Agency for Toxic Substances and Disease Registry 
Case Studies in Environmental Medicine (CSEM) 

Disease Clusters: An Overview
Evaluating a Disease Cluster

Evaluating a Disease Cluster

The interface between the physician and the public health department is essential in recognizing and responding to disease cluster concerns. It is impractical for the busy clinician to perform epidemiologic and detailed fact-finding. The public health department has expertise in evaluating disease clusters.

It is essential to understand the components involved the public health department investigation of a disease cluster and the physician's role in the process. The primary role of the physician is confirming diagnosis, completing the exposure history when applicable, recognizing abnormal patterns of events, and reporting information to the appropriate public health department for investigation. Thus, the effective management of disease clusters is initiated after case reporting by an astute clinician who has completed the appropriate diagnostic tests and taken an exposure history (Schuman 1997) (Figure 1).

An exposure history is of particular importance if the patient's illness (a) occurs at an atypical age, (b) is unresponsive to treatment, or (c) is an acute condition where a direct link might exist between current exposure and disease (e.g., asthma, first-trimester miscarriages, or dermatologic conditions).

Figure 1. Effective Management of Disease Clusters

ATSDR, Agency for Toxic Substances and Disease Registry; CDC, Centers for Disease Control and Prevention; MD, medical doctor.

The clinician must also keep in mind that many organ systems are affected by toxic exposure (Table 1). Exposure and effects can be acute or chronic. The latency period from exposure to manifestation of disease can vary, ranging from immediate to delayed (hours or days) to prolonged (decades). The exposure history is covered in detail in Case Studies in Environmental Medicine: Taking an Exposure History (ATSDR 2001). The exposure history form is included in Appendix A of this case study.

The public health department's role in the disease cluster investigation involves

• collecting accurate case information,
• conducting active surveillance through local surveys or use of health data registries,
• conducting environmental or occupational exposure assessments when warranted,
• ensuring that appropriate public and health professional communication and education occurs (specifically related to the existence of a disease cluster and any associated factors), and
• initiating timely and effective actions to mitigate factors associated with the disease cluster.

Table 1. Organs/Systems Often Affected by Toxic Exposure

An initial goal of the public health unit's evaluation should be to decide whether the cluster is "unusual" (i.e., whether an unexpectedly increased incidence of disease really exists) and, if so, whether some plausible biologic hypothesis can explain that unexpected disease rate. The public health department can perform the following cluster evaluation components (Figure 2):

• Establish a case definition.
• Confirm the suspected cases.
• Define a "population denominator" measured in person-years and search for additional numerator cases within that population. Draw conclusions about the "unusualness" of the cases.
• Review the literature for risk factors and exposure hypotheses.
• Perform an exposure assessment.
• Generate biologically plausible hypotheses.

Person-years are the most frequently used measure of person-time. Person-time is the sum of individual units of time that persons in the study population have been exposed to the condition of interest. This measurement is used as a denominator in person-time incidence and mortality rates.

With this approach, each subject contributes only as many years of observation to the population at risk as he or she is actually observed; if the subject leaves after 2 years, he or she contributes 2 person-years. This method can be used to measure incidence over extended and variable time periods.

Figure 2. Components of a Disease Cluster Evaluation

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