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Epidemiologic Investigation
Sukon Kanchanaraksa, PhD Johns Hopkins University

Section A
Objectives of Epidemiology

Insatiable Curiosity

I Keep six honest serving-men: (They taught me all I knew) Their names are What and Where and When And How and Why and Who. Rudyard Kipling (18651936)

Source: The Elephants Child in Just So Stories by Rudyard Kipling Photo source: http://www.online-literature.com/kipling. Public Domain

Epidemiology as a Science and a Method

Epi = upon, among Demos = people Ology = science, study of Epidemiology = the science or the study of epidemic It is the scientific method of disease investigation Typically, it involves the disciplines of biostatistics and medicine

John Snow (18131858)

An English physician and modern-day father of epidemiology He used scientific methods to identify the cause of the epidemic of cholera in London in 1854 He believed that it was the water pump on Broad Street that was responsible for the disease The removal of the pump handle ended the outbreak

Photo source of two color images: Sukon Kanchanaraksa Photo source of portrait: http://www.ph.ucla.edu/epi/snow/fatherofepidemiology.html. Public Domain

A Definition of Epidemiology
The study of distribution and determinants of health, disease, or injury in human populations and the application of this study to the control of health problems

Types of Epidemiology
Distribution Frequency of health events By person, time and place Determinants Search for causes or risk factors Response to a study hypothesis Use various epidemiologic methods Descriptive epidemiology Analytic epidemiology

Types of Epidemiology
Distribution Descriptive epidemiology Frequency of health events By person, time and place Analytic Determinants epidemiology Search for causes or risk factors Response to a study hypothesis Use various epidemiologic methods Disease-specific Health, disease, or injury epidemiology All health outcomes Application Applied epidemiology

Objectives of Epidemiology
Investigate the etiology of disease and modes of transmission Determine the extent of disease problems in the community Study the natural history and prognosis of disease Evaluate both existing and new preventive and therapeutic measures and modes of health care delivery Provide a foundation for developing public policy and regulatory decisions

Source: Gordis, Epidemiology, 2004.

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U.S. Mortality, 2001

Rank Cause of Death 1 2 3 4 5 6 7 8 9 10 Heart Diseases Cancer Cerebrovascular diseases Chronic lower respiratory diseases Accidents (Unintentional injuries) Diabetes mellitus Influenza and Pneumonia Alzheimers disease Nephritis Septicemia No. of Death 700,142 553,768 163,538 123,013 101,537 71,372 62,034 53,852 39,480 32,238 % of all Deaths 29.0 22.9 6.8 5.1 4.2 3.0 2.6 2.2 1.6 1.3
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Source: US Mortality Public Use Data Tape 2001, National Center for Health Statistics, Centers for Disease Control and Prevention, 2003.

Estimated U.S. Cancer Deaths, 2004

Lung and bronchus Prostate Colon and rectum Pancreas Leukemia Non-Hodgkin lymphoma Esophagus Liver and intrahepatic bile duct Urinary bladder Kidney All other sites 32% 10% 10% 5% 5% 4% 4% 3% 3% 3% 21%
ONS=Other nervous system

Men 290,890

Women 272,810

25% 15% 10% 6% 6% 4% 3% 3% 2% 2% 24%

Lung and bronchus Breast Colon and rectum Ovary Pancreas Leukemia Non-Hodgkin lymphoma Uterine corpus Multiple myeloma Brain/ONS All other sites

Source: American Cancer Society, 2004

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Trends in Obesity
45 40 35 31 Prevalence (%) 30 25 20 15 10 5 0
Both sexes NHES I (1960-62) NHANES I (1971-74) Men NHANES II (1976-80) NHANES III (1988-94) Women NHANES 1999-2000

Prevalence (%) of Obesity in Adults Aged 20 to 74 by Gender, U.S. 19602000

34 28 26 23 21 15 13 15 11 17 16 17 12 13

*Obesity is defined as a body mass index of 30 kg/m2 or greater.

Source: National Health Examination Survey 1960-1962, National Health and Nutrition Examination Survey, 1971-1974, 1976-1980, 1988-1994, 1999-2000, National Center for Health Statistics, Centers for Disease Control and Prevention, 2002.

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What Is it? (Prion, Virus, Bacteria)

Prion: http://en.wikipedia.org/wiki/Image:Prion.gif. Public Domain. HIV: http://commons.wikimedia.org/wiki/Image:800px-HIV_Viron.png. Public Domain. "Bacterial Cell Structure" from Epidemiology of Infectious Diseases. Available at: http://ocw.jhsph.edu. Copyright Johns Hopkins Bloomberg School of Public Health. Creative Commons BY-NC-SA.

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Mysterious Virus in the Four Corners Region of U.S.

An outbreak of sudden respiratory illness occurred in the Four Corners region of the southwestern U.S. in 1993 In similar outbreaks in 1918 and 1936, there was an increase in the number of mice in the region due to the abundance of pi-on nuts (food for rodents) brought on by increased rainfall Epidemiologic study confirmed the connection between rodents and households with sick occupants

http://www.amnh.org/exhibitions/epidemic/section_02/sectwo_pg_02.html http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/generalinfoindex.htm Wood Mouse by Andy Field. Creative Commons BY-NC-SA.

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Mysterious Virus in the Four Corners Region of U.S.

Hanta virus was discovered in rodents that excreted the virus in their feces and urine People inhaled the dust particles that contained the virus and became ill (hantavirus pulmonary syndrome) To prevent the spread of the virus: Mice-proof the home Wear a mask while sweeping in the home Wash the floor with an antiseptic solution
http://www.amnh.org/exhibitions/epidemic/section_02/sectwo_pg_02.html http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/generalinfoindex.htm Wood Mouse by Andy Field. Creative Commons BY-NC-SA.

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Epidemiology and Radon

Lung Cancer Mortality Colorado Plateau Uranium Miners Follow-up Date 1959 1962 1967 1974 1977 Mortality Relative Risk 2.0 3.6 6.2 4.8 4.8

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Epidemiology and Radon as Treatment

patients seeking a natural arthritis cure visit modern radon therapy clinics and underground galleries for the sole purpose of radon inhalation or radon balneology Clinical, double-blind and randomized controlled studies in those countries report findings substantiating claims of pain and symptom relief, supporting the observations of benefit equal to that reported by visitors to the Free Enterprise Radon Health Mine located at Boulder, Montana

http://www.radonmine.com/why.html

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Epidemiology and Polio Vaccine

The year 2005 commemorated the 50th anniversary of the announcement that the Salk polio vaccine was effective In April, 1955, Dr. Thomas Francis, director of Poliomyelitis Vaccine Evaluation Center at the University of Michigan, announced that the two-year field trial of the Salk vaccine against polio was up to 90% effective The results announced by Francis effectively marked the beginning of the end of polio as the most life-threatening and debilitating public health threat to the children of the United States

http://www.umich.edu/%7Ebhl/bhl/digpubs/polio/guideintro.htm http://www.med.umich.edu/medschool/chm/polioexhibit/salk_report.htm http://www.med.umich.edu/medschool/chm/polioexhibit/press_release.htm Image: http://en.wikipedia.org/wiki/Image:Iron_Lung_ward-Rancho_Los_Amigos_Hospital.gif. Public Domain.

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Uses of Epidemiology
In historical study of health and diseases in the population and in projecting into the future For community diagnosis of the presence, nature and distribution of health and diseases among the population To study the working of health services To estimate the individuals chances and risks of disease To help complete the clinical picture of diseases In identifying syndromes from the distribution of clinical phenomena among sections of the population In the search for causes of health and disease

Source: Morris, JN. Uses of Epidemiology. 1957.

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Review Questions
What is epidemiology? Choose a disease that is of interest to you Describe the disease by time, place, and person

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Section B
Dynamics of Disease Transmission

Describing a Disease: Epidemiologic Triad

Host

Vector Agent Environment

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Factors Associated with Increased Risk of Human Disease

HOST (Intrinsic) Age Gender Ethnicity Religion Customs Occupation Heredity Marital status Family background Previous diseases AGENTS Biological (bacteria, etc.) Chemical (poison, alcohol, smoke) Physical (auto, radiation, fire) Nutritional (lack, excess) ENVIRONMENT (Extrinsic) Temperature Humidity Altitude Crowding Housing Neighborhood Water Milk Food Radiation Air pollution Noise
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Dynamics of Disease Transmission

Interaction of agents and environmental factors with human hosts Distribution of severity of disease Modes of disease transmission Level of disease in a community when transmission stops

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The Iceberg Concept of Infectious Diseases

(At the level of the cell and of the host )
Cell response Lysis of cell Inclusion body formation or Cell transformation or Cell dysfunction Viral multiplication Without visible change or incomplete Viral maturation Exposure without attachment and/or cell entry
Source: Evans, 1991

Host response Death of organism Classical and severe disease Moderate severity Mild illness Infection without Clinical illness (asymptomatic infection) Exposure without infection
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Distribution of Clinical Severity for Three Infections

(not drawn to scale) Class A: unapparent infection frequent
Example: tubercle bacillus
0 100

Percentage of infections

Class B: clinical disease frequent; few deaths

Example: measles virus
0 Percentage of infections 100

Class C: infections usually fatal

Example: rabies virus
0 100

Unapparent

Mild

Moderate

Severe (nonfatal)

Fatal

Source: Mausner and Kramer, 1985 p.265

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Unapparent Infection
Preclinical disease: in the early stage of disease progression, disease is not clinically detected but is destined to become clinical disease Subclinical disease: disease is not detected but the host carries the organism or has antibody response. A well known example is the typhoid disease outbreaks in New York City in the early 1900s. Typhoid Mary (Mary Mallon) was a healthy carrier of Salmonella typhi; she continued to work as a cook and infected numerous people until she was quarantined for life against her will.
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Source: http://www.pbs.org/wgbh/nova/typhoid/

Pathway of Disease Infection

Infected host (or reservoir) Portal of exit

Modes of transmission

Portal of entry Susceptible host

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Portals of Exit and Entry

Mims CA, Dimmock NJ, Nash A, et al. Mims Pathogenesis of Infectious Disease, ed 4. London, 1995. p. 10

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Transmission of Agents
Direct contact (person-to-person) Skin, saliva via kissing, sexual contact, aerosol from sneezing or coughing Polio, hepatitis, HIV, influenza Indirect contact Via vector (an organism that carries disease-causing micro-organisms, such as mosquito), dust particles, air, food, water, blood, tissues, organs, fomites (inanimate objects that can carry disease-causing micro-organismse.g., toothbrush, cutting board, toys, etc. ) Diseases that are commonly spread by means of fomites include the common cold, cold sores, conjunctivitis, coxsackievirus (hand-footmouth disease), croup, E. coli infection, Giardia infection, influenza, lice, meningitis, rotavirus diarrhea, RSV, and strep

Source: http://tos.beastlet.com/gallerym3.html

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Transmission of Agents from Mother to Child

Vertical transmission (inter-generation) is the transmission of disease-causing agents from mother directly to baby Just before or just after birth Via placenta or breast milk Horizontal transmission: all other transmissions Diseases that can be transmitted from mother to baby include: HIV Hepatitis C

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SARS (Severe Acute Respiratory Syndrome)

Spreads by direct contact (person to person) from droplets from cough or sneeze (short distance) Droplets enter via the mucous membranes of the mouth, nose, or eyes Can also spread by indirect contact when the person touches contaminated objects and then touches his or her mouth, nose, or eyes

http://www.cdc.gov/niosh/topics/SARS/. Public Domain.

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Frequency of Exposure in Indirect Contact

Multiple Exposure

Single Exposure

Continuous Exposure

Common vehicle single exposure

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Common Vehicle Single Exposure

Group of individuals exposed to a common vehicle (food, water, air, etc.) The exposure was one time (for example, the food was served only once) Typical characteristic Explosive (abrupt) increase in the number of diseased individuals and then the number declines gradually over time Examples: food-borne outbreak at school, church, or on a cruise ship

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Quick Check: SARS Virus

SARS virus is known to be transmitted via aerosol spread from coughing. On March 15, 2003, a Boeing 737-300 carrying 120 persons flew for three hours from Hong Kong to Beijing. An individual with SARS was on board. Eighteen people were believed to contract the disease on the flight. Was this a common vehicle single exposure outbreak?

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Definition of Endemic, Epidemic, and Pandemic

Endemic The habitual presence of a disease within a given geographic area May also refer to the usual prevalence of a given disease within such an area (APHA) Epidemic The occurrence in a community or region of a group of illnesses of similar nature, clearly in excess of normal expectancy (APHA) Outbreak Pandemic A worldwide epidemic Endemic

Epidemic Time
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London Smog Disaster, 1952

Air pollution causes respiratory illnesses and death When fog and soot from coal burning created a dense smog in Winter, 1952, in London, the smog was around for five days fromDecember 510, 1952 There was a substantial increase in mortality Estimated premature death of 12,000 The death rate in London in the previous week was around 2,062 In the week of the smog, 4,703 died

AP

Source: NPR, http://www.npr.org/templates/story/story.php?storyId=873954

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Deaths in Greater London Each Day

From December 115, 1952

"1952 London Fog. High levels of pollution correspond to a similar pattern in daily mortality." from Biostatistics Lecture Series . Available at: http://ocw.jhsph.edu. Copyright Johns Hopkins Bloomberg School of Public Health. Creative Commons BY-NC-SA.

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Herd Immunity and Disease Transmission

In a population, disease transmission may stop before all susceptible individuals are infected Herd immunity is the resistance of a group to attack from a disease to which a large portion of members are immune, thus lessening the likelihood of a patient with a disease coming into contact with a susceptible individual

Immune Susceptible Diseased

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Some Requirements of Herd Immunity

The disease agent is restricted to a single-host species within which transmission occurs For example, smallpox in human; no reservoir There is relatively direct transmission from one member of the host species to another (direct contact only) Infections must induce solid immunity (also from immunization)

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Herd Immunity and Disease Control

The success of herd immunity in controlling the disease depends on the proportion of subjects with immunity in a population Immunity can be from immunization or infection So, when the population is immunized (e.g. ,vaccinated) at or above the herd immunity level (critical immunization threshold), the infectious disease will not spread and will be eliminated Herd immunity level differs for various diseases For example, it is estimated that 94% of the population must be immune before measles can be controlled For mumps, it is around 90% The more infectious the disease is, the higher the herd immunity level
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Review
What is the epidemiologic triad of disease transmission? How is preclinical disease different from subclinical disease? Distinguish direct from indirect contact Distinguish horizontal from vertical disease transmission Explain the iceberg concept of disease transmission Distinguish endemic, epidemic, and pandemic diseases from each other What is the concept of herd immunity in disease transmission?

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Section D
Investigation of an Outbreak

Importance of Outbreak Investigation

Stop the current outbreak from spreading Prevent future similar outbreaks Provide scientific explanation of the event Provide knowledge for the understanding of the disease process React to and calm public and political concerns Train epidemiologists

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Investigating an Outbreak
I Keep six honest serving-men: (They taught me all I knew) Their names are What and Where and When And How and Why and Who. Rudyard Kipling (18651936) Define what will be studied Find out where the problem is Who gets it When it is occurring Try to explain why the problem has such a distribution Do specific studies to find out how the problem is occurring
Source: The Elephants Child in Just So Stories by Rudyard Kipling Photo source: http://www.online-literature.com/kipling. Public Domain

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Common Steps in the Epidemiologic Approach

The steps in the epidemiologic approach to study a problem of disease etiology are: Perform an initial observation to confirm the outbreak Define the disease Describe the disease by time, place, and person Create a hypothesis as to the possible etiologic factors Conduct analytic studies Summarize the findings Recommend and communicate the interventions or preventative programs

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Steps
Conduct field work Perform initial observation Establish the existence of an outbreak Verify diagnosis Collect data Define disease Establish case definition Identify all cases Identify the population at risk Describe disease by time, place, and person Plot epidemic curve Plot spot map Tabulate data of exposure and other characteristics
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Steps
Develop hypothesis Hypothesis: exposure to X is associated with disease Y Conduct analytic studies Use appropriate analytic studies Calculate measures of risk Refine hypothesis Conduct additional studies if needed Summarize findings Recommend and communicate interventions or preventative programs

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Exercise
Foodborne Outbreak Following a Charity Luncheon (Initial observation has been conducted) Line listing of data in Excel Summary data from Stata Define disease and population at risk Describe disease (by time, place, and person), plot epidemic curves Develop hypothesis Analyze data (test hypothesis) by calculating attack rates and comparing attack rates in various subgroups Summarize findings Recommend interventions and preventative programs

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Submit A Case Study

The instructors of this course are using WikiEducator to collect case studies to illustrate different types of epidemiologic investigations. The instructors are particularly interested in studies conducted in Western Asia and the Arabian Peninsula, and they are looking to OCW users to help them find the best examples. Click here to visit WikiEducator and submit a case study by editing the wiki page. Registration is required to submit a case study.

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