Lesson 1: Introduction to Epidemiology

Section 5: The Epidemiologic Approach

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 agreed-upon 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.

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.

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).

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 SARS-associated 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)

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.

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.

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 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.

References (This Section)

25. Centers for Disease Control and Prevention. Case definitions for infectious conditions under public health surveillance. MMWR Recomm Rep 1997:46(RR-10):1–55.
26. 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.
27. Centers for Disease Control and Prevention. Outbreak of severe acute respiratory syndrome–worldwide, 2003. MMWR 2003: 52:226–8.
28. Centers for Disease Control and Prevention. Revised U.S. surveillance case definition for severe acute respiratory syndrome (SARS) and update on SARS cases–United States and worldwide, December 2003. MMWR 2003:52:1202–6.
29. Centers for Disease Control and Prevention. Indicators for chronic disease surveillance. MMWR Recomm Rep 2004;53(RR-11):1–6.
30. Centers for Disease Control and Prevention. Summary of notifiable diseases–United States, 2001. MMWR 2001;50(53).