Transcript History of Epidemiology HIPPOCRATES (400 BC): “On Airs, Waters, and Places” –Hypothesized that disease might be associated with the physical environment, including seasonal variation.

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” “geneenvironment” interactions, and
“gene-gene” interactions.
Levels of Inference from Epidemiologic
Evidence, and Attendant Concerns
Epidemiology provides varying levels of information:
INFERENCE
Relations between operational
measurements among study
measurements
Association between measured
exposure and disease among
study participants
Causal effect of exposure on
disease in the study population
REQUIREMENTS
None
Accurate measurement
of both exposure and
disease
Freedom from
“confounding”
Levels of Inference from Epidemiologic
Evidence, and Attendant Concerns
Epidemiology provides varying levels of information:
INFERENCE
REQUIREMENTS
Causal effect of exposure
on disease in external
populations
Generalizability
(external validity)
Prevention of disease
through elimination or
reduction of exposure
Amenability of
exposure to
modification
Substantial public health
impact from elimination or
reduction of exposure
Large “attributable
fraction”
EVOLVING FIELD OF EPIDEMIOLOGY
Chief Causes of Death in the U.S. -- 1900







Pneumonia/Influenza
Tuberculosis
Gastritis, enteritis, colitis
Heart disease
Senility, ill-defined conditions
Vascular lesions affecting CNS
Nephritis and renal sclerosis
11.8%
11.3%
8.3%
8.0%
6.8%
6.2%
4.7%
Chief Causes of Death in the U.S. -- 2001*
 Disease of heart






Malignant neoplasms
Cerebrovascular diseases
Chronic lower respiratory diseases
Unintentional injuries
Diabetes mellitus
Pneumonia & influenza
*Age-adjusted per 100,000
248
196
58
44
36
25
22
Leading Causes of Death in Children
In Developing Countries -- 2002
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
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 individual’s health
information is properly protected, while
allowing the flow of health information needed
to promote high-quality health care and to
protect the public’s 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
ANKYLOSING SPONDYLITIS
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)

THE HOST - ENVIRONMENT INTERACTION
“Virtually all chronic diseases have multi-factorial
etiologies” -- many may have infectious components.
Enteroviruses
Epstein Barr virus
Chlamydia pneumoniae
Helicobacter pylori
Hepatitis B and C
Borna disease virus
Type I diabetes
B-cell lymphomas
Heart disease
Peptic ulcers
Liver cancer
Schizophrenia
Natural history of disease
Exposure
Onset of
symptoms
Usual time of
diagnosis
Pathologic
changes
Stage of
susceptibility
PRIMARY
PREVENTION
Stage of
subclinical
disease
SECONDARY
PREVENTION
Stage of
clinical
disease
Stage of
recovery,
disability or
death
TERTIARY
PREVENTION
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
(cont’d)
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
(cont’d)
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
(cont’d)
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
(cont’d)
LEVEL:
DESCRIPTION:
Secondary
EXAMPLE:
Routine pulmonary
function tests for those at
risk; medicine to help
patients breath more
easily; smoking cessation
programs if patient
smokes
Early detection and
timely treatment
LEVELS OF PREVENTION
(cont’d)
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)
LEVELS OF PREVENTION (Review)
SECONDARY PREVENTION
Reduction in consequences of disease
by early diagnosis and treatment
(e.g., cervical cancer screening)
LEVELS OF PREVENTION (Review)
TERTIARY PREVENTION
Reduction in complications of disease
(e.g., MV crashes and ICU)