilization (Including lab test results)
Reports of individual case investigations
Reports of epidemic field investigations
Special surveys
Information on animal reservoir and vector distribution
Report of biologics and drug utilization
Knowledge of the population and environment

126
1) Passive case detection: detection in
course of normal operation of health services-via
self-reporting of patients to health institutions.
Health workers detect
diseases when people
come to health facilities

127
2) Active case detection: active search for
cases by special surveys or other non routine health
services.
(people undertaking surveillance facilitate data
collection)
Health workers going out
searching for health
problems in the community


128
Surveillance: types
Active Surveillance

Passive Surveillance

Sentinel Surveillance

129
Active Surveillance
A method of data collection usually on a specific disease,
for relatively limited period of time and with involvement of
persons who conduct the surveillance activity.

involves collection of data from communities such as:


- house-to-house surveys or
- mobilizing communities to central point.

130
Active Surveillance

Health Dept.

131
Active Surveillance: data
collection techniques
Sending out a letter

Alerting the public directly, usually through local media, to


visit a health facility

Asking patients of the particular disease if they know anyone


else with the same condition.

Conducting a survey of the entire population.

132
Active Surveillance
Advantages:
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

133
Conditions in which active
surveillance is appropriate
Periodic evaluation of an ongoing program
Programs with limited time of operation such as eradication
program.

In unusual situations such as:


New disease discovery
New mode of transmission
high-risk season/year is recognized.
disease is found to affect a new subgroup of the population.
reappearing eradicated disease.
134
Passive surveillance
/ passive case detection/
A mechanism for routine survey based on passive case
detection and on the routine recording and reporting
system.

Health issue may be more broad or general in nature

data is generated with out intervention, solicitation or contact


by the health agency carrying out the surveillance.

It involves collection of data as part of routine provision of


health services.

135
Passive Surveillance

Health Dept.

136
Passive surveillance
Advantages:
covers a wide range of problems

does not require special arrangement

it is relatively cheap

covers a wider area

137
Passive surveillance
Disadvantages:
The information generated is to a large extent unreliable,
incomplete and inaccurate.

Data are not available on time (mostly)

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


138
Sentinel Surveillance
Surveillance that uses a pre-arranged sample of reporting
sources to report all cases of one or more conditions.
Usually the sample sources are selected to be those most
likely to see cases of the specified condition, diagnose it
and report appropriately.
Provides a practical alternative to population-based
surveillance, in developing countries.
Health officials define homogenous population subgroups
and the regions to be sampled.
They then identify institutions that serve the population
subgroups of interest, and that can and will obtain data
regarding the condition of interest.

139
Sentinel Surveillance
Advantages:
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

140
Attributes of Surveillance
1. Sensitivity: to what extent the system identify all of the
events in the target population?

2. Timeliness: refers the entire cycle of information flow,


ranging from information collection to dissemination.

3. Representativeness: to what extent do events detected


through the surveillance system represents persons with the
condition of interest in the target population?

4. Predictive value: to what extent reported cases are really


cases?
141
Attributes of Surveillance
5. Accuracy and completeness of descriptive information: to
what extent forms are complete? Is the information
sufficiently reliable?

6. Simplicity: Are forms easy to complete? Are procedures


difficult? Are data collection kept to a necessary minimum?

7. Flexibility: Can the system change to address new


questions?
8. Acceptability: to what extent the participants are enthusiastic
to the system? Does the effort they invest yield useful
information?
142
Features of a good surveillance system
Using a combination of both active and passive surveillance
techniques.

Timely notification

Timely and comprehensive action

Availability of a strong laboratory service for accurate


diagnoses of cases

143
Limitations of the existing
surveillance system in Ethiopia
Deficiencies in data collection
diagnostic accuracy, completeness and representativeness
Deficiencies in reporting/ notification
multiplicity of case reporting forms, compliance, timeliness
Deficiencies in data analysis
central than local level, results in national indicators of
health status rather than local indicators
Deficiencies in dissemination
aggregate information, no feedback system
lack of follow-up for action

144
Integrated Disease Surveillance
and Response (IDSR)
An approach adapted to strengthen national disease
surveillance systems by coordinating and streamlining
all surveillance activities and ensuring timely
provision of surveillance data to all disease prevention
and control programmes in order to initiate timely
response (intervention).

145
List of Priority diseases and
conditions in Ethiopia
(A) Epidemic Prone Diseases
_ Cholera
_ Diarrhea with blood (Shigella)
_ Meningitis
_ Measles
_ Plague
_ Viral Haemorrhagic fevers
_ Yellow fever
_ Relapsing fever
_ Endemic Typhus
_ Malaria

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List of Priority diseases
(B) Diseases Targeted for Elimination/Eradication
Acute flaccid paralysis (AFP/Polio)
Neonatal Tetanus
Leprosy
Dracunculiasis (Guinea worm)
Measles

147
Epidemic Investigation
and
Management

148
Objectives
At the end of this chapter the student is
expected to:
Define epidemic
Identify types of epidemic
Describe the different steps in the investigain
of epidemic
Discuss the management of epidemic

149
Levels of Disease Occurrence
Diseases occur in a community at different
levels at a particular point in time.
Some diseases are usually present at a
predictable level.
This is called the expected level
Endemic
Hyperendemic
Sporadic
150
Levels of Disease Occurrence.
Some diseases can occur in excess of what is
expected.
Epidemic
Outbreak
Cluster
Pandemic

151
Expected Vs Excess Cases
Types of Epidemics
Common Source Epidemic
Point source
Continuous common sourse

Propagative /Progressive Epidemics

Mixed Epidemics

153
1. Common source epidemics
Occur as a result of the exposure of a group of persons
or population to a common source for the etiologic
agent.
Ex. Contaminated water supply
Food in a caf
Point source
Continuous common source
Intermittent common source
.
2. Propagated or progressive epidemics
serial transfer of infection
3. Mixed Epidemics
The epidemic begins with a single, common source
of an infectious agent with subsequent propagative
spread.
Many food borne pathogens result in mixed
epidemics
Epidemic Curve

X axis- time (of onset, of exposure)


Y axis- number of cases
Epidemic Curve:
advantages
o Magnitude over time
o Shape: point source vs propagated
o Type of epidemic
o Evaluation of intervention
o Estimating date of exposure
o Etiology of outbreak
o Incubation period
Point source epidemics
Point source: single exposure, no secondary
cases.
Exposure is brief and simultaneous.
Resulting cases develop within one incubation
period for the disease.
The shape of the epidemic curve is
characterized by a sharp rise and fall in the
number of cases, a unimodal peak, and short
duration.
Point source epidemics
Continuous Common source epidemics

It will result when exposure to a common source


continues over time.
A waterborne outbreak that is spread through a
contaminated community water supply is an
example of a common source epidemic.
The epidemic curve may have a wide peak
because of the range of exposures and the range
of incubation periods.
Intermittent common source
results in an irregular pattern of the epidemic
curve that reflects the intermittent nature of
the exposure.
Intermittent common source
Propagated epidemic
Occur as a result of transmission of an infectious
agent from one person to another.
Propagated source: secondary and tertiary cases
Ex. Measles, malaria, yellow fever, etc.
Its epidemic curve is characterized by an initial slow
rise in the number of cases, a succession of several
peaks, a prolonged duration, and usually a sharp fall.
Propagated epidemic
How do we detect excess
occurrences?
Outbreaks are detected in one of the following
ways:
Through timely analysis of routine
surveillance data, this may reveal an
increase in reported cases or unusual
clustering of cases.
Report from clinician.
Report from the community, either from the
affected group or concerned citizen.
166
Investigation of an Epidemic
Purpose is to determine the specific cause(s)
of the outbreak and to take measure for control
and prevention.
What is the etiological agent responsible for
the epidemic?
What is/are the predominant modes of
transmission?
What specific source/s of disease can be
identified?
167
Investigation of an Epidemic
What specific practices or environmental
deficiencies have contributed to the outbreak?
What is the chain of events that led to the
outbreak?

168
Steps in epidemic investigation
1. Prepare for field work
2. Verify the existence of an epidemic
3. Verify the diagnosis
4. Describe the epidemic with person, place and time
5. Formulate and test hypothesis
6. Search for additional cases
7. Analyze the data
8. Make a decision on the hypothesis tested
9. Intervention and follow up
10. Report of the investigation

169
1. Prepare for fieldwork
Preparations can be categorized into three:
A. Investigation related: scientific knowledge,
supplies, and equipment to carry out the
investigation. Discuss the situation with
knowledgeable people, review applicable
literature, and collect sample questionnaire.
B. Administration related: arrange transportation
and organize personnel
C. Consultation: clarify your team role in the field
170
2. Verify the existence of an epidemic
Compare the number of cases with the past
levels to identify whether the present
occurrence is in excess of its usual frequency.
Reasons for Unreal excess report:
Changes in local reporting procedures
Changes in case definition,
Improvement in diagnostics,
Increased awareness.
Changes in size of the population.
171
3. Confirm the diagnosis.
Carry out clinical and laboratory studies.
Classify depending on symptoms, laboratory
results, or both.
Establish criteria for labeling persons as cases.
Use a case definition i.e. a standard set of criteria
to differentiate between cases and non cases.

172
Cases can be one of the following:
Confirmed / definite: A case with laboratory
verification.
Probable: A case with typical clinical features
but without laboratory confirmation.
Possible: A case with fewer of typical clinical
features.

173
4. Describe the data in terms of
time, place and person.
Age, sex, educational status, occupation.
Use the following tools when characterizing
the epidemic:
Epidemic curve
Spot map
Attack rates

174
5. Formulate and test hypothesis
This step involves the assessment of the data
collected to date and the generation of
hypotheses that may explain the outbreak.
The goal is to explain the specific exposure
(s) that caused the outbreak.
The hypothesis should address source of
agent, mode of transmission and exposure
that caused the disease.

175
6. Search for additional cases.
Locate unrecognized or unreported cases:
Passively by inquiring if physicians or
hospitals have seen similar cases,
Actively by doing intensive investigation in
the community on asymptomatic persons or
contact of the cases.

176
7. Analyze the data.
Assemble all the results.
Interpret findings.

177
8. Make a decision on the
hypothesis tested.
The findings must be consistent with the
hypothesis.

178
9. Intervention and follow-up
Intervention must start as soon as possible
depending on the specific circumstances.
Aim control measures at the weak link or links
in the chain of infection.
One might aim control measures at the specific
agent, source, or reservoir.

179
10. Report of the investigation.
At the end prepare a comprehensive report and
submit to the appropriate agency.
The report should discuss in detail:
Factors leading to the epidemic.
Evaluation of measures used for the control
of the epidemic.
Recommendations for the prevention of
similar episodes in the future.
Managing Outbreak/epidemics 180
Management of epidemics
Requires an urgent use of appropriate
measures against the spread of the disease.

Action to be taken is dependent on the type of


the disease as well as the source of the
outbreak.

181
1. Measures Directed Against the
Reservoir
Domestic animals as reservoir:
Immunization
Testing of herds
Destruction of infected animals

Wild animals as reservoir:


post-exposure prophylaxis

182
Measures Against Reservoir. . .
Humans as reservoir
Removal of the focus of infection- e.g.
cholecystectomy for Typhoid fever.
Isolation of infected persons.
Treatment to make them noninfectious- e.g.,
tuberculosis.
Disinfection of contaminated objects.
Quarantine-
183
Measures that interrupt the
transmission of organisms
Action to prevent transmission of disease by
ingestion:
Purification of water
Pasteurization of milk
Inspection procedures designed to ensure
safe food supply.
Improve housing conditions.

184
Measures that reduce host
susceptibility
Active immunization, when either the
altered organism or its product is given to a
person to induce production of antibodies.
Passive immunization, provision of ready
made antibodies.
Chemoprophylaxis: use of antibiotics for
known contacts of cases- for example, in
meningitis.

185
186