Principles of Epidemiology

“I keep six honest serving men, they taught me all I

knew;
Their names are What, Why, When, How, Where &
Who” – Rudyard J Kipling
 Definition
• Study of distribution & determinants of health
related states or events in specified populations
and the application of this knowledge in solving
health problems – John M Last, 1988
 Aims of epidemiology
• To describe the distribution and magnitude of
health and disease in human pop
• To identify aetiological (risk) factors in the
pathogenesis of disease
• To provide the data essential to the planning,
implementation and evaluation of services for
the prevention, control and treatment of
diseases and to the setting up of priorities
among those services
 Epidemiological approach
• Asking questions
– What
– Why
– When
– Where
– How
– Who
• Making comparisons
 Measurements in epidemiology
• Mortality
• Morbidity
• Disability
• Natality (Fertility)
• Demographic variables
 Tools of measurement
• Rates
• Ratios
• Proportions
 Standardization for comparison
• Direct standardization:
– Feasible only if the actual specific rates in
subgroups of the observed population and the
numbers in each sub-group are available
• Indirect standardization:
– SMR = Observed deaths / Expected deaths X 100
– Used to compare mortality between different
exposure groups
Direct standardization
•The choice of the standard population is
to some extent arbitrary.
• The use of a different standard population
will give rise to a different value of the
standardized death rate
• It should be remembered that the purpose
of standardization is comparison
• There is no intrinsic meaning of this value
Indirect standardization
 Measurement of Morbidity
• Incidence = Number of new cases of specific
disease during a given time period /
Population at risk during that period X 1000
• Prevalence
– Point prevalence = No of all current cases at that
point / Population at that point X 100
– Period prevalence = No of all cases during a given
period of time interval / Mid-interval population at
risk X 100
• A particularly useful measure of events that
can occur repeatedly in individual subjects
under observation is
• a. The incidence density
• b. The incidence rate
• c. The period prevalence
• d. The risk ratio
 Secondary attack rate (SAR)
• In a class of 100 students, 33 are immunized for
measles. Another 33 had measles last year. A
student develops measles one day and within the
next week 22 more develop it. What is the SAR?
• SAR = No. of exposed developing disease in an I/c
period range / Total no of susceptible exposed
contacts X 100
• Primary case is always excluded both from
numerator & denominator
 Secondary Attack Rate
In a community of 800 households (population
4799), public health authorities found 120
persons with Condition D in 80 households. A
total of 480 persons lived in the 80 affected
households. Assuming that each household
had only one primary case, the secondary
attack rate is:
• A. 8.5% B. 10.0% C. 16.7%
• D. 25.0%
 Types of epidemiological studies
Type of epidemiological study Unit of study
1. Observational Studies
Descriptive studies (Hypothesis formulation)
Analytical studies (Hypothesis testing)
i. Cohort Individual
ii. Case control study Individual
iii. Cross sectional study Individual
iv. Ecological study Population
2. Experimental studies (Hypothesis testing)
a. Randomized controlled trial Patients
b. Field trial Healthy people
c. Community trial Community
• Residents of three villages with three different types of
water supply were asked to participate in a study to
identify chlolera carriers. Because several cholera
deaths had occurred in the recent past, virtually
everyone present at the time submitted to examination.
The proportion of residents in each village who were
carriers was computed and compared. The study is a:
a) Cross-sectional study
b) Case-control study
c) Concurrent cohort
d) Non-concurrent cohort study.
 Descriptive epidemiology
• Distribution of disease according to:
• Time
• Place
• Person
• Descriptive epidemiology / studies often result
in an aetiological hypothesis
 Time distribution
• Short term fluctuations
– Epidemic is a good example
• Common source
– Single exposure / point source
– Continuous / Multiple exposure
• Propagated
– Person-person
– Arthropod vector
– Animal reservoir
• Slow (Modern)
• Periodic fluctuations
– Seasonal trends
– Cyclic trends
• Long term or secular trends
 Investigation of an Epidemic
1. Verification of the diagnosis
2. Confirmation of the existence of an epidemic
3. Defining the population at risk
4. Rapid search for all cases and their characteristics
5. Data analysis
6. Formulation of hypotheses
7. Testing of hypotheses
8. Evaluation of ecological factors
9. Further investigation of population at risk
10. Writing the report
 Place distribution
• International variations
• National variations
• Rural-Urban differences
• Local distributions
– Spot maps / shaded maps - good tools
 Person distribution
• Age
• Gender
• Ethnicity
• Marital status
• Occupation
• Social class
• Behavior
• Stress
• Migration
 Case control study
• Four basic steps:
1. Selection of cases and controls
2. Matching
3. Measurement of exposure (Exposure rates)
4. Analysis & interpretation (Odds ratio)
• Odds ratio is nearly same as relative risk
when
a) OR is calculated from a prospective study
b) Relative risk is calculated from a
retrospective study
c) The risk factor is rare
d) The disease is rare
 Cohort study
1. Selection of study subjects
2. Obtaining data on exposure
3. Selection of comparison groups
4. Follow up
5. Analysis
• Three main types:
1. Prospective cohort
2. Retrospective cohort
3. Mixed
• Which one of the following examples might
represent a retrospective cohort study?
a) cases of lung cancer assessed for prior exposures
b) subjects with current angina followed for the
development of myocardial infarction
c) subjects with prior radiation exposure followed
for the development of lympho-proliferative
cancers
d) subjects with skin cancer assessed for life long
cumulative skin exposure
 Randomized control trial
1. Drawing up a protocol
2. Selecting reference & experimental
populations
3. Randomization
4. Manipulation / Intervention
5. Follow-up
6. Assessment of outcome
 Two types of RCTs
• Concurrent parallel design
• Cross-over design
• Cross-over design helps remove ethical
concerns
• The number of patients required in a clinical
trial to treat a specify disease increases as:

a) the incidence of the disease decreases

b) the significance level increases
c) the size of the expected treatment effect
increased
d) the drop out rate increases
 Non-randomized trials
1. Uncontrolled trials – e.g. pap smear
introduction; in case of remarkably beneficial
results
2. Natural experiments – smokers & non-smokers
; Exposed & Non-exposed
3. Before & After comparison studies:
1. Without controls – Subjects form their own controls e.g.
James Lind on Scurvy
2. With controls – A different population where the
intervention is not taking place serves as control
 Nested case control study
• A hybrid design where a case-control study is nested in a
cohort study
• Basically a type of cohort study due to its forward
direction
• Usefulness limited for rare diseases & whose diagnostic
tests are very expensive
• Design: A population is identified & baseline data is
obtained. Population is followed up for development of
disease. A case control study is then carried out
• Advantages: Elimination of recall bias; Maintenance of
temporal association; Economical
 Historical controls
• New treatment becomes available which is life
saving
• The same patients serve as their controls
• The past treatment is the placebo
 Association & Causation
• Association:
– Spurious association
– Indirect association
– Direct (Causal) association
• One to one causal association: Rare in nature;
Necessary & sufficient criterion
• Multi-factorial causation
 Hill’s criteria for causation
1. Temporal association: Most imp criteria
2. Strength of association: RR (> 2) & OR
3. Specificity of association: disease is caused only by the
risk factor under study; Weakest & most difficult to
establish
4. Consistency of association
5. Biological plausibility
6. Coherence of association
7. Dose response relationship
8. Cessation of exposure
 Preference of studies for establishing
causality
1. Meta-analysis
2. RCTs
3. Retrospective (Non-concurrent/Historical)
cohort study
4. Prospective cohort study
5. Case control study
6. Cross sectional study
7. Ecological study
All the following statements concerning meta analysis are
true except:
a) It is a study in which the units of analysis are populations
or groups of people, rather than individuals.
b) It is used to enhance the statistical power of research
findings where number in available studies is too small
c) It is applied by pooling results of small, randomized
controlled trials when no single trial has large enough
numbers to reach statistical significance
d) It combines results from different studies to obtain a
numerical estimate of an overall effect
 Bias
• Bias: Any systematic error in a study occurring at any stage
• Three main types: Subject bias (Hawthorne & recall); Investigator bias
(Selection) ; Analyzer bias
1. Apprehension bias
2. Attention bias (Hawthorne) – Anyone aware of being observed changes
behavior
3. Berksonian bias (Admission rate bias) - A spurious association between a
characteristic and a disease because of the different probabilities of
admission to a hospital for those with the disease, without the disease
and with the characteristic of interest; Applicable when hospital cases &
controls are used
4. Interviewer bias: More time with cases
5. Lead time (zero time shift ) bias: overestimation of survival time
6. Memory / recall bias
7. Neymann bias (prevalence-incidence bias): missing fatal, mild, silent cases
8. Selection bias
• It is probable that physician have a higher
index of suspicion for TB in children without
BCG scar than those with BCG scar. If this is
so and an association is seen between TB and
not having BCG scar, the association may be
due to:
a. Selection Bias b. Interviewer Bias
c. Surveillance Bias d. Non-response Bias
 Minimization of bias & confounding
Method Removes or minimizes
Matching Known confounding factors
Blinding - single Subject bias
Double Subject + Investigator bias
Triple Subject + Investigator + Analyzer bias
Randomization Known & Unknown confounding factors

• Randomization is superior to BOTH matching &

blinding
 Uses of Epidemiology
1. To study historically the rise and fall of
disease in populations
2. Community diagnosis
3. Planning & Evaluation
4. Evaluation of individual’s risks and chances
5. Syndrome identification
6. Completing the natural history of disease
7. Searching for causes and risk factors
 Infectious disease epidemiology
• Herd Immunity – The protection over and
above due to individual protection; Works for
diseases that spread from person-person;
Doesn’t work for Tetanus, Rabies; Herd
immunity threshold (HIT) of various vaccines -
Diphtheria-85%; Pertusis-92-94%; Measles-83-
94%; Mumps-75-86%; Rubella & polio-80-85%
 Source & Reservoir
• Source is the infective material or the point
where infection starts e.g. nasal secretions are
the source in a leprosy patient; Droplet nuclei
from a case is the source of measles.
• Reservoir is the organism / Place where the
infective agent normally lives & multiplies. E.g.
Soil is the reservoir for tetanus spores.
 Carriers
• Carriers: People or animals harboring the
infective agent but not showing the full range
of signs & symptoms. They are capable of
transmitting the infection to healthy people.
 Classification of carriers
1. Based on the type (stage of illness):
– Incubatory carriers: Infective during incubation period e.g. Measles, Polio,
Diphtheria, Pertusis
– Convalescent carriers: Infective during the period of convalescence (recovery)
e.g. Typhoid, Diphtheria, Pertusis
– Healthy (Asymptomatic) carriers: Derived from subclinical cases e.g. Polio,
Diphtheria, Meningococcal meningitis, Rabies in Bats
2. Based on duration:
– Temporary carriers: Infective for a short time e.g. Measles, chicken-pox
– Chronic carriers: Long term infective. E.g. Hepatitis-B, Typhoid, Malaria
3. Based on portal of exit:
– Urinary carriers: Typhoid
– Intestinal carriers: Polio, Typhoid
– Nasal carriers: Diphtheria
– Respiratory carriers: Meningococcal meningitis
 Some important terms & concepts
• Primary case: The first case to occur in a population
• Secondary case: The case(s) that occur after exposure to the primary case within
one incubation period range
• Index case: The first case to be notified (brought to the notice of health
authorities)
• Serial interval: Gap in onset b/w primary case & secondary case
• Generation time: Receipt of infection to development of max infectivity
• Communicable period: Till the time infection can be transmitted directly /
indirectly
• Incubation period: Receipt of infection to first sign / symptom
• Attributable Risk: Incidence among exposed – Incidence among non-exposed
• Incidence among non exposed
• AR is a good measure of extent of public health problem caused by the exposure
• A useful too for assessing priorities for health action. Also known as Absolute
risk / Excess risk / Risk difference
Screening
 Screening
• Definition: The search for an unrecognized
disease or defect, in apparently healthy
individuals, by means of rapidly applied tests,
examinations or other procedures
• It is rapid, relatively inaccurate, cannot be
used as a basis for treatment and the initiative
comes from the investigator
 Screening & Diagnostic test
Screening test Diagnostic test
Done on apparently healthy Done on those with indications or sick
Applied to groups Applied to single patients, all diseases are
considered

Test results are arbitrary and final Diagnosis is not final but modified in light of
new evidence, diagnosis is the sum of all
evidence

Based on one criterion or cut-off point Based on evaluation of a number of

symptoms, signs and laboratory findings

Less accurate More accurate

Less expensive More expensive
Not a basis for treatment Used as a basis for treatment
The initiative comes from the investigator or The initiative comes from a patient with a
agency providing care complaint
 Lead time

Yield
The amount of previously unrecognized disease that is diagnosed as a result
of the screening effort
 Examples of screening tests
Screening test(s) Disease

Papanicolaou smear Cervical cancer

Breast self examination Breast cancer

Mammography Breast cancer

Bimanual oral examination Oral cancer

ELISA HIV

Urine sugar; Random blood sugar Diabetes mellitus

Alpha Feto-protein Developmental anomalies

Digital rectal examination (DRE) Prostate cancer

Prostate specific antigen Prostate cancer

Fecal occult blood test Colorectal cancer

 2 X 2 table
Disease
Present Absent
Screening test Positive a (TP) b (FP)
Result
Negative c (FN) d (TN)

• Sensitivity; Specificity; PPV; NPV

• Screening in series & Screening in parallel
• PPV = Sensitivity X Prevalence / {Sensitivity X
Prevalence} + {(1 – Specifity) (1 - Prevalence)}
• NPV = Specificity X (1 – Prevalence) / Specificity X
(1 – Prevalence) + {(1-sensitivity) X Prevalence}
• The sensitivity of the screening test is 94%,
specificity is 90%. The prevalence of the
disease in a community is 5%. What
percentage of the persons in the community
who have a positive screening test result will
have the disease:
• a. 28% b. 33% c. 48% d. 67%
• A screening test is used in the same way in two similar
populations; but the proportion of false positive
results among those who test positive in population A
is lower than those who test positive in population B.
what is the likely explanation:
a) The specificity of the test is lower in population A.
b) The prevalence of the disease is lower in population A.
c) The prevalence of the disease is higher in population
A.
d) The specificity of the test is higher in population A
 Likelihood ratios
• Provides a direct estimate of how much a test
result will change the odds of having a disease
• Likelihood Ratio for a positive result
– LR+ = Sensitivity / 1-Specificity
• Likelihood Ratio for a Negative result
– LR - = 1-Sensitivity / Specificity
• A test for detection of baldness is devised. It is
applied to a population of 200 adults in the
Bangalore city who insist that they have hair.
Based on a gold standard – namely, asking the
subjects to remove their hats- 20 of the 200
persons are actually bald. The new test detects 12
cases of baldness, of which 8 are positive by the
gold standard and 4 are negative. The likelihood
ratio positive for these data is
• a. 2 b. 18 c. 42 d. 12
• A Colon Cancer screening study is being conducted at Rotary
Cancer Institute, AIIMS. Individuals 50-75 yrs old were screened
with the Hemoccult test. If the hemoccult test result is negative,
no further test is done. If the hemoccult test result is positive,
the individual will have a second stool sample tested with the
hemoccult II test. If this second sample is also positive for blood,
the individual will be referred for more extensive evaluation.
What is the net effect by this method of screening?

a) Net Sensitivity and net Specificity are both increased.

b) Net Sensitivity is decreased and net specificity is increased.
c) Net Senstivity remains the same and net specificity is increased.
d) Net Sensitivity is increased and net specificity is decreased.
e) The effect on net sensitivity and net specificity cannot be
determined from the data
 Immunization and vaccination
History:
• 1978 – Expanded program on Immunization (EPI) introduced
after smallpox eradication; Introduction of BCG, DPT, OPV &
Typhoid; Mainly in urban areas
• 1985 – EPI was renamed as Universal Immunization Program
(UIP); Measles was added; Expanded to the entire country
• 1986 – Technology mission
• 1990 – Vitamin A supplementation
• 1992 – Child survival & safe motherhood program (CSSM)
• 1995 – Polio National Immunization Days (Pulse polio rounds)
• 1997 – Reproductive & Child health program - I
• 2005 – RCH-II & The National Rural Health Mission (NRHM)
• 43.5% children are fully immunized (NFHS-III) ; Current
figure 61%
• Term vaccine coined by Louis Pasteur
• Vaccination coined by Edward Jenner
• First vaccine: against smallpox (1978) by Jenner
• Some special types: Polyvalent (more than 1 strain);
Autogenous (organism in the vaccine obtained from the
future recipient); Subunit (Hepatitis B); Conjugate (HiB)
• Contraindications: Pregnancy (All live except yellow
fever); HIV - Symptomatic (All live except BCG),
Asymptomatic (None); Fever (typhoid vaccines Typhoral,
Typhim-Vi, TAB); LBW (Hep B in < 2kg); Infants (Yellow
fever, meningococcal, Pneumococcal, Typhoid)
DPT-Booster 16-24 months 0.5 ml Intramuscular A/L thigh

OPV-Booster 16-24 months 2 drops Oral Mouth

Measles (2nd 16-24 months 0.5 ml Sub-cutaneous Right arm

dose)*
Vitamin A (2nd to 16 months with 200,000 IU = 2 ml Oral Mouth
9th dose) DPT/OPV- booster
& then every 6
months till the age
of 5 years

DPT Booster 5 – 6 years 0.5 ml Intramuscular Upper Arm

TT-1 10 years 0.5 ml Intramuscular Upper Arm

TT-2 16 years 0.5 ml Intramuscular Upper Arm

JE vaccine introduced in 104 endemic districts; SA-14-14-2 live vaccine; single dose
at 16-24 months
 Contraindications
• > 2 years of age: Pertusis
• Progressive neurological disease: Pertusis (NOT in
epilepsy controlled on medication & CP)
• Only absolute contraindication to killed vaccine:
Severe local or general reaction to a previous dose
• Side effects:
 Guillian Barre syndrome: Killed influenza vaccine
 Paralysis: OPV (sabin)
 TSS: DPT, Pertusis
 Hypersensitivity: Hep-B, Meningococcal, DPT, dT
 Some important con siderations
• Any number of vaccines (live &/or killed) can be given together
• No need for a gap of 1 month b/w a live and a killed vaccine
(required b/w 2 lives) (Cholera & Yellow fever cannot be given
together)
• Doses & schedule remain same irrespective of prematurity or
LBW
• In Delhi MMR & Typhoid also included
• OPV: Minimum 5 doses for immunity development
• DPT: Minimum 3 doses
• TT: A fully immunized adult (excluding pregnant women) would
have received 7 doses of TT
• If pregnant comes at 8th month: give her 2 doses, even if the
second dose is after delivery
 Maximum age for immunization under the
program
• BCG: 1 year
• OPV: 5 years (2 drops = 0.1 ml)
• DPT: 7 years
• Hep B: 1 year
• Measles: 5 years
• Vitamin A : 5 years
• DT: 7 years
Strains of commonly used vaccines
Vaccine Strain(s) / vaccines
BCG Danish – 1331 strain
OPV/IPV P1, P2, P3 strains (Mono or Tri-valent)
Measles Edmonston Zagreb strain (MC); Schwartz strain; Moraten strain

Mumps Jerryl Lynn strain

Rubella RA 27/3
Yellow fever 17 D strain
Varicella OKA strain
JE Nakayama strain (MC); Beijing P3 strain; SA 14-14-2; Indian
manufactured Jenvac
Malaria SPf 66 (Lytic cocktail); Pf 25 strain, RTS-S (In Phase III Trials)
HIV mVA (modified vaccinia Ankara) strain; rAAV (recombinant adeno
associated viral vaccine); CTL (Cytotoxic T-lymphocytic) strain ;
AIDSVAX strain; subunit vaccine strain; combination of AIDSVAX &
ALVAC
 Cold chain
1. Walk in cold rooms: Located at regional level; Stores
vaccines for upto 3 months; Can supply 4-5 districts
2. Deep freezers & Ice-lined refrigerators (Large 300 liters):
At the district level. Deep freezers are used for making
ice-packs & to store OPV and Measles
3. Deep freezers & ILRs (Small – 140 liters): At the PHC
level
4. Cold boxes:
5. Vaccine carriers: for carrying out immunization sessions;
16-20 vials can be stored for a few hours (4-6)
6. Day carriers: 6-8 vials
7. Ice-packs:
 AEFI
An AEFI is a medical incident that takes place after immunization, causes concern
and is believed to be caused due to immunization

AEFI Description
Vaccine reactions: (Minor reactions to Event caused or precipitated by the
Hypersensitivity) vaccine when given correctly, caused by
the inherent properties of the vaccine

Programme error Event caused by an error in vaccine

preparation, handling or administration

Coincidental Event happening after vaccination but not

caused by the vaccine

Injection reaction Event from anxiety about or pain from the

injection

Unknown No cause determined