2.1 - Case Definition

Suppose you are asked to estimate the population prevalence of attention deficit hypersensitivity disorder (ADHD) among U.S. school-age children. How will you identify the children who should be counted as cases of ADHD? What defines a ‘case’?

The definition of a ‘case’ is critical in planning an epidemiologic investigation. The case definition must be carefully formulated to meet objectives of the investigation, while also permitting valid comparisons with results from other studies. In this example, it may be of interest to consider whether the proportion of school age children with ADHD has changed over a period of time. If the case definition changes significantly from one time period to the next, comparisons with previous years are problematic.

Suppose instead of estimating prevalence, the task is to define cases for a case-control study that is examining the risk from an exposure. If the case definition is broad, it will be easier to include prospective cases, hastening the enrollment of study participants. However, variability among the cases will be greater than if the case definition was more narrow. A narrow case definition can slow the identification of sufficient numbers of cases but has the potential to reduce false positives.

Just as a clinical diagnosis for an individual requires meeting specific clinical and laboratory criteria, measuring disease frequency in populations requires prior stipulation of which clinical, laboratory, epidemiologic or quantitative criteria indicate the presence of the disease. Case definitions can include a degree of certainty (e.g. probable or confirmed, etc.) or specify the method to be used in assessing whether or not criteria are met.

In the United States, disease surveillance is not a responsibility directly given to the federal government. This means each state in the US may establish its own requirements for reporting diseases. Can you imagine the confusion if all 50 states had used their own definitions of an H1N1 case during the 2009-10 flu season? To assist the states, the U.S. Centers for Disease Control and Prevention (CDC) and the Council of State and Territorial Epidemiologists have published a set of uniform criteria for reporting cases of specific diseases. You can see a bit of the history of case definitions.

Case Definitions for Infectious Diseases Section

Cases of disease can be categorized as follows:

Clinically compatible case
A clinical syndrome generally compatible with the disease, as described in the clinical description. A general clinical impression that this is a case of disease
Confirmed case
A case that is classified as confirmed for reporting purposes. The case meets established criteria
Epidemiologically linked case
A case in which a) the patient has had contact with one or more persons who either have/had the disease or have been exposed to a point source of infection (i.e., a single source of infection, such as an event leading to a food borne-disease outbreak, to which all confirmed case-patients were exposed) and b) transmission of the agent by the usual modes of transmission is plausible. A case may be considered epidemiologically linked to a laboratory-confirmed case if at least one case in the chain of transmission is laboratory confirmed
Laboratory-confirmed case
A case that is confirmed by one or more of the laboratory methods listed in the case definition under laboratory criteria for diagnosis. Although other laboratory methods can be used in clinical diagnosis, only those listed are accepted as laboratory confirmation for national reporting purposes
Probable case
A case that is classified as probable for reporting purposes. Supportive or presumptive laboratory results: specified laboratory results that are consistent with the diagnosis, yet do not meet the criteria for laboratory confirmation
Suspected case
A case that has a lower certainty; classified as suspected for reporting purposes

Each type has utility in different settings. To investigate a highly infectious, transmissible or serious and deadly disease, casting a broad net will capture all suspected and probable cases. On the other hand, if declaring an individual to be a 'case' is likely to result in imposing severe restrictions, such as closing schools or removing a product from the market, the case definition should be more stringent. For example, a series of suspected cases of disease would not be sufficient to support a product recall. The epidemiologist would prefer to have a confirmed case or a laboratory confirmed case to justify such action. .

The CDC has established case definitions for public health reporting purposes. Let’s look at a specific case definition for Rubeola (measles).

Chapter 15. Congenital Rubella Syndrom. in Manual for the Surveillance of Vaccine-Preventable Diseases (5th Edition, 2012) at http://www.cdc.gov/vaccines/pubs/surv-manual/chpt15-crs.html

Example 2-1

Measles (Rubeola) Case Definition

Open the link and note the clinical case definition, laboratory criteria for diagnosis and the criteria for classifying cases as suspected, probable, or confirmed cases. Three of the six categories of case definitions are used in this example.

The CDC clinical case definition requires at least 3 characteristics to be present in a clinical case (rash, certain temperature and cough, coryza or conjunctivitis) A patient can be characterized clinically without any laboratory testing. With laboratory results, meeting any of 4 specific requirements characterizes a positive diagnosis, i.e., positive serological test, a rise in the measles antibody level, detection of measles-virus-specific nucleic acid using a specific method or isolation of the virus from the actual specimen. If any of these four criteria are met, the case of measles is laboratory confirmed.

This web site includes additional information needed for CDC’s charge of controlling disease in the U.S. The CDC is interested in whether the case originated from an international source or whether it was US acquired. There are also four subcategories of US acquired cases.

Can you sense the critical importance of the case definition when counting cases of disease? Suppose you work at CDC and are investigating a measles outbreak. What if you discover that one state is using a particular definition for a measles case and another state is using a different definition?. Such issues must be resolved. The CDC criteria posted on the Internet can help. Agreement of case definitions is necessary to compare data.

Example 2-2

Lyme Disease Case Definition

Let's look at the CDC case definition (above) and consider a child who is taken to the doctor's office in March because of an unexplained facial palsy and unsteadiness that occurred suddenly upon awakening that morning. The physician notes stiffness in the knee joint which the parent says has occurred sporadically over the past 3 months. The child resides in a county with endemic Lyme disease, but has no recollection of a tick bite. The mother does remember an unexplained fever the previous summer. Would you report this as a case of suspected Lyme disease using the CDC definition? (post your thoughts in this week's discussion)

In the following example, the case defintion affected the news report:

Example 2-3

CDC cuts US SARS Case Count in Half

During 2003, there was a worldwide epidemic of SARS. The news release below is titled “CDC cuts US SARS case count in half”. How was CDC able to cut the rates for this disease in half from one reporting period to the next? Read the news release....

July 17, 2003 (CIDRAP News) – Because of a change in the case definition for SARS (severe acute respiratory syndrome), the United States has had only half as many suspected and probable cases of the illness as previously reported, federal health officials said today.

The Centers for Disease Control and Prevention (CDC) said the total case count is now 211 instead of 418, a 49.5% reduction. The official tally now is 175 suspected and 36 probable cases, down from 344 suspected and 74 probable cases.

The change is a result of excluding all cases in which convalescent blood samples—those collected more than 21 days after illness onset — tested negative for the SARS coronavirus, the CDC said in a news release. "Exclusion of these cases with negative convalescent serum provides a more accurate accounting of the epidemic in the U.S.," the agency said.

The Council of State and Territorial Epidemiologists recommended changing the SARS case definition to exclude cases with negative convalescent serum tests. The recommendation is based on evidence that 95% of SARS patients mount a detectable antibody response in the convalescent phase, the CDC said.

The revised case definition and case count are detailed in the Jul 18 issue of Morbidity and Mortality Weekly Report, published online today.

"Serologic testing results suggest that a small proportion of persons who had illness consistent with the clinical and epidemiologic criteria for a U.S. case of suspect or probable SARS actually had SARS," the article states. "The case definition captures an array of respiratory illnesses that cannot be easily distinguished from SARS until laboratory testing results for SARS and other agents are performed." The sensitive case definition allowed for rapid investigation of possible cases and public health steps to prevent spread of the disease, the report adds.

So what happened? The CDC changed the case definition once lab results were available. With the new definition, the 21 day serum had to test positive for the SARS coronavirus or it was no longer considered a SARS case. 418 cases was diminished to 211 cases just by changing the case definition. The case definition for a disease has substantial impact.

Another example of a change in case definition occurred in the early 1990s when HIV was beginning to be understood. Epidemiological studies found that cervical cancer cases were resulting from infection with HIV. So, a revision resulted in including cervical cancer cases in the HIV count.

As you proceed through this course it will be important that you provide specific case definitions for diseases for which you are conducting an epidemiologic investigation.. You may use a medical reference or ICD codes that classify diseases. The ICD (International Classification of Disease), is an international organization that meets to assign three or four digit codes to every possible cause of death. These are very specific. We are currently using ICD revision 10.

Physicians or medical investigators may belong to professional organizations or societies that define cases somewhat differently than the CDC. It is important to be explicit about the case definition used in a study and to what else it is comparable. Below are further sources of case definitions that may be helpful to you in epidemiologic investigations for this course.

Sources of Case Definitions for Non-Infectious Diseases, Conditions, and Exposures in the U.S. Section

Chronic Disease: http://www.cdc.gov/mmwr/PDF/rr/rr5311.pdf

Chemical Poisoning: Consider the algorithm approach to case classification on p.2 Centers for Disease Control and Prevention. Case definitions for chemical poisoning. MMWR 2004;54(No. RR-1)

Occupational Health: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5147a5.htm

Perhaps your curiousity is aroused ...on what basis are cases of flu determined this season? Check it out and post in our General Discussion.

For discussion: Select a particular case definition from the chemical poisoning or infectious condition listings above. Write a description of the strengths and limitations of that particular case definition in 100 words or less and submit to the weekly discussion.

Continue in Week 2 Course Notes by clicking on Measures of Disease Frequency