Docstoc

Outbreak_Investigation

Document Sample
Outbreak_Investigation Powered By Docstoc
					 Outbreak Investigation:
   Discussion Group
    Ebbing Lautenbach, MD, MPH
  Assistant Professor of Medicine and
             Epidemiology
         Senior Scholar, CCEB
Associate Hospital Epidemiologist, HUP
                Initial Call
• Late June, 1997: Calls from 4 MDs
  reporting 6 patients with bloody diarrhea
  and E. coli O157:H7 infection
                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
First….
    Steps in Outbreak Investigation

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 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.
    Steps in Outbreak Investigation

1. Verify the Diagnosis
    Steps in Outbreak Investigation

1. Verify the diagnosis
2. Confirm the outbreak
Trends in MDCH E. Coli O157 Cases
   60

   50           # Cases

   40

   30

   20

   10

    0
        J   J    A    S     O N   D   J   F M A M   J
                     1996                 1997
What could account for the
   increase in cases?
        What could account for the
           increase in cases?
Real increase                   Artificial increase
• Increase in population size   • Increased cx of stools
• Changes in population         • New testing protocol
  characteristics               • Contamination of cxs
• Random variation              • Changes in reporting
• Outbreak                        procedures
          Initial Investigation

• No substantial changes in population size
• No appreciable changes in the population
  characteristics
• No laboratory based changes
  – Surveillance / testing
  – Reporting protocol
          Initial Investigation
• Any other way to see if there is a
  relationship between these E. coli isolates?
     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
PFGE pattern 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 Investigation

1. Verify the diagnosis
2. Confirm the outbreak
    Steps in Outbreak Investigation

1. Verify the diagnosis
2. Confirm the outbreak
3. 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 Definition?
            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 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 Investigation

•   Verify the diagnosis
•   Confirm the outbreak
•   Case definition
     Steps in Outbreak Investigation

•   Verify the diagnosis
•   Confirm the outbreak
•   Case definition
•   Descriptive Epidemiology
        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)

  Age group                                 Gender
  (years)                                                        TOTAL
                                 Male                 Female
  0-9                         2 (17%)*                2 (8%)      4 (11%)
  10-19                        2 (17%)                3 (12%)     5 (13%)
  20-39                        3 (25%)                9 (35%)    12 (32%)
  40-59                        2 (17%)                8 (31%)    10 (26%)
  60+                          3 (25%)                4 (15%)     7 (18%)
  TOTAL                      12 (101%)               26 (101%)   38 (100%)
    * percentages refer to column totals.
               Age group                     Gender
               (years)                                                             TOTAL
                                  Male                       Female
               0-9              2 (17%)*                     2 (8%)                4 (11%)
MI Cases       10-19            2 (17%)                  3 (12%)                   5 (13%)
               20-39            3 (25%)                  9 (35%)                  12 (32%)
               40-59            2 (17%)                  8 (31%)                  10 (26%)
               60+              3 (25%)                  4 (15%)                   7 (18%)
               TOTAL           12 (101%)                26 (101%)                 38 (100%)
           .                             Gender
               APPENDIX 1
               Age group                                               TOTAL
               (years)
                              Male                 Female
               0-<1           5 (3%)                5 (3%)             10 (3%)
FoodNet        1-9          77 (48%)               77 (43%)           154 (45%)
Data           10-19        36 (22%)               18 (10%)            54 (16%)
               20-29         10 (6%)               20 (11%)            30 (9%)
               30-39          6 (4%)               12 (7%)             18 (5%)
               40-49          7 (4%)                5 (3%)             12 (4%)
               50-59          7 (4%)               17 (10%)            24 (7%)
               60+           14 (9%)               24 (13%)            38 (11%)
               TOTAL        162 (100%)            178 (100%)          340 (100%)
              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
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
• How to set it up
• What it tells you
  – Mode of transmission
     • Propagated
     • Common source
  – Timing of exposure
  – Course of exposure
                       Epidemic Curves
            Propagated source: single exposure, no secondary cases
            (e.g., measles)
        8

        7
        6

        5
Cases




        4

        3
        2

        1
        0
              1    2    3    4    5    6    7    8    9   10   11    12
                                       Week
                     Epidemic Curves
         Propagated source: secondary and tertiary cases (e.g.,
         hepatitis A)
        10
        9
        8
        7
        6
Cases




        5
        4
        3
        2
        1
        0
             1   2    3    4     5    6    7    8    9   10   11   12
                                      Week
                       Epidemic Curves
            Common source: point exposure (e.g., salmonella)

        8

        7
        6

        5
Cases




        4

        3
        2

        1
        0
              1    2    3    4   5    6    7    8    9   10    11   12
                                       Days
                       Epidemic Curves
            Common source: Intermittent exposure (e.g.,
            contaminated blood product)
        8

        7
        6

        5
Cases




        4

        3
        2

        1
        0
              1    2    3    4    5    6   7    8    9    10   11   12
                                       Days
                  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 Investigation

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

•   Verify the diagnosis
•   Confirm the outbreak
•   Case definition
•   Descriptive Epidemiology
•   Develop a hypothesis
Developing a Hypothesis
Ask questions!!

But of whom….

 And when...
Determining the Probable Period
         of Exposure


• Mean/Median incubation period
• Minimum/maximum incubation period
             Estimating date of exposure
                                                                                              Peak
                                                         One incubation period
        10
                                                           Rubella = 18 days
        9            Probable time of exposure
        8
        7
        6
Cases




        5
        4
        3
        2
        1
        0
             1   3   5                           7   9   11   13   15     17   19   21   23    25    27   29

                                                                   Days
             Estimating date of exposure
                                                                   Maximum incubation
                                                                         21 days

                     Probable time of exposure
        10
        9
        8
        7
        6
Cases




        5
        4
        3
                                                     Minimum incubation
        2
        1                                                 14 days
        0
             1   3   5                           7   9   11   13    15    17   19   21   23   25   27   29

                                                                   Days
         E. Coli Epidemic Curve
Figure 3. Average incubation period = 4 days ( range 3-8 days)
Focus of Questions
              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
     Interview Results
Variable             Cases (n=38)
Female               26 (68%)
Med Age              31
Rec water exposure   13 (34%)
Other Ill person     6 (16%)
Day care             18 (47%)
Farm                 2 (5%)
Fair                 18 (47%)
Travel               9 (24%)
Hamburger            25 (66%)
Meat                 22 (58%)
Milk                 32 (84%)
Alfalfa sprouts      19 (50%)
Lettuce              24 (63%)
            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?
    Hypothesis of Investigators

• Lettuce and/or alfalfa sprout consumption is
  associated with E. coli infection
     Steps in Outbreak Investigation

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

•   Verify the diagnosis
•   Confirm the outbreak
•   Case definition
•   Descriptive epidemiology
•   Develop a hypothesis
•   Test the hypothesis
Pick a Control Group
           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

• Random digit dailing
• Neighborhood controls
• Other patients of same physician
         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.
              Interview Results
Variable             Cases (n=27)   Controls (n=54)
Female               18 (67%)       36 (67%)
Med Age              31             31
Rec water exposure   9 (33%)        21 (39%)
Other Ill person     6 (22%)        9 (17%)
Day care             16 (59%)       33 (61%)
Farm                 2 (7%)         2 (4%)
Fair                 12 (44%)       24 (44%)
Travel               8 (30%)        13 (24%)
Hamburger            17 (63%)       36 (67%)
Meat                 14 (52%)       26 (48%)
Milk                 21 (78%)       44 (81%)
Alfalfa sprouts      15 (56%)       4 (7%)
Lettuce              18 (67%)       34 (62%)
    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 Investigation

•   Verify the diagnosis
•   Confirm the outbreak
•   Case definition
•   Descriptive epidemiology
•   Develop a hypothesis
•   Test the hypothesis
     Steps in Outbreak Investigation
•   Verify the diagnosis
•   Confirm the outbreak
•   Case definition
•   Descriptive epidemiology
•   Develop a hypothesis
•   Test the hypothesis
•   Refine hypothesis / Execute additional studies
Refine Hypothesis/Additional Studies

  • What control measures might you consider at this
    point?

  • What further studies might you do?
             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
• 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
Traceback Results
                       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 Investigation
•   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
•   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
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 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 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 Investigation
•   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
•   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
          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
• 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

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:22
posted:9/21/2010
language:English
pages:73