INTRODUCTION TO EPIDEMIOLOGY
Recently, a news story described an inner-city neighborhood’s concern about the rise in the number of children with asthma. Another story reported the revised recommendations for who should receive influenza vaccine this year. A third story discussed the extensive disease-monitoring
strategies being implemented in a city recently affected by a massive hurricane. A fourth story described a finding published in a leading
medical journal of an association in workers exposed to a particular chemical and an increased risk of cancer. Each of these news stories included interviews with public health officials or researchers who called themselves epidemiologists. Well, who are these epidemiologists, and what do they do? What is epidemiology? This lesson is intended to answer those questions by describing what epidemiology is, how it has evolved and how it is used today, and what some of the key methods and concepts are. The focus is on epidemiology in public health practice, that is, the kind of epidemiology that is done at health departments.
Objectives
After studying this lesson and answering the questions in the exercises, you will be able to:
•Define epidemiology
•Summarize the historical evolution of epidemiology
•Name some of the key uses of epidemiology
•Identify the core epidemiology functions
•Describe primary applications of epidemiology in public health practice
•Specify the elements of a case definition and state the effect of changing the value of any of the elements
•List the key features and uses of descriptive epidemiology
•List the key features and uses of analytic epidemiology
•List the three components of the epidemiologic triad
•Describe the different modes of transmission of communicable disease in a population
Major Sections
Definition of Epidemiology ......................................................................................................... 1-2
Historical Evolution of Epidemiology ......................................................................................... 1-7
Uses ............................................................................................................................................ 1-12
Core Epidemiologic Functions .................................................................................................. 1-15
The Epidemiologic Approach .................................................................................................... 1-21
Descriptive Epidemiology ......................................................................................................... 1-31
Analytic Epidemiology .............................................................................................................. 1-46
Concepts of Disease Occurrence ............................................................................................... 1-52
Natural History and Spectrum of Disease .................................................................................. 1-59
Chain of Infection ...................................................................................................................... 1-62
Epidemic Disease Occurrence ................................................................................................... 1-72 Summary .................................................................................................................................... 1-80
Students of journalism are taught that a good news story, whether it be about a bank robbery, dramatic rescue, or presidential candidate’s speech, must include the 5 W’s: what, who, where, when and why (sometimes cited as why/how). The 5 W’s are the essential components of a news story because if any of the five are missing, the story is incomplete.
The same is true in characterizing
Definition of Epidemiology
The word epidemiology comes from the Greek words epi, meaning on or upon, demos, meaning people, and logos, meaning the study of. In other words, the word epidemiology has its roots in the study of what befalls a population. Many definitions have been proposed, but the following definition captures the underlying principles and public health spirit of epidemiology:
Epidemiology is the study of the distribution and determinants of health-related states or events in specified populations, and the application of this study to the control of health problems.1
Key terms in this definition reflect some of the important principles of epidemiology.
epidemiologic events, whether it be an outbreak of norovirus among cruise ship passengers or the use of mammograms to detect early breast cancer. The difference is that epidemiologists tend to use synonyms for the 5 W’s: diagnosis or health event (what), person (who), place (where), time (when), and causes, risk factors, and modes of transmission (why/how).
Study
Epidemiology is a scientific discipline with sound methods of scientific inquiry at its foundation. Epidemiology is data-driven and relies on a systematic and unbiased approach to the collection, analysis, and interpretation of data. Basic epidemiologic methods tend to rely on careful observation and use of valid comparison groups to assess whether what was observed, such as the number of cases of disease in a particular area during a particular time period or the frequency of an exposure among persons with disease, differs from what might be expected. However, epidemiology also draws on methods from other scientific fields, including biostatistics and informatics, with biologic, economic, social, and behavioral sciences.
In fact, epidemiology is often described as the basic science of public health, and for good reason. First, epidemiology is a quantitative discipline that relies on a working knowledge of probability, statistics, and sound research methods. Second, epidemiology is a method of causal reasoning based on developing and testing hypotheses grounded in such scientific fields as biology, behavioral sciences, physics, and ergonomics to explain health-related behaviors, states, and events. However, epidemiology is not just a research activity but an integral component of public health, providing the foundation for directing practical and appropriate public health action based on this science and causal reasoning.2
Determinant: any factor, whether event, characteristic, or other definable entity, that brings about a change in a health condition or other defined characteristic.1
Distribution
Epidemiology is concerned with the frequency and pattern of health events in a population:
Frequency refers not only to the number of health events such as the number of cases of meningitis or diabetes in a population, but also to the relationship of that number to the size of the population. The resulting rate allows epidemiologists to compare disease occurrence across different populations.
Pattern refers to the occurrence of health-related events by time, place, and person. Time patterns may be annual, seasonal, weekly, daily, hourly, weekday versus weekend, or any other breakdown of time that may influence disease or injury occurrence. Place patterns include geographic variation, urban/rural differences, and location of work sites or schools. Personal characteristics include demographic factors which may be related to risk of illness, injury, or disability such as age, sex, marital status, and socioeconomic status, as well as behaviors and environmental exposures.
Characterizing health events by time, place, and person are activities of descriptive epidemiology, discussed in more detail later in this lesson.
Determinants
Epidemiology is also used to search for determinants, which are the causes and other factors that influence the occurrence of disease and other health-related events. Epidemiologists assume that illness does not occur randomly in a population, but happens only when the right accumulation of risk factors or determinants exists in an individual. To search for these determinants, epidemiologists use analytic epidemiology or epidemiologic studies to provide the “Why” and “How” of such events. They assess whether groups with different rates of disease differ in their demographic characteristics, genetic or immunologic make-up, behaviors, environmental exposures, or other so-called potential risk factors. Ideally, the findings provide sufficient evidence to direct prompt and effective public health control and prevention measures.
Health-related states or events
Epidemiology was originally focused exclusively on epidemics of communicable diseases3 but was subsequently expanded to address endemic communicable diseases and non-communicable infectious diseases. By the middle of the 20th Century, additional epidemiologic methods had been developed and applied to chronic diseases, injuries, birth defects, maternal-child health, occupational health, and environmental health. Then epidemiologists began to look at behaviors related to health and well-being, such as amount of exercise and seat belt use. Now, with the recent explosion in molecular methods, epidemiologists can make important strides in examining genetic markers of disease risk. Indeed, the term healthrelated states or events may be seen as anything that affects the well-being of a population. Nonetheless, many epidemiologists still use the term “disease” as shorthand for the wide range of health-related states and events that are studied.
Specified populations
Although epidemiologists and direct health-care providers (clinicians) are both concerned with occurrence and control of disease, they differ greatly in how they view “the patient.” The clinician is concerned about the health of an individual; the epidemiologist is concerned about the collective health of the people in a community or population. In other words, the clinician’s “patient” is the individual; the epidemiologist’s “patient” is the community. Therefore, the clinician and the epidemiologist have different responsibilities when faced with a person with illness. For example, when a patient with diarrheal disease presents, both are interested in establishing the correct diagnosis. However, while the clinician usually focuses on treating and caring for the individual, the epidemiologist focuses on identifying the exposure or source that caused the illness; the number of other persons who may have been similarly exposed; the potential for further spread in the community; and interventions to prevent additional cases or recurrences.
Application
Epidemiology is not just “the study of” health in a population; it also involves applying the knowledge gained by the studies to community-based practice. Like the practice of medicine, the practice of epidemiology is both a science and an art. To make the proper diagnosis and prescribe appropriate treatment for a patient, the clinician combines medical (scientific) knowledge with experience, clinical judgment, and understanding of the patient. Similarly, the epidemiologist uses the scientific methods of descriptive and analytic epidemiology as well as experience, epidemiologic judgment, and understanding of local conditions in “diagnosing” the health of a community and proposing appropriate, practical, and acceptable public health interventions to control and prevent disease in the community.
Summary
Epidemiology is the study (scientific, systematic, data-driven) of the distribution (frequency, pattern) and determinants (causes, risk factors) of health-related states and events (not just diseases) in specified populations (patient is community, individuals viewed collectively), and the application of (since epidemiology is a discipline within public health) this study to the control of health problems.
Exercise 1.1
Below are four key terms taken from the definition of epidemiology, followed by a list of activities that an epidemiologist might perform. Match the term to the activity that best describes it. You should match only one term per activity.
A.Distribution
B.Determinants
C.Application
_____ 1. Compare food histories between persons with Staphylococcus food poisoning and those without
_____ 2. Compare frequency of brain cancer among anatomists with frequency in general population
_____ 3. Mark on a map the residences of all children born with birth defects within 2 miles of a hazardous waste site
_____ 4. Graph the number of cases of congenital syphilis by year for the country
_____ 5. Recommend that close contacts of a child recently reported with meningococcal meningitis receive Rifampin
_____ 6. Tabulate the frequency of clinical signs, symptoms, and laboratory findings among children with chickenpox in Cincinnati, Ohio
Epidemiology’s roots are nearly 2500 years old.
Historical Evolution of Epidemiology
Although epidemiology as a discipline has blossomed since World War II, epidemiologic thinking has been traced from Hippocrates through John Graunt, William Farr, John Snow, and others. The contributions of some of these early and more recent thinkers are described below.5
Circa 400 B.C.
Hippocrates attempted to explain disease occurrence from a rational rather than a supernatural viewpoint. In his essay entitled “On Airs, Waters, and Places,” Hippocrates suggested that environmental and host factors such as behaviors might influence the development of disease.
1662
Another early contributor to epidemiology was John Graunt, a London haberdasher and councilman who published a landmark analysis of mortality data in 1662. This publication was the first to quantify patterns of birth, death, and disease occurrence, noting disparities between males and females, high infant mortality, urban/rural differences, and seasonal variations.5
1800
William Farr built upon Graunt’s work by systematically collecting and analyzing Britain’s mortality statistics. Farr, considered the father of modern vital statistics and surveillance, developed many of the basic practices used today in vital statistics and disease classification. He concentrated his efforts on collecting vital statistics, assembling and evaluating those data, and reporting to responsible health authorities and the general public.4
1854
In the mid-1800s, an anesthesiologist named John Snow was conducting a series of investigations in London that warrant his being considered the “father of field epidemiology.” Twenty years before the development of the microscope, Snow conducted studies of cholera outbreaks both to discover the cause of disease and to prevent its recurrence. Because his work illustrates the classic sequence from descriptive epidemiology to hypothesis generation to hypothesis testing (analytic epidemiology) to application, two of his investigations will be described in detail.
Snow conducted one of his now famous studies in 1854 when an epidemic of cholera erupted in the Golden Square of London.5 He
began his investigation by determining where in this area persons with cholera lived and worked. He marked each residence on a map of the area, as shown in Figure 1.1. Today, this type of map, showing the geographic distribution of cases, is called a spot map.
Figure 1.1 Spot map of deaths from cholera in Golden Square area,
London, 1854 (redrawn from original)
Source: Snow J. Snow on cholera. London: Humphrey Milford: Oxford University Press; 1936.
Because Snow believed that water was a source of infection for cholera, he marked the location of water pumps on his spot map, then looked for a relationship between the distribution of households with cases of cholera and the location of pumps. He noticed that more case households clustered around Pump A, the Broad Street pump, than around Pump B or C. When he questioned residents who lived in the Golden Square area, he was told that they avoided Pump B because it was grossly contaminated, and that Pump C was located too inconveniently for most of them. From this information, Snow concluded that the Broad Street pump (Pump A) was the primary source of water and the most likely source of infection for most persons with cholera in the Golden Square area. He noted with curiosity, however, that no cases of cholera had occurred in a two-block area just to the east of the Broad Street pump. Upon investigating, Snow found a brewery located there with a deep well on the premises. Brewery workers got their water from this well, and also received a daily portion of malt liquor. Access to these uncontaminated rations could explain why none of the brewery’s employees contracted cholera.
To confirm that the Broad Street pump was the source of the epidemic, Snow gathered information on where persons with cholera had obtained their water. Consumption of water from the Broad Street pump was the one common factor among the cholera patients. After Snow presented his findings to municipal officials, the handle of the pump was removed and the outbreak ended. The site of the pump is now marked by a plaque mounted on the wall outside of the appropriately named John Snow Pub.
Figure 1.2 John Snow Pub, London
Source: The John Snow Society [Internet]. London: [updated 2005 Oct 14; cited 2006 Feb 6]. Available from: http://johnsnowsociety.org.
Snow’s second investigation reexamined data from the 1854 cholera outbreak in London. During a cholera epidemic a few years earlier, Snow had noted that districts with the highest death rates were serviced by two water companies: the Lambeth Company and the Southwark and Vauxhall Company. At that time, both companies obtained water from the Thames River at intake points that were downstream from London and thus susceptible to contamination from London sewage, which was discharged directly into the Thames. To avoid contamination by London sewage, in 1852 the Lambeth Company moved its intake water works to a site on the Thames well upstream from London. Over a 7-week period during the summer of 1854, Snow compared cholera mortality among districts that received water from one or the other or both water companies. The results are shown in Table 1.1.
Table 1.1 Mortality from Cholera in the Districts of London Supplied by the Southwark and Vauxhall and the Lambeth Companies, July 9–August 26, 1854
Districts with Water Supplied By: Population (1851 Census) Number of Deaths from Cholera Cholera Death Rate per 1,000 Population
Southwark and Vauxhall Only 167,654 844 5.0
Lambeth Only 19,133 18 0.9
Both Companies 300,149 652 2.2
Source: Snow J. Snow on cholera. London: Humphrey Milford: Oxford University Press; 1936.
The data in Table 1.1 show that the cholera death rate was more than 5 times higher in districts served only by the Southwark and Vauxhall Company (intake downstream from London) than in those served only by the Lambeth Company (intake upstream from London). Interestingly, the mortality rate in districts supplied by both companies fell between the rates for districts served exclusively by either company. These data were consistent with the hypothesis that water obtained from the Thames below London was a source of cholera. Alternatively, the populations supplied by the two companies may have differed on other factors that affected their risk of cholera.
To test his water supply hypothesis, Snow focused on the districts served by both companies, because the households within a district were generally comparable except for the water supply company. In these districts, Snow identified the water supply company for every house in which a death from cholera had occurred during the 7-week period. Table 1.2 shows his findings.
Table 1.2 Mortality from Cholera in London Related to the Water Supply of Individual Houses in
Districts Served by Both the Southwark and Vauxhall Company and the Lambeth Company, July 9– August 26, 1854
Water Supply of Individual House Population (1851 Census) Number of Deaths from Cholera Cholera Death Rate per 1,000 Population
Southwark and Vauxhall Only 98,862 419 4.2
Lambeth Only 154,615 80 0.5
Source: Snow J. Snow on cholera. London: Humphrey Milford: Oxford University Press; 1936.
This study, demonstrating a higher death rate from cholera among households served by the Southwark and Vauxhall Company in the mixed districts, added support to Snow’s hypothesis. It also established the sequence of steps used by current-day epidemiologists to investigate outbreaks of disease. Based on a characterization of the cases and population at risk by time, place, and person, Snow developed a testable hypothesis. He then tested his hypothesis with a more rigorously designed study, ensuring that the groups to be compared were comparable. After this study, efforts to control the epidemic were directed at changing the location of the water intake of the Southwark and Vauxhall Company to avoid sources of contamination. Thus, with no knowledge of the existence of microorganisms, Snow demonstrated through epidemiologic studies that water could serve as a vehicle for transmitting cholera and that epidemiologic information could be used to direct prompt and appropriate public health action.
19th and 20th centuries
In the mid- and late-1800s, epidemiological methods began to be applied in the investigation of disease occurrence. At that time, most investigators focused on acute infectious diseases. In the 1930s and 1940s, epidemiologists extended their methods to noninfectious diseases. The period since World War II has seen an explosion in the development of research methods and the theoretical underpinnings of epidemiology. Epidemiology has been applied to the entire range of health-related outcomes, behaviors, and even knowledge and attitudes. The studies by Doll and Hill linking lung cancer to smoking6and the study of cardiovascular disease among residents of Framingham, Massachusetts7 are two examples of how pioneering researchers have applied epidemiologic methods to chronic disease since World War II. During the 1960s and early 1970s health workers applied epidemiologic methods to eradicate naturally occurring smallpox worldwide.8 This was an achievement in applied epidemiology of unprecedented proportions.
In the 1980s, epidemiology was extended to the studies of injuries and violence. In the 1990s, the related fields of molecular and genetic epidemiology (expansion of epidemiology to look at specific pathways, molecules and genes that influence risk of developing disease) took root. Meanwhile, infectious diseases continued to challenge epidemiologists as new infectious agents emerged (Ebola virus, Human Immunodeficiency virus (HIV)/ Acquired Immunodeficiency Syndrome (AIDS)), were identified (Legionella, Severe Acute Respiratory Syndrome (SARS)), or changed (drug-resistant Mycobacterium tuberculosis, Avian influenza). Beginning in the 1990s and accelerating after the terrorist attacks of September 11, 2001, epidemiologists have had to consider not only natural transmission of infectious organisms but also deliberate spread through biologic warfare and bioterrorism.
Today, public health workers throughout the world accept and use epidemiology regularly to characterize the health of their communities and to solve day-to-day problems, large and small.
Uses
Epidemiology and the information generated by epidemiologic methods have been used in many ways.9 Some common uses are described below.
Assessing the community’s health
Public health officials responsible for policy development, implementation, and evaluation use epidemiologic information as a factual framework for decision making. To assess the health of a population or community, relevant sources of data must be identified and analyzed by person, place, and time (descriptive epidemiology).
•What are the actual and potential health problems in the community?
•Where are they occurring?
•Which populations are at increased risk?
•Which problems have declined over time?
•Which ones are increasing or have the potential to increase?
•How do these patterns relate to the level and distribution of public health services available?
More detailed data may need to be collected and analyzed to determine whether health services are available, accessible, effective, and efficient. For example, public health officials used epidemiologic data and methods to identify baselines, to set health goals for the nation in 2000 and 2010, and to monitor progress toward these goals.10-12
Making individual decisions
Many individuals may not realize that they use epidemiologic information to make daily decisions affecting their health. When persons decide to quit smoking, climb the stairs rather than wait for an elevator, eat a salad rather than a cheeseburger with fries for lunch, or use a condom, they may be influenced, consciously or unconsciously, by epidemiologists’ assessment of risk. Since World War II, epidemiologists have provided information related to all those decisions. In the 1950s, epidemiologists reported the increased risk of lung cancer among smokers. In the 1970s, epidemiologists documented the role of exercise and proper diet in reducing the risk of heart disease. In the mid-1980s, epidemiologists identified the increased risk of HIV infection associated with certain sexual and drug-related behaviors. These and hundreds of other epidemiologic findings are directly relevant to the choices people make every day, choices that affect their health over a lifetime.
Completing the clinical picture
When investigating a disease outbreak, epidemiologists rely on health-care providers and laboratorians to establish the proper diagnosis of individual patients. But epidemiologists also contribute to physicians’ understanding of the clinical picture and natural history of disease. For example, in late 1989, a physician saw three patients with unexplained eosinophilia (an increase in the number of a specific type of white blood cell called an eosinophil) and myalgias (severe muscle pains). Although the physician could not make a definitive diagnosis, he notified public health authorities. Within weeks, epidemiologists had identified enough other cases to characterize the spectrum and course of the illness that came to be known as eosinophilia-myalgia syndrome.13 More recently, epidemiologists, clinicians, and researchers around the world have collaborated to characterize SARS, a disease caused by a new type of coronavirus that emerged in China in late 2002.14 Epidemiology has also been instrumental in characterizing many non-acute diseases, such as the numerous conditions associated with cigarette smoking — from pulmonary and heart disease to lip, throat, and lung cancer.
Searching for causes
Much epidemiologic research is devoted to searching for causal factors that influence one’s risk of disease. Ideally, the goal is to identify a cause so that appropriate public health action might be taken. One can argue that epidemiology can never prove a causal relationship between an exposure and a disease, since much of epidemiology is based on ecologic reasoning. Nevertheless, epidemiology often provides enough information to support effective action. Examples date from the removal of the handle from the Broad St. pump following John Snow’s investigation of cholera in the Golden Square area of London in 1854,5 to the withdrawal of a vaccine against rotavirus in 1999 after epidemiologists found that it increased the risk of intussusception, a potentially life-threatening condition.15 Just as often, epidemiology and laboratory science converge to provide the evidence needed to establish causation. For example, epidemiologists were able to identify a variety of risk factors during an outbreak of pneumonia among persons attending the American Legion Convention in Philadelphia in 1976, even though the Legionnaires’ bacillus was not identified in the laboratory from lung tissue of a person who had died from Legionnaires’ disease until almost 6 months later.16
Exercise 1.2
In August 1999, epidemiologists learned of a cluster of cases of encephalitis caused by West Nile virus infection among residents of Queens, New York. West Nile virus infection, transmitted by mosquitoes, had never before been identified in North America.
Describe how this information might be used for each of the following:
1.Assessing the community’s health
2.Making decisions about individual patients
3.Documenting the clinical picture of the illness
4.Searching for causes to prevent future outbreaks
Core Epidemiologic Functions
In the mid-1980s, five major tasks of epidemiology in public health practice were identified: public health surveillance, field investigation, analytic studies, evaluation, and linkages.17 A sixth task, policy development, was recently added. These tasks are described below.
Public health surveillance
Public health surveillance is the ongoing, systematic collection, analysis, interpretation, and dissemination of health data to help guide public health decision making and action. Surveillance is equivalent to monitoring the pulse of the community. The purpose of public health surveillance, which is sometimes called “information for action,”18 is to portray the ongoing patterns of disease occurrence and disease potential so that investigation, control, and prevention measures can be applied efficiently and effectively. This is accomplished through the systematic collection and evaluation of morbidity and mortality reports and other relevant health information, and the dissemination of these data and their interpretation to those involved in disease control and public health decision making.
Figure 1.3. Surveillance Cycle
Morbidity and mortality reports are common sources of surveillance data for local and state health departments. These reports generally are submitted by health-care providers, infection control practitioners, or laboratories that are required to notify the health department of any patient with a reportable disease such as pertussis, meningococcal meningitis, or AIDS. Other sources of health-related data that are used for surveillance include reports from investigations of individual cases and disease clusters, public health program data such as immunization coverage in a community, disease registries, and health surveys.
Most often, surveillance relies on simple systems to collect a limited amount of information about each case. Although not every case of disease is reported, health officials regularly review the case reports they do receive and look for patterns among them. These practices have proven invaluable in detecting problems, evaluating programs, and guiding public health action.
While public health surveillance traditionally has focused on communicable diseases, surveillance systems now exist that target injuries, chronic diseases, genetic and birth defects, occupational and potentially environmentally-related diseases, and health behaviors. Since September 11, 2001, a variety of systems that rely on electronic reporting have been developed, including those that report daily emergency department visits, sales of over-the-counter medicines, and worker absenteeism.19,20 Because epidemiologists are likely to be called upon to design and use these and other new surveillance systems, an epidemiologist’s core competencies must include design of data collection instruments, data management, descriptive methods and graphing, interpretation of data, and scientific writing and presentation.
Field investigation
As noted above, surveillance provides information for action. One of the first actions that results from a surveillance case report or report of a cluster is investigation by the public health department. The investigation may be as limited as a phone call to the healthcare provider to confirm or clarify the circ*mstances of the reported case, or it may involve a field investigation requiring the coordinated efforts of dozens of people to characterize the extent of an epidemic and to identify its cause.
The objectives of such investigations also vary. Investigations often lead to the identification of additional unreported or unrecognized ill persons who might otherwise continue to spread infection to others. For example, one of the hallmarks of investigations of persons with sexually transmitted disease is the identification of sexual partners or contacts of patients. When interviewed, many of these contacts are found to be infected without knowing it, and are given treatment they did not realize they needed. Identification and treatment of these contacts prevents further spread.
For some diseases, investigations may identify a source or vehicle of infection that can be controlled or eliminated. For example, the investigation of a case of Escherichia coli O157:H7 infection usually focuses on trying to identify the vehicle, often ground beef but sometimes something more unusual such as fruit juice. By identifying the vehicle, investigators may be able to determine how many other persons might have already been exposed and how many continue to be at risk. When a commercial product turns out to be the culprit, public announcements and recalling the product may prevent many additional cases.
Occasionally, the objective of an investigation may simply be to learn more about the natural history, clinical spectrum, descriptive epidemiology, and risk factors of the disease before determining what disease intervention methods might be appropriate. Early investigations of the epidemic of SARS in 2003 were needed to establish a case definition based on the clinical presentation, and to
characterize the populations at risk by time, place, and person. As more was learned about the epidemiology of the disease and communicability of the virus, appropriate recommendations regarding isolation and quarantine were issued.21
Field investigations of the type described above are sometimes referred to as “shoe leather epidemiology,” conjuring up images of dedicated, if haggard, epidemiologists beating the pavement in search of additional cases and clues regarding source and mode of
transmission. This approach is commemorated in the symbol of the Epidemic Intelligence Service (EIS), CDC’s training program for disease detectives — a shoe with a hole in the sole.
Analytic studies
Surveillance and field investigations are usually sufficient to identify causes, modes of transmission, and appropriate control and prevention measures. But sometimes analytic studies employing more rigorous methods are needed. Often the methods are used in combination — with surveillance and field investigations providing clues or hypotheses about causes and modes of transmission, and analytic studies evaluating the credibility of those hypotheses.
Clusters or outbreaks of disease frequently are investigated initially with descriptive epidemiology. The descriptive approach involves the study of disease incidence and distribution by time, place, and person. It includes the calculation of rates and identification of parts of the population at higher risk than others. Occasionally, when the association between exposure and disease is quite strong, the investigation may stop when descriptive epidemiology is complete and control measures may be implemented immediately. John Snow’s 1854 investigation of cholera is an example. More frequently, descriptive studies, like case investigations, generate hypotheses that can be tested with analytic studies. While some field investigations are conducted in response to acute health problems such as outbreaks, many others are planned studies.
The hallmark of an analytic epidemiologic study is the use of a valid comparison group. Epidemiologists must be skilled in all aspects of such studies, including design, conduct, analysis, interpretation, and communication of findings.
•Design includes determining the appropriate research strategy and study design, writing justifications and protocols, calculating sample sizes, deciding on criteria for subject selection (e.g., developing case definitions), choosing an appropriate comparison group, and designing questionnaires.
•Conduct involves securing appropriate clearances and approvals, adhering to appropriate ethical principles, abstracting records, tracking down and interviewing subjects, collecting and handling specimens, and managing the data.
•Analysis begins with describing the characteristics of the subjects. It progresses to calculation of rates, creation of comparative tables (e.g., two-by-two tables), and computation of measures of association (e.g., risk ratios or odds ratios), tests of significance (e.g., chi-square test), confidence intervals, and the like. Many epidemiologic studies require more advanced analytic techniques such as stratified analysis, regression, and modeling.
•Finally, interpretation involves putting the study findings into perspective, identifying the key take-home messages, and making sound recommendations. Doing so requires that the epidemiologist be knowledgeable about the subject matter and the strengths and weaknesses of the study.
Evaluation
Epidemiologists, who are accustomed to using systematic and quantitative approaches, have come to play an important role in evaluation of public health services and other activities. Evaluation is the process of determining, as systematically and objectively as possible, the relevance, effectiveness, efficiency, and impact of activities with respect to established goals.22
•Effectiveness refers to the ability of a program to produce the intended or expected results in the field; effectiveness differs from efficacy, which is the ability to produce results under ideal conditions.
•Efficiency refers to the ability of the program to produce
the intended results with a minimum expenditure of time and resources.
The evaluation itself may focus on plans (formative evaluation), operations (process evaluation), impact (summative evaluation), or outcomes — or any combination of these. Evaluation of an immunization program, for example, might assess the efficiency of the operations, the proportion of the target population immunized, and the apparent impact of the program on the incidence of vaccine-preventable diseases. Similarly, evaluation of a surveillance system might address operations and attributes of the system, its ability to detect cases or outbreaks, and its usefulness.23
Linkages
Epidemiologists working in public health settings rarely act in isolation. In fact, field epidemiology is often said to be a “team sport.” During an investigation an epidemiologist usually participates as either a member or the leader of a multidisciplinary team. Other team members may be laboratorians, sanitarians, infection control personnel, nurses or other clinical staff, and, increasingly, computer information specialists. Many outbreaks cross geographical and jurisdictional lines, so co-investigators may be from local, state, or federal levels of government, academic institutions, clinical facilities, or the private sector. To promote current and future collaboration, the epidemiologists need to maintain relationships with staff of other agencies and institutions. Mechanisms for sustaining such linkages include official memoranda of understanding, sharing of published or on-line information for public health audiences and outside partners, and informal networking that takes place at professional meetings.
Policy development
The definition of epidemiology ends with the following phrase: “...and the application of this study to the control of health problems.” While some academically minded epidemiologists have stated that epidemiologists should stick to research and not get involved in policy development or even make recommendations,24 public health epidemiologists do not have this luxury. Indeed, epidemiologists who understand a problem and the population in which it occurs are often in a uniquely qualified position to recommend appropriate interventions. As a result, epidemiologists working in public health regularly provide input, testimony, and recommendations regarding disease control strategies, reportable disease regulations, and health-care policy.
A. Public health surveillance B. Field investigation C. Analytic studies
D. Evaluation E. Linkages
F. Policy development
_____ 1.
Reviewing reports of test results for Chlamydia trachomatis from public health clinics
_____ 2.
Meeting with directors of family planning clinics and college health clinics to discuss Chlamydia testing and reporting
_____ 3.
Developing guidelines/criteria about which patients coming to the clinic should be screened (tested) for Chlamydia infection
_____ 4.
Interviewing persons infected with Chlamydia to identify their sex partners
_____ 5.
Conducting an analysis of patient flow at the public health clinic to determine waiting times for clinic patients
_____ 6.
Comparing persons with symptomatic versus asymptomatic Chlamydia infection to identify predictors
Check your answers on page 1-82
The Epidemiologic Approach
An epidemiologist:
•Counts
•Divides
•Compares As with all scientific endeavors, the practice of epidemiology relies on a systematic approach. In very simple terms, the epidemiologist:
• Counts cases or health events, and describes them in terms
of time, place, and person;
•Divides the number of cases by an appropriate denominator to calculate rates; and
•Compares these rates over time or for different groups of people.
Before counting cases, however, the epidemiologist must decide what a case is. This is done by developing a case definition. Then, using this case definition, the epidemiologist finds and collects information about the case-patients. The epidemiologist then performs descriptive epidemiology by characterizing the cases collectively according to time, place, and person. To calculate the disease rate, the epidemiologist divides the number of cases by the size of the population. Finally, to determine whether this rate is greater than what one would normally expect, and if so to identify factors contributing to this increase, the epidemiologist compares the rate from this population to the rate in an appropriate comparison group, using analytic epidemiology techniques. These epidemiologic actions are described in more detail below. Subsequent tasks, such as reporting the results and recommending how they can be used for public health action, are just as important, but are beyond the scope of this lesson.
Defining a case
Before counting cases, the epidemiologist must decide what to count, that is, what to call a case. For that, the epidemiologist uses a case definition. A case definition is a set of standard criteria for classifying whether a person has a particular disease, syndrome, or other health condition. Some case definitions, particularly those used for national surveillance, have been developed and adopted as national standards that ensure comparability. Use of an agreedupon standard case definition ensures that every case is equivalent, regardless of when or where it occurred, or who identified it. Furthermore, the number of cases or rate of disease identified in one time or place can be compared with the number or rate from another time or place. For example, with a standard case definition, health officials could compare the number of cases of listeriosis that occurred in Forsyth County, North Carolina in 2000 with the number that occurred there in 1999. Or they could compare the rate of listeriosis in Forsyth County in 2000 with the national rate in
that same year. When everyone uses the same standard case definition and a difference is observed, the difference is likely to be real rather than the result of variation in how cases are classified.
To ensure that all health departments in the United States use the same case definitions for surveillance, the Council of State and Territorial Epidemiologists (CSTE), CDC, and other interested parties have adopted standard case definitions for the notifiable infectious diseases.25 These definitions are revised as needed. In 1999, to address the need for common definitions and methods for state-level chronic disease surveillance, CSTE, the Association of State and Territorial Chronic Disease Program Directors, and CDC adopted standard definitions for 73 chronic disease indicators.29
Other case definitions, particularly those used in local outbreak investigations, are often tailored to the local situation. For example, a case definition developed for an outbreak of viral illness might require laboratory confirmation where such laboratory services are available, but likely would not if such services were not readily available.
Components of a case definition for outbreak investigations
A case definition consists of clinical criteria and, sometimes, limitations on time, place, and person. The clinical criteria usually include confirmatory laboratory tests, if available, or combinations of symptoms (subjective complaints), signs (objective physical findings), and other findings. Case definitions used during outbreak investigations are more likely to specify limits on time, place, and/or person than those used for surveillance. Contrast the case definition used for surveillance of listeriosis (see box below) with the case definition used during an investigation of a listeriosis outbreak in North Carolina in 2000.25,26
Both the national surveillance case definition and the outbreak case definition require a clinically compatible illness and laboratory confirmation of Listeria monocytogenes from a normally sterile site, but the outbreak case definition adds restrictions on time and place, reflecting the scope of the outbreak.
Listeriosis — Surveillance Case Definition
Clinical description
Infection caused by Listeria monocytogenes, which may produce any of several clinical syndromes, including stillbirth, listeriosis of the newborn, meningitis, bacteriemia, or localized infections
Laboratory criteria for diagnosis
Isolation of L. monocytogenes from a normally sterile site (e.g., blood or cerebrospinal fluid or, less commonly, joint, pleural, or pericardial fluid)
Case classification
Confirmed: a clinically compatible case that is laboratory confirmed
Source: Centers for Disease Control and Prevention. Case definitions for
infectious conditions under public health surveillance. MMWR Recommendations and Reports 1997:46(RR-10):49-50.
Listeriosis — Outbreak Investigation
Case definition
Clinically compatible illness with L. monocytogenes isolated
•From a normally sterile site
•In a resident of Winston-Salem, North Carolina
•With onset between October 24, 2000 and January 4, 2001
Source: MacDonald P, Boggs J, Whitwam R, Beatty M, Hunter S, MacCormack
N, et al. Listeria-associated birth complications linked with homemade Mexican-style cheese, North Carolina, October 2000 [abstract]. 50th Annual Epidemic Intelligence Service Conference; 2001 Apr 23-27; Atlanta, GA.
Many case definitions, such as that shown for listeriosis, require laboratory confirmation. This is not always necessary, however; in fact, some diseases have no distinctive laboratory findings. Kawasaki syndrome, for example, is a childhood illness with fever and rash that has no known cause and no specifically distinctive laboratory findings. Notice that its case definition (see box below) is based on the presence of fever, at least four of five specified clinical findings, and the lack of a more reasonable explanation.
Kawasaki Syndrome — Case Definition
Clinical description
A febrile illness of greater than or equal to 5 days’ duration, with at least four of the five following physical findings and no other more reasonable explanation for the observed clinical findings:
•Bilateral conjunctival injection
•Oral changes (erythema of lips or oropharynx, strawberry tongue, or fissuring of the lips)
•Peripheral extremity changes (edema, erythema, or generalized or periungual desquamation)
•Rash
•Cervical lymphadenopathy (at least one lymph node greater than or equal to 1.5 cm in diameter)
Laboratory criteria for diagnosis None
Case classification
Confirmed: a case that meets the clinical case definition
Comment: If fever disappears after intravenous gamma globulin therapy is started, fever may be of less than 5 days’ duration, and the clinical case definition may still be met.
Source: Centers for Disease Control and Prevention. Case definitions for
infectious conditions under public health surveillance. MMWR Recommendations and Reports 1990:39(RR-13):18.
Criteria in case definitions
A case definition may have several sets of criteria, depending on how certain the diagnosis is. For example, during an investigation of a possible case or outbreak of measles, a person with a fever and rash might be classified as having a suspected, probable, or confirmed case of measles, depending on what evidence of measles is present (see box below).
Measles (Rubeola) — 1996 Case Definition
Clinical description
An illness characterized by all the following:
•A generalized rash lasting greater than or equal to 3 days
•A temperature greater than or equal to 101.0°F (greater than or equal to
38.3°C)
•Cough, coryza, or conjunctivitis
Laboratory criteria for diagnosis
•Positive serologic test for measles immunoglobulin M antibody, or
•Significant rise in measles antibody level by any standard serologic assay, or
•Isolation of measles virus from a clinical specimen
Case classification
Suspected: Any febrile illness accompanied by rash
Probable: A case that meets the clinical case definition, has noncontributory or no serologic or virologic testing, and is not epidemiologically linked to a confirmed case
Confirmed: A case that is laboratory confirmed or that meets the clinical case definition and is epidemiologically linked to a confirmed case. (A laboratory-confirmed case does not need to meet the clinical case definition.)
Comment: Confirmed cases should be reported to National Notifiable Diseases Surveillance System. An imported case has its source outside the country or state. Rash onset occurs within 18 days after entering the jurisdiction, and illness cannot be linked to local transmission. Imported cases should be classified as:
•International. A case that is imported from another country
•Out-of-State. A case that is imported from another state in the United States. The possibility that a patient was exposed within his or her state of residence should be excluded; therefore, the patient either must have been out of state continuously for the entire period of possible exposure (at least 7-18 days before onset of rash) or have had one of the following types of exposure while out of state: a) face-to-face contact with a person who had either a probable or confirmed case or b) attendance in the same institution as a person who had a case of measles (e.g., in a school, classroom, or day care center). An indigenous case is defined as a case of measles that is not imported. Cases that are linked to imported cases should be classified as indigenous if the exposure to the imported case occurred in the reporting state. Any case that cannot be proved to be imported should be classified as indigenous.
Source: Centers for Disease Control and Prevention. Case definitions for infectious conditions under public health surveillance. MMWR Recommendations and Reports 1997:46(RR-10):23–24.
A case might be classified as suspected or probable while waiting for the laboratory results to become available. Once the laboratory provides the report, the case can be reclassified as either confirmed or “not a case,” depending on the laboratory results. In the midst of a large outbreak of a disease caused by a known agent, some cases may be permanently classified as suspected or probable because officials may feel that running laboratory tests on every patient with a consistent clinical picture and a history of exposure (e.g., chickenpox) is unnecessary and even wasteful. Case definitions should not rely on laboratory culture results alone, since organisms are sometimes present without causing disease.
Modifying case definitions
Case definitions can also change over time as more information is obtained. The first case definition for SARS, based on clinical
symptoms and either contact with a case or travel to an area with
SARS transmission, was published in CDC’s Morbidity and Mortality Weekly Report (MMWR) on March 21, 2003 (see box below).27 Two weeks later it was modified slightly. On March 29, after a novel coronavirus was determined to be the causative agent, an interim surveillance case definition was published that included laboratory criteria for evidence of infection with the SARSassociated coronavirus. By June, the case definition had changed several more times. In anticipation of a new wave of cases in 2004, a revised and much more complex case definition was published in December 2003.28
CDC Preliminary Case Definition for Severe Acute Respiratory Syndrome (SARS) — March 21, 2003
Suspected case
Respiratory illness of unknown etiology with onset since February 1, 2003, and the following criteria:
•Documented temperature > 100.4°F (>38.0°C)
•One or more symptoms with respiratory illness (e.g., cough, shortness of breath, difficulty breathing, or radiographic findings of pneumonia or acute respiratory distress syndrome)
•Close contact* within 10 days of onset of symptoms with a person under investigation for or suspected of having SARS or travel within 10 days of onset of symptoms to an area with documented transmission of SARS as defined by the World Health Organization (WHO)
* Defined as having cared for, having lived with, or having had direct contact with respiratory secretions and/or body fluids of a person suspected of having SARS.
Source: Centers for Disease Control and Prevention. Outbreak of severe acute respiratory syndrome–worldwide, 2003. MMWR 2003:52:226–8.
Variation in case definitions
Case definitions may also vary according to the purpose for classifying the occurrences of a disease. For example, health officials need to know as soon as possible if anyone has symptoms of plague or anthrax so that they can begin planning what actions to take. For such rare but potentially severe communicable diseases, for which it is important to identify every possible case, health officials use a sensitive case definition. A sensitive case definition is one that is broad or “loose,” in the hope of capturing most or all of the true cases. For example, the case definition for a suspected case of rubella (German measles) is “any generalized rash illness of acute onset.”25 This definition is quite broad, and would include not only all cases of rubella, but also measles, chickenpox, and rashes due to other causes such as drug allergies. So while the advantage of a sensitive case definition is that it includes most or all of the true cases, the disadvantage is that it sometimes includes other illnesses as well.
On the other hand, an investigator studying the causes of a disease outbreak usually wants to be certain that any person included in a study really had the disease. That investigator will prefer a specific or “strict” case definition. For instance, in an outbreak of Salmonella Agona infection, the investigators would be more likely to identify the source of the infection if they included only persons who were confirmed to have been infected with that organism, rather than including anyone with acute diarrhea, because some persons may have had diarrhea from a different cause. In this setting, the only disadvantages of a strict case definition are the requirement that everyone with symptoms be tested and an underestimation of the total number of cases if some people with salmonellosis are not tested.
Exercise 1.4
Investigators of an outbreak of trichinosis used a case definition with the following categories:
Confirmed case: Signs and symptoms plus laboratory confirmation
Probable case: Acute onset of at least three of the following four features: myalgia, fever, facial edema, or eosinophil count greater than 500/mm3
Possible case: Acute onset of two of the four features plus a physician diagnosis of trichinosis
Suspect case: Unexplained eosinophilia
Not a case:
Failure to fulfill the criteria for a confirmed, probable, possible, or suspect case
Time: Onset after October 1, 2006
Place: Metropolitan Atlanta
Person: Any
Using this case definition, assign the appropriate classification to each of the persons included in the line listing below. Use the highest rate classification possible. (All were residents of Atlanta with acute onset of symptoms in November.)
ID# Last Name Myalgias Fever Facial
Edema Eosinophil Count Physician Diagnosis Laboratory Confirmation Classification
1 Anderson yes yes no 495 trichinosis yes
Buffington 2 yes yes yes pending possible trichinosis pending
Callahan 3 yes yes no 1,100 possible trichinosis pending
4 Doll yes yes no 2,050 EMS* pending
5 Ehrlich no yes no 600 trichinosis not done
*Eosinophilia-Myalgia Syndrome
Check your answers on page 1-82
1.Diagnosing and caring for individual patients
2.Tracking the occurrence of disease
3.Doing research to identify the cause of the disease
4.Deciding who should be quarantined (quarantine is the separation or restriction of movement of persons who are not ill but are believed to have been exposed to infection, to prevent further transmission)
Rate:
the number of cases
divided by
the size of the population per unit of time
Using counts and rates
As noted, one of the basic tasks in public health is identifying and counting cases. These counts, usually derived from case reports submitted by health-care workers and laboratories to the health department, allow public health officials to determine the extent and patterns of disease occurrence by time, place, and person. They may also indicate clusters or outbreaks of disease in the community.
Counts are also valuable for health planning. For example, a health official might use counts (i.e., numbers) to plan how many infection control isolation units or doses of vaccine may be needed.
frequency of disease in different locations whose populations differ in size. For example, in 2003, Pennsylvania had over twelve times as many births (140,660) as its neighboring state, Delaware (11,264). However, Pennsylvania has nearly ten times the population of Delaware. So a more fair way to compare is to calculate rates. In fact, the birth rate was greater in Delaware (13.8 per 1,000 women aged 15–44 years) than in Pennsylvania (11.4 per
1,000 women aged 15–44 years).31
Rates are also useful for comparing disease occurrence during different periods of time. For example, 19.5 cases of chickenpox per 100,000 were reported in 2001 compared with 135.8 cases per 100,000 in 1991. In addition, rates of disease among different subgroups can be compared to identify those at increased risk of disease. These so-called high risk groups can be further assessed and targeted for special intervention. High risk groups can also be studied to identify risk factors that cause them to have increased risk of disease. While some risk factors such as age and family history of breast cancer may not be modifiable, others, such as smoking and unsafe sexual practices, are. Individuals can use knowledge of the modifiable risk factors to guide decisions about behaviors that influence their health.
However, simple counts do not provide all the information a health department needs. For some purposes, the counts must be put into context, based on the population in which they arose. Rates are measures that relate the numbers of cases during a certain period of time (usually per year) to the size of the population in which they occurred. For example, 42,745 new cases of AIDS were reported in the United States in 2002.30 This number, divided by the estimated 2002 population, results in a rate of 15.3 cases per 100,000 population. Rates are particularly useful for comparing the
The 5W’s of descriptive epidemiology: What = health issue of concern Who = person
Where = place
When = time Why/how = causes, risk factors, modes of transmission
Descriptive Epidemiology
As noted earlier, every novice newspaper reporter is taught that a story is incomplete if it does not describe the what, who, where, when, and why/how of a situation, whether it be a space shuttle launch or a house fire. Epidemiologists strive for similar comprehensiveness in characterizing an epidemiologic event, whether it be a pandemic of influenza or a local increase in allterrain vehicle crashes. However, epidemiologists tend to use synonyms for the five W’s listed above: case definition, person, place, time, and causes/risk factors/modes of transmission. Descriptive epidemiology covers time, place, and person.
Compiling and analyzing data by time, place, and person is desirable for several reasons.
•First, by looking at the data carefully, the epidemiologist becomes very familiar with the data. He or she can see what the data can or cannot reveal based on the variables available, its limitations (for example, the number of records with missing information for each important variable), and its eccentricities (for example, all cases range in age from 2 months to 6 years, plus one 17-year-old.).
•Second, the epidemiologist learns the extent and pattern of the public health problem being investigated — which months, which neighborhoods, and which groups of people have the most and least cases.
•Third, the epidemiologist creates a detailed description of the health of a population that can be easily communicated with tables, graphs, and maps.
•Fourth, the epidemiologist can identify areas or groups within the population that have high rates of disease. This information in turn provides important clues to the causes of the disease, and these clues can be turned into testable hypotheses.
Time
The occurrence of disease changes over time. Some of these changes occur regularly, while others are unpredictable. Two diseases that occur during the same season each year include influenza (winter) and West Nile virus infection (August– September). In contrast, diseases such as hepatitis B and salmonellosis can occur at any time. For diseases that occur seasonally, health officials can anticipate their occurrence and
implement control and prevention measures, such as an influenza vaccination campaign or mosquito spraying. For diseases that occur sporadically, investigators can conduct studies to identify the causes and modes of spread, and then develop appropriately targeted actions to control or prevent further occurrence of the disease.
In either situation, displaying the patterns of disease occurrence by time is critical for monitoring disease occurrence in the community and for assessing whether the public health interventions made a difference.
Time data are usually displayed with a two-dimensional graph. The vertical or y-axis usually shows the number or rate of cases; the horizontal or x-axis shows the time periods such as years, months, or days. The number or rate of cases is plotted over time. Graphs of disease occurrence over time are usually plotted as line graphs (Figure 1.4) or histograms (Figure 1.5).
Figure 1.4 Reported Cases of Salmonellosis per 100,000 Population, by Year — United States, 1972– 2002
Source: Centers for Disease Control and Prevention. Summary of notifiable diseases–United States, 2002. Published April 30, 2004, for MMWR 2002;51(No. 53): p. 59.
Figure 1.5 Number of Intussusception Reports After the Rhesus Rotavirus Vaccine-tetravalent (RRV-
TV) by Vaccination Date—United States, September 1998–December 1999
Source: Zhou W, Pool V, Iskander JK, English-Bullard R, Ball R, Wise RP, et al. In: Surveillance Summaries, January 24, 2003. MMWR 2003;52(No. SS-1):1–26.
Sometimes a graph shows the timing of events that are related to disease trends being displayed. For example, the graph may indicate the period of exposure or the date control measures were implemented. Studying a graph that notes the period of exposure may lead to insights into what may have caused illness. Studying a graph that notes the timing of control measures shows what impact, if any, the measures may have had on disease occurrence.
As noted above, time is plotted along the x-axis. Depending on the disease, the time scale may be as broad as years or decades, or as brief as days or even hours of the day. For some conditions — many chronic diseases, for example — epidemiologists tend to be interested in long-term trends or patterns in the number of cases or the rate. For other conditions, such as foodborne outbreaks, the relevant time scale is likely to be days or hours. Some of the common types of time-related graphs are further described below. These and other graphs are described in more detail in Lesson 4.
Secular (long-term) trends. Graphing the annual cases or rate of a disease over a period of years shows long-term or secular trends in the occurrence of the disease (Figure 1.4). Health officials use these graphs to assess the prevailing direction of disease occurrence (increasing, decreasing, or essentially flat), help them evaluate programs or make policy decisions, infer what caused an increase or decrease in the occurrence of a disease (particularly if the graph indicates when related events took place), and use past trends as a predictor of future incidence of disease.
Seasonality. Disease occurrence can be graphed by week or month over the course of a year or more to show its seasonal pattern, if any. Some diseases such as influenza and West Nile infection are known to have characteristic seasonal distributions. Seasonal patterns may suggest hypotheses about how the infection is transmitted, what behavioral factors increase risk, and other possible contributors to the disease or condition. Figure 1.6 shows the seasonal patterns of rubella, influenza, and rotavirus. All three diseases display consistent seasonal distributions, but each disease peaks in different months – rubella in March to June, influenza in November to March, and rotavirus in February to April. The rubella graph is striking for the epidemic that occurred in 1963 (rubella vaccine was not available until 1969), but this epidemic nonetheless followed the seasonal pattern.
Figure 1.6 Seasonal Pattern of Rubella, Influenza and Rotavirus
Source: Dowell SF. Seasonal Variation in Host Susceptibility and Cycles of Certain Infectious Diseases. Emerg Infect Dis. 2001;5:369–74.
Day of week and time of day. For some conditions, displaying data by day of the week or time of day may be informative. Analysis at these shorter time periods is particularly appropriate for conditions related to occupational or environmental exposures that tend to occur at regularly scheduled intervals. In Figure 1.7, farm tractor fatalities are displayed by days of the week.32 Note that the number of farm tractor fatalities on Sundays was about half the number on the other days. The pattern of farm tractor injuries by hour, as displayed in Figure 1.8 peaked at 11:00 a.m., dipped at noon, and peaked again at 4:00 p.m. These patterns may suggest hypotheses and possible explanations that could be evaluated with further study. Figure 1.9 shows the hourly number of survivors and rescuers presenting to local hospitals in New York following the attack on the World Trade Center on September 11, 2001.
Figure 1.7 Farm Tractor Deaths by Day of Week Figure 1.8 Farm Tractor Deaths by Hour of Day
Source: Goodman RA, Smith JD, Sikes RK, Rogers DL, Mickey JL. Fatalities associated with farm tractor injuries: an epidemiologic study. Public Health Rep 1985;100:329–33.
Figure 1.9 World Trade Center Survivors and Rescuers
Source: Centers for Disease Control and Prevention. Rapid Assessment of Injuries Among Survivors of the Terrorist Attack on the World Trade Center — New York City, September 2001. MMWR 2002;51:1–5.
Epidemic period. To show the time course of a disease outbreak or epidemic, epidemiologists use a graph called an epidemic curve. As with the other graphs presented so far, an epidemic curve’s yaxis shows the number of cases, while the x-axis shows time as either date of symptom onset or date of diagnosis. Depending on the incubation period (the length of time between exposure and onset of symptoms) and routes of transmission, the scale on the xaxis can be as broad as weeks (for a very prolonged epidemic) or as narrow as minutes (e.g., for food poisoning by chemicals that cause symptoms within minutes). Conventionally, the data are displayed as a histogram (which is similar to a bar chart but has no gaps between adjacent columns). Sometimes each case is displayed as a square, as in Figure 1.10. The shape and other features of an epidemic curve can suggest hypotheses about the time and source of exposure, the mode of transmission, and the causative agent.
Epidemic curves are discussed in more detail in Lessons 4 and 6.
Figure 1.10 Cases of Salmonella Enteriditis — Chicago, February 13–21, by Date and Time of Symptom Onset
Source: Cortese M, Gerber S, Jones E, Fernandez J. A Salmonella Enteriditis outbreak in Chicago. Presented at the Eastern Regional Epidemic Intelligence Service Conference, March 23, 2000, Boston, Massachusetts.
Place
Describing the occurrence of disease by place provides insight into the geographic extent of the problem and its geographic variation. Characterization by place refers not only to place of residence but to any geographic location relevant to disease occurrence. Such locations include place of diagnosis or report, birthplace, site of employment, school district, hospital unit, or recent travel destinations. The unit may be as large as a continent or country or as small as a street address, hospital wing, or operating room. Sometimes place refers not to a specific location at all but to a place category such as urban or rural, domestic or foreign, and institutional or noninstitutional.
Consider the data in Tables 1.3 and 1.4. Table 1.3 displays SARS data by source of report, and reflects where a person with possible SARS is likely to be quarantined and treated.33 In contrast, Table 1.4 displays the same data by where the possible SARS patients had traveled, and reflects where transmission may have occurred.
Table 1.3 Reported Cases of SARS through
November 3, 2004 — United States, by Case Definition Category and State of Residence
Total Total Total
Total Suspect Probable Confirmed
Cases Cases Cases Cases
Location Reported Reported Reported Reported
Alaska 1 1 0 0
California 29 22 5 2
Colorado 2 2 0 0
Florida 8 6 2 0
Georgia 3 3 0 0
Hawaii 1 1 0 0
Illinois 8 7 1 0
Kansas 1 1 0 0
Kentucky 6 4 2 0
Maryland 2 2 0 0
Massachusetts 8 8 0 0
Minnesota 1 1 0 0
Mississippi 1 0 1 0
Missouri 3 3 0 0
Nevada 3 3 0 0
New Jersey 2 1 0 1
New Mexico 1 0 0 1
New York 29 23 6 0
North Carolina 4 3 0 1
Ohio 2 2 0 0
Pennsylvania 6 5 0 1
Rhode Island 1 1 0 0
South
Carolina 3 3 0 0
Tennessee 1 1 0 0
Texas 5 5 0 0
Utah 7 6 0 1
Vermont 1 1 0 0
Virginia 3 2 0 1
Washington 12 11 1 0
West Virginia 1 1 0 0
Wisconsin 2 1 1 0
Puerto Rico 1 1 0 0
Total 158 131 19 8
Adapted from: Centers for Disease Control and Prevention. Severe Acute Respiratory Syndrome (SARS) Report of Cases in the United States.
Table 1.4 Reported Cases of SARS through November 3, 2004 — United States, by High-Risk Area Visited
Area Count* Percent
Hong Kong City, China 45 28
Toronto, Canada 35 22
Guangdong Province, China 34 22
Beijing City, China 25 16
Shanghai City, China 23 15
Singapore 15 9
China, mainland 15 9
Taiwan 10 6
Anhui Province, China 4 3
Hanoi, Vietnam 4 3
Chongqing City, China 3 2
Guizhou Province, China 2 1
Macoa City, China 2 1
Tianjin City, China 2 1
Jilin Province, China 2 1
Xinjiang Province 1 1
Zhejiang Province, China 1 1
Guangxi Province, China 1 1
Shanxi Province, China 1 1
Liaoning Province, China 1 1
Hunan Province, China 1 1
Sichuan Province, China 1 1
Hubei Province, China 1 1
Jiangxi Province, China 1 1
Fujian Province, China 1 1
Jiangsu Province, China 1 1
Yunnan Province, China 0 0
Hebei Province, China 0 0
Qinghai Province, China 0 0
Tibet (Xizang) Province, China 0 0
Hainan Province 0 0
Henan Province, China 0 0
Gansu Province, China 0 0
Shandong Province, China 0 0
* 158 reported case-patients visited 232 areas
Data Source: Heymann DL, Rodier G. Global Surveillance, National Surveillance, and SARS. Emerg Infect Dis. 2004;10:173–175.
Although place data can be shown in a table such as Table 1.3 or Table 1.4, a map provides a more striking visual display of place data. On a map, different numbers or rates of disease can be depicted using different shadings, colors, or line patterns, as in Figure 1.11.
Figure 1.11 Mortality Rates for Asbestosis, by State — United States, 1968–1981 and 1982–2000
Source: Centers for Disease Control and Prevention. Changing patterns of pneumoconiosis mortality–United States, 1968-2000. MMWR 2004;53:627–32.
Another type of map for place data is a spot map, such as Figure 1.12. Spot maps generally are used for clusters or outbreaks with a limited number of cases. A dot or X is placed on the location that is most relevant to the disease of interest, usually where each victim lived or worked, just as John Snow did in his spot map of the Golden Square area of London (Figure 1.1). If known, sites that are relevant, such as probable locations of exposure (water pumps in Figure 1.1), are usually noted on the map.
Figure 1.12 Spot Map of Giardia Cases
“Person” attributes include age, sex, ethnicity/race, and socioeconomic status.
Analyzing data by place can identify communities at increased risk of disease. Even if the data cannot reveal why these people have an increased risk, it can help generate hypotheses to test with additional studies. For example, is a community at increased risk because of characteristics of the people in the community such as genetic susceptibility, lack of immunity, risky behaviors, or exposure to local toxins or contaminated food? Can the increased risk, particularly of a communicable disease, be attributed to characteristics of the causative agent such as a particularly virulent strain, hospitable breeding sites, or availability of the vector that transmits the organism to humans? Or can the increased risk be attributed to the environment that brings the agent and the host together, such as crowding in urban areas that increases the risk of disease transmission from person to person, or more homes being built in wooded areas close to deer that carry ticks infected with the organism that causes Lyme disease? (More techniques for graphic presentation are discussed in Lesson 4.)
Person
Because personal characteristics may affect illness, organization and analysis of data by “person” may use inherent characteristics of people (for example, age, sex, race), biologic characteristics (immune status), acquired characteristics (marital status), activities (occupation, leisure activities, use of medications/tobacco/drugs), or the conditions under which they live (socioeconomic status, access to medical care). Age and sex are included in almost all data sets and are the two most commonly analyzed “person” characteristics. However, depending on the disease and the data available, analyses of other person variables are usually necessary. Usually epidemiologists begin the analysis of person data by looking at each variable separately. Sometimes, two variables such as age and sex can be examined simultaneously. Person data are usually displayed in tables or graphs.
Age. Age is probably the single most important “person” attribute, because almost every health-related event varies with age. A number of factors that also vary with age include: susceptibility, opportunity for exposure, latency or incubation period of the disease, and physiologic response (which affects, among other things, disease development).
When analyzing data by age, epidemiologists try to use age groups that are narrow enough to detect any age-related patterns that may be present in the data. For some diseases, particularly chronic diseases, 10-year age groups may be adequate. For other diseases, 10-year and even 5-year age groups conceal important variations in
disease occurrence by age. Consider the graph of pertussis occurrence by standard 5-year age groups shown in Figure 1.13a. The highest rate is clearly among children 4 years old and younger. But is the rate equally high in all children within that age group, or do some children have higher rates than others?
Figure 1.13b Pertussis by <1, 4-Year, Then 5-
Figure 1.13a Pertussis by 5-Year Age Groups Year Age Groups
To answer this question, different age groups are needed. Examine Figure 1.13b, which shows the same data but displays the rate of pertussis for children under 1 year of age separately. Clearly, infants account for most of the high rate among 0–4 year olds. Public health efforts should thus be focused on children less than 1 year of age, rather than on the entire 5-year age group.
Sex. Males have higher rates of illness and death than do females for many diseases. For some diseases, this sex-related difference is because of genetic, hormonal, anatomic, or other inherent differences between the sexes. These inherent differences affect susceptibility or physiologic responses. For example, premenopausal women have a lower risk of heart disease than men of the same age. This difference has been attributed to higher estrogen levels in women. On the other hand, the sex-related differences in the occurrence of many diseases reflect differences in opportunity or levels of exposure. For example, Figure 1.14 shows the differences in lung cancer rates over time among men and women.34 The difference noted in earlier years has been attributed to the higher prevalence of smoking among men in the past. Unfortunately, prevalence of smoking among women now equals that among men, and lung cancer rates in women have been climbing as a result.35
Figure 1.14 Lung Cancer Rates — United States, 1930–1999
Data Source: American Cancer Society [Internet]. Atlanta: The American Cancer Society, Inc.
Ethnic and racial groups. Sometimes epidemiologists are interested in analyzing person data by biologic, cultural or social groupings such as race, nationality, religion, or social groups such as tribes and other geographically or socially isolated groups. Differences in racial, ethnic, or other group variables may reflect differences in susceptibility or exposure, or differences in other factors that influence the risk of disease, such as socioeconomic status and access to health care. In Figure 1.15, infant mortality rates for 2002 are shown by race and Hispanic origin of the mother.
Figure 1.15 Infant Mortality Rates for 2002, by Race and Ethnicity of Mother
Source: Centers for Disease Control and Prevention. QuickStats: Infant mortality rates, by selected racial/ethnic populations—United States, 2002, MMWR 2005;54(05):126.
Socioeconomic status. Socioeconomic status is difficult to quantify. It is made up of many variables such as occupation, family income, educational achievement or census track, living conditions, and social standing. The variables that are easiest to measure may not accurately reflect the overall concept. Nevertheless, epidemiologists commonly use occupation, family income, and educational achievement, while recognizing that these variables do not measure socioeconomic status precisely.
The frequency of many adverse health conditions increases with decreasing socioeconomic status. For example, tuberculosis is more common among persons in lower socioeconomic strata. Infant mortality and time lost from work due to disability are both associated with lower income. These patterns may reflect more harmful exposures, lower resistance, and less access to health care. Or they may in part reflect an interdependent relationship that is impossible to untangle: Does low socioeconomic status contribute to disability, or does disability contribute to lower socioeconomic status, or both? What accounts for the disproportionate prevalence of diabetes and asthma in lower socioeconomic areas?36,37
A few adverse health conditions occur more frequently among persons of higher socioeconomic status. Gout was known as the “disease of kings” because of its association with consumption of rich foods. Other conditions associated with higher socioeconomic status include breast cancer, Kawasaki syndrome, chronic fatigue syndrome, and tennis elbow. Differences in exposure account for at least some if not most of the differences in the frequency of these conditions.
Exercise 1.6
Using the data in Tables 1.5 and 1.6, describe the death rate patterns for the “Unusual Event.” For example, how do death rates vary between men and women overall, among the different socioeconomic classes, among men and women in different socioeconomic classes, and among adults and
children in different socioeconomic classes? Can you guess what type of situation might result in such death rate patterns?
Males Persons at risk 179 173 499 851
Deaths 120 148 441 709
Death rate (%) 67.0 85.5 88.4 83.3
Females Persons at risk 143 107 212 462
Deaths 9 13 132 154
Death rate (%) 6.3 12.6 62.3 33.3
Both sexes Persons at risk 322 280 711 1313
Deaths 129 161 573 863
Death rate (%) 40.1 57.5 80.6 65.7
Table 1.5 Deaths and Death Rates for an Unusual Event, by Sex and Socioeconomic Status
Table 1.6 Deaths and Death Rates for an Unusual Event, by Age and Socioeconomic Status
Age Group Measure High/Middle Low Total
Adults Persons at risk 566 664 1230
Deaths 287 545 832
Death rate (%) 50.7 82.1 67.6
Children Persons at risk 36 47 83
Deaths 3 28 31
Death rate (%) 8.3 59.6 37.3
All Ages Persons at risk 602 711 1313
Deaths 290 573 863
Death rate (%) 48.2 80.6 65.7
Check your answers on page 1-82
Key feature of analytic epidemiology = Comparison group
Analytic Epidemiology
As noted earlier, descriptive epidemiology can identify patterns among cases and in populations by time, place and person. From these observations, epidemiologists develop hypotheses about the causes of these patterns and about the factors that increase risk of disease. In other words, epidemiologists can use descriptive epidemiology to generate hypotheses, but only rarely to test those hypotheses. For that, epidemiologists must turn to analytic epidemiology.
The key feature of analytic epidemiology is a comparison group. Consider a large outbreak of hepatitis A that occurred in Pennsylvania in 2003.38 Investigators found almost all of the casepatients had eaten at a particular restaurant during the 2–6 weeks (i.e., the typical incubation period for hepatitis A) before onset of illness. While the investigators were able to narrow down their hypotheses to the restaurant and were able to exclude the food preparers and servers as the source, they did not know which particular food may have been contaminated. The investigators asked the case-patients which restaurant foods they had eaten, but that only indicated which foods were popular. The investigators, therefore, also enrolled and interviewed a comparison or control group — a group of persons who had eaten at the restaurant during the same period but who did not get sick. Of 133 items on the restaurant’s menu, the most striking difference between the case and control groups was in the proportion that ate salsa (94% of case-patients ate, compared with 39% of controls). Further investigation of the ingredients in the salsa implicated green onions as the source of infection. Shortly thereafter, the Food and Drug Administration issued an advisory to the public about green onions and risk of hepatitis A. This action was in direct response to the convincing results of the analytic epidemiology, which compared the exposure history of case-patients with that of an appropriate comparison group.
When investigators find that persons with a particular characteristic are more likely than those without the characteristic to contract a disease, the characteristic is said to be associated with the disease. The characteristic may be a:
•Demographic factor such as age, race, or sex;
•Constitutional factor such as blood group or immune status; • Behavior or act such as smoking or having eaten salsa; or
•Circ*mstance such as living near a toxic waste site.
Identifying factors associated with disease help health officials
appropriately target public health prevention and control activities.
It also guides additional research into the causes of disease.
Thus, analytic epidemiology is concerned with the search for causes and effects, or the why and the how. Epidemiologists use analytic epidemiology to quantify the association between exposures and outcomes and to test hypotheses about causal relationships. It has been said that epidemiology by itself can never prove that a particular exposure caused a particular outcome. Often, however, epidemiology provides sufficient evidence to take appropriate control and prevention measures.
Epidemiologic studies fall into two categories: experimental and observational.
Experimental studies
In an experimental study, the investigator determines through a controlled process the exposure for each individual (clinical trial) or community (community trial), and then tracks the individuals or communities over time to detect the effects of the exposure. For example, in a clinical trial of a new vaccine, the investigator may randomly assign some of the participants to receive the new vaccine, while others receive a placebo shot. The investigator then tracks all participants, observes who gets the disease that the new vaccine is intended to prevent, and compares the two groups (new vaccine vs. placebo) to see whether the vaccine group has a lower rate of disease. Similarly, in a trial to prevent onset of diabetes among high-risk individuals, investigators randomly assigned enrollees to one of three groups — placebo, an anti-diabetes drug, or lifestyle intervention. At the end of the follow-up period, investigators found the lowest incidence of diabetes in the lifestyle intervention group, the next lowest in the anti-diabetic drug group, and the highest in the placebo group.39
Observational studies
In an observational study, the epidemiologist simply observes the exposure and disease status of each study participant. John Snow’s studies of cholera in London were observational studies. The two most common types of observational studies are cohort studies and case-control studies; a third type is cross-sectional studies.
Cohort study. A cohort study is similar in concept to the experimental study. In a cohort study the epidemiologist records whether each study participant is exposed or not, and then tracks the participants to see if they develop the disease of interest. Note that this differs from an experimental study because, in a cohort study, the investigator observes rather than determines the participants’ exposure status. After a period of time, the investigator compares the disease rate in the exposed group with the disease rate in the unexposed group. The unexposed group serves as the comparison group, providing an estimate of the baseline or expected amount of disease occurrence in the community. If the disease rate is substantively different in the exposed group compared to the unexposed group, the exposure is said to be associated with illness.
The length of follow-up varies considerably. In an attempt to respond quickly to a public health concern such as an outbreak, public health departments tend to conduct relatively brief studies. On the other hand, research and academic organizations are more likely to conduct studies of cancer, cardiovascular disease, and other chronic diseases which may last for years and even decades. The Framingham study is a well-known cohort study that has followed over 5,000 residents of Framingham, Massachusetts, since the early 1950s to establish the rates and risk factors for heart disease.7 The Nurses Health Study and the Nurses Health Study II are cohort studies established in 1976 and 1989, respectively, that have followed over 100,000 nurses each and have provided useful information on oral contraceptives, diet, and lifestyle risk factors.40 These studies are sometimes called follow-up or prospective cohort studies, because participants are enrolled as the study begins and are then followed prospectively over time to identify occurrence of the outcomes of interest.
An alternative type of cohort study is a retrospective cohort study.
In this type of study both the exposure and the outcomes have already occurred. Just as in a prospective cohort study, the investigator calculates and compares rates of disease in the exposed and unexposed groups. Retrospective cohort studies are commonly used in investigations of disease in groups of easily identified people such as workers at a particular factory or attendees at a wedding. For example, a retrospective cohort study was used to determine the source of infection of cyclosporiasis, a parasitic disease that caused an outbreak among members of a residential facility in Pennsylvania in 2004.41 The investigation indicated that consumption of snow peas was implicated as the vehicle of the cyclosporiasis outbreak.
Case-control study. In a case-control study, investigators start by enrolling a group of people with disease (at CDC such persons are called case-patients rather than cases, because case refers to occurrence of disease, not a person). As a comparison group, the investigator then enrolls a group of people without disease (controls). Investigators then compare previous exposures between the two groups. The control group provides an estimate of the baseline or expected amount of exposure in that population. If the amount of exposure among the case group is substantially higher than the amount you would expect based on the control group, then illness is said to be associated with that exposure. The study of hepatitis A traced to green onions, described above, is an example of a case-control study. The key in a case-control study is to identify an appropriate control group, comparable to the case group in most respects, in order to provide a reasonable estimate of the baseline or expected exposure.
Cross-sectional study. In this third type of observational study, a sample of persons from a population is enrolled and their exposures and health outcomes are measured simultaneously. The cross-sectional study tends to assess the presence (prevalence) of the health outcome at that point of time without regard to duration. For example, in a cross-sectional study of diabetes, some of the enrollees with diabetes may have lived with their diabetes for many years, while others may have been recently diagnosed.
From an analytic viewpoint the cross-sectional study is weaker than either a cohort or a case-control study because a crosssectional study usually cannot disentangle risk factors for occurrence of disease (incidence) from risk factors for survival with the disease. (Incidence and prevalence are discussed in more detail in Lesson 3.) On the other hand, a cross-sectional study is a perfectly fine tool for descriptive epidemiology purposes. Crosssectional studies are used routinely to document the prevalence in a community of health behaviors (prevalence of smoking), health states (prevalence of vaccination against measles), and health outcomes, particularly chronic conditions (hypertension, diabetes).
In summary, the purpose of an analytic study in epidemiology is to identify and quantify the relationship between an exposure and a health outcome. The hallmark of such a study is the presence of at least two groups, one of which serves as a comparison group. In an experimental study, the investigator determines the exposure for the study subjects; in an observational study, the subjects are exposed under more natural conditions. In an observational cohort study, subjects are enrolled or grouped on the basis of their exposure, then are followed to document occurrence of disease. Differences in disease rates between the exposed and unexposed groups lead investigators to conclude that exposure is associated with disease. In an observational case-control study, subjects are enrolled according to whether they have the disease or not, then are questioned or tested to determine their prior exposure. Differences in exposure prevalence between the case and control groups allow investigators to conclude that the exposure is associated with the disease. Cross-sectional studies measure exposure and disease status at the same time, and are better suited to descriptive epidemiology than causation.
A.Experimental
B.Observational cohort C. Observational case-control
D.Observational cross-sectional
E.Not an analytical or epidemiologic study
_____ 1.
Representative sample of residents were telephoned and asked how much they exercise each week and whether they currently have (have ever been diagnosed with) heart disease.
_____ 2.
Occurrence of cancer was identified between April 1991 and July 2002 for 50,000 troops who served in the first Gulf War (ended April 1991) and 50,000 troops who served elsewhere during the same period.
_____ 3.
Persons diagnosed with new-onset Lyme disease were asked how often they walk through woods, use insect repellant, wear short sleeves and pants, etc. Twice as many patients without Lyme disease from the same physician’s practice were asked the same questions, and the responses in the two groups were compared.
_____ 4.
Subjects were children enrolled in a health maintenance organization. At 2 months, each child was randomly given one of two types of a new vaccine against rotavirus infection. Parents were called by a nurse two weeks later and asked whether the children had experienced any of a list of side-effects.
Check your answers on page 1-83
Concepts of Disease Occurrence
A critical premise of epidemiology is that disease and other health events do not occur randomly in a population, but are more likely to occur in some members of the population than others because of risk factors that may not be distributed randomly in the population. As noted earlier, one important use of epidemiology is to identify the factors that place some members at greater risk than others.
Causation
A number of models of disease causation have been proposed. Among the simplest of these is the epidemiologic triad or triangle, the traditional model for infectious disease. The triad consists of an external agent, a susceptible host, and an environment that brings the host and agent together. In this model, disease results from the interaction between the agent and the susceptible host in an environment that supports transmission of the agent from a source to that host. Two ways of depicting this model are shown in Figure 1.16.
Agent, host, and environmental factors interrelate in a variety of complex ways to produce disease. Different diseases require different balances and interactions of these three components. Development of appropriate, practical, and effective public health measures to control or prevent disease usually requires assessment of all three components and their interactions.
Figure 1.16 Epidemiologic Triad
Agent originally referred to an infectious microorganism or pathogen: a virus, bacterium, parasite, or other microbe. Generally, the agent must be present for disease to occur; however, presence of that agent alone is not always sufficient to cause disease. A variety of factors influence whether exposure to an organism will result in disease, including the organism’s pathogenicity (ability to cause disease) and dose.
Over time, the concept of agent has been broadened to include chemical and physical causes of disease or injury. These include chemical contaminants (such as the L-tryptophan contaminant responsible for eosinophilia-myalgia syndrome), as well as physical forces (such as repetitive mechanical forces associated with carpal tunnel syndrome). While the epidemiologic triad serves as a useful model for many diseases, it has proven inadequate for cardiovascular disease, cancer, and other diseases that appear to have multiple contributing causes without a single necessary one.
Host refers to the human who can get the disease. A variety of factors intrinsic to the host, sometimes called risk factors, can influence an individual’s exposure, susceptibility, or response to a causative agent. Opportunities for exposure are often influenced by behaviors such as sexual practices, hygiene, and other personal choices as well as by age and sex. Susceptibility and response to an agent are influenced by factors such as genetic composition, nutritional and immunologic status, anatomic structure, presence of disease or medications, and psychological makeup.
Environment refers to extrinsic factors that affect the agent and the opportunity for exposure. Environmental factors include physical factors such as geology and climate, biologic factors such as insects that transmit the agent, and socioeconomic factors such as crowding, sanitation, and the availability of health services.
Component causes and causal pies
Because the agent-host-environment model did not work well for many non-infectious diseases, several other models that attempt to account for the multifactorial nature of causation have been proposed. One such model was proposed by Rothman in 1976, and has come to be known as the Causal Pies.42 This model is illustrated in Figure 1.17. An individual factor that contributes to cause disease is shown as a piece of a pie. After all the pieces of a pie fall into place, the pie is complete — and disease occurs. The individual factors are called component causes. The complete pie, which might be considered a causal pathway, is called a sufficient cause. A disease may have more than one sufficient cause, with each sufficient cause being composed of several component causes that may or may not overlap. A component that appears in every pie or pathway is called a necessary cause, because without it, disease does not occur. Note in Figure 1.17 that component cause A is a necessary cause because it appears in every pie.
Figure 1.17 Rothman’s Causal Pies
Source: Rothman KJ. Causes. Am J Epidemiol 1976;104:587–592.
The component causes may include intrinsic host factors as well as the agent and the environmental factors of the agent-hostenvironment triad. A single component cause is rarely a sufficient cause by itself. For example, even exposure to a highly infectious agent such as measles virus does not invariably result in measles disease. Host susceptibility and other host factors also may play a role.
At the other extreme, an agent that is usually harmless in healthy persons may cause devastating disease under different conditions. Pneumocystis carinii is an organism that harmlessly colonizes the respiratory tract of some healthy persons, but can cause potentially lethal pneumonia in persons whose immune systems have been weakened by human immunodeficiency virus (HIV). Presence of Pneumocystis carinii organisms is therefore a necessary but not sufficient cause of pneumocystis pneumonia. In Figure 1.17, it would be represented by component cause A.
As the model indicates, a particular disease may result from a variety of different sufficient causes or pathways. For example, lung cancer may result from a sufficient cause that includes smoking as a component cause. Smoking is not a sufficient cause by itself, however, because not all smokers develop lung cancer. Neither is smoking a necessary cause, because a small fraction of lung cancer victims have never smoked. Suppose Component Cause B is smoking and Component Cause C is asbestos.
Sufficient Cause I includes both smoking (B) and asbestos (C).
Sufficient Cause II includes smoking without asbestos, and Sufficient Cause III includes asbestos without smoking. But because lung cancer can develop in persons who have never been exposed to either smoking or asbestos, a proper model for lung cancer would have to show at least one more Sufficient Cause Pie that does not include either component B or component C.
Note that public health action does not depend on the identification of every component cause. Disease prevention can be accomplished by blocking any single component of a sufficient cause, at least through that pathway. For example, elimination of smoking (component B) would prevent lung cancer from sufficient causes I and II, although some lung cancer would still occur through sufficient cause III.
1.Describe its causation in terms of agent, host, and environment.
a.Agent:
b.Host:
c.Environment:
2.For each of the following risk factors and health outcomes, identify whether they are necessary causes, sufficient causes, or component causes.
Risk Factor Health Outcome
_____ a.
_____ b.
_____ c.
_____ d.
Hypertension
Treponema pallidum
Type A personality
Skin contact with a strong acid Stroke
Syphilis
Heart disease
Burn
Anthrax Fact Sheet
What is anthrax?
Anthrax is an acute infectious disease that usually occurs in animals such as livestock, but can also affect humans. Human anthrax comes in three forms, depending on the route of infection: cutaneous (skin) anthrax, inhalation anthrax, and intestinal anthrax. Symptoms usually occur within 7 days after exposure.
Cutaneous: Most (about 95%) anthrax infections occur when the bacterium enters a cut or abrasion on the skin after
handling infected livestock or contaminated animal products. Skin infection begins as a raised itchy bump that resembles an insect bite but within 1–2 days develops into a vesicle and then a painless ulcer, usually 1–3 cm in diameter, with a characteristic black necrotic (dying) area in the center. Lymph glands in the adjacent area may swell. About 20% of untreated cases of cutaneous anthrax will result in death. Deaths are rare with appropriate antimicrobial therapy.
Inhalation: Initial symptoms are like cold or flu symptoms and can include a sore throat, mild fever, and muscle aches. After several days, the symptoms may progress to cough, chest discomfort, severe breathing problems and shock. Inhalation anthrax is often fatal. Eleven of the mail-related cases were inhalation; 5 (45%) of the 11 patients died.
Intestinal: Initial signs of nausea, loss of appetite, vomiting, and fever are followed by abdominal pain, vomiting of blood, and severe diarrhea. Intestinal anthrax results in death in 25% to 60% of cases.
While most human cases of anthrax result from contact with infected animals or contaminated animal products, anthrax also can be used as a biologic weapon. In 1979, dozens of residents of Sverdlovsk in the former Soviet Union are thought to have died of inhalation anthrax after an unintentional release of an aerosol from a biologic weapons facility. In 2001, 22 cases of anthrax occurred in the United States from letters containing anthrax spores that were mailed to members of Congress, television networks, and newspaper companies.
What causes anthrax?
Anthrax is caused by the bacterium Bacillus anthracis. The anthrax bacterium forms a protective shell called a spore. B. anthracis spores are found naturally in soil, and can survive for many years.
How is anthrax diagnosed?
Anthrax is diagnosed by isolating B. anthracis from the blood, skin lesions, or respiratory secretions or by measuring specific antibodies in the blood of persons with suspected cases.
Is there a treatment for anthrax?
Antibiotics are used to treat all three types of anthrax. Treatment should be initiated early because the disease is more likely to be fatal if treatment is delayed or not given at all.
How common is anthrax and where is it found?
Anthrax is most common in agricultural regions of South and Central America, Southern and Eastern Europe, Asia, Africa, the Caribbean, and the Middle East, where it occurs in animals. When anthrax affects humans, it is usually the result of an occupational exposure to infected animals or their products. Naturally occurring anthrax is rare in the United States (28 reported cases between 1971 and 2000), but 22 mail-related cases were identified in 2001.
Infections occur most commonly in wild and domestic lower vertebrates (cattle, sheep, goats, camels, antelopes, and other herbivores), but it can also occur in humans when they are exposed to infected animals or tissue from infected animals.
How is anthrax transmitted?
Anthrax can infect a person in three ways: by anthrax spores entering through a break in the skin, by inhaling anthrax spores, or by eating contaminate, undercooked meat. Anthrax is not spread from person to person. The skin (“cutaneous”) form of anthrax is usually the result of contact with infected livestock, wild animals, or contaminated animal products such as carcasses, hides, hair, wool, meat, or bone meal. The inhalation form is from breathing in spores from the same sources. Anthrax can also be spread as a bioterrorist agent.
Anthrax Fact Sheet (Continued)
Who has an increased risk of being exposed to anthrax?
Susceptibility to anthrax is universal. Most naturally occurring anthrax affects people whose work brings them into contact with livestock or products from livestock. Such occupations include veterinarians, animal handlers, abattoir workers, and laboratorians. Inhalation anthrax was once called Woolsorter’s Disease because workers who inhaled spores from contaminated wool before it was cleaned developed the disease. Soldiers and other potential targets of bioterrorist anthrax attacks might also be considered at increased risk.
Is there a way to prevent infection?
In countries where anthrax is common and vaccination levels of animal herds are low, humans should avoid contact with livestock and animal products and avoid eating meat that has not been properly slaughtered and cooked. Also, an anthrax vaccine has been licensed for use in humans. It is reported to be 93% effective in protecting against anthrax. It is used by veterinarians, laboratorians, soldiers, and others who may be at increased risk of exposure, but is not available to the general public at this time.
For a person who has been exposed to anthrax but is not yet sick, antibiotics combined with anthrax vaccine are used to prevent illness.
Sources: Centers for Disease Control and Prevention [Internet]. Atlanta: Anthrax. Available from:
http://www.bt.cdc.gov/agent/anthrax/ and Anthrax Public Health Fact Sheet, Mass. Dept. of Public Health, August 2002.
Natural History and Spectrum of Disease
Natural history of disease refers to the progression of a disease process in an individual over time, in the absence of treatment. For example, untreated infection with HIV causes a spectrum of clinical problems beginning at the time of seroconversion (primary HIV) and terminating with AIDS and usually death. It is now recognized that it may take 10 years or more for AIDS to develop after seroconversion.43 Many, if not most, diseases have a characteristic natural history, although the time frame and specific manifestations of disease may vary from individual to individual and are influenced by preventive and therapeutic measures.
Figure 1.18 Natural History of Disease Timeline
Source: Centers for Disease Control and Prevention. Principles of epidemiology, 2nd ed. Atlanta: U.S. Department of Health and Human Services;1992.
The process begins with the appropriate exposure to or accumulation of factors sufficient for the disease process to begin in a susceptible host. For an infectious disease, the exposure is a microorganism. For cancer, the exposure may be a factor that initiates the process, such as asbestos fibers or components in tobacco smoke (for lung cancer), or one that promotes the process, such as estrogen (for endometrial cancer).
After the disease process has been triggered, pathological changes then occur without the individual being aware of them. This stage of subclinical disease, extending from the time of exposure to onset of disease symptoms, is usually called the incubation period for infectious diseases, and the latency period for chronic diseases. During this stage, disease is said to be asymptomatic (no symptoms) or inapparent. This period may be as brief as seconds for hypersensitivity and toxic reactions to as long as decades for certain chronic diseases. Even for a single disease, the characteristic incubation period has a range. For example, the typical incubation period for hepatitis A is as long as 7 weeks. The latency period for leukemia to become evident among survivors of the atomic bomb blast in Hiroshima ranged from 2 to 12 years, peaking at 6–7 years.44 Incubation periods of selected exposures and diseases varying from minutes to decades are displayed in Table 1.7.
Table 1.7 Incubation Periods of Selected Exposures and Diseases
Exposure Clinical Effect Incubation/Latency Period
Saxitoxin and similar toxins from shellfish Paralytic shellfish poisoning
(tingling, numbness around lips and fingertips, giddiness, incoherent speech,
respiratory paralysis, sometimes death) few minutes–30 minutes
Organophosphorus ingestion Nausea, vomiting, cramps, headache, nervousness,
blurred vision, chest pain, confusion, twitching, convulsions few minutes–few hours
Salmonella Diarrhea, often with fever and cramps usually 6–48 hours
SARS-associated corona virus Severe Acute Respiratory Syndrome (SARS) 3–10 days, usually 4–6 days
Varicella-zoster virus Chickenpox 10–21 days, usually 14–16 days
Treponema pallidum Syphilis 10–90 days, usually 3 weeks
Hepatitis A virus Hepatitis 14–50 days, average 4 weeks
Hepatitis B virus Hepatitis 50–180 days, usually 2–3 months
Human immunodeficiency virus AIDS <1 to 15+ years
Atomic bomb radiation (Japan) Leukemia 2–12 years
Radiation (Japan, Chernobyl) Thyroid cancer 3–20+ years
Radium (watch dial painters) Bone cancer 8–40 years
Although disease is not apparent during the incubation period, some pathologic changes may be detectable with laboratory, radiographic, or other screening methods. Most screening programs attempt to identify the disease process during this phase of its natural history, since intervention at this early stage is likely to be more effective than treatment given after the disease has progressed and become symptomatic.
The onset of symptoms marks the transition from subclinical to clinical disease. Most diagnoses are made during the stage of clinical disease. In some people, however, the disease process may never progress to clinically apparent illness. In others, the disease process may result in illness that ranges from mild to severe or fatal. This range is called the spectrum of disease. Ultimately, the disease process ends either in recovery, disability or death.
For an infectious agent, infectivity refers to the proportion of exposed persons who become infected. Pathogenicity refers to the proportion of infected individuals who develop clinically apparent disease. Virulence refers to the proportion of clinically apparent cases that are severe or fatal.
Because the spectrum of disease can include asymptomatic and mild cases, the cases of illness diagnosed by clinicians in the community often represent only the tip of the iceberg. Many additional cases may be too early to diagnose or may never progress to the clinical stage. Unfortunately, persons with inapparent or undiagnosed infections may nonetheless be able to transmit infection to others. Such persons who are infectious but have subclinical disease are called carriers. Frequently, carriers are persons with incubating disease or inapparent infection. Persons with measles, hepatitis A, and several other diseases become infectious a few days before the onset of symptoms. However carriers may also be persons who appear to have recovered from their clinical illness but remain infectious, such as chronic carriers of hepatitis B virus, or persons who never exhibited symptoms. The challenge to public health workers is that these carriers, unaware that they are infected and infectious to others, are sometimes more likely to unwittingly spread infection than are people with obvious illness.
Chain of Infection
As described above, the traditional epidemiologic triad model holds that infectious diseases result from the interaction of agent, host, and environment. More specifically, transmission occurs when the agent leaves its reservoir or host through a portal of exit, is conveyed by some mode of transmission, and enters through an appropriate portal of entry to infect a susceptible host. This sequence is sometimes called the chain of infection.
Figure 1.19 Chain of Infection
Source: Centers for Disease Control and Prevention. Principles of epidemiology, 2nd ed. Atlanta: U.S. Department of Health and Human Services;1992.
Reservoir
The reservoir of an infectious agent is the habitat in which the agent normally lives, grows, and multiplies. Reservoirs include humans, animals, and the environment. The reservoir may or may not be the source from which an agent is transferred to a host. For example, the reservoir of Clostridium botulinum is soil, but the source of most botulism infections is improperly canned food containing C. botulinum spores.
Human reservoirs. Many common infectious diseases have human reservoirs. Diseases that are transmitted from person to person without intermediaries include the sexually transmitted diseases, measles, mumps, streptococcal infection, and many respiratory pathogens. Because humans were the only reservoir for the smallpox virus, naturally occurring smallpox was eradicated after the last human case was identified and isolated.8
Human reservoirs may or may not show the effects of illness. As noted earlier, a carrier is a person with inapparent infection who is capable of transmitting the pathogen to others. Asymptomatic or passive or healthy carriers are those who never experience symptoms despite being infected. Incubatory carriers are those who can transmit the agent during the incubation period before clinical illness begins. Convalescent carriers are those who have recovered from their illness but remain capable of transmitting to others. Chronic carriers are those who continue to harbor a pathogen such as hepatitis B virus or Salmonella Typhi, the causative agent of typhoid fever, for months or even years after their initial infection. One notorious carrier is Mary Mallon, or Typhoid Mary, who was an asymptomatic chronic carrier of Salmonella Typhi. As a cook in New York City and New Jersey in the early 1900s, she unintentionally infected dozens of people until she was placed in isolation on an island in the East River, where she died 23 years later.45
Carriers commonly transmit disease because they do not realize they are infected, and consequently take no special precautions to prevent transmission. Symptomatic persons who are aware of their illness, on the other hand, may be less likely to transmit infection because they are either too sick to be out and about, take precautions to reduce transmission, or receive treatment that limits the disease.
Animal reservoirs. Humans are also subject to diseases that have animal reservoirs. Many of these diseases are transmitted from animal to animal, with humans as incidental hosts. The term zoonosis refers to an infectious disease that is transmissible under natural conditions from vertebrate animals to humans. Long recognized zoonotic diseases include brucellosis (cows and pigs), anthrax (sheep), plague (rodents), trichinellosis/trichinosis (swine), tularemia (rabbits), and rabies (bats, raccoons, dogs, and other mammals). Zoonoses newly emergent in North America include West Nile encephalitis (birds), and monkeypox (prairie dogs).
Many newly recognized infectious diseases in humans, including HIV/AIDS, Ebola infection and SARS, are thought to have emerged from animal hosts, although those hosts have not yet been identified.
Environmental reservoirs. Plants, soil, and water in the environment are also reservoirs for some infectious agents. Many fungal agents, such as those that cause histoplasmosis, live and multiply in the soil. Outbreaks of Legionnaires disease are often traced to water supplies in cooling towers and evaporative condensers, reservoirs for the causative organism Legionella pneumophila.
Portal of exit
Portal of exit is the path by which a pathogen leaves its host. The portal of exit usually corresponds to the site where the pathogen is localized. For example, influenza viruses and Mycobacterium tuberculosis exit the respiratory tract, schistosomes through urine, cholera vibrios in feces, Sarcoptes scabiei in scabies skin lesions, and enterovirus 70, a cause of hemorrhagic conjunctivitis, in conjunctival secretions. Some bloodborne agents can exit by crossing the placenta from mother to fetus (rubella, syphilis, toxoplasmosis), while others exit through cuts or needles in the skin (hepatitis B) or blood-sucking arthropods (malaria).
Modes of transmission
An infectious agent may be transmitted from its natural reservoir to a susceptible host in different ways. There are different classifications for modes of transmission. Here is one classification:
•Direct
− Direct contact
− Droplet spread
•Indirect
− Airborne
− Vehicleborne
− Vectorborne (mechanical or biologic)
In direct transmission, an infectious agent is transferred from a reservoir to a susceptible host by direct contact or droplet spread.
Direct contact occurs through skin-to-skin contact, kissing, and sexual intercourse. Direct contact also refers to contact with soil or vegetation harboring infectious organisms. Thus, infectious mononucleosis (“kissing disease”) and gonorrhea are spread from person to person by direct contact. Hookworm is spread by direct contact with contaminated soil.
Droplet spread refers to spray with relatively large, short-range aerosols produced by sneezing, coughing, or even talking. Droplet spread is classified as direct because transmission is by direct spray over a few feet, before the droplets fall to the ground. Pertussis and meningococcal infection are examples of diseases transmitted from an infectious patient to a susceptible host by droplet spread.
Indirect transmission refers to the transfer of an infectious agent from a reservoir to a host by suspended air particles, inanimate objects (vehicles), or animate intermediaries (vectors).
Airborne transmission occurs when infectious agents are carried by dust or droplet nuclei suspended in air. Airborne dust includes material that has settled on surfaces and become resuspended by air currents as well as infectious particles blown from the soil by the wind. Droplet nuclei are dried residue of less than 5 microns in size. In contrast to droplets that fall to the ground within a few feet, droplet nuclei may remain suspended in the air for long periods of time and may be blown over great distances. Measles, for example, has occurred in children who came into a physician’s office after a child with measles had left, because the measles virus remained suspended in the air.46
Vehicles that may indirectly transmit an infectious agent include food, water, biologic products (blood), and fomites (inanimate objects such as handkerchiefs, bedding, or surgical scalpels). A vehicle may passively carry a pathogen — as food or water may carry hepatitis A virus. Alternatively, the vehicle may provide an environment in which the agent grows, multiplies, or produces toxin — as improperly canned foods provide an environment that supports production of botulinum toxin by Clostridium botulinum.
Vectors such as mosquitoes, fleas, and ticks may carry an infectious agent through purely mechanical means or may support growth or changes in the agent. Examples of mechanical transmission are flies carrying Shigella on their appendages and fleas carrying Yersinia pestis, the causative agent of plague, in their gut. In contrast, in biologic transmission, the causative agent of malaria or guinea worm disease undergoes maturation in an intermediate host before it can be transmitted to humans (Figure 1.20).
Portal of entry
The portal of entry refers to the manner in which a pathogen enters a susceptible host. The portal of entry must provide access to tissues in which the pathogen can multiply or a toxin can act. Often, infectious agents use the same portal to enter a new host that they used to exit the source host. For example, influenza virus exits the respiratory tract of the source host and enters the respiratory tract of the new host. In contrast, many pathogens that cause gastroenteritis follow a so-called “fecal-oral” route because they exit the source host in feces, are carried on inadequately washed hands to a vehicle such as food, water, or utensil, and enter a new host through the mouth. Other portals of entry include the skin (hookworm), mucous membranes (syphilis), and blood (hepatitis B, human immunodeficiency virus).
Figure 1.20 Complex Life Cycle of Dracunculus medinensis (Guinea worm)
Source: Centers for Disease Control and Prevention. Principles of epidemiology, 2nd ed. Atlanta: U.S. Department of Health and Human Services;1992.
Interventions are directed at:
•Controlling or eliminating agent at source of transmission
•Protecting portals of entry
•Increasing host’s defenses
Host
The final link in the chain of infection is a susceptible host. Susceptibility of a host depends on genetic or constitutional factors, specific immunity, and nonspecific factors that affect an individual’s ability to resist infection or to limit pathogenicity. An individual’s genetic makeup may either increase or decrease susceptibility. For example, persons with sickle cell trait seem to be at least partially protected from a particular type of malaria. Specific immunity refers to protective antibodies that are directed against a specific agent. Such antibodies may develop in response to infection, vaccine, or toxoid (toxin that has been deactivated but retains its capacity to stimulate production of toxin antibodies) or may be acquired by transplacental transfer from mother to fetus or by injection of antitoxin or immune globulin. Nonspecific factors that defend against infection include the skin, mucous membranes, gastric acidity, cilia in the respiratory tract, the cough reflex, and nonspecific immune response. Factors that may increase susceptibility to infection by disrupting host defenses include malnutrition, alcoholism, and disease or therapy that impairs the nonspecific immune response.
Implications for public health
Knowledge of the portals of exit and entry and modes of transmission provides a basis for determining appropriate control measures. In general, control measures are usually directed against the segment in the infection chain that is most susceptible to intervention, unless practical issues dictate otherwise.
For some diseases, the most appropriate intervention may be directed at controlling or eliminating the agent at its source. A patient sick with a communicable disease may be treated with antibiotics to eliminate the infection. An asymptomatic but infected person may be treated both to clear the infection and to reduce the risk of transmission to others. In the community, soil may be decontaminated or covered to prevent escape of the agent.
Some interventions are directed at the mode of transmission. Interruption of direct transmission may be accomplished by isolation of someone with infection, or counseling persons to avoid the specific type of contact associated with transmission. Vehicleborne transmission may be interrupted by elimination or decontamination of the vehicle. To prevent fecal-oral transmission, efforts often focus on rearranging the environment to reduce the risk of contamination in the future and on changing behaviors, such as promoting handwashing. For airborne diseases, strategies
may be directed at modifying ventilation or air pressure, and filtering or treating the air. To interrupt vectorborne transmission, measures may be directed toward controlling the vector population, such as spraying to reduce the mosquito population.
Some strategies that protect portals of entry are simple and effective. For example, bed nets are used to protect sleeping persons from being bitten by mosquitoes that may transmit malaria. A dentist’s mask and gloves are intended to protect the dentist from a patient’s blood, secretions, and droplets, as well to protect the patient from the dentist. Wearing of long pants and sleeves and use of insect repellent are recommended to reduce the risk of Lyme disease and West Nile virus infection, which are transmitted by the bite of ticks and mosquitoes, respectively.
Some interventions aim to increase a host’s defenses. Vaccinations promote development of specific antibodies that protect against infection. On the other hand, prophylactic use of antimalarial drugs, recommended for visitors to malaria-endemic areas, does not prevent exposure through mosquito bites, but does prevent infection from taking root.
Finally, some interventions attempt to prevent a pathogen from encountering a susceptible host. The concept of herd immunity suggests that if a high enough proportion of individuals in a population are resistant to an agent, then those few who are susceptible will be protected by the resistant majority, since the pathogen will be unlikely to “find” those few susceptible individuals. The degree of herd immunity necessary to prevent or interrupt an outbreak varies by disease. In theory, herd immunity means that not everyone in a community needs to be resistant (immune) to prevent disease spread and occurrence of an outbreak. In practice, herd immunity has not prevented outbreaks of measles and rubella in populations with immunization levels as high as 85% to 90%. One problem is that, in highly immunized populations, the relatively few susceptible persons are often clustered in subgroups defined by socioeconomic or cultural factors. If the pathogen is introduced into one of these subgroups, an outbreak may occur.
Exercise 1.9
Information about dengue fever is provided on the following pages. After studying this information, outline the chain of infection by identifying the reservoir(s), portal(s) of exit, mode(s) of transmission, portal(s) of entry, and factors in host susceptibility.
Reservoirs:
Portals of exit:
Modes of transmission:
Portals of entry:
Factors in host susceptibility:
Dengue Fact Sheet
What is dengue?
Dengue is an acute infectious disease that comes in two forms: dengue and dengue hemorrhagic fever. The principal symptoms of dengue are high fever, severe headache, backache, joint pains, nausea and vomiting, eye pain, and rash. Generally, younger children have a milder illness than older children and adults.
Dengue hemorrhagic fever is a more severe form of dengue. It is characterized by a fever that lasts from 2 to 7 days, with general signs and symptoms that could occur with many other illnesses (e.g., nausea, vomiting, abdominal pain, and headache). This stage is followed by hemorrhagic manifestations, tendency to bruise easily or other types of skin hemorrhages, bleeding nose or gums, and possibly internal bleeding. The smallest blood vessels (capillaries) become excessively permeable (“leaky”), allowing the fluid component to escape from the blood vessels.
This may lead to failure of the circulatory system and shock, followed by death, if circulatory failure is not corrected.
Although the average case-fatality rate is about 5%, with good medical management, mortality can be less than 1%.
What causes dengue?
Dengue and dengue hemorrhagic fever are caused by any one of four closely related flaviviruses, designated DEN-1, DEN-2, DEN-3, or DEN-4.
How is dengue diagnosed?
Diagnosis of dengue infection requires laboratory confirmation, either by isolating the virus from serum within 5 days after onset of symptoms, or by detecting convalescent-phase specific antibodies obtained at least 6 days after onset of symptoms.
What is the treatment for dengue or dengue hemorrhagic fever?
There is no specific medication for treatment of a dengue infection. Persons who think they have dengue should use analgesics (pain relievers) with acetaminophen and avoid those containing aspirin. They should also rest, drink plenty of fluids, and consult a physician. Persons with dengue hemorrhagic fever can be effectively treated by fluid replacement therapy if an early clinical diagnosis is made, but hospitalization is often required.
How common is dengue and where is it found?
Dengue is endemic in many tropical countries in Asia and Latin America, most countries in Africa, and much of the Caribbean, including Puerto Rico. Cases have occurred sporadically in Texas. Epidemics occur periodically. Globally, an estimated 50 to 100 million cases of dengue and several hundred thousand cases of dengue hemorrhagic fever occur each year, depending on epidemic activity. Between 100 and 200 suspected cases are introduced into the United States each year by travelers.
How is dengue transmitted?
Dengue is transmitted to people by the bite of an Aedes mosquito that is infected with a dengue virus. The mosquito becomes infected with dengue virus when it bites a person who has dengue or DHF and after about a week can transmit the virus while biting a healthy person. Monkeys may serve as a reservoir in some parts of Asia and Africa. Dengue cannot be spread directly from person to person.
Who has an increased risk of being exposed to dengue?
Susceptibility to dengue is universal. Residents of or visitors to tropical urban areas and other areas where dengue is endemic are at highest risk of becoming infected. While a person who survives a bout of dengue caused by one serotype develops lifelong immunity to that serotype, there is no cross-protection against the three other serotypes.
Dengue Fact Sheet (Continued)
What can be done to reduce the risk of acquiring dengue?
There is no vaccine for preventing dengue. The best preventive measure for residents living in areas infested with Aedes aegypti is to eliminate the places where the mosquito lays her eggs, primarily artificial containers that hold water.
Items that collect rainwater or are used to store water (for example, plastic containers, 55-gallon drums, buckets, or used automobile tires) should be covered or properly discarded. Pet and animal watering containers and vases with fresh flowers should be emptied and scoured at least once a week. This will eliminate the mosquito eggs and larvae and reduce the number of mosquitoes present in these areas.
For travelers to areas with dengue, as well as people living in areas with dengue, the risk of being bitten by mosquitoes indoors is reduced by utilization of air conditioning or windows and doors that are screened. Proper application of mosquito repellents containing 20% to 30% DEET as the active ingredient on exposed skin and clothing decreases the risk of being bitten by mosquitoes. The risk of dengue infection for international travelers appears to be small, unless an epidemic is in progress.
Can epidemics of dengue hemorrhagic fever be prevented?
The emphasis for dengue prevention is on sustainable, community-based, integrated mosquito control, with limited reliance on insecticides (chemical larvicides and adulticides). Preventing epidemic disease requires a coordinated community effort to increase awareness about dengue/DHF, how to recognize it, and how to control the mosquito that transmits it. Residents are responsible for keeping their yards and patios free of sites where mosquitoes can be produced.
Source: Centers for Disease Control and Prevention [Internet]. Dengue Fever. [updated 2005 Aug 22]. Available from http://www.cdc.gov/ncidod/dvbid/dengue/index.htm.
Epidemic Disease Occurrence
Level of disease
The amount of a particular disease that is usually present in a community is referred to as the baseline or endemic level of the disease. This level is not necessarily the desired level, which may in fact be zero, but rather is the observed level. In the absence of intervention and assuming that the level is not high enough to deplete the pool of susceptible persons, the disease may continue to occur at this level indefinitely. Thus, the baseline level is often regarded as the expected level of the disease.
While some diseases are so rare in a given population that a single case warrants an epidemiologic investigation (e.g., rabies, plague, polio), other diseases occur more commonly so that only deviations from the norm warrant investigation. Sporadic refers to a disease that occurs infrequently and irregularly. Endemic refers to the constant presence and/or usual prevalence of a disease or infectious agent in a population within a geographic area. Hyperendemic refers to persistent, high levels of disease occurrence.
Occasionally, the amount of disease in a community rises above the expected level. Epidemic refers to an increase, often sudden, in the number of cases of a disease above what is normally expected in that population in that area. Outbreak carries the same definition of epidemic, but is often used for a more limited geographic area. Cluster refers to an aggregation of cases grouped in place and time that are suspected to be greater than the number expected, even though the expected number may not be known. Pandemic refers to an epidemic that has spread over several countries or continents, usually affecting a large number of people.
Epidemics occur when an agent and susceptible hosts are present in adequate numbers, and the agent can be effectively conveyed from a source to the susceptible hosts. More specifically, an epidemic may result from:
•A recent increase in amount or virulence of the agent,
•The recent introduction of the agent into a setting where it has not been before,
•An enhanced mode of transmission so that more susceptible persons are exposed,
•A change in the susceptibility of the host response to the agent, and/or
•Factors that increase host exposure or involve introduction through new portals of entry.47
The previous description of epidemics presumes only infectious agents, but non-infectious diseases such as diabetes and obesity exist in epidemic proportion in the U.S.51,52
A. Sporadic disease B. Endemic disease
C.Hyperendemic disease
D.Pandemic disease
E.Epidemic disease
_____ 1.
22 cases of legionellosis occurred within 3 weeks among residents of a particular neighborhood (usually 0 or 1 per year)
_____ 2.
Average annual incidence was 364 cases of pulmonary tuberculosis per 100,000 population in one area, compared with national average of 134 cases per 100,000 population
_____ 3.
Over 20 million people worldwide died from influenza in 1918—1919
_____ 4.
Single case of histoplasmosis was diagnosed in a community
_____ 5.
About 60 cases of gonorrhea are usually reported in this region per week, slightly less than the national average
Check your answers on page 1-84
Epidemic Patterns
Epidemics can be classified according to their manner of spread through a population:
•Common-source
− Point
− Continuous
− Intermittent
•Propagated
•Mixed
•Other
A common-source outbreak is one in which a group of persons are all exposed to an infectious agent or a toxin from the same source.
If the group is exposed over a relatively brief period, so that everyone who becomes ill does so within one incubation period, then the common-source outbreak is further classified as a pointsource outbreak. The epidemic of leukemia cases in Hiroshima following the atomic bomb blast and the epidemic of hepatitis A among patrons of the Pennsylvania restaurant who ate green onions each had a point source of exposure.38,44 If the number of cases during an epidemic were plotted over time, the resulting graph, called an epidemic curve, would typically have a steep upslope and a more gradual downslope (a so-called “log-normal distribution”).
Figure 1.21 Hepatitis A Cases by Date of Onset, November–December, 1978
Source: Centers for Disease Control and Prevention. Unpublished data; 1979.
In some common-source outbreaks, case-patients may have been exposed over a period of days, weeks, or longer. In a continuous common-source outbreak, the range of exposures and range of incubation periods tend to flatten and widen the peaks of the epidemic curve (Figure 1.22). The epidemic curve of an intermittent common-source outbreak often has a pattern reflecting the intermittent nature of the exposure.
Figure 1.22 Diarrheal Illness in City Residents by Date of Onset and Character of Stool, December 1989–January 1990
Source: Centers for Disease Control and Prevention. Unpublished data; 1990.
A propagated outbreak results from transmission from one person to another. Usually, transmission is by direct person-to-person contact, as with syphilis. Transmission may also be vehicleborne (e.g., transmission of hepatitis B or HIV by sharing needles) or vectorborne (e.g., transmission of yellow fever by mosquitoes). In propagated outbreaks, cases occur over more than one incubation period. In Figure 1.23, note the peaks occurring about 11 days apart, consistent with the incubation period for measles. The epidemic usually wanes after a few generations, either because the number of susceptible persons falls below some critical level required to sustain transmission, or because intervention measures become effective.
Figure 1.23 Measles Cases by Date of Onset, October 15, 1970–January 16, 1971
Source: Centers for Disease Control and Prevention. Measles outbreak—Aberdeen, S.D.
MMWR 1971;20:26.
Some epidemics have features of both common-source epidemics and propagated epidemics. The pattern of a common-source outbreak followed by secondary person-to-person spread is not uncommon. These are called mixed epidemics. For example, a common-source epidemic of shigellosis occurred among a group of 3,000 women attending a national music festival (Figure 1.24). Many developed symptoms after returning home. Over the next few weeks, several state health departments detected subsequent generations of Shigella cases propagated by person-to-person transmission from festival attendees.48
Figure 1.24 Shigella Cases at a Music Festival by Day of Onset, August 1988
Adapted from: Lee LA, Ostroff SM, McGee HB, Johnson DR, Downes FP, Cameron DN, et al. An outbreak of shigellosis at an outdoor music festival. Am J Epidemiol 1991;133:608–15.
Finally, some epidemics are neither common-source in its usual sense nor propagated from person to person. Outbreaks of zoonotic or vectorborne disease may result from sufficient prevalence of infection in host species, sufficient presence of vectors, and sufficient human-vector interaction. Examples (Figures 1.25 and 1.26) include the epidemic of Lyme disease that emerged in the northeastern United States in the late 1980s (spread from deer to human by deer ticks) and the outbreak of West Nile encephalitis in the Queens section of New York City in 1999 (spread from birds to humans by mosquitoes).49,50
Figure 1.25 Number of Reported Cases of Lyme Disease by Year — United States, 1992–2003.
Data Source: Centers for Disease Control and Prevention. Summary of notifiable diseases– United States, 2003. Published April 22, 2005, for MMWR 2003;52(No. 54):9,17,71–72.
Figure 1.26 Number of Reported Cases of West Nile Encephalitis — New York City, 1999
Source: Centers for Disease Control and Prevention. Outbreak of West Nile-Like Viral Encephalitis–New York, 1999. MMWR 1999;48(38):845–9.
A.Point source
B.Intermittent or continuous common source
C.Propagated
_____ 1.
21 cases of shigellosis among children and workers at a day care center over a period of 6 weeks, no external source identified incubation period for shigellosis is usually 1–3 days)
_____ 2.
36 cases of giardiasis over 6 weeks traced to occasional use of a supplementary reservoir (incubation period for giardiasis 3–25 days or more, usually 7–10 days)
_____ 3.
43 cases of norovirus infection over 2 days traced to the ice machine on a cruise ship (incubation period for norovirus is usually 24–48 hours)
Check your answers on page 1-84
Summary
As the basic science of public health, epidemiology includes the study of the frequency, patterns, and causes of health-related states or events in populations, and the application of that study to address public health issues. Epidemiologists use a systematic approach to assess the What, Who, Where, When, and Why/How of these health states or events. Two essential concepts of epidemiology are population and comparison. Core epidemiologic tasks of a public health epidemiologist include public health surveillance, field investigation, research, evaluation, and policy development. In carrying out these tasks, the epidemiologist is almost always part of the team dedicated to protecting and promoting the public’s health.
Epidemiologists look at differences in disease and injury occurrence in different populations to generate hypotheses about risk factors and causes. They generally use cohort or case-control studies to evaluate these hypotheses. Knowledge of basic principles of disease occurrence and spread in a population is essential for implementing effective control and prevention measures.
Exercise 1.1
1.B
2.B
3.A
4.A
5.C
6.A
Exercise 1.2
1.Having identified a cluster of cases never before seen in the area, public health officials must seek additional information to assess the community’s health. Is the cluster limited to persons who have just returned from traveling where West Nile virus infection is common, or was the infection acquired locally, indicating that the community is truly at risk? Officials could check whether hospitals have seen more patients than usual for encephalitis. If so, officials could document when the increase in cases began, where the patients live or work or travel, and personal characteristics such as age. Mosquito traps could be placed to catch mosquitoes and test for presence of the West Nile virus. If warranted, officials could conduct a serosurvey of the community to document the extent of infection. Results of these efforts would help officials assess the community’s burden of disease and risk of infection.
2.West Nile virus infection is spread by mosquitoes. Persons who spend time outdoors, particularly at times such as dusk when mosquitoes may be most active, can make personal decisions to reduce their own risk or not. Knowing that the risk is present but may be small, an avid gardener might or might not decide to curtail the time spent gardening in the evening, or use insect repellent containing DEET, or wear long pants and long-sleeve shirts even though it is August, or empty the bird bath where mosquitoes breed.
3.What proportion of persons infected with West Nile virus actually develops encephalitis? Do some infected people have milder symptoms or no symptoms at all? Investigators could conduct a serosurvey to assess infection, and ask about symptoms and illness. In addition, what becomes of the persons who did develop encephalitis? What proportion survived? Did they recover completely or did some have continuing difficulties?
4.Although the cause and mode of transmission were known (West Nile virus and mosquitoes, respectively), public health officials asked many questions regarding how the virus was introduced (mosquito on an airplane? wayward bird? bioterrorism?), whether the virus had a reservoir in the area (e.g., birds), what types of mosquitoes could transmit the virus, what were the host risk factors for infection or encephalitis, etc.
Exercise 1.3
1.A
2.E
3.F
4.B
5.D
6.C
Exercise 1.4
1.Confirmed
2.Probable 3. Probable
4.Probable
5.Possible
Exercise 1.5
1.Third criterion may be limiting because patient may not be aware of close contact
2.Probably reasonable
3.Criteria do not require sophisticated evaluation or testing, so can be used anywhere in the world
4.Too broad. Most persons with cough and fever returning from Toronto, China, etc., are more likely to have upper respiratory infections than SARS.
Exercise 1.6
The following tables can be created from the data in Tables 1.5 and 1.6:
Table A. Deaths and Death Rates for an Unusual Event, By Sex and Socioeconomic Status
Female Male
High Middle Low High Middle Low
Persons at risk 143 107 212 179 173 499
Survivors 134 94 80 59 25 58
Deaths 9 13 132 120 148 441
Death rate (%) 6.3 12.1 62.3 67.0 85.5 88.4
Table B. Deaths and Death Rates for an Unusual Event, By Sex
Female Male Total
Persons at risk 462 851 1,313
Survivors 308 142 450
Deaths 154 709 863
Death rate (%) 33.3 83.3 65.7
Table C. Deaths and Death Rates for an Unusual Event, By Age Group
Persons at risk 83 1,230 1,313
Survivors 52 398 450
Deaths 31 832 863
Death rate (%) 37.3 67.6 65.7
By reviewing the data in these tables, you can see that men (see Table B) and adults (see Table C) were more likely to die than were women and children. Death rates for both women and men declined as socioeconomic status increased (see Table A), but the men in even the highest socioeconomic class were more likely to die than the women in the lowest socioeconomic class. These data, which are consistent with the phrase “Women and children first,” represent the mortality experience of passengers on the Titanic.
Data Sources: Passengers on the Titanic [Internet]. StatSci.org; [updated 2002 Dec 29; cited 2005 April]. Available from http://www.statsci.org/data/general/titanic.html.
Victims of the Titanic Disaster [Internet]. Encyclopedia Titanica; [cited 2005 April]. Available from http://www.encyclopediatitanica.org.
Note: the precise number of passengers, deaths, and class of service are disputed. The Encyclopedia Titanica website includes numerous discussions of these disputed numbers.
Exercise 1.7
1.D
2.B
3.C
4.A
Exercise 1.8
1.
a.Agent: Bacillus anthracis, a bacterium that can survive for years in spore form, is a necessary cause.
b.Host: People are generally susceptible to anthrax. However, infection can be prevented by vaccination. Cuts or abrasions of the skin may permit entry of the bacteria.
c.Environment: Persons at risk for naturally acquired infection are those who are likely to be exposed to infected animals or contaminated animal products, such as veterinarians, animal handlers, abattoir workers, and laboratorians. Persons who are potential targets of bioterrorism are also at increased risk.
2.
a.Component cause
b.Necessary cause
c.Component cause
d.Sufficient cause
Exercise 1.9
Reservoirs: humans and possibly monkeys
Portals of exit: skin (via mosquito bite)
Modes of transmission: indirect transmission to humans by mosquito vector
Portals of entry: through skin to blood (via mosquito bite)
Factors in host susceptibility: except for survivors of dengue infection who are immune to subsequent infection from the same serotype, susceptibility is universal
Exercise 1.10
1.E
2.C
3.D
4.A
5.B
Exercise 1.11
1.C
2.B
3.A
SELF-ASSESSMENT QUIZ
Now that you have read Lesson 1 and have completed the exercises, you should be ready to take the self-assessment quiz. This quiz is designed to help you assess how well you have learned the content of this lesson. You
may refer to the lesson text whenever you are unsure of the answer.
Unless instructed otherwise, choose ALL correct answers for each
question.
1.In the definition of epidemiology, “distribution” refers to:
A.Who
B.When C. Where
D. Why
2.In the definition of epidemiology, “determinants” generally includes:
A.Agents
B.Causes
C.Control measures
D.Risk factors
E.Sources
3.Epidemiology, as defined in this lesson, would include which of the following activities? A. Describing the demographic characteristics of persons with acute aflatoxin poisoning in District A
B.Prescribing an antibiotic to treat a patient with community-acquired methicillin-resistant Staphylococcus aureus infection
C.Comparing the family history, amount of exercise, and eating habits of those with and without newly diagnosed diabetes
D.Recommending that a restaurant be closed after implicating it as the source of a hepatitis A outbreak
4.John Snow’s investigation of cholera is considered a model for epidemiologic field investigations because it included a:
A.Biologically plausible hypothesis
B.Comparison of a health outcome among exposed and unexposed groups
C.Multivariate statistical model
D.Spot map
E.Recommendation for public health action
5.Public health surveillance includes which of the following activities:
A.Diagnosing whether a case of encephalitis is actually due to West Nile virus infection
B.Soliciting case reports of persons with symptoms compatible with SARS from local hospitals
C.Creating graphs of the number of dog bites by week and neighborhood
D.Writing a report on trends in seat belt use to share with the state legislature
E.Disseminating educational materials about ways people can reduce their risk of Lyme disease
6.The hallmark feature of an analytic epidemiologic study is: (Choose one best answer)
A.Use of an appropriate comparison group B. Laboratory confirmation of the diagnosis
C.Publication in a peer-reviewed journal
D.Statistical analysis using logistic regression
7.A number of passengers on a cruise ship from Puerto Rico to the Panama Canal have recently developed a gastrointestinal illness compatible with norovirus (formerly called Norwalk-like virus). Testing for norovirus is not readily available in any nearby island, and the test takes several days even where available. Assuming you are the epidemiologist called on to board the ship and investigate this possible outbreak, your case definition should include, at a minimum: (Choose one best answer) A. Clinical criteria, plus specification of time, place, and person
B.Clinical features, plus the exposure(s) you most suspect
C.Suspect cases
D.The nationally agreed standard case definition for disease reporting
8.A specific case definition is one that:
A.Is likely to include only (or mostly) true cases
B.Is considered “loose” or “broad”
C.Will include more cases than a sensitive case definition
D.May exclude mild cases
9.Comparing numbers and rates of illness in a community, rates are preferred for: (Choose one best answer)
A.Conducting surveillance for communicable diseases
B.Deciding how many doses of immune globulin are needed
C.Estimating subgroups at highest risk
D.Telling physicians which strain of influenza is most prevalent
10.For the cruise ship scenario described in Question 7, how would you display the time course of the outbreak? (Choose one best answer)
A.Endemic curve
B.Epidemic curve C. Seasonal trend
D. Secular trend
11.For the cruise ship scenario described in Question 7, if you suspected that the norovirus may have been transmitted by ice made or served aboard ship, how might you display “place”?
A.Spot map by assigned dinner seating location
B.Spot map by cabin
C.Shaded map of United States by state of residence
D.Shaded map by whether passenger consumed ship’s ice or not
12.Which variables might you include in characterizing the outbreak described in Question 7 by person?
A.Age of passenger
B.Detailed food history (what person ate) while aboard ship
C.Status as passenger or crew
D.Symptoms
13.When analyzing surveillance data by age, which of the following age groups is preferred?
(Choose one best answer)
A.1-year age groups
B.5-year age groups
C.10-year age groups
D.Depends on the disease
14.A study in which children are randomly assigned to receive either a newly formulated vaccine or the currently available vaccine, and are followed to monitor for side effects and effectiveness of each vaccine, is an example of which type of study?
A.Experimental
B.Observational
C.Cohort
D.Case-control
E.Clinical trial
15.The Iowa Women’s Health Study, in which researchers enrolled 41,837 women in 1986 and collected exposure and lifestyle information to assess the relationship between these factors and subsequent occurrence of cancer, is an example of which type(s) of study?
A.Experimental
B.Observational
C.Cohort
D.Case-control
E.Clinical trial
16.British investigators conducted a study to compare measles-mumps-rubella (MMR) vaccine history among 1,294 children with pervasive development disorder (e.g., autism and Asperger’s syndrome) and 4,469 children without such disorders. (They found no association.) This is an example of which type(s) of study?
A.Experimental
B.Observational
C.Cohort
D.Case-control
E.Clinical trial
Source: Smeeth L, Cook C, Fombonne E, Heavey L, Rodrigues LC, Smith PG, Hall AJ. MMR vaccination and pervasive developmental disorders. Lancet 2004;364:963–9.
17.A cohort study differs from a case-control study in that:
A.Subjects are enrolled or categorized on the basis of their exposure status in a cohort study but not in a case-control study
B.Subjects are asked about their exposure status in a cohort study but not in a casecontrol study
C.Cohort studies require many years to conduct, but case-control studies do not
D.Cohort studies are conducted to investigate chronic diseases, case-control studies are used for infectious diseases
18.A key feature of a cross-sectional study is that:
A.It usually provides information on prevalence rather than incidence
B.It is limited to health exposures and behaviors rather than health outcomes
C.It is more useful for descriptive epidemiology than it is for analytic epidemiology D. It is synonymous with survey
19.The epidemiologic triad of disease causation refers to: (Choose one best answer)
A.Agent, host, environment
B.Time, place, person
C.Source, mode of transmission, susceptible host
D.John Snow, Robert Koch, Kenneth Rothman
20.For each of the following, identify the appropriate letter from the time line in Figure 1.27 representing the natural history of disease. _______ Onset of symptoms
_______ Usual time of diagnosis _______ Exposure
21.A reservoir of an infectious agent can be:
A.An asymptomatic human
B.A symptomatic human
C.An animal
D.The environment
22.Indirect transmission includes which of the following?
A.Droplet spread
B.Mosquito-borne
C.Foodborne
D.Doorknobs or toilet seats
23.Disease control measures are generally directed at which of the following?
A.Eliminating the reservoir
B.Eliminating the vector C. Eliminating the host
D.Interrupting mode of transmission
E.Reducing host susceptibility
24.Which term best describes the pattern of occurrence of the three diseases noted below in a single area? A. Endemic
B.Outbreak
C.Pandemic
D.Sporadic
_______ Disease 1: usually 40–50 cases per week; last week, 48 cases
_______ Disease 2: fewer than 10 cases per year; last week, 1 case
_______ Disease 3: usually no more than 2–4 cases per week; last week, 13 cases
25.A propagated epidemic is usually the result of what type of exposure? A. Point source
B.Continuous common source
C.Intermittent common source
D.Person-to-person
Answers to Self-Assessment Quiz
1.A, B, C. In the definition of epidemiology, “distribution” refers to descriptive epidemiology, while “determinants” refers to analytic epidemiology. So “distribution” covers time (when), place (where), and person (who), whereas “determinants” covers causes, risk factors, modes of transmission (why and how).
2.A, B, D, E. In the definition of epidemiology, “determinants” generally includes the causes (including agents), risk factors (including exposure to sources), and modes of transmission, but does not include the resulting public health action.
3.A, C, D. Epidemiology includes assessment of the distribution (including describing demographic characteristics of an affected population), determinants (including a study of possible risk factors), and the application to control health problems (such as closing a restaurant). It does not generally include the actual treatment of individuals, which is the responsibility of health-care providers.
4.A, B, D, E. John Snow’s investigation of cholera is considered a model for epidemiologic field investigations because it included a biologically plausible (but not popular at the time) hypothesis that cholera was water-borne, a spot map, a comparison of a health outcome (death) among exposed and unexposed groups, and a recommendation for public health action. Snow’s elegant work predated multivariate analysis by 100 years.
5.B, C, D. Public health surveillance includes collection (B), analysis (C), and dissemination (D) of public health information to help guide public health decision making and action, but it does not include individual clinical diagnosis, nor does it include the actual public health actions that are developed based on the information.
6.A. The hallmark feature of an analytic epidemiologic study is use of an appropriate comparison group.
7.A. A case definition for a field investigation should include clinical criteria, plus specification of time, place, and person. The case definition should be independent of the exposure you wish to evaluate. Depending on the availability of laboratory confirmation, certainty of diagnosis, and other factors, a case definition may or may not be developed for suspect cases. The nationally agreed standard case definition for disease reporting is usually quite specific, and usually does not include suspect or possible cases.
8.A, D. A specific or tight case definition is one that is likely to include only (or mostly) true cases, but at the expense of excluding milder or atypical cases.
9.C. Rates assess risk. Numbers are generally preferred for identifying individual cases and for resource planning.
10.B. An epidemic curve, with date or time of onset on its x-axis and number of cases on the yaxis, is the classic graph for displaying the time course of an epidemic.
11.A, B, C. “Place” includes location of actual or suspected exposure as well as location of residence, work, school, and the like.
12.A, C. “Person” refers to demographic characteristics. It generally does not include clinical features characteristics or exposures.
13.D. Epidemiologists tailor descriptive epidemiology to best describe the data they have. Because different diseases have different age distributions, epidemiologists use different age breakdowns appropriate for the disease of interest.
14.A, E. A study in which subjects are randomized into two intervention groups and monitored to identify health outcomes is a clinical trial, which is type of experimental study. It is not a cohort study, because that term is limited to observational studies.
15.B, C. A study that assesses (but does not dictate) exposure and follows to document subsequent occurrence of disease is an observational cohort study.
16.B, D. A study in which subjects are enrolled on the basis of having or not having a health outcome is an observational case-control study.
Source: Smeeth L, Cook C, Fombonne E, Heavey L, Rodrigues LC, Smith PG, Hall AJ. MMR vaccination and pervasive developmental disorders. Lancet 2004;364:963–9.
17.A. The key difference between a cohort and case-control study is that, in a cohort study, subjects are enrolled on the basis of their exposure, whereas in a case-control study subjects are enrolled on the basis of whether they have the disease of interest or not. Both types of studies assess exposure and disease status. While some cohort studies have been conducted over several years, others, particularly those that are outbreak-related, have been conducted in days. Either type of study can be used to study a wide array of health problems, including infectious and non-infectious.
18.A, C, D. A cross-sectional study or survey provides a snapshot of the health of a population, so it assesses prevalence rather than incidence. As a result, it is not as useful as a cohort or case-control study for analytic epidemiology. However, a cross-sectional study can easily measure prevalence of exposures and outcomes.
19.A. The epidemiologic triad of disease causation refers to agent-host-environment.
20.C. Onset of symptoms D. Usual time of diagnosis
A.Exposure
21.A, B, C, D. A reservoir of an infectious agent is the habitat in which an agent normally lives, grows, and multiplies, which may include humans, animals, and the environment.
22.B, C, D. Indirect transmission refers to the transmission of an infectious agent by suspended airborne particles, inanimate objects (vehicles, food, water) or living intermediaries (vectors such as mosquitoes). Droplet spread is generally considered short-distance direct transmission.
23.A, B, D, E. Disease control measures are generally directed at eliminating the reservoir or vector, interrupting transmission, or protecting (but not eliminating!) the host.
24.A. Disease 1: usually 40–50 cases per week; last week, 48 cases
D. Disease 2: fewer than 10 cases per year; last week, 1 case
B.Disease 3: usually no more than 2–4 cases per week; last week, 13 cases
25.D. A propagated epidemic is one in which infection spreads from person to person.
