1. 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.

2. 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.

3. 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.

4. 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.)

5. 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.

6. 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.

7. 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

8. 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 REQUIREMENTSINFERENCE

9. EVOLVING FIELD OF EPIDEMIOLOGY Pneumonia/Influenza11.8% l Tuberculosis11.3% l Gastritis, enteritis, colitis8.3% l Heart disease8.0% l Senility, ill-defined conditions 6.8% l Vascular lesions affecting CNS6.2% l Nephritis and renal sclerosis 4.7% Chief Causes of Death in the U.S. -- 1900

10. Disease of heart248 l Malignant neoplasms196 l Cerebrovascular diseases58 l Chronic lower respiratory diseases 44 l Unintentional injuries 36 l Diabetes mellitus25 l Pneumonia & influenza 22 Chief Causes of Death in the U.S. -- 2001* *Age-adjusted per 100,000

11. Cause of Death% of all Deaths l Perinatal conditions23.1 l Lower respiratory infections18.1 l Diarrhoeal diseases 15.2 l Malaria 10.7 l Measles 5.4 l Congenital anomalies 3.8 l HIV/AIDS 3.6 l Pertussis2.9 l Other17.2 Leading Causes of Death in Children In Developing Countries -- 2002

12. Causes of Mortality Worldwide: 2002: Ages 15 - 59 CauseDeaths (000) HIV/AIDS2279 Ischemic heart disease1332 Tuberculosis1036 Road traffic injuries814 Cerebrovascular disease783 Self-inflicted injuries672 Violence473

13. Causes of Mortality Worldwide: 2002: Ages 60 and Older CauseDeaths (000) Ischemic heart disease5825 Cerebrovascular disease4689 COPD2399 Lower respiratory infections1396 Trachea, bronchus, lung cancers928 Diabetes mellitus754 Hypertensive heart disease735 Stomach cancer605

14. Causes of Disease Burden (DALYs) Worldwide: 2002: Ages 15 - 59 CauseDALYs (000) HIV/AIDS68661 Unipolar depressive disorders57843 Tuberculosis28380 Road traffic injuries27264 Ischemic heart disease26155 Alcohol use disorders19567 Hearing loss, adult onset19486 Violence18962

15. Causes of Disease Burden (DALYs) Worldwide: 2002: Ages 60 and Older CauseDALYs (000) Ischemic heart disease31481 Cerebrovascular disease29595 COPD14380 Alzheimers and other dementias8569 Cataracts7384 Lower respiratory infections6597 Hearing loss, adult onset6548 Trachea, bronchus, lung cancers5952

16. EVOLVING FIELD OF EPIDEMIOLOGY l Historically, in developed countries, there has been a marked shift in the leading causes of mortality from “infectious” to “chronic” diseases. l In the U.S. today, the fastest growing segment of the population is aged 85 and older. l Virtually all “chronic” diseases have multi-factorial etiologies.

17. 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?

18. 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.”

19. PRACTICAL AND ETHICAL ISSUES l Measures of disease and exposure occurrence are often not easy to obtain. l Many diseases occur infrequently in human populations.

20. PRACTICAL AND ETHICAL ISSUES l Unlike experimental science, the investigator cannot manipulate study variables (i.e those hypothesized to be causes of disease). l Investigator must deal with budgetary and subject privacy concerns.

21. EXAMPLES OF UNETHICAL “RESEARCH” l Criminal and unscientific behavior of physicians in concentration camps in Nazi Germany – led to adoption of Nuremberg Code (1947). l 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. l 1963- Jewish Chronic Diseases Hospital – 22 elderly patients injected with cancer cells without their knowledge to test immunological response. l Willowbrook State Hospital, NY: retarded children deliberately infected with viral hepatitis to study natural history.

22. ETHICS l 1974: Congress established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. l Requires the establishment of Institutional Review Boards (IRBs) for all research funded in whole or in part by the federal government. l 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.

23. HIPAA l 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

24. SOME PROFESSIONAL AND ETHICAL ISSUES l Should informed consent be required for routine review of medical records? l Who should have access to the study data, and when? l How should study findings be disseminated to the public? l Should epidemiologists be advocates for specific public health policies?

25. Discussion Question 4 What are the important criteria that IRBs consider in approving human research studies?

26. 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.

27. THE HOST - ENVIRONMENT INTERACTION l Persons with HLA-B27 approximately 90 times more likely to develop the disease (Genetic Susceptibility) l However, only 10% of the individuals with HLA-B27 will develop the disease (Environmental Exposure) ANKYLOSING SPONDYLITIS

28. 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

29. 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

30. 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

31. 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

32. 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

33. 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

34. 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

35. LEVELS OF PREVENTION (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

36. LEVELS OF PREVENTION (cont’d) LEVEL: Tertiary DESCRIPTION: Rehabilitation and prevention of further disease or disability EXAMPLE: Oxygen therapy; facilitating ambulation with technical devices

37. 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

38. 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.

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

40. Reduction in consequences of disease by early diagnosis and treatment (e.g., cervical cancer screening) LEVELS OF PREVENTION (Review) SECONDARY PREVENTION

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