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  1. Outbreak Investigation: Discussion Group Ebbing Lautenbach, MD, MPH Assistant Professor of Medicine and Epidemiology Senior Scholar, CCEB Associate Hospital Epidemiologist, HUP

  2. Initial Call • Late June, 1997: Calls from 4 MDs reporting 6 patients with bloody diarrhea and E. coli O157:H7 infection

  3. Initial Call • Late June, 1997: Calls from 4 MDs reporting 6 patients with bloody diarrhea and E. coli O157:H7 infection • 1 day later: Call from Michigan Department of Community Health (MDCH) • Increase in laboratory reports of E. coli O157:H7 • June 1997 = 52

  4. First….

  5. 1. Verify the Diagnosis Steps in Outbreak Investigation

  6. 1. Verify the Diagnosis • Escherichia coli O157:H7 first identified as a human pathogen in 1982 in the US • Sporadic infections and outbreaks since reported from many parts of the world (e.g., N. America, Western Europe, Australia, Asia, and Africa) • Cattle are the primary reservoir for E. coli O157:H7 • Implicated foods are typically those derived from cattle (e.g., beef, hamburger, raw milk); • Infection has also been transmitted through contact with infected persons, contaminated water, and other contaminated food products.

  7. 1. Verify the Diagnosis • Infection with E. coli O157:H7 is diagnosed by detecting the bacterium in the stool. • Only recently has E. coli O157:H7 infection become nationally notifiable in many parts of the U.S.

  8. 1. Verify the Diagnosis Steps in Outbreak Investigation

  9. Verify the diagnosis Confirm the outbreak Steps in Outbreak Investigation

  10. Trends in MDCH E. Coli O157 Cases 1996 1997

  11. What could account for the increase in cases?

  12. Real increase Increase in population size Changes in population characteristics Random variation Outbreak Artificial increase Increased cx of stools New testing protocol Contamination of cxs Changes in reporting procedures What could account for the increase in cases?

  13. Initial Investigation • No substantial changes in population size • No appreciable changes in the population characteristics • No laboratory based changes • Surveillance / testing • Reporting protocol

  14. Initial Investigation • Any other way to see if there is a relationship between these E. coli isolates?

  15. Molecular Epidemiology • DNA fingerprinting • Pulsed Field Gel Electrophoresis (PFGE) most common in outbreak investigations • A cluster of isolates with the same PFGE pattern suggests they arose from the same parent (same source) • Still need an epidemiologic investigation

  16. PFGE pattern of E. coli Isolates

  17. Molecular Epidemiology of E. coli Isolates • 17 of the first 19 E. coli O157:H7 isolates from June-July were indistinguishable. • They did not match any fingerprints from a convenience sample of isolates from patients with E. coli O157:H7 infection before May.

  18. Verify the diagnosis Confirm the outbreak Steps in Outbreak Investigation

  19. Verify the diagnosis Confirm the outbreak Case definition Steps in Outbreak Investigation

  20. 3. Develop a Case Definition • Incubation period for E. coli O157:H7 ranges from 3-8 days with a median of 3-4 days. • The infection often causes severe bloody diarrhea and abdominal cramps, but can also cause a non-bloody diarrhea or result in no symptoms. • In some persons, particularly children under 5 years of age and the elderly, infection can be complicated by hemolytic uremic syndrome (occurs in about 2-7% of infections)

  21. Case Definition?

  22. Case Definition • Outbreak investigation definition: 1. diarrhea (>3 loose bowel movements a day) and/or abdominal cramps 2. resident of Michigan 3. onset of symptoms between June 15 and July 15 4. stool culture yielding E. coli O157:H7 with the outbreak strain PFGE pattern. • Advantages? Disadvantages?

  23. Case Definition • Advantages: • Lab confirmation increases specificity of case definition • Reduces misclassification; maximizes power to detect source. • Disadvantages: • Lab confirmation • Excludes patients who did’nt see MD, were not cxd, or cxd without PFGE. • Decreases the sensitivity of the case definition • Possibly leads to a misrepresentation of case characteristics. • Limiting cases to Michigan residents • excludes visitors who became infected; inhibits recognition of extension of outbreak into other states. • Dates reasonable? • Need more information • Could limit the number of secondary cases included in the study that could interfere with identification of the initial source of the outbreak.

  24. Verify the diagnosis Confirm the outbreak Case definition Steps in Outbreak Investigation

  25. Verify the diagnosis Confirm the outbreak Case definition Descriptive Epidemiology Steps in Outbreak Investigation

  26. Characterization of Cases Of the initial 38 persons who met the case definition, 26 (68%) were female with a median age of 31 years. Table 1. Age group and gender distribution for persons with E. coli O157:H7 infection (with PFGE pattern), Michigan, June 15 - July 15, 1997. (N=38)

  27. MI Cases FoodNet Data

  28. Michigan counties The 38 cases of E. coli O157:H7 infection meeting the investigation case definition were reported from 10 counties in the lower peninsula of Michigan.

  29. Epidemic Curve Figure 3. Date of illness onset for persons with E. coli O157:H7 infection and the outbreak PFGE pattern, MI, June 15 - July 15, 1997. (N=38)

  30. Epidemic Curves • How to set it up • What it tells you • Mode of transmission • Propagated • Common source • Timing of exposure • Course of exposure

  31. Epidemic Curves Propagated source: single exposure, no secondary cases (e.g., measles)

  32. Epidemic Curves Propagated source: secondary and tertiary cases (e.g., hepatitis A)

  33. Epidemic Curves Common source: point exposure (e.g., salmonella)

  34. Epidemic Curves Common source: Intermittent exposure (e.g., contaminated blood product)

  35. Epidemic Curve Figure 3. Date of illness onset for persons with E. coli O157:H7 infection and the outbreak PFGE pattern, MI, June 15 - July 15, 1997. (N=38)

  36. Verify the diagnosis Confirm the outbreak Case definition Descriptive epidemiology Steps in Outbreak Investigation

  37. Verify the diagnosis Confirm the outbreak Case definition Descriptive Epidemiology Develop a hypothesis Steps in Outbreak Investigation

  38. Developing a Hypothesis

  39. Ask questions!!But of whom….And when...

  40. Determining the Probable Period of Exposure • Mean/Median incubation period • Minimum/maximum incubation period

  41. Estimating date of exposure Peak One incubation period Rubella = 18 days Probable time of exposure

  42. Estimating date of exposure Maximum incubation 21 days Probable time of exposure Minimum incubation 14 days

  43. E. Coli Epidemic Curve Figure 3. Average incubation period = 4 days ( range 3-8 days)

  44. Focus of Questions

  45. Focus of Questions • demographic information • clinical details of the illness with date of onset, duration, and severity of symptoms • visits to health care providers or hospitals, and laboratory results • a complete food history in the last 7 days • water exposure in the last 7 days (e.g., drinking water, exposure to recreational waters) • exposure to other ill persons in the last 7 days • exposure to children in day care in the last 7 days • exposure to a farm or farm animals in the last 7 days • travel outside the immediate area in the last 7 days

  46. Interview Results

  47. Findings Thus Far • Cases are spread over 10 counties • No uniform attendance at any common event • Onset of symptoms among known cases extends over approximately one month. • The median age of patients is 31 years (range 2-76); 68% of cases are among females. • Factors present in over 50% of cases: • Female, milk, hamburger, lettuce, alfalfa sprouts • Role of fair attendance, water exposure?

  48. Hypothesis?

  49. Hypothesis of Investigators • Lettuce and/or alfalfa sprout consumption is associated with E. coli infection

  50. Verify the diagnosis Confirm the outbreak Case definition Descriptive epidemiology Develop a hypothesis Steps in Outbreak Investigation