Epidemiology in the Classroom
Suspected Legionnaires' Disease in Bogalusa

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Case Study Developed by the
Centers for Disease Control and Prevention
(Version Adapted for Use in U.S. High Schools)

Goals

After completing this case study and reviewing the accompanying background materials, the student should be able to:

• Understand the basic principles and methods of epidemiology in relation to the process of scientific inquiry; Use epidemiological approaches for practical real-life problem solving; and
  
• Describe the roles of health care providers, epidemiologists (i.e., "disease detectives"), and other public health professionals in disease detection, control, and prevention activities.

Objectives

• After completing this case study and reviewing the accompanying background materials, the student should be able to:
• Identify and interpret the meaning of risk factors for health conditions (e.g., infectious and chronic diseases, injury, and disability);
• Use comparative reasoning to evaluate risks for health conditions;
• Apply the epidemiological/scientific method of investigating a disease outbreak to real-life situations affecting health in human populations;
• Understand and use basic concepts of mathematics and statistics in assessing risks for disease;
• Develop an epidemiological case definition;
• Design a basic case-control study including the selection of controls as part of the investigation of a disease outbreak;
• Define and use selected medical and epidemiological terms; and
• Describe the epidemiology and some clinical features of Legionnaires' disease.

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Suspected Legionnaires' Disease in Bogalusa
PART I

(time to completion: 50 minutes)

On October 31, 1989, the state health department in Louisiana was notified by two physicians in Bogalusa, Louisiana, that over 50 cases of acute pneumonia (severe infection of the lungs) had occurred among local residents. Most cases had occurred within a 3-week interval in mid- to late October; six persons had died. All cases had occurred in adults. Information doctors had obtained from several patients suggested that the cause of the illness may have been legionellosis, a disease caused by infection with the bacterium Legionella pneumophila.

You are the EIS Officer (CDC disease detective) assigned to the Louisiana health department who received a telephone call from the concerned physicians.

QUESTION 1:

Based on the scientific method used by disease detectives in an outbreak investigation, what additional information would help you decide whether this is potentially a real public health problem?

Continue only after completion of Question 1

Serologic testing is the analysis of samples of blood serum for the presence of antibodies to specific disease agents, including bacteria and viruses. Some antibodies indicate recent infection and are called IgM class; antibodies indicating more distant past infection are called IgG. In Bogalusa, blood samples obtained from several patients during the earliest (acute) phase of illness had been negative for antibody to the Legionella bacterium (note, however, that for most infectious diseases antibodies cannot be detected during the first few weeks in the course of illness). No sputum (substances produced by the lining of the lungs and other parts of the respiratory tract) specimens had been collected for Legionnaires' testing, since the hospital's laboratory was not able to perform the tests.

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QUESTION 2:

In general, besides a true outbreak, what else can account for a sudden increase in the number of cases of a particular disease to be reported to a health department?

 
QUESTION 3:

Before you leave your office to begin an investigation of this problem in the community, what sorts of preparations would you make?

Continue after completion of Question 3

Background about Legionnaires' disease

The following information about Legionnaires' disease is abstracted from the publication Control of Communicable Diseases Manual, sixteenth edition. (In an actual epidemiological investigation, you might consult a reference publication such as this to refresh your memory on pertinent details about a specific disease).

Legionnaires' disease, or legionellosis, is characterized by pneumonia caused by the bacterium Legionella pneumophila. The name "Legionnaires' disease" was given to this problem following a large outbreak among persons who attended a convention of American Legion military veterans in Philadelphia, Pennsylvania, in July 1976. The incubation period (the amount of time from initial exposure to the infectious bacteria to the actual onset of illness) for Legionnaires' disease ranges from 2 to 10 days. The disease often begins with anorexia (loss of appetite), malaise (fatigue and overall sense of poor well-being), myalgias (muscle aches and soreness), and headache, followed by rapidly rising fever and chills. Chest X-rays typically show patchy areas of inflammation and fluid accumulation in the lungs. The diagnosis is confirmed by:

1) isolation of the bacterium on special culture media; or

2) demonstration of the bacterium by immunofluorescent stain of involved tissue or respiratory secretions; or

3) fourfold or greater increase in titers (antibody levels) between acute (early illness) and convalescent (long-term [usually 3-4 weeks after the acute period]) phase serum samples; or

4) a single high titer in a patient with an illness characterized by the symptoms and/or signs of Legionnaires' disease.

Cases of Legionnaires' disease occur sporadically (individually) and in outbreaks. The reservoirs of the L. pneumophila bacteria responsible for many of these outbreaks have been primarily aqueous, such as hot water systems, air conditioning cooling towers, and evaporator condensers environments conducive to the growth of this bacterium. The mode of transmission is airborne via aerosol-producing devices. Because L. pneumophila is spread by the airborne route from environmental sources (and not from one person to another), when outbreaks are detected there is a need for a speedy investigative response in order to identify the common source in the environment and then decontaminate the source to prevent the occurrence of additional cases. Risk factors for serious illness include increasing age, especially in smokers; diabetes (high blood glucose levels often requiring treatment with the hormone insulin), chronic lung disease, renal (kidney) disease or cancer; or immunocompromised patients. The usual ratio of illness reported among men as compared to among women (i.e., male-to-female ratio) is about 2.5:1.

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Background about Bogalusa

Bogalusa is located in Washington Parish and has a population of about 16,000 persons. The largest employer is a paper mill located in the center of town adjacent to the main street. The paper mill includes 5 prominent industrial cooling towers. The mill also has three paper machines which emit large volumes of aerosol along the main street in town. Many persons suspected the cooling towers and/or paper mills to be the cause of the outbreak, since they were prominent sources of outdoor aerosols. In addition, attention was directed at a few public buildings with cooling towers that also were potential sources of indoor aerosol.

Bogalusa was served by a 98-bed private hospital (hospital A) and a 60-bed public hospital (hospital B). Three additional hospitals were located in the surrounding parish. All of the reported cases of Legionnaires' disease were for patients at Hospital A.

The number of patients discharged with a diagnosis of pneumonia at Hospital A since January 1986 is shown in Table 1. Between January 1986 and September 1989, only one pneumonia patient had been diagnosed as having Legionnaires' disease.

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Table 1

Number of Patients with a Diagnosis of Pneumonia Discharged from Hospital A by Month, 1986-1989

Review of charts of pneumonia patients at Hospital A during October revealed that many patients were admitted with a febrile illness (i.e., an illness especially including fever) characterized by weakness, lethargy, and mental confusion. Some patients had a dry cough, and several reported having watery diarrhea. Chest X-rays were consistent with a pneumonia. Most cases were residents of Bogalusa or the surrounding areas of Washington Parish.

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QUESTION 4:

What are possible interpretations for the data in the table above? What would you do next? (i.e., If you wanted to intensify the investigation, what steps would you take?)

Continue only after completion of Question 4

 
QUESTION 5:

Develop a case definition for this outbreak. Would you want a relatively sensitive or a relatively specific case definition in this setting?

(Tip: A "sensitive" case definition is one that will identify nearly all cases of the disease being investigated ["true positives"], but at the same time may include other similar illnesses resulting from different causes ["false positives"]. In contrast, a "specific" case definition is one that excludes similar illnesses resulting from causes different from the disease under investigation [false positives], but at the same time may exclude some true cases with slightly unusual symptoms and/or signs [true positives]. In other words, would you want a case definition that identifies the maximum number of possible cases [high sensitivity] or one that only identifies true cases [high specificity]?)

 
QUESTION 6:

How would you go about case-finding? Do you need to find every case

Continue only after completion of Question 6

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Suspected Legionnaires' Disease in Bogalusa
PART II

(time to completion: 20 minutes)

Discussions were held among staff of the Louisiana health department and the CDC. The health department felt capable of leading the epidemiologic investigation, but requested assistance with laboratory support. A second EIS Officer was sent from Atlanta to assist in the investigation, and CDC provided laboratory support. The field investigation team arrived in Bogalusa on November 8.

The EIS Officers were given the opportunity to address the hospital staff about this outbreak. In addition to being certain that hospital staff could recognize (diagnose) and appropriately treat patients with Legionnaires' disease, the investigators needed to enlist from the hospital staff their support, cooperation, and assistance in the investigation. Some of the points they covered during the meeting were:

• Clinical features of Legionnaires' disease, including how to diagnose the problem and what specimens are needed;
• The basic epidemiological features of Legionnaires= disease B including risk for disease and sources for infection, and that Legionnaires' disease is not spread directly from person to person;
• Why it is important to report cases promptly and how to report to public health authorities;
• How to treat the infection (the antibiotic erythromycin is recommended);
• What is known to date regarding the outbreak; and
• Plans for the continuing epidemiological investigation.

The investigators set up active surveillance (ongoing collection, analysis, and dissemination of data on illness) for finding cases at all five local hospitals in Bogalusa. In addition, they used a questionnaire to abstract information from the medical records of all persons admitted or discharged with a diagnosis of pneumonia, respiratory distress, or possible Legionnaires' disease (LD) since October 1, 1989.

A possible case of Legionnaires' disease was defined as illness in a resident or visitor of Washington Parish (where Bogalusa is located), >=20 years of age, admitted to one of the 5 local hospitals after October 1, 1989, with X-ray evidence of pneumonia or a chest radiograph consistent with pneumonia. A confirmed case had to meet the criteria for a possible case, plus have lab evidence of Legionnaires' disease (four-fold rise in antibody titer, a single elevated convalescent antibody titer, positive urine antigen test, positive sputum culture, or positive biopsy).

By November 19, investigators had identified 83 patients who met the definition of possible Legionnaires' disease (see the "epidemic curve" Figure 1; the epidemic curve is a simple graph of the number of new cases by date of onset or date of diagnosis). Fourteen of these patients had died without Legionella testing. Of the 83, 65% were female. About 3/4 of the case-patients were residents of Bogalusa; about half (41) resided on the east side of town. Most case-patients had been admitted to the hospital in mid-October; few if any new cases were occurring in mid-November (see Figure 1 on the following page). To date, no sputum culture had shown growth for Legionnaires' disease or other pathogens.

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Figure 1
Epidemic curve of pneumonia outbreak, Bogalusa, Louisiana, 1989

Before designing the analytic portion of the investigation, the investigators considered their leading hypotheses.

 
QUESTION 7:

How does one generate plausible hypotheses to test in this type of investigation? What, if any, are your ideas at this point?

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Continue only after completion of Question 7

At this point in the investigation, the leading hypothesis was outdoor exposure to cooling towers primarily because previous studies had demonstrated the role of cooling towers as sources of the Legionella pneumophila in other outbreaks, and there were several such towers in the town. However, rather than jumping to conclusions based on this information alone, investigators began to compile a list of retail stores and other commercial establishments which were frequently mentioned by some of the case-patients who had been interviewed. Investigators also noted the unusual preponderance of female cases.

 
QUESTION 8:

In this setting, what type of comparative study method would you use to test your hypotheses (i.e., case-control, cohort, or other)?

Continue only after completion of Question 8

Suspected Legionnaires' Disease in Bogalusa
PART III 

(time to completion: 10 minutes)

The investigators decided to conduct a case-control study to test their hypotheses. Sixty-six persons met the case definition for a possible case and were still alive. Laboratory results had come back confirming Legionnaires' disease in 15 of these patients, and ruling out Legionnaires' disease in 10. Laboratory results for the remainder were pending.

 
QUESTION 9:

What case definition would you use for the case-control study?

 
QUESTION 10:

What are some possible sources of controls?

Continue only after completion of Question 10

 
Suspected Legionnaires' Disease in Bogalusa
PART IV

(time to completion: 15 minutes)

The investigators decided to select controls from office records of physicians who admitted the cases and to enroll two controls per case. A total of 28 cases and 56 controls were enrolled in the case-control study. Cases and controls were asked about exposures to cooling towers and nearby buildings.

Of the 28 cases, 3 reported having visited a particular hospital with a cooling tower; on the other hand, of the 56 controls, 7 reported having visited that hospital (Hospital B). Similarly, 7 of the cases reported having visited the post office (1 was unsure), and 12 of the controls reported having visited the post office (6 were unsure).

 
QUESTION 11.

Calculate the odds ratios for illness with Legionnaires' disease among persons who visited these two locations. Why might the numbers of cases and controls included in these two calculations differ? What is your interpretation of the results?

Continue only after completion of Question 11

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Suspected Legionnaires' Disease in Bogalusa
PART V

 (time to completion: 15 minutes)

Important data from the case-control study are shown in Table 2 below.

Table 2
Exposures to buildings, Legionnaires' disease outbreak, Louisiana, 1989

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QUESTION 12:

What is your interpretation of these data? (i.e., Which of the exposures above suggest an association with illness, which accounts for the greatest number of cases, and what are the implications?)

Continue only after completion of Question 12

 
Suspected Legionnaires' Disease in Bogalusa
PART VI 

(time to completion: 15 minutes)

Additional epidemiological analysis demonstrated a dose-response relationship between time spent in grocery store A and risk of disease that is, there was a direct relation between the amount of time persons spent in the store and their risk for disease. The investigators visited grocery store A and looked for potential sources of aerosolized water. An ultrasonic mist machine was operating over one section of the produce display. No one at grocery store A was familiar with the maintenance or operation of this machine. Permission was obtained to culture a specimen of water from the reservoir of the misting device. The culture from the misting device contained Legionella pneumophila serotype 1 (LP-1). Cultures from various cooling towers around town also contained LP-1, but of different subtypes. The investigators were suspicious this misting device may have been related to the outbreak.

 
QUESTION 13:

At this point, is information sufficient to make recommendations have the basic criteria of causation been satisfied? How would you proceed with this investigation?

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Continue only after completion of Question 13

Four additional activities were undertaken: 1) a serosurvey (that is, a survey and analysis of blood specimens obtained from a sample of persons) was conducted among all grocery store employees in Bogalusa to determine antibody status against LP-1; 2) a second case-control study was undertaken to determine if exposure to the misting device was associated with developing Legionnaires' disease; 3) ten similar misting devices from other parts of the country were cultured; and 4) the investigators asked for permission to perform autopsies on two patients who had died of pneumonia early in the epidemic.

Employees at grocery store A were more likely to have elevated antibody titers to Legionella than employees at the other grocery stores (13/48 [27%] versus 7/75 [9%] the ratio of these two percentages is defined as the prevalence ratio [the ratio of the prevalence of antibody in each group]; prevalence ratio=3, p=0.02). Analysis of the second case-control study revealed a significant association between disease and purchasing produce which was nearest the mister. Of the 10 mist machines from other parts of the country, 6 grew Legionella. The subtype of Legionella found in the grocery store misting device was also isolated in a small cooling tower which was far from public access and not in proximity to Grocery Store A. Lung tissue from the two autopsied patients revealed Legionella of the same subtype as that found in grocery store A.

Until now, the news media had not been aware of the outbreak, the investigation, or the results.

 
QUESTION 14:

Who needs to know about these findings? How would you go about reporting the findings?

Continue only after completion of Question 14

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Suspected Legionnaires' Disease in Bogalusa
PART VII: Conclusion 

(time to completion: 5 minutes)

The investigators concluded that the misting device was the source of aerosols that caused the outbreak. They were reluctant to publish the results until the laboratory was able to demonstrate that viable Legionella could be isolated from aerosols produced by the machine. This was expected to take several weeks. In mid-December, the machine was removed from grocery store A and sent to CDC for further study. Since it was apparent that other mist machines were likely to be contaminated with Legionella, the Food and Drug Administration (FDA) was notified. The FDA developed guidelines for maintaining these mist machines. In early January, the Bogalusa newspaper printed the first article about the outbreak, without knowing its cause. This story was quickly picked up by the New Orleans paper and national news services. Soon, Bogalusa was overrun by reporters wanting to find out the cause of the outbreak. They focused their attention on the paper mill in the center of town, and demanded to know the culture results from the cooling towers.

The Louisiana state health department issued a press release and an electronic mail notification message to other health officials describing the mist machine findings. Grocery industry officials were notified about the potential problem in trade newspapers and at meetings. The electronic mail message became public and was widely quoted in newspaper articles.

The type of misting device implicated in the outbreak was new to the grocery industry. These misters produced a visible fog that attracted shoppers, but had no other practical use. They did not help to preserve produce. The health department received reports of similar types of machines used in other settings, such as amusement parks and indoor aquariums. The findings were published in CDC's weekly bulletin, the Morbidity and Mortality Weekly Report (MMWR), after laboratory staff were able to isolate Legionella organisms from aerosols produced by the machine. Subsequent publication of findings in the Journal of Infectious Diseases was used to reach an even wider audience of health care professionals and to ensure that physicians specializing in the treatment of Legionnaires' disease and other infectious diseases were aware of this previously unrecognized vehicle for transmission of Legionella.

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References

1. CDC. Legionnaires' disease outbreak associated with a grocery store mist machine - Louisiana, 1989. MMWR 1990;39:108-110.

2. Mahoney FJ, Hoge C, Farley TF, et al. Legionnaires' disease associated with a grocery store mist machine. J Infect Dis 1992;165:736-739.

3. Control of Communicable Diseases Manual, sixteenth edition. Abram S. Benenson, Editor. American Public Health Association, pp. 256-258.

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