OUT BREAK INVESTIGATION

Goals
• The goals of this presentation are to:
– Provide a general overview of the basic steps of disease
outbreak investigations
– Describe factors that may contribute to a decision to investigate
03/31/19
Prof Dr Muhammad Tauseef Jawaid King Khalid University KSA
2

Outbreak
• A sudden increase in the number of individuals who
contact a specific infectious disease in a population,
putting others at risk.
OR
• Spread of disease, which occurs in a short period of
time and in a limited geographic location (i.e,
neighborhood, community, school, or hospital)
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Why investigate an outbreak?
• Characterize a public health problem
• Identify preventable risk factors
• Provide new research insights into disease
• Train health department staff in methods of public
health investigations and emergency response
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4

When to Investigate
03/31/19 Prof Dr Muhammad Tauseef Jawaid King Khalid University KSA
5
•Consider the following factors:
– Severity of illness
– Transmissibility
– Unanswered questions
– Ongoing illness / exposure
– Public concern
– Prevention potential

Outbreak Investigations
• Three critical variables in investigating an
outbreak or epidemic are:
–When did the exposure take place?
–When did the disease begin?
–What was the incubation period for the
disease?
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6

In the Beginning…
 Successful investigations require a multidisciplinary
approach, effective communication and collaboration
 Steps:
 Assemble team members
 Present available information
 Outline plan for investigation and team communication
 Assign roles and responsibilities
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Prepare for Field Work
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8
•Identification of team
•Gather resources, supplies, equipment
– Computer, questionnaires, specimen collection kits
•Make necessary administrative, personal arrangements
for travel
– Determine role in the investigation
– Identify points of contact (field and office)
•What do you need to do to prepare?

Team Member Roles
 Team Leader
 Experience in outbreak investigation and epidemiology
 Selection can be result of outbreak setting or etiologic agent
 Role can be filled by:
 County health director,
 Public health nurse,
 Epidemiologist, or
 Environmental health specialist
 Role may change depending on stage of investigation
9

Team Member Roles
 Epidemiologist
 Develop study design and survey questionnaires
 Create database and conduct data analysis
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Team Member Roles
 Microbiologist
 Verify the diagnosis
 Subtype pathogens to help refine case definition
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Team Member Roles
 Environmental health specialists (EHS)
 Collect food and environmental samples
 Provide guidance on food safety regulations and engineering
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Team Member Roles
 Interviewers
 Collect data in person or by telephone
 Role can be filled by health department personnel, state
or federal personnel, or health science students
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Team Member Roles
 Clinicians
 Administer vaccines or prophylaxis
 Collect clinical specimens
 Role can be filled by health department or local medical
community
 May include veterinarians, depending on type of outbreak
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Team Member Roles
 Regulators
 Facilitate identification of the source of outbreak and
develop prevention strategies
 Role can be filled by state or federal agency employees
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15

Team Member Roles
 Media Spokesperson
 Deliver clear and consistent messages to community
 Role can be filled by one outbreak team member or
representatives from each agency
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Questions to Consider
 What resources, including personnel, are available?
 What resources could be provided by outside
collaborators?
 Who will direct the day-to-day investigation?
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17

More Questions to Consider
 Who will interact with the media?
 How will data be shared and analyzed?
 Who will write the final report and present the
information?
 How will the team communicate with each other?
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18

Team Equipment
• Computer with access to internet
– Email communication
– Literature searches (PUBMED)
– Data entry and analysis (Epi-Info 2002
http://www.cdc.gov/epiinfo/epiinfo.htm)
– Written reports
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Team Equipment
• Specimen collection tools
– Rectal swabs or specimen cups
– Phlebotomy equipment
– Cooler to transport specimens
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Communication
• Information flows in both directions
– Leader should update the team during meetings,
conference calls, or email
– Members provide regular updates to team leader
• Acts as tool for measuring progress
• Enables leader to provide feedback and direction to team
members
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Communication
• Keep lines of communication open through regular
meetings or phone
– Include local, state, and federal public health agencies
• Document progress
– Allows all members to remain up-to-date
– Assists in drafting final report
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Steps of an Outbreak
Investigation
03/31/19 23

Steps of an Outbreak Investigation
1. Preparation
2. Confirm the existence of outbreak
3. Verify the diagnosis
4. Establish a case definition
5. Find cases systematically & record information
6. Perform descriptive epidemiology
7. Develop hypotheses
8. Evaluate hypotheses epidemiologically
9. As necessary, reconsider, refine, and re-evaluate hypotheses.
10.Implement control and prevention measures
11. Communicate findings
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24

1. Preparation
• Investigation
– Scientific knowledge
• Review literature
• Consult experts
• Sample questionnaires
– Supplies
• Consult with laboratory
– Equipment
• Laptop, camera etc.
25

2. Establish existence of an outbreak
• Is an outbreak truly occurred?
– through surveillance records for notifiable diseases.
– hospital data.
– data from other facilities
– community survey.
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2. Establish Existence of an Outbreak
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27
• For non-notifiable conditions:
– National estimates
– Hospital discharge records
– Mortality data
– Other available records
– Use data from neighboring areas
– Call local health care providers
– Call community members

Example: Establish Existence of an Outbreak
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An Outbreak...To Be or Not To Be
100
80
60
40
20
0
Time

Example: Establish Existence of an
Outbreak
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29
An Outbreak...To Be or Not To Be
100
80
60
40
20
0
Time

3. Verify the Diagnosis
• Ensure proper diagnosis and rule out lab error
as the bias for increased diagnosis
– Review clinical findings, lab results
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30

Verify the Diagnosis
cont.
• See and talk with patients if at all possible
– Better understand clinical features
– Gather critical information
• Source of exposure
• What they think caused illness
• Knowledge of others with similar illness
• Helpful in generating ideas for hypothesis about etiology and spread
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31

4. Establish a case definition
• Case definition
– Includes clinical criteria and restrictions by time, place and person
• Classification
– Definite (confirmed)
• Laboratory confirmed
– Probable
• Typical clinical features without lab confirmation
– Possible (suspected)
• Fewer of the typical clinical features
03/31/19
32
Prof Dr Muhammad Tauseef Jawaid King Khalid University KSAProf Dr Muhammad Tauseef Jawaid King Khalid University KSA

Meningococcal Disease — Case Definition
Clinical case definition
• An illness with sudden onset of fever (>38.5°C rectal or >38.0°C
axillary) and one or more of the following: neck stiffness, altered
consciousness, other meningeal sign or petechial or puerperal rash.
Laboratory criteria for diagnosis
• Positive cerebrospinal fluid (CSF) antigen detection or positive
culture.
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Case classification
• Suspected: A case that meets the clinical case definition.
• Probable: A suspected case as defined above and turbid CSF
(with or without positive Gram stain) or ongoing epidemic
and epidemiological link to a confirmed case.
• Confirmed: A suspected or probable case with laboratory
confirmation.
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34

Example: Case Definition
for Hepatitis A
• Confirmed case:
– Anti-HAV IgM+
• Probable case:
– Pale skin
• Suspect case:
– Any two of the following:
– Abdominal pain, fever, nausea, anorexia, malaise
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35

• Target health care facilities where diagnosis is likely
to be made
– Enhanced passive surveillance e.g. letter describing
situation and asking for reports.
– Active surveillance e.g. phone or visit facility to collect
information
• Alerting the public
– Media alert to avoid contaminated food products and seek
medical attention if symptoms arise.
36

contd….
• Identifying information
• Name, address, and telephone number is essential if need to
contact patients additional questions.
• Also to Notify them of lab results and outcomes of investigation
• Names also helps in checking for duplicate records while addresses
allow for Mapping the geographic extent.
– Demographic information.
• Provide “person” characteristics for defining population at risk
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37

5. Find cases systematically & record
information contd….
• Clinical findings
• Signs and symptoms allow to Verify that the case definition has been
met
• Date of onset is needed to Chart the time course of outbreak.
– Reporter information
• Id of person making report
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38

contd….
• Line listing
– Abstraction of selected critical items
from above information
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39

What is a Line Listing?
• A rectangular database similar to spreadsheet
• Provides summary of key data about cases in an outbreak
• Each row represents one case
• Each column represents one variable
• First column usually identifier —name, initials, or ID number
• Can be paper or electronic
• Can be quickly reviewed and updated
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40

Develop Line List
Identifying Information

Example of a Line Listing
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42

Develop Line List
Clinical Information

Develop Line List
Laboratory & Case Classification Information
52

Develop Line List
Exposure Information

6. Perform Descriptive Epidemiology
• After collection of data characterize
the outbreak by:
–Time
–Place
–Person
03/31/19 46

Perform Descriptive Epidemiology
03/31/19 47
• What and why
–Provides systematic method
–Characterize, or describe what has occurred
–Person, place, time
useful for developing
hypotheses
• Components
–Line list
–Epi curve
–Others, but we will focus on line list and epi-curve

Tabulate and orient data
 Create line listing
 Person
 Who was infected?
 What do the cases have in common?
 Place
 Where were they infected?
 May be useful to draw a map
 Time
 When were they infected?
 Create an epidemic curve
03/31/19 48

Time (Epidemic curve)
• Epidemic curve
– Histogram of the number of cases by their date of onset
– Visual display of the outbreak’s magnitude and time trend
– Common source vs. Propagated
03/31/19 49

03/31/19 50
Line List• Person
• Place
• Time Epidemic curve (‘Epi curve’)

03/31/19 51
• Epi curve: visual representation of
– Ill persons (cases) over time
– Magnitude of outbreak
– Type of outbreak
• Point source
• Propagated (person-to-person)
– Exposure period / Time of exposure (if agent known)
– Incubation period
– Possible agents (if time of exposure known)

03/31/19 52
• How do I make an epi curve?
– Number of cases on the vertical (y) axis
– Time period (or date of illness onset) on the horizontal (x) axis

Example – X and Y axis
03/31/19 53
0
20
100
80
60
40
Y-
axis
Time
X-axis

03/31/19 54
•How do I choose the correct unit of time?
– Depends upon the incubation period
– If incubation period is not known, graph several
epi-curves with different time units

Example Epi Curve – Time Unit (Day)
03/31/19 55
100
80
60
40
20
0
1-Apr
3-Apr
5-Apr
7-Apr
9-Apr
11-Apr
13-Apr
15-Apr
17-Apr
Time

Example Epi Curve – Time Unit (Hours)
03/31/19 56
100
80
60
40
20
0
6am
12N
6pm
12M
N
6am
12N
6pm
12M
N
Time
April 9 April 10

03/31/19 57
– Progressively taller peaks, an incubation period apart
– Person to person transmission
– May last a long time
– May have multiple waves

Example Epi Curve – Person to person
(Propagated)
03/31/19 58
Epi Curve…Person to Person
100
80
60
40
20
0
Time

(Propagated)
03/31/19 59
100
80
60
40
20
0
Time

(Propagated)
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100
80
60
40
20
0
Time

03/31/19 61
• Epi curve: visual representation of
– Ill persons (cases) over time
– Magnitude of outbreak
– Type of outbreak
• Point source
– Exposure period / Time of exposure (if agent known)
– Incubation period
– Possible agents (if time of exposure known)

Example – Exposure Period
03/31/19 62
40
20
0
60
80
100
Time
Known
time of
Exposure
Average incubation
Exposure

Example – Exposure Period
03/31/19 63
60
40
20
0
80
100
Time
Known
Agent
Average incubation
Estimated
Exposure Period

Place (spot map, shaded map)
• Geographic extent of problem
• Clusters or patterns providing important etiologic
clues
• Spot maps
– Where cases live, work or may have been exposed
03/31/19 64

Person (Tables)
• Determine what population at risk
• Usually define population by host characteristics or
exposure
• Use rates to identify high-risk groups
– Numerator = number of cases
– Denominator = number of people at risk
03/31/19 65

Develop Hypotheses
 Hypotheses should address
 Source of the agent
 Mode of transmission
 Vector or vehicle
 Exposure that caused disease
03/31/19 66

Develop Hypotheses
03/31/19
• What are hypotheses?
– Statements which help us describe why and how the
outbreak occurred
• How do you generate hypotheses?
– Examine descriptive epidemiology: line list, epi-
curve
– Administer open-ended questionnaire to cases
– Review the existing body of knowledge

Develop Hypotheses
03/31/19
•Questions to ask yourself:
– What is the agent’s usual reservoir
– How is the agent usually transmitted
– What vehicles are commonly implicated
– What are the known risk factors
– In discussions with ill persons, what possible exposures were in
common

Example – Develop Hypothesis
03/31/19
• Case and clinical information:
– Acute gastroenteritis
– Most aged 14 – 18 years
– 307 ill persons (cases)
– Onset of illness: 12am Feb 12 – 10am Feb 14
• Common exposures:
– Attending youth conference

Example: Cases of Gastroenteritis by Time of Symptom Onset (n=307)
03/31/19
70
60
50
40
30
20
10
0
11-Feb 12-Feb 13-Feb 14-Feb
Date and Time of Illness Onset

03/31/19
50
40
30
20
10
0
60
70
Banquet dinner

Example: Cases of Gastroenteritis by Time of Symptom
Onset (n=307)
40
30
20
10
0
50
60
70
Banquet dinner
Catered
lunch

Example: Cases of Gastroenteritis by Time of Sym
Onset (n=307)
03/31/19
20
10
0
30
40
50
60
70
Banquet dinner
Catered
lunch
Catered
breakfas
t

Onset (n=307)
03/31/19
20
10
0
30
40
50
60
70
Banquet dinner
Catered
lunch
Catered
breakfas
t
Pizza

Onset (n=307)
03/31/19
20
10
0
30
40
50
60
70
Banquet dinner
Catered
lunch
Catered
breakfas
t
Pizza
Laboratory
Testing

Onset (n=307)
03/31/19
20
10
0
30
40
50
60
70
Banquet dinner
Catered
lunch
Catered
breakfas
t
Pizza
Laboratory
Testing 4 / 9
norovirus +

Onset (n=307)
03/31/19 77
20
10
0
30
40
50
60
70
Banquet dinner
Catered
lunch
Catered
breakfas
t
Pizza
Norovirus:
24 hour incubation

Example – Initial
Hypothesis
03/31/19
•We hypothesize that:
– norovirus was the causative agent of the
outbreak, and
– eating breakfast served on February 12 was the
most likely exposure to norovirus

Onset (n=307)
20
10
0
30
40
50
60
70
Banquet dinner
Catered
lunch
Catered
breakfas
t
Pizza
Epidemiology
Norovirus:
24 hour incubation

Onset (n=307)
03/31/19
20
10
0
30
40
50
60
70
Banquet dinner
Catered
lunch
Catered
breakfas
t
Pizza
Epidemiology:
Breakfast:
RR=1.1Dinner: RR=2.6
Norovirus:
24 hour incubation

03/31/19
10
0
20
30
40
50
60
70
Banquet dinner
Catered
lunch
Catered
breakfas
t
Pizza
Lab = Norovirus
Epi = Incubation
period too short for
norovirus
Norovirus:
24 hour incubation

Onset (n=307)
03/31/19
20
10
0
30
40
50
60
70
Banquet dinner
Catered
lunch
Catered
breakfas
t
Pizza
What has an
incubation period
this short?

Norovirus Infection
03/31/19
• RNA virus
• Resistant to environmental stress
• Incubation period usually 24 hours with range 12-72
hours
• Causes GI illness with watery diarrhea and >50% vomiting

Clostridium perfringens
Toxicoinfection
03/31/19
• Spore-forming Gram positive rod
– Arises after consumption of bacteria-containing food
– Toxin produced within the small intestine following ingestion
• Diarrhea predominant illness with little vomiting
• Incubation period usually 6–12 hours
• Associated with poorly cooked meat

Example – Additional Lab
Information
03/31/19
• Norovirus testing
– Reverse transcription PCR (RT-PCR)
– Sent to CDC for confirmation
• Clostridium perfringens enterotoxin
testing
– Oxoid toxin detection kit
– PCR

Example – Additional Lab
Information
03/31/19
• Testing did not confirm the presence of norovirus
• After 4 weeks at 4°C, stool tested for Clostridium
perfringens
enterotoxin
– Toxin present in 8 of 9 specimens tested
– Enterotoxin gene detected in 5 of 6 specimens tested

Example – Final
Hypothesis
03/31/19
– Clostridium perfringens toxicoinfection was the causative agent
of this point source outbreak
– Associated with consumption of inappropriately-cooked
chicken at the dinner served on February 12

Develop Hypotheses
03/31/19
• Questions to ask yourself regarding
hypothesis:
– Is hypothesis stated in a way that can be ‘tested’
– Does it address:
• agent
• vehicle / source
• mode of transmission
• exposure that caused illness

Test the Hypothesis
03/31/19
–Clostridium perfringens toxicoinfection was the causative
agent of this point source outbreak
–Associated with consumption of inappropriately-cooked
chicken at the dinner served on February 12
•Testable
•Agent
•Vehicle or source of agent
•Mode of transmission
•Exposure

Evaluate Hypotheses
03/31/19 90
• Two methods:
– Compare hypothesis with established facts
– Perform additional studies (e.g., analytic)
• Cohort or case-control
• Assess exposures equally among ill and non-ill persons

Evaluate Hypotheses
03/31/19 91
•Compare hypothesis with established facts
– Evidence is so strong that hypothesis does not need to be tested
– E.g., Salmonella Paratyphi B with PFGE pattern .1228 (the
outbreak strain) isolated from unpasteurized tempeh
– E.g., norovirus identified in a nursing home; norovirus is known
to be circulating in the community

7. Perform Additional Studies
Used when the relationship between exposure and
disease is less clear

Value of Analytic Studies
03/31/19
•Support for specific public health action (e.g., recall)
•Describe new diseases, learn more about known
diseases
•Address public and political concern
•Develop strategies to prevent future outbreaks
•Fulfillment of legal obligations and duty of care for
the public

Perform Additional Studies
03/31/19
•Cohort
– Able to identify every person in group (‘cohort’)
– Possible when group is well defined
– Include EVERYONE who could have been exposed
• E.g., Meeting attendees, students, wedding reception,
LTCF residents

Perform Additional Studies
03/31/19 95
•Case-control
– Compare exposures among ill persons (case) and non-ill persons (controls)
– Used when a complete list is not available or too large
– Controls are sample of same population from which cases
arose (e.g., source population)
• E.g., same city, attend same restaurant
– If a control had developed illness, would have been included as
a case

10. Implement Control /Prevention
Measures
• Implement control measures as soon as possible
• May be aimed at agent, source, or reservoir
– eliminate the source
– interrupt transmission
– reduce susceptibility
• Create mechanism to evaluate both short and long-term
effectiveness of control / prevention measures
03/31/19 96

Implement Control Measures
03/31/19
•Required response from public health
•Can occur at any point during the outbreak
•Prevent further exposure, future outbreaks
•Should be guided by epidemiologic results in
conjunction with environmental investigation
•Performed in conjunction with DPH, regulators,
industry, other agencies
•Balance between preventing further disease,
protecting credibility and reputation of institution
•Identify one person to communicate control measures

Example – Control Measures
03/31/19
• Summary:
– Attendees at a youth conference
• > 1,000 attendees
• 307 ill persons (cases)
– Clostridium perfringens toxicoinfection
– Associated with inappropriately cooked chicken
• Recommended control measures?

11. Communicate Findings
• Oral briefing for local authorities
– Local health authorities and persons responsible for
implementation of control and prevention measures
• Written reports;
– that follows intro, background, methods, results, discussion
and recommendations.
03/31/19 99

Communicate Findings
03/31/19 100
•Public and media:
– Single member of team should interact with media,
communicate progress and findings
– Media attention desirable if public action is needed
– Response to media attention important to address public
concerns about outbreak
– Opportunity to educate community
– Single overriding communication objective (SOCO)

Communicate Findings
03/31/19
• Daily updates (Situation Reports)
–Narrative
• Number of persons ill
• Number of persons potentially exposed (if known)
• Range of onset dates
• Type of symptoms
• Available laboratory results
• Number hospitalized / died
• Actions already taken
–Action Items
• Summary of recommendations and plans for surveillance, control

Communicate the Findings
102

Example – Outbreak
Report
03/31/19

Maintain Surveillance
03/31/19 Prof Dr Muhammad Tauseef Jawaid King Khalid
University KSA
104
126
•Evaluate / document effectiveness of control measures
•To ensure outbreak is over
•To ensure secondary outbreak is not occurring
•It is recommended to maintain surveillance for 2
average incubation periods following the last date of
illness onset

Conclusions
03/31/19 Prof Dr Muhammad Tauseef Jawaid King Khalid
University KSA
•Epidemiologic investigations essential component of
public health, present opportunities to:
– Characterize diseases
– Identify populations at risk
– Evaluate programs, policies, or existing prevention strategies
– Train public health staff
– Educate the public
– Fulfill legal obligations and duty of care for the public
•10 steps provide systematic framework necessary to
investigate any outbreak

References
 Michael Gregg. Field Epidemiology. 2nd
edition. Oxford University Press, 2012.
 Control of Communicable Disease in Man,
17th edition. Chin, J (ed). APHA, 2010.
 Principles & Practice of Infectious Diseases,
5th edition. Mandell GL, Bennett JE, Dolin R
(eds). Churchill Livingstone; 2010
03/31/19 106

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