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

History of EpidemiologyHistory 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.)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 EPIDEMIOLOGYROOTS OF MODERN EPIDEMIOLOGY

1. ACUTE DISEASE INVESTIGATION----- Emphasis on empirical systematic

investigation, biology, and environment/host manipulation

2. MEDICINE----- All early epidemiologists were

physicians.


3. STATISTICS----- Emphasis on the scientific method,

quantification and measurement,and hypothesis testing. In 1960s, manyepidemiologists were statisticians.

4. SOCIAL SCIENCES----- Investigation of human behavior in

relation to disease, and methods ofdata collection (surveys, etc.)


5. COMPUTER SCIENCES----- Emergence of “chronic” disease

epidemiology required the ability tohandle large amounts of data and toperform complex analyses.

6. MANAGERIAL SCIENCES----- Management principles for acquisition

of grants, research collaboration, and management of clinical trials.


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 Levels of Inference from Epidemiologic Evidence, and Attendant ConcernsEvidence, 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

NoneRelations between operational measurements among study measurements

REQUIREMENTSINFERENCE

Levels of Inference from Epidemiologic Levels of Inference from Epidemiologic Evidence, and Attendant ConcernsEvidence, 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

REQUIREMENTSINFERENCE

EVOLVING FIELD OF EPIDEMIOLOGYEVOLVING 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 heart248

Malignant neoplasms196

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 ChildrenIn 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)



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


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)



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 EPIDEMIOLOGYEVOLVING 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 3Discussion 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?


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 ISSUESPRACTICAL 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 ISSUESPRACTICAL 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”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.

ETHICSETHICS 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.

HIPAAHIPAA

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 ISSUESSOME 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?


What are the important criteria that

IRBs consider in approving human

research studies?


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 INTERACTIONTHE 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 INTERACTIONTHE HOST - ENVIRONMENT INTERACTION

“Virtually all chronic diseases have multi-factorialetiologies” -- 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 diseaseNatural history of disease

Stage ofsusceptibility

Stage of subclinical

disease

Stage of clinical disease

Stage of recovery,

disability or death

PRIMARY PRIMARY PREVENTIONPREVENTION SECONDARY SECONDARY

PREVENTIONPREVENTION TERTIARY TERTIARY PREVENTIONPREVENTION

Exposure

Pathologicchanges

Onset of symptoms

Usual time of diagnosis

The natural history of diseaseThe 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 diseaseThe natural history of disease (cont’d) (cont’d)

STAGE 2: Presymptomatic disease

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

clinically detectable

EXAMPLE: Alveoli deteriorate


STAGE 3: Clinical Disease

DESCRIPTION: Detectable signs and/or symptoms of disease exist

EXAMPLE: Emphysema detected by pulmonary function test


STAGE 4: Disability

DESCRIPTION: Disease has progressed to the point of causing a

residual effect

EXAMPLE: Person has difficulty breathing

LEVELS OF PREVENTIONLEVELS 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 PREVENTIONLEVELS OF PREVENTION (cont’d) (cont’d)

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 PREVENTIONLEVELS OF PREVENTION (cont’d) (cont’d)

LEVEL: Tertiary

DESCRIPTION: Rehabilitation and prevention of further

disease or disability

EXAMPLE: Oxygen therapy; facilitating ambulation with technical devices

PREVENTION APPROACHESPREVENTION 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 APPROACHESPREVENTION 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)LEVELS OF PREVENTION (Review)

PRIMARY PREVENTIONPRIMARY PREVENTIONPrevention 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)


SECONDARY PREVENTIONSECONDARY PREVENTION

Reduction in complications of disease

(e.g., MV crashes and ICU)


TERTIARY PREVENTIONTERTIARY PREVENTION

Documents

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