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

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outbreak investigation discussion group

Outbreak Investigation: Discussion Group

Ebbing Lautenbach, MD, MPH

Assistant Professor of Medicine and Epidemiology

Senior Scholar, CCEB

Associate Hospital Epidemiologist, HUP

initial call
Initial Call
  • Late June, 1997: Calls from 4 MDs reporting 6 patients with bloody diarrhea and E. coli O157:H7 infection
initial call3
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
1 verify the diagnosis
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.
1 verify the diagnosis7
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.
what could account for the increase in cases12
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?
initial investigation
Initial Investigation
  • No substantial changes in population size
  • No appreciable changes in the population characteristics
  • No laboratory based changes
    • Surveillance / testing
    • Reporting protocol
initial investigation14
Initial Investigation
  • Any other way to see if there is a relationship between these E. coli isolates?
molecular epidemiology
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
molecular epidemiology of e coli isolates
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.
steps in outbreak investigation19
Verify the diagnosis

Confirm the outbreak

Case definition

Steps in Outbreak Investigation
3 develop a case definition
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)
case definition22
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?
case definition23
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.
steps in outbreak investigation24
Verify the diagnosis

Confirm the outbreak

Case definition

Steps in Outbreak Investigation
steps in outbreak investigation25
Verify the diagnosis

Confirm the outbreak

Case definition

Descriptive Epidemiology

Steps in Outbreak Investigation
characterization of cases
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)

slide27

MI Cases

FoodNet Data

michigan counties
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.

epidemic curve
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)

epidemic curves
Epidemic Curves
  • How to set it up
  • What it tells you
    • Mode of transmission
      • Propagated
      • Common source
    • Timing of exposure
    • Course of exposure
epidemic curves31
Epidemic Curves

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

epidemic curves32
Epidemic Curves

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

epidemic curves33
Epidemic Curves

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

epidemic curves34
Epidemic Curves

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

epidemic curve35
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)

steps in outbreak investigation36
Verify the diagnosis

Confirm the outbreak

Case definition

Descriptive epidemiology

Steps in Outbreak Investigation
steps in outbreak investigation37
Verify the diagnosis

Confirm the outbreak

Case definition

Descriptive Epidemiology

Develop a hypothesis

Steps in Outbreak Investigation
determining the probable period of exposure
Determining the Probable Period of Exposure
  • Mean/Median incubation period
  • Minimum/maximum incubation period
estimating date of exposure
Estimating date of exposure

Peak

One incubation period

Rubella = 18 days

Probable time of exposure

estimating date of exposure42
Estimating date of exposure

Maximum incubation

21 days

Probable time of exposure

Minimum incubation

14 days

e coli epidemic curve
E. Coli Epidemic Curve

Figure 3. Average incubation period = 4 days ( range 3-8 days)

focus of questions45
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

findings thus far
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?
hypothesis of investigators
Hypothesis of Investigators
  • Lettuce and/or alfalfa sprout consumption is associated with E. coli infection
steps in outbreak investigation50
Verify the diagnosis

Confirm the outbreak

Case definition

Descriptive epidemiology

Develop a hypothesis

Steps in Outbreak Investigation
steps in outbreak investigation51
Verify the diagnosis

Confirm the outbreak

Case definition

Descriptive epidemiology

Develop a hypothesis

Test the hypothesis

Steps in Outbreak Investigation
controls selected
Controls Selected
  • 2 controls selected for every case
  • Matched to the case by:
    • Age group
      • (0-<2 years, 2-<5 years, 5-<12 years, 12-<18 years, 18-<60 years, and 60+ years)
    • Sex
methods to identify controls
Methods to Identify Controls
  • Random digit dailing
  • Neighborhood controls
  • Other patients of same physician
selection of controls
Selection of Controls
  • The investigators identified controls for the study using random digit dialing.
  • Exposure information among cases was collected for the 7 days before onset of illness.
  • For controls, exposure information was collected for the 7 days before the interview and for the 7 days before the onset of illness in the matching case.
  • Twenty-seven case-control sets were interviewed; the remaining case-patients could not be reached.
e coli and alfalfa sprouts
E. coli and Alfalfa Sprouts?

Variable Cases Controls OR (95%CI)

15 (56%) 4 (7%) 25 (4-528)

No other food item was significantly associated with

illness.

steps in outbreak investigation58
Verify the diagnosis

Confirm the outbreak

Case definition

Descriptive epidemiology

Develop a hypothesis

Test the hypothesis

Steps in Outbreak Investigation
steps in outbreak investigation59
Verify the diagnosis

Confirm the outbreak

Case definition

Descriptive epidemiology

Develop a hypothesis

Test the hypothesis

Refine hypothesis / Execute additional studies

Steps in Outbreak Investigation
refine hypothesis additional studies
Refine Hypothesis/Additional Studies
  • What control measures might you consider at this point?
  • What further studies might you do?
additional studies
Additional Studies
  • Culture implicated sprouts
  • Traceback study
    • distributor, processor, and producer; examination of the chain of production of the sprouts from the farm to the table
  • Applied research on E. coli
    • research on alfalfa sprouts and survival/growth of E. coli O157:H7 (e.g., the ability of E. coli to survive and grow on alfalfa seeds/sprouts at each step of the production process).
traceback studies
Traceback Studies
  • Often necessary to identify sources of contamination and quickly limit a public health threat by removing these sources.
  • Ascertain the distribution and production chain for a food product to facilitate effective recall.
  • Clarify the point or points at which the implicated food was likely to have become contaminated
follow up
Follow up
  • The implicated seed lot was a blend of 5 lots from fields of four farmers and was harvested between 1994 and 1996. The seed processor and the farmers were located in Idaho.
  • Inspection of the alfalfa fields revealed three possible sources of contamination: cattle manure, irrigation water, and deer feces.
    • Manure is not normally applied to alfalfa fields in Idaho
    • Cattle feed lots were common in this area and the alfalfa fields of one farmer were adjacent to a feed lot.
    • Manure may have leaked or been illegally dumped onto the alfalfa fields or run-off water from neighboring fields, contaminated by manure, may have been used to irrigate the alfalfa fields.
    • In addition, three of four farmers occasionally saw deer in their fields and one field was situated next to a wildlife refuge.
steps in outbreak investigation65
Verify the diagnosis

Confirm the outbreak

Case definition

Descriptive epidemiology

Develop a hypothesis

Test the hypothesis

Refine hypothesis / Execute additional studies

Steps in Outbreak Investigation
steps in outbreak investigation66
Verify the diagnosis

Confirm the outbreak

Case definition

Descriptive epidemiology

Develop a hypothesis

Test the hypothesis

Refine hypothesis / Execute additional studies

Implement control and prevention measures

Steps in Outbreak Investigation
what interventions are needed
What interventions are Needed?
  • 2 issues:
    • 1) the immediate problem with this implicated lot of seed
    • 2) the larger issue of seed sprouts as vehicles for pathogenic
what interventions are needed68
What interventions are Needed?
  • Implicated seed lot
  • all remaining seeds and alfalfa sprouts from the implicated lot should be removed from the market.
    • Persons who have purchased sprouts from the implicated lot should be instructed to destroy any remaining sprouts or return them to the store at which they were purchased.
  • The producers of these particular seeds should be informed of the need to protect alfalfa and other seeds used in sprouting from contamination during growing, harvesting, and packing.
  • Specific sources of contamination should be identified and eliminated from these growing sites.
what interventions are needed69
What interventions are Needed?
  • Seed sprouts are high risk vehicle for foodborne diseases
  • Continue applied research to find ways to successfully decontaminate the seeds/sprouts.
  • Educate sprout growers on appropriate growing conditions and handling of sprouts to limit contamination.
  • Educate the public about the riskiness of sprouts
    • Persons at high risk for complications of infection (e.g., children <5 years of age, immunocompromised individuals, and the elderly) avoid sprouts.
  • Require sprout producers to label sprouts as risky foods
  • Remove sprouts from the market for human consumption until their safety can be assured.
steps in outbreak investigation70
Verify the diagnosis

Confirm the outbreak

Case definition

Descriptive epidemiology

Develop a hypothesis

Test the hypothesis

Refine hypothesis / Execute additional studies

Implement control and prevention measures

Steps in Outbreak Investigation
steps in outbreak investigation71
Verify the diagnosis

Confirm the outbreak

Case definition

Descriptive epidemiology

Develop a hypothesis

Test the hypothesis

Refine hypothesis / Execute additional studies

Implement control and prevention measures

Communicate findings

Steps in Outbreak Investigation
communicate findings
Communicate Findings
  • The implicated seed lot was not distributed to any other sprouting companies. The remaining 6,000 lbs. of seed was immediately removed from the marketplace.
  • The Idaho Division of Food and Drugs held meetings at which public health officials explained to seed growers the need to protect alfalfa and other seeds used in sprouting from contamination during growing, harvesting, and packing.
  • Public television and radio announcements about the risk of contaminated sprouting seeds, recommending persons at high risk for complications from E. coli O157:H7 not eat sprouts.
  • The Center for Food Safety and Quality Enhancement began working with the sprout industry to identify ways to make sprouts safer for human consumption.
conclusions
Conclusions
  • Importance of applying the multi-step approach in outbreak investigation
  • Utility of new subtyping methods such as PFGE
  • Importance of disease reporting
  • Flexibility of hypothesis generation
    • New vehicle for the transmission of E. coli O157:H7
  • Increasing geographic dissemination of outbreaks