Epidemiology Toolkit for
Outbreak Investigation
Meirion Evans
Communicable Disease Surveillance Centre
Insert name of
presentation on
What is an outbreak?

Occurrence of more cases of disease
than expected
• Over a particular period of time
• In a given area
• Among a specific group of people

(incidents, clusters)
Key questions

What is going on?
ASSESS

Who is affected?
DESCRIBE

What is the cause?
ANALYSE

What should be done?
ACT
10 steps in outbreak investigation
1.
Confirm existence of an outbreak
2.
Corroborate diagnosis
3.
Define and identify cases
4.
Collect and collate data
5.
Characterise cases (person - place - time)
6.
Develop hypotheses
7.
Test hypotheses
8.
Verify biological coherence
9.
Communicate results and write report
10. Implement control measures
10 steps in outbreak investigation
Confirm existence of an outbreak
Descriptive
epidemiology
Corroborate
diagnosis
3.
Define and identify cases
4.
Collect and collate data
5.
Characterise cases (person - place - time)
6.
Develop hypotheses
7.
Test hypotheses
8.
Verify biological coherence
Communicate results and write report
Analytical epidemiology
Implement control measures
Descriptive epidemiology
Define & identify cases
Collect & collate data
Characterise cases
Develop hypotheses
Descriptive epidemiology
OBJECTIVES
To refine the case definition
 To develop a demographic profile
 To identify people at risk
 To develop hypotheses about
• Potential sources of exposure
• Potential routes of transmission

Case definition

Set of criteria…
• for deciding if a person should be classified as
•
having the disease
for the purposes of that stage of the investigation

Clinical and/or laboratory criteria
 Time
 Place
 Person
• Tiered definitions: confirmed, probable, possible
Case definition
outbreak of salmonellosis in Swansea, 2011
Confirmed case

diarrhoea
• (> 2 liquid stools per day)

Probable case

diarrhoea
• (> 2 liquid stools per day)
and/or fever > 38°C
• (for at least one day)
and
and

an isolate of S. Typhimurium

contact (same household) with a
confirmed case

in a resident of Swansea
after May 2011

in a resident of Swansea
after May 2011


Case definition
sensitivity vs. specificity
Low
Specificity
Possible
High
Sensitivity
High
Specificity
Probable
Confirmed
Low
Sensitivity
Identify &
count cases
reports from staff
laboratory data
occupational health
hospitals records
GPs, etc
Collect data
demographics
clinical details (outcome)
risk factors (exposure)
Collect data

Detailed interviews
• symptoms and date of onset
• case characteristics
• all relevant exposures in relevant period

Visit (examine) some cases

Speak with clinicians

Obtain lab confirmation
Collect data
Collate data
Line listing
Example line list
Case
No.
Name
1
2
3
4
5
6
XY
AB
CD
…
…
…
Date
of birth
Date of
onset
Date of
report
Lab
results
Line listing - principles






Constitutes a unique MASTER LIST
• avoids confusion with multiple versions
• suitable for sharing
Contains unique identifier for each record
Ensures confidentiality
Contains essential information on each case
• time, place, person, clinical, lab, etc.
Can be updated as the investigation develops
Prepares data for simple descriptive analysis
Collect data
Collate data
Characterise cases
describe in
- person
- place
- time
Characterise cases

Who are the cases?
 Where do they live, work, etc.?
 When did they become ill?

Classify cases by:
• Person
• Place
• Time
Characterise cases
Time
Person
25
1200
1000
800
600
400
200
0
Place
20
15
10
5
0
0-4
'5-14 '15-44 '45-64
1
'64+
2
3
4
5
6
7
8
9
Age Group
Develop hypotheses
Pathogen?
Source?
Transmission?
10
Person
WHO is getting the disease?
Sex and age group
 Ethnicity
 Pre-existing conditions
 Medication
 Invasive procedures
 Surgical treatment

Person
C. difficile outbreak in peri-partum women
Place
WHERE is the disease occurring?
In the community
• Place of residence
• Place of work
 In hospital
• Floor
• Ward or unit
• Operating theatre
• Outpatient departments

Place
Measles outbreak in a local community
Time
WHEN does the disease occur?
Figure
1. Reported
cases
campylobacteriosis
(n=45)
Svolvær,X,
Norway,
Figure.
Cases
of of
gastroenteritis
(n=45)
in in
Hospital
Walesby
date of onset January
and
1997.
by date
ofFebruary
onset, January
and February 2012
patientcase
case
= 11primary
10
= 11secondary
staff casehousehold case
5
22 23 24 25 26 27 28 29 30 31 1
January
2
3
4
5
6
February
7
8
9 10
Time - use of the epidemic curve

To describe the outbreak
• Start date, end date, duration
• Peak, shape, magnitude
• Outliers and atypical cases

To develop hypotheses
• Incubation period
• Aetiological agent
• Type of source and transmission
• Time of exposure
Time
C. difficile outbreak timeline
Time
Pseudomonas on a neonatal ICU
Develop hypotheses
What is the disease?
 Who is at risk of becoming ill?
 What is the source and the vehicle?
 What is the mode of transmission?

Analytical epidemiology
Test hypotheses
Verify biological coherence
Analytical epidemiology
OBJECTIVES

To test hypotheses
• Is there an association between exposure
•
•
•
and disease?
How strong is the association?
What proportion of cases are explained by
the exposure?
Is there an increased risk of disease with
increased exposure (dose-response)?
Test hypotheses


Analytical studies
• Cohort study
• Case-control study
These must test specific hypotheses
 Compare the predictions of your hypotheses
with further investigations
Testing hypothesis - comparing groups

Cohort study
- attack rate exposed group
- attack rate unexposed group
= risk ratio

Case control study
- proportion of cases exposed
- proportion of controls exposed
= odds ratio
Cohort Study

Identify a cohort
• Categorise individuals based on whether or
•
not they were exposed
Compare attack rates
 exposed vs unexposed

Suitable when a cohort is easily identifiable
e.g. specific ward(s), operating theatre list(s)
Case-Control Study

Identify cases
• that meet the case definition

Select non-diseased individuals from the
same population to act as controls
 Compare proportions exposed
• cases vs. controls

Suitable when a distinct group is not easily
identifiable e.g. long-term outbreak, OPD
Cohort study two-by-two table

Calculate association between exposure & disease
Ill
Well
Exposed
a
b
a+b
Unexposed
c
d
c+d
Total
Total
N
Risk ratio [RR] = a/(a+b) / c/(c+d)
CC study two-by-two table

Calculate association between disease & exposure
Case
Control
Exposed
a
b
Unexposed
c
d
Total
Total
N
Odds ratio [OR] = ad/bc
Table from a case control study
Risk factors for MRSA bacteraemia
Cases
n=42
Controls
n=90
Odds Ratio
Indwelling catheter on admission
5
3
3.9
Prior admission
35
66
1.8
Bed sore
5
1
12.0
Skin ulcer
5
5
2.3
Central line during admission
17
1
60.5
Urinary catheter during admission
22
2
48.4
Blood transfusion
15
7
6.6
Exposure
On admission
On or during admission
During admission
Verify biological coherence

Corroborative studies
• Microbiological investigation
 suspected sources or vehicles of transmission
 typing and molecular diagnostics
• Environmental investigation
• Traceback investigations (origin of supplies)
• Air circulation data
The reality….
time
Confirmation
Site visit
Recommendations
Case definition
Outbreak
report
Organise data
Confirm Diagnosis
Outbreak
suspected Form Outbreak
Control Team
Descriptive
Epidemiology
Line list
Analytical
Epidemiology
Control measures
Methodological issues
Keep things simple
 Stick to basic principles
 Get as much information as possible
 Be clear what the key questions are
 Design investigations to test
hypotheses appropriately
