History of Epidemiology

HIPPOCRATES (400 BC): On Airs, Waters, and

Places Hypothesized that disease might be
associated with the physical environment,
including seasonal variation in illness.

JOHN GRAUNT (1662): Nature and Political
Observations Made Upon the Bills of
Mortality First to employ quantitative
methods in describing population vital
statistics.

JOHN SNOW (1850): Formulated natural
epidemiological experiment to test the
hypothesis that cholera was transmitted by
contaminated water.
History of Epidemiology (cont.)
DOLL & HILL (1950): Used a case-control
design to describe and test the association
between smoking and lung cancer.

FRANCES at al. (1950): Huge formal field trial
of the Poliomyelitis vaccine in school
children.

DAWBER et al. (1955): Used the cohort
design to study risk factors for
cardiovascular disease in the Framingham
Heart Study.
ROOTS OF MODERN EPIDEMIOLOGY
1. ACUTE DISEASE INVESTIGATION
----- Emphasis on empirical systematic
investigation, biology, and
environment/host manipulation
2. MEDICINE
----- All early epidemiologists were
physicians.
ROOTS OF MODERN EPIDEMIOLOGY
3. STATISTICS
----- Emphasis on the scientific method,
quantification and measurement,
and hypothesis testing. In 1960s, many
epidemiologists were statisticians.
4. SOCIAL SCIENCES
----- Investigation of human behavior in
relation to disease, and methods of
data collection (surveys, etc.)
ROOTS OF MODERN EPIDEMIOLOGY
5. COMPUTER SCIENCES
----- Emergence of chronic disease
epidemiology required the ability to
handle large amounts of data and to
perform complex analyses.
6. MANAGERIAL SCIENCES
----- Management principles for acquisition
of grants, research collaboration, and
management of clinical trials.
ROOTS OF MODERN EPIDEMIOLOGY
7. GENOMICS
----- 2001 marked first publication of
draft sequences of the human
genome. Intensive investigations being
conducted to identify disease
susceptibility genes gene-
environment interactions, and
gene-gene interactions.
Levels of Inference from Epidemiologic
Evidence, and Attendant Concerns
Epidemiology provides varying levels of information:
Freedom from
confounding
Causal effect of exposure on
disease in the study population
Accurate measurement
of both exposure and
disease
Association between measured
exposure and disease among
study participants

None
Relations between operational
measurements among study
measurements

REQUIREMENTS
INFERENCE
Levels of Inference from Epidemiologic
Evidence, and Attendant Concerns
Epidemiology provides varying levels of information:
Large attributable
fraction
Substantial public health
impact from elimination or
reduction of exposure
Amenability of
exposure to
modification

Prevention of disease
through elimination or
reduction of exposure

Generalizability
(external validity)
Causal effect of exposure
on disease in external
populations

REQUIREMENTS INFERENCE
EVOLVING FIELD OF EPIDEMIOLOGY
Pneumonia/Influenza 11.8%
Tuberculosis 11.3%
Gastritis, enteritis, colitis 8.3%
Heart disease 8.0%
Senility, ill-defined conditions 6.8%
Vascular lesions affecting CNS 6.2%
Nephritis and renal sclerosis 4.7%
Chief Causes of Death in the U.S. -- 1900
Disease of heart 248
Malignant neoplasms 196
Cerebrovascular diseases 58
Chronic lower respiratory diseases 44
Unintentional injuries 36
Diabetes mellitus 25
Pneumonia & influenza 22

Chief Causes of Death in the U.S. -- 2001*
*Age-adjusted per 100,000
Cause of Death % of all Deaths
Perinatal conditions 23.1
Lower respiratory infections 18.1
Diarrhoeal diseases 15.2
Malaria 10.7
Measles 5.4
Congenital anomalies 3.8
HIV/AIDS 3.6
Pertussis 2.9
Other 17.2
Leading Causes of Death in Children
In Developing Countries -- 2002
Causes of Mortality Worldwide: 2002:
Ages 15 - 59
Cause Deaths (000)
HIV/AIDS 2279
Ischemic heart disease 1332
Tuberculosis 1036
Road traffic injuries 814
Cerebrovascular disease 783
Self-inflicted injuries 672
Violence 473
Causes of Mortality Worldwide: 2002:
Ages 60 and Older
Cause Deaths (000)
Ischemic heart disease 5825
Cerebrovascular disease 4689
COPD 2399
Lower respiratory infections 1396
Trachea, bronchus, lung cancers 928
Diabetes mellitus 754
Hypertensive heart disease 735
Stomach cancer 605
Causes of Disease Burden (DALYs)
Worldwide: 2002: Ages 15 - 59
Cause DALYs (000)
HIV/AIDS 68661
Unipolar depressive disorders 57843
Tuberculosis 28380
Road traffic injuries 27264
Ischemic heart disease 26155
Alcohol use disorders 19567
Hearing loss, adult onset 19486
Violence 18962
Causes of Disease Burden (DALYs)
Worldwide: 2002: Ages 60 and Older
Cause DALYs (000)
Ischemic heart disease 31481
Cerebrovascular disease 29595
COPD 14380
Alzheimers and other dementias 8569
Cataracts 7384
Lower respiratory infections 6597
Hearing loss, adult onset 6548
Trachea, bronchus, lung cancers 5952
EVOLVING FIELD OF EPIDEMIOLOGY
Historically, in developed countries,
there has been a marked shift in the
leading causes of mortality from
infectious to chronic diseases.
In the U.S. today, the fastest growing
segment of the population is aged 85
and older.
Virtually all chronic diseases have
multi-factorial etiologies.
Discussion Question 3
If a cure was found for heart
disease, how might this likely affect
mortality rates from: (1) AIDS; and
(2) Cancer in the United States?
Discussion Question 3
Most likely:
1. AIDS-related mortality would be largely
unaffected since most deaths from AIDS occur
in persons not at high risk (age) for heart
disease mortality.

2. Cancer mortality would increase since persons
who would have died from heart disease would
now be at risk of dying from cancer.

This concept of one cause of mortality affecting
another is know as competing risks.
PRACTICAL AND ETHICAL ISSUES
Measures of disease and exposure
occurrence are often not easy to
obtain.

Many diseases occur infrequently
in human populations.
PRACTICAL AND ETHICAL ISSUES
Unlike experimental science,
the investigator cannot
manipulate study variables
(i.e those hypothesized to be
causes of disease).

Investigator must deal with
budgetary and subject privacy
concerns.
EXAMPLES OF UNETHICAL RESEARCH
Criminal and unscientific behavior of physicians
in concentration camps in Nazi Germany led to
adoption of Nuremberg Code (1947).
1936 U.S. Public Health Service started study of
effects of untreated syphilis in Tuskegee, AL long
after effective treatment for the disease was
known.
1963- Jewish Chronic Diseases Hospital 22
elderly patients injected with cancer cells without
their knowledge to test immunological response.

Willowbrook State Hospital, NY: retarded children
deliberately infected with viral hepatitis to study
natural history.
ETHICS
1974: Congress established the National
Commission for the Protection of Human
Subjects of Biomedical and Behavioral
Research.

Requires the establishment of Institutional
Review Boards (IRBs) for all research funded
in whole or in part by the federal government.

1996: Health Insurance Portability and
Accountability Act (HIPAA): Privacy Rule
issued to assure that individuals health
information is properly protected, while
allowing the flow of health information needed
to promote high-quality health care and to
protect the publics health and well-being.
HIPAA
The HIPAA Privacy Rule protects individual
identifiable health information known as
protected health information transmitted or
maintained in any form or medium. Includes:
--- Demographic or other information relating
to past, current, or future physical or mental
health or condition of an individual
--- Provision or payment of health care to an
individual that is created or received by a
health care provider, health plan, employer, or
health care clearinghouse
--- Individual genetic information
SOME PROFESSIONAL AND ETHICAL ISSUES
Should informed consent be required for
routine review of medical records?

Who should have access to the study
data, and when?

How should study findings be
disseminated to the public?

Should epidemiologists be advocates for
specific public health policies?
Discussion Question 4
What are the important criteria that
IRBs consider in approving human
research studies?
Discussion Question 4
Criteria include:
1. Risks to study participants are minimized.
2. Risks are reasonable in relation to anticipated
benefits.
3. Selection of study participants is equitable.
4. Informed consent is obtained and
documented for each participant.
5. Adequate monitoring of data collection to
ensure the safety of study participants.
6. Privacy of participants and confidentiality of
data are protected.
THE HOST - ENVIRONMENT INTERACTION
Persons with HLA-B27 approximately
90 times more likely to develop the
disease (Genetic Susceptibility)
However, only 10% of the individuals
with HLA-B27 will develop the disease
(Environmental Exposure)

ANKYLOSING SPONDYLITIS
THE HOST - ENVIRONMENT INTERACTION
Virtually all chronic diseases have multi-factorial
etiologies -- many may have infectious components.
Enteroviruses Type I diabetes
Epstein Barr virus B-cell lymphomas
Chlamydia pneumoniae Heart disease
Helicobacter pylori Peptic ulcers
Hepatitis B and C Liver cancer
Borna disease virus Schizophrenia
Natural history of disease
Stage of
susceptibility
Stage of
subclinical
disease
Stage of
clinical
disease
Stage of
recovery,
disability or
death
PRIMARY
PREVENTION
SECONDARY
PREVENTION
TERTIARY
PREVENTION
Exposure
Pathologic
changes
Onset of
symptoms
Usual time of
diagnosis
The natural history of disease
STAGE 1: Susceptibility

DESCRIPTION: Risk factors which assist
the development of
disease exist, but disease
has not developed

EXAMPLE: Smoking
The natural history of disease
(contd)
STAGE 2: Presymptomatic disease

DESCRIPTION: Changes have occurred
to lead toward illness but
disease is not yet
clinically detectable

EXAMPLE: Alveoli deteriorate
The natural history of disease
(contd)
STAGE 3: Clinical Disease

DESCRIPTION: Detectable signs and/or
symptoms of disease exist

EXAMPLE: Emphysema detected by
pulmonary function test
The natural history of disease
(contd)
STAGE 4: Disability

DESCRIPTION: Disease has progressed to
the point of causing a
residual effect

EXAMPLE: Person has difficulty
breathing
LEVELS OF PREVENTION
LEVEL: Primary
DESCRIPTION: Promote general health
and avoid risk factors for
disease --- Utilize protective
measures to prevent
susceptibility and
presymptomatic disease
EXAMPLE: Stop smoking or choose
not to start; avoid areas
where people are smoking
LEVELS OF PREVENTION
(contd)
LEVEL: Secondary
DESCRIPTION: Early detection and
timely treatment
EXAMPLE: Routine pulmonary
function tests for those at
risk; medicine to help
patients breath more
easily; smoking cessation
programs if patient
smokes
LEVELS OF PREVENTION
(contd)
LEVEL: Tertiary

DESCRIPTION: Rehabilitation and
prevention of further
disease or disability

EXAMPLE: Oxygen therapy;
facilitating ambulation
with technical devices
PREVENTION APPROACHES
Population-Based Approach:
Preventive measure widely applied to
an entire population (public health
approach)

Strive for small absolute change
among many persons

Must be relatively inexpensive and
non-invasive

PREVENTION APPROACHES
High-Risk Approach:

Target group of individual at high risk

Strive for strong risk factor control

Often times requires clinical action to
identify the high risk group and to
motivate risk factor control.

LEVELS OF PREVENTION (Review)

PRIMARY PREVENTION
Prevention of disease by
controlling risk factors (e.g.,
non-smoking promotion)



Reduction in consequences of disease
by early diagnosis and treatment
(e.g., cervical cancer screening)


LEVELS OF PREVENTION (Review)

SECONDARY PREVENTION


Reduction in complications of disease
(e.g., MV crashes and ICU)
LEVELS OF PREVENTION (Review)

TERTIARY PREVENTION