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Steps of an Outbreak Investigation
Steps of an Outbreak Investigation
In investigating an outbreak, speed is essential, but getting the right answer is essential, too. To satisfy both requirements, Public Health personnel should approach investigations systematically, using the following 10 steps:
The steps are presented here in conceptual order. In practice, however, several may be done at the same time, or they may be done in a different order. For example, control measures should be implemented as soon as the source and mode of transmission are known, which may be early or late in any outbreak investigation.
Anyone about to embark on an outbreak investigation should be well prepared before leaving for the field. Preparations can be grouped into three categories: (a) investigation, (b) administration, and (c) consultation. Good preparation in all three categories will facilitate a smooth field experience.
Second, as an investigator, you must pay attention to administrative procedures. You may need to take care of personal matters before you leave, especially if the investigation is likely to be lengthy.
Third, as an investigator, you must know your expected role in the field. Before departure, all parties should agree on your role. For example, are you expected to lead the investigation, provide consultation, or simply lend a hand? In addition, you should know who your local contacts will be. Before leaving, you should know when and where you are to meet with local officials and contacts when you arrive in the field.
is the occurrence of more cases of disease than expected in a given
area or among a specific group of people over a particular period of time. In
an aggregation of cases in a given area over a particular period without regard
to whether the number of cases is more than expected. In an outbreak or
epidemic, we usually presume that the cases are related to one another or that
they have a common cause.
One of your first tasks as a field investigator, or disease detective, is to verify that a suspected outbreak is indeed a real outbreak. Some will turn out to be true outbreaks with a common cause, some will be unrelated cases of the same disease, and others will turn out to be unrelated cases of similar but unrelated diseases. Before you can decide whether an outbreak exists (i.e., whether the observed number of cases exceeds the expected number), you must first determine the expected number of cases for the area in the given time frame.
How, then, do you determine what is expected? Usually you can compare the current number of cases with the number from the previous few weeks or months, or from a comparable period during the previous few years. The sources of these data vary:
Even if the current number of reported cases exceeds the expected number, the excess may not necessarily indicate an outbreak. Reporting may rise because of changes in local reporting procedures, changes in the case definition, increased interest because of local or national awareness, or improvements in diagnostic procedures. For example, if a new physician, infection control nurse, or health care facility is reporting cases more consistently than they were reported in the past, the numbers would go up even though there might be no change in the actual occurrence of the disease. Finally, particularly in areas with sudden changes in population size, such as resort areas, college towns, and migrant farming areas, changes in the number of reported cases may simply reflect changes in the size of the population.
Whether or not you should investigate an apparent problem further is not strictly tied to your verifying that an epidemic exists (that is, that the observed number is greater than the number expected). As noted earlier, other factors may come into play, including, for example, the severity of the illness, the potential for spread, political considerations, public relations, and the availability of resources.
In addition to verifying the existence of an outbreak early in the investigation, you must also identify as accurately as possible the specific nature of the disease. Your goals in verifying the diagnosis are two-fold. First, you must ensure that the problem has been properly diagnosed—that it really is what it has been reported to be. Second, for outbreaks involving infectious or toxic-chemical agents, you must to be certain that the increase in diagnosed cases is not the result of a mistake in the laboratory.
Verifying the diagnosis requires that you review the clinical findings (the symptoms and features of illness) and laboratory results for the people who are affected. If you are at all uncertainty about the laboratory findings (e.g., if they are inconsistent with the clinical findings), you should have a laboratory technician review the techniques being used. If you expect a need for specialized laboratory work (e.g., special culturing or DNA analysis), you should begin obtaining the appropriate specimens, isolates, and other laboratory material from a sufficient number of patients as soon as possible.
Finally, you should visit several of the people who became ill. If you do not have the clinical background to verify the diagnosis, a doctor or other qualified clinician should do so. Regardless of your background, though, you should see and talk to some of these people to gain a better understanding of the disease and those affected by it. In addition, you may be able to gather critical information by asking such questions as, What were their exposures before becoming ill? What do they think caused their illness? Do they know anyone else with the disease? Do they have anything in common with others who have the disease? Conversations with patients are very helpful in generating hypotheses about the cause, source, and spread of disease.
Establish a case definition. Your next task as an investigator is to establish a case definition, or a standard set of criteria for deciding whether, in this investigation, a person should be classified as having the disease or health condition under study. A case definition usually includes four components:
You should base the clinical criteria on simple and objective measures. For example, you might require the presence of an elevated level of antibody to the disease agent, the presence of a fever of at least 101"F, three or more loose bowel movements per day, or muscle aching severe enough to limit the patient's activities. Regarding the characteristics of people, you might restrict the definition to those who attended a wedding banquet, or ate at a certain restaurant, or swam in the same lake. By time, the criterion might be onset of illness within the past 2 months; by place, it might be living in a nine-county area or working at a particular plant. Whatever your criteria, you must apply them consistently and without bias to all of the people included in the investigation.
Ideally, your case definition should be broad enough to include most, if not all, of the actual cases, without capturing what are called "false-positive" cases (when the case definition is met, but the person actually does not have the disease in question). Recognizing the uncertainty of some diagnoses, investigators often classify cases as "confirmed," "probable," or "possible."
To be classified as confirmed, a case usually must have laboratory verification. A case classified as probable usually has the typical clinical features of the disease without laboratory confirmation. A possible case usually has fewer of the typical clinical features. For example, in an outbreak of bloody diarrhea and severe kidney disease (hemolytic-uremic syndrome) caused by infection with the bacterium E. coli O157:H7, investigators defined cases in the following three classes:
Early in an investigation, a loose case definition that includes confirmed, probable, and even possible cases is often used to allow investigators to capture as many cases as possible. Later on, when hypotheses have come into sharper focus, the investigator may tighten the case definition by dropping the "possible" category. This strategy is particularly useful when you have to travel to different hospitals, homes, or other places to gather information, because it keeps you from having to go back for additional data. This illustrates an important axiom of field epidemiology: "Get it while you can."
Identify and count cases
When identifying cases, you should use as many sources as you can, and you may need to be creative and aggressive in identifying these sources. Initially, you may want to direct your case finding at health care facilities where the diagnosis is likely to be made; these facilities include physicians' offices, clinics, hospitals, and laboratories. You also may decide to send out a letter describing the situation and asking for reports (passive surveillance); or you may decide to telephone or visit the facilities to collect information (active surveillance).
In some outbreaks, public health officials may decide to alert the public directly, usually through the local media. For example, in outbreaks caused by a contaminated food product such as salmonellosis caused by contaminated milk (7) or L-tryptophan-induced EMS (8), announcements in the media have alerted the public to avoid the implicated product and to see a physician if they had symptoms of the disease.
If an outbreak affects a population in a restricted setting, such as a cruise ship, school, or worksite, and if a high proportion of cases are unlikely to be diagnosed (if, for example, many cases are mild or asymptomatic), you may want to conduct a survey of the entire population. In such settings, you could administer a questionnaire to determine the true occurrence of clinical symptoms, or you could collect laboratory specimens to determine the number of asymptomatic cases. Finally, you can ask people who are affected if they know anyone else with the same condition.
Regardless of the particular disease you are investigating, you should collect the following types of information about every person affected:
Traditionally, we collect the information described above on a standard case report form, questionnaire, or data abstraction form. We then abstract selected critical items in a table called a "line listing." In a line listing, each column represents an important variable, such as name or identification number, age, sex, and case classification, while each row represents a different case, by number. New cases are added to a line listing as they are identified. This simple format allows the investigator to scan key information on every case and update it easily. Even in the era of microcomputers, many epidemiologists still maintain a hand-written line listing of key data items and turn to their computers for more complex manipulations of data. Here is a portion of a line listing that might have been created for an outbreak of hepatitis A.
S*=Sclera;, N=Nausea; V=Vomiting; A=Anorexia; F=Fever; DU=Dark urine; J=Jaundice; HAIgM=Hepatitis AIgM antibody test
Once you have collected some data, you can begin to characterize an outbreak by time, place, and person. In fact, you may perform this step several times during the course of an outbreak. Characterizing an outbreak by these variables is called descriptive epidemiology, because you describe what has occurred in the population under study. This step is critical for several reasons. First, by becoming familiar with the data, you can learn what information is reliable and informative (e.g., the same unusual exposure reported by many of the people affected) and what may not be as reliable (e.g., many missing or "don't know" responses to a particular question). Second, you provide a comprehensive description of an outbreak by showing its trend over time, its geographic extent (place), and the populations (people) affected by the disease. This description lets you begin to assess the outbreak in light of what is known about the disease (e.g., the usual source, mode of transmission, risk factors, and populations affected) and to develop causal hypotheses. You can, in turn, test these hypotheses using the techniques of analytic epidemiology described later in Step 7: Evaluate Hypotheses.
Note that you should begin descriptive epidemiology early and should update it as you collect additional data. To keep an investigation moving quickly and in the right direction, you must discover both errors and clues in the data as early as possible.
Characterizing by time
Insert EPI Curve
How to draw an epidemic curve
Interpreting an epidemic curve
An epidemic curve with a steep up slope and a gradual down slope, such as the illustration above on the first outbreak of Legionnaires’ disease, indicates a single source (or "point source") epidemic in which people are exposed to the same source over a relatively brief period. In fact, any sudden rise in the number of cases suggests sudden exposure to a common source. In a point source epidemic, all the cases occur within one incubation period. If the duration of exposure is prolonged, the epidemic is called a "continuous common source epidemic," and the epidemic curve will have a plateau instead of a peak. Person-to-person spread (a "propagated" epidemic) should have a series of progressively taller peaks one incubation period apart.
Cases that stand apart (called "outliers") may be just as informative as the overall pattern. An early case may represent a background (unrelated) case, a source of the epidemic, or a person who was exposed earlier than most of the people affected (e.g., the cook who tasted her dish hours before bringing it to the big picnic). Similarly, late cases may be unrelated to the outbreak, may have especially long incubation periods, may indicate exposure later than most of the people affected, or may be secondary cases (that is, the person may have become ill after being exposed to someone who was part of the initial outbreak). All outliers are worth examining carefully because if they are part of the outbreak, their unusual exposures may point directly to the source. For a disease with a human host such as hepatitis A, for instance, one of the early cases may be in a food handler who is the source of the epidemic.
In a point-source epidemic of a known disease with a known incubation period, you can use the epidemic curve to identify a likely period of exposure. This is critical to asking the right questions to identify the source of the epidemic.
Characterizing by place
A spot map of cases in a community may show clusters or patterns that reflect water supplies, wind currents, or proximity to a restaurant or grocery store. On a spot map of a hospital, nursing home, or other such facility, clustering usually indicates either a focal source or person-to-person spread, while the scattering of cases throughout a facility is more consistent with a common source such as a dining hall. In studying an outbreak of surgical wound infections in a hospital, we might plot cases by operating room, recovery room, and ward room to look for clustering.
If the size of the overall population varies between the areas you are comparing, a spot map, because it shows numbers of cases, can be misleading. This is a weakness of spot maps. In such instances, you should show the proportion of people affected in each area (which would also represent the rate of disease or, in the setting of an outbreak, the "attack rate").
Characterizing by person
Age and sex are usually assessed first, because they are often the characteristics most strongly related to exposure and to the risk of disease. Other characteristics will be more specific to the disease under investigation and the setting of the outbreak. For example, if you were investigating an outbreak of hepatitis B, you should consider the usual high-risk exposures for that infection, such as intravenous drug use, sexual contacts, and health care employment.
Summarizing by time, place, and person
In real life, we usually begin to generate hypotheses to explain why and how the outbreak occurred when we first learn about the problem. But at this point in an investigation, after you have interviewed some affected people, spoken with other health officials in the community, and characterized the outbreak by time, place, and person, your hypotheses will be sharpened and more accurately focused. The hypotheses should address the source of the agent, the mode (vehicle or vector) of transmission, and the exposures that caused the disease. Also, the hypotheses should be proposed in a way that can be tested.
You can develop hypotheses in a variety of ways. First, consider what you know about the disease itself: What is the agent's usual reservoir? How is it usually transmitted? What vehicles are commonly implicated? What are the known risk factors? In other words, simply by becoming familiar with the disease, you can, at the very least, "round up the usual suspects."
Another useful way to generate hypotheses is to talk to a few of the people who are ill, as discussed under Step 3: Verifying the Diagnosis. Your conversations about possible exposures should be open-ended and wide-ranging and not confined to the known sources and vehicles. Sometimes investigators meet with a group of the affected people as a way to search for common exposures. Investigators have even found it useful to visit the homes of people who became ill and look through their refrigerators and shelves for clues.
Descriptive epidemiology often provides some hypotheses. If the epidemic curve points to a narrow period of exposure, ask what events occurred around that time. If people living in a particular area have the highest attack rates, or if some groups with particular age, sex, or other personal characteristics are at greatest risk, ask why. Such questions about the data should lead to hypotheses that can be tested.
The next step is to evaluate the credibility of your hypotheses. There are two approaches you can use, depending on the nature of your data: 1) comparison of the hypotheses with the established facts and 2) analytic epidemiology, which allows you to test your hypotheses.
You would use the first method when your evidence is so strong that the
hypothesis does not need to be tested. A 1991 investigation of an outbreak of
vitamin D intoxication in
The second method, analytic epidemiology, is used when the cause is less clear. With this method, you test your hypotheses by using a comparison group to quantify relationships between various exposures and the disease. There are two types of analytic studies: cohort studies and case-control studies. Cohort studies compare groups of people who have been exposed to suspected risk factors with groups who have not been exposed. Case-control studies compare people with a disease (case-patients) with a group of people without the disease (controls). The nature of the outbreak determines which of these studies you will use.
After collecting this information from each guests, you would be able to calculate an attack rate for people who ate a particular item (were exposed) and an attack rate for those who did not eat that item (were not exposed). For the exposed group, the attack rate is found by dividing the number of people who ate the item and became ill by the total number of people who ate that item. For those who were not exposed, the attack rate is found by dividing the number of people who did not eat the item but still became ill by the total number of people who did not eat that item.
To identify the source of the outbreak from this information, you would look for an item with:
Usually, you would also calculate the mathematical association between exposure (consuming the food or beverage item) and illness for each food and beverage. This is called the relative risk and is produced by dividing the attack rate for people who were exposed to the item by the attack rate for those who were not exposed.
The table on the next page is based on a famous outbreak of gastroenteritis
following a church supper in
*Excludes 1 person with indefinite history of consumption of that food. Source: 9
When you design a case-control study, your first, and perhaps most important, decision is who the controls should be. Conceptually, the controls must not have the disease in question, but should be from the same population as the case-patients. In other words, they should be similar to the case-patients except that they do not have the disease. Common control groups consist of neighbors and friends of case-patients and people from the same physician practice or hospital as case-patients.
In general, the more case-patients and controls you have, the easier it will be to find an association. Often, however, you are limited because the outbreak is small. For example, in a hospital, 4 or 5 cases may constitute an outbreak. Fortunately, the number of potential controls will usually be more than you need. In an outbreak of 50 or more cases, 1 control per case-patient will usually suffice. In smaller outbreaks, you might use 2, 3, or 4 controls per case-patient. More than 4 controls per case-patient will rarely be worth your effort.
In a case-control study, you cannot calculate attack rates because you do not know the total number of people in the community who were and were not exposed to the source of the disease under study. Without attack rates, you cannot calculate relative risk; instead, the measure of association you use in a case study is an odds ratio. When preparing to calculate an odds ratio, it is helpful to look at your data in a 2×2 table. For instance, suppose you were investigating an outbreak of hepatitis A in a small town, and you suspected that the source was a favorite restaurant of the townspeople. After questioning case-patients and controls about whether they had eaten at that restaurant, your data might look like this:
The odds ratio is calculated as ad/bc. The odds ratio for Restaurant A is thus 30 × 70 / 36 × 10, or 5.8. This means that people who ate at Restaurant A were 5.8 times more likely to develop hepatitis A than were people who did not eat there. Even so, you could not conclude that Restaurant A was the source without comparing its odds ratio with the odds ratios for other possible sources. It could be that the source is elsewhere and that it just so happens that many of the people who were exposed also ate at Restaurant A.
Testing statistical significance
The first step in testing for statistical significance is to assume that the exposure is not related to disease. This assumption is known as the null hypothesis. Next, you compute a measure of association, such as a relative risk or an odds ratio. These measures are then used in calculating a chi-square test (the statistical test most commonly used in studying an outbreak) or other statistical test. Once you have a value for chi-square, you look up its corresponding p-value (or probability value) in a table of chi-squares.
In interpreting p-values, you set in advance a cutoff point beyond which you will consider that chance is a factor. A common cutoff point is .05. When a p-value is below the predetermined cutoff point, the finding is considered "statistically significant," and you may reject the null hypothesis in favor of the alternative hypothesis, that is you may conclude that the exposure is associated with disease. The smaller the p-value, the stronger the evidence that your finding is statistically significant.
Additional epidemiological studies
An investigation of an outbreak of Salmonella muenchen
Even when your analytic study identifies an association between an exposure and
a disease, you often will need to refine your hypotheses. Sometimes you will
need to obtain more specific exposure histories or a more specific control
group. For example, in a large community outbreak of botulism in
When an outbreak occurs, whether it is routine or unusual, you should consider what questions remain unanswered about the disease and what kind of study you might use in the particular setting to answer some of these questions. The circumstances may allow you to learn more about the disease, its modes of transmission, the characteristics of the agent, and host factors.
Laboratory and environmental studies
Even though implementing control and prevention measures is listed as Step 9, in a real investigation you should do this as soon as possible. Control measures, which can be implemented early if you know the source of an outbreak, should be aimed at specific links in the chain of infection, the agent, the source, or the reservoir. For example, an outbreak might be controlled by destroying contaminated foods, sterilizing contaminated water, destroying mosquito breeding sites, or requiring an infectious food handler to stay away from work until he or she is well.
In other situations, you might direct control measures at interrupting transmission or exposure. For example, to limit the airborne spread of an infectious agent among residents of a nursing home, you could use the method of "cohorting" by putting infected people together in a separate area to prevent exposure to others. You could instruct people wishing to reduce their risk of acquiring Lyme disease to avoid wooded areas or to wear insect repellent and protective clothing. Finally, in some outbreaks, you would direct control measures at reducing susceptibility. Two such examples are immunization against rubella and malaria chemoprophylaxis (prevention by taking antimalarial medications) for travelers.
Your final task in an investigation is to communicate your findings to others who need to know. This communication usually takes two forms: 1) an oral briefing for local health authorities and 2) a written report.
Your oral briefing should be attended by the local health authorities and people responsible for implementing control and prevention measures. This presentation is an opportunity for you to describe what you did, what you found, and what you think should be done about it. You should present your findings in scientifically objective fashion, and you should be able to defend your conclusions and recommendations.
You should also provide a written report that follows the usual scientific format of introduction, background, methods, results, discussion, and recommendations. By formally presenting recommendations, the report provides a blueprint for action. It also serves as a record of performance, a document for potential legal issues, and a reference if the health department encounters a similar situation in the future. Finally, a report that finds its way into the public health literature serves the broader purpose of contributing to the scientific knowledge base of epidemiology and public health.
During the previous year, nine residents of a community died from the same type of cancer. List some reasons that might justify an investigation. (Exercise Answer Key)
During August, a county health department received reports of 12 new cases of tuberculosis and 12 new cases of aseptic meningitis. Tuberculosis does not have a striking seasonal distribution; however, aseptic meningitis, which is caused primarily by a viral infection, is highly seasonal and peaks from August–October. What additional information is needed to determine whether either of these groups of cases is an outbreak? (Exercise Answer Key)
Review the six case report forms in the Appendix and create a line listing based on the information. (Exercise Answer Key)
You are called to help investigate a cluster of 17 men who developed leukemia in a community. Some of them worked as electrical repair men, and others were ham radio operators. Which study design would you choose to investigate a possible association between exposure to electromagnetic fields and leukemia? (Exercise Answer Key)
The manager of a grocery store has reported a rash illness among the store’s workers. What type of study would you use to determine the source of the outbreak? Why? What is the appropriate measure of association? After reviewing the table in the Appendix showing the data on exposure to celery for these workers, calculate the measure of association and interpret your results. (Exercise Answer Key)
During the previous year, nine residents of a community died from the same type of cancer. List some reasons that might justify an investigation.
One reason to investigate is simply to determine how many cases you would expect in the community. In a large community, for instance, nine cases of a common cancer (e.g., lung, breast, or colon cancer) would not be unusual. In a very small community, nine cases of even a common cancer may seem unusual. If the particular cancer is rare, then nine cases even in a large community may be unusual.
If the number of cases turns out to be high for that community, we might pursue the investigation further. Our motive might be research—perhaps we will identify a new risk factor (workers exposed to a particular chemical) or predisposition (people with a particular genetic marker) for the cancer. Control and prevention may also be a justification. If we find a risk factor, control and prevention measures could be developed. Alternatively, if the cancer is generally treatable when found early and a screening test is available, then we might try to determine not why these people developed the disease, but why they died from it. For instance, if the problem were cancer of the cervix, detectable by Pap smear and generally treatable if caught early, we might find (1) problems with access to health care, or (2) physicians not following the recommendations to screen women at the appropriate intervals, or (3) laboratory error in reading or reporting the test results. We could then develop measures to correct the problems we found (public screening clinics, education of physicians, or laboratory quality assurance).
If new staff need to gain experience on a cluster investigation, training may be a reason to investigate. If there is public concern, it may generate political pressure. Perhaps one of the people affected is a member of the mayor's family. A health department must respond to such concerns, but does not usually need to conduct a full-blown investigation. Finally, legal concerns may prompt an investigation, especially if a particular site in the community is implicated.
During August, a county health department received reports of 12 new cases of tuberculosis and 12 new cases of aseptic meningitis. Tuberculosis does not have a striking seasonal distribution; however, aseptic meningitis, which is caused primarily by a viral infection, is highly seasonal, and peaks from August–October. What additional information is needed to determine whether either of these groups of cases is an outbreak?
You need to know how many cases of each of these diseases usually occurs in this county during August. Because tuberculosis is not seasonal, the number of cases could be compared with (a) the numbers reported during the preceding several months and (b) the numbers reported during August of the preceding few years. However, since aseptic meningitis is seasonal and peaks from August–October, the number of cases during August is expected to be higher than the number reported during the preceding several months, so you would need to compare with the numbers reported during August of the preceding few years.
Review the six case report forms in the Appendix and create a line listing based on the information.
The choice of information to include in a line listing is somewhat arbitrary. The following categories are often included:
Risk factors and possible causes
Here is one way that a line listing might be drawn up from the six case report forms on the Cleveland-McKay wedding outbreak:
You are called to help investigate a cluster of 17 men who developed leukemia in a community. Some of them worked as electrical repair men, and others were ham radio operators. Which study design would you choose to investigate a possible association between exposure to electromagnetic fields and leukemia?
Because the total population at risk is not well defined, you would use a case-control study. You would begin by enrolling the 17 people already identified with leukemia as the case group. You would also need to determine what group might serve as an appropriate comparison, or control, group. Neighbors might be used for the control group, for example. In your case-control study, you would determine whether each case-patient and each control had been exposed to electromagnetic fields (however you defined that exposure). Finally, you would compare the exposures of case-patients and controls.
The manager of a grocery store has reported a rash illness among the store’s workers. What type of study would you use to determine the source of the outbreak? Why? What is the appropriate measure of association? After reviewing the table in the Appendix showing the data on exposure to celery for these workers, calculate the measure of association and interpret your results.
You would use a cohort study because the outbreak is small and confined. The appropriate measure of association for a cohort study is relative risk, which is calculated in this case as the attack rate for workers exposed to celery divided by the attack rate for those who were not exposed.
The attack rate for exposed workers is 25 / 56, or 44.6%. The attack rate for workers who were not exposed is 5 / 70, or 7.1%. Thus, the relative risk for exposure to celery is 44.6 / 7.1, or 6.3. This means that workers who were exposed to celery were 6.3 times more likely to develop the rash illness than those who were not exposed, and it is therefore likely that celery was the source of the outbreak. However, before you could draw this conclusion, you would need to compare the relative risk for celery with that for other vegetables and fruits to see if the implication is stronger for any of them.
Then, to test the likelihood of your findings, you would need to calculate a test of statistical significance such as chi-square for the item with the highest relative risk and look up the corresponding p-value in a table of p-values. If the p-value was below .05, your findings would be considered statistically significant.
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