EPIDEMIOLOGY

EPIDEMIOLOGIC
PROCESS
Adrian Bancescu Assoc. Prof. MD. PhD.
Discipline of Epidemiology
The University of Medicine and Pharmacy “Carol Davila” Bucharest

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 C2. Epidemiologic Process

Subheadings

1. Source of infection

2. Modes and routes of transmission

3. Receptivity

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 EPIDEMIOLOGIC PROCESS (EP)

EF EF

IP IP IP IP

EF

The complex phenomenon of

• extension of infection in the population
• based on a continuous chain of infectious processes
• naturally expressed in the form of outbreaks (epidemiologic foci)
 EPIDEMIOLOGIC PROCESS (EP)

Determinant factors

• Source of infection

• Route of transmission
• Susceptible host
Contributory factors

• Natural

• Economic and social

EP CONTRIBUTORY FACTORS

ECONOMIC and SOCIAL FACTORS

• occupation
• housing NATURAL FACTORS
• nutrition (quantity, quality) • weather and climate
• individual and collective hygiene • cosmic
• healthcare (accessibility, addressability) • geographical
• culture and health education • telluric
• crowd: micro level / macro level
• economic and social disturbance

DETERMINANT FACTORS

SOURCE ROUTE OF
RECEPTIVITY
OF INFECTION TRANSMISSION
 Epidemiologic
Process CONTRIBUTORY FACTORS

ECONOMIC and SOCIAL FACTORS NATURAL FACTORS

DETERMINANTE FACTORS

ROUTES of
SOURCE of INFECTION
TRANSMISSION
Man RECEPTIVITY
Direct
• Ill
Indirect
• Subclinical infected Susceptibility
• air
• Carrier Resistance
• water
Animals • nonspecific
• soil
• domestic  mammals • specific
• food
• wild  birds
• objects
• synanthropic  arthropods
• hands
 aquatic
• vectors
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 The chain of infection

Infectious
agent

Susceptible Source -
host Reservoir

Portal Portal
of entry of exit
Mode of
transmission

 The chain of infection is made up of six different links.

 Each link has a unique role in the chain and

each can be interrupted, or 'broken', through various means.
6/2/2018 Krämer A., Kretzschmar M., Krickeberg K. Modern infectious disease. 2010 7
 SOURCE of INFECTION

 the living human or animal organism

• which harbours and
• creates conditions for pathogen to live and multiply and
 from where the susceptible individuals become infected through
a route of transmission

The Source of Infection generates the

outbreak (epidemiologic focus) giving
to infection an epidemic character.

An outbreak encompass
several Sources of Infection
• primary case
• secondary cases
 sick people
 carriers
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 Reservoir of infection

 all living species and environment

• where the pathogen
 lives and
 replicates and
• from where passes to a susceptible host

The usual habitat in which the agent lives and multiplies.

The reservoir may or may not be a source of infection

from which the agent is transmitted to a host.

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 Source of Infection has 2 main elements

 Specific epidemiological localization

of infectious agent

 Portal of exit

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 Specific epidemiological localization of infectious agent
• Anatomical site in the host organism
• Where is the most significant multiplication of the infectious agent
• Allowing then removing microorganism in the external environment

• Sometimes
 coincides with pathological localization
acute infectious diarrhoea
 urinary infections
 acute respiratory infections
 doesn’t coincides with pathological localization
 Poliomyelitis
 epidemiological localization is intestinal
 pathological localization is the anterior horns of the spinal cord
 Rabies
 epidemiological localization is in parotid gland
 pathological localization is in Ammon’s horn (in hippocampus)
 Tick encephalitis
 epidemiological localization is blood
 pathological location is the brain
• It may be:
 unique or
 multiple
 one principal,
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 Portal of exit
Is the route by which
the infectious agent
leaves the host

• natural way It usually depends on

• lesions caused by specific epidemiological localization
microorganisms of the infectious agent in the host

• the localized infections

 if they are accompanied by
clinical signs of septicaemia
 they could have also other portals
• It may be of elimination
 unique or
 multiple
 one principal
 others secondary

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Portal of exit

• depends on the specific epidemiological localization

 Respiratory tract
 droplets of nasal and throat secretions (e.g. influenza virus, measles virus,
mumps virus, rubella virus, Mycobacterium tuberculosis)
 Gastrointestinal tract
 saliva (rabies virus)
 faeces (hepatitis A virus, Salmonella, agents of enteritis)
 Genitourinary tract
 urine (Leptospirae found in the urine of infected animals)
 secretions of genital tract (STI: HIV, syphilis)
 through skin
 superficial lesions such as impetigo, syphilis, varicella
 needles, insect bites (e.g. hepatitis B virus, plasmodium)
 through placenta during pregnancy
 (e.g. rubella virus, cytomegalovirus, syphilis, toxoplasmosis) transmitted
from the mother to fetus, resulting a long line of abnormalities

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 Examples
Tuberculosis
● The main localization
● The main elimination route
 respiratory  sputum
● Other localizations
● Other elimination routes
 renal  urine
 intestinal  faeces
 genital  pus
 bones
 subcutaneous

Typhoid fever
● The main localization
● The main elimination route
 intestinal  faeces
● Other localizations
● Other elimination routes
 renal  urine
 osteo-cartilaginous  pus

Viral enteritis
● The main localization
● The main elimination route
 intestinal  faeces
• Other localizations ● Other elimination routes
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 respiratory  respiratory secretions 14
 Classification of Sources of Infection
according to the Portal of Exit

Complete
• possesses
 specific epidemiological localization
 elimination pathway
• active, it generates outbreaks

Incomplete (closed, cryptic)

• without elimination pathway
• inactive, it doesn’t generate outbreaks

They can become active, in some cases, creating

problems in infectious disease control.

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 SOURCE of INFECTION

Human being
• overt disease with clinical signs and symptoms
 typical
 atypical
• inapparent infected (subclinical)
• carrier

Animals
 Mammals
• Domestic
 Birds
• Wild
 Arthropods
• Synanthropic
 Aquatic
 According to the primary Source of Infection
Communicable diseases are
measles, rubella,
ANTHROPONOSIS scarlet fever,
man man
• human’s diseases syphilis, gonorrhea,
typhoid fever

ZOONOSIS
• animal’s diseases animal animal animal
• accidentally in humans

Zooanthroponosis
(active zoonosis) animal man man
rabies, influenza ,
Q fever, tularemia

animal animal animal

Zoonosis
(passive zoonosis)
anthrax, brucellosis , animal
leptospirosis, tetanus man
 SOURCE of INFECTION

PATIENTS INNAPARENT
INFECTED CARRIERS

Incubation stage
Former Healthy
ill carriers

Clinically manifest stage

Temporary
carriers
● period
 short Chronic
Convalescence stage carriers
 long
PATIENTS are sources during
the period of infectiousness
Incubatory carriers

Are people who are going to become ill but

begin transmitting their infection before their
PATIENTS symptoms start, (temporary carriers).

Example
A person infected with measles begins to shed
Incubation stage the virus in nasal and throat secretions
a day or two before any cold symptoms or rash
are noticeable.

Many other diseases also have an incubatory

Clinically manifest stage
carrier phase (typhoid fever, whooping cough,
poliomyelitis, viral hepatitis, cholera).

Most notably, HIV infection may be present for

years before the person develops any
Convalescence stage
symptoms.
 Acute clinical cases
(overt disease)

PATIENTS People who

• are infected with the disease agent and
• become ill (with typical and atypical forms).

Incubation stage They eliminate the pathogen

 virulent
 in large amount
 continuously
 long period
Clinically manifest stage
Because they are ill their contacts and
activities may be limited.

They are also more likely to be diagnosed

Convalescence stage and treated than carriers are.

Generally is a reduced number of case

but large in epidemics.
 Convalescent carriers
PATIENTS
Are people who continue to be infectious during
and even after their recovery from illness.
 temporary carrier
Incubation stage  short duration period (2-8 weeks)

This happens with many diseases: scarlet fever,

diphtheria, dysentery, typhoid fever, poliomyelitis.
Clinically manifest stage Example:
Salmonella patients may excrete the bacteria in
faeces for several weeks, and rarely even for a
year more.
Convalescence stage
This is most common in infants and young
children.

Treatment with inappropriate antibiotics may

prolong the convalescent carrier phase.
 Inapparent infection (syn. subclinical infection)
INAPPARENT
INFECTED The presence of infection in a host
• without occurrence of recognisable clinical signs
and symptoms.
• but with immunological changes like clinical cases.

Of epidemiologic significance because the hosts:

• so infected, though apparently well,

• may serve as silent or inapparent disseminators
 of the infectious agent
 in small amount for shorter periods of time
• have increased mobility
• are unknown and many
• difficult to identify (incidentally detected)
• remain untreated
• no measures towards the contacts and
the environment are taken

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 With some diseases the inapparent infections
are more common than the acute clinical cases
Example:
Of every 100 individuals infected with poliovirus ,
• only one becomes paralyzed
• four others will have a mild illness with fever, malaise, headache, nausea and vomiting
• ninety-five will have no symptoms at all, although they pass the virus in their faeces.

Inapparent infections and age

Sometimes the likelihood of an inapparent infection depends on an other epidemiologic

factor, such as age.

Hepatitis A is a good example of this.

• Over 50% of adults infected with this virus develop symptoms.
• However, among children under 5, there may be 10 inapparent infections
for every child who develops jaundice.
• So children are very effective spreaders of the hepatitis A virus, which is passed in
the faeces regardless of the presence of symptoms.

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 CARRIERS
 Carriers are people
• colonized with microorganisms
• without having signs of active infectious disease
(even if it existed in the person’s history)
• resistant to infection
 former sick
 former inapparent infected
 vaccinated

 The microorganisms
• localize and multiply
 on the skin
 on the mucous membranes of the open cavities
 in places where escape the action of humoral antibodies

• pathological changes there are frequently in these areas

• agents are isolated and identified through microbiological methods

 Asymptomatic carrier
(inapparent infection)
Incubatory
 carrier ?
Carrier
• a person or animal
• that harbours a specific infectious agent
CARRIER • in the absence of the discernible clinical disease
• and serves as a potential source of infection.

Healthy Former
carrier ill

Convalescent carrier
Post-convalescent carrier • temporay carrier 
• chronic carrier • short duration
• long duration
 intermittent
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 continuous 25
 Chronic carriers

Are people who continue to harbour infections for six months - a year or longer after
their recovery.
They are post-convalescence carriers.
Long duration of the period of spreading the pathogens :
 intermittent or
 continuous.

Example:
The chronic carrier state is not uncommon following hepatitis B infection, whether or
not the person became ill, and may be lifelong.

The risk of developing chronic hepatitis B depends on the person’s age at infection.
About 90% of infants infected at birth become chronic carriers of the disease,
compared with 1-10% infected after age five.

That’s why it is so important to give hepatitis B vaccine to newborns.

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 Healthy carriers
(through contact, occasional)
 people
• who have always been healthy and
• who being contaminated didn’t get ill
• having a state of immunity

 Immunity is conferred by :
• passing through clinical manifest infection
• passing through inapparent infection
• contact with repeated small doses of low virulent agents
(natural occult immunizations)
• artificial active immunization (vaccination)

 If the state of immunity disappears,

healthy carrier may manifest disease.

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 Healthy carriers
 Healthy carrier status
• usually lasts as long as
• the individual is in contact
• with a source of infection
(sick person or other carrier)

• poliomyelitis
 Temporary carriage • cholera
• the most common for healthy carriers • dysentery
• in many infectious diseases • diphtheria
• lasts for 1-3 weeks • scarlet fever
• meningococcal meningitis
• viral hepatitis

 Chronic carriage
• is uncommon for healthy carriers
• when there are local chronic predisposing factors
(anatomical, functional)
• lasts for months
• e.g. infections with staphylococcus
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  Carriers are sources of infection that:

• can generate new carriers or cases of disease

• maintain endemic communicable diseases in a certain area

• are often the origin of epidemics

 e.g., water borne disease epidemics
 food borne disease epidemics

 They are the hidden connection among cases apparently independent

(a link in the natural history of the disease)

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 Animal sources

Animal sources of infectious agents can be described in the same way as human sources.

They may be :
• acute clinical cases
• inapparent infected
• carriers

Depending on the disease, different carrier phases may be important in transmission.

e.g.
• Dogs infected with rabies may shed the virus in
their saliva 3-5 days prior to the onset of
symptoms.
• This is the reason that when a dog bites someone,
it must be held in isolation for 7-10 days.
• If the dog doesn’t develop signs and symptoms of
rabies within that time, it could not had been
infectious at the time of the bite.

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 Route of Transmission

Any mechanism by which The road of the pathogen

an infectious agent is spread from the source of infection to the host
from a source or reservoir in order to contaminate it and
to an other person. eventually produce a new disease.

These mechanisms are defined as follows:

• direct transmission
• indirect transmission
 Modes of transmission
Source of Infection of pathogens

route of transmission
route of transmission
DIRECT
INDIRECT
no intermediary
transmission factors in the presence
or absence of
SKIN-to-SKIN the source of infection
KISS
SEX
TRANSPLACENTAL SIMPLE
AT BIRTH
BREASTFEEDING WATER COMPLEX
BITE AIR
SOIL SOIL + WATER
contaminated SOIL + FOOD
FOOD
body fluids are FAECAL- ORAL
frequently involved OBJECTS
HAND
BLOOD VECTORS
SALIVA
SPERM
Susceptible
host
 Direct Transmission

Direct and essentially immediate transfer

of infectious agent to a receptive portal of entry
through which, human or animal infection may take place.

This may be
• direct contact such as
 touching
 kissing
 biting (insects or rabid animal)
 sexual intercourse

• direct projection of droplets spray (droplets spread )

onto the conjunctiva or
onto the mucous membranes of the nose, or mouth.

• transplacental transmission is another form of direct transmission.

6/2/2018 Last J. A dictionary of epidemiology. 2001

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 Indirect Transmission
Vehicle – borne

• Contaminated inanimate material or objects (fomites) such as

 toys
 handkerchiefs
 soiled cloths
 bedding
 cooking or eating utensils
 surgical instruments or dressing (indirect contact);
• water
• food
• soil
• hands
may or may not

have multiplied or developed

The agent
in or on the vehicle

before being transmitted.

6/2/2018 Last J. A dictionary of epidemiology. 2001
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 Vector - borne

A vector is an invertebrate animal (typically insects or arthropods)

that becomes infected from infected animals or persons and
transmits the infection to other persons.
e.g. the Anopheles mosquitoes that transmit malaria
parasites from person to person.
 Mechanical carriage
 Biological carriage

 Mechanical carriage

• includes simple mechanical carriage

• by a crawling or flying insect

• through soiling of its feet or proboscis, or

• by passage of organisms through its gastrointestinal tract.

This does not require multiplication or development of the organism.

6/2/2018 Last J. A dictionary of epidemiology. 2001. Krämer A., Kretzschmar M., Krickeberg K. Modern infectious disease. 2010
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  Biological carriage

• propagation (multiplication) this is required before

• cyclic development, or the arthropod can transmit
• a combination of these the infective form of the agent
(cyclo-propagative) to the man

An incubation period (extrinsic)

is required following infection
before the arthropod becomes infective.

passed vertically to succeeding generations

(trans-ovarian transmission) or
The infectious agent
may be
trans-stadial transmitted that is its passage
from one stage of the life cycle to another,
(as nymph to adult)

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 Transmission may be

• by saliva during biting or

• by regurgitation or
• by depositions on the skin
of faeces or other material
 capable of penetrating subsequently
 through the bite wound or
 through an area of trauma from scratching or rubbing.

Transmission may be differentiated from simple mechanical

by an infected carriage by a vector
non-vertebrate in the role of the
host for vehicle.
epidemiologic purposes

An arthropod in either role is termed a vector.

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Flea 39
Mosquito
 Airborne

The dissemination of
microbial aerosols to a
portal of entry, usually
the respiratory tract.

Microbial aerosols are suspensions in the air

of particles consisting partially or wholly of
microorganisms.

Particles in the 1-5 µ range

are easily drawn into
the alveoli of the lungs
and may retained there.

They may remain suspended in the air for long periods.

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 indirect transmission
direct transmission

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 Airborne transmission includes:

Droplet nuclei

Droplet nuclei are a type of particles implicated

in the spread of airborne infection.

Droplet nuclei are tiny particles (1-5 µ diameter) that represent the
dried residues that result from evaporation of fluid from droplets
emitted by an infected host.

They may be formed by

1) evaporation of droplets coughed or sneezed into the air or
2) aerosolization of infective materials.
• created purposely by a variety of atomizing devices, or
• accidentally, as
 in microbiology laboratories
 in abattoirs
 rendering plants
 autopsy rooms
They usually remain suspended in the air for long periods.
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 Airborne transmission includes:

Dust

• the small particles of widely varying size

Aspergillus
• that may arise from
 soil (fungus spores)
 clothes,
 bedding,
 contaminated floors

Dust mites

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 Portal of entry

It is the place an infectious agent enters a susceptible host.

The portal of entry is usually the same as the portal of exit from the host.

E.g.
Measles virus exits the respiratory tract of the host (source) and enters the
respiratory tract of the new host (a susceptible one).

In the case of gastrointestinal infections the infectious agent is located in faeces and
can be carried to the mouth of the new host by improperly washed hands.

Other portals of entry are :

• the skin (e.g. schistosomes),
• the mucus membrane (sexually transmitted infections),
• the blood (HIV)
• the transplacental mode of entry (toxoplasmosis).

Krämer A., Kretzschmar M., Krickeberg K. Modern infectious disease. 2010

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 Portal of entry

• measles
1 portal • whooping cough
of entry • influenza
• typhoid fever

2 portals Poliomyelitis Brucellosis

There are of entry • respiratory • digestive
diseases • principal
• accessory
• digestive • cutaneous
with

Anthrax
3 portals
• respiratory
of entry
• digestive
• cutaneous

 some microorganisms are  other microorganisms cause different diseases

pathogenic when enter on depending on the portal of entry
a specific portal of entry  group A streptococci  tonsils  tonsillitis
 digestive diseases  skin  erysipelas
 Transmission Mechanism

 Specific epidemiological localisation of the microorganism

in the Source of Infection

 Portal of Exit

 Route of transmission

 Portal of Entry
• the level at which the infectious agent approach
the host body at the end of transmission

 Portal of penetration
• the level at which the infectious agent approach
the target organ of the recipient organism for which
has elective tropism

Portal of entry could be the same as portal of penetration.

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 Transmission Mechanism

Portal Portal
of exit of entry

Susceptible
Source of
host
infection

Route of
transmission
Specific Portal of
epidemiological penetration
localisation

Portal of entry could be the same as portal of penetration.

 Susceptible host

The final link in the chain of infection is a susceptible host.

 Susceptibility of a host depends on

• genetic or constitutional factors

that affect an individual’s ability
• specific immunity to resist infection or
to limit pathogenicity.
• nonspecific factors

The individual’s genetic factors may either increase or decrease susceptibility.

E.g.,
• persons with sickle cell trait seem to be at least partially protected from a
particular type of malaria.
• genes do seem to play a role:
 in the progression of HIV disease,
 perhaps in individuals’ susceptibility to meningococcal meningitis

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 Specific immunity

refers to protective antibodies that are directed against a specific agent.

Such antibodies
• may develop actively in response to
 infection (clinical or subclinical) – natural immunity
 vaccine – artificial immunity
• may be passively acquired
 by transplacental transfer from mother to fetus
 by injection of antitoxin or immune globulin.

Active immunity

• Vaccination confers protection of susceptible individuals from communicable disease

by administration of
• a living modified agent (as in yellow fever, measles, rubella),
• a suspension of killed organisms (as in whooping cough), or
• an inactivated toxin (as in tetanus or diphtheria).
• Receiving a vaccine the recipient responds by producing his own antibodies.
Active immunity usually lasts much longer, even for a lifetime.
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 Passive immunity
is the transfer of humoral immunity in the form of ready-made antibodies,
from one individual to another.
• Passive immunity can occur naturally,
 when maternal antibodies are transferred
 to the fetus through the placenta
• can also be induced artificially,
 when high levels of human (or horse) antibodies
 specific for a pathogen or toxin
 are transferred to non- immune individuals
• Passive immunization is used when there is
 a high risk of infection and
 insufficient time for the body
 to develop its own immune response, or
 to reduce the symptoms of ongoing or immunosuppressive diseases.

Passive immunity provides immediate protection,

but the body does not develop memory,
therefore the patient is at risk of being
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 Nonspecific mechanisms

 Innate factors that defend against infection include

• physical and chemical barriers, and normal flora

 the intact skin and mucous membranes,
 the gastric acid,
 the cilia in the respiratory tract,
 the cough reflex

• nonspecific immune response

 phagocytic cells, mediating cells, complement

 Factors that may increase susceptibility to infection

by disrupting host defenses include:
• malnutrition
• alcoholism that impairs the nonspecific
• disease immune response
• therapy

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 The Infectious Disease Spectrum

The impact of disease agents on human host populations is complex.

If a large number of individuals are equally exposed to an infectious agent,

they do not all respond in the same manner.

In fact, there may be a broad range of responses:

• Some do not become infected at all

• Some become infected but develop no symptoms

• Some become infected and develop mild or moderate symptoms

• Some become infected and develop severe symptoms

• Some die as a result of their infection

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 Capacity of Resistance
the agent of the host
to produce
disease

Variation in the
disease spectrum

Difficult to find out the

extent of transmission in
Many diseases
a particular population
look alike

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 The Infectious Disease Spectrum

 Part of this variation is due to the capacity of the agent to produce disease.

Infection of a healthy adult population with salmonella is likely to result in

mostly inapparent or mild cases, with only a few people with more severe
symptoms and very few deaths.

On the other end of the spectrum, infections with rabies almost always result
in severe illness and death.

 Part of the variation is due to differing levels of resistance of the hosts.

If measles is introduced into a highly immunized population, then most individuals

do not become infected.

If measles is introduced into an unimmunized, nutritionally deprived population,

the spectrum shifts toward severe symptoms and a high death rate.

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 The Infectious Disease Spectrum

 The existence of the infectious disease spectrum can make it challenging (difficult)
to find out the extent of transmission in a particular population.

Most cases with inapparent or mild symptoms will never be discovered or reported,
since these people will not seek health care.

So when moderate or severe cases are reported, they may represent

the “tip of the iceberg.”

 Another challenge is posed by the fact that many diseases look alike.
A variety of agents may produce essentially similar clinical syndromes.
E.g.
The signs and symptoms of tuberculosis, other mycobacteria, and histoplasmosis may
be the same.

However, effective treatment and control measures are very different for these three
diseases.

This is why laboratory identification of the specific disease agent is so important in

any epidemiological investigation.
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 Forms of Manifestation of the Epidemiological Process

Susceptible Hosts
- immunized
• small number of cases • naturally
SPORADIC • disseminated territorially • artificially
• at irregular intervals of time Sources of Infection
• no apparent connection - small number
Routes of Transmission
- limited

Susceptible Hosts
• moderate incidence of cases - moderate number
• constant presence in the area Sources of Infection
• no apparent connection - small number
ENDEMIC • aspect Routes of Transmission
 sporadic or - limited
 small outbreaks Contributory Factors
• disappears if the cause is suppressed - present, maintain
Hyperendemic refers to persistent, high levels of Agents
disease occurrence. - low aggressiveness
CDC. Principles of Epidemiology in Public Health Practice , 3th Edition . 2012
 Susceptible hosts
• many cases, often sudden - high, > 80%
• incidence above what is Sources of Infection
normally expected - many
EPIDEMIC  in that population Routes of Transmission
 in that area or community - optimal
• variable time period Contributory factors
 Waterborne epidemic – modified environment
 Food-borne epidemic Agents
 Contact epidemic – imbalance host - agent

Susceptible hosts
- most people
• an epidemic Sources of Infection
• usually affecting a large number of people - many, mobile
PANDEMIC • spread over a large geographical area, Routes of Transmission
several countries or continents - optimal
• varying time period Contributory factors
– present
Agents
– new, reappear
 The question might be asked !
How many cases are required before a disease outbreak is considered
an epidemic
— 10 cases ?
— 100 cases ?
— 1,000 cases ?

The answer is that it depends upon the disease and the population,
• but any unexpectedly large number of cases of
 an illness,
 specific health-related behavior, or
 other health-related event
• in a particular population
• at a particular time and place

can be considered an epidemic.

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Jones & Bartlett. Epidemiology learning.
 Epidemics occur when :
 an agent and susceptible hosts are present in adequate numbers, and
 the agent can be effectively conveyed from a source to the susceptible hosts

More specifically, an epidemic may result from:

• a recent increase in amount or virulence of the agent,

• the recent introduction of the agent into a setting where it has not been before,

• an enhanced mode of transmission so that more susceptible persons are exposed,

• a change in the susceptibility of the host response to the agent, and/or

• factors that increase host exposure or involve introduction through new portals of
entry.

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CDC. Principles of Epidemiology in Public Health Practice , 3th Edition . 2012
 Host to host

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 George W. Comstock
American epidemiologist
1915 - 2007

“The art of epidemiological reasoning

is to make some reasonable conclusions

starting from imperfect data”.