CASE STUDY II: WORKING THROUGH AN INFECTIOUS DISEASE OUTBREAK

CASE STUDY II: WORKING THROUGH AN INFECTIOUS DISEASE OUTBREAK

Adapted from “A Multistate Outbreak of Cyclosporiasis.” The investigators of this study were Barbara L. Herwaldt, MD, MPH; Marta-Louise Ackers, MD; Michael J. Beach, PhD; and the Cyclospora Working Group from the Centers for Disease Control and Prevention. The case study was prepared by Jeanette K. Stehr-Green, MD and reviewed by Charles Haddad; Robert Tauxe, MD, MPH; and Roderick C. Jones, MPH

This case study is based on investigations undertaken in 1996 and 1997 in the United States and abroad that were published in the Morbidity and Mortality Weekly Report, the New England Journal of Medicine, and the Annals of Internal Medicine.

PART I: BACKGROUND

On May 20, 1996, the following article appeared on the front page of the Toronto Sun:

Exotic Parasite Sickens Canadian Businessmen by Xavier Onnasis

TORONTO – Public health officials today confirmed that three Canadian businessmen, two from Toronto and one from Ottawa, were diagnosed with cyclosporiasis, a parasitic disease seen only in tropical countries and overseas travelers. The three men, who had recently traveled to the United States, became seriously ill with diarrhea over the weekend (May 16–18). One of the men was hospitalized at Princess Margaret Hospital when he collapsed due to severe dehydration.

NEWS FILE CDC Cyclosporiasis Fact Sheet

Cyclospora cayetanensis (SIGH-clo-SPORE-uh KYE-uh-tuh-NEN-sis) is a parasite composed of one cell, too small to be seen without a microscope. The first known human cases of illness caused by Cyclospora infection (i.e., cyclosporiasis) were reported in 1979. Cases began being reported more often in the mid-1980s. In the last several years, outbreaks of cyclosporiasis have been reported in the United States and Canada.

How is Cyclospora spread?

Cyclospora is spread by people ingesting something, for example, water or food that was contaminated with infected stool. For example, outbreaks of cyclosporiasis have been linked to various types of fresh produce. Cyclospora needs time (days or weeks) after being passed in a bowel movement to become infectious. Therefore, it is unlikely that Cyclospora is passed directly from one person to another. It is unknown whether animals can be infected and pass infection to people.

Who is at risk for infection?

People of all ages are at risk for infection. In the past, Cyclospora infection was usually found in people who lived or traveled in developing countries. However, people can be infected worldwide, including the United States.

What are the symptoms of infection?

Cyclospora infects the small intestine (bowel) and usually causes watery diarrhea, with frequent, sometimes explosive, bowel movements. Other symptoms can include loss of appetite, substantial loss of weight, bloating, increased gas, stomach cramps, nausea, vomiting, muscle aches, low-grade fever, and fatigue. Some people who are infected with Cyclospora do not have any symptoms.

How soon after infection will symptoms begin?

The time between becoming infected and becoming sick is usually about 1 week.

How long will symptoms last?

If not treated, the illness may last from a few days to a month or longer. Symptoms may seem to go away and then return one or more times (relapse).

What should I do if I think I may be infected?

See your healthcare provider.

How is Cyclospora infection diagnosed?

Your healthcare provider will ask you to submit stool specimens to see if you are infected. Because testing for Cyclospora infection can be difficult, you may be asked to submit several stool specimens over several days. Identification of this parasite in stool requires special laboratory tests that are not routinely done. Therefore, your healthcare provider should specifically request testing for Cyclospora. Your healthcare provider may have your stool checked for other organisms that can cause similar symptoms.

How is infection treated?

The recommended treatment for infection with Cyclospora is a combination of two antibiotics, trimethoprim-sulfamethoxazole, also known as Bactrim*, Septra*, or Cotrim*. People who have diarrhea should rest and drink plenty of fluids.

I am allergic to sulfa drugs; is there another drug I can take?

No alternative drugs have been identified yet for people who are unable to take sulfa drugs. See your healthcare provider for other treatment recommendations.

How is infection prevented?

Avoiding water or food that may be contaminated with stool may help prevent Cyclospora infection. People who have previously been infected with Cyclospora can become infected again.

Dr. Richard Schabas, Ontario’s Chief Medical Officer, reported that cyclosporiasis was exceedingly rare in North America and that much was still unknown about this disease. Cyclosporiasis is caused by the microorganism Cyclospora cayetanensis. Cyclospora infects the small bowel and usually causes watery diarrhea, with frequent, sometimes explosive, bowel movements. Symptoms can include bloating, increased gas, stomach cramps, nausea, loss of appetite, and profound weight loss. The illness is diagnosed by examining stool specimens in the laboratory.

Dr. Schabas declined to identify a source of infection for the three businessmen but indicated that the parasite is transmitted through contaminated food or water but not by direct person-to-person spread. The time between exposure to the parasite and becoming sick is usually about 7 days.

Dr. Schabas reported that all three men had attended a meeting in Texas on May 9–10. He said Ontario Health Department staff would be investigating leads locally and in Texas.

CASE STUDY QUESTIONS

1. What is the incubation period for cyclosporiasis?

2. How will it be used in the investigation?

3. On what sources of infection should public health officials focus for the three cases of cyclosporiasis?

4. Is it possible that one of the men was the source of infection for the others?

5. Do you think that it is likely that the businessmen became infected with cyclosporiasis in Texas?

PART II: OUTBREAKS IN TEXAS

The chief medical officer of the Ontario Health Department notified the Texas Department of Health (TDH) about the Cyclospora infections in the three Canadian businessmen. The businessmen had attended a meeting at a private club in Houston, Texas on May 9–10.

A total of 28 people had attended the Houston business meeting. Participants came from three U.S. states and Canada. Meals served during the meeting were prepared at the restaurant operated by the private club. Rumors among restaurant staff suggested that other attendees at the meeting had also become ill.

TDH, the Houston Health & Human Services Department, and the Centers of Disease Control and Prevention (CDC) initiated an epidemiologic investigation to identify the source of the cyclosporiasis outbreak.

Because the outbreak appeared to affect a small, well-defined group of individuals (i.e., meeting attendees), investigators undertook a retrospective cohort study to investigate the source of the cyclosporiasis.

Investigators first surveyed people who attended the meeting to characterize the illness associated with the outbreak. (Twenty-seven of the 28 meeting attendees were interviewed.) All ill people experienced severe diarrhea and weight loss. In addition, 87% reported loss of appetite; 87% reported fatigue; 75% reported nausea; 75% reported stomach cramps; and 25% reported fever. Five ill people had stool specimens positive for Cyclospora.

Based on this information, investigators defined a case of cyclosporiasis for the cohort study as diarrhea of at least 3 days duration in someone who had attended the business meeting. Laboratory confirmation of Cyclospora infection was not required.

Of the 27 meeting attendees who were interviewed, 16 (59%) met the case definition for cyclosporiasis. Onsets of illness occurred from May 14 through May 19 (Figure I-5).

Investigators questioned both ill and well meeting attendees about travel history and food and water exposures during the meeting.

Restaurant management at the private club refused to take calls from investigators or cooperate with the investigation. As a result, a list of foods served at meals during the meeting was obtained from the meeting organizer. No menu items were confirmed by restaurant staff.

Twenty-four meeting attendees provided information on foods eaten during the meeting. (Four attendees, including three cases, did not provide the information.) Investigators examined the occurrence of illness among people who ate different food items.

Twelve (92%) of 13 attendees who ate the berry dessert became ill. Only one (9%) of 11 attendees who did not eat the berry dessert became ill. The relative risk for eating berries was 10.2 (p-value < 0.0001). No other exposures were associated with illness.

Case-patients reported that the berry dessert contained strawberries.

On June 4, before the first investigation had been completed, TDH was notified of another outbreak of cyclosporiasis involving physicians who attended a dinner on May 22 at a Houston, Texas restaurant. A second cohort study was undertaken. Nineteen attendees were interviewed, of which 10 met the case definition for cyclosporiasis (i.e., diarrhea of at least 3 days duration).

Attendees who ate dessert at the dinner were more likely to become ill than attendees who did not. Illness, however, was not associated with eating a particular type of dessert. No other exposures were associated with illness.

 

FIGURE I-5

Onset of illness among patients with cyclo-sporiasis, Houston business meeting, May 1996.

All desserts were garnished with either one fresh strawberry (for regular patrons) or with a strawberry, blackberry, and raspberry (for VIPs). Of the seven attendees who reported eating a strawberry, all seven became ill. Of the eight attendees who reported not eating a strawberry, only one became ill (relative risk = 8.0, p-value = 0.001). (Note: four attendees, including two cases, could not recall whether they had eaten a strawberry and were excluded from this analysis.)

Based on the results of the two cohort studies, investigators hypothesized that strawberries were the source of the cyclosporiasis outbreaks in Houston.

TDH staff examined invoices and other records from the two restaurants involved in the Texas cyclosporiasis outbreaks. The strawberries consumed at both the May 9–10 business meeting and the May 22 physician dinner were grown in California. The individual producers/distributors of the strawberries, however, were not determined.

On May 31, TDH released a public health advisory about the presumed link between the consumption of California strawberries and the cyclosporiasis outbreak. The State Health Officer advised consumers to wash strawberries “very carefully” before eating them, and recommended that people with compromised immune systems (e.g., people with HIV infection, patients on cancer chemotherapy) avoid them entirely.

A few days later, Ontario’s chief medical officer reported on an outbreak of cyclosporiasis in the Metro Toronto area affecting 40 people. Ontario public health officials believed California strawberries were also the source of the Toronto outbreak. A public health advisory, similar to the one from Texas, was issued.

Concurrent with the announcements from Texas and Ontario, CDC encouraged physicians from across the United States to report cases of cyclosporiasis to their local or state health department so that the source of the Cyclospora could be investigated further.

CASE STUDY QUESTIONS

1. What are the two most common types of epidemiologic studies used to investigate the source of an outbreak (or other public health problem)?

2. Which would you use to investigate the source of the cyclosporiasis outbreak in Texas? Why?

3. Why would you question people who did not become ill about possible sources of infection with Cyclospora?

4. In your own words, interpret the results of the cohort study.

5. What problems in study design or execution, should you consider when reviewing the results of this study (or any epidemiologic study)?

6. What additional studies might confirm (or refute) the hypothesis that strawberries were the source of the cyclosporiasis outbreaks?

7. You are writing a newspaper article about the cyclosporiasis outbreaks in Texas and Ontario. It is thought that the cyclosporiasis problem is ongoing. Four people are available for interview: the CDC expert on cyclosporiasis, one of the Canadian businessmen who became ill following the meeting in Houston, the owner of the private club in Houston where the first outbreak occurred, and the attorney for the California Strawberry Grower’s Association. Your deadline is looming. You have time to ask each of these people only three questions. What would you ask them?

PART III: OUTBREAKS IN OTHER STATES

Despite recommendations by health departments in Texas and Ontario to wash strawberries carefully before eating them, cases of cyclosporiasis continued to occur nationwide. By the end of June, over 800 laboratory-confirmed Cyclospora infections were reported to CDC from 20 states, the District of Columbia, and two Canadian provinces (Figure I-6).

Discrepancies began to appear in the link between California strawberries and the Cyclospora infections. Investigations undertaken by the New York City Health Department and South Carolina Department of Health and Environmental Control pointed toward raspberries as the source of the cyclosporiasis outbreaks in their jurisdictions.

In late June, the New Jersey Department of Health and Senior Services (NJDHSS) initiated an epidemiologic investigation to identify the source of infection among cyclosporiasis cases in New Jersey residents. The cases to be included in the New Jersey study were not linked together by a common event and did not occur in a well-defined group of people.

To assess possible risk factors for infection among the cases of cyclosporiasis in New Jersey, NJDHSS conducted a case-control study. In contrast to the Texas investigation, a case of cyclosporiasis for this study was defined as a patient with laboratory-confirmed Cyclospora infection and a history of diarrhea.

For the New Jersey case-control study, cases were identified by reviewing laboratory records from all clinical laboratories in the state. Forty-two cases were identified. Two controls were identified for each case through telephone calls to randomly selected households in the community. To be eligible for the study, controls could not have had loose stools during the previous 30 days.

Investigators interviewed 30 case-patients and 60 controls by telephone using a standardized questionnaire that asked about possible exposures (including consumption of 17 fruits and 15 vegetables, water and soil exposures, and animal contact) during the period of interest.

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